纤维蛋白原β-148C/T、448G/A基因多态性与脑梗死发病类型的相关性研究

目的:研究纤维蛋白原(Fibrinogen,Fg)Bβ-148C/T、448G/A基因多态性对血浆Fg浓度、分子功能的影响及其与脑梗死类型的关系。方法:选取2002.11～2003.10在开滦神经内科住院脑梗死患者160例,将其分为脑动脉主干支(Main—trunk cerebralinfarction,MCl)与穿通支梗死(Penetrating cerebral infarction,PCD组,同时选取162名正常志愿者为对照组,应用聚合酶链反应-限制性片段长度多态法检测其Fgβ-148C/T和448G/A基因多态性,并测定血浆Fg浓度、分子功能及各项相关指标。结果MCI组血浆Fg浓度、FMPV/AMAX高于对照组,FMPV/AMAX高于PCI组:Bβ148CC基因型人群MCI组FMPV/AMAX高于PCI组及对照组,突变基因型人群MCI组血浆Fg浓度高于PCI组及对照组;β448GG基因型人群MCI和PCI病人仅FMPV明显高于对照组,突变基因型人群MCI组血浆Fg浓度、FMPV、FMPV/AMAX高于对照组,但仅Fg浓度高于PCI组;三组中Bβ-148CC、CT、TT和Bβ448GG、CA、AA基因型构成比无差别,各基因型人群中各型脑梗死的分布频率也无差异;PCI纽CT+GA这一突变连锁基因型的构成比高于对照组.且此连锁基因型人群中MCI和PCI组的血浆Fg浓度高于对照组。结论:Bβ-148突变基因型通过直接影响血浆Fg浓度和与机体生理、环境等因素的交互作用对Fg的分子功能产生影响.而易发M     

纤维蛋白原β-148C/T基因多态性与脑梗死关系的研究

目的研究中国雷州半岛地区汉族人群纤维蛋白原(Fibrinogen,Fg)β-148C/T基因多态性与脑梗死的关系。方法采用病例-对照研究,应用聚合酶链反应-限制性酶切片段长度多态性分析方法(PCR-RFLP)检测Fgβ-148C/T基因多态性,分析其在正常人群及脑梗死(cerebrol infarction,CI)患者中的频率分布特点及与缺血性脑卒中的关系;同时,用比浊法测定Fg水平,分析Fgβ-148C/T多态性与血浆Fg水平的关系。结果CI组β-148C/T位点T等位基因频率为0.303,对照组为0.219,两组比较差异有显著性意义(P<0.05),携带-148T等位基因者患脑梗死的危险性是非携带者的2.058倍(OR=2.058,95%CI:1.184~3.577,P=0.01);CI组β-148C/T基因多态性与Fg浓度(S)存在相关关系。结论Fgβ-148C/T基因多态性可影响血浆Fg水平,其T等位基因是CI的遗传易感因素。     

青年急性脑梗死患者β-纤维蛋白原-148C/T基因多态性和血浆纤维蛋白原水平的研究

目的　探讨β 纤维蛋白原(Fg)启动子区-148C/T基因多态性、血浆Fg水平与青年急性脑梗 死(ACI)的关系。方法　用多聚酶链反应 限制性片段多态性方法对69例青年ACI患者进行β Fg-148C/T 基因多态性分析,应用凝血酶原时间衍生法检测血浆Fg水平,并与60名健康青年进行对照。结果　青年 ACI组血浆Fg水平明显高于对照组(P<0.01);T等位基因携带者较CC基因型者血浆Fg明显增高(P< 0.05);T等位基因频率在两组分别为21.7%和16.7%,差异无显著性(P>0.05)。结论　β Fg-148C/T基 因多态性影响血浆Fg水平,T等位基因可能通过与其他血栓危险因素或环境因素协同作用增高血浆Fg水 平,成为青年ACI的遗传易感因素     

