卡马西平所致药疹与CYP3A4*18B基因型的关联性初探

目的初步探讨卡马西平所致药疹与CYP3A4*18B基因型的关系,以寻找预测药疹的分子学手段。方法用PCR-RFLP法检测65例卡马西平所致药疹组患者(重型药疹患者11名,轻型药疹患者54名)、100例卡马西平耐受组患者及100例健康对照组患者的CYP3A4*18B(intron10,G20338→A)基因多态性。结果卡马西平所致药疹组CYP3A4*1/CYP3A4*1(G/G)基因型30例,CYP3A4*1/CYP3A4*18B(G/A)基因型30例,CYP3A4*18B/CYP3A4*18B(A/A)基因型5例,等位基因A频率为30.8%;卡马西平耐受组G/G基因型51例,G/A基因型42例,A/A基因型7例,等位基因A频率为28%;健康对照组G/G基因型44例,G/A基因型49例,A/A基因型7例,等位基因A频率为31.5%。各组间基因型与等位基因频率差异均无统计学意义。结论由于病例数较少,目前尚没有发现卡马西平药疹与CYP3A4*18B相关联。     

2例致死性家族性失眠症的临床特点、脑影像和朊蛋白基因分析

目的 探讨致死性家族性失眠症(fatal familial insomnia,FFI)的临床和生物学特征.方法 总结2例FFI患者的临床表现、治疗与转归特点,并追踪至死亡;对患者进行了较详细的生物学检查,包括生化、电生理、头颅MRI和PET-CT检查及朊蛋白(Prion Protein,PrP)基因测序.结果 2例FFI患者的共性:阳性家族史,临床主要表现睡眠紊乱伴精神、行为异常;影像检查示全脑轻度萎缩(额叶略明显),对称性顶、额叶及丘脑葡萄糖代谢降低;PrP基因532位碱基G突变为A和129MM纯合子变异.例1病情进展相对缓慢,死亡时总病程3年余,以运动系统损害突出,脑脊液14-3-3蛋白阴性;例2的病情进展迅速,死亡时总病程仅半年,以内分泌功能障碍突出,脑脊液14-3-3蛋白阳性,PrP基因173位碱基T-C变异.结论 2例FFI患者临床特点存在差异,可能与PrP基因突变及脑脊液14-3-3蛋白检测结果有关,有待进一步证实.     

癫痫妇女生殖内分泌状况调查及临床特征分析

目的 对育龄期癫痫妇女的生殖内分泌状况进行调查,并对生殖内分泌紊乱,尤其是多囊卵巢综合征(polycystic ovary syndrome,PCOS)患者的临床特征进行系统分析,便于发现问题,及时干预.方法 对139例育龄期女性癫痫患者进行人体测量学及体征评分、月经评估、性激素测定及盆腔超声检查,收集超重、中心性肥胖、月经稀发或闭经、黄体生成素(LH)/卵泡刺激素(FSH)、高雄激素血症、多囊卵巢(polycystic ovary,PCO)共6项指标,利用统计学方法 分析其生殖内分泌紊乱的特征.结果 139例育龄期女性癫痫患者年龄(22.5±7.0)岁,其中30岁以下的处于生殖能力高峰的育龄女性占84.89%;患者中PCOS患病率达12.75%,明显高于我国普通育龄女性PCOS患病率.诊断PCOS特异度高的指标分别为高雄激素血症(100%)、LH/FSH＞2(93%)、月经稀发或闭经(90%);诊断灵敏度高的指标分别为PCO(92%)、月经稀发或闭经(85%)、高雄激素血症(54%).LH[PCOS组(10.24±6.92)IU/L,非PCOS组(4.16±2.62)IU/L,t=-3.899]、LH/FSH值[PCOS组(2.20±1.16),非PCOS组(0.87±0.56),t=-4.240)和睾酮水平[PCOS组(1.07±0.35)ng/ml,非PCOS组(0.46±0.25)ng/ml,t=-4.918]在PCOS组和非PCOS组之间的差异具有统计学意义(P＜0.01).结论 性激素指标是诊断PCOS的客观指标;应重视对女性癫痫患者进行身高、体重、腹围、月经史、卵巢B超等指标的监测.当患者存在可疑生殖内分泌紊乱的临床特征时,必须检查性激素,以便及时发现异常,早期干预.

