BACKGROUND & AIMS: BACKGROUND:in men, the concomitant use of two or more benzodiazepines or two or more antipsychotics is associated with an increased risk of fracture(s). Potential associations between the concomitant use of drugs with central nervous system effects and fracture risk have not been studied. OBJECTIVE:the purpose was to describe the gender-specific risk of fractures in a population aged 65 years or over associated with the use of an opioid, antiepileptic or anticholinergic drug individually; or, their concomitant use with each other; or the concomitant use of one of these with a psychotropic drug. METHODS:this study was part of a prospective, population-based study performed in Lieto, Finland. Information about fractures in 1,177 subjects (482 men and 695 women) was confirmed with radiology reports. RESULTS:at 3 years of follow-up, the concomitant use of an opioid with an antipsychotic was associated with an increased risk of fractures in men. During the 6-year follow-up, the concomitant use of an opioid with a benzodiazepine was also related to the risk of fractures for males. No significant associations were found for females. CONCLUSION:the concomitant use of an opioid with an antipsychotic, or with a benzodiazepine may increase the risk of fractures in men aged 65 years and older.

背景与目标： 背景：在男性中，同时使用两种或多种苯二氮杂类或两种或多种抗精神病药会增加骨折的风险。尚未研究同时使用药物与中枢神经系统作用与骨折风险之间的潜在关联。
目的：目的是描述在65岁或65岁以上人群中因单独使用阿片类药物，抗癫痫药或抗胆碱能药物引起的骨折的性别特异性风险；或同时使用；或或将其中一种与精神药物同时使用。
方法：本研究是在芬兰利托进行的一项基于人群的前瞻性研究的一部分。放射学报告证实了有关1,177名受试者（482名男性和695名女性）骨折的信息。
结果：在随访的3年中，同时使用阿片类药物和抗精神病药会增加男性骨折的风险。在6年的随访期间，阿片类药物与苯二氮卓类药物同时使用也与男性骨折风险有关。没有发现与女性的显着关联。
结论：阿片类药物与抗精神病药或苯二氮卓类药物同时使用可能会增加65岁以上男性骨折的风险。

BACKGROUND & AIMS: :Twenty-four antimicrobial drugs were examined for rapidity of onset and magnitude of bactericidal activity against selected strains of Clostridium perfringens. Ceftriaxone, imipenem, metronidazole, mezlocillin, penicillin G, piperacillin, and teicoplanin reduced colony counts by at least 3 log10 units within 2-4 h after exposure. Clindamycin, fluoroquinolones, josamycin, and tetracycline caused delayed kill (greater than or equal to 99.9% reduction of viable counts at 4-22 h after exposure). Chloramphenicol and rifampin lacked bactericidal activity against 2 of 4 strains, whereas erythromycin, fusidic acid, and fosfomycin (with added glucose-6-phosphate) were merely inhibitory for all 4 strains. Imipenem and penicillin G were combined with 9 and 12 antimicrobial drugs, respectively. Essentially all drug combinations yielded indifferent effects; only penicillin G plus doxycycline resulted in an antagonistic effect against C. perfringens.

背景与目标： ：检查了二十四种抗微生物药物对产气荚膜梭状芽孢杆菌某些菌株的起效速度和杀菌活性的大小。头孢曲松，亚胺培南，甲硝唑，美洛西林，青霉素G，哌拉西林和替考拉宁在暴露后2-4小时内可将菌落数减少至少3 log10个单位。克林霉素，氟喹诺酮，乔沙霉素和四环素引起延迟杀灭（暴露后4-22 h内存活计数减少等于或大于99.9％）。氯霉素和利福平对4个菌株中的2个缺乏杀菌活性，而红霉素，夫西地酸和磷霉素（添加了6-磷酸葡萄糖）仅对全部4个菌株具有抑制作用。亚胺培南和青霉素G分别与9种和12种抗菌药物合用。基本上所有药物组合均产生无关紧要的作用。仅青霉素G加强力霉素可导致对产气荚膜梭菌的拮抗作用。

BACKGROUND & AIMS: :Novel treatment strategies for tuberculosis are urgently needed. Many different preclinical models assessing anti-tuberculosis drug activity are available, but it is yet unclear which combination of models is most predictive of clinical treatment efficacy. The aim of this study was to determine the role of our in vitro time kill-kinetics assay as an asset to a predictive preclinical modeling framework assessing anti-tuberculosis drug activity. The concentration- and time-dependent mycobacterial killing capacities of six anti-tuberculosis drugs were determined during exposure as single drugs or in dual, triple and quadruple combinations towards a Mycobacterium tuberculosis Beijing genotype strain and drug resistance was assessed. Streptomycin, rifampicin and isoniazid were most active against fast-growing M. tuberculosis. Isoniazid with rifampicin or high dose ethambutol were the only synergistic drug combinations. The addition of rifampicin or streptomycin to isoniazid prevented isoniazid resistance. In vitro ranking showed agreement with early bactericidal activity in tuberculosis patients for some but not all anti-tuberculosis drugs. The time-kill kinetics assay provides important information on the mycobacterial killing dynamics of anti-tuberculosis drugs during the early phase of drug exposure. As such, this assay is a valuable component of the preclinical modeling framework.

