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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.

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.

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.

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.

Persistence of mucosal gastric carcinomas for 8 and 6 years in two patients. A small gastric carcinoma was detected in a man, but he refused surgery. Eight years later, he was readmitted for a check-up, and a partial gastrectomy was performed. Pathologic examination revealed a well-differentiated adenocarcinoma restricted within the mucosa. In another man, an irregularly shaped, grossly depressed lesion indicating a malignancy was present at the gastric angle, and 6 years later he agreed to a partial gastrectomy. The lesion proved to be a well-differentiated adenocarcinoma confined to the mucosa. Retrospective examination of the original biopsy specimen revealed a small area of adenocarcinoma, presumably overlooked at the initial examination. Thus, some gastric carcinomas of the well-differentiated type can grow at an extremely slow rate, without extensive spread or invasion. Findings in these cases contribute to knowledge of the biological behavior of gastric carcinomas.

Serum and tissue magnesium concentrations in patients with heart failure and serious ventricular arrhythmias. OBJECTIVE: To compare magnesium concentrations in serum and tissue from patients with heart failure. Two groups of patients were compared, those with or without serious ventricular arrhythmias. DESIGN: Consecutive enrollment. Blinded laboratory analyses. SETTING: Referral inpatient service of the cardiology division of a university hospital. PATIENTS: Twenty-three patients with idiopathic dilated cardiomyopathy and mild to moderately severe congestive heart failure (New York Heart Association functional class II to IV) were divided into two groups: 9 patients with sustained ventricular tachycardias and 14 patients without serious ventricular arrhythmias (control). INTERVENTIONS: Medications for heart failure were withdrawn 12 hours or more before study. Antiarrhythmic therapy was continued throughout the study. MEASUREMENTS AND MAIN RESULTS: The patients had skeletal muscle biopsies, myocardial biopsies, and blood sampling for the analysis of magnesium concentrations. No statistically significant differences in the mean magnesium concentrations in serum, circulating mononuclear cells, skeletal muscle, and myocardium were found when the 9 patients with ventricular arrhythmias were compared with the 14 control patients without serious ventricular arrhythmias. CONCLUSIONS: In a general, ambulatory sample of patients with heart failure, magnesium depletion in serum and tissue does not appear to occur more commonly in patients with serious ventricular arrhythmias than in patients without serious ventricular arrhythmias.

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).

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.

Circulating Epstein-Barr virus-carrying B cells in acute malaria. Epstein-Barr virus (EBV) infection and Plasmodium falciparum malaria are two known cofactors in the aetiology of endemic Burkitt's lymphoma. To assess the relation between these factors, limiting dilution analysis was used to assess the number of EBV-carrying B cells in the circulation of Gambian children during and after acute malaria. Numbers of virus-carrying cells were five times higher in acute malaria patients and in UK patients with infectious mononucleosis than in convalescent malaria patients and in healthy control adults from the UK. Spontaneous outgrowth in limiting dilution cultures from acute malaria samples was inhibited by acyclovir, a viral DNA polymerase inhibitor. The mechanism of outgrowth, therefore, was virus release from the in-vivo infected cell, which led to infection and immortalisation of co-cultured normal B cells. The findings provide evidence that acute malaria is associated with an increase in the number of EBV-carrying B cells in the circulation. Because of this increase, there is a greater chance of a cytogenetic abnormality occurring in such a cell, with consequent evolution of Burkitt's lymphoma.

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.

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.

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.

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.

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.

Duodenal-caval fistula. Duodenal-caval fistula is a rare, often lethal disease that requires prompt diagnosis and surgical correction. A case of duodenal-caval fistula due to duodenal ulceration is presented and discussed.

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.

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%.

Somatostatin and analogues in the treatment of cancer. A review Somatostatin is a naturally occurring cyclic tetradecapeptide that inhibits release of growth hormone and all gastrointestinal hormones. The beneficial effect of somatostatin in the treatment of certain hypersecretory disorders of hormone excess in well recognized; however its clinical usefulness has been limited in the past by its extremely short plasma half-life. The development of long-acting somatostatin analogues has provided clinically useful agents for treatment of hormone-producing tumors. In addition to well-known inhibiting effects on hormone release and actions, recent studies using experimental tumor models have demonstrated an antiproliferative effect of somatostatin and its analogues on growth of a variety of neoplasms. The exact role of somatostatin analogues in cancer therapy has yet to be established; however studies suggest that these agents could provide a useful and relatively nontoxic adjuvant therapy in the treatment of certain tumors. In this review, the oncologic application of somatostatin and possible mechanism of action are examined and current clinical and experimental studies are summarized.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Decreased local toxicity with subcutaneous diamorphine (heroin): a preliminary report. We report the cases of 5 patients who developed severe local toxicity during the subcutaneous administration of morphine sulphate and hydromorphone hydrochloride. All patients required site changes more frequently than once every 24 h due to redness, swelling, or pain while receiving morphine or hydromorphone. All patients showed prolongation in the duration of sites of infusion once an equianalgesic dose of diamorphine hydrochloride (heroin) was started. No change in pain control or systemic toxicity was detected with diamorphine. These findings suggest that diamorphine could be a useful alternative for patients who develop severe toxicity to subcutaneous morphine or hydromorphone.

