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吸烟可使腹部主动脉瘤(AAA)的发病风险增高

    据英国路透社11月16日报道,一项研究表明,吸烟可使腹部主动脉瘤(AAA)的发病风险增高,如果这种动脉瘤破裂,或会造成生命危险。
    从美国国家医学图书馆(National Library of Medicine)可知,当主动脉(向下体供应血液的主血管)由于血管壁的弱化而扩大或凸起时,动脉便会出现腹主动脉瘤。这种动脉瘤若发现即使,则可以被治愈,但若发生撕裂或破裂现象,只有5分之1的人能够幸存。“吸烟是引发AAA的主要风险因素,”美国明尼苏达大学博士兼研究报告主要作者唐卫红(音)说。
    研究人员使用的数据来自1987至1989年终1.5万名被初步评估处于AAA扩展风险的人群。参与者随后在1998年进行了3次检查和测验。在2011至2013年,有将近6000人仍然活着,并在第五次跟访中进行了超声波检测。2011年,超声扫描发现了75例新增病例。经过22年的随访期,共有590例被诊断为AAA破裂或正在修复中。
    研究发现,戒烟者AAA的扩散风险比那些仍在吸烟的人群降低了29%。同时,与男性吸烟者相比,女性吸烟者的患AAA的风险要高得多。
    “AAA影响了5%至9%的65岁及以上的美国人群,”唐说,“吸烟可以引发慢性炎症,而慢性炎症反过来会激活能够降解主动脉壁的弹性蛋白和胶原纤维的酶。

日期:2016年11月18日 - 来自[心脑血管相关]栏目

9家中药企业被评为“AAA级信用企业”

日前,中国中药协会发布第二批中药行业信用评价结果,9家企业被评为AAA级信用企业。这9家企业是:北京同仁堂(集团)有限责任公司、药都制药集团股份有限公司、厦门中药厂有限公司、西藏奇正藏药股份有限公司、山东步长制药股份有限公司、青岛国风药业股份有限公司、康美药业股份有限公司、河南羚锐制药股份有限公司、广州市香雪制药股份有限公司。

据悉,中国中药协会于2011年12月启动了第二批中药行业信用评价工作,经过专业信用评价机构评级、行业信用评价专家委员会综合评议和协会信用评价领导小组复核等环节评出。评选结果在中国市场秩序网及协会网站公示10天。

日期:2013年4月3日 - 来自[企业观察]栏目

以创AAA为契机,规范疾控机构档案管理

【摘要】  抓住档案事业快速发展的有利时机,开展档案馆的达标升级工作,已经成为越来越多基层档案馆迫在眉睫的问题。本文就宜昌市疾控中心档案馆如何开展档案管理升省AAA级工作的好的经验进行了概括和总结,希望能对基层单位创等级档案馆有所帮助。

【关键词】  疾控;档案;管理;达标

 当许多档案馆已不满足于浅层次地保管和利用工作,正在思考和摸索新的发展模式的时候,宜昌市疾控中心档案馆率先抓住档案事业快速发展的有利时机,将档案管理升省AAA级纳入了全年工作计划,并从管理机制、业务建设和信息服务方面,以高标准、高水平为起点,扎扎实实地开展了各项准备工作,使档案管理水平又迈上了一个新的台阶。经过积极筹建申报,中心档案室被评为省AAA级档案室,从而成为宜昌市第一家,也是湖北省卫生系统第一家“AAA”级档案室。

  1 提高认识,加大档案管理力度

  为了确保升级达标有条不紊的进行,中心切实加强了对各项工作的组织领导,从始至终,坚持狠抓了“五个落实”:一是落实领导。成立了由中心主任亲自挂帅、办公室主任任副组长,各科室责任人任成员的一级抓一级的组织管理网络。统筹规划档案管理工作发展,及时解决档案达标工作中存在的困难,把对档案工作的重视提高到前所未有的程度。二是落实人员。中心在档案升级工作中实行“全员动员,人人参与”,抽调了各所、科、室力量投入升级达标工作中。配备专兼职业档案员17名,均具有大专以上文化水平。对各种门类、载体的档案实行集中统一管理,形成了主要领导(档案管理员)—分管领导—科室主任—科室档案资料员的较为完善的档案管理工作责任链,在创等级工作中发挥着重要的监督、指导作用。三是落实责任。多次召开各所、科、室负责人会和兼职档案员会,学习、宣传、贯彻《湖北省档案管理条例》(修订),并结合档案业务培训,对历年来的专业档案进行全面部署,将责任和要求逐一落实到科室,明确到人头。四是落实时间。中心咬住年末档案到达省AAA的既定目标不变,对科室和个人完成所负责任务的具体时间都作了严格规定。从达标升级的准备到最后的评审共细划了九个阶段,时间跨度为6个月 ,各阶段的工作均严格按规定时间完成。五是落实资金。在今年财力相当紧张的情况下,拨出专款用于档案升级,先后投资10多万元配备了新密集架40组、空调、电脑、数码相机、扫描仪等仪器设备,并在今年的国债楼建设项目中,拨出面积达300多平方米的档案用房,实现了办公、阅览、库房三分开,为稳步实施晋升省AAA奠定了坚实的基础。

  2 夯实基础,强化档案管理机制

  在中心领导的高度重视下,中心档案室把档案信息的管理作为信息资源和科研储备的重要内容来抓,寻求与中心业务工作同步发展、相互促进的档案管理惯性运行机制。一是把中心档案管理工作列入发展规划、重点专业学科建设规划及年度工作计划,并将其分解为中心、科两级综合目标管理责任制与岗位责任制,与考核奖惩挂钩。二是健全档案管理规章制度,建立了《专(兼)职档案员岗位职责》、《档案立卷归档制度》、《档案鉴定销毁制度》、《档案保管制度》、《档案查阅制度》、《档案保密工作制度》等一系列制度和岗位责任制,修订了文件材料的归档范围,规范了档案工作程序。对专兼职档案员及有关人员工作岗位责任履行情况定期检查,并作为考核工作实绩内容之一。三是充分发挥档案的监督管理职能,采取切实可行的控制措施,确保档案归档的完整、准确、系统。一方面综合档案室严格按照《档案分类方案》和《科技档案资料工作程序》,对各科室日常预立卷和年终归档情况进行检查指导;另一方面在中心管理和业务活动中坚决贯彻执行“四参加”、“四同步”制度,万元仪器设备开箱、重大科技课题,疾病控制重点项目等均有档案人员参与,对应该归档的文件材料及时审查和验收;再一方面充分发挥档案室的管理作用,科技人员评审鉴定成果同时验收鉴定档案材料的完整、准确、系统情况。上报登记和评审奖励科技成果以及科技人员提职考核,档案部门同时出具专题归档情况证明材料。从而提高全中心工作人员档案工作的积极性和主动性。

  3 突出特色,推进档案业务建设

  为了确保中心档案工作达到省AAA水平,中心在整个准备过程中,对照《科技事业单位档案管理升级标准》,采取请进来派出去的方法学习档案升级达标中的各个要素环节。由中心领导亲自率队赴襄樊、十堰等地参观学习档案管理先进经验,同时聘请省市档案局的专家上门指导,有效促进了晋升省AAA级档案工作的开展。

  3.1 加强新立卷法颁布后的档案规范化管理

  重点对分散保管在各所科室历年来专业档案,照片档案进行了收集、分类,并组织专班,对专业档案采用新的立卷方法进行整理。对1952—2003年的专业档案,重新分类、鉴定、划分保管期限、编制目录、更换统一卷盒,共整理专业档案10244件(914盒)。每张照片档案都附有说明,进行了规范整理,在整理中坚持从严把关,做到前后分类一致,排列有序,并根据立档单位的情况分为三个全宗,清晰地反映了我中心的整个历史面貌。同时对以前的文书档案和科技档案的编号不符合要求的2331卷(盒)重新进行了录入和整改。

  3.2 加强对机构改革中新建机构和撤并机关的档案管理

  宜昌市疾病预防控制中心原名为宜昌市卫生防疫站,成立于1952年,1992年与原宜昌地区卫生防疫站合并,2003年,由于两项体制改革,将宜昌市卫生防疫站划分为宜昌市疾病预防控制中心和宜昌市卫生监督中心。由于机构的不断变化,给档案的收集管理工作带来了难度。中心始终坚持做到机构撤档案存,人走档案留,保证机构变动中档案不丢,不散。收集、整理了各种不同门类的载体档案和专业档案,截止2003年档案室总藏文书、科技、会计、照片、专业档案等4584卷(盒),形成一个内容丰富、门类齐全、分类合理的管理体系。

