慢性乙型肝炎合并Gilbert综合征患者33例临床及其基因突变分析

目的 探讨慢性乙型肝炎合并Gilbert综合征患者的临床特点及其基因突变位点分析.方法 对33例慢性乙型肝炎合并Gilbert综合征患者的肝脏生物化学指标、病理组织学特点及基因检测位点分析,对基因检测结果根据不同突变位点进行分析,数据分析应用x2检验和t检验. 结果 33例患者Gilbert综合征特异性编码的UGT1A1基因检测显示突变位点集中表现在启动子上游PBREM-3263 (-3279)突变(23例)和启动子TATA盒TA插入突变(21例),以及编码区外显子EXON1上的GGA-AGA Gly71Arg突变(18例),3个常见位点突变之间差异无统计学意义(x2=1.640,P＞ 0.05).结论 慢性乙型肝炎合并Gilbert综合征患者诊断依靠传统方法仍比较困难,而基因检测为该疾病的诊断提供了更有利的帮助.     

The analysis of clinical features and prognosis factors in patients with severe fever with thrombocytopenia syndrome

正Objective To explore the influence of clinical indicators in patients with thrombocytopenia syndrome(SFTS)with severe fever on disease development and prognosis.Methods The SFTS patients who were admitted to the Department of Infection Diseases of Wuhan Union Hospital between April 1,2015 and October 30,2015 were included.Among 164 patients with SFTS,136     

Phenotypic features, androgen receptor binding, and mutational analysis in 278 clinical cases reported as androgen insensitivity syndrome

Androgen insensitivity syndrome (AIS) is the most common single entity that results in male under-masculinization, but large cohort studies of AIS have rarely been performed. Over the last decade, nationwide cooperation between pediatric endocrinologists in the United Kingdom has allowed the creation of a database of cases of intersex and ambiguous genitalia where detailed clinical information on every notified case has been collected via a questionnaire. Among the 816 entries recorded by January 1999, there were 105 clinically diagnosed cases of complete AIS (CAIS) and 173 cases of partial AIS (PAIS). A masculinization score was devised by scoring the external phenotype, and a score of 12 represented normal masculinization. Androgen receptor (AR) binding was determined by studying binding capacity (Bmax) and receptor affinity (K(d)), and cases were classified as either zero, abnormal, or normal binding. Mutation screening of all eight exons of the AR gene was performed by single-strand conformational polymorphism analysis, followed by direct DNA sequencing. All cases of PAIS presented within the first month of birth. The median age at presentation of children with CAIS was 1 yr (P10,P90: 0.1,10.4). The testes were palpable in the labioscrotal folds or the inguinal region in 77% and 41% of cases of CAIS and PAIS, respectively. There was marked overlap between the masculinization score of those children with PAIS reared as girls [2.5(P10,P90:1, 6)] and those reared as boys [3(P10,P90:2, 7.5)]. Gonadectomy was performed prepubertally in 66% and postpubertally in 29% of the cases of CAIS. The median age of the latter group was older at 14 yr (P10,P90:0.1,18). No cases of malignancy or carcinoma in situ were reported in the 121 cases of AIS where histology results were available. Biochemical endocrine investigations were reported to have been performed in a greater number of cases of PAIS than CAIS (98% vs. 48%). AR binding was abnormal in 44 of 51 (86%) and 40 of 113 (35%) cases of CAIS and PAIS, respectively. Zero binding was encountered in 29 of 43 (67%) and 1 of 55 (2%) cases of CAIS and PAIS, respectively. Mutational analysis of the AR gene, performed in 102 index cases was positive in 57 of 69 (83%) cases of CAIS and 12 of 43 (28%) cases of PAIS. In 24 of these cases, the mutation identified was novel. The mutations in PAIS cases were all missense, whereas in CAIS the mutations were more diverse. AR binding was only normal in 3 of 69 mutation-positive cases. In the PAIS group, mutation-positive cases had a significantly higher Kd and Bmax compared to the mutation negative cases. The clinical diagnosis of AIS can be confirmed in a significant number of cases by a combination of androgen-binding studies and mutational analysis. There is some correlation between the phenotypic features and the abnormalities discovered on mutational analysis of the AR gene, but there is a need to improve this further by developing optimal bioassays of AR function. The phenotypic heterogeneity among clinically diagnosed cases of AIS emphasizes the need for appropriate comprehensive evaluation of male under-masculinization.     

