Steroidogenesis in the adrenal dysfunction of critical illness: impact of etomidate

ABSTRACT: INTRODUCTION: This study was aimed at characterizing basal and adrenocorticotropic hormone (ACTH)-induced steroidogenesis in sepsis and nonsepsis patients with a suspicion of critical illness-related corticosteroid insufficiency (CIRCI), taking the use of etomidate-inhibiting 11β-hydroxylase into account. METHOD: This was a prospective study in a mixed surgical/medical intensive care unit (ICU) of a university hospital. The patients were 62 critically ill patients with a clinical suspicion of CIRCI. The patients underwent a 250-μg ACTH test (n = 67). ACTH, adrenal steroids, substrates, and precursors (modified tandem mass spectrometry) also were measured. Clinical characteristics including use of etomidate to facilitate intubation (n = 14 within 72 hours of ACTH testing) were recorded. RESULTS: At the time of ACTH testing, patients had septic (n = 43) or nonseptic critical illness (n = 24). Baseline cortisol directly related to sepsis and endogenous ACTH, independent of etomidate use. Etomidate was associated with a lower baseline cortisol and cortisol/11β-deoxycortisol ratio as well as higher 11β-deoxycortisol, reflecting greater 11β-hydroxylase inhibition in nonsepsis than in sepsis. Cortisol increases < 250 mM in exogenous ACTH were associated with relatively low baseline (HDL-) cholesterol, and high endogenous ACTH with low cortisol/ACTH ratio, independent of etomidate. Although cortisol increases with exogenous ACTH, levels were lower in sepsis than in nonsepsis patients, and etomidate was associated with diminished increases in cortisol with exogenous ACTH, so that its use increased, albeit nonsignificantly, low cortisol increases to exogenous ACTH from 38% to 57%, in both conditions. CONCLUSIONS: A single dose of etomidate may attenuate stimulated more than basal cortisol synthesis. However, it may only partly contribute, particularly in the stressed sepsis patient, to the adrenal dysfunction of CIRCI, in addition to substrate deficiency.     

010 中年男性广泛性缺血性心脏病的自然病程

从英国24家综合医疗机构随机抽取年龄为40～59岁的7 735例病人(均为男性),依据调查表和心电图结果分为以下7个病组：Ⅰ组：已确诊的心肌梗死病人;Ⅱ组：隐匿性心肌梗死病人;Ⅲ组：已确诊的心绞痛病人;Ⅳ组：有心绞痛症侯群的病人;V组：有可疑心肌梗死症侯群的病人;Ⅵ组：心电图示心肌缺血或可能心肌梗死的病人,Ⅶ组：无缺血性心脏病(IHD)证据的病人。对以上各组病人进行15年随访,将这期间调查对象发生的一系列致命及非致命的并发症分别与相应病组加以联系评估。     

Endothelial keratoplasty technique for aniridic aphakic eyes

We describe special techniques to visualize the donor tissue in Descemet's stripping endothelial keratoplasty and to prevent the tissue or stripped recipient Descemet's membrane from dropping onto the retina. The techniques were used successfully to treat corneal decompensation in 3 consecutive cases with no iris or lens present. The results indicate that with careful planning and a good technique, aniridic aphakic patients can benefit from the rapid corneal rehabilitation provided by endothelial keratoplasty.     

Timing of antibiotics in febrile children meeting sepsis criteria at a paediatric emergency department

Objective

Delay in antibiotic administration in paediatric sepsis is associated with increased mortality and prolonged organ dysfunction. This pre-intervention study evaluated performance in paediatric sepsis management.

Methods

Retrospective cohort study of febrile children admitted through the ED at The Children's Hospital at Westmead, Sydney, between 1 May and 31 July 2017. Participants were children aged 29 days to 60 months excluding children with simple febrile seizures, neonates and children who had received intravenous antibiotics elsewhere. We assessed the timing of antibiotic administration in children meeting local sepsis guidelines. We conducted a survey of clinicians in ED in 2018 to describe contributing factors.

Results

There were 160 febrile children admitted and 144 presentations were included in the analysis. Male 53% (n = 76); median age 20.1 months (interquartile range [IQR] 3.9–37 months). Thirty-seven (26%) febrile children met local sepsis criteria. The median time from triage to first dose of intravenous antibiotic was 109 min (IQR 62–183 min). Delay (>60 min) occurred in 26 (76%) children. Reported reasons contributing to delay included high patient load, long waiting times, difficult intravenous access, delayed prescribing, inadequate staffing and difficulty distinguishing between a viral infection and serious bacterial infection.

Conclusion

There was frequent delay in administering antibiotics in children meeting local sepsis criteria, more commonly in young infants. Reasons contributing to delay were specific to young children along with departmental factors that will require addressing through targeted quality improvement interventions.     

瞬时性受体电位通道香草酸受体5、6与骨代谢的关系

目的:探讨瞬时性受体电位通道香草酸受体5、6与骨代谢的关系。资料来源:应用计算机检索PubMed数据库1999-01/2006-07相关瞬时性受体电位通道方面的文献,检索词“TRPV”,限定文献语言种类为English。资料选择:对资料进行初审,选取包括瞬时性受体电位通道香草酸受体5、6的文献,开始查找全文。纳入标准:对两者及瞬时性受体电位通道家族进行研究的文章。排除标准:研究内容局限于瞬时性受体电位通道香草酸受体1～4的文章。资料提炼:共检索到106篇关于瞬时性受体电位通道香草酸受体的文献,最终纳入30篇符合标准的文献。资料综合:瞬时性受体电位通道香草酸受体5、6是瞬时性受体电位通道超家族中的成员,是专门的上皮样钙离子通道。目前研究已经证明它们在肠道和肾脏等组织中有表达,并对跨细胞钙离子转运起着关键性调控作用。但在骨组织中表达情况相关报道较少,在骨代谢机制上的研究更少,本文针对目前两者与骨代谢的关系进行综述。结论:深入研究瞬时性受体电位通道香草酸受体5、6钙离子通道在骨代谢中的作用,对于那些与骨代谢相关疾病的治疗将能从分子水平上找到解决的方法。     

卟啉类衍生物的合成

卟啉类衍生物的合成已有七十余年的历史,其合成方法有以吡咯为原料的全合成,也有以易得的天然产物,如血红素等为原料进行半合成。自报道血卟啉衍生物(hematoporphyrin derivatives简称HpD)与激光结合用于诊治癌症以后,有关卟啉类的化学和临床研究,也迅速开展起来。1982年报道了单乙酰血卟啉、双乙酰血卟啉和乙酰氧乙基乙烯次卟啉在动物体内有对肿瘤的光敏活性,而纯血卟啉、原卟啉和羟乙基乙烯次卟啉却无效。为