[Nuclear envelope autoantibodies and liver diseases].
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Biomedical subjects
Publications and source records attributed to K Lassoued.
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In 11 patients, sera displaying a ringlike nuclear immunofluorescent staining on sections of rat liver tissue were shown by Western blotting to contain antibodies to lamins. Sera from 8 patients contained autoantibodies reacting with lamin B, whereas sera from the other 3 patients reacted with lamins A and C. All patients (9 women and 2 men) had a chronic autoimmune disorder, which rarely fulfilled the usual criteria for a diagnosis of systemic lupus erythematosus. The disorder was characterized by acute or chronic (active or granulomatous) hepatitis; steroid-responsive blood cytopenia, often associated with a circulating anticoagulant, or anticardiolipin antibodies, or both; and cutaneous leukocytoclastic angiitis or probable brain vasculitis. Eight patients had at least two of these three conditions. Antilamin autoantibodies may thus be a marker for an unusual subset of autoimmune diseases.
Fifty sera which gave ring-like nuclear staining in immunofluorescence on rat liver tissue sections were characterized. Using immunoprecipitation and Western blotting we showed that 10 of the sera contained antibodies to 200 kD polypeptide(s) of nuclear envelope. Clinical and biological data were available for nine of the patients. Strikingly, all of these patients suffered from primary biliary cirrhosis with eight of them having anti-mitochondrial antibodies. As no control serum displayed such a reactivity, anti-200 kD polypeptide(s) antibodies can be considered as a new marker specific of a subset of primary biliary cirrhosis, being present even when anti-mitochondrial antibodies are absent. The exact identity of the target remains to be established, since several polypeptides of similar molecular weight have been reported to belong to the nuclear envelope.
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Seven patients with severe methicillin-resistant Staphylococcus aureus infections (5 with bacterial endocarditis, 1 with mediastinitis and 1 with meningitis and septicaemia) were treated with rifampicin combined with vancomycin in 6 cases and with gentamicin in 1 case. The 7 strains initially isolated from haemocultures were resistant to methicillin and sensitive to rifampicin. In 4 of these patients (3 of whom received vancomycin and 1 gentamicin) clinical and bacteriological failure was observed, with selection of rifampicin-resistant mutants. Bactericidal activity was always mediocre in both serum and cerebrospinal fluid, with insufficient vancomycin and gentamicin concentrations in 3 patients. An in vitro study of the combined antibiotics by the chequer-board method suggested antagonism in 3 of these 4 cases. Thus, in spite of its excellent activity and unquestionable effectiveness, rifampicin should be used with caution in severe staphylococcal infections.
Neutropenia developed in 13 patients during treatment with beta lactamines. The time of onset ranged from eight to 27 days after beginning treatment and occurred with doses as low as 40 mg/24 hours. Concomitant symptoms were eosinophilia, rashes, and fever. Leucoagglutinins were detected in eight out of nine patients by the microleucoagglutination technique. Clinical and serological findings suggested that neutrophils become sensitised as a result of absorption on the cell membrane of drug-antibody immune complexes. An immune mediated pathogenesis for neutropenia induced by beta lactamine seems highly probable.
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We describe the case of a 70-year-old man with unicentric grade 1 epitheloid hemangioendothelioma (EH) of the bone that favourably responded to intravenous pamidronate as a single agent. After 6 years of follow-up, the patient was in complete remisssion. We suggest that use of bisphosphonates should be considered in the treatment of osteolytic EH.
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