实时RT-PCR检测159例手足口病患儿样本中肠道病毒的结果分析

目的 了解2009年4-8月首都儿科研究所附属儿童医院手足口病患儿肠道病毒的感染状况,为临床诊治提供参考.方法 采集首诊手足口病159例患儿的咽拭子和疱疹液标本,以肠道病毒(EV)通用型、柯萨奇病毒A16(CA16)型、肠道病毒71(EV71)型核酸检测试剂盒,应用实时RT-PCR法检测标本中的肠道病毒.选取阳性标本扩增VP1区,产物进行序列测定和分析.结果 (1)EV、CA16、EV71的阳性病例数分别为152、102、43;阳性率为95.6%、64.2%、27.0%.(2)CA16占EV阳性的67.3%,EV71占EV阳性的28.3%,非CA16和EV71的EV病例7例,占EV阳性的4.6%.CA16:EV71为2.37:1.(3)部分阳性标本经测序验证与此法结果一致.结论 2009年我院手足口病患儿以EV71和CA16感染为主,EV71感染的手足口病比例较2007年出现明显上升.     

柯萨奇病毒A组6型与肠道病毒71型感染所致手足口病临床特征比较

目的 了解柯萨奇病毒A组6型、肠道病毒71型手足口病临床特点,为指导临床诊断,调整手足口病防控策略提供科学依据.方法 采用前瞻性调查的方法,收集2013至2014年在北京市西城区手足口病临床确诊病例信息,将手足口病原核酸检测阳性的病例分为CA6、EV71组,分析比较2组的临床特点、流行特征、预后等.结果 CA6组130例,EV71组121例.2组的年龄、性别分布差异无统计学意义.CA6组发热比例高达82.3％,明显高于EV71组(34.7％,P＜0.05),其中大于等于38℃占85.0％.CA6组出现大疱疹(7.4％)、恢复期脱皮(16.9％)、脱甲(10.0％)的比例高于EV71组(P＜0.05).不同年份流行主要毒株不同.结论 与EV71感染相比,CA6感染引起的高热比例较高,部分病例可表现为大疱疹、脱皮、脱甲,整体预后较好.CA6和EV71感染所致的HFMD发病高峰季节不一致.     

肠道病毒71型IgM抗体检测在手足口病早期诊断中的价值

目的 评估人肠道病毒71型(EV 71)IgM抗体在手足口病早期诊断中的价值.方法 自发病后连续每日采集2010年我院收治的38例手足口病患儿血清及咽拭子标本,分别检测EV 71IgM抗体、肠道病毒核酸、EV 71特异核酸.结果 38例手足口病患儿IgM抗体,按发病天数累加阳性率分别为:第1天60.5%、第2天71.1%、第3～4天81.5%、第5天92.1%、第6天92.1%;肠道病毒核酸阳性率为73.6%;EV 71特异核酸阳性率为60.5%.结论 EV 71 IgM抗体在手足口病发病的第1天即可出现,至第5天阳性率达到峰值,可作为手足口病早期诊断指标之一.     

肠道病毒71型IgM抗体检测在手足口病早期诊断中的价值

目的 评估人肠道病毒71型(EV 71)IgM抗体在手足口病早期诊断中的价值.方法 自发病后连续每日采集2010年我院收治的38例手足口病患儿血清及咽拭子标本,分别检测EV 71IgM抗体、肠道病毒核酸、EV 71特异核酸.结果 38例手足口病患儿IgM抗体,按发病天数累加阳性率分别为:第1天60.5%、第2天71.1%、第3～4天81.5%、第5天92.1%、第6天92.1%;肠道病毒核酸阳性率为73.6%;EV 71特异核酸阳性率为60.5%.结论 EV 71 IgM抗体在手足口病发病的第1天即可出现,至第5天阳性率达到峰值,可作为手足口病早期诊断指标之一.     

