缺血性血管疾病发病机制的研究：内皮素-1与前部缺血性视神经病变的关系

目的：探讨血浆内皮素-1(endothelin，ET-1)浓度与前部缺血性视神经病变(anterior ischemic ptic neuropathy，AION)的关系。方法：通过放射免疫法(radioimmuoassay，RIA)测定60例AION患者及年龄相匹配15例非病变人群正常对照组的血浆ET-1浓度。将AION患者按视盘水肿程度分为水肿重度组、水肿轻度组、水肿消退组；并以临床不同病程阶段分为4组，分别为发病14d内(病程1组)、15～30d(病程2组)、31～60d(病程3组)和61～180d(病程4组)。以性别、病变程度及临床病程阶段检测结果均值进行统计学分析。结果：60例AION患者的血浆ET-1浓度[(147．57&;#177;39．25)ng／L]比正常对照组[(108．72&;#177;16．66)ng／L]增高(t：5．85，P&;lt;0．05)，AION患者随着病程的延长，ET-1血浆浓度逐渐下降；水肿重度组[(167．21&;#177;34．79)ng／L]和水肿轻度组[(137．17&;#177;35．52)ng／L]、水肿消退组[(123．98&;#177;23．57)ng／L]比较差异均有显著性意义(t1=2．46，t2=3．81，P&;lt;0．05)；4组不同时段病程血浆ET-1浓度比较，病程1组[(182．13&;#177;38．25)ng／L]和病程3组[(135．12&;#177;38．57)ng／L]，病程4组[(125．14&;#177;35．81)ng／L]比较，病程2组[(153．58&;#177;36．89)ng／L]与病程3组，病程4组比较，病程3组和病程4组比较，差异均有显著性意义(F=4．51，P&;lt;0．05)；病程1，2，3组与正常对照组[(108．72&;#177;16．68)ng／L]血浆ET-1浓度均有统计学意义(t，=5．86，t2=3．79，t3=2．28，t4=1．89；P1&;lt;0．01，P2&;lt;0．05，P3&;lt;0．05，P4&;gt;0．05)。结论：AION患者血浆ET-1变化与病变程度相吻合，与病程长短相关联。血浆ET-1浓度的测定对病情判断和预后评估有一定的指导价值。     

脑梗死病变与内皮素-1及血管内皮细胞生长因子的关系

背景内皮素-1(endothelin-1,ET-1)和血管内皮细胞生长因子(vascular endothelial growthfactor,VEGF)在蛋白及核酸水平方面的研究多见于动物实验,而ET-1和VEGF与临床脑梗死病变方面关系的研究还未广泛开展.目的探讨脑梗死发病中ET-1和VEGF的变化规律及机制.设计完全随机对照研究.地点和对象选自2000-03/06中国医科大学第二临床学院神经内科住院脑梗死患者27例及同期在本院正常体检老年人22例.干预患者先行头CT或MRI检查,发病第3天及4周抽取肘静脉血,分别采用放免法及ELISA法测定血浆中ET-1和血清中VEGF含量.主要观察指标血浆中ET-1和血清中VEGF含量.结果脑梗死组ET-1及VEGF含量[(65.7±10.8)ng/L,(419.5±176.3)ng/L]均高于对照组[(48.8±6.9)ng/L,(205.7±101.8)ng/L],两组比较差异有显著性意义(t=2.015,P＜0.05,t=2.705,P＜0.01);到恢复期时有所下降[ET-1含量为(60.2±11.5)ng/L, VEGF含量为(309.4±138.9)ng/L],与对照组比较,差异有显著性意义(t=2.028,P＜0.05;t=2.724,P＜0.01).ET-1及VEGF含量与梗死灶的大小及病情程度有关.结论ET-1及VEGF与脑梗死的发生、发展密切相关,从而为脑卒中预防及康复干预提供实验依据.     

