Compound heterozygosity for the shared epitope and the risk and severity of rheumatoid arthritis in extended pedigrees

The objective was to explore the role of HLA-DRB1 genes in determining disease severity in rheumatoid arthritis (RA). The population comprised extended pedigrees of 17 multicase RA families. Family members were genotyped for both HLA-DRB1 alleles using restriction fragment length polymorphism (RFLP). Identification of HLA-DRB1*04 variants was performed using the Multiplex ARMS-RFLP technique. Compound heterozygote individuals carrying two different alleles containing the shared epitope (SE) were at greatest risk of developing RA (odds ratio = 36, 95% CI 9.1-143). A synergistic or additive effect of these alleles is suggested. Individuals carrying no SE alleles expressed milder disease, as measured by the Spread Severity (SS) index, compared to compound heterozygotes (P = 0.045). Compound heterozygosity was not invariably associated with severe disease with six (50%) having clinically mild disease at a median age of 57.5 yr and median disease duration of 16 yr. Inheriting two different SE-bearing alleles results in an increased risk of RA and, on average, greater disease severity. This is not, however, invariably associated with severe disease, making it of limited use as a predictor of prognosis.      

A variant of von Willebrand's disease with abnormal expression of factor VIII procoagulant activity

Reports on variants of von Willebrand's disease are numerous, but many of these are based on tests that will show marked fluctuations with time and tests that might not be similar in affected family members. This report describes 8 patients with a new variant of von Willebrand';s disease in which there is a normal APTT, slightly reduced one-stage factor VIII:C assay (VIII:C-1), and a drastically reduced two- stage factor VIII:C assay (VIII:C-2). The VIII:C in this variant is more readily adsorbed to AI(OH)3. This variability in VIII:C assays and excessive adsorption to AI(OH)3 are corrected by the addition of either hemophilic plasma or hemophilic factor-VIII-related antigen. This variant is stable with restudy on multiple occasions and is inherited in a stable fashion in three generations of one family. The multimeric structure of the VIIIR:Ag appears normal, although the concentration is moderately reduced. The differences in functional activity, the adsorption to AI(OH)3, and the differences between functional and antigenic (VIII:C Ag) assays of VIII:C support that this is a functional abnormality of type I von Willebrand's disease.     

Direct evidence of monocyte recruitment to inflammatory bowel disease mucosa

Alterations in phenotype and function of intestinal macrophages occur in inflammatory bowel disease (IBD) but it is unclear whether these changes result from the recruitment of circulating monocytes to the intestine or from proliferation of resident intestinal macrophages. We sought to demonstrate the arrival of blood monocytes, the precursors of macrophages, in IBD mucosa. Peripheral blood mononuclear cells were isolated from 23 patients with clinically active intestinal inflammation (13 Crohn's disease, eight ulcerative colitis, two infective colitis), then radiolabelled with ^99mtechnetium (Tc)-stannous colloid (n=13) or ¹¹¹indium (In)-oxine (n=10) before re-injection and abdominal scanning. Four patients had demonstrable intestinal monocyte uptake using [^99mTc]-stannous colloid, while six [¹¹¹In]-oxine-labelled monocyte scans were positive. Uptake sites correlated with actively inflamed regions. Patients demonstrating monocyte uptake had been treated with corticosteroids for a significantly (P < 0.02) shorter duration (median 3 vs 20 days) than those with negative scans. There was no significant difference between positive and negative scans for disease category, clinical or histological disease activity, or radioisotope used. Biopsies of inflamed mucosa from two patients suffering ulcerative colitis who had positive scans showed a high proportion of CD14-positive macrophages, 4–9% of which contained autoradiographic grains. These results demonstrate that blood monocytes are recruited to the mucosa of actively inflamed bowel, and suggest that this process may be inhibited by corticosteroids. Moreover, the phenotype of the recently-arrived monocytes indicates their susceptibility to stimulation by lipopolysaccharide, and suggests a mechanism for the continuing inflammation in the bacterial product-rich milieu of IBD.     

The psychological risks of Vietnam: the NVVRS perspective

In recent years, controversy concerning the psychological consequences of service in the Vietnam war has rearisen. In this article, the Co-Principal Investigators of the National Vietnam Veterans Readjustment Study (NVVRS) provide a perspective on new findings reported by B. P. Dohrenwend et al. (2006) that addresses criticisms of the NVVRS PTSD (posttraumatic stress disorder) prevalence findings, and on a perspective that was provided by R. J. McNally (2006) in an accompanying commentary. They find that Dohrenwend et al.'s study, which evaluated empirically a variety of the critics' alternative explanations and found little support for any of them, represents a landmark contribution to the trauma field. However, they found that McNally's commentary misrepresented the history and context of the NVVRS, and then misinterpreted Dohrenwend et al.'s findings and their importance.     

