WHO“癫痫社会控制”方案的扩展性试验研究

本研究对WHO“癫痫的社会控制”提案在山西和宁夏回族自治区农村进行了为期一年的扩展性观察试验。共选定癫痫大发作患者120例作为样本。两地各随机分为二组,一组由经过短期培训的乡村医生治疗,另一组由神经科医生治疗。规定使用同一种药物苯巴比妥。结果表明两组都取得了令人满意的疗效,乡村医生可以按规定方案担当起治疗和管理多数癫痫太发作病人的任务。从而再次证实此方案在我国大部分农村地区是可行的、适用的,值得逐步推广。     

重组组织纤溶酶原激活物预防蛛网膜下腔出血后迟发性脑血管痉挛的实验研究

目的实验研究重组组织纤溶酶原激活物预防蛛网膜下腔出血后迟发性脑血管痉挛(DVS).方法实验选取12只家犬,随机分成两组.采取"两次出血法"制成蛛网膜下腔出血(SAH)模型.SAH前先做基底动脉造影,然后行枕大池穿刺,抽出脑脊液4ml后注入等量自体动脉血.第一次"SAH"后48小时再次注入自体动脉血4ml.第二次注血后6小时治疗组6只动物经枕大池穿刺注入组织型纤维蛋白溶解酶原激活物(r-TPA)25mg;对照组注入生理盐水.7天后再次行基底动脉造影.结果动脉造影r-TPA治疗组基底动脉口径无明显变化(P＞0.05);解剖除1例基底动脉外膜上可见数点凝血外,其余动物颅底均无血块.对照组两次动脉造影基底动脉缩小极为明显(P＜0.01),有严重的血管痉挛.颅底充满血块,基底动脉被血块所包绕.结论r-TPA能充分地溶解未成熟的(SAH后48小时)蛛网膜下腔凝血块,从而有效的预防迟发性脑血管痉挛的出现.     

延髓损伤可能会引发局限型和广泛型急性胃粘膜出血

目的：通过动物实验，观察延髓损伤引起胃粘膜出血的表现形式和特点。方法：对１９只成年健康杂种狗，进行延髓一侧性损伤手术（１３只）和对照假损伤性手术（６只）；在损伤后，对胃粘膜表现进行胃镜的动态观察。结果：延髓损伤，可引起胃粘膜出血，而且发生率很高，达１００％；胃粘膜出血的严重程度及其预后有轻、重不同。结论：分析观察结果后认为：胃粘膜出血分可能有局限型和广泛型两个类型；延髓损伤的严重程度与胃粘膜出血的类型密切相关。     

多克隆CNTF抗体对肉毒毒素引起肌麻痹超微结构的影响

目的研究多克隆睫状神经营养因子(c iliary neurotroph ic factor,CNTF)抗体对肉毒毒素(botu linum toxin,BTX)引起的肌麻痹的作用。方法10只新西兰兔,分别在双侧眼外肌肌腹和面部皮下注射A型肉毒毒素(botu linum toxin A,BTXA),注射后第4天在右侧眼外肌和面部皮下注射多克隆CNTF抗体,左侧相同部位注射等量生理盐水作为对照,在注射后14 d,行电镜观察双侧眼外肌和面肌的肌细胞、运动终板及神经纤维的改变。结果注射BTXA后14 d眼外肌和面肌的肌纤维均明显萎缩,线粒体肿胀,肌纤维结构无明显破坏;神经髓鞘板层松散,可见髓样小体,运动终板处可见清亮的兴奋性神经递质小泡增多密集。右侧注射CNTF组可见肌细胞核内移,胞质内线粒体肿胀聚集,肌细胞呈空泡样改变,局部肌丝断裂溶解,变性的肌细胞坏死崩解成细胞碎片;运动终板处也可见大量清亮小泡聚集,神经髓鞘增多。结论注射多克隆CNTF抗体后,与单纯注射BTXA者比较,局部肌细胞结构出现不可逆性破坏,延长了肌肉麻痹恢复时间,提示多克隆CNTF抗体可能延长BTX的肌麻痹作用。     

