Routine mortality monitoring for detecting mass murder in UK general practice: test of effectiveness using modelling.

BACKGROUND: The Shipman Inquiry recommended mortality rate monitoring if it could be 'shown to be workable' in detecting a future mass murderer in general practice. AIM: To examine the effectiveness of cumulative sum (CUSUM) charts, cross-sectional Shewhart charts, and exponentially-weighted, moving-average control charts in mortality monitoring at practice level. DESIGN OF STUDY: Analysis of Scottish routine general practice data combined with estimation of control chart effectiveness in detecting a 'murderer' in a simulated dataset. METHOD: Practice stability was calculated from routine data to determine feasible lengths of monitoring. A simulated dataset of 405,000 'patients' was created, registered with 75 'practices' whose underlying mortality rates varied with the same distribution as case-mix-adjusted mortality in all Scottish practices. The sensitivity of each chart to detect five and 10 excess deaths was examined in repeated simulations. The sensitivity of control charts to excess deaths in simulated data, and the number of alarm signals when control charts were applied to routine data were estimated. RESULTS: Practice instability limited the length of monitoring and modelling was consequently restricted to a 3-year period. Monitoring mortality over 3 years, CUSUM charts were most sensitive but only reliably achieved >50% successful detection for 10 excess deaths per year and generated multiple false alarms (>15%). CONCLUSION: At best, mortality monitoring can act as a backstop to detect a particularly prolific serial killer when other means of detection have failed. Policy should focus on changes likely to improve detection of individual murders, such as reform of death certification and the coroner system.     

52 例病毒性肝炎患者肝组织中丙型肝炎病毒 RNA 和 HCAg-NS3 的测定

应用地高辛标记探针原位杂交法和单克隆抗ＨＣＶ－ＮＳ３－ＨＲＰ建立直接酶标免疫组化法分别测定５２例肝炎患者肝组织ＨＣＶＲＮＡ和ＨＣＡｇ－ＮＳ３。结果抗ＨＣＶ阳性组ＨＣＶＲＮＡ检出率５７．１％（１６／２８），ＨＣＡｇ－ＮＳ３检出率５３．６％（１５／２８）；抗ＨＣＶ阴性组其两项检出率均为１２．５％（３／２４）。肝组织中ＨＣＶＲＮＡ阳性物呈蓝紫色细小颗粒存在于肝细胞核或胞浆内，其在肝小叶中的分布可分为３型，即弥漫型、局灶型、散在型。肝组织中ＨＣＡｇ－ＮＳ３阳性物呈棕黄色细小颗粒分布于肝细胞核或胞浆内，以单个或数个阳性细胞散布于肝小叶中。２３例ＨＣＶＲＮＡ或／和ＨＣＡｇ－ＮＳ３阳性病例以肝炎后肝硬化（ＬＣ）病例占多数（１４／２３），其次为慢性重型肝炎（ＣＳＨ）和中度慢性肝炎（ＣＡＨ）。此两种检测方法具有较高符合率（９０．４％，４７／５２），表明病毒核酸及其表达产物均存在于肝细胞内，与ＨＣＶ感染密切相关。这为ＨＣＶ感染诊断提供了直接依据，有利于研究ＨＣＶ感染中病毒复制、慢性化进程、抗病毒治疗监测及重叠感染时病毒相互关系。     

肠系膜上静脉外科干及下腔静脉下段的应用解剖观察

本文解剖了30具成人尸体,对肠系膜上静脉外科干、下腔静脉下段的位置、长度、外径、两者的相互关系以及前者与肠系膜上动脉分支后者与腹主动脉分支的关系等进行了观察测量。认为国人的外科干至少80％能满足手术中行肠腔静脉吻合术应具备的四点要求。     

Multilineage potential of homozygous stem cells derived from metaphase II oocytes

Human stem cells derived from human fertilized oocytes, fetal primordial germ cells, umbilical cord blood, and adult tissues provide potential cell-based therapies for repair of degenerating or damaged tissues. However, the diversity of major histocompatibility complex (MHC) antigens in the general population and the resultant risk of immune-mediated rejection complicates the allogenic use of established stem cells. We assessed an alternative approach, employing chemical activation of nonfertilized metaphase II oocytes for producing stem cells homozygous for MHC. By using F1 hybrid mice (H-2-B/D), we established stem cell lines homozygous for H-2-B and H-2-D, respectively. The undifferentiated cells retained a normal karyotype, expressed stage-specific embryonic antigen-1 and Oct4, and were positive for alkaline phosphatase and telomerase. Teratomatous growth of these cells displayed the development of a variety of tissue types encompassing all three germ layers. In addition, these cells demonstrated the potential for in vitro differentiation into endoderm, neuronal, and hematopoietic lineages. We also evaluated this homozygous stem cell approach in human tissue. Five unfertilized blastocysts were derived from a total of 25 human oocytes, and cells from one of the five hatched blastocysts proliferated and survived beyond two passages. Our studies demonstrate a plausible "homozygous stem cell" approach for deriving pluripotent stem cells that can overcome the immune-mediated rejection response common in allotransplantation, while decreasing the ethical concerns surrounding human embryonic stem cell research.     

