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Early detection of gastric cancer OBJECTIVE--To see whether investigation of dyspeptic patients aged over 40 after their first consultation with the general practitioner would increase the proportions with early and operable gastric cancers. DESIGN--Prospective study of gastric cancer in dyspeptic patients aged over 40 from a defined population. SETTING--10 General practices (six in central Birmingham, four in Sandwell); the Queen Elizabeth Hospital, Birmingham; and Sandwell District General Hospital. PATIENTS--2659 Patients aged 40 or over referred with dyspepsia. MAIN OUTCOME MEASURE--Increase in early and operable gastric cancers detected in middle aged patients with dyspepsia. RESULTS--Disease was identified in 1992 patients (75%). Fifty seven were found to have gastric cancer, 36 being treated by potentially curative resection, including 15 with early cancer. CONCLUSIONS--The investigation of dyspeptic patients over 40 at first attendance can increase the proportion of early gastric cancers detected to 26% and the proportion of operable cases to 63%. Such a policy has the potential to reduce mortality from gastric cancer in the population.

Effect of baseline ovarian cysts on in vitro fertilization and gamete intrafallopian transfer cycles. The presence of ovarian cysts may compromise the success of in vitro fertilization (IVF) and gamete intrafallopian transfer (GIFT). We prospectively studied 212 consecutive ovulation induction cycles in 120 patients for IVF and/or GIFT. A baseline cyst was defined as any intraovarian cystic structure greater than or equal to 12 mm noted on ultrasonography before superovulation. Cycle outcomes were compared between patients with cysts (n = 62) versus those with no cysts (n = 150). There were no differences in follicular or luteal phase lengths or amount of human menopausal gonadotropins used. Peak estradiol (E2) levels were significantly lower and cancellation rates significantly higher in the cyst group. For noncanceled cycles, there were no significant differences in peak E2 levels, the mean number of follicles greater than or equal to 12 mm, mature oocytes retrieved, or ova transferred for GIFT or embryos for IVF. The pregnancy rates overall and for noncanceled cycles were not significantly different.

Introduction: nutritional aspects of palm oil. The production, composition, and food uses of palm oil are outlined in this introduction to a detailed appraisal of the nutritional and health implications of the use of palm oil in the food supply. The putative role of dietary fats and oils in general, and of palm oil in particular, in the etiology of coronary heart disease and cancer is critically assessed. It is concluded that the evidence available is difficult to interpret unambiguously. Some evidence to suggest that the minor components of palm oil might have useful biological effects is also discussed.

Putative mechanisms of cytoprotective effect of certain antacids and sucralfate. An investigation of cytoprotective activity of certain antacids and inert particles was carried out by treating ethanol-induced gastric mucosal damage in rats in order to clarify possible mechanisms by which aluminum-containing antacids act. Al(OH)3 inhibited gastric mucosal damage in a dose-related and time-dependent manner. Neither aluminum ions themselves nor the particle size of the Al(OH)3 complex were responsible for the observed cytoprotection, since neither AlCl3, chemically inert Al2O3*C, nor sea sand showed protective effects. Hyperosmolality in the gastric lumen was not a deciding factor in inducing cytoprotection. Silicic acid and titanium dioxide, with superficial charge similar to Al(OH)3 proved to be effective in inhibiting gastric hemorrhagic lesions and releasing PGE2, suggesting that the surface charge of Al(OH)3 may be important in its cytoprotective properties. The same may also be valid for sucralfate. Since antacid-induced cytoprotection was only partly reduced by pretreatment with indomethacin, it is likely that additional mechanisms and mediators other than prostaglandins, such as nonprotein sulfhydryls, also are involved in gastric cytoprotection arising from aluminum-containing antacids.

Carotid artery disease in patients with head and neck carcinoma. Irradiation has been shown experimentally to cause accelerated development of atherosclerosis in exposed large arteries. However, occurrence of such an entity in carotid arteries of patients after treatment for head and neck carcinoma is unknown. Therefore, we reviewed 179 patient charts who had undergone head and neck operations with or without irradiation between 1979-1987. Of these 179 patients, 107 (59.8%) were dead at time of follow-up. Cause of death was unknown in 42 (40%) patients; in the remainder included: respiratory arrest--33; carcinoma-related--18; cardiac--6;pneumonia--7; and trauma--1. Average interval from treatment to death was 23.5 months. Of the 72 patients known to be alive, follow-up was obtained in 52 patients. Their average age was 64.9 years. Risk factors for atherosclerosis included: male gender--43; smoking--50; hypertension--9; diabetes--4; coronary artery disease--12; and peripheral vascular disease--4. Seventy-five per cent of these patients received postoperative irradiation. Average follow-up was 64.5 months. Duplex scans were performed on 34 patients. Three patients had common or internal carotid stenoses greater than 75 per cent. All of these patients had received irradiation and none of them were symptomatic. Seven patients had carotid stenoses between 50 to 75 per cent; five of these had received irradiation. Of these five patients, one had a stroke 60 months postoperatively, and one had a TIA 36 months postoperatively. The remaining 58 patients (of which 48 had irradiation) had carotid stenoses less than 50 per cent and none were symptomatic.

Surgical decompression without transposition for ulnar neuropathy: factors determining outcome. Fifty-one surgical decompressions without nerve transposition for ulnar neuropathy were performed in 46 patients. All of the patients were men with an average age of 59 years at the time of surgery. The follow-up range was between 5 and 32 months (average, 17.8 months). The disease involved the nondominant arm in 24 patients (52%) and was bilateral in 5 (11%). In 23 cases (50%), no predisposing condition could be identified, whereas 15 patients (33%) abused alcohol and 8 patients (17%) had diabetes mellitus. Fifty-seven percent of the patients helped by surgery had symptoms for less than 1 year, whereas only 30% of patients with symptoms for more than 1 year had symptomatic improvement. The relative magnitude of the slowing of ulnar nerve conduction velocity across the elbow was not significantly correlated with the success of decompression in relieving symptoms. Ulnar nerve conduction velocities across the elbow were 36.13 +/- 11.76 m/s in those responding to surgery and 38.97 +/- 13.91 m/s in those not responding (c = 0.06, dF = 50, P less than 0.3). A total of 37 patients showed symptomatic improvement after decompression. Simple decompression of the ulnar nerve was performed under local anesthesia without transposition of the nerve. In all of these cases, compression of the nerve occurred predominantly in the epicondylar groove. Narrowing of the nerve in the groove was present in 28 cases (55%); scar tissue was found adhering to the nerve in 21 cases (41%); and two pseudoneuromas were found (4%). Forty-one operations (80%) resulted in symptomatic improvement, typically noted by the patient within the first month postoperatively.

The effectiveness of double-gloving in otolaryngology. Thirty-four sets of consecutively used double gloves (68 pairs) used by otolaryngologists and their assistants in operations known to have a high risk of glove punctures were studied. The perforation rates for the outer and inner layers were 35.3 and 8.8% respectively, indicating that a second set of gloves substantially improves the likelihood of maintaining an intact barrier between medical staff and patient.

Clinical and angiographic determinants of primary coronary angioplasty success. M-HEART Investigators. Clinical and anatomic determinants of the initial success of percutaneous transluminal coronary angioplasty were prospectively evaluated in 826 patients enrolled in the Multi-Hospital Eastern Atlantic Restenosis Trial (M-HEART). The 639 men and 187 women ranged in age from 31 to 85 years. Successful angioplasty (residual stenosis less than 50% and no major complications) was achieved in 886 (88.6%) of 1,000 lesions. Success rates were uniform among the eight individual centers. Outcome was not influenced by gender, age or other clinical features, including severity and duration of angina, prior myocardial infarction, rest pain, transient ST segment elevation, history of smoking or diabetes. In contrast, procedural outcome was significantly associated with lesion-specific angiographic factors. Stenoses 60% to 74%, 75% to 89%, 90% to 99% and 100% were associated with success rates of 96%, 90%, 84% and 69%, respectively (p less than 0.001). Angioplasty was less successful in calcified than in noncalcified lesions (82% versus 90%, p less than 0.01), in thrombotic than in nonthrombotic lesions (82% versus 90%, p less than 0.05) and in lesions in the right coronary artery than in other vessels (84% versus 90%, p less than 0.01). Outcome was not related to other anatomic variables, including lesion location (proximal versus distal), vessel size, eccentricity, stenosis length or translesional gradient. By multivariate logistic regression, preangioplasty percent stenosis, right coronary artery location and lesion calcification were demonstrated to be significant independent predictors of angioplasty success. Alternative clinical and angiographic variables did not contribute to this regression model.

Gastroesophageal reflux and respiratory symptoms: is there an association? Proposed mechanisms and treatment. Gastroesophageal reflux (GER) is a dysfunction of the distal esophagus causing movement of stomach contents into the esophagus. Patients may develop heartburn, regurgitation, dysphagia, odynophagia, and hemorrhage. Respiratory symptoms occur in 10-60 percent of patients with GER or hiatal hernia. Although there is evidence associating pulmonary symptoms and GER, causality has not been proven. The appropriate use of antireflux therapy or surgery to treat GER may consequently alleviate respiratory symptoms.

Therapy of diseased stroke-prone spontaneously hypertensive rats with nimodipine. We investigated the therapeutic effect of nimodipine or parathyroidectomy in old, diseased stroke-prone spontaneously hypertensive rats by observing 98 male 1-year-old rats over 5 months. After stroke had occurred, the rats were divided into three groups: 1) parathyroidectomy, 2) nimodipine, and 3) controls. In the nimodipine group, the rats survived longer than those in the other groups. Blood pressure of the controls did not differ from the nimodipine-treated and parathyroidectomy animals. The increase in calcium content of brain and kidney tissues and of plasma renin activity, urea, and creatinine was attenuated by nimodipine or parathyroidectomy. The histology of the kidneys revealed widespread fibrinoid necrosis of arteries in all rats. In the nimodipine-treated or parathyroidectomy groups, healing of the lesions was detectable. Cerebral lesions were mainly characterized by fibrinoid necrosis. Nimodipine-treated as well as parathyroidectomied animals showed significantly fewer hypertensive cerebral lesions. In old, diseased stroke-prone spontaneously hypertensive rats, therapy with nimodipine or parathyroidectomy increased their survival rate. The cerebrovascular and renovascular lesions of treated animals were attenuated, and morphologic signs of healing were observed. Reduction of calcium overload by nimodipine or parathyroidectomy, even in an advanced stage of disease, had a therapeutic effect.

Comparison of methods for checking surgical margins. Surgical margins of a cutaneous neoplasm can be evaluated by various combinations of three major types of sections: vertical (perpendicular), horizontal (parallel), and oblique (Mohs method). Vertical sections may run transversely through tumor (breadloaf method), longitudinally through tumor (breadloaf-cross method), or peripheral to the tumor. The peripheral (perimeter) sectioning methods are the only methods that can evaluate almost 100% of the margin, but they have the disadvantage of not showing the relationship of the tumor to its margin, which can be seen clearly with the vertical transverse sections. Seven methods of checking surgical margins are compared and contrasted. None of these is judged to be perfect or best.

Liver transplant for metastatic neuroendocrine tumor. Generally, the results of liver transplantation for metastatic liver disease have not been favorable. One exception has been the unique group of neuroendocrine tumors, the slow growth of which allows liver transplantation to effectively palliate and control symptoms. We report two cases: (a) A 51-year-old man who underwent orthotopic liver transplantation and resection of the pancreatic primary tumor for a nonfunctioning malignant neuroendocrine tumor with features of both carcinoid and islet-cell glucagonoma remains symptom-free and without evidence of tumor recurrence at 13 months follow-up. (b) A 47-year-old man who underwent orthotopic liver transplantation and Whipple resection for a metastatic islet-cell tumor in the head of the pancreas is fully recovered at 5 months follow-up.

Arterial vasodilator effects of the dihydropyridine calcium antagonist amlodipine alone and in combination with verapamil in systemic hypertension. The arterial vasodilator properties of the dihydropyridine calcium antagonist amlodipine were compared with the effects of vascular muscle cyclic guanosine monophosphate production by sodium nitroprusside and with the effects of a combined infusion of amlodipine and the nondihydropyridine calcium antagonist verapamil in 8 untreated patients with primary hypertension. Arterial vasodilation was assessed by measurement of changes of forearm blood flow by mercury in Silastic strain-gauge plethysmography during brachial artery drug infusions. Forearm blood flow increased during amlodipine infusions (0.4 to 45 micrograms/min/100 ml forearm tissue) from 2.9 +/- 1.7 to a maximum of 23.6 +/- 7.6 ml/min/100 ml (687%), while sodium nitroprusside caused an increase from 3.0 +/- 1.8 to 16.2 +/- 5.4 ml/min/100 ml (449%), attesting to the importance of transmembrane calcium influx for the maintenance of vascular tone. The addition of verapamil 40 micrograms/min/100 ml to an infusion of amlodipine 44.5 micrograms/min/100 ml resulted in a further increase of forearm blood flow, from 23.6 +/- 7.6 to 34.4 +/- 9.8 ml/min/100 ml (p less than 0.05). The precise mechanisms of this finding have yet to be elucidated but may be due to interactions of the effects of the binding of these 2 chemically and pharmacologically different calcium antagonists to distinct binding sites at calcium channels. The clinical relevance of this observation for the treatment of coronary artery disease and systemic hypertension needs further study.