运动对冠心病患者血浆内皮素的影响

内皮素是近10年来发现的强有力的缩血管物质,由内皮细胞产生,已被证实在局部缺血性疾病、持续性血管收缩及血管痉挛中起重要作用。对20例冠心病患者运动前后内皮素浓度的变化进行了观察,探讨负荷运动对冠心病患者的意义。     

不同剪切力作用与不同时间点血管内皮细胞内皮素-1和一氧化氮含量变化的差异

目的:应用不同剪切力作用体外培养的脐静脉内皮细胞,观察其在不同时间点内皮素-1和一氧化氮含量表达的差异。方法:实验于2002-07/2004-05在解放军总医院基础医学研究所生化研究室完成。利用流室装置通过精密蠕动泵提供剪切力,以50Pa和100Pa两种剪切力作用体外培养的脐静脉内皮细胞,并分别从30,60,120,300,420min5个时间点取灌流液,对照组为没有施加剪切力的脐静脉内皮细胞。用放射免疫法和硝酸还原酶法检测50Pa和100Pa剪切力作用下及空白对照组脐静脉内皮细胞内皮素-1和一氧化氮的含量。结果:①两组剪切力作用内皮细胞,其内皮素-1的表达量在开始前120min均有升高趋势,在30,60,120min时,50Pa组和100Pa组内皮素-1含量明显高于对照组[(28.7±2.1),(37.8±3.5),(26.0±2.8)ng/L;(33.6±5.8),(43.3±7.2),(26.5±3.6)ng/L;(45.3±9.4),(53.6±8.6),(32.2±4.7)ng/L,(t=1.835～6.079,P<0.05)]。②一氧化氮含量:在30,60,120min时,50Pa组和100Pa组一氧化氮含量明显高于对照组[(37.5±5.4),(40.2±6.7),(20.7±3.0)μmol/L;(52.7±6.3),(63.7±7.2),(21.4±3.3)μmol/L;(67.8±6.9),(84.5±8.6),(23.5±4.1)μmol/L,(t=1.835～6.079,P<0.05)]。100Pa组在60,120min时明显高于50Pa组(t=2.556,3.376,P<0.05)。结论:在一定层流剪切力和时间范围内内皮细胞表达内皮素-1和一氧化氮呈递增趋势,保持相对稳定,当时间进一步延长时,其表达失去平衡,具有强烈收缩血管活性的内皮素-1相对增多,提示损伤内皮细胞的因素增加。     

运动与内皮素关系的最新研究

目的：内皮素是近10年来发现的强有力的缩血管物质，由血管内皮细胞产生，已证实在局部缺血性疾病、持续性血管收缩及血管痉挛中起重要作用。运动作为一种特殊刺激将引起机体内皮细胞分泌内皮素水平发生改变，而内皮素具有强缩血管效应。为此，回顾了不同运动强度、运动形式及运动训练对内皮细胞内皮素分泌的影响结果，以此促进今后进一步研究运动过程中内皮素分泌的变化情况，从而了解心血管系统对运动过程的适应性。资料来源：应用计算机检索Medline数据库1980—01／2003—12期间的相关文章，检索词“athletic sports，endothelin，corporeity resistance”，限定文章语言种类为英文。同时计算机检索中国期刊全文数据库、万方数据库和相关杂志1990—01／2003—12期间的相关文章，检索词“体育运动，内皮素，身体耐力”，限定文章语言种类为中文。资料选择：对资料进行初审，选取内皮素生物化学特点和内皮素分泌的影响因素研究的文献。资料提炼：重点查阅影响因素之一的运动与内皮素分泌的关系，筛除其余因素与内皮素分泌关系的文献，共检索到25篇文献。资料综合：急性运动，耐力运动影响内皮素分泌的研究，大多数学者以小鼠为研究对象，少数学者以人为研究对象，观察运动后研究对象的内皮素分泌状况，同时也突出了运动对高血压患者内皮素分泌的影响。结论：急性运动时血浆内皮素含量升高，这可能是机体应激状态的一种代偿性反应．长期耐力运动可使血浆内皮素一1浓度适度升高，并可能与运动性心脏的形成有关。适量运动对高血压患者的降压作用有可能与血浆内皮素水平下降有关。     

