• 【良性和恶性原发性甲状腺滤泡性甲状腺肿瘤患者血清中p53和可溶性Fas配体(sFasL)血清浓度的评估作为细胞凋亡的指标。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Kołomecki K,Maciaszczyk P,Stepień H,Cywiński J,Cielecka J,Stepień T,Kuzdak K
    BACKGROUND & AIMS: INTRODUCTION:Apoptosis (programmed cell death) is the best described mode of physiological cell death. During embryonal development and morphogenesis, apoptosis may be induced by two pathways. The first is external protein signal originating from other cell--also named as "death signal". Another one is specific cell reaction for external stress factors. Blood concentration of proteins regulating both pathways of apoptosis may be useful in early diagnosis and staging of thyroid tumors. The aim of study was evaluation of p53 and sFasL blood concentration in patients with benign follicular adenoma and follicular thyroid cancer. MATERIALS AND METHODS:The study population was composed of 28 patients: 14 with thyroid carcinoma and 14 patients with follicular neoplasm (NF). All patients underwent surgical treatment. P53 and sFasL levels were evaluated before surgery and related to the histopathological diagnosis obtained post-surgery. RESULTS:The analysis revealed high sFasL blood concentration in patients with follicular thyroid cancer in comparison with the group with follicular adenoma. There was no statistically significant difference between levels of p53 in both groups. CONCLUSIONS:Evaluation of sFasL serum level concentration may be useful in preoperative diagnosis of follicular thyroid tumors.
    背景与目标: 简介:细胞凋亡(程序性细胞死亡)是描述性的生理性细胞死亡方式。在胚胎发育和形态发生过程中,可能通过两种途径诱导细胞凋亡。第一个是源自其他细胞的外部蛋白质信号-也称为“死亡信号”。另一个是针对外部应激因素的特异性细胞反应。调节细胞凋亡的两种途径的蛋白质的血药浓度可能对甲状腺肿瘤的早期诊断和分期有用。研究的目的是评估良性滤泡性腺瘤和滤泡性甲状腺癌患者的p53和sFasL血药浓度。
    材料与方法:研究人群由28例患者组成:14例甲状腺癌和14例滤泡性肿瘤(NF)。所有患者均接受手术治疗。在手术前评估P53和sFasL水平,并与手术后获得的组织病理学诊断有关。
    结果:分析显示,与滤泡性腺瘤相比,滤泡性甲状腺癌患者的sFasL血药浓度较高。两组中p53水平之间无统计学差异。
    结论:血清sFasL水平的评估可能对甲状腺滤泡性肿瘤的术前诊断有帮助。
  • 【从俄罗斯图拉地区的监狱犯人中分离出的结核分枝杆菌中,耐多药的LAM和北京家族菌株占优势。】 复制标题 收藏 收藏
    DOI:10.1099/jmm.0.46575-0 复制DOI
    作者列表:Ignatova A,Dubiley S,Stepanshina V,Shemyakin I
    BACKGROUND & AIMS: :The genotypic characteristics and drug susceptibility profiles of clinical isolates of Mycobacterium tuberculosis recovered from prison hospital patients in the Tula region (central Russia) during 2001 and 2002 are reported. The emergence of multi-drug-resistant tuberculosis (TB) poses a major health risk to the population, with economic implications for TB control. Prisons serve as a continuous source of TB transmission. The results showed that members of the LAM and Beijing families are major contributors to the epidemiological picture of TB in the population studied. The two families of strains accounted for most of the drug-resistant TB in the population. The genotypic characteristics of the M. tuberculosis predominant LAM strain that was responsible for 31 % of TB cases in this setting are presented.
    背景与目标: :报告了2001和2002年从图拉地区(俄罗斯中部)的监狱医院患者中回收的结核分枝杆菌临床分离株的基因型特征和药物敏感性分布。耐多药结核病(TB)的出现给人们带来了重大的健康风险,对结核病控制产生了经济影响。监狱是结核病传播的持续来源。结果表明,LAM和北京家庭的成员是所研究人群中结核病流行病学特征的主要贡献者。菌株的两个家族占人口中大多数耐药结核病的比例。呈现了结核分枝杆菌占主导地位的LAM菌株的基因型特征,该菌株在这种情况下占31%的结核病病例。
  • 【药物见解:男性激素避孕的最新进展。】 复制标题 收藏 收藏
    DOI:10.1038/ncpendmet0069 复制DOI
    作者列表:Amory JK,Page ST,Bremner WJ
    BACKGROUND & AIMS: :As there are limitations to current methods of male contraception, research has been undertaken to develop hormonal contraceptives for men, analogous to the methods for women based on estrogen and progestogens. When testosterone is administered to a man, it functions as a contraceptive by suppressing the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the pituitary gland. Since these hormones are the main stimulatory signals for spermatogenesis, low levels of LH and FSH markedly impair sperm production. After 3-4 months of testosterone treatment, 60-70% of men no longer have sperm in their ejaculate, and most other men exhibit markedly diminished sperm counts. Male hormonal contraception is well tolerated, free of serious adverse side effects, and 95% effective in the prevention of pregnancy. Importantly, male hormonal contraception is reversible, with sperm counts usually recovering within 4 months of the discontinuation of hormone treatment. Because exogenous testosterone administration alone does not completely suppress sperm production in all men, researchers have combined testosterone with second agents, such as progestogens or gonadotropin-releasing-hormone antagonists, to further suppress secretion of LH and FSH and improve suppression of spermatogenesis. Recent trials have used combinations of long-acting injectable or implantable forms of testosterone with progestogens, which can be administered orally, by injection or by a long-acting implant. Such combinations suppress spermatogenesis to zero without severe side effects in 80-90% of men, with near-complete suppression in the remainder of individuals. One of these testosterone and progestogen combination regimens might soon bring the promise of male hormonal contraception to fruition.