Vigabatrin: rational treatment for chronic epilepsy. Vigabatrin is a selective, irreversible suicide inhibitor of GABA transaminase and thus increases brain and CSF GABA. In 33 adult patients with long standing refractory epilepsy on treatment with one or two standard anti-convulsant drugs, the addition of vigabatrin up to 3g daily for eight weeks was associated with a 48.2% reduction in seizure frequency. Twenty patients who had exhibited a 50% or more reduction in frequency of one or more seizure types entered an eight week double-blind placebo controlled phase. Patients on vigabatrin maintained a 54.7% reduction of seizure frequency, whereas those on placebo showed an 18.6% increase in seizure frequency, a highly significant difference between the two groups. In the open phase, seven patients were withdrawn due to unacceptable and reversible adverse events. The commonest side effects were drowsiness, depression and mood instability, and headaches. Vigabatrin is a potentially valuable new treatment for chronic epilepsy, especially partial seizures with or without secondary generalisation.

Elevated serum bromide concentrations following repeated halothane anaesthesia in a child. A 20-month-old child received 25 brief halothane general anaesthetics over a five-week period to allow cranial irradiation treatments for a posterior fossa ependymoma. Personality change during the last week of the treatment protocol raised the question of possible bromide intoxication. Serum bromide concentrations, using a gold chloride assay technique, were monitored at that time, and at four- and six-week intervals thereafter. Serum bromide concentrations demonstrated a four-fold change during this period ranging from peak levels of 2.2 mEq.L-1 (176 micrograms.kg-1) during the fifth week of treatment decreasing to less than 0.5 mEq.L-1 (less than 40 micrograms.ml-1) six weeks following the end of treatments. This demonstrates the possibility for repetitive, short halothane exposures to result in elevations of serum bromide and the potential of bromide intoxication in paediatric neuro-oncology patients.

Human immunodeficiency virus-associated Hodgkin's disease. Clinicopathologic studies of 24 cases and preponderance of mixed cellularity type characterized by the occurrence of fibrohistiocytoid stromal cells. Hodgkin's disease (HD) was diagnosed in 24 patients who were either seropositive for human immunodeficiency virus (HIV) (21) or members of a high-risk group (three), but had not developed acquired immune deficiency syndrome (AIDS). Clinical presentation of the disease was characterized by constitutional symptoms in all, especially fever (23/24) and disseminated disease (22/24) at diagnosis. Mediastinal adenopathy was rare. Bone marrow involvement was particularly frequent (12/24), and a positive bone marrow biopsy preceded lymph node biopsy in 5 of the 12. Histopathologic features of these tumors included an increased number of nonlymphoid stromal cells, i.e., histiocytic and/or fibroblastoid. In some tumors these fibrohistiocytoid stromal cells were arranged in bundles, but distinct nodule with birefringent collagen band formation was not observed. Twenty-two patients were treated, most with combination chemotherapy; one was untreated; one, unknown. Sixteen, including the one untreated, died with disease at 3 to 25 months; one died of an unrelated cause; four were alive at 3 to 24 months; three were lost to follow-up. Frequent bone marrow involvement at presentation suggests the usefulness of the bone marrow biopsy for diagnosis in subjects at risk, especially when they present with spiking fever of unknown origin. Contrary to most previous series, virtually all of our cases were of mixed cellularity type, characterized by increased fibrohistiocytoid stromal cells in place of depleting lymphocytes. The classic nodular sclerosing feature with birefringent collagen band formation was not observed. In conclusion, HIV-associated HD was characterized by advanced stage with fever at presentation, preponderance of mixed cellularity histologic type with increased fibrohistiocytoid stromal cells, and poor outcome. Hodgkin's disease in AIDS patients presents an intriguing biological model to study the role of stromal histiocytes in immunodeficient patients.

Dependence of Doppler echocardiographic transmitral early peak velocity on left ventricular systolic function in coronary artery disease. The influence of systolic function on pulsed Doppler echocardiographic transmitral flow velocity patterns was assessed before and after postextrasystolic (PES) potentiation in 12 normal subjects (control group) and in 25 patients with previous healed myocardial infarction (MI) group. Simultaneous high-fidelity left ventricular pressure measurements were performed in all patients. A programmed single-coupled right ventricular extrasystole was induced during echocardiographic and subsequent cineangiocardiographic recordings. Adequate angiograms for volumetric analysis in both baseline and PES beats were obtained in 23 patients (7 in the control group and 16 in the MI group). PES potentiation of contraction was more pronounced in the MI group than in the control group. PES changes in ejection fraction, stroke volume and end-systolic volume were significantly greater in the MI group than in the control group (11 vs 5%, p less than 0.005; 15 vs 5 ml/m2, p less than 0.005; and -13 vs -4 ml/m2, p less than 0.01, respectively). In contrast, PES potentiation prolonged the time constants of left ventricular pressure decline derived from exponential curve fits with a zero (Tw) and non-zero (Tb) asymptote pressure in the MI group to the same extent as in the control group (4 vs 5 ms, difference not significant [NS], and 9 vs 11 ms, NS, respectively). In the PES beat, peak E velocity remained unaltered (48 vs 49 cm/s, NS) in the control group, whereas it increased significantly (p less than 0.0001) from 47 to 51 cm/s in the MI group.

Survival and quality of life among patients receiving unproven as compared with conventional cancer therapy. BACKGROUND. Cancer treatments without proved efficacy have achieved new levels of popularity, particularly among well-educated patients. The value of these therapies is vigorously debated. METHODS. We compared the length of survival and quality of life in patients who received treatment at a prominent unorthodox cancer clinic in addition to conventional treatment and in matched control patients from an academic cancer center who received only conventional treatment. All the patients had documented extensive malignant disease associated with a predicted median survival time of less than one year. The study sample consisted of 78 pairs of patients matched according to sex, race, age, diagnosis, and time from the diagnosis of metastatic or recurrent disease, who were enrolled over a period of 3 1/2 years. Periodic follow-up (approximately every two months) continued until death. RESULTS. There was no difference between the two patient groups in length of survival. Median survival for both groups was 15 months (P = 0.22; relative risk, 1.23; 95 percent confidence interval, 0.88 to 1.72). Quality-of-life scores were consistently better among conventionally treated patients from enrollment on. CONCLUSIONS. For this sample of patients with extensive disease and for this particular unorthodox treatment regimen, conventional and unorthodox treatments produced similar results.

Special considerations for research with pharmacologic agents. As physical medicine and rehabilitation becomes more and more complicated, the medical rehabilitation research teams are often bewildered by the sweeping changes occurring in the application of therapeutic drugs for rehabilitation. Society, through the instrument of governmental regulations, dictates that all new treatments must be efficacious before "release.".

Anticardiolipin antibodies in polymyalgia rheumatica-giant cell arteritis: association with severe vascular complications. PURPOSE: We studied a group of patients with polymyalgia rheumatica (PMR) with or without biopsy-proven giant cell arteritis (GCA) in order to determine the prevalence of anticardiolipin antibodies (aCL) in these disorders and their association with vascular complications. PATIENTS AND METHODS: The study consisted of 50 patients, 30 with PMR alone and 20 with associated GCA. Determinations of IgG and IgM aCL by enzyme-linked immunosorbent assay were done in the patients and in 50 age- and sex-matched healthy control subjects. We also measured von Willebrand factor (vWF) antigen, C-reactive protein, and erythrocyte sedimentation rate. RESULTS: Twenty-four (48%) of the 50 patients had aCL. Eleven were positive for IgG and five for IgM, whereas eight were positive for both. In the group of patients with PMR alone, only eight (26.6%) had aCL, while 16 of 20 patients (80%) with GCA had these antibodies (p less than 0.01). In the control group, 10 of 50 patients (20%) had positive aCL, a finding that was statistically significantly different only when compared with the finding in patients with GCA (p less than 0.01). Both isotypes of aCL were seen mainly in patients with GCA, and five of these patients had severe vascular complications. Levels of vWF antigen were significantly higher in patients with GCA as compared with patients with PMR alone; however, the highest titers did not correlate with vascular complications. Erythrocyte sedimentation rate and C-reactive protein were increased but comparable in both groups. CONCLUSION: This study demonstrates that aCL are prevalent in patients with GCA. These antibodies might imply severe vascular damage and could play an important role in the pathogenesis of the vasculopathy observed in this disease.

Angiographic assessment of the culprit coronary artery lesion before acute myocardial infarction. Serial angiographic studies of patients with myocardial infarction and unstable angina suggest that the culprit plaque underlying a thrombus need not have produced severe luminal obstruction before onset of the event. An atherosclerotic coronary artery lesion can, therefore, have 2 important characteristics. First, it may be obstructive. Second, it may be "vulnerable" in that it has the potential to become thrombogenic if exposed to the appropriate triggering stimulus. A lesion need not be obstructive to become thrombogenic, nor do all obstructive lesions have thrombogenic potential. The cause of an infarction may thus be rupture of a nonobstructive plaque leading to occlusive thrombus formation. Because it may be difficult to predict the site of a subsequent occlusion from a coronary angiogram, coronary bypass surgery or angioplasty directed only at discernible stenotic lesions may not be effective for preventing subsequent myocardial infarctions. Appropriate therapy may need to be directed at the entire coronary tree. Such therapy might include cholesterol lowering, beta blockade and aspirin.

Piezoelectric lithotripsy: stone disintegration and follow-up results in patients with symptomatic gallbladder stones. One hundred symptomatic patients with radiolucent gallbladder stones were treated with a new piezoelectric lithotripter and oral chemolitholytic agents. Stone disintegration was achieved in 99 of these patients (99%) with a mean (+/- SD) maximum fragment size of 5.1 +/- 4.1 mm. Significant differences were found when the mean (+/- SD) fragment sizes of single stones less than or equal to 20 mm (4.2 +/- 2.5 mm) were compared with those of single stones greater than 20 mm (5.8 +/- 3.4 mm; P less than 0.05) and multiple stones (6.2 +/- 3.8 mm; P less than 0.05), respectively. None of the patients required anesthesia, analgesics, or sedatives before or during the treatment. The stone-free rates for all patients followed up for up to 4-12 months (mean +/- SD, 10.7 +/- 2.9 months) were 18% (1 month), 25% (2 months), 38% (4 months), 52% (8 months), and 67% (12 months). Partly significant differences were obtained in stone-free rates for single stones (less than or equal to 20 mm) compared with larger stones (greater than 20 mm) and multiple stones (P less than 0.05), respectively. Serious adverse reactions (i.e., cholestasis and pancreatitis) were observed in only 3 patients (3%). These conditions were induced by fragment impaction in the common bile duct. In 2 of these patients, endoscopic retrograde cholangiopancreatography with endoscopic sphincterotomy was required. It is concluded that piezoelectrically generated shock waves are suitable for the effective and safe disintegration of gallbladder stones in humans. The anesthesia-free and analgesia-free shock-wave application opens up the possibility to perform biliary lithotripsy as an outpatient procedure. The stone-free rate achieved in combination with oral bile acids is most promising for single stones (less than or equal to 20 mm).

Human immunodeficiency virus infection of megakaryocytic cells. The human immunodeficiency virus (HIV) is capable of infecting certain cells of hematopoietic lineage, particularly monocyte-macrophages and T lymphocytes. Recently, the possibility that cells of megakaryocytic lineage are susceptible to HIV infection has been raised. We have characterized infection of the permanent megakaryocytic cell line CMK by HIV in vitro. CMK cells were easily infected by HIV type 2 (HIV-2), producing significant amounts of virus in culture. Infection appeared to be mediated by the CD4 surface antigen on CMK cells. Three different strains of HIV-1 were able to minimally infect CMK cells, suggesting there may be isolates of HIV tropic for megakaryocytes. Infection of CMK cells led to downregulation of the CD4 surface antigen but no discernable change in expression of megakaryocyte-associated proteins glycoprotein Ib and glycoprotein IIb/IIIa. These observations support the likelihood that megakaryocytes are susceptible to HIV infection, and cell lines of megakaryocytic origin may provide a useful model to study effects of the retrovirus on megakaryocyte function.

Gd-HP-DO3A in clinical MR imaging of the brain. As part of a phase II clinical trial, 14 patients with presumed intracranial neoplastic disease underwent magnetic resonance (MR) imaging before and after intravenous injection of gadolinium 1,4,7-tris(carboxymethyl)-10-(2'-hydroxypropyl)-1,4,7,10-tetraazacycl ododecane (HP-DO3A). This neutral (nonionic) gadolinium chelate has lower osmolality, when formulated at equimolar concentrations, and superior in vitro stability compared with gadopentetate dimeglumine. The safety profile of Gd-HP-DO3A permitted administration of doses up to 0.3 mmol/kg, three times the dose of gadopentetate dimeglumine approved by the U.S. Food and Drug Administration. In this limited clinical trial, Gd-HP-DO3A proved to be a safe and efficacious agent in MR imaging of the head. The only change documented in patient monitoring was that of slight skin redness at the injection site immediately after administration in two patients. No statistically significant changes due to administration of the agent were noted in laboratory evaluations. These results differ from those obtained with gadopentetate, which induces a transient rise in serum iron and bilirubin levels in up to 26% of patients. Administration of higher doses of Gd-HP-DO3A, either 0.2 or 0.3 mmol/kg, appeared to provide improved enhancement. No decrease in efficacy at these high doses was noted.

Phase I study of interleukin-2 and interferon alfa-2a as outpatient therapy for patients with advanced malignancy. Twenty-six patients were treated in this phase I study with the combination of interleukin-2 (IL2) administered as a continuous infusion and interferon alfa-2a (IFN alpha-2a) administered intramuscularly to patients in an outpatient setting. The maximum-tolerated dose of both agents given as outpatient therapy was 2 x 10(6) U/m2 days 1 to 5 of IL2 and 9 x 10(6) U/m2 days 1, 3, and 5 of IFN alpha-2a for 4 consecutive weeks. A 2- to 4-week rest period was permitted after each 4 weeks of treatment. Fatigue was the treatment-limiting toxicity, and serious clinical or laboratory abnormalities occurred infrequently during this study. Patients with colon cancer metastatic to the liver tolerated treatment worse than patients with other tumors. Twelve of the 15 patients with renal cell cancer were assessable for response determinations. Of these 12 patients, three exhibited complete tumor regression, three have had partial objective regression, and three patients experienced stabilization of rapidly progressive disease. This therapy appears to be well tolerated in an outpatient treatment setting and shows significant activity against advanced renal cell cancer.

