抽动秽语综合征共患注意缺陷多动障碍男性儿童的反应抑制和精细调节

目的:了解抽动秽语综合征(TS)与注意缺陷多动障碍(ADHD)可能存在的神经心理缺陷的异同点。方法:选择符合疾病和有关健康问题的国际统计分类第十次修订本(ICD-10)诊断标准的6~16岁门诊TS男性患儿30名,TS共病ADHD男性患儿36名,ADHD男性患儿36名以及性别、年龄、智商匹配的健康男性儿童50名作为对象,选择Stroop色-字干扰测验(Stroop)和Purdue钉板测验(Purdue)分别对反应抑制和精细调节经行评估。结果:ADHD组的Stroop测验得分高于TS、TS共病ADHD、正常对照组(均P0.05),而TS和TS共病ADHD组间Stroop得分差异无统计学意义(P0.05)。TS组、TS共病ADHD组以及ADHD组Purdue测验中得分均高于正常对照组(均P0.05)。结论:男性ADHD儿童可能存在反应抑制缺陷,而TS与TS共病ADHD儿童未发现上述现象,反应抑制功能可能代表了TS神经发育过程中的补偿机制;TS、TS共病ADHD组以及ADHD组均存在精细调节缺陷。     

抽动秽语综合征汉族患者的执行功能及与多巴胺D4受体第3外显子48bp可重复序列多态性

目的:了解多巴胺D4受体基因第3外显子48bp可重复序列多态性(DRD4 exonIII NTR)与抽动秽语综合征(Gillesdela Tourette syndrome,GTS)患者执行功能缺陷之间的关系。方法:对86例GTS患者进行威斯康星卡片测验(Modified Wisconsin Card sortingtest,WCST)、Stroop色词测验(Strooptest)和连线测验,并和51例正常对照组进行比较;利用PCR技术对GTS患者进行了DRD4exonIII48bpVNTR分析。结果:与正常对照组比较,GTS组在Stroop测验中的C错误数[(44.39±65.3)vs.(20.50±10.85),P0.01]等(包括C纠错数、C时间、CW正确数、CW错误数、CW纠错数和CW时间)、连线测验A时间[(69.80±25.84)vs.(35.69±8.25),P0.01](包括连线B时间、错误数、犯规数)、WCST正确数[(44.39±65.37)vs.(27.49±10.85),P0.01](错误数、持续错误数、非持续错误数和分类数)等测验项目上成绩较差,从共病情况来看,注意缺陷多动综合征共病组在Stroop测验部分项目上比单纯GTS组要差;从GTS组内分析来看,DRD4exonIII48bpVNTR和各神经心理学测验成绩没有关联。结论:抽动秽语综合征患者存在执行功能缺陷,DRD4exonIII48bpVNTR和抽动秽语综合征执行功能缺陷之间可能没有关联。     

中国汉族人群LPHN3基因与注意缺陷多动障碍的关联研究

目的:探讨中国汉族儿童注意缺陷多动障碍与a-latrotoxin受体基因latrophilin 3(LPHN3)基因多态之间的统计学关联。方法:选取符合美国精神障碍诊断与统计手册第4版(DSM-IV)中ADHD诊断标准的1052例ADHD儿童和921例健康对照。采用儿童临床诊断性会谈量表评定患儿临床亚型,该量表将ADHD分为3个亚型:注意缺陷为主型(ADHD-I)、多动冲动为主型(ADHD-HI)和混合型(ADHD-C)。采用ADHD评定量表对患儿ADHD核心症状进行评估,包括注意缺陷分、多动分、冲动分。通过病例对照关联研究方法,对LPHN3基因的3个单核苷酸多态性(SNPs)位点的基因型进行检测,通过χ2检验对单个SNP位点与ADHD及其各亚型、性别间进行等位基因与基因型的关联分析;采用协方差分析探讨LPHN3基因与ADHD核心症状之间的关联。结果:rs11131347与ADHD总体存在名义统计学意义[P0.05,OR=0.86(0.76~0.98)],最小等位基因C在病例与对照组中的分布频率为0.409vs.0.445;分性别分析发现,rs11131347与男性ADHD存在关联[P0.05,OR=0.82(0.71~0.96)],最小等位基因C在病例与对照组中的分布频率为0.402 vs.0.449。分亚型分析,结果显示rs11131347位点与ADHD-C[P0.05,OR=0.85(0.74~0.98)]及男性ADHD-C存在名义统计学关联[P0.05,OR=0.82(0.70~0.97)],最小等位基因C在病例与对照组中的分布频率分别为0.407 vs.0.445及0.401vs.0.449。基因型分析结果显示,rs11131347位点基因型分布频率在ADHD(隐性模型,P0.05)、在ADHD男孩(加法模型,P0.05;显性模型,P0.05;隐性模型,P0.05),ADHD-C(隐性模型,P0.05)及男性ADHD-C(显性模型,P0.05)中,病例与对照组的基因型分布频率存在名义统计学差异,校正后关联消失。进行基因型与ADHD核心症状间的协方差关联分析,发现rs11131347位点与ADHD冲动症状存在名义统计学差异(P0.05)。结论:LPHN3基因多态可能参与ADHD的病理机制并对ADHD的冲动症状有一定影响。     

