MGMT在恶性胶质瘤中的表达对替莫唑胺化疗预后的影响

目的 通过检测肿瘤组织O6-甲基鸟嘌呤-DNA甲基转移酶(O6-methylguanine-DNA methyltransferase,MGMT)的表达,探讨其对恶性胶质瘤替莫唑胺化疗预后的影响,以期为个体化化疗方案的选择提供临床依据.方法 经病理学确诊为恶性胶质瘤患者60例,使用免疫组织化学方法检测肿瘤组织MGMT表达,根据表达情况分为MGMT阴性组和MGMT阳性组;所有患者均接受手术治疗及术后常规放射治疗和替莫唑胺化疗,并对其长期随访,进行无进展生存时间、实体肿瘤客观疗效和药物安全性的评定.结果 肿瘤组织MGMT表达阴性者(-～±)为33例,MGMT表达阳性者(+～++)为27例;应用替莫唑胺化疗6个疗程末,MGMT阴性组客观有效率(CR+PR)为20/33,明显高于MGMT阳性组的5/27;MGMT阴性组平均无进展生存时间为(18±6.42)个月,明显长于MGMT阳性组的(9.0±1.91)个月,两组间差异具有统计学意义(P＜0.01).结论 替莫唑胺化疗方案的疗效与MGMT在肿瘤组织中的表达程度密切相关,MGMT的检测对于指导恶性胶质瘤患者制定个体化化疗方案具有重要意义.     

抗血管生成靶向药物治疗恶性胶质瘤的临床研究

目的探讨抗血管生成靶向药物贝伐单克隆抗体联合细胞毒性化疗药物替莫唑胺或拓扑替康治疗恶性胶质瘤的效果。方法4例复发或残留恶性胶质瘤患者,3例行贝伐单克隆抗体(10mg/kg)联合替莫唑胺[50mg/(m2·d)]治疗(分别治疗14、15和6个周期);1例给予贝伐单克隆抗体(10mg/kg)联合拓扑替康[1.20mg/(m2·d)]治疗3个周期。结果3例复发性胶质母细胞瘤患者,2例完全缓解,1例肿瘤进展但疗效尚满意;1例残留间变性星形细胞瘤患者部分缓解。化疗期间,4例患者均出现Ⅰ度骨髓抑制现象,1例血清转氨酶水平轻度升高,2例发生轻度鼻出血。结论贝伐单克隆抗体联合替莫唑胺或拓扑替康治疗复发或残留恶性胶质瘤患者临床疗效满意,可作为重要的辅助治疗方法。     

MGMT表达指导下的恶性脑胶质瘤预见性化疗近期疗效分析

目的评价根据O~6-甲基鸟嘌呤-DNA甲基转移酶(O~6-methylguanine-DNA methyhransferase,MGMT)表达指导的恶性脑胶质瘤化疗的近期疗效和毒副反应。方法经手术后病理确诊的恶性脑胶质瘤患者28例,用免疫组织化学方法检测肿瘤组织MGMT蛋白表达,对MGMT表达阳性者采用不含亚硝脲类和替莫唑胺的方案进行化疗,MGMT表达阴性者用药不受限。按WHO疗效评价标准评价近期疗效。不良反应评价按美国国立癌症研究所评价标准。结果28例中有4例进行了两个方案化疗,共32化疗例次进入疗效评价。5例次完全缓解(complete response,CR),6例次部分缓解(partial response,PR),12例次稳定(stable disease,sD),9例次进展(progressive disease,PD)。客观有效率(CR PR)为35%,疾病控制率(CR PR SD)为73%。化疗的主要剂量限制性毒性为骨髓抑制。非血液学毒性主要为恶心呕吐和脱发。结论对恶性脑胶质瘤病人在化疗之前检测MGMT蛋白表达,指导选择化疗方案,可以明显提高近期化疗疗效(有效率35%,传统亚硝脲类药物对恶性胶质瘤的有效率仅20%),毒副反应耐受性好。     

P53表达对胶质母细胞瘤替莫唑胺疗效的影响

目的 探讨突变型P53表达情况对胶质母细胞瘤替莫唑胺(蒂清胶囊)化疗临床预后的影响.方法 入选经手术、放疗和替莫唑胺联合治疗的伴O6-甲基鸟嘌呤-DNA转移酶(MGMT)低表达的胶质母细胞瘤患者,利用生存分析比较突变型P53高表达组患者与低表达组患者的临床预后是否存在统计学差异.结果 患者性别、年龄、Karnofsky生活状态(KPS)评分及肿瘤切除程度在两组患者问无统计学意义,突变型P53低表达组患者的肿瘤无进展生存时间明显长于高表达组(P＜0.05),两组患者的生存时间无统计学意义.结论 P53可能参与多形性胶质母细胞瘤替莫唑胺化疗的耐药机制,是影响其临床预后的一种生物指标.     

