基于Roussel uclaf因果关系评估量表的药物性肝损伤140例诊治分析

目的 探讨药物性肝损伤(DILI)的病因构成及临床和预后特点. 方法 回顾性分析解放军第八一医院全军肝病中心2012年7月至2013年7月诊断为DILI的140例患者的临床资料,采用RUCAM量表评价药物应用史与肝损伤的相关性,并分析药物种类构成、DILI的临床类型及预后特点.结果 引起本组患者DILI的前3位药物为中药87例(62.1％)、解热镇痛药14例(10％)、抗生素7例(5％).男女性别比为1∶1.69.＞40 ～ ＜60岁患者71例(50.7％).患者RUCAM分值均≥3,临床表现无明显特异性,肝细胞损伤型DILI最多见,共72例(51.4％),胆汁淤积型43例(30.7％),混合型25例(17.9％);胆汁淤积型DILI患者的中位年龄(55.6岁)较肝细胞型(47.1岁)及混合型DILI (49.9岁)高.药物性急性肝衰竭患者占7.86％.结论 本研究患者中因中药引起的DILI所占比例最高,应引起高度重视;其次为解热镇痛药物和抗生素类药物.DILI的临床表现缺乏特异性,但老年患者相对易出现胆汁淤积.绝大多数DILI患者预后良好.     

184例儿童药物性肝损伤的临床特征及转归状况评价

目的通过对儿童药物性肝损伤(DILI)的临床特征及转归的研究,提高对儿童DILI的认识。方法收集184例2004年1月-2014年1月于解放军第三〇二医院住院的年龄16岁的DILI患儿,对其临床和病理资料进行回顾性分析。结果儿童各年龄段均可能发生DILI,并可见于婴幼儿,最小2月龄。临床有症状者143例(77.7%),主要表现为食欲减退、眼黄、尿黄等。引起肝损伤的药物主要有:中药(28.3%)、抗菌药(24.5%)、解热镇痛药(19.6%)等。儿童DILI病理特点主要为:嗜酸性粒细胞为主的炎性细胞浸润(78.7%),混合性肝细胞脂肪变性(73.5%),毛细胆管性淤胆(38.7%)。病程中有4例(2.2%)患儿转化为自身免疫性肝炎,29例(15.8%)患儿发生肝衰竭,其中3例肝衰竭患儿死亡。经治疗后,177例(96.2%)患儿肝功能恢复正常出院。结论儿童DILI可见于各年龄段,引起该病的药物主要以中药、抗菌药、解热镇痛药为主。肝脏病理检查为诊断儿童DILI的重要依据,虽然大多数患儿预后较好,但也应警惕肝衰竭的发生,并注意定期随访。     

2006年-2011年国内老年药物性肝损伤的临床特点

目的总结5年来国内老年药物性肝损伤病例分析文献报道的总体临床特点。方法以"老年"和"药物性肝损伤"为关键词,检索2006年-2011年万方学术论文数据库,记录文献中患者性别、年龄、用药种类、临床表现、临床分型和预后的相关数据进行总结分析。结果 7篇文献记录了465例患者性别,其中男312例(67.10%),女153例(32.90%)。平均年龄76岁。收集5篇文献记录了328例用药信息,导致肝损伤的药物主要为抗微生物类药70例(21.34%)、心血管类药64例(19.51%)、中药47例(14.33%)、解热镇痛类药45例(13.72%)。7篇文献记录了443例临床表现,较常见的临床症状为:乏力(65.32%)、纳差(64.96%)、腹胀(48.5%)、黄疸(46.75%)等。5篇文献记录240例临床分型,其中肝细胞型136例,胆汁淤积型55例,混合型49例。5篇文献记录了176例预后,其中治愈117例(66.48%),好转例52(29.54%),无效或恶化5例(2.84%),死亡2例(1.14%)。结论国内文献报道老年药物性肝损伤男性多于女性,导致肝损伤药物主要为抗微生物类药、心血管类药、中药、解热镇痛药和抗肿瘤药,临床分型以肝细胞型最为常见,患者大多预后良好。     

