RRT incidence continues to rise but at various rates in the European countries studied, tending to widen the gap between them. This mainly results from enlarging differences in incidence in the elderly and, to a lesser extent, in that due to diabetes, hypertension and renal vascular disease.

While type 1 hyperlipidemia is associated with lipoprotein lipase or apoCII deficiencies, the etiology of type 5 hyperlipidemia remains largely unknown. We explored a new candidate gene, APOA5, for possible causative mutations in a pedigree of late-onset, vertically transmitted hyperchylomicronemia. A heterozygous Q139X mutation in APOA5 was present in both the proband and his affected son but was absent in 200 controls. It was subsequently found in 2 of 140 cases of hyperchylomicronemia. Haplotype analysis suggested the new Q139X as a founder mutation. Family studies showed that 5 of 9 total Q139X carriers had hyperchylomicronemia, 1 patient being homozygote. Severe hypertriglyceridemia in 8 heterozygotes was strictly associated with the presence on the second allele of 1 of 2 previously described triglyceride-raising minor APOA5 haplotypes. Furthermore, ultracentrifugation fraction analysis indicated in carriers an altered association of Apoa5 truncated and WT proteins to lipoproteins, whereas in normal plasma, Apoa5 associated with VLDL and HDL/LDL fractions. APOB100 kinetic studies in 3 severely dyslipidemic patients with Q139X revealed a major impairment of VLDL catabolism. Lipoprotein lipase activity and mass were dramatically reduced in dyslipidemic carriers, leading to severe lipolysis defect. Our observations strongly support in humans a role for APOA5 in lipolysis regulation and in familial hyperchylomicronemia. IntroductionRaised plasma triglyceride (TG) levels are an independent risk factor for coronary artery disease (1) and are influenced by both genetic and environmental factors. Severe hypertriglyceridemia (HTG) is a general condition with a few well-documented genetic contributors, including lipoprotein lipase (LPL), APOC2, and APOE, as well as environmental factors such as diet and/or conditions such as pregnancy and diabetes (2-5). While genetic factors account for a large proportion of the rare type 1 hyperlipidemia, the complex interaction between genetics and environment is only partly understood in the more common type 5 hyperlipidemia.A strong candidate for severe HTG is the recently discovered human apolipoprotein A-V (APOA5) gene based on its profound modulation of plasma TG concentration. In mice, apoa5 overexpression lowered plasma TG concentration (6-8) whereas mice lacking Apoa5 had a 4-fold increase in plasma TG concentration (6). In humans, independent studies have demonstrated that variant haplotypes with either the S19W or the c.A-3G APOA5 polymorphisms are strong determinants of plasma TG

ObjectiveThe inhalation of radon, a well-established human carcinogen, is the principal—and omnipresent—source of radioactivity exposure for the general population of most countries. Scientists have thus sought to assess the lung cancer risk associated with indoor radon. Our aim here is to assess this risk in France, using all available epidemiologic results and performing an uncertainty analysis.MethodsWe examined the exposure–response relations derived from cohorts of miners and from joint analyses of residential case-control studies and considered the interaction between radon and tobacco. The exposure data come from measurement campaigns conducted since the beginning of the 1980s by the Institute for Radiation Protection and Nuclear Safety and the Directorate-General of Health in France. We quantified the uncertainties associated with risk coefficients and exposures and calculated their impact on risk estimates.ResultsThe estimated number of lung cancer deaths attributable to indoor radon exposure ranges from 543 [90% uncertainty interval (UI), 75–1,097] to 3,108 (90% UI, 2,996–3,221), depending on the model considered. This calculation suggests that from 2.2% (90% UI, 0.3–4.4) to 12.4% (90% UI, 11.9–12.8) of these deaths in France may be attributable to indoor radon.DiscussionIn this original work we used different exposure–response relations from several epidemiologic studies and found that regardless of the relation chosen, the number of lung cancer deaths attributable to indoor radon appears relatively stable. Smokers can reduce their risk not only by reducing their indoor radon concentration but also by giving up smoking.

A case-control study nested in the cohort of French uranium miners took smoking information into account in investigating the effect of radon exposure on lung cancer risk. This study included 100 miners who died of lung cancer and 500 controls matched for birth period and attained age. Data about radon exposure came from the cohort study, and smoking information was retrospectively determined from a questionnaire and occupational medical records. Smoking status (never vs. ever) was reconstructed for 62 cases and 320 controls. Statistical analyses used conditional logistic regression. The effect of radon exposure on lung cancer risk was assessed with a linear excess relative risk model, and smoking was considered as a multiplicative factor. Mean cumulative radon exposures were 114.75 and 70.84 Working Level Months (WLM) among exposed cases and controls, respectively. The crude excess risk of lung cancer per 100 WLM was 0.98 (95% CI: 0.18-3.08%). When adjusted for smoking, the excess risk was 0.85 per 100 WLM (95% CI: 0.12-2.79%), which is still statistically significant. The relative risk related to smoking was equal to 3.04 (95% CI: 1.20-7.70). This analysis shows a relative risk of lung cancer related to smoking similar to that estimated from previous miners' cohorts. After adjustment for smoking, the effect of radon exposure on lung cancer risk persists, and its estimated risk coefficient is close to that found in the French cohort without smoking information.

A 75-year-old female known to have a chronic myelomonocytic leukaemia and an acquired FXI deficiency (FXI level, 5%) related to a FXI inhibitor (38 Bethesda units) was admitted to the hospital for acute pneumonia associated with a bulky pleural effusion. A therapeutic puncture was found to be essential for the patient. But, such a procedure is a haemostatic challenge which requires adequate preparation. A first treatment composed of intravenous immunoglobulins and immunosuppressive therapy failed to eradicate the inhibitor and to restore a normal FXI level. In this context, steroids or FXI concentrates were not recommended. Thus, small doses of recombinant activated factor VII were used to achieve haemostasis. The procedure was successful, the tolerance was good and no adverse events occurred.