青光眼视功能损害中内皮素-1的作用及其机制

目的:为从分子生物学水平对青光眼的防治提供新的思路,探讨内皮素-1在青光眼患者视功能损害中的作用及作用机制.方法:实验于2002-07/2003-06在广东医学院附属医院中心实验室完成.根据视功能损害程度和沿盘面积比分为早期青光眼患者16例、进展期青光眼患者21例、晚期青光眼患者18例和正常志愿者30例.应用放射免疫法测定其血浆中内皮素-1的含量.结果:青光眼组,正常对照组,视功能损害早期,视功能损害进展期及视功能损害晚期血浆内皮素-1平均水平分别为(82.17&;#177;14.88),(65.35&;#177;18.45),(69.07&;#177;25.28),(91.23&;#177;13.26)及(107.06&;#177;34.02)mg/L.在视功能损害早期比正常对照组增加,但差异无显著性意义(t=3.98,P＞0.01).视功能损害进展期、晚期,均较正常对照组明显增加,差异有显著性意义(t=4.62,t=4.89,P＜0.01);视功能损害进展期、晚期较损害早期明显增加,差异有显著性意义(t=4.37,t=4.53,P＜0.01).青光眼患者视功能损害早期、进展期、晚期沿盘面积比分别为0.43&;#177;0.11,0.76&;#177;0.23,0.94&;#177;0.21.沿盘面积比与内皮素-1的关系:r=0.912 4,P＜0.001,呈正相关.结论:青光眼患者血浆中内皮素-1的含量增加与其视功能损害程度有关.     

川崎病患儿血清内皮素-1的变化与冠状动脉病变的关系

【目的】观察川崎病(KD)患儿血清内皮素-1(ET-1)的变化及其与冠状动脉病变之间的关系。【方法】42例KD患儿根据病期分为急性期和恢复期;依据心脏超声检查分为冠脉病变组和非冠脉病变组。采用放免法测定ET-1水平并进行各期组间的比较。【结果】KD急性期患儿ET-1为(87.46±16.79)ng/L明显高于恢复期组(52.53±19.26)ng/L和健康对照组(43.31±18.35)ng/L(P<0.01)。冠脉病变组急性期水平(96.82±18.34)ng/L高于非冠脉病变组(75.21±14.50)ng/L(P<0.01)。【结论】内皮素可能参与了KD的发病机制,ET-1水平可反映KD冠脉血管受累的严重程度。     

内皮素及一氧化氮与心脏X综合征发病的关系

X综合征是指一组临床有典型的劳力型心绞痛,心电图运动试验阳性（ST段下降≥1mV）,麦角新碱激发试验前后冠状动脉造影正常,并排除其他心源性疾病的征候群,此类患者约占临床典型心绞痛患者的10％～30％。但其发病机制及诊断方面的研究均未得到满意结果。有临床研究证实,其病理生理学基础可能是细小冠状动脉及心肌内微循环结构或功能异常,冠状动脉血流储备降低,通过多种机制引起心肌缺血和心绞痛。内皮素（ET-1）、一氧化氮（NO）是内皮细胞合成和分泌的维持血管基础张力的主要活性物质,本研究通过运动观察X综合征患者静息状况下和运动负荷时ET-1、NO含量及其平衡关系变化,探讨ET-1、NO及其比值在X综合征发病中的作用。     

高压氧治疗前后脑梗死患者血浆内皮素的变化

目的 探讨高压氧治疗对脑梗死后患者血浆高水平内皮素的影响。方法 选择2002-03／11中山大学附属第一医院神经内科收治的脑梗死患者64例，均知情同意，根据病程分为3组，≤7d组38例，8～14d组16例，≥15d组10例。所有患者均进行高压氧治疗，加压25-30min，舱内绝对压力达0．2MPa后，面罩式吸纯氧40min，共2次，休息吸氧舱内压缩空气10min，1次／d，12次为1个疗程，共治疗2个疗程。于高压氧治疗前后清晨空腹抽外周静脉血进行内皮素水平测定，采用放免法。结果64例患者全部进入结果分析，无脱落。患者治疗前后的血浆内皮素水平比较：①64例脑梗死患者治疗后的平均血浆内皮素水平显著高于治疗前[（60．42&;#177;17．38），（42．92&;#177;8．42）ng／L （t=2．667，P〈0．01）]。②≤7d、8～14d组患者治疗后的血浆内皮素水平均显著高于治疗前[（67．76&;#177;21．41），（65．49&;#177;50．28）ng／L；（45．68&;#177;13．58），（38．35&;#177;13．82）ng／L（t=2．056，2．343，P〈0．05）]。③≥15d组患者治疗后的血浆内皮素水平显著低于治疗前[（22.84&;#177;28．96），（39．94&;#177;91．32）ng／L，（t=2.552，P〈0．05）]。结论 高压氧治疗脑梗死的显著效果不是以降低血浆内皮素水平起作用，可能是通过其他途径起作用。     