体外药敏试验及化疗耐药和敏感分子特征指导的恶性脑胶质瘤临床个体化化疗研究

目的 探讨恶性脑胶质瘤临床个体化化疗的策略.方法 恶性脑胶质瘤新鲜肿瘤组织用MTT法进行化疗药物体外药敏试验;用免疫组织化学方法 检测肿瘤组织O6-甲基鸟嘌呤-DNA甲基转移酶(O6-methylguanine-DNA methyltransferase,MGMT)蛋白表达,据MGMT测定结果选择化疗方案;经手术后病理确诊的MGMT表达阳性的恶性脑胶质瘤患者,接受3组化疗方案化疗:含亚硝脲类药物化疗组,含替莫唑胺化疗组,不含亚硝脲和替莫唑胺化疗组.评价3组化疗方案的近期疗效和不良反应;用FISH方法 检测间变性少突胶质细胞瘤组织1p/19q LOH,据检测结果选择化、放疗模式.结果体外药敏试验阴性符合率较高,为14/15.据MGMT表达情况选择化疗方案的客观有效率为34%,疾病控制率为72%.MGMT阳性表达的恶性脑胶质瘤,含亚硝脲类化疗组、含替莫唑胺化疗组、不含亚硝脲和替莫唑胺化疗组的客观有效率及疾病控制率分别为:0和2/11、3/18和11/18、7/22和17/22.不含亚硝脲和TMZ化疗组的客观有效率和疾病控制率均较含亚硝脲化疗组高,有统计学差异(P<0.05).结论 据体外药敏试验及MGMT测定选择化疗方案,可提高近期疗效;MGMT阳性表达的恶性胶质瘤病人,不含亚硝脲和替莫唑胺化疗方案有较好疗效;但含替莫唑胺化疗方案也可应用.     

替莫唑胺治疗胶质母细胞瘤的长期疗效评价

目的 以卡莫司汀(BCNU)为对照,观察替莫唑胺(TMZ)对胶质母细胞瘤化疗的疗效,并探讨O6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)的表达对胶质母细胞瘤预后的影响. 方法 天津市环湖医院神经外科自2004年1月至2009年1月使用化疗药物治疗胶质母细胞瘤患者283例,其中应用TMZ 97例(TMZ组),BCNU 186例(BCNU组),免疫组织化学染色检测手术切除的肿瘤组织中MGMT的表达,对患者进行随访并比较2组患者的生存率、客观有效率和并发症的发生. 结果 TMZ组患者累积生存率高于BCNU组,差异有统计学意义(x2=27.944,P=0.000);TMZ组、BCNU组患者的客观有效率分别是75.26％(73/97)和45.16％(84/186),差异有统计学意义(x2=24.753,P=0.000);与BCNU组比较,TMZ组白细胞减少症的发生率较低,差异有统计学意义(x2=15.681,P=0.000). 结论 TMZ治疗胶质母细胞瘤疗效较BCNU显著,副作用小,耐受性好,是一种理想的胶质母细胞瘤术后化疗药物.     

恶性脑胶质瘤MGMT基因启动子甲基化状态与患者临床预后的相关性

目的 探讨恶性脑胶质瘤组织O6-甲基鸟嘌呤-DNA-甲基转移酶(MGMT)基因启动子甲基化状态及MGMT蛋白表达与患者生存预后的关系,评价MS-MLPA技术检测MGMT基因启动子甲基化状态对脑胶质瘤化疗的意义. 方法 选择自2006至2010年南方医科大学珠江医院神经外科手术治疗且病理证实为恶性脑胶质瘤(WHOⅢ级、Ⅳ级)的39例患者为研究对象,应用免疫组化染色法检测肿瘤组织MGMT蛋白表达,应用MS-MLPA技术检测MGMT基因启动子甲基化状态,并观察患者化疗后总生存时间. 结果 肿瘤组织中MGMT蛋白表达阳性、弱阳性者与表达阴性者生存时间比较差异有统计学意义(P=0.003),MGMT蛋白表达阳性者比表达阴性者预后更差.肿瘤组织中MGMT基因启动子未甲基化者、低度过甲基化者、中度过甲基化者、高度过甲基化者生存时间两两比较差异均有统计学意义(P＜0.05),MGMT基因启动子过甲基化率越高者预后越好.MGMT蛋白表达与MGMT基因启动子甲基化状态存在统计学相关性(r=0.697,P=0.000),基因甲基化程度越高者蛋白表达越低. 结论 MGMT蛋白表达与MGMT基因启动子甲基化状态均可以作为接受烷化剂化疗的恶性胶质瘤患者生存期的预测指标.MS-MLPA技术是一种可靠的检测MGMT基因启动子甲基化状态的方法.     

