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611.
利用常规心电图鉴别长QT综合征的基因类型 总被引:10,自引:0,他引:10
一、引言和背景 近年来 ,先天性长 QT综合征 ( long QT syn-drome,LQTS)的临床和基础研究在国际上取得了突破性进展。截止目前 ,已从 5个致病基因上鉴定出1 77个基因突变点 ,包括 KVLQTI( LQT1) 42 % ,HERG( LQT2 ) 45% ,SCN5A( LQT3 ) 8% ,KCNE1( LQT5) 3 %和 KCNE2 ( LQT6) 2 % [1] 。LQTS在遗传学上的多样性和复杂性又给临床诊治带来困难。基于目前的技术条件 ,对于一个临床上确诊的 LQTS家系 ,找出其病变基因一般需要 1~ 3年的时间 ,而且费用昂贵 ,其阳性检出率也只有 50 %左右。为了加速实验室的基因检出率… 相似文献
612.
目的分析血管紧张素原基因启动子区A-20C和A-6G单核苷酸多态性与蒙古族人群原发性高血压的相关性.方法实验于2005-08/2006-01在北京华大实验室完成.选取对象均为生活在内蒙古乌拉特后旗的蒙古族牧民,三代血亲内无其他民族.采用基因测序技术对内蒙古蒙古族人群中107例原发性高血压患者和108例正常对照者进行A-20C和A-6G基因分型,观察高血压组和正常对照组不同基因型的分布和等位基因频率的差异.结果①两组受试者在性别、年龄及吸烟、饮酒、体质量指数和l临床化验检查指标有较好的匹配(P均>0.05).②两组血管紧张素原基因A-20C位点AA,AC,CC基因型频率比较差异无显著性意义(高血压组分别为0.51,0.29,0.20;正常对照组分别为0.49,0.28,0.23,x2=0.395,P=0.529).A,C等位基因频率比较差异无显著性意义(高血压组分别为0.65,0.35;正常对照组分别为0.63,0.37,x2=0.015,P=0.904).③两组血管紧张素原基因A-6G位点AA,AG,GG基因型频率比较差异无显著性意义(高血压组分别为0.50,0.33,0.17;正常对照组分别为0.55,0.34,0.11,x2=1.924,P=0.165).A,G等位基因频率比较差异无显著性意义(高血压组分别为0.66,0.34;正常对照组分别为0.72,0.28,x2=1.728,P=0.189).④高血压组协同存在血管紧张素原基因A-20C基因型CC时,血管紧张素原基因A-6G基因型GG频率稍高于正常对照组,但差异无显著性意义(x2=2.395,P=0.122,OR=7.52,95%CI 0.014~1.250),高血压组G等位基因明显高于正常对照组(分别为0.37,0.22,x2=4.658,P=0.034),携带该等位基因的蒙古族人群发生原发性高血压的相对危险度升高(OR=2.80,95%CI.087~7.271).结论血管紧张素原基因A-20C和A-6G单核苷酸多态性与蒙古族人群原发性高血压相关,并可能具有协同作用. 相似文献
613.
G Cerisano L Bolognese N Carrabba P Buonamici GM Santoro D Antoniucci A Santini G Moschi PF Fazzini 《Circulation》1999,99(2):230-236
BACKGROUND: The relation between remodeling and left ventricular (LV) diastolic function has not yet been fully investigated. The aim of this study was to determine whether early assessment of Doppler-derived mitral deceleration time (DT), a measure of LV compliance and filling, may predict progressive LV dilation after acute myocardial infarction (AMI). METHODS AND RESULTS: Fifty-one patients (aged 61+/-11 years; 6 women) with anterior AMI successfully treated with direct coronary angioplasty underwent 2-dimensional and Doppler echocardiographic examinations within 24 hours of admission, at days 3, 7, and 30 and 6 months after the index infarction. Mitral flow velocities were obtained from the apical 4-chamber view with pulsed Doppler. End-diastolic volume index (EDVI) and end-systolic volume index (ESVI) were calculated with the Simpson's rule algorithm. Patients were divided according to the DT duration assessed at day 3 in 2 groups: group 1 (n=33) with DT >130 ms and group 2 (n=18) with DT =130 ms. Patency and restenosis rate at 6 months were similar between the 2 groups (94% group 1 vs 89% group 2; P=0.52; 27% group 1 vs 33% group 2; P=0.64, respectively). LV volume indexes were similar in both groups at baseline (EDVI: 71+/-3 group 1 vs 70+/-3 mL/m2 group 2, P=0.42; ESVI: 43+/-3 group 1 vs 48+/-3 mL/m2 group 2, P=0.13, respectively). From day 3 on, LV volume indexes progressively increased in group 2 and were significantly larger than those of group 1 at 6 months (LVEDVI 61+/-3 group 1 vs 104+/-6 mL/m2 group 2, P=0.00001; LVESVI 31+/-3 group 1 vs 73+/-6 mL/m2 group 2, P=0.00001, respectively). A significant inverse correlation was found between DT and changes in EDVI at 6 months (r=-0.68; P<0.0000001). By stepwise multiple regression analysis among several clinical, demographic, angiographic, and echocardiographic variables, DT was the most powerful predictor of EDVI changes at 6 months (P=0.02). CONCLUSIONS: These data suggest that early estimation (day 3) of Doppler-derived mitral DT provides a simple and accurate mean to predict late LV dilation after reperfused AMI. 相似文献
614.
