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Coagulation studies in the syndrome of haemolysis, elevated liver enzymes and low platelets. The presence of disseminated intravascular coagulation (DIC) in the syndrome of haemolysis, elevated liver enzymes and low platelets (HELLP) is debated. We assessed the occurrence of decompensated and compensated DIC (using predefined criteria) in 15 consecutive nulliparous pregnant patients with gestational hypertension combined with the HELLP syndrome and in 12 consecutive nulliparous controls with pregnancy induced hypertension (PIH) but without the HELLP syndrome. A combination of routine coagulation assays revealed the absence of decompensated DIC in all studied patients. However, using more specific and sensitive coagulation assays, compensated DIC was observed in all HELLP patients and in three patients in the control group. The mean values of antithrombin III, thrombin-antithrombin III complexes and protein C in the HELLP and the control group were 66 vs 87% (P = 0.0004), 21 vs 8 ng/ml (P = 0.0008) and 57 vs 90% (P = 0.0018) respectively. We conclude that HELLP patients show evidence of compensated DIC which may have pathophysiological significance for the observed organ damage.

Human dose-response relationship for decompression and endogenous bubble formation. The dose-response relationship for decompression magnitude and venous gas emboli (VGE) formation in humans was examined. Pressure exposures of 138, 150, and 164 kPa (12, 16, and 20.5 ft of seawater gauge pressure) were conducted in an underwater habitat for 48 h. The 111 human male volunteer subjects then ascended directly to the surface in less than 5 min and were monitored for VGE with a continuous-wave Doppler ultrasound device over the precordium or the subclavian veins at regular intervals for a 24-h period. No signs or symptoms consistent with decompression sickness occurred. However, a large incidence of VGE detection was noted. These data were combined with those from our previously reported experiments at higher pressures, and the data were fit to a Hill dose-response equation with nonlinear least-squares or maximum likelihood routines. Highly significant fits of precordial VGE incidences were obtained with the Hill equation (saturation depth pressure at which there is a 50% probability of detectable VGE [D(VGE)50] = 150 +/- 1.2 kPa). Subclavian monitoring increased the sensitivity of VGE detection and resulted in a leftward shift [D(VGE)50 = 135 +/- 2 kPa] of the best-fit curve. We conclude that the reduction in pressure necessary to produce bubbles in humans is much less than was previously thought; 50% of humans can be expected to generate endogenous bubbles after decompression from a steady-state pressure exposure of only 135 kPa (11 ft of seawater). This may have significant implications for decompression schedule formulation and for altitude exposures that are currently considered benign. These results also imply that endogenous bubbles arise from preexisting gas collections.

Development of antibodies to thrombin and factor V with recurrent bleeding in a patient exposed to topical bovine thrombin. A 65 year old patient who was exposed to topical bovine thrombin during cardiac surgery developed markedly prolonged clotting times and a severe bleeding diathesis. Mixing studies with normal plasma failed to correct the clotting times. Platelet transfusions, immunosuppressive and immunomodulatory therapies were ineffective, but plasmapheresis was effective in decreasing clotting times and in the resolution of clinical bleeding events. The patient's purified IgG reacted with bovine thrombin by immunoblotting and enzyme-linked immunosorbent assay (ELISA). However, the IgG reacted minimally with human thrombin. In view of the severe bleeding, a coexisting inhibitor was sought. The patient's factor V activity was 1% of normal and was not corrected by mixing with normal plasma, demonstrating the presence of an inhibitor against factor V. The patient's IgG reacted with both bovine and human factor V. Immunoblotting localized the site of antibody binding to the light chain of activated bovine factor V. Detectable amounts of bovine factor V were found in commercial bovine thrombin preparations by ELISA. The data suggest that patients exposed to topical bovine thrombin may develop antibodies to thrombin and factor V. Anti-thrombin antibodies may mask coexisting factor V inhibitors responsible for clinical bleeding.

Extracranial repair of cerebrospinal fluid fistulas: technique and results in 37 patients. Although neurosurgeons have traditionally preferred intracranial repair for the management of cerebrospinal fluid (CSF) fistulas, this approach is associated with the complications of a craniotomy, anosmia, and a high incidence of recurrent fistulas. Extracranial repair, on the other hand, produces no central nervous system morbidity, preserves olfaction, and is associated with a low incidence of recurrence. Although there have been several reports of extracranial repair of CSF fistulas by otorhinolaryngologists, this approach has received scant mention in the neurosurgical literature. We report here our experience with 37 patients with CSF rhinorrhea or otorrhea who underwent extracranial repair. The etiology of the fistula was postoperative in 22, traumatic in 6, and spontaneous in 9. The fistulas were repaired using one of four techniques: external ethmoid-sphenoid in 18 patients, transmastoid in 9, transseptosphenoid in 7, and osteoplastic frontal sinusotomy in 3. In 32 of the 37 patients (86%) the fistulas were successfully repaired with the initial procedure. Of the 5 patients requiring a second operation, the fistula was successfully closed in 4 for an overall success rate of 97%. Complications were few and consisted of a transient facial paresis in a patient undergoing transmastoid repair and one death from meningitis. The authors conclude that because of low morbidity and mortality and a high success rate in closing fistulas, extracranial repair is the preferred technique for the operative management of CSF rhinorrhea and otorrhea.

18F-2-deoxy-2-fluoro-D-glucose uptake into human tumor xenografts. Feasibility studies for cancer imaging with positron-emission tomography. The positron-emitting glucose analogue 18F-2-fluoro-2-deoxy-d-glucose (FDG) was evaluated for its accretion into the following subcutaneous human tumor xenografts in nude mice: B-cell lymphoma (Namalwa or Raji), ovarian carcinoma (HTB77), colon cancer (SW948), choriocarcinoma (BEWO), bladder cancer (UM-UC-2), renal cell carcinoma (UM-RC-3), neuroblastoma (Mey), melanoma (HTB63), and small cell lung carcinoma (NCI69). Two hours postinjection, tumor uptakes ranged from 0.027 (colon cancer) to 0.125% kg injected dose/g (melanoma); and was greater than 0.085 in the Namalwa lymphomas and the renal cell carcinomas. Tumor-blood ratios of up to 23:1 were seen 2 hours postinjection (melanoma) with a mean tumor-blood ratio for all tumors of 12.3 +/- 1.8. Uptake in the other tumors was intermediate. When evaluated, tumor uptake was slightly greater at 1 than at 2 hours postinjection, although target-background ratios were generally higher at 2 hours postinjection. This compound, FDG, may have broad applicability as a tracer for positron-emission tomographic imaging of many human malignancies.

Magnetic resonance imaging and tomographic evaluation of occlusal appliance treatment for advanced internal derangement of the temporomandibular joint. This study evaluates the positional relationship of the disc and mandibular condyle in patients with late opening clicks treated with appliance therapy. A total of 30 joints (18 patients) were studied. Twenty-seven of these 30 joints were treated with the appliance until the joints were silent to auscultation. The patients were then evaluated with axial corrected tomography and magnetic resonance imaging (MRI) in the centric occlusion position and with their bite appliance (Sved-type) in place. Comparisons were made between condyle position in centric occlusion and with the appliance in place. Magnetic resonance imaging was then used to evaluate disc positional changes. Each imaging procedure was made in the same sagittal plane. Only changes in condyle positioning could be identified. Evidence of disc repositioning with the appliance in place was seen in only three MRI examinations. The remaining 27 joints continued to exhibit disc displacement with various changes in disc morphology. It is concluded that the concept of "disc capture" is a clinical term only, and that such perceived clinical success should not lead to the assumption that an actual change in intra-articular anatomic relationships has occurred. Joint noises may decrease because joint space is increased, allowing smoother condylar translation beyond disc surface irregularities and positional abnormalities.

Therapy for acute infectious diarrhea in children. This article reviews current recommendations of therapy with antidiarrheal compounds and antimicrobial agents for acute infectious diarrhea in children. In most infants and children with acute infectious diarrhea, treatment with antidiarrheal compounds is not indicated. Many of these compounds interfere with identification of enteropathogens in stool specimens, and the antimotility class has an overdose potential. Antimicrobial therapy is given to reduce symptoms and to prevent the spread of infection by decreasing fecal shedding of organisms. Although effective therapy is not available for patients with enteric viruses, Cryptosporidium, and Microsporidium, therapy is useful for children with amebiasis, antimicrobial-associated colitis, cholera, giardiasis, various forms of Escherichia coli diarrhea and Salmonella disease, isosporiasis, shigellosis, and strongyloidiasis. For several other conditions, antimicrobial therapy is of questionable benefit (infection with Campylobacter jejuni or Yersinia enterocolitica, intestinal salmonellosis and enterohemorrhagic E. coli infection). Compounds such as the fluoroquinolones, which are effective in the treatment of acute infectious diarrhea in adults, are not approved for use in children because of potential side effects. Many bacterial, viral, and parasitic organisms cause acute infectious diarrhea; appropriate antimicrobial therapy requires the accurate, rapid identification of the offending enteropathogen. In children with an underlying illness such as acquired immunodeficiency syndrome, manifestations may be prolonged, severe, and recurrent despite appropriate therapy.

Parathyroid hormone-related peptide in lactation and in umbilical cord blood. Parathyroid hormone-related peptide (PTHrP) is expressed in lactating rat mammary glands after suckling, as a result of increases in prolactin rather than suckling per se. In addition, PTHrP produced in the fetal parathyroid glands and placenta may be responsible for stimulation of placental calcium transport. In the current study, we used a radioimmunoassay for human PTHrP to measure levels of the peptide in (1) human breast milk, cow's milk, and two infant formulas; (2) sequential plasma samples in prepartum and postpartum lactating women; (3) women with pathologic hyperprolactinemia; and (4) human umbilical cord blood. In normal subjects, plasma PTHrP levels ranged from less than 2 to 5 pmol/liter. In contrast, human breast milk contained substantially increased levels of immunoreactive PTHrP. Similar elevations were found in cow's milk and in one infant formula. Column chromatography of breast milk demonstrated that PTHrP immunoreactivity included a region of adenylate cyclase stimulating activity, consistent with the presence of biologically active PTHrP. Plasma prepartum PTHrP values did not differ from corresponding postpartum values in lactating women. Women with hyperprolactinemia had a mean plasma PTHrP value in the high-normal range. Umbilical cord blood had considerably suppressed parathyroid hormone values but PTHrP levels that were indistinguishable from those in normal human plasma. Thus, PTHrP is present in high concentrations in breast milk but apparently does not gain access to the maternal circulation in significant amounts. In addition, women with pathologic hyperprolactinemia seem not to have increased levels of circulating PTHrP.

Primary renal lymphoma. Lymphoma arising in the kidney is rare. Although 31 cases have been reported in the literature, it is likely that most of these neoplasms do not arise in the kidney. This report describes two cases of primary renal lymphoma and compares their clinical presentation, diagnostic modalities, treatment, and survival with the previously reported patients who satisfied our criteria for the diagnosis of primary renal lymphoma.

Deceptive bizarre stromal cells in polyps and ulcers of the gastrointestinal tract. The clinical and pathologic features of 33 pseudomalignant lesions of the gastrointestinal tract with bizarre stromal cells are reported. Deceptive histologic changes were identified in ulcers of seven patients and in inflammatory polyps of 26. A misdiagnosis of malignant neoplasm was made in six of the 33 patients (three polyps and three ulcers). A history of gastrointestinal bleeding and/or inflammatory bowel disease was common. The bizarre stromal cells were usually distributed beneath the ulcerated mucosa or within granulation tissue. They stained strongly for vimentin in 20 of 23 cases. Some of the bizarre cells also stained for muscle specific actin (seven of 23 cases). The cells appear to be reactive fibroblasts or myofibroblasts. Follow-up information obtained on 24 of the 33 patients (including four of the six cases initially diagnosed as malignant) revealed 22 patients to be alive without evidence of a malignant neoplasm (average follow-up, 13 months). Two patients died of other causes. Correct recognition of these bizarre stromal cells in gastrointestinal ulcers and inflammatory polyps will prevent a potentially serious diagnostic pitfall.

New chemotherapies for ovarian cancer. Systemic and intraperitoneal podophyllotoxins. The epipodophyllotoxin derivatives etoposide and teniposide have been evaluated intermittently for possible use in the treatment of ovarian cancer. Conflicting studies suggest that variables such as dose and prior treatment have a major influence on outcome. Response rates ranged from 0% to 40% in five series with teniposide, and from less than a 10% overall response rate to greater than a 10% complete response rate in nine studies with etoposide. One study documented activity with oral etoposide. However, because all patients had received various prior chemotherapies, firm conclusions regarding the activity of etoposide could not be drawn. These results, and the expectation of synergy with etoposide and cisplatin, led to several studies that combined etoposide with platin compounds by the systemic and intraperitoneal (IP) routes. Various studies have used intravenous drug combinations of these agents in both previously treated and untreated patients. One study, which used carboplatin instead of cisplatin, reported only seven failures among 26 previously untreated patients. Conversely, the prominent toxicities reported by another study were discouraging, and responses did not exceed what might be expected from cisplatin alone. Studies of analogous combinations administered IP are ongoing. A favorable experience, which was initially reported by the University of California (San Diego group), is being confirmed by other investigators. This has prompted the incorporation of etoposide into first-line strategies. The pharmacologic advantage of etoposide by the IP route (related to its high protein binding) may provide appropriate dose intensity against IP disease while sparing systemic toxicities. Finally, systemic dose intensity with autologous bone marrow support indicates some promise for etoposide in combination with high-dose alkylating drugs.

