奥卡西平诱发的Stevens-Johnson综合征的临床特点及基因表达

目的 探讨奥卡西平诱发的Stevens-Johnson综合征(SJS)的临床特点及易感基因HLA-B*1502基因检测的意义.方法 回顾性分析1例由奥卡西平诱发的SJS患儿的临床表现、实验室检查以及基因学检测特点,同时对SJS的流行病学、病因学及发病机制等相关文献进行复习,尤其是对芳香族抗癫药物诱发SJS的基因学研究进行分析.结果 本文1例继发性癫患儿在奥卡西平加量治疗过程中出现发热、皮疹,进而发展至大疱及脓疱,并出现表皮松弛脱落.实验室检查结果提示外周血白细胞增多、红细胞沉降率升高、ALT升高(337 U·L-1)、AST升高、尿蛋白++.结合该患儿的临床资料判断皮损为奥卡西平所致.利用基因学检测提示HLA-B*1502阳性.该患儿停用奥卡西平后改为托吡酯等治疗,住院2周后体温正常,皮疹消退,临床痊愈出院.结论 奥卡西平诱发的SJS是临床少见的严重药物不良反应,典型的临床表现为严重的皮损、发热及内脏器官损害,基因学检查显示该药物不良反应和HLA-B*1502基因呈显著相关,对HLA-B*1502易感基因进行检测可预测芳香族抗癫药物诱发的此项不良反应.     

抗癫(疒间)药物与Stevens-Johnson综合征和中毒性表皮坏死溶解症

Stevens-Johnson综合征(SJS)和中毒性表皮坏死溶解症(TEN)是两种严重的变应性疾病,其临床症状非常相似,互有交叉,均表现为高热、全身不适及快速进行性的皮肤斑丘疹和疱疹,常伴有黏膜损伤及内脏损害.导致SJS和TEN的关键性病理环节是外周血单个核细胞分泌的可溶性Fas配体与角化细胞表面表达的Fas受体相互作用,从而导致角化细胞凋亡及表皮损伤.SJS和TEN与芳香族抗癫(疒间)药物(苯巴比妥、苯妥英钠、卡马西平)的应用密切相关,也可由新型抗癫(疒间)药物,如拉莫三嗪引起.研究显示,在抗癫(疒间)治疗的最初8周内发生SJS和TEN的危险性最高.由于芳香族抗癫(疒间)药物之间的交叉过敏性,一旦发生SJS和TEN而又必须继续抗癫(疒间)治疗时,可改用丙戊酸钠或新型抗癫(疒间)药物,由于它们的代谢途径和代谢产物与前者不同,通常是安全的.     

非综合征型唇腭裂易感基因位点研究进展

非综合征型唇腭裂是一种常见的出生缺陷,病因复杂,目前普遍认为是遗传因素和环境因素共同作用的结果.先天性唇腭裂易感基因是自全基因组测序以来的研究热点,筛选出的众多候选基因正不断被基因位点多态性检测、病例对照研究、Meta分析等方法验证,但结果迥异.该文就近年来研究较多的非综合征型唇腭裂易感基因以及环境因素与唇腭裂相互关系方面的研究进展展开综述.     

穿孔素基因多态性与儿童噬血细胞综合征的相关性研究

目的了解穿孔素基因(PRF1)多态性在噬血细胞综合征(HLH)患儿中的分布情况,探讨PRF1基因多态性与HLH是否存在易感相关性。方法收集2009年1月至2013年12月确诊为HLH的48例患儿(HLH组)及100名健康体检儿童(对照组)的临床资料,应用聚合酶链反应(PCR)结合直接测序方法对两组患儿的PRF1基因编码区(包括3个外显子和2个内含子)进行基因多态性位点筛查。结果 48例HLH患儿中,在PRF1基因编码序列中共发现3个SNP位点,而在非编码序列中共发现7个SNP位点;PRF1基因非编码序列中还有2个SNP位点rs10999426和rs10999427分别仅在5例对照组儿童中发现(5%);以上12个SNP位点在HLH组和对照组中的基因型及等位基因频率分布差异均无统计学意义(P0.05)。连锁不平衡分析提示rs10999426和rs10999427紧密连锁(D=1,r2=1),但上述2个位点构建的A-T单体型在HLH组和对照组中的分布频率差异无统计学意义(P0.05)。结论 PRF1基因多态性与HLH发病存在易感相关性的可能性不大;rs10999426和rs10999427存在连锁不平衡关系,其构建的A-T单体型虽仅在对照组中发现,但发生率低,可能不是家族性HLH的保护性因素。     