儿童药物性肝损伤的病因及临床特点分析

目的了解药物性肝损伤患儿的致病原因及其临床特点。方法对2008年1月至2019年6月平煤神马医疗集团总医院病历管理系统进行检索,发现年龄小于14岁患有药物性肝损伤患者共41例,疾病诊断要求符合2004年版药物性肝损伤标准。药物性肝损伤的临床分型采纳的是Danan方案。结果 41例患儿中,男24例,女17例,平均年龄(8.3±3.5)岁,最小为5月龄,最大14岁,其中1岁以下3例,1至3岁4例,4至9岁16例,10至14岁18例。ALT为925(458,1655)U/L,AST为525(175,1284)U/L,碱性磷酸酶325(248,486)U/L,总胆汁酸108(28,198)μmol/L。共有14例患儿行肝活组织检查,符合药物性肝损伤临床分型中肝细胞型9例,胆汁淤积型2例,混合型3例。引起肝损伤的药物包括16例应用抗菌类药物,其中9例应用大环类酯类,4例应用青霉素类,3例应用头孢菌素类;13例应用中成药或中药制剂;6例应用化疗或免疫抑制药物;2例应用抗结核药物;其他还包括4例应用解热镇痛药、精神类药物。临床特点包括乏力23例,食欲下降31例,恶心16例,皮肤黄染或尿液色黄11例,呕吐7例,皮肤瘙痒或皮疹6例。结论儿童药物性肝损伤在各年龄层均可出现,主要药物为抗菌药物、中药、化疗或免疫抑制药物等,在儿童用药过程中应对这些药物重点防控、酌情使用。     

解热镇痛药致肝损伤的发病机理

解热镇痛药又称为阿斯匹林类或非甾体抗炎药(NSALDs),据浪久氏等及沟口氏统计446例药物性肝损伤中解热镇痛药占5～19％,主要为肝细胞损伤,少数为淤胆型或混合型损伤。     

老年人急性药物性肝病临床分析30例

目的:探讨老年人急性药物性肝病的常见诱发药物、临床表现、分型及预防,以提高对该病的诊断水平.方法:对符合诊断标准的30例急性药物性肝病患者的临床资料进行回顾性分析.结果:诱发老年人急性药物性肝病的药物中,中草药9例(30.3%),抗生素5例(16.7%),解热镇痛药,碘油造影剂和抗甲亢药均3例(10.0%),其他7例(23.3%).临床表现为急性肝细胞型20例(66.7%),急性胆汁淤积型3例(10%),混合型7例(23.3%).其中治愈18例(60.0%),好转8例(26.7%),恶化2例(6.7%),死亡2例(6.7%).结论:老年人对药物敏感性增加,容易引起急性药物性肝损伤和不良反应,临床医生必须加以高度重视,谨慎用药.     

药物性肝损伤临床特征及预后多学科专家共识

目的:分析药物性肝损伤(drug-induced liver injury,DILI)的临床特征,探讨影响其预后的危险因素.方法:回顾性总结西安交通大学第一附属医院、西安交通大学第二附属医院、西京医院西安三所医院近5年的572例药物性肝损伤患者的临床资料,分析其性别、年龄、既往史、用药时间、临床表现、临床分型、用药史、生化指标、用药方式、治疗方法等临床特征,及其对预后的影响.结果:(1)纳入本研究的DILI患者共572例,男性280例(48.95%),女性292例(51.05%),平均年龄45.56岁±15.11岁;(2)既往有吸烟史的226例,有饮酒史的205例,有过敏史的115例,有基础肝病史的155例;肝损伤发生时间绝大多数8 wk,为490例;临床表现主要为皮肤巩膜黄染或尿色加深占59.44%,乏力占57.52%,纳差占55.42%;临床分型肝细胞型为402例,胆汁淤积型为62例,混合型为53例;导致DILI的前3类药物依次为中药299例、抗结核药71例、抗微生物用药48例;用药方式为口服用药533例,静脉注射20例,外用给药14例;预后情况治愈194例,好转323例,未愈39例,死亡16例;(3)影响药物性肝损伤预后的因素有用药时间、临床分型、用药种类、用药方式及总胆红素指标.其中总胆红素为DILI的独立危险因素.结论:药物性肝损伤的临床表现缺乏特异性,致病药物种类较多,中药为最常见的原因,影响DILI预后的因素较多,总胆红素为独立危险因素.     

