环氧合酶抑制剂与心血管事件的发生和预防

2004年,罗非昔布（万络）因致心血管疾病风险而撤市。市场上能增加心血管疾病风险的相关药物和环氧合酶（COX-2）抑制剂以及非选择性非甾体抗炎药（NSAID）也遭到质疑。本文论述是否新的证据能改进现有的临床实践和监管条例。过多的抑制COX-2会增加心血管疾病的发生风险,除非同时对血小板血栓素合成的抑制达95%以上,这可通过全血分析检测。最近研究证实,对乙酰氨基酚（扑热息痛）也是一种COX-2选择性抑制剂。流行病学调查指出,对乙酰氨基酚作为一种易得的非处方药物,也存在增加心血管事件的风险。目前尚无足够证据认为罗非昔布的替代药品是安全的。对NSAID的药品监管及处方应遵循“首要不伤害”的预警性原则,药品应强制性加注此类药物心血管风险的告示,以警示处方者和患者。     

同型半胱氨酸—糖尿病血管病变的新型危险因素

同型半胱氨酸（Hcy）是蛋氨酸代谢中间产物,是一种含硫基的氨基酸。1964年Gibson等首先报道高同型半胱氨酸血症与血管性疾病和血栓形成相关,1969年Mcully提出Hcy可能与动脉粥样硬化有关。随着近30年的深入研究,众多资料表明高Hcy血症（hHcy）是心脑血管病变的一个独立危险因素。     

The EndoAssist? Robotic Camera Holder as an Aid to the Introduction of Laparoscopic Colorectal Surgery

INTRODUCTION

Introducing laparoscopic colorectal surgery is a challenge to the whole surgical team. It is usual for an assistant to hold the laparoscope and be responsible for the surgeon''s view of the operative field and a lack of expertise in the assistant can add significant difficulties. The EndoAssist™ is a robotic device that replaces the human assistant and ensures steady visualisation of the operative field and a view which can be controlled by the surgeon. This study describes its use in the introduction of laparoscopic colorectal surgery to a unit.

PATIENTS AND METHODS

The EndoAssist was employed for the introduction of laparoscopic colorectal surgery in a unit with previous experience of this device for laparoscopic cholecystectomy. It was used in a consecutive series of 77 laparoscopic colectomy operations.

RESULTS

The robotic device proved successful in the whole range of colorectal operations and a reliable assistant. No problems specific to the device were encountered.

CONCLUSIONS

The EndoAssist robot is a useful laparoscopic assistant and aided in the introduction of laparoscopic colorectal surgery.     

Attitudes towards new HIV biomedical prevention technologies among a cohort of HIV‐negative gay men in Sydney,Australia

Objectives

The aim of the study was to explore the awareness of rectal microbicides, the use of pre‐exposure prophylaxis (PREP) and the willingness to participate in biomedical HIV prevention trials in a cohort of HIV‐negative gay men.

Methods

In a community‐based cohort study, HIV‐negative homosexually active men in Sydney, Australia were questioned about awareness of rectal microbicides, use of PREP, and willingness to participate in trials of such products. Predictors of awareness and willingness to participate were analysed by logistic regression. Use of PREP was examined prospectively.

Results

Overall, 14% had heard of rectal microbicides. Older (P=0.05) and university‐educated men (P=0.001) were more likely to have knowledge of rectal microbicides. Almost one‐quarter (24%) of men reported that they were likely/very likely to participate in rectal microbicide trials. Among those men with definite opinions on participation, awareness of rectal microbicides was significantly associated with unwillingness to participate [odds ratio (OR) 0.78, 95% confidence interval (CI) 0.65–0.93, P=0.007]. Willingness to participate in trials using antiretroviral drugs (ARVs) to prevent HIV infection was reported by 43% of men, and was higher among those who reported unprotected anal intercourse (UAI) with HIV‐positive partners (OR 1.88, 95% CI 0.99–3.56). There was no evidence of current PREP use.

Conclusions

This study demonstrates that Australian gay men have had little experience with PREP use and rectal microbicides. About half would be willing to consider participation in trials using ARVs to prevent HIV infection. Extensive community education and consultation would be required before PREP or rectal microbicides could be trialled in populations of gay Australian men.

     

Efavirenz directly modulates the oestrogen receptor and induces breast cancer cell growth

Objectives

Efavirenz‐based HIV therapy is associated with breast hypertrophy and gynaecomastia. Here, we tested the hypothesis that efavirenz induces gynaecomastia through direct binding and modulation of the oestrogen receptor (ER).