多药耐药基因在肾病综合征患儿外周血单个核细胞中的表达研究

目的 探讨肾病综合征(NS)患儿外周血单个核细胞(PBMC)中多药耐药基因(MDR1)的表达与不同激素(GC)效应患儿的关系.方法 收集2007年5月-2008年2月收治的原发特发性肾病(PNS)患儿47例,按照GC对患儿的效应分为GC敏感组(SSNS)、GC耐药组(SRNS)两组,根据GC敏感患儿临床疗效又分为非频反复组(NFR)和频反复(FR)及GC依赖(SD)组(简称FR&SD)两组,采用荧光定量PCR方法检测NS患儿的外周血中PBMC中MDR1 mRNA表达水平,以12例健康正常儿童为对照.结果 GC治疗后NS患儿PBMC中MDR1 mRNA的表达均高于正常对照组,而SRNS组PBMC中MDR1 mRNA的表达高于SSNS组;且FR&SD组患儿MDR1 mRNA的表达量要比NFR更高;SSNS患儿MDR1 mRNA的表达与缓解时间、复发次数、病程呈正相关.尤其是FR&SD组患儿MDR1 mRNA的表达与其缓解时间呈正相关(r=0.796,P<0.01).结论 GC治疗后NS患儿MDR1的高表达与GC耐药、GC依赖和复发有关.     

哮喘易感基因多态性与哮喘预测指数阳性婴幼儿喘息的相关性

目的探讨3个哮喘易感基因单核苷酸多态性(SNPs)位点与哮喘预测指数(API)阳性婴幼儿喘息的相关性。方法将201例喘息婴幼儿分为API阳性组(68例)和API阴性组(133例)。选取儿童哮喘易感基因SNPs位点ADRβ2R16G、FcεR1 E237G和IL13 A2044G,采用TaqMan探针法对两组患儿进行基因分型,分别比较上述基因多态性位点在阳性组和阴性组间的分布差异。结果多态性位点FcεR1 E237G AG杂合子在API阳性组的频率明显高于阴性组(分别为41.2%和24.1%),差异有统计学意义(χ2=6.30,P=0.012,OR=2.21,95%CI=1.18～4.13),而ADRβ2 R16G和IL13 A2044G位点在两组间的分布差异无统计学意义(χ2=1.72、1.85,P均>0.3)。结论儿童哮喘易感基因单核苷酸多态性FcεR1 E237G AG杂合子与API阳性患儿喘息相关,未发现ADRβ2 R16G和IL13 A2044G多态性与API阳性患儿喘息相关。     

儿童遗传性肿瘤易感综合征和TP53基因种系突变

儿童遗传性肿瘤易感综合征是由于肿瘤相关基因的种系突变所导致的一类遗传性疾病,患者具有明显的肿瘤易感倾向。TP53基因的种系突变占到所有遗传性肿瘤的20%~30%,是最常见的肿瘤突变基因。通过对TP53基因的检测,可以帮助临床医师更好的对遗传性肿瘤患者及家庭成员进行管理。     

ACE2基因多态性与儿童原发性肾病综合征的相关性研究

目的血管紧张素转换酶2(ACE2)基因多态性与高血压病、糖尿病肾病等多种疾病相关,是否参与儿童原发性肾病综合征(PNS)的发病尚不明确,该研究探讨广东汉族儿童ACE2基因A9570G多态性与PNS的相关性。方法选取广东汉族PNS患儿66例为肾病组,健康体检者60例为对照组,采用聚合酶链反应-限制性核酸内切酶片段长度多态性技术分析肾病组与对照组的ACE2基因A9570G基因型分布和等位基因频率。结果在女性和男性,两组间等位基因频率及基因型分布差异均无统计学意义(P0.05)。肾病组按糖皮质激素治疗反应分为激素敏感组和激素耐药组,亚组分析发现,在女性,激素敏感组GG基因型频率低于激素耐药组(17%vs 45%,P0.05),激素敏感组G等位基因频率亦低于激素耐药组(31%vs 61%,P0.05);在男性,激素敏感组G基因型/G等位基因频率低于激素耐药组(36%vs 64%,P0.05)。结论 ACE2基因A9570G多态性与儿童PNS的发生无明确关联,但可能与PNS患儿对糖皮质激素治疗的反应有关,G等位基因可能是儿童PNS激素耐药的遗传易感因素。     

