Paradigme éclectique, modèle Uppsala… Quoi de neuf pour analyser les décisions et modes d’investissement à l’international ?

International audienc

Effect of amlodipine, atenolol and their combination on myocardial ischemia during treadmill exercise and ambulatory monitoring

Objectives.This study compared the effects of amlodipine, atenolol and their combination on ischemia during treadmill testing and 48-h ambulatory monitoring.Background.It is not known whether anti-ischemic drugs exert similar effects on ischemia during ambulatory monitoring and exercise treadmill testing.Methods.Patients with stable coronary artery disease and ischemia during treadmill testing and ambulatory monitoring were randomized to receive amlodipine (n = 51) or atenolol (n = 49). Each group underwent a counterbalanced, crossover evaluation of single drug and placebo, followed by evaluation of the combination.Results.Amlodipine and the combination prolonged exercise time to 0.1-mV ST segment depression by 29% and 34%, respectively (p < 0.001) versus 3% for atenolol (p = NS). During ambulatory monitoring, the frequency of ischemic episodes decreased by 28% with amlodipine (p = 0.083 [NS]), by 57% with atenolol (p < 0.001) and by 72% with the combination (p < 0.05 vs. both single drugs; p < 0.001 vs. placebo). Suppression of ischemia during exercise testing and ambulatory monitoring was similar in patients with and without exercise-induced angina. Exercise time to angina improved by 29% with amlodipine (p < 0.01), by 16% with atenolol (p < 0.05) and by 39% with the combination (p < 0.005 vs. placebo, atenolol and amlodipine). In patients with angina, total exercise time improved by 16% with amlodipine (p < 0.001), by 4% with atenolol (p = NS) and by 19% with the combination (p < 0.05 vs. placebo and either single drug). In those patients without angina, no therapy significantly improved total exercise time.Conclusions.Ischemia during treadmill testing was more effectively suppressed by amlodipine, whereas ischemia during ambulatory monitoring was more effectively suppressed by atenolol. The combination was more effective than either single drug in both settings

Endoscopic submucosal dissection specimens in early colorectal cancer: lateral margins, macroscopic techniques, and possible pitfalls.

Endoscopic submucosal dissection (ESD) allows en-bloc resection of superficial gastrointestinal tumors, providing specimens on which lateral margin analysis can be performed reliably. Positive lateral margins have been linked to higher rates of recurrence/residual tumor. There are no guidelines for macroscopic processing of lateral margins. Currently, most institutions use parallel lateral sections, which are difficult to interpret. We use perpendicular lateral sections, hypothesizing that it decreases potential artifactually positive lateral margins. We analyzed positive lateral margin rates in colorectal ESD specimens according to sectioning method. We also looked at morphological factors associated with margin positivity as a function of technique used. We studied 166 ESD specimens, on which parallel sectioning practiced from 2006 to 2011 (n = 75). Perpendicular sectioning was used from 2010 to 2015 (n = 91). We recorded the number of positive margins, along with grade of dysplasia/carcinoma. Other information such as histopathological type, specimen size, lesion location, and patient follow-up was also recorded for evaluation. Forty of seventy-five (63%) margins were positive for parallel sections. In contrast, perpendicularly cut margins were significantly less frequently positive: 22/91 (24%) (p = 0.0001). Positive margins were found significantly more frequently in tubulo-villous lesions compared to tubular lesions in both the parallel and perpendicular groups (p = 0.03 and p = 0.02, respectively). Specimen size was not significantly associated with positive margins. Using perpendicular sectioning of colorectal ESD specimens, the proportion of cases with a positive lateral margin was significantly lower than when parallel sectioning was used. We suggest perpendicular sectioning to improve accuracy in histopathological analysis. This method is particularly important to use in future studies, as it may prevent authors from making conjectures based on overestimation of positive lateral margins

Sclerostin-Antibody Treatment Decreases Fracture Rates in Axial Skeleton and Improves the Skeletal Phenotype in Growing oim/oim Mice

In osteogenesis imperfecta (OI), vertebrae brittleness causes thorax deformations and leads to cardiopulmonary failure. As sclerostin-neutralizing antibodies increase bone mass and strength in animal models of osteoporosis, their administration in two murine models of severe OI enhanced the strength of vertebrae in growing female Crtap−/− mice but not in growing male Col1a1Jrt/+ mice. However, these two studies ignored the impact of antibodies on spine growth, fracture rates, and compressive mechanical properties. Here, we conducted a randomized controlled trial in oim/oim mice, an established model of human severe OI type III due to a mutation in Col1a2. Five-week-old female WT and oim/oim mice received either PBS or sclerostin antibody (Scl-Ab) for 9 weeks. Analyses included radiography, histomorphometry, pQCT, microcomputed tomography, and biomechanical testing. Though it did not modify vertebral axial growth, Scl-Ab treatment markedly reduced the fracture prevalence in the pelvis and caudal vertebrae, enhanced osteoblast activity (L4), increased cervico-sacral spine BMD, and improved the lumbosacral spine bone cross-sectional area. Scl-Ab did not impact vertebral height and body size but enhanced the cortical thickness and trabecular bone volume significantly in the two Scl-Ab groups. At lumbar vertebrae and tibial metaphysis, the absolute increase in cortical and trabecular bone mass was higher in Scl-Ab WT than in Scl-Ab oim/oim. The effects on trabecular bone mass were mainly due to changes in trabecular number at vertebrae and in trabecular thickness at metaphyses. Additionally, Scl-Ab did not restore a standard trabecular network, but improved bone compressive ultimate load with more robust effects at vertebrae than at metaphysis. Overall, Scl-Ab treatment may be beneficial for reducing vertebral fractures and spine deformities in patients with severe OI

Therapeutics and Vaccines Against Chikungunya Virus

Erratum in Correction to: Vector Borne Zoonotic Dis 2015;15(4):250-257 DOI: 10.1089/vbz.2014.1681. [Vector Borne Zoonotic Dis. 2015]International audienceCurrently, there are no licensed vaccines or therapies available against chikungunya virus (CHIKV), and these were subjects discussed during a CHIKV meeting recently organized in Langkawi, Malaysia. In this review, we chart the approaches taken in both areas. Because of a sharp increase in new data in these fields, the present paper is complementary to previous reviews by Weaver et al. in 2012 and Kaur and Chu in 2013. The most promising antivirals so far discovered are reviewed, with a special focus on the virus-encoded replication proteins as potential targets. Within the vaccines in development, our review emphasizes the various strategies in parallel development that are unique in the vaccine field against a single disease