    背景与目标: :由于目前男性避孕方法的局限性,已经进行了研究以开发男性荷尔蒙避孕药,类似于基于雌激素和孕激素的女性避孕方法。当男人服用睾丸激素时,它通过抑制垂体促黄体生成激素(LH)和促卵泡激素(FSH)的分泌而起避孕作用。由于这些激素是精子发生的主要刺激信号,因此低水平的LH和FSH明显损害了精子的产生。经过3-4个月的睾丸激素治疗后,60-70%的男性不再有精子射精,其他大多数男性的精子数量也明显减少。男性荷尔蒙避孕药耐受性好,没有严重的不良副作用,并且95%的预防怀孕有效。重要的是,男性荷尔蒙避孕是可逆的,在停止激素治疗后的4个月内,精子数量通常会恢复。由于单独使用外源性睾丸激素并不能完全抑制所有男性的精子产生,因此研究人员已将睾丸激素与第二种药物(如孕激素或促性腺激素释放激素拮抗剂)联合使用,以进一步抑制LH和FSH的分泌并改善对精子发生的抑制作用。最近的试验已将长效可注射或可植入形式的睾丸激素与孕激素结合使用,可以口服,注射或长效植入物给药。这样的组合在80-90%的男性中将精子发生抑制为零而没有严重的副作用,而在其余个体中则几乎完全被抑制。这些睾丸激素和孕激素联合治疗方案之一可能很快会带来雄激素避孕的希望。
  • 【体外药物活性和药代动力学在预测抗分枝杆菌疗法有效性中的价值:一项重要综述。】 复制标题 收藏 收藏
    DOI:10.1097/00000441-199706000-00008 复制DOI
    作者列表:Burman WJ
    BACKGROUND & AIMS: Marked increases in case rates of drug-resistant tuberculosis and nontuberculous mycobacterial infections have brought renewed urgency to the development of new treatment regimens for mycobacterial infections. Preclinical data, such as in vitro measures of drug activity and pharmacokinetics, are used in the design of new treatment regimens. This review surveys the extensive published clinical experience concerning the treatment of drug-susceptible tuberculosis to evaluate the use of these preclinical measures in predicting clinical outcomes of antimycobacterial therapy. In vitro measures of drug activity predict the potency of a drug to prevent the emergence of resistance to other antimycobacterial drugs but do not predict the sterilizing activity of a drug or the activity of drug combinations. In vitro measures of drug activity do not allow reliable predictions of the level at which an organism should be considered resistant. Assays of drug penetration in tissues and activity against intracellular bacilli add modestly to the predictive value of in vitro measures of drug activity but still do not predict sterilizing activity. In contrast, animal models of tuberculosis have predicted relative drug potency (including sterilizing activity), the efficacy of multidrug regimens, and the duration of therapy needed. Despite pharmacokinetic parameters that would suggest the need for multiple doses per day, all of the first-line antituberculous drugs are active when given as infrequently as twice weekly. It is difficult to predict the efficacy of therapy for an intracellular pathogen that has the capacity for dormancy. Better in vitro models are needed, particularly ones that predict sterilizing activity.