感染肠道病毒71型尸检病例的分子病原学诊断

目的 探讨感染肠道病毒71型(EV71)的尸检病例石蜡包埋组织病原学分子检测的应用价值.方法 尸体解剖2例怀疑因EV71感染死亡的患儿,对脑组织进行了组织学观察和免疫组织化学EnVision法标记;应用逆转录聚合酶链反应检测尸检后的石蜡组织中肠道病毒的核酸并测序分析.结果 2例均有中枢神经系统脑干脑炎的病理学特点.坏死神经元周围可见大量的小胶质细胞(CD68阳性)和少量的中性粒细胞(CD15阳性)浸润.2例延髓石蜡组织中均检测出EV71的核酸序列,与GenBank最新公布的安徽阜阳暴发EV71感染的病毒株序列同源性为100%.结论 从甲醛固定、石蜡包埋的EV71感染患儿脑组织中检测出病毒特异性核酸序列,及时明确诊断临床误诊、漏诊的死亡病例,深化认识了手足口病,为公共卫生管理机构及时加强EV71病原学监测提供决策依据.     

西安地区2008年肠道病毒71型基因特征分析

目的 研究西安地区2008年引起手足口病病原构成及EV71的基因特征.方法 采集124例临床诊断手足口病病例标本,RT-PCR检测肠道病毒血清型别;挑选EV71阳性标本进行病毒分离,扩增7株EV71病毒,扩增其VP1区,测序并与EV71各血清型代表株序列比对,进行进化分析.结果 2008年西安地区手足口病（HFMD）的病原中CA16占49.45%,EV71占30.76%,其他肠道病毒占19.78%.7株EV71 VP1区与标准株序列比对,亲缘进化分析显示本地区EV71与中国大陆其他地区毒株相似.结论 2008年西安地区引起手足口病的病原以CA16为主,而EV71属于C4亚型.     

2019—2021年西安市手足口病的病原学特征分析

目的分析2019—2021年西安市手足口病(hand, foot and mouth disease, HFMD)的病原构成及其流行病学特征, 为防控HFMD提供科学依据。方法收集临床诊断为HFMD的肛拭子或粪便标本, RT-PCR法检测肠道病毒(enterovirus, EV), 鉴别出肠道病毒71型(enterovirus 71, EV71)、柯萨奇病毒A组16型(coxsackievirus A16, CVA16)、柯萨奇病毒A组6型(CVA6)、柯萨奇病毒A组10型(CVA10)。使用Excel 2007和SPSS18.0软件进行数据收集和统计学分析, 对HFMD进行描述性流行病学分析和病原学特征分析。下载CVA6各基因型代表株的VP1区序列, 用MEGA X软件构建基因进化树, 分析其基因特征。结果共收集到1 531例HFMD病例, EV的阳性率为89.16%(1 365/1 531), EV71、CVA16、CVA6、CVA10和其他EV的检出率分别为1.31%(20/1 531)、32.46%(497/1 531)、38.47%(589/1 531)、5.09%(78/1...     

手足口病病原体实时荧光RT-PCR反应体系的建立与临床应用

目的 建立一种快速、准确、特异件高的方法 检测手足口病病原体.方法 根据引起手足口病常见致病原肠道病毒71(EV71)、柯萨奇病毒A16(CA16)及肠道病毒(EV),设计相应的引物、探针对35例临床诊断的手足口病患儿及20例正常健康婴儿的粪便进行EV、EV71、CA16三种病原体实时荧光RT-PCR检测,同时对55分标本进行EV71病毒培养分离.结果 35例临床诊断手足口病患儿粪便中EV全部阳性,EV71阳性25例,CA16阳性8例,其中3例为EV71、CA16同时阳性,与临床诊断符合率为85.71%,20例健康体检婴儿粪便中EV病毒5例阳性,EV71、CA16均阴性.结论 荧光RT-PCR对手足口病病原体检测准确性高、特异性强,具有快速、廉价等特点,适合于手足口病的早期诊断.     