TIM-1基因多态性与原发性肾病综合征的关系

目的 研究TIM-1基因多态性与儿童原发性肾病综合征(PNS)的相关性.方法 采用病例对照研究,选取PNS患儿57例,应用PCR-限制性片段长度多态性分析、PCR-聚丙烯酰胺凝胶电泳分析、基因测序技术检测PNS患儿和144例健康儿童(健康对照组)的TIM-1基因启动子区-1454G/A的SNP与外显子4 ins/del多态性,计算基因型和等位基因频率.结果 健康对照组TIM-1启动子区-1454位G/G、G/A和A/A基因型频率分别为0.608、0.328、0.064,而PNS组频率分别为0.772、0.228、0.000,其基因型频率与健康对照组比较差异有统计学意义(χ2=6.561,P=0.038),且PNS组患儿携带-1454G等位基因的频率增高(OR=2.295,95%CI:1.199～4.390,P=0.011);健康对照组TIM-1外显子4 del/del、del/ins和ins/ins基因型频率分别为0.611、0.340、0.049,而PNS组频率分别为0.579、0.368、0.053,其基因型频率与健康对照组比较差异无统计学意义(χ2=0.176,P=0.916).结论 TIM-1基因启动子-1454G/A的单核苷酸多态性可能与儿童PNS的易感性相关.     

原发性肾病综合征与细胞毒性T淋巴细胞相关抗原-4基因启动子区-318位点基因多态性的相关性

目的探讨细胞毒性T淋巴细胞相关抗原-4(CTLA-4)与糖皮质激素(GC)耐药型原发性肾病综合征(PNS)中系膜增生性肾小球肾炎(MsPGN)的相关性。方法应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测36例PNS-MsPGN患儿和30例正常对照儿童CTLA-4基因启动子区-318位点基因型。结果肾病组CTLA-4基因启动子区-318位点基因型频率分别为CC型38.9%、TC型61.1%和TT型0,等位基因频率为C等位基因69.4%、T等位基因30.6%。肾病组各基因型及等位基因频率与对照组相比均无显著差异(P均>0.03)。结论CTLA-4基因启动子区-318位点基因C/T双态性同GC耐药型PNS-MsPGN患儿无相关性,提示该基点基因多态性可能不参与GC耐药型PNS-MsPGN的发病机制及耐药机制。     

丙戊酸钠致Stevens-Johnson综合征1例并文献复习

目的 探讨丙戊酸钠单药治疗致Stevens-Johnson综合征(SJS)的临床诊断与治疗措施.方法 通过对1例丙戊酸钠致SJS的临床表现及辅助检查、治疗效果进行归纳总结,结合文献进行综合分析.结果 患儿为3.5岁女童,初次诊断癫(痫),口服丙戊酸钠单药治疗14 d后,面部开始出现红色斑丘疹,逐渐蔓延至躯干、四肢,瘙痒明显.皮疹迅速加重,融合成片,出现疱疹,伴口唇黏膜肿胀和破溃.皮疹出现2d后体温开始升高,最高达39.5 ℃.体检发现淋巴结大、肝右肋下2 cm.辅助检查示ALT 139 IU/L,血氨108 μmol/L.立即停用丙戊酸钠,予甲泼尼龙15 mg/(kg·d)冲击治疗.2d后体温下降至正常,7d后皮疹逐渐消退,肝功能恢复正常.结论 保持对丙戊酸钠致SJS的高度警惕性是临床早期诊断和治疗的关键.早期停用致敏药物并予足量皮质类固醇激素治疗可取得良好效果.     

Drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in children: 20 years study in a tertiary care hospital