A clinicopathological study of the paraneoplastic neuromuscular syndromes associated with lung cancer. The highest incidence of remote neuromuscular disorders in cancer has previously been reported in lung carcinoma. The clinical incidence of neuromuscular disorder was estimated and correlated with muscle histology and the histological type of lung tumour in 100 patients with lung carcinoma who were studied prospectively. Thirty-five patients had small cell carcinoma and 65 patients non-small cell lung cancer. Clinically, 33 patients had a polymyopathy, of whom 18 had a cachectic myopathy and 15 had a proximal myopathy (two patients had Lambert-Eaton myasthenic syndrome, one presented with dermatomyositis and one had evidence of ectopic ACTH production). Cachexia was more common in non-small cell cancer; proximal myopathy was more common in small cell cancer. Ninety-nine patients had abnormal muscle histology; 74 had type II atrophy, 12 had type I and II atrophy, one had type I atrophy and 12 had necrosis. The majority of patients were affected sub-clinically and the clinical entities of cachectic and proximal myopathy did not correspond to previous pathological classifications. Atrophy was not related to the duration of tumour symptoms, ageing, clinical type of myopathy or histological type of lung tumour, and was statistically different from that seen in controls. Qualitatively, the presence of weight loss, muscle wasting and metastatic disease were not factors in the development of atrophy. Similarly, necrosis was not related to the type of lung tumour, the presence of metastases, ageing, weight loss, muscle wasting, duration of tumour symptoms or the clinical form of myopathy. This study demonstrates that lung carcinoma has a direct effect on the motor unit, including atrophy, a necrobiotic myopathy and Lambert-Eaton myasthenic syndrome. Clinical assessment does not accurately assess the 'remote' neuromuscular effects of cancer on the motor unit.

Parental history is an independent risk factor for coronary artery disease: the Framingham Study. Family history of CAD, defined as parental death by CAD, was found to be a significant independent predictor of CAD in a logistic regression model controlling for standard risk factors and length of follow-up among the 5209 participants in the Framingham Study. Persons with a positive parental history have a 29% increased risk of CAD, and the strength of the association between parental history and CAD is similar to that found for other standard risk factors such as systolic blood pressure, cholesterol level, and cigarette smoking. No evidence was found that persons with a family history of CAD have a decreased capacity to cope with the deleterious effects of known risk factors; that is, no significant interaction was found between any of the risk factors and parental history of CAD. Among men with low risk for CAD by risk-factor profile (i.e., nonsmoking, thin, nonhypertensive persons), more than two thirds of those who experience CAD have a positive parental history. This study suggests that CAD among persons who are predicted to be at low risk by standard risk factors may have a substantial genetic component and that the risk associated with parental history may not be reduced by modification of these factors. Nevertheless, among persons with a positive family history, those with a favorable risk profile are at substantially less risk for CAD than those with an unfavorable risk profile.

Razor-blade surgery. The razor blade can be a valuable tool in the performance of many minor surgical procedures. It is extremely sharp, flexible, inexpensive, readily available, and easy to use. The technique and specific applications are reviewed and discussed.

Strabismus caused by melanoma metastatic to an extraocular muscle. Nonocular melanoma rarely metastasizes to the orbit. We report the case of a melanoma presumably arising from an axillary lymph node sinus that metastasized to the left medial rectus muscle causing proptosis, diplopia, and reduced saccadic velocity measurements. Clinical, radiographic, and histopathologic data are presented and discussed.

A randomized, controlled trial of prophylactic ganciclovir for cytomegalovirus pulmonary infection in recipients of allogeneic bone marrow transplants; The City of Hope-Stanford-Syntex CMV Study Group BACKGROUND. Cytomegalovirus (CMV)-associated interstitial pneumonia is a major cause of death after allogeneic bone marrow transplantation. We conducted a controlled trial of ganciclovir in recipients of bone marrow transplants who had asymptomatic pulmonary CMV infection. We also sought to identify risk factors for the development of CMV interstitial pneumonia. METHODS. After bone marrow transplantation, 104 patients who had no evidence of respiratory disease underwent routine bronchoalveolar lavage on day 35. The 40 patients who had positive cultures for CMV were randomly assigned to either prophylactic ganciclovir or observation alone. Ganciclovir (5 mg per kilogram of body weight intravenously) was given twice daily for two weeks and then five times per week until day 120. RESULTS. Of the 20 culture-positive patients who received prophylactic ganciclovir, 5 (25 percent) died or had CMV pneumonia before day 120, as compared with 14 of the 20 culture-positive control patients (70 percent) who were not treated prophylactically (relative risk, 0.36; P = 0.01). No patient who received the full course of ganciclovir prophylaxis went on to have CMV interstitial pneumonia. Four patients treated with ganciclovir had maximal serum creatinine levels greater than or equal to 221 mumol per liter (2.5 mg per deciliter), as compared with none of the controls (P = 0.029). Of the 55 CMV-negative patients who could be evaluated, 12 (22 percent) had CMV pneumonia--a significantly lower rate than in the untreated CMV-positive control patients (relative risk, 0.33; P = 0.003). The strongest predictors of CMV pneumonia were a lavage-fluid culture that was positive for CMV and a CMV-positive blood culture, both from specimens obtained on day 35. CONCLUSION. In recipients of allogeneic bone marrow, asymptomatic CMV infection of the lung is a major risk factor for subsequent CMV interstitial pneumonia. Prophylactic ganciclovir is effective in preventing the development of CMV interstitial pneumonia in patients with asymptomatic infection.

Pharmacological versus non-pharmacological prophylaxis of recurrent migraine headache: a meta-analytic review of clinical trials. In order to generate information about the relative effectiveness of the most widely used pharmacological and non-pharmacological interventions for the prophylaxis of recurrent migraine (i.e., propranolol HCl and combined relaxation/thermal biofeedback training), meta-analysis was used to integrate results from 25 clinical trials evaluating the effectiveness of propranolol and 35 clinical trials evaluating the effectiveness of relaxation/biofeedback training (2445 patients, collectively). Meta-analysis revealed substantial, but very similar improvements have been obtained with propranolol and with relaxation/biofeedback training. When daily recordings have been used to assess treatment outcome, both propranolol and relaxation/biofeedback have yielded a 43% reduction in migraine headache activity in the average patient. When improvements have been assessed using other outcome measures (e.g., physician/therapist ratings), improvements observed with each treatment have been about 20% greater. In both cases, improvements observed with propranolol and relaxation/biofeedback have been significantly larger than improvement observed with placebo medication (14% reduction) or in untreated patients (no reduction). Meta-analysis thus revealed substantial empirical support for the effectiveness of both propranolol and relaxation/biofeedback training, but revealed no support for the contention that the two treatments differ in effectiveness. These results suggest that greater attention should be paid to determining the relative costs and benefits of widely used pharmacological and non-pharmacological treatments.

Results of treatment of displaced patellar fractures by partial patellectomy. The results of partial patellectomy as a treatment for displaced patellar fractures were assessed retrospectively with use of clinical, radiographic, and isokinetic strength-testing criteria. Forty patients who had been followed for an average of 8.4 years were studied. In the extremity that had been operated on, the mean active range of motion was 94 per cent, the circumference of the thigh was 100 per cent, and the strength of the quadriceps was 85 per cent of these measurements in the contralateral extremity. The over-all result was rated as excellent in twenty patients, good in eleven, fair in six, and poor in three. There was a significant statistical correlation between the type of fracture and the outcome. The results of this study indicate that partial patellectomy can be an effective treatment for selected patellar fractures.

Predictors of morbidity and mortality in neonates with herpes simplex virus infections. The National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. BACKGROUND. In a controlled trial comparing acyclovir with vidarabine in the treatment of neonatal herpes simplex virus (HSV) infection, we found no significant difference between the treatments in adjusted mortality and morbidity. Hence, we sought to define for the entire cohort (n = 202) the clinical characteristics that best predicted the eventual outcome in these neonates. METHODS. Data were gathered prospectively at 27 centers between 1981 and 1988 in infants less than one month of age who had virologically confirmed HSV infection. We examined the outcomes by multivariate analyses of 24 variables. Disease was classified in one of three categories based on the extent of the involvement at entry into the trial: infection confined to skin, eyes, or mouth; encephalitis; or disseminated infection. RESULTS AND CONCLUSIONS. There were no deaths among the 85 infants with localized HSV infection. The mortality rate was significantly higher in the 46 neonates with disseminated infection (57 percent) than in the 71 with encephalitis (15 percent). In addition, the risk of death was increased in neonates who were in or near coma at entry (relative risk, 5.2), had disseminated intravascular coagulopathy (relative risk, 3.8), or were premature (relative risk, 3.7). In babies with disseminated disease, HSV pneumonitis was also associated with greater mortality (relative risk, 3.6). In the survivors, morbidity was most frequent in infants with encephalitis (relative risk, 4.4), disseminated infection (relative risk, 2.1), seizures (relative risk, 3.0), or infection with HSV type 2 (relative risk, 4.9). With HSV infection limited to the skin, eyes, or mouth, the presence of three or more recurrences of vesicles was associated with an increased risk of neurologic impairment as compared with two or fewer recurrences.

The management of pseudomyxoma peritonei. The management of nine patients with pseudomyxoma peritonei was reviewed. Aggressive surgical resection of tumor is the standard of treatment, with many patients requiring multiple laparotomies. Chemotherapy, including the use of cisplatin is not effective. Long-term nutritional support provides a better quality of survival for select patients.

Trans-scleral application of a semiconductor diode laser. We used a diode laser with an output power of 1 W through a fiberoptic light pipe (200 microns diameter) to deliver laser energy through the sclera of pigmented rabbits. Ciliary body destruction occurred with energy levels of 300-400 mW and exposure time of 0.5 sec. Retinal photocoagulation was achieved with energy levels of 200-500 mW in 0.5 sec. Histologic examination of acute lesions demonstrated thermal destruction of ciliary body processes and retina. Chorioretinal scar formation was observed clinically and histologically within 2-3 weeks. Our data indicate that the transscleral diode laser may be used for destruction of the ciliary body processes or peripheral retinal coagulation in pigmented eyes.

Dose-dependent reduction of myocardial infarct size with the perfluorochemical Fluosol-DA. The perfluorochemical Fluosol-DA has been shown to reduce infarct size. However, the dose-response relationship of the agent is unknown. Because perfluorochemicals (PFC) can potentially saturate the reticuloendothelial system and decrease carbon clearance as well as cause a transient elevation in liver enzymes, the present study was conducted to determine the lowest effective dose. New Zealand White rabbits (n = 73) were randomly selected prior to infarction to receive 10, 15, 20, 25, or 30 ml/kg PFC or an equivalent volume of 5% dextran (control) intravenously. Animals underwent 30 minutes of coronary artery occlusion with PFC or dextran infused over a 30-minute period starting at 20 minutes into the occlusion. Animals were put to death at 24 hours and infarct size was determined histologically and quantitated by computerized planimetry. Neutrophil infiltration into the ischemic myocardium was evaluated semiquantitatively. No hemodynamic differences were noted within groups. Infarct size was similar to that of controls in animals treated with 10 or 15 ml/kg PFC. Significant infarct size reduction, however, was noted in animals treated with 20, 25, and 30 ml/kg PFC versus controls; (p = 0.05, 0.04, and 0.02, respectively). Maximal infarct size reduction was seen with 30 ml/kg PFC (35%). Neutrophil infiltration was significantly decreased in all groups treated with PFC. These results show that intravenous Fluosol-DA significantly reduces infarct size at a minimal dose of 20 ml/kg.

Sudden death caused by coronary artery aneurysms: a late complication of Kawasaki disease. The authors describe three cases (two blacks and one Latin American) of sudden death caused by late complications of Kawasaki disease (mucocutaneous lymph node syndrome). At autopsy each heart contained multiple coronary artery aneurysms with luminal stenosis caused by intimal hyperplasia and thrombi. Although virtually all fatal cases of Kawasaki disease occur within six months of the onset of symptoms, there have been other reported deaths up to 14 years after the acute illness. The coronary artery aneurysms of Kawasaki disease may persist and cause death years after the acute illness.

Small non-cleaved-cell lymphoma (undifferentiated lymphoma, Burkitt's type) in American adults: results with treatment designed for acute lymphoblastic leukemia. PURPOSE: Small non-cleaved-cell lymphoma (SNCL) "Burkitt's type," a rapidly growing lymphoma, has been rare among adults in the United States, but has greatly increased in incidence with the acquired immunodeficiency syndrome epidemic. This report details the results of treatment of adult SNCL with a series of protocols originally designed for the treatment of acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Between July 1973 and May 1987, 29 adults with newly diagnosed SNCL were treated at Memorial Hospital with intensive chemotherapy originally designed for ALL: the cyclophosphamide L-2, L-10, L-17, and L-20 protocols. Nine patients had positive serologies for human immunodeficiency virus (HIV) infection. One patient with all measurable disease resected was not evaluable for response. RESULTS: Sixteen of 28 evaluable patients (57%) achieved a complete remission with treatment. With follow-up as long as 153 months (median, 47 months), 50% of all patients and 59% of patients with negative or unknown HIV serologies have survived and are probably cured. Patients with an initial serum lactic acid dehydrogenase (LDH) level of greater than 500 U/L had a significantly shortened survival as compared with those with a lower serum LDH. Other pretreatment patient characteristics associated with a shortened survival of borderline statistical significance were high National Cancer Institute stage (C, D) and bone marrow involvement. These results are similar to those for ALL and lymphoblastic lymphoma and are comparable to those for American SNCL in the literature. CONCLUSIONS: Approximately one half of adults with SNCL are curable with intensive chemotherapy. More intensive chemotherapy with hematopoietic growth factor and/or autologous bone marrow or peripheral stem cell support may increase curability.

