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No effect of an antiaggregant treatment with aspirin in small cell lung cancer treated with CCAVP16 chemotherapy. Results from a randomized clinical trial of 303 patients. The "Petites Cellules" Group.

BACKGROUND: Experimental, and more recently, clinical data have suggested the influence of hemostasis in the spread of malignant disease. METHODS: To complete research in this type of coagulation and cancer, a multicentric randomized clinical trial was performed, including 303 patients with small cell lung cancer (SCLC), treated by the addition of aspirin at 1 g/day (a dosage at which aspirin is considered to be a platelet aggregation inhibitor) to combined chemotherapy. RESULTS: Survival was not increased in the aspirin-treated group (P = 0.90). The analysis according to the extent of disease (limited or extensive disease) did not modify that conclusion. CONCLUSIONS: This result does not confirm the hypothesis that, in SCLC, aspirin (a platelet aggregation inhibitor) reduces metastasis formation and local tumor thrombogenesis.

Adult↗

Subcutaneous heparin treatment increases survival in small cell lung cancer. "Petites Cellules" Group.

BACKGROUND: A positive influence of anticoagulant treatment in small cell lung cancer (SCLC) has been suggested by experimental and clinical data. METHODS: In a multicenter clinical trial, 277 patients with SCLC were randomized either to receive or not to receive subcutaneous heparin injections for 5 weeks at effective doses, which were monitored by blood coagulation tests. All patients received one of the two chemotherapy regimens studied in this trial, for eight courses in the case of patients with complete or partial response, and subsequently were randomized to receive delayed thoracic radiotherapy after these eight courses. RESULTS: In comparison to the 139 patients who did not receive heparin, the 138 patients who received anticoagulant treatment obtained better complete response rates (37% vs. 23%, P = 0.004), better median survival (317 days vs. 261 days, P = 0.01), and better survival rates at 1, 2, and 3 years (40% vs. 30%, 11% vs. 9% and 9% vs. 6%, respectively). At subgroups analysis, the results on survival were obtained for limited forms (P = 0.03) but not for extensive diseases (P = 0.31). No important bleeding or thrombocytopenia was related to heparin treatment. CONCLUSIONS: These results confirm the value of anticoagulant treatment in SCLC, already suspected for warfarin and now proven for heparin, but the modes of administration and the biologic explanations for this activity still warrant further investigation.

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Anticardiolipin antibodies and giant cell arteritis: a prospective, multicenter case-control study. Groupe de Recherche sur l'Artérite à Cellules Géantes.

OBJECTIVE: To assess the prevalence and thrombogenic role of anticardiolipin antibodies (aCL) in giant cell arteritis. METHODS: Two hundred eighty-four patients with newly diagnosed temporal arteritis or polymyalgia rheumatica and 210 age- and sex-matched controls randomly selected from the general population were included in a multicenter, prospective case-control study. Blood samples were obtained at the time of diagnosis, data on initial clinical features were collected in a questionnaire, and temporal artery biopsy findings were reviewed by an experienced pathologist. RESULTS: Anticardiolipin antibodies were present in 20.7% of patients compared with 2.9% of controls (P = 1.45 x 10(-9)). The prevalence of aCL was higher in samples found positive for temporal arteritis than in those found negative on biopsy (31.2% versus 16.7%; P = 0.04), and was similarly higher in the biopsy-positive temporal arteritis group compared with the polymyalgia rheumatica and control groups. Although aCL were associated with thrombotic complications in univariate analysis, the positivity of the biopsy findings remained the only predictive variable in stratified analysis. CONCLUSION: In giant cell arteritis, aCL seem to function as reactive antibodies in relation to endothelial lesions.

Aged↗

Giant cell arteritis and cardiovascular risk factors: a multicenter, prospective case-control study. Groupe de Recherche sur l'Artérite à Cellules Géantes.

OBJECTIVE: To assess the role of cardiovascular risk factors, measured at the time of diagnosis, in the pathogenesis of giant cell (temporal) arteritis (GCA). METHODS: Four hundred new patients with GCA or polymyalgia rheumatica (PMR) and population-based, individually age- and sex-matched controls were included in this multicenter, prospective case-control study. Each participant was evaluated by review of the medical history and by clinical and laboratory assessments. RESULTS: Among women, smoking was associated with a 6-fold increase in risk (P = 0.00006, 95% confidence interval [95% CI] 2-17), heavy smoking with a 17-fold increase in risk, and previous atheromatous disease with a 4.5-fold increase in risk (P = 0.0003, 95% CI 2-11) of GCA in both the biopsy-positive and biopsy-negative GCA groups; only smoking appeared to be a risk factor for PMR in women (odds ratio 3.64, 95% CI 1.07-12.40). Among men, no risk factor was found to be significant. CONCLUSION: Smoking and previous arterial disease were independently associated with GCA in women. In order to avoid matching bias, risk factors for diseases with an unbalanced sex distribution should be studied separately in each sex, using a sex-matched, case-control study design.