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.

Reduction in infarct size by the phospholipase inhibitor quinacrine in dogs with coronary artery occlusion. It has been suggested that activation of tissue phospholipases may contribute to the development of ischemic cell injury. In the present study we sought to assess whether administration of the phospholipase inhibitor quinacrine would reduce the extent of myocardial necrosis after coronary artery occlusion. In open-chest, anesthetized dogs the left anterior descending coronary artery was ligated, and technetium-99-labeled albumin microspheres were injected into the left atrium to measure the area at risk. The animals were then randomly divided into a control group (n = 8) and a group receiving quinacrine (5 mg/kg intravenous bolus followed by a 40 micrograms/kg/min infusion for 6 hours; n = 9). The animals were killed 6 hours after occlusion, and the infarcted area was delineated by triphenyltetrazolium chloride staining. The extent of the risk region was similar in the two groups (32.3 +/- 2.1% of the left ventricle in control dogs and 34.2 +/- 3.4% in quinacrine-treated dogs). Infarct size was 86.4 +/- 8.8% of the risk region in control animals, whereas in treated dogs it averaged 62.3 +/- 6.4% of the risk region (p = 0.05). No differences were found in heart rate, arterial pressure, and rate-pressure product between the two groups. Thus administration of the phospholipase inhibitor quinacrine reduced the extent of myocardial necrosis in a model of fixed coronary artery occlusion. Preservation of membrane phospholipids, reduced formation of lipoxygenase metabolites, or both may mediate this phenomenon.

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.

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.

Effect of mitral regurgitation and volume loading on pressure half-time before and after balloon valvotomy in mitral stenosis. Doppler pressure half-time (PHT) is frequently used to assess mitral valve area (MVA), but the reliability of PHT has recently been challenged, specifically in the setting of balloon mitral valvotomy when hemodynamics have been abruptly altered. The effect of volume loading both before and after balloon mitral valvotomy on computation of MVA by Gorlin and by PHT in 18 patients with high-fidelity micromanometer measurements of left atrial and left ventricular pressure was therefore examined. Echocardiographic MVA increased from 0.91 +/- 0.15 to 1.97 +/- 0.42 cm2 after valvotomy. Volume loading produced significant increases in left atrial pressure (16 to 23 before and 12 to 20 mm Hg after valvotomy), in cardiac output (3.7 to 4.1 before and 3.9 to 4.6 liters/min after valvotomy), and in mitral valve gradient (11 to 14 before and 5 to 7 mm Hg after valvotomy). These hemodynamic changes were associated with modest but significant decreases in PHT and increases in MVA estimated by 220/PHT (0.66 to 0.81 before and 1.64 to 1.96 cm2 after valvotomy), whereas the MVA by Gorlin was not affected in a consistent fashion by volume loading (0.85 to 0.89 before and 1.66 to 1.69 cm2 after valvotomy). The correlation between Gorlin MVA and 220/PHT was only fair (r = 0.73, p less than 0.001) and was significantly poorer among patients with greater than 1+ mitral regurgitation (r = 0.72) than among those with less or no regurgitation (r = 0.79) (p = 0.001 by analysis of covariance for mitral regurgitation effect).

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.

Racial differences in the anterior circulation in cerebrovascular disease. How much can be explained by risk factors? The entry characteristics of 1367 patients enrolled into the Extracranial/Intracranial Bypass Study were examined to determine if site differences in intracranial and extracranial arterial lesions among racial groups could be explained by differences in risk factors. Blacks were more often hypertensive, diabetic, or cigarette smokers, while whites had higher systolic blood pressure and hemoglobin values. Orientals had the lowest prevalence of vascular risk factors. Despite these differences in risk factors, multivariate analysis showed race to be an independent and strong predictor of the location of cerebrovascular lesions. To our knowledge, this study is unique in documenting risk factors prospectively and systematically in three racial groups simultaneously. Although generalization is limited by possible biases related to patient selection, the results affirm previous tentative conclusions about the role of race in determining the location of cerebrovascular disease.

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.

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).

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.

Peptic ulcer disease. How to treat it now. Options for treatment of peptic ulcer disease are becoming more diverse. Most new agents are effective yet offer no real advantage over more traditional therapy. However, omeprazole (Prilosec) may be of benefit owing to its potent inhibition of acid secretion, but it is not yet approved for this purpose. Whether treatment of Helicobacter pylori infection will prove beneficial is not yet known, but the answer should be forthcoming. Finally, as with any disease process, alleviation of risk factors is always important. Appropriate counseling regarding use of nonsteroidal anti-inflammatory drugs and cigarette smoking is a necessity.

