Journal of internal medicine
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Repolarization abnormalities, including those induced by the congenital or acquired long QT (LQT) syndrome, provide a substrate for life-threatening cardiac arrhythmias. In this article, we use computational biology to link HERG mutations mechanistically to the resulting abnormalities of the whole-cell action potential. We study how the kinetic properties of I(Ks) (the slow delayed rectifier) that are conferred by molecular subunit interactions, facilitate its role in repolarization and 'repolarization reserve'. A new noninvasive imaging modality (electrocardiographic imaging) is shown to image cardiac repolarization on the epicardial surface, suggesting its possible role in risk stratification, diagnosis and treatment of LQT syndrome.
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We aimed to characterize the clinical experiences of patients in whom heparin-induced thrombocytopenia (HIT) complicated heparin therapy for venous thromboembolism (VTE) and who switched to argatroban. ⋯ For VTE patients with HIT, argatroban provides effective anticoagulation, with outcomes comparable with those reported for other argatroban-treated HIT patients. New thrombosis in this setting occurred most often in patients with existing HIT-associated thrombosis, before HIT recognition or either at/after argatroban discontinuation.
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Apoptosis is a highly regulated process of cell deletion and plays a fundamental role in the maintenance of tissue homeostasis in the adult organism. Numerous studies in recent years have revealed that apoptosis is a constitutive suicide programme expressed in most, if not all cells, and can be triggered by a variety of extrinsic and intrinsic signals. ⋯ In addition, defective macrophage engulfment and degradation of cell corpses may also contribute to a dysregulation of tissue homeostasis. An increased understanding of the signalling pathways that govern the execution of apoptosis and the subsequent clearance of dying cells may thus yield novel targets for therapeutic intervention in a wide range of human maladies.
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Cardiovascular fitness represents the ability of active skeletal muscle to utilize oxygen during aerobic exercise. Elevated homocysteine, causing tissue injury by such mechanisms as oxidative stress, endothelial damage, and protein homocysteinylation, is associated with increased risk of cardiovascular disease, dementia and osteoporotic fracture. However, the association between elevated homocysteine and cardiovascular fitness has not been reported. ⋯ A total of 1444 noninstitutionalized adults aged 20--49 years with reliable measures of cardiovascular fitness and non-missing values in homocysteine. Main outcome measures. Cardiovascular fitness, estimated maximal oxygen uptake or VO(2)max (mL kg(-1) min(-1)), was obtained by a submaximal exercise test. Levels of homocysteine were measured by the Abbott homocysteine assay, a fully automated fluorescence polarization immunoassay method and were natural-log-transformed due to right skewness. RESULTS. After adjustment for age, race and body mass index, there was a 0.70 mL kg(-1) min(-1) decrease (P=0.033) in the estimated VO(2)max for each standard deviation (SD) increase in the natural-log-transformed homocysteine level for women. Additional adjustment of hypertension, diabetes, smoking status, alcohol intake, use of lipid-lowering agents, physical activity, self-report health condition, as well as levels of folate, vitamin B(12), creatinine, C-reactive protein, total cholesterol and haemoglobin seemed to influence the association. In the fully adjusted model, we observed a 1.18 mL kg(-1) min(-1) decrease (P=0.003) in the estimated VO(2)max for each SD increase in the natural-log-transformed homocysteine level in women. There was no association between cardiovascular fitness and homocysteine levels in men. CONCLUSION. High homocysteine levels were inversely associated with cardiovascular fitness in women, but not in men. The results suggest that homocysteine levels are important indicators of exercise tolerance amongst women and may be useful in targeting female individuals requiring endurance intervention to prevent loss of cardiovascular fitness and function.