Methods

To determine the effect of efavirenz on growth, the oestrogen‐dependent, ER‐positive breast cancer cell lines MCF‐7, T47D and ZR‐75‐1 were treated with efavirenz under oestrogen‐free conditions in the presence or absence of the anti‐oestrogen ICI 182,780. Cells treated with 17β‐oestradiol in the absence or presence of ICI 182,780 served as positive and negative controls, respectively. Cellular growth was assayed using the crystal violet staining method and an in vitro receptor binding assay was used to measure the ER binding affinity of efavirenz.

Results

Efavirenz induced growth in MCF‐7 cells with an estimated effective concentration for half‐maximal growth (EC₅₀) of 15.7 μM. This growth was reversed by ICI 182,780. Further, efavirenz binds directly to the ER [inhibitory concentration for half maximal binding (IC₅₀) of ～52 μM] at a roughly 1000‐fold higher concentration than observed with 17β‐oestradiol.

Conclusions

Our data suggest that efavirenz‐induced gynaecomastia may be caused, at least in part, by drug‐induced ER activation in breast tissues.     

The gap between clinical gaze and systematic assessment of movement disorders after stroke

Background

In rehabilitation, training intensity is usually adapted to optimize the trained system to attain better performance (overload principle). However, in balance rehabilitation, the level of intensity required during training exercises to optimize improvement in balance has rarely been studied, probably due to the difficulty in quantifying the stability level during these exercises. The goal of the present study was to test whether the stabilizing/destabilizing forces model could be used to analyze how stability is challenged during several exergames, that are more and more used in balance rehabilitation, and a dynamic functional task, such as gait.

Methods

Seven healthy older adults were evaluated with three-dimensional motion analysis during gait at natural and fast speed, and during three balance exergames (50/50 Challenge, Ski Slalom and Soccer). Mean and extreme values for stabilizing force, destabilizing force and the ratio of the two forces (stability index) were computed from kinematic and kinetic data to determine the mean and least level of dynamic, postural and overall balance stability, respectively.

Results

Mean postural stability was lower (lower mean destabilizing force) during the 50/50 Challenge game than during all the other tasks, but peak postural instability moments were less challenging during this game than during any of the other tasks, as shown by the minimum destabilizing force values. Dynamic stability was progressively more challenged (higher mean and maximum stabilizing force) from the 50/50 Challenge to the Soccer and Slalom games, to the natural gait speed task and to the fast gait speed task, increasing the overall stability difficulty (mean and minimum stability index) in the same manner.

Conclusions

The stabilizing/destabilizing forces model can be used to rate the level of balance requirements during different tasks such as gait or exergames. The results of our study showed that postural stability did not differ much between the evaluated tasks (except for the 50/50 Challenge), compared to dynamic stability, which was significantly less challenged during the games than during the functional tasks. Games with greater centre of mass displacements and changes in the base of support are likely to stimulate balance control enough to see improvements in balance during dynamic functional tasks, and could be tested in pathological populations with the approach used here.     

A genome-wide linkage scan reveals CD53 as an important regulator of innate TNF-α levels

Cytokines are major immune system regulators. Previously, innate cytokine profiles determined by lipopolysaccharide stimulation were shown to be highly heritable. To identify regulating genes in innate immunity, we analyzed data from a genome-wide linkage scan using microsatellites in osteoarthritis (OA) patients (The GARP study) and their innate cytokine data on interleukin (IL)-1β, IL-1Ra, IL-10 and tumor necrosis factor (TNF)α. A confirmation cohort consisted of the Leiden 85-Plus study. In this study, a linkage analysis was followed by manual selection of candidate genes in linkage regions showing LOD scores over 2.5. An single-nucleotide polymorphism (SNP) gene tagging method was applied to select SNPs on the basis of the highest level of gene tagging and possible functional effects. QTDT was used to identify the SNPs associated with innate cytokine production. Initial association signals were modeled by a linear mixed model. Through these analyses, we identified 10 putative genes involved in the regulation of TNFα. SNP rs6679497 in gene CD53 showed significant association with TNFα levels (P=0.001). No association of this SNP was observed with OA. A novel gene involved in the innate immune response of TNFα is identified. Genetic variation in this gene may have a role in diseases and disorders in which TNFα is closely involved.