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.

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.

The changing clinical spectrum of thromboangiitis obliterans (Buerger's disease). Between 1970 and 1987, 112 patients were diagnosed as having thromboangiitis obliterans (TAO). The age was 42 +/- 11 years (mean +/- SD; range, 20-75 years); 23% were women, and 7% were more than 60 years old when they were first diagnosed. Ischemic ulcerations were present in 85 (76%) patients: 24 (28%) patients with upper-extremity, 39 (46%) patients with lower-extremity, and 22 (26%) patients with both upper- and lower-extremity lesions. Ninety-one (81%) patients had rest pain, 49 (44%) patients had Raynaud's phenomenon, and 43 (38%) patients had superficial thrombophlebitis. We were able to follow up 89 of the 112 (79%) patients for 1-460 months (mean follow-up time, 91.6 +/- 84 months). Sixty-five (73%) patients had no amputations, while 24 (27%) had one or more of the following amputations: finger, six (15%) patients; toe, 13 (33%) patients; transmetatarsal, four (10%) patients; below knee, 14 (36%) patients; and above knee, two (5%) patients. Forty-three (48%) patients stopped smoking for a mean of 80 +/- 105 months (median, 46.5 months; range, 1-420 months), and only two (5%) patients had amputations after they stopped smoking, while 22 (42%) patients had amputations while continuing to smoke (p less than 0.0001). The spectrum of patients with TAO is changing in that the male-to-female ratio is decreasing (3:1), more older patients are being diagnosed, and upper-extremity involvement is commonly present. In the 48% of patients who stopped smoking, amputations and continued disease activity were uncommon.

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.

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.

Postencephalitic acquired Tourette-like syndrome in a child. We report a 6-year-old girl who developed a Tourette-like syndrome following presumed herpes encephalitis. This case suggests that tics can be acquired in childhood and may be associated with lesions involving basal ganglia or limbic circuitry.

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.

Clue cells in predicting infections after abdominal hysterectomy. Seventy women scheduled for abdominal hysterectomy were examined for the presence of clue cells in the vaginal discharge in an attempt to identify a possible risk group for development of postoperative infection. Seven of 20 women (35%) with clue cells developed vaginal cuff infections or wound infections, compared with four of 50 women (8%) without clue cells (P less than .01). Women with bacterial vaginosis, diagnosed by air-dried vaginal smears, are therefore at risk for postoperative infection.

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.

Mucous cell hyperplasia in an odontogenic cyst from a patient with Muir-Torre syndrome. Mucous cell proliferation in a periapical radicular cyst from a patient with a family history of colonic malignancies and multiple sebaceous neoplasms of the skin, so-called Muir-Torre syndrome, is reported. Such goblet cell hyperplasia has not been previously reported to be associated with any known syndrome. We believe the finding of mucous cell hyperplasia in an odontogenic cyst may not simply be coincidental, but should raise suspicion of paraneoplastic potential and warrant further evaluation for possible occult neoplastic disease.

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.

Quality of life research in oncology. Past achievements and future priorities. The status of quality of life research in oncology is assessed, and priorities for future research with regard to conceptual and theoretical developments, focus and content of research, research designs and practical strategies for research implementation, and transferring information to clinical practice and medical policy decision-making are identified. There is general agreement that quality of life is a subjective and multidimensional construct, yet comprehensive theoretical models have not been developed and applied fully. We recommend that future research be based on conceptual models that explicate the interrelationships among quality of life domains throughout the stages of cancer care. These models, and the longitudinal research that follows from them, should attend specifically to cross-class and cross-cultural issues to avoid overgeneralization from theory and research that are based largely on the views of the majority culture. We encourage the inclusion of this theory-based quality of life assessment as a standard component of clinical trials. Success in this endeavor will require additional standardization of quality of life measures for use across a range of cancer patient populations, including the development of age-specific norms and instruments designed to assess the entire family system.

Cardiac pathology in 470 consecutive forensic autopsies. Cardiovascular disease continues to be the single most common generic cause of sudden and unexpected deaths. Atherosclerotic coronary heart disease and acute myocardial infarction are the most prevalent forms of fatal cardiac disease observed at autopsy. Other cardiac lesions are frequently listed as causes of death, but the prevalence of such lesions as incidental findings in the general population is unknown. In this study, 470 consecutive forensic autopsies were evaluated for minor and major anomalies. The most frequently observed major congenital finding was floppy mitral valve (5%). Tunneled coronary arteries, considered minor congenital findings, were seen in 29%. Atherosclerotic coronary heart disease was the most common major acquired finding, observed in 16% of cases. Of the 470 hearts, only 8% were considered normal.

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.

