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Biomedical subjects

U Gafter

Publications and source records attributed to U Gafter.

At least 55 records · Page 3Linked to original sources
PubMed1996

Blood transfusion enhances production of T-helper-2 cytokines and transforming growth factor beta in humans.

1. Blood transfusion confers immune suppression with improved allograft survival. The aim of this study was to evaluate the effect of blood transfusion on the production of T-helper-2 cytokines and transforming growth factor beta, which are associated with suppression of allograft rejection. An additional aim was to try to identify which blood cell type is mostly responsible for the blood transfusion effect. Production of interleukin-4, interleukin-10 and transforming growth factor beta by peripheral blood mononuclear cells isolated from patients with end-stage renal disease was measured in vitro. These assays were performed before, and 4h, 4, 7 and 14 days after a single blood transfusion and the transfusion of one unit of leucocyte-free erythrocytes. 2. Blood transfusion stimulated a significant rise in the production of all three cytokines measured. Transfusion of erythrocytes had no effect on the production of interleukin-4 or interleukin-10. 3. It is suggested that blood transfusion enhances the production of interleukin-4, interleukin-10 and transforming growth factor beta. These cytokines may inhibit production of T-helper 1 and pro-inflammatory cytokines, deactivate cytotoxic cells and thereby suppress allograft rejection. It is further suggested that the leucocyte is the transfused cell type which is mostly associated with induction of this immunosuppressive response.

Adult↗
PubMed1996

Haemodialysis arteriovenous access--a prospective haemodynamic evaluation.

BACKGROUND: Factors affecting cardiac function in dialysis patients include arterial blood pressure, anaemia, intravascular volume, and the arteriovenous (a-v) access. Cardiac failure has been directly attributed to dialysis a-v access in several cases. The contribution of the a-v access to cardiac performance has been tested, in the past, by a short manual compression on the fistula, but this technique has obvious limitations. METHODS: The present study examined prospectively the effect of dialysis a-v access on both cardiac function and various hormonal responses. Ten patients (age, mean +/- SD, 59.6 +/- 12.3) with end-stage renal failure being prepared for chronic dialysis therapy were included. All patients underwent an echocardiographic study before and 2 weeks after the creation of the a-v access. Plasma atrial natriuretic peptide (ANP), plasma renin activity (PRA), and plasma aldosterone were measured at the same time periods. RESULTS: Following the creation of the a-v fistula or graft, shortening fraction increased by 15.8 +/- 6.3% (P < 0.01), stroke volume increased by 21.9 +/- 5.3% (P < 0.01), ejection fraction increased by 10.6 +/- 4.5% (P < 0.02), cardiac output increased by 19.0 +/- 6.9% (P < 0.02), and cardiac index increased by 18.3 +/- 7.1% (P = 0.05). Systemic vascular resistance decreased by 23.5 +/- 7.1% (P < 0.01). There was no change in blood pressure, heart rate, weight, haemoglobin or serum creatinine. ANP increased by 83.7 +/- 17.0% following the a-v access operation (P < 0.001), PRA decreased by 41.2 +/- 10.0% (P < 0.05), and plasma aldosterone did not change. None of the patients developed overt high-output cardiac failure. CONCLUSIONS: This study shows that at least in the short term following the creation of a dialysis a-v access, a mild state of volume overload develops, which is offset by the ¿unloading' effect of the decreased peripheral vascular resistance; the latter is probably mediated by secretion of ANP in response to atrial stretching.

Adult↗
PubMed1996

Acute necrotizing pancreatitis, lactic acidosis and prolonged hypoglycemia in a hemodialysed patient--a logical but unfortunately fatal combination.

A hemodialysed patient with abdominal pain, severe lactic acidosis and prolonged hypoglycemia is described. The diagnosis of acute necrotizing pancreatitis was delayed and the patient died from both systemic and peripancreatic complications of the acute pancreatitis. The article deals with the problem of diagnosing acute pancreatitis in an end-stage renal failure (ESRF) patient; on the possible surgical options open to the physician in the management of acute pancreatitis and on a pathophysiological explanation behind both the lactic acidosis and hypoglycemia in this patient.

Acidosis, Lactic↗
PubMed1996

Bullous dermatosis of end-stage renal disease: a possible association between abnormal porphyrin metabolism and aluminium.