抽动秽语综合征儿童行为问题及家庭影响因素调查

目的:探讨抽动秽语综合征儿童行为问题及家庭影响因素.方法:对132例抽动秽语综合征儿童采用Achenbach儿童行为量表(CBCL)、家庭环境量表(Family Environment Scale,FES)及自拟家庭影响因素调查表进行测评分析.结果:抽动秽语综合征儿童存在行为问题(26.52%),较正常儿童(13.64%)高(P<0.01).主要家庭影响因素为情感表达、独立自主、娱乐活动及道德宗教,Logistic回归分析中Wald值依次为13.727、10.346、7.969、5.624(P均<0.01).结论:抽动秽语综合征儿童在接受药物治疗的同时,应保持良好的家庭环境,避免行为问题的发生,使其身心健康地发展.     

西藏藏族人群白细胞介素1受体拮抗剂基因多态性

目的:研究白细胞介素-1受体拮抗剂(IL-1Ra)在西藏藏族健康人群中的分布特点,并与其他不同人群进行比较.方法:采用PCR的方法,对125名西藏拉萨市藏族人群IL-1Ra基因的可变数目串联重复序列多态性进行检测,计算其基因型频率和等位基因频率,并结合文献与其他不同人群进行比较分析.结果:西藏藏族人群IL-1Ra位点基因型以A1/A1纯合子型最为多见(频率为90.40%),A1/A2杂合子型次之(频率为9.60%),A2/A2纯合子型未检测到;其等位基因分布也是以A1等位基因最为多见 (频率为95.20%),其次为A2等位基因(频率为4.80%).西藏藏族人群的等位基因频率分布与美国人、德国人、非洲白人差异较大,具有统计学意义.而与亚洲人群包括日本人和中国汉族差异较小.结论:西藏拉萨市藏族人群中IL-1Ra位点以A1等位基因为主,其多态性分布与其他人群之间存在明显的差异,为进一步研究IL-1Ra基因多态性与疾病的关系奠定了基础.     

BAIAP2基因多态与儿童注意缺陷多动障碍共患学习困难的关联分析

目的:探讨脑特异性血管发生抑制剂1相关蛋白2(BAIAP2)基因多态与儿童注意缺陷多动障碍(ADHD)共患学习困难(LD)的关联。方法:选取符合美国精神障碍诊断与统计手册第4版(DSM-IV)诊断标准731例共患LD的ADHD儿童和957例健康对照,采用高通量实时荧光定量PCR方法检测基因型,探讨BAIAP2基因的9个单核苷酸多态性(SNPs)位点与共患LD的儿童ADHD的关联。结果:BAIAP2的SNP位点rs8079626/G(病例对照频率0.638 vs.0.604)和rs4969385/T(0.179 vs.0.150)与儿童ADHD共患LD关联,rs3934492/C(0.572 vs.0.532)和rs4969385/T(0.180 vs.0.142)与男性儿童ADHD共患LD关联,rs4969239/G(0.426 vs.0.329)和rs4969358/A(0.472 vs.0.389)与女性儿童ADHD共患LD关联(均P0.05);由rs4969239-rs4969358-rs6565531-rs8079626组成的单体型AAGG与共患LD的儿童ADHD共患LD(0.100 vs.0.065)和男性儿童ADHD共患LD(0.101 vs.0.065)关联(均P0.05)。结论:BAIAP2基因多态性可能与汉族儿童ADHD共患LD的病理机制有关,且这种作用机制可能存在性别差异。     

