Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Synthèse électrochimique de films minces d'hydroxydes doubles lamellaires

Conférence du 02 au 06 Juillet 2007. Communication par affiche

Progress in faunal correlation of Late Cenozoic fluvial sequences 2000-4: the report of the IGCP 449 biostratigraphy subgroup.

Vertebrate and invertebrate faunal biostratigraphy is a well-tested method for establishing relative chronologies for fluviatile sequences that has proved useful in many parts of the world. The robust bones and teeth of large mammals are commonly found in fluviatile deposits, whereas small vertebrates can be readily recovered through systematic sieving of calcareous sediments, as can molluscs, the other major faunal group that has been used for biostratigraphical analysis of fluvial sequences. Because of their rapid and quantifiable rates of evolution, extinction, body mass change and dispersal during the Late Cenozoic, mammals are especially useful for ordering the fragmentary terrestrial sequence of interglacials and glacials, and proposing correlation with the global marine climatostratigraphic record. Other groups (e.g. reptiles and amphibians, ostracods) are as yet only in the initial stages of development as a dating tool, whereas some (e.g. fish, birds) still require substantial development in order to fully explore their utility. As part of IGCP 449, vertebrate and molluscan assemblages have made important contributions to datasets from a number of areas, notably northern France, central Germany, the Czech Republic and the Ukraine. Further south, mammalian assemblages have proved useful in separating discrete periods of climatic change in Iberia and Syria. At greater distances from the core area of fluvial biostratigraphical archives, significant contributions have come from South America (Uruguay River), South Africa (Vaal) and Australia (Riverine Plain and Lake Eyre drainage basin)