BACKGROUND: Bullous dermatosis (BD) is becoming increasingly recognized in patients with end-stage renal disease (ESRD). It is clinically reminiscent of porphyria cutanea tarda, but its detailed pathogenesis remains unclear. Studies have shown increased porphyrin levels in dialysis patients, and this may partly explain the skin lesions and photosensitivity evident in these patients. In experimental studies, aluminum can induce various abnormalities in porphyrin and haem metabolism. This study investigated a possible involvement of porphyrin metabolism and aluminum in the development of bullous dermatosis in chronically dialysed patients. METHODS: Three groups were studied (12 healthy controls; 12 patients on chronic dialysis without BD and six patients on chronic dialysis with BD). Clinical characteristics of these patients were evaluated and the levels of plasma porphyrins, erythrocyte porphyrins and enzymes involved in the porphyrin chain were determined. RESULTS: The patients with BD were predominantly male, 50% had ADPKD, all had been on dialysis for a long period of time (7.8 +/- 2.1 years) and all were anuric. CAPD and haemodialysis were used equally in the affected patients. Aminolaevulinic dehydratase activity was significantly reduced in all ESRD patients (892 +/- 47 versus 302 +/- 36 versus 408 +/- 37 nmol/ml RBC/h). Plasma uroporphyrins as well as RBC protoporphyrin were significantly elevated in ESRD patients (1.7 +/- 0.6 versus 21.6 +/- 4.7 versus 43.4 +/- 12.0 nmol/L) and (1.43 +/- 0.14 versus 2.4 +/- 0.42 versus 4.19 +/- 2.44 mumol/l) respectively. Serum A1 levels were markedly elevated in patients with BD (28.3 +/- 10.0 micrograms/l). Both uroporphyrin and protoporphyrin were significantly more elevated in ESRD patients with BD compared to ESRD patients without BD. CONCLUSIONS: Elevated plasma porphyrin levels in ESRD patients are caused by lack of urinary excretion and the inability of haemodialysis and CAPD therapy to remove them. These elevated porphyrin levels may lead to the development of porphyria cutanea tarda symptoms. Elevations in plasma uroporphyrin, red blood cell protoporphyrin, and elevated A1 levels suggest a possible relationship between an A1 'load' and abnormal porphyrin metabolism in the development of overt skin disease in the dialysed patient.

Aged↗
PubMed1996

Cirrhotic glomerulonephritis: an underdiagnosed condition.

Glomerular pathology in liver cirrhosis is common in autopsies but is underdiagnosed antemortem. The most common pathologic findings are mesangial disease with immunoglobulin A deposits, and membranoproliferative glomerulonephritis. The latter is associated, most frequently, with hepatitis C infection and cryoglobulinemia. We describe a patient with longstanding liver cirrhosis who presented with a nephritic and nephrotic syndrome. Membranoproliferative glomerulonephritis was diagnosed on kidney biopsy. There was no clinical, laboratory or histologic evidence of hepatitis C infection or cryoglobulinemia. The different aspects of "cirrhotic glomerulonephritis" are discussed and the need for searching for this underdiagnosed condition in patients with chronic liver disease is emphasized.

Biopsy↗
PubMed1995

Decreased uroporphyrinogen decarboxylase activity in patients with end-stage renal disease undergoing hemodialysis.

Raised plasma uroporphyrin levels were found in all the 14 patients with end-stage renal disease studied, 7 of whom were on continuous ambulatory peritoneal dialysis (CAPD) and 7 on hemodialysis (HD). The elevation observed in the HD group was higher than that noted in the CAPD group; 18-fold in the former and 13-fold in the latter. The difference in uroporphyrin plasma levels between the two dialysis populations might be explained, at least partially, by the reduced activity of uroporphyrinogen decarboxylase (UROD), the enzyme which converts uroporphyrinogen to coproporphyrinogen. A decrease of 48% was noted in the HD group, whereas no change was observed in the CAPD group. A significant negative correlation (r = -0.37, p < 0.01) was found between the concentration of uroporphyrin in plasma and the activity of UROD. In view of the data shown, it is suggested that erythrocyte UROD activity should be interpreted with caution in HD patients suspected of having porphyria cutanea tarda.

Chromatography, High Pressure Liquid↗
PubMed1995

Effect of nifedipine on the renal functional reserve in cyclosporine-treated renal-transplant recipients.

