Associations of weight change and weight variability with cardiovascular and all-cause mortality in the Chicago Western Electric Company Study

Few studies of associations between weight loss or weight fluctuations and mortality have been sufficiently long term to permit exclusion of early deaths for a portion of follow-up long enough to eliminate likely effects of illness-related weight loss. This study examined associations of the variation (standard deviation and standard deviation about the trend (slope)) and trend (weight loss or weight gain) in body mass index (weight (kg)/height (m2) between 1958 and 1966 (minimum of five measurements) with subsequent 25-year mortality among 1,281 men originally aged 40-56 years from the Chicago Western Electric Company Study. In multivariate Cox regression models that included two slope variables representing weight loss and weight gain and each variability measure separately, weight loss and weight gain were significantly related to 15-year mortality but weight variability was not. Relative risks for cardiovascular disease mortality were 1.25 (95% confidence interval (CI): 1.09, 1.45) and 1.14 (95% CI: 0.97, 1.33), respectively, for weight loss and weight gain slopes larger by 0.12 kg/m2 per year; corresponding relative risks for all-cause mortality were 1.23 (95% CI: 1.10, 1.38) and 1.15 (95% CI: 1.03, 1.29), respectively. For follow-up years 16-25, none of these weight variables were significantly related to mortality. These results indicate that an association between weight loss and mortality may not persist beyond 15 years, and that weight variability may not be related to mortality independently of weight loss or weight gain.     

治疗糖尿病及糖尿病足的疼痛

病史:T.N.,男性,55岁,两年前确诊患有糖尿病。近来他的糖化血红蛋白(GHbA1c)达到11.8%,他的医生在他服用格列甲嗪XL20mg/d及吡格列酮(Actos,武田/礼来)15mg/d的基础上,又增加了晚间最小剂量的中效胰岛素。T.N.同时每天还服用阿托伐他汀(Lipitor,辉瑞)10mg和雷米普利(Altace,安万特)10mg。另外,医生给T.N.处方卡马西平治疗其糖尿病足。对此,你有什么想法,能给出一些建议吗?点评一综合各方面因素制订治疗方案,以下是一些需要考虑的问题。首先是CYPT2C8/9酶诱导剂卡马西平与该酶的底物格列甲嗪及吡格列酮之间的药物相互作用问题。治疗…     

The impact of follicular lymphoma on health-related quality of life.

BACKGROUND: The purpose of this study was to determine whether there was a relationship between disease activity and health functioning, as measured by a range of patient-reported outcome (PRO) measures in patients with follicular lymphoma (FL). PATIENTS AND METHODS: A total of 222 patients with FL were recruited from eight sites across the UK and they completed a number of PRO measures. The participants were analyzed across five disease states: 'active disease-newly diagnosed', 'active disease-relapsed', 'partial response', 'complete response' and 'disease free'. The relationship between these disease states and their level of health functioning was assessed as well as the relationship between being 'on' or 'off' chemotherapy and disease state. RESULTS: In terms of health-related quality of life (HRQoL), participants in the relapsed category had the lowest mean physical well-being, emotional well-being, functional well-being and social well-being score. In a regression analysis, the 'active disease-relapsed' group acted as a significant predictor for each PRO variable. In addition, the remission group acted as a significant predictor of high anxiety scores as measured by the Hospital Anxiety and Depression Scale. CONCLUSION: The results of this study demonstrate that various aspects of patient-reported health outcomes differ according to disease state in patients with FL. For those patients who have relapsed, they are more likely to experience worse HRQoL and other patient-reported health outcomes than patients newly diagnosed, in partial or complete remission or when completely disease free.     

Kinetics of the SARS-CoV-2 Antibody Avidity Response Following Infection and Vaccination

Serological assays capable of measuring antibody responses induced by previous infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been critical tools in the response to the COVID-19 pandemic. In this study, we use bead-based multiplex assays to measure IgG and IgA antibodies and IgG avidity to five SARS-CoV-2 antigens (Spike (S), receptor-binding domain (RBD), Nucleocapsid (N), S subunit 2, and Membrane-Envelope fusion (ME)). These assays were performed in several cohorts of healthcare workers and nursing home residents, who were followed for up to eleven months after SARS-CoV-2 infection or up to six months after vaccination. Our results show distinct kinetic patterns of antibody quantity (IgG and IgA) and avidity. While IgG and IgA antibody levels waned over time, with IgA antibody levels waning more rapidly, avidity increased with time after infection or vaccination. These contrasting kinetic patterns allow for the estimation of time since previous SARS-CoV-2 infection. Including avidity measurements in addition to antibody levels in a classification algorithm for estimating time since infection led to a substantial improvement in accuracy, from 62% to 78%. The inclusion of antibody avidity in panels of serological assays can yield valuable information for improving serosurveillance during SARS-CoV-2 epidemics.     

Norepinephrine amplifies human chorionic gonadotropin-stimulated androgen biosynthesis by ovarian theca-interstitial cells

Ovarian theca-interstitial cells, when cultured in serum-free medium, secreted androgens in response to hCG stimulation. This production was dependent on time (maximum production attained after 96 h) and dose (half-maximal effective dose of hCG, 9 ng/ml). When the sympathomimetics norepinephrine, epinephrine, and isoproterenol were added to the medium, androgen production in response to hCG was enhanced by 100-300%. The ability of the catecholamines to stimulate androgen production was dependent on the continuous presence of hCG. Treatment with catecholamines alone did not induce theca-interstitial cells to produce androgens. Catecholamine stimulation of steroid hormone metabolism was selective for intermediates in the delta 4-pathway, with greatest increases occurring in the production of androstenedione and testosterone. It was found that the effect of the catecholamines on androgen production was dependent on both beta 1-and beta 2-adrenergic receptors. The acquisition of catecholamine responsiveness was specific to hCG; if theca-interstitial cells were induced to differentiate with either prostaglandin E2 or cholera toxin, then isoproterenol did not enhance androgen synthesis. The catecholamine-induced increases in androgen production were not due to a granulosa cell contribution of steroid. The interstitial cells are the only steroid-producing cells in the ovary that are directly innervated by norepinephrine-containing fibers of the sympathetic nervous system. Our finding of catecholamine-augmented androgen production provides a direct link between the autonomic nervous system and regulation of ovarian steroid synthesis.