• 【血管紧张素转换酶抑制剂和主动脉破裂:基于人群的病例对照研究。】 复制标题 收藏 收藏
    DOI:10.1016/S0140-6736(06)69250-7 复制DOI
    作者列表:Hackam DG,Thiruchelvam D,Redelmeier DA
    BACKGROUND & AIMS: BACKGROUND:Angiotensin-converting enzyme (ACE) inhibitors prevent the expansion and rupture of aortic aneurysms in animals. We investigated the association between ACE inhibitors and rupture in patients with abdominal aortic aneurysms. METHODS:We did a population-based case-control study of linked administrative databases in Ontario, Canada. The sample included consecutive patients older than 65 (n=15,326) admitted to hospital with a primary diagnosis of ruptured or intact abdominal aortic aneurysm between April 1, 1992, and April 1, 2002. FINDINGS:Patients who received ACE inhibitors before admission were significantly less likely to present with ruptured aneurysm (odds ratio [OR] 0.82, 95% CI 0.74-0.90) than those who did not receive ACE inhibitors. Adjustment for demographic characteristics, risk factors for rupture, comorbidities, contraindications to ACE inhibitors, measures of health-care use, and aneurysm screening yielded similar results (0.83, 0.73-0.95). Consistent findings were noted in subgroups at high risk of rupture, including patients older than 75 years and those with a history of hypertension. Conversely, such protective associations were not observed for beta blockers (1.02, 0.89-1.17), calcium channel blockers (1.01, 0.89-1.14), alpha blockers (1.15, 0.86-1.54), angiotensin receptor blockers (1.24, 0.71-2.18), or thiazide diuretics (0.91, 0.78-1.07). INTERPRETATION:ACE inhibitors are associated with a reduced risk of ruptured abdominal aortic aneurysm, unlike other antihypertensive agents. Randomised trials of ACE inhibitors for prevention of aortic rupture might be warranted.
    背景与目标: 背景:血管紧张素转换酶(ACE)抑制剂可防止动物主动脉瘤的扩张和破裂。我们调查了腹主动脉瘤患者中ACE抑制剂与破裂之间的关系。
    方法:我们在加拿大安大略省的相关行政数据库中进行了基于人群的病例对照研究。该样本包括1992年4月1日至2002年4月1日之间入院的65岁以上的连续患者(n = 15,326),其主要诊断为腹主动脉瘤破裂或完整。
    结果:与未接受ACE抑制剂的患者相比,入院前接受ACE抑制剂的患者出现动脉瘤破裂的可能性显着降低(优势比[OR] 0.82,95%CI 0.74-0.90)。调整人口统计学特征,破裂危险因素,合并症,ACEI禁忌症,卫生保健措施和动脉瘤筛查得出相似的结果(0.83,0.73-0.95)。在高破裂风险的亚组(包括75岁以上和有高血压病史的患者)中发现了一致的发现。相反,对于β受体阻滞剂(1.02,0.89-1.17),钙通道阻滞剂(1.01,0.89-1.14),α受体阻滞剂(1.15,0.86-1.54),血管紧张素受体阻滞剂(1.24,0.71-2.18)未观察到这种保护性关联。 ,或噻嗪类利尿剂(0.91、0.78-1.07)。
    解释:与其他降压药不同,ACE抑制剂与降低腹主动脉瘤破裂的风险有关。 ACE抑制剂预防主动脉破裂的随机试验可能是必要的。
  • 【雌二醇调节反应的遗传控制的证据。对正常和病理性激素依赖性表型变异的影响。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Griffith JS,Jensen SM,Lunceford JK,Kahn MW,Zheng Y,Falase EA,Lyttle CR,Teuscher C
    BACKGROUND & AIMS: :The ovarian steroid hormone estrogen (E2) elicits a multiplicity of both systemic and uterotropic responses in vivo. For example, the administration of E2 to ovariectomized (Ovx) and sexually immature rodents leads to uterine-specific inflammatory infiltrates. In this study, we quantitated the number of eosinophils and BM8+, Ia+, and CD4+ cells in uteri obtained from adult Ovx control and E2-treated C57BL/6J, C3H/HeJ, and (C57BL/6J x C3H/HeJ) (B6C3) F1 hybrid mice. All three strains exhibited a significant increase in the number of uterine eosinophils and BM8+ macrophages after E2 treatment. However, C57BL/6J and B6C3 F1 hybrid mice responded with a greater number of infiltrating eosinophils and macrophages as compared with C3H/HeJ. A similar analysis of Ia+ and CD4+ cells showed that E2 treatment either down-regulates or does not affect the number of such cells in all three strains. Genome exclusion mapping using a (C57BL/6J x C3H/HeJ) x C3H/HeJ backcross population localized Est1, the major locus controlling the number of eosinophils infiltrating the uterus after E2 treatment, to chromosome 4. In addition, suggestive linkage to marker loci on chromosomes 10 and 16 was detected and evidence for locus interaction is presented. Our results conclusively demonstrate that E2-regulated/ dependent responses can be genetically controlled, indicating that the phenotypic variation observed in both the normal and pathological effects of E2 may, in part, be due to a genetic component.
