拉米夫定联合阿德福韦酯治疗活动性乙型肝炎肝硬化的疗效观察

目的观察拉米夫定联合阿德福韦酯治疗活动性乙型肝炎肝硬化的临床疗效。方法将96例活动性乙型肝炎肝硬化患者分成A、B、C3组,每组32例。A组采用拉米夫定联合阿德福韦酯治疗,B组予拉米夫定治疗,C组予阿德福韦酯治疗,疗程均为48周。观察治疗中3组ALT复常率、HBVDNA阴转率、HBeAg/抗HBe血清转换率等变化情况,及随访2年的耐药发生率。结果 A组HBVDNA转阴率在第12周、24周优于C组（P〈0.05）;ALT复常率第12周优于B组（P〈0.05）、C组（P〈0.01）;第24周优于C组。随访2年,A组耐药发生率最低。结论拉米夫定与阿德福韦酯联合用药较单独用药疗效更佳。     

两组核苷类似物治疗耐药性HBeAg阴性慢性乙型肝炎的疗效比较

目的 比较恩替卡韦和阿德福韦酯治疗拉米夫定耐药的HBeAg阴性慢性乙型病毒性肝炎的疗效及安全性。方法 拉米夫定耐药的HBeAg阴性慢性乙型病毒性肝炎患者65例随机分为两组：恩替卡韦治疗组33例,给予恩替卡韦1.0 mg/d;阿德福韦酯治疗组32例,给予阿德福韦酯10mg/d;动态观察患者血清HBV DNA、肝功能、血清磷酸肌酸激酶、肌酐的变化以及不良事件发生的情况。结果 恩替卡韦治疗组ALT复常率在治疗后12周、24周、48周均高于阿德福韦酯治疗组,但直到48周时两组之间的差异仍无统计学意义（P＞0.05）;恩替卡韦治疗组HBV DNA转阴率在治疗12周时明显高于阿德福韦酯治疗组,差异有统计学意义（P＜0.05）。结论 恩替卡韦与阿德福韦酯对于拉米夫定耐药的HBeAg阴性慢性乙型病毒性肝炎均有较好疗效,恩替卡韦可能有更好的治疗效果。     

聚乙二醇干扰素α-2a治疗拉米夫定耐药的慢性乙型肝炎疗效观察

目的 观察聚乙二醇干扰素α-2a（PEG-IFNa-2a）治疗拉米夫定（LAM）耐药的慢性乙型肝炎（CHB）的疗效和安全性.方法 将81例拉米夫定耐药的HBeAg（＋）慢性乙型肝炎患者分为聚乙二醇干扰素α-2a（派罗欣）治疗组40例及阿德福韦酯（ADV）对照组41例.两组病例开始均联合LAM治疗12周,观察治疗第12周、24周、48周的ALT复常、HBV DNA阴转、HBeAg阴转及HBeAg转换的变化.结果 治疗12周、24周派罗欣治疗组ALT复常率为62.5%、80.0%,高于ADV 对照组,治疗48周派罗欣治疗组HBeAg阴转率及HBeAg转换率为60%、57.5%,高于ADV对照组,差异有统计学意义（P〈0.05）.结论 聚乙二醇干扰素α-2a治疗拉米夫定耐药的HBeAg（＋）慢性乙型肝炎的疗效优于阿德福韦酯,安全性较好.     

阿德福韦酯单药及其联合拉米夫定治疗拉米夫定耐药型HBeAg阳性慢性乙型肝炎的疗效比较

目的比较阿德福韦酯（ADV）单药及其联合拉米夫定治疗拉米夫定耐药型HBeAg阳性慢性乙型肝炎（chronic hepatitis B,CHB）的临床疗效。方法对24例ADV单药及28例ADV联合拉米夫定治疗拉米夫定耐药型HBeAg阳性慢性乙型肝炎患者的疗效进行回顾性分析,比较两组患者HBVDNA、ALT水平及HBV DNA检测不到率、ALT复常率的差异。结果两组患者的性别、年龄、治疗前的HBV DNA及ALT水平差异均无统计学意义。两组的HBV DNA、ALT水平在治疗48周、72周时分别与同组治疗前比较均有明显降低（P〈0．05）。治疗48周时,联合组的HBV DNA检测不到率虽高于单药组,但差异无统计学意义（50％vs25％,P〉0．05）;ALT复常率两组间无明显差别（67．9％vs75％,P〉0．05）。治疗72周时,联合组的HBV DNA检测不到率为68％,要显著高于单药组的33．3％（P〈0．05）;联合组的ALT复常率为93％,显著高于单药组的70．8％（P〈0．05）。结论ADV单药或联合拉米夫定均是治疗拉米夫定耐药HBeAg阳性CHB的有效方法,联合治疗的疗效要优于单药治疗。     

恩替卡韦与阿德福韦酯治疗拉米夫定耐药慢性乙肝患者效果的比较

目的比较恩替卡韦与阿德福韦酯治疗拉米夫定耐药慢性乙型肝炎患者的效果。方法检索2010年6月以前公开发表的有关恩替卡韦（剂量1mg/d）与阿德福韦酯（剂量10mg/d）治疗拉米夫定耐药慢性乙型肝炎患者（疗程≥48周）的随机对照临床研究。采用χ2检验分析研究间的异质性,以相对危险度为疗效分析统计量进行合并分析并绘制森林图。疗效判定指标为血清HBVDNA检测不到（阴转）。结果 Meta分析结果显示,阿德福韦酯与恩替卡韦对拉米夫定耐药株的疗效差异有统计学意义（Z=2.26,P=0.02）,相对危险度的95%置信区间为0.51～0.95。结论恩替卡韦（1mg/d）治疗拉米夫定耐药患者的48周疗效（血清HBVDNA阴转率）好于阿德福韦酯（10mg/d）。     