Seizure outcome from anterior and complete corpus callosotomy. Eighty patients underwent anterior corpus callosotomy for treatment of generalized seizures. The patients' mean age was 18.3 years (range 4 to 53 years); the mean age at seizure onset was 5.27 years (range 0.1 to 27 years). The mean intelligence quotient (IQ) of 41 testable patients was 71.12 (range less than 30 to 114). The seizure outcome was as follows: 13% were seizure-free, 65% were significantly improved, and 22% were unchanged. Ten patients subsequently underwent a second operation to complete the callosal sectioning which resulted in additional seizure improvement in only five of them. Five complications resulted from 90 operations: two epidural hematomas, one delayed subdural hematoma, one bone-flap infection, and one postcallosotomy disconnection syndrome; two patients died. A younger age at onset of seizures, a higher IQ, and generalized tonic-clonic, atonic, complex-partial, and mixed seizure types were associated with improved seizure outcome.

High incidence of antibodies to HTLV-I tax in blood relatives of adult T cell leukemia patients. Adult T cell leukemia (ATL) is caused by the human T cell leukemia virus type I (HTLV-I). Although the mechanisms of the leukemogenic process are unknown, the tax gene may have a role in this process. Because clustering occurs with HTLV-I and ATL, members of ATL families were examined for antibodies to the tax protein and compared with matched HTLV-I-positive blood donors. To investigate the antibody response to this protein, a plasmid, pBHX-4, was constructed to express a recombinant tax protein (r-tax). For ATL patients and their HTLV-I antibody-positive blood relatives, the rate of seroreactivity with the r-tax protein was 67.3% (35/52), compared with 51.6% (97/188) for HTLV-I antibody-positive control blood donors (P less than .05). The difference between direct offspring of ATL patients and matched HTLV-I blood donors was even greater (84.2% [16/91] vs. 44.2% [42/95]; P less than .005). Thus, tax antibody positivity in direct offspring of ATL patients may reflect differences in time or route of HTLV-I infection. Alternatively, it might reflect genetic differences in host susceptibility or virus strain.

Intrapericardial infusion of 5-fluorouracil. An unusual complication of a Hickman catheter. Venous access devices (VAD) have become an important tool in the management of patients with cancer. Multiple complications can occur as a consequence of insertion of a VAD. The authors report a case of a Hickman catheter perforating the wall of the superior vena cava into the pericardium, resulting in accidental intrapericardial infusion of 5-fluorouracil (5-FU). Pericarditis and cardiac arrhythmias developed, but the patient did not have cardiac tamponade. She recovered from the event without apparent chronic cardiac dysfunction.

Coumadin-induced gastrointestinal hemorrhage associated with an ileal duplication. A 31-year-old man had recurrent gastrointestinal hemorrhage after aortic valve replacement and initiation of anticoagulation therapy with coumadin. Radionuclide bleeding scan and subsequent contrast angiogram demonstrated a site of hemorrhage in the distal ileum, and at surgery a 1.8-cm spherical duplication was found. On histologic examination, the duplication was lined with normal ileal mucosa, and near the mouth of the duplication an inflammatory ulceration proved to be the site of hemorrhage. In a young patient with anticoagulation-associated gastrointestinal hemorrhage, alimentary tract duplication should be considered.

Response rates in relapsed Wilms' tumor. A need for new effective agents. Three hundred eighty-one children with Wilms' tumor were treated in the United Kingdom Children's Cancer Study Group WT1 Study (1982 to 1986). Seventy-one patients had relapses during or after treatment with surgery and chemotherapy, and radiation therapy, depending on stage and histologic characteristics. Forty-nine patients were evaluable for disease response to second-line chemotherapy alone. Evaluation of response to chemotherapy was impossible in the remaining patients because either surgery or radiation therapy was used at the time of relapse. With second-line combination chemotherapy (which included ifosfamide, etoposide/VM26, cisplatin/carboplatin, bleomycin, melphalan, and Thiotepa [Lederle Laboratories, Pearl River, NY]), there were five complete responses and 12 partial responses. In patients with favorable histologic findings, six of nine with Stage I, five of ten with Stage II, none of 11 with Stage III, three of 16 with Stage IV, and one of five with Stage V disease survived. Two survivors were treated with chemotherapy alone; the others received combined treatment with chemotherapy, radiation therapy, and/or surgery. For those with unfavorable histologic findings of any stage, only two of 20 survived. The authors conclude that, even for patients with localized disease with favorable histologic findings, the "salvage" rate is little more than 50%, and for all other stages and histologic findings the likelihood of cure after relapse is remote. There is clearly a need for additional effective chemotherapeutic agents for these patients.

Prostatic urethra dilatation with the Gianturco self-expanding metallic stent: a feasibility study in cadaver specimens and dogs. In an effort to develop a transcatheter technique for dilatation of the prostatic urethra without the use of balloons, the feasibility of using Gianturco self-expanding stents was evaluated. Initially, eight human cadaveric prostatic urethras were stented to evaluate the ability of the stent to dilate the lumen. In all cases, the device attained its unconstrained diameter immediately on placement. Subsequently, stents were placed in the prostatic urethra of 12 dogs and followed up for 1 month (four dogs), 3 months (one dog), and 6 months (seven dogs). Five bare straight-end prostheses, one nylon-covered straight-end device, and six flared-end stents were used. Three of the bare straight-end stents migrated during the follow-up, whereas the nylon-covered and flared-end stents did not. Stent diameters greater than 1.3 times the urethral diameter caused moderate to marked edema and inflammation. After 6 months, white deposits were found on the solder points, presumably from electrolysis. Our experience suggests that placement of Gianturco self-expanding stents may be a useful method of dilating and maintaining the luminal diameter of the prostatic urethra, although care must be taken to select the proper stent size.

Reverse coitus: mechanism of urethral injury in male partner. Reverse coitus, a rarely used sexual position, makes the male urethra more vulnerable to injury from the pubic arch and symphysis pubis of the female partner. Severe pain, bleeding and immediate detumescence were observed in 3 patients. The lesion usually occurred at the fossa navicularis, responded well to conservative management and did not hinder micturition. Potency has been well preserved in all 3 patients.

In vitro anticolon antibody production by mucosal or peripheral blood lymphocytes from patients with ulcerative colitis [published erratum appears in Gut 1991 Apr;32(4):460] Serum anticolon antibody and in vitro anti-colon antibody production by peripheral blood and mucosal lymphocytes was investigated in patients with ulcerative colitis. The frequency of serum anticolon antibody was 71% in 41 patients with ulcerative colitis, estimated by enzyme linked immunosorbent assay (ELISA) using isolated rat colon epithelial cells. This finding confirms our previous report on the frequency of serum anticolon antibody detected by flow cytometry analysis. The estimated frequencies of IgG anticolon antibody secreting cells were 1.5-12.5/10(6) cells in the colonic mucosa and 0.1-0.5/10(6) cells in peripheral blood, from patients with ulcerative colitis when Epstein-Barr virus (EBV) was used as a B cell polyclonal activator. Poisson analysis of limiting dilution culture showed that about one per 140 IgG cells in the colonic mucosa synthesised anticolon antibody. Two monoclonal IgG antibodies were obtained from EBV transformed anticolon antibody secreting cells by limiting dilution method. One reacted with goblet cells in the intestine, and the other reacted mainly with colonic epithelial cells. These results suggest that heterogeneous anticolon antibodies are present in patients with ulcerative colitis and that colonic mucosa may be the main source of anticolon antibody. Local autoimmune reaction might have an important role in causing the inflammation of colonic mucosa in this disease.

Very low birth weight children: behavior problems and school difficulty in a national sample We addressed three questions concerning the behavioral and academic status of low and very low birth weight infants through a secondary analysis of the 1981 National Health Interview Survey--Child Health Supplement: (1) in children born with very low birth weight, what is the risk of behavior problems and school difficulty compared with that in heavier low birth weight and normal birth weight children? (2) What are the correlates of school difficulty? (3) Are behavior problems associated with school difficulty when variables are controlled for these correlates? The analysis revealed that 34% of very low birth weight children could be characterized as having school difficulty, compared with 20% and 14% of the other groups, respectively, and that they were more likely to have higher scores on the hyperactive subscale of the Behavior Problems Index. Although a broad array of sociodemographic factors correlated with school difficulty, very low birth weight and hyperactivity scores contributed independently to the risk of academic problems. We conclude that very low birth weight infants are at risk of having school problems that are in part associated with hyperactive behavior.

Postischemic seizures and necrotizing ischemic brain damage: neuroprotective effect of postischemic diazepam and insulin. Insulin has recently been shown experimentally to modify ischemic brain damage when administered either before or after the episode of ischemia. In controlled studies in the rat, high doses of insulin (greater than or equal to 8 IU/kg) result in seizures and early death. The present study was undertaken to determine whether diazepam, a potent, centrally penetrating GABAmimetic, alone or in combination with insulin, could mitigate postischemic seizures or regional selective neuronal necrosis and infarction. Forebrain ischemia was induced in rats for 10 1/2 minutes by carotid clamping and hypotension. The animals were observed clinically until elective perfusion-fixation and quantitative pathologic examination at 1-week recovery. Diazepam, either alone or with insulin, reduced regional brain necrosis and reduced the seizure rate. Insulin alone also led to reduced regional necrosis. However, the combination of diazepam plus insulin yielded the greatest proportion of undamaged brains in the hippocampus, thalamus, and midbrain. In the neocortex, the diazepam-only group showed the greatest number of normal hemispheres. Hypothalamic infarction was eliminated by all three treatments. Seizures per se were associated with increased damage in the cerebral cortex, thalamus, and brainstem, irrespective of treatment group. The findings indicate that ischemic brain necrosis can be mitigated by diazepam and insulin treatment begun in the immediate postischemic period.

Dietary intake in patients with acquired immunodeficiency syndrome (AIDS), patients with AIDS-related complex, and serologically positive human immunodeficiency virus patients: correlations with nutritional status. One of the major clinical manifestations of the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC) is the development of cachexia. This most likely results from a multifactorial interplay of poor diet, malabsorption, and altered metabolism. To assess the potential role of nutrient intake in the development or persistence of malnutrition, a detailed analysis was performed of a 72-hr diet record in clinically stable patients with AIDS (N = 18), ARC (N = 12) and in human immunodeficiency virus (HIV) seropositive controls without significant manifestations of disease (N = 13). Total calorie intake was 39.1 +/- 13.2 kcal/kg/day in AIDS patients vs 34.6 +/- 7.8 kcal/kg/day in ARC patients or 31.9 +/- 17.7 kcal/kg/day in HIV seropositive cases (all p = NS). Likewise, mean protein intakes were similar among the groups and exceeded recommended daily dietary allowance (RDA) guidelines. The mean body weight changes from the inception of illness were -11 +/- 1% in AIDS, -6 +/- 7% in ARC, vs +3 +/- 2% in HIV-seropositive-only cases (p less than 0.05 vs AIDS and ARC). Dietary vitamin and mineral analysis revealed that 88% of AIDS, 88% of HIV seropositive, and 89% of ARC patients were ingesting less than 50% RDA for at least one nutrient. The mean number of deficiencies per patient was 1.8 +/- 1.3 in AIDS, 3.8 +/- 3.5 in ARC, and 2.9 +/- 2.5 in HIV-seropositive-only cases (p less than 0.05 AIDS vs ARC). There were no significant correlations between specific anthropometric measurements and dietary intakes of protein or fat.

Measurement of D-dimer in plasma as diagnostic aid in suspected pulmonary embolism The potential of plasma measurement of D-dimer (DD), a specific derivative of crosslinked fibrin, for diagnosis or exclusion of pulmonary embolism was investigated in a prospective series of 171 consecutive patients who attended an emergency department with suspected pulmonary embolism. The diagnosis was made or excluded by means of a clinical decision-making process which included clinical evaluation, ventilation-perfusion (VQ) lung scan, and, as indicated, pulmonary angiography, venography, or non-invasive examination of the leg veins. Pulmonary embolism was diagnosed by this process in 55 (32%) of 170 patients with sufficient data. All but 1 of these 55 patients had a DD concentration of 500 micrograms/l or above. The sensitivity and specificity of this cutoff concentration for the presence of pulmonary embolism were 98% and 39%, respectively, which give positive and negative predictive values of 44% and 98%. Among the 115 patients (68%) who had inconclusive VQ scans, 31 were diagnosed as having pulmonary embolism. 29 of the remaining 84 patients without pulmonary embolism had DD concentrations below 500 micrograms/l, which means that further diagnostic procedures could have been avoided in a quarter of the patients with inconclusive VQ scans. The sensitivity of the plasma measurement of DD remained high even 3 and 7 days after presentation (96% and 93%). Plasma measurement of DD therefore has a definite place in the diagnostic procedure for suspected acute pulmonary embolism in attenders at emergency departments: a concentration below 500 micrograms/l rules out the diagnosis.