    背景与目标: :卵巢类固醇激素雌激素(E2)在体内引起多种全身和子宫促反应。例如,将E2给予去卵巢(Ovx)和性不成熟的啮齿动物会导致子宫特异性炎症浸润。在这项研究中,我们量化了从成年Ovx对照和经E2处理的C57BL / 6J,C3H / HeJ和(C57BL / 6J x C3H / HeJ)(B6C3)获得的子宫中嗜酸性粒细胞和BM8,Ia和CD4细胞的数量F1杂种小鼠。在E2处理后,所有三个菌株均表现出子宫嗜酸性粒细胞和BM8巨噬细胞数量的显着增加。但是,与C3H / HeJ相比,C57BL / 6J和B6C3 F1杂种小鼠反应的浸润性嗜酸性粒细胞和巨噬细胞数量更多。对Ia和CD4细胞的类似分析显示,E2处理在所有三个菌株中均下调或不影响此类细胞的数量。使用(C57BL / 6J x C3H / HeJ)x C3H / HeJ回交群体定位的基因组排斥定位于Est1,Est1是控制E2处理后浸润子宫的嗜酸性粒细胞数量的主要基因座,并指向染色体4。检测到10号和16号染色体上的基因并提供了基因座相互作用的证据。我们的结果最终证明,E2调节/依赖性反应可以通过基因控制,这表明在E2的正常和病理效应中观察到的表型变异可能部分归因于遗传成分。
  • 【ColE1质粒复制的控制。 Rom蛋白与RNA I和RNA II形成的不稳定复合物的相互作用。】 复制标题 收藏 收藏
    DOI:10.1016/0022-2836(90)90231-a 复制DOI
    作者列表:Tomizawa J
    BACKGROUND & AIMS: :A transcript (RNA I) from ColE1 inhibits initiation of replication of the plasmid DNA by binding to the precursor of the primer RNA (RNA II). The ability of RNA I to inhibit replication is altered by the presence of a plasmid-specified small protein, Rom. In vitro, RNA I binds to RNA II to form a very unstable complex, C*. Binding of a single molecule of Rom converts C* to a more stable complex, Cm*. Each of these complexes, C* or Cm*, transforms to a more stable complex, C** or Cm**, respectively. While formation of complex C* or Cm* is inferred from the inhibition of binding caused by a second RNA I species, that of complex C** or Cm** is detected by alteration of RNase sensitivity. Complex C* converts to complex Cm* very rapidly upon addition of Rom to the medium and complex Cm* converts to complex C* very rapidly by removal of Rom from the medium. On the other hand, complexes C** and Cm** do not rapidly interconvert, but can eventually transform to the same stable final product. Thus, Rom affects binding of RNA I to RNA II through conversion of a very unstable early intermediate to a more stable complex, creating a second pathway for their stable binding.
    背景与目标: :来自ColE1的转录本(RNA I)通过与引物RNA(RNA II)的前体结合,抑制质粒DNA复制的开始。质粒指定的小蛋白质Rom的存在改变了RNA I抑制复制的能力。在体外,RNA I与RNA II结合形成非常不稳定的复合物C *。 Rom单个分子的结合将C *转化为更稳定的复合物Cm *。这些复合物C *或Cm *分别转换为更稳定的复合物C **或Cm **。虽然可以通过抑制第二种RNA I物种的结合来推断复合物C *或Cm *的形成,但可以通过改变RNA酶的敏感性来检测复合物C **或Cm **的形成。在向培养基中添加Rom时,复合物C *非常迅速地转化为复合物Cm *,并且通过从培养基中去除Rom,复合物Cm *非常迅速地转化为复合物C *。另一方面,复合物C **和Cm **不会快速相互转换,但最终可以转换为相同的稳定最终产物。因此,Rom通过将非常不稳定的早期中间体转化为更稳定的复合物,从而影响RNA I与RNA II的结合,从而为它们的稳定结合创造了第二条途径。
  • 【保护患者和环境-医院感染控制的新方面和新挑战。】 复制标题 收藏 收藏
    DOI:10.1016/s0195-6701(97)90086-4 复制DOI
    作者列表:Daschner FD,Dettenkofer M
    BACKGROUND & AIMS: Environmental pollution has become a major concern for the future of life on our planet; medical care, especially in hospitals, contributes significantly to this pollution. The increasing usage of highly-developed medical devices, drugs and disposable products are a drain on natural resources as well as financial ones. In this situation, it is a major task for hospital epidemiologists to maintain high standards of hygiene while reducing environmental pollution, reducing consumption of limited natural resources, and minimizing costs. The reduction of hospital waste, the control of polluting and toxic emissions, the avoidance of unnecessary disinfection procedures and disposables, the implementation of energy and water saving technologies are practicable measures in hospital ecology. To realize a sustainable development within hospitals, it is necessary that the need to maintain a balance between effective infection control and a good ecological environment is recognized and supported by health-care workers and the hospital management.