682株鲍曼不动杆菌分布及耐药性分析 FREE

目的方法结果结论为了解鲍曼不动杆菌临床分布及其耐药情况,对某院2005-2007年间分离的鲍曼不动杆菌的耐药性进行监测分析。共分离鉴定鲍曼不动杆菌682株,其中674株分离自住院患者：重症监护室（ICU）248株,内科221株,外科205株;8株分离自门诊患者。标本来源以痰为主,共分离443株,占64.95%;其次为分泌物、脓液标本,分离91株,占13.34%。药敏结果显示,鲍曼不动杆菌对头孢他啶和头孢吡肟的耐药率较高,分别为69.17%和58.58%;对头孢哌酮/舒巴坦、哌拉西林/他唑巴坦、亚胺培南和美罗培南的耐药率分别为25.85%、66.46%、3.80%和7.10%。提示鲍曼不动杆菌在ICU的分离率高,对常用抗菌药物的耐药率高,必须加强抗菌药物合理使用的管理。     

Correlates of Heterosexual Anal Intercourse Among At-Risk Adolescents and Young Adults

Objectives. We sought to learn what factors are associated with anal intercourse among adolescents and young adults. We examined demographic, behavioral, relationship context, attitudinal, substance use, and mental health correlates of recent heterosexual anal intercourse among adolescents and young adults who reported engaging in recent unprotected sex.Methods. Among 1348 at-risk adolescents and young adults aged 15 to 21 years in 3 US cities, we assessed sexual risk behavior with each sexual partner in the past 90 days. Data were collected from 2000 to 2001.Results. Recent heterosexual anal intercourse was reported by 16% of respondents. Females who engaged in anal intercourse were more likely to be living with a sexual partner, to have had 2 or more partners, and to have experienced coerced intercourse. For males, only a sexual orientation other than heterosexual was a significant predictor of engaging in heterosexual anal intercourse.Conclusions. Our findings document the prevalence of heterosexual anal intercourse among adolescents and young adults who had recent unprotected sex. Among females, the variables associated with anal intercourse relate to the context and power balance of sexual relationships. Different influences for males and females suggest different foci for interventions.Unprotected anal intercourse is a significant HIV risk because the odds of contracting HIV are calculated as 5 times as risky for receptive anal intercourse than for receptive vaginal intercourse.¹ In addition, anal intercourse appears to be increasing: a survey of adults aged 18 to 39 years showed that the rate of anal sex had doubled from 1995 to 2004.² In the most recent National Survey of Family Growth, 35% of women and 40% of men reported engaging in heterosexual anal intercourse in their lifetime.³Many adolescents have engaged in anal intercourse, and the prevalence increases with age. In the National Survey of Family Growth, 8% of adolescent boys and 6% of adolescent girls aged 15 to 17 years reported having had heterosexual anal intercourse. Among those aged 20 to 24 years, 33% of men and 30% of women reported the experience. Data also show that anal intercourse among adolescents and young adults is often unprotected^4–6 and that condom use is less likely than during vaginal intercourse.^5,7 Most studies that have examined race as a factor have not found a significant correlation,^7–9 although some evidence exists that Whites engage in anal intercourse more frequently.⁴Despite the prevalence of anal intercourse among adolescents and young adults, little research exists about related factors. Among adults, substance use is often described as a precipitant or cofactor for heterosexual anal intercourse. In one study, adults who had engaged in anal intercourse were more likely than were those who had not to use alcohol once a week or more; to have used marijuana in the past year; to have used cocaine, crack, or LSD in the past year; or to have ever injected drugs.⁸ Among injection drug users, amphetamine use has been associated with heterosexual anal intercourse,¹⁰ and in a sample of adult women, drug use was significantly associated with engaging in anal intercourse.⁹ This relationship may reflect lowered inhibition during drug use or a common attitude that fosters experimentation with both substances and anal intercourse.A significant relationship exists between anal intercourse and other sexual behaviors. Heterosexual anal intercourse has been associated with a greater number of sexual partners for adults,⁸ college students,^11,12 and male injection drug users.¹⁰ Women who had engaged in anal intercourse also reported more episodes of unprotected vaginal intercourse than did women who had not.¹³ In addition, anal intercourse has been found to be related to other HIV risk behaviors, including injection drug use, having sex with an HIV-positive partner, having sex with a man who has sex with men, or exchanging drugs or money for sex.^4,6–8Halperin has suggested that power in relationships exerts a strong influence in the practice of anal intercourse.¹⁴ Indeed, having a main partner dictate sexual practices was associated with unprotected anal intercourse in a study of women aged 18 to 24 years.⁹ This may be particularly relevant for adolescents and young adults, who may be less sexually experienced and more likely to follow a partner''s lead in sexual activities.Because little is known about factors associated with anal intercourse among adolescents and young adults or their prevalence, we sought to identify demographic, behavioral, relationship context, attitudinal, substance use, and mental health correlates of recent (previous 90 days) experience with anal intercourse among adolescents and young adults. The scant adolescent literature, along with the adult literature, led us to hypothesize that older age, other risky sexual practices (e.g., multiple sexual partners, unprotected vaginal intercourse), and more substance use would be significantly associated with recently engaging in anal intercourse. We also hypothesized that those with a history of aggression (as a proxy for power) in relationships would be more likely to engage in anal intercourse. Because we identified no previous research on the association between anal intercourse and sexual attitudes or mental health, we formulated no hypotheses about these variables.     

