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J Bernheim

Publications and source records attributed to J Bernheim.

At least 127 records · Page 7Linked to original sources
PubMed1995

Effect of recurrent pregnancies on the evolution of adriamycin nephropathy.

BACKGROUND: In rats with incipient adriamycin nephropathy, pregnancy increases urine protein excretion and mean arterial pressure, with no changes in the glomerular filtration rate. Renal histology is normal and the glomerular TxB2/PGE2 ratio is increased. METHODS: In the present study we evaluated the influence of repeated pregnancies on the evolution of adriamycin nephropathy. Two weeks after a first delivery, rats were mated again and were followed till 35 days after the second delivery. RESULTS: In pregnant rats with adriamycin nephropathy, urine protein excretion and mean arterial pressure returned to values identical to those found in age-sex-matched virgin rats with adriamycin nephropathy. At the end of the second pregnancy, mean arterial pressure and urine protein excretion were again elevated, compared with virgin rats with adriamycin nephropathy. Thirty-five days after the second delivery, urine protein excretion and mean arterial pressure remained elevated, 296 +/- 50 mg/day vs 115 +/- 26 and 121 +/- 4 vs 110 +/- 1 mmHg respectively, P < 0.05. Glomerular filtration rate remained unchanged 0.84 +/- 0.09 vs 0.79 +/- 0.09 ml/min in virgin rats with adriamycin nephropathy. The glomerular TxB2/PGE2 ratio was decreased, contrasting with the first pregnancy. At the end of the second pregnancy, histological examination of the kidneys in rats with adriamycin nephropathy revealed a significant increase in mesangial expansion. It was even more marked 35 days later, at the last follow-up, with a semiquantitative score of 162 +/- 29 vs 81 +/- 20 in virgin adriamycin nephropathy rats, P < 0.05. CONCLUSIONS: In rats with adriamycin nephropathy, repetitive pregnancies seem to aggravate the natural course of the disease in an irreversible fashion. The earlier changes in glomerular prostanoid synthesis, particularly on thromboxane, may play a pathogenic role by activating mesangial cell matrix synthesis.

Animals↗
PubMed1995

Inhibition by uraemic sera of CD4+ T-cell adhesion to extracellular matrix components.

BACKGROUND: T-cell-mediated immune responses are impaired in patients with chronic renal failure. The migration, proliferation, differentiation, biological functioning, and interaction with other T cells are mediated by cell surface adhesion proteins, which include integrins. METHODS: To elucidate how uraemia can impair T-cell-mediated responses in vivo, the effects of sera from uraemic patients on T-cell proliferation and adhesion to extracellular matrix (ECM) components were examined. RESULTS: Preincubation of human CD4+ T cells with sera from undialysed and dialysed (haemodialysis or peritoneal dialysis) uraemic patients inhibited the capacity of the cells to be stimulated by phytohaemmagglutinin and by anti-CD3 monoclonal antibody plus immobilized fibronectin (FN). Sera from uraemic and dialysed patients, but not from healthy individuals, inhibited significantly, and in a dose-dependent fashion, human CD4+ T cell adhesion to immobilized FN and laminin (LN). The degree of inhibition of adhesion was similar whether the sera were continuously present, even during the adhesion assay, or removed by washing. The adhesion inhibiting capacity of the uraemic sera was not due to modification of the expression of beta 1 integrins on the surfaces of the T cells. CONCLUSIONS: These results suggest that uraemia can impair the proliferative capacity and adhesion of immune cells, and thus may affect normal immune processes and contribute to the overall immune deficiency observed in patients with renal failure.

CD4-Positive T-Lymphocytes↗
PubMed1995

Effect of 1-28 alpha-h atrial natriuretic peptide on acute renal failure in cadaveric renal transplantation.

