Genetic contributions to Parkinson's disease

Sporadic Parkinson's disease (PD) is a common neurodegenerative disorder, characterized by the loss of midbrain dopamine neurons and Lewy body inclusions. It is thought to result from a complex interaction between multiple predisposing genes and environmental influences, although these interactions are still poorly understood. Several causative genes have been identified in different families. Mutations in two genes [α-synuclein and nuclear receptor-related 1 (Nurr1)] cause the same pathology, and a third locus on chromosome 2 also causes this pathology. Other familial PD mutations have identified genes involved in the ubiquitin–proteasome system [parkin and ubiquitin C-terminal hydroxylase L1 (UCHL1)], although such cases do not produce Lewy bodies. These studies highlight critical cellular proteins and mechanisms for dopamine neuron survival as disrupted in Parkinson's disease. Understanding the genetic variations impacting on dopamine neurons may illuminate other molecular mechanisms involved. Additional candidate genes involved in dopamine cell survival, dopamine synthesis, metabolism and function, energy supply, oxidative stress, and cellular detoxification have been indicated by transgenic animal models and/or screened in human populations with differing results. Genetic variation in genes known to produce different patterns and types of neurodegeneration that may impact on the function of dopamine neurons are also reviewed. These studies suggest that environment and genetic background are likely to have a significant influence on susceptibility to Parkinson's disease. The identification of multiple genes predisposing to Parkinson's disease will assist in determining the cellular pathway/s leading to the neurodegeneration observed in this disease.     

小儿急性肺损伤的短期肺功能随访

Objective To study the pulmonary functions of pediatric ALI/ARDS(acute lung injury/acute respiratory distress syndrome) survivors. Method A prospective cohort study of all survivors of ALI/ARDS in the PICU of Beijing Children's Hospital was performed. Patients were divided into three groups(0-3 years of age,3 ～ 7 years of age, and over 7 years of age) and followed up three months after diagnosis. Results There were 36 survivors in total of 44 ALl patients, three patients lost follow-up, 12 died and 21 survived. Five survivors refused to participate in the study because of asymptomatic, and one was unable to participate because of lymphoma com-bined with sepsis. A total of 15 children completed the whole survey (11 patients were less than 3 years old, andfour were over 7 years of age). Twelve patients had no discomfort in their respiratory tracts. Three months after be-ing enrolled, the pulmonary functions of all children improved, especially in terms of tidal volume and respiratory compliance (P<0.05). Conclusions The abnormal respiratory symptoms and signs in most children disap-peared three months after discharge. Most survivors still have pulmonary dysfunction at 3 monthes after discharge, but better than discharge.     

Singularities explained: Response to Klein.

Klein [Klein, A. S. (2006). Separating transducer nonlinearities and multiplicative noise in contrast discrimination. Vision Research, 46, 4279-4293] questions the existence of intrinsic singularities in two-alternative force-choice (2AFC) Signal Detection Theory (SDT) models, suggesting that the singularities found in Katkov et al. [Katkov, M., Tsodyks, M., & Sagi, D. (2006a). Singularities in the inverse modeling of 2AFC contrast discrimination data. Vision Research, 46, 259-266; Katkov, M., Tsodyks, M., & Sagi, D. (2006b). Analysis of two-alternative force-choice Signal Detection Theory model. Journal of Mathematical Psychology, 50, 411-420] are due to discarding higher order terms in the Taylor expansion of d' and/or limited to steep psychometric functions. Here we provide some simple intuitive examples that illustrate the results described in Katkov et al. (2006a, 2006b). We show, for the constant noise model, that singularities exist when exact values of d' are computed and that the singularities are not limited to steep psychometric functions. In these cases the disambiguation of the different models requires millions of trials.     

基于临床流程功能需求的生理监测仪配置评估

病人生理监测仪是临床医学的主要仪器之一，由于所涉及的技术流程定位不同，功能需求也就不同，其功能配置也应有所不同。本文从分解分析生理监测仪相关应用领域的技术定位功能需求出发，讨论卫生技术装备管理的功能配置评估。     

XD—1型微电脑程序刺激器在心血管病中的临床应用

本文应用XD—Ⅰ型微电脑程序刺激器检查26例患者,在窦房结功能检查中测定了窦房结恢复时间、窦房传导时间及固有心率;在房室传导功能的估计中测定了文氏点,2∶1阻滞点及房室结的有效不应期;在室上性心动过速中测定了旁路不应期,房室结双通道,折返区及折返性心动过速区;还进行了心脏负荷试验及右束支不应期等方面的测定。并就其方法,判断标准及临床意义等分别作了讨论。     