    背景与目标: 耐药结核病和非结核分枝杆菌感染的病例率显着增加,这为开发针对分枝杆菌感染的新治疗方案带来了新的紧迫性。临床前数据,例如药物活性和药代动力学的体外测量,用于设计新的治疗方案。这篇综述调查了有关药物敏感性肺结核治疗的广泛发表的临床经验,以评估这些临床前措施在预测抗分枝杆菌治疗的临床结果中的应用。药物活性的体外量度可以预测药物对其他抗分枝杆菌药物产生抗药性的能力,但不能预测药物的灭菌活性或药物组合的活性。药物活性的体外测量不能可靠地预测应将生物体视为抗药性的水平。药物在组织中的渗透和针对细胞内细菌的活性的测定适度地增加了药物活性体外测量的预测价值,但仍不能预测灭菌活性。相反,结核病的动物模型预测了相对的药效(包括杀菌活性),多种药物疗法的疗效以及所需的治疗时间。尽管药代动力学参数表明每天需要多剂量,但每隔一周两次不频繁使用时,所有一线抗结核药物均具有活性。难以预测具有休眠能力的细胞内病原体的治疗效果。需要更好的体外模型,尤其是预测杀菌活性的模型。

  • 【进入三级医院内科病房的患者不良药物反应的直接费用和临床方面】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Tribiño G,Maldonado C,Segura O,Díaz J
    BACKGROUND & AIMS: INTRODUCTION:Adverse drug reactions (ADRs) occur frequently in hospitals and increase costs of health care; however, few studies have quantified the clinical and economic impact of ADRs in Colombia. OBJECTIVES:These impacts were evaluated by calculating costs associated with ADRs in patients hospitalized in the internal medicine ward of a Level 3 hospital located in Bogotá, Colombia. In addition, salient clinical features of ADRs were identified and characterized. MATERIAL AND METHODS:Intensive follow-ups for a cohort of patients were conducted for a five month period in order to detect ADRs; different ways to classify them, according to literature, were considered as well. Information was collected using the INVIMA reporting format, and causal probability was evaluated with the Naranjo algorithm. Direct costs were calculated from the perspective of payer, based on the following costs: additional hospital stay, medications, paraclinical tests, additional procedures, patient displacement to intermediate or intensive care units, and other costs. RESULTS:Of 836 patients admitted to the service, 268 adverse drug reactions were detected in 208 patients (incidence proportion 25.1%, occurence rate 0.32). About the ADRs found, 74.3% were classified as probable, 92.5% were type A, and 81.3% were moderate. The body system most often affected was the circulatory system (33.9%). Drugs acting on the blood were most frequently those ones associated with adverse reactions (37.6%). The costs resulting from medical care of adverse drug reactions varied from COL dollar 93,633,422 (USD dollar 35,014.92) to COL dollar 122,155,406 (USD dollar 45,680.94), according to insurance type, during the study period. CONCLUSIONS:Adverse drug reactions have a significant negative health and financial impact on patient welfare. Because of the substantial resources required for their medical care and the significant proportion of preventable adverse reactions, active programs of institutional pharmacovigilance are highly recommended.
    背景与目标: 简介:药物不良反应(ADR)在医院中经常发生,并增加了医疗保健费用;但是,很少有研究能够量化ADR在哥伦比亚的临床和经济影响。
    目的:通过计算在哥伦比亚波哥大三级医院内科病房住院的患者与ADR相关的费用来评估这些影响。此外,ADR的显着临床特征已得到鉴定和表征。
    材料与方法:对一组患者进行了为期五个月的强化随访,以检测ADR。根据文献,还考虑了不同的分类方法。使用INVIMA报告格式收集信息,并使用Naranjo算法评估因果概率。直接费用是根据以下费用从付款人的角度计算的:额外的住院时间,药物,辅助临床检查,其他程序,将患者转移到中级或重症监护室以及其他费用。
    结果:836例入院患者中,208例患者发生了268例药物不良反应(发生率25.1%,发生率0.32)。关于发现的ADR,有74.3%被归为可能,A型为92.5%,中度为81.3%。受影响最严重的身体系统是循环系统(33.9%)。作用于血液的药物最常见于那些与不良反应有关的药物(37.6%)。根据保险类型,在研究期间,药物不良反应的医疗费用从93,633,422美元(35,014.92美元)到122,155,406美元(45,680.94美元)不等。
    结论:药物不良反应会对患者的健康产生重大的负面健康和财务影响。由于其医疗服务所需的大量资源以及可预防的不良反应的比例很大,因此强烈建议积极进行机构药物警戒计划。
  • 【沙漠木匠蚂蚁的两个密切相关的物种在脂肪存储的个体层次分配上有所不同。】 复制标题 收藏 收藏
    DOI:10.1086/505995 复制DOI
    作者列表:Hahn DA
    BACKGROUND & AIMS: :Comparison of closely related species that differ in their life histories is a powerful method for studying the underlying physiological mechanisms contributing to life-history variation. I investigated whether two closely related members of the Camponotus festinatus species complex of desert carpenter ants, C. nr. festinatus Desert Light and C. nr. festinatus Desert Dark, differed in their life-history tactics with respect to fat storage. Newly mated queens were collected in the field, and colonies were reared under common conditions in the laboratory for 2 yr before sampling. I show that the two species differ in fat storage at the individual level. While the basic scaling relationship between lean mass and fat content did not differ between the two species, Dark workers and soldiers stored significantly more fat per unit lean mass than Light workers or soldiers. There were no significant demographic differences in the proportions of workers or soldiers involved in fat storage between the two species, although there was a trend toward Light colonies having a greater proportion of soldiers storing large amounts of fat. There was also no significant difference in the total amount of fat stored by the two species at the colony level. The detection of strong individual-level effects but no colony-level effects was likely due to the low statistical power of colony-level analyses. Showing that these two closely related species differ in fat storage at the individual level in a common environment demonstrates their utility as a model for understanding the physiological and behavioral mechanisms regulating life-history variation in fat storage in ants.