Resuscitation of patients with cardiac arrest by ambulance staff with extended training in West Yorkshire OBJECTIVE--To investigate the results of resuscitation of patients with cardiac arrest by ambulance staff with extended training in West Yorkshire. DESIGN--Study of all such attempts at resuscitation over 32 months, based on the standard report form for each call made by the ambulance staff and the electrocardiogram that showed the initial rhythm in each patient. SETTING--Area covered by West Yorkshire ambulance service. SUBJECTS--1196 Patients with cardiac arrests attended by 29 ambulance staff with extended training. MAIN OUTCOME MEASURE--Result of resuscitation. RESULTS--The initial rhythm was asystole or electromechanical dissociation in 740 patients and ventricular fibrillation in 456 patients; overall 65 patients survived to be discharged from hospital. Sixty four of the 456 patients in whom ventricular fibrillation was the initial rhythm recorded, and 46 in whom ventricular fibrillation persisted after the ambulance staff arrived, survived. Only one of the 740 patients who initially had asystole or electromechanical dissociation survived. Factors associated with a greater chance of ventricular fibrillation occurring were: age less than 71, the arrest being witnessed by a bystander, resuscitation by a bystander, the arrest occurring in a public place, and a response time by the ambulance staff of less than six minutes. For patients found in ventricular fibrillation a shorter response time was associated with improved survival but resuscitation by a bystander was not. Additional skills learnt during extended training were used for 51 of the 65 patients who survived. CONCLUSIONS--Ambulance staff with extended training can save the lives of patients with cardiac arrest due to fibrillation, though asystole and electromechanical dissociation have a poor prognosis and should perhaps receive little attention during extended training.

Superior protective effect of low-calcium, magnesium-free potassium cardioplegic solution on ischemic myocardium. Clinical study in comparison with St. Thomas' Hospital solution. The protective effect of low-calcium, magnesium-free potassium cardioplegic solution on ischemic myocardium has been assessed in adult patients undergoing heart operations. Postreperfusion recovery of cardiac function and electrical activity was evaluated in 34 patients; 16 received low-calcium, magnesium-free potassium cardioplegic solution (group I) and 18 received St. Thomas' Hospital solution, which is enriched with calcium and magnesium (group II). There were no significant differences between the two groups in age, sex, body weight, and New York Heart Association functional class. Aortic occlusion time (107.3 +/- 46.8 minutes versus 113.6 +/- 44.3 minutes), highest myocardial temperature during elective global ischemia (11.5 degrees C +/- 3.1 degrees C versus 9.3 degrees C +/- 3.2 degrees C), and total volume of cardioplegic solution (44.2 +/- 20.5 ml/kg versus 43.4 +/- 17.6 ml/kg) were also similar in the two groups. On reperfusion, electrical defibrillation was required in four cases (25.5%) in group I and in 15 cases (83.3%) in group II (p less than 0.005), and bradyarrhythmias were significantly more prevalent in group II (6.3% versus 44.4%; p less than 0.05). Serum creatine kinase MB activity at 15 minutes of reperfusion (12.3 +/- 17.0 IU/L versus 42.6 +/- 46.1 IU/L; p less than 0.05) and the dose of dopamine or dobutamine required during the early phase of reperfusion (1.8 +/- 2.5 micrograms/kg/min versus 6.1 +/- 3.3 micrograms/kg/min; p less than 0.0002) were both significantly greater in group II. Postischemic left ventricular function, as assessed by percent recovery of the left ventricular end-systolic pressure-volume relationship in patients who underwent aortic valve replacement alone, was significantly better in group I (160.4% +/- 45.5% versus 47.8% +/- 12.9%; p less than 0.05). Serum level of calcium and magnesium ions was significantly lower in group I. Thus low-calcium, magnesium-free potassium cardioplegic solution provided excellent protection of the ischemic heart, whereas St. Thomas' Hospital solution with calcium and magnesium enabled relatively poor functional and electrical recovery of the heart during the early reperfusion period. These results might be related to differing levels of extracellular calcium and magnesium on reperfusion.

A rodent model of cirrhosis, ascites, and bacterial peritonitis. We sought to develop a rodent model of spontaneous bacterial peritonitis and report here the preliminary results of carbon tetrachloride-induced cirrhosis in which ascites and bacterial peritonitis predictably develop. Of 41 rats that survived the initial carbon tetrachloride toxicity, 38 (92.7%) developed cirrhosis with ascites. Of these 38, 21 (55.3%) developed 24 episodes of ascitic fluid infection without iatrogenic colonization. No surgically treatable source of infection was identified at autopsy in any rat; therefore, the infections were presumed to be "spontaneous." Eight (50%) of the 16 rats with culture-positive ascitic fluid at postmortem examination also had spontaneous pleural fluid infection with the same organism. Escherichia coli and Proteus sp. were the organisms most commonly isolated. This rodent model of cirrhosis with ascites appears to be the first high-yield animal model of spontaneous bacterial peritonitis. Ascitic fluid infection in these rats resembles ascitic fluid infection in humans. This model will allow further investigation of the mechanisms of pathogenesis of ascitic fluid infection and provide insight into the prevention and treatment of spontaneous bacterial peritonitis and pleural fluid infection in patients with cirrhosis.

Screening for biotinidase deficiency in children with unexplained neurologic or developmental abnormalities. To test the hypothesis that the frequency of biotinidase deficiency is greater in children with unexplained developmental delay or neurologic abnormalities than in the general population, we studied children seen at a large outpatient clinic over a four-year period who had one or more of these neurologic abnormalities and for whom no specific cause for their abnormalities could be found. The group totaled 274 children (163 boys; 111 girls) whose ages ranged from 2 weeks to 17 years. Characteristics were IQ/DQ, 30 to 70 in the 115 for whom scores were available; 41% had seizures; 15% had sensorineural hearing loss; 54% showed gross motor delay or ataxia; and 27% had decreased muscle tone. One patient with a classical clinical picture of biotinidase deficiency was diagnosed during the study period and was not included in the study. None of the patients with nonclassic findings had a deficiency of biotinidase activity. Our results suggest that biotinidase deficiency does not account for a large proportion of children with unexplained neurologic abnormalities or developmental delay. This does not negate the importance of biotinidase testing in children with clinical patterns specifically suggestive of the deficiency.

Current strategies in the management of locoregional and metastatic gastric carcinoma. Gastric carcinoma remains a significant cause of death worldwide. A patient's prognosis depends on the degree of gastric wall penetration, presence of lymph node metastases, and location of the primary site. Metastatic gastric carcinoma is currently incurable. However, chemotherapy continues to evolve at a rapid pace. Active agents include 5-fluorouracil (5-FU), doxorubicin, cisplatin, methotrexate, mitomycin, and etoposide. Combination etoposide, doxorubicin, and cisplatin (EAP) has been reported to result in encouragingly high response rates, including a 10% complete response rate in patients with metastatic gastric carcinoma. Trials are now under way to confirm these results. Similarly, another etoposide-based combination, etoposide, leucovorin, and 5-FU (ELF), has resulted in an equally good response rate but less toxicity than EAP. The 5-FU, doxorubicin, and methotrexate (FAMTX) regimen, previously reported to have an excellent response rate, is also being investigated further. For patients with locoregional carcinoma, curative resection rate is often unsatisfactorily low; however, curative resection is consistently associated with improved survival (between 23 and 26 months). In patients with potentially resectable carcinoma, two significant problems must be recognized: (1) a low rate of curative resection and (2) the development of widespread carcinoma despite curative resection. Despite many attempts, the postoperative strategies of adjuvant chemotherapy have been ineffective. New strategies must be investigated aggressively. Combination etoposide, 5-FU, and cisplatin (EFP) has been administered preoperatively and postoperatively to patients with resectable gastric carcinoma, resulting in an encouraging curative resection rate (greater than 70%) and manageable toxicity. Based on promising results reported with EAP in patients with unresectable locoregional carcinoma of the stomach, a trial of preoperative and postoperative EAP in potentially resectable carcinoma of the stomach is now under way.

Inflammatory nodular reactions after hepatitis B vaccination due to aluminium sensitization. In 2 patients, pruritic nodules appeared after revaccination against hepatitis B. Aluminium was found to be responsible for this side effect: contact allergy to aluminium was present in both patients, whereas controls were negative.

Melanoma in pregnancy. The clinical course of malignant melanoma in pregnancy has been a subject of controversy, but current evidence indicates that it is similar to the clinical course in non-pregnant patients. Early detection and biopsy of localized disease is crucial because early treatment provides an excellent prognosis. Surgical excision is the primary therapy for this disease. As the primary care provider for many women in the reproductive age group, obstetrician-gynecologists have an opportunity to detect these lesions at their earliest stages when they are amenable to cure. Overall, maternal metastases to the fetus and placenta are very rare events and do not warrant elective termination based on the maternal diagnosis. However, a thorough examination of the infant and placenta should be done in all cases of melanoma complicating pregnancy. After treatment, long-term follow-up is recommended. Since most recurrences develop within 3 years after the diagnosis, it remains prudent to recommend that these patients avoid a subsequent pregnancy during this interval.

No finding of increased myocardial ischemia during or after carotid endarterectomy under anesthesia with nitrous oxide. Nitrous oxide (N2O) has been implicated as a cause of myocardial ischemia. We investigated whether substitution of N2O for a portion of the anesthesia supplied by isoflurane increased myocardial ischemia in patients at risk for such ischemia. Seventy patients having carotid endarterectomies (63 patients) or other carotid surgery (seven patients) were prospectively, randomly assigned to an anesthetic regimen that included or excluded N2O. All other aspects of anesthetic management were similar, except for greater concentrations of oxygen and isoflurane in patients not given N2O. Perioperative monitoring for myocardial ischemia and infarction included 12- or 5-lead electrocardiography, transesophageal echocardiography, and creatine kinase isoenzyme levels. By transesophageal echocardiographic or electrocardiographic criteria, 44% of patients given oxygen but only 21% of those given N2O had myocardial ischemia intraoperatively (P = 0.065). Similarly, myocardial infarction, identified by changes in creatine kinase isoenzymes, occurred in only one patient given N2O but in three given oxygen (not significantly different). Thus we found no trend indicating a greater incidence of myocardial ischemia or infarction associated with the use of N2O.

Low-level lead exposure in the prenatal and early preschool periods: language development. Inconsistent results continue to be reported from studies linking low-level lead exposure and child development. This inconsistency is seen for both prenatal exposure and exposure in the preschool years. The primary outcome measures in most reports are indices of cognitive development, including IQ. Verbal skills may be particularly vulnerable to toxic insult. The fact that 2 y of age is both a time of peak exposure and also a time of rapid language development suggests that this may be a critical period for such an effect. The later prenatal and early infancy period, at which time the nervous system is developing rapidly, may also be critical exposure period. We examined the relationship of maternal and cord blood lead (PbB) at birth and venous PbB at 6 mo, 2 y, and 3 y with language measures at 1, 2, and 3 y of age. The sample consisted of disadvantaged urban children. Multivariate analyses revealed no statistically significant relationship of either prenatal PbB or early preschool PbB with language measures after control of cofactors. Supplementary partial correlations revealed a marginal relationship of cord PbB and mean length of utterance (MLU), which describes a child's ability to form meaningful word combinations. Because this analysis was one of a large number of analyses with both positive and negative regression coefficients, the possibility that this was a chance effect was considered. If there is an effect of low-level lead exposure on language development, that effect is not robust.

Baroreflex control of renal sympathetic nerve activity is potentiated at early phase of two-kidney, one-clip Goldblatt hypertension in conscious rabbits. Conscious normotensive and two-kidney, one-clip Goldblatt hypertensive rabbits were studied to determine the sensitivity of the arterial baroreflex control of renal sympathetic nerve activity (RSNA) and heart rate. The relations of the mean arterial pressure-RSNA and mean arterial pressure-heart rate were examined over a wide range of blood pressures produced by infusions of phenylephrine and nitroglycerin. The maximum slope obtained by logistic function analysis was considered to represent the baroreflex sensitivity. In the early hypertensive group (n = 8; mean arterial pressure +/- SEM, 88 +/- 2 mm Hg) on day 5 after renal clip application, the maximum slope of the mean arterial pressure-RSNA relation was -11.3 +/- 1.2, which was significantly greater than that of the sham normotensive group (-6.9 +/- 0.3, p less than 0.05). The maximum slope (-4.3 +/- 0.2) of the mean arterial pressure-RSNA relation in the late hypertensive group (n = 8; mean arterial pressure, 96 +/- 3 mm Hg) on day 21 after renal clipping was significantly smaller than that of another sham group (-7.2 +/- 0.2, p less than 0.05). In contrast to these changes in the baroreflex control of RSNA, the control of heart rate was attenuated according to the magnitude of mean arterial pressure. To elucidate the mechanisms underlying the potentiated baroreflex, the effects of endogenous neuropeptides were investigated. First, plasma concentrations of angiotensin II and arginine vasopressin that are known to affect the baroreflex were determined. Plasma concentrations of vasopressin (3.1 +/- 0.6 pg/ml) as well as of angiotensin II (34 +/- 7 pg/ml) were increased in the early hypertensive group, and the plasma vasopressin returned to a similar level to the sham group in the late hypertensive group (1.3 +/- 0.4 pg/ml). Second, to study endogenous effects of these neuropeptides on the baroreflex, the maximum slopes of the baroreflex curves during infusions of antagonists for the peptides were determined in the early hypertensive group. The maximum slope of mean arterial pressure-RSNA during intravertebral arterial [Sar1, Ala8]-angiotensin II (-16.4 +/- 1.5) was significantly greater (p less than 0.05), whereas the maximum slope during intravertebral arterial infusion of d(CH2)5Tyr(Me)arginine vasopressin (-4.7 +/- 0.5) was significantly smaller (p less than 0.05) than that during vehicle infusion (-11.3 +/- 1.2).(ABSTRACT TRUNCATED AT 400 WORDS).