背景与目标： ：迫切需要新的结核病治疗策略。目前已有许多评估抗结核药物活性的临床前模型，但尚不清楚哪种模型组合最能预测临床治疗效果。这项研究的目的是确定我们在体外时间杀伤动力学测定中作为评估抗结核药物活性的预测性临床前建模框架的一项资产的作用。在暴露于结核分枝杆菌北京基因型菌株的单药或双重，三重和四重组合暴露期间，确定了六种抗结核药物的浓度和时间依赖性分枝杆菌杀伤能力，并评估了耐药性。链霉素，利福平和异烟肼对快速增长的结核分枝杆菌最为活跃。异烟肼与利福平或大剂量乙胺丁醇是唯一的协同药物组合。在异烟肼中添加利福平或链霉素可防止异烟肼耐药。在体外排名显示，对于某些但不是全部抗结核药物，结核病患者的早期杀菌活性与之一致。时间杀灭动力学测定法提供了有关药物暴露初期抗结核药物分枝杆菌杀灭动力学的重要信息。因此，该测定是临床前建模框架的重要组成部分。

BACKGROUND & AIMS: :Achieving 'universal access' to antiretroviral HIV treatment (ART) in lower income and transitional settings is a global target. Yet, access to ART is shaped by local social condition and is by no means universal. Qualitative studies are ideally suited to describing how access to ART is socially situated. We explored systemic barriers to accessing ART among people who inject drugs (PWID) in a Russian city (Ekaterinburg) with a large burden of HIV treatment demand. We undertook 42 in-depth qualitative interviews with people living with HIV with current or recent experience of injecting drug use. Accounts were analysed thematically, and supplemented here with an illustrative case study. Three core themes were identified: 'labyrinthine bureaucracy' governing access to ART; a 'system Catch 22' created by an expectation that access to ART was conditional upon treated drug use in a setting of limited drug treatment opportunity; and 'system verticalization', where a lack of integration across HIV, tuberculosis (TB) and drug treatment compromised access to ART. Taken together, we find that systemic factors play a key role in shaping access to ART with the potential adverse effects of reproducing treatment initiation delay and disengagement from treatment. We argue that meso-level systemic factors affecting access to ART for PWID interact with wider macro-level structural forces, including those related to drug treatment policy and the social marginalization of PWID. We note the urgent need for systemic and structural changes to improve access to ART for PWID in this setting, including to simplify bureaucratic procedures, foster integrated HIV, TB and drug treatment services, and advocate for drug treatment policy reform.

背景与目标： ：在较低的收入和过渡环境中实现对抗逆转录病毒HIV治疗（ART）的“普遍获得”是全球目标。然而，获得抗逆转录病毒药物的途径取决于当地的社会状况，绝不是普遍的。定性研究非常适合描述获得抗逆转录病毒疗法在社会上的位置。我们探索了在俄罗斯城市（叶卡捷琳堡）注射艾滋病毒（HIV）需求量很大的注射毒品者（PWID）中获取ART的系统性障碍。我们对具有当前或最近注射吸毒经验的艾滋病毒感染者进行了42次深入的定性访谈。对帐目进行了主题分析，并在此处补充了说明性的案例研究。确定了三个核心主题：控制获取抗逆转录病毒药物的“迷宫式官僚主义”；期望在有限的药物治疗机会的情况下获得抗病毒药物的条件是要获得抗逆转录病毒药物而创建的“系统捕​​获22”；以及“系统垂直化”，即艾滋病毒，结核病和药物治疗之间缺乏整合，影响了抗逆转录病毒疗法的获取。综上所述，我们发现系统性因素在影响获得ART的过程中起着关键作用，并具有再生治疗起始延迟和脱离治疗的潜在不利影响。我们认为影响PWID获得抗逆转录病毒疗法的中观系统性因素与更广泛的宏观结构性因素相互作用，包括那些与毒品治疗政策和PWID的社会边缘化有关的因素。我们注意到迫切需要进行系统和结构上的改革，以改善在这种情况下PWID获得抗病毒治疗的途径，包括简化官僚程序，促进艾滋病毒，结核病和药物治疗的综合服务，以及倡导药物治疗政策的改革。