Background:Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe life-threatening skin conditions.The most common cause of these manifestations is medications.Beside discontinued of the culprit drug,systemic corticosteroids were used as a primary treatment option among pediatric population.This study aimed to explore causative drugs (drug group/ latent period),treaments,complications,and treatment outcome (morbidity,mortality,length of hospital stay) of SJS and TEN in children.Methods:A retrospective chart was reviewed during the period of 1992 to 2012 at Srinagarind Hospital,Faculty of Medicine,Khon Kaen University,Thailand.SJS and TEN were clinically diagnosed and confirmed by pediatric dermatologists.Other possible causes other than drug-induced SJS and TEN were excluded.Results:A total of 30 patients was recorded,including 24 (80％) SJS patients and 6 (20％) TEN patients.The mean age was 6.9 years (SD 4.4).Male to female ratio was 1.5:1.Antiepileptic drug group was the most common causative drug (n=18,60％),followed by antibiotic drug group (n=8,26.6％),and others (n=4,13.3％) which included nonsteroidal antiinflammtory drugs (NSAIDs) and chemotherapy drugs.Systemic corticosteroids were used in 29 patients (96.6％).Intravenous immunoglobulin was used in one TEN patient (3.3％).There was a medium correlation between time to treatment (systemic corticosteroids) and the length of hospital stay (Spearman correlation coefficient=0.63,P=0.005).Two TEN patients (6.6％) died.Conclusions:Carbamazepine was the most common causative drug of SJS and TEN in our study.The severity of skin detachment is not correlated to severity of ocular findings.However,the persistent of ocular complications up to one year is suggested for promptly appropriate ocular treatment in all SJS and TEN patients.Our data suggested that early administration of systemic corticosteroid may reduce the length of hospital stay and should be considered for the treatment of pediatric drug-induced SJS and TEN.     

���ݱ����������B-18�����̬�������������������ۺ����׸��Թ�ϵ����

目的了解肺泡表面活性物质蛋白B(SPB)-18基因多态性与新生儿呼吸窘迫综合征(NRDS)易感性的关系。方法 (1)高分辨率熔解曲线法和基因测序法检测2009年5月至2010年12月武汉市妇女儿童医疗保健中心和华中科技大学同济医学院附属同济医院100例NRDS患儿及186名同胎龄儿SPB-18多态性位点基因型和等位基因的差异。(2)应用蛋白印记法分析技术(WB)检测2009年5月至2010年12月武汉市妇女儿童医疗保健中心31例基因型为SPB-18AA和36例SPB-18CC的足月新生儿支气管肺泡灌洗液中SPB水平,比较两组之间差异。结果 (1)SPB-18A/C基因在NRDS组和对照组中AA、AC、CC的基因型频率分别为11.0%、40.0%、49.0%和6.5%、31.7%、61.8%,两组基因型分布差异无统计学意义(χ2=4.83,P>0.05。);但等位基因A频率在NDRS组和对照组间分别为31.0%和22.3%,差异有统计学意义(χ2=5.19,P<0.05)。(2)基因型为SPB-18AA者比CC者支气管肺泡灌洗液中SPB蛋白水平低。WB灰度值分别为8002.3±452.9和14339.2±107...     

MPO基因多态性与川崎病及其临床表型的相关性分析

目的探讨我国中部汉族人群中MPO基因的单核苷酸多态性(SNP)位点(rs2333227,—643G/A)多态性与川崎病(KD)及其临床特点的相关性。方法采用病例对照研究方法,选取237例典型KD患儿和249例正常儿童作为研究对象。利用PCR-RFLP的方法测定SNP位点多态性分布;并收集KD患儿临床资料。结果 KD患儿SNP位点(rs2333227)的基因型(GG、GA、AA)频率与正常儿童相比差异有统计学意义(P=0.039),且等位基因频率差异亦存在统计学意义(P=0.012),G等位基因为风险因子。该SNP位点GG基因型的患儿手足水肿的比例高于其他基因型的患儿,差异具有统计学意义(P=0.029)并与腹腔积液的特点相关(P=0.028);该SNP位点多态性与结膜充血、皮疹、冠状动脉损伤肝脏肿大、脾脏肿大、小叶性肺炎等影像学特点无关(P0.05)。结论 MPO基因SNP位点(rs2333227)与KD的易感性相关,G等位基因为风险因子;且该SNP位点多态性可能与部分临床特点相关。     

IL-17F基因多态性和儿童哮喘易感性相关性分析

目的探讨IL-17F基因多态性和哮喘易感性、IL-17水平的关系。方法选择133例哮喘患儿和114例对照儿童,测定IL-17F基因rs763780、rs1889570位点多态性,并分析其与儿童支气管哮喘易感性及外周血IL-17水平的相关性。结果哮喘组和对照组两组间等位基因、基因型频数分布在rs1889570位点的差异有统计学意义(P=0.049、P=0.043),哮喘组携带A等位基因者明显高于对照组(OR=1.43,95%CI:1.001～2.004,P=0.049);rs763780位点等位基因、基因型分布在两组间的差异均无统计学意义(P0.05)。哮喘组rs763780和rs1889570位点各基因型间IL-17水平差异均无统计学意义(P0.05)。结论 IL-17F基因rs1889570位点与儿童哮喘易感性有关,携带A等位基因者发生哮喘的危险性高。     

