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Introduction: objectives of herpes simplex virus vaccines seen from a historical perspective. 简介:从历史的角度看单纯疱疹病毒疫苗的目的。
Pub Date : 1991-11-01 DOI: 10.1093/clind/13.supplement_11.s892
B Roizman

Herpes simplex virus (HSV) types 1 and 2 cause a variety of severe manifestations in humans. A major characteristic of HSVs is their ability to establish latent infection in sensory ganglia, where these viruses are shielded from the immune system and are impervious to the action of antiviral drugs known to date. Ideally, HSV-induced clinical syndromes should be prevented by vaccination, but two major problems arise. First, although many antiviral vaccines have successfully prevented disease, none have prevented infection. Once the virus infects cells at the portal of entry of the infection, it can establish latent infection in sensory neurons that innervate the cell. Second, while HSV disease primarily affects adults greater than 18 years of age, mass immunization in the United States is effectively carried out in the interval between nursery school and high school, and yet the vaccines must confer protection for a long time after vaccination. The central issues involved in the development of an anti-HSV vaccine include what type of vaccine should be developed, what we should expect from an HSV vaccine, and how we should monitor the effectiveness of the vaccine.

单纯疱疹病毒(HSV) 1型和2型在人类中引起各种严重的表现。单纯疱疹病毒的一个主要特征是它们能够在感觉神经节中建立潜伏感染,在那里这些病毒被免疫系统屏蔽,并且对迄今为止已知的抗病毒药物不起作用。理想情况下,单纯疱疹病毒引起的临床综合征应该通过接种疫苗来预防,但是出现了两个主要问题。首先,尽管许多抗病毒疫苗成功地预防了疾病,但没有一种能预防感染。一旦病毒在感染的入口处感染细胞,它可以在支配细胞的感觉神经元中建立潜伏感染。其次,虽然HSV疾病主要影响18岁以上的成年人,但在美国,大规模免疫接种有效地在幼儿园和高中之间进行,但疫苗必须在接种后很长一段时间内提供保护。开发抗单纯疱疹病毒疫苗的核心问题包括应该开发哪种疫苗,我们对单纯疱疹病毒疫苗的期望是什么,以及我们应该如何监测疫苗的有效性。
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引用次数: 23
Catheter-related infections caused by the Mycobacterium fortuitum complex: 15 cases and review. 偶发分枝杆菌引起导管相关感染15例并复习。
Pub Date : 1991-11-01 DOI: 10.1093/clinids/13.6.1120
I I Raad, S Vartivarian, A Khan, G P Bodey

Fifteen cancer patients have developed catheter-related infections caused by the Mycobacterium fortuitum complex (M. fortuitum and Mycobacterium chelonae) at M. D. Anderson Cancer Center since 1978. Eleven patients had bacteremia and four had catheter site infections. Nine infections were caused by M. fortuitum and six by M. chelonae. All four bacteremic patients whose catheters were initially removed and who were treated with antibiotics recovered, whereas for all of the seven bacteremic patients whose catheters remained in place, the infection relapsed or treatment failed. Six (86%) of the latter group ultimately responded to additional antibiotic therapy when the catheter was removed. Successful treatment of local catheter infections was accomplished by catheter removal alone or in combination with antibiotic therapy. Fourteen additional cases have been reported, and eight (57%) of these patients also had underlying cancer. Patients with septicemia or an infection at the catheter insertion site responded to catheter removal and appropriate antibiotics. Patients with infection in the catheter tunnel (tunnel infection) responded only after surgical excision of the tissue surrounding the infected tunnel. M. fortuitum complex is a cause of catheter-related bacteremia in patients with cancer. Appropriate treatment consists of antibiotic therapy and catheter removal. Tunnel infections usually also require surgical excision.

