Natural anticoagulant proteins in adult nephrotic syndrome.
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Biomedical subjects
Publications and source records attributed to G Rostoker.
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A case of idiopathic nephrotic syndrome (INS) evolving since more than 7 years with 4 successive corticosensitive relapses is reported. At the time of a 5th relapse corticosteroid treatment was refused by the parents and evolution went on without any spontaneous tendency to remission. Three months later, allergy tests detected various sensitizations, especially for food allergens. An antiallergic treatment including dietary exclusions induced a complete and durable remission. Five similar cases are reported. These facts, compared to data from the literature, indicate the possible role of food hypersensitivity in INS. Its mechanism has been discussed; the possible part of a lymphocyte activation has been emphasized.
The coexistence of a T-cell lymphoma with a myelodysplatic syndrome seems to be exceptional. In the case reported here the diagnostic problems raised by the appearance of cutaneous nodules in a patient with chronic myeloid leukaemia (CML) were solved by histo-immunological examinations. A 70-year old male patient had been presenting since 1976 with a psoriasis-like skin disease. He was first seen at the Argenteuil hospital in 1984. Physical examination showed psoriasiform finger-like erythemato-squamous lesions, infiltrated plaques and an ulcerated tumoral swelling of the right elbow. A diagnosis of mycosis fungoides was made on histological and immunological examination results. At histology, this epidermotropic lymphoma was peculiar in that the atypical infiltrate was clearly centred on vessels. Electron microscopy confirmed that the vascular walls were invaded by the mycosis cells. Additional examinations showed hyperleucocytosis and myelaemia which were rapidly attributed to a chronic myelocytic leukaemia since the Philadelphia chromosome was present and the leucocytes had a low alkaline phosphatase score. Bone marrow biopsy disclosed a myeloproliferative syndrome of the CML type. Biopsy of a right axillary lymph node showed myelocytic infiltration associated with dermopathic lymphadenitis. There were no circulating Sezary cells, and a search for extension proved negative. From May, 1984 to June, 1985 the patient's CML was treated with busulfan which produced blood and bone marrow remission. The skin lesions were treated first with mechlorethamine, then with topical corticosteroids. Superficial electron therapy was applied to the tumoral lesions.(ABSTRACT TRUNCATED AT 250 WORDS)
Thromboembolic events remain one of the most serious complications in patients with nephrotic syndrome (NS). The natural anticoagulant system protein C-protein S was evaluated in patients with proteinuria and NS. Protein C levels were found to be normal or increased in NS. Protein C levels correlated positively with proteinuria, cholesterol and triglycerides and negatively with serum albumin. All of the 17 patients with NS exhibited urinary loss of protein C. Total protein S and C4BP were increased in mild and moderate forms of NS. Free protein S was identical in controls and NS patients. Nine of ten patients had urinary loss of protein S. No correlation was found between protein S and the various usual biologic parameters of NS. However, two patients with NS and thrombosis of the renal veins had an acquired deficit in either free protein S or protein C. Thus, in some patients, an acquired deficit in free protein S and/or protein C may contribute to the development of thrombotic complications in NS.
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In IgA glomerulonephritis (GN), the pathogenic role of IgA is well documented, but the specificity of these IgA is unknown. Cases of celiac disease associated with IgA GN have been reported and led us to investigate the role of gliadin sensitivity. We measured IgA, IgG and IgM antibodies to gliadin, beta-lactoglobulin and ovalbumin by ELISA (results expressed as optical density; OD) in 27 patients with primary IgA GN, 14 with membranous GN (MGN), 21 with idiopathic nephrotic syndrome (INS) and 21 healthy controls. The normal value for antigliadin IgA was less than 0.650 OD. 19/27 patients with IgA GN had a raised level versus 2/14 in MGN and 2/21 INS (p less than 0.001: IgA GN vs. MGN, INS and controls). Antibodies to beta-lactoglobulin were rarely found and were not more frequent in IgA GN. Cross-reactivity with reticulin was investigated in 16 patients who were serum-positive for IgA antigliadin: no reticulin antibodies were detected by immunofluorescence. Antigliadin IgA are of diagnostic value for distinguishing IgA GN from other GN, with a sensitivity of 70%, a specificity of 89%, a positive predictive value of 83% and a negative one of 79%.
