The imprecision in heart rate correction may lead to artificial observations of drug induced QT interval changes

Because of the known limitations of the Bazett and other heart rate correction formulas, it has been proposed that studies of drug induced QT interval changes should use several different heart rate correction formulas and that the consistency of findings by a majority of such formulas should be considered as valid. The aim of this article was to show that such an approach is inappropriate. Using the database of the EMIAT trial, data of QT and RR intervals were taken from electrocardiograms of the first postrandomization visit of 1,402 patients. Of these, 309 were on amiodarone and beta-blockers, 395 on amiodarone and off beta-blockers, 318 on beta-blockers and off amiodarone, and 380 off amiodarone and off beta-blockers. An investigation of drug induced QT interval changes was modeled by evaluating the corrected QT (QTc) interval differences between patients on and off amiodarone, and on and off beta-blockers. A set of 31 previously published heart rate correction formulas was used. In addition to calculating the QTc difference between on and off drug for each formula, the success of heart rate correction was judged by computing correlation coefficients between QTc and RR intervals (ideally corrected QTc values should be independent of heart rate). The difference between on and off drug QT intervals was also evaluated by logarithmic regression models between uncorrected QT and RR intervals in data taken from patients on and off treatment. The QTc interval prolongation on amiodarone was confirmed by all heart rate correction formulas but the extent of the prolongation differed from formula to formula and ranged from 13.6 to 30.9 ms. Of the 31 formulas, 3 reported QTc interval shortening on beta-blockers (up to -11.8 ms) and 28 reported QTc interval prolongation (up to +16.8 ms). The distribution of the results provided by the different formulas suggested that beta-blocker treatment led to a QTc interval prolongation by approximately 7 ms (e.g., +7.4 ms by the Fridericia formula, P = 0.002). The on treatment QTc changes obtained by different formulas were closely correlated to their correction success. Formulas that provided QTc intervals almost independent of the RR intervals estimated approximately 20 ms QTc prolongation on amiodarone and no QTc change on beta-blockers. QT/RR regression analysis confirmed that while amiodarone led to substantial QT prolongation, there was no change of QT interval on beta-blockers beyond the change in heart rate. The study showed that the concept of "majority voting" by different heart rate correction formulas is inappropriate and may lead to erroneous conclusions.     

氯离子通道阻断剂对肺血管内皮细胞氧化损伤的保护作用

目的:研究氯离子通道阻断剂在肺血管内皮细胞氧化损伤中的作用。方法:以肉联厂检疫合格的健康小牛为研究对象,过氧化氢(H2O2)诱导体外培养的牛肺动脉内皮细胞损伤,观察Cl-通道阻断剂对受损细胞细胞活力、乳酸脱氢酶(LDH)释放量、三磷酸腺苷(ATP)含量、细胞内钙离子浓度犤Ca2+犦i和DNA降解程度的影响。结果:Cl-通道阻断剂可使受损细胞的细胞活力得到提高,NPPB组和NFA组分别恢复到0.449±0.015和0.535±0.023;LDH释放量下降,分别为(12.4±0.4)%,(6.4±0.6)%。ATP含量分别回升为18.22nmol/mg蛋白质和21.96nmol/mg蛋白质,犤Ca2+犦i下降和DNA降解程度减轻。结论:Cl-通道参与了氧化剂对肺血管内皮细胞损伤的病理过程,Cl-通道阻断剂对肺血管内皮细胞的损伤具有保护作用。     

胃复安、非那根联合用药与格拉斯琼在防治化疗引起呕吐的疗效观察

目的观察以胃复安、非那根联合用药防治顺铂化疗引起呕吐的疗效。方法随机分为两组，一组为观察组，接受胃复安、非那根联合止吐，一组为对照组，接受格拉斯琼止吐。结果联合用药取得与格拉斯琼相似的止吐效果。结论胃复安＋非那根药价低，疗效好，在非禁忌病人及经济困难病人可选用。     