Pulmonary involvement in the eosinophilia-myalgia syndrome. We describe the cases of three women with pulmonary involvement in the eosinophilia-myalgia syndrome. The illness was characterized by elevated peripheral blood eosinophil counts, myalgias, fatigue, and dyspnea. Two of three patients had bilateral infiltrates on chest roentgenograms. All three had markedly decreased carbon monoxide diffusing capacities and pulmonary hypertension. High-dose prednisone therapy provided only partial resolution of the pulmonary symptoms. Open lung biopsy specimens showed chronic interstitial and perivascular infiltrates in two of the patients and moderate fibrointimal hyperplasia of pulmonary vasculature in the third. High-dose prednisone therapy prior to the biopsies may have modified the original histologic features.

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.

Endocapsular hematoma. Description and treatment of a unique form of postoperative hemorrhage. Endocapsular hematoma, to our knowledge, is a previously unreported type of postoperative hemorrhage. In this condition, blood collects in the narrow space between the anterior surface of the posterior capsule and the posterior optic surface of a posterior chamber intraocular lens. Endocapsular hematoma differs from anterior chamber hyphema in several ways: the location of the blood is in the endocapsular space, a small amount of endocapsular blood can cause visually disabling symptoms, the blood in the endocapsular space often fails to reabsorb, and neodymium-YAG laser capsulotomy can be used to drain the endocapsular blood into the vitreous cavity. We present six cases of endocapsular hematoma. Neodymium-YAG laser capsulotomy was successfully used to drain the endocapsular hematoma in three of these cases.

Reproducibility of image interpretation in immunoscintigraphy performed with indium-111- and iodine-131-labeled OC125 F(ab')2 antibody injected into the same patients. An important criterion for the clinical use of a new imaging technique is the correct reproducibility of interpretation. Forty-six paired immunoscintigraphic examinations were performed on 43 patients with suspected ovarian carcinoma recurrence using F(ab')2 fragments of OC125 antibody labeled first with indium-111 and then with iodine-131. Planar scintigraphy (PS) and emission computed tomography (ECT) images were interpreted blindly and separately by three observers, and reproducibility was evaluated by a kappa concordance index. Intra- and interobserver reproducibility were generally satisfactory (kappa values of 0.6 and 0.7, respectively). Binomial analysis of kappa values for ECT showed the superiority of indium-111 for intraobserver (p = 0.035) and interobserver (p = 0.0039) study. However, for PS there was no significant difference in reproducibility with the two radionuclides.

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.

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.

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.

Double-blind comparison of topical lignocaine-prilocaine cream (EMLA) and lignocaine infiltration for arterial cannulation in adults. In a double-blind, double-dummy study, the efficacy of topical 5% EMLA cream was compared with that of lignocaine infiltration in alleviating the pain of arterial cannulation. Forty unpremedicated adults were allocated randomly to four groups to receive EMLA cream alone, EMLA and 0.9% saline infiltration, EMLA and 1% lignocaine infiltration or placebo cream and 1% lignocaine infiltration. Following arterial cannulation, pain was assessed by the patient using a visual analogue score and by an independent observer using a four-category verbal rating score. Significantly lower pain scores were observed in all patients receiving EMLA compared with those receiving placebo cream and lignocaine infiltration by both patient (P less than 0.01) and observer (P less than 0.001) assessments. There were no significant differences between the three EMLA groups.

Computed tomography of metastatic cervical lymph nodes. A clinical, computed tomographic, pathologic correlative study. A retrospective comparative study of 63 neck dissections was undertaken to evaluate further the accuracy of high-resolution computed tomography (CT) in the detection of nodal metastases, as previous studies have indicated a trend toward the superiority of CT scanning over palpation. The respective values of neck examination, CT scanning, and histopathologic examination were assessed in 51 patients with head and neck cancer who underwent a total of 63 neck dissections. The overall agreement between clinical examination findings and histopathologic findings was 92% vs 81% for CT scanning. A retrospective analysis of the CT findings failed to reveal greater accuracy. We found nodes measuring 10 mm or more with central low density always to be malignant. Because CT scanning seems to offer little advantage over palpation in the nonirradiated neck, it should not be regarded as an essential tool in the staging of nodal disease. After radiation therapy, as neck dissection is only performed because of clinical or radiologic suspicion, CT scanning is of utmost importance.

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).