    背景与目标: :比较生活史不同的密切相关物种是研究导致生活史变异的潜在生理机制的有力方法。我调查了沙漠木匠蚂蚁C. nr的Camponotus festinatus物种复合体的两个密切相关的成员。 festinatus沙漠之光和C. nr。 festinatus Desert Dark,在脂肪储存方面的生活史策略有所不同。在田间收集新交配的皇后,在常规条件下在实验室中饲养菌落2年,然后取样。我证明了这两个物种在个体水平上的脂肪储存不同。虽然这两个物种之间瘦体重和脂肪含量之间的基本比例关系没有区别,但深色工人和士兵每单位瘦体重的脂肪存储量明显多于轻工人或士兵。在这两个物种之间,从事脂肪储存的工人或士兵的比例在人口统计学上没有显着差异,尽管有一个趋势,即轻型殖民地的士兵储存大量脂肪的比例更高。这两个物种在菌落水平上储存的脂肪总量也没有显着差异。由于菌落级分析的统计能力低,因此很可能检测到较强的个体水平效应,但没有菌落级效应。表明这两个密切相关的物种在共同环境中的个体水平上的脂肪存储量不同,这表明它们可作为模型来了解调节蚂蚁脂肪存储中生命史变化的生理和行为机制的模型。
  • 【吸毒规则:古代世界中的葡萄酒和罂粟衍生物。六。罂粟是食物和毒品的来源。】 复制标题 收藏 收藏
    DOI:10.3109/10826089709039375 复制DOI
    作者列表:Nencini P
    BACKGROUND & AIMS: :Poppies were widely used during antiquity as a source of food, therapeutics, and poisons. It is likely that the alimentary value of poppy seeds was known in the Neolithic age, and there is some evidence that the neuropsychopharmacological effects of poppy juice were exploited during the Minoan civilization in the eastern Mediterranean basin. The Minoan civilization dates the attribution to poppies of symbolic meanings connected with rites of agricultural fertility. The persistence throughout antiquity of this symbolism is testified by literary and iconographic evidence of the attribution of poppies to goddesses of fertility, such as Demeter, Aphrodite, and Ceres.
    背景与目标: :在古代,罂粟被广泛用作食物,治疗剂和毒药的来源。罂粟种子的营养价值很可能是在新石器时代就已经知道的,并且有一些证据表明,罂粟汁的神经心理药理作用是在地中海东部的米诺斯文明期间被利用的。米诺斯文明可追溯到象征意义的罂粟的归属,这些象征意义与农业生育的仪式有关。这种象征主义在整个上古时代的持久性通过文学和肖像学证据证明,罂粟归因于狄特耳特,阿芙罗狄蒂和谷神星等生育女神。
  • 【耐药细胞提取物中癌基因依赖性细胞凋亡。】 复制标题 收藏 收藏
    DOI:10.1101/gad.11.10.1266 复制DOI
    作者列表:Fearnhead HO,McCurrach ME,O'Neill J,Zhang K,Lowe SW,Lazebnik YA
    BACKGROUND & AIMS: Many genotoxic agents kill tumor cells by inducing apoptosis; hence, mutations that suppress apoptosis produce resistance to chemotherapy. Although directly activating the apoptotic machinery may bypass these mutations, how to achieve this activation in cancer cells selectively is not clear. In this study, we show that the drug-resistant 293 cell line is unable to activate components of the apoptotic machinery-the ICE-like proteases (caspases)-following treatment with an anticancer drug. Remarkably, extracts from untreated cells spontaneously activate caspases and induce apoptosis in a cell-free system, indicating that drug-resistant cells have not only the apoptotic machinery but also its activator. Comparing extracts from cells with defined genetic differences, we show that this activator is generated by the adenovirus E1A oncogene and is absent from normal cells. We provide preliminary characterization of this oncogene generated activity (OGA) and show that partially purified OGA activates caspases when added to extracts from untransformed cells. We suggest that agents that link OGA to caspases in cells would kill tumor cells otherwise resistant to conventional cancer therapy. As this killing relies on an activity generated by an oncogene, the effect of these agents should be selective for transformed cells.

    背景与目标: 许多遗传毒性剂通过诱导细胞凋亡杀死肿瘤细胞。因此,抑制细胞凋亡的突变产生了对化学疗法的抗性。尽管直接激活凋亡机制可能绕过这些突变,但是如何在癌细胞中选择性地实现这种激活尚不清楚。在这项研究中,我们显示了抗药性293细胞系无法激活凋亡机制的成分(如ICE样蛋白酶(胱天蛋白酶)),随后进行了抗癌药物治疗。值得注意的是,未经处理的细胞提取物会自发激活胱天蛋白酶并在无细胞系统中诱导凋亡,这表明耐药细胞不仅具有凋亡机制,还具有其激活剂。比较具有确定的遗传差异的细胞提取物,我们表明该激活剂是由腺病毒E1A癌基因产生的,而正常细胞中却不存在。我们提供了此致癌基因产生的活性(OGA)的初步表征,并表明当添加到未转化细胞的提取物中时,部分纯化的OGA会激活胱天蛋白酶。我们建议将OGA与细胞中的半胱氨酸蛋白酶连接的药剂会杀死肿瘤细胞,否则它们会对常规癌症治疗产生抵抗力。由于这种杀伤作用依赖于癌基因产生的活性,因此这些药剂对转化细胞的作用应该是选择性的。

  • 【腺病毒对细胞蛋白质合成的抑制作用被药物2-氨基嘌呤阻止。】 复制标题 收藏 收藏
    DOI:10.1073/pnas.87.18.7115 复制DOI
    作者列表:Huang JT,Schneider RJ
    BACKGROUND & AIMS: :Adenovirus infection results in the suppression of cellular protein synthesis, but the mechanism has not been established. In this report we demonstrate that the shut-off of cellular protein synthesis by adenovirus is prevented in cells by treatment with the drug 2-aminopurine. Treatment with 2-aminopurine is shown to prevent suppression of cellular translation without disrupting the normal viral block in the transport of cellular mRNAs from the nucleus to the cytoplasm. We show that viral suppression of cellular protein synthesis occurs concomitant with activation of the interferon-induced double-stranded RNA-activated inhibitor (DAI), a protein kinase, and phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (eIF-2 alpha), but that prevention of host cell shut-off by 2-aminopurine occurs without a decrease in kinase activity or a dephosphorylation of eIF-2 alpha. Results are presented that indicate that activation of DAI kinase and phosphorylation of eIF-2 alpha may be required but are not sufficient to achieve inhibition of cellular protein synthesis during adenovirus infection. We suggest that other events, in particular the modification of additional initiation factors, are likely involved in viral inhibition of cellular translation.
