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Biomedical subjects

J Clèdes

Publications and source records attributed to J Clèdes.

At least 19 recordsLinked to original sources

[Symptomatic treatment of nephrotic syndrome].

OBJECTIVES OF SYMPTOMATIC TREATMENT: The goal is to maintain quality of life, prevent immediate complications (thromboembolic events, infection, drug reactions), prevent late complications related to atherosclerosis, and limit the progression of the chronic renal failure. THERAPEUTIC ARMAMENTARIUM: Six categories can be described. i) A reduction in proteinuria, essential for controlling the intensity of other manifestations, can be improved with a normal protein content (1 g/kg ideal weight/d) low-salt diet, strict blood pressure control, and most importantly, CEI given alone or in combination with AA2. ii) Restoration of a normal extracellular fluid (edema and high BP) can be achieved by low sodium intake and loop diuretics in fractionated increasing doses (sometimes with combination regimens). It is advisable to keep blood pressure below 125/75 mmHg. iii) Prevention of thromboembolic events (risk level dependent on urine protein output) relies on antivitamin K anticoagulants and low-molecular weight heparins. iv) Adapted prescription of protein-bound drugs. v) Lowering LDL-cholesterol, a risk factor for atherosclerosis, with an adapted diet and HMG CoA inhibitors. vi) Prevention of chronic renal failure. The development and course of chronic renal failure depend not only on the histological glomerular lesion and/or the etiology but also on supplementary glomerular and tubulointerstitial damage directly related to the degree of proteinuria. MORE THAN SYMPTOM RELIEF: Symptomatic treatment of nephrotic syndrome must be considered as an integral part of a rigorous goal-oriented therapeutic strategy.

Combined Modality Therapy↗

Cytochrome P450 4A and 2E1 expression in human kidney microsomes.

Laurate and arachidonate omega and (omega-1)-hydroxylase activities, cytochrome P450 2E1 (CYP2E1), and CYP4A content were measured in 18 human kidney microsomal samples. The rates of laurate and arachidonate were found to be very different from those measured in human liver samples, with a laurate omega/omega-1 ratio of approximately 22 in human kidney vs 0.75 in human liver. Immunoblot analysis of the 18 human kidney microsomal samples identified 1 CYP4A electrophoretic band, but CYP2E1 was not detectable in human kidney, contrary to liver. Laurate and arachidonate omega-hydroxylase activities were significantly correlated with CYP4A content (r = 0.86 and 0.75, respectively). Polyclonal antirat CYP2E1 antibody did not affect omega-hydroxylase activity, whereas the polyclonal antirat CYP4A1 antibody inhibited it by 60%. These results suggest that, in contrast to other species, human kidney microsomes do not contain significant amounts of CYP2E1, but possess CYP4A and fatty acid omega-hydroxylase activity.

Adult↗

Aberrant glycosylation of IgA from patients with IgA nephropathy.

Despite the prominent role of IgA, particularly IgA1, in the pathogenesis of IgA nephropathy (IgAN), the precise role of this molecule in the process remains unclear. Four biotin-conjugated lectins in sandwich-type enzyme-linked immunosorbent assays were devised to determine the glycosylation profiles of total IgA and its subclasses. We took advantage of differential binding properties of these lectins to sugar residues to dissect the oligosaccharide chains O-linked to the hinge and those N-linked to the Fc region of total IgA and IgA subclasses in 47 patients with IgAN and an equal number of controls. The proportion of sialylated IgA1 was higher in patients compared with controls (p < 0.02), whereas IgA2 in patients appeared less well sialylated. A reduction of galactose in pathological IgA as detected by RCA-I became significant after treatment of the molecule with neuraminidase (p < 0.01). Defective galactosylation was also observed for patient IgA1 when it was probed with ECL, a lectin that has a specificity for Gal 1,4 N-acetylglucosamine groupings on N-linked oligosaccharides. The RCA and ECL results, therefore, suggest that increased sialylation on the IgA1 is on O-linked oligosaccharides in the hinge region. This was partly confirmed by a small increase in the binding of PNA to IgA1 from the patient group. This lectin binds preferentially to Gal 1,3 N-acetylgalactosamine groups that are found on O-linked oligosaccharides.