  3.3 加强特色档案管理

  一是建立了荣誉室。本中心成立五十年以来,各项工作成绩斐然,先后获得“全国卫生先进集体”等284次荣誉称号,获得全国、省、市科技成果72项,国家专利5项。为了更好的展示我市疾控体系建设发展壮大的光辉历程和辉煌业绩,展示改革开放以来疾控人的精神面貌,中心特设了170平方米的荣誉室,通过文字、图片与实物相结合的方式介绍了我中心取得的各项荣誉,极大的激励广大干部职工开拓创新,再展宏图的信心,促进了三个文明建设全面发展。二是建立了动物标本室。近二十年来,本中心结合疾病的防治工作,广泛进行各种病媒生物标本的采集,并根据动物分类和疾病防治工作的要求,将标本分为医学动物、医学昆虫和医学寄生虫三大部分,共500余种,标本藏量26500余号。标本室的建立对认识和了解医学动物,掌握其本底资料,对开展三峡自然疫源性疾病调查及相关疾病的预测和防治具有特别重要的意义。三是建立了重点疾病控制项目档案。为激励专业技术人员钻研业务,拓展工作,我中心以立定项目形式加强重点疾病防制和促进重点工作开展。并对所有重点项目逐一建立了项目档案。其中包括工作方案、原始调查记录、半年工作小结及全年总结分析报告。档案规范程度与年终项目考核直接挂钩。

  3.4 加强档案的现代化管理

  实现档案的现代化管理是档案管理向更高水平迈进的重要基础,也是这次中心档案晋升省AAA级狠抓的一项重点工作。历年来,我中心非常注重网络建设,建有中心局域网和中心自己的网站,2010年中心又花大力气推进档案信息化建设,将档案信息化纳入办公自动化的总体格局之中。拨专款为综合档案室购置了计算机、打印机、数码相机、扫描仪等高档仪器设备,并根据省卫生厅的要求,引进了“科怡·卫生版”档案管理软件。将1952—2003年长期保存的文书档案、专业级档案按文件级目录全部输入电脑管理,对于近5年来的文书档案进行了全文录入和部分专业档案的全文录入工作,基本实现了计算机目录检索,档案的全文查询、统计、数据对比分析等,同时,根据科怡档案管理系统(单机版)的特点,自行研制了一套软件,实现了科怡和中心局域网的链接,使中心各所科室的电脑终端均可通过局域网共享科怡档案管理系统中的数据库,利用网络进行高效便捷的档案查询,达到远程使用的效果。为确保计算机档案管理系统和网络的安全,本中心多次派档案人员、保密人员、网管人员参加由市保密局和市档案局举办的档案人员培训班,计算机信息系统保密管理培训班等,并制订了切实有效的网络安全防护措施。

  3.5 加强所辖县市区疾控机构的档案管理

  将档案管理工作纳入各县市区疾控机构年度目标管理之中,下发了关于加强全市疾病控制机构档案管理工作的指导意见,制定了档案管理工作技术方案,工作目标考评细则及定级标准,使全市疾病控制系统档案管理工作逐步进入规范化管理的轨道。并注重加强对所属各县市疾病预防控制中心档案管理的检查和指导工作,对其档案管理工作中的各项业务建设、开发利用、档案目标管理达到相应等级等做了具体详细的技术指导。针对所辖远安县、夷陵区的档案管理滞后的情况,本中心的档案人员多次亲临现场进行业务指导,对存在的问题,提出了整改意见。到1998年底所属9县市疾控中心的档案管理全部达到省级标准,其中兴山县防疫站达到国家二级标准。

  4 开发信息,发挥档案资源效益

  档案信息的开发利用是大力提高档案管理水平的最终目的,也是档案管理工作的出发点和落脚点。在档案达标工作中,中心把档案信息资源的开发利用作为又一重点,编制了档案检索工具13种,即:案卷目录、案卷文件目录、著录人名索引卡、发文目录、简报目录、科技成果与新技术目录、论文目录、发文汇集、专题汇编、全宗介绍、组织沿革、大事记、基础数字汇编等。并建立了全宗卷,较全面地、系统地反应了全宗内容以及历史面貌,也为业务利用创造了有利条件。近5年来,提供各种不同门类档案利用1960卷,借阅479人次,是过去5年的2倍。由于档案信息工作的有效利用,中心完成了全国、省、市科技成果72项,国家专利5项,公开发表论文780篇。档案信息提供利用对提高单位管理水平、促进科技进步、降低管理成本等发挥了显著的作用。近几年来,中心利用档案资料为编史修正、专业技术职务晋升、开展专题业务资料汇编、房屋维修等工作提供了大量依据,充分发挥了档案资料的凭证和依据作用,也为中心业务工作的开展提供了有利的档案信息支撑。

  4.1 为业务工作开展提供有针对性和实效性服务

  本中心编制的《科技成果与新技术汇编》、《疫情资料汇编》、《计量认证资料汇编》等编研材料在1997创建全国地级市一等卫生防疫站和1998年创建全国卫生城市中发挥了重要作用,提供了充分、翔实的数据资料,使上述业务工作均跨入了全省先进行列。

  4.2 为科学研究服务

  自1996年以来,中心工作人员通过借阅利用综合档案室的档案材料,撰写了200余篇有价值的学术论文,在国家级和省级各专业杂志上发表。其中,有2篇论文在国际性杂志刊登。此外,利用档案信息资料进行15项预防医学科学研究,取得了多项科研成果奖。其中,有6项获得省级以上科技进步及推广应用奖。这些科研成果运用到防病、灭病的卫生监督监测工作中,取得了较好的社会效益和经济效益。

  4.3 为基建工作服务

  1998年,本单位为解决部分职工宿舍住宅狭小,利用基建档案为职工宿舍维修、扩建、加层660平方米,节省资金2万余元,发挥了明显的经济效益。1999年修建办公楼和宿舍,由于红线图保存完整,为站内规划提供了便利的条件,节约了时间,保证了工期,收到了良好的效益。

  4.4 为建站50周年撰写站志服务

  2002年是站建站50周年。为纪念和庆祝50周年来各个时期的卫生防疫工作发展情况和所取得的辉煌成绩,根据站领导的安排,不论职能管理和业务专业工作都需要查阅50年来的档案。俗语说:“养兵千日,用兵一时”,在短暂的十天时间,查阅者为38人次,查(借)阅档案610卷,是2000—2001年查阅总数的三倍。许多查阅者深有感触地说:“档案是历史的忠实记录,是反映各个历史阶段疾控工作的重要依据,通过参阅档案中心了解了过去,档案真是一项为后人着想的千秋万代的事业。”总之,中心将以这次档案升级为契机,全面提升中心的档案管理水平,切实克服升级工作中的形式主义,把各项工作真正落到实处。相信,在自觉、自为的基础上,为神圣的事业达成共识,为崇高的目标努力奋斗,疾控档案事业的明天一定会比今天更美好。

日期:2011年6月29日 - 来自[2010年第8卷第12期]栏目

我校6家附属医院被评为广州医保“AAA”信用等级单位

    日前,广州市医疗保险服务管理局发布《关于2007-2008社保年度广州市医疗保险定点医疗机构信用等级评定情况的通报》(穗医管〔2009〕14号),评定出广州市医疗保险门诊及住院服务的定点医疗机构的信用等级,其中“AAA”级单位31家,“AA”级单位72家、“A”级单位39家。我校附属第一医院、孙逸仙纪念医院、附属第三医院、中山眼科中心、肿瘤防治中心、附属口腔医院6家医院被评为2007-2008社保年度广州市医疗保险定点医疗机构“AAA”信用等级单位。     此外,经各定点医药机构推荐、广州市医疗保险服务管理局确认,共评选出2007-2008社保年度定点医药机构医保服务之星共97名,我校附属医院共有13名医务人员获此荣誉称号。他们分别是:附属第一医院:郑彦如、黄桂新、文序;孙逸仙纪念医院:彭韩伶、李佩琼;附属第三医院:蔡月桃、张莹;肿瘤防治中心:姚鸣红、刘婉清;中山眼科中心:林晓峰、吴雁凌;附属口腔医院:凌均棨、赖亚力。

日期:2009年12月16日 - 来自[中山医科大学(中山大]栏目

中山三院荣获广州医保“AAA”信用等级医院

    2007、2008社保年度,在上级医保部门的大力支持和指导下,在医院党政领导班子高度重视和各相关科室及全院职工的共同努力下,我院严格遵守国家有关医疗保险的政策与法规,坚持以“服务于广大参保患者”为宗旨,认真贯彻履行广州市医疗保险、工伤保险、生育保险医疗服务协议,不断探索医保服务管理的有效模式,尽力完善各项医保服务管理制度,医保工作取得了卓越成效,最近被评为广州医保“AAA”信用等级医院。    今年4-11月,广州市医保局开展了对169家医疗保险门诊及住院定点医疗机构2007-2008社保年度执行医疗保险政策及履行医疗服务协议情况的年度检查及信用等级评定工作,经现场检查、病历评审、结果反馈、省市相关部门专向评审、社会公示及报人力资源和社会保障局确认等程序,共评出我院等31家“AAA”级单位,以及“AA”级单位72家,“A”级单位39家,另外,27家因服务协议未满一年或存在严重违规问题而未评定信用等级。    “AAA”信用等级医院的获得,对我院的医保工作是一种肯定,更是一种激励。在今后的工作中,我院将继续高度重视医保工作,真抓实干、全力以赴、恪守诚信、主动作为,自觉规范内部医保服务管理机制,抓住机遇、开拓思路、健全创新机制,不断提高履约能力,尽力做到“医、保、患”三赢,并以特色吸引参保人,以服务留住参保人,以满意回馈参保人,切实做好医保服务管理工作,共促医保和谐发展。

日期:2009年12月12日 - 来自[中山医科大学(中山大]栏目

Abdominal Aortic Aneurysm

【摘要】  Abdominal aortic aneurysm (AAA) affects approximately 5% of elderly men and is responsible for a significant number of deaths in Western Countries. At present surgery by open or endovascular means is the only widely used therapy for this condition. In this review we examine the risk factors, serum, and genetic associations of AAA. Epidemiology studies suggest that smoking cessation and control of cholesterol and blood pressure should reduce the number of patients developing AAA. Natural history studies suggest that smoking cessation should reduce the rate of progression of AAA. Clear level 1 evidence for drug treatments of AAA are presently lacking; however, animal and human in vitro studies suggest that medication targeted at reducing inflammation and proteolysis are most likely to be beneficial, with limited data to support the use of statins, Angiotensin II inhibitors, and macrolides. Work has commenced in understanding which patients, identified by clinical, serum, and genotype, are more at risk of AAA progression and thus should be selected out for aggressive treatment. Well designed large multicenter randomized controlled trials are required to examine the medical treatment of AAA.