Refeeding of infants with acute diarrheal disease. The purpose of this study was to determine which infant formula among five would be the most efficacious for the refeeding of infants during an acute episode of diarrhea. Fifty male infants less than 12 months of age with severe diarrhea and at least 5% dehydration were admitted to a metabolic unit and studied in a prospective, single-blind protocol. Ten infants randomly received one of five types of formula: two-thirds diluted cow milk, cow milk formula (Nanon, Nestle, Inc., Sao Paulo, Brazil), Portagen, Pregestimil, or Prosobee (Mead Johnson & Co. Division, Evansville, Ind.). They continued to receive the same formula for 72 hours unless dehydration occurred. There were no associated infections, and they received no prior antibiotic treatment. Oral hydration together with intravenous fluid therapy was given to all patients during the initial treatment. During the first 72 hours of refeeding, patients fed Portagen excreted the least amount of stool and required reduced quantities of intravenous fluids or oral hydration. In contrast, patients fed diluted cow milk or any other formula had more severe diarrhea. Nine of the 10 patients fed Portagen completed the 72-hour treatment, whereas only 2 of 10 fed diluted cow milk tolerated it. Similarly, the cumulative proportions for high purging rate, dehydration, carbohydrate intolerance, and vomiting were more favorable for Portagen and least acceptable for diluted cow milk. No differences were found among the remaining three formulas tested. These data show that diluted cow milk is poorly tolerated by infants with severe diarrhea, whereas Portagen is more effective.

Effective ultraviolet irradiation of platelet concentrates in teflon bags. Several plastic materials used in blood storage were evaluated for their ability to transmit ultraviolet B (UVB) light. A plastic bag manufactured from sheets of transparent Teflon efficiently (78-86%) transmitted UVB light and was employed in subsequent functional studies of lymphocytes and platelets exposed to UVB light while contained in these bags. In vitro experiments showed a UVB dose-dependent abrogation of lymphocyte responder and stimulator functions, with concurrent preservation of platelet aggregation responses. In a phase I pilot study, UVB-treated platelet concentrates were administered to four bone marrow transplant recipients. Adverse effects attributable to the transfusions were not observed, and patients showed clinically effective transfusion responses. No patient developed lymphocytotoxic HLA or platelet antibodies. These studies suggest that platelets can be effectively irradiated with UVB light in a closed system. However, numerous variables, including container material, volume and composition of contents, steady exposure versus agitation, and exact UV wavelength, must be considered.

Otogenic Fusobacterium necrophorum meningitis. A case of meningitis secondary to acute suppurative otitis media in a previously healthy child is reported. The only organism isolated from blood after aerobic and prolonged anaerobic culture was identified as Fusobacterium necrophorum. Complete recovery followed treatment with surgery and prolonged antibiotic therapy. The role of anaerobes in the development of meningitis, the isolation and identification of Fusobacterium necrophorum, the clinical presentations of F. necrophorum infection and the choice of antibiotics in the treatment of these infections are discussed.

Lymphoedema/hypercalcaemia syndrome mediated by parathyroid-hormone-related protein. A 24-year-old woman presented with a cryptogenic, hypercalcaemic syndrome with metastatic pulmonary calcification and leg and massive breast enlargement and bilateral chylous pleural effusions compatible with a generalised lymphatic abnormality. The patient's serum parathyroid hormone-related protein concentration was very high at a time when she was significantly hypercalcaemic, implying that the hypercalcaemia was mediated by this protein.

Localization and surgical treatment of occult insulinomas. Management of patients with biochemical evidence of insulinoma and negative preoperative imaging studies (occult) tumors is controversial, varying from primarily medical management to aggressive, blind nearly total pancreatectomy to extirpate the tumor. Since 1982, 12 consecutive patients with occult insulinoma underwent preoperative portal venous sampling (PVS) for insulin followed by surgical exploration with intraoperative ultrasound (IOUS). Eleven of twelve patients (92%) had insulinoma removed and were cured. Portal venous sampling correctly predicted the location of the insulinoma in 9 patients (75%) and that no tumor would be found in another patient. A fourfold insulin gradient in the pancreatic tail of one patient correctly predicted that a distal pancreatectomy would remove the insulinoma despite the fact that neither palpation nor IOUS identified any tumor. Intraoperative ultrasound was the single best method to identify occult tumors because it correctly identified 10 of 11 insulinomas that were found, including five pancreatic head tumors that were not palpable. Palpation identified five insulinomas. Of the 10 tumors that were identified during operation by palpation or ultrasound, IOUS identified significantly more (100% versus 50%, p = 0.03) and guided the successful enucleation of each. The results support the strategy of preoperative PVS and operation with IOUS to localize and remove insulinoma in patients with occult tumors. Most tumors (75%) will be correctly localized to a specific pancreatic region by preoperative PVS and identified by IOUS (83%), allowing simple enucleation and biochemical correction of hypoglycemia. Morbid blind pancreatic resections are no longer indicated and long-term medical management of hypoglycemia should be reserved for the occasional patient (8%) who fails preoperative PVS and operation guided by IOUS.

Ewing's sarcoma. Radiotherapy versus surgery for local control. Significant strides in the treatment of Ewing's sarcoma, the second most common bone tumor of childhood, have resulted in cure for approximately 50% of patients. Successful therapy requires systemic chemotherapy for the eradication of microscopic or overt metastatic disease and surgery or irradiation therapy for control of the primary lesion. The article debates the controversy over the extent to which surgical resection should play a role in the local management of this disease.

Nonsurgical management of breast infections in nonlactating women. A word of caution. Management options for infectious mastitis have traditionally been limited to surgical drainage. With the advent of percutaneous fine needle aspiration (FNA), nonoperative treatment may be an alternative, though criteria for use have not been defined. During a 30-month period, 22 women presented with breast infection. Treatment was instituted based upon the clinical stage of infection. Patients with cellulitis (n = 8) were managed with diagnostic FNA/antibiotics. Those with focal abscess (n = 10) underwent FNA of the cavity/antibiotics. Patients with multiloculated abscess (n C = 3) underwent urgent surgical drainage. Of the 19 patients initially treated nonoperatively, resolution occurred in nine (47%); stage of infection did not effect outcome. Surgical drainage was required in the remainder; two cancers were found. FNA cytology in these (and all) patients was negative for malignancy. All underwent mammography during treatment. In 17 (77%) cancer was considered of low probability. The only patient with a mammogram highly suspicious for cancer had fat necrosis on biopsy. Bacterial cultures were positive in 79 per cent, virtually all with Gram (+) cocci. Four patients harbored Gram (-) organisms as well, two in concert with breast cancer. Conclusions: 1) select breast infections can be successfully managed nonoperatively, 2) the accuracy of FNA and mammography in the diagnosis of breast cancer may be impaired by coincident infection, 3) the finding of a Gram (-) breast infection warrants abandonment of nonoperative management in favor of tissue confirmation of the disease process.

Adjuvant chemotherapy with 5-fluorouracil, vincristine and CCNU for patients with Dukes' C colorectal cancer. The Swedish Gastrointestinal Tumour Adjuvant Therapy Group. A prospective controlled randomized trial testing adjuvant postoperative combination chemotherapy (5-fluorouracil, lomustine (CCNU) and vincristine) versus no adjuvant therapy in patients operated on for Dukes' C colorectal cancer is reported. In total 334 patients aged less than 70 years were recruited: 205 patients with colonic and 99 with rectal cancer, but there were three protocol violations and these cases are excluded from further consideration. Twenty-seven patients had a limited resection of their cancer. After 5 years' follow-up there was no significant difference in the tumour-free survival rate or in the survival rate between the treated and control groups. Twenty-nine of the 147 patients who started chemotherapy discontinued this treatment because of side-effects, mainly from the gastrointestinal tract. In 30 patients treatment was discontinued because of recurrent disease. The conclusion is that systemic administration of combination chemotherapy for colorectal cancer after operation is not worthwhile in routine clinical practice.

MRI, CT, SPECT, PET: their use in diagnosing dementia. The differential diagnosis of the dementia syndrome may pose a difficult clinical problem, since the most common dementia, Alzheimer's disease (AD), is marked by normal laboratory tests. Neuroimaging has played an important role in evaluating the demented patient, and its uses are growing. Computed tomography (CT) is useful for excluding reversible and treatable causes of dementia, such as subdural hematoma and tumor. More recently, magnetic resonance imaging (MRI) has improved our ability to diagnose vascular disease and may show the presence of cerebral infarcts and white matter disease not visible on CT. Single photon emission computed tomography (SPECT) and positron emission tomography (PET), techniques that visualize such cerebral functions as glucose metabolism and blood flow, may provide positive evidence supportive of the diagnosis of AD.

Improved flow cytometric determination of proliferative activity (S-phase fraction) from paraffin-embedded tissue. Recent studies suggest that proliferative activity (S-phase fraction [SPF]) may have greater prognostic significance than total nuclear DNA content; however, relatively few studies have examined SPF from paraffin-embedded tissue because of significant contamination of histograms with debris. In this study, cell cycle analysis was performed on 124 matched tissue specimens. Fresh tissue was divided into two equal portions; one portion was frozen, whereas the other portion was processed and embedded in paraffin. S-phase could be determined for both frozen and paraffin-embedded tissue in 81 cases. Correlation between SPF from frozen and paraffin-embedded tissue was demonstrated (r = 0.80) when debris was subtracted from histograms with the use of two new subtraction algorithms referred to as multicut and singlecut. Unlike other debris-subtraction algorithms, the quantity and distribution of debris calculated by these algorithms are dependent on the magnitude and position of histogram peaks. A lesser degree of correlation was demonstrated with the use of a standard exponential debris subtraction algorithm (r = 0.67). Correlation of SPF for aneuploid cases was greater when SPF was calculated as a percentage of the aneuploid cell population rather than as a percentage of the entire cell population. This was attributed to the observation that the proportion of aneuploid cells from paraffin-embedded tissue was less than that from frozen tissue. The results of this study indicate that SPF can be calculated from paraffin-embedded tissue with values comparable to those obtained from frozen tissue. The ability to calculate SPF reliably from paraffin-embedded tissue should allow additional evaluation of this parameter as a prognostic indicator.

A comparison of regulatory cells in spinal fluid and blood in patients with multiple sclerosis and other neurologic diseases. Multiple sclerosis is a disease in which immune abnormalities are present both in the CNS and peripheral blood. Whether these changes are primary or secondary to the disease process is not known. We tested T-cell clones derived from activated lymphocytes in the blood and CSF of MS patients and controls for their capacity to regulate T-cell responses to alloantigens. A wide spectrum of regulatory functions were observed, ranging from marked enhancement to almost complete suppression. Clones from different patient populations and anatomic sites were equivalent in their regulatory functions with the net effect of clones in each compartment being suppression. However, certain clones from CSF and peripheral blood had the capacity to stimulate autologous T cells. Percentages of such clones in the peripheral blood of MS patients were significantly higher than in controls, while percentages in MS and other neurologic diseases (OND) CSF were equivalent. Our data suggest that (1) functional suppressor cells are not lost from the blood or CSF or MS and OND patients, (2) lymphocytes that have entered the CNS in patients with MS and other CNS diseases have equivalent regulatory functions, (3) MS may be an illness in which peripheral immunologic events are important in perpetuating the disease process, and (4) responses to autologous antigens may also play a role in this perpetuation.

Pleomorphic (anaplastic) neuroblastoma in nude mice. Two pleomorphic (anaplastic) neuroblastomas, from two children aged 1 and 6 years, were transplanted into nude mice. Two noteworthy observations were made. In one case, the transplanted tumor gave rise to a soft-tissue sarcoma. Moreover, in both cases hepatic metastases were associated with a striking modification of murine hepatocytes, resulting in hyperchromatic and dysplastic nuclei. The latter finding was particularly evident in the hepatic areas surrounding all metastases of pleomorphic (anaplastic) neuroblastoma cells.

Conditioning prepulse of biphasic defibrillator waveforms enhances refractoriness to fibrillation wavefronts. The mechanism of biphasic waveform defibrillation threshold reduction is unknown. We tested the hypothesis that, during refractory period stimulation, sarcolemmal hyperpolarization by the first pulse of biphasic waveforms facilitates excitation channel recovery, which enhances graded responses produced by the second depolarizing pulse. This prolongs cellular refractoriness to fibrillation wavefronts when compared with a monophasic depolarizing stimulus. Monophasic (10 msec, rectangular wave) or symmetrical biphasic (10 msec, each pulse) current injection S2 stimuli at 1.5 and two times S1 threshold were used to scan the S1 action potential refractory period (S1 cycle length, 600 msec) in myocardial cell aggregates. S2 waveforms were delivered with normal and reversed polarity to test the hyperpolarizing action of biphasic waveforms. Responses to an S3 stimulus, which simulated a potential incoming fibrillation wavefront, were also determined. Results showed that biphasic S2 waveforms produced longer graded responses during and immediately after the S1 refractory period than did corresponding monophasic S2 waveforms. The maximum difference in response duration produced by the biphasic and monophasic waveforms was 58.6 +/- 10.0 msec (p less than 0.001). This maximum difference occurred 10 msec before the end of the S1 refractory period. The longer response durations produced by biphasic S2 also produced longer refractoriness to the S3 stimulus. The maximum difference in total refractoriness to S3 of 51.8 +/- 2.8 msec (p less than 0.002) occurred at the same S1S2 coupling interval as the maximum difference in S2 response duration. Prolonged refractoriness may protect ventricular cells from refibrillation wavefronts and act as the cellular basis for greater biphasic waveform defibrillation efficacy.

