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Biomedical subjects

Y Bar-Khayim

Publications and source records attributed to Y Bar-Khayim.

At least 19 recordsLinked to original sources

Extracorporeal losses of insulin-like growth factor-I and insulin-like growth factor binding protein-3 in adult patients on CAPD.

The effects of extracorporeal (urinary plus peritoneal) losses of insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) on their respective serum levels were studied in 10 adult patients (aged 42-74 years) with end-stage renal failure and residual renal function of 0-4.5 mL/min. All patients had been on continuous ambulatory peritoneal dialysis (CAPD) for a period of 2-27 months. Morning serum, 24-hour urine, and 8-hour overnight peritoneal concentrations of IGF-I and IGFBP-3 were measured by radioimmuno- (Incstar) and immunoradiometric (Active) assays. CAPD patients showed extracorporeal losses (mean +/- SEM) of 118.7 +/- 10.6 micrograms (urinary 6.4 +/- 2.8 and peritoneal 112.3 +/- 8.5 micrograms) of IGF-I/24 hour and 1.5 +/- 0.1 mg (urinary 0.2 +/- 0.1 mg and peritoneal 1.3 +/- 0.1 mg) of IGFBP-3/24 hour. Extracorporeal losses of IGF-I accounted for about 4% of the daily production rate of this polypeptide, and the peritoneal and urinary concentrations of IGFBP-3 did not exceed 4% and 14%, respectively, of their serum levels. Serum concentrations of IGF-I (227.7 +/- 64.2 micrograms/L) and IGFBP-3 (5.3 +/- 2.4 mg/L) were not significantly correlated with extracorporeal, peritoneal, or urinary losses of these proteins or with residual renal function. We suggest that extracorporeal losses of IGF-I and IGFBP-3 in adult patients on CAPD do not influence their serum levels and that IGF-I may therefore be used as a marker of malnutrition.

Adult↗

Increased urinary trypsin-inhibitory activity in mercuric chloride induced nephrotoxicity in Wistar rats.

UNLABELLED: The relationship between trypsin-inhibitory activity (TIA) and the nephrotoxic effects of mercuric chloride (HgCl2)--as illustrated by proteinuria and by a drop in the glomerular filtration rate (GFR) measured by creatinine clearance test (CCT)--was investigated in Wistar rats. HgCl2, 150 or 250 micrograms/100 g BW per day was injected intraperitoneally three times a week for 2 weeks. Both groups showed a significant degree of proteinuria and urinary TIA. Group B (250 micrograms HgCl2/100 g BW) displayed a greater drop in GFR than group A (150 micrograms HgCl2/100 g BW). The urinary TIA was significantly correlated with proteinuria (group A: r = 0.87, group B: r = 0.84), but it was also significantly inversely correlated with the CCT (A: r = -0.96; B: r = -0.88). IN CONCLUSION: these results suggest that increased urinary TIA may be involved in and indicative of the pathogenesis of mercuric chloride induced nephrotoxicity.

Animals↗

Role of peritoneal loss of albumin in the hypoalbuminemia of continuous ambulatory peritoneal dialysis patients: relationship to peritoneal transport of solutes.

The effects of peritoneal albumin loss and the consequences of heterogeneous peritoneal solute transport on serum albumin levels were investigated in 25 adult patients on standard continuous ambulatory peritoneal dialysis (0-58 months). The patients were divided into three groups according to their albumin concentrations (g/l/l.73 m2) in 8-hour overnight effluents: group 1 ( < 0.6, n = 5), group 2 (0.6-1.1; n = 14), and group 3 ( > 1.1;n= 6). Significant differences (mean +/- SD) were observed in serum albumin levels (4.4 +/- 0.2, 3.7 +/- 0.3, and 3.1 +/- 0.5 g/dl, respectively) and in net ultrafiltration (0.37 +/- 0.13, 0.19 +/- 0.21, and -0.06 +/- 0.20 liters/8 h/1.73m2, respectively). The serum albumin levels were strongly correlated with 8-hour peritoneal mass transfer, clearance of albumin, 8-hour effluent concentrations of protein and glucose, and ultrafiltration rate. Moreover, the serum albumin levels showed significant negative correlations with dialysate-to-serum ratios of small solutes (urea, creatinine, and uric acid) and macromolecules (IgG, IgA, and IgM) estimated from 8-, 4-, and 1-hour dwell times. In addition, an overnight dialysate glucose-to-protein ratio < 1.0 was highly predictive of low serum albumin levels ( < or = 3.5 g/dl) and poor ultrafiltration. From the results of this study we conclude that peritoneal loss of albumin as well as peritoneal transport of other solutes of wide size ('permeability') contribute to the low serum albumin levels during continuous ambulatory peritoneal dialysis, especially in patients with a high peritoneal permeability.

