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Biomedical subjects

N A Halasz

Publications and source records attributed to N A Halasz.

At least 19 recordsLinked to original sources

Nuclear export of phosphorylated C/EBPbeta mediates the inhibition of albumin expression by TNF-alpha.

Decreased albumin expression is a frequent feature of cachexia patients afflicted with chronic diseases, including cancer, and a major contributor to their morbidity. Here we show that tumor necrosis-alpha (TNF-alpha) treatment of primary mouse hepatocytes or TNF-alpha overexpression in a mouse model of cachexia induces oxidative stress, nitric oxide synthase (NOS) expression and phosphorylation of C/EBPbeta on Ser239, within the nuclear localization signal, thus inducing its nuclear export, which inhibits transcription from the albumin gene. SIN-1, a NO donor, duplicated the TNF-alpha effects on hepatocytes. We found similar molecular abnormalities in the liver of patients with cancer-cachexia. The cytoplasmic localization and association of C/EBPbeta-PSer239 with CRM1 (exportin-1) in TNF-alpha-treated hepatocytes was inhibited by leptomycin B, a blocker of CRM1 activity. Hepatic cells expressing the non-phosphorylatable C/EBPbeta alanine mutant were refractory to the inhibitory effects of TNF-alpha on albumin transcription since the mutant remained localized to the nucleus. Treatment of TNF-alpha mice with antioxidants or NOS inhibitors prevented phosphorylation of C/EBPbeta on Ser239 and its nuclear export, and rescued the abnormal albumin gene expression.

Active Transport, Cell Nucleus↗

Traumatic abdominal wall hernia caused by persistent cough.

We report a rare case of traumatic abdominal wall hernia caused by persistent and severe cough. We believe this is the first reported case of such an entity. We present computed tomography findings and a pertinent review of the literature.

Aged↗

The superficial femoral vein. A potentially lethal misnomer.

OBJECTIVE: To assess the potential for error in interpretation of venous duplex reports that use the term "superficial femoral vein." DESIGN: Three surveys conducted by mail. SETTING: Three multispecialty medical groups, anatomy departments of all US medical schools, and vascular laboratories. PARTICIPANTS: A total of 46 family practitioners and general internists, 95 chairpersons of departments of anatomy, and 85 laboratory directors. MAIN OUTCOME MEASURES: Proposed treatment of a patient with leg pain and an acute thrombosis of the superficial femoral vein; what nomenclature(s) for the deep thigh veins is (are) felt to be correct, what are acceptable alternatives, what is taught to students and which is preferred; and what terminology is being used in lower limb venous duplex reports. RESULTS: Only 24% (11/46) of the respondents would have administered anticoagulants to the patient as described. Only 3% (3/95) of anatomists felt the term "superficial femoral vein" was correct, 22% (21/95) felt it was an acceptable alternative (though only 9% [9/95] taught it to medical students), and only 7% (7/95) of anatomists felt the term was preferred for everyday use. The term "superficial femoral vein" is used by 93% (79/85) of vascular laboratories in lower limb venous duplex reports. CONCLUSION: Although the overwhelming majority of vascular laboratories use the term "superficial femoral vein" in venous duplex reports, the use of this term is potentially hazardous to patients. Most primary care physicians have not been taught and are not aware that the superficial femoral vein is a deep vein and that acute thrombosis of this vessel is potentially life threatening.

Family Practice↗

Effect of daily oral vitamin D and calcium therapy, hypophosphatemia, and endogenous 1-25 dihydroxycholecalciferol on parathyroid hormone and phosphate wasting in renal transplant recipients.

Ten stable, normocalcemic renal transplant patients with good allograft function, hyperparathyroidism, and variable hypophosphatemia were treated for 2 to 9 months with oral calcium carbonate and replacement doses of vitamin D analogues. Parathyroid hormone levels (PTH) and renal phosphate wasting were not autonomous or fixed but decreased with therapy. Although serum 1-25(OH)2D3 levels could be shown to rise appropriately during oral vitamin D therapy and fall afterwards, a separate study in a larger group of patients showed no effect of elevated parathyroid hormone or hypophosphatemia to increase endogenous 1-25(OH)2D3 levels. Some 42% of patients with elevated carboxy-terminal PTH, had elevated N-terminal PTH, which was closely associated with more severe phosphate wasting. Aggressive oral calcium and vitamin D supplementation in certain normocalcemic renal transplant patients may decrease endogenous PTH levels, improve hypophosphatemia, and provide a physiologic increase in levels of 1-25(OH)2D3.

Administration, Oral↗

Cholecystectomy and hepatic artery injuries.

This study included 71 cadavers used for anatomical dissection that had undergone cholecystectomies. Of these five, 7% had some type of hepatic artery injury. The subjects all had survived at least 1 year after cholecystectomy and had normal livers. The mechanisms of this injury, its pathophysiology, and its prevention are discussed.

Cholecystectomy↗

Medicine and ethics. How to allocate transplantable organs.