    背景与目标: 环境污染已经成为我们星球上未来生活的主要关注点;医疗服务,尤其是医院的医疗服务,是造成这种污染的重要原因。高度发达的医疗设备,药物和一次性产品的使用日益增加,这既浪费了自然资源,也浪费了金融资源。在这种情况下,医院流行病学家的主要任务是保持较高的卫生标准,同时减少环境污染,减少有限自然资源的消耗并最大程度地降低成本。减少医院浪费,控制污染和有毒物质排放,避免不必要的消毒程序和一次性用品,实施节能节水技术是医院生态学中的切实可行的措施。为了实现医院内部的可持续发展,必须在卫生保健工作者和医院管理人员的认识和支持下,在有效的感染控制和良好的生态环境之间保持平衡。

  • 【皮肤生物学中的神经肽控制机制:生理和临床意义。】 复制标题 收藏 收藏
    DOI:10.1038/sj.jid.5700429 复制DOI
    作者列表:Peters EM,Ericson ME,Hosoi J,Seiffert K,Hordinsky MK,Ansel JC,Paus R,Scholzen TE
    BACKGROUND & AIMS: :The skin as a barrier and immune organ is exposed to omnipresent environmental challenges such as irradiation or chemical and biologic hazards. Neuropeptides released from cutaneous nerves or skin and immune cells in response to noxious stimuli are mandatory for a fine-tuned regulation of cutaneous immune responses and tissue maintenance and repair. They initialize host immune responses, but are equally important for counter regulation of proinflammatory events. Interaction of the nervous and immune systems occurs both locally - at the level of neurogenic inflammation and immunocyte activation - and centrally - by controlling inflammatory pathways such as mononuclear activation or lymphocyte cytokine secretion. Consequently, a deregulated neurogenic immune control results in disease manifestation and frequently accompanies chronic development of cutaneous disorders. The current understanding, therapeutic options, and open questions of the role that neuropeptides such as substance P, calcitonin gene-related peptide, vasoactive intestinal peptide/pituitary adenylate cyclase-activating polypeptide, neuropeptide Y, or others play in these events are discussed. Progress in this field will likely result in novel therapies for the management of diseases characterized by deregulated inflammation, tissue remodeling, angiogenesis, and neoplasm.
    背景与目标: :作为屏障和免疫器官的皮肤暴露于无处不在的环境挑战中,例如辐射或化学和生物危害。皮肤神经或皮肤释放的神经肽以及对有害刺激作出反应的免疫细胞对于皮肤免疫反应以及组织维持和修复的微调调节是必不可少的。它们可以启动宿主的免疫反应,但对于调节促炎事件也同样重要。通过控制诸如单核激活或淋巴细胞细胞因子分泌之类的炎症途径,神经和免疫系统的相互作用既在局部发生(在神经源性炎症和免疫细胞激活的水平),也发生在中央。因此,神经源性免疫控制失调导致疾病表现,并经常伴随皮肤疾病的慢性发展。讨论了有关神经肽(例如P物质,降钙素基因相关肽,血管活性肠肽/垂体腺苷酸环化酶激活多肽,神经肽Y或其他物质)在这些事件中的作用的当前理解,治疗选择和开放性问题。该领域的进展可能会导致新的疗法来治疗以炎症失调,组织重塑,血管生成和肿瘤为特征的疾病。
  • 【I型糖尿病易感性候选基因的分析:2q31-35号染色体上基因的病例对照和家庭关联研究。】 复制标题 收藏 收藏
    DOI:10.2337/diab.46.6.1069 复制DOI
    作者列表:Owerbach D,Naya FJ,Tsai MJ,Allander SV,Powell DR,Gabbay KH
    BACKGROUND & AIMS: Recent genome searches suggest a putative linkage of many loci to susceptibility to type I diabetes. The chromosome 2q31-35 region is reported to be linked to susceptibility to type I diabetes and is thought to contain several diabetes susceptibility loci. These candidate genes include the HOXD gene cluster, BETA2, CTLA4, CD28, IGFBP2, and IGFBP5. Association studies in populations and families are required to confirm and/or identify the actual susceptibility loci. We hereby report several previously unknown DNA polymorphisms for HOXD8, BETA2, and IGFBP5, which we have used along with previously known polymorphisms of HOXD8 and CTLA4 to test whether these candidate loci are the susceptibility genes on chromosome 2q31-35. Using a case-control design with a subsequent family-association approach to confirm associations, we find no evidence that these candidate genes are associated with susceptibility to type I diabetes.

    背景与目标: 最近的基因组搜索表明,许多基因位点与I型糖尿病易感性的推测联系。据报道,染色体2q31-35与I型糖尿病易感性相关,并被认为含有几个糖尿病易感性基因座。这些候选基因包括HOXD基因簇,BETA2,CTLA4,CD28,IGFBP2和IGFBP5。需要在人群和家庭中进行协会研究,以确认和/或识别实际的易感基因座。我们在此报告了HOXD8,BETA2和IGFBP5的几种先前未知的DNA多态性,并将其与HOXD8和CTLA4的先前已知多态性一起用于测试这些候选基因座是否为2q31-35染色体上的易感性基因。使用病例对照设计和随后的家庭关联方法来确认关联,我们没有发现这些候选基因与I型糖尿病易感性相关的证据。

  • 【临床试验中缺少的数据:基于对照的均值插补和敏感性分析。】 复制标题 收藏 收藏
    DOI:10.1002/pst.1817 复制DOI
    作者列表:Mehrotra DV,Liu F,Permutt T
    BACKGROUND & AIMS: :In some randomized (drug versus placebo) clinical trials, the estimand of interest is the between-treatment difference in population means of a clinical endpoint that is free from the confounding effects of "rescue" medication (e.g., HbA1c change from baseline at 24 weeks that would be observed without rescue medication regardless of whether or when the assigned treatment was discontinued). In such settings, a missing data problem arises if some patients prematurely discontinue from the trial or initiate rescue medication while in the trial, the latter necessitating the discarding of post-rescue data. We caution that the commonly used mixed-effects model repeated measures analysis with the embedded missing at random assumption can deliver an exaggerated estimate of the aforementioned estimand of interest. This happens, in part, due to implicit imputation of an overly optimistic mean for "dropouts" (i.e., patients with missing endpoint data of interest) in the drug arm. We propose an alternative approach in which the missing mean for the drug arm dropouts is explicitly replaced with either the estimated mean of the entire endpoint distribution under placebo (primary analysis) or a sequence of increasingly more conservative means within a tipping point framework (sensitivity analysis); patient-level imputation is not required. A supplemental "dropout = failure" analysis is considered in which a common poor outcome is imputed for all dropouts followed by a between-treatment comparison using quantile regression. All analyses address the same estimand and can adjust for baseline covariates. Three examples and simulation results are used to support our recommendations.