纤维蛋白原β基因148C/T及亚甲基四氢叶酸还原酶基因677C/T多态性与脑梗死的关系研究

目的 探讨纤维蛋白原（Fg）β基因148（β148）C／T及亚甲基四氢叶酸还原酶基因（MTHFR）677C／T多态性与脑梗死易感性的关系。方法按年龄、性别、有无高血压病史及糖尿病史选取相匹配的病例组及对照组各100例．利用聚合酶链反应-变性高效液相色谱法（PCR-DHPLC）确定Fgβ148及MTHFR677基因型。结果大动脉粥样硬化组（TOAST分型）及相应对照组Fgβ148CC、CT／TT基因型分布差异有显著性（P=0．035）．余各组两个多态位点的基因型分布差异无显著性。吸烟或饮酒的FgβCT／TT基因型携带者在病例组和对照组的分布差异有显著性（均P〈0．05）。结论Fgβ148CT／TT基因型可能是大动脉粥样硬化性脑梗死的危险因素。携带FgβCT／TT基因型同时吸烟或饮酒可能是脑梗死的危险因素。     

吸烟与FgBβ链基因多态性和功能表达的关系

目的研究吸烟与纤维蛋白原(fibrinogen,Fg)Bβ链-854G/A-、455G/A-、249C/T-、148C/T、448G/A和Bcl-1G/A位点基因多态性及其血浆Fg水平和聚合功能表达的关系,并探讨二者在脑梗死发病中的作用。方法选取开滦集团离退休职工1386人,均抽取清晨空腹静脉血测定血浆白细胞介素(IL)、Fg水平以及纤维蛋白单体聚合反应速率(FMPV)、最大吸光度(Amax)、FMPV/Amax指标,应用聚合酶链反应-限制性内切酶片段长度多态性技术检测FgBβ链6个位点的基因多态性。记录并分析吸烟与否人群FgBβ链基因多态性及其功能表达的特点。结果吸烟组与非吸烟组FgB-β854位点变异基因型者血浆Fg系列指标均高于其野生基因型人群,且吸烟人群FgB-β249变异基因型人群的血浆Fg水平、FMPV〔分别为(424.93±89.42)mg/dL,0.73±0.20〕也明显高于其野生基因型人群〔分别为(383.63±80.28)mg/dL,0.67±0.17〕(P<0.05);吸烟组血浆IL-6水平〔(21.41±5.76)pg/mL〕高于不吸烟组〔(14.95±4.82)pg/mL〕(P<0.05);以脑梗死与否为因变量的Logistic回归分析依次筛选出高血压、Bcl-1基因型、体重指数及吸烟为影响因素(P<0.05)。结论 FgB-β854基因多态性位点是影响血浆Fg水平和分子功能表达的重要部位;吸烟可能通过与FgB-β249位点变异基因型相互作用而使血浆Fg水平升高,并通过促进IL-6等细胞因子分泌而使Fg分子功能表达增强,因而成为脑梗死发病的重要危险因素。     

纤维蛋白原Bβ—249C／T和BβBcl-1G／A基因多态性与其浓度和分子聚合功能的关系

目的 研究纤维蛋白原(Fg)Bβ-249C/T和BβBcl-1G/A基因多态性在多种生理和环境因素条件下对血浆Fg浓度和分子聚合功能的影响.方法 采用整体抽样方法选取开滦集团职工1507人,样本均空腹抽取静脉血测定血糖等12项生化指标;应用聚合酶链反应-限制性酶切法进行两位点基因多态性分析;采用血浆Fg功能自动监测系统测定血浆Fg浓度和Fg单体聚合反应速率(FMPV)、最大吸光度(Amax)、FMPV/Amax等反映Fg分子活性的参数并进行体检和问卷调查.结果 在有脑梗死史组BβBcl-1G/A的A等位基因和AA+GA基因型分布频率高于无脑梗死史人群(P<0.05),Bβ-249C/T的TT+CT组与CC组间Fg浓度、FMPV、Amax、FMPV/Amax差异均无统计学意义(P>0.05),BβBcl-1G/A的AA+GA组Fg浓度及FMPV均高于GG组(P<0.05).结论 Bβ-249C/T和BβBcl-1G/A位点基因多态性对于Fg分子聚合功能均无影响,BβBcl-1G/A变异基因型人群为脑梗死易感人群,有可能通过影响血浆Fg浓度而使脑梗死发病危险性增加.     