老年药物性肝损伤139例临床分析

目的回顾性分析解放军302医院2003年-2010年间老年药物性肝损伤的临床特点。方法将患者分为老年组（139例）和中青年组（105例）,比较二者之间的临床特征和生化学指标。结果导致药物性肝损伤的药物有14种,老年组药物性肝损伤前5位的药物分别是中药（31．7％）、抗生素（13．7％）、解热镇痛药（12．2％）、心血管药（11．5％）和抗结核药（6．5％）;而中青年组则是中药（43．8％）、解热镇痛药（18．1％）、抗生素（13_3％）、抗结核药（6．7％）和治疗甲状腺功能亢进药（4．8％）,两组之间存在统计学差异。老年组y-谷氨酰基转肽酶及治愈患者平均住院时间均较中青年组为高。老年组黄疸发生率为77．1％,肝衰竭发生率为2．9％;中青年组黄疸发生率82．0％,肝衰竭发生率为4．8％,二者之间无统计学差异。老年组肝损伤类型分别为胆汁淤积型（45．9％）、肝细胞型（28．6％）和混合型（25．5％）,中青老年组上述3种损伤类型分别为39．3％、34．8％和25．8％,两组间无统计学差异。结论导致药物性肝损伤的药物以中药占首位,老年与中青年患者药物性肝损伤均以胆汁淤积型为主,有少数患者可发展为肝衰竭,老年患者临床治愈时间长;建议对中药、抗生素、解热镇痛药等易导致肝损伤的药物慎重选用;预防措施之一是用药后要定期检测肝功能的峦化．     

62例儿童药物性肝损伤的回顾性分析

目的 研究药物性肝损伤(DILI)患儿的临床特征。方法 回顾性分析河南省儿童医院62例DILI患儿的年龄分布、临床症状、致肝损伤的药物种类、治疗药物、临床转归、肝功能指标、Roussel Uclaf因果关系评估分值(RUCAM)积分。结果 临床分型中以肝细胞型最为常见，占87.1%(54/62)。高发年龄段为>1～3岁和>3～6岁，分别为33.9%(21/62)和41.9%(26/62)。DILI患儿的临床症状以食欲下降最为常见，占59.7%(37/62)。致患儿DILI的药物种类主要为抗菌药、解热镇痛药、中药等。肝细胞型患儿ALT(765.26±217.52)U/L,胆汁淤积型患儿ALT(132.24±76.51)U/L,混合型患儿ALT(337.26±103.28)U/L,差异有统计学意义(F=21.357,P=0.000);肝细胞型患儿ALP(130.42±87.61)U/L,胆汁淤积型患儿ALP(315.64±105.62)U/L,混合型患儿ALP(201.36±171.35)U/L,差异有统计学意义(F=6.200,P=0.004);肝细胞型患儿AST(571.3...     

186例药物性肝损伤组织病理学及临床特征分析

目的探讨药物性肝损伤的组织病理学特点及临床特征,为早期诊治提供帮助。方法回顾性分析186例经肝活组织穿刺病理学诊断的药物性肝损伤患者的用药史、病理特点、临床表现、生化、血清学标志以及治疗转归等。结果引起药物性肝损伤前3位的药物是中药91例（49％）、抗生素41例（22％）、解热镇痛药23例（12．4％）;临床分类：药物性肝功能衰竭8例（4．4％）、急性药物性肝损伤93例（50％）、慢性药物性肝损伤83例（44．6％）、药物性肝硬化2例（1．1％）;临床分型：肝细胞损伤型98例（52．7％）、胆汁淤积型35例（18．8％）、混合型55例（29．6％）。病理学特征主要表现为：肝细胞坏死、汇管区扩大、肝细胞脂肪变性、汇管区或窦周混合炎细胞浸润、嗜酸性粒细胞浸润、肝细胞胆汁淤积、肝细胞凋亡、可见吞噬色素的Kuffer细胞。治愈79例（42．5％）,好转102例（54．8％）,无效5例（2．7％）。无一例患者死亡或病情恶化。结论引起药物性肝损伤的首位药物为中药,临床表现无特异性,但组织病理学改变有一定特征。     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

