非综合征性耳聋家系的临床分析与基因检测

目的:探讨母系遗传氨基糖甙类抗生素致聋家系的临床表型与基因突变的关系。方法:收集贵州省遵义地区不同民族的6个母系遗传非综合征性耳聋家系的临床资料及血液样本,经PCR-RFLP及测序技术检测线粒体DNA 1555G、3243G、7445G突变,并通过对各家系线粒体DNA高变区序列测定及编码区限制性片段多态性分析以划分单倍型类群。结果:经酶切及测序证实其中4个家系存在线粒体DNA 1555G突变,但未发现线粒体DNA 3243G、7445G突变。6个耳聋家系分别属于A、D6、D、G、B5 a及M*单倍型。结论:该地区线粒体DNA 1555G突变引起氨基糖甙类抗生素高度敏感致聋的家系发生率较高,提示线粒体DNA 1555G突变检测有一定的临床应用价值。     

氨基糖苷类抗生素致聋的遗传易感性

氨基糖苷类抗生素是一类临床上常用的抗生素,他们在分子结构、体内代谢、抗菌谱和毒副作用等多方面具有一些共同的特点.其主要副作用是氨基糖苷类抗生素致聋(aminoglycoside antibiotic induced deafness, AAID). 氨基糖苷类抗生素损害第8对脑神经、前庭和耳蜗的细胞造成耳聋.个体对氨基糖苷类抗生素致的听力的损伤显示了母系遗传的特点.线粒体DNA基因12S rRNA的A1555 G突变是AAID的主要易感因素,C1494T突变和961insC可强化A1555 G突变造成的AAID风险.通过基因检测可以预防AAID的发生.     

线粒体DNA A1555G位点突变与氨基糖甙类抗生素致聋遗传易感性的研究

应用PCR-限制性内切酶酶切片段长度多态性技术,对83例过去应用过氨基糖甙类抗生素药物而目前有听力下降的患者的外周血线粒体DNA的A1555G位点突变情况进行了研究.结果发现6例患者线粒体DNA的12S rRNA基因A1555G位点发生了点突变的阳性率7.2%.而其余77例患者及50例正常人无一例在此位点有突变.研究显示mtDNA A1555G点突变是药物性耳聋遗传易感性最常见的基因突变类型.     

邢台市聋哑学生线粒体DNA C1494T和A1555G突变分析

目的调查邢台市聋哑学校耳聋患者线粒体DNA m.C1494T和m.A1555G突变情况。方法对2013-2014年河北省邢台市聋哑学校的115例耳聋学生进行遗传性耳聋问卷调查、体格检查和听力学评估。采用Sanger测序法检测线粒体12SrRNA m.C1494T和m.A1555G两个突变位点。结果 2例(1.7%)携带线粒体DNA m.A1555G均质性突变,1例(0.9%)携带线粒体DNA m.C1494T均质性突变。结论邢台地区线粒体DNA m.A1555G突变发生率与其他地区比较偏低,m.C1494T突变发生率与其他地区比较偏高。在地区性耳聋病因调查中运用基因诊断技术,可以用于早期诊断,遗传咨询和指导该家系成员预防药物性耳聋。     

线粒体基因的分子诊断:早期氨基糖苷类抗生素耳毒作用的发现与预防

氨基糖苷类抗生素如庆大霉素、链霉素和托普霉素等都是在临床上非常重要的药物,而这些药物的使用常常会导致部分病人听力不可逆的损伤,在耳聋病人中,有很高比例是由于氨基糖苷类抗生素的耳毒性引起的.在家族性的药物损伤性耳聋中,氨基糖苷类抗生素耳毒性的高度敏感通常为母系遗传,提示线粒体DNA上的突变可能是导致此类症状的分子生物学基础.突变分析发现在线粒体12S rRNA上发现了多个和严重的药物性耳聋相关的基因突变,其中尤以A1555G和C1494T突变在氨基糖苷类抗生素引发的耳聋病例中占有显著的比重.A1555G或C1494T突变在12S rRNA的A区形成一个新的结合碱基对,使12S rRNA的二级结构与细菌的16S rRNA更为相似,促进了氨基糖苷类抗生素与之结合,使得带该类突变的个体在使用氨基糖苷类抗生素后会发生或者加重听力缺失.一系列的研究数据提供了有价值的信息和技术,使得预测哪些人具有氨基糖苷类抗生素耳毒性的高风险成为可能,同时提高了氨基糖苷类抗生素治疗的安全性,对于降低耳聋的发病率具有重大的意义.     

