[Iatrogenic angioedema due to estrogen, angiotensin conversion enzyme inhibitors, angiotensin receptor antagonists and dialysis membranes].
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Biomedical subjects
Publications and source records attributed to L Bouillet.
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INTRODUCTION: To the request of total plasma homocysteine determination in the investigation of vascular disease, diagnosis of homocystinuria in young adult patients with mild phenotype is not so rare. EXEGESIS: A 26-year-old man developed embolic cerebral infarction and a 22-year-old woman presented a right renal venous thrombosis one week after delivery. In each case, high concentration of total plasma homocysteine was first found and plasma and urinary amino acids analysis later on directed the diagnosis towards homocystinuria. Finally, reduced skin fibroblast cystathionine beta-synthase activity confirmed the diagnosis of homocystinuria. CONCLUSION: Total plasma homocysteine determination must be determined for screening for hyperhomocysteinemia in young adults with venous thromboembolism without characteristic phenotypic features of homocystinuria.
OBJECTIVE: To assess the tolerance and efficacy of rituximab in patients with various autoimmune diseases seen in daily rheumatological practice. METHODS: 866 rheumatology and internal medicine practitioners were contacted by e-mail to obtain the files of patients treated with rituximab for systemic autoimmune diseases. Patients with lymphoma were analysed if the evolution of the autoimmune disease could be evaluated. RESULTS: In all, 43 of 49 cases could be analysed, including 14 with rheumatoid arthritis (RA), 13 with systemic lupus erythematosus (SLE), six with primary Sjogren's syndrome (pSS), five with systemic vasculitis, and five with other autoimmune diseases. Rituximab was prescribed for lymphoma in two patients with RA and two with pSS. In the 39 other cases, rituximab was given because of the refractory character of the autoimmune disease. The mean follow up period was 8.3 months (range 2 to 26). There were 11 adverse events in 10 patients and treatment had to be discontinued in six. Efficacy was observed in 30 patients (70%): RA 11, SLE 9, pSS 5, vasculitis 2, antisynthetase syndromes 2, sarcoidosis 1. The mean decrease in corticosteroid intake was 9.5 mg/d (range 0 to 50) in responders. Seven patients experienced relapse after mean 8.1 months (5 to 15). Three patients died because of refractory autoimmune disease. CONCLUSIONS: Despite absence of marketing authorisation, rituximab is used to treat various refractory autoimmune diseases in daily rheumatological practice. This study showed good tolerance and short term clinical efficacy, with marked corticosteroid reduction in patients with SLE, pSS, vasculitis, and polymyositis.
INTRODUCTION: The diagnosis of chronic angioedema (localised and reversible oedema) is sometimes very difficult when there is no efficiency of anti-histaminics and corticosteroids. In these cases, bradykinin angioedema must be mentioned. Tranexamic acid is efficient and must be proposed. STUDY: We reported seven patients who have a non-histaminergic angioedema since an average of 8 years. Corticosteroids and histamine-1 blockers were not efficient. Daily tranexamic acid treatment (1 g x 3 per day) controlled the disease. Three patients had no more attack. The C1Inh antigen and function levels were normal. No secondary effect was described and all patients are still being treated (average of 20 months). CONCLUSION: When a non-histaminergic angioedema is suspected, tranexamic acid must be proposed as attack's treatment and as prophylactic treatment.
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BACKGROUND: Oral contraceptives can precipitate attacks of hereditary angioedema (ANE) or induce acquired forms. OBJECTIVE: We studied 5 patients who had an ANE which had begun under oral contraception and disappeared after stopping the pill. METHODS: We explored the clinical and biological characteristics of these patients. RESULTS: The symptoms developed during the first year or later after starting contraception; the patients reported relapsing swelling of the lips, hands, larynx and abdomen. All women had normal serum C4 and C1 inhibitor (C1Inh) antigen levels, but a lowered C1Inh activity, with a marked protein cleavage on the immunoblot. The suppression of the pill was associated with the regression of the edema and normalization of C1Inh function. CONCLUSION: The mechanism of these ANE is unknown. The could be due to a modulation of C1Inh expression upon androgens or an imbalance between coagulation proteins favoring C1Inh cleavage by its target proteases.
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PURPOSE: Nonallergic isolated angioedema is an uncommon clinical syndrome raising difficult diagnosis and therapeutic problems. Occurrences linked to a C1Inh are the predominant ones and have to be examined as a priority, taking into account the specificity of the associated follow-up. CURRENT KNOWLEDGE AND KEY POINTS: Diseases with a clinical profile close to hereditary angioneurotic edema, but without C1Inh anomaly, have been described recently. It is in fact family cases, concerning only women, where estrogens seem to play a dominant role. Angioedema's secondary aspects are gathering various pathologies (vasculitis, Gleich's syndrome, angioedema initiated by physical agents). The role played by some drugs must not be forgotten, mainly angiotensin converting enzyme inhibitors, which are at the origin of angiodema in nearly 0.5% of users. FUTURE PROSPECT AND PROJECTS: Uncontrolled activation of the contact system seems to play a major role in the main part of these angiodemas. The efficiency of the tranexaminic acid (which modulates its activation) is to be taken as evident. The key to the future seems to be the development of plasmin and bradykinin inhibitors.
