BACKGROUND & AIMS: AIMS:Falling in older persons is a frequent and serious clinical problem. Several drugs have been associated with increased fall risk. The objective of this study was to identify differences in the incidence of falls after withdrawal (discontinuation or dose reduction) of fall-risk-increasing drugs as a single intervention in older fallers. METHODS:In a prospective cohort study of geriatric outpatients, we included 139 patients presenting with one or more falls during the previous year. Fall-risk-increasing drugs were withdrawn, if possible. The incidence of falls was assessed within 2 months of follow-up after a set 1 month period of drug withdrawal. Multivariate adjustment for potential confounders was performed with a Cox proportional hazards model. RESULTS:In 67 patients, we were able to discontinue a fall-risk-increasing drug, and in eight patients to reduce its dose. The total number of fall incidents during follow-up was significantly lower in these 75 patients, than in those who continued treatment (mean number of falls: 0.3 vs. 3.6; P value 0.025). The hazard ratio of a fall during follow-up was 0.48 (95% confidence interval (CI) 0.23, 0.99) for overall drug withdrawal, 0.35 (95% CI 0.15, 0.82) for cardiovascular drug withdrawal and 0.56 (95% CI 0.23, 1.38) for psychotropic drug withdrawal, after adjustment for age, gender, use of fall-risk-increasing drugs, baseline falls frequency, comorbidity, Mini-Mental State Examination score, and reason for referral. CONCLUSIONS:Withdrawal of fall-risk-increasing drugs appears to be effective as a single intervention for falls prevention in a geriatric outpatient setting. The effect was greatest for withdrawal of cardiovascular drugs.

背景与目标：

BACKGROUND & AIMS: :Parkinson's disease (PD) afflicts millions of people worldwide. There are numerous drugs available for PD; however, levodopa remains the gold standard of pharmacotherapy to which all other therapies are compared. Levodopa is quite effective for many motor symptoms (bradykinesia, tremor, rigidity) of PD; however, non-levodopa-responsive motor symptoms (postural instability) and nonmotor symptoms are frequently the most troublesome in middle and later stages of disease. Although motor symptoms remain an important focus for emerging drugs, current research is largely geared to identify and develop disease-slowing therapies. Another important area of focus has become treatment of the nonmotor symptoms of PD (especially depression and dementia). This review discusses emerging drugs in the management of the motor and nonmotor symptoms of PD and drugs under study as disease-slowing/neuroprotective agents.

背景与目标： : 帕金森氏病 (PD) 困扰着全世界数百万人。有许多可用于PD的药物; 但是，左旋多巴仍然是药物治疗的金标准，所有其他疗法都可以与之进行比较。左旋多巴对PD的许多运动症状 (运动迟缓，震颤，僵硬) 非常有效; 但是，非左旋多巴反应的运动症状 (姿势不稳) 和非运动症状通常在疾病的中期和晚期最麻烦。尽管运动症状仍然是新兴药物的重要焦点，但目前的研究主要是为了识别和开发减缓疾病的疗法。另一个重要的重点领域是治疗PD的非运动症状 (尤其是抑郁症和痴呆症)。这篇综述讨论了治疗PD的运动和非运动症状的新兴药物以及正在研究的作为疾病减缓/神经保护剂的药物。

BACKGROUND & AIMS: There is evidence that neutrophil functions such as chemotaxis and oxygen radical formation are disturbed in rheumatoid arthritis (RA). Medication might also influence these functions. Cyclic formation and depolymerisation of actin microfilaments is crucial in cell motility, but this phenomenon has not been studied in RA. The aim of this study was to investigate basal and dynamic (formyl-methionyl-leucyl-phenylalanine (fMLP)-induced) neutrophil actin polymerisation in ten RA patients (a) during therapy with non-steroidal anti-inflammatory drugs (NSAIDS) and (b) after stopping NSAIDS> The results were compared with those of ten age-matched controls. Basal F-actin content in RA patients with NSAIDS was significantly lower than in RA patients without NSAIDS and controls35.5 (25.0-49.0), 50.5 (27.0-75.0) and 52.5 (32.0-85.0), respectively. Conversely, upon stimulation with fMLP, the actin polymerisation curve of RA patients with NSAIDS was higher than for RA patients without NSAIDS and controls. These results suggest that, in RA, the effects orf NSAIDS on neutrophil functions might be related to changes in the actin polymerisation-depolymerisation cycle.