BACKGROUND & AIMS: :Rheumatoid arthritis (RA) is characterized by inflammation and an increased risk for cardiovascular disease (CVD). This study investigates possible associations between CVD and the use of conventional disease-modifying antirheumatic drugs (DMARDs) in RA. Using a case control design, 613 RA patients (5,649 patient-years) were studied, 72 with CVD and 541 without CVD. Data on RA, CVD and drug treatment were evaluated from time of RA diagnosis up to the first cardiovascular event or the end of the follow-up period. The dataset was categorized according to DMARD use: sulfasalazine (SSZ), hydroxychloroquine (HCQ) or methotrexate (MTX). Odds ratios (ORs) for CVD, corrected for age, gender, smoking and RA duration, were calculated per DMARD group. Patients who never used SSZ, HCQ or MTX were used as a reference group. MTX treatment was associated with a significant CVD risk reduction, with ORs (95% CI): 'MTX only', 0.16 (0.04 to 0.66); 'MTX and SSZ ever', 0.20 (0.08 to 0.51); and 'MTX, SSZ and HCQ ever', 0.20 (0.08 to 0.54). The risk reductions remained significant after additional correction for the presence of rheumatoid factor and erosions. After correction for hypertension, diabetes and hypercholesterolemia, 'MTX or SSZ ever' and 'MTX, SSZ and HCQ ever' showed significant CVD risk reduction. Rheumatoid factor positivity and erosions both increased CVD risk, with ORs of 2.04 (1.02 to 4.07) and 2.36 (0.92 to 6.08), respectively. MTX and, to a lesser extent, SSZ were associated with significantly lower CVD risk compared to RA patients who never used SSZ, HCQ or MTX. We hypothesize that DMARD use, in particular MTX use, results in powerful suppression of inflammation, thereby reducing the development of atherosclerosis and subsequently clinically overt CVD.

背景与目标： 类风湿关节炎（RA）的特征在于炎症和心血管疾病（CVD）的风险增加。这项研究调查了CVD与RA中使用传统疾病缓解风湿药（DMARDs）之间的可能联系。使用病例对照设计，研究了613名RA患者（5,649患者-年），其中72例患有CVD，541例没有CVD。从RA诊断到首次心血管事件或随访期结束，评估了RA，CVD和药物治疗的数据。数据集根据DMARD使用进行了分类：柳氮磺胺吡啶（SSZ），羟氯喹（HCQ）或甲氨蝶呤（MTX）。每个DMARD组均计算出经年龄，性别，吸烟和RA持续时间校正后的CVD的赔率（OR）。从未使用过SSZ，HCQ或MTX的患者被用作参考组。 MTX治疗可显着降低CVD风险，OR为（95％CI）：“仅MTX”，0.16（0.04至0.66）； ``MTX和SSZ曾经''，0.20（0.08至0.51）;和“ MTX，SSZ和HCQ”，0.20（0.08至0.54）。在对类风湿因子和糜烂的存在进行了进一步校正后，风险降低仍然很显着。在校正了高血压，糖尿病和高胆固醇血症后，“曾经有过MTX或SSZ”以及“曾经有过MTX，SSZ和HCQ”显示出可显着降低CVD风险。类风湿因子阳性和糜烂均增加了CVD的风险，OR分别为2.04（1.02至4.07）和2.36（0.92至6.08）。与从未使用过SSZ，HCQ或MTX的RA患者相比，MTX和较小程度的SSZ与较低的CVD风险相关。我们假设使用DMARD，尤其是使用MTX可以有效抑制炎症，从而减少动脉粥样硬化的发展，进而减少临床上明显的CVD的发生。

BACKGROUND & AIMS: :The intricate problems associated with the delivery and various unnecessary in vivo transitions of proteins and drugs needs to be tackled soon to be able to exploit the myriad of putative therapeutics created by the biotechnology boom. Nanomedicine is one of the most promising applications of nanotechnology in the field of medicine. It has been defined as the monitoring, repair, construction and control of human biological systems at the molecular level using engineered nanodevices and nanostructures. These nanostructured medicines will eventually turn the world of drug delivery upside down. PEGylation (i.e. the attachment of polyethylene glycol to proteins and drugs) is an upcoming methodology for drug development and it has the potential to revolutionise medicine by drastically improving the pharmacokinetic and pharmacodynamic properties of the administered drug. This article provides a total strategy for improving the therapeutic efficacy of various biotechnological products in drug delivery. This article also presents an extensive analysis of most of the PEGylated proteins, peptides and drugs, together with extensive clinical data. Nanomedicines and PEGylation, the latest offshoots of nanotechnology will definitely pave a way in the field of drug delivery where targeted delivery, formulation, in vivo stability and retention are the major challenges.