Local injection treatment of tennis elbow--hydrocortisone, triamcinolone and lignocaine compared. Corticosteroid injections are the mainstay of treating tennis elbow even though their effectiveness has not been well established by controlled studies. A survey of consultant rheumatologists confirmed a widespread preference for this treatment but they varied in their choice of steroid dose and preparation. We examined the value of some practices by comparing local injections of 2 ml 1% lignocaine with either 10 mg triamcinolone or 25 mg hydrocortisone made up to 2 ml with 1% lignocaine (Study 1). The investigation was conducted double blind. Within the first 8 weeks, pain relief was greater for triamcinolone than hydrocortisone although the differences were not statistically significant. The response to both steroid preparations was significantly better than for lignocaine up to this point but at 24 weeks, the degrees of improvement were similar for all three groups and many patients still had pain. Relapse was common. In a separate but similarly designed study, triamcinolone 10 mg was compared with 20 mg of the same agent. Improvements of pain were similar and followed the same time scale. Post-injection worsening of pain occurred in approximately half of all steroid treated patients in both studies and this was sometimes severe and persistent. It was less frequent amongst those given lignocaine alone. Skin atrophy was reported in all groups but was more frequent amongst those given triamcinolone in Study 1. In conclusion, more rapid relief of symptoms was achieved with 10 mg triamcinolone than with 25 mg hydrocortisone or lignocaine alone and there was less needed to repeat injections. Results obtained with 20 mg triamcinolone were similar to those of the smaller dose.

Noninvasive discrimination of right atrial ectopic tachycardia from sinus tachycardia in "dilated cardiomyopathy". Right atrial ectopic tachycardia (RAET) with secondary cardiac dysfunction can be difficult to differentiate from primary dilated cardiomyopathy (CMP) with sinus tachycardia. In an attempt to separate RAET from CMP by noninvasive testing, routine surface electrocardiograms (EGGs), 24-hour ambulatory ECGs (Holter monitors), and echocardiograms of patients with RAET (n = 34) and CMP (n = 33) were reviewed. RAET atrial rates were significantly faster than CMP rates on the resting ECG and on Holter monitoring; 12 of 33 patients with RAET had resting ECG rates greater than 150% of predicted normal values for age but none of 32 patients with CMPs had resting ECG rates in this range. Mean P wave axis in the horizontal plane was more posterior in patients with RAET and was less than 0 degrees (negative in lead V2) in 8 of 29 patients with RAET but in 1 of 33 patients with CMP. Second-degree atrioventricular (AV) block was observed in 12 of 33 patients with RAET but in none of 33 with CMP. Shortening fraction less than 10% was found in 13 of 33 individuals with CMP but in only 1 of 27 with RAET. We conclude that noninvasive studies can help identify RAET among patients with poor functioning hearts and right atrial tachycardia.

Disruption of the human SCL locus by "illegitimate" V-(D)-J recombinase activity. A fusion complementary DNA in the T cell line HSB-2 elucidates a provocative mechanism for the disruption of the putative hematopoietic transcription factor SCL. The fusion cDNA results from an interstitial deletion between a previously unknown locus, SIL (SCL interrupting locus), and the 5' untranslated region of SCL. Similar to 1;14 translocations, this deletion disrupts the SCL 5' regulatory region. This event is probably mediated by V-(D)-J recombinase activity, although neither locus is an immunoglobulin or a T cell receptor. Two other T cell lines, CEM and RPMI 8402, have essentially identical deletions. Thus, in lymphocytes, growth-affecting genes other than immune receptors risk rearrangements.

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.

Alcoholics and liver transplantation. The Ethics and Social Impact Committee of the Transplant and Health Policy Center. Two arguments underlie a widespread unwillingness to consider patients with alcoholic cirrhosis of the liver as candidates for transplantation. First, alcoholics are morally blameworthy, their condition the result of their own misconduct; such blameworthiness disqualifies alcoholics in unavoidable competition for organs with others who are equally sick but blameless. Second, because of their habits, alcoholics will not exhibit satisfactory rates of survival after transplantation; good stewardship of a scarce lifesaving resource therefore requires that alcoholics not be considered for liver transplantation. These arguments are carefully analyzed and shown to be defective. There is not good moral or medical reason for categorically precluding alcoholics as candidates for liver transplantation. It would, in addition, be unjust to implement such a preclusion simply because others might respond negatively if we do not.

Absorption and motility of the bypassed human ileum. The authors assessed absorption and motility of the human ileum after a prolonged period of disuse. In eight patients with ulcerative colitis, a manometric-catheter assembly was placed via the ileostomy into the unused portion of distal ileum two months after ileal pouch-anal anastomosis and temporary diverting loop ileostomy. The distal ileum was perfused at 5 ml/min with an isosmotic solution of either sodium chloride or ileal chyme diluted with sodium chloride for three hours before and three hours after a meal on two consecutive days. Absorption was measured, single and clustered pressure waves were identified and quantitated with the aid of a computer program, and a motility index was calculated. Mean absorption +/- S.E.M. of both perfusates was poor on day 1 (-10 +/- 2 ml/25 cm x 30 min), and the meal induced no ileal motor response. By day 2, however, absorption of both perfusates was much improved (-1 +/- 2 ml/25 cm x 30 min; P less than 0.05), and the number of discrete clustered contractions and the motility index now clearly increased after the meal (2.6 +/- 0.6 vs. 7.2 +/- 1.0 clustered waves/hr; 7.5 +/- 0.5 vs. 9.7 +/- 0.2 motility units/30 min; P less than 0.05). The conclusion was that absorption and motility of the human ileum were impaired after two months of disuse, but that ileal absorption and motility improved one day after the introduction of isosmotic ileal perfusates.