自1978年以来,安德森癌症中心有15名癌症患者因偶发分枝杆菌复合物(偶发分枝杆菌和chelon分枝杆菌)而发生导管相关感染。11例有菌血症,4例有导管部位感染。9例为福氏支原体感染,6例为螯合支原体感染。所有四名最初拔除导管并接受抗生素治疗的菌血症患者都恢复了,而所有七名留置导管的菌血症患者,感染复发或治疗失败。后一组中有6例(86%)最终对移除导管后的额外抗生素治疗有反应。局部导管感染的成功治疗是通过单独拔管或联合抗生素治疗完成的。另有14例病例报告,其中8例(57%)患者也有潜在癌症。败血症或导管插入部位感染的患者对拔管和适当的抗生素有反应。导管隧道感染的患者(隧道感染)只有在手术切除感染隧道周围的组织后才有反应。偶发分枝杆菌复合体是癌症患者导管相关性菌血症的一个原因。适当的治疗包括抗生素治疗和导管拔除。隧道感染通常也需要手术切除。
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引用次数: 146
Estrogens and infection. 雌激素和感染。
Pub Date : 1991-11-01 DOI: 10.1093/clinids/13.6.1139
B Styrt, B Sugarman

The multiple effects of estrogens on infectious processes are only beginning to be understood. The existence of such effects is suggested by gender-related differences in the incidence and severity of some infections and by the association of certain infections with predictable hormonal changes. Current information indicates that estrogens may depress cell-mediated immunity, impair the activity of natural killer cells, and suppress some aspects of neutrophil function. Estrogens potentiate the production of systemic antibody, but local antibody responses may be impaired. Direct effects of estrogens on microorganisms have thus far been best studied in fungi; these hormones may either stimulate or suppress fungal virulence, depending on the species involved. Recent research also suggests responsiveness to estrogens in a wider variety of microorganisms. Studies in cell culture, animals, and humans indicate that pregnancy, estrogen supplementation, and menstrual stage can affect the acquisition and severity of certain bacterial, parasitic, and viral infections. This interaction depends on multiple attributes of both the microbe and the host in a given setting and thus may lead to disparate outcomes; however, there appears to be a predisposition to increased infectious morbidity in certain high-estrogen states. In view of the widespread use of estrogen supplementation, the clinical impact of estrogens on the incidence and outcome of infection needs to be better defined.

雌激素对感染过程的多重影响才刚刚开始被了解。某些感染的发病率和严重程度与性别有关的差异以及某些感染与可预测的激素变化的关联表明存在这种影响。目前的信息表明,雌激素可能会抑制细胞介导的免疫,损害自然杀伤细胞的活性,并抑制中性粒细胞功能的某些方面。雌激素增强了全身抗体的产生,但局部抗体反应可能受损。迄今为止,雌激素对微生物的直接影响在真菌中得到了最好的研究;这些激素可能刺激或抑制真菌的毒力,这取决于所涉及的物种。最近的研究还表明,对雌激素的反应在更广泛的微生物。细胞培养、动物和人类的研究表明,怀孕、雌激素补充和月经阶段可以影响某些细菌、寄生虫和病毒感染的获得和严重程度。这种相互作用取决于特定环境中微生物和宿主的多种属性,因此可能导致不同的结果;然而,在某些高雌激素状态下,似乎有增加感染性发病率的倾向。鉴于雌激素补充的广泛应用,雌激素对感染发生率和结局的临床影响需要更好地定义。
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引用次数: 118
Metronidazole-induced acute pancreatitis. 甲硝唑致急性胰腺炎。
Pub Date : 1991-11-01 DOI: 10.1093/clinids/13.6.1213
W A Corey, B N Doebbeling, K J DeJong, B E Britigan

Three cases of metronidazole-induced acute pancreatitis have been reported recently in three women who were being treated for nonspecific vaginitis. We report the fourth such case in a 63-year-old woman with long-standing Crohn's disease who developed acute pancreatitis that was temporally associated with the initiation of metronidazole therapy for a rectovaginal fistula. No other risk factors for pancreatitis were identified except for possibly Crohn's disease itself. We review the literature with regard to metronidazole-induced acute pancreatitis and suggest a possible mechanism. Metronidazole should be considered as a possible cause of acute pancreatitis, and its use should be discontinued if no other risk factor is found.

