Search PubMed⌕ Search

Biomedical subjects

U Gafter

Publications and source records attributed to U Gafter.

At least 73 records · Page 4Linked to original sources

Angiotensin-converting enzyme inhibition and anaemia in renal patients.

A 35-year-old renal transplant patient with stable renal function developed an unexplained anaemia. Appropriate investigations proved non-diagnostic. Only when enalapril therapy was stopped did the anaemia reverse and haemoglobin levels returned to pre-treatment levels. An association between angiotensin-converting enzyme inhibitors and anaemia in patients with renal failure is becoming more evident. A literature review of this problem and its possible pathogenesis in patients with renal failure is given.

Adult↗

Tubulointerstitial nephritis and uveitis: association with suppressed cellular immunity.

It is suggested that tubulointerstitial nephritis and uveitis (TINU) is a cell-mediated immune disease with a favourable response to treatment with steroids. However, long-term follow-up has not been described and data on immunological studies are limited. The aim of this study was to evaluate the clinical features in patients with TINU who have had a long follow-up period, and in parallel to assess their cellular immunity and HLA typing. Four women with TINU were followed for 5.7 +/- 3.6 years. On remission they were studied for T-cell-mediated immunity by skin tests, T-cell subpopulations, and lymphokine secretion in vitro. The lymphokines included interleukin-2, gamma-interferon, tumour necrosis factor, and colony-stimulating factor. The in vitro response to AS101, a previously described immunomodulator, was evaluated. HLA-typing was also performed. The nephritis, which occurred once, was resolved in all patients and did not recur. In contrast, numerous relapses of uveitis occurred despite topical or systemic steroid treatment. The patients' T-cell subpopulations did not differ from controls, but they revealed anergy to skin tests and a very low secretion rate of lymphokines. AS101 corrected the suppressed secretion in vitro. A high frequency of HLA-DR6 antigen was found in the TINU patients. TINU is probably a systemic disease with a chronic relapsing course of the uveitis but with complete clinical recovery of the nephritis. Both in vivo and in vitro T-cell functions are suppressed during remission.

Adolescent↗

Mechanism of radioprotection conferred by the immunomodulator AS101.

AS101 [ammonium trichloro (dioxyethylene-0-0') tellurate] is a new synthetic compound previously described by us as having immunomodulating properties and minimal toxicity. Clinical trials are currently in progress with AS101 in AIDS and cancer patients. AS101 has recently been found to have radioprotective effects on hemopoiesis in irradiated mice when administered prior to irradiation. Since the early progenitors, spleen colony-forming units (CFU-S), are the critical cells needed for the reconstitution of the hemopoietic system, the mechanisms of action of AS101 were explored in this study by examining the compound's effect on the recovery of CFU-S, its protective effect on endogenous CFU-S and its effect on self-renewal of CFU-S. We also studied the effect of AS101 on the induction of progenitor cells into the radioresistant S-phase of the cell cycle. On days 1 and 5 after irradiation, the number of CFU-S in the bone marrow and spleen of AS101-treated mice was significantly higher than that of PBS-injected mice. Nine days after sublethal doses of irradiation, the number of endogenous spleen colonies was highest in mice given AS101 every 24 hours or every other day for 1 week prior to irradiation. AS101 administered immediately after irradiation, however, also resulted in an increase in the endogenous CFU-S. The higher number of CFU-S found in each 9-day endogenous spleen colony suggests increased self-renewal of CFU-S in AS101-treated mice. Moreover, we found that AS101 induced a higher number of progenitor cells in the S-phase of the cell cycle. These findings suggest that the radioprotection conferred by AS101 results from induction of progenitor cells in DNA synthesis (S-phase) and from the enhanced stimulation of CFU-S, not only toward proliferation but also toward CFU-S self-renewal.

Animals↗

Red blood cell calcium level is elevated in women: enhanced calcium influx by estrogens.

Red blood cell (RBC) calcium level had been found to be higher in women than in men. This study was designed to evaluate whether this is a general phenomenon and to elucidate a possible mechanism for a gender-related difference in RBC calcium levels. Differences in RBC calcium levels between women and men were examined in normal subjects, in patients with chronic renal failure (CRF) who were known to have elevated RBC calcium levels, and in female and male rats. RBC calcium level was higher in healthy women (6.1 +/- 0.5 mumol/L in women vs 4.4 +/- 0.3 mumol/L in men; p < 0.01), in women with CRF (45.8 +/- 11.8 mumol/L vs 15.4 +/- 1.1 mumol/L in men with CRF; p < 0.025) and women undergoing hemodialysis treatment (43.4 +/- 4.7 mumol/L vs 8.8 +/- 0.9 mumol/L in men undergoing hemodialysis p < 0.001). RBC calcium levels in female rats were also significantly higher than those in male rats. Ovariectomy reduced RBC calcium levels in female rats to those of male rats, whereas castration of male rats had no effect on RBC calcium levels. These in vivo findings suggest that the elevated RBC calcium level is associated with activity of female sex hormones. To investigate a possible mechanism, the in vitro effect of beta-estradiol on calcium 45 influx into RBCs and its effect on basal and calmodulin-stimulated Ca adenosine triphosphatase (CaATPase) activity in RBC membranes was determined. CaATPase activity was not affected by beta-estradiol at various concentrations and different incubation periods.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Assessment of combined 24,25(OH)2D3 and 1 alpha (OH)D3 therapy for bone disease in dialysis patients.