2012～2019年北京佑安医院手足口病流行特征及中性粒细胞/淋巴细胞比值的分析

目的 分析2012～2019年北京佑安医院手足口病(HFMD)流行趋势变化,比较不同型别HFMD中性粒细胞/淋巴细胞比值(NLR).方法 回顾分析2012年6月至2019年12月北京佑安医院收治HFMD流行病学资料和临床资料,统计分析各型别肠道病毒(EV)的流行趋势及NLR水平变化.结果 共收集8726例经临床确诊的手足口病例,好发年龄为1～3岁和3～6岁,男性多于女性,在2014年发病例数达到高峰(n=2032),随后逐年下降,2012、2014和2016年EV71、CA16为主要感染型别,2017年后EV71感染比例下降,CA16感染比例上升.其他EV型别在2013、2015和2018为主要型别,与EV71、CA16交替出现高峰,对2017、2018年97例样本分型显示主要型别为CA6、CA10,且存在共感染病例.EV71病例住院比例最高为30.88％,但NLR维持在低水平为1.54,CA6、CA10共感染病例NLR水平最高为4.26,但住院比例较低为8.33％.结论 不同型别EV的共同流行与共感染增加了病毒之间基因重组和病例重症化的风险,长期、持续监测其流行趋势变化,对H FMD及时、早期预防与控制具有重要意义.     

肠道病毒71型IgM抗体检测在手足口病早期诊断中的价值

目的评估人肠道病毒7l型（EV71）IgM抗体在手足口病早期诊断中的价值。方法自发病后连续每日采集2010年我院收治的38例手足口病患儿血清及咽拭子标本,分别检测EV 71 IgM抗体、肠道病毒核酸、EV71特异核酸。结果38例手足口病患儿IgM抗体,按发病天数累加阳性率分别为：第1天60．5％、第2天71．1％、第3～4天81．5％、第5天92．1％、第6天92．1％;肠道病毒核酸阳性率为73．6％;EV71特异核酸阳性率为60．5％。结论EV 7l IgM抗体在手足口病发病的第1天即可出现,至第5天阳性率达到峰值,可作为手足口病早期诊断指标之一。     

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.     

The universal muscular chain reaction,muscle spasm,Torsions, ruptures and extravasations. Chameleons of pathology and some manifestations of simple muscular disorders

Most bodily functions require the coordinated actions of complementary and supplementary paired muscle groups. Where this essential muscular cooperation is lacking, hollow organs may burst and others become literally screwed up, giving rise to many similar spastic diseases such as Torticollis, Twisted ovarian cyst, Torsion of the Testis, Volvulus of the intestines, Varicose Veins, Megacolon, Aortamegaly, Scoliosis, Erb's Palsy, Peyronie's Disease, Main-en-Griffe, Undescended Foot (Pes Cavus), Talipes, Strabismus. Spasm is “panenepidemic” and unclassified examples of Torsion Dystonia and Dyskinesia really are as common as debt and taxes.     

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.     

Hypo- und Hypermagnesämie aus kardiologischer Sicht

Zusammenfassung Eine Reihe pathologischer Zustände bedingen Magnesiummangel. Zustände mit Hypermagnesämie sind ebenfalls bekannt, doch wesentlich seltener. Für den Kardiologen beachtenswert ist, daß unter Therapie mit bestimmten Diuretica bei Herzinsuffizienz, bei Herzinfarkt, Kardiomyopathie, Digitalisintoxikation und bestimmten Herzrhythmusstörungen Hypomagnesämie beobachtet wurde. Leider kann in der klinischen Routine nur ein extracelluläres Magnesiumdefizit durch Serumbestimmungen gemessen werden; über Magnesiummangel einzelner Organe kann nichts ausgesagt werden. Hinweise für Magnesiummangel geben aber neben der Messung des Serumspiegels Anamnese, klinischer Befund, bestimmte EKG-Veränderungen wie auch evtl. Hypokalämie, ein Zustand, bei dem sich oft — besonders bei Aldosteronismus — parallele Veränderungen zeigten.Tierexperimente deuten darauf hin, daß infarktähnliche Läsionen unter Magnesiummangel entstehen, doch ob Herzinfarkt beim Menschen durch Magnesiummangel ausgelöst werden kann, ist noch ungeklärt. In Leichenherzen zeigte sich im Infarktgebiet neben Calciumakkumulation signifikanter Magnesiumverlust, wobei unklar blieb, ob sich Ursache oder Folge des Infarktes widerspiegelten. Falls ein ursächlicher Zusammenhang besteht, ist er im Myokardstoffwechsel selbst zu suchen, wie bei der Alkoholkardiomyopathie, wo myokardialer Magnesiummangel zumindest als pathogenetischer Teilfaktor anerkannt wird. Andererseits versucht man aber auch Beziehungen zwischen Atherosklerose, Blutgerinnung und Hypomagnesämie herzustellen, in der Meinung, daß Magnesiummangel auch über den coronaren Pathomechanismus des Herzinfarktes wirken könnte. Sicher scheint, daß gewisse EKG-Veränderungen und Herzrhythmusstörungen durch einen irritierten Magnesiumhaushalt bedingt sein können, da sie bei Gabe bzw. Entzug von Magnesium verschwinden. Daß Magnesiummangel die Glykosidtoleranz verringert, wird tierexperimentell bestätigt. Unter Hypomagnesämie bewirkt Acetylstrophanthidin eher und länger Rhythmusstörungen als ohne, außerdem lassen diese sich durch Magnesiumgaben eliminieren. Da in gewissen Fällen spontane und digitalisinduzierte Herzrythmusstörungen durch Magnesiuminjektionen beseitigt wurden, scheint Magnesium als Therapeuticum angebracht. Einsatz verschiedener Magnesiumsalze bei Angina pectoris, degenerativen Herzerkrankungen und Herzinsuffizienz ohne geprüften und offensichtlich gestörten Magnesiumhaushalt ist fragwürdig, weil keine eindeutigen klinischen Erfolgsbeweise vorliegen. Immerhin mag es aber larvierte, durch Serumbestimmungen nicht erfaßbare Mangelzustände geben. Allgemein erscheint es aus kardiologischer Sicht ratsam, den Magnesiumhaushalt zu überwachen und in entsprechenden Fällen auszugleichen, um möglichen Myokardläsionen oder fatalen Herzrhythmusstörungen entgegenzuwirken.     

