A novel 196Leu to Pro substitution in the beta3 subunit of the alphaIIbbeta3 integrin in a patient with a variant form of Glanzmann thrombasthenia

Glanzmann thrombasthenia (GT) is an inherited disorder where an absence of platelet aggregation is associated with quantitative or qualitative abnormalities of the alphaIIbbeta3 integrin. In rare patients, amino acid substitutions have provided information on the functional significance of specific domains within alphaIIb or beta3. We now report an elderly male GT patient (R.M.) from the south west of France whose platelets possess a small residual expression of alphaIIbbeta3. Furthermore, the integrin failed to undergo the necessary conformational changes following platelet activation to permit the binding of fibrinogen or activation-dependent monoclonal antibodies despite the presence of an RGD-binding site. Screening of the alphaIIb and beta3 genes by PCR-SSCP revealed a heterozygous mutation at position 685 in exon 5 of the beta3 gene leading to a 196Leu to Pro substitution. 196Leu is a highly conserved amino acid of beta3. The other beta3 allele appeared to be silent. This mutation, inherited from his mother and present in other family members with intermediate levels of alphaIIbbeta3, was close to the MIDAS-like domain of beta3, a fact that appears to explain its effect on alphaIIbbeta3 activation and fibrinogen binding.     

HIV incidence, retention rate, and baseline predictors of HIV incidence and retention in a prospective cohort study of injection drug users in Xinjiang, China.

OBJECTIVE: To determine HIV seroincidence, study participant retention rate, and baseline predictors of HIV incidence and study retention among high-risk injection drug users (IDUs) in Xinjiang, China. METHODS: A total of 508 eligible seronegative high-risk IDUs were enrolled. Study participants were tested for HIV-1 and counseled at the baseline, 6-month, and 12-month follow-up visits. Sociodemographic and behavioral data were collected during each study visit. The HIV-1 incidence rate and the retention rate were analyzed as a function of sociodemographic, behavioral, and recruitment variables. RESULTS: At 12 months of follow-up, the HIV-1 incidence rate was 8.8 per 100 person-years (95% CI 6.3-12.0%) and the participant retention rate was 93%. Marital status at baseline was the only predictor of HIV incidence. No baseline variables were predictive of study retention. CONCLUSIONS: HIV incidence is high among IDUs in Xinjiang, China. Baseline predictors of incidence and retention were minimal. The participant retention rate in this study is promising for the undertaking of future HIV intervention studies.     

黄芪和丹参注射液联用对早期糖尿病肾病血液流变学和肾功能的影响

目的　探讨黄芪和丹参注射液联用对早期糖尿病肾病 (EDN)血液流变学和肾功能的影响。方法　将2 0 0 1- 0 3～ 2 0 0 4 - 0 3广东省东莞市人民医院 16 0例EDN患者随机分为治疗组和对照组各 80例。两组均采用饮食控制和糖尿病常规治疗。治疗组加用黄芪和丹参注射液治疗 ,疗程 4周。结果　治疗组血液流变学各项指标较治疗前显著下降 (P <0 0 5或P <0 0 1) ;尿白蛋白排泄率 (UAER)、血肌酐 (SCr)、尿素氮 (BUN)和血脂明显下降 (P <0 0 5或P <0 0 1) ,且明显优于对照组 (P <0 0 1或P <0 0 5 )。结论　黄芪和丹参注射液联用能改善EDN患者的血液流变学、血脂和微循环 ,减少尿白蛋白的排出 ,减轻肾损害 ,改善肾功能。     

Antioxidant gene polymorphisms and susceptibility to a rapid decline in lung function in smokers

Oxidative stress is believed to play an important role in the pathogenesis of smoking-induced chronic obstructive pulmonary disease. We hypothesized that polymorphisms of antioxidant genes glutathione S-transferase M1 (GSTM1), GSTT1, GSTP1, and heme oxygenase-1 (HMOX1) would be associated with susceptibility to accelerated decline of lung function in smokers. We genotyped 621 subjects (299 rapid decliners [change in forced expiratory volume in 1 second (DeltaFEV(1)) = -152 +/- 2.5 ml/year] and 322 nondecliners [DeltaFEV(1) = +15 +/- 1.5 ml/year]) selected from among smokers followed for 5 years in the National Heart, Lung, and Blood Institute Lung Health Study. Because genotype frequencies were different between ethnic groups, we limited the association study to 594 whites (286 rapid decliners and 308 nondecliners). None of the genotypes studied had a statistically significant effect on decline of lung function when analyzed separately. There was an association between rapid decline of lung function and presence of all three GST polymorphisms (odds ratio [OR] = 2.83; p = 0.03). A combination of a family history of chronic obstructive pulmonary disease with GSTP1 105Ile/Ile genotype was also associated with rapid decline of lung function (OR = 2.20; p = 0.01). However, due to the multiple comparisons that were made, these associations may represent type 1 error. There was no association between HMOX1 (GT)n alleles and the rate of decline in lung function in smokers.     

