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.     

Morphological and biochemical correlates of chemical induced injury in the lung

We have reviewed some of the factors which contribute to lung damage by various toxicants. These include disposition of the chemical, its metabolism, individual cell type susceptibility and the potential for the tissue to repair. We have discussed the use of biochemical parameters to measure the functional activity of individual cell types in order to predict the damage to specific cell types and concluded that careful morphological analysis of lung tissue is likely to provide a more sensitive and informative measure of specific cell type injury. However, in order to investigate the mechanism of toxicity of pulmonary toxicants it is essential to establish the primary biochemical event that leads to cell damage and morphological change. The importance of separating the relevant biochemical change(s) from the cascade of biochemical events associated with dead and dying cells and the reparative response of the lung is emphasised.This report results from a discussion sponsored and organised by the Advisory Subgroup in Toxicology (AST) of the European Science Foundation's Standing Committee for the European Medical Research Councils and held at the Medical Research Council Toxicology Unit, Carshalton, U. K. Those taking part were: W. N. Aldridge (AST; as above); J. Bignon (Unit for Research in Renal and Pulmonary Pathology, University of Paris, Creteil, France); P. H. Burri (Section of Developmental Biology, Institute of Anatomy, University of Berne, Switzerland); G. M. Cohen (as above); D. Dinsdale (MRC Toxicology Unit, Carshalton U. K.); P. Hedqvist (Dept. of Physiology, Karolinska Institute, Stockholm, Sweden); D. Henschler (AST; Dept. of Toxicology and Pharmacology, University of Wurzburg, FDR); G. J. Laurent (Biochemistry Unit, Cardiothoracic Institute, University of London, London, U. K.); R. Lauwerys (AST Industrial and Medical Toxicology Unit, University of Louvain, Brussels, Belgium); F. Lembeck (AST; Dept. for Experimental and Clinical Pharmacology, University of Graz, Austria); N. Lery (AST; Poison Control Centre, Lyon, France); P. Moldeus (Dept. of Forensic Medicine, Karolinska Institute, Stockholm, Sweden); B. Nemery (MRC Toxicology Unit, Carshalton, U. K.); A. Saria (Dept. for Experimental and Clinical Pharmacology, University of Graz, Austria); L. L. Smith (as above);B. Terracini (AST; Dept. of Pathology and Cancer Epidemiology, University of Turin, Italy)     

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。     

多希紫杉醇联合顺铂治疗晚期非小细胞肺癌疗效观察

目的观察和评价多希紫杉醇联合顺铂(DP方案)治疗晚期非小细胞肺癌的疗效和毒性。方法将我科近几年收治的48例晚期非小细胞肺癌患者随机分为治疗组和对照组。治疗组采用多希紫杉醇联合顺铂(DP方案),对照组采用长春瑞滨联合顺铂(NP方案)。2周期化疗后进行疗效、毒性对比研究。结果治疗组和对照组近期有效率分别为45.5%和37.5%,疾病进展时间(TTP)分别为6.3和5.9个月,中位生存期分别为10.1和9.0个月,1年生存率分别为45.8%和39.4%,两组间比较差异均无显著性(P>0.05)。治疗组在恶心呕吐、骨髓抑制等毒性反应发生率方面低于对照组,差异有显著性(P<0.05)。结论多希紫杉醇联合顺铂治疗晚期非小细胞肺癌与NP方案相比较,疗效相似,但毒性反应低于NP组,患者更易耐受,可广泛应用于临床。     

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.