替莫唑胺治疗难治性垂体腺瘤一例报告并文献复习

目的 探讨难治性垂体腺瘤有效的综合治疗方法.方法 采用手术、伽玛刀及再次手术治疗1例难治性垂体腺瘤患者,然后根据其原代肿瘤细胞培养结果,选用替莫唑胺治疗2个疗程,总结分析其疗效.结果 由于肿瘤生长迅速,常规手术、放疗、药物等治疗方法均难以控制难治性垂体腺瘤生长.根据切除肿瘤病理(Ki-67 LI,MGMT表达水平)及原代肿瘤细胞替莫唑胺敏感实验结果选用替莫唑胺治疗,患者肿瘤停止快速生长,并有肿瘤液化坏死.结论 对于常规手术、放疗及药物治疗无效的难治性垂体腺瘤,替莫唑胺化疗可能是一种替代治疗方法.

Abstract：

Objective To explore the effective treatment for refractory pituitary adenomas.Method Based on MGMT expression and sensitive test of the primary pituitary adenoma cells to temozolomide, we treated a refractory pituitary adenoma patient.Results MGMT expression in this case was at low level,and primary pituitary adenoma cells were sensitive to temozolomide in vitro.The tumor volume decreased after the first cycle temozolomide therapy.Conclusions Temozolomide may be a salvage therapy for those refractory pituitary adenomas with low MGMT expression.     

阿帕替尼联合替莫唑胺密集方案治疗复发恶性胶质瘤

目的观察阿帕替尼或阿帕替尼联合替莫唑胺密集方案治疗复发恶性胶质瘤的临床效果。方法选取郑州大学第一附属医院45例病理确诊的复发恶性胶质瘤患者进行随机分组化疗,其中替莫唑胺密集方案15例,单纯应用阿帕替尼15例,阿帕替尼联合替莫唑胺密集方案15例,比较3组患者治疗2周后MMSE、KPS评分的改善情况及1个月后肿瘤减小和瘤周水肿范围缩小程度,观察持续治疗20个月患者生存情况和无进展生存疗期情况,评估3组患者的治疗效果。结果单纯阿帕替尼和联合治疗组2周后MMSE、KPS评分的改善情况均明显优于单纯替莫唑胺治疗组(均P0.05),且1个月后的肿瘤和瘤周水肿缩小程度亦明显优于单纯替莫唑胺治疗组(均P0.05)。3组患者1个月内的临床缓解率:替莫唑胺组为13.3%,阿帕替尼组为40%,联合治疗为53.4%;持续治疗观察20个月,无进展生存期分别为替莫唑胺组(5.27±3.79)月、阿帕替尼组(9.07±4.04)月、联合治疗组(11.87±4.78)月,后2组明显长于单纯替莫唑胺组(均P0.05);联合治疗组的总生存期较单纯替莫唑胺组有所延长(P0.05)。结论阿帕替尼治疗或阿帕替尼联合替莫唑胺密集方案,可以在短期内明显改善患者症状,减轻肿瘤周围水肿,并可以延长患者无进展生存期,与单纯替莫唑胺方案相比,甚至可以延长总生存期,使复发恶性胶质瘤患者获益。     

脑胶质瘤放射治疗后的假性进展

恶性胶质脑瘤治疗以手术、放疗和化疗为主,术后放疗联合化疗较单纯术后放疗可明显延长病人的生存期。近年来,由于放化疗的联合应用,特别是放疗合并替莫唑胺化疗,假性进展(Pseudoprogression)的发生率明显增加。为此,本文对胶质瘤放疗后假性进展的临床特征及发生机制进行综述,为临床提供参考。     