Adolescent↗

Insulin-like growth factor-I in patients on CAPD and hemodialysis: relationship to body weight and albumin level.

The relationship between insulin-like growth factor-I (IGF-I), body weight, and serum albumin was studied in 17 patients on continuous ambulatory peritoneal dialysis (CAPD) and 17 patients on hemodialysis. Patients were matched for gender, age (33-83 years), body mass index (16.7-36.1 kg/m2), hematocrit, concentrations of serum growth hormone, and duration of dialysis (1-210 months). Serum IGF-I concentration was measured by radioimmunoassay (Incstar) and albumin by a standard laboratory technique. CAPD patients had significantly lower serum albumin concentrations than hemodialysis patients, whereas IGF-I levels in the two groups were similar and did not differ from those in 18 normal subjects. We did not find significant positive correlations between IGF-I and serum albumin levels in CAPD or in hemodialysis patients. On the other hand, IGF-I showed a strong positive correlation with body weight (for the CAPD group r = 0.523; for both groups together r = 0.493). Both groups (CAPD and hemodialysis) and CAPD patients who weighted less than 60 kg (44%) had significantly lower serum IGF-I levels (113.5 +/- 10.2 and 108.8 +/- 15.7 micrograms/l +/- SEM, respectively) than patients who weighed 60-80 kg (38.3%; 181.2 +/- 20.9 and 196.6 +/- 27.2 micrograms/L +/- SEM, respectively) or above 80 kg (17.6%; 205.2 +/- 37.7 and 229.5 +/- 43.5; micrograms/L +/- SEM, respectively). It therefore appears that a low serum IGF-I level is a better indicator of malnutrition in CAPD and hemodialysis patients than low serum albumin.

Adult↗

Effect of 1 alpha-hydroxyvitamin D3 treatment on production of tumor necrosis factor-alpha by peripheral blood mononuclear cells and on serum concentrations of soluble tumor necrosis factor receptors in hemodialysis patients.

The effect of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] deficiency, as well as of replacement therapy with 1 alpha-hydroxyvitamin D3[1 alpha-(OH)D3], on the production of tumor necrosis factor-alpha (TNF-alpha) by peripheral blood mononuclear cells (PBMC) and on the serum levels of soluble TNF receptors (sTNFRs) in hemodialysis (HD) patients was investigated. PBMC from HD patients without prior therapy with hydroxylated vitamin D3 analogs and from normal controls produced similar amounts of TNF-alpha, either spontaneously or after stimulation with lipopolysaccharide (LPS). After oral administration of 1 alpha-(OH)D3, a precursor of 1,25-(OH)2D3, LPS-induced TNF-alpha production by PBMC of HD patients was significantly higher than that of HD patients prior to the treatment or of healthy controls. Such treatment did not, however, affect spontaneous TNF-alpha production by PBMC. Serum concentrations of both soluble TNF receptors [sTNFR-A(p75) and sTNFR-B(p55)] were significantly higher in HD patients than in controls. The ratio of sTNFR-A/sTNFR-B decreased significantly in HD patients following 1 alpha-(OH)D3 therapy. These results suggest that therapy with 1 alpha-hydroxylated vitamin D3 analogs normally given to HD patients for the management of renal osteodystrophy may also regulate the in vivo activity of TNF-alpha.

Administration, Oral↗

Heterogeneity in peritoneal transport during continuous ambulatory peritoneal dialysis and its impact on ultrafiltration, loss of macromolecules and plasma level of proteins, lipids and lipoproteins.

