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重症监护病房中的分子生物学。从了解到治疗脓毒症。

Molecular biology on the ICU. From understanding to treating sepsis.

作者信息

Winning J, Claus R A, Huse K, Bauer M

机构信息

Department for Anesthesiology and Intensive Care Medicine, Friedrich-Schiller-University, Jena, Germany.

出版信息

Minerva Anestesiol. 2006 May;72(5):255-67.

Abstract

Mounting evidence suggests that beside well established factors, such as virulence of pathogens or site of infection, individual differences in disease manifestation are a result of the genetic predisposition of the patient on an Intensive Care Unit (ICU). Specific genetic factors might not only predict the risk to acquire severe infections but also to develop organ dysfunction or ultimately to die. Thus, the advent of molecular techniques allowing screening for a wide variety of genetic factors, such as single nucleotide polymorphisms in genes controlling expression of important mediator systems in patients as well as their purposeful targeting in animal models of sepsis, are revolutionizing understanding of pathophysiology in the critically ill. Molecular tools are about to challenge ''state-of-the-art'' diagnostic tests such as blood culture as they not only increase sensitivity but dramatically reduce time requirements to identify pathogens and their resistance patterns. Similarly, knowledge of genetic factors might in the near future help to identify ''patients at risk'', i.e. those with a high likelihood to develop organ dysfunction or to guide therapeutic interventions in particular regarding resource-consuming and/or expensive therapies (''theragnostics''). While therapeutic options in molecular intensive care medicine, such as stem cells in the treatment of organ failure or therapeutic gene transfer are possible along the road and might become an option in the future, recombinant DNA technology has already a well defined role in the production of recombinant human proteins from insulin to activated protein C.

摘要

越来越多的证据表明,除了已确定的因素,如病原体的毒力或感染部位外,重症监护病房(ICU)患者疾病表现的个体差异是由其遗传易感性导致的。特定的遗传因素不仅可能预测获得严重感染的风险,还可能预测发生器官功能障碍或最终死亡的风险。因此,分子技术的出现使得能够筛查多种遗传因素,例如在控制患者重要介质系统表达的基因中进行单核苷酸多态性筛查,以及在脓毒症动物模型中有目的地靶向这些因素,正在彻底改变对危重病人生理病理学的理解。分子工具即将挑战“最先进”的诊断测试,如血培养,因为它们不仅提高了敏感性,而且大大缩短了鉴定病原体及其耐药模式所需的时间。同样,对遗传因素的了解在不久的将来可能有助于识别“高危患者”,即那些发生器官功能障碍可能性高的患者,或指导治疗干预,特别是在涉及资源消耗和/或昂贵治疗(“治疗诊断学”)方面。虽然分子重症医学中的治疗选择,如用于治疗器官衰竭的干细胞或治疗性基因转移,沿着这条路是有可能的,并且未来可能成为一种选择,但重组DNA技术在从胰岛素到活化蛋白C等重组人蛋白的生产中已经发挥了明确的作用。

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