非综合征型神经性耳聋的线粒体基因突变研究(英文)

目的探讨国人非综合征型神经性耳聋患者线粒体基因突变。方法收集非综合征型神经性耳聋病例262例,其中散发病例168例,69例同代有耳聋患者,25例不止1代有耳聋患者,采用限制性片段长度多态性分析线粒体基因中的下列3个点突变:1555A→G,3243A→G,7445A→G。结果在5个母系遗传家系和10个散发病例中发现线粒体基因突变,占全部病例的5.7%。结论应考虑在非综合征型神经性耳聋中患者线粒体基因突变的筛查,特别是母系遗传家系成员。     

近亲婚配致聋家系中患者GJB2和线粒体DNA 12S rRNA基因突变热点分析

目的:分析GJB2和线粒体DNA12S rRNA两种常见耳聋致病基因突变热点在近亲婚配致聋家系患者中的发生频率。方法:对25个近亲结婚致聋核心家系的后代进行全面的体格检查和纯音测试,共发现患者48例,采静脉血3 ml,提取DNA,针对特定基因,进行聚合酶链式反应(Polymerase chain reaction,PCR)及限制性片段长度多态性(Restriction fragmentlength polymorphism,RFLP)分析,发现突变者测序验证。结果:发现GJB2基因235delC纯合突变1例,杂合突变3例;未发现线粒体DNA12S rRNA A1555G突变。结论:近亲结婚家系中遗传性聋多为常染色体隐性遗传,但GJB2基因235delC突变的发生率较低。     

氨基糖甙类抗生素致聋患儿的线粒体基因突变研究

为探讨遗传因素在氨基糖甙类抗生素致聋 (AAID)患者发生中的作用 ,对湖北省聋儿康复中心及部分门诊聋儿进行了听力测试和问卷调查 ,对确诊为 AAID的 93例患儿 ,采外周血做 PCR- RFLP分析 ,对照组为本地 50例正常儿童。研究发现 :93例患儿中 1 2例具有 mt DNA A1 555G均质性突变 ,9例为异质性突变 ,该位点突变率为2 2 .6%。对照组均无此突变。认为 mt DNA A1 555G突变是个体对氨基糖甙类抗生素易感的分子基础之一 ,对易感个体及其母系成员应严禁使用氨基糖甙类抗生素 ,以防止易感致聋的发生     

Leber遗传性视神经病变线粒体DNA原发性突变位点的分析

目的探讨Leber遗传性视神经病变(LHON)线粒体DNA原发性突变特征。方法利用Pyrosequencing和测序技术对11个LHON家系的13例典型患者及其30位家系成员11778G>A等12余种线粒体DNA突变位点进行分析。结果本地区LHON患者均为线粒体DNA同质性突变(homoplasmy)。11个LHON家系中有7个分别含有11778G>A,14484T>C和3460G>A原发性突变位点,占63.6%(7/11例)。13例患者线粒体DNA突变以11778G>A为主(53.8%,7/13例)。13708G>A和3552T>A突变单独存在于2个LHON家系中。3460G>A与3394T>C合并存在。未发病家系成员中可见11778G>A,14484T>C,13708G>A纯合性或杂合性突变体。结论继发性突变位点可单独存在,也可与原发性突变位点合共同导致LHON的发病。11719 G>A可能成为人线粒体有用的生物标签。     

绍兴市聋哑学校非综合性耳聋分子病因学分析

目的对绍兴市聋哑学校非综合性耳聋患者进行分子病因学分析。方法对绍兴市聋哑学校116名学生进行病因问卷调查和听力检测,应用PCR扩增及焦磷酸测序法对112名非综合性耳聋患者进行GBJ2 235delC和线粒体DNA 12SrRNA A1555G基因突变检测。结果在112例非综合征性耳聋患者中,6例（5．36％）存在线粒体DNA 12srRNAA1555G点突变,其中3例有明确的氨基糖甙类抗生素应用史,11例（9．82％）存在GBJ2 235delC纯合突变,5例（4．46％）存在GBJ2 235delC杂合突变。结论绍兴地区线粒体DNA 12SRrRNAA1555G突变率高于全国水平,GBJ2 235delC突变处于较低水平。通过耳聋基因检测可以明确或提示部分非综合性耳聋的病因,对防聋和指导聋儿家庭婚育起到积极作用。     

Calcium intake in the elderly: validation of a dietary questionnaire

Epidemiological studies of calcium and osteoporosis have been hampered by the lack of a suitable tool for assessing calcium intake. This report describes a new frequency and amount questionnaire for measuring present and past calcium intake in the elderly. The validity of the questionnaire was tested against two commonly used standards of dietary assessment, five-day duplicate diets and seven-day weighed dietary inventories. The resulting correlation coefficients were, respectively, r = 0.76 and r = 0.69, while that for repeatability was r = 0.84. Furthermore, the questionnaire categorized subjects into thirds of the distribution of intake with almost no gross misclassification. It is suggested that the present findings may be extended to the majority of normal, healthy elderly subjects, implying wide application for the questionnaire in the assessment of calcium intake in the elderly.     

