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Genotypic resistance tests for the management of patients at simplification of highly active antiretroviral therapy. 基因型耐药试验对简化高活性抗逆转录病毒治疗患者的管理。
Fredy Suter, Florio Ghinelli

Witness for the prosecution: There is a growing interest in exploring simpler protease inhibitor (PI)-sparing regimens that could improve patients' quality of life and adherence, provide relief from adverse events and, at the same time, preserve virological and immunological success. Simplified maintenance studies have used switch regimens with equivalent antiretroviral efficacy to PI-containing highly active antiretroviral therapy (HAART), replacing the PI with non-nucleoside reverse transcriptase inhibitors (NNRTI) such as efavirenz and nevirapine or with a 3 nucleoside-based maintenance regimen. As simplification strategies apply to patients with undetectable viral load, the conventional methods to measure viral resistance on plasma RNA cannot be applied. The only possibility relies on the determination of mutations within the integrated HIV-DNA in peripheral blood mononuclear cells. A careful anamnestic examination is therefore the only tool the caregiver has to direct his choices. In this respect and in our opinion it would be wise not to simplify treatment with abacavir in those patients who underwent a previous suboptimal therapy with lamivudine or thymidine analogues. Witness for the defence: The antiretroviral therapy that includes PI and 2 nucleoside analogue reverse transcriptase inhibitors (NRTI) was the first HAART in HIV infection: this combination results in a reduction of the risk of progression to AIDS and death, but it shows many problems caused by high tablet volume, dietary restrictions, multiple daily dosing and development of toxicity. Simplifying antiretroviral treatment regimens would increase patients' adherence and minimize toxicity.

控方证人:人们对探索更简单的蛋白酶抑制剂(PI)保护方案越来越感兴趣,这种方案可以改善患者的生活质量和依从性,缓解不良事件,同时保持病毒学和免疫学上的成功。简化维持研究使用了与含有PI的高活性抗逆转录病毒治疗(HAART)具有同等抗逆转录病毒疗效的切换方案,用非核苷类逆转录酶抑制剂(NNRTI)如依非韦伦和奈韦拉平或以3核苷为基础的维持方案替代PI。由于简化策略适用于无法检测到病毒载量的患者,因此传统方法无法测量病毒对血浆RNA的耐药性。唯一的可能性依赖于外周血单个核细胞中整合HIV-DNA的突变测定。因此,仔细的健忘症检查是护理人员指导其选择的唯一工具。在这方面,在我们看来,对于那些先前使用拉米夫定或胸苷类似物治疗效果不佳的患者,不要简化阿巴卡韦的治疗是明智的。辩方证人:包括PI和2核苷类似物逆转录酶抑制剂(NRTI)在内的抗逆转录病毒疗法是艾滋病毒感染的第一个HAART疗法:这种组合可以降低进展为艾滋病和死亡的风险,但它显示出许多问题,包括高片剂量、饮食限制、每日多次给药和毒性的发展。简化抗逆转录病毒治疗方案将增加患者的依从性并将毒性降到最低。
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引用次数: 0
Molecular biology of the Chlamydia pneumoniae surface. 肺炎衣原体表面的分子生物学。
G Christiansen, L Ostergaard, S Birkelund

Chlamydia pneumoniaeis a fastidious microorganism with a characteristic biphasic lifecycle causing a variety of human respiratory tract infections. There is limited knowledge about the molecular biology of C. pneumoniae, and only a few genes have been sequenced. The structure of the chlamydial surface differs from that of Chlamydia trachomatis. In order to study the surface of C. pneumoniae we generated monoclonal antibodies (MAbs) against C. pneumoniae strain VR-1310 and selected 14 MAbs that reacted with the surface of C. pneumoniae. All MAbs reacted in immunoelectron microscopy with the surface of both whole C. pneumoniae VR-1310 elementary bodies and with purified sarcosyl extracted outer membrane complexes. However, only 2 of the MAbs reacted in immunoblotting with C. pneumoniae proteins and only with antigen that had not been heat treated in SDS-sample buffer. This indicates the dominance of conformational epitopes at the C. pneumoniae surface.