    背景与目标: :腺病毒感染导致细胞蛋白质合成受到抑制,但该机制尚未建立。在本报告中,我们证明了通过用2-氨基嘌呤药物治疗可防止腺病毒关闭细胞蛋白质合成。已显示用2-氨基嘌呤处理可防止细胞翻译受到抑制,而不会破坏细胞mRNA从细胞核到细胞质的运输过程中的正常病毒阻滞。我们显示病毒抑制细胞蛋白质合成的发生与干扰素诱导的双链RNA激活的抑制剂(DAI),蛋白激酶和真核生物起始因子2(eIF-2 alpha)的α亚基的磷酸化的激活同时发生。 ,但可以防止2-氨基嘌呤阻止宿主细胞的关闭,而不会降低激酶活性或eIF-2α的去磷酸化。结果表明,可能需要DAI激酶的激活和eIF-2α的磷酸化,但不足以抑制腺病毒感染期间细胞蛋白质合成。我们建议其他事件,特别是其他起始因子的修饰,可能与细胞翻译的病毒抑制有关。
  • 【CHADS2评分与阵发性房颤患者抗心律失常药物治疗疗效之间的关系。】 复制标题 收藏 收藏
    DOI:10.1253/circj.cj-12-0854 复制DOI
    作者列表:Komatsu T,Sato Y,Ozawa M,Kunugita F,Ueda H,Tachibana H,Morino Y,Nakamura M
    BACKGROUND & AIMS: BACKGROUND:The Cardiac failure, Hypertension, Age, Diabetes, Stroke [Doubled] (CHADS(2)) score is a useful scheme for risk stratification of thromboembolism patients, but there is little information about its usefulness for the evaluation of antiarrhythmic drug (AAD) therapy. METHODS AND RESULTS:This study included 459 paroxysmal atrial fibrillation (AF) patients (309 men, mean age 66 ± 12 years, mean follow-up 50 ± 35 months) and prophylactic efficacy was analyzed on the basis of CHADS(2) score. (1) Survival rates free from AF recurrence at 1, 6, 12 and 24 months were, respectively, 89%, 74%, 63% and 47% in score-0 group (n=152); 92%, 68%, 59% and 48% in score-1 group (n=158); 86%, 64%, 56% and 46% in score-2 group (n=84); 81%, 65%, 51% and 35% in score-3 group (n=43); and 68%, 50%, 36% and 18% in ≥ score-4 group (n=22) (P<0.05; score-0, score-1 or score-2 vs. ≥ score-4 group). (2) Survival rates free from progression to chronic AF at 12, 36, 60 and 90 months were, respectively, 95%, 93%, 91% and 89% in score-0 group; 97%, 91%, 89% and 88% in score-1 group; 96%, 93%, 88% and 83% in score-2 group; 91%, 74%, 67% and 60% in score-3 group; and 91%, 82%, 68% and 55% in ≥ score-4 group (P<0.01; score-0, score-1 or score-2 vs. ≥ score-4 group). (3) In multivariate logistic regression analysis adjusted for potentially confounding variables, CHADS(2) score was associated with AF recurrence (odds ratio [OR] 1.45, 95% confidence interval [CI] 1.16-1.81, P<0.001), and progression to chronic AF during AAD therapy (OR 1.64, 95% CI 1.04-2.69, P<0.001). CONCLUSIONS:When using a rhythm control strategy, the CHADS(2) score is a useful scheme for predicting the outcome of AAD treatment of patients with paroxysmal AF.  