Cyclosporine decreases renal perfusion and impairs the renal hemodynamic response to a protein load. High-dose nifedipine has been shown to elevate renal plasma flow (RPF). We measured the renal functional reserve of 6 cyclosporine-treated renal-transplant recipients following intravenous administration of an amino acid solution, before and 2 weeks after therapy with high-dose nifedipine (up to 120 mg/day). Pretreatment renal functional reserve was nil Following administration of nifedipine, RPF increased by 22% (p < 0.01), filtration fraction decreased by 14% (p < 0.005) and renal vascular resistance declined by 39% (p < 0.005). Renal functional reserve remained unchanged. High-dose nifedipine increases renal perfusion but does not restore renal functional reserve in cyclosporine-treated renal-transplant recipients.

Adult↗
PubMed1995

Modifications in glomerular polyanion distribution in adriamycin nephrosis.

Previous reports have suggested that, in proteinuria induced by adriamycin (ADR), the functional size barrier of the glomerular basement membrane (GBM) is altered as the result of a sieving defect, whereas the functional charge barrier of the glomeruli remains intact. The aim of this study was to reevaluate the effect of ADR on anionic constituents in the glomerular capillary wall (GCW). Kidneys of nephrotic rats, induced by the injection of 7.5 mg/kg ADR, and controls were resected, and cortices were isolated 24 h and 10 days postinjection, fixed with formaldehyde, and embedded in paraffin. For the histochemical evaluation of sialyl residues, deparafinized sections were treated with biotin-labeled peanut agglutinin (PNA), before or after neuraminidase treatment. PNA binding was visualized by the avidin-biotin-peroxidase complex and interacted with hydrogen peroxide and diaminobenzidine. For electron microscopy, kidney cortices were fixed with glutaraldehyde and embedded in araldite or LR-white. The postembedding localization of anionic sites was carried out by cationic colloidal gold (CCG), directly applied on thin LR-white sections. Although in the 24-h ADR group, kidney functions and glomerular morphology were generally unaltered, the 10-day ADR group exhibited severe proteinuria, hypoalbuminemia, and massive fusion of intercalated foot processes of the podocytes. Intense PNA binding was observed after neuraminidase treatment in the GCW of the controls. This was gradually decreased in the 24-h ADR kidneys and further decreased in the 10-day ADR, indicating a gradual decrease in glomerular sialic acid content.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Glycerol-induced augmentation of sensitivity to endotoxin in rats.

Combined sepsis and rhabdomyolysis result in a mortality rate much higher than that caused by each process alone. An analogous rat model is obtained by simultaneous i.p. administration of a nonlethal dose of lipopolysaccharide (LPS 0.025 mg/100 g) and a nonlethal i.m. injection of glycerol (1 ml/100 g). The aim of this study was to determine the factors contributing to the high mortality rate in this rat model. The factors examined include: Dehydration, plasma volume expansion, 'immunization' to glycerol, induction of LPS tolerance and the effect of free radicals formed in this model. Neither dehydration nor volume expansion affected mortality. 'Immunization' with glycerol was also not effective. In contradistinction, tolerance to LPS achieved by a daily injection with gradual increasing doses of LPS (from 0.05 mg/100 g to 1 mg/100 g) for 6 days reduced the mortality rate by 60% (P < 0.001). Moreover, decreasing free radical activity using the natural antioxidant (NAO) (5 mg/100 g) reduced mortality rates by 50%. A different antioxidant, dimethylthiourea (DMTU) (50 mg/100 g) failed to reduce mortality rates. This study suggests that the synergism between glycerol and LPS is apparently due to an increase in the rats' sensitivity to endotoxin following glycerol injection. However, endotoxin apparently does not enhance sensitivity to glycerol in the rat. The new antioxidant NAO significantly reduced the high mortality rate.

Animals↗
PubMed1994

Anemia of uremia is associated with reduced in vitro cytokine secretion: immunopotentiating activity of red blood cells.

