Is ochratoxin a nephrotoxic in human beings?
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Biomedical subjects
Publications and source records attributed to M Godin.
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BACKGROUND: Coronary artery disease is an uncommon event in lupus erythematosus. The mechanisms responsible for coronary occlusion are probably complex and intermixed. We report three patients with lupus erythematosus and antiphospholipid antibodies who had coronary artery disease diagnosed with coronary angiogram. OBSERVATION: Coronary artery disease occurred in three young patients aged from 21 to 35 years 3 to 11 years after the onset of lupus. They all had antiphospholipid antibodies. They had been treated with corticosteroids for 6 to 36 months. Two of them were smokers. Angiograms showed coronary occlusion two patients while the third one had probable myocardial microvasculopathy. The lupus was quiescent in all cases when coronary artery disease occurred. DISCUSSION: Antiphospholipid antibodies associated with smoking may be involved in the pathogenesis of coronary artery disease in these 3 patients.
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The pharmacokinetics of a single oral 200 mg dose of netivudine (1-(beta-D-arabinofuranosyl)-5-(1-propynyl)uracil), a nucleoside analogue under development for use in varicella zoster virus infections, were studied in 12 renal failure (RF) subjects (creatinine clearance 15 +/- 7 mL/min) and 12 age-matched healthy subjects with normal creatinine clearance. Blood and urine samples were collected up to nine days after drug administration. Concentrations of netivudine and of its main metabolite, the pyrimidine base 5-(1-propynyl)uracil (5 PU), were determined by a specific high performance liquid chromatography assay. The mean peak plasma concentrations of netivudine, Tmax, and volume of distribution were not significantly affected by RF. The elimination half-life of netivudine was approximately 15 h in subjects with normal renal function and 60 h in RF patients. Plasma and renal clearances of netivudine were significantly reduced in RF patients and AUC was three to four times higher in these patients. Cmax and AUC of 5 PU were higher in RF patients, and the half-life was also significantly longer. However, the half-life of this metabolite was much lower than that of the parent compound. Tmax and the lag time were similar in the two groups. There were highly significant correlations for netivudine and 5 PU between half-life and creatinine clearance and between renal clearance and creatinine clearance. These findings suggest that netivudine dosage may need to be reduced in patients with severe renal failure, and confirm that formation of the 5 PU is independent of the elimination of netivudine from plasma.
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We studied the efficacy and safety of ramipril and the kinetics of its active moiety ramiprilat in 12 hypertensive patients receiving regular hemodialysis, after a single dose and after long-term (28 days) administration. Patients received 2.5 mg ramipril after each hemodialysis. On days 1 and 29, ramipril was administered 4 h before the hemodialysis and serial blood samples were obtained for 9 h for determination of pharmacokinetic parameters. Tolerability was good, and all patients completed the study. There was a high degree of angiotensin-converting enzyme (ACE) inhibition throughout the study. Ramipril had a clear-cut antihypertensive effect. Long-term administration of ramipril did not modify the time to peak ramiprilat concentration, but increased the mean maximal concentration significantly: 20.2 +/- 12.7 vs. 10.4 +/- 7.1 ng center dot ml-1. The mean accumulation ratio was 2.2. Ramiprilat hemodialysis clearance was 31.7 ml/min (range 4.2-64.9 ml/min) on day 1 and 21.0 ml/min (range 7.9-56.5 ml/min) on day 29. Ramipril 2.5 mg, administered after hemodialysis, appears to be safe and effective in hypertensive patients receiving periodic hemodialysis. Despite an increase in ramiprilat concentration from day 1 to day 29, the steady state was reached. We describe the role of nonrenal clearance of ramiprilat.