Renal function in obstructive jaundice in man: cholangiocarcinoma model. Renal function with respect to water clearance and renal hemodynamics was studied in 15 patients with obstructive jaundice due to cholangiocarcinoma. The results were compared with those of the control normal subjects. There was no change in renal function in the patients with mild to moderate jaundice, with total serum bilirubin from 8.0 to 15.1 mg/dl. Increased urinary sodium excretion and decreased free water and negative water clearances were observed in the patients with severe jaundice with total serum bilirubin from 27.0 to 40.4 mg/dl and normal serum albumin. Renal blood flow was normal, but creatinine clearance was decreased. In severely jaundiced patients with serum bilirubin from 30.5 to 40.1 mg/dl and hypoalbuminemia urinary sodium excretion, free water clearance, negative water clearance, renal blood flow and creatinine clearance were decreased. There was salt and water retention in this group. The findings suggest that in severe jaundice there is inhibition of sodium chloride reabsorption in the thick ascending limb of Henle's loop. ADH and increased hydraulic conductivity of the collecting tubules possibly contribute to decreased free water clearance. In severely jaundiced patients with hypoalbuminemia this salt losing effect is converted to salt retention by increased proximal tubular reabsorption of sodium.

Treatment of congenital coronary arteriovenous malformations with micro-particle embolization. The successful treatment of a symptomatic coronary arteriovenous malformation (CAVM) by a percutaneous embolization technique with micro-particles is described. Objective evidence of ischemia and its subsequent disappearance after embolization is presented. The embolization technique and possible indications and contraindications are discussed.

Immunohistochemical detection of P-glycoprotein in endometrial adenocarcinoma. P-glycoprotein (Pgp) has emerged as the central mediator in classic multidrug resistance in model systems in vitro. High levels of Pgp also have been detected in many normal human tissues and tumors; and its role in clinical drug resistance is currently under investigation. Recently significant levels of Pgp were localized to gravid and secretory endometrium; and it was demonstrated that the combination of estrogen and progesterone is sufficient to induce high levels of both Pgp mRNA and Pgp in uterine secretory epithelium. These findings suggest that increased Pgp expression also may be present in hormone-responsive malignancies such as endometrial adenocarcinoma. To determine whether Pgp is expressed in endometrial adenocarcinoma, 36 endometrial adenocarcinomas (grade I [n = 17]; grade II [n = 6]; grade III [n = 13]) were investigated retrospectively by the avidin-biotin-complex immunohistochemical procedure using three murine monoclonal antibodies (MAb) MAb C219, MAb C494, and MAb JSB-1, which recognize spatially distinct cytoplasmic epitopes of Pgp. Seventy-two percent of the tumors showed positive immunostaining with at least one MAb; 67% showed immunostaining with MAb C219, 50% with MAb C494, and 62% with MAb JSB-1. Forty-six percent of tumors were immunoreactive to two and 29% to all three antibodies. Membranous and Golgi/paranuclear type staining patterns were observed. Overall the intensity of immunostaining varied from one sample to another for a given tumor type, and considerable heterogeneity of expression was commonly seen within a given tumor. Strong to moderate immunoreactivity was seen in diffusely infiltrating, adenosquamous, and serous papillary carcinomas. In general, immunoreactivity to MAb C494 was weaker than MAb C219 or MAb JSB-1. Adenomatous and non-neoplastic endometrium adjacent to the tumors displayed strong membranous immunostaining with MAb JSB-1. Endometrial capillaries showed weak-to-moderate immunostaining to all three antibodies. It is concluded that Pgp is commonly expressed in endometrial adenocarcinoma and may be a significant factor responsible for their drug-resistant nature subject to modulation by progesterone.

Acute dissection of the internal mammary artery: a fatal complication of coronary artery bypass grafting. A case of acute traumatic dissection of the right internal mammary artery is presented in a patient who had both IMAs grafted for recurrent angina 10 years after initial vein coronary revascularisation. The event was mistaken for spasm, but because of severe circulatory collapse no time was available to treat the patient appropriately. The purpose of this report is to facilitate the early recognition and avoidance of this potentially fatal complication.

Protection of the small intestine against irradiation by means of a removable prosthesis. In radiation therapy of tumors, several techniques are used to prevent injury of the intestinal loops. Their purpose is to drive the intestine out of the external beam. Understanding the disadvantages they present, a temporary prosthesis which effectively protects the small bowel, and is easy to remove, has been developed. The device is a 600 to 1,000 ml, silicone rubber, expandable balloon. When implanted in the pelvis or retroperitoneal cavity, and filled, this balloon displaces the intestinal loops out of the pelvic irradiation field. It may remain either filled or empty between each irradiation session. Due to its particular elliptical shape, once empty, the balloon can be removed through a 3 cm incision under local or peridural anesthesia at the completion of radiotherapy. Eleven patients with recurrent (8) or primary (3) cancer have been implanted. The protective effect has been evaluated on successive biologic tests, performed during treatment. No problem related to the prosthesis, no alteration of the biologic tests, nor bowel injury have been observed after several months follow-up. This device is suitable for preventing intestinal complications during therapy, allowing a higher dose of radiations in some cases.

Chromosomes in childhood acute lymphoblastic leukaemia: karyotypic patterns in disease subtypes. To define further the clinical importance of cytogenetic analysis in acute lymphoblastic leukaemia (ALL) a prospective study was performed on 139 unselected children. Analyses were considered adequate in 104, of whom 35 were normal and 69 had clonal abnormalities. Abnormalities were categorised according to banded chromosome analysis as well as chromosome count. Karyotypes were correlated with clinical and laboratory features at diagnosis and with survival. Of the successful analyses, thirty five (34%) children had no abnormalities; this group contained an excess of T cell disease. Twenty five (24%) had a "characteristic" hyperdiploid karyotype and as a group had lower presenting white counts, a tendency to CD10, and periodic acid schiff positivity of the blast cells and smaller spleens. None was an infant and only one was over 10 years old. Seven (7%) children with t(9; 22), t(8; 14), or t(4; 11) translocations were grouped together as "specific" translocations. Collectively they had a significantly worse prognosis than the remainder. Nine children developed central nervous system relapse, six of whom had either t(4; 11) or abnormalities of 9p or 19p. A descriptive classification taking into account chromosome bonding pattern is cytogenetically more appropriate and may be more clinically useful than grouping children simply by chromosome number. As knowledge and techniques improve, the classification of cytogenetic abnormalities in ALL will need to be kept under frequent review.

Variceal rebleeding after portosystemic shunting. Strategies and solutions to a vexing problem. The purpose of this review was to discuss an approach to the treatment of recurrent bleeding from esophageal or gastric varices after portosystemic shunt. From our own clinical experience, as well as that of others, it appears that re-establishment of portal decompression should offer the best chance at long-term survival. Luckily, innovations in angiographic technique have allowed attainment of this goal without the inordinate risk of an operative procedure. However, not all patients' situations will be amenable to such treatment. For some of them, operative decompression of the portal venous system can be carried out in an anatomic area previously untouched. For those patients in whom no decompression is possible, direct endoscopic treatment of the varices will offer an alternative, albeit temporizing, approach.

Increased risk of leukemia relapse with high-dose cyclosporine A after allogeneic marrow transplantation for acute leukemia. Eighty-one patients with acute myeloid leukemia (ANLL, n = 44) or acute lymphoblastic leukemia (ALL, n = 37), aged 10 to 50 years were randomized to receive 1 mg/kg per day (n = 41, group A) or 5 mg/kg per day (n = 40, group B) of cyclosporine A (CyA) from day -1 to day +20 after bone marrow transplant (BMT). All patients received CyA orally thereafter. All patients were prepared with cyclophosphamide (CY) 120 mg/kg and fractionated total body irradiation (TBI), and received unfractionated BM from an HLA-identical sibling. The two groups were comparable for diagnosis, disease status, French-American-British (FAB) classification, WBC count at diagnosis, cytogenetic abnormalities, extramedullary disease before BMT, donor/recipient age and sex, number of cells infused, and number of days with intravenous (IV) CyA. Median follow-up for surviving patients in group A was 983 v 632 days in group B. Patients in group A had lower serum levels of CyA (295 v 686 ng/mL, P = .004), lower bilirubin levels (1.9 v 2.6 mg/dL, P = .07), lower creatinine levels (0.9 v 1.4 mg/dL, P = .06), and a lower proportion of CD8+ cells in the peripheral blood (PB) within day +21 (19% v 28%, P = .07). First day to 0.5 x 10(9)/L neutrophils was comparable in the two groups (13 v 14 days; P = .1). In a Cox model, the actuarial risk of acute graft-v-host disease (GVHD) grade II+, after stratification for age (less than 20 years greater than) was significantly lower in group B patients (0.54, P = .04). The actuarial risk of developing chronic GVHD was comparable (P = .9). Actuarial transplant-related mortality (TRM) at 240 days was 28% and 26% (P = .8) in group A and B: the major cause of death was GVHD in group A (P = .02) and multiorgan toxicity in group B (P = .07). The actuarial risk of relapse at 2 years overall was 20% in group A and 52% in group B (P = .001); it was 9% v 43%, respectively, for patients in first remission (P = .0001) and 48% v 63% for patients in non-first complete remission (CR) (P = .1). Actuarial 2-year disease-free survival (DFS) in group A and B was 58% v 32% (P = .02) for all patients, 71% v 35% (P = .01), in first remissions, and 30% v 23% (P = .2) in advanced disease.(ABSTRACT TRUNCATED AT 400 WORDS).

Intermittent pneumatic compression to prevent proximal deep venous thrombosis during and after total hip replacement. A prospective, randomized study of compression alone, compression and aspirin, and compression and low-dose warfarin. A prospective, randomized study of the effectiveness of intraoperative and postoperative use of intermittent pneumatic compression, alone or in combination with oral administration of either aspirin or low-dose warfarin, was done of a consecutive series of patients who had a total hip replacement and were more than thirty-nine years old. All patients began walking by the third postoperative day. One hundred and ninety-six patients who had 217 total hip arthroplasties were included. Twenty-eight per cent of the procedures were revisions of a previous total hip replacement or of an endoprosthesis, and the remainder were primary arthroplasties. Patients were randomized as to the type of prophylaxis that they received: intermittent pneumatic compression alone, seventy-six hips; intermittent pneumatic compression and aspirin, seventy-two hips; or intermittent pneumatic compression and low-dose warfarin, sixty-nine hips. Before discharge from the hospital, and at an average of seven days after the operation, all patients were evaluated for the presence of proximal deep-vein thrombosis with either venography on the side of the operation or with bilateral venous ultrasonography. The relative frequency with which thrombosis occurred in a proximal vein was not significantly different in the three groups; the over-all relative frequency was 10 per cent. Intermittent compression during and after the operation effectively reduces the rate of proximal-vein thrombosis after total hip replacement. With the number of patients in our study, the effectiveness of this technique could not be shown to be augmented by oral administration of either aspirin or low-dose warfarin.

Venous infarction following the interhemispheric approach in patients with acute subarachnoid hemorrhage. Postoperative venous infarction following aneurysm surgery was studied in 48 patients with anterior communicating artery aneurysms operated on through the interhemispheric approach at the acute stage of subarachnoid hemorrhage (SAH). Of 23 patients whose bridging veins were sacrificed during surgery, 11 (47.8%) showed venous infarction in the frontal lobes. In contrast, only one (5.9%) of 17 patients whose bridging veins were preserved developed cerebral edema. None of eight patients who were operated on after Day 11 (the day of SAH was defined as Day 0) showed this complication, although bridging veins were sacrificed in six of them. Venous infarction following acute aneurysm surgery tended to occur more frequently in patients of higher SAH grade and/or more advanced age, but these correlations were not significant. However, the correlation between the sacrifice of veins and venous infarction was significant (p less than 0.025). Because this potential complication may compromise the benefit of acute aneurysm surgery and cause damage, it is important to preserve the venous system and in some instances to select another surgical approach based on the pattern of venous drainage in the frontal lobe.

Breast cancer during pregnancy and lactation. Breast cancer is the most frequently seen cancer in pregnancy and lactation, but the incidence is low, the disease being seen in approximately 0.03% of pregnancies. Only 1% to 2% of breast cancer overall is diagnosed during pregnancy or lactation. There is no evidence to implicate pregnancy or lactation in either the etiology or the progression of breast cancer. Careful breast examination early in the pregnancy is very important to find solid masses that require biopsy before breast engorgement hides them. Therapeutic options vary, depending on the stage of disease and the stage of the pregnancy. Operable disease in the first 6 to 7 months of the pregnancy should be treated by mastectomy, as irradiation is contraindicated. Late in the pregnancy, a lumpectomy and axillary dissection can be done, with irradiation being delayed until after delivery. General anesthesia is safe if the usual precautions are taken to compensate for the physiologic changes induced by pregnancy. Unfortunately, delay in diagnosis is common, and 70% to 89% of patients with operable primary lesions have positive axillary lymph nodes. Late stage appears to be the only reason for the generally worse prognosis in these patients, as stage for stage, they have a course similar to that of nonpregnant patients. Adjuvant chemotherapy can be considered late in the pregnancy but should usually be delayed until after delivery. In patients with locally advanced or metastatic cancer diagnosed early in the pregnancy, for whom both chemotherapy and radiation therapy would normally be recommended, consideration must be given to termination of the pregnancy. There is no evidence that termination of pregnancy improves the outlook for the patients, but it does permit standard aggressive therapy in advanced disease.