An increasing body of experimental data suggests a role for 24,25(OH)2D3 in bone metabolism. The present study was carried out to assess a possible therapeutic role of this vitamin D metabolite in renal osteodystrophy. Twenty-two chronic dialysis patients, most of whom were previously maintained on 1 alpha (OH)D3 therapy, received additional treatment with 10 micrograms/day 24,25(OH)2D3 and were compared to 19 patients receiving 1 alpha (OH)D3 alone. Analysis of transiliac bone biopsies obtained at study entry and following 10-16 months of treatment revealed that the combined therapy produced a decrease in bone turnover. Specifically, the addition of 24,25(OH)2D3 inhibited an increase in trabecular bone volume (BV/TV) and suppressed osteoclastic parameters. Thus BV/TV increased from 26.2 +/- 8.6 to 32.1 +/- 7.5% (p < 0.01) in the 1 alpha (OH)D3 group, but it remained unchanged in the combined therapy group. In contrast, the eroded surface (ES/BS), the osteoclast surface (Oc.S/BS), and the osteoclast numbers were significantly suppressed in patients receiving both 24,25(OH)2D3 and 1 alpha (OH)D3, as compared with those receiving 1 alpha (OH)D3 alone (p < 0.01, p < 0.01, and p < 0.001, respectively). These improvements were independent of changes in 1 alpha (OH)D3 dosage. The extent of bone aluminium deposits was unrelated to the administration of 24,25(OH)2D3 or to its effect. 24,25(OH)2D3 therapy was not associated with any adverse effects.

24,25-Dihydroxyvitamin D 3↗

Induction of a subpopulation of suppressor cells by a single blood transfusion.

Blood transfusion induces immunosuppression by a mechanism which is probably multifactorial and, in large part, obscure. In this study cellular immune suppression was examined in patients with end-stage renal disease (ESRD) following a single blood transfusion (BT). OKT8+ cells proliferated within four hours, their count increasing significantly, and reached their peak after four days. Since OKT4+ cells tended to decrease, the OKT4/OKT8 ratio declined significantly from the fourth day. Evidence in support of the above results is offered in studies on ability of concanavalin A reagent (ConA)-activated T cells to form autorosettes with human red blood cells (RBC); these T cells have been shown to function as suppressor effector cells. Autorosetting cells (RFC) proliferated in a similar pattern to OKT8+ cells. Moreover, the percentage of rise at one and two weeks of OKT8+ and RFC correlated directly, suggesting that the proliferating OKT8+ cells are in large part a subset of suppressor cells. Functional studies were performed to establish the suppressor activity of T cells before and at various times after blood transfusion. A significant increase in T cell ConA-induced suppressor activity was found one week after BT, peaking at two weeks following BT. Monocytes increased significantly from day 4 following BT, but prostaglandin E2 (PGE2) started to rise immediately, peaking at day 4. PGE2 might induce suppression by induction of suppressor cells or by direct suppression of interleukin-2. Both monocytes and suppressor cells respond immediately, but they probably induce suppression most effectively four days or more after BT.

Adult↗

Generation of T cell lines with suppressive activity derived from autorosette-forming cells of patients with autoimmune diseases.

A unique subpopulation of human suppressor autorosette-forming T cells was fractionated from peripheral blood of healthy donors and patients with various immune disorders. These cells have been maintained in long-term cultures and evinced suppressor activity in their supernatants. The study indicates the existence of a competitive relationship between the suppressor factors secreted by the cell lines and IL-2. It was found that impaired suppressor function can be related to a decrease in suppressors cell number, impaired function of individual suppressor cells, or failure to respond to active suppressor factors.

Autoimmune Diseases↗

Syndrome of inappropriate antidiuretic hormone secretion in cancer of the head and neck.