背景与目标： 有证据表明，类风湿性关节炎 (RA) 的中性粒细胞功能 (例如趋化性和氧自由基形成) 受到干扰。药物也可能影响这些功能。肌动蛋白微丝的循环形成和解聚对细胞运动至关重要，但尚未在RA中研究这种现象。这项研究的目的是研究10名RA患者 (a) 在非甾体类抗炎药 (nsaid) 治疗期间的基础和动态 (甲酰基-甲硫氨酸-亮氨酸-苯丙氨酸 (fMLP) 诱导的) 中性粒细胞肌动蛋白聚合反应 (a) 和 (b) 停止nsaid后的结果进行比较有十个年龄匹配的对照。患有NSAIDS的RA患者的基础F-肌动蛋白含量显着低于没有NSAIDS和对照组的RA患者35.5 (25.0-49.0)，50.5 (27.0-75.0) 和52.5 (32.0-85.0)。相反，用fMLP刺激后，患有NSAIDS的RA患者的肌动蛋白聚合曲线高于没有NSAIDS的RA患者和对照组。这些结果表明，在RA中，orf nsaid对中性粒细胞功能的影响可能与肌动蛋白聚合-解聚周期的变化有关。

BACKGROUND & AIMS: :The strategic use of fluorine substitution in drug discovery and drug development is well documented. The small size and high electronegativity of fluorine are among properties of this element that lend special advantages. Applications in drugs targeted to the central nervous system (CNS) have been particularly fruitful in addition to favorable properties seen in many peripherally acting drugs. Fluorine substitution can be used to solve problems unique to the CNS, such as blood brain barrier (BBB) penetration. Likewise, use of the positron emitting isotope, (18)F, provides a unique tool for non-invasive imaging and diagnoses in the CNS. In this review, fluorine in CNS drugs and drug discovery are discussed.

背景与目标： : 氟替代在药物发现和药物开发中的战略用途已得到充分证明。氟的小尺寸和高电负性是该元素的特殊优点之一。除了在许多外周作用药物中看到的有利特性外，针对中枢神经系统 (CNS) 的药物中的应用特别富有成效。氟替代可用于解决CNS特有的问题，例如血脑屏障 (BBB) 渗透。同样，使用正电子发射同位素 (18)F为CNS中的非侵入性成像和诊断提供了独特的工具。本文对中枢神经系统药物中的氟和药物发现进行了讨论。

BACKGROUND & AIMS: :There are numerous analytic and methodological limitations to current measures of drug market activity. This paper explores the structure of markets and individual user behavior to provide an integrated understanding of behavioral and economic (and market) aspects of illegal drug use with an aim toward developing improved procedures for measurement. This involves understanding the social processes that structure illegal distribution networks and drug users' interactions with them. These networks are where and how social behaviors, prices, and markets for illegal drugs intersect. Our focus is upon getting an up close measurement of these activities. Building better measures of consumption behaviors necessitates building better rapport with subjects than typically achieved with one-time surveys in order to overcome withholding and underreporting and to get a comprehensive understanding of the processes involved. This can be achieved through repeated interviews and observations of behaviors. This paper also describes analytic advances that could be adopted to direct this inquiry including behavioral templates, and insights into the economic valuation of labor inputs and cash expenditures for various illegal drugs. Additionally, the paper makes recommendations to funding organizations for developing the mechanisms that would support behavioral scientists to weigh specimens and to collect small samples for laboratory analysis-by providing protection from the potential for arrest. The primary focus is upon U.S. markets. The implications for other countries are discussed.

背景与目标： : 目前对药品市场活动的衡量有许多分析和方法上的限制。本文探讨了市场结构和个人用户行为，以提供对非法药物使用的行为和经济 (和市场) 方面的综合理解，旨在开发改进的测量程序。这涉及了解构成非法分销网络的社会过程以及吸毒者与他们的互动。这些网络是非法药物的社会行为，价格和市场相交的地方和方式。我们的重点是对这些活动进行近距离测量。与一次性调查相比，建立更好的消费行为衡量标准需要与受试者建立更好的融洽关系，以克服预扣和漏报并全面了解所涉及的过程。这可以通过反复采访和观察行为来实现。本文还介绍了可以用来指导此查询的分析进展，包括行为模板，以及对各种非法药物的劳动力投入和现金支出的经济评估的见解。此外，本文还向资助组织提出了建议，以开发支持行为科学家称重标本并收集小样本进行实验室分析的机制-通过提供保护免受逮捕的可能性。主要重点是美国市场。讨论了对其他国家的影响。

