Prospective assessment of CYP2D6 by genotyping, phenotyping and measurement of tamoxifen, PD 05-09 4-hydroxy-tamoxifen and endoxifen in breast cancer patients treated with tamoxifen.

Tamoxifen (tam) is a widely used endocrine therapy in the treatment of early and advanced stage breast cancer in women and men. It is a pro-drug having weak affinity with the estrogen receptor and needs to be converted to its main metabolite, endoxifen (endox), to have full anticancer activity. Cytochrome 2D6 (CYP2D6) plays a major role in the metabolism of tamoxifen to endoxifen. It is genetically highly polymorphic and its activity influences profoundly the synthesis of endoxifen and potentially the efficacy of tamoxifen treatment. Genotyping is currently the most widely used approach in studies and also in clinical practice to categorize patients as poor- (PM), intermediate- (IM), extensive- (EM) and ultra rapid-metabolizers (UM). Some clinicians already use genotyping in order to tailor the endocrine therapy of their patients. Owing to the large inter-individual variations in concentrations of the active moitey due to genetic and non-genetic influences renders the predictive value of the test uncertain for an individual patient. A significant number of patients classified as EM or IM by genotyping have indeed relatively low endoxifen levels similar to PMs1. This suggests that genotyping is probably not the opti ma l meth o d f or predi cti ng end oxif en l evels.

Prevalence and Clinical Characteristics of HIV Type 1-Infected Patients Receiving Dialysis in Spain: Results of a Spanish Survey in 2006: GESIDA 48/05 Study

End-stage renal diseases (ESRD) are becoming more frequent in HIV-infected patients. In Europe there is little information about HIV-infected patients on dialysis. A cross-sectional multicenter survey in 328 Spanish dialysis units was conducted in 2006. Information from 14,876 patients in dialysis was obtained (81.6% of the Spanish dialysis population). Eighty-one were HIV infected (0.54%; 95% CI, 0.43-0.67), 60 were on hemodialysis, and 21 were on peritoneal dialysis. The mean (range) age was 45 (28-73) years. Seventy-two percent were men and 33% were former drug users. The mean (range) time of HIV infection was 11 (1-27) years and time on dialysis was 4.6 (0.4-25) years. ESRD was due to glomerulonephritis (36%) and diabetes (15%). HIV-associated nephropathy was not reported. Eighty-five percent were on HAART, 76.5% had a CD4 T cell count above 200 cells, and 73% had undetectable viral load. Thirty-nine percent of patients met criteria for inclusion on the renal transplant (RT) waiting list but only 12% were included. Sixty-one percent had HCV coinfection. HCV-coinfected patients had a longer history of HIV, more previous AIDS events, parenteral transmission as the most common risk factor for acquiring HIV infection, and less access to the RT waiting list (p < 0.05). The prevalence of HIV infection in Spanish dialysis units in 2006 was 0.54% HCV coinfection was very frequent (61%) and the percentage of patients included on the Spanish RT waiting list was low (12%).

31 mai 1916, bataille du Jutland : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 54226

Bataille du Jutland, 31 mai 1916 : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 54225

31 mai 1916, bataille du Jutland, à droite le "Queen Mary", à gauche le "Lion" : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 54224

[Monument commémoratif de la victoire de 1916 à Verdun, érigé au rond-point des Champs-Élysées] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 55015

Occurrence, risk factors, diagnosis and treatment of syphilis in the prospective observational Swiss HIV Cohort Study.

BACKGROUND: Annual syphilis testing was reintroduced in the Swiss HIV Cohort Study (SHCS) in 2004. We prospectively studied occurrence, risk factors, clinical manifestations, diagnostic approaches and treatment of syphilis. METHODS: Over a period of 33 months, participants with positive test results for Treponema pallidum hemagglutination assay were studied using the SHCS database and an additional structured case report form. RESULTS: Of 7244 cohort participants, 909 (12.5%) had positive syphilis serology. Among these, 633 had previously been treated and had no current signs or symptoms of syphilis at time of testing. Of 218 patients with newly detected untreated syphilis, 20% reported genitooral contacts as only risk behavior and 60% were asymptomatic. Newly detected syphilis was more frequent among men who have sex with men (MSM) [adjusted odds ratio (OR) 2.8, P < 0.001], in persons reporting casual sexual partners (adjusted OR 2.8, P < 0.001) and in MSM of younger age (P = 0.05). Only 35% of recommended cerebrospinal fluid (CFS) examinations were performed. Neurosyphilis was diagnosed in four neurologically asymptomatic patients; all of them had a Venereal Disease Research Laboratory (VDRL) titer of 1:>or=32. Ninety-one percent of the patients responded to treatment with at least a four-fold decline in VDRL titer. CONCLUSION: Syphilis remains an important coinfection in the SHCS justifying reintroduction of routine screening. Genitooral contact is a significant way of transmission and young MSM are at high risk for syphilis. Current guidelines to rule out neurosyphilis by CSF analysis are inconsistently followed in clinical practice. Serologic treatment response is above 90% in the era of combination antiretroviral therapy.

Somme 1916, Hangard-en-Santerre, pièce de 320 tirant sur Chaulnes : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 57254

Somme 1916, Rosières-en-Santerre, éclatement d'un obus face au poste de secours, en face Lihons et Chaulnes : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 57261

Somme 1916, route de Rosières-en-Santerre, Lihons et Chaulnes : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 57266

Somme 1916, route de Rosières-en-Santerre, Lihons et Chaulnes, les fourrés sont remplis [d'obus] de 75 : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 57264

La voix de M. Paul Deschanel, Président de la Chambre des députés : discours prononcé le 25 octobre 1916. La voix de M. René Viviani, Président du Conseil des ministres : discours de clôture, séance du 4 aôut 1914

Collection : Série des documents historiques

La voix de M. Léon Bourgeois, Président du Conseil des ministres : discours prononcé le 9 novembre 1917. La voix de M. Gaston Doumergue, Président du Conseil des ministres : discours prononcé le 5 septembre 1916

Collection : Série des documents historiques

La voix de M. Paul Deschanel, Président de la Chambre des députés : discours prononcé le 5 août 1915. La voix de M. Paul Deschanel, Président de la Chambre des députés : discours prononcé à l'Institut, le 25 octobre 1916

Collection : Série des documents historiques