Hypersideremic and hyperbilirubinemic effect of nicotinic acid in patients with Gilbert's syndrome

Nicotinic acid test (NA) administration is followed by a rise in unconjugated bilirubin and serum total iron in healthy man. A similar concomitant effect has never been investigated in Gilbert's syndrome (GS) patients, who by definition have a hyperbilirubinemia higher than that of controls. The aim of this study was to verify whether, in addition to the hyperbilirubinemic action, NA could induce parallel hypersideremia in GS subjects. The data we obtained confirm in GS patients: 1. the well-known hyperbilirubinemia; 2. a delayed NA plasma concentration curve, and document that in GS the hypersideremic effect is comparable to that of controls. Previous investigators reported that NA produces an equimolar rise of bilirubin and iron levels in healthy man. In our study the extent of the sideremic response to NA occurring in GS patients is comparable to that seen in controls, and appears unrelated to the bilirubinemic values. If the NA effects are based on the documented hemolytic properties of NA, a disturbance in bilirubin handling by the liver of GS subjects appears to be plausible in the presence of almost normal behavior of NA-induced hypersideremia.     

老年2型糖尿病并阻塞性睡眠呼吸暂停低通气综合征患者的免疫与临床相关性

目的 探讨2型糖尿病(T2DM)并阻塞性睡眠呼吸暂停低通气综合征(OSAS)患者T淋巴细胞亚群(CD3+、CD4+、CD8+、CD19+)和自然杀伤细胞(NK)百分率变化的意义及其临床相关性.方法 2011年6月至2012年6月在上海交通大学附属第六人民医院老年科住院患者符合1999年WHO关于2型糖尿病诊断标准的患者50例,按照2002年<中华结核和呼吸杂志>公布的阻塞性睡眠呼吸暂停低通气综合征诊治指南(草案),根据患者是否存在OSAS分为T2DM组(30例)、T2DM+OSAS组(20例),同期选择单纯OSAS患者为OSAS组(25例),正常对照组(NC组25例).采用稳态模型计算胰岛素抵抗指数(HOMA-IR);应用流式细胞仪单克隆免疫荧光法和放射免疫法检测外周血T淋巴细胞、NK细胞和胰岛素水平,并分别对T细胞亚群和NK细胞百分率的变化与睡眠呼吸紊乱主要参数(AHI)、体质量指数(BMI)、空腹血糖(FBG)、空腹胰岛素(FINS)及胰岛素抵抗指数(HOMA-IR)指数进行了多元回归分析.结果 (1)本研究中,T2DM+OSAS组的BMI、血氧饱和度(SpO2)及心脑血管并发症的差异有显著性(P<0.01).(2)各实验组的AHI、FBG、FINS和HOMA-IR指数均高于正常对照组,夜间最低SpO2低于NC组(P<0.05,P<0.01).(3)各实验组的外周血CD3+、CD4+、CD19+、NK及CD4+/CD8+比值均明显低于NC组(P<0.01);CD8+T细胞数量与NC组比较,差异无统计学意义(P>0.05).(4)直线相关性分析提示,AHI变化与FINS及HOMA-IR呈正相关.(5)多元回归分析提示,外周血CD4+T细胞亚群及NK细胞的变化与AHI、BMI、FBG、HOMA-IR具有明显相关性.结论 免疫调节异常参与了T2DM和OSAS的发生发展,合理使用免疫调节治疗可能是治疗糖尿病并睡眠呼吸暂停综合征的另一新途径.     