Abdominal aortic aneurysm is associated with significant morbidity and mortality. Presently medical therapy for this condition has been neglected. This article summarises efforts to better understand the pathology of AAA to develop such treatments.

【关键词】  abdominal aortic aneurysm pathogenesis medication


Introduction


Abdominal aortic aneurysms (AAAs) usually occur in the infrarenal part of the aorta. An AAA is generally defined as a maximal aortic diameter of 3 cm, although definitions such as 4 cm and an infrarenal to suprarenal diameter ratio of 1.2 to 1.5 have also been used. 1,2 Irrespective of the definition, the underlying problem in aneurysmal disease is weakening of the aortic wall, resulting in progressive dilatation and, left untreated, eventual aortic rupture. Less common complications include distal embolization, aortoenteric or aortocaval fistulae, and iliac vein compression resultant in deep vein thrombosis. As a result, AAA is estimated to be the tenth commonest cause of mortality and is responsible for 2% of all deaths. Estimates of mortality are hampered by low rates of postmortems and it is likely that some sudden deaths attributable to ruptured AAA are certified as cardiac deaths unless a preexisting AAA was documented. Unlike coronary heart disease, the incidence of AAA is reported to be increasing in Western Countries. 3,4 In Scotland, for example, the mortality rates from AAA increased 2.6-fold between 1981 and 2000. 4 Larger increases in admissions and operations have been reported. 3 Although improved detection and reduction in mortality from other types of cardiovascular disease may have contributed to these increases, the rising age-standardized mortality appears to indicate a genuine increase in the incidence of AAA. 4


Two large randomized controlled trials have indicated that survival is not improved by elective surgery for AAAs <5.5 cm in diameter. 5,6 Small abdominal aortic aneurysms are followed by periodic ultrasound surveillance until the aortic diameter approaches 5.5 cm when repair by open or endoluminal surgery is indicated for those patients deemed suitable. Trials comparing conservative treatment, open or endoluminal repair have identified shortcomings in both forms of intervention: a case fatality of 2.7 to 5.5% for open repair and a cumulative reintervention rate at 5 years of 20% for endoluminal repair. 5-8 Trials comparing surveillance with endoluminal treatment of small (4 to 5.4 cm) AAAs have now commenced. 9


The increased incidence of AAA suggests that the public health measures that have helped reduce the burden of occlusive cardiovascular disease are not effective for this condition. Surgery is currently the only therapy for individuals with AAA, but intervention is costly and associated with morbidity and mortality. This highlights the need for further research into the cause of AAAs to facilitate the development of medical therapies. With the possible introduction of screening for AAAs, large numbers of small aneurysms will be diagnosed over the next decade. 10 The growing interest in treating small AAAs by endovascular repair may eliminate the opportunity to scientifically investigate drug therapies for the condition. This review outlines recent developments in the understanding of AAA pathogenesis and its relevance to the medical treatment of the condition.


Risk Factors for Abdominal Aortic Aneurysm


Our best understanding of the risk factors for AAAs comes from epidemiological screening studies ( Table 1 ). 1,2,11-20 Male gender and increasing age are consistently identified as non-modifiable risk factors for AAA. A positive family history of AAA is reported in 1% to 5% of patients (see below). 1,15 Ethnicity may also be important with some evidence that AAAs are more common in Northern Europeans than Asians or Africans. 1,15


TABLE 1. Risks Factors Associated With Aortic Aneurysm in Population Screening Studies


All case control studies report that smoking is a significant risk factor for AAA ( Table 1 ). The relative risk for current smokers is at least 2 and the association of ever smoking with AAA is 2.5 times greater than the association of ever smoking with CHD. 21 Continued smoking also results in increased AAA expansion, a greater risk of rupture and a worse prognosis. 22 There is some evidence of a slow decline of risk after cessation of smoking. 23 These studies indicate that smoking cessation is a priority in any patient with an AAA.


A history of, or being treated for, high plasma cholesterol concentrations has been associated with an increased risk of identifying an AAA in large screening studies. 1,15 Most, but not all, case-control studies in which fasting lipids have been measured indicate modest elevations of total cholesterol and LDL-cholesterol concentrations in individuals with AAAs. 2,11 Reducing cholesterol concentrations in patients is therefore desirable, although there is no evidence that this either prevents or slows the expansion of AAAs.


Hypertension has only a weak association with AAA ( Table 1 ). Assessment of the correlation between blood pressure and AAA is complicated because the definition of hypertension is often based on whether the patient is receiving treatment for this condition. 2,11-13,15 Interestingly, in subgroup analysis of data from the Chichester and Huntington population screening study, Wilmink and colleagues reported an association between aortic aneurysm and treatment of hypertension only in patients receiving calcium channel blockers (adjusted odds ratio 2.6, 1.5 to 4.3). 24 The authors related the worse prognosis in these patients to increased aortic stiffness and reduced collagen turn-over. 24 Because medications prescribed for hypercholesterolemia or hypertension may themselves affect the development of AAA, the relationship between these risk factors and aneurysm presence is difficult to assess. Interestingly diabetes mellitus has a negative association with AAA, although the reasons for this are not known ( Table 1 ).


Studies on Human Tissue and Serum


To identify critical mechanisms underlying aortic weakening and subsequent aneurysm formation, a large number of studies have assessed aortic histology, protein abundance and gene expression, and circulating markers in patients and controls. 25-37 The findings of these studies have been recently reviewed in detail. 25 Gene array studies have highlighted loss of extracellular matrix, accumulation of proteolytic enzymes, and cytokines as reproducible findings in human AAA biopsies ( Table 2 ).


TABLE 2. Examples of Gene Products Altered in Human AAA Formation or Expansion


The assessment of circulating markers has identified a number of lipids, cytokines, extracellular matrix, and thrombogenic proteins altered in the presence of AAAs, including high-density lipoprotein, lipoprotein (a), antibodies to Chlamydia, the proteolytic enzyme metalloproteinase 9, plasminogen activator inhibitor (PAI)-1, Tenascin-X, and homocysteine ( Table 2 ). 38-43 The findings from different studies are not always in agreement. Sangiorgi et al reported higher serum levels of matrix metalloproteinase (MMP)-9 in patients with aortic aneurysm; however, a much larger study by Eugster and colleagues did not confirm these findings. 43,44 Although these aortic biopsy and blood assessments give clues as to the mechanisms taking place in end-stage AAA they cannot clarify the initiating pathways since many of the abnormalities demonstrated will be a consequence of the underlying pathological processes.


Genetics and AAA


Screening studies suggest that having a first-degree relative with an AAA is associated with an odds ratio of 1.9 to 2.4 of developing a similar problem ( Table 1 ). AAAs develop in 20% of brothers of patients with the condition. 45 These and other findings including the presence of multiple aneurysms and systemic abnormalities in aneurysm patients eg, increased connective tissue laxity, all highlight a role for genetic factors in AAAs. 46


A variety of strategies have been used to identify possible genes important in AAA development. A small number of studies have concentrated on multiplex AAA families (with at least 2 affected members). 47,48 Genome-wide scans of these patients have suggested a role for genes located on chromosome 19q13 and 4q31. 47 Candidate genes in these regions include interleukin (IL)-15, endothelin receptor A, programmed cell death 5, and LDL receptor-related protein 3. 47 More commonly, a candidate gene approach has been used with testing of the association between genetic variants and the presence of an AAA. 41,49-61 Because it is likely that any single polymorphism will only impart a modest increased risk (odds ratio 1.2 to 2), association studies require very large numbers (up to 12 000 for alleles present in 5% of the population), appropriate controls, clear categorisation of phenotype, and careful analysis, as has been highlighted in a number of reviews and editorials. 62