Sciatic nerve monitoring during revision total hip arthroplasty. This study presents a simple method of intraoperative sciatic nerve monitoring during revision total hip arthroplasty (THA), utilizing intraoperative, somatosensory evoked potentials. Using this method, the sciatic nerve was protected when surgical correction of shortened limb length was necessary during revision THA. Twenty-three revision THAs were performed using intraoperative sciatic nerve monitoring. No postoperative peripheral nerve complications occurred, with an average increase of 18 mm in leg length, ranging from 6 mm to 43 mm.

The Caspar microsurgical discectomy and comparison with a conventional standard lumbar disc procedure. The outcome in 119 patients who were operated on with a conventional standard lumbar discectomy procedure was retrospectively compared with that in 299 patients who were operated on with a microsurgical discectomy technique developed in Homburg/Saar, Federal Republic of Germany by the senior author (W.C.). All patients in this consecutive series had "virgin" lumbar radiculopathy evaluated and operated upon by two experienced surgeons at one institution. Determination of the final outcome was made objectively by an impartial third party using identical criteria for both groups, and with a patient self-evaluation form. The study looked at various pertinent aspects of the treatment course and at final outcome. The results in the microsurgical group were significantly favorable: fewer levels were explored: there was less operative blood loss and a decreased incidence of deep venous thrombosis, urinary tract infections, pulmonary emboli, and bladder catheterization; the time to full ambulation, discharge, and return to work was faster: and there was a decrease in change of occupation and a greater percentage of satisfactory final outcomes, as measured both objectively and subjectively. A description of the microsurgical technique used in this study, which differs significantly from existing microdisectomy techniques, is presented. The authors conclude that the microsurgical disectomy technique presented in this study is a safe and effective approach to the treatment of lumbar radiculopathy.

Left ventricular passive diastolic properties in chronic mitral regurgitation. BACKGROUND. In chronic mitral regurgitation, the myocardium responds to the increased filling volume by geometric alteration and eccentric hypertrophy. This study was designed to evaluate the effects of a pure volume overload on left ventricular diastolic chamber and myocardial properties and to assess the relation of passive diastolic function to systolic ejection performance. METHODS AND RESULTS. By use of simultaneous cineangiography and left ventricular micromanometry, left ventricular passive diastolic stiffness was evaluated in nine normal controls (group 1), 14 patients with chronic mitral regurgitation and a normal ejection fraction (greater than or equal to 57%, group 2), and 13 patients with mitral regurgitation and a reduced ejection fraction (less than 57%, group 3). Passive diastolic function was evaluated by using a three-constant elastic model. Left ventricular chamber properties were represented by the relation of pressure to volume; myocardial properties were evaluated by relating myocardial midwall stress to midwall strain. The constant of left ventricular chamber stiffness was decreased in group 2 compared with controls (p less than 0.05) but it was normal in group 3. The constant of myocardial stiffness was increased in group 3 compared with groups 1 and 2 (p less than 0.01). Among patients with mitral regurgitation, there was a significant inverse relation between ejection fraction and the constant of myocardial stiffness (r = -0.83). CONCLUSIONS. The chronic adaptation to volume overload in chronic mitral regurgitation tends to decrease left ventricular chamber stiffness. Patients with mitral regurgitation and a depressed ejection fraction demonstrated diastolic myocardial dysfunction. Compromised diastolic function in patients with chronic mitral regurgitation and reduced systolic performance may contribute to the clinical manifestations of congestive heart failure.

Intraperitoneal lymphokine-activated killer-cell and interleukin-2 therapy for malignancies limited to the peritoneal cavity. Autologous lymphokine-activated killer (LAK) cells and recombinant human interleukin-2 (rIL-2) were administered intraperitoneally (IP) to 24 patients with malignancies limited to the peritoneal space. Ten patients had ovarian cancer, 12 had colorectal cancer, and one patient each had endometrial carcinoma and primary small-bowel adenocarcinoma. All ovarian cancer patients, three of twelve colorectal cancer patients, and one patient with endometrial carcinoma had received prior therapy. Patients received IL-2 100,000 U/kg every 8 hours intravenously (IV) for 3 days, and 2 days later underwent daily leukapheresis for 5 days. LAK cells were generated in vitro by incubating the peripheral blood mononuclear cells in IL-2 for 7 days and were then administered IP daily for 5 days through a Tenckhoff catheter (Davol, Inc, Cranston, RI) together with IL-2 25,000 U/kg IP every 8 hours. All but one patient completed at least one cycle of therapy. Toxic side effects included minor to moderate hypotension, fever, chills, rash, nausea, vomiting, abdominal pain and distension, diarrhea, oliguria, fluid retention, thrombocytopenia, and minor elevations of liver function tests; all of these rapidly improved after discontinuation of IL-2. One patient had a grand mal seizure, and one suffered a colonic perforation; these were felt to be treatment-related. IP fibrosis developed in 14 patients and limited repeated cyclic administration of this therapy in five patients. Two of 10 (20%) ovarian cancer patients and five of 12 (42%) colorectal cancer patients had laparoscopy- or laparotomy-documented partial responses. We conclude that LAK cells and rIL-2 can be administered IP to cancer patients, resulting in moderate to severe short-term toxicity and modest therapeutic efficacy. Further investigation of this form of adoptive immunotherapy modified to address the problem of IP fibrosis and with lower IP IL-2 doses is justified by these initial results.

Iatrogenic saphenous neuralgia: successful therapy with neuroma resection. We report the case of a patient with saphenous neuralgia secondary to iatrogenic trauma resulting from bypass surgery in the femoral-popliteal region. Early symptoms of this condition were medial calf and ankle pain, with no findings of motor and reflex abnormalities. Exploration of the thigh 2 years later revealed a neuroma of the nerve in the distal dissection site, medial to the knee. Resection of the neuroma alleviated this condition. It is noted that saphenous neuropathy is seen as a spontaneous entrapment syndrome as well as a complication of orthopedic and vascular procedures performed on the medial area of the knee. Saphenous neuralgia is often not recognized by neurosurgeons. If the condition is intractable, it does respond to surgical therapy.

Hepatic portal venous gas identified by computed tomography in a patient with blunt abdominal trauma: a case report. An abdominal computed tomographic (CT) scan in a middle-aged man injured in a high-speed motor vehicle accident demonstrated the presence of portal venous gas. Findings on initial peritoneal lavage were entirely negative. Exploratory celiotomy performed because of increasing abdominal pain and leukocytosis revealed gangrene of the cecum. This report illustrates the importance of the finding of portal venous gas on CT scan in patients with blunt abdominal trauma.

Severe gastrointestinal hemorrhage in Crohn's disease. Twenty-one of fifteen hundred twenty-six patients with Crohn's disease (CD) treated at The Mount Sinai Hospital between 1960 and 1986 developed severe gastrointestinal hemorrhage. There were 26 separate episodes of severe hemorrhage: 17 patients bled only once, three bled twice and one bled three times. The frequency of bleeding was significantly higher among patients with colonic involvement (17 of 929; 1.9%) than among those with small bowel disease alone (4 of 597; 0.7%) (p less than 0.001). Twelve patients required surgery on 13 occasions, which involved colon resection in all but one case. Eleven of these patients underwent surgery during their first hemorrhagic episodes, and 1 of 11 had a second operation for recurrent bleeding; the 12th patient, whose first hemorrhage had been treated medically, had surgery during a repeated episode of hemorrhage. The precise bleeding points could be located in only 2 of the 26 bleeding episodes, both at the ileocecal area. Three patients died, of whom two had not undergone surgery when they had bled a few weeks earlier. Primary bleeding episodes subsided without surgery in 10 of 21 cases, but 3 of these 10 patients (30%) rebled massively. By contrast primary excisional surgery was followed by recurrent hemorrhage in only 1 of 11 cases (9%). These differences in mortality and in recurrent bleeding rates, although not statistically significant, seem to favor removal of diseased bowel at the time of the first episode of massive hemorrhage.

Importance of the omentum in the development of intra-abdominal metastases. Areas of trauma are preferred sites for metastatic tumour growth. In extensive intra-abdominal tumour recurrence the omentum is invariably involved. The importance of the omentum in the development of tumours at sites of intra-abdominal trauma has been investigated. Colonic anastomoses were performed in Hooded-Lister rats with and without omentectomy. Animals received intraluminal or intraperitoneal injections of a syngeneic tumour. With intraluminal injection, tumour occurred at the anastomosis and in the omentum in 38 and 43 per cent of animals respectively but following omentectomy the values were 14 and 9 per cent (omental remnant). With intraperitoneal administration tumour occurred in 53 per cent at the anastomosis and in 79 per cent in the omentum compared with 16 and 29 per cent (in omental remnant) following omentectomy. In this model a reduced ability of an anastomosis to support 'seeded' tumour following removal of the omentum is demonstrated and the development of local recurrence from spilled tumour cells during operation may be enhanced by, or be dependent on, the proximity of the omentum.

Thoracoscopic treatment of spontaneous pneumothorax using carbon dioxide laser. In an effort to improve the success rate of the previously described thoracoscopic electrocautery ablation technique of spontaneous pneumothorax, the carbon dioxide laser was evaluated in 12 patients. The recurrent (5 patients) or persistent (7 patients) spontaneous pneumothoraces were caused by rupture of (1) blebs in 6 patients, (2) intrapulmonary apical type II bullae in 3 patients, and (3) diffuse bullous emphysema, type III, in 3. The air leaks were successfully sealed in all but 1 patient with ruptured type II bulla. Surgical specimen from this single failure suggested that the entire inner lining of the bullae must be thermocoagulated. This technical modification led to successful outcome in 2 subsequent cases. With the use of carbon dioxide laser, it was possible to treat not only small blebs but all types of bullae causing spontaneous pneumothorax. Laser thoracoscopy is effective and safe in treating spontaneous pneumothorax.

Upper GI bleeding in an urban hospital. Etiology, recurrence, and prognosis. Acute upper gastrointestinal bleeding (UGIB) continues to be a common cause of hospital admission and morbidity and mortality. This study reviews 469 patients admitted to a surgical service of an urban hospital. There were 562 total admissions because 53 patients were readmitted 93 times (recurrence rate, 20%). The most common causes of bleeding, all endoscopically diagnosed, included acute gastric mucosal lesion (AGML) (135 patients, 24%), esophageal varices (EV) (121 patients, 22%), gastric ulcer (108 patients, 19%), duodenal ulcer (78 patients, 14%), Mallory-Weiss tear (61 patients, 11%), and esophagitis (15 patients, 3%). Nonoperative therapy was sufficient in 504 cases (89.5%). Endoscopic treatment was used in 144 cases. Operations were performed in 58 cases (10.5%), including 29% of ulcers. Emergency operations to control hemorrhage were required in only 2.5% of all cases. The rate of major surgical complications was 11% and the mortality rate was 5.2%. There were 58 deaths (12.6%), with 36 deaths directly attributable to UGIB. Factors correlating with death include shock at admission (systolic blood pressure less than 80), transfusion requirement of more than five units, and presence of EV (all p less than 0.001). Most cases of UGIB can be treated without operation, including endoscopic treatment, when diagnostic endoscopy establishes the source. Subsequent operation in selected patients can be done with low morbidity and mortality rates.

Replacement of the aortic valve or root with a pulmonary autograft in children. Between January 1967 and December 1988, 34 patients ranging in age from 3 to 18 years (mean, 14 +/- 3.6 years) underwent replacement of the aortic valve or root with their own pulmonary valve. The indication for operation was left ventricular outflow obstruction in 16 patients (47%), aortic regurgitation in 14 (41%), mixed aortic valve disease in 3 (9%), and failure of a previously implanted aortic homograft in 1 (3%). There were four early deaths, all before 1971, giving a hospital mortality of 11.8% (70% confidence interval, 6% to 20%). Surviving patients have been followed up a cumulative total of 214 patient-years, the longest period of observation being 16 years 8 months. Late mortality was 13.3% (70% confidence interval, 7% to 23%), and 4 other patients required removal of the pulmonary autograft for endocarditis. Actuarial rates at 16 years were 74% +/- 11% for freedom from reoperation on the left ventricular outflow tract, 80% +/- 10% for freedom from reoperation on the right ventricular outflow tract, and 77% +/- 10% for late survival. There was no instance of primary structural degeneration in the pulmonary autograft, and all surviving patients were in New York Heart Association functional class I without medication. This experience demonstrates that the pulmonary autograft can achieve good early and medium-term results in young patients. Should growth potential be realized, it might constitute the ideal biological valve for the left ventricular outflow in children.

Fine structure of active and healed duodenal ulcer. In order to characterize the fine structure of active and healed duodenal ulcers, we examined tissue specimens of patients with active duodenal ulcer disease (n = 30) before and after treatment with either antacids (n = 16) or H2-receptor antagonists (n = 14), by light microscopy and various electron microscopic techniques, e.g., scanning and transmission electron microscopy. The characteristic histological feature of both the active and healed duodenal ulcer was the appearance of periodic acid-Schiff (PAS)-positive epithelial cells at the edge of the ulcers. Electron microscopy revealed that these cells were similar to a special type of mucus-secreting cell in the antrum (surface mucous cell). Their mucus granules contained mainly neutral glycoproteins. Helicobacter pylori were found attached to these cells in tissue specimens from 12 of 30 patients (40%). The mucous structure destroyed during the ulcerative phase regained its normal net-like structure after treatment. The ultrastructural healing process of duodenal ulcer was characterized by the presence of gastric metaplasia, by stunted microvilli of the duodenal epithelium (p less than 0.001 vs. control group), and an increased number of lysosome-like bodies (p less than 0.001 vs. control group) of the epithelial cells. These results were independent of the type of treatment, and showed that the repair mechanisms were incomplete after a 4-wk period of treatment.