Many in vitro studies demonstrate various stimulatory effects of red blood cells (RBC) on T cell reactivity. Only a few suggest a role for RBC in vivo, such as decreased B and T cell function in iron deficiency anemia. Immune deficiency of uremia is only partially corrected by dialysis treatment. We postulated therefore that this anemia may contribute in part to the immune deficiency of uremia. The aim of our study was to evaluate this postulate and to investigate the role RBC may have in the immune system in vivo. The in vitro secretion of interleukin-2 (IL-2), gamma-interferon (gamma-IFN), tumor necrosis factor (TNF) and colony stimulating factor (CSF) by human peripheral blood mononuclear cells isolated from patients and controls was used as a measure of immune function. The following protocols were carried out: IL-2 secretion was measured in patients with end-stage renal disease (ESRD) and in controls. RBCs were transfused to patients with ESRD and secretion of cytokines was measured before, and 4 hours, 4, 7 and 14 days afterwards; patients with ESRD received recombinant human erythropoietin (rHuEpo) and secretion of cytokines was measured before treatment and two and four months later. Finally, the effect of phlebotomy and transfusion of the autologous blood on cytokine secretion in healthy subjects was measured. Secretion of IL-2 by patients with ESRD was substantially lower than that of healthy subjects. In each group, IL-2 secretion correlated positively with hemoglobin level, r = 0.73, P < 0.01 and r = 0.71, P < 0.01.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Effects of erythropoietin on glucose tolerance in hemodialysis patients.

Erythropoietin (EPO) therapy is widely used to correct the anemia of end-stage renal disease. It has been reported that this treatment affects various hormonal systems. The aim of the present study was to evaluate the effects of EPO therapy on glucose tolerance. Anemia was corrected with EPO in 10 patients on chronic hemodialysis therapy. Oral glucose tolerance tests (OGTT) were performed before and after correction of anemia. The following measurements were made: the areas under the glucose curves (AUCglue), the areas over basal glucose values (OABVglue), the areas under the insulin curves (AUCins) and the areas over basal insulin values (AOBVins). Hemoglobin concentration increased from 70 +/- 1.4 milligrams to 111 +/- 1 milligram. Fasting plasma glucose, insulin and glucagon levels were were not affected by correction of the anemia. Following administration of EPO, AOBVglue increased by 19%, from 2101 +/- 243 to 2508 +/- 230 mmol.min/l (p < 0.02), while AOBVins remained unchanged. AUCins and AUCglue remained unchanged. These data show that correction of anemia with EPO in hemodialyzed patients causes an increase in the glycemic response to an oral glucose load while not affecting the insulin response.

Anemia↗
PubMed1994

Systemic distribution of beta 2-microglobulin-derived amyloidosis in patients who undergo long-term hemodialysis. Report of seven cases and review of the literature.

A search for visceral amyloid deposits was performed on autopsy material from 20 patients who had been receiving long-term hemodialysis treatment for 4 to 21 years. Visceral amyloid was found in seven patients who had undergone hemodialysis for more than 10 years. Histochemically, the amyloid was permanganate sensitive, and immunohistochemically, it stained positively for beta 2-microglobulin. The amyloid was found mainly in the wall of blood vessels, in the form of subendothelial nodules, bulging into the vessel's lumen. The amount of amyloid increased with increasing years of hemodialysis treatment. The organs most frequently involved were the heart, gastrointestinal tract, and lungs. Smaller deposits were seen in medium blood vessels of all other visceral organs. Only the spleen was "resistant" to amyloid deposition; the reason for this splenic resistance is unknown. A similar organ distribution was found in the 19 previously reported autopsy cases. Clinically, one patient experienced a perforation of the small intestine, probably related to the narrowing of the intestinal blood vessels by amyloid deposits, and this patient died of peritonitis.

Adult↗
PubMed1994

Effect of enalapril on the microvascular albumin leakage in patients with diabetic microangiopathy and normal or mildly elevated blood pressure.