N-acetyl-L-cysteine combined with mesalamine in the treatment of ulcerative colitis： Randomized,placebo-controlled pilot study

AIM： To evaluate the effectiveness and safety of oral N-acetyl-L-cysteine （NAC） co-administration with mesalamine in ulcerative colitis （UC） patients.
METHODS： Thirty seven patients with mild to moderate UC were randomized to receive a four-wk course of oral mesalamine （2.4 g/d） plus N-acetyl-L-cysteine （0.8 g/d） （group A） or mesalamine plus placebo （group B）. Patients were monitored using the Modified Truelove-Witts Severity Index （MTWSI）. The primary endpoint was clinical remission （MTWSI ≤ 2） at 4 wk. Secondary endpoints were clinical response （defined as a reduction from baseline in the MTWSI of ≥ 2 points） and drug safety. The serum TNF-α, interleukin-6, interleukin-8 and MCP-1 were evaluated at baseline and at 4 wk of treatment. RESULTS： Analysis per-protocol criteria showed clinical remission rates of 63% and 50% after 4 wk treatment with mesalamine plus N-acetyl-L-cysteine （group A） and mesalamine plus placebo （group B） respectively （OR = 1.71; 95% CI： 0.46 to 6.36; P = 0.19; NNT = 7.7）. Analysis of variance （ANOVA） of data indicated a significant reduction of MTWSI in group A （P = 0.046） with respect to basal condition without significant changes in the group B （P = 0.735） during treatment. Clinical responses were 66% （group A） vs 44% （group B） after 4 wk of treatment （OR = 2.5; 95% CI： 0.64 to 9.65; P = 0.11; NNT = 4.5）. Clinical improvement in group A correlated with a decrease of IL-8 and MCP-1. Rates of adverse events did not differ significantly between both groups.
CONCLUSION： In group A （oral NAC combined with mesalamine） contrarily to group B （mesalamine alone）, the clinical improvement correlates with a decrease of chemokines such as MCP-1 and IL-8. NAC addition not produced any side effects.     

Delorme's transrectal excision for internal rectal prolapse

Surgical therapy of functional outlet obstruction in patients with internal rectal intussusception may include abdominal, perineal, or transrectal procedures. Because abdominal procedures often result in significant physiologic impact but unrelieved constipation, the authors have elected Delorme's transrectal excision for management of these patients. Since a short-term placebo effect attends many therapies, this report describes results of transrectal excision only after a threeyear postoperative period. Delorme's transrectal excision of internal intussusception accomplished sustained symptomatic relief in over 70 percent of otherwise refractory constipated patients. The association of internal intussusception with other abnormalities underscores the importance of defining both anatomic and functional components when selecting patients whose constipation may require surgical therapy. Critical technical elements, surgical pitfalls, and potential complications of the procedure are discussed.Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, Toronto, Canada, June 11 to 16, 1989.     

The oral glucose tolerance test: A comparison of the time points on the basis of limit values,normal dispersion,and reproducibility

Summary Time points in the glucose tolerance test (GTT) are compared on the basis of limit values, dispersion within a reference population, and reproducibility. We suggest using the distance between a limit value and the median reference value as a measure of the magnitude of abnormality. The distance between 140 mg/100 ml and the median fasting plasma glucose value is chosen as a standard distance and limits for other points in the GTT are calculated to equal this standard distance of abnormality. We suggest that the probability of correctly interpreting an inividual result is directly related to the reproducibility of the test and inversely related to the percentage of the total range of values which is dispersed among the normal population. The ratio of reproducibility to percentage normal dispersion is proposed as an index of the probability of correctly interpreting an individual result. According to this index, the probability of correct interpretation varies in order: fasting plasma glucose concentration>3-h>2-h>0.5-h>1-h plasma glucose concentration.