62例老年非病毒性肝损伤患者临床特点和病因分析

目的探讨老年非病毒性肝损伤患者的临床特点和病因,指导临床诊断和治疗。方法回顾性分析62例2006年1月至2009年6月期间复旦大学附属中山医院收治的非病毒（已知甲～戊型肝炎病毒、单纯疱疹病毒、巨细胞病毒、EB病毒和柯萨奇病毒）感染所致的60岁及以上肝功能异常患者的临床资料,并与98例同期住院的60岁以下成年人非病毒性肝损伤患者进行比较。结果老年jE病毒性肝损伤患者临床表现无特异性,乏力和纳差的发生率明显高于非老年组（P〈0．05）;老年组患者中引起肝功能异常的病因以药物性肝病（DILD）居首位（40．32％）,其它依次为非酒精性脂肪性肝病（NAFLD）（20．97％）、胆源性疾病（17．74％）、心肺功能不全（9．68％）;丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）在DILD患者中增高最为明显,老年组DILD患者ALT和AST高于非老年组[ALT：（775．83±478．51）vs（526．44±401．54）U／L,AST：（663．61±464．85）VS（457．45±521．78）U／L;P〈0．01]。引起老年人肝损伤的药物主要是中药（40％）、非甾体类消炎药（12％）和HMG-CoA还原酶抑制剂（12％）。结论老年非病毒性肝损伤患者以DILD最为多见,其次为NAFLD和非肝源性疾病导致肝损伤,临床医师应特别重视老年人药物性肝病的防治。     

肝组织活检诊断为药物性肝损伤的肝功能异常患者临床特征分析

 目的 分析179例肝组织活检诊断药物性肝损伤的肝功能异常患者临床特征。方法 回顾性分析2010-01至2015-01解放军总医院第五医学中心收治的符合条件的诊断为肝功能异常且可排除甲乙丙戊型病毒性肝炎、EB病毒及CMV病毒性感染、自身免疫性肝病、酒精性肝病、非酒精性脂肪性肝病,以及遗传代谢性肝病导致的肝损伤病例179例。依据肝组织活检病理结果将病例分为急性/亚急性组和慢性组,分析两组间临床特征及病理表现差异。结果 在发病类型方面,急性/亚急性肝损伤以青年为主(64.3%),而对于慢性肝损伤以老年为主(53.7%),差异具有统计学意义(P＜0.05)。临床症状表现中,乏力、肝区不适、发热、皮肤瘙痒方面,两组之间相比差异无统计学意义;而急性/亚急性组中纳差(50.0% vs 30.9%)和尿黄(58.9% vs 35.0%)症状较慢性组更明显(P＜0.05)。肝功能生化检测指标方面,急性/亚急性组在ALT、AST、TBIL、DBIL方面明显高于慢性组,有统计学差异(P＜0.01),但两组在ALP、GGT、ANA的分布比例无统计学差异。急性/亚急性组与慢性组药物性肝损伤的病理表现不同,两组在胆汁淤积病理表现方面没有差异,而急性/亚急性组多见于混合型病理表现,慢性组多见肝细胞损伤病理表现。结论 老年人易发生慢性药物性肝损伤,并且多以肝细胞损伤病理表现为主,对于病因不明的反复肝功能异常老年患者,应警惕慢性药物性肝损伤的可能。     

24例甲巯咪唑致胆汁淤积性肝损伤文献分析

目的 分析甲巯咪唑致胆汁淤积性肝损伤发生特点与规律,为防治及临床安全用药提供参考。方法 检索国内外文献数据库中有关甲巯咪唑致胆汁淤积性肝损伤（黄疸）的个案报道,并进行计量学分析。结果 获8篇个案报道,共计24例患者,其中男性1例,女性23例;年龄48~58岁共8例,均为女性,占33.33%;其次为37~47岁共7例,均为女性,占29.17%。合并用药与甲巯咪唑单次给药相比,致胆汁淤积性肝损伤发生率未见差异（25.00% vs 25.00%,P>0.05）;诱导期以21~35 d为主,占比58.33%,其次为7~21 d,占比37.50%。药物与不良事件因果关系诺氏（Naranjo''s）评分肯定4例（16.67%）,很可能20例（83.33%）。结论 中年女性甲亢患者为甲巯咪唑致胆汁淤积性肝损伤的高危人群,宜对其进行中短期用药监护,权衡利弊,尽量避免和减少药源性胆汁淤积性肝损伤发生。     

Drug-induced bone loss: a major safety concern in Europe

Introduction: Drug-induced bone loss remains the major cause of vertebral and hip fractures and significantly associated to morbidity and mortality. This article will review the common drugs identified as the causes of bone loss and the risk factors and management in European countries.

