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Lymphomatous polyneuropathy. Biopsy of clinically involved nerve and successful treatment. We present a patient with large-cell lymphoma in remission who, over several weeks, developed widespread multifocal polyneuropathy. There was involvement of all four limbs, most severely the left upper extremity that had become useless. Biopsy of the left saphenous nerve within an area of sensory loss showed lymphoma in the endoneurium. There was no other evidence of recurrent lymphoma despite extensive investigation, including bone marrow, lumbar puncture, magnetic resonance imaging of the spine, and computed tomography of the abdomen and pelvis. Intensive systemic chemotherapy was accompanied by nearly complete recovery. Biopsy of a symptomatic nerve is preferable to routine sural nerve biopsy in this condition because of its patchy distribution. Treatment with systematic chemotherapy can be effective.

An unusual complication of cardiac transplantation--infected aortic pseudoaneurysm. Infections after cardiac transplantation are a frequent cause of early morbidity and mortality. An unusual site for such a complication is at the aortic anastomotic suture line. We report a case of an infected aortic pseudoaneurysm, seen as recurrent septicemia, during the first 6 months after cardiac transplantation.

Diagnostic modalities in abdominal trauma. Peritoneal lavage, ultrasonography, computed tomography scanning, and arteriography. Numerous algorithms encompassing the diagnostic studies described above have been published in recent years. For practical purposes, diagnostic peritoneal lavage and CT scanning are the diagnostic studies most commonly used in patients without obvious indications for celiotomy after blunt or penetrating abdominal trauma. Diagnostic peritoneal lavage is invasive, rapidly performed, cheap, and accurate and has a primary role in documenting intra-abdominal bleeding or contamination in hypotensive patients with blunt trauma or selected stable patients with penetrating stab wounds. It misses small and large injuries to the diaphragm and cannot rule out injury to retroperitoneal structures. Computed tomography is noninvasive, time consuming to perform, expensive, and accurate and has a primary role in defining the location and magnitude of intra-abdominal injuries in stable patients with blunt trauma or with penetrating trauma to the flank or back. In many hospitals, it misses gastrointestinal perforations or ruptures. Both studies may be needed in the same stable patient, and both should be available and used in a complementary fashion in the modern trauma center.

Preliminary report: the antegrade continence enema. The principles of antegrade colonic washout and the Mitrofanoff non-refluxing catheterisable channel were combined to produce a continent catheterisable colonic stoma. The intention was that antegrade washouts delivered by this route would produce complete colonic emptying and thereby prevent soiling. The procedure has been successfully carried out in five patients with intractable faecal incontinence.

Adoptive immunotherapy of human pancreatic cancer with lymphokine-activated killer cells and interleukin-2 in a nude mouse model. A pancreatic cancer cell line was grown in orthotopic and heterotopic positions in young Swiss/NIH nude mice, which were tested with adoptive immunotherapy. Mice were injected with 1 x 10(7) human cancer cells in the subcutaneous tissue and duodenal lobe of the pancreas. The mice were randomly divided into four groups: group IA (LAK + IL-2) (N = 25) received 2 X 10(7) human lymphokine-activated killer (LAK) cells from normal donors by tail vein injection followed by 10,000 units of human recombinant interleukin-2 (IL-2) given intraperitoneally every 12 hours for 28 days; group IB (IL-2) (N = 27) was given the same dose of IL-2 alone; group IC (RPMI-1640) (N = 18) received a placebo consisting of 1 ml of RPMI-1640 intraperitoneally every 12 hours; and group ID (LAK) (N = 14) received 2 X 10(7) LAK cells but no IL-2. Toxicity was significantly higher in group IB, with a mortality rate of 45.5% (10/22 animals) versus a 0% mortality (0/25) in group IA. None of the group IA or IB animals died of pancreatic cancer during the experiment. The animals that did not receive IL-2 died before 28 days in 14.2% of group IC and in 16.7% of group ID. The area under the growth curve of subcutaneous tumors during the course of treatment and the pancreatic tumor weight at the end of treatment were compared in each group. Subcutaneous tumors had a reduced rate of growth in group IA animals compared to all the other treatments. Pancreatic tumor growth was slowed in group IA. The animals treated with IL-2 alone (group IB) showed some slowing of tumor growth that was intermediate between group IA, group IC, and group ID. A similar experiment was done with irradiated (375 rad) mice. Nine nude mice with tumors were treated with LAK + IL-2 (group IIA), eight received IL-2 alone (group IIB), and seven received placebo (group IIC). The antitumor effect of IL-2 alone was not present in the irradiated mice. A highly significant difference persisted between group IIA and all other groups. There was no difference in the histologic characteristics of tumors in control mice and in mice with inhibited tumor growth treated with IL-2 or IL-2 and human LAK cells. These results show that adoptive immunotherapy with human LAK cells and human recombinant IL-2 is effective against human pancreatic cancer growing in nude mice. This effect is independent from antitumor activity from IL-2 administrations alone.

Starch peritonitis. A case report and clinicopathologic review. A case of starch peritonitis is presented with a review of the history of this continuing problem. The syndrome's presentation, diagnosis, histopathology and treatment are discussed. The rarity of starch peritonitis today may be due to more attention to glove washing by surgeons, fewer impurities in the glove powder or lack of recognition of the syndrome. In order to prevent a resurgence of the starch peritonitis syndrome we must continue to emphasize the importance of washing gloves, maintain the quality control and purity of the powder used, and be cognizant of the signs and symptoms so that such cases may be managed nonoperatively.

Transcranial Doppler in reversible migrainous vasospasm causing cerebellar infarction: report of a case. A young woman with a history of classic migraine suffered a large cerebellar infarction. Comprehensive evaluation did not disclose any potential causes for the stroke and she had no other risk factors. Transcranial Doppler (TCD) was useful in identifying vasospasm of the vertebral arteries. Following treatment with propranolol, angiography and repeat TCD revealed resolution of the vasospastic disorder. TCD is a useful noninvasive tool in detecting vasospasm associated with ischemic lesions in certain patients with migraine.

Stroke in systemic lupus erythematosus [published erratum appears in Stroke 1991 Mar;22(3):417] We investigated the clinical and pathologic characteristics of stroke in 234 patients with systemic lupus erythematosus. Thirteen patients (5.6%) developed cerebrovascular disease. Cerebral infarction was noted in eight, cerebral hemorrhage in two, and subarachnoid hemorrhage in three. In seven (54%) of these 13 patients, stroke occurred less than or equal to 5 years after systemic lupus erythematosus was diagnosed. Among the predisposing risk factors for stroke, hypertension was the most important. Lupus anticoagulant was detected in three (38%) and anticardiolipin antibody in three (43% of seven investigated) of the patients with infarction. Evaluation of the clinical manifestations and autoantibodies indicated that renal involvement and high titers of anti-deoxyribonucleic acid antibody were more frequent in the stroke group than in the non-stroke group. Autopsy studies on six of the patients with stroke revealed small infarcts and hemorrhages in all, but in no case was true angiitis observed. Libman-Sacks endocarditis was found in two of the three patients with infarction. In conclusion, the important contributory factor to the development of stroke in patients with systemic lupus erythematosus is considered to be hypertension mediated by immunologic abnormalities. Antiphospholipid antibodies and Libman-Sacks endocarditis are closely associated with occlusive cerebrovascular disease.

CT and MR imaging in staging non-small cell bronchogenic carcinoma: report of the Radiologic Diagnostic Oncology Group. The accuracies of magnetic resonance (MR) imaging and computed tomography (CT) in determining tumor classification and assessing mediastinal node metastases were compared in a prospective cooperative study of 170 patients with non-small cell bronchogenic carcinoma. The sensitivity of CT in distinguishing T3-T4 tumors from T0-T2 tumors was 63%; specificity was 84%. These values for MR imaging were not significantly different (56% and 80%). With receiver operating characteristic (ROC) analysis, no difference existed between the accuracies of CT and MR imaging in diagnosis of bronchial involvement or chest wall invasion, but MR imaging was significantly more accurate than CT (P = .047) in diagnosis of mediastinal invasion. Lymph node sampling was performed in 155 patients (642 node stations). Cancerous nodes were found in 14% of stations in 21% of patients. There was no significant difference between the accuracies of CT and MR imaging in detecting mediastinal node metastases (N2 or N3); the sensitivities were 52% and 48%, respectively, and specificities were 69% and 64%. ROC analysis also showed no difference between CT and MR imaging.

Crico-tracheal disruption and common carotid artery occlusion: a case of blunt trauma. A case of blunt trauma to the neck is presented. While driving an all terrain vehicle (ATV), a 20-yr-old male was struck across the anterior neck by a cord suspended between two poles. Initial findings were suggestive of an isolated laryngeal injury; 48 hours later, however, a dense left hemiplegia became manifest. A CT scan demonstrated a large right frontoparietal cerebral infarct, and an angiogram confirmed occlusion of the right common carotid artery. Intractable cerebral oedema developed, and the patient died five days after the initial insult. Such injuries should alert the clinician to the possibility of major vascular injury, and if suspected, angiography is warranted.

Significance of natural polymerized albumin and its receptor in hepatitis B infection of hepatocytes. Lack of information regarding the presence of native albumin polymer in serum and its structural similarity to the one produced by glutaraldehyde treatment casts doubt on the postulate that hepatitis B virus attachment to hepatocytes is mediated through polymerized albumin. We used a sandwich enzyme-linked immunosorbent assay with murine monoclonal antibodies raised against glutaraldehyde-polymerized albumin to detect native albumin polymer in human serum and its cross-reactivity with other albumin polymers. Presence of polymerized albumin receptor on the HepG2 cell was studied by radioreceptor assay. Purified hepatitis B virus and synthetic peptide analogous to part of pre-S2 sequence (120-145) were used to study polymerized albumin-dependent attachment of the virus to HepG2 cells. Antibodies raised against pre-S2 peptide were used to inhibit the pre-S2 and hepatitis B virus attachment to HepG2 cells. Glutaraldehyde-treated polymerized albumin was found to be immunologically cross-reactive with native albumin polymer. Its levels were found to be significantly raised in sera of patients with liver diseases. Polymerized albumin has specific saturable receptor on HepG2 cells with two classes of binding sites of different equilibrium dissociation constant (Kd1 = (16 +/- 9.6)pmol/L and Kd2 = (1,019 +/- 172)pmol/L. Albumin monomer was unable to compete for the polymerized albumin receptor sites on HepG2 cells. Anti-pre-S2 antibodies inhibit hepatitis B virus and pre-S2 binding to hepatocyte by 40% and 70%, respectively. Added extraneous polymerized albumin and the antibody against it did not interfere with virus attachment to HepG2 cells.

Whole-body lipolysis and triglyceride-fatty acid cycling in cachectic patients with esophageal cancer. Whole-body lipolytic rates and the rate of triglyceride-fatty acid cycling (reesterification of fatty acids released during lipolysis) were measured with stable isotopic tracers in the basal state and during beta-adrenergic blockade with propranolol infusion in five cachectic patients with squamous cell carcinoma of the esophagus, five cachectic cancer-free, nutritionally-matched control patients, and 10 healthy volunteers. Resting energy expenditure and plasma catecholamines were normal in all three groups. The basal rate of glycerol appearance in blood in the patients with cancer (2.96 +/- 0.45 mumol.kg-1.min-1) was similar to that in the nutritionally matched controls (3.07 +/- 0.28 mumol.kg-1.min-1), but 48% greater than in the normal-weight volunteers (2.00 +/- 0.16 mumol.kg-1.min-1) (P = 0.028). The antilipolytic effect of propranolol and the rate of triglyceride-fatty acid cycling in the patients with cancer were also similar in the cachectic control group and approximately 50% greater than in the normal-weight volunteers, but the differences were not statistically significant because of the variability in the data. We conclude that the increase in lipolysis and triglyceride-fatty acid cycling in "unstressed" cachectic patients with esophageal cancer is due to alterations in their nutritional status rather than the presence of tumor itself. Increased beta-adrenergic activity may be an important contributor to the stimulation of lipolysis.

Collagen phenotypes during development and regression of myocardial hypertrophy in spontaneously hypertensive rats. The myocardium contains collagen matrix that is a major determinant of its architecture, structural integrity, and mechanical properties. This fibrillar matrix consists primarily of type I and type III collagens having epimysial, perimysial, and endomysial components. The present study shows the alteration of collagen phenotypes during the evolution of hypertensive hypertrophy. Therapy with captopril, an angiotensin-converting enzyme inhibitor that regresses cardiac hypertrophy, not only reduces the total amount of collagen but reverses the altered distribution of type I and type III collagen. In normotensive rats, captopril did not significantly reduce collagen content or alter the ratio of type I to type III collagen.