拉米夫定联合阿德福韦酯治疗慢性乙型肝炎应答不佳者基因型演变特点研究

目的 了解拉米夫定初始联合阿德福韦酯治疗慢性乙型肝炎应答不佳者基因型特点及其演变规律.方法 应用克隆测序法检测3例患者(S1患者、S2患者、S3患者)拉米夫定初始联合阿德福韦酯治疗12个月以上病毒学应答不佳慢性乙型肝炎患者基线、治疗4周、12周、24周、48周、60周HBV基因型,每个时间点各随机挑取25个克隆进行鉴定并测序.结果 3例初始联合拉米夫定和阿德福韦酯治疗慢型乙型肝炎应答不佳患者各时间点的总克隆数为398份,其中S1患者在基线时C基因型(8.3％)和B基因型(91.7％)共同表达,但B基因型占绝对优势(22/24).治疗60周时C基因型占绝对优势(100％).S2和S3患者在基线时仅表达B基因型,在治疗过程中,B基因型逐渐“漂移”为C基因型,治疗60周时,C基因型占绝对优势(S2中占75％,S3中占100％).结论 克隆测序可以更好的反应整体的基因型水平；在长期药物压力下HBV基因型从B基因型逐渐向C基因型演变,是导致拉米夫定初始联合阿德福韦酯治疗应答不佳的主要原因.     

阿德福韦酯对乙型肝炎抗肝纤维化的临床研究

目的 观察阿德福韦酯抗乙型肝炎病毒所致肝纤维化的临床疗效.方法 将35例慢性乙肝患者随机分为A、B组,A组给予阿德福韦酯及基础保肝治疗,B组采用常规治疗,均治疗156周.结果 治疗后,A组4项指标与B组相比均明显降低,具有显著差异.结论 阿德福韦酯是治疗乙型肝炎病毒所致肝纤维化有效药物之一.     

阿德福韦酯单药治疗的慢乙肝患者聚合酶RT区变异位点及临床意义

目的 通过对慢性乙型肝炎（CHB）患者血清HBV聚合酶逆转录（RT）区基因序列分析,探讨阿德福韦酯（ADV）单药抗病毒治疗失败,聚合酶RT区变异位点特点及临床意义.方法 采用回顾性分析方法,对接受阿德福韦单药抗病毒治疗出现病毒学突破,经聚合酶RT基因测序,证实存在基因突变的44例患者的聚合酶RT区变异位点、临床特点及随访资料进行分析.结果 44例阿德福韦酯单药治疗患者,至出现RT区变异最短治疗时间8个月,最长5年,平均（32.2＆#177;6.7）个月.出现病毒学突破后,病毒水平波动在103拷贝/ml～108拷贝/ml之间;变异位点A181T 11例（25.0％）、A181V 8例（18.2％）、A181T/N236T 10例（22.7％）、A181V/N236T 6例（13.6％）、N236T9例（20.4％）;出现生化学突破40例（90.9％）,ALT指标波动在37 IU/L～ 946 IU/L;挽救治疗采用联合拉米夫定23例、联合恩替卡韦6例,联合替比夫定1例,改单药拉米夫定4例,改单药恩替卡韦10例.预后出现疾病重症化3例,经挽救治疗病情得到恢复41例.结论 ①阿德福韦单药耐药RT区A181T（A181T/N236T）变异约占半数（47.7％）,随访2年,其肝癌发生率呈现高于非A181T患者趋势.②条件允许,初始治疗应首选HBV抑制作用强、耐药发生率低的药物,避免疾病重症化或肝癌等不良事件发生.     

阿德福韦酯联合双环醇片治疗HBeAg(+)慢性乙型肝炎疗效分析

目的 研究阿德福韦酯联合双环醇片治疗慢性乙型肝炎的疗效.方法 选择91例轻、中度慢性乙型肝炎患者随机分2组接受试验.试验组,46例,每日口服阿德福韦酯10 mg,同时每日服用双环醇片150 mg;对照组,45例,仅给予每日口服阿德福韦酯10 mg.2组均连续用药48周.观察治疗前后血清氨基转移酶水平及病毒学标志方面的改变.结果 2组血清氨基转移酶均得到明显下降,试验组更为显著(P<0.05).试验组HBV DNA阴转率(47.8%)显著高于对照组(31.1%),P<0.05,试验组HBeAg阴转率(32.6%)及HBeAg血清转换率(24.4%)虽高于对照组(19.6%、15.6%),但差异无统计学意义.2组均未发生明显的不良反应.结论 阿德福韦酯与双环醇片联合应用治疗慢性乙型肝炎在肝功能及病毒学方面取得较好疗效.     

阿德福韦联合双环醇治疗慢性乙型肝炎疗效观察

目的研究阿德福韦酯联合双环醇治疗慢性乙型肝炎的疗效。方法77例慢性乙型肝炎患者随机分为两组,试验组（39例）每日口服阿德福韦酯10mg、双环醇75mg;对照组（38例）每日仅口服阿德福韦酯10mg。两组均连续用药48周。观察治疗前后血清氨基转移酶、病毒学指标、肝脏影像学指标的改变。结果治疗48周后,试验组ALT复常率（87.18%）显著高于对照组（65.79%）,HBV-DNA转阴率（64.10%）显著高于对照组（39.47%）,影像学指标改善优于对照组,差异均有统计学意义（P〈0.05）。结论阿德福韦酯与双环醇联合应用治疗慢性乙型肝炎能取得更好的生化学应答、病毒学应答和影像学改善。     

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.