背景与目标： ：与蛋白质和药物的递送以及各种不必要的体内过渡相关的复杂问题需要尽快解决，以便能够利用由生物技术繁荣发展而来的无数推定疗法。纳米医学是纳米技术在医学领域最有前途的应用之一。它已被定义为使用工程化的纳米器件和纳米结构在分子水平上监测，修复，构建和控制人类生物系统。这些纳米结构药物最终将颠覆药物输送的世界。聚乙二醇化（即聚乙二醇与蛋白质和药物的连接）是药物开发的一种新方法，它具有通过彻底改善所给药药物的药代动力学和药效学性质来革新药物的潜力。本文提供了用于提高各种生物技术产品在药物输送中的治疗功效的总体策略。本文还对大多数PEG化的蛋白质，肽和药物进行了广泛的分析，并提供了广泛的临床数据。纳米药物和聚乙二醇化是纳米技术的最新分支，无疑将在药物递送领域铺平道路，在这些领域中，靶向递送，制剂，体内稳定性和保留性是主要挑战。

BACKGROUND & AIMS: :The purpose of the present research is to establish a novel nanosizing technique starting from wet nano-milling, named "dry nanosuspension" technique for poorly water-soluble drugs. The spray freeze-drying (SFD) method was applied instead of the spray-drying one previously developed. Drug particles were milled in the aqueous solution of dispersing agents using an oscillating beads-milling apparatus. The milled nanosuspension was sprayed to the surface of liquid nitrogen, and the resultant iced droplets were freeze-dried to obtain the powdery product. The loading ratio of a dispersing agent was investigated to enhance its redispersing property. Dry nanosuspension, which could be spontaneously dispersed into original nanosuspension in water, was obtained by SFD process. It was assumed that self dispersion property would be attributed to its structure with porous network, in which the primary milled drug crystals were embedded. Such unique structure contributed greatly to immediate release behaviors of the drug in gastrointestinal buffered media. These pharmaceutical properties were enhanced by increasing the ratio of the dispersing agent to the drug and the solid content in suspension to be sprayed. The present technique via wet milling and spray freeze-drying processes would be a novel dissolution-enhanced technology for poorly water-soluble drugs.

背景与目标： ：本研究的目的是建立一种从湿法纳米研磨开始的新型纳米技术，该技术被称为“干纳米悬浮”技术，用于水溶性差的药物。应用喷雾冷冻干燥（SFD）方法代替先前开发的喷雾干燥方法。使用振荡珠磨设备在分散剂的水溶液中研磨药物颗粒。将研磨后的纳米悬浮液喷雾至液氮表面，并将所得的冰滴冷冻干燥，以获得粉状产物。为了提高分散剂的再分散性，对分散剂的负载率进行了研究。通过SFD工艺获得了可以自发分散在水中的纳米悬浮液的干燥纳米悬浮液。假定自分散性归因于其具有多孔网络的结构，其中嵌入了原始研磨的药物晶体。这种独特的结构极大地促进了药物在胃肠缓冲介质中的立即释放行为。通过增加分散剂与药物的比例和待喷雾悬浮液中的固体含量，可以提高这些药物的性能。通过湿磨和喷雾冷冻干燥方法的本技术将是用于水溶性差的药物的新型溶解增强技术。

BACKGROUND & AIMS: :Little evidence or advice exists in the medical literature on 'medical kit' that could be usefully carried by physicians to prepare them for unexpected emergencies. The aim of this study was to establish what, in the opinion of Emergency Physicians, is an appropriate medical kit for doctors to carry to prepare them for 'Good Samaritan' acts. A telephone survey, using a proforma, of United Kingdom Emergency Physicians was conducted. Of the responders to the survey, 10% routinely undertook prehospital work. Seventy-two percent thought it appropriate to carry equipment, but only 43% thought it appropriate to carry medications. Over 80% considered basic airway equipment useful to carry, whereas other items of medical kit were considered appropriate much less commonly. A large proportion of emergency physicians consider it appropriate to carry some medical kit for 'Good Samaritan' acts and, in general, the consensus of opinion as to what medical kit should be carried agreed with the evidence-base for prehospital interventions.

背景与目标： ：在医学文献中，关于“医疗工具包”的证据或建议很少，医师可以有用地为他们准备以应对突发事件。这项研究的目的是确定急诊医师认为什么是适合医生随身携带的医疗工具箱，以使他们为“好撒玛利亚人”行为做好准备。使用形式表对英国急诊医师进行了电话调查。在接受调查的受访者中，有10％的人定期进行院前工作。 72％的人认为适合携带设备，但只有43％的人认为适合携带药物。超过80％的人认为基本的呼吸道设备可用于携带，而其他医疗用品则不太合适。大部分急诊医生认为为“好撒玛利亚人”行为携带一些医疗箱是合适的，并且一般而言，对于应该携带哪种医疗箱的意见与院前干预的证据基础相一致。