肾上腺素能α1A受体基因多态与注意缺陷多动障碍共患学习困难的关联分析

目的:探讨肾上腺素能α1A受体基因(ADRA1A)多态性与注意缺陷多动障碍(ADHD)共患学习困难(LD)的关联.方法:依据美国精神障碍诊断与统计手册第4版(DSM-Ⅳ)标准,诊断ADHD、划分临床亚型并评定共患病.采用中国韦氏儿童智力量表(Chinese Wechsler Intelligence Scale for Children,C-WISC)评估智商.入组678例ADHD共患LD的儿童(含457个核心家系),1137例ADHD未共患LD的儿童(含792个核心家系)及936名正常对照.进行ADRA1A基因3个单核苷酸多态性位点(SNPs)的基因型检测,采用传递不平衡检验、x2检验对单个SNP位点及单体型与ADHD及其表型进行关联分析,采用协方差分析探讨基因与ADHD儿童智商的关联.结果:家系研究显示,rs17426222位点的C等位基因(校正P=0.026)及由rs17426222、rs573514、rs3808585组成的CAC单体型(校正P=0.011),在ADHD共患LD家系中存在过度传递.在ADHD共患LD样本中,rs573514位点的A等位基因频率具有高于对照组的趋势(0.596 vs.0.557,校正P=0.071),控制性别、年龄后该关联仍存在(P＜0.05).在ADHD未共患LD中,家系与病例对照研究均未发现任何关联(P＞0.05);将ADHD共患/未共患LD合并后,关联均消失(P＞0.05).协方差分析显示,rs573514位点基因型与ADHD儿童的操作智商存在关联(P＜0.05),AA基因型携带者操作智商低于AG[(95±15) vs.(97±15),P＜0.05]、GG[(95±15)vs.(98±14),P=0.007]基因型携带者.结论:ADRA1A可能与ADHD共患LD存在关联,ADHD共患LD与否可能存在遗传学差异;ADRA1A可能与ADHD操作性智商存在关联.     

多巴胺D4受体第3外显子48 bp可变重复序列多态性与抽动障碍的传递不平衡检测

目的研究多巴胺D4受体第3外显子48 bp可变重复序列(DRD4 exonⅢ48bpVNTR)多态性是否与抽动障碍(tic disorder, Tic)存在关联.方法采用国际标准化的<Tourette综合征及其相关疾病遗传研究定式检查提纲>收集病史,运用核心家系传递不平衡分析方法(transmission disequilibrium test, TDT)对122个核心家系进行关联分析,根据是否合并注意缺陷多动障碍(attention deficit and hyperactivity disorder, ADHD),将122个核心家系分为合并ADHD的抽动障碍组[合并ADHD的Tourette综合征(Tourette syndrome, TS)和慢性抽动障碍(chronic tic, CT),共40例,TS&ADHD]和抽动障碍组[TS和CT,共82例,TS&CT]两组,采用聚合酶链反应、可变重复序列多态性分析等技术,进行抽动障碍与DRD4 exonⅢ48 bpVNTR多态性的TDT分析.结果在这一多态性位点存在5个等位基因,分别为DRD4 exonⅢ48 bp的2～6个重复等位基因.总体上没有发现抽动障碍与DRD4 exonⅢ48 bpVNTR多态性存在传递不平衡(χ2＝7.44,P＝0.12),进一步对不伴ADHD的抽动障碍组进行的TDT分析也没有发现存在这一位点的传递不平衡(χ2＝3.38,P＝0.50);而在合并ADHD的抽动障碍组中发现,合并ADHD的抽动障碍与DRD4 exonⅢ48 bpVNTR多态性在总体上存在传递不平衡(χ2＝11.74,P＝0.02),进一步对单个等位基因的TDT分析显示,合并ADHD的抽动障碍与DRD4 exonⅢ48 bp的5个重复和6个重复等位基因(长重复等位基因)存在传递不平衡(χ2＝10.57,P＝0.032,χ2＝6.13,P＝0.01).结论 DRD4 exonⅢ48 bpVNTR长重复等位基因与合并ADHD的抽动障碍存在关联,DRD4 exonⅢ48 bpVNTR长重复等位基因可能是中国人群合并ADHD的抽动障碍的遗传危险因素.     