纤溶酶原激活物抑制剂-1-675 4G/5G基因及纤维蛋白原β-148C/T基因多态性与脑梗死关系的研究

目的探讨纤溶酶原激活物抑制剂-1（PAI-1）-675 4G/5G及纤维蛋白原（Fg）β-148C/T基因多态性与脑梗死的关系。方法检测140例健康体检者（对照组）和220例脑梗死患者（CI组）PAI-1-675 4G/5G及Fgβ-148C/T基因多态性,并分析两组基因在正常人群及脑梗死患者中的频率分布特点。结果CI组Fgβ-148C/T位点T等位基因频率为0.33,对照组为0.225,两组比较差异具有统计学意义（P=0.0026）。CI组PAI-1-675 4G等位基因频率为0.48,对照组为0.56,两组比较差异具有统计学意义（P=0.037）,以5G/5G基因型作为参考,4G/4G基因型发生CI的OR值为0.52（95%CI：0.282～0.958,P=0.027）;携带CC和4G/4G基因型发生CI的OR值为0.48（95%CI：0.253～0.91,P=0.023）。结论本研究发现Fgβ-148T等位基因是CI发病的危险因素,4G/4G纯合子是CI的保护因素,CC基因型加强4G/4G基因型的CI保护作用。     

脑梗死与ACE、APOE、MTHFR和Fgβ四种基因多态性的关系研究

目的探讨肾素-血管紧张素转换酶基因(ACE)插入/缺失多态性(I/D)、载脂蛋白E基因(APOE)多态性、纤维蛋白原(Fg)β基因148C/T及亚甲基四氢叶酸还原酶基因(MTHFR)677C/T多态性与脑梗死易感性之间的关系。方法选取按年龄、性别、有无高血压及糖尿病病史相匹配的脑梗死病例组及非心脑血管病对照组各100例,根据TOAST分型法将100例脑梗死患者分成大动脉粥样梗死组(n=31)及小动脉闭塞组(n=69),并调查其危险因素。利用聚合酶链反应-变性高效液相色谱法(PCR-DHPLC)确定四种多态性的基因型。结果在大动脉粥样硬化组及相应对照组Fgβ148CT/TT基因型分布差异有统计学意义(OR9.757,95%CI1.168～81.467,P=0.035);ACEID/DD基因型,MTHFRCT/TT基因型和Fgβ CT/TT基因型之间有协同作用(OR3.907,95%CI1.160～13.162,P=0.028);吸烟的Fgβ CT/TT或APOEε4ε3基因型携带者在病例组的分布明显高于对照组(OR4.854,95%CI1.817～12.970,P=0.002。OR7.792,95%CI1.517～40.010,P=0.014);饮酒与Fgβ CT/TT基因型之间亦有明确的协同作用(OR:22.647,95%CI2.952～173.756,P=0.003)。结论Fgβ 148CT/TT基因型可能是大动脉粥样硬化性脑梗死的危险因素;同时携带ACEID/DD基因型、MTHFRCT/TT基因型和Fgβ CT/TT基因型,携带Fgβ CT/TT基因型同时吸烟或饮酒,携带APOEε4ε3基因型同时吸烟均增加脑梗死的易感性。     

MMP-2、MMP-9基因多态性与缺血性脑卒中临床分型及预后

目的探讨基质金属蛋白酶2(Matrix Metalloproteinase-2,MMP-2)基因C1306T、C735T和MMP-9基因C1562T多态性位点与缺血性脑卒中的关系。方法采用限制性片段长度多态性分析技术,检测缺血性脑卒中组232例和健康对照组235例MMP-2基因C1306T、C735T和MMP-9基因C1562T多态的分布。结果缺血性脑卒中组和对照组MMP-2 C1306T基因型和等位基因频率分布无统计学意义。在动脉粥样硬化性血栓性脑梗死组MMP-9 C1562T的CT+TT基因型频率和T等位基因频率、MMP-2 C735T的CC基因型频率和C等位基因频率明显高于对照组(P<0.05),而在脑栓塞组、腔梗组差异无统计学意义(P>0.05)。多因素Logistic回归分析,MMP-2、MMP-9不同基因型别与缺血性脑卒中预后无显著相关性(P>0.05)。结论 MMP-2 C735T的C等位基因、MMP-9 C1562T的T等位基因是动脉粥样硬化性血栓性脑梗死的遗传易感基因之一。MMP-2、MMP-9基因多态性与缺血性脑卒中预后无关。     