As with other complex diseases, replication of gene association studies has been inconsistent. Strauss and colleagues reported an association between the C677T variant of the methylenetetrahydrofolate reductase gene and AAA in a small study (63 cases & 75 controls), a finding confirmed by Sofi and colleagues. 41,63 Jones et al in a larger study (428 cases & 270 controls) were unable to replicate this result. 52 Table 3 summarizes some of the larger genetic association studies of AAA carried out to date. 41,49-61 The type of controls used in these studies are important to consider. They must have aortic imaging to exclude AAA and be sourced from the same population with matching for ethnicity, age, and gender, and this is often not the case ( Table 3 ). The identification of genes of importance in AAA requires multicenter collaborative establishment of large numbers of patients and controls with accurate aortic imaging, recording of clinical risk factors, and DNA. Such collaborative data sets are presently being generated and will allow the assessment of a large number of candidate genes using rapidly developing technology able 1500) of single nucleotide polymorphisms in a sample using high through-put assays. The use of the HapMap will aid in the selection of appropriate polymorphisms. 64


TABLE 3. Genetic Polymorphisms Associated With AAA


Natural History of AAA


Our understanding of the rates of expansion of AAA and risk factors for expansion comes from longitudinal studies of cohorts with small (3 to 5.5 cm) AAAs. 22,65,66 Data about larger AAAs and risk factors for rupture come from studies of patients deemed unsuitable for surgery. 67


The study of the expansion of AAAs presents a number of methodological challenges. Firstly, the change in aortic diameter over time is small and characterized by periods of rapid growth and quiescence. Simple estimates of growth usually overestimate the rate of progression, and, given that losses to follow-up are inevitable, estimation techniques such as a Bayesian multilevel random effect model have been recommended. 22 Secondly, the measurement of aortic diameter using ultrasound (and to a lesser extent CT) has an error margin of 2 to 3 mm, 22,65,68 which is larger than the annual expansion of many small AAAs. Finally, larger AAAs are regularly lost to surveillance when clinicians recommend surgical intervention on the basis of risk of rupture. This is a particular problem in studies of 4 to 5 cm AAA (the group most likely to require medical treatment) where the intervention rate is around 10, 25, and 40% at 1, 2, and 3 years, respectively, even in centers with conservative surgical protocols. 1,6


Determinants of AAA Expansion


Understanding the cause of AAA progression can help identify secondary prevention strategies aimed at slowing expansion. The importance of diameter in predicting subsequent aneurysm growth has been clearly identified in studies of small AAAs. 5,6,22,65,66 Maximum aortic diameter is also the best determinant of the risk of rupture. In a study of 198 patients unsuitable for surgery, in which postmortems were carried out in 46%, rupture rate was estimated as 8%, 10%, and 20% per year for aneurysms measuring 5.5 to 5.9, 6.0 to 6.9, and 7.0 cm, respectively. 67


Current cigarette smoking is associated with AAA growth resulting in an estimated increase in expansion rate of 15% to 20%. 22,69 Other atherosclerotic risk factors such as hypertension and dyslipidemia are of uncertain importance with many studies finding no association. 22,65 Conversely, diabetes and peripheral vascular disease have been negatively associated with expansion. 22,70 Of the risk factors known to be associated with AAA presence, only smoking and diabetes mellitus have been consistently shown to predict AAA progression. Thus different factors may promote progression as opposed to initiation of AAA.


A number of investigators have assessed circulating and genetic predictors of AAA growth. Weak associations between polymorphisms in Apo E and Cystatin C with AAA growth rate have been identified. 71,72 The adjusted mean expansion rate for men with E2E4 and E3E4 Apo E genotypes were 4.2 (2.7 to 5.6) and 1.3 (0.7 to 1.9) mm/year, respectively, P =0.001. 71 Because of the variety of Apo E genotypes, however, only 3 and 17 patients, respectively, had these genotypes. The growth rate of patients with GG (n=263) and AA (n=20) genotypes for the +148 G to A polymorphism of Cystatin C were reported as 0.37 and 0.30 cm/year ( P =0.03 adjusted for smoking, gender, and age). 72


As outlined above, genotype is likely to play a role in AAA development and would also be expected to influence expansion; however, because the effect of most single polymorphisms is small, large studies are required. 62 Identification of phenotypically distinct groups of AAAs probably requires a minimum follow-up of five years. As many patients will require intervention during follow-up, the generation of adequately-sized cohorts is extremely difficult.


The investigation of the association between circulating proteins and AAA progression may identify factors which are influenced by both environmental and genotypic factors. Circulating markers associated with AAA growth or rapid progression include osteoprotegerin, 31 tissue-type plasminogen activator (t-PA), 73 anti-chlamydia pneumoniae antibodies, 74,75 macrophage migration inhibitory factor (MIF), 33 Cystatin C (negative correlation), 76 P-plasmin-antiplasmin-complexes, 77 serum-elastin-peptides, 78,79 procollagen-IIIN-terminal propeptide (PIIINP), 80 and MMP-9 81 ( Table 2 ). Circulating biomarkers such as these could be used to monitor the progress and response to treatment of AAA. Sufficiently powered multicenter studies with long follow-up of aortic diameter are required so that the relative merits of a number of these potential biomarkers can be compared. Such studies may identify characteristics associated with different growth patterns such as AAA regression, stasis, or rapid progression.


Role of Medication for AAA: Animal Studies


A number of animal models of aortic aneurysm have been developed in rabbits, rats, and mice. 82-84 The rabbit and rat models have principally relied on a chemically induced aortic degeneration stimulated by painting or infusion of elastolytic solution onto the infrarenal aorta. 82,83 The availability of a range of genetically modified mice has allowed for a greater variety of models in this species (see review by Daugherty and Cassis 84 ). These studies have highlighted the importance of inflammation, proteolysis, and antioxidant mechanisms in aortic degeneration. A number of investigators have assessed the role of medication in suppressing aneurysm development in these models ( Table 4 ). 83,85-106 These studies demonstrate the potential of a wide range of medications including those inhibiting MMPs, Angiotensin II synthesis and receptors, and oxidative stress. A recent study using 2 mice models reported the regression of aortic aneurysm using a c-Jun N-terminal kinase inhibitor. 106 Most studies indicate an independent effect of the medication on aneurysm and atherosclerosis in these models ( Table 4 ).


TABLE 4. Medication Demonstrated To Inhibit AAA in Animal Models


Role of Medication for AAA: Human Studies


Three types of human studies have been carried out to investigate the efficacies of putative medical therapies for AAA, namely explant studies, medication association studies, and randomized controlled trials. In explant studies biopsies retrieved from AAA at the time of open surgery are incubated with drugs to assess their ability to modulate biological factors associated with AAA progression. In this type of study allowance needs to be made for patient heterogeneity and the concurrent use of drugs by subjects from which the biopsies are removed. The viability of cultured samples is also limited (usually around one week). These studies have highlighted the potential of statins, Angiotensin II inhibitors (Angiotensin Converting Enzyme inhibitors and Angiotensin II blockers), macrolides, and cyclooxygenase inhibitors in reducing the production of proteinases and cytokines from human AAA biopsies. 31,107-109 Indomethacin for example has been demonstrated to reduce IL-1ß, IL-6, and PGE 2 secretion from explants but had no effect on MMP production. 109 Similarly, Angiotensin II blockers have been shown to reduce the production of the cytokine osteoprotegerin from aortic aneurysm explants. 31 Tetracyclines have been shown to reduce MMP production, 108 while the MMP-3 and MMP-9 concentrations are reduced in the AAA biopsies of patients receiving statins. 107 The findings of human in vitro and animal studies ( Table 4 ) suggest potential benefit from statins, Angiotensin II inhibitors, beta adrenoceptor blockers, nonsteroidal antiinflammatory medications, and macrolides in the treatment of AAA.


Unfortunately, clinical studies to examine the role of these medications in slowing AAA progression have been limited to date. 110-112 In a cohort of patients in the UK small aneurysm trial the concurrent use of nonsteroidal antiinflammatory medication was noted to be associated with reduced aortic expansion. 113 Concerns regarding the cardiac effect of cyclooxygenase inhibitors might limit the use of this medication. 114 The largest and best conducted study to date examined the effect of propranolol in a randomized controlled trial of 548 patients with small (3 to 5 cm) AAAs followed for a mean of 2.5 years. 110 No effect on AAA growth, intervention rate, or mortality could be demonstrated for the treatment group. Furthermore, 42% of patients receiving propranolol had to discontinue the medication and the patients randomized to this group reported a worse health-related quality of life. 110 The effect of antibiotics targeting Chlamydia pneumoniae in patients with AAAs have been studied in two small randomized trials. 111,112 In addition, the antibiotics used, doxycycline and roxithromycin, have also been shown to reduce MMP production in animal models and/or human explants, and inhibit aneurysm development experimentally ( Table 4 ). Mosorin and colleagues randomized 32 patients with small aneurysms to doxycycline or placebo and followed them for 18 months, reporting a nonsignificant reduction in expansion overall. 111 Vammen et al randomized 92 patients with small aneurysms between roxithromycin and placebo over a mean of 1.5 years and reported a significant reduction in aortic expansion from 2.75 to 1.56 mm/year, although growth rate appears to have been calculated by linear regression. 112 Neither of the medications were associated with significant side-effects and drop-outs were minimal. 111,112


Larger studies with longer follow-up incorporating these and other medications are needed to clarify the role of these treatments on a range of end points, including expansion and intervention rates. In addition to considering the effect of variable growth rate, losses to follow-up, measurement error, and calculation of expansion, investigators should also pay attention to concurrent medication. A recent follow-up study of 150 patients with small AAAs reported an association between concurrent statin therapy and reduced AAA expansion. 115 However, without a randomized controlled trial it is impossible to be clear that the medication rather than another associated factor, such as other risk factors in these patients or other concurrent medications, were responsible 40% of patients with AAA are routinely prescribed statins, beta adrenoceptor blockers, and angiotensin II inhibitors. Use of these drugs will probably increase as evidence for their benefit accumulates. Although it is plausible that concurrent use of these drugs would inhibit AAA expansion, it may now be impossible to assess this in a large randomized controlled trial.