Restoration of liver function in Gunn rats without immunosuppression using transplanted microencapsulated hepatocytes. Microencapsulation of cells within synthetic semipermeable membranes is a novel technique that enables the transplantation of cell cultures without the need for immunosuppression. We have previously shown that transplanted isolated encapsulated hepatocytes can provide sufficient short-term metabolic support to improve the survival of animals with galactosamine-induced fulminant hepatic failure. Here we have demonstrated the feasibility of isolated encapsulated hepatocyte transplantation in providing long-term metabolic liver support in Gunn rats. Gunn rats have a congenital inability to conjugate bilirubin and thus exhibit lifelong hyperbilirubinemia. We studied the feasibility of isolated encapsulated hepatocyte transplantation in restoring this specific liver function. Free hepatocytes, isolated from male Wistar rats, were microencapsulated with collagen within a trilayered sodium alginate-poly-L-lysine-sodium alginate membrane using techniques developed in our laboratory. A total of 45 Gunn rats underwent intraperitoneal transplantation with free hepatocytes (5 x 10(7], isolated encapsulated hepatocytes (5 x 10(7], control (empty) microcapsules or no transplant (untreated controls). Serum bilirubin levels were monitored daily for 10 days after transplantation, and subsequent weekly samples were obtained for up to 1 mo. Microcapsules were studied by light and electron microscopy 1 mo after transplantation. During the first week after transplantation, the mean maximum reduction in serum bilirubin levels for the isolated encapsulated hepatocytes, free hepatocytes and control microcapsule transplanted groups was 45.7%, 18.6% and 14.3%, respectively. For up to 1 mo thereafter the mean reduction in serum bilirubin levels in these respective groups was 34.8%, 13.5% and 3.3%.

Successful control of bleeding from gastric antral vascular ectasia (watermelon stomach) by laser photocoagulation. We report a case of gastric antral vascular ectasia in a patient with primary biliary cirrhosis in whom chronic blood loss was a major problem. She required repeated blood transfusions that were complicated by reactions and still had persistent anaemia. She was treated with laser phototherapy in the form of quadrantic photocoagulation with a neodynium yttrium-aluminium-garnet laser. This greatly improved the endoscopic appearance of the gastric lesions and effectively controlled blood loss. She required no further transfusions. Bleeding recurred after 11 months which was controlled by further laser photocoagulation.

Stress response protein (srp-27) determination in primary human breast carcinomas: clinical, histologic, and prognostic correlations Expression of an estrogen-regulated protein known as the 27,000-d heat-shock or stress-response protein (srp-27) was evaluated in human breast carcinomas and established breast cancer cell lines. Results obtained by Northern and Western blot analyses and immunohistochemical methods were concordant. Immunohistochemical assessment of srp-27 expression in 300 breast carcinomas (with median patient follow-up of 8 years) was performed. Twenty-six percent of lymph node-negative and 45% of lymph node-positive tumors were overexpressors. Univariate analysis demonstrated significant correlations between srp-27 overexpression and estrogen receptor (ER) content, pS2 protein expression, nodal metastases, advanced T stage, lymphatic/vascular invasion, and a shorter disease-free survival period (but not a shorter overall survival) for the study population as a whole. Regression tree analysis showed that srp-27 expression was an independent prognostic indicator for disease-free survival only in patients with one to three positive lymph nodes. The Cox proportional hazards model confirmed the independent prognostic significance of nodal involvement, T stage, and ER content but failed to recognize srp-27 overexpression as a significant independent parameter predictive of patient outcome in the patient population as a whole. The observed associations between srp-27 overexpression and more aggressive tumors suggest a biologic role for srp-27 in human breast carcinomas.

Large-scale neurocognitive networks and distributed processing for attention, language, and memory. Cognition and comportment are subserved by interconnected neural networks that allow high-level computational architectures including parallel distributed processing. Cognitive problems are not resolved by a sequential and hierarchical progression toward predetermined goals but instead by a simultaneous and interactive consideration of multiple possibilities and constraints until a satisfactory fit is achieved. The resultant texture of mental activity is characterized by almost infinite richness and flexibility. According to this model, complex behavior is mapped at the level of multifocal neural systems rather than specific anatomical sites, giving rise to brain-behavior relationships that are both localized and distributed. Each network contains anatomically addressed channels for transferring information content and chemically addressed pathways for modulating behavioral tone. This approach provides a blueprint for reexploring the neurological foundations of attention, language, memory, and frontal lobe function.

Medroxyprogesterone acetate lowers plasma corticotropin and cortisol but does not suppress anterior pituitary responsiveness to human corticotropin releasing factor. The endocrine action of medroxyprogesterone acetate (MPA) has been claimed to be of a glucocorticoid-like nature. Upon clinical observation, MPA has been shown to improve life quality and overall well-being in patients with advanced breast cancer, renal carcinoma, prostatic carcinoma, and uterine adenocarcinoma. The authors have evaluated MPA endocrine action by the administration of human corticotropin releasing factor (hCRF) in a 90-minute assay in 15 patients with advanced breast cancer or renal cell carcinoma both, before the initiation of oral high-dose MPA treatment (1000 mg MPA) as well as after at least 10 days of therapy. The curves for corticotropin, beta-endorphin, and cortisol responses to hCRF of tumor patients who were tested before the initiation of MPA treatment were parallel to the curves of a healthy control group of probands tested under equal conditions, although at significantly higher respective hormone levels. In patients with malignant disorders assayed after MPA administration, both basal and peak hormone levels were found to be comparable with values obtained in healthy controls. In conclusion, MPA appeared to act at a suprapituitary level since pituitary responsiveness to hCRF was preserved under MPA treatment. Moreover, it appeared that MPA brought the hormonal stress state found in patients with malignant tumors back to normal.

Ultrasound screening of first-degree relatives of patients with an abdominal aortic aneurysm. The pedigrees were constructed of 43 patients (probands) who underwent resection of an abdominal aortic aneurysm. Seven probands (16.2%) had a first-degree relative (parent, sibling, child) known to have had an abdominal aortic aneurysm (multiplex family). To determine the prevalence of undiagnosed abdominal aortic aneurysm, ultrasound screening of first-degree relatives over age 40 years was undertaken. Of 202 eligible relatives, 103 (51.0%) were screened. An occult abdominal aortic aneurysm was defined as an infrarenal aortic diameter greater than 3.0 cm or an infrarenal/suprarenal aortic diameter ratio of greater than 1.5. An incipient abdominal aortic aneurysm was defined as a clear focal bulge of the infrarenal aorta, which was less than 3.0 cm in greatest diameter. Four of 103 relatives (3.9%) were found to have an occult abdominal aortic aneurysm (age/sex: 57M, 60M, 62F, 65M), and three (2.9%) were found with an incipient abdominal aortic aneurysm (age/sex: 56M, 60M, 67F). These smaller abdominal aortic aneurysms were in patients younger than the operated probands (average age men, 67 years; women, 69 years). Six of seven individuals were in families previously considered simplex, increasing the actual multiplex family frequency from 16.2% to 27.9%. All seven new abdominal aortic aneurysms were found in the 49 siblings age 55 years or older. There were no abdominal aortic aneurysms found in the 39 relatives under age 55 years, in 14 children ages 50 to 59 years or in one parent. Therefore of the siblings age 55 years or older, 5/20 men (25.0%) and 2/29 women (6.9%) were found to have a previously undiagnosed abdominal aortic aneurysm.

Captopril-stimulated renal vein renin in hypertensive patients with or without renal artery stenosis. To examine the efficacy and usefulness of captopril-enhanced renal vein renin (RVR) measurements in detecting the functional significance of renal artery stenosis found in hypertensives, we compared these values in 22 patients with arteriographically documented renovascular hypertension due to unilateral (URVH: 14 patients) or bilateral renal artery stenosis (BRVH: 8 patients) and 12 patients with high renin essential hypertension (EHT). Before captopril administration, RVR ratio was less than 1.5 in 8 patients (36.4%) with renovascular hypertension and all patients (100%) with EHT. Captopril enhanced the lateralization of renal vein renin in renovascular hypertension; the postcaptopril RVR ratio was greater than 2.0 in 18 patients (81.8%) and greater than 1.5 in all the patients (100%). On the other hand, RVR ratio remained unchanged in most patients with EHT. There was no significant difference in the postcaptopril RVR ratios between URVH and BRVH. However, the postcaptopril RVR ratio was higher in atherosclerosis (10 patients) than in fibromuscular dysplasia (11 patients) (P less than .05). Captopril also elucidated contralateral renin suppression as expressed by a contralateral/peripheral renin ratio of less than 1.0, which was associated with a favorable outcome of unilateral surgical intervention. Captopril-stimulated RVR indices were valuable in detecting the functionally significant renal artery stenosis and predicting surgical curability in renovascular hypertension.

Hemodynamic effects of a new right ventricular assist device. A right ventricular assist device (VAD) based on the principle of counterpulsation has been developed at our institution. The device is a valveless, pneumatically actuated, 40 cc, sac-type pump, with a single inlet-outlet port. For right ventricular support, the "Uniport" pump is anastamosed end-to-side to the pulmonary artery. In previous experimental trials, the device has been shown to impart minimal trauma to blood components. In this study, biventricular failure was induced in eight Holstein calves by normothermic ischemia during cardiopulmonary bypass. A Pierce-Donachy left VAD (LVAD) was used for left ventricular support following the ischemic insult. Hemodynamic measurements were obtained throughout the study, and each animal served as its own control. A significant increase in post injury cardiac output (33.5 +/- 11.4%) was obtained with use of the Uniport and LVAD, as compared to use of the LVAD alone (p less than or equal to 0.005). Other hemodynamic parameters of right heart failure, including right atrial pressure (RAP), pulmonary artery pressure (PAP), and left atrial pressure (LAP) were not significantly affected. These data suggest that the Uniport right ventricular assist device significantly improves cardiac output in this model of moderate right ventricular failure. Additional studies are required, however, to optimize pump stroke volume, and to further define the performance envelope of the device.

Peptic ulcer disease: CT evaluation. The authors retrospectively describe the computed tomographic (CT) findings in 35 patients with peptic ulcer disease. Three of eight patients with gastritis or duodenitis had bowel-wall thickening. Ten of the remaining 27 patients had CT evidence of ulcer perforation (n = 2) or penetration (n = 8), four cases of which were unsuspected clinically. Both patients with acute free perforation had pneumoperitoneum, and one showed free extravasation of orally administered contrast material. The precise site of perforation could not be established in either case with CT. The eight patients with ulcer penetration had CT evidence of bowel-wall thickening (n = 3) and inflammatory changes in adjacent soft tissues and organs (n = 8), including the pancreas (n = 4), liver (n = 1), and lesser omentum (n = 1). Ulcer craters were seen in only two. The CT findings of penetration can mimic other disease processes. CT was not useful in detecting uncomplicated peptic ulcer disease.

Transitional cell carcinomatous meningitis after M-VAC (methotrexate, vinblastine, doxorubicin, and cisplatin) chemotherapy. The M-VAC (methotrexate, vinblastine, doxorubicin, and cisplatin) regimen has been utilized at our two institutions to treat 17 patients with advanced stage transitional cell carcinoma of the bladder. We report 2 cases of carcinomatous meningitis resulting from metastatic transitional cell carcinoma which occurred in patients treated with M-VAC. Review of the literature suggests that our experience with central nervous system metastases is not unique, and that treatment of advanced stage transitional cell carcinoma of the bladder with M-VAC may enhance the incidence of meningeal metastases. Carcinomatous meningitis, although rare, is a rapidly fatal manifestation of metastatic transitional cell carcinoma if left untreated. However, prompt diagnosis and early aggressive therapy may result in palliation and stabilization of neurologic status. We review the pathophysiology, diagnosis, and treatment of transitional cell carcinomatous meningitis.

Intraoperative coronary artery endarterectomy with excimer laser. Compared with continuous-wave lasers, excimer lasers exhibit several in vitro advantages: nonthermal ablation process and linear relation between the number of pulses and the depth of the crater. A 308 nm, 20 nsec pulse duration, 1 to 5 repetition rate laser was specifically designed for clinical application. At the time of cardiopulmonary bypass in 10 symptomatic patients, before bypass grafting, a 1 mm diameter core specifically ultraviolet-tipped fiberoptic scope was introduced via the coronary arteriotomy and placed upstream (seven patients) and downstream (three patients) in contact with the stenosis. Laser power was increasingly delivered up to the clearing of the stenosis or occlusion. Quality of angioplasty was controlled by calibration of the neolumen, cardioplegic solution output through the laser-treated segment, and an eighth day or sixth month coronary arteriogram. In the first three patients studied on the eighth day, all laser-treated coronary artery segments showed an early parallel-linked patent neolumen despite competitive bypass graft flow. In the patients studied after 6 months, all recanalized segments were patent except one; in one patient the venous graft was occluded, but the upstream laser angioplasty was patent. The main limitation of the method lies in the fact that laser coronary recanalization is confined to the fiber core diameter. We conclude that (1) excimer laser angioplasty may be safe and efficient during surgical procedure and (2) as catheter flexibility remains the most critical problem, we are now assuming an appropriate tool with a multifiber system that is suitable for intraoperative as well as percutaneous routes.

