丙型肝炎病毒血清型对慢性丙型肝炎干扰素抗病毒疗效影响的研究

目的研究丙型肝炎病毒血清型对慢性丙型肝炎于扰素抗病毒疗效的影响。方法对慢性丙型肝炎患者的血清进行ALT检测，采用Cobas amplicor monitor test，version 2．0（v2．0）试剂进行HCVRNA定量和Abbott公司的Murex HCV Serotyping 1-6 Assay试剂进行HCV血清学分型检测。对慢性丙型肝炎患者进行聚乙二醇于扰素a-2a（派罗欣）与罗荛愫（Roferon—A）治疗24周和24周随访结束的生化指标和病毒学应答进行观察，分析不同HCV血清型患者在抗病毒治疗后生化和病毒学应答的差异。结果98例患者共检出血清6型2例、5型1例、4型1例、3型10例、2型23例和1型44例，仍有17例未能分出血清型。派罗欣治疗组24周治疗结束时各血清型和未分型组之间的ALT复常率和病毒应答率无差异，而48周随访结束血清非1型的ALT复常率（76．2％）和持续病毒应答率（66．7％）高于血清1型，血清1型ALT复常率和持续病毒应答率分别为27.3％和27．3％，差异有统计学意义（P=0．035）。罗荛愫组末分型组、血清1型和非1型之间24周治疗结束时和随访结束时的ALT复常率和病毒学应答率均无差异。结论在6个月的IFN抗病毒疗程时，HCV血清型仅在派罗欣治疗组影响慢性丙型肝炎抗病毒治疗的持续病毒应答率。     

聚乙二醇干扰素联合利巴韦林治疗慢性丙型肝炎的疗效研究

目的 观察聚乙二醇干扰素联合利巴韦林对慢性丙型肝炎初治与复发患者的疗效,并分析可能影响疗效的因素.方法 对64例慢性丙型肝炎的初治和复发患者应用聚乙二醇干扰素联合利巴韦林抗病毒治疗.对上述病例进行回顾性研究,分析两组患者的快速病毒学应答、完全早期病毒学应答、治疗结束时病毒学应答及持续病毒学应答,并探讨影响病毒学应答的相关因素.结果 初治组患者获得快速病毒学应答、完全早期病毒学应答、治疗结束应答、持续应答的概率明显高于复发组,差异具有统计学意义（P＜0.05）;初治组与复发组复发率不具有统计学意义（P＞0.05）,但复发组慢性丙型肝炎患者治疗结束后复发率明显高于初治组（33.33％与6.38％）.发生持续应答患者的快速病毒学应答、完全早期病毒学应答率明显高于未发生持续应答患者,且差异有统计学意义（P＜0.05）.结论 初治CHC患者较复发患者可获得较高病毒学应答率,复发率较低,获得快速病毒学应答和完全早期病毒学应答是疗效的阳性预测指标.     

难治性慢性丙型肝炎强化治疗疗效研究

目的探讨难治性慢性丙型肝炎强化治疗疗效,通过优化治疗剂量和疗程来提高慢性丙型肝炎患者对干扰素联合利巴韦林治疗的持续病毒应答率。方法对常规治疗的干扰素剂量（聚乙二醇干扰素α每周皮下注射1次）和利巴韦林（每天10．5mg／kg）经治的无应答和部分患者,根据患者的意愿进行标准干扰素α10 MU隔日注射1次或聚乙二醇干扰素α-2a（PEG—IFN α-2a）360μg每周注射1次,并根据体重每天给予15mg／kg的利巴韦林的强化剂量治疗,在治疗的0、4、12周和以后的每间隔12周、治疗结束后的24周进行HCV RNA含量检测,根据患者治疗过程中的病毒应答情况给予72～96周的疗程,以持续病毒应答（sustained viral response,SVR）作为疗效的评判指标。结果18例患者完成全程治疗和观察,12例获得持续病毒学应答,5例治疗无效,1例复发。3例患者获得RVR,RVR获得者的cEVR和SVR均为3／3,RVR组治疗前的病毒载量显著低于未获得RVR组（t=4．687,P〈0．001）。15例无快速病毒应答者,8例获得完全早期病毒应答,9例获得SVR。聚乙二醇干扰素α-2a 360μg每周注射1次的SVR为4／5。11例获得cEVR患者均获得SVR,7例无cEVR的患者,仅1例获得SVR。结论强化剂量的干扰素和RBV可以使较高比例的既往规范抗病毒治疗无应答、部分应答获得SVR。在强化治疗过程中根据病毒的应答情况及时调整和延长HCV RNA阴性的疗程是提高难治性慢性丙型肝炎持续病毒应答率的重要措施。     