创伤修复与创伤性休克大鼠肝脏内皮素-1基因表达的变化

目的:研究内皮素-1基因在创伤性休克大鼠肝脏中表达的变化,探讨创伤修复中降低重要组织器官功能致残的机制.方法:实验于2004-03/09在第一军医大学全军病理生理学实验室完成.采用下肢创伤法建立创伤性休克大鼠模型,运用反转录-聚合酶链反应选用磷酸甘油醛脱氢酶基因为内参照,分别检测创伤前,休克30,90min和复苏后1,3,5 h各组内皮素mRNA表达情况.结果:创伤前大鼠肝脏组织内皮素mRNA有少量表达,创伤后各组内皮素mRNA的表达产物显增加(P＜0.05),复苏后各组仍呈高水平表达(与休克末比P＞0.05).结论:内皮素-1参与了创伤性休克的病理生理过程,有效抑制其异常表达可能对创伤性休克致残的康复有意义.     

前部缺血性视神经病变的眼底荧光血管造影检查

前部缺血性视神经病变(anterior ischem ic optic neuropathy,AION)是由于供应视神经乳头的睫状后短动脉发生缺血性改变,突然视力减退、视盘水肿和视野缺损为主要表现的缺血性疾病。本病确切的确切病因和发病机制目前仍然不甚清楚[1,2]。本文回顾分析了我科2004年10月至2006年2     

前部缺血性视神经病变的危险因素及诊断分析

目的探讨非动脉炎性前部缺血性视神经病变(NAION)的危险因素及诊断。方法收集2014年1月至2015年6月在山西医科大学第一医院眼科诊断为NAION的患者42例(44眼)行眼底荧光素血管造影(FFA)、视野、图形视觉诱发电位(VEP)、颈动脉多普勒超声检查及血压、血糖、血脂等检测,设对照组30例,年龄范围42~71岁,平均(55.43±8.03)岁。结果 NAION组与对照组比较,年龄、颈动脉病变、高血压病及高脂血症差异均有统计学意义(P<0.05);糖尿病、性别及吸烟差异均无统计学意义(P>0.05)。FFA早期44患眼视盘均呈部分荧光充盈延迟或缺损,晚期表现多样;视野检查37眼(84.09%)表现为与生理盲点相连的象限或扇形缺损;VEP检查P100波振幅异常的比例(92.50%)明显高于潜伏期异常的比例(67.50%),NAION患眼组与健眼组及对照组比较,P100波潜伏期延长及振幅降低(P<0.05),而健眼组与对照组比较P100波潜伏期也有延长(P<0.05);颈动脉超声异常率(61.09%)较高,NAION患眼组与对照组比较,颈总动脉内膜中层厚度(IMT)增加,颈内动脉收缩期峰值血流速度(PSV)及舒张末期血流速度(EDV)降低(P<0.05),阻力指数(RI)值升高(P<0.05),患眼组与健眼组颈动脉各测量值无统计学差异(P>0.05)。结论 NAION的发生与多种因素有关,尤其与颈动脉病变、高血压病、高脂血症明显相关。FFA和视野对NAION有较高的诊断价值,但表现复杂;颈动脉彩超及VEP也具有明显异常,可为临床早期诊断及提前干预提供新的方向。     