    背景与目标: 背景:心脏衰竭,高血压,年龄,糖尿病,中风[加倍](CHADS(2))评分是对血栓栓塞患者进行风险分层的有用方案,但有关其对抗心律不齐药物(AAD)评估的有用性的信息很少) 治疗。
    方法与结果:这项研究纳入459例阵发性房颤(AF)患者(309名男性,平均年龄66±12岁,平均随访50±35个月),并根据CHADS(2)评分分析了其预防性疗效。 (1)得分为0的组在1、6、12和24个月无房颤复发的生存率分别为89%,74%,63%和47%(n = 152);得分1组(n = 158)为92%,68%,59%和48%;得分2组分别为86%,64%,56%和46%(n = 84);得分3组(n = 43)分别为81%,65%,51%和35%; ≥分数4组的患者分别为68%,50%,36%和18%(n = 22)(P <0.05;分数≥0,分数1或得分2与≥分数4组相比)。 (2)在0级评分组中,在12、36、60和90个月无进展为慢性房颤的生存率分别为95%,93%,91%和89%;得分1组分别为97%,91%,89%和88%;得分2组分别为96%,93%,88%和83%;分数3组的比例分别为91%,74%,67%和60%; ≥4分组分别为91%,82%,68%和55%(P <0.01; 0分,1分或2分与≥4分组比较)。 (3)在针对潜在混杂变量进行调整的多因素logistic回归分析中,CHADS(2)评分与房颤复发相关(优势比[OR] 1.45、95%置信区间[CI] 1.16-1.81,P <0.001)和进展到AAD治疗期间的慢性房颤(OR 1.64,95%CI 1.04-2.69,P <0.001)。
    结论:使用节律控制策略时,CHADS(2)评分是预测阵发性房颤患者AAD治疗结果的有用方案。
  • 【TeamSTEPPS创伤护士学院在1级创伤中心的影响力。】 复制标题 收藏 收藏
    DOI:10.1016/j.jen.2017.05.007 复制DOI
    作者列表:Peters VK,Harvey EM,Wright A,Bath J,Freeman D,Collier B
    BACKGROUND & AIMS: PROBLEM:Nurses are crucial members of the team caring for the acutely injured trauma patient. Until recently, nurses and physicians gained an understanding of leadership and supportive roles separately. With the advent of a multidisciplinary team approach to trauma care, formal team training and simulation has transpired. METHODS:Since 2007, our Level I trauma system has integrated TeamSTEPPS (Team Strategies & Tools to Enhance Performance & Patient Safety; Agency for Healthcare Research and Quality, Rockville, MD) into our clinical care, joint training of nurses and physicians, using simulations with participation of all health care providers. With the increased expectations of a well-orchestrated team and larger number of emergency nurses, our program created the Trauma Nurse Academy. This academy provides a core of experienced nurses with an advanced level of training while decreasing the variability of personnel in the trauma bay. Components of the academy include multidisciplinary didactic education, the Essentials of TeamSTEPPS, and interactive trauma bay learning, to include both equipment and drug use. Once completed, academy graduates participate in the orientation and training of General Surgery and Emergency Medicine residents' trauma bay experience and injury prevention activities. RESULTS:Internal and published data have demonstrated growing evidence linking trauma teamwork training to knowledge and self-confidence in clinical judgment to team performance, patient outcomes, and quality of care. IMPLICATIONS FOR PRACTICE:Although trauma resuscitations are stressful, high risk, dynamic, and a prime environment for error, new methods of teamwork training and collaboration among trauma team members have become essential.
    背景与目标: 问题:护士是护理严重受伤的创伤患者的团队的关键成员。直到最近,护士和医师还分别了解领导和支持角色。随着多学科团队创伤治疗方法的问世,正式的团队培训和模拟已经出现。
    方法:自2007年以来,我们的I级创伤系统已将TeamSTEPPS(提高绩效和患者安全的团队策略和工具;医疗研究与质量局,马里兰州罗克维尔)集成到我们的临床护理中,使用模拟对护士和医生进行联合培训在所有医疗保健提供者的参与下。随着团队的精心安排和急诊护士人数的增加,我们的计划创建了创伤护士学院。该学院为经验丰富的护士提供了高级培训,同时又减少了外伤部位人员的变异性。该学院的组成部分包括多学科的教学教育,TeamSTEPPS的基础知识以及交互式创伤海湾学习(包括设备和毒品使用)。完成后,学院的毕业生将参加普通外科和急诊科住院医师的创伤湾经验和伤害预防活动的指导和培训。
    结果:内部和公开的数据表明,越来越多的证据将创伤团队合作训练与临床判断的知识和自信心与团队绩效,患者结果和护理质量联系起来。
    实践的意义:尽管创伤复苏具有压力,高风险,动态且是错误的主要环境,但创伤团队成员之间进行团队合作培训和协作的新方法已变得至关重要。
  • 【氯苯诱导的大鼠肝中谷胱甘肽代谢异常对半胱氨酸水平的影响。】 复制标题 收藏 收藏
    DOI:10.3177/jnsv.31.69 复制DOI
    作者列表:Yoshida M,Hara I
    BACKGROUND & AIMS: :Effects of chlorobenzene-induced alteration in glutathione levels on cysteine metabolism in rat liver were investigated. Male Wistar rats were intraperitoneally injected with chlorobenzene (0.2, 0.5, 1.0 or 2.0 mmol/kg body weight). Both hepatic glutathione and cysteine levels were dose-dependently decreased by the chlorobenzene 6 h after the injection. However, at 24 h, the glutathione in the rats with chlorobenzene increased significantly as compared to that in the rats without chlorobenzene. Concomitant to the elevation in glutathione levels, hepatic glutathione synthesis activities were increased by the chlorobenzene by 68-111%. On the other hand, no significant difference between the rats with and without chlorobenzene was observed as regards cysteine levels at 24 h. Hepatic glutamate, glycine, methionine and serine levels were unaltered but hepatic taurine levels were significantly decreased by the chlorobenzene at both 6 and 24 h. Chlorobenzene administration had no effect on hepatic cystathionine synthase and cystathionase activities. These results indicate that a transient loss of hepatic glutathione, caused by the administration of chlorobenzene, resulted in an acceleration of glutathione synthesis and an increase of cysteine demand in the liver.