    背景与目标: :在一些随机(药物与安慰剂)临床试验中,关注的估计是临床终点的人群平均治疗间差异,其不受“挽救”药物的混杂影响(例如,HbA1c在24岁时偏离基线)不论是否或何时终止指定的治疗,都无需救援药物即可观察到的数周时间)。在这种情况下,如果某些患者在试验期间过早中断试验或开始抢救药物,则会出现数据丢失的问题,后者需要丢弃救援后的数据。我们提醒您,通常使用的混合效应模型重复测量分析会在随机假设的情况下出现嵌入缺失,从而可能对上述感兴趣的估计值进行夸大的估计。之所以会发生这种情况,部分原因是由于对药物部门中的“辍学”(即缺少目标终点数据缺失的患者)过于乐观的平均值的隐式估算。我们提出了另一种方法,即用安慰剂(主要分析)下整个终点分布的估计均值(主要分析)或临界点框架内一系列越来越保守的均值(敏感性分析)明确替换掉药物臂退出的均值);不需要患者级别的估算。考虑进行补充的“辍学=失败”分析,在该分析中,对所有辍学的普遍不良结果进行了归因,然后使用分位数回归进行了治疗之间的比较。所有分析都针对相同的估计值,并且可以针对基线协变量进行调整。三个示例和仿真结果用于支持我们的建议。
  • 【严峻环境中的破坏控制手术研究组(DCSAERG):一个动态程序,可帮助进行实时远程指导/远程诊断,以解决极端严酷环境中的失血问题。】 复制标题 收藏 收藏
    DOI:10.1097/TA.0000000000001483 复制DOI
    作者列表:Kirkpatrick AW,McKee JL,McBeth PB,Ball CG,LaPorta A,Broderick T,Leslie T,King D,Wright Beatty HE,Keillor J,Tien H
    BACKGROUND & AIMS: :Hemorrhage is the most preventable cause of posttraumatic death. Many cases are potentially anatomically salvageable, yet remain lethal without logistics or trained personnel to deliver diagnosis or resuscitative surgery in austere environments. Revolutions in technology for remote mentoring of ultrasound and surgery may enhance capabilities to utilize the skill sets of non-physicians. Thus, our research collaborative explored remote mentoring to empower non-physicians to address junctional and torso hemorrhage control in austere environments. Major studies involved using remote-telementored ultrasound (RTMUS) to identify torso and junctional exsanguination, remotely mentoring resuscitative surgery for torso hemorrhage control, understanding and mitigating physiological stress during such tasks, and the technical practicalities of conducting damage control surgery (DCS) in austere environments. Iterative projects involved randomized guiding of firefighters to identify torso (RCT) and junctional (pilot) hemorrhage using RTMUS, randomized remote mentoring of MedTechs conducting resuscitative surgery for torso exsanguination in an anatomically realistic surgical trainer ("Cut Suit") including physiological monitoring, and trained surgeons conducting a comparative randomized study for torso hemorrhage control in normal (1g) versus weightlessness (0g). This work demonstrated that firefighters could be remotely mentored to perform just-in-time torso RTMUS on a simulator. Both firefighters and mentors were confident in their abilities, the ultrasounds being 97% accurate. An ultrasound-naive firefighter in Memphis could also be remotely mentored from Hawaii to identify and subsequently tamponade an arterial junctional hemorrhage using RTMUS in a live tissue model. Thereafter, both mentored and unmentored MedTechs and trained surgeons completed resuscitative surgery for hemorrhage control on the Cut-Suit, demonstrating practicality for all involved. While remote mentoring did not decrease blood loss among MedTechs, it increased procedural confidence and decreased physiologic stress. Therefore, remote mentoring may increase the feasibility of non-physicians conducting a psychologically daunting task. Finally, DCS in weightlessness was feasible without fundamental differences from 1g. Overall, the collective evidence suggests that remote mentoring supports diagnosis, noninvasive therapy, and ultimately resuscitative surgery to potentially rescue those exsanguinating in austere environments and should be more rigorously studied.