前部缺血性视神经病变的综合治疗临床观察

目的观察综合治疗前部缺血性视神经病变的临床疗效。方法收集2014年1月至2015年6月来山西医科大学第一附属医院就诊的前部缺血性视神经病变患者40例(42眼)作为研究对象。所有患者均积极治疗全身疾病,同时全身及局部给予激素、扩血管、神经营养药物以及颞浅动脉旁注射复方樟柳碱等综合治疗,以15 d为一个疗程,随访观察30~45 d。结果 40例(42眼)患者中,男25例,女15例;发病年龄42~71岁,平均为55.52岁,伴高血压病者24例、糖尿病者10例、高脂血症者22例,有吸烟史者18例。就诊时间最短者2 d,最长者1个月,平均11.48 d。40例(42眼)患者治疗15 d后视力有显著提高(P<0.01),随访观察30~45 d后视力较治疗15 d时提高(P=0.029);治疗前平均视野缺损值为(16.14±5.05)d B,治疗15 d后平均视野缺损值为(11.56±3.74)d B,明显降低(t=12.63,P<0.01),随访观察30~45 d时平均视野缺损值(9.53±3.89)d B,较治疗15 d时降低(t=8.94,P<0.01);随访观察30~45 d后总有效率(90.48%)与治疗15 d时总有效率(78.57%)比较,P=0.113,尚不能认为差异有统计学意义。结论综合治疗前部缺血性视神经病变的临床疗效显著,能有效提高患眼视力,降低视野缺损,明显减轻视盘水肿程度。     

Sildenafil citrate use and the incidence of nonarteritic anterior ischemic optic neuropathy

Nonarteritic anterior ischemic optic neuropathy (NAION) has been reported rarely in men after taking sildenafil or other phosphodiesterase 5 inhibitors for erectile dysfunction (ED). The incidence of NAION in men receiving sildenafil treatment for ED was estimated using pooled safety data from global clinical trials and European observational studies. Based on clinical trial data in more than 13,000 men and on more than 35,000 patient-years of observation in epidemiologic studies, we estimated an incidence of 2.8 cases of NAION per 100,000 patient-years of sildenafil exposure. This is similar to estimates reported in general US population samples (2.52 and 11.8 cases per 100,000 men aged >or=50 years). The data cited herein do not suggest an increased incidence of NAION in men who took sildenafil for ED.     

非动脉炎性前部缺血性视神经病变缺血部位和程度的评估及病因探讨

目的:探讨非动脉炎性前部缺血性视神经病变(nonarteriticanterioris-chemicopticneuropathy,NAION)的临床特征。方法:分析广州医学院第二附属医院眼科2000-01/2003-01已确诊的NAION患者72例(80眼),男39例(44眼),女33例(36眼);单眼发病64例(89%),双眼发病8例(11%)。排除标准:所有患者均无巨细胞性动脉炎的表现。纳入标准:病史、症状、眼底、视野、FFA结果均符合NAION的诊断标准。经视力、视野、眼底和荧光眼底血管造影(flouresceinfundusangiography,FFA)等检查确诊的前部缺血性视神经病变72例(80眼)的临床资料进行分析。结果:72例中伴有高血压动脉硬化28例(30眼),伴有糖尿病20例(24眼),伴高血脂症14例(15眼),青光眼4例(5眼),白内障术后2例(2眼),原因不明4例(4眼)。眼底视盘水肿色淡,其中呈象限性水肿21眼,半侧水肿19眼,全视盘水肿28眼,无水肿12眼。FFA早期视盘全部或部分荧光充盈延缓或缺损,显示缺血的部位和范围;晚期荧光充盈各异,缺血区呈强荧光或弱荧光,其中主要为强荧光,有68眼(85%),多见于病程较短者;视盘持续弱荧光者12眼(15%),见于病程较长者。FFA显示缺血累及的部位和范围伴有相应视野缺损者60眼(75%)。结论:前部缺血性视神经病变是一种多因性眼病,而高血压、视网膜动脉硬化、糖尿病、高血脂症     