Sequential or fixed sample trial design? A case study by stochastic simulation. The properties of Wilcoxon's rank sum test for fixed sample size and a Wilcoxon-type two-sample sequential test have been illustrated and compared by means of stochastic simulation. Data from a real fixed sample trial have been used, both for resampling from the original data, and for construction of an idealized theoretical distribution. The sequential and the fixed sample test obtain equal power, but the sequential test mostly includes considerably fewer patients to reach a conclusion, i.e. the mean and median number of patients included are both much lower than the fixed sample size. Under the hypotheses only a small fraction of the simulation runs exceed the fixed sample size. These findings exemplify results obtained in theoretical analyses and simulation studies covering a wide range of distributions. In our opinion sequential tests have obvious advantages and are in many cases better alternatives than fixed sample tests in clinical trials.

Granulomatous hepatitis and fever of unknown origin. An 11-year experience of 23 cases with three years' follow-up. Granulomatous hepatitis is a common cause of fever of unknown origin in up to 13% of patients with prolonged fever. Attempts to define an exact etiology of the granulomatous hepatitis frequently does not yield a precise diagnosis, so that the physician must consider empiric treatment. In this paper we retrospectively review 23 patients in whom granulomatous hepatitis was found as part of the initial assessment of fever of unknown origin, and we report on their outcomes after an overall prospective follow-up of 37 months. In 26% a precise diagnosis was established at the time of assessment: Q-fever in three, mycobacterial disease in two, and histoplasmosis in one. In the remaining 74% no etiology was established after 44 months follow-up. Forty-one percent of the idiopathic group resolved spontaneously without therapy, and 18% received short-term prednisone or indomethacin with a favourable outcome. The remaining 41% required long-term prednisone therapy for a mean of 33.1 months, but all have remained afebrile and otherwise healthy after 59.6 months follow-up. We conclude that patients with fever of unknown origin who are diagnosed as having idiopathic granulomatous hepatitis have an excellent prognosis, even the minority who require long-term corticosteroids.

Afibrinogenemia and hypobetalipoproteinemia in a kindred. A 3-year-old boy with minor bleeding problems had no plasma fibrinogen measured by both clottable assay and immuno-precipitation. Low normal fibrinogen levels were present in the mother and father. Markedly decreased plasma cholesterol and apolipoprotein B levels were found in the father, proband's brother, and the paternal side of the kindred. The proband and his mother had normal plasma total cholesterol and apolipoprotein B levels. These findings are compatible with autosomal dominant transmission of hypobetalipoproteinemia and autosomal recessive transmission of afibrinogenemia. Two members of the father's family had plasma cholesterol levels below the fifth percentile but elevated levels of fibrinogen (6.0 and 4.4 g/L). Both have symptomatic coronary heart disease. Finding coronary heart disease with very low cholesterol but elevated fibrinogen levels is consistent with fibrinogen levels being an independent risk factor for coronary heart disease.

Lack of neural control and reactivity to vasoactive agents in malignant glioma arteries. Vessels in malignant brain tumors have a defective blood-brain barrier. It is important to know if tumor vessels respond to vasoactive agents, since systemic administration of vasodilatory agents together with chemotherapy could increase the access of these drugs to the tumor. It was found that arteries in human malignant gliomas have no neural control and are totally nonreactive to various vasoactive agents. The vessels lose their reactivity within 1 to 2 mm outside the visible tumor front.

Aspiration in bilateral stroke patients. Seventy patients with bilateral strokes underwent neurologic and videofluoroscopic barium swallowing examinations; 34 (48.6%) aspirated. Patients with aspiration were more likely to have posterior circulation strokes, abnormal cough, abnormal gag, and dysphonia. However, patients likely to aspirate can be identified best by the presence of an abnormal voluntary cough, an abnormal gag reflex, or both. The prediction of patients at risk for aspiration was not improved by additional clinical information (ie, presence of dysphonia or bilateral neurologic signs).

Choice of emergency operative procedure for bleeding duodenal ulcer In a consecutive series of 201 emergency operations in patients with bleeding duodenal ulcer the size of the ulcer was the only factor that showed a significant correlation with the procedure chosen. Vagotomy, pyloroplasty and underrunning of the bleeding point was performed in 101 cases with ten deaths (10 per cent), partial (Billroth II) gastrectomy in 81 cases with ten deaths (12 per cent), and vagotomy and antrectomy in 16 cases with one death (6 per cent). A patient was more likely to be treated by partial gastrectomy if a giant ulcer with an internal diameter of greater than or equal to 2 cm was found. The results suggest that while vagotomy and pyloroplasty, combined with a direct attack on the bleeding point or excision of an anterior ulcer is an acceptable standard emergency operation for bleeding duodenal ulcer, gastric resection proved to be a satisfactory alternative procedure and should be considered in the technically difficult case with a very large ulcer. A giant ulcer was present in 37 per cent of cases coming to surgery.

Cereal-based oral rehydration therapy. II. Strategic issues for its implementation in national diarrheal disease control programs. Field studies in Bangladesh demonstrated that after proper training, village mothers were able to prepare and use rice-based, salt-enriched oral rehydration solutions containing safe concentrations of sodium, and were capable of achieving significantly fewer treatment failures and a reduction in the duration of diarrhea than with glucose-based oral rehydration solutions (ORS). An additional longitudinal study showed that improved growth and weight gain occurred with the consistent use of ORS; the effect was greater when rice-based ORS were used. In addition, the following possible limitations and benefits of cereal-based oral rehydration therapy, which are relevant to the strategies for its implementation in national diarrheal disease control programs, are discussed: safety, osmolarity, hypernatremia, spoiling, effectiveness, rehydration ability, reduction in diarrhea volume and duration, nutritional effects, effect on food intake, acceptance and usage by care givers, training of health workers, self-reliance of families, effect on other child survival activities, costs, potential problems in changing to cereal-based ORS, and the role of industrial production in packaged cereal-based ORS.

Major depression, panic disorder, and mitral valve prolapse in patients who complain of chest pain. PURPOSE: Patients with chest pain but without angiographic evidence of significant atherosclerotic coronary artery disease (CAD) are often found to have other medical or psychiatric disorders, including mitral valve prolapse, panic disorder (PD), and major depressive disorder (MDD). The purpose of this study was to determine the degree of comorbidity between MDD/PD and mitral valve prolapse in a group of patients with non-CAD chest pain. PATIENTS AND METHODS: Patients referred for cardiac catheterization and coronary angiography for suspected CAD who were 70 years of age or younger and without other significant medical illnesses or cardiac complications were eligible for study. The first 100 patients who agreed to a psychiatric diagnostic interview were recruited. RESULTS: Forty-eight of the 100 patients were found to be without significant CAD. Forty-two percent of these patients, compared to 19% of the patients with significant CAD, were found to have either MDD, PD, or both. Eighty percent of the patients without CAD who had mitral valve prolapse also had either MDD or PD (p less than 0.006). CONCLUSIONS: The finding that mitral valve prolapse was significantly associated with MDD/PD has implications for the diagnosis and treatment of patients with non-CAD chest pain, and may explain why these patients complain of symptoms.

Possible transmission of serum hepatitis in liver surgery with the ultrasonic dissector. When the ultrasonic dissector is used during liver surgery, the possibility exists of the transmission of virus to the attending hospital personnel because of unavoidable splashing of the irrigating solution. It becomes apparent from this study that the titer of hepatitis B surface antigen in the aspirated irrigating solution is almost the same level as that in the serum. We therefore strongly recommend that eye shields should be used in hepatic surgery when the ultrasonic dissector is in use.

Vertical partial laryngectomy on demand. The author proposes the term 'vertical partial laryngectomy on demand' for all modifications of vertical laryngectomies (frontal, frontolateral, vertical and hemilaryngectomy). This term includes two conditions: the first is complete oncological removal of the tumour (proven by histological examination and with the use of magnification or the operating microscope during the operation); secondly, reconstruction of the laryngeal defect by various procedures. The author uses the sternohyoid fascia in vertical and frontolateral partial laryngectomies. From 120 operated cases, a five-year survival rate of 81 per cent was achieved. The fascia showed resistance to post-operative complications and irradiation.

Historical review of pancreaticoduodenectomy. The performance of pancreaticoduodenectomy by Whipple in 1935 demonstrated that the operation was feasible technically and compatible with reasonable function after recovery. From the mid- to late 1940s until the last 10 years, the procedure was condemned by many because of its associated mortality and morbidity. For reasons that are not clear, the risk of pancreaticoduodenectomy in the last 10 years has fallen to less than 10% and in several centers, less than 5%. Postoperative complications have been reduced and blood transfusions are unnecessary in an increasing number of patients. Furthermore, a normal productive life without the need for medication and with no digestive disorder is expected. Seventy-one percent of patients are able to return to their preoperative occupation.

Diagnostic relevance of clonal cytogenetic aberrations in malignant soft-tissue tumors. BACKGROUND. Malignant soft-tissue tumors often present substantial diagnostic challenges. Chromosome aberrations that might be diagnostic have been identified in some types of soft-tissue tumors, but the overall frequency and diagnostic relevance of these aberrations have not been established. METHODS. We attempted to determine the karyotypes of a series of 62 consecutive, unselected malignant spindle-cell or small round-cell soft-tissue tumors (from 46 adults and 16 children) after direct harvesting of cells or short-term culture. All tumors were examined independently by immunohistochemical staining in addition to routine light-microscopical evaluation, and all but two tumors were examined by electron microscopy. RESULTS. Metaphases were obtained from 61 of the 62 tumors, and clonal chromosome aberrations were identified in 55 (89 percent). In the six tumors that yielded metaphases but lacked apparent clonal aberrations, the normal metaphases were found to originate from non-neoplastic stromal elements within the tumor specimens. Thus, all tumors in which karyotyping was successful contained clonal chromosome aberrations. Forty of 62 tumors (65 percent) contained clonal chromosome aberrations that either suggested or confirmed a specific diagnosis; in 15 of these tumors (24 percent of all tumors), the aberrations were important in establishing the final diagnosis. Cytogenetic analyses were particularly informative about small round-cell tumors from children: 8 of 14 round-cell tumors contained diagnostically important chromosome aberrations. Using the combined approaches of light and electron microscopy, immunohistochemistry, and cytogenetics, we established an unambiguous diagnosis for 60 of 62 tumors. CONCLUSIONS. Cytogenetic analyses reveal clonal chromosome aberrations in virtually all malignant soft-tissue tumors. These clonal chromosome aberrations, particularly in small round-cell tumors in children, often have diagnostic relevance.

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.

Hepatic venoocclusive disease in autologous bone marrow transplantation of solid tumors and lymphomas. Retrospective review of 291 solid tumor and lymphoma patients undergoing autologous bone marrow transplantation (BMT) was performed to determine the influence of pretransplant characteristics and preparative regimen to the development of hepatic venoocclusive disease (VOD). Twelve patients (4.1%) developed a clinical syndrome of right upper quadrant (RUQ) tenderness or hepatomegaly, jaundice, and ascites, with or without encephalopathy, within 40 days of marrow reinfusion. Evidence of metastatic liver disease was the only pretransplant characteristic predictive for VOD (P = .0002). Sex, age, histology, hepatitis B serology, and elevated liver function tests were not predictive. No individual preparative agent had a significant effect on the development of VOD. However, a single 2-hour infusion of carmustine (BCNU) (greater than or equal to 450 mg/m2) led to an increased incidence of VOD when compared with the same dose administered in a fractionated schedule (P = .0258) when given with two other chemotherapeutic agents. Seven of eight autopsy specimens confirmed the clinical diagnosis of VOD. The four patients in whom clinical VOD resolved had lower median peak bilirubins (7.3 v 15.9 mg/dL), lower median peak creatinines (2.1 v 4.1 mg/dL), and relatively quick engraftment of neutrophils (mean, 18.7 days). One of the four patients in whom VOD resolved had other grade 4 (life-threatening) toxicities in contrast to eight of eight who succumbed. In summary, VOD is an uncommon complication in autotransplantation of solid tumors and lymphomas. Our data suggest caution in selecting patients with known metastatic liver disease and consideration of a fractionated BCNU schedule especially in combination with other alkylating agents.

Low-molecular-weight heparinoid compared with warfarin for prophylaxis of deep-vein thrombosis in patients who are operated on for fracture of the hip. A prospective, randomized trial. In a randomized, prospective trial, a low-molecular-weight heparinoid (Org 10172 [Lomoparan]) was compared with warfarin for efficacy and safety in preventing deep-vein thrombosis in 263 patients who had an operatively treated fracture of the hip. One group of patients received Org 10172 in a dose of 750 units subcutaneously every twelve hours until the ninth postoperative day; on the seventh postoperative day, warfarin was added to the regimen. The other group received only warfarin. Both drugs were begun preoperatively, immediately after the admission evaluation. In the patients who received warfarin, the desired prothrombin time was one and one-half times the control level. Deep-vein thrombosis was detected by 125I-fibrinogen scanning and impedance plethysmography and was confirmed by phlebography and compression ultrasonography. Deep-vein thrombosis was found in nine (7 per cent) of the 132 patients who received Org 10172 and in twenty-eight (21 per cent) of the 131 patients who received warfarin (p less than 0.001). Adverse reactions were not significantly different in the two groups. Major bleeding complications occurred in eight patients in the Org-10172 group, only four of whom were receiving the drug at the time of bleeding, and in five patients who were receiving warfarin (not significant). There was no difference in intraoperative loss of blood or in requirements for transfusion. We concluded that the low-molecular-weight heparinoid Org 10172 is a safe, convenient, effective antithrombotic agent for the prevention of venous thrombosis after an operation for fracture of the hip.