Primary and metastatic pulmonary meningioma. Patient 1 was a 53-year-old man who had a very rare primary pulmonary meningioma that developed in the left lingular segment. When this report was written, 7 years had passed since he underwent operation, and no recurrence of the meningioma had been detected. In Patient 2, a 61-year-old woman, multiple pulmonary metastases were confirmed 19 years after she had undergone operation for multiple cerebellar meningiomas, and the metastases were resected. After 2 years, multiple intraperitoneal metastases were found, and thus aggressive surgery was performed. Currently, 22 years after the operation for the primary cerebellar meningioma, the patient is alive without any subjective symptoms, although intraperitoneal metastases have recurred. To date, only four cases (all in women) of primary pulmonary meningioma have been reported. Case 1 reported in this article is thus the first case in a male patient to be reported, and, in addition, this patient also has the first reported case to have been evaluated for more than 5 years. In Case 2, however, each of the excised extracranial tumor lesions was histologically homogeneous and showed a hemangiopericytomatous pattern. The histologic picture of those tumor lesions was exactly the same as the picture of a small portion of the cerebellar meningiomas excised 19 years earlier. Thus, all those extracranial tumor lesions were diagnosed to be metastatic meningiomas. However, it is difficult to explain why there had been no symptoms for as long as 19 years until the pulmonary metastases were discovered.

Spontaneous rupture of hepatocellular carcinoma: a review of 172 Japanese cases. The spontaneous rupture of a primary hepatocellular carcinoma (HCC) accounts for 10% mortality of HCC patients in Japan. Because this problem occurs much less frequently in western countries, it is often difficult for clinicians practicing in such countries to decide upon the best course of action during the crisis accompanying the spontaneous rupture of a HCC. In an effort to advance the general knowledge of this disease and clarify a selection for its treatment, we review 172 cases of spontaneous rupture of a HCC reported in the Japanese literature. The chief complaint of the patients was sudden epigastralgia or right hypochondriac pain. Abdominal paracentesis was positive in 86% of the patients. Liver failure was the cause of death in 42% of the patients. Therefore, it is important to evaluate liver reserve quickly. In addition, emergency hemostatic procedures must be implemented to avoid hemorrhagic shock. Although two-stage hepatectomy was performed in only 12% of the cases, these had the highest survival rates. Consequently, this is the procedure of choice for the treatment of spontaneous rupture of a HCC.

Esophageal contribution to chest pain in patients with coronary artery disease. We conducted a prospective study to determine the role of the esophagus in causing chest pain in patients with established CAD on optimum therapy. Thirty-two men with documented CAD who complained of frequent and usually daily retrosternal chest pain were evaluated. Following a standard esophageal manometry and acid perfusion test, simultaneous two-channel ambulatory Holter monitor and esophageal pH record tests were performed for 24 hours. Fifty-three episodes of chest pain were documented in 20 patients; 11 patients were free of pain. Of the 20 patients who complained of chest pains, 17 (85 percent) demonstrated at least one episode of PPR, defined as a drop in distal esophageal pH to less than 4 within ten minutes before or after the onset chest pain. Episodes of asymptomatic GER were common. The correlation of PPR with chest pain was 70 percent (37/53 episodes) and of ischemic ECG changes with chest pain 13 percent (7/53); in the remaining, there was no correlation with either. Two patients demonstrated simultaneous PPR and ischemic ECG changes. Seventeen esophageal motility abnormalities were observed in 14 patients (45 percent). It is our conclusion that esophageal disorders contribute to chest pain in patients with documented CAD. In this group, GER plays a greater role than in those with normal coronary arteries. In addition, esophageal motility disorders are common in these patients. Esophageal testing can be undertaken safely in these patients.

A case of unilateral posterior ischemic optic neuropathy after radical neck dissection. We present a case of unilateral posterior ischemic optic neuropathy after bilateral radical neck dissection. Etiologic factors are discussed.

Successful treatment of metastatic thymic carcinoma with cisplatin, vinblastine, bleomycin, and etoposide chemotherapy. Thymic carcinomas are rare malignant neoplasms of the thymic epithelium that are distinguished from the malignant thymomas by the presence of cytologic atypia. Thymic carcinomas may metastasize outside of the thorax and are associated with a very poor prognosis. Complete responses of thymic carcinoma to chemotherapy alone have not been reported. A 21-year-old man with metastatic undifferentiated carcinoma of probable thymic origin is presented who achieved a pathologic complete response with cisplatin, vinblastine, and bleomycin chemotherapy. Additional consolidative chemotherapy with cisplatin and etoposide was administered. The patient remains disease-free 5 years after diagnosis. Cisplatin, vinblastine, and bleomycin chemotherapy appears to have significant activity against thymic carcinoma.

Association of hepatitis B surface antigen and core antibody with acquisition and manifestations of human immunodeficiency virus type 1 (HIV-1) infection. We examined the associations between seropositivity for hepatitis B virus (HBV) with the presence or development of antibodies to human immunodeficiency virus (HIV-1) and with HIV-1 induced T-helper lymphocyte deficiency or acquired immunodeficiency syndrome (AIDS). Serologic data on HBV and HIV-1, cytometric enumeration of CD4+ lymphocytes, clinical events (AIDS by Centers for Disease Control criteria) and hepatitis B vaccination histories were available on 4,498 homosexual participants in the Multicenter AIDS Cohort Study, Men were classified as to previous infection with HBV and prevalent or incident infection with HIV-1. Although there was an association between seropositivity for HBV infection and HIV-1 infection at enrollment (odds ratios anti-HBc 2.6; HBsAg 4.2), the relation between HBV seropositivity and subsequent seroconversion to HIV-1 was weaker (odds ratios 1.3 and 1.6). HIV-1 seroconversion was also associated with a history of certain other sexually transmitted diseases, but predisposing sexual practices did not account for the association between HBV and HIV-1 infection. Seropositivity for HBV infection at entry was not related to initially low or more rapid subsequent decline in T-helper lymphocyte counts and was not associated with an increased incidence of AIDS during 2.5 years of follow-up. History of vaccination against HBV did not appear to decrease susceptibility to HIV-1 infection or to subsequent progression of immunodeficiency. We conclude that prior HBV infection is unlikely to be specifically associated with acquisition of HIV-1 infection and is unrelated to more rapid progression of HIV-1-induced immunodeficiency.

Localization of stereotactic targets by microrecordings of thalamic somatosensory evoked potentials. To improve the localization of stereotactic targets, somatosensory evoked potentials (SEPs) were recorded from the thalamus and subthalamic area using a specially designed semimicroelectrode in 61 patients and a conventional "macroelectrode" in 17 patients. By means of the semimicroelectrode, median nerve stimulation evoked two distinct SEPs, consisting of a diphasic wave with a huge positivity restricted to the nucleus ventrocaudalis (Vc) and a triphasic wave of lower amplitude with a major negativity in the ventral part of the nucleus ventrointermedius (Vim) and nucleus ventrooralis posterior (Vop) as well as the subthalamic lemniscal pathway. The Vim-Vc junction could thus be clearly delineated by an abrupt transition of SEPs from one type to the other with a precision of 1 mm. The parvicellular part of the Vc (Vcpc), situated in its basal region, was distinguishable from the Vc proper by a significant reduction of the positivity elicited by stimulation of the median nerve and by a rapid growth of a diphasic SEPs to stimulation of the posterior tibial nerve. In the other thalamic nuclei, stimulation of the median nerve elicited triphasic SEPs of a very small amplitude, suggesting a volume conduction current from the lemniscal pathway. With the macroelectrode, the positivity in the Vc was sensitive to electrode manipulation and the thalamic nuclei could not be distinctly outlined. SEP monitoring using the semimicroelectrode significantly improved the precision of target localization, which allowed minimizing of the volume of the therapeutic lesion without losing surgical effectiveness, while avoiding complications associated with increased penetration of the coagulating electrode. It is suggested that recording serial thalamic SEPs with the semimicroelectrode is a practical method to refine stereotactic targets in the thalamus.

Effects of hypertension on pregnancy monitoring and results. The effect of severity of hypertension on fetal heart rate tracing changes and neonatal outcomes was evaluated on all patients with hypertension seen in 1980 and 1981 (666 cases, 10% of the pregnant population) in the Chicago-Lying In Hospital. The patients were grouped according to severity of hypertension, and the fetal heart rate monitoring, drugs administered, mode of delivery, and neonatal outcome were analyzed. Half of the patients (326) had mild hypertension and 13% (87) had severe hypertension; the remainder (253) had moderate hypertension. There were 49% primiparous and 51% multiparous women. The diagnosis of preeclampsia was made in 76% of cases, and chronic hypertension in 19%. Only 12% of the total were premature by dates, but 47% of this group were among the severe group. Oxytocin was given to 50%, whereas delivery was spontaneous in 56% of cases, and by cesarean section in 22%. This was higher among the severe hypertension group (37%), and the prematurity rate was 47%. Nonstress testing was done in one third of cases and only nonreactivity was associated with neonatal death. Neonatal depression (Apgar score less than 6 at 5 minutes) was significantly associated with intrapartum fixed baseline and late decelerations; these were the best predictors of fetal outcome. The administration of magnesium sulfate, hydralazine, meperidine, or morphine did not predictably affect the fetal heart rate pattern. The perinatal mortality was 21% in the mild group and 36% and 138%, respectively, among moderate and severe cases of hypertension. Close antepartum and intrapartum surveillance, including proper fetal monitoring, should help to reduce risks for mother and fetus through timely intervention.

Persistence of monosodium urate crystals and low-grade inflammation in the synovial fluid of patients with untreated gout. Synovial fluid (SF) from 74 asymptomatic knees of patients with gout was analyzed. These patients had never been treated with serum uric acid-lowering agents. SF samples were analyzed for the presence of crystals and for cell counts, using undiluted SF directly in a Niebauer cell counting chamber. Thirty-seven of the aspirated knees had previously been inflamed, and monosodium urate (MSU) crystals were seen in SF aspirates from 36 of them (97%). Of the 37 knees that had never been inflamed, only 8 contained MSU crystals (P less than 0.00001). After reaching the joint, MSU crystals will persist in the SF as long as the serum uric acid level has not been lowered by appropriate treatment. In this situation, analysis of SF is an excellent diagnostic test for the intercritical gout. The mean cell count in the 44 SF samples that contained MSU crystals was 449/mm3 (95% confidence interval 310-589); the mean cell count in the 30 SF without MSU crystals was 64/mm3 (95% confidence interval 34-95) (P less than 0.00002). The SF samples that contained MSU crystals also had a higher percentage of polymorphonuclear leukocytes than those without MSU crystals (P less than 0.002). These data suggest that there is a low-grade inflammation present in the knees of patients with MSU crystals, the consequences of which should be investigated.

Transcatheter treatment of splenic artery aneurysms (SAA). Report of two cases. Splenic artery embolization with steel coils was performed in two patients who both had large splenic artery aneurysms and hepatic cirrhosis complicated by hypersplenism. A good clinical effect was noticed after the procedure. It was concluded that this treatment is safe and effective and decreases the risk of splenic artery rupture. It also corrects hypersplenism. Transcatheter embolization appears to be a preferable alternative to surgery in such cases.

Parapharyngeal abscess and torticollis. The combination of a parapharyngeal abscess and torticollis in an adult, due to a spastic contraction of the sterno-cleido-mastoid muscle is an extremely rare condition. We have recently been exposed to such case, in which it was very difficult to make the diagnosis and where CT of the neck gave us the answers without any difficulty. The indication for CT at an early stage in unexplained neck infections is stressed.

Dual association of HLA DR2 and DR3 with primary sclerosing cholangitis. Human leukocyte antigen typing was performed in 81 patients with primary sclerosing cholangitis to investigate reported associations between human leukocyte antigen type and this disease. The results showed a significant increase in the frequency of the antigens B8 and DR3 compared with controls (53% vs. 23%, p less than 0.0005, and 56% vs. 21%, p less than 0.0005). This was caused by a significant rise in the frequency of the human leukocyte antigen A1 B8 DR3 haplotype (32 of 81 patients, 40% vs. 12 of 100 patients, 12%, p less than 0.0005). By contrast, a significant reduction was seen in the frequency of the antigens B44 and DR4 (12% vs. 31%, p less than 0.005, and 12% vs. 34%, p less than 0.001, pc less than 0.011) because of the complete absence of the B44 DR4 haplotype in the patient group (p = 0.027, Fisher's exact test). When all the DR3-positive individuals (including the DR2/DR3 heterozygotes) were eliminated, a significant secondary association with DR2 was noted, 25 (69%) of 36 remaining patients being DR2-positive compared with 27 (34%) of 79 DR3 negative controls (p less than 0.0005, pc less than 0.006). Only 9% of the patients were DR2-positive and DR3-positive. Kaplan-Meier analysis demonstrated that survival was not influenced by the presence of either haplotype nor by the individual antigens. Patients who were DR3-positive were first seen at a significantly younger age than those who were DR2-positive (mean ages = 33 yr and 44 yr, respectively, p less than 0.002, Student's t test).