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.

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.

Decreased expression of integrin adhesive protein receptors in adenocarcinoma of the breast. The integrin superfamily represents a major class of receptors mediating cell-substrate adhesion. Our recent study of the tissue distribution of the alpha 2 beta 1 integrin, a cell-surface collagen receptor, revealed that high levels of receptor expression were associated with orderly, regulated epithelial cell proliferation. Those observations prompted the present investigation of alpha 2 beta 1 and other integrins in adenocarcinoma of the breast. The alpha 2 beta 1 integrin was highly expressed on the epithelium of the ducts and ductules of normal breast tissue. Normal or nearly normal levels of the receptor were expressed in fibroadenomas. In contrast, markedly decreased or undetectable alpha 2 beta 1 expression was typical of poorly differentiated adenocarcinomas. Well-differentiated lesions exhibited intermediate levels of expression. Similar, but less extensive, decreases in expression were observed for the alpha 5 beta 1 (fibronectin receptor) and alpha v beta 3 (vitronectin receptor). Significant expression of the beta 1 subunit on even poorly differentiated tumors suggests that the expression of other undefined members of the beta 1 family is not reduced to the same low level as alpha 2 beta 1 and alpha 5 beta 1. Expression of the alpha 2 beta 1 integrin was highly correlated with estrogen-receptor expression. Decreased expression of alpha 2 beta 1 and other integrin adhesive protein receptors probably contributes to the altered adhesive properties of tumor cells characteristic of the malignant phenotype.

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.

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.

Accelerated fractionation for high-grade cerebral astrocytomas. Preliminary treatment results. A Phase I/II accelerated fractionation study for high-grade cerebral astrocytomas began in October 1987. Forty-two patients, 25 men and 17 women, were entered in the study. Median age was 58.5 years of age (range, 32 to 78 years). Performance status was 0, 1, 2, and 3 on Eastern Cooperative Oncology Group (ECOG) scale for 13, 19, 9, and 1 patients, respectively. Thirty-six patients had undergone partial resection, and six had stereotactic biopsy only. All patients had histologically proven astrocytomas (6 Grade 3, and 36 Grade 4). Treatment consisted of radiation therapy doses of 4400 cGy in 22 daily fractions to the whole brain plus a boost of 1600 cGy in 8 fractions given concomitantly with the last 8 whole-brain treatments using a twice daily schedule with an interfraction interval of 8 hours. Median survival time was 57 weeks from the date of starting irradiation. Survival was 50% and 28% at 1 and 2 years, respectively. Alopecia and scalp erythema were seen in all patients; nine patients had localized areas of moist desquamation in the retroauricular region. Decreased hearing and serous otitis media were seen in five patients within 1 to 2 months from the end of treatment. Increasing somnolence was marked in eight patients with progressive deterioration of performance status; computerized axial tomography (CAT) scan studies in all eight patients showed evidence of disease recurrence with associated brain edema and mass effect. Three patients had a second resection for a recurrent tumor with no evidence of brain necrosis at craniotomy. To date, the accelerated fractionation schedule appears to be well tolerated with valuable shortening of overall treatment time. The preliminary results are encouraging, and longer follow-up time is required to evaluate tumor control and toxicity.

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.

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.

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.

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.

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.

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.

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.

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.

The erythrocyte sedimentation rate in congestive heart failure. BACKGROUND AND METHODS. Physicians have long believed that the erythrocyte sedimentation rate is low in patients with congestive heart failure, but this concept is based on a misinterpretation of the results in a single report published in 1936. To reevaluate this concept in the modern era, we measured the sedimentation rate in 242 patients who were referred for treatment of chronic heart failure. RESULTS. The sedimentation rate was low (less than 5 mm per hour) in only 24 patients (10 percent) but was increased (above 25 mm per hour) in 50 percent. Patients with low or normal sedimentation rates (less than or equal to 25 mm per hour) had more severe hemodynamic abnormalities than patients with elevated rates: lower cardiac index (mean +/- SEM, 1.7 +/- 0.1 vs. 2.0 +/- 0.1 liters per minute per square meter of body-surface area) and higher mean right atrial pressure (mean +/- SEM, 12 +/- 1 vs. 9 +/- 1 mm Hg) (both P less than 0.0001). New York Heart Association functional class IV symptoms were present in 66 percent of the patients with a low or normal sedimentation rate, as compared with 42 percent of those with elevated rates (P less than 0.0001). After one to three months of therapy, patients whose sedimentation rates decreased showed little hemodynamic or clinical response to treatment, whereas both cardiac performance and functional status improved in patients whose rates increased (P less than 0.02 for the comparison between groups). The sedimentation rate was correlated with the plasma fibrinogen level (r = 0.64, P = 0.0025), and changes in the sedimentation rate during treatment were correlated inversely with changes in mean right atrial pressure (r = -0.57, P = 0.0002). During long-term follow-up, patients with low or normal sedimentation rates had a worse one-year survival than patients with elevated rates (41 vs. 66 percent, P = 0.01). CONCLUSIONS. These data indicate that the erythrocyte sedimentation rate is correlated with the severity of illness in patients with chronic heart failure. Because of its lack of discriminatory power, however, the test is of limited value in the clinical management of this disorder.