BACKGROUND & AIMS: PURPOSE OF REVIEW:This paper updates the treatment of Stevens-Johnson syndrome and toxic epidermal necrolysis supported by relevant views about the pathogenesis. RECENT FINDINGS:Building on the thesis that Stevens-Johnson syndrome and toxic epidermal necrolysis are due to dermal cell apoptosis, molecular pathways that may lead to this have been proposed. Intravenous immunoglobulin is postulated to block apoptosis via the Fas pathway. Most series on the use of intravenous immunoglobulin in toxic epidermal necrolysis have been favourable. Tumour necrosis factor is also thought to be an important mediator of cell death in toxic epidermal necrolysis. There was impressive control of the progression of toxic epidermal necrolysis with intravenous anti-tumour necrosis factor antibody infliximab in two cases. Strong associations between human leukocyte antigen subtypes and severe cutaneous reactions due to allopurinol and carbamazepine have been described. SUMMARY:To date, there is no established treatment of Stevens-Johnson syndrome/toxic epidermal necrolysis. With advancing knowledge of the pathogenesis, it is hoped that better forms of treatment may result.

背景与目标： 审查目的：本文更新了史蒂文斯-约翰逊综合征和中毒性表皮坏死溶解的治疗方法，并提供了有关发病机理的相关观点。
最近的发现：在史蒂文斯-约翰逊综合征和中毒性表皮坏死溶解是由于真皮细胞凋亡所致的论点的基础上，已经提出了可能导致这种情况的分子途径。假定静脉内免疫球蛋白可通过Fas途径阻断细胞凋亡。关于在有毒的表皮坏死溶解中使用静脉注射免疫球蛋白的大多数系列都是有利的。肿瘤坏死因子也被认为是毒性表皮坏死溶解过程中细胞死亡的重要介质。静脉注射抗肿瘤坏死因子抗体英夫利昔单抗对毒性表皮坏死溶解的进展有令人印象深刻的控制，其中有2例。已经描述了人白细胞抗原亚型与别嘌呤醇和卡马西平引起的严重皮肤反应之间的强关联。
摘要：迄今为止，尚无史蒂文斯-约翰逊综合征/毒性表皮坏死溶解的既定治疗方法。随着对发病机理的深入了解，希望可以产生更好的治疗形式。

BACKGROUND & AIMS: OBJECTIVES:The objectives of this study were 1) to obtain information regarding the prescribing pattern of nonsteroidal anti-inflammatory drugs (NSAIDs) in the primary care setting at a Malaysian university, 2) to determine the prevalence and types of potential NSAID prescription related problems (PRPs), and 3) to identify patient characteristics associated with exposure to these potential PRPs. METHODS:We retrospectively collected data from 1 academic year using the electronic medical records of patients in the University Sains Malaysia (USM) primary care system. The defined daily dose (DDD) methodology and the anatomical therapeutic chemical (ATC) drug classification system were used in the analysis and comparison of the data. Statements representing potential NSAID PRPs were developed from authoritative drug information sources. Then, algorithms were developed to screen the databases for these potential PRPs. Descriptive and comparative statistics were used to characterize DRPs. RESULTS:During the study period, 12,470 NSAID prescriptions were prescribed for 6,509 patients (mean ± SD = 1.92 ± 1.83). This represented a prevalence of 35,944 per 100,000 patients, or 36%. Based on their DDDs, mefenamic acid and diclofenac were the most prescribed NSAIDs. 573 potential NSAID-related PRPs were observed in a cohort of 432 patients, representing a prevalence of 6,640 per 100,000 NSAIDs users, or 6.6% of all NSAID users. Multivariate logistic regression analysis revealed that patients with a Malay ethnic background (p < 0.001), members of the staff (p < 0.001), having 4 or more prescribers (p < 0.001) or having 2 - 3 prescribers (p = 0.02), and representing 4 or more long-term therapeutic groups (LTTGs) (p < 0.001) or 2 - 3 LTTGs (p < 0.001) were significantly associated with an increased chance of exposure to potential NSAID related PRPs. CONCLUSIONS:This is the first study in Malaysia that presents data on the prescribing pattern of NSAIDs and the characteristics of potential NSAID-related PRPs. The prevalence of potential NSAID-related PRPs is frequent in the primary care setting. Exposure to these PRPs is associated with specific sociodemographic and health status factors. These results should help to raise the awareness of clinicians and patients about serious NSAID PRPs.