增生期和分化期大鼠神经干细胞过氧化氢预处理氧化耐受的体外实验研究

目的探讨神经干细胞(NSCs)在增生期和分化期过氧化氢(H2O2)预处理后H2O2损伤氧化耐受的变化。方法分别用浓度为0.05 mmol/L、0.10 mmol/L、0.25 mmol/L、0.50 mmol/L、1.0 mmol/L的H2O2处理增生期NSC(PNSC)和分化期NSC(DNSC)。用0.50 mmol/L的H2O2处理10 m in后,间隔6 h和12 h后再次给予0.50 mmol/L H2O2,观察细胞和损伤的情况。检测热休克蛋白27(Hsp27)、热休克蛋白70(Hsp70)、过氧化氢酶(CAT)、超氧化物歧化酶(SOD)的变化。透射电镜(TEM)检测NSC超微结构变化。结果经0.50 mmol/L H2O2预处理10 m in,间隔12 h后DNSC可以产生H2O2耐受,并至少持续12 h;而PNSC并不能产生H2O2耐受。预处理后的DNSC在Hsp27和Hsp70阳性细胞比例显著上升(P<0.05),TEM示存活的细胞均为比较原始的细胞。结论在给予0.5 mmol/L H2O2预处理10 m in后,间隔12 h后DNSC后产生对H2O2耐受;而PNSC不能产生耐受。这可能与Hsp27和Hsp70的增加有关。此外,这与原始状态NSC H2O2氧化耐受要高于分化状态的细胞有关。     

胚胎发育不良性神经上皮肿瘤12例

目的探讨胚胎发育不良性神经上皮瘤(DNT)的临床特点、诊断和治疗方法。方法分析2003年1月至2005年2月,北京天坛医院收治的12例DNT患者的临床和病理资料。结果除2例以头痛发病外,其余10例患者均以癫痫为临床首发症状。MR I检查结果为T1低信号,T2高信号病灶,无水肿,无占位效应,可见脑回样或内部分隔改变。手术治疗后癫痫发作控制满意,病理学检查可见特异性胶质神经元。结论DNT手术效果良好,准确诊断对该病的治疗有重要意义。     

Functional analysis of gene expression in risperidone treated cells provide new insights in molecular mechanism and new candidate genes for pharmacogenetic studies

Risperidone is a potent antagonist of both dopamine and serotonin receptors. However, little is known about the underlying molecular mechanism by which risperidone acts. Although a number of genetic variants have been observed to correlate with treatment response there are no definitive predictors of response. We performed a genome-wide gene expression analysis (Human Genome U219 Array Plate) of a human neuroblastoma cell line (SK-N-SH) exposed to risperidone to identify molecular mechanisms involved in the cellular response to risperidone and thus identify candidate genes for pharmacogenetic studies. Our results revealed that cellular risperidone treatment is associated with a range of gene expression changes, which are time (6–48 h) and dose related (0.1–10 μM). We found that functional clusters of these changes correspond to Gene Ontology categories related to neural cell development functions, and synaptic structure and functions. We also identified Canonical Pathways related to these functional categories: neurogenesis and axon guidance; synaptic vesicle; and neurotransmitter signaling (dopamine, serotonin and glutamate). Finally, we identified candidate genes for pharmacogenetic studies related to the main risperidone secondary effects: motor disorders, cardiovascular disorders and metabolic disorders. Our results suggest that risperidone treatment affects the neurogenesis and neurotransmission of neuroblastoma cells, which is in agreement with the “initiation and adaptation” model to explain the mechanism of action of psychotropic drugs.     

Sex Differences in Ischemic Stroke Readmission Rates and Subsequent Outcomes After Coronary Artery Bypass Graft Surgery

Background and PurposePrior studies examining sex-related risk of readmission for ischemic stroke (IS) after coronary artery bypass grafting (CABG) did not adjust for preoperative comorbidities and used small study samples that were single-center or otherwise poorly generalizable. We assessed risk of readmission for IS after CABG for females compared to males in a nationwide sample.MethodsThe 2013 Nationwide Readmissions Database contains data on 49% of all U.S. hospitalizations. We used population weighting to determine national estimates. Using all follow-up data up to 1 year after discharge from CABG hospitalization, we estimated Kaplan-Meier cumulative risk of IS, stratified by sex, using the log-rank test for significance. We created Cox proportional hazard models to calculate hazard ratios (HR) and 95% confidence intervals (CI) for IS readmission, with sex as the main independent variable. We ran unadjusted models and models adjusted for age, vascular risk factors, estimated severity of illness and risk of mortality, hospital characteristics, and income quartile of patient's zip code.ResultsAn estimated 53,270 females and 147,396 males survived index CABG admission in 2013. There was a consistently elevated cumulative risk of readmission for IS after CABG for females versus males (log-rank p-value = 0.0014). In the unadjusted Cox model, the HR of IS in females vs. males was 1.35 (95% CI 1.12–1.62, p = 0.0015). The elevated risk for females remained after adjusting for severity of illness (1.30 [1.08–1.56], p = 0.0056) and risk of mortality (1.28 [1.07–1.54], p = 0.0086). This elevated risk persisted after adjusting for multiple vascular risk factors, hospital characteristics, and income quartile of patient's zip code (1.23 [1.02–1.48], p = 0.03).ConclusionsWe found a 23% increased risk of readmission for IS up to 1 year after CABG for females compared to males in a fully adjusted model utilizing a large, contemporary, nationwide database. Further research would clarify mechanisms of this increased risk among women.     