The efficacy and safety of (1-28) alpha-human ANP in preventing acute tubular necrosis (ATN) in cadaveric renal transplantation was tested by comparing ANP infusion with a maximal hydration (MH) regimen which we previously reported as effective in lowering the incidence of ATN (1, 2). Since the production of endogenous ANP increases with volume overloading (3), we hypothesized that increased endogenous ANP production may contribute to the beneficial effects of MH in renal transplant recipients. We thus conducted an open randomized study comparing the effect on early renal allograft function of MH (control group) versus moderate hydration plus ANP infusion (ANP group). Forty patients were blindly paired in two groups of 20 according to the duration of cold ischemia time (mean +/- 2 h). The demographic characteristics of donors and recipients were similar. Using a Swan-Ganz catheter, hemodynamic parameters were monitored for 4 h after transplantation. The group receiving ANP and moderate hydration was perfused to a mean pulmonary arterial pressure (PAP) of < or = 20 mmHg. The PAP in patients receiving MH was driven to > or = 25 mmHg. In the ANP group, a bolus of 100 micrograms of ANP was infused into the graft's renal artery at the time of unclamping, followed by 24 h of continuous intravenous infusion at 0.03 microgram/kg/min. Thereafter, the patients received ANP at a rate of 0.01 microgram/kg/min until the serum creatinine reached < 2 mg/dl. As a consequence of the hydration regimen, the PAP at unclamping was lower in the ANP group than in the control group; 20 +/- 3 and 26 +/- 4 mmHg, respectively (p < 0.05). The ANP plasma levels were significantly higher during the first 3 d in the ANP group (p < 0.001). The median recovery rate of renal function was similar in both groups. No patients in the ANP group experienced ATN while 4 patients (20%) in the control group did (p = 0.125). The need for hemodialysis was markedly reduced in the ANP group compared to the control group (1 ANP-treated patient required dialysis once whereas 5 patients from the control group underwent dialysis a total of 26 times; p = 0.068). ANP administration was well-tolerated and no hypotensive episodes were reported. This preliminary study suggests that ANP infusion is at least as effective as maximal hydration in preventing ATN and represents an efficient alternative for transplantation centers which do not use maximal hydration as a standard regimen in managing kidney allograft recipients.

Acute Kidney Injury↗
PubMed1994

Increased thromboxane mediates the adverse renal effects of interleukin-2 in rats.

The capillary leak syndrome with decreased GFR and renal water and sodium retention after recombinant interleukin-2 (IL-2) administration may arise from endothelial activation via an increase in prostaglandin synthesis. This study was undertaken to better define the role of the prostaglandin system in the renal and metabolic effects of IL-2 administration in rats. The chronic administration of IL-2 (100,000 U/kg, thrice daily, ip) resulted in a significant increase in body weight, a decrease in GFR and in the urinary excretion of sodium and potassium, and an increase in the urinary excretion of thromboxane (TXB2). After combined IL-2 and low-dose indomethacin (1.7 mg/kg per day po), a significant decrease in body weight with normalization of GFR, of the urinary excretion of Na, and of urinary TXB2 was noted in animals receiving combined therapy as compared with those receiving IL-2 alone. In contrast, high-dose indomethacin administration (33.3 mg/kg po for the last 3 days of the study) was associated with a further decrease in GFR, enhancement of the sodium and potassium retention, and suppression of prostaglandin E2 excretion. The administration of the thromboxane receptor antagonist SQ 29548 in IL-2-treated rats led to a reversal of the fall in GFR induced by the lymphokine without significant changes in urinary sodium excretion. These results support the hypothesis that thromboxane is an important mediator of the renal and systemic effects of IL-2. These effects are reversed at least partly by low-dose indomethacin, which selectively suppresses thromboxane A2 (TXA2) synthesis, or by TXA2 receptor antagonism.

Animals↗
PubMed1994

Antiviral activity of mice with chronic renal failure--an assessment using peritoneal effluents.

Antiviral activity (AVA) determined by the inhibition of the cytopathic effect (CPE) of vesicular stomatitis virus (VSV) on mice fibroblasts, was measured in the peritoneal effluent of mice. Four groups of animals (each group numbering 30 mice) were studied. Group 1 consisted of sham operated mice and served as the control group. Group 2 underwent implantation of silastic matter (of which the Tenckhoff catheter is made). In group 3, chronic renal failure was induced. Group 4 comprised those mice in which both chronic renal failure was induced and silastic matter implanted. Optical density readings, directly related to the inhibition of CPE were 0.66 +/- 0.01, 0.59 +/- 0.08, 0.85 +/- 0.06 and 0.86 +/- 0.13 for groups 1, 2, 3 and 4, respectively (p < 0.01 for groups 1 and 2 versus 3 and 4). Virus control readings indicative of the CPE of VSV without the presence of peritoneal effluent were 0.58 +/- 0.07, not significantly different from those obtained in groups 1 and 2. They were, however, significantly below values from groups 3 and 4 (p < 0.05). These data show that AVA is undetectable in the peritoneal effluent of normal mice. Chronic renal failure produces an enhancement of AVA. Silastic matter (Tenckhoff catheter) implantation does not play a role in the production of AVA.