Juvenile chronic arthritis (JCA) was diagnosed in 2 young girls. In one of them, antinuclear antibodies (ANA) were strongly positive during the course of erosive polyarthritis. After 5 years followup, severe renal insufficiency occurred. Antineutrophil cytoplasmic antibodies (ANCA) were positive with a perinuclear pattern on indirect immunofluorescence (IIF) and antimyeloperoxidase (MPO) specificity. Renal biopsy showed severe crescentic glomerulonephritis without significant deposits on IIF. Treatment consisted of prednisone and monthly intravenous cyclophosphamide pulse. Renal failure worsened and hemodialysis was necessary. A 2nd patient was referred for polyarthritis with positive rheumatoid factors without positive ANA. The presence of microscopic hematuria led to the discovery of crescentic glomerulonephritis with positive ANCA of anti-MPO specificity. At latest examination, after prednisone for 10 months and azathioprine for 6 months, the patient had moderate proteinuria with normal renal function. These observations emphasize that in juvenile onset chronic polyarthritis, renal microscopic angiitis with ANCA of anti-MPO specificity may occur.
Hypertension is one of the major cardiovascular risk factors. However it seldom occurs alone in a patient and the antihypertensive treatment should be taken into account when assessing global cardiovascular status. The PRIHAM study was an open study which enrolled 3,216 hypertensive atheromatous patients who already has had a clinical ischaemic accident. Patients were followed-up for 3 years. The lowering effect on cardiovascular risk, starting from the fifteenth month was confirmed to the end of 36-month study. The effect on blood pressure was observed from the third month. Stabilized blood pressure observed within the first year persisted throughout the three years without tachyphylaxis. It was effective on SBP (-14.4%) and on DBP (-15%) while maintaining a stable heart rate both in the supine position or immediately upon standing or after 3 minutes in the standing position. Tolerance was globally judged as good or very good by the investigating practitioners and the patients expressed an improvement in their feeling of well-being. In conclusion, from the level of effectiveness obtained and the low incidence of adverse effects, urapidil appears well adapted and easy to manage in a population with a particularly high cardiovascular risk.
Prerenal acute renal failure is defined as a reduction in the glomerular filtration rate due to a primary disturbance in renal hemodynamics in the absence of any structural kidney damage. In case of moderate hypotension or hypovolemia, a number of adaptative systemic and intrarenal responses preserve renal perfusion and filtration rates, particularly by inducing a marked reduction in preglomerular arteriolar resistance and an increase in postglomerular resistance. However, these mechanisms are inherently limited. In the presence of advanced circulatory failure or iatrogenic pharmacologic interventions compromising these renal defense mechanisms, prerenal failure becomes evident. Therefore, prerenal failure may occur during acute hemodynamic disturbances due to hypovolemia or systemic vasodilatation, in severe cardiac failure, in cirrhosis with ascites, and in certain clinical situations following administration of nonsteroidal antiinflammatory agents or angiotensin converting enzyme inhibitors. The treatment depends on the underlying cause.
We examined the effects of two therapeutic oral (p.o.) doses of cicletanine (50 and 100 mg daily) on renal hemodynamics and segmental tubular handling of sodium. Six normotensive (NT) healthy subjects (group 1) received 50 mg cicletanine, and 12 moderately hypertensive (HT) patients with normal sodium diet and randomly divided into two groups of 6 were treated either with cicletanine 50 mg (group II) or with cicletanine 100 mg (group III). Studies were performed both acutely and after 4 weeks of cicletanine administration. After 28-day treatment, blood pressure (BP) was significantly reduced in HT patients. In NT subjects (group I) and HT patients (groups II and III), acute administration of cicletanine 50 or 100 mg at day 0 did not significantly modify glomerular filtration rate (GFR) or renal blood flow (RBF), but markedly increased fractional excretion of Na (FENa) by 67% in group I and by 62 and 135% in groups II and III, respectively. Fractional distal reabsorption of Na (FDRNa) was significantly reduced in the three groups after cicletanine administration. After 4-weeks treatment, GFR and RBF were not significantly modified. The increase in FeNa and decrease in FDRNa were of the same magnitude as that at day 0. No major changes occurred in hormonal profile [renin, aldosterone, atrial natriuretic factor (ANF)]. Even at low doses, cicletanine has a natriuretic effect in NT and HT subjects. Unchanged fractional reabsorption of lithium and a significant decrease in FDRNa in the three groups suggest that this natriuretic effect occurs at the distal tubule.