青年缺血性卒中的TOAST病因分型及相关基因研究

目的：探讨青年缺血性卒中的TOAST病因分型，各分型与血浆纤维蛋白原（Fg）、总同型半胱氨酸（tHcy）浓度及相关基因Fgβ-148C／T、MTHFR 677C／T多态性的关系。方法：98例中国北方汉族青年急性缺血性卒中按照TOAST标准进行病因分型，检测血浆Fg和tHcy浓度；应用聚合酶链式反应-限制性片段长度多态性对患者和60例相匹配的青年对照者进行Fgβ-148C／T、MTHFR 677C／T多态性分析。结果：本组TOAST病因分型心源性脑栓塞（CE）13．27％，大动脉粥样硬化性卒中（LAA）23．47％，小动脉闭塞性卒中（SAO）28．57％，其他原因引发的卒中（OC）19．39％，原因不明性缺血性卒中（UND）15．31％。TOAST各型青年缺血性卒中血浆Vg、tHcy浓度均明显高于对照组（P〈0．05）。其中，LAA型血浆Fg、tHcy浓度最高，但与其他各型无显著差异（P〉0．05）。缺血性卒中组Fgβ-148和MTHFR 677 T等位基因频率和各基因型与对照组无显著差异（P〉0．05）。LAA型Fgβ-148T等位基因频率和CT＋TT型比例显著高于对照组（P〈0．05），其余各型无显著差异（P〉0．05）。与吸烟、饮酒进行联合分析，缺血性卒中组Fgβ-148或MTHFR 677基因T携带者同时吸烟或饮酒所占比例均高于对照组，但仅Fgβ-148CT／TT同时吸烟及MTHFR 677 CT／TT同时饮酒比例显著高于对照组（P〈0．05）。结论：青年缺血性卒中病因复杂，血浆Fg和tHcy浓度增高是青年缺血性卒中的独立危险因素。Fgβ-148T等位基因可能是大动脉粥样硬化性卒中的遗传易感因素。Fgβ-148与MTHFR 677T等位基因分别与吸烟、饮酒协同作用影响青年缺血性卒中的发病。     

Factors associated with satisfaction with care among patients with epilepsy

OBJECTIVE: The purpose of the work described here was to determine those variables associated with satisfaction with care among patients with epilepsy. METHODS: We interviewed patients followed at a tertiary epilepsy center. Predictor variables included age, gender, race, education, income, insurance, seizure frequency, and Quality of Life in Epilepsy-10 inventory (QOLIE-10) results. Target variables were the subscales of the Short Form Patient Satisfaction Questionnaire (PSQ-18). We used univariate analysis to identify those variables significantly associated with the subscales and multiple linear regression to determine those independently significant. RESULTS: The study population comprised 193 patients. Lower education and better QOLIE-10 scores were independently associated with general satisfaction with care. The mental health scale was associated with general satisfaction with care. Lower educational level was the only variable independently associated with patient satisfaction with communication, the financial aspect of care, and time spent with physician. CONCLUSION: Lower educational level and better quality of life are the main variables associated with higher general satisfaction with care among patients with epilepsy.     

Treatment with rituximab in patients with polyneuropathy with anti-MAG antibodies

Journal of Neurology -     

Surgical Outcome in Patients with Epilepsy with Occult Vascular Malformations Treated with Lesionectomy

Summary: Purpose: This retrospective study reports the long-term surgical outcome of patients with medically refractory epilepsy and vascular malformations who were treated with lesionectomy. A detailed analysis of surgical failures had been performed in an attempt to define predictors of surgical success and failure.
Methods: Fifteen patients with medically intractable epilepsy and angiographically occult vascular malformations (AOVMs) were treated surgically with lesionectomy at Duke University Medical Center. Lesionectomy consisted of removal of the AOVM and surrounding hemosiderin-stained brain only, without the use of electrocorticography (ECoG) to guide resection.
Results: Eleven (73%) patients are seizure free after lesionectomy. Three showed no significant improvement, and one patient died, presumably after a seizure. Age of onset, duration of seizures, age at resection, and gender did not affect outcome. All patients with neocortical AOVMs in whom EEG findings correlated with the site of the lesion were seizure free after lesional resection. Treatment failures were associated with the presence of multiple intracranial lesions, poorly localized or diffuse EEG findings, discordant positron emission tomography (PET) imaging, or with a lesion in close proximity to the limbic system.
Conclusions: Lesionectomy, with removal of surrounding hemosiderin-stained brain, can be considered the procedure of choice in carefully selected patients with epilepsy with occult vascular malformations.     