米索前列醇在产程中的临床应用研究

目的研究米索前列醇（米索）在产程中的应用效果。方法对足月妊娠符合引产指征者行米索前列醇或常规催产素引产，对潜伏期延长和活跃期停止的产妇行米索前列醇或催产素加强宫缩（简称催产）。统计本站分娩272例孕产妇随机分成两组，即米索组172例（引产104例，催产68例），催产素组100例（引产60例，催产40例）。米索前列醇25^ug（1／8片）q4h舌下含化，催产素0．3u＋5％GNS500ml，静脉滴注。结果米索组引产成功率73．08％，有效23．07％，无效3．85％，催产成功率73．57％，有效19．12％，无效7．35％。催产素组引产成功率为46．67％，有效35％，无效18．33％。催产成功率70％，有效22．5％，无效7．5％。剖宫产率：烛索组20．35％，催产素组30％。结论米索前列醇用于足月妊娠引产和宫缩乏力强加宫缩（催产），此方法经济、方便、完全、稳定、可靠，大大提高了病人对药物的可接受性，临床上可推广应用。     

下腰痛患者下肢或下腹牵涉痛的发生机制

目的:利用荧光素逆行双标法和免疫组化法探讨下腰痛患者下肢或下腹部牵涉痛的发病机制。方法:将14只Wistar大鼠分两组。Ⅰ组中将荧光素碘化丙啶(PI)注入背肌,双苯甲亚胺(Bb)注入膀胱壁;Ⅱ组中将荧光素快蓝(Fb)注入背肌,维生素B2(NY)注入坐骨神经。此后在有双标细胞的切片上行免疫组化检查。结果:在腰部的后根神经节(DRG)中发现荧光素双标细胞;部分荧光素双标细胞含降钙素基因相关肽(CGRP)。腰部的DRG细胞周围突有分支投射到背肌和膀胱及背肌和坐骨神经;部分有分支投射的细胞含CGRP。结论:由下腰痛引起的下肢或下腹部牵涉痛的发生机制可能与发生在DRG水平的轴突反射有关。     

In Vivo Evaluation of a Closed Loop Monitoring Strategy for Induced Paralysis

Objective. Reliable closed loop infusion systems for regulating paralysis level can be a great convenience to the anesthesiologists in automating their task. This paper describes the in vivo performance evaluation of a self-tuning controller that is designed to accommodate large varations in patient drug sensitivity, drug action delays and environmental interfering noise. Methods. The infusion system was evaluated in six adult mongrel dogs. Following the manual induction of paralysis by an anesthesiologist, the controller regulated the infusion of vecuronium to maintain a desired level of paralysis. The integrated EMG response of the hypothenar muscle to a train-of-four stimulation of the ulnar nerve quantified the depth of paralysis. The controller's robustness was tested by contaminating the sensed twitch signal with electrocautery noise and electrode disconnection. Results. The controller reached the initial level of paralysis of 100% in about 4.0 minutes and arrived at the desired level of 90% with an overshoot of 6.38% (±6.82). It maintained the desired level of paralysis with a 2.04% (±1.20) mean offset at 90% and 0.4% (±0.5) mean offset at 80% steady state level, respectively. The mean infusion rate to sustain 90% and 80% paralysis were 2.70 (±2.05) and 2.15 (±2.57) ((mg/kg)/min), respectively. Conclusions. The system adapted to a large variation in the sample subject drug sensitivity. It remained stable despite large amplitude disturbances and maintained the paralysis at the desired level following the removal of the disturbances.     

笑气吸入镇痛用于人工流产术的临床观察

目的：观察笑气吸入镇痛用于人工流产术的临床疗效。方法：选择300例采用笑气吸入镇痛行人工流产术的早孕妇女为观察组，随机选取同期100例未采用任何镇痛措施行人工流产术的早孕妇女为对照组，分别观察两组的镇痛效果、宫颈松弛程度、人工流产综合征发生率、术中出血量及不良反应。结果：观察组镇痛效果及宫颈松弛程度显著优于对照组，人工流产综合征发生率明显低于对照组，两组差异有显著性（P〈0.01）。观察组与对照组的术中平均出血量差异无显著性（P〉0．05）。观察组术中无明显不良反应发生。结论：笑气吸入用于人工流产术镇痛效果好，起效快，患者不良反应少，操作简便安全，值得临床推广应用。     