聚乙二醇干扰素联合利巴韦林治疗慢性丙型肝炎

目的评价聚乙二醇（PEG）干扰素联合利巴韦林治疗慢性丙型肝炎的临床疗效。方法使用聚乙二醇干扰素α-2a（40000Mr）联合利巴韦林治疗22例慢性丙型肝炎患者，其中7例为难治性慢性丙型肝炎患者。聚乙二醇干扰素α-2a 180μg，肌注，每周1次，利巴韦林按体重900～1200mg／d，口服，疗程均为48周。分别于治疗中的12周、24周、48周及治疗结束后24周评价疗效，并观察药物副反应。结果所有患者均完成治疗，在治疗结束后随访24周，持续应答率为63．6％（14／22），7例难治性慢性丙型肝炎的持续应答率为42．8％（3／7）。在治疗12周时的早期应答率为72．7％（16／22），治疗结束时的应答率为77．2％（17／22）。3例患者在随访24周内出现ALT升高，血清HCV．RNA阳转，其中1例为难治性慢性丙型肝炎患者，复发率为17．6％（3／17）。副反应主要为不同程度的血WBC、血小板、血红蛋白下降及低热、肌肉酸痛，1例患者于疗程近结束时出现甲状腺机能亢进．个别患者睡眠受影响，大多不影响治疗。结论PEG干扰素联合利巴韦林治疗慢性丙型肝炎具有较好的临床疗效．副反应较轻，患者可以耐受。     

慢性丙型肝炎干扰素治疗失败患者的干扰素再治疗研究

目的探讨慢性丙型肝炎干扰素治疗失败患者的再治疗获得持续病毒学应答（SVR）的方案。方法回顾54例慢性丙型肝炎干扰素治疗失败患者所采用的PEG—IFNα联合利巴韦林标准治疗或强化方案再治疗方案,比较SVR率的差异并进行统计学分析,讨论标准治疗或强化方案的适用人群。结果54例慢性丙型肝炎干扰素治疗失败患者,再治疗后SVR率可达75．92％。其中复发者再次治疗SVR率为88．46％,无应答者再治疗SVR率64．29％。在初始普通干扰素治疗失败组、普通干扰素联合利巴韦林失败组、单用PEG—IFNα-2a失败组,再治疗后SVR率分别为95．45％、64．71％、60％。初治复发患者再治疗SVR率明显高于初治无应答患者。结论初治失败的慢性丙型肝炎患者选择标准或强化方案再治疗仍可获得60％～90％的SVR率。初始治疗单用普通干扰素失败或普通干扰素联合利巴韦林治疗复发患者可选择标准方案再治疗;初始治疗采用普通干扰素联合利巴韦林治疗无应答、单用PEG-IFNα-2a无应答及初始治疗选用标准治疗失败患者需选择强化方案再治疗。     

聚乙二醇干扰素治疗慢性丙型肝炎临床疗效、影响因素及安全性分析(附89例临床分析)

目的 观察聚乙二醇干扰素（PEG IFN）α-2a治疗慢性丙型肝炎的效果、疗效影响因素及安全性.方法 观察了89例慢性丙肝患者,对46例慢性丙肝患者予PEG IFNα-2a（180μg或135μg/周）联合利巴韦林（RBV）900mg/d抗病毒治疗,对照组为43例慢性丙肝患者予IFNα-2a（5 MIU/隔天）联合RBV 900mg/d抗病毒治疗.疗程48周,随访24周.两组治疗前HCV-RNA、基因型等临床资料具有可比性,以病毒学应答和生化学应答作为疗效的主要评价指标.同时观察药物不良反应.结果 PEG IFNα-2a组持续应答率（SVR）显著高于IFNα-2a组（分别是56.5%和19.5%,P＜0.0001）.PEGIFNα-2a组治疗基因1型、高病毒载量慢性丙型肝炎的SVR明显高于IFNd-2a组（P＜0.001）,但非基因1型、低病毒载量的SVR两组之间差异无统计学意义（P值分别为0.664、0.116）.PEG IFNα-2a与IFNα-2a有相似的不良反应,但除白细胞减少的程度及体重减轻发生率PEG IFNα-2a组高于IFNα-2a组外（P值为0.001）,余不良反应间差异无统计学意义.结论 PEG IFNα-2a对慢性丙型肝炎患者的疗效优于干扰素IFNα-2a,尤其对基因1型、高病毒载量的患者更应选择PEG IFNα-2a,且具有较好的安全性和耐受性.     