血浆同型半胱氨酸水平与冠心病的关系

目的探讨血浆同型半胱氨酸（HCY）水平与冠心病（cHD）的关系。方法采用循环酶法分别测定CHD患者（117例）及健康对照组（50例）血浆中HCY水平。CHD患者按不同临床类型分为稳定型心绞痛（SAP）组（35例）、不稳定型心绞痛（uAP）组（39例）和急性心肌梗死（AMI）组（43例）;CHD患者根据冠状动脉造影术进一步分为1支病变组（31例）、2支病变组（40例）和3支病变组（46例）。结果1）CHD组血浆HCY水平明显高于健康对照组（P〈0．01）。2）不同临床类型的CHD患者,HCY水平显示AMI组〉UAP组〉SAP组,其中SAP组、UAP组、AMI组与健康对照组比较差异均有统计学意义（P〈O．01）,SAP组与UAP组、AMI组比较差异有统计学意义（P〈O．01）,UAP组与AMI组比较,差异有统计学意义（P〈O．01）。3）1、2、3支血管病变者血浆HCY浓度呈逐级增高趋势,1支与3支病变组、2支与3支病变组之间差异有统计学意义（P〈O．01）,1支与2支病变组之间差异无统计学意义（P〉0．05）。结论CHD患者血浆HCY水平明显增高,冠状动脉病变支数越多,血浆HCY水平越高,提示HCY水平变化与CHD的发生、发展密切相关,是CHD的一个危险因素。     

Macular ganglion cell complex injury in different stages of anterior ischemic optic neuropathy

BACKGROUNDAnterior ischemic optic neuropathy (AION) is a group of ophthalmic diseases in which the optic nerve is injured causing blindness. However, the pathogenesis, clinical manifestations, and clinical treatments of AION are yet elusive. Only a few related experimental or clinical reports are available on the disease. In this study, spectral domain optical coherence tomography (SD-OCT) was used to examine the morphology of thickness swelling and atrophic changes of macular ganglion cell complex (mGCC) in the different stages of AION that were then compared with the visual fields. Thus, the clinical value of mGCC examination was alleged to be similar to that of the visual field.AIMTo explore the mGCC injury at different stages in AION and the clinical significance.METHODSCases with AION were analyzed in a retrospective study. SD-OCT was used to analyze the correlation between mGCC and peripapillary retinal nerve fiber layer thicknesses at different stages of AION and the changes in the corresponding stages of visual fields.RESULTSA total of 21 cases (28 eyes) presented AION. The onset time of AION was defined as early stage (within 3 wk of onset), middle stage (from 3 wk to 2 mo), and late stage (disease span > 2 mo). In the early stage, the mGCC thickness of SD-OCT was within the normal high limit, and the perioptic nerve fibers thickness was more than the normal. The changes in the visual field in early stage were not consistent with the swelling changes in mGCC and peri-disc nerve fibers. In addition, atrophy and thinning appeared in mGCC, and the perioptic nerve fibers were swollen. However, the thickness was lower in the middle period than that in the early stage. The change in visual field was consistent with that of mGCC in this period. In the late stage, mGCC shrank and thinned, and the thickness of the nerve fibers around the optic disc in the corresponding region shrank and thinned.CONCLUSIONThe changes in mGCC thickness in patients with AION showed early, middle, and late stages of development by SD-OCT. Although the early stage visual field changes of AION were not consistent with the swelling changes of mGCC, the horizontal delimitation or annular atrophy of mGCC was consistent with that in the middle and late stage of the disease. The atrophy of peripheral nerve fibers was later than that of the mGCC atrophy.     

血浆Hcy与血管性帕金森综合征的相关性分析

目的 探讨血浆同型半胱氨酸(Hcy)对血管性帕金森综合征(VP)影响及临床意义.方法 测定56例血管性帕金森综合征患者及52例健康对照者的血浆Hcy、叶酸(FA)、维生素B12水平.对Hcy增高的VP患者予以叶酸、维生素B12等药物治疗,并记录治疗前后的Webster评分.结果 VP组的Hcy水平显著高于对照组(P＜0.05);血浆FA、维生素B12的水平低于对照组(P＜0.05);Hcy水平增高的VP患者Webster评分明显高于Hcy水平正常的患者(P＜0.05);而经药物治疗后,Webster评分较治疗前明显降低(P＜0.05).结论 Hcy与VP发病及VP的严重程度可能存在相关性;对Hcy增高的VP患者常规给予降低Hcy治疗,对VP患者的治疗和预后有益.     