最近报道了三例甲硝唑诱导的急性胰腺炎,三名妇女因非特异性阴道炎而接受治疗。我们报告的第四个这样的情况下,63岁的妇女长期克罗恩病谁发展急性胰腺炎是暂时与甲硝唑治疗直肠阴道瘘开始相关。除了可能的克罗恩病本身外,没有发现胰腺炎的其他危险因素。我们回顾了有关甲硝唑诱导急性胰腺炎的文献,并提出了可能的机制。甲硝唑应被认为是急性胰腺炎的可能原因,如果没有发现其他危险因素,则应停用甲硝唑。
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引用次数: 29
A case of human endocarditis due to Streptococcus suis in North America. 北美猪链球菌致人心内膜炎1例。
Pub Date : 1991-11-01 DOI: 10.1093/clinids/13.6.1251
S Trottier, R Higgins, G Brochu, M Gottschalk
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引用次数: 87
Bronchiolitis obliterans-organizing pneumonia associated with Cryptococcus neoformans infection. 闭塞性细支气管炎-与新型隐球菌感染相关的组织性肺炎。
Pub Date : 1991-11-01 DOI: 10.1093/clinids/13.6.1253
C F Carey, L Mueller, C L Fotopoulos, L Dall
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引用次数: 26
Use of the polymerase chain reaction for the specific and direct detection of Clostridium difficile in human feces. 应用聚合酶链反应对人类粪便中艰难梭菌进行特异性和直接检测。
Pub Date : 1991-11-01 DOI: 10.1093/clinids/13.6.1053
P H Gumerlock, Y J Tang, F J Meyers, J Silva

The polymerase chain reaction was used for the detection of Clostridium difficile, the etiologic agent of antibiotic-associated colitis. An upstream primer identical to a coding region (segment I) of the C. difficile 16S rRNA gene and a downstream primer complementary to a highly conserved region of eubacterial 16S rRNA served to amplify a targeted 270-base-pair fragment of genomic DNA. This technique allowed the detection of as few as 10 C. difficile organisms among 10(6) Escherichia coli bacteria. This level of sensitivity represents a 100-fold increase over that of conventional anaerobic culture. C. difficile was detected in DNA extracted directly from the stools of 23 patients with antibiotic-associated colitis and from those of four patients with diarrhea whose stools had been negative for C. difficile when assessed in a cytotoxicity assay. No amplification products were found in the stools of asymptomatic patients. When detected in stools of symptomatic patients, amplification products of C. difficile were confirmed by Southern blotting with a nonradioactive, horseradish peroxidase-catalyzed, chemiluminescent probing system in which biotin-labeled oligonucleotides were used. This system discriminates between C. difficile and similar organisms, such as Clostridium sordellii and Clostridium bifermentans. The combination of the polymerase chain reaction with enzyme-linked probing results in a faster and more sensitive assay for C. difficile than standard culture.

应用聚合酶链反应检测抗生素相关性结肠炎病原艰难梭菌(Clostridium difficile)。与艰难梭菌16S rRNA基因编码区(片段I)相同的上游引物和与真细菌16S rRNA高度保守区域互补的下游引物用于扩增目标270碱基对的基因组DNA片段。该技术允许在10(6)个大肠杆菌中检测到10个艰难梭菌。这种敏感性水平比传统的厌氧培养提高了100倍。在直接从23例抗生素相关性结肠炎患者和4例腹泻患者的粪便中提取的DNA中检测到艰难梭菌,这些患者的粪便在细胞毒性试验中检测出艰难梭菌阴性。无症状患者粪便中未发现扩增产物。当在有症状的患者的粪便中检测到艰难梭菌的扩增产物时,采用非放射性的、辣根过氧化物酶催化的、使用生物素标记的寡核苷酸的化学发光探测系统,用Southern印迹法证实了艰难梭菌的扩增产物。该系统区分艰难梭菌和类似的生物,如梭状芽胞杆菌和双歧梭状芽胞杆菌。与标准培养相比,聚合酶链反应与酶联探针的结合可以更快、更敏感地检测艰难梭菌。
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引用次数: 102
Splenic tuberculosis in patients with AIDS. 艾滋病患者的脾结核。
Pub Date : 1991-11-01 DOI: 10.1093/clinids/13.6.1069
J Pedro-Botet, M T Maristany, R Miralles, J L López-Colomés, J Rubiés-Prat

Splenic tuberculosis is an uncommonly considered diagnosis in clinical practice. We report splenic tuberculosis in three patients with AIDS who were admitted to the hospital because of fever and constitutional syndrome. In all of the patients, abdominal sonography and abdominal computed tomography revealed multiple hypoechoic and hypodense lesions, respectively. In two patients needle aspiration of the spleen with sonographic control was the diagnostic procedure. In the third patient the diagnosis was confirmed after splenectomy. In AIDS patients tuberculosis must be included in the differential diagnosis of hypoechoic and hypodense lesions by means of sonography and computed tomography, respectively, especially in those patients with active tuberculosis.