Chinese-white differences in the distribution of occlusive cerebrovascular disease. The distribution of cerebrovascular lesions is affected by race. Blacks and Japanese have more intracranial occlusive cerebrovascular disease, while whites have more extracranial disease. Despite a high incidence of stroke in China, there are few formal studies of the distribution of vascular occlusive disease in Chinese populations. We compared clinical and angiographic features of 24 white and 24 Chinese patients with symptomatic occlusive cerebrovascular disease. In symptomatic vascular territories, whites had more severe (greater than or equal to 50% stenosis) extracranial lesions, while Chinese had more severe intracranial lesions. When we counted mild and severe lesions in a symptomatic territory, whites had more extracranial lesions while Chinese had more intracranial lesions. When we combined symptomatic and asymptomatic territories, whites had more extracranial lesions, while Chinese had more intracranial lesions. White patients reported more transient ischemic attacks. The distribution of lesions, however, was not explained by differences in incidence of transient ischemia, hypertension, diabetes, hypercholesterolemia, or ischemic heart disease between the groups. The preponderance of intracranial vascular lesions in Chinese patients is similar to that seen in blacks and Japanese. Racial differences in the occurrence of extracranial and intracranial lesions raise the possibility of a different underlying pathophysiology for the 2 locations.

Neurologic abnormalities in a patient with human ehrlichiosis. Human ehrlichiosis is a tick-borne rickettsial disease characterized by fever, headache, myalgias, anorexia, and occasionally rash. In our patient, changes in mental status, upper motor neuron signs, cerebrospinal fluid pleocytosis, and increased serum protein levels were found in association with serologically confirmed ehrlichiosis and were most likely due to vasculitis involving the central nervous system. Intraleukocytic inclusions, although observed in our case, have been infrequently found in other reported cases of ehrlichiosis.

Exercise thallium-201 imaging in complete left bundle branch block and the prevalence of septal perfusion defects. To determine the prevalence of septal defects in a generalized referral population, the records of 93 consecutive patients with complete left bundle branch block (BBB) who underwent symptom-limited treadmill exercise testing with thallium-201 myocardial imaging over a 3-year period were reviewed. Segmental analysis of the planar thallium-201 images was performed in a blinded fashion with agreement by consensus. Computerized quantitative analysis of the images also was independently performed, and was correlated with the visual interpretations. Forty-seven patients (51%) had normal images, and 46 (49%) had defects of greater than or equal to 2 segments. In the abnormal studies, only 13 patients (14% of the total population) had septal defects, while a much higher number of patients, 33 (39%), had inferior or apical defects, or both. Coronary angiography was performed in 6 patients with septal defects: Significant narrowing of the left anterior descending coronary artery was found in 4 patients, a narrowed right coronary artery was found in 1, and normal coronary arteries were seen in the other patient. In conclusion, whereas previous studies have suggested a high percentage of false-positive septal defects in patients with left BBB, this study demonstrates a low prevalence (14%) of septal defects in a large population of unselected patients presenting for exercise thallium-201 imaging. Therefore, exercise thallium-201 imaging remains a useful procedure for evaluating patients with complete left BBB.

Changes in the basal dendrites of cortical pyramidal cells from alcoholic patients--a quantitative Golgi study. Although a variety of pathological changes have been described in the brains of chronic alcoholic patients, there have been no studies which have addressed the question of alterations in cortical neuronal dendritic arborisation. Loss of neurons from the superior frontal gyrus and shrinkage of neurons from both the superior frontal gyrus and motor cortex has been documented in chronic alcoholic patients; these areas were chosen for this study. Using a modified rapid Golgi technique the basal dendritic arborisation of layer III pyramidal neurons was compared in 15 male alcoholic patients and 15 age-matched male controls. All parameters measuring basal dendritic arborisation were significantly less in the alcoholic cases for both the superior frontal and motor cortices. Changes in the arbor are in the terminal branches, which is consistent with other models of dendritic plasticity. Such changes may explain both permanent and reversible functional deficits in chronic alcoholic patients.

Effect of neurotransmitter-selective drugs in mice selected for differential sensitivity to the hypothermic actions of ethanol. Mice selectively bred for resistance (HOT) and sensitivity (COLD) to the hypothermic effect of EtOH were tested for their hypothermic response to neurotransmitter-specific drugs and for the effect of such drugs on EtOH induced hypothermia (HT). The drugs administered were the opiate drugs morphine, levorphanol and U50488H, the dopamine agonists apomorphine, LY171535 and SKF38393, the dopamine antagonist chlorpromazine, the alpha adrenergic agonist St587, the cholinergic agonist nicotine and amphetamine, which increases the release of catecholamines. All of the drugs tested, with the exception of SKF38393 and amphetamine, induced a hypothermic response in HOT and COLD mice. SKF38393 had no effect on body temperature or HT produced by EtOH. Amphetamine caused HT at low doses and hyperthermia at high doses. COLD mice were more sensitive than HOT mice to the hypothermic effect of morphine and levorphanol, mu-opiate agonists, and U50488H, a relatively specific kappa agonist. All of the other drugs tested were approximately equally potent in HOT and COLD mice. These results suggest that the differential sensitivity of HOT and COLD mice to EtOH-induced HT may be partially mediated through genetic changes in opiate mechanisms.

Heart rate variability before and after myocardial infarction in conscious dogs at high and low risk of sudden death. Heart rate variability has been demonstrated both experimentally and clinically to be of prognostic importance in determining mortality after myocardial infarction. However, no paired studies have been reported to examine heart rate variability before and after myocardial infarction. The hypothesis was tested that low values of heart rate variability provided risk assessment both before and after myocardial infarction with use of an established canine model of sudden cardiac death. Risk for sudden death was assessed 1 month after myocardial infarction by a protocol in which exercise and myocardial ischemia were combined; dogs that developed ventricular fibrillation were classified at high risk for sudden death (susceptible) and the survivors were considered low risk (resistant). In resistant dogs, myocardial infarction did not affect any measure of heart rate variability: 1) mean RR interval, 2) standard deviation of the mean RR interval, and 3) the coefficient of variance (standard deviation/RR interval). By contrast, after myocardial infarction, susceptible dogs showed significant decrease in all measures of heart rate variability. Before myocardial infarction, no differences were seen between susceptible and resistant dogs. However, 30 days after infarction, epidemiologic analysis of the coefficient of variance showed high sensitivity and specificity (88% and 80%, respectively), predicting susceptibility. Therefore, results of analysis of 30 min of beat to beat heart period at rest 30 days after myocardial infarction are highly predictive for increased risk of sudden death.

Split-thickness skin grafting of the myelomeningocele defect: a subset at risk for late ulceration. The appropriate method and timing of the management of the myelomeningocele defect have prompted considerable discussion. Use of split-thickness skin grafts acutely has accomplished wound closure with low morbidity and mortality. This study was designed to address the question of long-term suitability of the technique of split-thickness skin grafting of the myelomeningocele patient. The incidence of late and/or severe skin ulceration and the presence of gibbus deformity were correlated with the method of skin closure. Long-term follow-up revealed a higher incidence of chronic skin ulceration in the split-thickness skin graft group as compared with the primary closure group. All skin breakdowns appeared in the presence of a gibbus deformity, and gibbus deformity was more prevalent in the split-thickness skin graft group. The incidence of skin ulceration and gibbus deformity was site-dependent. A thoracic or thoracolumbar myelomeningocele repair with split-thickness skin graft was significantly more likely to be complicated by skin problems than the defect in the lumbar, lumbosacral, or sacral region. This relationship was secondary to the frequency of gibbus deformity in the more cephalad defects than defects caudad. A treatment plan is outlined that is based on the primary variable of the location of the myelomeningocele and secondarily by defect size.

Effects of stress on gastric mucosal prostaglandin generation in intact, adrenalectomized, and sham-operated rats. To study the effects of (a) cold restraint stress and (b) adrenalectomy in association with cold restraint stress on gastric mucosal ulceration and prostaglandin generation, we performed two experiments. In the first, 40 rats were divided into four groups of 10 rats each: (a) unstressed and (b) stressed for 0.5 h, (c) stressed for 2 h, and (d) stressed for 4 h. In the second experiment, another 80 rats were divided into four groups of 20 rats each: (a) adrenalectomy plus cold restraint stress for 2 h, (b) adrenalectomy plus no stress, (c) sham operated plus 2 h of stress, and (d) sham operated plus no stress. In both experiments we recorded an ulcer index and measured mucosal generation of prostaglandin E2 (PGE2) and prostaglandin I2 (6-keto-PGF1a). In conclusion: (a) Cold restraint stress is associated with a time-dependent decrease in gastric mucosal PGE2 generation, but no change in 6-keto-PGF1a generation, and an increase in mucosal injury that is maximal by 2 h. (b) Adrenalectomy augments the effects of stress on mucosal injury but has no effect on prostaglandin generation; thus, the ulcerogenic effect of adrenalectomy appears to be independent of an effect on prostaglandin generation.

Evaluation of vigabatrin as an add-on drug in the management of severe epilepsy. The effects of the addition of Vigabatrin, a new anti-epileptic drug, to the therapy of 128 patients with severe medically refractory epilepsy is reported. Forty two (33%) of patients experienced side effects, which were predominantly neurotropic. In 28 (22%), the drug was withdrawn because of these side effects. The commonest side effects were drowsiness and behavioural change. The remaining 100 patients were followed for a mean of 30 weeks (range 12-75). Forty one of these patients showed a marked improvement in seizure frequency (a 50% or more reduction when compared with the pre-trial period), and nine (7%) were rendered seizure free. Apparent tolerance to the effects of the drug were noted in five patients. An exacerbation of seizures may occur if the drug is withdrawn too quickly. Vigabatrin appears to be a promising new anti-epileptic drug.

Fatty liver hepatitis (steatohepatitis) and obesity: an autopsy study with analysis of risk factors. Steatohepatitis (fatty liver hepatitis), histologically identical to alcoholic disease, occurs in some obese patients after jejunoileal bypass. A similar lesion occurs rarely in obese patients without bypass surgery, but the risk factors are poorly understood. Hepatic steatosis, steatohepatitis and fibrosis were sought in 351 apparently nonalcoholic patients at autopsy and various risk factors were evaluated. Incidence of steatosis and steatohepatitis correlated with the degree of obesity. Steatohepatitis was found in 18.5% of markedly obese patients and 2.7% of lean patients. Additional risk factors for steatohepatitis were type II diabetes, weight loss in the preterminal period shortly before death and intravenous glucose therapy in the last week of life. Severe fibrosis was found in 13.8% of markedly obese patients and in 6.6% of lean patients; this difference was largely explained by the higher prevalence of diabetes in obese groups. The risk factors defined in this study are known to be associated with abnormalities of free fatty acid metabolism. Obesity, type II diabetes and intravenous glucose therapy are associated with hyperinsulinemia, which may inhibit fatty acid oxidation. Obesity and weight loss increase the presentation of fatty acids to the liver. Similar metabolic changes may occur in obese patients after jejunoileal bypass surgery. Thus this study supports the hypothesis that fatty acids have a role in the hepatocellular necrosis found in some obese individuals.

Platelet norepinephrine and epinephrine concentration in patients with pheochromocytoma. Platelet and plasma catecholamine concentrations were determined in 17 patients with surgically proven pheochromocytoma (mean age 42.3 years); in 31 patients with borderline hypertension (mean age 35.3 years) and in 9 healthy controls (mean age 39.3 years). Both platelet norepinephrine and epinephrine were significantly increased in patients with pheochromocytoma when compared with hypertensive and control groups (P less than .001). No correlation between platelet and plasma catecholamines was detected in all studied groups. The diagnostic accuracy of platelet catecholamine in pheochromocytoma is limited since increased platelet norepinephrine was found in 35.5% and increased platelet epinephrine was found in 19.4% of patients with essential hypertension.

Diaphragmatic force and substrate response to resistive loaded breathing in the piglet. Inspiratory resistive loaded (IRL) breathing results in hypoventilation and diaphragmatic fatigue in the piglet. We studied the effects of 6 h of IRL on ten 1-mo-old piglets. The load was adjusted to increase spontaneously generated transdiaphragmatic pressure five to six times baseline. Six 1-mo-old piglets acted as controls and were identically instrumented but were not subjected to IRL. Measurements of ventilation, blood gases and pH, diaphragmatic electromyogram, force-frequency curve, blood flow, and end-expiratory lung volume were obtained hourly. Diaphragmatic muscle samples were obtained after 6 h for determination of ATP, phosphocreatine, lactate, and glycogen levels. No changes occurred in the control animals. IRL resulted in a significant decrease in ventilation, an increase in diaphragmatic EMG, onset of abdominal expiratory muscle activity, and a fall in end-expiratory lung volume by 1 h. The force-frequency curve adjusted for lung volume change fell by 20% at all frequencies of stimulation at 1 h and by 40% at 6 h. Blood flow to the costal and crural diaphragm increased by 51 and 141%, respectively. No differences were noted in ATP, phosphocreatine, lactate, or glycogen between control and IRL animals. It is concluded that submaximal spontaneous contractions of the piglet diaphragm over a 6-h period cause a substantial decrease in its maximal force-generating capacity that is not related to substrate depletion.