碘缺乏和甲状腺功能减退对大鼠仔鼠海马钙调磷酸酶表达的影响

目的 观察碘缺乏和甲状腺功能减退对大鼠仔鼠海马钙调磷酸酶蛋白表达的影响.方法 健康2月龄雌性Wistar大鼠,交配妊娠后,取孕鼠28只,按体质量随机分成对照组、甲状腺功能减退组和碘缺乏组,甲状腺功能减退组根据饮水中含丙基硫尿嘧啶剂量分为5 ppm组和15 ppm组.每组7只孕鼠.分别于出生后7 d(PN7)、14 d(PN14)和31 d(PN21)时,每组随机取5只仔鼠,灌流固定大脑,进行组织病理切片和免疫组化染色,观察分析海马钙调磷酸酶的表达.结果 PN14和PN21时,在海马CA1和CA3区15 ppm组和碘缺乏组仔鼠海马钙调磷酸酶表达显著高于对照组(P<0.05),而海马DG区则相反.PN7时,各区均几乎观察不到阳性反应产物,各组间蛋白表达无显著差异.结论 碘缺乏和甲状腺功能减退可增加海马CA1和CA3区钙调磷酸酶的蛋白表达.     

广州地区呼吸道疾病患儿16种常见变应原检测分析

目的 了解广州地区呼吸道疾病患儿对16种常见变应原的过敏情况,同时探讨不同年龄组之间的变应原阳性率差异,并比较致敏程度.方法 选择2007年8月至2008年3月广州医学院第一附属医院呼吸科门诊和儿科门诊初诊为支气管哮喘、过敏性鼻炎、呼吸道感染等患儿320例为研究对象,其中婴幼儿组(≤3岁)214例,儿童组(>3岁)106例.采用德国FOOKE ALLERG-O-LIQ-SYSTEM变应原检测系统,通过免疫捕获法检测血清中常见的16种变应原特异性免疫球蛋白E(SIgE)抗体.结果 在所有患儿中,其中261例(81.56%)SIgE呈阳性.59例(18.44%)呈阴性.16种变应原SIgE阳性率为屋尘螨(36.88%)、粉尘螨(35.31%)、热带螨(24.06%)、狗毛(6.56%)、猫毛(8.75%)、德国小蠊(16.56%)、蜜蜂毒素(0.94%)、屋尘(45.63%)、全蛋(45.94%)、牛奶(46.25%)、小麦面粉(6.88%)、玉米粉(1.25%)、花生(9.06%)、大豆(5.94%)、螃蟹(2.81%)、虾(4.38%).婴幼儿组SIgE的阳性率为81.78%,以食物性变应原(牛奶、全蛋)为主;儿童组的阳性率为81.13%,以吸人性变应原(尘螨)为主(X2=0.02,P=0.89).儿童组尘螨的过敏阳性率均高于婴幼儿组(P<0.05),且儿童组屋尘螨和粉尘螨的过敏程度多在3级以上.婴幼儿组各级阳性率比较平均.两组对热带螨的过敏程度均较低,多在3级以下.婴幼儿组牛奶和全蛋过敏阳性率高于儿童组(P<0.05),两组的过敏程度均在3级以下.结论 儿童组与婴幼儿组对常见变应原的总阳性率差异无统计学意义,只是对不同变应原阳性率及过敏程度的差异.儿童组主要是对吸人性变应原产生过敏,婴幼儿组主要是对食物性变应原产生过敏,应以不同年龄段来分析儿童变应原检测结果.