Age at first drink and the first incidence of adult-onset DSM-IV alcohol use disorders

Background: Existing studies of the association between age at first drink (AFD) and the risk of alcohol use disorders (AUD) suffer from inconsistent levels of control and designs that may inflate associations by failure to control for duration of exposure to risk. Methods: This study examined associations between AFD (ages <15 and 15–17 vs. 18+ years) and first incidence of DSM‐IV alcohol dependence, abuse, and specific AUD criteria over a 3‐year follow‐up in a longitudinal study of U.S. drinkers 18 years of age and older at baseline (n = 22,316), controlling for duration of exposure, family history, and a wide range of baseline and childhood risk factors. Results: After adjusting for all risk factors, the incidence of dependence was increased for AFD < 15 years (OR = 1.38) and for women only with AFD at ages 15 to 17 (OR = 1.54). The incidence of abuse was increased at AFD <15 and 15 to 17 years (OR = 1.52 and 1.30, respectively). Most dependence criteria showed significant associations with AFD, but hazardous drinking and continued drinking despite interpersonal problems were the only abuse criteria to do so. All associations were nonsignificant after controlling for volume of consumption, except that AFD at all ages <18 combined was associated with a reduced likelihood of impaired control, and AFD at ages 15 to 17 was associated with lower odds of drinking more/longer than intended among heavy‐volume drinkers. In a population of low‐risk drinkers that excluded those with positive family histories, personality disorders, and childhood risk factors, there were strong associations between early AFD (<18) and the incidence of dependence (OR = 3.79) and continued drinking despite physical/psychological problems (OR = 2.71), but no association with incidence of abuse. Conclusions: There is a robust association between AFD and the risk of AUD that appears to reflect willful rather than uncontrolled heavy drinking, consistent with misuse governed by poor decision‐making and/or reward‐processing skills associated with impaired executive cognitive function (ECF). Additional research is needed to determine causality in the role of impaired ECF, including longitudinal studies with samples of low‐risk adolescents.     

罗格列酮联合阿司匹林对糖尿病伴代谢综合征的疗效

目的:探讨罗格列酮联合阿司匹林对糖尿病伴代谢综合征的治疗效果。方法:纳入观察和统计的糖尿病伴代谢综合征患者80例,随机分为对照组与观察组,每组40例。对照组治疗药物为阿司匹林肠溶片,观察组治疗药物为罗格列酮分散片加阿司匹林肠溶片,比较两组治疗前后胰岛素、血脂、尿微量白蛋白(M-Alb)和不良反应发生率。结果:两组治疗后与治疗前比较,空腹血清胰岛素(F-INS)和胰岛素抵抗指数(HOMA-IR)水平均明显降低、胰岛素分泌指数(HOMA-IS)水平明显升高(P<0.05或P<0.01),总胆固醇(TC)、甘油三酯(TG)和尿M-Alb水平均明显降低(P<0.05或P<0.01)。观察组治疗后与对照组比较,F-INS和HOMA-IR水平降低更显著(P<0.05)、HOMA-IS水平升高更显著(P<0.01),TC、TG和尿M-Alb水平降低更显著(P<0.05或P<0.01)。两组不良反应发生率差异无统计学意义(P>0.05)。结论:罗格列酮联合阿司匹林治疗糖尿病伴代谢综合征的疗效显著,可使机体血脂与胰岛素抵抗得到有效调节。     

The emergence of HIV-1 primary drug resistance genotypes among treatment-naïve men who have sex with men in high-prevalence areas in China

The prevalence of HIV-1 infection in men who have sex with men (MSM) in China has drastically increased, and circulating strains may have acquired transmitted drug resistance (TDR). We determined TDR genotypes among antiretroviral therapy (ART)-naïve MSM in 19 provinces/cities where HIV-1 prevalence among MSM is high, and found an overall 4.9 % TDR rate. Although protease inhibitors (PI) were not in the first-line antiretroviral drug list provided through the National ART Program, 70.4 % of the detected TDR belongs to this category. Our findings confirm the urgent need for TDR surveillance in order to optimize treatment effects of the National ART Program.