Areas covered: Beyond glucorticoid – the most cause of osteoporosis, many different drugs could cause harmful skeletal disorders. The antiepileptics, hormonal therapy, GnRH antagonists, aromatase inhibitors are well-known cause of bone loss. Osteoporosis and fractures risk also increased with calcineurin inhibitors, antiretroviral drugs, selective inhibitors of serotonin reuptake, loop diuretics, heparins, oral anticoagulants, high doses of thyroxine and proton pump inhibitors.

Expert opinion: Drugs are an important secondary cause of osteoporosis. Healthcare professionals should reassess the requirement for drugs and use the lowest dosage and shortest duration. Lifestyle changes, adequate calcium, vitamin D supplement, appropriate monitoring of bone status and initiating osteoporosis treatment if indicated are recommended when drugs having potential deleterious effects on bone are used, particularly in high risk patients. The update and further studies would provide concluded evidences of controversial drugs induced bone loss and determine the best prevention and treatment strategies.     

茵栀黄口服液联合硫普罗宁治疗药物性肝损伤的临床研究

目的探讨茵栀黄口服液联合注射用硫普罗宁治疗药物性肝损伤的临床疗效。方法选取2015年8月—2017年9月成都市新都区人民医院收治的药物性肝损伤患者100例为研究对象,根据随机区组设计法将患者分为对照组和治疗组,每组各50例。对照组静脉滴注注射用硫普罗宁,400 mg加入到5%葡萄糖注射液500 mL中,1次/d。治疗组在对照组基础上口服茵栀黄口服液,10 mL/次,3次/d。两组均连续治疗1个月。观察两组的临床疗效,比较两组的肝功能、临床症状和炎性因子。结果治疗后,对照组和治疗组的总有效率分别为72.0%、92.0%,两组比较差异具有统计学意义(P0.05)。治疗后,两组丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转氨酶(AST)、总胆红素(TBIL)水平均显著下降,白蛋白(ALB)水平显著升高,同组治疗前后比较差异具有统计学意义(P0.05);且治疗组这些肝功能指标的改善程度明显优于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,治疗组腹胀、乏力、纳差、黄疸、肝脾大改善率均显著高于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组血清肿瘤坏死因子-α(TNF-α)、干扰素-γ(TNF-γ)水平显著降低,血清白细胞介素-10(IL-10)水平显著升高,同组治疗前后比较差异具有统计学意义(P0.05);且治疗组这些炎症因子的改善程度明显优于对照组,两组比较差异具有统计学意义(P0.05)。结论茵栀黄口服液联合注射用硫普罗宁治疗药物性肝损伤具有较好的临床疗效,可改善患者的肝功能和临床症状,降低炎性因子水平,具有一定的临床推广应用价值。     

莲必治注射液致药源性肾损害126例分析

目的分析莲必治注射液致药源性肾损害发生的原因与发生规律,为临床安全用药提供参考。方法检索2000~2013年国内医学期刊报道应用莲必治注射液致药源性肾损害案例126例,并进行统计分析。结果莲必治注射液致药源性肾损害的发生存在性别差异,男性（90例）显著多于女性（36例）;年龄段以21~50 a的青壮年发生率为最高,占76.19%;所致肾损害中以引发肾功能衰竭为最多（104例）;出现ADR时间呈多样性,以1~2 d为多;出现ADR停药后并做应对处理,预后均良好。结论临床应用莲必治注射液时应密切观察患者身体状况,注意用药前后患者尿常规和肾功能的监测,尽量避免与其他药物联合应用,一旦发生ADR及时停药,并进行对症处理。     

Detection of QTc interval prolongation using jacket telemetry in conscious non-human primates: comparison with implanted telemetry