The effect of age of onset of PD on risk of dementia

Background Dementia occurs in the majority of patients with Parkinson’s disease (PD). Late onset of PD has been reported to be associated with a higher risk for dementia. However, age at onset (AAO) and age at baseline assessment are often correlated. The aim of this study was to explore whether AAO of PD symptoms is a risk factor for dementia independent of the general effect of age. Methods Two community-based studies of PD in New York (n = 281) and Rogaland county, Norway (n = 227) and two population-based groups of healthy elderly from New York (n = 180) and Odense, Denmark (n = 2414) were followed prospectively for 3–4 years and assessed for dementia according to DSM-IIIR. All PD and control cases underwent neurological examination and were followed with neurological and neuropsychological assessments. We used Cox proportional hazards regression based on three different time scales to explore the effect of AAO of PD on risk of dementia, adjusting for age at baseline and other demographic and clinical variables. Findings In both PD groups and in the pooled analyses, there was a significant effect of age at baseline assessment on the time to develop dementia, but there was no effect of AAO independent of age itself. Consistent with these results, there was no increased relative effect of age on the time to develop dementia in PD cases compared with controls. Interpretation This study shows that it is the general effect of age, rather than AAO that is associated with incident dementia in subjects with PD. Received in revised form: 22 December 2005     

腺垂体功能减退症临床特征变化分析

目的探讨腺垂体功能减退症患者的病因结构变化及临床表现。方法回顾性分析我院2013-01—2016-12住院及门诊78例腺垂体功能减退症患者的临床资料。结果男32例(41.03%),女46例(58.97%);诊断时年龄11~89岁,平均62.5岁;鞍区占位(包括术前及术后)52例(66.67%),席汉综合征8例(10.26%),空泡蝶鞍9例(11.65%),病因不明8例(10.26%),垂体-下丘脑发育不良1例(1.28%)。首次就诊科室:纳差厌食、恶心呕吐就诊于消化内科36例(46.15%)最常见。ACTH+TSH+Gn+G激素缺乏为19例最多,占24.36%,ACTH+TSH+Gn缺乏15例,占19.23%。结论腺垂体功能减退症病因结构发生变化,发病人群、首发症状及受累激素也不同,患者女性多于男性,发病年龄偏高,症状不典型,分布于临床多个科室,其中以低钠血症为首发临床表现就诊消化内科最多。     

Standards of instrumentation of EMG

Standardization of Electromyography (EMG) instrumentation is of particular importance to ensure high quality recordings. This consensus report on “Standards of Instrumentation of EMG” is an update and extension of the earlier IFCN Guidelines published in 1999. First, a panel of experts in different fields from different geographical distributions was invited to submit a section on their particular interest and expertise. Then, the merged document was circulated for comments and edits until a consensus emerged.The first sections in this document cover technical aspects such as instrumentation, EMG hardware and software including amplifiers and filters, digital signal analysis and instrumentation settings. Other sections cover the topics such as temporary storage, trigger and delay line, averaging, electrode types, stimulation techniques for optimal and standardised EMG examinations, and the artefacts electromyographers may face and safety rules they should follow. Finally, storage of data and databases, report generators and external communication are summarized.     

帕金森病运动症状进展分析

目的分析帕金森病(PD)患者运动症状进展特点。方法采用PD统一评分量表(UPDRS)Ⅲ对912例PD患者进行评估。结果与病程1年的患者比较,除病程1~2年的患者外,其他病程患者的UPDRSⅢ评分、强直分、姿势或步态异常分、轴性症状总分、言语分、步态分显著升高(均P0.05),病程5~6年及14年患者的震颤分,病程5~6年、7~8年、9~13年、14年患者的运动迟缓分、姿势分显著升高(P0.05~0.01)。轴性症状进展速度高于UPDRSⅢ评分。结论 PD患者病程早期UPDRSⅢ评分进展快,震颤症状进展独立于其他症状,轴性症状评分较UPDRSⅢ更敏感地反映疾病加重趋势。     

Frequency of accumulation of filaments in adaxonal cytoplasm of Schwann cells of myelinated fibers of rat spinal roots

Summary The frequency of accumulation of 6-nm filaments in the adaxonal cytoplasm of Schwann cells in the 6th lumbar dorsal and ventral roots was evaluated in 4-, 8-, 26- and 45-week-old Sprague-Dawley rats. The frequency was higher in 4- and 8-week-old (growing) rats than in 26- and 45-week old (mature) rats, and also higher in ventral than in dorsal roots in 4-, 8- and 26-week old rats. There were no clusters on certain groups of myelinated fibers according to the size of transverse axonal area, in both the ventral and dorsal roots. Therefore, this accumulation may reflect certain functions of the adaxonal cytoplasm of Schwann cell during natural growth and maturation of the axon and myelin sheath.     