Future Directions


Data from epidemiological studies highlight the potential benefit of smoking cessation and control of blood pressure and lipids in reducing the development of AAA. In patients who already have an AAA, treatments which reduce aortic inflammation and proteolysis and support vascular smooth muscle cell (VSMC) recovery are required. In vitro and animal studies highlight the potential of statins, Angiotensin II inhibitors, macrolides, and medication blocking inflammatory pathways. Work has commenced on understanding how traditional risk factors, circulating markers, and genotype can be used to define risk of AAA progression and therefore select out patients for aggressive treatment.


The further development of specific medical therapies for AAAs requires a number of carefully planned large randomized trials using such promising medications in at risk patients. When effective medications have been identified it may be possible to incorporate these with surgical treatments. Thus oral medications or drugs coated onto an endoluminal graft may improve the results of endovascular AAA repair.


Acknowledgments


Sources of Funding


This work was supported by grant numbers R01 HL080010-01 from the National Institutes of Health, and 279408 and 379600 from the National Health and Medical Research Council, Australia.


Disclosures


None.

【参考文献】
  Lederle FA, Johnson GR, Wilson SE, Chute EP, Littooy FN, Bandyk D, Krupski WC, Barone GW, Acher CW, Ballard DJ. Prevalence and associations of abdominal aortic aneurysm detected through screening. Aneurysm Detection and Management (ADAM) Veterans Affairs Cooperative Study Group. Ann Intern Med. 1997; 126: 441-449.

Alcorn HG, Wolfson SK Jr, Sutton-Tyrrell K, Kuller luteinizing hormone (LH), O?Leary D. Risk factors for abdominal aortic aneurysms in older adults enrolled in The Cardiovascular Health Study. Arterioscler Thromb Vasc Biol.; 16:963-970.

Gillum RF. Epidemiology of aortic aneurysm in the United States. J Clin Epidemiol. 1995; 48: 1289-1298.

Best VA, Price JF, Fowkes FG. Persistent increase in the incidence of abdominal aortic aneurysm in Scotland, 1981-2000. Br J Surg. 2003; 90: 1510-1515.

Lederle FA, Wilson SE, Johnson GR, Reinke DB, Littooy FN, Acher CW, Ballard DJ, Messina LM, Gordon IL, Chute EP, Krupski WC, Busuttil SJ, Barone GW, Sparks S, Graham LM, Rapp JH, Makaroun MS, Moneta GL, Cambria RA, Makhoul RG, Eton D, Ansel HJ, Freischlag JA, Bandyk D. Immediate repair compared with surveillance of small abdominal aortic aneurysms. N Engl J Med. 2002; 346: 1437-1444.

Mortality results for randomised controlled trial of early elective surgery or ultrasonographic surveillance for small abdominal aortic aneurysms. The UK Small Aneurysm Trial Participants. Lancet. 1998; 352: 1649-1655.

Endovascular aneurysm repair versus open repair in patients with abdominal aortic aneurysm (EVAR trial 1): randomised controlled trial. Lancet. 2005; 365: 2179-2186.

Endovascular aneurysm repair and outcome in patients unfit for open repair of abdominal aortic aneurysm (EVAR trial 2): randomised controlled trial. Lancet. 2005; 365: 2187-2192.

Cao P. Comparison of surveillance vs Aortic Endografting for Small Aneurysm Repair (CAESAR) trial: study design and progress. Eur J Vasc Endovasc Surg. 2005; 30: 245-251.

Fleming C, Whitlock EP, Beil TL, Lederle FA. Screening for abdominal aortic aneurysm: a best-evidence systematic review for the U.S. Preventive Services Task Force. Ann Intern Med. 2005; 142: 203-211.

Pleumeekers HJ, Hoes AW, van der Does E, van Urk H, Hofman A, de Jong PT, Grobbee DE. Aneurysms of the abdominal aorta in older adults. The Rotterdam Study. Am J Epidemiol. 1995; 142: 1291-1299.

Pleumeekers HJ, Hoes AW, Hofman A, van Urk H, van der Does E, Grobbee DE. Selecting subjects for ultrasonographic screening for aneurysms of the abdominal aorta: four different strategies. Int J Epidemiol. 1999; 28: 682-686.

Singh K, Bonaa KH, Jacobsen BK, Bjork L, Solberg S. Prevalence of and risk factors for abdominal aortic aneurysms in a population-based study : The Tromso Study. Am J Epidemiol. 2001; 154: 236-244.

Simoni G, Pastorino C, Perrone R, Ardia A, Gianrossi R, Decian F, Cittadini G Jr, Baiardi A, Bachi V. Screening for abdominal aortic aneurysms and associated risk factors in a general population. Eur J Vasc Endovasc Surg. 1995; 10: 207-210.

Jamrozik K, Norman PE, Spencer CA, Parsons RW, Tuohy R, Lawrence-Brown MM, Dickinson JA. Screening for abdominal aortic aneurysm: lessons from a population-based study. Med J Aust. 2000; 173: 345-350.

Smith FC, Grimshaw GM, Paterson IS, Shearman CP, Hamer JD. Ultrasonographic screening for abdominal aortic aneurysm in an urban community. Br J Surg. 1993; 80: 1406-1409.

Kanagasabay R, Gajraj H, Pointon L, Scott RA. Co-morbidity in patients with abdominal aortic aneurysm. J Med Screen. 1996; 3: 208-210.

Krohn CD, Kullmann G, Kvernebo K, Rosen L, Kroese A. Ultrasonographic screening for abdominal aortic aneurysm. Eur J Surg. 1992; 158: 527-530.

Lee AJ, Fowkes FG, Carson MN, Leng GC, Allan PL. Smoking, atherosclerosis and risk of abdominal aortic aneurysm. Eur Heart J. 1997; 18: 671-676.

Lindholt JS, Henneberg EW, Fasting H, Juul S. Hospital based screening of 65-73 year old men for abdominal aortic aneurysms in the county of Viborg, Denmark. J Med Screen. 1996; 3: 43-46.

Lederle FA, Nelson DB, Joseph AM. Smokers? relative risk for aortic aneurysm compared with other smoking-related diseases: a systematic review. J Vasc Surg. 2003; 38: 329-334.

Brady AR, Thompson SG, Fowkes FG, Greenhalgh RM, Powell JT. Abdominal aortic aneurysm expansion: risk factors and time intervals for surveillance. Circulation. 2004; 110: 16-21.

Wilmink TB, Quick CR, Day NE. The association between cigarette smoking and abdominal aortic aneurysms. J Vasc Surg. 1999; 30: 1099-1105.

Wilmink AB, Vardulaki KA, Hubbard CS, Day NE, Ashton HA, Scott AP, Quick CR. Are antihypertensive drugs associated with abdominal aortic aneurysms? J Vasc Surg. 2002; 36: 751-757.

Shimizu K, Mitchell RN, Libby P. Inflammation and Cellular Immune Responses in Abdominal Aortic Aneurysms. Arterioscler Thromb Vasc Biol. 2006; 26: 987-994.

Armstrong PJ, Johanning JM, Calton WC Jr, Delatore JR, Franklin DP, Han DC, Carey DJ, Elmore JR. Differential gene expression in human abdominal aorta: aneurysmal versus occlusive disease. J Vasc Surg. 2002; 35: 346-355.

Tung WS, Lee JK, Thompson RW. Simultaneous analysis of 1176 gene products in normal human aorta and abdominal aortic aneurysms using a membrane-based complementary DNA expression array. J Vasc Surg. 2001; 34: 143-150.

Kowalewski R, Sobolewski K, Malkowski A, Wolanska M, Gacko M. Evaluation of enzymes involved in proteoglycan degradation in the wall of abdominal aortic aneurysms. J Vasc Res. 2006; 43: 95-100.

Jones KG, Brull DJ, Brown LC, Sian M, Greenhalgh RM, Humphries SE, Powell JT. IL-6 (IL-6) and the prognosis of abdominal aortic aneurysms. Circulation. 2001; 103: 2260-2265.

Liu J, Sukhova GK, Yang JT, Sun J, Ma L, Ren A, Xu WH, Fu H, Dolganov GM, Hu C, Libby P, Shi GP. Cathepsin L expression and regulation in human abdominal aortic aneurysm, atherosclerosis, and vascular cells. Atherosclerosis. 2006; 184: 302-311.