Nonarteritic anterior ischemic optic neuropathy: associations with homozygosity for the C677T methylenetetrahydrofolate reductase mutation

The association between nonarteritic anterior ischemic optic neuropathy (NAION) and coagulation disorders was prospectively assessed at least 3 months after the occurrence of ocular vascular events in 12 white patients in an outpatient clinical research center. Two community-based ophthalmologists evaluated the 12 NAION patients in the consecutive order of their referral. Polymerase chain reaction-complementary DNA assays of gene mutations associated with coagulation disorders and serologic coagulation measurements in study patients were compared with those in 36 healthy, normal race-, sex-, and age-matched controls, with 3 controls matched for each case. Of the 12 patients, 4 men and 8 women (mean age 62 +/- 15 years, 3 of them 55 years or older), 8 had unilateral NAION (bilateral in 4). The 12 patients with NAION were more likely than controls to demonstrate homozygosity for the methylenetetrahydrofolate reductase (MTHFR) C677T mutation (50% vs 11 %; Fisher's P =.009, with the likelihood of a type I error quite small, 0.9%). Our sample size had a power of 80% to detect this case-control difference in C677T MTHFR homozygosity at an alpha value of.05. Of the 12 NAION patients, 7 (58%) had at least 1 gene mutation in the C677T MTHFR, G1691A V Leiden, or G20210A prothrombin gene, compared with 5 of 36 controls (14%) (chi(2) = 9.48, P =. 002, with the likelihood of a type I error quite small, 0.2%). Our sample size had a power of 85% to detect this case-control difference at alpha =. 05. Of the 8 women with NAION, 5 (63%) first experienced the condition while taking hormone replacement therapy (n = 4) or during pregnancy (n = 1), with superposition of estrogen-induced thrombophilia on heritable thrombophilia and hypofibrinolysis. Confirmation of a causal relationship between coagulation disorders and NAION should facilitate its prevention and treatment and help protect against thrombi in other vascular beds.     

Impairment of homocysteine metabolism in patients with retinal vascular occlusion and non-arteritic ischemic optic neuropathy.

Mild hyperhomocysteinemia is established as an independent risk factor for atherothrombotic disease, including ocular pathologies such as retinal vascular occlusion and non-arteritic ischemic optic neuropathy (NAION). Low intake or low status of B-vitamins explains elevated total homocysteine (tHcy) concentrations only in part. The underlying cause for disturbed homocysteine metabolism requires further insight. We investigated whether the combined determinations of plasma tHcy, methylmalonic acid (MMA) and cystathionine provide more information on the causes of impaired homocysteine metabolism as compared with vitamin B12, vitamin B6 and folate in patients with ocular ischemic vascular disease. A total of 51 hyperhomocysteinemic (>12 micromol/L) patients with retinal vascular occlusion (n=42) and NAION (n=9) were included. Mild renal dysfunction was an important determinant of tHcy, indicated by the positive correlation between creatinine and tHcy (r=0.47, p=0.001). The assessment of MMA in addition to tHcy identified at least 12 out of 51 patients (23%) who were most likely to have a functional vitamin B12 deficiency. An additional 14 patients (27%) with elevated MMA and cystathionine levels also had slightly elevated concentrations of creatinine, pointing to the need for discrimination between renal dysfunction and vitamin B12 deficiency in this group. In contrast, measurement of cystathionine is very sensitive for renal dysfunction and this marker was strongly related to serum creatinine (r=0.56, p<0.001) and to tHcy (r=0.50, p<0.001). Measurement of the vitamins folate, vitamin B12 and vitamin B6 in plasma did not provide sufficient information on intracellular disturbances in homocysteine metabolism. In conclusion, the metabolites homocysteine, cystathionine and MMA are sensitive indicators and valuable for discrimination of the underlying cause of mild to moderate hyperhomocysteinemia, with implications for therapeutic targeting.