Animals↗
PubMed1994

Does diurnal variation in blood pressure exist in CAPD patients?

The existence of diurnal variation in CAPD remains controversial. We therefore attempted to delineate the blood-pressure (BP) pattern in CAPD patients by ambulatory blood-pressure monitoring (ABPM). Initially ABPM was performed in 31 patients (21 M, 10 F), mean age 65.4 years (26-87) using the Spacelabs model 90207. The maximal normal BP preset on the recorder was 140/90 mmHg. Daytime and night-time readings, recorded every 30 min, were defined as those from 0600 to 2100 and 2100 to 0600 hours respectively. Mean duration of dialysis was 15.2 months (3-76). There were 14 hypertensive patients, defined as a basal BP > 140/90 mmHg, or those on antihypertensive medications. Taking the group as a whole a significant difference between day and night-time readings was found as regards minimal systolic BP (118 versus 107.6 mmHg), maximal systolic BP (181.6 versus 171.2 mmHg), mean diastolic BP (83.9 versus 79.6 mmHg), and maximal diastolic BP (121.7 versus 104.5 mmHg), P < 0.05. Diurnal variation, defined in the initial study as a 10% decrease of MAP occurring during any consecutive 4-h period, was present in 21 patients. In three the diurnal variation manifested as a paradoxical reduction of BP during the day. The only significant difference between those with diurnal variation and those without was the duration of dialysis, being 19.2 +/- 19.9 versus 13.3 +/- 17.3 months respectively, (P < 0.05). In a second study 18 hypertensive CAPD patients were subjected to ABPM. Nine of them had participated in the first study. These patients were specifically asked to detail their periods of sleep and arousal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Pregnancy-induced hypertension in rats with early adriamycin nephropathy.

In up to 60% of women with chronic renal disease an elevation of blood pressure is seen during pregnancy. The pathogenesis of this complication may be related to a diminished synthesis of vasodilatory substances by endothelial cells and to an increased sensitivity to vasopressor hormones such as angiotensin II. Previous experimental studies in rats with early chronic renal disease (adriamycin nephropathy, AN) have shown that this pregnancy-induced hypertension is associated with a lowered synthesis of glomerular PGE2. In the present study the vascular response to vasoactive substances was evaluated. In AN rats the sensitivity to an acute infusion of angiotensin II was augmented, whilst it was blunted in normal pregnant rats. Chronic treatment with the thromboxane-(Tx)-receptor antagonist, daltroban (60 mg/kg/day, p.o.) administered from mid-pregnancy induced a similar reduction in blood pressure in both AN virgin and pregnant rats. This suggests that adriamycin per se may induce vascular damage which may interfere with the normal vascular adaptation to pregnancy. Stimulation of NO synthesis with L-arginine decreased MAP values significantly in PAN rats but did not modify them during normal pregnancy. In additional experimental inhibition of the endothelial-derived relaxing factor (EDRF), nitric oxide (NO) synthesis with NAME from mid-pregnancy significantly increased SBP and MAP in normal rats. By contrast, in PAN rats chronic NAME treatment had no effect. In summary, the development of hypertension in pregnant rats with AN may be associated to endothelial cell dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1993

[Widespread gastrointestinal CMV infection as the presenting manifestation of AIDS].

A 53-year-old man is reported who developed a widespread gastrointestinal infection due to cytomegalic (CMV) virus and was found to be suffering from AIDS. He died of overwhelming pulmonary infection. There is need for awareness of the rapid increase of AIDS in our local population, particularly in groups not regarded as at high risk. It is imperative to keep this diagnosis in mind when dealing with patients with gastroenterocolitis not responding to standard treatments. CMV has a broad spectrum of clinical manifestations, from carrier state to life-threatening infection. In the gastrointestinal system it causes inflammation and ulcers in the mucosa that may bleed or perforate. There are increasing numbers of reports of CMV ileocolitis in homosexuals with AIDS. The rate of sero-positive CMV in healthy homosexual populations is 94-100% and in 14% there is active infection. CMV is the main infective agent in patients suffering from AIDS; 90% will develop an infection with this virus and in most cases it will be fatal.