背景与目标： 目的：本研究的目的是：1）获得有关马来西亚大学初级保健机构中非甾体抗炎药（NSAIDs）处方模式的信息； 2）确定与NSAID处方相关的潜在问题的患病率和类型（PRPs），以及3）识别与暴露于这些潜在PRPs相关的患者特征。
方法：我们使用马来西亚赛恩斯大学（USM）初级保健系统中患者的电子病历，回顾性收集了1个学年的数据。定义的日剂量（DDD）方法和解剖治疗化学（ATC）药物分类系统用于数据的分析和比较。代表潜在的NSAID PRP的陈述是从权威的药物信息来源中得出的。然后，开发了用于筛选数据库以查找这些潜在PRP的算法。描述性统计数据和比较统计数据用于表征DRP。
结果：在研究期间，为6,509名患者开出了12,470份NSAID处方（平均±SD = 1.92±1.83）。这表示每100,000名患者中有35,944名患病率，占36％。根据其DDDs，甲芬那酸和双氯芬酸是处方最多的非甾体抗炎药。在432名患者中观察到573种潜在的与NSAID相关的PRP，占每100,000个NSAID使用者中6,640的患病率，占所有NSAID使用者的6.6％。多元logistic回归分析显示，具有马来族裔背景（p <0.001），职员（p <0.001），有4名或更多处方者（p <0.001）或有2-3名处方者（p = 0.02）的患者，代表4个或更多长期治疗组（LTTG）（p <0.001）或2-3个LTTG（p <0.001）与暴露于潜在的与NSAID相关的PRPs的机会增加显着相关。
结论：这是马来西亚的第一项研究，其提供了关于非甾体抗炎药处方模式和潜在的非甾体抗炎药相关PRPs特征的数据。在初级保健机构中，潜在的与NSAID相关的PRP的患病率很高。接触这些PRP与特定的社会人口统计学和健康状况因素相关。这些结果应有助于提高临床医生和患者对严重NSAID PRP的认识。

BACKGROUND & AIMS: OBJECTIVES:Dysthymia is a depressive disorder of chronic nature but of less severity than major depression, which depressive symptoms are more or less continuous for at least two years. The aim of this review was to conduct a systematic review of all RCTs comparing drugs and placebo for dysthymia. SEARCH STRATEGY:Electronic searches of Cochrane Library, EMBASE, MEDLINE, PsycLIT, Biological Abstracts and LILACS; reference searching; personal communication; conference abstracts; unpublished trials from the pharmaceutical industry; book chapters on the treatment of depression. SELECTION CRITERIA:The inclusion criteria for all randomised controlled trials were that they should focus on the use of drugs versus placebo for dysthymic patients. Exclusion criteria were: non randomised, mixed major depression/ dysthymia (trials not providing separate data) and depression secondary to other disorders (e.g. substance abuse). DATA COLLECTION AND ANALYSIS:The reviewers extracted the data independently. In order to achieve an intention-to-treat analysis, when trials failed to report it was assumed that people who died or dropped out had no improvement. Authors of relevant trials were contacted for additional and missing data. Absence of treatment response as defined by authors was the main measure of outcome used. Relative Risks (RR) and 95% confidence intervals (CI) of dichotomous data were calculated with the Random Effects Model. Where possible, number needed to treat (NNT) and number needed to harm (NNH) were estimated, taking the reciprocal of the absolute risk reduction. MAIN RESULTS:Currently the review includes 15 trials. Similar results were obtained in terms of efficacy for different groups of drugs, such as tricyclic (TCA), selective serotonin reuptake inhibitors (SSRI), monoamine oxidase inhibitors (MAOI) and other drugs (sulpiride, amineptine, and ritanserin). The pooled RR for absence of treatment response was 0.68 (95% CI 0.59-0.78) for TCA and the NNT was 4.3 (95% CI 3.2-6.5). SSRIs showed similar RR for this outcome: 0.64 (95% CI 0.55-0.74), the NNT being 4.7 (95% CI 3.5-6.9). Concerning MAOIs, the RR was 0.59 (95% CI 0.48-0.71) and the NNT was 2.9 (95% CI 2.2-4.3). Other drugs (amisulpride, amineptine and ritanserin) showed similar results in terms of absence of treatment response. Using more stringent criteria for improvement - full remission - the results were unchanged. Patients treated on TCA were more likely to report adverse events, compared with placebo. REVIEWER'S CONCLUSIONS:Drugs are effective in the treatment of dysthymia with no differences between and within class of drugs. Tricyclic antidepressants are more likely to cause adverse events and dropouts. As dysthymia is a chronic condition, there remains little information on quality of life and medium or long-term outcome.