Peripheral blood harvest of unaffected CD34+ CD38- hematopoietic precursors in paroxysmal nocturnal hemoglobinuria 总被引:1,自引:0,他引:1
Paroxysmal nocturnal hemoglobinuria (PNH) arises from somatic mutation of a bone marrow progenitor that disrupts glycosylinositol phospholipid (GPI) anchoring of cell surface proteins. We recently characterized the expression of GPI-anchored decay acclerating factor (DAF) and CD59 during hematopoietic development in PNH marrow. We found that, although a subset of early hematopoietic precursors identified by the CD34+CD38- phenotype exhibits normal DAF and CD59 expression, DAF and CD59 are absent on the majority of CD34+CD38- cells. Pluripotent CD34+CD38- hematopoietic stem cells normally circulate in the peripheral blood and can be collected by apheresis, cryopreserved, and later used for reconstitution of hematopoiesis. In this study, we examined the phenotypes of CD34+ cells that are released into the blood of PNH patients. Analyses of apheresis samples from three affected individuals showed discrete populations of circulating DAF+CD59+CD34+ and DAF-CD59- CD34+ cells. Variable proportions of CD34+CD38- cells were present within the peripheral blood CD34+ cells of each patient, but in all three cases the DAF+CD59+CD34+CD38- cell subset subset. Because CD34+ cells lacking CD38 antigen are highly enriched for self-renewing hematopoietic stem cells, these findings indicate that apheresis samples can serve as a source of unaffected stem cells for autologous marrow transplantation of PNH patients. 相似文献
615.
Parker PM; Chao N; Nademanee A; O'Donnell MR; Schmidt GM; Snyder DS; Stein AS; Smith EP; Molina A; Stepan DE 《Blood》1995,86(9):3604-3609
Thalidomide has been reported to be an effective agent for treatment of chronic graft-versus-host disease (CGVHD). To determine the efficacy of this agent in patients with refractory CGVHD a total of 80 patients who failed to respond to prednisone (PSE) or PSE and cyclosporine (CSA) were treated with thalidomide. Sixteen patients (20%) had a sustained response, 9 with a complete remission and 7 with a partial response. Twenty-nine patients (36%) had thalidomide discontinued because of side effects, which included sedation, constipation, neuritis, skin rash, and neutropenia. Side effects were reversible with drug discontinuation except for mild residual neuritis in one case. Rashes and neutropenia have not previously been reported as thalidomide side effects when used for CGVHD treatment. We conclude thalidomide is immunosuppressive and active in the treatment of CGVHD. A high incidence of reversible side effects limited dose intensity and reduced the number of patients who could benefit from treatment. 相似文献
616.
Marrow transplantation from unrelated donors for treatment of hematologic malignancies: effect of mismatching for one HLA locus 总被引:3,自引:5,他引:3
Beatty PG; Anasetti C; Hansen JA; Longton GM; Sanders JE; Martin PJ; Mickelson EM; Choo SY; Petersdorf EW; Pepe MS 《Blood》1993,81(1):249-253
One hundred twelve patients less than 36 years old received marrow grafts from unrelated donors as treatment for hematologic malignancy. Seventy donor/recipient pairs were phenotypically identical for HLA-A, - B, and -D, while 42 had a "minor" disparity at one HLA locus. There was an increase in the risk of acute graft-versus-host disease (GVHD) in patients receiving HLA-partially matched grafts compared with those receiving HLA-matched grafts (51% v 36% probability of grades III-IV acute GVHD). However, in this cohort of patients, there was no significant difference in survival (at 1.5 years, 46% v 51% for good- risk patients, 44% v 30% for poor-risk patients). This finding suggests that some degree of HLA disparity can be tolerated in young patients transplanted from unrelated donors for malignant disease, thus making transplantation an option available to larger numbers of patients. 相似文献
617.
Prognostic importance of chromosome number in 136 untreated children with acute lymphoblastic leukemia 总被引:1,自引:2,他引:1
Williams DL; Tsiatis A; Brodeur GM; Look AT; Melvin SL; Bowman WP; Kalwinsky DK; Rivera G; Dahl GV 《Blood》1982,60(4):864-871
Leukemia cell karyotypes were determined at diagnosis for 136 of 159 consecutive patients with acute lymphoblastic leukemia (ALL) who were followed for up to 35 mo. Ninety patients (67%) had abnormal karyotypes. Five chromosome categories were designated, based on the distribution of modal numbers: hyperdiploid greater than 50 (n = 41), hyperdiploid 47-50 (n = 18), pseudodiploid (n = 28), normal (n = 46), and hypodiploid (n = 3). Treatment response was assessed for the categories in terms of time to failure (induction failure, first relapse, or death). Children in the hyperdiploid greater than 50 category had the best responses to treatment, with only 2 failures, and those in the pseudodiploid category had the poorest (p less than 0.001). The remaining 3 chromosome categories had intermediate responses and formed a third prognostic group. This same influence of chromosome number on time to failure was evident within the 2 clinical prognostic groups: high risk, signified by a leukocyte count greater than 100 X 10(9)/liter, meningeal leukemia, mediastinal mass, or the presence of blasts that formed rosettes with sheep erythrocytes at 37 degrees C, and standard risk, indicated by the absence of these features. The influence of chromosome number on time to failure was also the same within the historically favorable prognostic group that had common ALL. Results of a multivariate analysis indicated that chromosome number was the strongest single predictor of outcome (p less than 0.001) and was the only variable that added significant prognostic information to leukocyte count (p less than 0.001). The combination of chromosome number and leukocyte count should more clearly distinguish patients with ALL at low or high risk of relapse. 相似文献