Loss of function,missense, and intronic variants in NOTCH1 confer different risks for left ventricular outflow tract obstructive heart defects in two European cohorts

Loss of function variants in NOTCH1 cause left ventricular outflow tract obstructive defects (LVOTO). However, the risk conferred by rare and noncoding variants in NOTCH1 for LVOTO remains largely uncharacterized. In a cohort of 49 families affected by hypoplastic left heart syndrome, a severe form of LVOTO, we discovered predicted loss of function NOTCH1 variants in 6% of individuals. Rare or low-frequency missense variants were found in 16% of families. To make a quantitative estimate of the genetic risk posed by variants in NOTCH1 for LVOTO, we studied associations of 400 coding and noncoding variants in NOTCH1 in 1,085 cases and 332,788 controls from the UK Biobank. Two rare intronic variants in strong linkage disequilibrium displayed significant association with risk for LVOTO amongst European-ancestry individuals. This result was replicated in an independent analysis of 210 cases and 68,762 controls of non-European and mixed ancestry. In conclusion, carrying rare predicted loss of function variants in NOTCH1 confer significant risk for LVOTO. In addition, the two intronic variants seem to be associated with an increased risk for these defects. Our approach demonstrates the utility of population-based data sets in quantifying the specific risk of individual variants for disease-related phenotypes.     

含左氧氟沙星及卷曲霉素方案治疗耐多药肺结核近期疗效分析

目的　观察和评价含左氧氟沙星和卷曲霉素联合化疗方案在耐多药肺结核 (MDR PTB)治疗中的疗效。方法　将 177例MDR PTB患者分为治疗组 88例和对照组 89例。化疗方案 :治疗组以左氧氟沙星和卷曲霉素为主 ,联合利福喷汀、异烟肼、对氨基水杨酸钠、吡嗪酰胺 ;对照组用链霉素、乙胺丁醇 ,联用药物同治疗组 ,疗程均为 2 1个月。结果　共有 16 1例患者完成化疗疗程 ,治疗组 82例 ,痰菌阴转率 83% ;对照组 79例 ,痰菌阴转率 5 8% ;痰菌阴转率治疗组明显高于对照组 (P <0 0 1) ;治疗组病灶显效率 5 0 % ,空洞闭合率 6 3% ,治疗组优于对照组 (P <0 0 1) ;治疗组的药物不良反应率为 31% ,对照组为 35 % ,两组比较差异无显著性 (P >0 0 5 )。结论　含左氧氟沙星和卷曲霉素的方案治疗MDR PTB ,有助于痰菌阴转和病变吸收好转 ,药物不良反应低 ,值得在临床上推广应用     

创伤性休克病人的早期急救护理体会

目的:讨论在院前和急诊科对创伤性休克病人施行早期急救护理,对挽救病人的生命及伤情预后有重要的意义.方法:对我科1997年2月至2001年4月27例创伤性休克病人进行早期,快速,积极的补液,输血增加有效循环量,监测生命体征等综合性抢救治疗与护理措施.结果:经早期积极急救护理,26例病人收缩压维持在60mmHg以上,意识清醒,脉搏有力,转入手术室或专科治疗,1例病人伤势严重抢救无效死亡.结论:创伤性休克病人,伤势复杂,死亡率高,伤后早期院前与急诊科的有效救护,是提高抢救成功率的关键.