背景与目标： 目的：心律失常是一种慢性抑郁症，具有严重程度，但不如重度抑郁症严重，抑郁症的症状至少持续了两年。这篇综述的目的是对所有比较药物和安慰剂治疗心律不齐的RCT进行系统的综述。
搜索策略：Cochrane图书馆，EMBASE，MEDLINE，PsycLIT，生物摘要和LILACS的电子搜索；参考搜索；个人交流；会议摘要；制药行业未发表的试验；本书章节介绍了抑郁症的治疗方法。
选择标准：对于所有有困难的患者，所有随机对照试验的纳入标准均应侧重于使用药物而非安慰剂。排除标准为：非随机，混合性重度抑郁/心律失常（试验未提供单独的数据）和继发于其他疾病的抑郁症（例如，药物滥用）。
数据收集与分析：审阅者独立提取数据。为了进行意向性分析，当试验未能报告时，假定死亡或退学的人没有改善。联系了相关试验的作者，以获取其他和缺少的数据。作者定义的缺乏治疗反应是所用结局的主要指标。用随机效应模型计算二分数据的相对风险（RR）和95％置信区间（CI）。在绝对风险降低的倒数范围内，尽可能估算需要治疗的数量（NNT）和造成伤害的数量（NNH）。
主要结果：目前，该评价包括15项试验。对于不同种类的药物，例如三环（TCA），选择性5-羟色胺再摄取抑制剂（SSRI），单胺氧化酶抑制剂（MAOI）和其他药物（舒必利，氨普汀和利坦色林），在功效方面获得了相似的结果。对于TCA，缺乏治疗反应的合并RR为0.68（95％CI 0.59-0.78），NNT为4.3（95％CI 3.2-6.5）。 SSRI对此结果显示相似的RR：0.64（95％CI 0.55-0.74），NNT为4.7（95％CI 3.5-6.9）。关于MAOI，RR为0.59（95％CI 0.48-0.71），NNT为2.9（95％CI 2.2-4.3）。就没有治疗反应而言，其他药物（阿米舒必利，阿米汀和利坦色林）也显示出相似的结果。使用更严格的改善标准-完全缓解-结果没有改变。与安慰剂相比，接受TCA治疗的患者更有可能报告不良事件。
审评人员的结论：药物可有效治疗心境障碍，且药物类别之间和类别之间均无差异。三环类抗抑郁药更可能引起不良事件和辍学。由于心境障碍是一种慢性疾病，因此关于生活质量以及中长期结果的信息很少。

BACKGROUND & AIMS: :The present paper reviews evidence on the effect of antidepressant treatments on dopamine transmission. Chronic treatment with antidepressant drugs potentiates the behavioural stimulant responses elicited by the stimulation of dopamine receptors, including reward-related behaviours. Moreover, antidepressants affect dopamine release in several brain areas. The reviewed literature is discussed in terms of the possible mechanisms underlying antidepressant-induced supersensitivity to dopamine-mediated behavioural responses, and of the possible implications for the therapeutic effect of these drugs. It is concluded that the potentiation of dopaminergic neurotransmission induced by chronic antidepressant treatments might contribute to their therapeutic effect.

背景与目标： ：本文综述了抗抑郁药对多巴胺传播的影响的证据。长期用抗抑郁药治疗可增强多巴胺受体的刺激引起的行为刺激反应，包括与奖励有关的行为。此外，抗抑郁药会影响多个大脑区域的多巴胺释放。就抗抑郁药引起的对多巴胺介导的行为反应的超敏性的潜在机制以及对这些药物的治疗作用的潜在影响进行了讨论。结论是，慢性抗抑郁药诱导的多巴胺能神经传递增强可能有助于其治疗效果。

BACKGROUND & AIMS: -2

背景与目标： -2

BACKGROUND & AIMS: Class I antiarrhythmic drugs do not decrease, but increase, the risk of ventricular fibrillation in the ischemic myocardium. On the contrary, vulnerability to fibrillation related to ischemia appears to be substantially reduced by calcium antagonists. We assessed whether the calcium antagonist diltiazem (0.50 mg/kg bolus plus 0.02 mg/kg/min infusion) could prevent the profibrillatory effect or even partially restore the antifibrillatory effect of a class I antiarrhythmic drug, flecainide (1 mg/kg bolus plus 0.04 mg/kg/min infusion) in the ischemic myocardium of anesthetized, open-chest pigs. Ischemia was obtained by completely occluding the left anterior descending coronary artery near its origin. Vulnerability to fibrillation was assessed by electrical fibrillation threshold (EFT), measured with diastolic impulses of 100 msec duration delivered at a rate of 180 beats/minute. Diltiazem did not oppose the rise in EFT induced by flecainide in the absence of ischemia (6.8 +/- 1.2 to 9.9 +/- 0.9 mA, p<0.001). It limited the fall in EFT observed under the dual influence of ischemia and flecainide (4.2 +/- 0.9 vs 1.3 +/- 0.6 mA, p<0.001). By reducing calcium entry into myocardial fibers, diltiazem delayed ischemic depolarization, as evidenced by reduced shortening of the monophasic action potential duration from 215 +/- 7 to 200 +/- 4 msec, instead of 178 +/- 6 (p<0.001), and reduced lengthening of intraventricular conduction time from 33 +/- 5 to 43 +/- 4 msec, instead of 53 +/- 4 (p<0.01). Therefore, diltiazem is likely to prevent the loss and even the reversal of the antifibrillatory properties of flecainide due to myocardial ischemia in dosages that do not adversely affect myocardial contractility or atrioventricular conduction to a large extent.