Background and Purpose: During repeat-dose toxicity studies, ECGs are collected from chemically or physically-restrained animals over a short timeframe. This is problematic due to cardiovascular changes caused by manual restraint stress and anesthesia, and limited ECG sampling. These factors confound data interpretation, but may be overcome by using a non-invasive jacket-based ECG collection (JET). The current study investigated whether a jacketed external telemetry system could detect changes in cardiac intervals and heart rate in non-human primates (NHPs), previously implanted with a PCT transmitter.Experimental Approach: Twelve male cynomolgus monkeys were treated weekly with vehicle or sotalol (8, 16, 32 mg kg⁻¹) p.o. ECGs were collected continuously for 24 hours, following treatment, over 4 weeks. A satellite group of six NHPs was used for sotalol toxicokinetics.Key Results: Sotalol attained C_max values 1–3 hours after dosing, and exhibited dose-proportional exposure. In jacketed NHPs, sotalol dose-dependently increased QT/QTc intervals, prolonged PR interval, and reduced heart rate. Significant QTc prolongation of 27, 54 and 76 msec was detected by JET after 8, 16, and 32 mg kg⁻¹ sotalol, respectively, compared with time-matched vehicle-treated animals. Overall, JET-derived PR, QT, QTc intervals, QRS duration, and heart rate correlated well with those derived from PCT.Conclusions and Implications: The current findings clearly support the use of JET to quantify cardiac interval and rhythm changes, capable of detecting QTc prolongation caused by sotalol. JET may be a preferred method compared to restraint-based ECG because high-density ECG sampling can be collected in unstressed conscious monkeys, over several weeks.     

164例住院患者药物性肝损害临床分析

目的 分析药物性肝损害（DILI）的致病药物和临床特点,为临床合理用药提供参考。方法 收集本院2013-01~12住院患者中发生药物性肝损害的病例,对患者的基础疾病、用药史、肝损害分型及预后进行回顾性分析。结果 共筛选到符合DILI诊断标准的患者164例,导致药物性肝损害的前五类药物分别是化疗药（51.98%）、中药（8.42%）、抗结核药（8.42%）、抗菌药（7.43%）和心血管系统用药（5.45%）;肝损害类型以肝细胞型为主,占71.34%,其次为胆汁淤积型（15.24%）和混合型（13.41%）;经过保肝治疗,19.51%的患者治愈,64.63%的患者好转,9.15%的患者无效,1.22%的患者死亡。结论 本院导致肝损害的药物以化疗药为主,多数为肝细胞型,经治疗后预后较好。     

Use of proton pump inhibitors during pregnancy and rates of major malformations: a meta-analysis

Proton pump inhibitors are used to treat gastroesophageal reflux, a symptom common in pregnancy. The aim of this study was to systematically analyze the available data on the risk for malformations following use of these agents in the first trimester of pregnancy. Medline, EMBASE, published abstracts, and reference lists were searched for articles reporting on proton pump inhibitor use in pregnancy. Summary relative risks and 95% confidence intervals (95% CI) were calculated using the Mantel-Haenszel method. Five cohort studies met the inclusion criteria for this meta-analysis. With almost 600 exposed pregnancies, the overall relative risk was 1.18 with a 95%CI of 0.72–1.94. In conclusion, proton pump inhibitors do not present a major teratogenic risk when used in recommend doses. These data are reassuring for the countless patients who have used these agents in the early part of their pregnancies.     

抗结核急性药物性肝损伤患者外周血CD_8~+T细胞上CD_(28)表达及意义

[目的]通过对抗结核急性药物性肝损伤患者外周血CD+8CD-28、CD+8CD+28细胞百分率检测,探讨其在抗结核急性药物性肝损伤中表达及意义。[方法]应用流式细胞术检测抗结核急性药物性肝损伤组42例、抗结核治疗肝功能正常组232例外周血中CD+8CD-28、CD+8CD+28细胞百分率;两组间均数的比较采用t检验,P0.05为差异有统计学意义。[结果]抗结核急性药物性肝损伤组外周血CD+8CD-28细胞百分率低于抗结核肝功能正常组(12.2±7.7%和23.6±10.4%),两组间差异有统计学意义(t=4.782,P0.01);抗结核急性药物性肝损伤组CD+8CD+28细胞高于抗结核肝功能正常组(23.5±9.1%和10.2±6.7%),两组间差异有统计学意义(t=5.356,P0.01)[结论]抗结核急性药物性肝损伤外周血CD+8CD-28T细胞百分率减少,CD+8CD+28T细胞百分率增加;CD+8T细胞上CD28表达可作为抗结核急性药物性肝损伤免疫学检测标志。