Although smooth muscle tone is a key determinant of mechanical properties of arteries in animal experiments, it has not yet been studied in humans because of technical limitations. To assess the influence of tone on arterial properties in humans and to emphasize the interest of calculation at specific stress, we used echo tracking and photoplethysmographic measurement of arterial pressure to study radial arterial mechanics during a cold pressor test (CPT) in 12 healthy volunteers (28 +/- 2 yr). During CPT, mean arterial pressure rose from 83 +/- 3 to 106 +/- 5 mmHg (P < 0.05), internal diameter decreased from 2.75 +/- 0.15 to 2.54 +/- 0.14 mm (P < 0.05), and wall thickness increased from 0.576 +/- 0.027 to 0.634 +/- 0.029 mm (P < 0.05). At a specific pressure (105 mmHg), midwall stress and incremental modulus decreased whereas arterial compliance increased. The incremental modulus of elasticity and compliance were fitted as functions of pressure and of midwall stress. CPT decreased the modulus about equally at all wall stresses measured. The modulus decreased and the compliance increased at every level of pressure measured. At all levels of midwall stress, the compliance was decreased. Thus acute sympathetic stimulation induced by CPT decreases the wall stiffness of human arteries in vivo. This may be explained by an unloading of stiffer wall components during active arterial constriction.
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Hypertension is one of the major cardiovascular risk factors. However seldom occurs alone in a patient and the antihypertensive treatment should be taken into account when assessing global cardiovascular status. The PRIHAM study was an open study which enrolled 3,216 hypertensive atheromatous patients who already has had a clinical ischaemic accident. Patients were followed-up for 3 years. The lowering effect on cardiovascular risk, starting from the fifteenth month was confirmed to the end of 36-month study. The effect on blood pressure was observed from the third month. Stabilized blood pressure observed within the first year persisted throughout the three years without tachyphylaxis. It was effective on SBP (-14.4%) and on DBP (-15%) while maintaining a stable heart rate both in the supine position or immediately upon standing or after 3 minutes in the standing position. Amongst diabetic and dyslipidemic patients, an absence of deleterious metabolic effects was noticed, parallel with the effectiveness. Tolerance was globally judged as good or very good by the investigating practitioners and the patients expressed an improvement in their feeling of well-being. In conclusion, from the level of effectiveness obtained and the low incidence of adverse effects, urapidil appears well adapted and easy to manage in a population with a particularly high cardiovascular risk.
OBJECTIVE: To compare the ability of angiotensin converting enzyme inhibitors and beta blockers to slow the development of end stage renal failure in non-diabetic patients with chronic renal failure. DESIGN: Open randomised multicentre trial with three year follow up. SETTING: Outpatient departments of six French hospitals. PATIENTS: 100 hypertensive patients with chronic renal failure (initial serum creatinine 200-400 mumol/l. 52 randomised to enalapril and 48 to beta blockers (conventional treatment). INTERVENTIONS: Enalapril or beta blocker was combined with frusemide and, if necessary, a calcium blocker or centrally acting drug in patients whose diastolic pressure remained above 90 mm Hg. RESULTS: 17 patients receiving conventional treatment and 10 receiving enalapril developed end stage renal failure. The cumulative renal survival rate was significantly better in the enalapril group than in the conventional group (P < 0.05). The slope of the reciprocal serum creatinine concentration was steeper in the conventionally treated patients (-6.89 x 10(-5)l/mumol/month) than in the enalapril group (-4.17 x 10(-5)l/mumol/month; P < 0.05). No difference in blood pressure was found between groups. CONCLUSION: In hypertensive patients with chronic renal failure enalapril slows progression towards end stage renal failure compared with beta blockers. This effect was probably not mediated through controlling blood pressure.
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