The human drama of genetics: 'hard' and 'soft' media representations of inherited breast cancer

This paper examines media coverage of 'breast cancer genetics', and explores its implications for public understanding. We present a content analysis of coverage in British newspapers and look at a variety of popular forms, including women's magazines, television soap opera and radio drama. Genetic/inherited risk receives a great deal of coverage across a wide range of media formats and outlets. Much of this attention has focused on individuals from 'high risk families' and dilemmas around prophylactic mastectomies. Through examining media coverage, combined with interviews with media personnel and their sources, we show why this story proved so attractive to the media and highlight the different production values which influence coverage. Finally, we introduce preliminary findings from focus group discussions to demonstrate how such 'human interest' framing has engaged audience attention and influenced public understandings. The paper concludes by highlighting the implications for analysing, predicting, and engaging with, media representations of science.     

The occurrence of antimicrobial substances in toilet,sink and shower drainpipes of clinical units: A neglected source of antibiotic residues

Antibiotics represent one of the most important drug groups used in the management of bacterial infections in humans and animals. Due to the increasing problem of antibiotic resistance, assurance of the antibacterial effectiveness of these substances has moved into the focus of public health. The reduction in antibiotic residues in wastewater and the environment may play a decisive role in the development of increasing rates of antibiotic resistance. The present study examines the wastewater of 31 patient rooms of various German clinics for possible residues of antibiotics, as well as the wastewater of five private households as a reference.To the best of our knowledge, this study shows for the first time that in hospitals with high antibiotic consumption rates, residues of these drugs can be regularly detected in toilets, sink siphons and shower drains at concentrations ranging from 0.02?μg·L^?1 to a maximum of 79?mg·L^?1. After complete flushing of the wastewater siphons, antibiotics are no longer detectable, but after temporal stagnation, the concentration of the active substances in the water phases of respective siphons increases again, suggesting that antibiotics persist through the washing process in biofilms. This study demonstrates that clinical wastewater systems offer further possibilities for the optimization of antibiotic resistance surveillance.     

Worker education in the primary prevention of occupational dermatoses

This paper reports the evaluation of a skin care education programmeconducted on a fine chemicals manufacturing site where over1,000 employees are located. Approximately 60% are involvedin chemical manufacture. Over a 12 month period production staffreceived training in prevention of occupational dermatoses linkedto a site-wide poster initiative. The incidence of new casesof occupational dermatoses fell from 0.055 (70 cases in 1,277employees) to 0.021 (27 cases in 1,277 employees) before andafter the intervention respectively (p<0.0001). After otherfactors such as chemicals handled, observer bias and changesin reporting related to socioeconomic climate were taken intoaccount it is concluded that this study demonstrates the importanceof worker education as a tool for primary prevention of disease.Training materials such as video and poster presentations maybe effectively used in the chemical manufacturing industry asan adjunct to prevention and control of exposure to substanceshazardous to the skin. Such methods may also be used in otherindustries where there are significant risks of dermatoses.     

Regional Variation in Travel-related Illness acquired in Africa,March 1997–May 2011

To understand geographic variation in travel-related illness acquired in distinct African regions, we used the GeoSentinel Surveillance Network database to analyze records for 16,893 ill travelers returning from Africa over a 14-year period. Travelers to northern Africa most commonly reported gastrointestinal illnesses and dog bites. Febrile illnesses were more common in travelers returning from sub-Saharan countries. Eleven travelers died, 9 of malaria; these deaths occurred mainly among male business travelers to sub-Saharan Africa. The profile of illness varied substantially by region: malaria predominated in travelers returning from Central and Western Africa; schistosomiasis, strongyloidiasis, and dengue from Eastern and Western Africa; and loaisis from Central Africa. There were few reports of vaccine-preventable infections, HIV infection, and tuberculosis. Geographic profiling of illness acquired during travel to Africa guides targeted pretravel advice, expedites diagnosis in ill returning travelers, and may influence destination choices in tourism.     