肺炎衣原体是一种挑剔的微生物,具有典型的双相生命周期,可引起多种人类呼吸道感染。关于肺炎球菌的分子生物学知识有限,只有少数基因被测序。衣原体表面结构与沙眼衣原体不同。为了研究肺炎原胞菌的表面,我们制备了针对肺炎原胞菌VR-1310的单克隆抗体(mab),并选择了14种能与肺炎原胞菌表面反应的单克隆抗体。在免疫电镜下,所有单克隆抗体均与整个肺炎c - VR-1310基本体的表面和纯化的肌基提取的外膜复合物发生反应。然而,在免疫印迹中,只有2个单克隆抗体与肺炎衣原体蛋白反应,并且仅与未在sds样品缓冲液中热处理的抗原反应。这表明肺炎球菌表面的构象表位占主导地位。
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引用次数: 0
Interaction between infection and exercise with special reference to myocarditis and the increased frequency of sudden deaths among young Swedish orienteers 1979-92. 感染和运动之间的相互作用,特别是心肌炎和1979- 1992年瑞典年轻定向运动员猝死频率的增加。
G Friman, E Larsson, C Rolf

Infection and fever evoke a cytokine-mediated host response resulting in negative nitrogen balance, muscle protein degradation, which includes the skeletal muscles as well as the heart muscle, and deteriorated muscle function. Physical training has an opposite effect. Moderate physical training also stimulates the immune system, whereas exhaustive and longlasting exercise is followed by a temporary immunodeficiency and an increased susceptibility to respiratory tract infections. Exercise in the acute phase of an infection may promote complications including myocarditis. Exercise in myocarditis is associated with increased organism-associated as well as immune mediated tissue damage. An increased sudden death (SUD) rate among young Swedish male orienteers existed in 1979-92, suggesting (a) common underlying cause(s). Myocarditis was one of the most conspicuous histopathological features. Chlamydia pneumoniae, or a similar organism cross reacting in diagnostic tests, is hypothesized to be a factor causing this increased death rate. High frequency of intense exercise sessions, which was a common practice among the deceased, may have been immunosuppressive, promoting the development of severe myocardial disease.

感染和发烧引起细胞因子介导的宿主反应,导致负氮平衡,肌肉蛋白降解,包括骨骼肌和心肌,以及肌肉功能恶化。体育锻炼有相反的效果。适度的体育锻炼也会刺激免疫系统,而彻底和持久的运动之后会出现暂时的免疫缺陷和呼吸道感染的易感性增加。在感染的急性期进行运动可能会引起并发症,包括心肌炎。心肌炎患者的运动与机体相关以及免疫介导的组织损伤增加有关。1979- 1992年间,瑞典年轻男性定向运动员猝死(SUD)率有所上升,这表明存在(a)共同的潜在原因。心肌炎是最明显的组织病理特征之一。据推测,肺炎衣原体或在诊断试验中产生交叉反应的类似生物是导致死亡率增加的一个因素。高频率的高强度运动是死者的常见做法,可能会抑制免疫,促进严重心肌疾病的发展。
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引用次数: 0
Antimicrobial susceptibility testing in Sweden. IV. Quality assurance. 瑞典的抗菌药物敏感性试验。四、质量保证。
G Kahlmeter, B Olsson-Liljequist, S Ringertz

The performance of susceptibility testing depends on high-quality material (disks and media), good laboratory practice (robust methodology and correct handling of material) and antimicrobial breakpoints being set in such a way that they allow for some intralaboratory variation. Thus, breakpoints must not divide homogeneous bacterial populations. Routine susceptibility testing should be checked with both internal and external quality control programs. The internal quality control should be designed to demonstrate the importance of minimizing random errors and to rapidly disclose systematic errors. This can be achieved either through the repeated testing of defined control strains or by systematic comparison of histograms of routine zone diameters with reference histograms supplied by the Swedish Reference Group for Antibiotics (SRGA and SRGA-M). The SRGA-M offers an external quality control program which by its design also functions as an epidemiological surveillance program. The quality control programs are supported by an educational program for laboratory personnel.