    背景与目标: :出血是创伤后死亡的最可预防原因。许多病例在解剖学上可能是可挽救的,但如果没有后勤人员或训练有素的人员在严酷的环境中进行诊断或复苏手术,则可能致死。超声和手术的远程指导技术的革命可能会增强利用非医师技能的能力。因此,我们的研究合作探索了远程指导,以使非医师能够在严峻的环境中解决交界处和躯干出血的控制问题。重大研究涉及使用远程元素超声(RTMUS)识别躯干和关节血流失血,远程指导复苏手术以控制躯干出血,了解和缓解此类任务期间的生理压力以及在严格的条件下进行损伤控制手术(DCS)的技术实用性环境。迭代项目涉及使用RTMUS随机指导消防员以识别躯干(RCT)和交界处(飞行员)出血,在解剖学上现实的外科培训师(Cut Suit)中进行进行复苏性躯干放血手术的MedTechs的随机远程指导,包括生理监测,以及训练有素的外科医生,对正常(1g)和失重(0g)的躯体出血控制进行比较随机研究。这项工作表明,可以远程指导消防员在模拟器上执行即时躯干RTMUS。消防员和指导者都对自己的能力充满信心,超声波准确率达97%。孟菲斯市的一名初次使用超声的消防员也可以从夏威夷进行远程指导,以在活组织模型中使用RTMUS识别并随后压塞动脉结膜出血。此后,受指导和未受指导的MedTechs以及受过训练的外科医生都完成了复苏手术,以控制Cut-Suit上的出血,证明了所有参与者的实用性。尽管远程指导并没有减少MedTechs的失血量,但它增加了程序的置信度并降低了生理压力。因此,远程指导可能会增加非医师执行心理艰巨任务的可行性。最终,失重的DCS是可行的,与1g的差异不大。总体而言,集体证据表明,远程指导支持诊断,无创治疗以及最终的复苏手术,以挽救那些在严酷环境中放血的人,因此应进行更严格的研究。
  • 【羊膜移植在急性史蒂芬-约翰逊综合征和毒性表皮坏死溶解治疗中的适应症和结局:病例对照研究。】 复制标题 收藏 收藏
    DOI:10.1097/ICO.0b013e31823d02a8 复制DOI
    作者列表:Hsu M,Jayaram A,Verner R,Lin A,Bouchard C
    BACKGROUND & AIMS: PURPOSE:To evaluate the indications and outcomes of amniotic membrane transplantation (AMT) performed within the first 2 weeks of presentation in the management of patients with acute Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). METHODS:A retrospective chart review from January 1998 to May 2011 identified 128 SJS/TEN patients admitted to Loyola University Medical Center Burn intensive care unit. The degree of initial ocular surface inflammation was graded as mild, moderate, or severe within the first 2 weeks of admission. Patients were managed either medically or with amniotic membrane (AM). Outcomes were graded as good [best-corrected visual acuity (BCVA)>20/40], fair (BCVA 20/40 to 20/200 or with ocular surface discomfort, requiring contact lens or reconstructive surgeries), or poor (BCVA<20/200). RESULTS:Of the 182 eyes (91 patients) with documented inpatient eye examinations, 108 eyes (59.4%) had mild or no initial ocular involvement, 37 eyes (20.3%) had moderate, and 37 eyes (20.3%) had severe inflammation. Of the 29 patients (58 eyes) with greater than 1 month of follow-up, 17 patients (33 eyes) were treated with medical management and 13 patients (25 eyes) were treated with early AM. One of the 23 eyes with moderate or severe presentation treated with early AMT (4.3%) resulted in a poor outcome within 3 months compared with 8 of 23 eyes (34.8%) that were medically managed (P=0.022). CONCLUSIONS:We present the first case-control study of the use of AM in the management of acute SJS/TEN. Early use of AMT prevents severe vision loss in SJS/TEN patients with initial moderate or severe ocular surface inflammation.
    背景与目标: 目的:评估在急性史蒂文斯-约翰逊综合征(SJS)和中毒性表皮坏死溶解症(TEN)患者治疗的前两周内进行羊膜移植(AMT)的适应症和结果。
    方法:回顾性分析1998年1月至2011年5月的病历,确定了128名SJS / TEN患者,他们被洛约拉大学医学中心烧伤重症监护室收治。在入院的前两周内,初期眼表炎症的程度分为轻度,中度或重度。患者接受药物治疗或羊膜(AM)治疗。结果分为好[最佳矫正视力(BCVA)> 20/40],一般(BCVA 20/40至20/200或眼表不适,需要隐形眼镜或重建手术)或差(BCVA <20 / 200)。
    结果:在有住院眼科检查的182眼(91例患者)中,有108眼(59.4%)有轻度或无初期眼部受累,有37眼(20.3%)为中度,有37眼(20.3%)有严重的炎症。在随访时间超过1个月的29例患者(58眼)中,有17例患者(33眼)接受了药物治疗,有13例患者(25眼)接受了早期AM治疗。接受早期AMT治疗的23眼中度或重度表现之一(4.3%)在3个月内导致不良结局,相比之下,接受药物治疗的23眼中有8眼(34.8%)(P = 0.022)。
    结论:我们提出了在急性SJS / TEN治疗中使用AM的首例病例对照研究。早期使用AMT可防止SJS / TEN患有初期中度或严重眼表炎症的患者严重视力下降。
  • 【患有重度抑郁症的儿童和青少年的气质和性格特征:一项病例对照研究。】 复制标题 收藏 收藏
    DOI:10.1016/j.comppsych.2012.10.009 复制DOI
    作者列表:Zappitelli MC,Bordin IA,Hatch JP,Caetano SC,Zunta-Soares G,Olvera RL,Soares JC
    BACKGROUND & AIMS: OBJECTIVES:To evaluate temperament and character traits using the Junior Temperament and Character Inventory (JTCI) in children and adolescents with major depressive disorder (MDD) in comparison with healthy control subjects (HC), and to verify if comorbidity with disruptive behavioral disorders and being currently depressed influence JTCI scores. METHODS:A case-control study comprising 41 MDD children/adolescents matched to 40 HC by gender and age (8-17years). All participants were assessed diagnostically with the Kiddie Schedule for Affective Disorders and Schizophrenia - Present and Lifetime (K-SADS-PL). Temperament and character traits were measured with the parent and child versions of JTCI, and depression was evaluated with the Children's Depression Rating Scale (CDRS). RESULTS:According to child and parent data, MDD subjects had significantly higher scores on harm avoidance and novelty seeking, and lower scores on reward dependence, persistence, self-directedness and cooperativeness compared with HC. According to parent data only, MDD subjects significantly differed from HC on self-transcendence (lower spirituality scores and higher fantasy scores). Comorbidity with disruptive behavioral disorders exerted influence on almost all dimensions, in general increasing the mean differences between MDD and HC subjects. Also, being currently depressed did not influence the results, except for reward dependence according to parent data. LIMITATIONS:The cross-sectional nature of the study and its limited sample size. CONCLUSIONS:MDD children/adolescents have a different temperament and character profile compared to HC subjects. This study supports previous findings of trait-like characteristics of harm avoidance and self-directedness.