肺腺癌患者基因突变与临床特征的相关性

目的 分析肺腺癌患者基因突变与临床特征的相关性.方法 选取87例经病理或细胞学明确诊断为肺腺癌患者,所有患者经二代测序技术(NGS)进行肺癌驱动基因检测.采集所有患者基本资料、临床特征、基因突变情况,分析基因突变与患者临床特征、分子表型的相关性.结果 基因突变型61例(70.11％),野生型26例(29.89％),基因...     

Decreased oxidation susceptibility of plasma low density lipoproteins in patients with Gilbert's syndrome

Background and Aim: The association of hyperbilirubinemia in Gilbert's syndrome (GS) with a decrease in prevalence of coronary artery disease is a well‐known phenomenon. In this study, the state of low‐density lipoprotein (LDL) oxidation which has been postulated to be a significant determinant at the etiopathogenesis of atherosclerotic disorders was investigated among individuals with GS. Methods: For this purpose, serum cholesterol, LDL cholesterol, high‐density lipoprotein cholesterol, triglycerides, uric acid, apolipoprotein A and B, bilirubins, thiobarbituric acid‐reactive substances, and the sensitivity of LDL oxidation levels, as well as serum alanine aminotransferase, aspartate aminotranserfase, gamma glutamil transferase, and alkaline phosphatase activities, were determined in 17 patients with Gilbert's syndrome and 15 healthy adults. Results: There was no significant difference between the groups except the indirect bilirubin parameter (P < 0.001). In comparison with the healthy individuals, LDL oxidation levels between 75 and 120 min were significantly lower (P < 0.005) along with prolonged lag‐phase in GS patients, indicating a delay in oxidation susceptibility. Conclusion: It is suggested that the chronic hyperbilirubinemia leading to a lag‐phase prolongation in LDL oxidation and a decrease in LDL oxidation may be reason for the low percentage of coronary artery disease.     

合并代谢综合征的急性心肌梗死患者临床特征

目的 探讨合并代谢综合征(MS)的急性心肌梗死(AMI)患者的临床特征.方法 对81例合并MS的AMI患者及94例无MS的AMI患者进行回顾性研究,比较两组患者的基础临床情况、诱发因素、临床表现、梗死部位及心肌酶.结果与非 MS组相比,MS组年龄较大,女性患者所占比率较高(34.6%比17.0%,P＜0.01),吸烟和冠心病家族史比率较低(分别为43.2%比59.6%,13.6%比25.5%,均P＜0.05),饱餐后或情绪激动时发病率较高(分别为18.5%比7.4%,13.6%比4.3%,均P＜0.05),有胸痛者少(66.7%比81.9%,P＜0.05),心功能≥KillipⅡ级者较多(35.8%比22.3%,P＜0.05),住院病死率高(22.2%比10.6%.P＜0.05),前壁范围所占比率较高(51.9%比36.2%,P＜0.05),肌酸激酶同工酶较高[(147±19)U/L比(122±14)U/L,P＜0.01].结论 与无MS的AMI患者相比,合并MS的AMI患者年龄较大,女性患者较多,近期预后较差.     