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.

Cumulative AIDS incidence and altered mortality from bacterial infections. To determine whether populations with high cumulative incidence of acquired immunodeficiency syndrome (AIDS) experienced increased deaths from sepsis, central nervous system abscess, or endocarditis, New Jersey AIDS patients were grouped according to their age, sex, race, and residence-specific cumulative incidence of AIDS since the onset of the AIDS epidemic. Between 1980 and 1986, among 25-44 year olds in the highest cumulative incidence group for AIDS, sepsis mortality increased from 3.3 to 15.2 deaths/100,000/year, an increase of 11.9 deaths/100,000/year (95% confidence interval (6.9, 17.0) deaths/100,000/year); mortality from central nervous system abscesses increased from zero to 1.7 (0.1, 3.2) deaths/100,000/year; and mortality from endocarditis increased from 0.8 deaths/100,000/year to 2.4 deaths/100,000/year, an increase of 1.6 (-0.5, 3.7) deaths/100,000/year. Age-matched New Jersey patient populations with low cumulative incidence of AIDS did not sustain a similar increase. The HIV disease-associated increase in sepsis mortality among young populations represents a new component of the substantial increase in U.S. sepsis mortality that occurred over the last two decades, but was previously limited to older populations.

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.

Antigen CA 19-9: presence in mucosa of nondiseased mullerian duct derivatives and marker for differentiation in their carcinomas. CA 19-9, a side branch of the Lewis blood group system, is a sialylated Lewis A antigen that is highly expressed by many adenocarcinomas of the digestive tract. The mullerian duct-derived mucosa of the uterus and fallopian tubes also synthesizes Lewis blood group antigens. To test whether the expression of CA 19-9 is enhanced in carcinomas of mullerian duct origin, we performed immunohistochemical staining for CA 19-9 in normal tissues from 33 women and in adenocarcinomas from 88 patients. In the normal uterine cervix, CA 19-9 was expressed in the cytoplasm of scattered glandular cells in 26 of 29 specimens. It was observed in the apical regions of mucosal cells in six of 26 normal endometrial samples and two of 13 normal fallopian tube specimens. These results are consistent with the presence of antigen CA 19-9 on a secretory product of the nondiseased mucosa of the mullerian duct. In adenocarcinomas of the endocervix, endometrium, and fallopian tubes, CA 19-9 was found in seven of 11, 57 of 71, and five of six samples, respectively. Progressive loss of differentiation was accompanied by disruption of subcellular localization of CA 19-9 and its secretion toward the glandular lumina. In well-differentiated regions of tumors, the antigen was detected mainly at the luminal surface of cancerous glands, whereas the staining was mostly cytoplasmic or vacuolar in less differentiated areas. The degree of CA 19-9 expression was inversely related to tumor differentiation (P less than .001).

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.

Continuous epidural hydromorphone for postthoracotomy pain relief Forty-four patients were treated with a continuous infusion of lumbar epidural hydromorphone (0.05%) after thoracic operations. Postoperatively, visual analog pain scores were obtained. On postoperative day 1 and 2, more than 90% of the patients experienced either no pain (visual analog pain scale = 0) or mild pain (visual analog pain score = 1 to 3) at rest. The incidence of side effects (hypoventilation, pruritis, and nausea) was less than reported with other epidurally administered opioids. Continuous infusion of lumbar epidural hydromorphone produced safe, predictable analgesia after thoracotomy.

Congenital biliary tract disease. Jaundice in the pediatric patient requires prompt and directed evaluation. This dictum is highlighted in infants with biliary atresia, in whom the progressive sclerosing process results in complete obliteration of patent but microscopic hilar biliary structures by 4 months of age. Kasai's operation, if done before that time, will re-establish bile drainage in 90% of infants. One fourth to one third of patients achieve long-term jaundice-free survival. Complications of cholangitis, portal hypertension, and fat malabsorption are experienced by many patients. In children with early or late operative failure, liver replacement now offers legitimate hope for extended survival. Choledochal cyst is a conglomerate of pancreaticobiliary anomalies consisting of a choledochal cyst, a common-channel-type pancreaticobiliary junction, intrahepatic cystic disease, and partial obstruction of the distal common bile duct. Many patients have one or more of these malformations. It is now widely accepted that the preferred treatment of choledochal cyst is total excision of the diseased biliary duct with reconstruction by Roux-en-Y choledochojejunostomy. "Internal" excision avoids injury to other structures in the hepatoduodenal ligament, particularly if pericystic inflammation is present. Congenital perforation of the common bile duct responds in most cases to simple peritoneal drainage of the perforation. Retention of the tube cholecystostomy is useful for subsequent cholangiographic follow-up. Tube cholecystostomy may also be useful for irrigation of the biliary tract in infants with inspissated bile syndrome.