BACKGROUND & AIMS: :Novel double-capped triplet drugs, which have one pharmacophore unit and two epoxymethano or dimethylepoxymethano structures (termed cap or diMe-cap structures, respectively) were synthesized. Key intermediate oxazoline 16 derived from acetone enabled the effective synthesis of double-capped triplets. SYK-134 (7a) and SYK-135 (8a) with N-cyclopropylmethyl substituent and cap structures showed selectivities for the κ opioid receptor. On the other hand, the N-Me series exhibited selectivities for the μ opioid receptor. The double-capped triplet drugs with diMe-cap structures preferred the μ receptor independently of their N-substituents. SYK-385 (19b), one of the μ-selective double-capped triplet drugs, showed the highest selectivity for the μ receptor among the reported μ-selective nonpeptide ligands.

背景与目标： : 合成了具有一个药效单位和两个环氧甲氧基或二甲氧基甲氧基结构 (分别称为cap或derme-cap结构) 的新型双冠三联体药物。由丙酮衍生的关键中间体恶唑啉16能够有效合成双端三联体。具有N-环丙基甲基取代基和帽结构的SYK-134 (7a) 和SYK-135 (8a) 显示了 κ 阿片受体的选择性。另一方面，N-Me系列对 μ 阿片受体表现出选择性。具有一角帽结构的双盖三重态药物独立于其N取代基而偏爱 μ 受体。SYK-385 (19b) 是 μ 选择性双封端的三联体药物之一，在报道的 μ 选择性非肽配体中显示出对 μ 受体的最高选择性。

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：

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24种抗菌药物对选定的产气荚膜梭菌菌株的起效速度和杀菌活性。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小时内将菌落计数减少至少3 log10单位。克林霉素，氟喹诺酮类，交沙霉素和四环素引起延迟杀伤 (暴露后4-22小时活菌计数大于或等于99.9% 减少)。氯霉素和利福平对4株菌株中的2株缺乏杀菌活性，而红霉素，夫西地酸和磷霉素 (添加了6-磷酸葡萄糖) 仅对所有4株菌株具有抑制作用。亚胺培南和青霉素g分别与9种和12种抗菌药物联合使用。基本上所有的药物组合都产生不同的效果; 只有青霉素g加强力霉素导致对产气荚膜炎的拮抗作用。

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。有许多不同的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的体外时间杀伤动力学测定法作为评估抗结核药物活性的预测性临床前建模框架的资产的作用。在暴露于结核分枝杆菌北京基因型菌株的过程中，确定了六种抗结核药物的浓度和时间依赖性的分枝杆菌杀伤能力，并评估了耐药性。链霉素，利福平和异烟肼对快速生长的结核分枝杆菌最有效。异烟肼与利福平或高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性。体外排名显示，对于某些 (但不是所有) 抗结核药物，结核病患者的早期杀菌活性一致。时间杀伤动力学测定法提供了有关药物暴露早期抗结核药物的分枝杆菌杀伤动力学的重要信息。因此，该测定是临床前建模框架的有价值的组成部分。

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： : 在低收入和过渡环境中实现抗逆转录病毒艾滋病毒治疗的 “普遍获得” 是一个全球目标。然而，获得艺术的途径是受当地社会条件的影响，绝不是普遍的。定性研究非常适合描述获得艺术的社会地位。我们探讨了在俄罗斯城市 (叶卡捷琳堡) 中注射毒品 (PWID) 的人获得ART的系统性障碍，该城市的HIV治疗需求负担很大。我们对目前或最近有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。对帐户进行了主题分析，并在此处进行了说明性案例研究。确定了三个核心主题: “迷宫式官僚” 管理获得ART的机会; 由于期望在有限的药物治疗机会中获得ART的条件下以治疗药物的使用为条件而创建的 “系统Catch 22”; 和 “系统垂直化”，其中缺乏艾滋病毒之间的融合，结核病 (TB) 和药物治疗损害了获得ART的机会。综上所述，我们发现系统性因素在塑造获得ART的途径方面起着关键作用，并具有重现治疗开始延迟和脱离治疗的潜在不利影响。我们认为，影响PWID获得ART的中观系统因素与更广泛的宏观结构力量相互作用，包括与药物治疗政策和PWID的社会边缘化有关的力量。我们注意到，在这种情况下，迫切需要进行系统性和结构性改革，以改善PWID获得抗逆转录病毒疗法的机会，包括简化官僚程序，促进艾滋病毒，结核病和药物治疗综合服务，并倡导药物治疗政策改革。

