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Biomedical subjects

G Rostoker

Publications and source records attributed to G Rostoker.

At least 37 records · Page 2Linked to original sources
PubMed1995

Immunomodulation with low-dose immunoglobulins for moderate IgA nephropathy and Henoch-Schönlein purpura. Preliminary results of a prospective uncontrolled trial.

Recently, our group has shown that a 3-month course of intravenous immunoglobulin (2 g/kg/monthly) followed by 6 months of intramuscular immunoglobulins (IMIG, 16.5%, 0.35 ml/kg every 15 days) was able to slow or to stop the decline in the glomerular filtration rate, to reduce proteinuria, hematuria, leukocyturia and the histological index of activity on renal biopsy in patients with severe forms of IgA nephropathy (IGAN) and Henoch-Schönlein purpura (HSP). The aim of this open prospective trial was to evaluate the efficacy and safety of low-dose immunoglobulin therapy in moderate IGAN and HSP with permanent proteinuria. Fourteen patients with moderate IGAN [idiopathic IGAN: n = 11; chronic idiopathic HSP: n = 3] and permanent albuminuria were treated with polyvalent IMIG (16.5%) for 9 months (0.35 ml/kg once a week for 1 month, followed by 0.35 ml/kg every 15 days for a further 8 months). Eligibility criteria in the study were Lee histological stage I, II or III, albuminuria between 300 and 2,000 mg/day and a glomerular filtration rate > 70 ml/min/1.73 m2. IMIG were well tolerated and only 1 patient withdrew from the trial. No viral, renal or immunological side effects were observed. IMIG induced a significant decrease in albuminuria as well as in the histological activity index in the 11 cases in which a follow-up biopsy was performed. There was also a decrease in serum IgA, serum beta 2-microglobulin and IgA immune complex levels, and an increase in serum IgG1 levels. Twelve of the 13 evaluable patients improved during treatment.

Adjuvants, Immunologic↗
PubMed1995

Low-dose angiotensin-converting-enzyme inhibitor captopril to reduce proteinuria in adult idiopathic membranous nephropathy: a prospective study of long-term treatment.

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.

Adult↗
PubMed1994

[Mediastinal parathyroid adenoma. Localization by scintigraphy with methoxy-isobutylisonitrile].

Cases of inaccessible mediastinal parthyroid adenomas are rare (1% of parathyroid tumours). Previously, when the localization had been confirmed by imaging techniques, we performed exploratory cervicotomy, followed by sternotomy after explorations had been completed. This procedure required two operations and sternotomy sometimes gave blank results. We therefore prospectively evaluated technitium-99m labelled methoxy-isobutyl isonitrile scintigraphy to localize an adenoma in the anterior mediastinum. A 39-year-old patient was hospitalized for primary hyperparathyroidism which had caused nephrocalcinosis and decalcification. Serum calcium was 130 g/L and phosphorus 16 mg/L. Cervical echography, thallium scintigraphy and computed tomography were negative. Scintigraphy with technitium-99m labelled methoxy-isobutyl isonitrile visualized a tumoural formation in the upper mediastinum near the ascending aorta. Magnetic resonance imaging centered on this zone revealed a 13 x 8 mm formation. Cervicosternotomy was performed initially. A 280 mg parathyroid adenoma was removed. The three other parathyroid glands were found to be normal. Follow-up was uneventful and the serum levels of calcium and phosphorus rapidly returned to normal. This preliminary case has demonstrated that methoxy-isobutyl-isonitrile scintigraphy can be an effective first intention exploration for primary hyperparathyroidism. Further results should indicate its sensitivity and specificity.

Adenoma↗
PubMed1994

High-dose immunoglobulin therapy for severe IgA nephropathy and Henoch-Schönlein purpura.

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.

Adolescent↗
PubMed1994

Split tolerance in chimeric GVH mice.

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.

Animals↗
PubMed1994

Histone-reactive IgA antibodies in adult IgA nephropathy and other primary glomerulonephritis.

The levels of histone-reactive IgA antibodies in the sera of adult patients with IgA mesangial glomerulonephritis, membranous glomerulonephritis, membranoproliferative glomerulonephritis and idiopathic nephrotic syndrome (minimal change disease+segmental glomerulosclerosis+IgM nephropathy) were evaluated by an enzyme-linked immunosorbent assay. Increased levels of IgA antibodies to all five major histones (H1, H2A, H2B, H3, H4) were found in all four disease groups when compared to normal controls. These histone-reactive IgA antibodies were restricted to the IgA1 subclass and their levels did not correlate with the levels of total serum IgA, nor with serum creatinine, creatinine clearance, and 24-hour proteinuria. Increasing ionic strength resulted in only partial inhibition of the binding to histones and, in individual patients, levels of reactivity with individual histones were usually correlated. This study shows that elevated levels of IgA antibodies reactive with self antigens are present in primary glomerulonephritis and extends previous observations indicating that anomalies of the IgA system occur in various forms of primary glomerulonephritis and are not limited to IgA nephropathy.