Children with ADHD and motor dysfunction compared with children with ADHD only

The purpose of this study was to identify group differences in children with attention-deficit-hyperactivity disorder and motor dysfunction (ADHD-MD) and ADHD only, and to evaluate the medication responsiveness of ADHD-MD. Sixty-three children (49 males and 14 females; mean age 9 years 10 months, SD 2 years 10 months) underwent a triple blind, placebo-controlled crossover study evaluating two dose levels of methylphenidate (0.3 mg/kg and 0.5 mg/kg [corrected], twice daily) and placebo. Forty-nine trials were completed. Nineteen were children with ADHD-MD, 44 had ADHD only. Behavior and functioning were assessed at home and at school. Treatment effects were assessed using the Abbreviated Symptom Questionnaire for Parents and Teachers. Children with ADHD-MD were more likely to have severe ADHD-combined type and other neurodevelopmental and behavioral problems. Both groups of children had a linear dose response to medication (placebo, low, high) and there was no evidence of a group by dose interaction or an overall group effect at home or school. The lack of group effect suggests that these children responded to medication like the other subgroups.     

Valproate is associated with new-onset oligoamenorrhea with hyperandrogenism in women with bipolar disorder.

BACKGROUND: Preliminary evidence suggests that valproate is associated with isolated features of polycystic ovarian syndrome (PCOS), while contradictory data support an association between epilepsy and PCOS. The development of PCOS features after initiation of valproate was therefore examined in women with bipolar disorder using a standardized definition of PCOS. METHODS: Three hundred women 18 to 45 years old with bipolar disorder were evaluated for PCOS at 16 Systematic Treatment Enhancement for Bipolar Disorder sites. A comparison was made between the incidence of hyperandrogenism (hirsutism, acne, male-pattern alopecia, elevated androgens) with oligoamenorrhea that developed while taking valproate versus other anticonvulsants (lamotrigine, topiramate, gabapentin, carbamazepine, oxcarbazepine) and lithium. Medication and menstrual cycle histories were obtained, and hyperandrogenism was assessed. RESULTS: Among 230 women who could be evaluated, oligoamenorrhea with hyperandrogenism developed in 9 (10.5%) of 86 women on valproate and in 2 (1.4%) of 144 women on a nonvalproate anticonvulsant or lithium (relative risk 7.5, 95% confidence interval [CI] 1.7-34.1, p = .002). Oligoamenorrhea always began within 12 months of valproate use. CONCLUSIONS: Valproate is associated with new-onset oligoamenorrhea with hyperandrogenism. Monitoring for reproductive-endocrine abnormalities is important when starting and using valproate in reproductive-aged women. Prospective studies are needed to elucidate risk factors for development of PCOS on valproate.     

血管内栓塞治疗未破裂脑动静脉畸形并发癫痫患者的预后分析

目的分析血管内栓塞治疗未破裂脑动静脉畸形(CAVM)并发癫痫患者的预后情况。方法选择2013年3月至2017年6月收治的符合诊断标准的CAVM并发癫痫发作患者49例为研究对象,分析血管内栓塞治疗后患者的临床症状、生活质量(QOLIE-31)改善情况。结果患者经血管内栓塞治疗后,QOLIE-31各项指标(除了药物影响)评分均明显提高,高于治疗前(P0.05);Spetzler-Martin分级与Engel分级的I~II级例数多于治疗前(P0.05),同时Spetzler-Martin分级I~II级生活质量评分(76.04±18.33)分明显高于III~V级的(65.65±16.76)分(P0.05);Engel分级I~II级的生活质量评分(75.25±17.78)分明显高于III~V级的(66.23±13.22)分(P0.05);血管内栓塞比例80%的生活质量总评分(78.37±18.87)分明显高于栓塞比例80%的(64.16±16.92)分(P0.05);术后患者的头疼症状中重度例数明显低于治疗前(P0.01);患者的NIHSS评分和MRS评分均明显低于治疗前,头疼症状的生活质量评分高于治疗前(均P0.05)。结论血管内栓塞能明显改善未破裂脑动静脉畸形并发癫痫患者的头疼症状、癫痫发作情况、神经功能缺损,提高血管内栓塞比例能够提高患者生活质量。