[Therapeutic prospects in primary extramembranous glomerulonephritis in adults].
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Biomedical subjects
Publications and source records attributed to B Weil.
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Glutamate excretion due to amino acid starvation was investigated in "stringent" and "relaxed" strains of Escherichia coli. The observed excretion process is relA-dependent, carrier-mediated, and glutamate-specific. After induction, excretion was detected within less than 2 min and continued for more than 5 h with a rate of 7-10 nmol (mg dry weight)-1 min-1. Using carbonyl cyanide m-chlorophenylhydrazone or polymyxin B nonapeptide, together with valinomycin, it was shown that glutamate excretion is driven by the membrane potential.
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The objective of this trial was to determine the long-term antiproteinuric effect of a low-dose of the angiotensin-converting-enzyme inhibitor (ACEI) captopril in patients with idiopathic membranous nephropathy (IMN), stable renal function, and no indicators of poor long-term prognosis. Fourteen adult IMN outpatients (median age 53 years) with a median duration of disease of 3 years received 12.5 mg of captopril twice a day for 12 months in a prospective trial. The effects of therapy were evaluated on the basis of plasma creatinine, 24-h proteinuria, the proteinuria selectivity index, albuminaemia, and serum IgG levels. Data were compared by means of the non-parametric paired Wilcoxon test. Three patients withdrew from the trial. Renal function remained stable in the 11 who completed the study. A clear decrease in proteinuria was observed after 1 month of therapy, which persisted with time and was associated with a trend towards a further long-term decrease. An increase in serum albumin was only observed after 6 months of therapy, again with a trend towards an increase over time. Serum IgG levels increased during therapy. This study together with data from the literature suggests a potential long-term benefit of angiotensin-converting-enzyme inhibitors in moderately proteinuric IMN. Prospective trials comparing low-dose and high-dose ACEI to no treatment or a placebo in non-severe IMN are now required.
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OBJECTIVE: To determine if polyvalent IgG is promising therapy for severe IgG nephropathy. DESIGN: Open prospective cohort study. SETTING: Referral nephrology unit. PATIENTS: 11 adult patients with severe IgA nephropathy (9 who had idiopathic disease and 2 who had Henoch-Schönlein purpura) and indicators of poor prognosis. INTERVENTION: Patients were given high-dose immunoglobulins (2 g/kg each month) for 3 successive months, followed by intramuscular immunoglobulins (preparation content, 16.5%; 0.35 mL/kg every 15 days) for another 6 months. MEASUREMENTS: Histologic changes were analyzed by comparing pre- and post-therapy renal biopsy specimens blindly, using an activity index (14-point scale), a sclerosis index (10-point scale), and a semiquantitative immunofluorescence test of immune deposits. Proteinuria, hematuria, leukocyturia, enzymuria, and global renal function (creatinine and polyfructosan clearances) were evaluated before and after intervention. RESULTS: Proteinuria (median level before intervention, 5.20 g/d; median level after intervention, 2.25 g/d), hematuria, and leukocyturia decreased substantially. The decrease in glomerular filtration rate was greatly slowed or stopped (median rate of decline in glomerular filtration before, -3.78 mL/min per month; after, 0 mL/min per month). The histologic index of activity (median index before, 5; after, 2) and the staining intensity of glomerular IgA and C3 deposits also decreased. Immunoglobulin therapy was well tolerated. CONCLUSIONS: Immunoglobulin therapy may be effective in treating severe IgA nephropathy and protecting renal function. However, prospective controlled trials must confirm these preliminary results.
Pulmonary involvement remains the main complication of cytomegalovirus (CMV) infection in renal transplantation (RT). Early diagnosis is required for the best management of patients, and preemptive therapy could be a successful approach. In order to define the predictive value of lung alveolocapillary abnormalities. We prospectively studied 26 renal transplant recipients for their diffusing capacity of carbon monoxide (DLCO) and their pulmonary clearance of a 99mTc-DTPA aerosol. Patients were studied before transplantation and then every 2 weeks up to the end of the 3rd month following RT. Viral blood cultures and serological determinations were performed every week during these first 3 months. Bronchoalveolar lavage (BAL) was done in case of CMV disease. Statistic analysis was done using Student's t-test and Pearson's chi-square test. During the 3-month follow-up, 13 patients remained free of CMV infection. Three non-infected and 8 infected patients showed DTPA clearance abnormalities (P < 0.05). Six non-infected and 7 infected patients showed DLCO disturbance (P > 0.50). DTPA clearance were significantly modified on days 45 and 60 in the infected group. Serial DTPA scanning, in association with viral blood cultures, could be a useful test to avoid unnecessary BAL in a preemptive therapy strategy.
The i.v. inoculation of parental spleen cells into unirradiated adult F1 hybrid mice results in a graft-versus-host reaction (GVHR). In the strain combination B10D2 --> (B10.BRx B10.D2) F1, this reaction is associated with thymic injury and transient but profound cellular immune deficiency. We further analysed the immune status of these mice 60 days after GVHR induction. Phenotypic studies of spleen cells showed that these mice were repopulated with parental lymphocytes resulting in a high degree of chimerism (85%). At this time, the mice looked healthy and recovered a normal cytotoxic T cell response (CTL) against allogeneic cells. GVH chimeric splenocytes were unresponsive against F1 hybrid cells in mixed lymphocyte culture (MLC), but exhibited anti-F1 CTL reactivity. We also analysed the anti-F1 reactivity of these mice in vivo. GVH chimeric splenocytes were unable to induce GVHR after injection into a new F1 hybrid and F1 GVH mice specifically rejected F1 bone marrow (BM) cells after lethal irradiation. Grafting a neonatal parental thymus prevented the rejection of F1 BM cells and restored CTL alloreactivity. It is concluded that the chimeric state induced by GVHR is associated with a split tolerance and that a radiosensitive thymic-dependent mechanism is involved in maintaining self-tolerance in these mice.
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Medical records were reviewed retrospectively to determine the causes of chronic polyarthritis in patients attending a hospital outpatient clinic in Lomé (Togo). Among 2812 patients seen over 44 months, 70 (2.5%; 28 female, 42 male) had polyarthritis of at least three months' duration. Twenty-six patients (17 female, 9 male), with a mean age of 30 years at disease onset, had isolated, nondestructive polyarthritis mainly involving the distal appendicular joints and responsible for short-lived flares usually adequately controlled by nonsteroidal antiinflammatory agents alone; antinuclear antibodies were looked for in 16 of these patients with positive results in eight. The favorable outcome and negative tests for rheumatoid factors differentiated this condition from rheumatoid arthritis. None of the 26 patients had systemic manifestations possibly suggestive of connective tissue disease. Diagnoses in the 44 remaining patients included gout (n = 15), spondyloarthropathy (n = 12), rheumatoid arthritis (n = 12), juvenile chronic arthritis (n = 2) and human immunodeficiency virus infection (n = 3). These data confirm that rheumatoid arthritis is infrequent in West Africa. The leading cause of chronic polyarthritis in Lomé may be mild isolated nondestructive polyarthritis reminiscent of adult-onset oligoarthritis with antinuclear antibodies. Long-term follow-up and immunological evaluation of patients with this condition can be expected to provide valuable pathogenic and nosologic information.