米非司酮药物流产后发生恶性滋养细胞肿瘤四例临床分析

目的探讨米非司酮药物流产 (简称药流 )后发生恶性滋养细胞肿瘤的临床特点。方法对 1995年 7月至 2 0 0 1年 12月米非司酮药流后发生恶性滋养细胞肿瘤 4例的临床资料进行回顾性分析。结果4例恶性滋养细胞肿瘤包括侵蚀性葡萄胎 1例、绒癌 3例。自米非司酮流产至恶变的潜伏期较短 ,仅 4～ 6个月 ,4例药流时未证实为葡萄胎 ,流产后均有不规则阴道出血。 2例并发子宫穿孔 ,经手术病理证实分别为侵蚀性葡萄胎和绒癌 ;尿HCG持续阳性 ,血 β HCG值异常增高 ,B超检查 2例有宫旁低回声包块、1例子宫角部蜂巢状低回声区 ;X线胸片 1例有肺转移。结论米非司酮药物流产后可发生滋养细胞肿瘤 ,药物流产前应常规B超检查删除葡萄胎及异位妊娠 ;流产后如出现阴道异常出血等特殊情况 ,应动态行血清 β HCG测定及影像检查以明确诊断。     

慢性阻塞性肺疾病患者气道局部氧化应激与体重指数及肺功能下降的关系

目的：研究慢性阻塞性肺疾病（COPD）患者气道局部氧化应激水平的变化及其与体重指数（BMI）、肺功能下降的相关性。方法：对70例COPD患者（A组）、30例健康对照（B组）进行痰诱导及肺功能、BMI测定,并测定诱导痰中丙二醛（MDA）、还原型谷胱甘肽（GSH）含量,超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-PX）活性。结果：COPD患者诱导痰MDA含量较健康对照高,P〈0.05;而诱导痰GSH含量、SOD、GSH-PX活性较健康对照下降,P〈0.05;BMI与痰SOD、痰MDA、GSH、GSH-PX的相关系数分别为0.751、-0.694、0.685、0.701,P〈0.05;3.FEV1与痰SOD、痰MDA、GSH、GSH-PX的相关系数分别为0.874、-0.826、0.853、0.809,P〈0.05。结论：COPD患者气道局部均存在氧化/抗氧化失衡;气道局部氧化应激是导致COPD患者BMI及肺功能水平下降的原因之一。     

妊娠高血压综合征患者血浆血管性血友病因子及其裂解酶的测定及临床意义

目的检测正常孕妇及妊娠高血压综合征(PIH)患者血浆血管性血友病因子(vWF:Ag)水平及vWF裂解酶(vWF-CP)活性,探讨vWF及vWF-CP在PIH中的临床意义。方法采用残余胶原结合实验法及ELISA法分别对35例正常孕妇及52例PIH患者血浆vWF-CP活性及vWF:Ag水平进行检测。结果正常妊娠妇女血浆vWF:Ag(103．4±68．4)％显著高于正常非孕妇(78．4±51．6)％(P＜0．01),而血浆vWF-CP活性(76．3±1 8．4)％显著低于正常非孕妇(84．7±2．1)％(P＜0．05)。轻度妊高征妇女血浆vWF:Ag(98．8±48．5)％及vWF-CP活性(70．4±2 1．8)％与正常妊娠妇女无显著性差别(P＞0．05),而中、重度妊高征妇女血浆vWF:Ag(148．4±75．6)％显著高于正常妊娠妇女(P＜0．01),血浆vWF-CP活性(60．8±19．8)％显著低于正常妊娠妇女(P＜0．05)。结论妊高征患者血浆vWF升高,vWF-CP活性低下,参与妊高征的发生、发展,内皮损伤可能是致妊高征患者血浆vWF升高,vWF-CP活性低下的原因。