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Biomedical subjects

O Kourilsky

Publications and source records attributed to O Kourilsky.

At least 19 recordsLinked to original sources
PubMed2000

Pathophysiology of cardiovascular disease in hemodialysis patients.

Cardiovascular disease is the principal cause of morbidity and mortality in dialysis patients. The principal alterations responsible are left ventricular hypertrophy and arterial disease characterized by an enlargement and hypertrophy of arteries and the high prevalence of atheromatous plaques. Left ventricular hypertrophy is the consequence of combined effects of chronic hemodynamic overload and nonhemodynamic biochemical and neurohumoral factors characteristic of uremia. The hemodynamic overload is due to flow and pressure overload. The flow overload is tightly related to hyperkinetic circulation caused by anemia, arteriovenous fistula, or overhydration and is characterized by an enlargement of the left ventricular cavity. The pressure overload in these patients is more tightly related to abnormal geometry and function of large conduit arteries, principally the stiffening of arterial tree. The flow overload is also in large part responsible for remodeling of arterial tree, and as the heart and vessels are a coupled interactive physiological system, cardiac and vascular alterations occur in parallel, being induced to a great extent by the same hemodynamic abnormalities. The principal clinical consequences of left ventricular hypertrophy and arterial alterations are heart failure, ischemic heart disease, and peripheral artery disease. Cardiovascular alterations are only partly reversible, and efforts should be directed toward early prevention.

Humans↗
PubMed1999

Nodular glomerulosclerosis with deposition of monoclonal immunoglobulin heavy chains lacking C(H)1.

The objective of this study was to further characterize the clinical and immunopathologic features of heavy chain deposition disease (HCDD), a recently described entity. Four patients were diagnosed as having HCDD on a kidney biopsy. All presented with nodular glomerulosclerosis with deposition of gamma1 heavy chains lacking CH1 epitopes, but without light chains. Two different patterns were observed in the serum. First, patients 1 and 2 had a circulating monoclonal IgGlambda containing a short gamma1 heavy chain lacking CH1 epitopes, with an apparent molecular weight of 40 kD consistent with a complete CH1 deletion. Biosynthetic experiments also showed that the deleted heavy chain was produced in excess compared with light chains, and was secreted in vitro together with half Ig molecules, although these abnormal components were not detected by Western blot analysis of whole serum. Second, patients 3 and 4 had a circulating monoclonal IgG1lambda with an apparently normal, nondeleted heavy chain subunit, but serum fractionation followed by immunoblotting revealed an isolated monoclonal gamma1 chain lacking CH1 epitopes. These data strongly suggest that renal deposition of a CH1-deleted heavy chain circulating in low amounts in the serum as a free unassembled subunit is a major feature of HCDD. The CH1 deletion is most likely responsible for the premature secretion in blood of the heavy chain by a clone of plasma cells.

Adult↗
PubMed1995

[Contribution of renal biopsy to the diagnosis and treatment of acute kidney failure].

The mortality rate of acute renal failure is still high, about 50%. About 10% of the survivors have chronic renal failure, sometimes requiring dialysis. The course of some of these cases can be improved by appropriate therapeutic measures, if they are undertaken early. Early identification of these lesions is therefore mandatory. The clinical diagnosis is often difficult: 1. rare atypical forms of acute tubular necrosis, with renal or extrarenal signs, may lead to renal biopsy; 2. vascular and glomerular disease are most often recognized clinically (sometimes misdiagnosed), but the histological type (and therefore the appropriate treatment) cannot be determined; 3. acute interstitial nephritis is rarely diagnosed clinically and the nature of the infiltrate remains unknown. In certain cases of acute renal failure, the contribution of early renal biopsy to the etiological diagnosis and to prognosis and therapy is obvious. In acute renal failure, renal biopsy should be considered early in a rather limited number of patients (about 20%), everytime the diagnosis of tubular necrosis is doubtful, especially in acute renal failure associated with persistent infection, in order to guide the therapy.

Acute Kidney Injury↗
PubMed1995

[Cyclophosphamide during pregnancy: a safe prescription].