药敏试验的性能取决于高质量的材料(磁盘和介质)、良好的实验室规范(稳健的方法和正确的处理材料)和以允许实验室内部一些变化的方式设置的抗菌断点。因此,断点不能分裂同质细菌群。常规药敏试验应通过内部和外部质量控制程序进行检查。内部质量控制的设计应体现出尽量减少随机误差和迅速发现系统误差的重要性。这可以通过重复检测确定的对照菌株或将常规区直径直方图与瑞典抗生素参考组(SRGA和SRGA- m)提供的参考直方图进行系统比较来实现。SRGA-M提供外部质量控制程序,其设计也可作为流行病学监测程序。质量控制程序由实验室人员的教育计划支持。
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引用次数: 0
Chlamydia pneumoniae and myocarditis. 肺炎衣原体和心肌炎。
H Gnarpe, J Gnarpe, B Gästrin, H Hallander

Sera from 20 male patients with a diagnosis suggestive of myocarditis, perimyocarditis or pericarditis were found significantly more often to have specific IgA antibodies to Chlamydia pneumoniae than sera from healthy blood donors of the same age and from the same time period. A less pronounced difference in IgG titres was found between patients and blood donors, and IgM antibodies were found only in one patient. A striking variation over time in the prevalence of specific antibodies to C. pneumoniae was seen in consecutive male blood donors over a 5-year observation period. The findings were discussed and it was concluded that C. pneumoniae may be associated with inflammatory heart disease.

20例诊断为心肌炎、心包炎或心包炎的男性患者血清中发现肺炎衣原体特异性IgA抗体的发生率明显高于同一年龄、同一时期的健康献血者血清。IgG滴度在患者和献血者之间的差异不太明显,IgM抗体仅在一名患者中被发现。在5年的观察期内,在连续的男性献血者中发现了肺炎原胞杆菌特异性抗体流行率的显著变化。对研究结果进行了讨论,并得出结论:肺炎梭菌可能与炎症性心脏病有关。
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引用次数: 0
Antimicrobial susceptibility testing in Sweden. II. Species-related zone diameter breakpoints to avoid interpretive errors and guard against unrecognized evolution of resistance. 瑞典的抗菌药物敏感性试验。2物种相关的区直径断点,以避免解释错误和防止未被识别的进化抗性。
S Ringertz, B Olsson-Liljequist, G Kahlmeter, G Kronvall

The Swedish Reference Group for Antibiotics appointed a subcommittee on methodology (SRGA-M) in 1987 to investigate ways of defining interpretive breakpoints for antimicrobial susceptibility testing. The minimum inhibitory concentration (MIC) breakpoints for susceptibility categories are mainly based on pharmacological properties of the antibiotic, and they are, with few exceptions, valid for all species. However, for several species the MIC breakpoints have failed to distinguish strains with reduced susceptibility from normal susceptible strains. Disk diffusion is the routine method for susceptibility testing in Sweden. Studies of distribution of MICs and zone diameters for clinically important bacterial species have resulted in an emphasis on resistance rather than on susceptibility. The SRGA-M chose to place the zone diameter breakpoints close to the native (often susceptible) population of each species or group of related species. Such species-related zone diameter breakpoints used for susceptibility categories no longer correspond to the pharmacological MIC breakpoints, but divide each species into the fully susceptible (native) population and into those isolates/populations that have acquired a resistance mechanism, resulting in high- or low-grade resistance. By this method the risk of reports of false susceptibility is minimized and early detection of the emergence of antibiotic resistance is ensured.

瑞典抗生素参考小组于1987年任命了一个方法学小组委员会(SRGA-M),研究确定抗菌素敏感性试验解释断点的方法。药敏类别的最小抑制浓度(MIC)断点主要基于抗生素的药理学性质,除了少数例外,它们对所有物种都有效。然而,对于一些物种,MIC断点无法区分敏感性降低的菌株和正常敏感的菌株。圆盘扩散法是瑞典药敏试验的常规方法。对临床重要细菌种类的mic分布和带直径的研究导致强调耐药性而不是敏感性。SRGA-M选择将区域直径断点放置在接近每个物种或亲缘种的本地(通常是易感的)种群的位置。这种用于药敏分类的物种相关带直径断点不再对应药理学MIC断点,而是将每个物种划分为完全敏感(本地)种群和已获得耐药机制的分离株/种群,从而产生高或低级别耐药。通过这种方法,可以最大限度地减少假药敏报告的风险,并确保早期发现抗生素耐药性的出现。
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引用次数: 0
Assay of antibiotic susceptibility of Chlamydia pneumoniae. 肺炎衣原体抗生素敏感性测定。
E Hjelm, K Hultén, C Nyström-Rosander, I Gustafsson, L Engstrand, O Cars

It is well known that treatment of Chlamydia pneumoniae infections is difficult. High doses and prolonged treatment is often needed to achieve clinical cure despite good in vitro effect of the drugs used. We here discuss different methodological problems in the determination of MIC and MBC values of C. pneumoniae. The length of the preincubation time and the lack of fluctuation of the antibiotic concentrations may affect the outcome of the currently used assay.