Heart rate response to breathing: dependency upon breathing pattern

Summary. Heart rate responses to stepwise and periodic changes in lung volume were studied in seven young healthy males. Stepwise inspiration and expiration both resulted in an increase in heart rate followed by a rapid decrease in heart rate. The fastest heart rate was reached in 1·6 ± 0·5 s and in 3·6 ± 1·4 s in response to inspiration and expiration, respectively (P < 0·01). The slowest heart rate was reached in 4·8± 1·0 s and in 7·6± 1·9 s in response to inspiration and expiration, respectively (P < 0·01). Following this biphasic change the heart rate returned to a steady level. The difference between the fastest and the slowest heart rates was significantly larger in response to inspiration (21·7 ± 7·3 beats per minute) than in response to expiration (12·0±7·3 beats per minute; P < 0·01). Periodic changes in lung volume were performed with frequencies from 3·0 to 12·0 respirations per minute (r.p.m.). The changes in heart rate showed a constant amplitude in the frequency range below 5·5 r.p.m. Maximal heart rate changes were found at frequencies of 5·5 to 7·0 r.p.m. Changes in heart rate decreased in a linear manner on a log-log scale in the frequency range above 7·0 r.p.m. The relation between frequency and changes in heart rate is explained by interference between the transient changes in heart rate induced both by inspiration and by expiration. It is concluded that if heart rate changes in response to periodic changes in lung volume are to be used as a measure of vagal function a number of factors have to be taken into consideration and to simplify the analysis of heart rate responses to breathing we recommend, instead, the use of the transient changes in heart rate induced by stepwise changes in lung volume.     

经皮椎体成形术中骨水泥对老年骨质疏松症患者凝血功能的影响

目的 观察经皮椎体成形术(PVP)中骨水泥对老年骨质疏松症患者凝血功能的影响.方法 于椎弓根穿刺前10 min、注入骨水泥后1、20 min、2 h分别抽血检测11例患者的凝血功能相关指标,包括血浆凝血酶原时间(PT)、活化的部分凝血酶原时间(APTT)、血浆纤维蛋白原(FIB)和鱼精蛋白副凝固实验(3P实验),并汇总数据进行统计学分析.结果 PVP中骨水泥注入后20 min,PT缩短、FIB增高、3P实验阳性率升高(P<0.05),骨水泥注入2 h后基本恢复至注入前水平.除1例患者PTA术后2 h稍高于正常值(126%),其余患者各个时间点的各项指标均在正常参考值范围内.结论 PVP术中注入骨水泥对于凝血功能正常的患者基本安全,但在注入后会产生一过性轻微的高凝倾向.     

前列腺素E1对大鼠肝移植肾功能的保护作用

目的探讨术中应用前列腺素E1（prostaglandin E1，PGE1）对大鼠肝移植肾功能的保护作用。方法大鼠原位肝移植术中经颈内静脉灌注PGE1为治疗组，生理盐水和空白为对照组，观察术后1周存活率、1h的尿量，测定血浆肌酐、尿素氮和肾组织中丙二醛（malondjaldehyde，MDA）、谷胱甘肽（glutathione，GSH）含量，肾组织病理检查。结果PGE1治疗组术后1h尿量较对照组明显增加，肌酐和尿素氮水平均较对照组降低，PGE1治疗组肾组织中GSH含量显著高于两对照组，MDA含量低于两对照组。病理检查PGE1治疗组肾脏组织形态学损伤明显减轻。结论术中应用PGE1能显著改善大鼠肝移植后的肾功能，其机制可能与对抗氧自由基损伤作用有关。     

慢性肾脏病非透析患者脑钠素与动脉粥样硬化及心功能的关系

目的 研究脑钠素（BNP）与慢性肾脏病（CKD）非透析患者动脉粥样硬化及心功能不全的关系。 方法 采用双抗夹心免疫荧光法检测203例CKD非透析患者与16例高血压患者对照组全血BNP水平，分析其与颈动脉超声结果、心脏彩超结果及既往心血管疾病史的关系。 结果 CKD非透析患者BNP水平与对照组相比显著升高[M（范围）：54.40(15.10～ 173.00) ng/L比9.35(7.35～15.00) ng/L，P < 0.01]。Spearman相关分析显示CKD患者BNP与颈动脉内膜中层厚度（IMT）、左室心肌重量指数（LVMI）等呈正相关。存在颈动脉斑块、左室肥厚或既往发生过心血管事件的患者血BNP水平显著增高。多元回归分析显示LVMI、既往心血管事件均是影响BNP水平的独立因素。 结论 CKD非透析患者BNP水平和动脉粥样硬化性疾病、左室肥厚及心功能不全相关，提示BNP水平可作为一项评价CKD非透析患者心功能及动脉粥样硬化的敏感生物学指标。