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： 类风湿性关节炎 (RA) 的特征是炎症和心血管疾病 (CVD) 的风险增加。这项研究调查了CVD与RA中常规缓解疾病的抗风湿药 (DMARDs) 的使用之间的可能关联。使用病例对照设计，研究了613例RA患者 (5,649患者年)，72例CVD患者和541例无CVD患者。从RA诊断到第一次心血管事件或随访期结束，评估RA，CVD和药物治疗的数据。根据DMARD用途对数据集进行分类: 柳氮磺吡啶 (SSZ)，羟基氯喹 (HCQ) 或甲氨蝶呤 (MTX)。每个DMARD组计算CVD的比值比 (ORs)，校正年龄，性别，吸烟和RA持续时间。从未使用SSZ，HCQ或MTX的患者被用作参考组。MTX治疗与显著降低CVD风险相关，ORs (95% CI): “仅MTX”，0.16 (0.04至0.66); “MTX和SSZ”，0.20 (0.08至0.51); 和 “MTX，SSZ和HCQ”，0.20 (0.08至0.54)。在对类风湿因子和侵蚀的存在进行进一步校正后，风险降低仍然显着。校正高血压，糖尿病和高胆固醇血症后，'MTX或SSZ ever' 和 'MTX，SSZ和HCQ ever' 显示出明显的CVD风险降低。类风湿因子阳性和糜烂均增加了CVD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SSZ，HCQ或MTX的RA患者相比，MTX和SSZ在较小程度上与CVD风险显着降低相关。我们假设使用DMARD，特别是使用MTX，可以有效抑制炎症，从而减少动脉粥样硬化的发展，并随后在临床上明显减少CVD。

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和各种不必要的体内转化相关的复杂问题需要尽快解决，以便能够利用生物技术繁荣带来的无数推定疗法。纳米医学是纳米技术在医学领域最有前途的应用之一。它被定义为使用工程纳米设备和纳米结构在分子水平上监视，修复，构建和控制人类生物系统。这些纳米结构的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结合) 是药物开发的一种即将到来的方法，它有可能通过大幅改善所给药药物的药代动力学和药效学特性来彻底改变药物。本文提供了提高各种生物技术产品在药物输送中的治疗效果的总体策略。本文还对大多数聚乙二醇化蛋白，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，其中靶向递送，配方，体内稳定性和保留是主要挑战。

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上浆技术，称为水溶性差的药物的 “干法纳米悬浮液” 技术。采用喷雾冷冻干燥 (SFD) 方法代替了先前开发的喷雾干燥方法。使用振荡珠磨设备在分散剂水溶液中研磨药物颗粒。将研磨的纳米悬浮液喷洒到液氮表面，并将所得的冰滴冷冻干燥以获得粉末状产品。研究了分散剂的负载比，以提高其再分散性能。通过SFD工艺获得了干燥的纳米悬浮液，该悬浮液可以自发地分散到水中的原始纳米悬浮液中。假定自分散特性归因于其具有多孔网络的结构，其中嵌入了初级研磨的药物晶体。这种独特的结构极大地促进了药物在胃肠道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以及要喷洒的悬浮液中的固体含量，可以增强这些药物性能。本技术通过湿法研磨和喷雾冷冻干燥工艺将是一种新型的水溶性药物溶出增强技术。

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： : 医学文献中关于 “医疗包” 的证据或建议很少，医生可以有效地携带这些证据或建议，以使他们为意外的紧急情况做好准备。这项研究的目的是确定急诊医生认为是合适的医疗包，供医生携带以准备 “好撒玛利亚人” 的行为。使用形式形式对英国急诊医生进行了电话调查。在调查的响应者中，10% 经常进行院前工作。72% 的人认为携带设备是合适的，但只有43% 的人认为携带药物是合适的。超过80% 的人认为基本的气道设备可用于携带，而其他医疗套件则被认为不太合适。很大一部分急诊医生认为携带一些用于 “好撒玛利亚人” 行为的医疗工具包是适当的，并且通常，关于应携带哪种医疗工具包的意见共识与院前干预的证据基础一致。

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：