Moran CS, McCann M, Karan M, Norman P, Ketheesan N, Golledge J. Association of osteoprotegerin with human abdominal aortic aneurysm progression. Circulation. 2005; 111: 3119-3125.

Shi GP, Sukhova GK, Grubb A, Ducharme A, Rhode LH, Lee RT, Ridker PM, Libby P, Chapman HA. Cystatin C deficiency in human atherosclerosis and aortic aneurysms. J Clin Invest. 1999; 104: 1191-1197.

Pan JH, Lindholt JS, Sukhova GK, Baugh JA, Henneberg EW, Bucala R, Donnelly SC, Libby P, Metz C, Shi GP. Macrophage migration inhibitory factor is associated with aneurysmal expansion. J Vasc Surg. 2003; 37: 628-635.

Walton LJ, Franklin IJ, Bayston T, Brown LC, Greenhalgh RM, Taylor GW, Powell JT. Inhibition of prostaglandin (PG) E2 synthesis in abdominal aortic aneurysms: implications for smooth muscle cell viability, inflammatory processes, and the expansion of abdominal aortic aneurysms. Circulation. 1999; 100: 48-54.

Meijer A, van Der Vliet JA, Roholl PJ, Gielis-Proper SK, de Vries A, Ossewaarde JM. Chlamydia pneumoniae in abdominal aortic aneurysms: abundance of membrane components in the absence of heat shock protein 60 and DNA. Arterioscler Thromb Vasc Biol. 1999; 19: 2680-2686.

Porqueddu M, Spirito R, Parolari A, Zanobini M, Pompilio G, Polvani G, Alamanni F, Stangalini D, Tremoli E, Biglioli P. Lack of association between serum immunoreactivity and Chlamydia pneumoniae detection in the human aortic wall. Circulation. 2002; 106: 2647-2648.

Blasi F, Denti F, Erba M, Cosentini R, Raccanelli R, Rinaldi A, Fagetti L, Esposito G, Ruberti U, Allegra L. Detection of Chlamydia pneumoniae but not Helicobacter pylori in atherosclerotic plaques of aortic aneurysms. J Clin Microbiol. 1996; 34: 2766-2769.

Wanhainen A, Bergqvist D, Boman K, Nilsson TK, Rutegard J, Bjorck M. Risk factors associated with abdominal aortic aneurysm: a population-based study with historical and current data. J Vasc Surg. 2005; 41: 390-396.

Hobbs SD, Claridge MW, Quick CR, Day NE, Bradbury AW, Wilmink AB. LDL cholesterol is associated with small abdominal aortic aneurysms. Eur J Vasc Endovasc Surg. 2003; 26: 618-622.

Blanchard JF, Armenian HK, Peeling R, Friesen PP, Shen C, Brunham RC. The relation between Chlamydia pneumoniae infection and abdominal aortic aneurysm: case-control study. Clin Infect Dis. 2000; 30: 946-947.

Sofi F, Marcucci R, Giusti B, Pratesi G, Lari B, Sestini I, Lo Sapio P, Pulli R, Pratesi C, Abbate R, Gensini GF. High levels of homocysteine, lipoprotein (a) and plasminogen activator inhibitor-1 are present in patients with abdominal aortic aneurysm. Thromb Haemost. 2005; 94: 1094-1098.

Zweers MC, Peeters AC, Graafsma S, Kranendonk S, van der Vliet JA, den Heijer M, Schalkwijk J. Abdominal aorticaneurysm is associated with high serum levels of tenascin-X and decreased aneurysmal tissue Tenascin-X. Circulation. 2006; 113: 1702-1707.

Sangiorgi G, D?Averio R, Mauriello A, Bondio M, Pontillo M, Castelvecchio S, Trimarchi S, Tolva V, Nano G, Rampoldi V, Spagnoli LG, Inglese L. Plasma levels of metalloproteinases-3 and -9 as markers of successful abdominal aortic aneurysm exclusion after endovascular graft treatment. Circulation. 2001; 104: I288-I295.

Eugster T, Huber A, Obeid T, Schwegler I, Gurke L, Stierli P. Aminoterminal propeptide of type III procollagen and matrix metalloproteinases-2 and -9 failed to serve as serum markers for abdominal aortic aneurysm. Eur J Vasc Endovasc Surg. 2005; 29: 378-382.

Salo JA, Soisalon-Soininen S, Bondestam S, Mattila PS. Familial occurrence of abdominal aortic aneurysm. Ann Intern Med. 1999; 130: 637-642.

Wilmink AB, Quick CR, Hubbard CS, Day NE. The association between connective tissue laxity and the risk of an abdominal aortic aneurysm. Eur J Vasc Endovasc Surg. 2000; 20: 290-295.

Shibamura H, Olson JM, van Vlijmen-Van Keulen C, Buxbaum SG, Dudek DM, Tromp G, Ogata T, Skunca M, Sakalihasan N, Pals G, Limet R, MacKean GL, Defawe O, Verloes A, Arthur C, Lossing AG, Burnett M, Sueda T, Kuivaniemi H. Genome scan for familial abdominal aortic aneurysm using sex and family history as covariates suggests genetic heterogeneity and identifies linkage to chromosome 19q13. Circulation. 2004; 109: 2103-2108.

Kuivaniemi H, Shibamura H, Arthur C, Berguer R, Cole CW, Juvonen T, Kline RA, Limet R, Mackean G, Norrgard O, Pals G, Powell JT, Rainio P, Sakalihasan N, van Vlijmen-van Keulen C, Verloes A, Tromp G. Familial abdominal aortic aneurysms: collection of 233 multiplex families. J Vasc Surg. 2003; 37: 340-345.

Fatini C, Pratesi G, Sofi F, Gensini F, Sticchi E, Lari B, Pulli R, Dorigo W, Azas L, Pratesi C, Gensini GF, Abbate R. ACE DD genotype: a predisposing factor for abdominal aortic aneurysm. Eur J Vasc Endovasc Surg. 2005; 29: 227-232.

Pola R, Gaetani E, Santoliquido A, Gerardino L, Cattani P, Serricchio M, Tondi P, Flore R, Grande M, Carbonin P, Fadda G, Pola P. Abdominal aortic aneurysm in normotensive patients: association with angiotensin-converting enzyme gene polymorphism. Eur J Vasc Endovasc Surg. 2001; 21: 445-449.

Hamano K, Ohishi M, Ueda M, Fujioka K, Katoh T, Zempo N, Fujimura Y, Okamura A, Rakugi H, Higaki J, Ogihara T, Esato K. Deletion polymorphism in the gene for angiotensin-converting enzyme is not a risk factor predisposing to abdominal aortic aneurysm. Eur J Vasc Endovasc Surg. 1999; 18: 158-161.

Jones GT, Harris EL, Phillips LV, van Rij AM. The methylenetetrahydrofolate reductase C677T polymorphism does not associate with susceptibility to abdominal aortic aneurysm. Eur J Vasc Endovasc Surg. 2005; 30: 137-142.

Jones GT, Phillips VL, Harris EL, Rossaak JI, van Rij AM. Functional matrix metalloproteinase-9 polymorphism (C-1562T) associated with abdominal aortic aneurysm. J Vasc Surg. 2003; 38: 1363-1367.

Rossaak JI, Van Rij AM, Jones GT, Harris EL. Association of the 4G/5G polymorphism in the promoter region of plasminogen activator inhibitor-1 with abdominal aortic aneurysms. J Vasc Surg. 2000; 31: 1026-1032.

Fatini C, Sofi F, Sticchi E, Bolli P, Sestini I, Falciani M, Azas L, Pratesi G. eNOS G894T polymorphism as a mild predisposing factor for abdominal aortic aneurysm. J Vasc Surg. 2005; 42: 415-419.

Massart F, Marini F, Menegato A, Del Monte F, Nuti M, Butitta F, Ferrari M, Balbarini A, Brandi ML. Allelic genes involved in artery compliance and susceptibility to sporadic abdominal aortic aneurysm. J Steroid Biochem Mol Biol. 2004; 92: 413-418.

Ghilardi G, Biondi ML, Battaglioli L, Zambon A, Guagnellini E, Scorza R. Genetic risk factor characterizes abdominal aortic aneurysm from arterial occlusive disease in human beings: CCR5 Delta 32 deletion. J Vasc Surg. 2004; 40: 995-1000.

Brown MJ, Burton PR, Hornsburgh T, Nicholson ML, Bell PRF, Sayers R. The role of cytokine gene polymorhisms in the pathogenesis of abdominal aortic aneurysms: a case control study. J Vasc Surg. 2003; 37: 999-1005.

Schillinger M, Exner M, Mlekusch W, Domanovits H, Huber K, Mannhalter C, Wagner O, Minar E. Heme oxygenase-1 gene promoter polymorphism is associated with abdominal aortic aneurysm. Thromb Res. 2002; 106: 131-136.

