Myocardial cell death in fibrillating and dilated human right atria.

OBJECTIVES: The aim of the present study was to determine if myocytes can die by apoptosis in fibrillating and dilated human atria. BACKGROUND: The cellular remodeling that occurs during atrial fibrillation (AF) may reflect a degree of dedifferentiation of the atrial myocardium, a process that may be reversible. METHODS: We examined human right atrial myocardium specimens (n = 50) for the presence of apoptotic myocytes. We used immunohistochemical and Western blotting analysis to examine the expression of a final effector of programmed cell death, caspase-3 (CASP-3) and of regulatory proteins from the BCL-2 family. RESULTS: Sections from atria in AF contained a high percentage of large myocytes with a disrupted sarcomeric apparatus replaced by glycogen granules (64.4 +/- 6.3% vs. 12.2 +/- 5.8%). These abnormal myocytes, which also predominated in atria from hearts with decreased left ventricular ejection fraction (42.3 +/- 10.1%), contained large nuclei, most of which were TUNEL positive, indicating a degree of DNA breakage. None of these abnormal myocytes expressed the proliferative antigen Ki-67. A small percentage of the enlarged nuclei (4.2 +/- 0.8%) contained condensed chromatin and were strongly TUNEL positive. Both the pro- and activated forms of CASP-3 were detected in diseased myocardial samples, which also showed stronger CASP-3 expression than controls. Expression of the antiapoptotic BCL-2 protein was decreased in diseased atria, whereas that of the proapoptotic BAX protein remained unchanged. CONCLUSIONS: In fibrillating and dilated atria, apoptotic death of myocytes with myolysis contributes to cellular remodeling, which may not be entirely reversible.     

Eurogin Roadmap 2015: How has HPV knowledge changed our practice: Vaccines

This review is one of two complementary reviews that have been prepared in the framework of the Eurogin Roadmap 2015 to evaluate how knowledge about HPV is changing practices in HPV infection and disease control through vaccination and screening. In this review of HPV vaccine knowledge, we present the most significant findings of the past year which have contributed to our knowledge of the two HPV prophylactic vaccines currently in widespread use and about the recently licensed nonavalent HPV vaccine. Whereas anal cancer is dealt with in the companion mini‐review on screening, we also review here the rapidly evolving evidence regarding HPV‐associated head and neck cancer and priority research areas.     

The pharmacokinetics and pharmacodynamics of enoxaparin in obese volunteers

OBJECTIVES: The objective of this study was to compare the pharmacokinetics of the low-molecular-weight heparin enoxaparin in obese and nonobese volunteers, by means of two administration regimens. METHODS: Enoxaparin was administered subcutaneously (1.5 mg/kg once daily for 4 days) and in a single 6-hour infusion (1.5 mg/kg) to 24 obese volunteers and 24 age-, sex-, and height-matched nonobese volunteers in a randomized, open-label, 2-way crossover design. Blood plasma was assessed for anti-Xa and anti-IIa activity and activated partial thromboplastin time. RESULTS: After subcutaneous administration, steady-state exposure was achieved after the second dose in nonobese volunteers and after the third dose in obese volunteers. Time to maximum anti-Xa activity was 1 hour longer in obese volunteers, but maximum anti-Xa activity was similar in both groups. For anti-Xa activity, exposure at steady-state was 16% higher in obese volunteers than in nonobese volunteers (90% confidence interval, 108%-125%). After intravenous infusion, total body clearance and volume of distribution at steady state were higher in obese volunteers than in nonobese volunteers, but when adjusted for weight, these values were about 10% lower in obese volunteers. Anti-IIa activity after subcutaneous administration did not differ significantly between obese and nonobese volunteers. Pharmacodynamic analysis of activated partial thromboplastin time showed similar results in obese and nonobese volunteers after both intravenous and subcutaneous administration. No deaths or serious adverse events occurred during the study. CONCLUSIONS: Enoxaparin was well tolerated when administered subcutaneously or intravenously, and there appears to be no need to modify the currently recommended dose for obese volunteers.     