    背景与目标: 目的:使用青少年气质和性格量表(JTCI)评估患有重性抑郁症(MDD)的儿童和青少年与健康对照对象(HC)的气质和性格特征,并验证合并症是否伴有破坏性行为障碍和当前沮丧的影响力JTCI得分。
    方法:一项病例对照研究,包括41位MDD儿童/青少年(按性别和年龄(8-17岁)与40 HC相匹配)。所有患儿均接受了《儿童情感障碍和精神分裂症的时间表-今生与终生》(K-SADS-PL)的诊断评估。用父母和孩子的JTCI量度气质和性格特征,并用儿童抑郁量表(CDRS)评估抑郁症。
    结果:根据儿童和父母的数据,与HC相比,MDD受试者在避免伤害和寻求新颖性方面得分较高,而在奖励依赖,持久性,自我导向和合作性方面得分较低。仅根据父母的数据,MDD受试者在自我超越方面与HC显着不同(较低的灵性得分和较高的幻想得分)。破坏性行为障碍的合并症几乎影响所有方面,总体上增加了MDD和HC受试者之间的平均差异。而且,除了根据父母数据得到的奖励依赖外,当前处于沮丧状态不会影响结果。
    局限性:研究的横断面性质及其有限的样本量。
    结论:与HC受试者相比,MDD儿童/青少年的气质和性格特征有所不同。这项研究支持先前发现的避免伤害和自我指导的特质样特征。
  • 【使用5选择序列反应时间任务研究不同单胺递质的作用和脉冲控制。】 复制标题 收藏 收藏
    DOI:10.1177/0269881112466182 复制DOI
    作者列表:Humpston CS,Wood CM,Robinson ES
    BACKGROUND & AIMS: :Previous studies have shown that drugs which block the reuptake of catecholamine neurotransmitters improve impulse control in diseases such as attention deficit hyperactivity disorder (ADHD). Serotonin-specific reuptake inhibitors (SSRI) lack efficacy in ADHD and have been linked to increased suicide risk. The present study investigated drugs with affinity for one or more of the monoamine reuptake transporters using the 5-choice serial reaction time task, a model of attention and impulsivity in rodents. We also tested the effects of the alpha(2)-adreoceptor antagonist, idazoxan and novel antidepressant, agomelatine, which both increase cortical noradrenaline concentrations through non-reuptake mechanisms. Improvements in impulse control were observed with venlafaxine, a serotonin and noradrenaline re-uptake inhibitor (SNRI) but not bupropion (dopamine and noradrenaline re-uptake inhibitor). Sibutramine (SNRI) reduced premature responses by ~50% at the highest dose tested but this was not significant. All three of the SSRIs tested reduced premature responding in a dose-dependent manner, although also slowed response and collection latencies. Neither idazoxan nor agomelatine significantly reduced premature responding, suggesting a lack of efficacy at the doses tested. None of the drugs tested improved attention in this task but sibutramine (SNRI), fluoxetine (SSRI) and paroxetine (SSRI) all increased omissions at the highest dose tested. These data suggest that the SNRIs and SSRIs reduce premature responding but tend to be less specific than noradrenaline specific reuptake inhibitors in this model. SSRIs did not induce any specific impairment in impulse control in this model.
    背景与目标: :以前的研究表明,阻断儿茶酚胺神经递质再摄取的药物可改善诸如注意缺陷多动障碍(ADHD)等疾病的冲动控制。血清素特异性再摄取抑制剂(SSRI)在ADHD中缺乏疗效,并且与自杀风险增加有关。本研究使用5-choice系列反应时间任务(一种在啮齿动物中引起注意和冲动的模型)对一种或多种单胺再摄取转运蛋白具有亲和力的药物进行了研究。我们还测试了α(2)-肾上腺素受体拮抗剂,咪唑烷和新型抗抑郁药阿戈美拉汀的作用,它们均通过非重摄取机制增加了皮质去甲肾上腺素的浓度。使用文拉法辛,5-羟色胺和去甲肾上腺素再摄取抑制剂(SNRI)观察到冲动控制有所改善,但安非他酮(多巴胺和去甲肾上腺素再摄取抑制剂)观察不到。西布曲明(SNRI)在测试的最高剂量下可将早反应降低〜50%,但这并不明显。测试的所有三个SSRI均以剂量依赖的方式降低了过早的反应,尽管也减慢了反应和收集潜伏期。依达唑烷和阿戈美拉汀均未显着降低过早反应,表明在所测试的剂量下缺乏疗效。在最高测试剂量下,西布曲明(SNRI),氟西汀(SSRI)和帕罗西汀(SSRI)均未增加所测试药物的注意力。这些数据表明,在该模型中,SNRI和SSRI降低了过早反应,但特异性低于去甲肾上腺素特异性再摄取抑制剂。在该模型中,SSRI并未在冲动控制中引起任何特定的损害。
  • 【NLRX1通过控制线粒体活性来抑制组织损伤中的氧化应激和细胞凋亡。】 复制标题 收藏 收藏
    DOI:10.1084/jem.20161031 复制DOI
    作者列表:Stokman G,Kors L,Bakker PJ,Rampanelli E,Claessen N,Teske GJD,Butter L,van Andel H,van den Bergh Weerman MA,Larsen PWB,Dessing MC,Zuurbier CJ,Girardin SE,Florquin S,Leemans JC
    BACKGROUND & AIMS: :Mitochondrial dysfunction is the most prominent source of oxidative stress in acute and chronic kidney disease. NLRX1 is a receptor of the innate immune system that is ubiquitously expressed and localized in mitochondria. We investigated whether NLRX1 may act at the interface of metabolism and innate immunity in a model of oxidative stress. Using a chimeric mouse model for renal ischemia-reperfusion injury, we found that NLRX1 protects against mortality, mitochondrial damage, and epithelial cell apoptosis in an oxidative stress-dependent fashion. We found that NLRX1 regulates oxidative phosphorylation and cell integrity, whereas loss of NLRX1 results in increased oxygen consumption, oxidative stress, and subsequently apoptosis in epithelial cells during ischemia-reperfusion injury. In line, we found that NLRX1 expression in human kidneys decreased during acute renal ischemic injury and acute cellular rejection. Although first implicated in immune regulation, we propose that NLRX1 function extends to the control of mitochondrial activity and prevention of oxidative stress and apoptosis in tissue injury.