We investigated the effect of heterogeneity in the peritoneal transport of plasma proteins on dialysis efficiency and plasma levels of proteins, lipids and lipoproteins in 32 patients undergoing long-term continuous ambulatory peritoneal dialysis (CAPD; 9 females and 23 males, 18-76 years old). Eleven patients were studied on several occasions (at 0-42 months) and the remainder at 6-60 months on CAPD (n = 49). We have divided our patients arbitrarily into two equal groups according to their protein concentration in the peritoneal effluent at the end of an 8-hour cycle. Patients with a high peritoneal protein concentration (> or = 2 g/l/1.73 m2) have lower ultrafiltration capacity, higher glucose absorption rate and increased loss of most plasma proteins [including albumin, immunoglobulins (Ig), complement components and high-density lipoproteins (HDL)] compared to patients with a low peritoneal protein concentration (< 2 g/l/1.73 m2). Consequently, plasma levels of albumin, IgM and HDL were lower in patients with a high peritoneal protein concentration. The latter had also increased levels of plasma triglycerides and very-low-density lipoproteins. The difference observed in peritoneal transport between the groups could be ascribed only in part to the duration of CAPD treatment, and hence to the number of peritonitis episodes but not to medications. Therefore, we suggest that inherent constitutional factors may be responsible for some of the observed heterogeneity in the peritoneal transport of these patients which is already evident at the start of CAPD treatment. Patients with high peritoneal transport are exposed to an augmented atherogenic plasma lipid profile in addition to a reduction in dialysis efficiency (ultrafiltration failure). These patients may become prone also to nutritional and immunological disturbances. Therefore, we suggest taking these effects into consideration before choosing the appropriate dialysis modality in patients with increased peritoneal transport for plasma proteins.

Adolescent↗

Serum concentrations and peritoneal loss of growth hormone and growth-hormone-binding protein activity in older adults undergoing continuous ambulatory peritoneal dialysis: comparison with haemodialysis patients and normal subjects.

Serum concentrations and peritoneal losses of growth hormone (GH) and of growth-hormone-binding protein (GH-BP) activity in 13 patients undergoing continuous ambulatory peritoneal dialysis (CAPD) were compared with those of 13 patients on haemodialysis and 13 normal subjects. The individuals in the three groups were matched by age (40-83 years), gender, and serum glucose concentration. In addition CAPD and haemodialysis patients were matched by haematocrit, serum creatinine and albumin concentrations, and period of time on dialysis (0.5-127 months). GH in the serum and in the peritoneal effluent were measured by radioimmunoassay (RIA) and NB2 bioassay. GH-BP activity was analysed by binding assay and expressed as a percentage of the specific binding of GH. In the haemodialysis patients, serum GH was significantly greater and serum GH-BP activity significantly less than in the CAPD patients and control subjects. Between the two latter groups no significant differences in GH or in GH-BP activity were observed. GH bioactive/immunoactive ratios in the three groups were similar. Both GH and GH-BP were detected in the peritoneal effluent of CAPD patients, in whom an overnight (8-h) peritoneal loss of GH (8.0 +/- 1.4 x 10(-3) micrograms/h/1.73 m2) was strongly correlated with serum GH (r = 0.840). Circulating GH and GH-BP activity were influenced by serum creatinine and haematocrit. In addition a positive relationship was observed between GH-BP activity and body mass index and between GH and time on dialysis. These data reaffirm that older adults undergoing haemodialysis, unlike CAPD patients, exhibit persistent abnormalities in GH-GH-BP axis.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

ECG changes and cardiac arrhythmias in chronic renal failure patients on hemodialysis.

Serial 12-lead electrocardiogram (ECG) recordings and 24-hour Holter monitoring were carried out in 39 patients with chronic renal failure, starting just before a routine dialysis session. In an attempt to identify risk factors for cardiac arrhythmias, the results obtained from each patient were correlated with a variety of clinical, hematological, and biochemical data. All patients exhibited ECG changes, which were most pronounced during the first 2 hours of dialysis. The most frequent of these changes were a decrease in T wave amplitude and increase in Tmax time (all patients), an increase of QRS amplitude (61% of patients), shortened or prolonged QTc interval (61%) and ischemic-like ST-T changes (22% and 39%, respectively). Potentially clinically significant arrhythmias occurred in 12 patients (31%) of which 8 were supraventricular, 3 were combined ventricular and supraventricular, and 1 was pure ventricular. The only clinically identified risk factor for complex ventricular and supraventricular arrhythmia was advanced age. The arrhythmia and nonarrhythmia groups differed significantly in their predialysis hematocrit, O2 content, serum urea, and osmolarity, and in their postdialysis serum phosphorus and osmolarity. The results indicate that patients with chronic renal failure frequently exhibit ECG changes and a high incidence of ventricular and supraventricular arrhythmias, which may be prognostically significant, during and after hemodialysis.