众所周知,治疗肺炎衣原体感染是困难的。尽管所使用的药物体外效果良好,但要达到临床治愈往往需要大剂量和长时间的治疗。我们在此讨论不同的方法问题,在确定MIC和MBC值的肺炎原体。预孵育时间的长度和抗生素浓度波动的缺乏可能会影响目前使用的测定结果。
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引用次数: 0
Epidemic patterns and carriage of Chlamydia pneumoniae in Norway. 挪威肺炎衣原体的流行模式和携带。
B P Berdal, O Scheel, G N Thomas, C M Black, N K Meidell

Chlamydia pneumoniae infection, in earlier days misdiagnosed as ornithosis, is very common in Norway. The disease develops slowly, a feature that may account for the very large number of subclinical cases, which may be seven fold more common than clinical cases. Subclinical cases produce an antibody response similar to that seen in overt clinical disease. Silent carriage of C. pneumoniae in healthy individuals may be frequent. Therapy based on positive cell culture or polymerase chain reaction (PCR) in the absence of pneumonic symptoms may be questionable. PCR has, however, given the slow development of disease, revealed itself as a handy epidemiological technique useful for the survey of healthy populations.

肺炎衣原体感染,在早期被误诊为鸟类病,在挪威很常见。这种疾病发展缓慢,这一特征可能是大量亚临床病例的原因,亚临床病例可能比临床病例多7倍。亚临床病例产生与显性临床疾病相似的抗体反应。在健康个体中,隐性携带肺炎原体可能是常见的。在没有肺炎症状的情况下,基于阳性细胞培养或聚合酶链反应(PCR)的治疗可能值得怀疑。然而,鉴于疾病发展缓慢,聚合酶链反应显示其本身是一种方便的流行病学技术,可用于健康人群的调查。
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引用次数: 0
Chlamydia pneumoniae and atherosclerosis--an update. 肺炎衣原体和动脉粥样硬化——最新进展。
P Saikku

The role of Chlamydia pneumoniae in atherosclerosis is at present controversial and neglected by researchers studying the pathogenesis of the disease. Numerous seroepidemiological studies have shown an association of C. pneumoniae infection with coronary heart disease and recent studies have indicated the ubiquitous presence of C. pneumoniae in the atherosclerotic lesions. The majority of cardiologists are, as yet, more apt to consider the finding of C. pneumoniae in atherosclerotic lesions as benign particles deposited from the circulation into preformed lesions rather than as a known pathogenic Gram-negative bacterium participating in or initiating an inflammatory process. The latter possibility would result in the oxidation of lipoproteins and the induction of cytokines and proteolytic enzyme production. These phenomena are typical for atherosclerosis. Chlamydia are amenable for treatment with antibiotics, and the therapeutic importance of the verification of bacterial involvement could be significant.

肺炎衣原体在动脉粥样硬化中的作用是目前研究该病发病机制的研究人员存在争议和忽视的问题。大量的血清流行病学研究表明,肺炎支原体感染与冠心病有关,最近的研究表明,肺炎支原体在动脉粥样硬化病变中普遍存在。到目前为止,大多数心脏病专家更倾向于认为,在动脉粥样硬化病变中发现的肺炎梭菌是良性颗粒,从循环沉积到预先形成的病变中,而不是作为参与或启动炎症过程的已知致病性革兰氏阴性细菌。后一种可能会导致脂蛋白氧化,并诱导细胞因子和蛋白水解酶的产生。这些现象是动脉粥样硬化的典型表现。衣原体可以用抗生素治疗,并且验证细菌感染的治疗重要性可能是显著的。
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引用次数: 0
Chlamydia pneumoniae and myocarditis. 肺炎衣原体和心肌炎。
Pub Date : 1997-01-01 DOI: 10.1007/0-306-48741-1_13
H. Gnarpe, J. Gnarpe, B. Gästrin, H. Hallander
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引用次数: 19
期刊
Scandinavian journal of infectious diseases. Supplementum
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