Galactose↗

HLA class II typing and idiopathic IgA nephropathy (IgAN): DQB1*0301, a possible marker of unfavorable outcome.

Previous studies have reported associations between HLA antigens and Idiopathic IgA Nephropathy (IgAN). Nevertheless most of the studies were performed by serology. Thus we decided to perform the HLA class II typing of 58 patients by molecular biology techniques. We report a small increase of DRB1*04. But the main result of our study is the identification of a strong association between HLA DQB1*0301 and IgAN patients with an unfavorable outcome.

Gene Frequency↗

Relationship of interleukin-4 to isotypic distribution of anti-double-stranded DNA antibodies in systemic lupus erythematosus.

IgG subclasses of anti-double-stranded DNA antibodies were determined in 182 patients with systemic lupus erythematosus. All isotypes were detected, but IgG1 and IgG3 were predominant (62 and 51% of the cases, respectively). An average of 64 +/- 27% was IgG1, 16 +/- 22% IgG2, 16 +/- 19% IgG3 and 4 +/- 10% IgG4. The rank order or frequency was IgG1, IgG3, IgG2 and IgG4 in patients with musculoskeletal involvement; IgG1, IgG2, IgG3 and IgG4 in those with renal complications; IgG3, IgG1, IgG2 and IgG4 in those with cutaneous involvement; and IgG1, IgG3, IgG2 and IgG4 in those with hematological manifestations. Interleukin-4 (IL-4) was detectable in 17 of 36 selected patients, as opposed to 1 of 40 normal controls. The percentage of the total autoantibody contributed by IgG1 was significantly higher (p < 0.03) in these patients than in the remainder with undetectable levels of IL-4.

Adolescent↗

[Chronic lead nephropathy. Epidemiology and diagnosis].

Chronic lead nephropathy has recently been rediscovered. Its usual manifestations are hypertension, gout and renal impairment. Retrospective epidemiological data suggest that prolonged exposure to lead increases the risk of hypertension and nephropathy. An increase in EDTA-induced urinary lead concentration (above 600 micrograms/72 hours), perfectly representative of lead concentration in bone, has been found with a 5 to 12 percent prevalence in chronic renal impairment irrespective of its cause. The origin of lead impregnation and its influence on the course of the renal disease have not yet been elucidated.

Chronic Disease↗

[Original removing technique of the kidneys for transplantation. An experimental study (author's transl)].

The depicted procedure minimizes the hazards of aggressive manipulations, and excludes any possibility of so-called "warm ischaemia". The kidneys are flushed out in situ with cool pulsatile perfusion through an aortic cannula. Kidneys, aorta and inferior vena cava are then removed en-bloc without interrupting the perfusion, and preserved in Collins' solution at 4 degrees C. After a 6 to 19 hour storage time, one of the kidneys is transplanted on another dog, while the second one is submitted to histological examination. Nine transplantations were carried out, followed in 7 cases with a most satisfactory diuresis resuming, and with urinary ionic levels, as well as daily urea output, normalization within 48 hours. Histologic examination showed an unaffected glomerular apparatus, but some mild tubular lesions.

Humans↗

[Removal of human kidneys under "in situ" hypothermia by aortic and caval cannulations. Technique and first clinical results (author's transl)].

After dissection and cannulation of aorta and vena cava, the kidneys are washed out "in situ" with a cooling perfusion, avoiding any possibility of so-called warm ischaemia. The kidneys and their vessels, still attached to aorta and vena cava, are then en bloc removed, which enables a satisfactory preparation of the vessels for subsequent anastomosis to be performed. After an experimental study [6], four kidneys were removed according to this procedure, and transplanted after an average cold-storage time of 23 hours. Diuresis recovery was immediate, and normalization of serum creatinin, and of urinary sodium and potassium levels, was achieved within 6 days.

Adolescent↗