Transvascular intracardiac applications of a miniaturized phased-array ultrasonic endoscope. Initial experience with intracardiac imaging in piglets. BACKGROUND. Recent advances in miniaturization of phased-array and mechanical ultrasound devices have resulted in exploration of alternative approaches to cardiac and vascular imaging in the form of transesophageal or intravascular imaging. Preliminary efforts in adapting phased-array endoscopes designed for transesophageal use to a transvascular approach have used full-sized phased-array devices introduced directly into the right atrium in open-chested animals. The purpose of this study was to assess the feasibility of using a custom-made, very small phased-array endoscope for intracardiac imaging introduced intravascularly through a jugular venous approach in young piglets. METHODS AND RESULTS. Experimental atrial septal defects created in four piglets (3-4 weeks old) had been closed with a buttoned atrial septal defect closure device consisting of an occluder in the left atrium and a counteroccluder in the right atrium. Five to 15 days after atrial septal defect closure, the piglets were returned to the experimental laboratory, where a 6.3-mm, 17-element, 5-MHz phased-array probe mounted on a 4-mm endoscope was introduced through a cutdown incision of the external jugular vein and advanced to the right atrium. From the right atrium all four cardiac chambers, their inflows and outflows, and all four valves were well imaged with minimal superior and inferior rotation. High-resolution imaging of the atrial septum defined with anatomical accuracy, later verified by autopsy, the exact placement of both the occluder and counteroccluder in the left and right sides of the atrial septal defects and the absence of any shunting across the atrial septum in any of the four animals. CONCLUSIONS. Our efforts indicate that transvascular passage of small phased-array probes can be easily accomplished and is a promising technique for detailed visualization of cardiac structures. This approach may provide an alternative to transesophageal echocardiography, particularly for guiding interventional procedures such as placement of transcatheter closure devices in pediatric patients.

Fundoplication and gastrostomy in familial dysautonomia. Fundoplication with gastrostomy has become a frequent treatment for patients with familial dysautonomia, so we evaluated the use of both procedures in 65 patients. Although patients differed widely in presenting signs and age, from 5 weeks to 40 years, gastroesophageal reflux was documented in 95% of patients by cineradiography or pH monitoring. Panendoscopy was a useful adjunct. Preoperative symptoms of gastroesophageal reflux included vomiting, respiratory infections, and exaggerated autonomic dysfunction. Severe oropharyngeal incoordination frequently coexisted and resulted in misdirected swallows with aspiration, dependence on gavage feedings, or poor weight gain and dehydration. Follow-up after surgical correction ranged from 3 months to 11 years; 55 patients (85%) were available for a 1-year postoperative assessment. We had no instances of surgical death. The long-term mortality rate was 14%, primarily related to severe preexisting respiratory disease. Beyond the first postoperative year, 30 patients had pneumonia attributed to continued aspiration, exacerbation of preexisting lung disease, or recurrence of gastroesophageal reflux. Of 11 patients who vomited postoperatively, six had recurrence of reflux. Recurrence of gastroesophageal reflux was documented in eight patients (12%), and we revised the fundoplication in three patients. The number of patients with cyclic crises was reduced from 18 to 7; retching replaced overt vomiting in all but two of these seven patients, neither of whom had recurrence of reflux. Because oropharyngeal incoordination was prominent, concomitant use of gastrostomy and an antireflux procedure was especially effective in the treatment of younger patients with familial dysautonomia, before the development of severe respiratory disease. Despite the development of severe morning nausea in 15 patients, the combination procedure resulted in significantly improved nutritional status, decreased vomiting, and decreased respiratory problems. Appropriate use of gastrostomy feedings also contributed to success of the operation. The generally good outcome of fundoplication with gastrostomy confirms the benefit of this procedure in familial dysautonomia.

Grinspan's syndrome: a drug-induced phenomenon? Three cases of apparently drug-induced Grinspan's syndrome involving the triad of oral lichen planus, diabetes mellitus, and hypertension are reported. Because drug therapy for diabetes mellitus and hypertension is capable of producing lichenoid reactions of the oral mucosa, the question arises as to whether Grinspan's syndrome is an iatrogenically induced syndrome.

Carcinoma of female urethra. Manitoba experience: 1958-1987. Fourteen female patients with primary urethral carcinoma were treated at the Manitoba Cancer Foundation in the last twenty-nine years. The relationship of natural history to the stage, location, and therapeutic modality has been reviewed. A higher stage and length of urethral involvement affected prognosis negatively, whereas lower stage had a positive prognostic effect and location of tumor had no prognostic influence. Two patients with Stage C, who failed to received inguinal node radiotherapy, died of disease recurring in the inguinal area. Patients who received inguinal radiation (3 patients Stages B, C, and D1) had no regional recurrence. It is suggested that, for all female urethral carcinoma, bilateral ilioinguinal nodes be included in the radiation field. For radical treatment, iridium 192 insertion in combination with external beam treatment is recommended.

An empirical study of diagnostic criteria for delirium. OBJECTIVE: The objective of this study was to determine empirically how many patients are identified as delirious or nondelirious according to DMS-III, DMS-III-R, and ICD-10 criteria. METHOD: Daily, a trained research assistant using a structured instrument to detect the presence of symptoms of delirium evaluated 325 elderly patients who were admitted to a general hospital for acute medical problems. Each patient's symptoms were then compared with these diagnostic criteria sets to determine if the patient met criteria for delirium. RESULTS: DSM-III criteria were the most inclusive: they identified 125 patients as delirious. DSM-III-R identified a somewhat different group of 106 patients as delirious. ICD-10 criteria identified only 30 patients as delirious. CONCLUSIONS: The development of new criteria for delirium (e.g., DSM-IV) will have to balance the need to define a pure group of patients for research purposes with the need to include cases of clinical interest. Changes in criteria should be based on data such as those presented in this paper.

The "all-autogenous" tissue policy for infrainguinal reconstruction questioned. In 33% of patients referred for infrainguinal reconstruction for limb-threatening ischemia (mean preoperative ankle-arm index [AAI] = 0.26), no suitable autogenous reconstruction was possible. In 40% of cases, intraoperative pre-bypass contrast arteriography was necessary to identify a graftable tibial or pedal artery. The results of polytetrafluoroethylene (PTFE) and autogenous bypasses were compared after 1 to 3 years. After 1 year, patency was 85% and 67% for autogenous and PTFE bypasses, respectively. Limb salvage was 90% for autogenous bypass and 70% for PTFE bypass. Cumulative patency rates at 3 years were 80% for autogenous and 57% for PTFE grafts. Graft surveillance with duplex scanning and AAI was valuable in detecting failing grafts. For both types of reconstruction, secondary procedures were required to maintain patency. We attribute the excellent results with PTFE in part to long-term aspirin and warfarin therapy. In cases of combined superficial femoral and severe infra-popliteal occlusive disease, PTFE bypass is an excellent alternative when no autogenous conduit is available.

A hematologist's view of contrast media, clotting in angiography syringes and thrombosis during coronary angiography. While ionic contrast media (CM) are stronger anticoagulants and antiplatelet agents, both nonionic and ionic CM retard clotting, fibrinopeptide A generation and platelet aggregation (at least by Born-O'Brien aggregometry). Thus, nonionic CM do not cause clots and thrombi. Rather, the driving force for clot or thrombus formation, when it occurs, is blood contact with and activation by the foreign surface of a syringe or catheter itself. A marked enhancement of clotting by glass syringes in comparison to plastic ones supports this view. Blood in any syringe or catheter, therefore, will clot more slowly in the presence of nonionic or ionic CM, the inhibitory effects of the latter being more profound. With respect to models of thrombosis at sites of vascular injury or stenosis, the antithrombotic effects of CM may either be transient owing to the dynamic nature of blood flow (local endothelial cell denudation model), or as in the case of ionic CM, actually to enhance local platelet aggregation (stenosis model). In these situations, preservation of the antithrombotic functions of endothelium with nonionic CM may be quite critical.

Three mixed venous saturation catheters in patients with circulatory shock and respiratory failure Thirty-one critically ill patients with acute respiratory failure and circulatory shock were divided into three groups. Group 1 included 11 patients with an inserted mixed venous saturation (SvO2) catheter using three-reference wavelengths and characterized by one transmitting and one detecting fiberoptic filament (Oximetrix opticath catheter); group 2 included eight patients with an inserted SvO2 catheter using two-reference wavelengths and characterized by one transmitting and one detecting fiberoptic filament; (Edwards sat-one catheter); group 3 included 12 patients with an inserted SvO2 catheter using two-reference wavelengths and characterized by one transmitting and two detecting fiberoptic filaments. Once calibration procedures were performed, SvO2 measured by the catheter and by an hemoximeter OSM 3 (reference value) were compared following each therapeutic intervention. Over a period of 1.5 to 6 hours during which the hematocrit value remained unchanged, 119 measurements were obtained in group 1, 91 in group 2 and 181 in group 3. The dispersion of SvO2 values was much more pronounced with the two-reference wavelength systems using either one or two detecting fiber optic filaments, and the correlation coefficient was significantly higher with the three-reference wavelength system (r = 0.970 for the Oximetrix catheter vs r = 0.855 for the Edwards catheter and r = 0.826 for the Spectramed catheter, p less than 0.001). After 24 hours, the spontaneous drifts in the two-reference wavelength systems, using either one or two detecting fiber optic filaments (expressed as the SvO2 value measured by the catheter minus the reference SvO2 value) were significantly higher than the spontaneous drift in the three-reference wavelength system (9.3 +/- 7 percent for the Edwards catheter and +/- 6 +/- 4.1 percent for the Spectramed catheter vs 3.3 +/- 3.1 percent for the Oximetrix catheter, p less than 0.05). This study shows that a three-wavelength system is more accurate than a two-wavelength system for measuring acute changes in SvO2. The addition of a second detecting fiber optic filament does not seem to improve the accuracy of the system when SvO2 changes occur in conditions of stable hematocrit.

Rhabdomyosarcomas in the head and neck: MR imaging evaluation. To determine the typical magnetic resonance (MR) signal intensity characteristics of rhabdomyosarcomas, short repetition time (TR)/short echo time (TE) (T1-weighted) and long TR (proton density and T2-weighted) images of 13 patients with rhabdomyosarcomas of the head and neck were retrospectively reviewed. Seven patients received gadopentetate dimeglumine injections. The most common MR appearance was that of a homogeneous mass, hyperintense to both muscle and fat on long TR/long TE images and isointense or minimally hyperintense to muscle on short TR/short TE images. All lesions of the patients who received gadopentetate dimeglumine enhanced markedly. Two lesions had intratumoral hemorrhage, and six were markedly heterogeneous in signal intensity. Similar MR signal intensity patterns have been described for lymphomas and nasopharyngeal carcinomas. The forte of MR imaging lies in its ability to delineate precisely the extent of the rhabdomyosarcoma.

Prevalence of primary sclerosing cholangitis in patients with ulcerative colitis. All patients greater than or equal to 16 years old with a diagnosis of ulcerative colitis were identified in five well-defined catchment areas, representing 12.7% of the Swedish population. Exactly 1500 patients were retrieved, giving a point prevalence of 170/10(5) inhabitants. It was possible to obtain liver function test results less than 2 years old in 94% of the patients and to obtain endoscopic retrograde cholangiographic results in 65 of the 72 patients with abnormal serum alkaline phosphatase values. Primary sclerosing cholangitis was diagnosed in 55 of the patients (3.7%). The prevalence of the disease was 5.5% in patients with substantial colitis and 0.5% in patients with distal colitis. There was a marked male predominance in cholangitis patients compared with colitis patients without cholangitis. Ninety-five percent of the patients with cholangitis had substantial colitis, which was more than the 62% of patients without cholangitis who had colitis. Female patients with cholangitis were older than male patients at the time of diagnosis of both cholangitis and colitis, which contrasted to the equal age at diagnosis of colitis in male and female patients without cholangitis.