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Leucémogénése et régénération du systémé lymphoïde chez des hybrides f1 (c3h x akr/t1ald) restaurés par des cellules médullaires et thymiques parentales.

Luekaemogenesis and repopulation of the lymphoid system have been studied in sub-lethally irradiated (c3h x akr/t1ald) f1 hybrids which have been restored with parental Bone Marrow (BM) cells with or without thymic cells. The metacentric marker of the T1ALD sub-strain made it possible to identify the host or donor orgin of leukaemias. Leukaemias occur either in the thymuc (lymphosarcomas) or in the other lymphoid tissues (extra-thymic leukaemias). After irradiation, the precentage of lymphosarcomas increases from 5 to 95%. The rate of leukaemias in hybrids which have been restored only with BM cells is 55, 56 and 100% respectively depending on the origin of BM: syngenic, C3H and AKR. In this last group 75% of the lymphosarcomas originate from donor cells. The inhibitory efficiency of the three kinds of BM on luekaemogenesis seems to be related to their respective abilities to spontaneous malignant transformation. When AKR or C3H thymic cells are injected together with BM cells, leukaemogenesis is altered. The effect is indirect as these cells are not actually concerned by the malignant transformation. The percentage of LS is significantly reduced and the mean survival improved in hybrids restored with C3H thymic, mixed AKR or C3H BM cells. AKR thymic cells are less efficient. In both cases, the percentage of extra thymic leukaemias increases at the expense of lymphosarcomas. Thymic cells do not change the kinetics of repopulation in thymus and lymph-node by the BM cells, except when C3H thymic cells are mixed with T1ALD BM cells; in this case, the lymph-node repopulation is temporarily enhanced. Different hypotheses might explain the effect of thymic cells on leukaemogenesis: enhanced recovery of the postirradiation immunological deficiency, transfer of virus by the AKR thymic cells, and more probably influence of the thymic cells on the maturation or/and differentiation of the lymphoid cells.

Animals↗

Standard combination versus alternating chemotherapy in small cell lung cancer: a randomised clinical trial including 394 patients. 'Petites Cellules' Group.

PURPOSE: to compare standard and alternating administration of chemotherapy combinations in small cell lung cancer (SCLC) patients. MATERIAL AND METHODS: in a multicenter clinical trial, 394 previously untreated SCLC patients were randomised to receive, every 4 weeks, eight courses of either a standard regimen with CCNU, cyclophosphamide, adriamycin (CCA) and VP16 or an alternating regimen (CCA regimen alternating with cisplatin-vindesine-VP16). RESULTS: overall response rate was higher in the standard group (78%) than in the alternating group (64%) (P = 0.0001). Complete response rate was also higher in the standard group (32%) than in the alternating group (18%) (P = 0.004). The median survival in the overall SCLC population was 306 days in the standard group and 272 days in the alternating group (P = 0.08). In limited SCLC patients, median survival was higher in the standard group (421 days) than in the alternating group (328 days) (P = 0.01). Grade III/IV haematological toxicity was lower in patients in the alternating group (25 versus 47%) (P < 0.001). CONCLUSION: the standard regimen was better than the alternating regimen for patients with limited forms of SCLC. The alternating regimen, associated with better haematological safety and ensuring a fairly similar survival, may be considered in patients with extensive SCLC. Pleiomorphic resistance mechanisms to chemotherapy make it difficult to define a non-cross-resistant chemotherapy regimen.

Adult↗

Giant cell arteritis and polymyalgia rheumatica: are pregnancies a protective factor? A prospective, multicentre case-control study. GRACG (Groupe de Recherche sur l'Artérite à Cellules Géantes).