干扰素抵抗与JAK／STAT信号通道系统

干扰素(interferon，IFN)是人体受到病毒或双股RNA刺激物的刺激产生免疫应答，由细胞合成及分泌的一族蛋白质类，可作用于其它细胞干扰病毒的复制。1957年Isaacs和Lindenmann发现IFN并证实其有抗病毒活性，近来还发现IFN具有抑制某些细胞生长、免疫调节抑制和杀伤肿瘤细胞、影响细胞分化和机体的发育等作用。目前IFN是国内外慢性乙型肝炎与丙型肝炎抗病毒治疗主要药物，然而慢性乙肝患者采用IFN治疗后出现持续性反应率不高，HBeAg阴转率约为30％，IFN与利巴韦林联合治疗慢性丙型肝炎持续反应率也仅仅约为54％～56％。IFN疗效主要和机体免疫耐受、病毒基因变异、细胞内病毒基因整合、IFN抗体产生等有关．IFN抵抗(IFN resistance)出现的原因包括了宿主、病毒和IFN三方面因素，目前IFN抵抗的机制尚未完全明了。     

PEG—IFN α-2a治疗慢性丙型肝炎的临床分析

目的观察PEG-IFN α-2a小剂量长疗程治疗慢性丙型肝炎患者的病毒学应答。方法选择2004年9月至2006年9月住院的慢性丙型肝炎患者92例,根据对干扰素耐受情况将其分为A组（PEG—IFN α-2a 67．5μg／周）、B组（PEG—IFN α-2a 90μg／周）及C组（PEG-IFN α-2a 180μg／周）,同时联合利巴韦林（900～1200mg／d）。A组和B组中HCV基因1b型患者疗程延长至96周,2a型疗程48周;C组HCV基因1b型疗程48周,2a型疗程24周,均随访24周;分别观察各组患者的快速病毒学应答（RVR）、早期病毒学应答（EVR）及持续病毒学应答（SVR）率。结果三组RVR、EVR、SVR率之间无统计学差异（P〉0．05）,基因1b型患者的RVR、EVR和SVR率明显低于2a型（P〈0．05）,经logistic回归分析,HCV基因型为SVR独立预测因子（OR=12．78,95％CI=11．97—82．89,P=0．0075）。结论小剂量长疗程PEG—IFN α-2a联合利巴韦林与标准方案治疗慢性丙型肝炎病毒学应答状况相当;基因型是SVR的独立预测因素。     

铁与慢性丙型肝炎的关系

近年来的研究表明,α-干扰素(IFN)对部分慢性丙型肝炎(CHC)有效,其应答率可达50%,应答率与年龄、性别、感染时间、感染方式、肝组织学表现、HCVRNA水平及病毒基因型等因素有关。最近的研究表明,铁也影响着CHC对IFN的应答〔1〕,用去铁的静脉放血疗法可提高部分患者的应答率。本文就近年的研究情况作一综述。1　铁与CHC的应答VanThiel〔2〕等首先报导了肝铁浓度(HIC)对CHC患者用IFN治疗后应答率的影响。他们选择了79例慢性病毒性肝炎患者,其中CHC患者54例,IFN治疗6个月后,发现对IFN应答者的HIC低于不应答者,不应答者中57%的…     

干扰素抵抗与JAK/STAT信号通道系统

干扰素(interfferon,IFN)是人体受到病毒或双股RNA刺激物的刺激产生免疫应答,由细胞合成及分泌的一族蛋白质类,可作用于其它细胞干扰病毒的复制.1957年Isaacs和Lindenmann发现IFN并证实其有抗病毒活性,近来还发现IFN具有抑制某些细胞生长、免疫调节抑制和杀伤肿瘤细胞、影响细胞分化和机体的发育等作用.目前IFN是国内外慢性乙型肝炎与丙型肝炎抗病毒治疗主要药物,然而慢性乙肝患者采用IFN治疗后出现持续性反应率不高,HBeAg阴转率约为30%[1],IFN与利巴韦林联合治疗慢性丙型肝炎持续反应率也仅仅约为54%～56%[2].IFN疗效主要和机体免疫耐受、病毒基因变异、细胞内病毒基因整合、IFN抗体产生等有关,IFN抵抗(IFN resis-tance)出现的原因包括了宿主、病毒和IFN三方面因素,目前IFN抵抗的机制尚未完全明了.     

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.     

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.     

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.     

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.