Pulmonary arterial systolic pressure and susceptibility to high altitude pulmonary edema

There is evidence that pulmonary arterial hypertension plays a major role in the occurrence of high altitude pulmonary edema (HAPE). We tested the hypothesis that the pulmonary arterial systolic pressure response to a challenge associated with hypoxia and mild exercise may be considered a predictive factor of HAPE. Pulmonary arterial systolic pressure was measured by Doppler echocardiography in 8 HAPE susceptible (HAPE-S) subjects and 8 HAPE resistant mountaineers (HAPE-R) during a hypoxic exercise challenge established by the French Association for Sport Medicine (Richalet's test). Pulmonary arterial systolic pressure during hypoxic exercise allowed a significant discrimination between the groups, although an overlap of values was observed. When expressed as individual variations from baseline to hypoxic exercise level however, we found a highly significant difference. No overlap was observed between HAPE-R (range: 6.7-18.5 mmHg) and HAPE-S (range: 19.2-30.4 mmHg) groups, with a cut-off value at 19 mmHg. Plasma Vascular Endothelial growth factor (VEGF) and malondialdehyde (MDA) increased in response to hypoxic exercise only in HAPE-S group. Individual increases in pulmonary arterial systolic pressure during hypoxic exercise from basal resting normoxic values seem relevant to estimate HAPE susceptibility when measured during the Richalet's test.     

Prevalence of and risk factors for lifetime suicide attempts among Caribbean people in the French West Indies

It has been suggested that Black people show lower suicidality than White people. The few conflicting studies estimating lifetime prevalence of suicide attempts in Caribbean populations were mainly carried out in the UK and the USA. Our aim was to investigate the prevalence of lifetime suicide attempts among the French Caribbean general population still living in the West Indies. As part of an international epidemiological multicenter study under the authority of the World Health Organization French Collaborating Centre, we interviewed 887 individuals selected from the general population in the Caribbean island of Martinique, using the Mini International Neuropsychiatric Interview. Among the interviewed individuals, 4.4% (N=39) reported having attempted suicide. Younger age, lifetime diagnoses of major mood disorder, panic disorder and alcohol dependence were all associated with a lifetime history of suicide attempts. Lifetime prevalence of suicide attempts among the French Caribbean general population was almost half as much as that measured in continental France.     

La contusion pulmonaire expose-t-elle au risque de prolifération bactérienne à pneumocoque ? Résultats d’une étude expérimentale

ObjectiveTo create a reliable and reproducible model of pulmonary contusion (PC) in rats in order to evaluate the influence of PC on bacterial lung proliferation.Study designExperimental.AnimalsMale albino CD rats.MethodsAnimals were anesthetized and a PC was performed using a spring-loaded metal bar. The existence of an isolated right PC was confirmed by macroscopic, histological and radiological analysis. This model was used to compare four randomized groups of animals. These were either injured or only anesthetized and inoculated with a pneumococcal solution concentrated in 2 or 4 log(CFU/mL). The animals’ lungs were collected for microbiological culture at 24 hours. The bacterial count evolution per gram of lung was the primary endpoint.ResultsTwelve rats were needed to validate the model, 84 to determine the morbidity and mortality and its reproducibility and 66 to assess the intra-pulmonary bacterial proliferation. The PC obtained was unilateral and isolated in 95% of cases. Mortality rate was 43%. For a low initial inoculum concentration (2 log [CFU/mL]), there is bacterial overgrowth in the PC group versus the no-PC group (P = 0.0017). This difference was not found when the inoculum was more concentrated.ConclusionThis experimental model is reliable and reproducible. The initially high mortality seems to decrease with the experience of operators. The CP significantly increases intra-pulmonary bacterial proliferation when the inoculation is low. A high inoculum neutralizes the effect of CP. These results suggest that enhanced prevention of micro-inhalation could be beneficial in cases of CP.     

To join or not to join: an investigation of individual facilitators and inhibitors of medical faculty participation in interdisciplinary research teams

Interdisciplinary research (IDR) teams are an important mechanism for facilitating medical breakthroughs. This study investigates the role of individual-level predictors of the choice to join a new IDR team at a major medical institution. We collected survey data from a sample of 233 faculty members who were given the opportunity to participate in IDR teams that had recently formed around a wide range of medical topic areas. Our results suggest that even under supportive organizational conditions, some medical experts were more likely to participate than others. Specifically, basic and translational researchers, associate professors, and faculty with distinctive topic area expertise and with more experience collaborating across departmental boundaries participated at a greater rate than their peers. Our findings have implications for research, practice, and policy focused on overcoming the challenges of drawing together diverse medical experts into IDR teams with the potential to advance knowledge to prevent, cure, and treat complex medical conditions.