Parietal cell vagotomy and dilatation for peptic duodenal stricture. Gastric outlet obstruction due to peptic duodenal stricture (pyloric stenosis) was treated with parietal cell vagotomy and dilatation of the stricture in 32 patients. Follow-up is in the range of 5 years in 37.4% of the patients, while 6 to 10 years follow-up is available in 62.4% of the patients. At their last follow-up, 74.9% of the patients were in either Visick 1 or 2 clinical status. Recurrence rates have been 3.1% at 1 year, 9.3% at 5 years, and 21.8% after 6 to 10 years follow-up. There has been only one instance (3.1%) of restenosis. Two patients required reoperation because of recurrence and one of them died.

The ectopic ovary. A case report and review of the literature. We describe an ectopic ovary in a stillborn female. To our knowledge, this is the first report of an extra ovary in an infant. This case prompted a review of ectopic ovarian tissue, which is known by a variety of terms, the most common being accessory ovary and supernumerary ovary. We suggest that (1) many of the past cases should be classified as ovarian implants rather than true embryologically derived ectopic tissue; and (2) the terms accessory ovary and supernumerary ovary are imprecise and should be modified.

Clinical choices for circulatory assist devices. Approximately 1.0% of open heart surgery patients become unweanable from cardiac bypass during the surgical procedure. In addition, nearly 20% of patients accepted for cardiac transplantation die while waiting for a donor heart. Pulsatile pneumatic ventricular assist devices (VADs) provide a realistic solution to these dilemmas. Currently, there are five manufacturers who are competing for the major market share in the clinical use of these devices. Novacor, Thermetics, Thoratec, Symbion, and Abiomed all have competitive VAD systems. Because no one system is optimal for all patients, the limitations, similarities, and strengths of each system should be known to enhance the patient's outcome when using these devices. Successful use of VAD systems, either as a bridge to transplantation or to ventricular recovery, is best approached by adherence to strict patient selection. Once instituted, VAD management centers on detailed attention to anticoagulation and prompt diagnosis and treatment of various complications.

Failure of Hancock pericardial xenografts: is prophylactic bioprosthetic replacement justified? The incidence of major valve-related complications was evaluated in a series of patients in whom the Hancock pericardial xenograft was used for aortic (AVR; n = 84), mitral (MVR; n = 17) and mitral-aortic (MAVR; n = 13) valve replacement. At 7 years actuarial survival is 66% +/- 8% after AVR, 64% +/- 13% after MVR, and 41% +/- 15% after MAVR, whereas actuarial freedom from valve-related death is 79% +/- 7% after AVR, 78% +/- 13% after MVR, and 81% +/- 12% after MAVR. Actuarial freedom from thromboemboli and anticoagulant-related hemorrhage at 7 years is 93% +/- 4% and 98% +/- 2% after AVR and 83% +/- 10% and 88% +/- 11% after MVR; no such complications occurred after MAVR. Structural valve deterioration determined at reoperation, at autopsy, or by clinical investigation was observed in 34 patients with AVR (10.0 +/- 0.2%/patient-year), in 10 with MVR (10.6 +/- 3.3%/patient-year), and in 9 with MAVR (16.6 +/- 5.5%/patient-year). After AVR, 19 patients underwent reoperation and 2 died before reoperation; 4 patients with MVR underwent reoperation, and 7 patients with MAVR underwent reoperation and 1 died before reoperation. Seventy-eight percent of the current survivors (13 patients with AVR, 7 with MVR, and 1 with MAVR) have clinical evidence of valve failure. At 7 years actuarial freedom from structural deterioration of the Hancock pericardial xenograft is 25% +/- 7% after AVR, 29% +/- 14% after MVR, and 0% after MAVR.

Can the status of tubal pregnancy be predicted with transvaginal sonography? A prospective comparison of sonographic, surgical, and serum hCG findings Results of transvaginal sonography were compared prospectively with surgical findings and levels of serum human chorionic gonadotropin in 120 women with a proved tubal pregnancy. The most common sonographic finding was a saclike adnexal ring, which was seen in 74 of the women (61.7%). This finding was strongly associated with functioning trophoblasts and with an intact fallopian tube. In 39 of the women (32.5%) an adnexal mass with a complex texture was found. Of these 39 women, 20 had a tubal hematoma and six had a ruptured fallopian tube. The size of the tubal mass created by ectopic pregnancy was predicted precisely (r = .91, P less than .001), and transvaginal sonography enabled detection of hemoperitoneum with a sensitivity of 91% (68 of 75 women). This study suggests that the status of a tubal pregnancy can be predicted reliably on the basis of transvaginal sonographic findings.

Pharmacokinetics and clinical experience of 20-h infusions of methohexitone in intensive care patients with postoperative pyrexia. We have studied the pharmacokinetics of 20-h infusions of methohexitone in young patients with postoperative fever undergoing artificial ventilation of the lungs. The infusion rate was adjusted so that patients were unresponsive to vocal stimulation but reacted to tracheal suction. The mean steady state concentration of methohexitone required was 2.6 mg litre-1 (unbound 0.53 mg litre-1). The mean (SD) total clearance of methohexitone was 16.3 (4.2) ml min-1 kg-1, which is greater than that for volunteers or normal surgical patients. The unbound clearance correlated positively with body temperature during the infusion (r = 0.796, P = 0.017). The terminal half-life of methohexitone was 6.3 (3.8) h and that of the 4'-hydroxy metabolite 5.8 (2.1) h. There were no marked haemodynamic effects of the infusion, and no excessive sedation after the infusion. However, the clearance of methohexitone was high and variable, possibly as a direct effect of postoperative fever. Consequently, the need for individual titration of the rate of infusion is emphasized.

Esophageal 24-h pH monitoring: is prior manometry necessary for correct positioning of the electrode? In 24-h esophageal pH monitoring, the electrode is usually positioned 5 cm above the manometrically localized esophagogastric junction. In order to replace esophageal manometry for this purpose, we tested whether the esophagogastric junction can be identified correctly by fluoroscopy or the determination of the pH-step between stomach and esophagus, compared with esophageal manometry. The distance from the nares to the esophagogastric junction was determined three times with each of the three methods in 46 patients and 14 volunteers. Fluoroscopy assumed the esophagogastric junction 1.23 +/- 0.23 cm (mean +/- SE) lower than the peak pressure point determined at manometry, pH-step only 0.45 +/- 0.16 cm. With pH-step, only one subject had a difference of more than 3 cm to the manometrically defined esophagogastric junction, whether gastroesophageal reflux disease (as proven by pH monitoring) was present or not. We conclude that the esophagogastric junction can usually be identified with sufficient accuracy by the measurement of the pH-step between stomach and esophagus. Fluoroscopy is far less accurate than pH-step, and should not be used.

Contributions of the Zollinger-Ellison syndrome. The salient contributions of the Zollinger-Ellison syndrome have made it unique. No pancreatic endocrine tumor described before (insulinoma) or subsequently (glucagonoma, somatostatinoma, vipoma, pancreatic-polypeptidoma) has been the topic of such a variety of studies, or has been such an inspiration and rich source of new ideas for investigation and ultimate improvement in patient care.

Comparison of Delphin and BioMedicus pumps. There is an increasing use of centrifugal pump systems for cardiopulmonary bypass (CPB) and circulatory assistance. The BioMedicus and Delphin centrifugal pump systems were tested in two side-by-side, identical in vitro flow loops for blood trauma and flow probe accuracy. Blood parameters tested were hemoglobin, hematocrit, lactate dehydrogenase, free plasma hemoglobin, and platelet counts. The Delphin pump demonstrated significant increases in plasma hemoglobin levels at the three flow rates tested: 2 L/min (p less than 0.05), 4 L/min (p less than 0.005), and 6 L/min (p less than 0.05). After 4 hr of pumping, the drop in platelet counts was significantly greater in the BioMedicus loop as compared with the Delphin loop (p less than 0.05) at the 2 L/min and 4 L/min flow rates; however, platelet levels remained within normal ranges in both systems. At 6 L/min, no statistical difference in platelet counts was noted. The flow probe readings were found to deviate by as much as 58% of stopwatch timed flow rate comparisons at low flow rates, but improved to within 10% or better at 6 L/min.

Radiographic manifestations of congenital anomalies affecting the airway. Congenital anomalies of the airway are generally uncommon, but a vast array of possibilities exists. Some present life-threatening emergencies at birth, and others go undiagnosed for years. Clinical symptoms are often nonspecific, and radiographic evaluation is frequently requested to localize and characterize the lesion before endoscopy, surgery, or medical management. The most common intrinsic congenital anomalies causing airway compromise in infants include choanal atresia, mandibular hypoplasia, laryngomalacia, vocal cord paralysis, and congenital subglottic stenosis. The radiologist must be on the alert for unsuspected additional anomalies involving the airway, lungs, and esophagus, which occur with relative frequency. Numerous extrinsic congenital masses of the head, neck, and mediastinum may compromise the airway. Hemangiomas, lymphangiomas, and teratomas are more likely to be noted at birth, whereas branchial cleft cysts, thyroglossal duct anomalies, and dermoid cysts frequently present later. Mass location and radiographic characteristics usually allow accurate preoperative diagnosis. Intracranial involvement by nasal or nasopharyngeal masses, intrathoracic involvement by lower neck mass, and intraspinal involvement by posterior neck mass must always be sought for radiographically. Persistence of respiratory symptoms after removal of such masses is not uncommon because tracheal deformity and laxity may take months or years to resolve. Recent advances in cine CT and MR imaging promise to improve imaging of the airway in general and in the pediatric population in particular. Significant limitations in imaging of the pediatric larynx remain. As a result, endoscopy continues to be the primary diagnostic tool for airway anomalies of this region.

Cervical spine stabilization. A three-dimensional, biomechanical evaluation of rotational stability, strength, and failure mechanisms. The three-dimensional rotational biomechanical properties of several different types of posterior stabilizing procedures are reported. A severe ligamentous and bony injury was simulated with three vertebral body human cervical spine segments. Good stabilization was noted for all of the repairs in flexion loading. Without polymethylmethacrylate supplementation, none of the repairs was stable in extension. All of the repairs provided reasonable stabilization for lateral bending except for the posterior wiring without methacrylate, and all but the posterior wiring and facet fusion provided reasonable stabilization against axial rotation loading. The supplementation of all of these repairs with polymethylmethacrylate added considerably to the stability of all the constraints. These findings may be useful in clinical decision-making for determining the kind of repairs and postoperative brace protection to use.

Association of bcl-1 rearrangements with lymphocytic lymphoma of intermediate differentiation. Previous studies using classical cytogenetics have demonstrated the presence of the t(11;14) (q13;q32) chromosomal translocation in some cases of lymphocytic lymphoma of intermediate differentiation (IDL), a distinct type of low grade B-cell lymphoma. This finding suggested that the bcl-1 region (located at band q13 of chromosome 11) might be involved in this neoplasm. Using a genomic probe from the major breakpoint area of the bcl-1 locus, we identified rearrangements of the bcl-1 region in 10 of 19 cases, 2 of which comigrated with a rearranged allele of the immunoglobulin heavy chain gene joining region. In contrast, bcl-1 rearrangements were not found in other types of low grade B-cell lymphoma, specifically in 36 cases of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and 27 cases of follicular lymphoma (FL). To further assess the molecular pathology of IDL, we analyzed these cases for rearrangements of the bcl-2 proto-oncogene, which is associated primarily with follicular lymphomas. None of the 19 cases of IDL had rearrangements. Furthermore, none of the 36 cases of CLL/SLL showed bcl-2 rearrangements, whereas, as expected, 21 of 27 cases of FL had rearrangements of the bcl-2 locus. Our findings demonstrate an association between a rearranged bcl-1 region with approximately 50% of IDLs and suggest that abnormalities of this locus may be important in the pathogenesis of IDL.

Tumor-secreted vascular permeability factor increases cytosolic Ca2+ and von Willebrand factor release in human endothelial cells. Vascular permeability factor (VPF), a tumor-secreted heparin-binding protein (Mr approximately 38,000), is responsible for increased vessel permeability and fluid accumulation associated with tumor growth. Vascular permeability factor also promotes the growth of human umbilical vein endothelial cells (EC) and bovine pulmonary ECs in vitro. It is shown for the first time that guinea pig VPF (half-maximal and maximal dose approximately 0.4 and 22 pmol/l (picomolar), respectively), as well as human VPF, are potent stimuli for human ECs resulting in [Ca2+]i increases (maximal three- to fourfold) and inositol triphosphate (IP3) formation. Unlike the maximal responses to thrombin and histamine, the [Ca2+]i response to a maximal VPF dose was preceded by a characteristic 10- to 15-second delay. Guinea pig VPF also selectively increased [Ca2+]i in cultured aortic and pulmonary artery ECs, but not aortic smooth muscle cells, human fibroblasts, or neutrophils. Affinity-purified rabbit antibody (raised to a synthetic peptide representing VPF N-terminal amino acids 1 to 24) adsorbed all vessel permeability-increasing activity, EC growth-promoting activity, and specifically all activity responsible for increasing EC [Ca2+]i. Similar to other mediators that increase [Ca2+]i in cultured ECs, VPF also induced a 200% increase in von Willebrand factor release. Together these data indicate that VPF acts directly on ECs and that rapid cellular events in its in vivo/in vitro actions are likely to involve phospholipase C activation, [Ca2+]i increase, and von Willebrand factor release.

Can clinicians accurately assess esophageal dilation without fluoroscopy? This study questioned whether clinicians could determine the success of esophageal dilation accurately without the aid of fluoroscopy. Twenty patients were enrolled with the diagnosis of distal esophageal stenosis, including benign peptic stricture (17), Schatski's ring (2), and squamous cell carcinoma of the esophagus (1). Dilation attempts using only Maloney dilators were monitored fluoroscopically by the principle investigator, the physician and patient being unaware of the findings. Physicians then predicted whether or not their dilations were successful, and they examined various features to determine their usefulness in predicting successful dilation. They were able to predict successful dilation accurately in 97% of the cases studied; however, their predictions of unsuccessful dilation were correct only 60% of the time. Features helpful in predicting passage included easy passage of the dilator (98%) and the patient feeling the dilator in the stomach (95%). Excessive resistance suggesting unsuccessful passage was an unreliable feature and was often due to the dilator curling in the stomach. When Maloney dilators are used to dilate simple distal strictures, if the physician predicts successful passage, he is reliably accurate without the use of fluoroscopy; however, if unsuccessful passage is suspected, fluoroscopy must be used for confirmation.