OBJECTIVE: To assess the potential role of allo-immunization, either by former pregnancies, or by a history of blood transfusion, in the pathogenesis of giant cell arteritis and polymyalgia rheumatica. METHODS: Two hundred and eighty-five incident female cases and 186 age-matched, population-based female controls were prospectively included in a multicentre case-control study. RESULTS: The number of pregnancies was significantly lower in cases than in controls (nulliparous: 21.55% vs 12.90%; > or =4 pregnancies: 16.25% vs 27.42%; Wilcoxon rank sum test: P = 0.0019) in biopsy-proven or negative temporal arteritis and, to a lesser extent, in polymyalgia rheumatica. No difference was found for history of blood transfusion. Pregnancies remained negatively associated with the disease in a multivariate analysis including cardiovascular risk factors such as smoking or a pre-existing peripheral vascular disease. CONCLUSION: Former pregnancies are not a risk factor for giant cell arteritis. Pregnancies may be protective thanks to an effect of the associated hyperoestrogenic state against alterations of the artery wall, as suggested in animal models.

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Recurrence of lymphoedema-associated cellulitis (erysipelas) under prophylactic antibiotherapy: a retrospective cohort study.

OBJECTIVE: To identify the predictors of successful antibiotic prophylactic treatment using benzathin-penicillin G to prevent recurrence of erysipelas in patients with secondary upper limb lymphoedema. DESIGN: A retrospective cohort study. SETTING AND PATIENTS: Patients with secondary arm lymphoedema were recruited in a single lymphology unit between 1990 and 2003. All patients had had at least three recurrences of erysipelas. Patients were given 2.4 MU benzathin-penicillin G intramuscularly at 14-day intervals. For each patient, the following data were recorded: characteristics of breast cancer treatment (type of surgery, radiotherapy, hormone therapy), number of erysipelas recurrences before inclusion, patient characteristics including body mass index (BMI) and lymphoedema volume at inclusion. MAIN OUTCOME MEASURES: The outcome studied was the occurrence of erysipelas on the affected arm under antibiotic prophylactic treatment. RESULTS: With a 4.2-year median follow-up from the onset of antibiotic prophylactic treatment, 23 of 48 women experienced recurrence of erysipelas. The median duration of erysipelas recurrence-free period under this treatment was 2.7 years. The estimated rate of recurrence was 26%[95% confidence interval (CI) 13-38%] at 1 year and 36% (95% CI 22-50%) at 2 years. No patient stopped the treatment because of side-effects. No predictive factor of erysipelas recurrence under antibiotic prophylactic treatment was identified. CONCLUSIONS: Antibiotic prophylaxis using benzathin-penicillin is a well-tolerated treatment of erysipelas recurrence in patients with upper limb lymphoedema secondary to breast cancer. The rate of erysipelas recurrence was 26% at 1 year in patients who had a history of at least one erysipelas. We did not find any predictor of erysipelas recurrence.

Adult↗

Biopsy proven and biopsy negative temporal arteritis: differences in clinical spectrum at the onset of the disease. Groupe de Recherche sur l'Artérite à Cellules Géantes.

OBJECTIVES: To assess the clinical features of biopsy proven and negative biopsy temporal arteritis at the time of diagnosis and during a three year follow up. METHODS: Newly diagnosed cases of giant cell arteritis were included in a prospective, multicentre study. Initial clinical and biological features, season of diagnosis, and cardiovascular events occurring during the follow up were recorded. Biopsy proven and negative biopsy cases were compared. RESULTS: Two hundred and seven biopsy proven, and 85 negative biopsy cases were included from 1991 to 1997. Fifty eight per cent of the biopsy proven cases, compared with 39.29% of the negative biopsy cases, were diagnosed during the autumn or winter (p = 0.003). Visual problems (31.5%, v 19.1%, p = 0.031), blindness (9.7% v 2.38%, p = 0.033), jaw claudication (40.8%, v 28.243%, p = 0.044), and temporal artery palpation abnormalities (61.3% v 29.5%, p = 7.10(-7)) were more frequent in the biopsy proven than in the negative biopsy group. Less specific symptoms, such as headache (82.5% v 92. 9%, p = 0.021), or associated polymyalgia rheumatica (40.1% v 65.9%, p = 9 x 10(-5)) were more prevalent in the negative biopsy cases. Biological markers of inflammation were significantly more increased in the biopsy proven group. All cases of blindness occurring after treatment belonged to the biopsy proven group. CONCLUSION: Biopsy proven cases seem to be more severe than biopsy negative cases at the time of diagnosis and during follow up. Seasonal difference at diagnosis may suggest a different aetiological pattern.

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