Adolescent↗

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↗

Plasma tumor necrosis factor soluble receptors in chronic renal failure.

Two soluble tumor necrosis factor receptors (sTNFRs) were detected in the plasma of patients with different degrees of chronic renal failure (CRF) and of long-term hemodialysis (HD) patients. In uremic undialyzed patients, plasma levels of both sTNFRs increased progressively with declining renal function. A linear correlation was found between sTNFR plasma levels and plasma creatinine concentration. sTNFR levels in end-stage uremic patients shortly before commencement of first HD treatment were approximately tenfold higher than in normal subjects. Long-term HD patients showed a further increase in plasma sTNFRs. The origin of sTNFRs, as well as their physiological role remains to be elucidated.

Adult↗

Acute oliguric renal failure complicating type A nonfulminant viral hepatitis. A case presentation and review of the literature.

Nonfulminant acute renal failure very rarely complicates type A viral hepatitis. So far only eight patients have been described in the English language, Japanese, or Israeli literature who had type A viral hepatitis with renal failure without any association with "hepatorenal syndrome," pregnancy, or other types of viral hepatitis. We describe a 52-year-old man with type A viral hepatitis, proven by IgM anti-A virus antibodies complicated by oliguric renal failure, which required hemodialysis. The patient recovered completely after a few weeks. Kidney biopsy demonstrated interstitial nephritis with no glomerular involvement. Review of the literature in relation to the causes and the rarity of the renal failure is included.

Acute Kidney Injury↗

Antimicrobial gentamicin activity in the presence of exogenous protease inhibitor (Bowman-Birk inhibitor) in gentamicin-induced nephrotoxicity in rats.

In our previous studies, we found increased levels of urinary trypsin inhibitory activity in gentamicin-induced nephrotoxicity in rats. Following administration of the Bowman-Birk trypsin and chymotrypsin inhibitor (BBI), no proteinuria was detected in gentamicin-treated rats, and a decrease in creatinine clearance was noted in only 50% of the injected rats. In the present study, we examined the antimicrobial activity of gentamicin against Escherichia coli in the presence of BBI in gentamicin-induced nephrotoxicity in rats. We found that 50% of rats with E. coli-positive blood cultures died of septicemia. All the rats injected with E. coli plus gentamicin or E. coli plus gentamicin plus BBI survived, the latter showing no proteinuria or deterioration in creatinine clearance. In conclusion, BBI, which is an effective inhibitor of gentamicin-induced nephrotoxicity, does not affect the antimicrobial activity of gentamicin sulfate.

Animals↗

Effect of interaction between gentamicin and pyridoxal-5-phosphate on functional and metabolic parameters in kidneys of female Sprague-Dawley rats.

Daily intraperitoneal (i.p.) injection of genatmicin at a dose of 70 mg/kg for 11 days produced nephrotoxicity in female Sprague-Dawley rats as evidenced by increased excretion of urinary protein and trypsin inhibitory activity as well as rise in renal individual class and total phospholipid. The observed proteinuria was associated with a significant twofold fall in creatinine clearance and histopathological changes, including the presence of hyaline casts and flattened epithelial cells within the lumen of proximal convoluted tubules. Although pyridoxal-5-phosphate (50 mg/kg) administered i.p. did not significantly alter creatinine clearance, histopathology, proteinuria, and urinary trypsin inhibitory activity, an increase in individual class and total phospholipid was noted in kidney. In rats simultaneously administered gentamicin and pyridoxal-5-phosphate, the observed fall in renal gentamicin content was associated with a return of individual class and total phospholipid to control values. However, the decline in creatinine clearance, enhanced proteinuria, and increase in urinary trypsin inhibitory activity in the simultaneous-treated group was similar or greater than that seen in the gentamicin-only injected rats. Morphological examination of simultaneous-treated rats revealed extensive alterations in proximal tubules including numerous mitotic figures, large vesicular nucleii, and prominent nucleoli in epithelial cells as well as hyaline casts within the lumen. Our data combined with results of previous studies suggest that sex and type of rat strain are important factors in aminoglycoside-induced nephrotoxicity. It is evident that a specific concentration of pyridoxal-5-phosphate may be necessary to provide protection against all manifestations of aminoglycoside-induced renal damage.

Animals↗