Association between white blood cell count and components of metabolic syndrome

Background:  Components of metabolic syndrome (MetS) were found to be associated with several inflammatory factors including white blood cell count (WBCC), which is an easily available test in clinical practice. In the present study, the relationships between WBCC and MetS components were investigated in children.
Methods:  A total of 288 Taiwanese children, under 10 years old, with normal WBCC, were enrolled in the study. They were divided into quartiles according to WBCC (lowest, WBCC1; highest, WBCC4). The mean values of each MetS component for every group were compared in boys and girls separately. Multivariate linear regression between the WBCC and the MetS components after adjusting for age and body mass index (BMI) were also evaluated.
Results:  In group comparison, only the high-density lipoprotein-cholesterol (HDL-C) was found to be significantly lower in WBCC4 in boys. Other components were not different. After multivariate linear regression, WBCC was negatively correlated to HDL-C and positively to BMI in boys. Although not significant, similar relationships were also observed in girls. Interestingly, borderline positive correlation was noted between triglyceride (TG) and WBCC in girls.
Conclusion:  BMI was positively and HDL-C was negatively related to WBCC in boys. A similar trend could also be observed in girls but without significance. Borderline significant correlation between TG and WBCC was noted in girls. These findings suggest that cardiovascular risks might commence even in childhood. Early detection of children with these abnormalities may help to prevent cardiovascular disease and diabetes in adolescence or even adulthood.     

血清高迁移率族蛋白B1与新生儿呼吸窘迫综合征的相关性研究

目的探讨血清高迁移率族蛋白B1(HMGB1)水平与新生儿呼吸窘迫综合征(NRDS)的相关性。方法选取NRDS患儿35例(观察组)及正常新生儿35例(对照组),收集两组新生儿生后12~24 h内外周静脉血,采用酶联免疫法(ELISA)检测两组新生儿血清HMGB1水平。结果 NRDS患儿血清HMGB1水平高于对照组(P0.05),重度NRDS患儿血清HMGB1水平高于轻度患儿(P0.05),死亡的NRDS患儿血清HMGB1水平高于存活患儿(P0.05)。ROC曲线分析显示预测NRDS的AUC值为0.846(95%CI:0.755~0.936),血清HMGB1 625.3 pg/m L为预测NRDS的最佳界值,预测NRDS患儿死亡风险的AUC为0.916(95%CI:0.813~1.000),血清HMGB1 772.2 pg/L为预测NRDS患儿死亡的最佳界值。结论 NRDS患儿血清HMGB1水平显著升高,血清HMGB1可较好地预测NRDS的发生及预后。     

Association between sudden infant death syndrome and diphtheria-tetanus-pertussis immunisation: an ecological study

Background

Sudden infant death syndrome (SIDS) continues to be one of the main causes of infant mortality in the United States. The objective of this study was to analyse the association between diphtheria-tetanus-pertussis (DTP) immunisation and SIDS over time.

Methods

The Centers for Disease Control and Prevention provided the number of cases of SIDS and live births per year (1968–2009), allowing the calculation of SIDS mortality rates. Immunisation coverage was based on (1) the United States Immunization Survey (1968–1985), (2) the National Health Interview Survey (1991–1993), and (3) the National Immunization Survey (1994–2009). We used sleep position data from the National Infant Sleep Position Survey. To determine the time points at which significant changes occurred and to estimate the annual percentage change in mortality rates, we performed joinpoint regression analyses. We fitted a Poisson regression model to determine the association between SIDS mortality rates and DTP immunisation coverage (1975–2009).

Results

SIDS mortality rates increased significantly from 1968 to 1971 (+27% annually), from 1971 to 1974 (+47%), and from 1974 to 1979 (+3%). They decreased from 1979 to 1991 (−1%) and from 1991 to 2001 (−8%). After 2001, mortality rates remained constant. DTP immunisation coverage was inversely associated with SIDS mortality rates. We observed an incidence rate ratio of 0.92 (95% confidence interval: 0.87 to 0.97) per 10% increase in DTP immunisation coverage after adjusting for infant sleep position.

Conclusions

Increased DTP immunisation coverage is associated with decreased SIDS mortality. Current recommendations on timely DTP immunisation should be emphasised to prevent not only specific infectious diseases but also potentially SIDS.