    背景与目标: 线粒体功能障碍是急性和慢性肾脏疾病中最主要的氧化应激源。 NLRX1是先天免疫系统的受体,在线粒体中普遍表达和定位。我们调查了NLRX1是否可能在氧化应激模型中的新陈代谢和先天免疫的界面上起作用。使用针对肾缺血-再灌注损伤的嵌合小鼠模型,我们发现NLRX1以氧化应激依赖性的方式防止死亡,线粒体损伤和上皮细胞凋亡。我们发现NLRX1调节氧化磷酸化和细胞完整性,而NLRX1的缺失导致缺血再灌注损伤期间上皮细胞的耗氧量增加,氧化应激和随后的细胞凋亡。一致地,我们发现在急性肾缺血性损伤和急性细胞排斥期间,人肾脏中的NLRX1表达降低。尽管首先涉及免疫调节,但我们认为NLRX1功能扩展到线粒体活性的控制以及组织损伤中氧化应激和细胞凋亡的预防。
  • 【按年龄和性别划分的霍奇金淋巴瘤的体重和风险:康涅狄格州和马萨诸塞州的一项基于人群的病例对照研究。】 复制标题 收藏 收藏
    DOI:10.1007/s10552-012-0100-1 复制DOI
    作者列表:Li Q,Chang ET,Bassig BA,Dai M,Qin Q,Gao Y,Zhang Y,Zheng T
    BACKGROUND & AIMS: PURPOSE:Descriptive studies have indicated a rising trend in Hodgkin's lymphoma (HL) incidence in young adults, especially females. Increasing evidence has suggested that some risk factors associated with HL may vary by age or gender. Recent studies have reported an increased risk of HL associated with increasing body mass index (BMI), but the results have been inconsistent. The objectives of this study were to examine whether the associations between measures of body size (height, weight, and BMI) and HL risk vary by age and/or gender. METHODS:A population-based case-control study was conducted in Connecticut and Massachusetts. A total of 567 HL cases and 679 controls were recruited in 1997-2000. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95 % confidence intervals (CIs). RESULTS:Among younger women <35 years old, being overweight (25-29.9 kg/m(2)) versus normal weight (18.5-24.9 kg/m(2)) was significantly associated with an increased risk of HL (OR = 2.1, 95 % CI = 1.1-4.0). The risk increased with increasing weight and BMI (p trends <0.01). Among women ≥35 years old, by contrast, higher weight and BMI were associated with a reduced risk of HL (p trends <0.01). Conversely, there was no significant association between BMI and risk of HL in younger or older males. CONCLUSIONS:These findings show that the associations between body size and risk of HL vary by gender and age, and require confirmation in other populations.
    背景与目标: 目的:描述性研究表明,霍奇金淋巴瘤(HL)的发病率在年轻人中,尤其是女性中呈上升趋势。越来越多的证据表明,与HL相关的某些危险因素可能随年龄或性别而变化。最近的研究报告了与体重指数(BMI)增加相关的HL风险增加,但结果不一致。这项研究的目的是检查身体大小(身高,体重和BMI)与HL风险之间的关系是否随年龄和/或性别而变化。
    方法:在康涅狄格州和马萨诸塞州进行了一项基于人群的病例对照研究。在1997-2000年间,共招募了567例HL病例和679例对照。使用无条件逻辑回归来计算比值比(OR)和95%置信区间(CIs)。
    结果:<35岁的年轻女性中,超重(25-29.9 kg / m(2))与正常体重(18.5-24.9 kg / m(2))与HL风险增加显着相关(OR = 2.1 ,95%CI = 1.1-4.0)。风险随着体重和BMI的增加而增加(p趋势<0.01)。相比之下,≥35岁的女性中,体重增加和BMI升高与HL风险降低相关(p趋势<0.01)。相反,年轻或老年男性的BMI与HL风险之间没有显着相关性。
    结论:这些发现表明,体型与HL风险之间的关联因性别和年龄而异,需要在其他人群中进行确认。
  • 【线粒体靶向视蛋白的线粒体代谢和Ca2信号的光遗传学控制。】 复制标题 收藏 收藏
    DOI:10.1073/pnas.1703623114 复制DOI
    作者列表:Tkatch T,Greotti E,Baranauskas G,Pendin D,Roy S,Nita LI,Wettmarshausen J,Prigge M,Yizhar O,Shirihai OS,Fishman D,Hershfinkel M,Fleidervish IA,Perocchi F,Pozzan T,Sekler I
    BACKGROUND & AIMS: :Key mitochondrial functions such as ATP production, Ca2+ uptake and release, and substrate accumulation depend on the proton electrochemical gradient (ΔμH+) across the inner membrane. Although several drugs can modulate ΔμH+, their effects are hardly reversible, and lack cellular specificity and spatial resolution. Although channelrhodopsins are widely used to modulate the plasma membrane potential of excitable cells, mitochondria have thus far eluded optogenetic control. Here we describe a toolkit of optometabolic constructs based on selective targeting of channelrhodopsins with distinct functional properties to the inner mitochondrial membrane of intact cells. We show that our strategy enables a light-dependent control of the mitochondrial membrane potential (Δψm) and coupled mitochondrial functions such as ATP synthesis by oxidative phosphorylation, Ca2+ dynamics, and respiratory metabolism. By directly modulating Δψm, the mitochondria-targeted opsins were used to control complex physiological processes such as spontaneous beats in cardiac myocytes and glucose-dependent ATP increase in pancreatic β-cells. Furthermore, our optometabolic tools allow modulation of mitochondrial functions in single cells and defined cell regions.