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.

Pseudoaneurysm: diagnosis with color Doppler ultrasound. Increasing numbers of interventional radiologic procedures, often with large arterial catheters, have led to increasing total numbers of complications. Pseudoaneurysm is not an infrequent complication. It is often difficult to differentiate pseudoaneurysm clinically from hematoma. In the past, we have used gray scale duplex scanning to aid in this differentiation. We have recently found color Doppler scanning to allow quicker, easier, and more accurate diagnosis. Color Doppler imaging also can often demonstrate the track between the artery and the aneurysm.

Bilateral papillary cystadenoma lymphomatosum of the parotid gland without accumulation of technetium 99m pertechnetate: report of a case and review of the literature. An unusual case of bilateral papillary cystadenoma lymphomatosum of the parotid with multiple lesions showing no active uptake of 99mTc pertechnetate is presented. Similar cases showing no accumulation of radionuclide are reviewed.

The efficacy of palliative and definitive percutaneous versus surgical drainage of pancreatic abscesses and pseudocysts: a prospective study of 85 patients. We compared the efficacy of percutaneous to surgical drainage in a prospective study in 85 patients with pancreatic abscesses and pseudocysts. Percutaneous drainage of pancreatic abscesses in 18 patients cured three and palliated 12 who were eventually cured by elective surgical ablation; three patients died. This compares well to our 15 surgical patients, of whom four were cured by surgery alone and six were palliated. All were subsequently cured by additional computerized tomography-guided or ultrasound-guided percutaneous drainage and medical management or surgery. Five of the 15 died. Percutaneous drainage cured 11 of 14 infected pseudocysts and palliated two, which were subsequently cured by surgery; one was palliated but the patient was lost to follow-up. Surgical drainage cured six of 12 infected pseudocysts and palliated the other six, of which four were cured by further surgery and the other two were cured by secondary percutaneous drainage. Nine of 12 noninfected pseudocysts were cured by percutaneous aspiration, and two were palliated and later cured. In one patient, disease progressed, and he was ultimately lost to follow-up. Thirteen of 14 noninfected pseudocysts were cured by surgical drainage. The other patient died of pulmonary embolus. In patients treated by percutaneous techniques, there were four major complications. Our study established distinct advantages of percutaneous drainage under computerized tomographic and ultrasonic guidance: (1) the procedures can be carried out under ultrasonic guidance in an intensive care unit on critically ill patients, (2) the technique proved highly effective for initial palliation, with defervescence and stabilization occurring in most critically ill patients within 48 hours, (3) findings from fine needle aspiration provided valuable information as to microorganisms and antibiotic sensitivities and differed in 29 of 85 patients from those of concomitant blood cultures, and (4) definitive eradication of the process (surgical ablation of residual necrotic material) can be elected after the patient's clinical condition stabilizes.

The effect on skin blood flow of short-term venous hypertension in normal subjects. Plugging of skin capillaries by activated white blood cells is one of the proposed mechanisms by which skin damage may be initiated in chronic venous insufficiency. The aim of this study was to determine whether a microcirculatory deficit was induced in the skin by raising the venous pressure proximally for thirty minutes. Seventeen subjects with no evidence of venous or arterial disease had laser Doppler velocimetry performed in the goiter region of the leg; 8 different subjects had the measurement done on the dorsum of the hand. Peak hyperemic response following three minutes of ischemia was measured before and after a thirty-minute period of sustained venous hypertension applied by a proximal tourniquet inflated to 80 mm Hg. A decrease in the peak flow: baseline flow ratio (median ratio 2.25 before, 1.70 after, p less than 0.02) and an increase in the time taken to reach maximal hyperemia (median time ten seconds before, twenty seconds after, p less than 0.01) were observed after the period of venous hypertension in the lower limb. The second parameter, but not the first, was significantly affected in the upper limb. The authors conclude that a microvascular deficit in the skin is demonstrable after a short period of venous hypertension. This is consistent with the white-cell-trapping theory, but other possible explanations are discussed.

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.

Dilated cardiomyopathy complicated by a pedunculated and mobile left ventricular thrombus on ruptured false tendons. A 68-year-old man was admitted with congestive heart failure. He was treated with diuretics and digitalis; thereafter, the two-dimensional echocardiogram suggested a pedunculated and mobile left ventricular thrombus. He underwent surgical thrombectomy because of the high risk of systemic embolization. To our knowledge, this is the first case of dilated cardiomyopathy with a mobile left ventricular thrombus that was attached to ruptured false tendons.

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.