Cyclophosphamide is an alkylating agent used to treat haematologic malignant diseases and multisystem diseases with progressive glomerulonephritis. It is rarely prescribed during pregnancy. We report a case of Henoch-Schönlein purpura discovered at the end of the first trimester of pregnancy. Despite steroid therapy, glomerulonephritis worsened and 100 mg/day cyclophosphamide per os was administered from 28th week till delivery. The infant, prematurely born, was normal and did not have any haematological disorder. Congenital malformations are often reported (5 out of 19 newborns exposed in utero to cyclophosphamide), but in all those cases, there was another potentially teratogenic agent: either radiotherapy or another antineoplastic drug. Therefore, if mother's life is in jeopardy, cyclophosphamide therapy should be given and not postponed.

Adult↗
PubMed1994

The effect of renal impairment on the pharmacokinetics of oxcarbazepine and its metabolites.

We have studied the effect of renal impairment on the pharmacokinetics of oxcarbazepine, its active monohydroxy-metabolite (which predominates in plasma), their glucuronides, and the inactive dihydroxy-metabolite after a single oral dose of oxcarbazepine (300 mg). Six subjects with normal renal function and 20 patients with various degrees of renal impairment participated. The mean areas under the plasma concentration-time curves of oxcarbazepine and its monohydroxy-metabolite were 2-2.5-times higher in patients with severe renal impairment (CLCR < 10 ml.min-1) than in healthy subjects. The apparent elimination half-life of the monohydroxy-metabolite [19 (SD 3) h] in these patients was about twice that in healthy subjects. The effect of renal impairment on the plasma concentrations of glucuronides was more marked. The renal clearances of the unconjugated monohydroxy-metabolite and its glucuronides (the main compounds recovered in urine) correlated well with creatinine clearance. The maximum target dose in patients with slight renal impairment (CLCR > 30 ml.min-1) should not be changed. In patients with moderate renal impairment (CLCR 10-30 ml.min-1) it should be reduced by 50%. In patients with severe renal impairment (CLCR < 10 ml.min-1), the glucuronides of oxcarbazepine and its monohydroxy-metabolite are likely to accumulate during repeated administration, and dosage adjustment of oxcarbazepine in these patients could not be proposed from this single administration study.

Adult↗
PubMed1993

Methylprednisolone and cyclophosphamide pulse therapy in crescentic glomerulonephritis: safety and effectiveness.

In a previous study, we found that aggressive immunosuppressive therapy with continuous high-dose oral steroid and cyclophosphamide combined with plasma exchanges for extracapillary crescentic glomerulonephritis gave controversial results since, although disease activity was controlled, iatrogenic complications had led to death in some aged patients. We then modified our therapeutic regimen, and we analyze here the evolution of 30 consecutive patients who were admitted for biopsy-proven crescentic glomerulonephritis between 1989 and 1991. The mean plasma creatinine level at admission was 393 +/- 59 mumol/L (range 70 to 1100), and 15 patients had crescent formation in more than 50% of glomeruli on initial renal biopsy. Ten patients did not receive any immunosuppressive treatment since they either had a normal renal function or they had terminal renal failure and no severe extrarenal manifestation. The 20 other patients received initial steroid pulses 500 mg x3 (n = 17), low oral steroid treatment (n = 20), cyclophosphamide pulses (n = 13), or oral cyclophosphamide (n = 3). In 4 cases plasma exchanges were also used. As a whole, 10 patients (33%) were discharged with a normal renal function, and 18 patients (60%) had chronic renal failure, 7 of them requiring dialysis or transplantation; only 2 patients died of pulmonary hemorrhage. No severe iatrogenic complication was observed. These results indicate that reduction in oral steroid dosage, cyclophosphamide pulse therapy rather than continuous oral treatment, and plasma exchanges do not induce overimmunosuppression and iatrogenic complication. It can be safe, well tolerated, and as effective as a more intensive immunosuppressive regimen for the treatment of crescentic extracapillary glomerulonephritis.

Actuarial Analysis↗
PubMed1993

[Prognosis of rapidly progressive glomerulonephritis: the influence of age].