Ventricular peritoneal shunt malfunction after operative correction of scoliosis: report of three cases

Background contextTwo of the most common disease processes associated with hydrocephalus in children are spina bifida and intraventricular hemorrhage of prematurity, both of which are known to be also associated with spinal deformity in later childhood. The occurrence of shunt malfunction after mechanical injury or stress to the hardware has been well documented. Newer techniques in the treatment of neuromuscular scoliosis, including anterior release with segmental fixation, have resulted in more powerful corrections of these large spinal deformities. A new potential cause of shunt malfunction is the aggressive correction of scoliosis.PurposeTo report patients with neuromuscular curves averaging 100° who were subsequently recognized to have perioperative shunt malfunction.Study designThree case studies from a university hospital setting were included.Patient sampleAll three children were young adolescents and had-long term shunts. Two of the children had spina bifida and a third had cerebral palsy. All children underwent anterior release of their scoliosis with posterior segmental instrumentation, with unit rods and sublaminar wires. All had significant correction of their scoliosis.Outcome measuresMalfunctioning of the ventriculoperitoneal shunts were recorded.MethodsChart reviews of three cases were analyzed.ResultsTwo children had shunt malfunctions within a month of their surgery, and one child had intraoperative recognition and externalization of the shunt.ConclusionsOlder children undergoing repair of neuromuscular scoliosis are often preadolescents or adolescents who have the same indwelling shunt systems originally implanted in early infancy. The shunt may be brittle and calcified, and the peritoneal catheter may be short. The correction of scoliosis often results in an almost instantaneous growth of a few inches. Because of the potential difficulty in recognizing shunt malfunction in the perioperative period, consideration should be given for elective revision of the peritoneal catheter in children at risk.     

Silencing of MicroRNA-21 confers the sensitivity to tamoxifen and fulvestrant by enhancing autophagic cell death through inhibition of the PI3K-AKT-mTOR pathway in breast cancer cells

Tamoxifen (TAM) and fulvestrant (FUL) represent the major adjuvant therapy to estrogen receptor-alpha positive (ER⁺) breast cancer patients. However, endocrine resistance to TAM and FUL is a great impediment for successful treatment. We hypothesized that miR-21 might alter the sensitivity of breast cancer cells to TAM or FUL by regulating cell autophagy. Using the ER⁺ breast cancer cells, we knockdown miR-21.by transfection with miR-21 inhibitor, then the cells were exposed to TAM or FUL and the percentages of apoptosis and autophagy were determined. Knockdown of miR-21 significantly increased the TAM or FUL-induced apoptosis in ER⁺ breast cancer cells. Further, silencing of miR-21 in MCF-7 cells enhanced cell autophagy at both basal and TAM or FUL-induced level. The increase of autophagy in miR-21-knockdown MCF-7 cells was also indicated by increase of beclin-1, LC3-II and increased GFP-LC3 dots. Importantly, knockdown of miR-21 contributed to autophagic cell death, which is responsible for part of TAM induced cell death in miR-21 inhibitor-transfected cells. Further analysis suggested that miR-21 inhibitor enhance autophagic cell death through inhibition of PI3K-AKT-mTOR pathway. MiR-21 coordinated the function of autophagy and apoptosis by targeting Phosphatase and tensin homolog (PTEN) through inhibition of PI3K-AKT-mTOR pathway. In conclusion, silencing of miR-21 increased the sensitivity of ER⁺ breast cancer cells to TAM or FUL by increasing autophagic cell death. Targeting autophagy-related miRNAs is a potential strategy for overcoming endocrine resistance to TAM and FUL.