Environmental risk factors and their role in the management of atopic dermatitis

Introduction: The etiology of atopic dermatitis (AD) is multifactorial with interaction between genetics, immune and environmental factors.

Areas covered: We review the role of prenatal exposures, irritants and pruritogens, pathogens, climate factors, including temperature, humidity, ultraviolet radiation, outdoor and indoor air pollutants, tobacco smoke exposure, water hardness, urban vs. rural living, diet, breastfeeding, probiotics and prebiotics on AD.

Expert commentary: The increased global prevalence of AD cannot be attributed to genetics alone, suggesting that evolving environmental exposures may trigger and/or flare disease in predisposed individuals. There is a complex interplay between different environmental factors, including individual use of personal care products and exposure to climate, pollution, food and other exogenous factors. Understanding these complex risk factors is crucial to developing targeted interventions to prevent the disease in millions. Moreover, patients require counseling on optimal regimens for minimization of exposure to irritants and pruritogens and other harmful exposures.     

'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 genes in Amerindians from Mexico San Vicente Tancuayalab Teenek/Huastecos

Huastecos or Teenek Amerindians are presently living at North East Mexico (San Luis Potosi State). They have probably one of the most ancient culture of Mexico and Central America together with Mayas and Olmec groups with which also show close relationships. Proximity to Atlantic Ocean/Mexican Gulf originated that Spaniards had very early contact with them at about 1519 CE or before. In the present paper we have aimed to study HLA gene profile which may be useful for HLA and disease epidemiology and transplant programs in Teeneks. HLA-DRB1*04:07, -DRB1*14:06 and -DRB1*04:11 have been found in high frequency like in other Amerindian groups. High frequency typical Amerindians HLA extended haplotypes have been found, such as A*02-B*35-DRB1*04:07-DQB1*03:02; A*68-B*39-DRB1*04:07-DQB1*03:02 and A*02-B*39-DRB1*04:07-DQB1*03:02; also new haplotypes have been described, like A*02-B*52-DRB1*04:11-DQB1*03:02, A*68-B*35-DRB1*14:02-DQB1*03:01 and A*68-B*40-DRB1*16:02-DQB1*03:01. Genetic proximity is observed not only to linguistically close Mayans, but also to Mazatecans, Mixtecans and Zapotecans, who speak an altogether different languages; it shows once more that genes and languages do not correlate. This population was greatly diminished after European contact between 1500 and 1600 years CE; in fact, North and South America First Inhabitants population was brought from 80 down to 8 million people because of diseases (i.e.: measles, smallpox or influenza), slavery and war.     

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.