    背景与目标: :研究了氯苯诱导的谷胱甘肽水平改变对大鼠肝脏半胱氨酸代谢的影响。给雄性Wistar大鼠腹膜内注射氯苯(0.2、0.5、1.0或2.0mmol / kg体重)。注射后6小时,氯苯使肝谷胱甘肽和半胱氨酸水平均呈剂量依赖性降低。然而,在24小时时,与不含氯苯的大鼠相比,含氯苯的大鼠中的谷胱甘肽显着增加。伴随谷胱甘肽水平升高,氯苯使肝谷胱甘肽合成活性提高了68-111%。另一方面,在有和没有氯苯的大鼠之间,在24小时的半胱氨酸水平上没有观察到显着差异。肝谷氨酸,甘氨酸,蛋氨酸和丝氨酸水平未改变,但在6小时和24小时时,氯苯可显着降低肝牛磺酸水平。施用氯苯对肝脏胱硫醚合酶和胱硫醚酶活性没有影响。这些结果表明,由于施用氯苯而引起的肝性谷胱甘肽的瞬时损失导致了谷胱甘肽合成的加速和肝脏中半胱氨酸需求的增加。
  • 【低水平激光治疗对链脲佐菌素诱发的糖尿病大鼠骨缺损愈合的影响:组织学和形态计量学评估。】 复制标题 收藏 收藏
    DOI:10.1080/14764172.2017.1341048 复制DOI
    作者列表:Yildirimturk S,Sirin Y,Soluk Tekkesin M,Gurler G,Firat D
    BACKGROUND & AIMS: BACKGROUND:The aim of the present study was to evaluate the effects of low-level laser therapy (LLLT) on the healing of bone defects in rats with streptozotocin (STZ)-induced DM. METHODS:28 male Sprague-Dawley rats were used in this study. 14 animals received a single dose of STZ intraperitoneally (65 mg/kg) to induce Type I DM, whereas others were injected only with sterile saline solution. Four weeks later, standard bone defects were created in the tibiae of rats. Surgical wounds in one group from each of the diabetic and non-diabetic animals were irradiated with diode laser for every other day for 4 weeks and they were described as DM + LLLT and CONT + LLLT groups, respectively. Remaining two groups received no laser treatment. New bone formation, osteoblast and blood vessel counts were calculated in histologic sections. RESULTS:DM group had significantly smaller bone area and lower blood vessel count when compared to DM + LLLT, CONT and CONT + LLLT groups (p < 0.05 for each). CONT and CONT + LLLT groups had significantly larger bone area than DM + LLLT group (p < 0.05 for both). CONCLUSIONS:LLLT application promoted vascularization and new bone formation in animals with DM to a limited extent, since it was unable to support the healing process up to the level of non-diabetic animals.
    背景与目标: 背景:本研究的目的是评估低剂量激光疗法(LLLT)对链脲佐菌素(STZ)诱导的DM大鼠骨缺损愈合的作用。
    方法:采用28只雄性Sprague-Dawley大鼠。 14只动物腹膜内接受单剂STZ(65 mg / kg)诱导I型DM,而其他动物仅注射无菌盐溶液。四周后,在大鼠胫骨中形成了标准的骨缺损。每隔一天用二极管激光照射来自糖尿病和非糖尿病动物中每组的一组手术伤口,持续4周,分别称为DM LLLT组和CONT LLLT组。其余两组未接受激光治疗。在组织学切片中计算新的骨形成,成骨细胞和血管计数。
    结果:与DM LLLT,CONT和CONT LLLT组相比,DM组的骨面积显着更小,血管计数更低(每组p <0.05)。 CONT和CONT LLLT组的骨面积明显大于DM LLLT组(两者均p <0.05)。
    结论:LLLT的应用在一定程度上促进了DM动物的血管化和新骨形成,因为它不能支持非糖尿病动物的愈合过程。
  • 【手性识别多沙唑嗪对映体在3个靶标中的治疗作用以及在动物实验中的不良药物反应。】 复制标题 收藏 收藏
    DOI:10.1139/y2012-129 复制DOI
    作者列表:Zhao D,Duan LH,Wang FY,Wang M,Lu HG,Wu ZG,Wang X,Ren LM
    BACKGROUND & AIMS: :Doxazosin used in benign prostatic hyperplasia has the side effects of causing hypotension and the risk of heart failure. The 3 targets of α(1A)-adrenoceptors (in the prostate), α(1D)-adrenoceptors (in the aorta), and an unknown mechanism (in the heart) are involved, respectively. We hypothesized that there is a chiral recognition of doxazosin enantiomers in the 3 targets. Using isolated rat aorta (α(1D)-adrenoceptors) and rabbit prostate (α(1A)-adrenoceptors), we examined pA(2) and pK(B) values of doxazosin enantiomers. We observed chronotropic and inotropic effects of doxazosin enantiomers in isolated rat and rabbit heart tissues. (-)Doxazosin and (+)doxazosin produced a shift to the right of concentration-contraction curves for noradrenalin (aorta) and phenylephrine (prostate smooth muscle). The pA(2) value of (-)doxazosin (8.625 ± 0.053) was smaller than (+)doxazosin (9.503 ± 0.051) in rat aorta, but their pK(B) values in rabbit prostate were the same. In rat and rabbit heart tissues, (+)doxazosin (3-30 µmol·L(-1)) significantly decreased atrial rate, and produced negative inotropic effects; however, (-)doxazosin did not affect the atrial rate, and produced positive inotropic effects in the atria. Thus, the chiral carbon atom of doxazosin does not affect its activity at the therapeutic target of α(1A)-adrenoceptors in the prostate, but significantly changes its blocking activity against α(1D)-adrenoceptors in the aorta, and produces opposite inotropic effects in the atria via an α(1)-adrenoceptor-independent mechanism.