Evidence for platelet-activating factor as a late-phase mediator of chronic pancreatitis in the rat. The role of platelet-activating factor (PAF) as a mediator of pancreatic inflammation was examined in the rat pancreatic duct ligation model of obstructive pancreatitis. Pancreatic generation of PAF, as measured by bioassay (ie, platelet [3H]serotonin secretion), was determined at various times after induction of inflammation. Tissue levels of PAF in the normal pancreas averaged 600 +/- 49 pg/g, but PAF was not detectable during the initial 24 hours of pancreatitis, a time when the inflammatory reaction would be considered acute, that is, during the period of maximal serum amylase release and the development of interstitial edema. However a substantial increase in pancreatic PAF levels (12 times control levels) was observed 7 to 14 days after duct ligation during the late-phase response interval similar to the situation characteristic of chronic pancreatitis in which parenchymal atrophy, fibrosis, and pancreatic insufficiency evolve. One week after duct ligation when PAF levels peaked, an evaluation was made of the effects of PAF antagonists (BN52021 and WEB2170) on pancreatic lesions using Evan's blue extravasation, pancreatic myeloperoxidase (MPO) activity, and acid phosphatase activity in peritoneal lavage fluid. BN52021 or WEB2170 treatment was shown to reduce pancreatic damage and inflammation significantly. Long-term in vivo administration of exogenous PAF (20 micrograms/kg/hr for 7 days) exhibited a reduction of [3H]thymidine uptake into and amylase release from pancreatic acini in vitro. Our observations 1) that pancreatic PAF levels increased significantly during the chronic phase of obstructive pancreatitis induced by duct ligation; 2) that inhibition of the action of PAF, through specific receptor antagonism, caused an attenuation of pancreatic lesions; and 3) that chronic administration of PAF resulted in decreased pancreatic regeneration and exocrine function are consistent with a pivotal role for PAF as a late-phase inflammatory mediator in chronic pancreatitis in rats.

Primary adrenal insufficiency: a new cause of reversible gastric stasis. Primary adrenal insufficiency is known to cause a wide spectrum of sometimes severe upper gastrointestinal symptoms; however, it has not previously been shown to be the cause of reversible gastric stasis. We have documented such a case in which the symptoms and physiologic abnormalities associated with gastric stasis were reversed by steroid replacement. A follow-up radionuclide gastric-emptying study after physiologic steroid replacement showed complete normalization of gastric emptying. Although gastric stasis has long been suspected of being present with primary adrenal insufficiency, this represents the first case in which it has been documented, and so should be included in the differential diagnosis of patients presenting with chronic nausea and vomiting.

Turner's syndrome, fibromuscular dysplasia, and stroke. We report a 43-year-old woman who presented with a right frontoparietotemporal ischemic stroke. She had been diagnosed with Turner's syndrome during childhood and had a history of chronic estrogen therapy. Cerebral angiography showed lesions characteristics of fibromuscular dysplasia involving the right internal carotid and right vertebral arteries. We are not aware of any previous reports describing an association between fibromuscular dysplasia and Turner's syndrome. Although chronic estrogen therapy cannot be ruled out as a cause of this patient's stroke, we suggest a possible etiologic relation between these two entities.

Efficacy and safety of vagus nerve stimulation in patients with complex partial seizures. A clinical trial of chronic intermittent vagal stimulation in five patients suggests that the procedure may be safe and effective as adjunctive treatment of medically intractable seizures of partial onset. Patients tolerated well the implantation of the neurocybernetic prosthesis and the vagal stimulation without serious physiological or lifestyle changes. Stimulation of the vagus nerve either reduced the seizure frequency or decreased the duration or intensity of seizures. Adverse side effects were limited to a tingling sensation in the throat and hoarseness during stimulation. A major complication was mechanical interruption of the wire-electrode circuitry, with consequent cessation of stimulation. The small number of patients and the relatively short follow-up period make this a pilot study, but the results are promising.

Occlusive arterial disease as a form of presentation of homocystinuria. Homocystinuria was first described in 1962. The disease affects several systems including the eyes, skeletal and nervous and vascular systems. We present the case of a 28-year old woman who presented with a severe occlusive arteriopathy. Screening for the most usual causes of arterial disease in young patients was negative, but a study of aminoaciduria and column chromatography confirmed the diagnosis of B6-responsive homocystinuria. Although it was necessary to amputate her left leg, the patient remains asymptomatic 16 months after B6 therapy was started.

The variable extent of jeopardized myocardium in patients with single vessel coronary artery disease: quantification by thallium-201 single photon emission computed tomography To assess the extent of jeopardized myocardium in patients with single vessel coronary artery disease of variable severity and location, quantitative exercise thallium-201 single photon emission computed tomography was performed in 158 consecutive patients with angiographically proved single vessel coronary artery disease. The extent of abnormal left ventricular perfusion was quantified from computer-generated polar maps of three-dimensional myocardial radioactivity. Patients with only a moderate (51% to 69%) stenosis tended to have a small perfusion defect irrespective of the coronary artery involved. Whereas a perfusion defect measuring greater than or equal to 10% of the left ventricle was found in 78% of patients with no prior infarction and severe (greater than or equal to 70%) stenosis, this was observed in only 24% of patients with moderate stenosis. Perfusion defect size increased with increasing severity of stenosis for the entire group without infarction and for those with left anterior descending, right and circumflex coronary artery stenosis. However, the correlation between stenosis severity and perfusion defect size was at best only modest (r = 0.38, p = 0.0001). The left anterior descending artery was shown to be the most important of the three coronary arteries for providing left ventricular perfusion. Proximal stenosis of this artery produced a perfusion defect approximately twice as large as that found in patients with a proximal right or circumflex artery stenosis. However, marked heterogeneity in perfusion defect size existed among all three vessels despite comparable stenosis severity. This was most apparent for the left anterior descending coronary artery, where mid vessel stenosis commonly produced a perfusion defect similar in size to that found in proximally stenosed vessels.

Rehabilitation of physically disabled dentists: a model for a vocationally specific rehabilitation program. A unique collaborative program whose goal is to facilitate the return of disabled dentists to active dental practice is described. This approach includes comprehensive interdisciplinary evaluation and remediation, and it has succeeded in revealing previously undiagnosed impairments which should be considered in the formulation of a rehabilitation plan. A case report illustrates the process. This program can serve as a model for similar programs addressing the needs of other disabled health care professionals.

Oral magnetic particles in MR imaging of the abdomen and pelvis. Two phase 2 clinical trials of an oral superparamagnetic contrast agent for enhancement on magnetic resonance images of the intestine were performed. In trial 1, 31 male patients with cancer of the testis underwent follow-up examinations of the abdomen at 0.5 and 1.5 T after oral administration of magnetic particles. In trial 2, 31 female patients with pelvic and lower abdominal disease were examined at 1.5 T after administration of the contrast material. The patients each ingested 800 mL of contrast material over approximately 2 hours. Concentrations of 0.25 and 0.5 g/L did not induce blurring or metallic artifacts. Distribution was homogeneous through the gastrointestinal tract. In all patients, a loss of signal intensity was observed on proton density-, T1-, and T2-weighted images. The diagnostic information from postcontrast images in trial 2 was greater in 16 patients (52%). Contrast enhancement was independent of field strength; no major side effects were observed. Artifacts from moving bowels were less troublesome, and delineation of intraabdominal and pelvic organs was better with the use of oral magnetic particles.

Pharyngeal volume in asymptomatic snorers compared with nonsnoring volunteers. STUDY OBJECTIVE: to determine if asymptomatic snorers have smaller pharyngeal volumes than age- and height-matched nonsnorers. DESIGN: we recruited asymptomatic heavy snorers and nonsnorers for a study. Each snorer was matched by age (+/- 3 years) and height (+/- 2 inches) with a nonsnorer. The nonsnorers were required to be near ideal body weight. All volunteers underwent overnight polysomnography, pulmonary function testing, and magnetic resonance imaging of the pharynx while awake. The volume of the pharynx was determined by a computer with data input from a digitizing instrument. SETTING: Veterans Administration Hospital and University of Florida Teaching Hospital PARTICIPANTS: Nine volunteers were recruited for both the snorer and nonsnorer groups. Each participant was paid $50. There were no interventions. MEASUREMENTS and RESULTS: There were no differences in sleep variables between the two groups. There was also no significant difference between pharyngeal volumes for the two groups. CONCLUSIONS: The volume of the pharynx in asymptomatic snorers is similar to the volume in age- and height-matched nonsnorers.

The association of carotid artery stenosis with carotid sinus hypersensitivity. Transitory cerebral ischaemic attack provoked by carotid sinus reflex The association of internal carotid stenosis with the carotid sinus syndrome represents a special clinical entity. Transitory cerebral ischaemic attack (TIA) will usually be manifested by activation of carotid sinus reflex. Eighteen patients were observed suffering from both carotid sinus hypersensitivity and TIA. The patients had had TIA's for many years. Unilateral internal carotid stenosis was detected in 15 cases, while 3 patients had bilateral carotid stenosis. On carotid sinus stimulation, syncope appeared and a TIA could be provoked. The mean duration of the syncopic attack was 5500 ms and was based on sinus arrest in 14 cases and on third degree AV block in 4 cases. In all patients carotid artery disobliteration was performed; in 14 patients pacemaker implantation was necessary, while 4 patients could be treated by atropine medication. The development of a TIA could be abolished in every patient and 14 patients remained totally symptom free.

Host genetic influences on fetal susceptibility to murine cytomegalovirus after maternal or fetal infection. Genetically determined resistance to murine cytomegalovirus is observed in adult mice and is mediated in part by genes of the H-2 complex, with the H-2k haplotype conferring resistance. This model was used to examine the effect of primary maternal infection on fetal outcome. The severity of fetal growth retardation and death after primary maternal infection on day 8 of pregnancy was found to be genetically determined. Fetal viability and weight were significantly lower in infected BALB/c mothers (H-2d) than in CBA(H-2k) and BALB.K(H-2k) mothers. However, fetal infection was not detected, suggesting that the resistance mechanisms operate at the level of the mother or placenta. By directly inoculating fetuses in utero, it was shown that genetic factors in the fetus can influence the level of fetal infection and viability. These results point to the possibility that host genetic factors may modulate maternal and fetal cytomegalovirus infections in humans.

The heterogeneity of anticentromere antibodies in immunoblotting analysis. We tested anticentromere antibody positive sera from 37 patients by immunoblotting techniques. Three antigenic polypeptides were recognized when immunoblotted against protein extracts from HeLa cell nuclei or from chromosomal segments enriched with centromere region. These were a 17 kDa (CENP-A recognized by 34 sera), an 80 kDa (CENP-B recognized by 33 sera), and a 140 kDa polypeptide (CENP-C recognized by 26 sera). There was no disease specific pattern of antigenic polypeptides, although Raynaud's phenomenon was frequent in patients with anti-CENP-B reactivities (p less than 0.01). The heterogeneity of the anticentromere antibody response in Japanese patients shows anticentromere antibody may not be a disease specific autoantibody and diagnostic marker.

Clinical perspective on celiprolol: cardioprotective potential. beta-Adrenergic blockers have had widespread use in the treatment of cardiovascular disease. Some agents of this class have been shown to reduce the incidence of total mortality, cardiovascular mortality, sudden death, and nonfatal reinfarction in survivors of acute myocardial infarction. The mechanism for this cardioprotective action is not known. Antiarrhythmic action and hemodynamic alterations have been suggested as possible mechanisms. An anticoagulant mechanism is another possibility, although the antiplatelet effects of beta-blockers are weak. It is now believed that antithrombotic effects may be related to the prevention of coronary artery plaque rupture and the subsequent propagation of an occlusive arterial thrombus rather than a direct anticoagulant action. The therapeutic ability beta-blockers to attenuate the hemodynamic consequences of catecholamine surgers, as they do in aortic dissection, may protect a vulnerable plaque from fracture, reducing the risk of coronary thrombosis, myocardial infarction, and death. Celiprolol, a third-generation beta 1-selective adrenergic blocker with partial beta 2-agonist activity, is comparable to other beta-blockers in antihypertensive and antianginal activity. It has additional actions that may be beneficial to patients: (1) it does not adversely affect lipids and lipoproteins; (2) it does not appear to depress the myocardium in patients with left ventricular dysfunction; (3) it can lower serum fibrinogen levels; and (4) it can cause regression of myocardial mass in patients with left ventricular hypertrophy.

Increased expression of the laminin receptor in human colon cancer. It has been proposed that among the various cell-surface proteins capable of interacting with laminin, the 67-kd high-affinity laminin receptor plays a crucial role during tumor invasion and metastasis. In this study, the expression of laminin-receptor-precursor messenger RNA (mRNA) and 67-kd protein was analyzed in human colon adenocarcinoma. In 22 of 23 patients with colon cancer, we found a 2- to 23-fold increase in levels of laminin-receptor-precursor mRNA in the cancer tissues compared with those in matched normal adjacent colonic mucosa. In 10 of 11 cases studied, the level of 67-kd laminin receptor, detected by affinity-purified anti-laminin-receptor synthetic peptide antibodies on immunoblots of matched tumor and normal tissue extracts, was higher in the colon carcinoma tissue. Immunodetection of laminin receptor in tissue sections using anti-laminin-receptor-peptide antibodies confirmed that the increased expression of laminin receptor was specifically associated with the cancer cells. In a series of 72 paraffin sections of colon lesions, we observed a correlation between the expression of the laminin receptor and the Dukes' classification. Our observations indicate that increased expression of laminin-receptor-precursor mRNA is associated with enhanced levels of the 67-kd laminin receptor as well as with the invasive phenotype of colon carcinoma. Detection of this metastasis-associated gene product may be a valuable adjunct in the evaluation of human colon cancer.