    背景与目标: :线粒体的关键功能(例如ATP的产生,Ca2的吸收和释放以及底物的积累)取决于跨内膜的质子电化学梯度(ΔμH)。尽管几种药物可以调节ΔμH,但其作用几乎不可逆,并且缺乏细胞特异性和空间分辨率。尽管通道视紫红质被广泛用于调节可兴奋细胞的质膜电位,但线粒体迄今仍未进行光遗传学控制。在这里,我们描述了一种基于选择性具有选择性功能的通道视紫红质靶向完整细胞内部线粒体膜的光代谢构建物的工具包。我们表明,我们的策略能够实现线粒体膜电位(Δψm)的光依赖性控制和线粒体功能,如通过氧化磷酸化,Ca2动力学和呼吸代谢的ATP合成等。通过直接调节Δψm,靶向线粒体的视蛋白被用于控制复杂的生理过程,例如心肌细胞的自发搏动和胰腺β细胞的葡萄糖依赖性ATP增加。此外,我们的光代谢工具允许调节单个细胞和定义的细胞区域中的线粒体功能。
  • 【马凡氏综合症妇女的出生特征,妊娠的产科和新生儿结局-一项全国队列研究和病例对照研究。】 复制标题 收藏 收藏
    DOI:10.1016/j.ejogrb.2017.05.026 复制DOI
    作者列表:Kernell K,Sydsjö G,Bladh M,Josefsson A
    BACKGROUND & AIMS: OBJECTIVE:The aim was to investigate birth characteristics, obstetric and neonatal outcomes of the first childbirth in women with Marfan syndrome by use of Swedish national registers since pregnancy-related outcomes in women with Marfan syndrome have only been sparsely investigated. STUDY DESIGN:In this national population-based cohort study and matched case-control study of Swedish women born 1973-1993, women with Marfan syndrome (n=273) were compared to women without the condition (n=1 017 265). The study population was followed until 2013. A total of 364 553 mother-firstborn-offspring pairs were analyzed. Sixty-one women with Marfan syndrome became mothers. Women with Marfan syndrome were also compared to 543 healthy controls. RESULTS:Women with Marfan syndrome were more often born preterm (p<0.001), small-for-gestational age (p<0.001), and delivered by cesarean section (p=0.001). Women with Marfan syndrome had no increased risk of giving birth by cesarean section (p=0.079). No increased neonatal risks in their children were found. Women with Marfan syndrome were less likely to give birth than those without (p<0.001). There were no maternal deaths. CONCLUSIONS:Women with Marfan syndrome were more likely to be born preterm, SGA and by cesarean section. These increased risks of preterm birth and SGA babies were not found in connection with their own first childbirth. Pregnancies with known fetal Marfan syndrome have to be carefully monitored. The results are important for obstetricians giving preconception counseling and treating women with Marfan syndrome. Further studies are needed to evaluate risks during pregnancy and long-term effects of pregnancy on the cardiovascular status of women with Marfan syndrome.
    背景与目标: 目的:目的是通过瑞典国家登记簿调查马凡综合征女性的首次分娩的出生特征,产科和新生儿结局,因为仅对马凡综合征女性的妊娠相关结局进行了稀疏调查。
    研究设计:在这项基于全国人群的队列研究和匹配的病例对照研究中,对1973年至1993年出生的瑞典妇女进行了比较,将患有马凡氏综合症(n = 273)的妇女与没有该病的妇女(n = 1 017 265)进行了比较。研究人群一直追踪到2013年。共分析了364 553对母亲-第一胎-后代。六十一名患有马凡氏综合症的妇女成为母亲。还比较了患有马凡氏综合症的女性和543名健康对照者。
    结果:马凡氏综合征的妇女更早产(p <0.001),小胎龄(p <0.001),并通过剖宫产分娩(p = 0.001)。患有马凡氏综合症的妇女通过剖宫产术分娩的风险没有增加(p = 0.079)。没有发现孩子的新生儿患病风险增加。患有马凡氏综合症的妇女比没有马芬综合症的妇女分娩的可能性更低(p <0.001)。没有孕产妇死亡。
    结论:马凡氏综合征的女性更可能早产,SGA和剖宫产。未发现早产和SGA婴儿的这些增加的风险与他们的初生有关。患有已知胎儿马凡氏综合征的孕妇必须进行仔细监测。这些结果对于产科医生进行孕前咨询和治疗患有马凡氏综合症的妇女非常重要。需要进一步的研究来评估妊娠期间的风险以及妊娠对马凡氏综合症女性心血管状况的长期影响。

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