    背景与目标: :多沙唑嗪用于前列腺增生症具有引起低血压和心力衰竭风险的副作用。 α(1A)-肾上腺素受体(在前列腺中),α(1D)-肾上腺素受体(在主动脉中)和未知机制(在心脏中)的3个靶点分别涉及。我们假设在3个靶标中有手性识别多沙唑嗪对映体。使用分离的大鼠主动脉(α(1D)-肾上腺素受体)和兔前列腺(α(1A)-肾上腺素受体),我们检查了多沙唑嗪对映体的pA(2)和pK(B)值​​。我们观察到了多沙唑嗪对映异构体在离体大鼠和兔心脏组织中的变时性和变力作用。 (-)多沙唑嗪和()多沙唑嗪使去甲肾上腺素(主动脉)和去氧肾上腺素(前列腺平滑肌)的浓度-收缩曲线向右移动。大鼠主动脉中(-)恶唑烷的pA(2)值(8.625±0.053)小于()恶唑烷(9.503±0.051),但它们在兔前列腺中的pK(B)值​​相同。在大鼠和兔子的心脏组织中,()多沙唑嗪(3-30 µmol·L(-1))显着降低心房率,并产生负性变力作用;然而,(-)doxazosin不会影响心房率,并在心房产生正性肌力作用。因此,多沙唑嗪的手性碳原子不影响其对前列腺中α(1A)-肾上腺素受体治疗靶点的活性,但会显着改变其对主动脉中α(1D)-肾上腺素受体的阻断活性,并产生相反的正性肌力作用通过独立于α(1)-肾上腺素受体机制的心房。
  • 【药房中抗肿瘤药污染水平的常规环境监测的应用和评估-MEWIP项目。】 复制标题 收藏 收藏
    DOI:10.1093/annhyg/mes081 复制DOI
    作者列表:Kiffmeyer TK,Tuerk J,Hahn M,Stuetzer H,Hadtstein C,Heinemann A,Eickmann U
    BACKGROUND & AIMS: :A large-scale study was carried out in order to determine the contamination level of antineoplastic drugs in pharmacies and to investigate the suitability and effects of wipe sample monitoring at regular intervals. A specific study design was developed. The 130 participating pharmacies were divided into a study and a control group, carrying out five and two wipe sampling cycles, respectively. The work practice was analyzed using questionnaires to identify factors that influence the contamination level. From 1269 wipe samples, 774 (61%) were contaminated with at least one of the analyzed cytotoxic drugs: cyclophosphamide, docetaxel, etoposide, 5-fluorouracil, gemcitabine, ifosfamide, methotrexate, and paclitaxel. A significant decrease of the contamination with cyclophosphamide and 5-fluorouracil was observed in the study group. The Monitoring-Effect Study of Wipe Sampling in Pharmacies method has proven to be a reliable and affordable tool for contamination control. Based on the 90th percentile of the contamination values, a substance-independent performance-based guidance value of 0.1ng cm(-2) has been derived.
    背景与目标: :进行了一项大规模研究,以确定药房中抗肿瘤药的污染水平,并定期调查擦拭样品监测的适用性和效果。开发了具体的研究设计。将130家参与活动的药店分为研究组和对照组,分别进行了5次和2次擦拭采样。使用调查表对工作实践进行了分析,以找出影响污染水平的因素。从1269个擦拭样品中,有774个(61%)被至少一种分析的细胞毒性药物污染:环磷酰胺,多西他赛,依托泊苷,5-氟尿嘧啶,吉西他滨,异环磷酰胺,甲氨蝶呤和紫杉醇。在研究组中观察到环磷酰胺和5-氟尿嘧啶的污染显着降低。药房擦拭采样的监测效果研究方法被证明是一种可靠且负担得起的污染控制工具。基于污染值的第90个百分位数,得出了与物质无关的基于性能的指导值0.1ng cm(-2)。

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