Function of circle of Willis

Nearly 400 years ago, Thomas Willis described the arterial ring at the base of the brain (the circle of Willis, CW) and recognized it as a compensatory system in the case of arterial occlusion. This theory is still accepted. We present several arguments that via negativa should discard the compensatory theory. (1) Current theory is anthropocentric; it ignores other species and their analog structures. (2) Arterial pathologies are diseases of old age, appearing after gene propagation. (3) According to the current theory, evolution has foresight. (4) Its commonness among animals indicates that it is probably a convergent evolutionary structure. (5) It was observed that communicating arteries are too small for effective blood flow, and (6) missing or hypoplastic in the majority of the population. We infer that CW, under physiologic conditions, serves as a passive pressure dissipating system; without considerable blood flow, pressure is transferred from the high to low pressure end, the latter being another arterial component of CW. Pressure gradient exists because pulse wave and blood flow arrive into the skull through different cerebral arteries asynchronously, due to arterial tree asymmetry. Therefore, CW and its communicating arteries protect cerebral artery and blood–brain barrier from hemodynamic stress.     

Release of endogenous catecholamines from slices of hypothalamus of rats

The release of endogenous catecholamines from superfused slices of rat hypothalamus was studied under basal conditions and during release evoked by 40 mM K⁺. Catecholamines in superfusates, and in extracts of the tissue after stimulation, were isolated by column chromatography and quantitated by liquid chromatography with electrochemical detection. Norepinephrine (NE) was not consistently demonstrable in superfusate collected under basal conditions, but 40 mM K⁺ caused the release of from 2 to 4 ng/g of tissue per min. The addition of cocaine to the superfusate caused increases in basal and evoked release of NE. Epinephrine (E) could be measured in superfusates of slices from male but not female rats and then only when cocaine was added to the superfusate. Accordingly, the concentration of E in hypothalamus was greater in male rats than in female rats. Dopamine (DA) was not consistently measurable in the spontaneous overflow from slices either in the presence or absence of cocaine. K⁺-evoked release of DA could be demonstrated in slices from female rats. The addition of cocaine increased the evoked release of DA from slices from both sexes. Corticosterone, added to cocaine, had no effects on the efflux of any of the catecholamines. The experiments suggest that neuronal reuptake of all catecholamines is very efficient in the hypothalamus both under basal conditions and during evoked release.     

Effects of prevention of afferentation of the development of the chick optic lobe

BONDY, S. C., M. E. HARRINGTON AND C. L. ANDERSON. Effects of prevention of afferentation on the developmentof the chick optic lobe. BRAIN RES. BULL. 3(5) 411–413, 1978.—The effects of unilateral extirpation of the right optic cup of the three-day incubated chick embryo upon the rate of synthesis and the stability of DNA in the non-innervated optic lobe, have been studied. This surgical procedure prevents innervation of the optic lobe contralateral to the removed eye, while the other optic lobe is normally innervated by retinal ganglion cells of the remaining eye. At the 20th day of incubation, the DNA content of the non-innervated lobe was below that of the paired lobe receiving normal innervation. This deficiency of cell number was caused by two events; death of an excess number of neurons formed early in embryogenesis and a reduced rate of glial proliferation in the later stages of incubation.     

《绵阳市社会心理服务工作管理办法》解读

2018年,国家卫生健康委员会等10部委联合发布《关于印发全国社会心理服务体系建设试点工作方案的通知》,四川省绵阳市被列为全国第一批试点地区。绵阳市人民政府依据《中华人民共和国精神卫生法》等相关法律法规和文件精神,结合前期调查研究和社会心理服务工作的试点实际,编制出台了《绵阳市社会心理服务工作管理办法》,并于2021年12月25日起施行。本文围绕社会心理服务的相关概念、办法总则、重点内容、保障措施等方面进行解读,以期为社会心理服务工作的规范、持续和有效开展提供参考。     

阿立哌唑对精神分裂症患者生活质量的影响

目的:比较阿立哌唑与利培酮对精神分裂症患者生活质量的影响。方法:60例精神分裂患者随机平分为两组各30例,分别给予阿立哌唑和利培酮治疗。疗程8周。用生活质量综合评定问卷-74(GQOLI-74)、阳性与阴性症状量表(PANSS)及副反应量表(TESS)评定疗效及不良反应。结果:阿立哌唑与利培酮均能显著提高精神分裂症患者生活质量,但阿立哌唑在改善GQOLI-74总分、躯体健康及社会功能维度优于利培酮。结论:阿立哌唑治疗有利于提高精神分裂症患者生活质量。