Epitope mapping and characterization of a novel CD4-induced human monoclonal antibody capable of neutralizing primary HIV-1 strains

Human immunodeficiency virus (HIV-1) enters target cells by binding its gp120 exterior envelope glycoprotein to CD4 and one of the chemokine receptors, CCR5 or CXCR4. CD4-induced (CD4i) antibodies bind gp120 more efficiently after CD4 binding and block the interaction with the chemokine receptor. Examples of CD4i antibodies are limited, and the prototypes of the CD4i antibodies exhibit only weak neutralizing activity against primary, clinical HIV-1 isolates. Here we report the identification of a novel antibody, E51, that exhibits CD4-induced binding to gp120 and neutralizes primary HIV-1 more efficiently than the prototypic CD4i antibodies. The E51 antibody blocks the interaction of gp120-CD4 complexes with CCR5 and binds to a highly conserved, basic gp120 element composed of the beta 19-strand and surrounding structures. Thus, on primary HIV-1 isolates, this gp120 region, which has been previously implicated in chemokine receptor binding, is accessible to a subset of CD4i antibodies.     

大鼠三角肌前,后部的运动神经元

为了解主动肌与拮抗肌的运动神经元，应用ＨＲＰ逆行追踪技术研究了大鼠三角肌前部、后部的运动神经元。三角肌前部的运动神经元池位于Ｃ４－６脊髓前外侧核背部及其与后外侧核之间。三角肌后部的运动神经元池位于Ｃ４－７脊髓外侧核及其与前外侧核之间。与前池略有重叠。     

An autopsy-proved case of AIDS in Taiwan

The first case of AIDS positively identified in a non-foreigner in Taiwan was a 25-year-old unmarried male who had practiced homosexuality for ten years. The patient began to have abdominal pain accompanied with loose stools and weight loss in June 1985, followed by fever, cough, headache, dizziness, and loss of memory. Facial hyperpigmentation and extensive oroesophageal candidiasis were noted. Laboratory studies showed severe lymphopenia with a reversed T-helper to T-suppressor ratio, cutaneous anergy and polyclonal gammopathy. Human immunodeficiency virus (HIV) antibodies were positive by ELISA and Western blot, and the virus was isolated from the blood. At autopsy, disseminated cytomegalovirus infection, extensive CNS toxoplasmosis and early lesions of Kaposi's sarcoma were demonstrated. The detection of HIV in the adrenal medulla supports the consensus that the virus is neurotropic.     

大鼠坐骨神经干内S—100蛋白检测

用Ｗｅｓｔｅｍ Ｂｌｏｔ方法确认周围神经于内含有Ｓ－１００，然后运用免疫组化ＰＡＰ方法对Ｗｉｓｔａｒ大鼠坐骨神经的近侧和远侧进行Ｓ－１００检测，染色结果用电子图像进行系统分析处理。结果显示：Ｓ－１００分布于周围神经束间膜，雪旺氏细胞浆内及细胞膜上，神经轴内未见有Ｓ－１００存在，图像处理结果证实，正常大鼠坐骨神经干内的Ｓ－１００呈均匀分布。     

Studies on Alternaria allergens. I. Isolation of allergens from Alternaria tenuis and Alternaria solani.

Extracts of Alternaria tenuis and Alternaria solani were separated into dialyzable (molecular weight less than 10,000) and non-dialyzable forms. The latter was further fractionated by gel filtration through Sephadex G-100 followed by ion-exchange chromatography on DEAE-cellulose. The dialyzable material was fractionated by gel filtration through Sephadex G-50. The allergenic activities of the fractions obtained from the A. tenuis extract was measured in vitro by the radioallergosorbent test assay and the allergenic potency was measured by radioallergosorbent test inhibition assay. Allergenic activity was detected in most of the non-dialyzable fractions, the majority of the activity being in the last G-100 fraction (MW approximately 20,000) which was predominantly protein in nature. The same component may be responsible for the activity found in the dialyzate and its first G-50 fraction since the immunodiffusion studies indicated that the last G-100 fraction has antigenic components in common with those of the first G-50 fraction. In addition, cross-reactions between A. tenuis and A. solani extracts show that the two species share common antigenic determinants.     

恶性疟原虫113肽抗原基因重组的减毒鼠伤寒沙门菌在家兔中免疫应答的研究

我们已经在减毒鼠伤寒沙门菌ＳＬ３２６１以融合蛋白的形式表达了人工合成的恶性疟原虫杂合１１３肽基因ＡＢ（ＧＺ－ＡＢ）。活菌以２×１０９ＣＦＵ经口服免疫新西兰家兔，用ＥＬＩＳＡ测定抗体水平，结果于首次免疫或加强免疫后都可检测到一定水平的特异性抗体。所免疫的家免可以诱发针对恶性疟原虫抗原及ＧＺ－ＡＢ的迟发性超敏反应（ＤＴＨ）。我们的研究表明，含有多个恶性疟原虫抗原表位的人工合成基因可以在减毒鼠伤寒沙门菌中表达，活菌可诱发家兔产生特异的体液免疫及细胞免疫，为恶性疟口服活菌苗的制备打下基础。