Rapid baroreceptor resetting in Dahl salt-sensitive rats. Dahl salt-sensitive rats rapidly become hypertensive when exposed to a high salt diet, but Dahl salt-resistant rats maintain normal blood pressure on a high salt diet. A defect in baroreceptor afferents is thought to play a key role in the low sensitivity of baroreceptor reflexes in Dahl salt-sensitive rats even in the prehypertensive stage during low salt treatment. In the present study, we tested whether differences in rapid resetting ability might contribute to differences in baroreceptor function in Dahl rats. Four groups of rats were tested: salt-sensitive and salt-resistant rats on low salt and high salt diets (0.15% and 8.0% NaCl). We compared the rapidly resetting responses of baroreceptors from each group using an in vitro preparation. Rapid resetting was assessed for each aortic baroreceptor (n = 46) by linear fit of the relation of pressure threshold and conditioning mean arterial pressure. Each group had a wide range of resetting ratios (the slope of the resetting relation). Despite higher initial pressure thresholds in salt-sensitive rats on a high salt diet, resetting ratios among the four groups were similar. Thus, the ability of Dahl salt-sensitive baroreceptors to rapidly reset is preserved, despite high dietary salt and a genetic predisposition to dysfunction. The present findings in Dahl rats reinforce the results of recent studies of rapid resetting during spontaneous and renal hypertension, which suggests that the rapid resetting process is remarkably resistant to factors that compromise baroreceptor function.

Spontaneous renal rupture during pregnancy. Spontaneous rupture of the renal parenchyma or renal pelvis during pregnancy has been previously reported in 16 cases. In the case we describe in this report, the patient initially had right flank pain and nausea for 48 hours, which progressed to severe abdominal symptoms that necessitated exploratory laparotomy. Cystoscopic placement of a ureteral stent relieved the obstruction and allowed spontaneous healing of the renal pelvis. Dilatation of the urinary collecting system commonly occurs during pregnancy. Spontaneous rupture of the renal parenchyma or renal pelvis, however, is unusual and often associated with diseased kidneys. Our case is the 8th one of spontaneous rupture of the renal collecting system with no identifiable underlying pathologic condition and the 17th case of spontaneous renal rupture overall.

Isolation of sequences that span the fragile X and identification of a fragile X-related CpG island [published erratum appears in Science 1991 Apr 26;252(5005):494] Yeast artificial chromosomes (YACs) were obtained from a 550-kilobase region that contains three probes previously mapped as very close to the locus of the fragile X syndrome. These YACs spanned the fragile site in Xq27.3 as shown by fluorescent in situ hybridization. An internal 200-kilobase segment contained four chromosomal breakpoints generated by induction of fragile X expression. A single CpG island was identified in the cloned region between markers DXS463 and DXS465 that appears methylated in mentally retarded fragile X males, but not in nonexpressing male carriers of the mutation nor in normal males. This CpG island may indicate the presence of a gene involved in the clinical phenotype of the syndrome.

Invasive squamous cell carcinoma in a patient with epidermodysplasia verruciformis. A patient with epidermodysplasia verruciformis died of intracranial invasion by squamous cell carcinoma (SCC). A biopsy of clinically normal skin had revealed perineural invasion by malignant keratinocytes. Because SCCs arising in patients with epidermodysplasia verruciformis may be biologically aggressive, it is best to excise them with careful control of the surgical tissue margins.

The natural history of thrombocytopenia associated with preeclampsia. Sixty-one of 375 women with hypertension and preeclampsia in a 48-month period had thrombocytopenia. By postpartum day 3, 90% of these women had rising platelet counts, and by day 4, 59 of 61 women had counts greater than 100,000/mm3. The two exceptions had other pathologic conditions in addition to preeclampsia. Thrombocytopenia associated with preeclampsia should resolve by postpartum day 4.

Patients with mental disorders who work. Mental illness can devastate persons intellectually and emotionally; with maintenance therapy, however, certain patients with chronic mental illnesses are capable of holding a variety of jobs. From the total population of psychiatric patients in our VA outpatient clinic, the 87 who were gainfully employed were identified to determine common factors among them. Affective disorders were the predominant diagnoses among patients who worked, while schizophrenia was more common among those who did not. Alcoholism was diagnosed in approximately 25% of working and nonworking groups.

Bilateral familial carotid body paragangliomas. Report of a case with DNA flow cytometric and cytogenetic analyses. A case study of bilateral familial carotid body paragangliomas with DNA flow cytometric and cytogenetic analyses is presented. Analysis of tumor cell nuclear DNA content by flow cytometry revealed aneuploid cell populations in both tumors. Standard cytogenetic analysis (Giemsa-banding technique used) of the right carotid body paraganglioma showed no evidence of numerical or structural abnormalities. We describe parameters currently used to "predict" biological behavior in these tumors.

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

Malignancy associated with chronic empyema: radiologic assessment. Radiologic findings of six cases of malignancy associated with chronic empyema 5-39 years in duration were reviewed. Pathologic examination confirmed three B-cell non-Hodgkin lymphomas, one round-cell sarcoma, one mesothelioma, and one adenocarcinoma. Retrospective findings on plain chest radiographs suggested the occurrence of malignancy: increased radiopacity in the thoracic cavity, soft-tissue bulgings and/or unsharpness of fat planes in the chest walls, destruction of bone near the empyema, and extensive medial deviation of the calcified pleurae. Computed tomography delineated masses with soft-tissue attenuation more clearly than radiography in all cases. Magnetic resonance images of three cases were informative because empyema cavities were surrounded by low-intensity rims, and two of them showed a signal intensity different from that of necrotic tumors. Scintigraphy revealed increased uptake of gallium in all cases. Ultrasonography was useful for biopsy guidance. Every radiologist should know this entity in observation of chest radiographs obtained in patients with chronic empyema, and further radiologic assessment and aggressive biopsy are recommended if malignancy is suspected.

Deficiencies of coagulation-inhibiting and fibrinolytic proteins in outpatients with deep-vein thrombosis BACKGROUND. Isolated deficiencies of antithrombin III, protein C, protein S, and plasminogen have been implicated as a cause of deep-vein thrombosis. It is assumed that patients with recurrent, familial, or juvenile thrombosis are very likely to have such a deficiency. METHODS. We studied the prevalence of isolated deficiencies of these proteins in 277 consecutive outpatients with venographically proved acute deep-vein thrombosis, as compared with 138 age-matched and sex-matched controls without deep-vein thrombosis, and calculated the positive predictive value of a history of recurrent, familial, or juvenile venous thromboembolism for the presence of such a deficiency. RESULTS. The overall prevalence of deficiencies of any of these proteins in the patients with venous thrombosis was 8.3 percent (23 of 277 patients) (95 percent confidence interval, 5.4 to 12.4), as compared with 2.2 percent in the controls (3 of 138 subjects) (95 percent confidence interval, 0.5 to 6.1; P less than 0.05 for the comparison between groups). The positive predictive values for the presence of an isolated protein deficiency in patients with recurrent, familial, or juvenile deep-vein thrombosis, defined as the proportion of patients with the clinical finding who had a deficiency of one or more of the proteins, were 9, 16, and 12 percent, respectively. CONCLUSIONS. The cause of acute venous thrombosis in most outpatients (91.7 percent) cannot be explained by abnormalities of coagulation-inhibiting and fibrinolytic proteins. The information obtained from the medical history concerning recurrent or familial venous thrombosis or the onset of the disease at a young age is not useful for the identification of patients with protein deficiencies.

The clinical utility of carotid duplex scanning. We retrospectively compared the results of duplex scanning (DS) with contrast angiography (CAN) in the evaluation of 119 patients whose 238 carotid arteries were evaluated by both methods within a four-week period. The results of all patients were then categorized by two different definitions of severity of stenosis. Category A classified 1-29% stenosis as mild, 30-69% stenosis as moderate, and 70-99% diameter reduction as severe stenosis. Category B defined mild stenosis as 1-19% lumen diameter reduction, moderate as 20-49% stenosis, and severe as 50-99% stenosis. The findings by each classification were compared in 60 patients with hemispheric symptoms and in 59 patients with nonspecific symptoms. CAN was our "gold standard", and exhibited greater sensitivity, specificity, accuracy, and predictive values than DS. Carotid arteries with 70% stenosis were identified by DS with greater specificity, accuracy, and predictive values than were arteries with 50% stenoses. Only the sensitivity was comparable in categorizations A and B (80% and 83%). All parameters of measurement were superior in patients with hemispheric symptoms. DS alone cannot substitute for CAN in selecting patients for carotid endarterectomy because its error rate exceeded acceptable rates of complications for carotid artery surgery. The false positive rate of DS was 4%. DS failed to diagnose 7 of 19 carotid artery occlusions, 9 of 11 ulcerated plaques, 7 of 119 instances of aortic arch disease, and 13 cases of severe intracranial artery stenosis.

Long survival and prognostic factors in hepatocellular carcinoma. We studied survival and prognostic factors in all cases of hepatocellular carcinoma seen at a Midwestern teaching hospital from 1947 through 1986. Of the 70 cases, 56 were diagnosed during life and 14 at autopsy. There were 47 males and 23 females with age at diagnosis ranging from 14 to 88. Median survival for the 56 patients diagnosed during life was 106 days. Only 11 patients lived longer than one year. Two patients were long survivors and presumed cured, one living 27 years after diagnosis and surgical treatment and the other 19 years. Cox regression model showed young age at diagnosis and low stage of disease at diagnosis to be significant predictors of long survival. White patients survived nearly twice as long as black patients but the difference was not significant. Gender and year of diagnosis did not appear to be important determinants of survival. Pathologic material was still available for one of the two long survivors and the histology was that of fibrolamellar carcinoma of young adults.

What affects continence after anterior resection of the rectum? Functional results after anterior rectal resections are commonly considered satisfactory but variable percentages of postoperative incontinence are often reported. Continence was evaluated after 20 low anterior resections (LAR) and 13 high anterior resections (HAR) by means of clinical assessment, anorectal manometry, and evacuation proctography. Whereas all HAR patients had perfect continence, 10 patients (50 percent of the LAR group had occasional episodes of soiling from liquid feces, 5 patients (25 percent had frequent soiling or occasional incontinence for solid feces, and 1 patient (5 percent had frequent solid stool loss requiring surgical treatment. Anal canal resting pressure at 3 and 4 cm from the anal verge was significantly lower in the LAR group (P less than 0.02 and P less than 0.05, respectively) than in the HAR group. However, the maximum voluntary contraction did not differ between the two groups. Rectoanal inhibitory reflex was found to be present in 17 of the 20 patients with LAR and in all patients with HAR. The volume at which the anal sphincter is continuously inhibited was significantly reduced in the LAR group (P less than 0.001). Also, the conscious rectal sensibility volumes were found to be significantly reduced for threshold, constant, and maximum tolerated volume. Threshold volume for internal sphincter relaxation was lower than the threshold volume for rectal sensation in some patients with LAR. This could allow postoperative fecal soiling. Rectal compliance was decreased (P less than 0.001) in the LAR group. Evacuation proctography, performed in six LAR patients affected by major soiling or solid stool loss, revealed an abnormal obtuse anorectal angle and pathologic lowering of the perineum at rest and during defecation. The concomitance of internal and sphincter impairment, reduction in rectal compliance, and previous pelvis floor muscle damage are postulated as cause affecting continence in patients who underwent LAR.

B-mode imaging and histomorphometric evaluation of carotid atherosclerosis. The quantitative and qualitative evaluation of atherosclerotic lesions by the ultrasonography has presented several problems, above all, the determination of accuracy and reproducibility of this methodology in humans. The present study aims to evaluated the results of B-mode imaging of extracranial carotid arteries in patients selected for surgery as compared with histologic results of the observations of the samples obtained by endarterectomy. Shrinkage effects of the histologic samples were taken into consideration. Several bidimensional images of atherosclerotic lesions, as obtained by ultrasound at different incident angles, were used to establish their maximum thickness. The maximum degree of the vessel stenosis calculated by ultrasound showed a high correlation (Y = 0.47X + 42.4, se = 0.11, r = 0.5, p less than 0.001) compared with the one obtained by histology. The imaging methodology provided however, a mean overestimation of the stenosis of about 7%. Relationships among the amount of calcium (p less than 0.03); necrotic core p less than 0.056); and echogenic types, ie, soft, mixed, and hard; have been suggested by a statistical trend. The results suggested that of the vascular lumen due to advanced atherosclerotic lesions. Qualitative interpretation of atherosclerosis by B-mode imaging, ie, morphologic characteristics, seem, at present, to be of value, but more investigations in depth are needed.

N-[18F]fluoroacetyl-D-glucosamine: a potential agent for cancer diagnosis Positron labeled substrates such as sugars, amino acids, and nucleosides have been investigated for the in-vivo evaluation of biochemical processes in cancerous tissue. Hexosamines are obligatory structural components of many biologically important macromolecules, including membrane glycoproteins and mucopolysaccharide. We evaluated a new synthesized pharmaceutical, N-[18F]fluoroacetyl-D-glucosamine (18F-FAG), which is a structural analog of N-acetyl-D-glucosamine. C3H/HeMsNRS mice bearing spontaneous hepatomas were used for the tissue distribution study. At 60 min after injection, high uptakes were found in tumor (5.16, mean value of %dose/g), liver (3.71), and kidney (3.27). The tumor uptake of 18F-FAG showed the highest value in all tissue. In the PET study, VX-2 carcinoma of the rabbit was clearly visualized. Our preliminary results suggest that 18F-FAG has potential as a new agent for tumor imaging.