The transcapillary escape rate of albumin (TERalb) is often elevated in patients with diabetic microangiopathy. The objective of this study was to examine the effect of enalapril on the TERalb of diabetic patients with albuminuria and normal or mildly elevated blood pressure. Seventeen diabetic patients with diabetic retinopathy, albuminuria, a diastolic blood pressure below 100 mmHg and increased TERalb participated in the study. Blood pressure and TERalb were measured before and after 14 days of therapy with enalapril, 20 mg daily for 14 days. Systolic and diastolic blood pressure fell from 168 +/- 6 to 155 +/- 6 (p < 0.001) and from 87 +/- 2 to 81 +/- 2 mmHg (p < 0.005) respectively. Mean arterial pressure declined from 114 +/- 3 to 105 +/- 3 mmHg (p < 0.0001). The elevated TERalb decreased from 9.5 +/- 0.5 to 7.2 +/- 0.5%/hr (p < 0.005). In the hypertensive subset, systolic, diastolic and mean arterial pressure decreased significantly by 15, 7 and 10 mmHg (p < 0.005, p < 0.005 and p < 0.005 respectively); TERalb decreased from 9.5 +/- 0.6 to 7.3 +/- 0.6 (p < 0.03). In the normotensive subset, arterial pressure remained unchanged and TERalb decreased from 9.0 +/- 0.8 to 6.8 +/- 1.0%/hr (p < 0.03). Plasma fructosamine decreased from 373 +/- 23 to 347 +/- 20 (p < 0.05) in the hypertensive group and remained unchanged in the normotensive patients. No correlation could be demonstrated between variation in TERalb and changes in blood pressure. In conclusion, enalapril decreases microvascular albumin leakage in patients with diabetic microangiopathy and normal or mildly elevated blood pressure.

Blood Pressure↗
PubMed1993

Enhancing effects of autologous erythrocytes on human or mouse cytokine secretion and IL-2R expression.

We have recently shown that a single transfusion of red blood cells to normal human volunteers significantly increases the secretion of a variety of cytokines. In the present study we explored the in vitro effect of whole red blood cells on various T cell and monocytes functions of autologous human or mouse origin. This in vitro model would allow us to further determine in future studies the membranal determinants or the intracellular products of the RBC responsible for the enhancing effect. We demonstrate in this study that addition of autologous erythrocytes to human mononuclear cells or mouse spleen cell cultures results in enhancement of cellular responses to suboptimal concentrations of mitogens. These include cell proliferation, the secretion of IL-2, colony stimulating factor (CSF), interferon-gamma, tumor necrosis factor, and interleukin-6 by human MNC, and cell proliferation, IL-2, IL-3, and CSF by mouse spleen cells. The enhancing effect was dose dependent. Moreover, RBC are shown to directly enhance the expression of IL-2 receptors on both human and mouse cells without the need for the presence of mitogenic stimulation. The expression of IL-2R was measured both by acquisition of responsiveness to exogenous recombinant IL-2 and by immunofluorescence staining. We suggest that whole red blood cells exert a general enhancing effect on the secretion of a variety of cytokines and induce IL-2 receptor expression, probably through nonspecific interaction between membranal domains on erythrocytes and CD2 antigen on T cells.

Adult↗
PubMed1993

Deteriorating renal function with acetazolamide in a renal transplant patient with pseudotumor cerebri.

Treatment with acetazolamide for pseudotumor cerebri (PTC) in a renal transplant patient led to an acute, but reversible deterioration in renal function. Possible pathogenetic mechanisms behind acute renal failure and acetazolamide are detailed. In summary, caution should be exercised in all patients with chronic renal failure who require acetazolamide. It should be avoided if possible, used in reduced doses when necessary, and coupled with a high fluid intake to avoid dehydration and/or intraluminal obstruction.

Acetazolamide↗
PubMed1993

DNA repair and recovery of RNA synthesis in uremic patients.

A high frequency of cancer appears among uremic patients. As depressed DNA repair ability is thought to be one of the causes for malignancy in cancer prone diseases, the present study was undertaken to examine DNA repair in uremic patients. Unscheduled DNA repair synthesis in peripheral lymphocytes was measured after both ultraviolet (UV) and gamma irradiations. In hemodialysis (HD) patients the repairs were normal, but in chronic renal failure (CRF) patients not yet on dialysis treatment, both UV- and gamma-induced DNA repair abilities were depressed to about 60% of the control. Recovery of RNA synthesis after UV irradiation followed the same pattern: it was reduced in CRF but normal in HD cells. When CRF lymphocytes were incubated in normal plasma, the UV-stimulated DNA repair improved to a nearly normal level, whereas incubation of normal cells in CRF plasma depressed their repair capacity to 70% of the initial level. These results suggest that a plasmatic substance such as the carcinogenic heterocyclic amines may be involved in the impairment of DNA repair in chronic renal failure.

Adult↗