Epstein-Barr virus associated oesophageal ulcers in AIDS. Epstein-Barr virus (EBV) associated ulceration has not previously been included in the differential diagnosis of oesophageal ulcers in AIDS. We report five cases of oesophageal ulceration in homosexual men with advanced human immunodeficiency virus infection in whom this was considered to be the most likely cause. DNA in situ hybridisation studies showed EBV in biopsy material from three of four patients with oesophageal ulcers and in none of three controls. Of other viruses studied, only human papillomavirus was present, and this was found in both patients and control subjects. These findings support the hypothesis that EBV is an aetiological factor in some cases of AIDS-associated oesophageal ulceration.

Quincke's edema, revisited. Angioneurotic edema involving the uvula is sometimes referred to as Quincke's edema. The term angioneurotic edema describes several closely related diseases manifested by recurrent, acute edema of the skin or mucosa. We report a case of uvular edema secondary to food allergy, treated successfully with steroids. A short review of angioneurotic edema and its management is also presented.

Valve replacement in patients with endocarditis and cerebral septic emboli. Cerebral septic emboli complicate the cases in 20% to 40% of patients with left-sided endocarditis but the management of these patients who require a valvar operation remains unclear. From 1980 to 1988, the incidence of cerebral septic embolus was 42% (n = 45) among 106 patients with endocarditis who underwent valve replacement at the University of Illinois Hospital in Chicago. Of these 45 patients, 69% (n = 31) had symptomatic cerebral septic infarctions and 31% (n = 14) were asymptomatic. Findings on cerebral computed tomographic scans included ischemic infarcts (n = 36, 80%), hemorrhagic infarcts (n = 5, 11%), normal studies (n = 2, 4%), and unknown (n = 2, 4%). Neurological complications after valve replacement included postoperative strokes (n = 6, 6%), cerebral abscesses (n = 2, 2%), and seizure (n = 1, 1%). The presence of a hemorrhagic infarct preoperatively predisposed to a perioperative stroke (p less than 0.05). In conclusion, cerebral septic infarctions, both symptomatic and asymptomatic, are common among patients with endocarditis referred for valvar operation. In the absence of a hemorrhagic infarct, valve replacement can be performed with minimal risk of a perioperative stroke.

Amplification of oncogenes in mammary carcinoma shown by fine-needle biopsy. A procedure that measures the amplification of oncogenes in human cancer cells is described. The cells were obtained by fine-needle biopsy to allow repeated sampling from individual metastases. A drawback was the low number of cells obtained, but this could be overcome by using a slot-blot hybridization technique to measure gene amplification. Two patients with mammary cancer (primary tumors or metastases), analyzed for the levels of amplification of the oncogene erb-B2, are described in detail. This technique is suitable for analyzing alterations occurring during cancer progression and for identifying subgroups of mammary cancer with different characteristics.

A critical review of chemical lymph node clearance and staging of colon and rectal cancer at Ferguson Hospital, 1977 to 1982 A unique opportunity to evaluate the method of chemical lymph node clearance for colorectal cancer exists at Ferguson Hospital. Lymph node clearance has been used at the institution since 1977, and this retrospective analysis was undertaken to ascertain its validity there. Furthermore, the node positive group was evaluated to ascertain if the current staging system (Turnbull, 1967) is prognostically accurate for the Dukes' C group. Specifically evaluated for possible prognostic variance was the survival of those patients whose tumors demonstrated partial bowel wall penetration and only one to four positive nodes, a "C1 subset," previously reported to have favorable prognosis. Eight hundred sixty-four cases of colon and rectal cancer treated surgically from 1977 to 1982 were analyzed. There was a mean of 27 lymph nodes retrieved per specimen and a mean of 4.5 positive nodes per Dukes' C specimen. There were 43 C1 and 201 C2 cases with five-year survival rates of 73 and 38 percent, respectively. The results of chemical clearance at Ferguson Hospital were found to be comparable with that of other centers using chemical clearance and superior to hand dissection. The C1 subset clearly is noted to have prognostic advantage and should occupy a separate designation in any staging system.

The intracolonic bypass tube for left colon and rectal trauma. The avoidance of a colostomy. Traumatic perforations of the left colon and rectum are most frequently managed by procedures that include the formation of a colostomy. Primary repair without colostomy is much less commonly employed. We report nine patients with traumatic perforations of the left colon and rectum treated with the intracolonic bypass tube (ICBT) without concomitant colostomy. In all these patients we believe the standard treatment would have included fecal diversion. Four patients sustained blunt trauma and five sustained penetrating trauma. Healing of the colonic anastomosis occurred in all cases, and the ICBTs were passed per rectum between the tenth and nineteenth days postoperatively. On the basis of this study, we conclude that the ICBT has a role in the treatment of selected injuries of the left colon and rectum as a safe means of avoiding a colostomy.

Percutaneous biliary drainage for high obstruction. PBD is the preferred route of palliative drainage for patients with high biliary obstruction. The frequency of bifurcational obstruction in this setting requires familiarity with drainages from both the right and the left transhepatic approach. The preferred right transhepatic approach is fluoroscopically guided; on the left, ultrasonography is the guidance of choice. Large caliber drainage catheters are required, and dilatation of the necessary transhepatic tracts is extremely painful unless adequate inhalation anesthesia or, preferably, epidural anesthesia, is provided. Long-term biliary drainage requires a choice between internal-external external drainage catheters and endoprostheses that is made by considering the patient's life expectancy and his or her adjustment to a stent extending to the outside. The feasibility of corrective procedures if an internal-external drainage catheter or an endoprosthesis becomes blocked needs to be considered before definitive placement. The interventional radiologist becomes intimately involved in the follow-up care of patients and frequently has to direct appropriate patient evaluation. Familiarity with antibiotic regimens is important.

Selection of patients with acute myocardial infarction for thrombolytic therapy PURPOSE: To critically review the current recommendations regarding the eligibility of patients with myocardial infarction for thrombolytic therapy. DATA IDENTIFICATION: Relevant studies published from January 1980 to January 1990 were identified through a computerized search of the English-language literature using MEDLINE and by a manual search of the bibliographies of all identified articles. STUDY SELECTION: All randomized, controlled trials of intravenous thrombolysis in acute myocardial infarction and unstable angina were reviewed. Smaller, observational studies and previous review articles were included when relevant to the discussion. DATA EXTRACTION: Key data were extracted from each article, including the proportions of patients eligible for thrombolysis, the reasons for exclusion from thrombolytic therapy, and the clinical outcomes of patients treated and of those excluded from treatment. The validity of certain exclusion criteria was examined using subgroup analysis from the large, randomized mortality trials of intravenous thrombolysis and observations from smaller, nonrandomized studies. RESULTS OF DATA SYNTHESIS: To date, relatively few patients with myocardial infarction have been considered eligible for fibrinolytic therapy. In this group, both early and late mortality have been significantly reduced. Patients excluded from thrombolysis, however, continue to have a high early mortality. The data suggest that the potential benefits of this treatment might be extended to selected high-risk subgroups. In particular, the risk-benefit ratio may favor the inclusion of otherwise healthy elderly patients; certain patients presenting more than 6 hours after the onset of symptoms; and patients with a history of controlled systolic hypertension or brief, nontraumatic cardiopulmonary resuscitation. The data do not support the use of fibrinolytic therapy as primary treatment in patients with unstable angina or suspected myocardial infarction in the absence of confirmatory electrocardiographic changes. CONCLUSIONS: The full potential of thrombolytic therapy to alter the natural history of acute myocardial infarction can only be realized through the continued evaluation of selection criteria and the identification and treatment of the greatest possible number of eligible patients.

Coexpression patterns of vimentin and glial filament protein with cytokeratins in the normal, hyperplastic, and neoplastic breast. The authors studied by immunohistochemistry the intermediate filament (IF) protein profile of 66 frozen samples of breast tissue, including normal parenchyma, all variants of fibrocystic disease (FCD), fibroadenomas, cystosarcoma phylloides, and ductal and lobular carcinomas. Monoclonal antibodies (MAbs) to cytokeratins included MAb KA 1, which binds to polypeptide 5 in a complex with polypeptide 14 and recognizes preferentially myoepithelial cells; MAb KA4, which binds to polypeptides 14, 15, 16 and 19; individual MAbs to polypeptides 7, 13, and 16, 17, 18, and 19, and the MAb mixture AE1/AE3. The authors also applied three MAbs to vimentin (Vim), and three MAbs to glial filament protein (GFP). Selected samples were studied by double-label immunofluorescence microscopy and by staining sequential sections with some of the said MAbs, an MAb to alpha-smooth muscle actin, and well-characterized polyclonal antibodies for the possible coexpression of diverse types of cytoskeletal proteins. Gel electrophoresis and immunoblot analysis also were performed. All samples reacted for cytokeratins with MAbs AE1/AE3, although the reaction did not involve all cells. Monoclonal antibody KA4 stained preferentially the luminal-secretory cells in the normal breast and in FCD, whereas it stained the vast majority of cells in all carcinomas. Monoclonal antibody KA1 stained preferentially the basal-myoepithelial cells of the normal breast and FCD while staining tumor cell subpopulations in 4 of 31 carcinomas. Vimentin-positive cells were found in 8 of 12 normal breasts and in 12 of 20 FCD; in most cases, Vim-reactive cells appeared to be myoepithelial, but occasional luminal cells were also stained. Variable subpopulations of Vim-positive cells were noted in 9 of 20 ductal and in 1 of 7 lobular carcinomas. Glial filament protein-reactive cells were found in normal breast lobules and ducts and in 15 of 20 cases of FCD; with rare exceptions, GFP-reactivity was restricted to basally located, myoepithelial-appearing cells. Occasional GFP-reactive cells were found in 3 of 31 carcinomas. Evaluation of sequential sections and double-label immunofluorescence microscopy showed the coexpression of certain cytokeratins (possibly including polypeptides 14 and 17) with vimentin and alpha-smooth muscle actin together with GFP in some myoepithelial cells. The presence of GFP in myoepithelial cells was confirmed by gel electrophoresis and immunoblotting. Our results indicate that coexpression of cytokeratin with vimentin and/or GFP is comparatively frequent in normal basal-myoepithelial cells of the breast.(ABSTRACT TRUNCATED AT 400 WORDS).

Emergency portosystemic shunt in patients with variceal bleeding. Thirty-five patients for whom emergency sclerotherapy or conservative treatment, or both, failed to arrest variceal bleeding, or who had early rebleeding and required emergency portosystemic shunts (EPSS) were studied. EPSS permanently controlled the variceal bleeding in all but one patient. In this patient, the shunt was patent as demonstrated by angiography. Esophageal varices disappeared in 18 patients and were reduced in 14. Three patients died before the endoscopic examination could be performed. The causes of death were hepatic failure in two and bleeding ulcerations of the gastric fundus in the other patient. One patient was classified in Child's category B and two in Child's category C. Thirty-two patients submitted to EPSS and were discharged alive. Twelve of these patients subsequently died, at an average of 11.2 months after undergoing the shunt procedure. Four of 12 patients died of hepatic failure; two patients died of hepatomas; two, other neoplasia; three, hemorrhaging duodenal ulcers, and one patient, renal failure. Analysis of actuarial survival rates showed that the five year survival rate was 43 per cent. The long term survival rates were fewer for patients with Child's category C than for those with combined Child's categories A and B (five year survival rates were 21 versus 55 per cent; p less than 0.05). During the follow-up period, none of the patients had variceal bleeding. Chronic encephalopathy developed in six, which was mild in three, moderate in one instance and severe in two. It developed soon after EPSS, with onset in the first month after discharge in three. Thus, when conservative treatment fails to arrest variceal bleeding, EPSS should be performed to guarantee definitive control of hemorrhage and prolong the survival period.

Extradural abscess following local anaesthetic and steroid injection for chronic low back pain. A case is described of extradural abscess following extradural injection of local anaesthetic and steroid for the management of chronic low back pain. The common signs and symptoms are reviewed, possible causes discussed and the association with diabetes stressed.

Location of port-wine stains and the likelihood of ophthalmic and/or central nervous system complications. Of 310 patients with port-wine stains, 68% had more than one dermatome involved; 85% had unilateral and 15% had a bilateral distribution of their port-wine stain. At the time of examination, 8% of all patients with trigeminal port-wine stains had evidence of eye and/or central nervous system (CNS) involvement. Extensive involvement, with port-wine stain over the trunk and extremities as well as the head and neck, was observed in 12%. Patients who did not have port-wine stains on the areas served by branches V1 and V2 of the trigeminal nerve had no signs or symptoms of eye and/or CNS involvement. Port-wine stains of the eyelids, bilateral distribution of the birthmark, and unilateral port-wine stains involving all three branches of the trigeminal nerve were associated with a significantly higher likelihood of having eye and/or CNS complications. Twenty-four percent of those with bilateral trigeminal nerve port-wine stains had eye and/or CNS involvement compared with 6% of those with unilateral lesions. All those who had eye and/or CNS complications had port-wine stain involvement of the eyelids; in 91% both upper and lower eyelids were involved, whereas in 9% only the lower eyelid was involved. None of those with upper eyelid port-wine stains alone had eye and/or CNS complications. In addition, 3 (75%) of the 4 subjects with seizures alone had bilateral port-wine stain involvement. A third group, these with unilateral V1, V2, and V3 port-wine stains, had eye and/or CNS complications in 3 (19%) of 16 subjects.