Abstract：

Objective To investigate the reproductive endocrine status of women with epilepsy at childbearing age and to systematically analyze the clinical features of reproductive endocrine disorders,especially polycystic ovarian syndrome (PCOS),to facilitate early detection and timely intervention.Methods In this study,scoring of anthropometry and physical signs,menstrul assessment,examination of sex hormone and pelvic ultrasound in women with epilepsy at childbearing age were performed,and the data such as overweight,central obesity,oligo/amenorrhea,luteinizing hormone (LH)/follicule-stimulating hormone (FSH),hyperandrogenism and polycystic ovary (PCO) were collected. The characteristics of their reproductive endocrine hormone disorders were analyzed statistically. Results The age of these patients was (22. 5 ± 7.0 ) years,and women younger than 30 years old and at their peak fertility accounted for 84. 89%. The prevalence rate of PCOS in women with epilepsy at childbearing age (12. 75% ) was significantly higher than that of ordinary women at childbearing age (7.2%) in China.Highly specific indicators for PCOS were hyperandrogenism (100%),LH/FSH ＞ 2 (93%) and oligo/amenorrhea (90%),whilst the highly sensitive indicators for PCOS were PCO (92%), oligo/amenorrhea (85%) and hyperandrogenism (54%). This study revealed statistically significant difference in LH,LH/FSH and testosterone (T) between PCOS group (LH: (10.24 ± 6.92) IU/L; LH/FSH;(2.20 ± 1.16);T: ( 1.07 ± 0. 35) ng/ml) and non-PCOS group ( LH: (4. 16 ± 2.62 ) IU/L; LH/FSH:( 0. 87 ± 0. 56 );T: (0. 46 ±0. 25) ng/ml,t = -3. 899,-4. 240 and -4. 918 respectively,all P ＜0. 01 ). Conclusions Hormone indices are objective indicators for the diagnosis of PCOS. In clinical practice,attention should be paid to height,weight,abodominal circumference,menstrul history and ultrasound examination of the ovary in women with epilepsy.When reproductive endocrine hormone disorders are suspected from clinical features,the sex hormones (T,LH,and FSH ) should be checked to allow timely detection and early interventions.     

丙戊酸单药治疗与癫痫患者血浆同型半胱氨酸水平间关系的Meta分析

目的分析癫痫患者血浆同型半胱氨酸水平变化与丙戊酸单药治疗间的关系。方法选择epileDsv、valproate、homocysteine和epilep。为检索词,计算机检索1990年1月-2013年8月美国国立医学图书馆、科学引文索引数据库、荷兰医学文摘等数据库,获得丙戊酸单药治疗与癫痫患者血浆同型半胱氨酸水平间关系的相关英文文献,均为丙戊酸单药治疗的癫痫患者与正常对照受试者血浆同型半胱氨酸水平比较的病例．对照临床研究。通过Newcastle—Ottawa量表独立进行文献质量评价和数据提取,Stata12．0统计软件行Meta分析。结果共纳入符合条件的英文文献8篇,包括266例行丙戊酸单药治疗的癫痼患者和489例正常对照受试者,所有纳入文献质量评分均〉6分。Meta分析显示,丙戊酸单药治疗组患者血浆同型半胱氨酸水平显著高于正常对照组[标准化均数差（SMD）：0．620,95％CI：0．320-0．920;P=0．000];经异质性检验存在显著异质性（I^2=65．600％,P=0．005）,根据不同地区和受试者年龄差异行进一步亚组分析,结果显示西亚组癫痫患者异质性风险（I^2=47．400％,P=0．107）较整体（I^2=65．600％,P=0．005）降低。采用敏感性分析评价Meta分析之稳定性,当任何一项研究被剔除后,相应的SMD值均不发生变化,表明分析结果稳定性良好。结论丙戊酸单药治疗可显著增加癫痫患者血浆同型半胱氨酸水平,后者是否受种族因素的影响尚待进一步研究。