Dissociation between pain and autonomic disturbances in cluster headache. The relationship between pain and autonomic disturbances in cluster headache was studied in 54 patients whose attack always recurred on the same side, and in 7 others whose attack had affected either side on different occasions. In one of these seven patients, facial flushing and ocular sympathetic deficit was observed on the original side of headaches. In most patients, the orbital region was warmer on the painful side but in three cases this region was cooler during and between attacks. Lacrimation and rhinorrhoea were more common in severe attacks, and the temperature difference between the orbits increased with increasing severity of pain. These findings support the view that certain autonomic disturbances in cluster headache are provoked by pain. Residual autonomic dysfunction could influence autonomic activity during cluster headache. If so, residual dysfunction on the pain-free side could explain the dissociation between autonomic disturbances and pain observed in a few cases.

Pancreaticopleural fistula. Report of 7 patients and review of the literature. Pancreaticopleural fistula is an uncommon clinical condition. Its presentation is often confusing because of the paucity of clues suggestive of pancreatic disease and the preponderance of pulmonary symptoms and signs. Most patients are alcoholics but only one-half will have a clinical history of previous pancreatitis. Pleural effusions are large, recurrent, and highly exudative in nature. Many patients go through extensive pulmonary evaluation before the pancreas is identified as the site of primary pathology. An elevated serum amylase may be the first clue to the diagnosis. However, the key to the diagnosis is a dramatically elevated pleural fluid amylase. Effusions in association with acute pancreatitis, esophageal perforation, and thoracic malignancy are important to consider in the differential diagnosis of an elevated pleural fluid amylase but are usually easy to exclude. Computed tomography is excellent in defining pancreatic abnormalities and should be the first abdominal imaging study in suspected cases. Endoscopic retrograde cholangiopancreatography (ERCP) is used as a diagnostic tool only in confusing cases. Although no systematic study evaluates medical versus surgical therapy, we recommend an initial 2 to 4-week trial of medical therapy, including allowance of no oral intake, total parenteral nutrition, chest tube thoracostomy, and possibly a regimen of somatostatin or its analogs. The major complication in these patients is superinfection, which results in significant morbidity and mortality. Failure of medical therapy should be considered failure of pleural effusion(s) to clear, recurrence after reinstatement of oral intake, or superinfection. For those patients who fail to benefit from medical therapy, surgery is indicated.

Epidermoid tumors of the 4th ventricle: report of seven cases. Epidermoid tumors occur very rarely in the 4th ventricle. We discuss the history, clinical course, and the surgical results for seven patients. One patient had a remittal of symptoms, probably due to the emergence of the tumor from the 4th ventricle into the cisterna magna. Total removal of the capsule was possible only in the youngest patient. At present, four patients (mean follow-up, 6 years) enjoy good general and neurological health.

Contribution of transesophageal echocardiography to patient diagnosis and treatment: a prospective analysis. The capability of transesophageal (TEE) versus transthoracic (TTE) echocardiography as a diagnostic tool in clinical practice was prospectively examined in 86 consecutive cases. A conclusive diagnosis was possible in 95% with TEE, whereas the same result was achieved in 48% by TTE. Specifically, TEE provided a conclusive diagnosis in 14 of 16 cases of infective endocarditis, while TTE gave this result in 4 of the 16 cases (p less than 0.001). Similarly, TEE allowed a conclusive diagnosis in 11 of 11 instances of aortic dissection, while TTE gave this indication in two cases (p less than 0.001). TEE was similarly effective in eight of eight cases of atrial thrombi, whereas TTE gave the diagnosis in three of eight cases (p less than 0.01). In five subjects with intracardiac masses, TEE gave a conclusive diagnosis in all five, whereas TTE was able to diagnose conclusively in one subject (p less than 0.02). In seven patients with mitral regurgitation, TEE gave the conclusive diagnosis in all seven and TTE was able to provide this information in four (p = NS). TEE was able to provide a conclusive diagnosis in four patients with aortic insufficiency, and TTE gave the same information in two of the four (p = NS). In 14 patients with prosthetic valve dysfunction, TEE gave the diagnosis in 12 and TTE gave it in eight patients (p = NS). Both methods gave a conclusive diagnosis in 13 out of 13 cases of mitral stenosis (p = NS). Also, TEE provided a conclusive diagnosis in eight of eight patients with adult congenital heart disease and TTE gave this information in four (p = NS).

Echographic diagnosis of dural carotid-cavernous sinus fistulas. I used standardized ophthalmic echography to identify specific abnormalities in four patients with low-pressure, low-flow dural arteriovenous malformations. In all of the patients, B-scan ultrasonography showed engorgement of the ipsilateral vertical vein. A-scan ultrasonography dynamically imaged rapid blood flow through the superior ophthalmic vein and enlargement of the culpable ocular muscles in patients with restrictive ophthalmopathy. The 30-degree test distinguished between venous engorgement of the optic nerve sheath and apical compression of the optic nerve by enlarged ocular muscles.

Are people more health conscious? A longitudinal study of one community. Secular changes in cardiovascular health awareness, knowledge and behavior were observed in four biennial cross-sectional surveys and a cohort survey in a New England community. These changes are not related to more health promotion activities in the social milieu of respondents, but are more likely due to national mass media health campaigns, the effects of which may influence outcomes of community-based cardiovascular disease prevention studies.

Roles of renal and vascular renin in spontaneous hypertension and switching of the mechanism upon nephrectomy. Lack of hypotensive effects of inhibition of renin, converting enzyme, and angiotensin II receptor blocker after bilateral nephrectomy. Inhibitors of angiotensin converting enzyme, renin, and the angiotensin II (Ang II) receptor lower the blood pressure of spontaneously hypertensive rats (SHR) used as a model of essential hypertension. Since their plasma renin levels were normal or subnormal, renin in the vascular tissue was considered to play a key role in the maintenance of the hypertension. To clarify the source and localization of renin in SHR, antirenin antibodies, the converting enzyme inhibitors delapril, enalapril, and the Ang II receptor antagonist DuP 753 were administered to intact and bilaterally nephrectomized SHR and their normotensive controls. The efficient hypotensive action of the renin antibody indicated that renin of renal origin is a dominant factor. Gradual but complete disappearance of antihypertensive action of these inhibitors of the renin-angiotensin system upon bilateral nephrectomy indicated the importance of membrane-associated renin of the renal origin and angiotensin converting enzyme in the maintenance of the spontaneous hypertension.

Intraoperative anaphylaxis: an association with latex sensitivity. Latex products have recently been identified as the cause of severe intraoperative anaphylactic reactions. We have identified a group of pediatric patients who appear to be at increased risk for such reactions. Fifteen patients with either spina bifida or congenital urologic abnormalities experienced 19 intraoperative anaphylactic reactions. All patients had frequent previous exposures to rubber materials since infancy as part of their management and/or investigative procedures. Seven of 15 patients had a previous history of local skin reactions to rubber. Only four patients were atopic. All patients had undergone multiple (two of 26) operative procedures before their reactions, the onset of which ranged from 40 to 290 minutes after induction of anesthesia. The reactions varied in intensity from urticaria to severe cardiorespiratory collapse. All these patients subsequently had positive allergy skin tests and positive RAST to latex antigen. We conclude that this group is at risk when they are exposed to latex intraoperatively as a result of frequent past exposure to these materials. Allergic evaluation for latex allergy may assist in the preoperative evaluation of similar patients. In sensitized patients, appropriate prophylactic measures, particularly the avoidance of latex, is required.

Auto-PEEP during CPR. An "occult" cause of electromechanical dissociation? A 64-year-old man with severe COPD developed refractory nonperfusing sinus rhythm after intubation and positive-pressure ventilation. Fifteen minutes after resuscitative efforts were halted, the patient was noted to have spontaneous respirations and blood pressure, suggesting that dynamic hyperinflation was responsible for the observed electromechanical dissociation (EMD). We recommend a brief trial of apnea for patients with COPD and EMD when conventional measures are unsuccessful.

Chronic arterial occlusion with PGE1-resistant skin lesions treated by glycosaminoglycan compound--case reports. The authors report on 2 patients with chronic arterial occlusion in whom the intravenous administration of the glycosaminoglycan compound FPFD 101 was markedly effective. One patient suffered from thromboembolic episodes of the left hand, and the other had peripheral circulatory impairment related to collagen disease. In these patients, the oral administration of anticoagulants and antiplatelet agents in combination with intravenous infusion of prostaglandin E1 was not adequately effective. However, the addition of intravenous injection of FPFD 101 resulted in a marked improvement in their symptoms. FPFD 101, which has an anticoagulant effect and also inhibits platelet aggregation, seems to be useful for the treatment and prevention of chronic arterial occlusion when combined with drugs such as anticoagulants, antiplatelet agents, and vasodilators.

Spontaneous bacterial peritonitis due to Salmonella enteritidis in cirrhotic ascites. Spontaneous bacterial peritonitis due to Salmonella is uncommon. We report three patients with ascites infected by Salmonella. All three patients had advanced chronic liver disease, typically cirrhosis with portal hypertension. Salmonella enteritidis grew in the ascite fluid culture of the three patients. There was no clinical or microbiological evidence of Salmonella infection other than in the ascitic fluid. One patient died before antibiotic treatment was started, but the other two were treated with different combinations of antimicrobial drugs. One of them died on the fourteenth day of hospitalization, and the other survived.

Retroviral expression of transforming growth factor-alpha does not transform fibroblasts or keratinocytes. Transforming growth factor alpha (TGF alpha) is a peptide so named because it helps to impart anchorage-independent growth to normal rat kidney (NRK) cells in vitro and is secreted by many rodent and human tumor cells. To directly investigate the transforming properties of this factor, we constructed a replication-defective murine retrovirus that expresses the human sequence coding for TGF alpha. Infection of NIH/3T3 cells with the TGF alpha retrovirus led to the integration of a transcriptionally active provirus and overexpression of biologically active TGF alpha, but failed to induce morphologic transformation. Similarly, the TGF alpha retrovirus failed to induce morphologic transformation of five other types of rodent fibroblasts. We also investigated the effect of TGF alpha expression on the growth of BALB/MK mouse keratinocytes, which require epidermal growth factor (EGF) for proliferation. We show that exogenously added TGF alpha is an extremely potent mitogen for BALB/MK cells. However, retroviral expression of TGF alpha in BALB/MK cells failed to relieve dependence on exogenously added EGF (or TGF alpha) for cell growth. These results suggest that overexpression of TGF alpha does not, by itself, transform rodent fibroblasts or keratinocytes.

Rising incidence of adenocarcinoma of the esophagus and gastric cardia Analyses of cancer incidence data from nine areas of the United States revealed steadily rising rates from 1976 to 1987 of adenocarcinomas of the esophagus and gastric cardia. The increases among men in this period ranged from 4% to 10% per year, and thus exceeded those of any other type of cancer. In contrast, there were relatively stable trends for squamous cell carcinoma of the esophagus and slight declines for adenocarcinoma of more distal portions of the stomach. Adenocarcinomas of the esophagus and gastric cardia disproportionately affected white men and rarely occurred among women. By the mid-1980s, among white men, adenocarcinomas accounted for about one third of all esophageal cancers, while cardia cancers accounted for about one half of all stomach cancers with specified subsites. The rising incidence rates and similar demographic patterns point to the need for investigation into the causes of these poorly understood cancers.

Radical prostatectomy for clinical stage T1-2N0M0 prostatic adenocarcinoma: long-term results. A total of 441 stage T1-2N0M0 and 11 stage T1-2N0M0 cancer patients with an elevated acid phosphatase level only, and 18 stage T1-2N+M0 cancer patients underwent radical prostatectomy. Analysis of the 441 stage T1-2N0M0 cancer patients demonstrated that failure and survival were a function of the disease being organ-confined, specimen-confined or margin-positive, with 10-year failure rates of 12, 30 and 60%, respectively. Of the patients with positive margins 44 were and 79 were not irradiated postoperatively. Postoperative radiation produced no survival advantage. No difference in interval to failure or of survival could be identified between 105 patients whose disease was diagnosed by transurethral resection and 328 who had a palpable abnormality. Eleven patients had negative bone and node findings but they had an elevated acid phosphatase level. All 8 patients not treated with immediate androgen deprivation failed within 36 months.

Current management of varicoceles. In spite of all that has been written about the varicocele, it is still not clear who will benefit from occlusion of the spermatic vein or why improvement in semen takes place in some patients but not in others. Because fertility is usually assessed in the framework of a couple who are trying to establish a pregnancy, it is important to evaluate both partners before making any recommendations regarding therapy. If the man is found to have a varicocele and semen analyses that indicate deficits in either the quantity or quality of the sperm, surgical ligation or transvenous occlusion should be considered as one appropriate form of therapy. Varicocele ligation and embolotherapy both can be performed as an outpatient procedure with minimal morbidity and equal effectiveness regarding pregnancy outcome. The cost, if the procedures are done in an outpatient facility, should be approximately equal. The obvious benefits of the percutaneous technique are a slightly lower recurrence rate and a more rapid return to full physical activity. The surgical procedure described by Marmar and associates appears to have a similar rate of recurrence and short postoperative period of recovery. Greater experience by more urologists using this technique needs to be gained to compare it adequately with the other methods described. Varicocele ligation by the inguinal or retroperitoneal routes is familiar to most urologists and does not require the operating microscope or other special instruments. With greater understanding of the venous anatomy and with careful dissection, the persistence and recurrence rate can be acceptably low and the postoperative recovery relatively rapid and smooth.