The syndrome of inappropriate secretion of arginine vasopressin (AVP) known as the syndrome of inappropriate antidiuretic hormone secretion (SIADH) is characterized by hyponatremia that results from water retention attributable to persistent AVP release. It may occur in a variety of malignant and nonmalignant lesions, with small cell or oat cell carcinoma of the lung by far responsible for the largest number of these cases. Cancer of the head and neck may be a rare cause of SIADH, and only a few such cases have been reported. We describe four patients with advanced cancer of the head and neck region with coexisting SIADH. Diagnosis and treatment are reported and the literature is reviewed. The possible occurrence of SIADH in the head and neck surgical practice should be kept in mind. Since SIADH is usually transient, water restriction and parenteral sodium chloride may be sufficient in overcoming the acute phase.

Adult↗

Impaired DNA repair in patients with end-stage renal disease and its improvement with hemodialysis.

DNA repair following ultraviolet (UV)-induced DNA damage is decreased in some cancer-prone diseases. Cancer frequency in end-stage renal disease patients is higher than in the normal population. Therefore, DNA repair from UV-induced damage in lymphocytes was determined in 11 hemodialysis (HD) patients, 11 patients on continuous ambulatory peritoneal dialysis (CAPD), 10 patients with chronic renal failure (CRF) who had not yet been dialyzed and in 12 controls. UV irradiation at 254 nm was followed by 3H-thymidine incorporation in the presence of hydroxyurea. DNA repair synthesis in CAPD and CRF was significantly reduced to only 69 and 54% of the control, respectively, whereas the repair of HD patients was close to normal (86%, p = n.s.). The impaired ability to correct DNA damage may contribute to the increased cancer incidence in uremic patients.

Adult↗

The effect of a single whole-blood transfusion on cytokine secretion.

The effect of a single whole-blood transfusion on the cascade of cytokine secretion was studied in patients with chronic renal failure. The results indicate that 1 week after blood transfusion, no significant changes were observed in the secretion of interleukin-2, colony-stimulating factor, tumor necrosis factor, and gamma-interferon. However, 2 weeks after blood transfusion, a sharp decrease was observed in the generation of these cytokines. A decrease of about 70% was observed in interleukin-2, tumor necrosis factor, and gamma-interferon secretion. The production of colony-stimulating factor 2 weeks after blood transfusion amounted to about 30% less than baseline levels. No statistical differences in interleukin-1 production were observed throughout the study. In addition, we found that the decrease in cytokine secretion was paralleled by a sharp increase in the in vitro secretion of prostaglandin E2. Thus the beneficial effect of blood transfusion on graft survival might be due in part to an immunosuppressive effect brought about by immunoregulatory changes via the cascade of cytokine secretion.

Adult↗

Castration inhibits glomerular hypertrophy and proteinuria in uninephrectomized male rats.

Renal mass reduction may lead to glomerular hypertrophy, proteinuria and focal glomerulosclerosis (FGS) in humans and rats. In humans and rats, females are less susceptible than males to these phenomena. This study was undertaken to evaluate the effect of male rat castration on the pathogenesis of proteinuria and FGS. Urinary protein was measured in 60-day-old male and female rats. Uninephrectomy was performed in all rats, and castration in half of the males. After 180 days, proteinuria, glomerular filtration rate (GFR) and blood biochemistry were determined. Kidneys were resected, weighed and subjected to morphologic studies. Following uninephrectomy, male rats developed severe proteinuria: 132.3 +/- 40.9 mg 24 h-1, most of which was accounted for by an albuminuria of 70.9 +/- 19.3 mg 24 h-1. In contrast, protein excretion in female and castrated male rats remained within normal limits: 8.0 +/- 1.8 and 4.2 +/- 0.5 mg 24 h-1, respectively. Mean glomerular volume in male rats was 1.18 +/- 0.08 x 10(6) microns3; much higher than in female rats, 0.84 +/- 0.04 x 10(6) micron3, and castrated male rats, 0.87 +/- 0.03 x 10(6) micron3 (P less than 0.005). On light and electron microscopy, glomeruli of female and castrated male rats were completely normal. In contrast, in four of seven male rats, mild glomerular changes were observed. They consisted mainly of mesangial expansion, electron-dense deposits and collapse of capillary loops. These data suggest that castration confers protection against the development of glomerular hypertrophy and proteinuria in uninephrectomized male rats. Endogenous testosterone may be associated with this development.

Animals↗

Unusual case of crescentic glomerulonephritis associated with malignant lymphoma. A case report and review of the literature.

Renal lesions in non-Hodgkin's lymphoma are rare. Furthermore, to the best of our knowledge, only 5 cases of crescentic glomerulonephritis associated with non-Hodgkin's lymphoma have been previously described. We report a case of crescentic glomerulonephritis and renal failure which preceded the diagnosis of non-Hodgkin's lymphoma. Following steroid therapy there was a resolution of these histological findings a year later.