背景与目标： I类抗心律失常药物不会减少但会增加缺血性心肌室颤的风险。相反，钙拮抗剂似乎大大降低了与缺血相关的原纤维形成的脆弱性。我们评估了地尔硫卓钙拮抗剂（0.50 mg / kg推注加0.02 mg / kg / min输注）是否可以预防I类抗心律不齐药物氟卡尼（1 mg / kg推注加0.04）的原纤化作用或什至部分恢复其抗原纤化作用mg / kg / min输注量）在麻醉的开胸猪的缺血心肌中。缺血是通过完全闭塞左冠状动脉前降支来实现的。通过电颤动阈值（EFT）评估颤动的脆弱性，该阈值是通过以180次搏动/分钟的速率传递100毫秒持续时间的舒张脉冲来测量的。在没有缺血的情况下，地尔硫卓不反对氟卡尼诱导的EFT升高（6.8 /-1.2至9.9 /-0.9 mA，p <0.001）。它限制了在缺血和氟卡尼的双重影响下观察到的EFT下降（4.2 /-0.9对1.3 /-0.6 mA，p <0.001）。通过减少钙进入心肌纤维，地尔硫卓可延迟局部缺血去极化，这可通过单相动作电位持续时间从215 /-7缩短为200 /-4毫秒而不是178 /-6缩短（p <0.001）来证明，并减少脑室内传导时间从33 /-5延长至43 /-4毫秒，而不是53 /-4（p <0.01）。因此，地尔硫卓可能预防在很大程度上不会不利地影响心肌收缩力或房室传导的剂量下因心肌缺血而导致氟卡尼的损失，甚至逆转抗纤颤性。

BACKGROUND & AIMS: :We investigated the induction of a stress response gene by anticancer drugs that damage and covalently modify DNA and other cellular macromolecules. Two human colon adenocarcinoma cell lines (HT-29 and BE) which differ in sensitivity to chloroethylnitrosoureas were treated with 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) or with 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU). Both of these drugs can alkylate, crosslink and carbamoylate cellular macromolecules. Treated cells were compared to controls for cytoplasmic levels of HSP70 RNA and for synthesis of heat shock proteins. We also tested for induction of stress response gene expression by equitoxic or greater concentrations of other nitrosourea analogues which can alkylate only, alkylate and crosslink only or carbamoylate only, as well as other DNA crosslinking agents (chlorambucil and cis-platinum). Of these, only BCNU and CCNU, the chloroethylnitrosoureas having all three of the macromolecule-modifying activities, strongly induce HSP70 RNA levels in a dose-dependent and time-dependent manner. Induction of HSP70 by BCNU occurred in both cell lines at dose ranges that were cytocidal to the BCNU-resistant HT-29 cells. No induction was seen in BE cells at the lower BCNU concentrations that were equitoxic to that more sensitive cell line. These observations suggest that induction of HSP70 by BCNU and CCNU is neither a direct consequence of DNA crosslinks nor an invariable result of cytocidal drugs.

背景与目标： ：我们研究了抗癌药物对应激反应基因的诱导作用，这些药物会破坏并共价修饰DNA和其他细胞大分子。用1,3-双-（2-氯乙基）-1-亚硝基脲（BCNU）或1-（2-氯乙基）-尿素处理对氯乙基亚硝基脲敏感性不同的两种人结肠腺癌细胞系（HT-29和BE）。 3-环己基-1-亚硝基脲（CCNU）。这两种药物都可以使细胞大分子烷基化，交联和氨基甲酸酯化。将处理过的细胞与对照的细胞质水平的HSP70 RNA和热休克蛋白的合成进行比较。我们还测试了通过等毒性或更高浓度的其他亚硝基脲类似物（仅可烷基化，仅烷基化和交联或仅氨基甲酸酯）以及其他DNA交联剂（苯丁酸氮芥和顺铂）诱导的应激反应基因表达。其中，只有BCNU和CCNU（具有全部三种大分子修饰活性的氯乙基亚硝基脲）以剂量依赖和时间依赖的方式强烈诱导HSP70 RNA水平。在两种细胞系中，BCNU诱导HSP70的剂量范围均对BCNU抗性HT-29细胞具有杀细胞作用。在较低BCNU浓度的BE细胞中未见诱导作用，而该浓度对较敏感的细胞系具有同等毒性。这些观察结果表明，BCNU和CCNU诱导HSP70既不是DNA交联的直接结果，也不是杀细胞药物的不变结果。