小儿抽动秽语综合征脑电图分析

目的探讨儿童抽动秽语综合征(TS)脑电图与临床的关系,以了解儿童TS患儿脑功能.脑电波的变化情况.方法 382例TS患儿,4岁以下者(包括4岁者)均是自然入睡下描记.5岁以上者均是安静清醒闭目下描记,所有记录时间均大于20分钟.清醒者均作过度换气及视反应常规刺激反应.结果阵发性慢活动86例;中度异常19例;额、中央、颞区3～4Hz尖慢综合波26例;左侧3～3.5Hz5例;左颞 3～3.5Hz尖慢综合波6例;右额 3～3.5Hz尖慢综合波7例;过量β活动16例;异常者共165例(43%).其它均为正常脑电图.     

抽动秽语综合征适应行为的研究

目的 :比较抽动秽语综合征 (TS)患儿与正常儿童的适应行为能力。方法 :采用儿童适应行为量表对 33例 (TS)患儿和 33名正常儿童进行了评定。结果 :TS患儿除感觉运动和时空定向项目与正常儿童接近外 ,其它分量表、因子和适应能力商数均低于正常儿童 ,差异有统计学显著意义 (P <0 0 5～P <0 0 1 )且与该病的严重程度呈负相关。结论 :TS患儿适应能力低于正常儿童 ,且患儿的适应能力评估对TS的严重程度的判断有重要作用 ,并对治疗措施的拟定具有指导作用     

Schizophrenia in a North Swedish geographical isolate, 1900–1977. Epidemiology, genetics and biochemistry

Over 200 schizophrenic patients belonging to three major and interrelated pedigree complexes have been investigated over the past 30 years in a North Swedish geographically isolated population, presently numbering about 6,000. An intensive investigation of a number of biochemical correlates and genetic markers in a few selected families belonging to one of the major pedigrees has indicated new strategies for the current research program.
Schizophrenia, as defined operationally, is significantly associated with decreased activities of two enzymes (1) blood platelet monoamine oxidase, (2) plasma dopamine-β-hydroxylase, and (3) with the genetic marker Gc² (group specific antigen). Both enzymes are subject to genetic variation. A positive score for linkage between schizophrenia and low plasma DBH activity has been calculated, but, so far, available data are insufficient for discrimination between linkage and partial contribution of genetically controlled low plasma DBH to the pathogenesis of the disease. Alternatively, both mechanisms could be involved.
As a model for continued research, schizophrenia is explained as based on a double dominant-recessive genotype (Aabb), representing a vulnerability which in about 50 % of cases develops into clinical schizophrenia. It is suggested that the dominant mutation (A) operates on or affects MAO activity, and that the recessive genotype (bb) is instrumental in low variates of DBH activity and very likely such variates within the normal range of physiological variation. Moreover, it is suggested that the combined effects of MAO- and DBH-reduced efficiency on the metabolism of e.g. dopamine could be an essential pathogenic mechanism for the schizophrenic illness which is segregating in this population.     

Renal dysplasia and asplenia in two sibs

A family is reported in which two sibs, one male and the other female, both died within 24 hours of birth with enlarged polycystic kidneys. Postmortem histology in the second child showed gross renal dysplasia. In both children the pancreas was enlarged, nodular and cystic but the liver appeared macroscopically normal. In the second child, histological examination confirmed pancreatic fibrosis with cystic dilation of ducts, but showed portal fibrosis with bile duct proliferation in the liver.
This combination of findings is very reminiscent of those in a girl and her brother reported by Ivemark et al. (1959). The children reported here also showed absence or hypoplasia of the spleen, cardiac anomalies and other features of the Ivemark syndrome (Ivemark 1955), a quite different, usually sporadic, congenital disorder. It is suggested that the children described here have a distinct lethal congenital disorder, probably inherited in an autosomal recessive manner.     