Acute Kidney Injury↗

Genetic counseling in adult polycystic kidney disease in Israel.

45 patients with autosomal dominant polycystic kidney disease (APKD) were interviewed with regard to their knowledge about the familial nature of their disease. 22 patients (mean age up to 57 years) were treated with chronic dialysis, and 23 (mean age up to 49 years) had either normal serum creatinine or chronic renal failure without dialysis (serum creatinine range 1-7 mg/dl). Most of the patients knew the name and prognosis of their disease, but only 9% of them knew that half of their children might be at risk. Only 38% of the patients wanted to know that they had APKD before they had children and only 18% would not have had children if they had known beforehand that they were ill. 45% of the patients on dialysis and 78% of the patients not on dialysis would have had children in spite of their disease. The difference between the two groups is significant (p = 0.006). There was a correlation between the duration of follow-up of the patients and their children's knowledge (r = 0.38; p = 0.017). Genetic counseling in Israel is similar to that in other countries, but there is a large difference between the patients in Israel and others regarding their attitude towards childbearing. The finding of a linkage between a polymorphic region on chromosome 16 (3' HVR) to the locus of APKD makes a prenatal diagnosis of the disease possible. This could be a valuable tool for efficient counseling in the future.

Female↗

Erythrocytosis associated with renal artery thrombosis in a patient with polycystic kidney disease on hemodialysis.

We report a case of erythrocytosis in a patient with end-stage renal failure on chronic hemodialysis. The patient with polycystic kidney disease had an average Hb level of 10 g/dl while on hemodialysis for 3 years. He developed erythrocytosis (Hb 17.6 g/dl) following a cadaveric renal transplantation. No signs suggesting polycythemia vera were found. Nonrenal causes of secondary erythrocytosis such as anoxia, hemoglobinopathies or tumors were excluded. Angiography showed renal artery occlusion of the native kidney. Serum erythropoietin level was 85 U/l (normal 52 +/- 31 U/l) as measured by 3H-thymidine uptake. It is suggested that ischemia caused by the renal artery thrombosis stimulated the erythropoietin production in the native polycystic kidney.

Anemia, Hypochromic↗

Effect of verapamil on intestinal absorption of calcium in the rat.

The effect of verapamil in vitro, and the in vivo effect of both oral and parenteral verapamil administration on intestinal absorption was tested using everted gut sacs of duodenum, jejunum, distal ileum and proximal colon in rats. In the in vivo study, the effect of verapamil on blood levels of calcium, phosphorus and 1.25(OH)2D3, was investigated and a complete calcium balance was performed. In vitro, verapamil (1.5 mM) inhibited calcium absorption by the duodenum and colon only. Oral verapamil led to a reduction in the blood level of 1.25(OH)2D3. However, both oral and parenteral verapamil had no effect on the intestinal absorption, urinary secretion and consequently on the calcium balance.

Animals↗

Red blood cell calcium level in chronic renal failure: effect of continuous ambulatory peritoneal dialysis.

Red blood cell (RBC) calcium, calcium 45 influx, and calcium extrusion as indicated by Ca-stimulated, Mg-dependent adenosine triphosphatase (CaATPase) was determined in patients with chronic renal failure (CRF), patients with CRF receiving continuous ambulatory peritoneal dialysis (CAPD) treatment, and controls. Cell calcium, which in the controls was 5.5 mumol/L of cells, was elevated in patients with CRF--30.6 +/- 6.8 mumol/L of cells (p less than 0.002)--and in patients receiving CAPD-23.6 +/- 6.7 mumol/L of cells (p less than 0.02). Basal CaATPase activity in controls was 850.7 +/- 66.7 nmol inorganic phosphate per milligram of protein per hour. It was suppressed in patients with CRF and patients receiving CAPD: 504.9 +/- 34.4 nmol inorganic phosphate per milligram of protein per hour and 618.2 +/- 47.3 nmol inorganic phosphate per milligram of protein per hour, respectively (p less than 0.01). Calmodulin-stimulated CaATPase revealed a pattern similar to that of CaATPase basal activity. RBC calcium showed an inverse correlation with CaATPase activity (r = -0.935, p less than 0.005) in patients with CRF. Calcium influx was increased in patients with CRF and in patients receiving CAPD: 12.00 +/- 1.34 mumol/L of cells per hour and 13.60 +/- 1.70, respectively, compared with 4.61 +/- 0.39 mumol/L of cells per hour in controls (p less than 0.001). Patients with CRF have elevated RBC calcium levels mainly related to decreased extrusion and to increased influx. CAPD fails to improve substantially these abnormalities. Plasma vanadium levels were markedly elevated in patients undergoing hemodialysis and marginally in patients receiving CAPD.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium↗