The evolution and prognosis of extracapillary glomerulonephritis were compared in two cohorts of patients treated between 1981 and 1986 (n = 39) and between 1989 and 1991 (n = 30). In the first group, the classical immunosuppressive treatment (steroids and cyclophosphamide) was given daily and combined with plasma exchanges. In the second group, IV pulses of methylprednisolone and cyclophosphamide were administered, followed by daily low-dose steroid therapy. Plasma exchanges were performed only in cases of extrarenal disease, particularly pulmonary hemorrhage. Although the two groups are not strictly similar, it could be concluded that aggressive immunosuppression including plasma exchanges impairs the vital prognosis by inducing infectious and/or hemorrhagic complications, especially in the elderly. On the other hand, methylprednisolone and cyclophosphamide pulses appear to have effectively treated extracapillary glomerulonephritis and were well tolerated. Thus they could be administered to all patients with rapidly progressive glomerulonephritis, including aged patients.

Adolescent↗
PubMed1990

Efficacy and tolerance of cefodizime in the treatment of acute pyelonephritis.

The efficacy and tolerance of cefodizime in the treatment of acute pyelonephritis were evaluated in an open, international, multicentre study. In total, 128 patients were treated with 1 g cefodizime bd iv or im for a mean of 8.3 days. Underlying urinary tract abnormalities were present in 35% of cases. The most frequently isolated bacteria were Escherichia coli (79/97 evaluable cases) and Proteus mirabilis (8/97 evaluable cases). The overall clinical and bacteriological success rate was 89.7% (87/97). The drug was well tolerated, with only a few mild and transitory adverse events. Tolerance at the site of injection was good in 97.5% (78/80) of those treated iv, and 79% (38/48) of those treated im. Three patients had skin reactions which were probably related to cefodizime. Alterations of laboratory parameters were seen transiently in five patients (3.9%). Cefodizime is effective and well tolerated in the treatment of acute pyelonephritis.

Acute Disease↗
PubMed1983

Immunopathological studies of polyarteritis nodosa and Wegener's granulomatosis: a report of 43 patients with 51 renal biopsies.

Although it is generally considered that vasculitis of the polyarteritis nodosa (PAN) group and Wegener's granulomatosis (WG) is immune complex (IC) mediated, there are no simultaneous data on circulating IC, complement levels and deposits of Ig and complement in the kidney. Therefore we have performed a retrospective study of 43 patients suffering from PAN and WG. Ig glomerular deposits were uncommon and scanty, except in two patients with WG; C3 deposits were detected in 12 patients, whereas fibrinogen was constantly found when lesions were recent and active. Similar data were obtained for the renal vessel walls. Contrasting with these results, rheumatoid factors and cryoglobulins, suggestive of the presence of circulating IC, were detected respectively in nine of 39 and seven of 37 patients, and IC 'activity' assessed by the Raji cell assay and the Clq binding assay was found respectively in six of 17 and nine of 10 patients before treatment, and in none of 10 and five of seven patients in remission. Haemolytic complement activity and complement components were never decreased, but the C3d breakdown product of C3 was elevated in all the eight patients studied before treatment. Signs of persistent hepatitis B virus (HBV) infection were detected in five of 25 patients of the PAN group, whereas three of eight patients with WG had only anti-HBV antibodies. Furthermore, cytomegalovirus (CMV) could be isolated from the blood in a case of WG before the treatment was started. Persistent interferonaemia was detected in one of five patients. These results suggest either that renal deposition of CIC is transient, the paucity of Ig deposits being due to rapid clearance of IC by phagocytic cells; or alternatively that vascular and glomerular lesions are not caused by CIC, as in some cases of experimental vasculitis induced by infectious agents.

Adolescent↗
PubMed1983

Acute endocapillary glomerulonephritis in adults: a histologic and clinical comparison between patients with and without initial acute renal failure.

30 renal biopsies were performed in 20 adult patients with acute diffuse endocapillary glomerulonephritis. 11 patients who presented with acute renal failure (ARF) and 9 patients who had normal or mildly altered renal function were compared in order to look for clinical or pathologic features peculiar to each group and possible differences in outcome. All patients underwent early renal biopsy, and 8 had repeat biopsies. There were no significant differences in clinical, immunologic or histologic features between the two groups. In repeat biopsies, there were no histologic nor immunohistologic differences between patients with or without initial ARF. After a mean follow-up period of 18 months, the overall clinical outcome appeared favorable and was similar in the two groups. Thus, initial ARF in patients with acute endocapillary glomerulonephritis does not imply a bad prognosis. The recognition of pure endocapillary proliferation in patients with anuric acute glomerulonephritis by means of renal biopsy may avoid unnecessary and potentially hazardous treatment.

Acute Kidney Injury↗