Pancreatic cancer versus chronic pancreatitis: diagnosis with CA 19-9 assessment, US, CT, and CT-guided fine-needle biopsy. The authors prospectively performed serum CA 19-9 assessment, ultrasound (US), computed tomography (CT), and CT-guided fine-needle aspiration biopsy (FNAB) of the pancreas in 81 consecutive patients with suspected chronic pancreatitis or pancreatic neoplasm. The final diagnosis was pancreatic cancer in 54 patients and chronic pancreatitis in 27 patients. CA 19-9 assessment, US, CT, and FNAB were considered nondiagnostic, respectively, in 0%, 25%, 19%, and 6% of cases. When a definite diagnosis was rendered, the positive predictive value was 90% for CA 19-9 assessment, 95% for US, 98% for CT, and 100% for FNAB; the negative predictive value was, respectively, 69%, 95%, 86%, and 100%. The accuracy of all diagnostic and nondiagnostic studies was 81% for CA 19-9 assessment, 72% for US, 77% for CT, and 94% for FNAB. It is concluded that CT-guided pancreatic FNAB is the most reliable examination for enabling differential diagnosis of pancreatic cancer and chronic pancreatitis. When the pancreas is well visualized at US, the negative predictive value for pancreatic cancer is more accurate than that of CA 19-9 assessment and CT.

Squamous carcinoma of the posterior pharyngeal wall. We have reviewed a 12-year experience with 295 patients treated for squamous carcinoma of the pharynx in order to focus on 78 patients whose lesions arose in the posterior wall. Surgery was the definitive therapy for the primary tumor in 57 (73%), including 3 treatment groups. Thirty-two patients had limited resections that preserved the larynx, involving local excision (7 patients), anterior pharyngotomy (7 patients), lateral pharyngotomy (6 patients), median labiomandibular glossotomy (6 patients), or median mandibulotomy with paralingual extension (6 patients). The second group consisted of 21 patients with more extensive tumors who required a laryngectomy and complex reconstruction, often with postoperative radiotherapy. Finally, there were four patients who developed metachronous second primaries in the pharynx subsequent to a laryngectomy. All required flap reconstruction. Of the 21 patients whose primary treatment was radiotherapy, 5 had lesions that were implanted after access was provided by a mandibulotomy. Cumulative 5-year survival was 32% and ranged from 44% in those with favorable lesions to 15% in those with extensive tumors. Our experience highlights the variety of treatment approaches available in patients with pharyngeal carcinomas confined to the posterior wall. Surgery in this setting carries acceptable morbidity and yields survival rates that compare favorably with those achieved by external radiation therapy alone. Results in patients with extensive lesions still leave much to be desired, despite radical surgery and aggressive radiotherapy. Innovative brachytherapy techniques using surgery for access deserve further investigation.

Cognitive function testing in comprehensive geriatric assessment. A comparison of cognitive test performance in residential and clinic settings. Tests of cognitive function are frequently used in geriatric assessment, but the effect of test setting has rarely been explored. To determine the effect of testing site on the performance of elderly patients undergoing a comprehensive geriatric assessment, we administered the Mini-Mental State Exam to 116 geriatric patients in the clinic and at their residence. Their cognitive abilities varied from normal to severely impaired. The patients' scores were 1.5 +/- 3.6 (mean +/- SD) higher at their residence. The clinical importance of a difference in score of 1.5 is not clear. For this reason a second analysis was performed in which a difference in scores of five points or greater between settings was considered clinically meaningful. Twenty-five percent (29 of 116) differed by five points or more. Of these 29 patients, 22 (76%) tested better in the residential setting. These differences were statistically significant (P = .001). We conclude that the testing site may affect test performance and that in-home assessment may reveal the optimal cognitive function of geriatric patients.

Interaction of chloramphenicol and metabolites with colony stimulating factors: possible role in chloramphenicol-induced bone marrow injury. We have recently demonstrated that two chloramphenicol (CAP) metabolites known to be produced by intestinal bacteria, dehydro-CAP (DH-CAP) and nitrophenylaminopropane (NPAP), are much more cytotoxic to bone marrow in vitro than CAP itself. Since colony stimulating factors (CSFs) play an essential role in hematopoietic cell growth, toxicity from CAP metabolites could also involve interaction with CSF or CSF-producing cells. In the present study, we found that increasing concentrations of rhGM-CSF or rhG-CSF completely reversed the inhibitory effect of CAP (2 x 10(-4) M) on human CFU-GM growth and on the growth of KG-1 cells. GM-CSF also reversed the inhibitory effect of CAP on HL-60 cells. Inhibition by DH-CAP (50% at 5 x 10(-7) M), nitroso-CAP (NO-CAP) (60% at 5 x 10(-6) M) and NPAP (35% at 10(-5) M) was not affected by either CSF. In addition to their inhibitory effect on cell growth, DH-CAP (5 x 10(-6) M) and NO-CAP (5 x 10(-6) M) inhibited CSF production by buffy coat cells 50-70% without affecting cell viability. Neither CAP nor NPAP inhibited CSF production. It is suggested that the dual toxic-inhibitory effect of some intestinal metabolites of CAP such as DH-CAP on hematopoietic cell growth on the one hand, and on CSF production on the other, renders them very potent as potential mediators of CAP induced aplastic anemia.

Papillary endothelial hyperplasia in the thyroid following fine-needle aspiration. A 74-year-old woman was found to have exuberant papillary endothelial hyperplasia within her thyroid gland subsequent to multiple fine-needle aspiration biopsies of a Hurthle cell neoplasm. To our knowledge, this histologic alteration in the thyroid has not been previously reported. We describe this unusual complication following fine-needle aspiration, and we delineate the clinicopathologic and differential diagnostic features.

Follow-up results of balloon angioplasty of native coarctation in neonates and infants. The purpose of this study is to present intermediate-term results of balloon angioplasty of native aortic coarctation in neonates and infants less than 1 year of age. During a 60-month-period that ended in January 1990, 19 infants ages 3 days to 12 months (median, 2.5 months), underwent balloon angioplasty of native coarctation with resultant reduction in peak-to-peak systolic pressure gradient from 39 +/- 12 mm Hg (mean +/- SD) to 11 +/- 7 mm Hg (p less than 0.001) and increase in coarctation segment size from 2.2 +/- 0.8 mm to 4.7 +/- 1.0 mm. None required immediate surgical intervention. Thirteen of the 19 (68%) had severe associated cardiac defects. There was one death (5%) 2 days after balloon angioplasty, and it was related to associated cardiac defect. One infant was lost to follow-up. It is too soon to restudy one infant. The remaining 16 infants had clinical (36 +/- 18 months) and catheterization (12 +/- 4 months) follow-up data. The residual coarctation gradient (22 +/- 15 mm Hg) and coarcted segment size (4.4 +/- 1.6 mm) remain improved (p less than 0.01) when compared with pre-balloon angioplasty values. Five of the 16 (31%) infants (four were neonates at the time of balloon angioplasty) had evidence for recoarctation (defined as gradient greater than 20 mm Hg) and underwent surgical resection (two) or repeat balloon angioplasty (three), all with success. None developed aneurysms.

Effective intraperitoneal antiprotease therapy for taurocholate-induced pancreatitis in rats In canine pancreatitis, irreversible hypotension and death follow saturation of the antiprotease molecules in peritoneal exudate by activated proteolytic enzymes which are released from the pancreas. This study has examined, in rats with taurocholate-induced pancreatitis, the efficacy of removal of the peritoneal exudate by aspiration and a single lavage, followed by instillation of an exogenous antiprotease solution. Instillation of human fresh frozen plasma, containing alpha 2-macroglobulin and alpha 1-antiprotease, was associated with the longest median survival. Aprotinin, although possessing a much greater trypsin inhibitory capacity, just failed to significantly improve the median survival time compared with the control group. Intraperitoneal antiprotease therapy is simple to perform, has a beneficial effect on survival time in this model and merits investigation in man.

Development of multiple necrotizing enteritis induced by a tumor necrosis factor-like cytokine from lipopolysaccharide-stimulated peritoneal macrophages in rats. We report the development of an animal model of multiple necrotizing enteritis (MNE) in rats. When rats were injected directly with a culture supernatant of lipopolysaccharide (LPS)-stimulated rat peritoneal macrophages into the abdominal aorta, the overt pathologic lesions of MNE developed within 30 minutes after injection. The rats showed an elevated level of blood fibrinogen degradation product content even 30 minutes after injection. Furthermore the rats that were pretreated intravenously with heparin sulfate did not develop MNE, indicating the acute disturbances of blood microcirculation in the intestine. Multiple necrotizing enteritis was developed also by the injection with recombinant tumor necrosis factor (rTNF) but rarely was observed with even a high dose of recombinant interleukin-1 (rIL-1) or platelet-activating factor (PAF). The supernatant was cytotoxic in vitro to TNF-susceptible LM and many other cells but was less cytotoxic to the TNF-resistant LR line. Partial purification of the supernatant suggested that the supernatant contained a cytokine that has biochemical features of TNF. Furthermore polyclonal anti-TNF antibody could inhibit not only the cytotoxicity in vitro but also MNE development in vivo by this factor. These data strongly indicate that MNE possibly could be caused by a TNF-like cytokine produced by macrophages that are stimulated by the endotoxin.

Acetazolamide in the treatment of abnormal oculovestibular response. We treated seven patients with incapacitating vertigo elicited by walking down a grocery store aisle or driving a car. Results of neurologic, neuro-ophthalmic, and neuroradiologic examinations were normal. Episodic vertigo secondary to an abnormal oculovestibular response was diagnosed. Each patient was given a trial of 250 to 500 mg of acetazolamide daily. Symptoms resolved completely in four patients, two patients had near resolution of symptoms, and one patient had no relief. Carbonic anhydrase activity has been demonstrated in the inner ear, and acetazolamide has been shown to affect the ion balance of the inner ear fluids.

Post-traumatic basal ganglia hemorrhage: analysis of 52 patients with emphasis on the final outcome. A series of 52 patients suffering post-traumatic basal ganglia hemorrhage (BGH) after closed head injury is reviewed. Post-traumatic BGH was associated with other intracranial lesions in most cases. The outcome in this series is rather good, with 53.8% of patients having a functional survival. Radiologically, the post-traumatic intraventricular hemorrhage (IVH) and brainstem hemorrhage usually coexisted with a poor outcome. Old age (greater than 60), abnormal pupil reaction, impaired oculocephalic response, and abnormal motor response to pain stimuli are reliable clinical hallmarks for poor prognosis.

Puppet-like syndrome of Angelman: a pathologic and neurochemical study. We present the first pathologic descriptions of the puppet-like syndrome of Angelman based on autopsy studies of a 21-year-old woman. The noteworthy findings were a small brain with mild cerebral atrophy but normal gyral development. There was marked cerebellar atrophy with loss of Purkinje and granule cells and extensive Bergmann's gliosis. Study of dendrite morphology using Golgi impregnations of the visual cortex revealed a prominent decrease in dendritic arborization of layer 3 and layer 5 pyramidal neurons. Quantitative Golgi analysis also revealed a significant decrease in the numbers of dendritic spines in apical layer 3 dendrites and both apical and basal layer 5 dendrites. Neurochemical studies of frozen brain tissue demonstrated markedly reduced gamma-aminobutyric acid content in the cerebellar cortex, as well as elevated glutamate content in the frontal and occipital cortices. Although there are no definite morphologic correlates of many of the clinical signs, the pronounced dendritic pathology and neurochemical abnormalities in cerebral cortex may provide a physiologic basis for mental retardation.

Multifocal gastric carcinoma arising from hyperplastic and adenomatous polyps. This paper is a presentation of the unusual case of a 61-yr-old woman operated on for multiple gastric cancers. Two of the cancers were found in the hyperplastic polyps and one in the adenoma. Apart from cancers that arose from these polyps, there were four separate polypoid or flat gastric carcinomas and three other hyperplastic polyps with no signs of malignancy, in this case. The presentation is followed by a detailed discussion focusing on the possible development of carcinoma in gastric hyperplastic polyps in view of the data from the literature.