Organ transplantation has made tremendous strides in the last decade. The demand for transplantable organs has far outstripped the supply; waiting lists have grown long and patients are dying for want of vital organs. Therefore policies and criteria that guide the allocation of transplantable organs become ever more important. Over the years, allocation policies have evolved by including both medical and ethical considerations, and much work has gone into defining and analyzing components of such policies. However, they have often grown by accretion, and a parallel analysis of both sets of approaches did not occur. This article attempts to integrate medical and ethical considerations, and to develop a schema that will permit review, redefinition, and--it is hoped--development of a fairer, more equitable and responsive allocation system.

Age Factors↗

Abdominal catastrophes and other unusual events in continuous ambulatory peritoneal dialysis patients.

Primary bacterial peritonitis and catheter-associated infections compose the large majority of abdominal events in continuous ambulatory peritoneal dialysis (CAPD) patients. Yet occasionally primary pathology involving the abdominal viscera develops, and surgery is frequently considered. The early manifestations of intraabdominal inflammation or bleeding in patients undergoing CAPD depend on the pathological process, its access to the peritoneal cavity, and whether generalized bacterial peritonitis supervenes to obscure helpful physical findings. Clear dialysate is not a reliable sign that major pathology is absent, nor does initial stabilization of the clinical course with antibiotic therapy uniformly indicate that surgery will not be necessary. Polymicrobial peritonitis may develop in cholecystitis, pancreatitis, or from a colonic source, the latter featuring more bacterial species and more gram-negative and anaerobic organisms. A history directed at progression of symptoms and sites of abdominal discomfort and an examination for deep local tenderness and bowel incarcerated in an abdominal wall hernia are essential. Measurement of dialysate amylase and Gram stain of dialysate for food fibers may be helpful. Imaging techniques such as abdominal radiographs for dilated bowel or free subdiaphragmatic air, ultrasonography of the gallbladder or pancreas, computed tomographic (CT) scanning of the lower abdomen, and water-soluble contrast colonic studies may help identify the pathologic process. Special studies such as these should be considered early in the course of suspected unusual abdominal events in patients on CAPD.

Digestive System Diseases↗

Recent trends in the management of desmoid tumors. Summary of 19 cases and review of the literature.

Recent advances in the understanding of desmoid tumor biology affect therapeutic choices. This series of 19 patients and review of the literature outlines historic perspectives and discusses the options in the management of these locally aggressive tumors. Desmoid tumors tend to grow steadily, regardless of tumor location. However differences in the aggressive nature of these tumors are seen when age and sex distributions are scrutinized. Although recurrence rates are high, excisional therapy is the best first approach. An exception is the case in which tumor excision is either particularly dangerous or likely to result in significant physical handicap. Radiation or drug therapy are most often used with recurrent disease or as an alternative to mutilating surgery. Although many pharmacologic approaches have been advocated, (including antiestrogen therapy, cyclic-AMP, and prostaglandin inhibition), results are anecdotal at best.

Abdominal Muscles↗

Lack of effect of oxygen-radical scavenging systems in the preserved reperfused rabbit kidney.

Previous studies showed the beneficial effects of superoxide dismutase +/- catalase in perfusion-preserved rabbit kidneys but failed to show benefit in flush-cooled organs. The current studies undertook to evaluate scavengers, xanthine oxidase inhibitors, and agents that prevent the release of myeloperoxidase in 3 systems: kidneys preserved by perfusion or by flush cooling for 24 hr, studied immediately, and warm ischemia-injured kidneys evaluated after a 24-hr recovery period. In none of these groups could we demonstrate any protective effects against preservational or warm ischemic injury by the above modalities. Even though biochemical and other evidence from previous studies suggested free radical-induced injury to occur in preserved rabbit kidneys, these studies using renal function as the indicator did not do so.

Animals↗

Vascular resistance vs. perfusate osmolarity: the short term microvascular effect of hypotonic and hypertonic perfusion in the isolated kidney.

Vascular resistance changes were measured in response to alteration in perfusate osmolarity in isolated rabbit kidneys perfused at 10 degrees C. The data obtained were found to fit a simple mathematical model of the vascular resistance of the microcirculation in which it was assumed that variation in this parameter depended solely upon osmotic alterations in the size of the cells within and around the blood vessel walls. The model predicts that the volumetric changes due to the different osmolarities are produced in a tissue layer whose thickness is 30% relative to a fixed outer radius. This result is compatible with the hypothesis that the effects are predominantly due to changes of endothelial cell volume and other perivascular capillary cells. The analysis illustrates the significance of perfusate osmolarity as a determinant of vascular resistance, can be used to investigate the hemodynamic effects that occur during the introduction and removal of cryoprotective agents, and is relevant to the interpretation of results obtained with hypertonic solutions in blood volume restoration after hypovolemic shock.

Animals↗

Kidney transplantation in the cyclosporine era.

Seventy-seven patients underwent transplantation, using a cyclosporine-prednisone immunosuppression protocol. No recipients died, and graft survival at one year was 100% for living related donor (LRD) recipients and 84% for cadaver donor (CD) recipients. Nineteen percent of locally harvested, flush-cooled kidney recipients required dialysis, whereas imported kidneys had a 66% dialysis rate. Infectious complications occurred in 17% of patients. Mean hospitalization was 12.8 days for LRD recipients and 13.6 days for CD recipients. Twenty-eight patients required 37 readmissions, mostly for treatment of rejection and infections. Total two-year cost for LRD transplants was +21,400; for CD transplants, +23,900.

Cyclosporins↗