Ogata T, Shibamura H, Tromp G, Sinha M, Goddard KA, Sakalihasan N, Limet R, MacKean GL, Arthur C, Sueda T, Land S, Kuivaniemi H. Genetic analysis of polymorphisms in biologically relevant candidate genes in patients with abdominal aortic aneurysms. J Vasc Surg. 2005; 41: 1036-1042.

Rasmussen TE, Hallett JW Jr, Schulte S, Harmsen WS, O?Fallon WM, Weyand CM. Genetic similarity in inflammatory and degenerative abdominal aortic aneurysms: a study of human leukocyte antigen class II disease risk genes. J Vasc Surg. 2001; 34: 84-89.

Hattersley AT, McCarthy MI. What makes a good genetic association study? Lancet. 2005; 366: 1315-1323.

Strauss E, Waliszewski K, Gabriel M, Zapalski S, Pawlak AL. Increased risk of the abdominal aortic aneurysm in carriers of the MTHFR 677T allele. J Appl Genet. 2003; 44: 85-93.

International HapMap Consortium. A haplotype map of the human genome. Nature. 2005; 437: 1299-1320.

Norman P, Spencer CA, Lawrence-Brown MM, Jamrozik K. C-reactive protein levels and the expansion of screen-detected abdominal aortic aneurysms in men. Circulation. 2004; 110: 862-866.

Brown LC, Powell JT. Risk factors for aneurysm rupture in patients kept under ultrasound surveillance. UK Small Aneurysm Trial Participants. Ann Surg. 1999; 230: 289-296;discussion 296-287.

Lederle FA, Johnson GR, Wilson SE, Ballard DJ, Jordan WD Jr, Blebea J, Littooy FN, Freischlag JA, Bandyk D, Rapp JH, Salam AA. Rupture rate of large abdominal aortic aneurysms in patients refusing or unfit for elective repair. J Am Med Assoc. 2002; 287: 2968-2972.

Lederle FA, Wilson SE, Johnson GR, Reinke DB, Littooy FN, Acher CW, Messina LM, Ballard DJ, Ansel HJ. Variability in measurement of abdominal aortic aneurysms. Abdominal Aortic Aneurysm Detection and Management Veterans Administration Cooperative Study Group. J Vasc Surg. 1995; 21: 945-952.

Lindholt JS, Heegaard NH, Vammen S, Fasting H, Henneberg EW, Heickendorff L. Smoking, but not lipids, lipoprotein(a) and antibodies against oxidised LDL, is correlated to the expansion of abdominal aortic aneurysms. Eur J Vasc Endovasc Surg. 2001; 21: 51-56.

Santilli SM, Littooy FN, Cambria RA, Rapp JH, Tretinyak AS, d?Audiffret AC, Kuskowski MA, Roethle ST, Tomczak CM, Krupski WC. Expansion rates and outcomes for the 3.0-cm to the 3.9-cm infrarenal abdominal aortic aneurysm. J Vasc Surg. 2002; 35: 666-671.

Gerdes LU, Lindholt JS, Vammen S, Henneberg EW, Fasting H. Apolipoprotein E genotype is associated with differential expansion rates of small abdominal aortic aneurysms. Br J Surg. 2000; 87: 760-765.

Eriksson P, Jones KG, Brown LC, Greenhalgh RM, Hamsten A, Powell JT. Genetic approach to the role of cysteine proteases in the expansion of abdominal aortic aneurysms. Br J Surg. 2004; 91: 86-89.

Lindholt JS, Jorgensen B, Shi GP, Henneberg EW. Relationships between activators and inhibitors of plasminogen, and the progression of small abdominal aortic aneurysms. Eur J Vasc Endovasc Surg. 2003; 25: 546-551.

Lindholt JS, Ashton HA, Scott RA. Indicators of infection with Chlamydia pneumoniae are associated with expansion of abdominal aortic aneurysms. J Vasc Surg. 2001; 34: 212-215.

Lindholt JS, Juul S, Vammen S, Lind I, Fasting H, Henneberg EW. Immunoglobulin A antibodies against Chlamydia pneumoniae are associated with expansion of abdominal aortic aneurysm. Br J Surg. 1999; 86: 634-638.

Lindholt JS, Erlandsen EJ, Henneberg EW. Cystatin C deficiency is associated with the progression of small abdominal aortic aneurysms. Br J Surg. 2001; 88: 1472-1475.

Lindholt JS, Jorgensen B, Fasting H, Henneberg EW. Plasma levels of plasmin-antiplasmin-complexes are predictive for small abdominal aortic aneurysms expanding to operation-recommendable sizes. J Vasc Surg. 2001; 34: 611-615.

Lindholt JS, Ashton HA, Heickendorff L, Scott RA. Serum elastin peptides in the preoperative evaluation of abdominal aortic aneurysms. Eur J Vasc Endovasc Surg. 2001; 22: 546-550.

Lindholt JS, Heickendorff L, Henneberg EW, Fasting H. Serum-elastin-peptides as a predictor of expansion of small abdominal aortic aneurysms. Eur J Vasc Endovasc Surg. 1997; 14: 12-16.

Lindholt JS, Heickendorff L, Vammen S, Fasting H, Henneberg EW. Five-year results of elastin and collagen markers as predictive tools in the management of small abdominal aortic aneurysms. Eur J Vasc Endovasc Surg. 2001; 21: 235-240.

Lindholt JS, Vammen S, Fasting H, Henneberg EW, Heickendorff L. The plasma level of matrix metalloproteinase 9 may predict the natural history of small abdominal aortic aneurysms. A preliminary study. Eur J Vasc Endovasc Surg. 2000; 20: 281-285.

Freestone T, Turner RJ, Higman DJ, Lever MJ, Powell JT. Influence of hypercholesterolemia and adventitial inflammation on the development of aortic aneurysm in rabbits. Arterioscler Thromb Vasc Biol. 1997; 17: 10-17.

Kalyanasundaram A, Elmore JR, Manazer JR, Golden A, Franklin DP, Galt SW, Zakhary EM, Carey DJ. Simvastatin suppresses experimental aortic aneurysm expansion. J Vasc Surg. 2006; 43: 117-124.

Daugherty A, Cassis LA. Mouse models of abdominal aortic aneurysms. Arterioscler Thromb Vasc Biol. 2004; 24: 429-434.

Ricci MA, Slaiby JM, Gadowski GR, Hendley ED, Nichols P, Pilcher DB. Effects of hypertension and propranolol upon aneurysm expansion in the Anidjar/Dobrin aneurysm model. Ann N Y Acad Sci. 1996; 800: 89-96.

Slaiby JM, Ricci MA, Gadowski GR, Hendley ED, Pilcher DB. Expansion of aortic aneurysms is reduced by propranolol in a hypertensive rat model. J Vasc Surg. 1994; 20: 178-183.

Brophy C, Tilson JE, Tilson MD. Propranolol delays the formation of aneurysms in the male blotchy mouse. J Surg Res. 1988; 44: 687-689.

Steinmetz ejection factor (EF), Buckley C, Shames ML, Ennis TL, Vanvickle-Chavez SJ, Mao D, Goeddel LA, Hawkins CJ, Thompson RW. Treatment with simvastatin suppresses the development of experimental abdominal aortic aneurysms in normal and hypercholesterolemic mice. Ann Surg. 2005; 241:92-101.

Manning MW, Cassis LA, Daugherty A. Differential effects of doxycycline, a broad-spectrum matrix metalloproteinase inhibitor, on angiotensin II-induced atherosclerosis and abdominal aortic aneurysms. Arterioscler Thromb Vasc Biol. 2003; 23: 483-488.

Petrinec D, Liao S, Holmes DR, Reilly JM, Parks WC, Thompson RW. Doxycycline inhibition of aneurysmal degeneration in an elastase-induced rat model of abdominal aortic aneurysm: preservation of aortic elastin associated with suppressed production of 92 kD gelatinase. J Vasc Surg. 1996; 23: 336-346.

Curci JA, Petrinec D, Liao S, Golub LM, Thompson RW. Pharmacologic suppression of experimental abdominal aortic aneurysms: acomparison of doxycycline and four chemically modified tetracyclines. J Vasc Surg. 1998; 28: 1082-1093.

Bigatel DA, Elmore JR, Carey DJ, Cizmeci-Smith G, Franklin DP, Youkey JR. The matrix metalloproteinase inhibitor BB-94 limits expansion of experimental abdominal aortic aneurysms. J Vasc Surg. 1999; 29: 130-138.

Moore G, Liao S, Curci JA, Starcher BC, Martin RL, Hendricks RT, Chen JJ, Thompson RW. Suppression of experimental abdominal aortic aneurysms by systemic treatment with a hydroxamate-based matrix metalloproteinase inhibitor (RS 132908). J Vasc Surg. 1999; 29: 522-532.

Liao S, Miralles M, Kelley BJ, Curci JA, Borhani M, Thompson RW. Suppression of experimental abdominal aortic aneurysms in the rat by treatment with angiotensin-converting enzyme inhibitors. J Vasc Surg. 2001; 33: 1057-1064.