Adult↗
PubMed1994

Pneumocystis carinii pneumonia in the course of connective tissue disease: report of 34 cases.

OBJECTIVE: To determine the circumstances, the clinical features and the outcome of Pneumocystis carinii pneumonia (PCP) in human immunodeficiency virus (HIV)-free patients with connective tissue diseases (CTD). METHODS: Retrospective analysis of all cases referred 10 medical units in the last 10 years. RESULTS: A total of 34 cases of PCP in patients with CTD were studied (Wegener's granulomatosis, n = 12; systemic lupus erythematosus, n = 6; polyarteritis nodosa, n = 4; poly/dermatomyositis, n = 5; others, n = 7). The majority of patients (25/34 patients; 74%) presented PCP during the first 8 months following the diagnosis of CTD. At the time of diagnosis of PCP, most patients (32/34; 94%) were receiving corticosteroids (mean prednisone equivalent dose: 1.2 mg/kg/day) associated in 24 cases with cytotoxic agents (cyclophosphamide, n = 19; methotrexate, n = 5). Most patients were lymphocytopenic at the onset of PCP: 91% (31/34) of patients had fewer than 1.5 x 10(9)/l circulating lymphocytes and 76% (26/34) had fewer than 0.8 x 10(9)/l. The mean duration of prodromal symptoms was 6 days: this is much shorter than for AIDS associated PCP. Half the patients required intensive care for respiratory failure. Mortality was high (11/34 patients; 32%) although deaths were partly due to infections acquired in intensive care units. Among the 23 survivors, 10 (43%) received secondary prophylaxis for PCP and 13 (57%), received the usual therapeutic regimen. No relapse has been observed in either group with a mean followup of 22 months. CONCLUSION: Although rare, PCP must be considered in patients with any type of CTD and receiving cytotoxic agents and corticosteroids, particularly if they are lymphocytopenic. Thus, bronchoalveolar lavage must be rapidly performed in patients with CTD presenting with fever, pulmonary infiltrates, hypoxemia and lymphopenia.

Adult↗
PubMed1993

Mucosal immunity in primary glomerulonephritis. III. Study of intestinal permeability.

To study the specificity of gut hyperpermeability in primary glomerulonephritis, we investigated intestinal permeability by means of 51Cr-EDTA testing in 20 healthy individuals and in 30 patients with Immunoglobulin A nephropathy (IgA GN), 25 with idiopathic nephrotic syndrome (INS) and 20 with immune complex glomerulonephritis (IC-GN; membranous+membranoproliferative glomerulonephritis). Gut permeability was statistically increased in each patient group versus the controls [controls: 2% (0.4-3.9); IgA GN: 3.25% (0.7-17.70); INS: 3.71% (0.82-10); IC-GN: 3.40% (0.30-16); results are median (range); p < 0.005, nonparametric Mann-Whitney test]. An increase in intestinal permeability exceeding the upper limit of control values (95th percentile) was observed in 36% of IgA GN, 60% of INS and 50% of IC-GN patients. We conclude that intestinal permeability is frequently increased in primary glomerulonephritis and may also be increased in types of glomerulonephritis other than IgA GN.

Adult↗
PubMed1993

Long-term cyclosporin A therapy for severe idiopathic membranous nephropathy.

Fifteen patients with nephrotic idiopathic membranous nephropathy (MN) with predictors of poor outcome were treated with a long cyclosporin A (CyA) regimen at the dose of 4-5 mg/kg/day for a median period of 15 months (range 12-30). Four of the 15 patients did not respond to CyA, and the therapy was discontinued after 4 months. A partial remission (proteinuria < 2 g/day) was observed in 7 of 15 patients and a complete remission (proteinuria < 0.2 g/day) in 4 of 15 patients; good results (partial+complete remission) were, thus, obtained in 11 of 15 patients (73%). Two patients are still receiving therapy. A relapse of the nephrotic syndrome occurred in 3 of 9 patients on withdrawal of CyA, but the relapse remained sensitive to CyA. Side effects were mild. We conclude that CyA may be efficient in the treatment of MN and should be evaluated in controlled trials.

Adult↗
PubMed1993

Proteinuria selectivity index--prognostic value in lipoid nephrosis and related diseases.

In order to predict the steroid response in lipoid nephrosis (LN), we studied age, sex, proteinuria level, histological features and proteinuria selectivity index (SI; ratio between IgG and transferrin clearances) in 52 LN cases (minimal-change disease: n = 39; focal glomerulosclerosis+IgM nephropathy: n = 13). The multivariate analysis showed that age, sex and proteinuria level were not contributive, whereas histology and SI were. The predictive value of SI was much higher than that of histological type (McFadden's r2: 47% vs. 22%, p < 0.001). Thus, SI should be systemically assessed in idiopathic nephrotic syndrome for reviewing the pathologic classification obtained by histology. However, if its prognostic value is lower than that of selectivity, initial renal biopsy remains necessary for diagnosis in adults.

Adolescent↗