Treatment of cervical spondylotic myelopathy by enlargement of the spinal canal anteriorly, followed by arthrodesis. Thirty-seven patients who had enlargement of the spinal canal anteriorly and stabilization of the spine for cervical spondylotic myelopathy were followed for an average of forty-nine months (range, twenty-eight to seventy months). Myelography and computed tomographic myelography were performed preoperatively on all patients to determine the location and features of the areas of decompression. The canal was enlarged by discectomy; by subtotal corpectomy and removal of the anteromedial parts of the pedicles; or by removal of osteophytes or of the posterior longitudinal ligament, or both. Partial corpectomy and interbody arthrodesis was performed in nine patients; subtotal corpectomy, including removal of the posterior parts of the vertebral bodies and of the posterior longitudinal ligament, and strut bone-grafting, in fifteen patients; and subtotal corpectomy, with detachment of the remaining thin posterior parts of the vertebral bodies and of the posterior longitudinal ligament, and strut bone-grafting, in thirteen patients. Postoperatively, radiographic examinations, including myelography and computed tomographic myelography, were performed for thirty-six patients and magnetic resonance imaging, for twenty-eight. A satisfactory neurological result was obtained in twenty-nine patients. Atrophy of the spinal cord, as seen on preoperative computed-tomographic myelograms, was predictive of an unsatisfactory result of the decompression, as was weakness of the peroneal muscles. All but one of the thirty-seven patients had improved walking ability at the most recent follow-up examination: seventeen patients improved by 1 point; fourteen, by 2 points; four, by 3 points; and one, by 4 points. The remaining patient reverted to the preoperative status after an initial improvement. The ability to walk at the interim examinations was compared with that at the most recent examination; three patients had continuing improvement, while three others had deterioration. The main cause of deterioration was new spondylotic changes associated with stenosis of the spinal canal, occurring at the level of the disc just cephalad to the fused levels. We concluded that anterior decompression followed by a secure arthrodesis should be an extensive procedure for patients who have cervical spondylotic myelopathy, as determined preoperatively from a myelogram or computed tomographic myelogram. Excision of the vertebral bodies should also be wide and should include the anteromedial parts of the pedicles. The third or fourth cervical vertebra should be included in the arthrodesis prophylactically in patients who have stenosis of the spinal canal when either of these vertebrae is adjacent to the level of fusion.

Abnormal vitamin B6 status in childhood leukemia. Vitamin B6 is involved in many biological processes of potential relevance to carcinogenesis and tumor growth, including DNA synthesis and maintenance of immunocompetence, yet very little information exists on B6 nutritional status in childhood leukemia. Using a radioenzymatic assay, the authors measured plasma pyridoxal 5'-phosphate (PLP), the biologically active form of B6, in 11 newly diagnosed untreated children with leukemia and 11 age-matched controls. The children with leukemia had significantly lower PLP levels than the controls. In 26 additional leukemia patients and 26 additional controls, a high-performance liquid chromatography assay also demonstrated lower plasma PLP levels in childhood leukemia compared with controls. These differences were significant for both acute lymphoblastic leukemia (ALL) and for acute nonlymphoblastic leukemia (ANLL). The PLP values did not correlate with indices of leukemia cell burden, but did correlate with reported B6 intake, suggesting that illness-related diet changes are at least partially responsible for the low PLP levels. Before any chemotherapy, overall nutritional status was suboptimal in 53% of ALL cases and 57% of ANLL cases. Newly diagnosed children with leukemia have suboptimal overall nutrition as well as suboptimal vitamin B6 status.

A study of the effects of delapril, a new angiotensin converting enzyme inhibitor, on the diurnal variation of arterial pressure in patients with essential hypertension using indirect and direct arterial pressure monitoring methods. In order to investigate the effect of delapril, a new angiotensin converting enzyme inhibitor, on the diurnal variation of arterial pressure in patients with essential hypertension, this study examined 24 h arterial pressure using an indirect or a direct monitoring system. When the effect of twice-a-day administration of delapril at daily doses of 30 to 90 mg was examined using the indirect monitoring system in 12 outpatients, delapril decreased systolic and diastolic arterial pressures significantly only at limited points during the day. However, each of the averaged 24 h daytime and nighttime arterial pressures showed significant reductions. The 24 h intraarterial pressure monitoring demonstrated that delapril decreased systolic and diastolic arterial pressure at most of the measurement points. The arterial pressure reductions during daytime and nighttime were not significantly different, that is, there was no excessive reduction in nighttime arterial pressure. Heart rate and its variability were virtually unaffected by the delapril treatment in either monitoring study. No adverse reactions were observed in the indirect or direct monitoring studies. Thus, it is concluded that twice-a-day administration of delapril at daily doses of 30 to 90 mg brings about a safe and stable antihypertensive effect, without affecting the diurnal variation of arterial pressure.

Chronic oral etoposide. Etoposide is an important drug that has been recently incorporated with other agents in the curative treatment of patients with advanced neoplasms, including germ cell tumors, non-Hodgkin's lymphomas (NHL), and small cell lung cancer (SCLC). Etoposide demonstrates remarkable schedule dependency. A randomized comparison has shown an impressive survival difference for patients with extensive SCLC receiving a 5-day course versus those receiving a 1-day course. Because of these and previous clinical and laboratory data, etoposide is now given intravenously or orally in a 3-day to 5-day schedule. It is generally accepted that approximately 50% of the orally administered drug is absorbed. The authors have initiated several etoposide studies using an extended administration schedule, believing that a prolonged schedule may be superior to the standard 3-day to 5-day schedule. This was initially tested in a Phase I study. Results showed that etoposide (50 mg/m2/d) given over 21 days was feasible and was associated with only moderate toxicity. Several Phase II studies have been completed or are nearing completion, including studies in patients with SCLC, NHL, germ cell tumors, soft tissue sarcoma, renal carcinoma, and ovarian carcinoma. Responses have been seen in all of these groups, particularly in patients with SCLC, lymphoma, and germ cell tumors. In these groups we saw responses in patients who were clearly resistant to etoposide plus cisplatin given in a standard schedule or in some patients who were resistant to high-dose etoposide with bone marrow transplantation. Investigators at Indiana University Medical Center who studied oral etoposide in a similar fashion in patients with advanced germ cell tumors and SCLC achieved results similar to those reported here. The authors have initiated a number of combination chemotherapy programs using the chronic oral form of etoposide. These include patients with SCLC, non-small cell lung cancer, and elderly patients with high-grade and intermediate forms of NHL. In addition, chronic intravenous oral etoposide is being used in salvage approaches for patients with acute myelocytic leukemia and recurrent resistant intermediate-grade and high-grade NHL. Preliminary pharmacokinetic data suggest that a 50-mg/m2 oral dose is highly bioavailable (91% to 96%). Therefore, during a prolonged oral course at 50 mg/m2, many patients maintain a minimum plasma concentration of 1 microgram/ml. Further studies of multiple dose or continuous infusion etoposide to maintain a potentially critical plasma level are in progress. Etoposide administered in this way could represent a "new" drug because many of its features are different, and its activity spectrum may be broader.

Coeliac disease and malignancy of the duodenum: diagnosis by endoscopy, successful treatment of the malignancy, and response to a gluten free diet. A patient presented with subtotal villous atrophy and a malignant duodenal tumour of uncertain histogenesis. He was successfully treated by resection and chemotherapy and the small bowel mucosa recovered on a gluten free diet. The tumour was diagnosed at upper gastrointestinal endoscopy when barium studies and abdominal computed tomography were normal, thus making this one of the earliest coeliac malignancies diagnosed.

Traumatic subarachnoid-pleural fistula in a child. A case report. A seven-year-old girl sustained a gunshot wound to the chest and spine. Evaluation of a persistent pleural effusion demonstrated a subarachnoid-pleural fistula. Surgical closure of the dural defect resulted in resolution of the fistula. Traumatic subarachnoid-pleural fistulae are rare. The diagnosis is reached by an awareness of fistula formation from penetrating or blunt trauma to the chest.

In situ hybridization of prostate-specific antigen mRNA in human prostate. Prostate-specific antigen (PSA) mRNA was detected by in situ hybridization utilizing a 428 base pair [35S]-labelled cDNA probe from the 3' noncoding region of the PSA gene. Thirty six fresh surgical specimens were collected from patients undergoing radical retropubic prostatectomy for carcinoma of the prostate. Quantitative analysis of the levels of PSA mRNA in both the benign and malignant tissues was performed using an IBAS 2000 Image Analysis System. The results of this study demonstrated that there is a significant decrease in the expression of PSA mRNA in the carcinoma tissue when compared to the benign epithelium. The average binding (number of silver grains/1 x 10(4) microns. 2) for 20 specimens of malignant epithelium was 475 +/- 161 and 586 +/- 140 for 16 specimens of benign epithelium (p less than 0.05). Eleven patients had both benign and malignant tissue from the same surgical specimen available for study. From these paired specimens, the PSA mRNA expression was also significantly reduced in the malignant epithelium when compared to the benign epithelium, 445 +/- 162 and 588 +/- 135 respectively (p less than 0.005). The PSA protein was detected using a monoclonal antibody to PSA with an immunohistochemical staining technique. The PSA protein expression paralleled the expression of the PSA mRNA in the majority of the tissue sections. Many of the tumor specimens showed a heterogeneous expression of PSA, whereas all of the benign epithelium had a uniform high level of PSA expression. In conclusion, PSA mRNA and protein are located only within the glandular epithelial tissue, the expression of PSA protein parallels that of the PSA mRNA, and both the PSA protein and PSA mRNA are significantly decreased in the malignant epithelium when compared to benign prostatic epithelium.

Experience with the Sarns centrifugal pump as a ventricular assist device. The authors used the Sarns centrifugal pump (Sarns 3M, Ann Arbor, MI) as a ventricular assist device (VAD) in 30 patients between May 1985 and February 1990. Sixteen patients were unweanable from cardiopulmonary bypass at the time of surgery; nine were patients who developed cardiogenic shock postoperatively in the intensive care unit. One was a donor organ failure; one had a failed PTCA; and one an acute myocardial infarction with cardiogenic shock preoperatively. Two patients were bridged to cardiac transplantation. Of the 28 nontransplant candidates, 20 (71.4%) were weaned successfully, 14 (50%) were discharged from the hospital, and 13 (46%) are alive from 1 to 46 months postoperatively (mean, 21.1 months). Three patients received right ventricular support alone; all three were weaned, and two (66.7%) were discharged. Ten patients received left ventricular assistance alone. Six (60%) were weaned, and four (40%) were discharged. Two patients received left ventricular support initially but were taken back for right VAD insertion because of right-sided heart failure; one (50%) is alive. Fifteen patients received biventricular support. Eleven (77.3%) were weaned, and eight (53.3%) were discharged. Patient ages ranged from 19 to 73 years, with a mean age for men of 59 years and 50.5 years for women. There were no thromboembolic events. Various clinical parameters were evaluated to determine effect on weanability and survival. These results show survival equivalent to any other VAD at this time. The centrifugal pump is a convenient and effective means of maintaining ventricular support in individuals who are believed to have salvageable myocardium.

Pancreaticobiliary ductal union. The main pancreatic duct and the common bile duct open into the second part of the duodenum alone or after joining as a common channel. A common channel of greater than 15 mm (an anomalous pancreaticobiliary duct) is associated with congenital cystic dilatation of the common bile duct and carcinoma of the gall bladder. Even a long common channel (greater than or equal to 8 mm) is associated with a higher frequency of carcinoma of the gall bladder. Gall stones smaller than the common channel and a long common channel predispose to gall stone induced acute pancreatitis. Separate openings for the two ductal systems predisposes to development of gall stones and alcohol induced chronic pancreatitis. The role of ductal union has also been investigated in primary sclerosing cholangitis and biliary atresia.

Primary rhabdomyosarcoma of the ileum in an adult. We report a case of primary rhabdomyosarcoma of the ileum occurring in a 45-year-old man. The rhabdomyoblastic nature was immunohistochemically confirmed by positivity with anti-myoglobin and anti-striated actin antisera. We discuss the differential diagnosis with similar tumors. To our knowledge, ileal rhabdomyosarcomas have not been previously reported in adults.

The role of a critical care unit in an epidemic. The role of a critical care unit in life-threatening situations is well established. The management of 52 children with acute gastroenteritis and 22 children with acute paralytic poliomyelitis as part of recent epidemics is described. The solutions to the problems in the critical care management of these 74 victims (out of a total of 6197 patients admitted during the epidemics) are discussed.

Comparison of intravenous amrinone and dobutamine in congestive heart failure due to idiopathic dilated cardiomyopathy. A prospective randomized study was performed in 46 consecutive patients with refractory congestive heart failure (CHF) due to idiopathic dilated cardiomyopathy to compare the hemodynamic responses to 48-hour infusions of amrinone and dobutamine. Both drugs substantially reduced pulmonary arterial wedge pressure, right atrial pressure and systemic vascular resistance and increased cardiac index. Amrinone caused a greater decrease in right atrial pressure than dobutamine (p less than 0.02) and had a positive chronotropic effect not observed with dobutamine (p less than 0.01). The increase in heart rate produced by amrinone correlated inversely with the changes in right atrial and pulmonary arterial wedge pressures, suggesting a baroreceptor response to reduced preload. Dobutamine produced a larger increase in stroke volume index than amrinone (p less than 0.01). Ninety-one percent of patients receiving amrinone and only 65% receiving dobutamine had reduction of greater than or equal to 30% in pulmonary arterial wedge pressure (p less than 0.05). Cardiac index increased greater than or equal to 30% in similar numbers of patients given amrinone (74%) and dobutamine (65%). Negative fluid balance was recorded in all patients receiving amrinone and in 78% of patients receiving dobutamine (p less than 0.05). Target hemodynamic criteria were achieved in 83% of patients receiving 10 micrograms/kg/min of amrinone. The effective maintenance dose of dobutamine was extremely variable. No clinically important adverse effects were observed with either drug regimen. Both amrinone and dobutamine are effective and safe agents for short-term parenteral therapy of patients with dilated cardiomyopathy in severe CHF that is unresponsive to oral medication.