The dominant diseases of modernized societies as omega-3 essential fatty acid deficiency syndrome: Substrate beriberi

About 1900, modern food selection and processing caused widespread $\text{epidemics}$ of the B vitamin deficiency diseases of beriberi and pellagra which, for genetic reasons, often expressed as different diseases ranging from bowel and heart disease to dermatoses and psychoses. But the B vitamins merely help convert essential fatty acids (EFA) into the prostaglandin (PG) tissue regulators and it now turns out that, through hydrogenation, milling and selection of w3-poor southern foods, we have also been systematically depleting, by as much as 90%, a newly discovered trace Nordic EFA (w3) of special importance to primates and sole precursor of the PG3(4) series, even as a concurrent fiber deficiency increases body demand for EFA. Since substrate EFA is processed by many B vitamin catalysts, an EFA deficiency will mimic a $\text{panh}$ypovitaminosis B, i.e., a mixture of $\text{substrate}$ beriberi and $\text{substrate}$ pellagra resembling vitamin beriberi and pellagra but exhibiting as even more diverse $\text{endemic}$ disease. This would consitute a second stage of the Modern Malnutrition and explain why some workers now hold the dominant diseases of modermized societies to be new, nutritionally based, pellagraform yet lipid-related and to range, once again, from heart disease to psychosis. It is an assumption that our dominant diseases are unrelated to each other or are merely revealed by our diagnostic acumen and therapeutic success; and that hydrogenating millions of tons of food oils annually, to destroy the rancidity producing w3-EFA, is safe for $\text{primates}$. Extensive beriberiform disease is reported here in 32 typical cases taken from medical practice which responds strikingly to linseed oil supplements (60% w3-EFA) in confirmation of identical results in Capuchins.     

'Very sore nights and days': the child's experience of illness in early modern England, c.1580-1720

Sick children were ubiquitous in early modern England, and yet they have received very little attention from historians. Taking the elusive perspective of the child, this article explores the physical, emotional, and spiritual experience of illness in England between approximately 1580 and 1720. What was it like being ill and suffering pain? How did the young respond emotionally to the anticipation of death? It is argued that children’s experiences were characterised by profound ambivalence: illness could be terrifying and distressing, but also a source of emotional and spiritual fulfilment and joy. This interpretation challenges the common assumption amongst medical historians that the experiences of early modern patients were utterly miserable. It also sheds light on children’s emotional feelings for their parents, a subject often overlooked in the historiography of childhood. The primary sources used in this article include diaries, autobiographies, letters, the biographies of pious children, printed possession cases, doctors’ casebooks, and theological treatises concerning the afterlife.     

Guidelines for the Validation and Use of Immunoassays for Determination of Introduced Proteins in Biotechnology Enhanced Crops and Derived Food Ingredients

Recent advancements in agricultural biotechnology have created a need for analytical techniques to determine introduced proteins in crops enhanced through modern biotechnology techniques. These proteins are expressed in plant tissues and may be present in food ingredients. Immunoassays are ideally suited for protein detection and may be used as both quantitative and threshold methods. Microplate ELISA and lateral flow devices are two of the most commonly used immunoassay formats for agricultural biotechnology applications. This paper provides general background information and a discussion of criteria for the validation and application of immunochemical methods to the analysis of proteins introduced into plants and food ingredients using biotechnology methods. It is the result of a collaborative effort of members of the Analytical Environmental Immunochemical Consortium. This collaborative effort represents the combined expertise of several organizations to reach consensus on establishing guidelines for the validation and use of immunoassays. Further, the paper offers developers and users a consistent approach to adopting the technology as well as aid in producing accurate and meaningful results.     

HLA in North Colombia Chimila Amerindians

HLA-A,-B,-C,-DRB1 and -DQB1 alleles have been studied in Chimila Amerindians from Sabana de San Angel (North Colombian Coast) by using high resolution molecular typing. A frequent extended haplotype was found:HLA-A*24:02-B*51:10-C*15:02-BRB1*04:07-DQB1*03:02 (28.7%) which has also been described in Amerinndian Mayos Mexican population (Mexico, California Gulf, Pacific Ocean). Other haplotypes had already been found in Amerindians from Mexico (Pacific and Atlantic Coast), Peru (highlands and Amazon Basin), Bolivia and North USA. A geographic pattern according to HLA allele or haplotype frequencies is lacking in Amerindians, as already known. Also, five new extended haplotypes were found in Chimila Amerindians. Their HLA-A*24:02 high frequencies characteristic is shared with aboriginal populations of Taiwan; also, HLA-C*01:02 high frequencies are found in New Zealand Maoris, New Caledonians and Kimberly Aborigines from Australia. Finally, this study may show a model of evolutionary factors acting and rising one HLA allele frequency (-A*24:02), but not in others that belong to the same or different HLA loci.     