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OBJECTIVE: Angioneurotic edema (AE) is a rare but severe disease. Hereditary AE is the more well-known form. The acquired form is exceptional: the symptoms are the same but there are some biologic and treatment differences. We investigated the clinical and biochemical features in nine patients with acquired angioneurotic edema (AAE). PATIENTS AND METHODS: Four of the patients with type I AAE presented an accelerated metabolism of C1Inh, associated with a hematology disease. Their C4, C1q and C1Inh plasma levels were low. Four patients had type II AAE associated with an autoantibody to C1Inh. Their C1Inh plasma levels were normal or low but the functional levels were low in all four. One patient had AAE induced by oral contraceptives. The C1Inh plasma level was normal but the functional level was very low; there were no autoantibodies. Symptoms resolved when oral contraceptives were withdrawn and the C1Inh level returned to normal. DISCUSSION: Treatment of AAE is a difficult matter. For type I AAE, it consists in treating the associated disease. For type II AAE, the treatment goal is to lower the autoantibody level. Management of these diseases requires close collaboration between clinicians and biologists.
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BACKGROUND: The diagnosis of uveitis is a difficult one and subject to much debate between ophthalmologists and internists. In 1992, we carried out a prospective study to assess the importance of the internist's consultation, the contribution of an extensive laboratory evaluation and to propose a well considered diagnostic strategy. MATERIAL: and methods: From 1992 to 1995, all patients seen at consultation at the Grenoble University Hospital had a complete ophthalmologic evaluation, an internist's consultation, an extensive laboratory evaluation and a follow-up for at least 6 months. RESULTS: One hundred twenty five patients were included. The rate of diagnosis was 72%. The internist's help was useful in at least 68% of the diagnoses. Laboratory and radiography tests provided pertinent information in 77% of the cases. Follow-up allowed finding 11% of the diagnoses. The analysis of the clinical and laboratory tests enabled us to establish a diagnostic strategy chart where the key pint is clinical and ophthalmologic evaluation. A minimal laboratory evaluation systematically performed for all cases of uveitis is proposed and, according to some characteristics of uveitis, a well-targeted laboratory evaluation is recommended. CONCLUSION: This diagnostic strategy enabled establishment of the diagnosis in 92% of the cases and limited laboratory evaluation for 68 patients. We are performing a new prospective study to better validate this diagnostic chart.
Both NS3 protein (1007-1657) and its protease moiety (NS3p, 1027-1207) were able to interact in vitro with C1 Inhibitor (C1Inh) to give a 95-kDa Mr C1Inh cleavage product similar to that obtained upon proteolysis by complement protease C1s. High-Mr reaction products were also detected after incubation of C1Inh with NS3 but not with NS3p; they correspond to ester-bonded complexes from their hydroxylamine lability. Similar reactivity of NS3 was observed upon incubation with alpha2-antiplasmin. Serpin cleavage was prevented by treatment of NS3 with synthetic serine protease inhibitors. This interaction between viral NS3 and host serpins suggests that NS3 is likely to be controlled by infected cell protease inhibitors.
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The in vitro antibacterial activity of cefotaxime, cefepime and cefpirome was evaluated alone and in association with two beta-lactamase inhibitors: clavulanic acid and sulbactam against 65 extended broad spectrum beta-lactamase producing enterobacteriaceae strains [Klebsiella pneumoniae (35), Proteus mirabilis (9), Escherichia coli (11), Enterobacter aerogenes (10)]. The lowest MICs were observed for cefepime and cefpirome used alone. In association with inhibitors cefotaxime was less effective against E. aerogenes. Most isolates of K. pneumoniae, P. mirabilis, E. coli were susceptible to all the different tested associations.
A broth dilution method was used to measure the minimal inhibitory concentrations of pefloxacin, a new quinolone derivative. Because this new agent could be used in systemic infections, mezlocillin, cefotaxime, ceftazidime and amikacin were used as comparative agents. Pefloxacin was found to be more active than mezlocillin and as active as or more active than cefotaxime, ceftazidime and amikacin. With the exception of Serratia marcescens, only 7% of Enterobacteriaceae strains were resistant to pefloxacin with a MIC greater than 8 micrograms/ml. Pefloxacin was also found to be the best agent against the non-fermenters Staphylococcus aureus and St. epidermidis. Resistance to ampicillin, carbenicillin and gentamicin did not affect the effectiveness of pefloxacin. However, pefloxacin appeared more susceptible to nalidixic acid resistance, with MICs four to sixfold higher.