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To evaluate the prevalence of food hypersensitivity in idiopathic nephrotic syndrome (INS), an oligoantigenic diet was given for 10 days to 13 patients with INS who had not steadily responded to corticosteroids; 5 of these patients were corticodependent, 3 were corticoresistant and 5 had multiple relapses. A history of allergy was present in 8 cases and an increase in total serum IgE levels in 6. Sensitivity to food antigens was documented by skin tests in 5, by the radioallergosarbent test (RAST) in 5 and by the human basophil degranulation test (HBDT) in 11. At the end of the oligoantigenic diet, proteinuria was significantly reduced in the 13 patients as compared to the initial level. It decreased by more than 50% in 9 patients and disappeared completely in 5. It seems that an oligoantigenic diet is helpful in cases of INS that do not respond to corticosteroids. This argues for a role of food hypersensitivity in this disease and suggests that avoidance of specific foods on the longer term may be of benefit. This diet must be tried in INS before the initiation of immunosuppressive therapy.
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The cases of three patients who had dermatosis that was caused by an orthopaedic implant are reported. The main clinical pattern was localized or generalized eczema or urticaria. The diagnostic criteria that have been proposed by various authors are reviewed. Removal of the implant did not always result in rapid disappearance of the dermatosis, presumably because a few particles of metal remained in the area of the implant.
Thrombo-embolic events remain one of the most serious complications in patients with nephrotic syndrome (NS). A causal relationship between coagulation abnormalities and the occurrence of thrombosis in NS has been searched. Several studies have demonstrated multiples abnormalities in the coagulation factors and platelets; however those studies did not provide adequate explanations for the thrombotic tendency of NS. This thrombotic tendency could be related to deficiency in natural coagulation inhibitors. Plasma ATIII level has been reported to be decreased both in some adults and children. Protein C is found normal or high in NS whereas protein S is increased. Nevertheless a possible decrease in functional protein S cannot be excluded.
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The protein C-protein S natural anticoagulant system was evaluated in 32 patients with proteinuria, 11 without nephrotic syndrome (NS) and 21 with NS of different grade. Antithrombin III (AT III), factors II, VII, X were also measured in the same groups of patients. In addition to plasma levels of these proteins, urinary loss of protein C was evaluated in concentrated urine specimens from 17 of the 21 patients with NS. The protein C antigen level was found to be normal or high in NS, but the difference between the control group and nephrotic patients was statistically significant only in severe NS. For all proteinuric patients, the plasma concentration of protein C correlated positively with the degree of proteinuria, cholesterol level, triglyceride level, and correlated inversely with serum albumin concentration; 17/17 patients with NS exhibited urinary loss of protein C and the degree of protein C excretion correlated positively with the degree of proteinuria. Plasma protein S antigen was measured in only 11 patients with NS and was found to be significatively increased, with a negative correlation with serum albumin concentration. AT III did not differ between the control group and the proteinuric patients with or without NS. Factors II and X were in the normal range for all patients. Factor VII was increased even in mild NS. Thus, the plasma levels of protein C and protein S antigens were normal or increased in patients with NS and this is probably related to an increased liver synthesis rate of these proteins, which is secondary to proteinuria.(ABSTRACT TRUNCATED AT 250 WORDS)
The case of a multiple myeloma secreting IgG kappa in both mother and daughter is reported and discussed in the light of previous reports of familial myeloma and myeloma occurring in spouses. In March 1981, the 60-year-old daughter complained of fatigue leading to the discovery of anemia. The diagnosis of myeloma was based on the association of a monoclonal IgG kappa (57.5 g/l) with low serum levels of IgM and IgA and of an increase (38%) in bone marrow plasma cells. She was treated by chemotherapy and by radiotherapy on bone lesions which appeared during the course of treatment. She died in June 1983. In October 1984, the 84-year-old mother was also found to have anemia. The diagnosis of myeloma was based on the association of a monoclonal IgG kappa (24.5 g/l) with low serum levels of IgM and IgA, 0.6 g/l of Bence-Jones protein in urine, an increase (12%) of atypical plasma cells, and of multiple lytic lesions on X-ray. Familial myeloma has been exceptionally reported. We have found only one case in mother and daughter where the myeloma protein was respectively IgA and IgG. The light chain isotype was not determined. Cases of myeloma occurring in spouses have equally been rarely reported in the medical literature. Genetic transmission of chromosomal determinants for myeloma or a type of response to environmental factors have been suspected as well as environmental determinants for myeloma. Genetically abnormal regulation of immunoglobulin synthesis is another possibility.