Ultracryotomy: development and application (with examples from the yeast cytology) (author's transl)

The preparation steps usually necessary for obtaining ultrathin frozen sections of biological material (chemical prefixation, enclosing, cryoprotective treatment, freezing, sectioning, and post-staining the sections for transmission electron microscopy) are submitted to a critical analysis. The application of cryo-ultramicrotomy, in particularly for cytochemical purposes, is reviewed. Fundamental considerations of chemical prefixation and poststaining are supported by examples from yeast cytology. Furthermore, the efficiency of the cryo-ultramicrotomy (electron optical resolution of ultrastructural details) is demonstrated on yeast cells and protoplasts.     

The universal muscular chamber. A basic unit of the genitourinary, cardiovascular, gastro-intestinal, skeletal, cutaneous, respiratory and other systems, endocameral hypertension; and spasm, the key to their idiopathic diseases and arthropathies

Starting with the integument, we see many organs are contractile sacs or multiples thereof, which tubes or bags constitute the major part of the entire body. Recognition of this basic unit and its characteristics sheds new light, individually and collectively, on many disorders previously considered unrelated. Muscular tears and perforations develop in the walls of these chambers, being no way peculiar to those organs, wherein, hydrochloric acid occurs. So, it is not necessary to explain the absence of excessive acid from patients who exhibit holes in the gastric, uterine, aortic, duodenal, rectal, pulmonary, retina, and other walls. Muscle, not acid is the great common factor relating idiopathic disorders in the gastrointestinal tract to each other and to similar diseases in other systems. When the units are linked together, the lesions tend to appear as arthropathies, i.e. at the joints. Rephrasing common-place observations, frees us from conventional, conceptual cul-de-sacs. An observation is only as good as its interpretation, so all possibilities must be considered, otherwise, we will remain blinded by our misconceptions.     

Der Einfluß von Nahrungsmitteln und Rauchen auf die klinisch-chemische Diagnostik von Phäochromozytom,Neuroblastom und Karzinoid-Syndrom

Zusammenfassung Der Einfluß von verschiedenen Nahrungsmitteln auf Methoden zur Bestimmung von Adrenalin (AD), Noradrenalin (NA), Vanillinmandelsäure (VMS), Metanephrinen (MN), Homovanillinsäure (HVS) und 5-Hydroxyindolessigsäure (5-HIE) im 24 h-Harn zur Diagnose des Phäochromozytoms bzw. Karzinoid-Syndroms wurde untersucht. Die in die Untersuchung einbezogenen Nahrungsmittel waren: Tee, Kaffee, Mandeln, Ananas, Käse, Walnüsse, Vanillepudding, Bananen, Tomaten und Milchschokolade. Außerdem wurde der Einfluß des Zigarettenrauchens auf die Bestimmung von AD, NA, VMS und MN untersucht.Walnüsse führten zu einer starken Erhöhung der 5-HIE-Ausscheidung. Bananen erhöhten die Ausscheidung von AD, NA, VMS, MN und 5-HIE. Kaffee und Ananas bewirkten eine geringe Zunahme der MN-Werte. Rauchen von 20–30 Zigaretten/Tag beeinflußte keine der vier Variablen.Wenn die beschriebenen Methoden benutzt werden, sollte lediglich auf den Verzehr von Bananen und Walnüssen vor und während der Harnsammelperioden verzichtet werden, da die oberen Normgrenzen im Harn überschritten werden könnten. Ein Verzicht auf Kaffee und Ananas in normalen Mengen ist nicht erforderlich. Es besteht kein Anlaß, weiterhin die bisherigen umfangreichen Restriktionen der übrigen Nahrungsmittel beizubehalten.