A genome-wide scan for asthma phenotypes was conducted in the whole sample of 295 EGEA families selected through at least one asthmatic subject. In addition to asthma, seven phenotypes involved in the main asthma physiopathological pathways were considered: SPT (positive skin prick test response to at least one of 11 allergens), SPTQ score being the number of positive skin test responses to 11 allergens, Phadiatop (positive specific IgE response to a mixture of allergens), total IgE levels, eosinophils, bronchial responsiveness (BR) to methacholine challenge and %predicted FEV(1). Four regions showed evidence for linkage (P
A semi-parametric generalization of the proportional hazards regression model is defined, whereby the hazard functions can cross for different values of the covariates. In the two-sample comparison, it includes in particular the case of two Weibull distributions differing in scale and shape parameters. A global test of the proportional hazards assumption is proposed against such defined alternatives. Its power in the two-sample case is compared to that of previously described tests by using simulation experiments. Survival data of patients with breast carcinoma, including several prognostic factors, are presented as an illustration.
Cyclosporine A (CsA) is characterized by high interindividual variations in oral bioavailability and a narrow therapeutic index. CsA is a substrate for P-glycoprotein, a member of the ABC transporter family encoded by the multiple drug-resistant gene MDR1.Because MDR1 gene exon 26 C3435T polymorphism influences intestinal P-glycoprotein expression, we investigated whether this polymorphism was correlated with variation in CsA dose requirement and concentration/dose ratio in 44 liver-transplant recipients during 1 month after transplantation. CsA concentration was measured 2 hours after administration (C2), according to international recommendations.The MDR-1 wild-type genotype (3435CC) was observed in 15 patients (34%), whereas 21 (48%) patients were heterozygous (3435CT), and 8 (18%) patients were homozygous for the mutation (3435TT). There was no significant difference between the three groups regarding corticosteroids treatment or renal function during this period. One to 3 days after liver transplantation, when every patient received a similar CsA weight-adjusted dose, the concentration/dose ratio was correlated with exon 26 single nucleotide polymorphism and was significantly higher in subjects homozygous for the mutation (P=0.012). This was confirmed 1 month after transplantation (P=0.049), when the dose was adjusted to maintain the C2 target level of 1,000 microg/L and we observed that TT patients required approximately 50% lower weight-adjusted CsA dose than wild-type patients (P=0,033).These findings demonstrate that the MDR1 exon 26 C3435T polymorphism is a major determinant of CsA concentration/dose ratio in liver-transplant recipients and is predictive of the dose of CsA to be administered to achieve the target C(2) concentration.
After oral administration of 10(2) to 10(5) CFU of Escherichia coli B41 (0101:K 99+:ST+) to 24-48 h old suckling mice (Swiss OF1), a 80 to 100% mortality rate is observed within three days. We compared the effect of the oral treatment with a lyophilized preparation of heat-killed Lactobacillus acidophilus and with sterile water on the mortality rate of newborn mice. In six out of seven assays, the heat-killed L. acidophilus administration extended survival of infected suckling mice (P ranging from 0.019 to less than 0.001). In another test, result was contradictory. A global analysis indicated that the two treatments were statistically different (P less than 0.001). Lactic acid was unable to induce protection.