Multimodality therapy for advanced and recurrent vulvar squamous cell carcinoma. A pilot project. From 1985 to 1989 eight women with advanced or recurrent vulvar carcinoma were treated at the Women's Cancer Center of the University of Minnesota Hospital and Clinic. Each received a combination of 5-fluorouracil, mitomycin C and cisplatin during radiotherapy. Five of the eight women who underwent posttreatment radical vulvectomy had acceptable operative morbidity. Six patients experienced a complete clinical response. Of them, one had microscopic residual disease in the surgical specimen. One patient with recurrent vulvar carcinoma experienced progression of disease on therapy. One death was attributable to chemotherapy toxicity, and two patients died of intercurrent disease. The overall survival rate at 27 months was 33%. This multimodality approach to the treatment of advanced vulvar carcinoma should be considered when designing a therapeutic approach to treating extensive or resistant vulvar carcinoma.

Early diastolic clicks after the Fontan procedure for double inlet left ventricle: anatomical and physiological correlates. M mode echocardiograms and simultaneous phonocardiograms were recorded in four patients with early diastolic clicks on auscultation. All had double inlet left ventricle and had undergone the Fontan procedure with closure of the right atrioventricular valve orifice by an artificial patch. The phonocardiogram confirmed a high frequency sound occurring 60-90 ms after aortic valve closure and coinciding with the time of maximal excursion of the atrioventricular valve patch towards the ventricular mass. One patient had coexisting congenital complete heart block. The M mode echocardiogram showed "reversed" motion of the patch towards the right atrium during atrial contraction. Doppler flow studies showed that coincident with this motion there was forward flow in the pulmonary artery with augmentation when atrial contraction coincided with ventricular systole. The early diastolic click in these patients was explained by abrupt cessation of the motion of the atrioventricular valve patch towards the ventricular mass in early diastole. In one patient atrial contraction led to a reversal of this motion and was associated with forward flow in the pulmonary artery.

Continuous arteriovenous rewarming: experimental results and thermodynamic model simulation of treatment for hypothermia. We evaluated a technique for treating hypothermia that uses extracorporeal circulation but does not require heparin or pump assistance. Hypothermia to 29.5 degrees C was induced in eight anesthetized dogs, and thermistors placed in the pulmonary artery, liver, bladder, esophagus, rectum, muscle, and skin. Four experimental animals were rewarmed by creating a fistula which connected arterial and venous femoral lines to an interposed counter-current heat exchanger. External rewarming was used in four controls. Bleeding time (BT), coagulation profile (PT, PTT, TT), and cardiac output (CO) were measured during rewarming. Core temperature (T) rose significantly faster with CAVR (0.00001). Average time to rewarming was 45 min, vs. 4 hrs in controls. Haptoglobin, platelet, fibrinogen, and fibrin split product levels were unaffected. Continuous arteriovenous rewarming (CAVR) improved T, CO, BT, and coagulation profile faster than any method yet reported not requiring heparin or cardiac bypass. The application of CAVR in post-traumatic hypothermia warrants further investigation.

Immunodetection of the metastasis-associated laminin receptor in human breast cancer cells obtained by fine-needle aspiration biopsy. Fine-needle aspiration biopsy of the breast is a very useful technique for the evaluation of a suspect lesion before surgical removal. Increased expression of the 67-kd laminin receptor has been associated with the metastatic phenotype of cancer cells, particularly in colon and breast cancers. In this study, the expression of laminin receptor was evaluated using the immunoperoxidase technique in 81 breast aspirates (26 benign and 55 neoplastic lesions). Cells obtained from benign samples exhibited a low level of laminin receptor antigen detected by affinity-purified antibody raised against a cDNA-derived laminin receptor peptide. In contrast, 71% of smears obtained from malignant breast lesions contained cells that were strongly stained by the antibody. Heterogeneous expression of the laminin receptor was noted in both breast aspirates and fixed tissue specimens. These data suggest that the immunodetection of laminin receptor in cells obtained by fine-needle aspiration of breast lesions could be a valuable adjunct in the prognostic evaluation of breast lesions.

Postoperative hypoxemia after nonabdominal surgery: a frequent event not caused by nitrous oxide. We tested whether anesthesia that includes nitrous oxide (N2O) results in the development of intraoperative and postoperative pulmonary complications, including hypoxemia. We also tested whether aging contributes to the development of such complications, particularly when anesthesia includes N2O. We randomly allocated patients having total hip replacements, carotid endarterectomies, or transsphenoidal hypophysectomies (total n = 270) to an anesthetic regimen with and without N2O (stratified within surgical group). A heat-and-moisture exchanger was included in the anesthetic circuit of all patients. Patients were monitored perioperatively and for 1 wk after surgery using intermittent and continuous pulse oximetry to determine oxyhemoglobin saturation. Intraoperatively, mean oxygen (O2) saturations were lower in patients given N2O, particularly older patients. Hypoxemia (O2 saturation less than 86%) developed in five patients receiving N2O and in one receiving O2. This difference was not significant. Administration of N2O did not decrease postoperative O2 saturation, nor did it alter the incidence of postoperative hypoxemia, cough, or sputum production.

p53 expression in colorectal tumors. The expression of the nuclear phosphoprotein p53 was studied immunohistochemically in a series of 150 benign and malignant colorectal tumors. Using monoclonal antibody PAb1801, tumors divided unequivocally into two groups on the basis of immunohistochemistry. Forty of the carcinomas (46.5%) showed positive staining but only 4 of the adenomas (8.7%) were positive (P less than 0.001). The few positive adenomas always showed moderate or severe dysplasia. Metaplastic polyps (n = 9) and small familial adenomatous polyposis-related adenomas (n = 9) were uniformly negative. Carcinomas with p53 expression did not differ from those without in terms of site, differentiation or the prognostic indicators of Dukes' stage, DNA ploidy, or tumor histology. The improved morphologic resolution available in periodate lysine paraformaldehyde dichromate (PLPD)-fixed, paraffin-embedded tissue permitted several conclusions to be made: p53 is confined to neoplastic nuclei; staining in positive tumors is heterogeneous and often more marked at the infiltrative margins; and staining intensity is dramatically reduced in mitotic cells. It is concluded that expression of immunohistochemically detectable p53 (probably representing mutated forms of the protein) occurs in some adenomas around the time of transition to carcinoma. Therefore there is an association with the appearance of infiltrative behavior but not with degree of tumor progression (including metastasis) at the time of resection.

Achieving pH control in the critically ill patient: the role of continuous infusion of H2-receptor antagonists. Stress-related gastric mucosal damage is a common occurrence in intensive care unit (ICU) patients. Because of the significant morbidity and mortality associated with this mucosal damage, many ICU patients routinely receive prophylactic therapy, usually with histamine H2-receptor antagonists (H2RAs). Gastric acid secretion occurs in a circadian pattern, with late afternoon and evening surges. H2RAs by continuous infusion may control this uneven pattern of secretion more effectively than H2RAs given by bolus injection. More studies are needed to identify the target ICU population for prophylactic treatment.

Neurofibromatosis type 2: report of a family and review of current evaluation and treatment. Significant advances during the past decade have greatly improved our understanding of neurofibromatosis type 2, a genetic disease which results in bilateral acoustic neuromas. The emergence of gadolinium-enhanced magnetic resonance imaging has allowed early detection of minute intracanalicular eighth-nerve tumors, less than 1 cm in diameter. Recombinant DNA studies have clarified the genetics that underlie neurofibromatosis type 2 and separate it from a variety of related conditions, such as von Recklinghausen's neurofibromatosis. Early diagnosis and surgical removal of these tumors may offer the only hope of preserving hearing and facial nerve function. A report of the evaluation and treatment of a family with multiple affected individuals will exemplify these conclusions.

A syndrome characterized by nodular eosinophilic infiltration of the skin and immunoglobulin isotype imbalance. A 9-year-old boy had recurrent acute, plaquelike, nodular infiltrations with overlying vesicles and bullae of the face and right hand. Histologically, the lesions consisted of a perivascular and periadnexal lymphohistiocytic infiltrate with many eosinophils. The lesions responded to dapsone therapy. Laboratory studies revealed blood eosinophilia, hyperimmunoglobulinemias E and G4, and hypoimmunoglobulinemias M and G1-3, which normalized after treatment. The patient's immune deviation is consistent with a transient imbalance of lymphokine production in helper T cells.

Immunophenotypic characteristics of cerebrospinal fluid cells in children with acute lymphoblastic leukemia at diagnosis. The presence of meningeal involvement in children with acute lymphoblastic leukemia (ALL) may have important prognostic and therapeutic implications. Conventional methods of diagnosing central nervous system (CNS) leukemia rely on the interpretation of cerebrospinal fluid (CSF) cell morphology, which may produce ambiguous results in the presence of minimal leukemic involvement. A methodology has been developed for immunophenotyping small numbers of CSF cells while preserving cell morphology. CSF samples from 33 children with CD10 (common ALL antigen [CALLA]) positive ALL were examined at initial presentation using both conventional morphology and this combined immunohistopathologic technique. Six (18%) of the samples contained lymphoblasts or cells considered morphologically suspicious for leukemic involvement. Nine additional samples (27% of the total) had normal CSF morphology, but contained increased numbers of CALLA positive cells. Twelve of the 33 samples were also examined for the simultaneous presence of nuclear terminal deoxynucleotidyl transferase (TdT) and demonstrated increased numbers of cells positive for both TdT and CD10. These data suggest that a large proportion of children with ALL may have abnormalities of CSF cells at initial diagnosis consistent with the presence of occult leukemic involvement.

ECMO assisted angioplasty for cardiomyopathy patients with unstable angina. Patients who are otherwise unsuitable candidates for coronary bypass surgery or standard coronary angioplasty (PTCA) may be successfully treated with PTCA during ECMO. Five patients (3 men, 2 women), with a mean age of 57 years, are reported on here. They were not considered good candidates for standard therapy because of poor left ventricular function (mean EF, 24; range, 16 to 28%). Patients were supported by percutaneous femoral bypass using a BARD CPS machine, and underwent successful PTCA of either two vessels (three patients) or three vessels (two patients); in addition, one patient had dilatation of a stenotic aortic valve. Patients were supported with ECMO for 26 to 140 (mean 104) minutes, and required transfusion with 0 to 4 (mean 2) units of blood during or after the procedure. Complications included groin hematoma in two patients. All were discharged within 4 days of the procedure. Follow-up of the patients has been completed (4-7 mo) with no further hospitalizations for unstable angina. All patients remain in NYHA Class II or III. These data suggest that ECMO-assisted angioplasty is a safe and effective method of palliation of unstable angina associated with cardiomyopathy.

Radionuclide imaging in otolaryngology-head and neck surgery. Radionuclide imaging provides both qualitative and quantitative information that can have dramatic effects on patient management in diseases of the head and neck. The general concepts of nuclear medicine imaging, including radiopharmaceuticals and radiation effects, are discussed. The principles and techniques of thyroid, parathyroid, bone, and salivary radionuclide imaging studies will be reviewed. The intent of this article is to provide a concise and current review of head and neck radionuclide imaging that will be useful in the day-to-day practice of otolaryngology-head and neck surgery.

Choroid plexus tumors in the breast cancer-sarcoma syndrome. Choroid plexus neoplasms are rare epithelial tumors of the central nervous system. A carcinoma of the choroid plexus occurred in a child from a family with the breast cancer-sarcoma syndrome (Li-Fraumeni or SBLA syndrome), an inherited condition characterized by the development of diverse neoplasms (sarcoma, breast cancer, brain tumors, leukemia, adrenal cortical carcinoma, and others). Choroid plexus carcinomas were identified in two kindreds previously reported with the syndrome. The literature contains reports of choroid plexus neoplasms occurring in families and in individuals with multiple primary tumors. Choroid plexus neoplasm may be a manifestation of the inherited proclivity to tumor development in the breast cancer-sarcoma syndrome.

Intraoperative pathologic diagnosis of thyroid neoplasms. Report on experience with 504 specimens. Intraoperative pathologic examination with frozen section (FS) was performed on 504 specimens of thyroid tissue obtained from 457 patients over a period of 9 years. After examination of permanent sections (PS) a malignant neoplasm was diagnosed in 57 specimens (11.3%); 50 (87%) of these were primary thyroid carcinoma, four (8%) metastatic carcinoma, and three (5%) malignant lymphoma. The FS diagnosis was "benign" in 448 (88.9%), "malignant" in (30) 5.9%, and "deferred" in 26 (5.2%). The sensitivity of FS diagnosis of malignancy was 53% and the specificity and positive predictive value 100%. The negative predictive value was 97.8% and overall accuracy 97.9%. The PS disclosed a malignant neoplasm in 62% of specimens in which FS diagnosis was "deferred." Sixty-eight percent of papillary carcinomas, 87% of undifferentiated carcinomas, and a single case of medullary carcinoma were diagnosed with FS examination. A FS diagnosis of malignancy was not made in any of the ten specimens containing follicular carcinoma; in all ten the neoplasms were well-differentiated and eight were encapsulated and minimally invasive. The inability to diagnose follicular carcinoma intraoperatively with FS is the most significant factor accounting for the relatively low sensitivity of FS diagnosis of malignant thyroid neoplasms.