Fatigue and health in a seafaring population

Background Occupational fatigue is relatively common withinthe general population and has been linked to reduced performance,injury and longer term ill-health. Despite growing acknowledgementof this problem in the maritime sector, little research hasbeen conducted into the risk factors, prevalence and consequencesof seafarers' fatigue. Aims To examine the prevalence of fatigue among seafarers, identifypotential risk factors and assess possible links with poor performanceand ill-health. Methods Cross-sectional questionnaire survey of seafarers workingin the offshore oil support, short-sea and deep-sea shippingindustries. A number of tools were used including the fatiguesubscale of the profile of fatigue-related symptoms, the CognitiveFailures Questionnaire, the General Health Questionnaire andthe SF36 General Health scale. Results In all, 1855 questionnaires were completed giving anoverall response rate of 20%. Fatigue symptoms were associatedwith a range of occupational and environmental factors, manyunique to seafaring. Reporting a greater number of risk factorswas associated with greater fatigue [e.g. OR = 2.53 (1.90–3.35)for those with three or four risk factors and OR = 9.54 (6.95–13.09)for those with five or more risk factors]. There was also astrong link between fatigue and poorer cognitive and healthoutcomes, with fatigue the most important of a number of riskfactors, accounting for 10–14% of the variance. Conclusions Seafarers' fatigue could impact on safety withinthe industry and may be linked to longer term individual ill-health.It can only be addressed by considering how multiple factorscombine to contribute to fatigue.     

深圳公立医院管理体制改革制度设计

深圳公立医院管理体制改革实行政事分开、管办分开,在理事会架构下按法定机构模式组建市医管中心,落实公立医院运营管理自主权.作者从当前公立医院管理体制的弊端入手,介绍了深圳市进行公立医院管理体制改革的基本思路及改革方案设计的主要举措,深入剖析了的改革方案的特点,并对改革效果进行了预测.     

The design of hazard risk assessment matrices for ranking occupational health risks and their application in mining and minerals processing

Two hazard risk assessment matrices for the ranking of occupational health risks are described. The qualitative matrix uses qualitative measures of probability and consequence to determine risk assessment codes for hazard-disease combinations. A walk-through survey of an underground metalliferous mine and concentrator is used to demonstrate how the qualitative matrix can be applied to determine priorities for the control of occupational health hazards. The semi-quantitative matrix uses attributable risk as a quantitative measure of probability and uses qualitative measures of consequence. A practical application of this matrix is the determination of occupational health priorities using existing epidemiological studies. Calculated attributable risks from epidemiological studies of hazard-disease combinations in mining and minerals processing are used as examples. These historic response data do not reflect the risks associated with current exposures. A method using current exposure data, known exposure-response relationships and the semi-quantitative matrix is proposed for more accurate and current risk rankings.     

Self-reported health problems among Swedish miners one year after unemployment

Unemployment is considered to be a public health concern sincedeterioration in the health of the unemployed is often anticipated.However, for some groups, such as miners, unemployment mightimprove health due to a cessation of potentially harmful occupationalexposures. This study evaluates the health of 79 miners in oneSwedish iron-ore mine, and 226 age-matched controls from thegeneral population, during one year after the closure of themine. The participants received a questionnaire regarding medicalhistory and subjective symptoms at the beginning of the studyperiod, and after one year. Statistically significant negativeeffects on self-reported health attributable to unemploymentwere not found, although neuropsychiatric symptoms were morecommon among the unemployed miners. The miners reported a statisticallysignificant improvement in grip force (p=0.031). They had asignificantly higher prevalence of symptoms associated withmining related exposures when compared with the population controls;pain in the upper extremities [relative risk (RR)=2.27, 95%confidence interval (Cl)=1.44–3.59), back pain (RR=1.84;Cl=1.237–2.75), vasospastic disease of the fingers (RR=2.05;Cl=1.18–3.57) and obstructive respiratory symptoms (attacksof dyspnea and wheezing: RR=3.67; Cl=1.167–11.6).     

Excès de cas humains et animaux de tularémie en France au cours de l’hiver 2007–2008 : émergence ou phénomène isolé ?

Context

Tularemia is a zoonosis affecting humans and hares in France. We describe the results of surveillance in both species, in 2007 and 2008.

Methods

Human tularemia cases are mandatorily notifiable in France since 2003. In hares, surveillance relies on volunteer hunter associations in all districts of the country. Data from mandatory reports and volunteer surveillance in 2007/2008 were analyzed and compared with previous results.

Results

In 2007/2008, 144 cases were reported in humans and 117 cases in hares. This was a 100% increase compared to previous years. Human cases differed from those of previous years only by the frequency of contact with breeding animals. Human cases without any documented risk exposure were also more frequent.

Conclusion

An increase of tularemia cases occurred in 2007/2008 in both species. Complementary studies are needed to identify the species reservoir in France to understand the causes of this peak of cases.