Delayed gastric emptying in subjects with Gilbert's syndrome

BACKGROUND/AIMS: Recently, it has been proposed that decreased intestinal motility in fasting-induced hyperbilirubinemic rats probably results in an increase in the enterohepatic cycling of unconjugated bilirubin. We investigated the association among gastric emptying, intestinal transit time, and serum unconjugated levels in subjects with Gilbert's syndrome. METHODOLOGY: Ten subjects with Gilbert's syndrome were included in this study according to the following criteria: fasting hyperbilirubinemia; no hemolysis or gastrointestinal disorders and free of any medication. Five normal, healthy volunteers acted as controls. Gastric emptying and intestinal transit time were evaluated after overnight fasting by administration of a standard meal mixed with 1-2ci of 99Tc-labeled diethylene-triamine-pentacetic acid. Serum unconjugated bilirubin levels were determined by high-performance liquid chromatography. RESULTS: The gastric emptying in Gilbert's syndrome subjects was 134.1 +/- 38.9 and 90.9 +/- 6.5 min in controls, P < 0.03. It was a tendency to have a shorter intestinal transit time in subjects with Gilbert's syndrome, 138.3 +/- 59.0, than in control subjects, 183.8 +/- 11.3 min. Serum unconjugated bilirubin levels (mg/dL) were 2.6 +/- 1.04 and 0.95 +/- 0.34, P < 0.01. CONCLUSIONS: Gastric emptying is delayed significantly in Gilbert's syndrome, and intestinal transit time differences between Gilbert's syndrome subjects and controls were not significantly different.     

肝肾综合征83例临床特征分析

目的探讨在肝硬化腹水基础上发生肝肾综合征(HRS)患者的临床特点,指导临床对HRS进行有效的预防和治疗。方法回顾性分析2005年1月至2009年1月温州医学院附属第一医院消化内科收治的83例HRS患者及92例肝硬化腹水而未发生HRS患者(non-HRS)的临床资料,对两组患者的常见诱因、肝功能分级、交感神经张力、一般情况、病死率及预后等进行比较分析。结果(1)大量腹水及继发感染多见于HRS患者,而消化道出血则多见于non-HRS患者,在HRS患者中大量腹水多见于Ⅱ型HRS,而诱因不明者多见于Ⅰ型HRS。(2)Ⅰ型HRS患者肝功能最差,Ⅱ型居中,non-HRS最好。(3)HRS患者交感神经张力明显高于non-HRS患者。(4)一般情况比较中HRS患者血肌酐(Scr)明显高于non-HRS患者,而血钠(Na+)、24h尿量及平均动脉压均较后者低。(5)Ⅰ型HRS的病死率最高,Ⅱ型次之,non-HRS患者最低。HRS患者的存活时间明显低于non-HRS患者。结论(1)HRS常见诱因有大量腹水、感染、消化道出血、大量放腹水、水与电解质紊乱等,应尽量避免,一旦发现,应积极采取措施,及时治疗。(2)HRS患者交感神经张力明显高于非HRS患者,此可为临床诊治提供参考依据。(3)较之non-HRS患者,HRS患者的病情非常严重,病死率极高,预后极差,尤以Ⅰ型为甚。     

Isoniazid acetylation in Gilbert's syndrome

Phenotyping of isoniazid acetylators in 19 Caucasoid patients with Gilbert's syndrome was achieved by evaluating the percentual of acetylisoniazid in the urine. The proportion of slow acetylators among the patients with Gilbert's syndrome was similar to those found among Caucasoids of control group. The conclusion was that Gilbert's syndrome doesn't interfere in the hepatic capacity of isoniazid acetylation.     

A case of Gilbert's syndrome combined with macroamylasemia

A 30-year-old Japanese male, who had no remarkable family history, visited our hospital with a complaint of abdominal pain, and unconjugated hyperbilirubinemia and hyperamylasemia were observed. He showed negative hemolysis tests, positive nicotinic acid test, low hepatic bilirubin UDP-glucuronyltransferase activity, decreased bilirubin diglucuronide and increased bilirubin monoglucuronide in bile, and a decrease in serum bilirubin after phenobarbital administration. He also showed high serum amylase level, low urine amylase level, and low amylase-creatinine clearance ratio. Gel filtration of serum with Sephadex G-200 revealed the existence of macroamylase. Countercurrent immunoelectrophoresis proved binding of serum amylase to lambda type IgA. From these results, the case was diagnosed as Gilbert's syndrome combined with macroamylasemia.     

Liver ultrastructure in Gilbert's syndrome.