Cerebellar degeneration and Meige's syndrome. We have reported a case of Meige's syndrome in a middle-aged man who eventually had a cerebellar degeneration syndrome. The extrapyramidal symptoms preceded cerebellar signs and symptoms by 5 years. Most patients with idiopathic Meige's syndrome show some improvement with high-dose anticholinergic therapy. Our patient's lack of response to such agents and his subsequent cerebellar symptoms are reminiscent of the situation seen with parkinsonian patients who do not respond to medications, indicating a more widespread degenerative disease. The association of extrapyramidal symptoms with some spinocerebellar disorders, and the pathologic changes seen in the one reported autopsy case, should place the group of spinocerebellar disorders high on the differential list.

Role of calcium and the calcium channel in the initiation and maintenance of ventricular fibrillation. The cellular events during the initiation and maintenance of ventricular fibrillation (VF) are poorly understood. We developed a nonischemic, isolated, perfused rabbit Langendorff preparation in which sustained VF could be induced by alternating current (AC) and which allowed changes in perfusate composition. We also used Na(+)-K+ pump inhibition (10 microM ouabain or K(+)-free perfusate) to induce VF. AC stimulation or Na(+)-K+ pump inhibition always initiated VF. Calcium channel blockade by verapamil or nitrendipine uniformly inhibited the initiation of VF in both models. During Na(+)-K+ pump inhibition, 1) VF was prevented by calcium channel blockade, despite evidence of Ca2+ overload, and 2) abolition of spontaneous sarcoplasmic reticulum-generated cytosolic Ca2+ oscillations by ryanodine or Na+ channel blockade with tetrodotoxin did not prevent VF initiation. Lowering extracellular [Ca2+] to 80 microM uniformly prevented the initiation of VF due to Na(+)-K+ pump inhibition but not that due to AC stimulation. VF maintenance also was studied using 1) reduction in perfusate [Ca2+], 2) blockade of Ca2+ channels, or 3) electrical defibrillation. Decreasing the perfusate [Ca2+] to 80 microM resulted in defibrillation during VF whether induced by AC or Na(+)-K+ pump inhibition. Verapamil or nitrendipine also resulted in defibrillation regardless of the initiation method. Electrical defibrillation was successful only in AC-induced VF. The results demonstrate that VF can be initiated and maintained in a nonischemic rabbit Langendorff preparation. The data suggest that increases in slow channel Ca2+ flux, as opposed to increases in cytosolic Ca2+ per se, were necessary for the initiation and maintenance of VF. The data, however, do not exclude an important role for cytosolic Ca2+ in the modulation of VF.

Varicella with delayed hemiplegia. We report 4 children who developed acute hemiplegia 7 weeks to 4 months after varicella infection. In 2 patients, carotid angiography demonstrated segmental narrowing and occlusion of the middle cerebral artery. Their clinical and angiographic features were similar to those associated with contralateral hemiplegia after herpes zoster ophthalmicus, the pathogenesis of which comprises cerebral angiitis due to varicella zoster viral infection. We believe that our patients had the same pathogenesis. In a survey of infectious diseases in our region, the frequency of varicella with delayed hemiparesis was roughly 1:6,500 varicella patients.

Correlation of the testicular determinant factor sequence zinc finger Y with varying gonadal phenotypes in a series of 13 subjects with gonadal dysgenesis due to Y aneuploidy. Deoxyribonucleic acid samples from a series of 13 subjects with 45,X/46,X,altered Y, and varying gonadal phenotypes (streak-streak, n = 9; streak-testis, n = 2; testis-testis, n = 2) were analyzed for the presence of the candidate testicular determinant factor sequence zinc finger Y. The Y-specific probes Y97 mapped to Y centromere, pDP105 A,B mapped to Yp and distal Yq11, respectively, hybridized with the deoxyribonucleic acid from all the 13 study subjects. The same deoxyribonucleic acid samples were analyzed for the presence of the zinc finger Y sequence. Eleven of the 13 subjects were positive for the zinc finger Y sequence. Four zinc finger Y-positive subjects had unilateral (n = 2) or bilateral (n = 2) testicular differentiation. Among the nine subjects with bilateral streak gonads, seven showed the presence of this sequence. The lack of testicular differentiation in the presence of quantitatively normal or almost normal zinc finger Y bands could not be explained by mosaicism alone. Mutations not detectable by analysis with the method of Southern with pDP1007, may occur in the testicular determinant factor gene vitiating testicular development.

Noninvasive determination of pulmonary artery wedge pressure: comparative analysis of pulsed Doppler echocardiography and right heart catheterization. To compare left ventricular filling variables as derived by transmitral pulsed Doppler echocardiography (tpDE) and hemodynamic variables as assessed at right heart catheterization (RHC), 104 ICU patients (64 male, 40 female) aged 26 to 73 yr (mean 54.6 +/- 10.3) without valvular heart disease were examined. Simultaneously with RHC, transmitral flow velocity profiles were obtained by tpDE, and the ratio of the velocity-time integrals of late diastolic active (A wave) and early diastolic passive inflow into the left ventricle (E wave) was calculated (A/E ratio). Invasively determined pulmonary capillary wedge pressure (WP) ranged from 3 to 36 mm Hg (median 13.35, 5%/95% 6/31 mm Hg). Linear regression analysis showed a highly significant correlation between the A/E ratio and WP (r = .98, p less than .001, standard error of the estimate [SEE] = 0.10). The A/E ratio also correlated with other hemodynamic variables such as cardiac output (r = -.68, p less than .001, SEE = 0.33), cardiac index (r = -.74, p less than .001, SEE = 0.31), and stroke volume index (r = -.68, p less than .001, SEE = 0.34). The interobserver agreement (derived by intraclass correlation analysis between two examiners) on the A/E ratio was high (r = .95, p less than .001, n = 26). We conclude that WP can be accurately determined noninvasively by tpDE. For the assessment of systolic ventricular function, tpDE is of limited diagnostic value.

Treatment of phenobarbital poisoning with multiple dose activated charcoal in an infant. A 28-day-old infant developed lethargy, hypotonia, and hypothermia following a phenobarbital overdose secondary to a pharmacist's error. He was treated with multiple dose activated charcoal (MDAC) and alkalinization of the urine, which resulted in prompt recovery with rapid elimination of the drug (t1/2-11.2 hours, expected 45 to 118 hours). The use of MDAC in this newborn was safe and effective. We suggest that age should not pose a barrier to the use of MDAC, when indicated.

Ten cases of transitional cell carcinoma of bladder causing ureteric obstruction. A review was carried out on 10 patients with superficial transitional cell carcinoma of the bladder (Ta lesions) that were causing ureteric obstruction. Evidence of upper tract obstruction did not necessarily indicate deep invasion.

High risk of recurrent stroke after discontinuance of five to twelve years of transfusion therapy in patients with sickle cell disease. Although long-term transfusion therapy is at least 90% effective in preventing recurrent strokes after an initial cerebrovascular accident in patients with sickle cell disease, it is unknown how long transfusion therapy should be continued. To address this question, we prospectively discontinued transfusions in 10 patients with sickle cell disease whose median duration of transfusion therapy after an initial stroke was 9 1/2 years (range 5 to 12 years). Before the transfusions were discontinued, patients were examined by cerebral angiography, magnetic resonance imaging of the head, neuropsychologic testing, electroencephalography, and a complete neurologic examination. Within 12 months after transfusion therapy was stopped, 5 of 10 patients had had an ischemic event. Three events caused relatively mild deficits in the same areas as those originally affected. Two were associated with massive intracranial hemorrhage, including one on the contralateral side of original involvement. An additional patient died suddenly of unknown causes. Of the four remaining patients, three declined to resume transfusion and are relatively well at greater than or equal to 18 months after therapy was stopped. The studies performed before transfusions were stopped were not predictive of recurrent stroke. The risk of recurrent cerebrovascular accident in this group was significantly greater than the estimated risk of 10% in patients who are receiving long-term transfusion therapy (p = 0.002). This adverse outcome suggests that patients with sickle cell disease who have had a stroke must receive long-term transfusion indefinitely or a suitable therapeutic alternative must be devised.

Vascular and calcemic effects of plasma of spontaneously hypertensive rats. Circulating substances that increase intracellular calcium, and other circulating substances that increase blood pressure, have been described in hypertensive animals and humans. In this study, we report the existence of a factor of the plasma of spontaneously hypertensive rats that does both. These effects were dose-dependent, and the time course for such effects was correlated with the time course for potentiation of pressor agents by the plasma. In addition, the plasma of spontaneously hypertensive rats was found to inhibit the depressor effects of parathyroid hormone. Our results confirm the presence of a circulating hypertensive factor in the plasma of spontaneously hypertensive rats, which may act by increasing calcium uptake in vascular smooth muscle. These findings may also help explain the secondary increase in parathyroid hormone noted in some forms of human and experimental hypertension.

The blink reflex in cluster headache. To investigate the involvement of the trigeminal system in cluster headache, in twelve subjects the electrically-elicited blink reflex during a symptomatic period was examined. In eleven cases, the amplitude of the contralateral R2 response on the symptomatic side was significantly lower, at the same stimulus intensity, than on the asymptomatic side (p = 0.005). The blink reflex can be useful to evaluate biological and drug-induced phenomena in cluster headache.

A prospective study of magnetic resonance imaging in lymphoma staging. In this prospective study, magnetic resonance imaging (MRI) was compared with computed tomography (CT) in patients with non-Hodgkin's lymphoma (NHDL), and with CT and laparotomy in patients with Hodgkin's disease (HD). Among 31 patients with NHDL, there was agreement between MRI and CT findings in 21 patients; MRI findings were positive and CT findings were negative in 8 patients; and MRI findings were negative and CT findings were positive in 2 patients. The false-negative findings of MRI included a laparotomy-proven mesenteric mass and a 6.6-cm lesion in the spleen, both shown by CT. In 13 evaluable patients with HD, there was agreement between MRI and laparotomy findings in 8 patients; MRI findings were positive and laparotomy findings were negative in 4 patients; and MRI findings were negative and laparotomy findings were positive in 1 patient. CT findings agreed with laparotomy findings in nine patients; CT findings were positive and laparotomy findings were negative in one patient: and CT findings were negative and laparotomy findings were positive in three patients. This suggested that MRI, although more sensitive than CT, was less specific with more false-positive findings. The spin-lattice relaxation time (T1) for the spleen was generally higher in patients with HD who had pathologically confirmed splenic involvement, and tended to increase with increasing spleen weight. This study was performed on a prototype 0.15 Tesla (Technicare Inc., Solon, OH) resistive unit at a time when methods and reporting for MRI were still being developed. Although MRI appears to have fewer false-negative findings than CT in evaluating the abdomen of lymphoma patients, the lack of a gastrointestinal contrast agent and specificity of T1 elevations in the spleen would not suggest that MRI could replace CT or laparotomy as a staging technique.

Splenic septic emboli in endocarditis. The significance of septic emboli to the spleen is inferred by the frequency of septic emboli in general seen in patients with left-sided infective endocarditis who are referred for valve replacement. To determine the proper management of splenic infarcts and abscess due to septic emboli, we retrospectively reviewed the records of 108 patients with left-sided endocarditis who underwent valvular surgery at the University of Illinois Hospital from 1980 through 1988. Intravenous drug abuse was the etiology in 68% (n = 73). The incidence of splenic infarcts and abscess was 19% (n = 20), but an incidental finding of splenic infarcts was found in 38% (n = 11) of 29 asymptomatic patients who had computed tomograms. Streptococci and staphylococci were the causative organisms in 85% (n = 17). Localized findings were absent in 90% of splenic infarcts and abscesses. Abdominal computed tomograms were diagnostic of the sequelae of splenic septic emboli in 100%. No patient had intra-abdominal bleeding complications associated with cardiopulmonary bypass. Splenectomy was performed in 50% (n = 10) of patients 3-24 days (mean, 11.2 days) after valve replacement. Indications for splenectomy included persistent sepsis in 60% (n = 6), large (greater than 2 cm) and peripheral lesions in 30% (n = 3), and splenic rupture in 10% (n = 1). Perioperative mortality of patients who underwent splenectomy was 30% (n = 3). The following conclusions can be drawn: 1) Splenic septic embolus is common in endocarditis. 2) Abdominal computed tomography should be performed for all patients.