AIDS-Related Opportunistic Infections↗
PubMed1993

Sodium loading and renal prostaglandins in old rats.

1. Previous studies have shown that altered synthesis of prostaglandins (PGs) in the kidney of ageing rats contributes to impaired Na conservation during sodium deprivation. In the present study, we wished to assess whether the disturbance of prostaglandin synthesis also affects the response to sodium loading in old rats. 2. We measured the urinary excretion of thromboxane B2 (TXB2), 6-keto PGF1 alpha (6KPGF1 alpha) and PGE2 in young (3-4 months) and old (20-21 months) rats after 24, 48 and 72 h of Na loading. In a separate protocol, we measured prostanoid synthesis by isolated glomeruli, cortical homogenates, medullary and papillary slices from young and old rats in basal conditions and after 15 days of dietary Na loading. 3. Young and old rats excreted similarly the Na load. The urinary excretion (U) of TXB2 and 6KPGF1 alpha were unchanged during Na load in young rats. U6KPGF1 alpha, which was significantly higher in old rats and UTXB2 which also tended to be elevated, decreased in old rats with Na loading. Sodium loading was associated with a transient increase of UPGE2 in young, but not in old rats. 4. TXB2 synthesis was increased in all portions of the kidneys of old rats. 6KPGF1 alpha production was elevated in glomeruli and cortex and that of PGE2 in cortex. In medulla and papilla only TXB2 synthesis was enhanced. 5. Sodium loading did not significantly change prostanoid synthesis in the kidneys of young rats. In old rats, glomerular and cortical TXB2 decreased whereas medullary and papillary 6KPGF1 alpha increased.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1993

Effect of timing of antihypertensive therapy on glomerular injury: comparison between captopril and diltiazem.

Recent studies have suggested that the progression of experimental chronic renal disease may be prevented by early use of antihypertensive drugs. It is unclear, however, whether such therapies may also affect established and progressive renal disease. In the present study we compared the effects of captopril (CEI) and diltiazem (CCB), started either at week 10 or at week 24 on the evolution of adriamycin nephropathy (AN). Rats were studied at weeks 7, 16, 24, 32, and 38 of the disease. None of the treatments influenced the development of nephrotic range proteinuria. The use of CCB from week 10 was even associated with increased proteinuria. The moderate hypertension of ADR rats was reduced to the same degree with both drugs. Inulin clearance (GFR) was significantly reduced in all ADR rats. However, in ADR rats treated with CEI from week 10 and in those treated with CCB from week 24, the GFR was relatively higher. Glomerular injury, evaluated by semiquantitative methods, was not ameliorated by CEI treatment. Earlier CCB treatment (week 10) worsened glomerular lesions, whilst CCB treatment initiated at week 24 reduced significantly the degree of mesangial expansion and focal glomerular sclerosis. We conclude that, in addition to their common antihypertensive action, the specific effect of drug therapy seems to be crucially time dependent.

Animals↗
PubMed1993

Is renal biopsy justified for the diagnosis and management of the nephrotic syndrome in the elderly?

During the past decade, controversy has raged about the necessity of renal biopsy for the management of the idiopathic nephrotic syndrome. The debate has centered on whether a precise diagnosis is imperative for steroid treatment or whether such therapy can be given blindly. The above question has not been addressed in the elderly. In this retrospective study 30 patients aged > 60 years, all of whom underwent a renal biopsy for an unexplained nephrotic syndrome, were categorized according to histological findings and clinical evolution of their disease. The spectrum of histology was diverse, the most common renal lesion diagnosed being membranous glomerulopathy (MGN) (23%). At variance with other works is the relatively high incidence of membranoproliferative glomerulonephritis (MPGN) (20%) found by us. Minimal change disease (MCD) and amyloidosis were encountered in 5 (17%) and 4 patients (13%), respectively. Specific therapy (steroids) was administered in 11 patients. No benefit of steroid treatment was shown in patients with either MGN or MPGN. The only lesion which responded to steroids was MCD (3 complete remissions, 1 partial). Only one biopsy was complicated by a clinically significant perirenal hematoma requiring blood transfusion. No surgical intervention was necessary. Our findings tend to favor a positive approach to the performance of a renal biopsy in the management of the nephrotic syndrome in the elderly.

Aged↗