Electron microscopy of hepatic tissue obtained by percutaneous needle biopsy from nine patients with Gilbert's syndrome has revealed in every case gross hypertrophy of hepatocyte agranular endoplasmic reticulum but no other important abnormality. While this may have relevance to impairment of microsomal enzyme activity controlling bilirubin conjugation within liver cells, the serum bilirubin levels in all nine patients were below that normally associated with demonstrable UDP-glucuronyl transferase deficiency. Gross hypertrophy of agranular endoplasmic reticulum may be, therefore, a constant feature of this form of Gilbert's syndrome and may have some diagnostic value in the investigation of unconjugated hyperbilirubinaemia.     

风疹患者408例临床流行病学和临床特征回顾性分析

目的 研究风疹患者的临床流行病学和临床特征.方法 对哈尔滨医科大学附属第二医院2002年至2004年收治风疹患者的临床流行病学、临床表现及实验室检查资料进行回顾性分析.阳性率比较采用X~2检验.结果 408例风疹患者中,90.0%有与风疹患者接触史;75.5%为学生.71.1%患者发热,100.0%皮疹,90.0%淋巴结肿大.10.3 0A患者肝功能异常,11.8%心肌酶学升高,60.0%WBC减少,70.1%淋巴细胞增多.成人组(125例)与儿童组(283例)患者相比,1～2 d出疹的患者比例分别为102和264例(X~2=12.823,P＜0.01),1～3 d皮疹消退者分别为43和129例(X~2=4.447,P=0.035),散在性皮疹分别为108和263例(X~2=4.487,P=0.034),出现淡红色皮疹的分别为99和247例(X~2=4.392,P=0.036),符合由面部至躯干出疹顺序的分别为104和256例(X~2=4.402,P=0.036);PLT减少发生率分别为10.4%和2.5%(X~2=11.686,P＜0.01),肝功能异常率分别为17.6%和7.1%(X~2=10.416,P＜0.01),心肌酶异常率分别为20.0%和8.1%(X~2=11.774,P＜0.01);合并支气管肺炎患者比例分别为0.8%和6.7%(X~2=6.505,P=0.011),合并肝炎的分别为17.6%和7.1%(X~2=7.117,P=0.008),合并心肌炎的分别为18.4%和7.1%(X~2=11.811,P＜0.01),合并关节炎的分别为12.0%和2.8%(X~2=13.715.P＜0.01).结论 成人与儿童风疹患者相比,全身症状重,皮疹不典型病例多,肝脏和心脏酶谱异常的比例高,应引起重视.     

噬血细胞综合征30例临床分析

目的:探讨噬血细胞综合征(HPS)的临床特点、诊断、治疗以及预后的危险因素。方法:对我院30例HPS患者的病因、临床表现、实验室检查指标、治疗方案及临床转归进行回顾性分析。结果:30例HPS病因以感染最多见(30%),其中EB病毒感染达20%,然而病因不明者也高达56.7%。HPS临床表现为持续高热(100%)、脾肿大(93.3%)、全血细胞减少(83.3%)、乳酸脱氢酶(100%)及血清铁蛋白(100%)升高。肝功能损害(90%)及心肌酶谱(60%)升高也较为常见。30例经治HPS患者30d、100d、1年的生存率分别为36.7%、23.3%、10.0%。其中7例给予包含VP16的化疗方案,30d、100d、1年的生存率分别为85.1%、71.4%、42.9%。结论:HPS可由多种病因所致,EB病毒最为常见,临床表现多样。发热、血清铁蛋白、乳酸脱氢酶升高在诊断中的灵敏度较高。包含VP16的化疗方案是有效的治疗方案。     

Gilbert's syndrome co-existing with and masking hereditary spherocytosis

 An unusual case of co-existing Gilbert's syndrome and hereditary spherocytosis is reported. Diagnostic strategies are presented, and the literature is reviewed for simultaneous presence of these disorders. Received: 6 January 1997 / Accepted: 14 March 1997