Armstrong PJ, Franklin DP, Carey DJ, Elmore JR. Suppression of experimental aortic aneurysms: comparison of inducible nitric oxide synthase and cyclooxygenase inhibitors. Ann Vasc Surg. 2005; 19: 248-257.

Johanning JM, Franklin DP, Han DC, Carey DJ, Elmore JR. Inhibition of inducible nitric oxide synthase limits nitric oxide production and experimental aneurysm expansion. J Vasc Surg. 2001; 33: 579-586.

Wang YX, Martin-McNulty B, da Cunha V, Vincelette J, Lu X, Feng Q, Halks-Miller M, Mahmoudi M, Schroeder M, Subramanyam B, Tseng JL, Deng GD, Schirm S, Johns A, Kauser K, Dole WP, Light DR. Fasudil, a Rho-kinase inhibitor, attenuates angiotensin II-induced abdominal aortic aneurysm in apolipoprotein E-deficient mice by inhibiting apoptosis and proteolysis. Circulation. 2005; 111: 2219-2226.

Gavrila D, Li WG, McCormick ML, Thomas M, Daugherty A, Cassis LA, Miller FJ Jr, Oberley LW, Dellsperger KC, Weintraub NL. Vitamin E inhibits abdominal aortic aneurysm formation in angiotensin II-infused apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol. 2005; 25: 1671-1677.

Parodi FE, Mao D, Ennis TL, Bartoli MA, Thompson RW. Suppression of experimental abdominal aortic aneurysms in mice by treatment with pyrrolidine dithiocarbamate, an antioxidant inhibitor of nuclear factor-kappaB. J Vasc Surg. 2005; 41: 479-489.

Lawrence DM, Singh RS, Franklin DP, Carey DJ, Elmore JR. Rapamycin suppresses experimental aortic aneurysm growth. J Vasc Surg. 2004; 40: 334-338.

Miralles M, Wester W, Sicard GA, Thompson R, Reilly JM. Indomethacin inhibits expansion of experimental aortic aneurysms via inhibition of the cox2 isoform of cyclooxygenase. J Vasc Surg. 1999; 29: 884-892;discussion 892-883.

King VL, Trivedi D, Gitlin JM, Loftin CD. Selective cyclooxygenase-2 inhibition with celecoxib decreases angiotensin II-induced abdominal aortic aneurysm formation in mice. Arterioscler Thromb Vasc Biol. 2006; 26: 1137-1143.

Ailawadi G, Eliason JL, Roelofs KJ, Sinha I, Hannawa KK, Kaldjian EP, Lu G, Henke PK, Stanley JC, Weiss SJ, Thompson RW, Upchurch GR Jr. Gender differences in experimental aortic aneurysm formation. Arterioscler Thromb Vasc Biol. 2004; 24: 2116-2122.

Martin-McNulty B, Tham DM, da Cunha V, Ho JJ, Wilson DW, Rutledge JC, Deng GG, Vergona R, Sullivan ME, Wang YX. 17 Beta-estradiol attenuates development of angiotensin II-induced aortic abdominal aneurysm in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol. 2003; 23: 1627-1632.

Grigoryants V, Hannawa KK, Pearce CG, Sinha I, Roelofs KJ, Ailawadi G, Deatrick KB, Woodrum DT, Cho BS, Henke PK, Stanley JC, Eagleton MJ, Upchurch GR. Tamoxifen up-regulates catalase production, inhibits vessel wall neutrophil infiltration, and attenuates development of experimental abdominal aortic aneurysms. J Vasc Surg. 2005; 41: 108-114.

Yoshimura K, Aoki H, Ikeda Y, Fujii K, Akiyama N, Furutani A, Hoshii Y, Tanaka N, Ricci R, Ishihara T, Esato K, Hamano K, Matsuzaki M. Regression of abdominal aortic aneurysm by inhibition of c-Jun N-terminal kinase. Nat Med. 2005; 11: 1330-1338.

Wilson WR, Evans J, Bell PR, Thompson MM. 3hydroxy3methylglutaryl (HMG)-coenzymeA (CoA) reductase inhibitors (statins) decrease MMP-3 and MMP-9 concentrations in abdominal aortic aneurysms. Eur J Vasc Endovasc Surg. 2005; 30: 259-262.

Franklin IJ, Harley SL, Greenhalgh RM, Powell JT. Uptake of tetracycline by aortic aneurysm wall and its effect on inflammation and proteolysis. Br J Surg. 1999; 86: 771-775.

Franklin IJ, Walton LJ, Greenhalgh RM, Powell JT. The influence of indomethacin on the metabolism and cytokine secretion of human aneurysmal aorta. Eur J Vasc Endovasc Surg. 1999; 18: 35-42.

Propranolol for small abdominal aortic aneurysms: results of a randomized trial. J Vasc Surg. 2002; 35: 72-79.

Mosorin M, Juvonen J, Biancari F, Satta J, Surcel HM, Leinonen M, Saikku P, Juvonen T. Use of doxycycline to decrease the growth rate of abdominal aortic aneurysms: a randomized, double-blind, placebo-controlled pilot study. J Vasc Surg. 2001; 34: 606-610.

Vammen S, Lindholt JS, Ostergaard L, Fasting H, Henneberg EW. Randomized double-blind controlled trial of roxithromycin for prevention of abdominal aortic aneurysm expansion. Br J Surg. 2001; 88: 1066-1072.

Franklin IJ, Walton LJ, Brown L, Greenhalgh RN, Powell JT. Vascular surgical society of Great Britain and Ireland: non-steroidal anti-inflammatory drugs to treat abdominal aortic aneurysm. Br J Surg.. 1999; 86: 707.

Juni P, Nartey L, Reichenbach S, Sterchi R, Dieppe PA, Egger M. Risk of cardiovascular events and rofecoxib: cumulative meta-analysis. Lancet. 2004; 364: 2021-2029.

Schouten O, van Laanen JH, Boersma E, Vidakovic R, Feringa HH, Dunkelgrun M, Bax JJ, Koning J, van Urk H, Poldermans D. Statins are associated with a reduced infrarenal abdominal aortic aneurysm growth. Eur J Vasc Endovasc Surg. 2006; 32: 21-26.


作者单位:Jonathan Golledge; Juanita Muller; Alan Daugherty; Paul NormanFrom the Vascular Biology Unit (J.G., J.M.), School of Medicine, James Cook University, Townsville, Australia; Cardiovascular Research Center (A.D.), Gill Heart Institute, University of Kentucky, Lexington; and the School of Surgery and P

日期:2008年12月28日 - 来自[2006年第26卷第12期]栏目

哈药集团被评为“AAA”级信用企业

    近日,经国内权威信用认证机构——中国企业信用评价中心审定,哈药集团有限公司因其在医药商务领域及其诚信经营方面的卓越表现被评为中国“AAA”级信用企业。哈药集团成为黑龙江省及哈尔滨市首家获此殊荣的企业。此前,哈药集团还曾获得“2007年度全国对外贸易信用AAA企业”荣誉称号,这标志着哈药集团获得了进一步扩大国际市场的通行证。

    “AAA”级是国际企业信用等级评价的最高等级。它是根据企业的资本实力、偿债能力、运营能力、融资完税等综合指标进行评定的。哈药集团的本次信用等级评价总得分为99.7分。

    近年来,哈药集团有限公司坚持“做地道药品,做厚道企业”的经营宗旨,积极落实国家“走出去”的发展战略,积极开拓海外药品进出口市场,创造了突出成绩,主营业务收入大幅增长,资产规模显著扩大,资产质量和财务实力不断提高。哈药集团在海关、商检、银行、税务、工商及其他政府主管部门均具有良好的信用记录。截至目前,哈药集团所属生产企业已全部通过GMP认证,主要流通企业已通过GSP认证,哈药总厂、三精制药等部分集团所属企业通过了ISO9001、ISO14001、OHSAS18001国际管理体系认证。哈药集团已在美国等13个国家取得国际通行的药物主文件(DMF)47件,其中头孢菌素、青霉素、氨苄系列等7个品种于2006年分别获得德国、印度、日本、坦桑尼亚等国家的注册认证。哈药集团2006年实现出口创汇5104万美元,同比增长26%。(作者:郑晓波)

日期:2007年12月7日 - 来自[企业观察]栏目

哈药集团被评为对外贸易AAA级信用企业


  中国医药报讯 日前,经北京国商国际资信评估有限公司评定,哈药集团有限公司获得“2007年度全国对外贸易信用AAA级企业”殊荣。
  据悉,近年来,哈药集团积极落实国家“走出去”的发展战略,积极开拓药品进出口市场,使主营业务收入大幅增长,资产规模显著扩大,资产质量和财务实力不断提高。哈药集团在海关、商检、银行、税务、工商等政府主管部门及金融机构均具有良好的信用记录。截至目前,哈药集团已在美国等13个国家取得国际通行的药物主文件(DMF)47件,其中头孢菌素、青霉素、氨苄系列等7个品种于2006年分别获得德国、印度、日本、坦桑尼亚等国家的注册认证。哈药集团2006年实现出口创汇5104万美元,同比增长26%。
   (郑晓波)
日期:2007年8月24日 - 来自[企业观察]栏目
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