脾结核在临床上是一种罕见的诊断。我们报告了三例因发热和体质综合征而住院的艾滋病患者的脾结核。在所有患者中,腹部超声和腹部计算机断层扫描分别显示多发低回声和低密度病变。在两例患者的诊断程序针吸脾超声控制。第三例患者在脾切除术后确诊。在艾滋病患者中,肺结核必须分别通过超声和计算机断层扫描进行低回声和低密度病变的鉴别诊断,特别是在活动性肺结核患者中。
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引用次数: 30
Disseminated infection with Fusarium in recipients of bone marrow transplants. 骨髓移植受者镰孢菌播散性感染。
Pub Date : 1991-11-01 DOI: 10.1093/clinids/13.6.1077
A S Gamis, T Gudnason, G S Giebink, N K Ramsay

Clinical data from 10 episodes of disseminated infection with Fusarium among eight recipients of bone marrow transplants and from 31 cases reported previously in the literature were analyzed in an effort to characterize the natural history of this rare infection and its response to therapy. The characteristic signs of fusarial infection--disseminated skin nodules, fungemia, and multiple-organ involvement--are results of its propensity for early spread. From a review of the literature and our own experience, it appears that recovery of phagocytic mechanisms (the primary immunologic defenses against Fusarium) in the form of rising neutrophil counts is mandatory for clinical resolution. Even after a graft begins to function adequately, Fusarium may not be completely eradicated, as evidenced by the high incidence of recurrence among patients with subsequent neutropenic episodes. Fusarium is highly resistant to conventional antifungal drugs in vitro, but its progression may be slowed by intensive antifungal therapy until the recovery of adequate neutrophil levels.

我们分析了8例骨髓移植受者中10例播散性镰刀菌感染的临床资料和先前文献报道的31例镰刀菌感染的临床资料,以描述这种罕见感染的自然历史及其对治疗的反应。镰孢菌感染的特征性体征——弥散性皮肤结节、真菌血症和多器官受累——是其早期传播倾向的结果。从文献回顾和我们自己的经验来看,似乎以中性粒细胞计数上升的形式恢复吞噬机制(对镰刀菌的主要免疫防御)是临床解决的必要条件。即使在移植物开始充分发挥功能后,镰刀菌也可能不会被完全根除,这一点在随后的中性粒细胞减少发作的患者中复发率很高。镰刀菌对体外常规抗真菌药物具有高度耐药性,但强化抗真菌治疗可减缓其进展,直至中性粒细胞水平恢复正常。
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引用次数: 93
Live vaccinia virus recombinants expressing herpes simplex virus genes. 表达单纯疱疹病毒基因的活痘苗病毒重组体。
Pub Date : 1991-11-01 DOI: 10.1093/clind/13.supplement_11.s898
J F Rooney, C R Wohlenberg, B Moss, A L Notkins

Vaccinia virus recombinants expressing antigens from herpes simplex virus (HSV) have been tested as potential live virus vaccines for prevention of HSV infection. We describe three vaccinia virus/HSV recombinants. The first expresses the HSV-1 glycoprotein D (vaccinia/gD), the second expresses the HSV-1 glycoprotein B (vaccinia/gB), and the third expresses both the HSV-1 glycoprotein D and the influenza A hemagglutinin (vaccinia/HSVgD/influenza). Mice immunized with vaccinia/gD or vaccinia/gB developed antibodies capable of neutralizing HSV in vitro and were protected against both lethal and latent infection with HSV. Protection against HSV challenge persisted for greater than 1 year in mice immunized with vaccinia/gD. The immune response to HSV in mice immunized with vaccinia/gD could be increased by a booster vaccination with vaccinia/gD. However, the immune response to HSV was decreased in animals immunized with a vaccinia recombinant that expressed non-HSV genes before vaccination with vaccinia/gD. In separate experiments, a bivalent vaccinia recombinant, vaccinia/HSVgD/influenza, was constructed and was found to be comparable to the vaccinia/gD single recombinant in immunogenicity and protective efficacy against lethal HSV challenge. We conclude that vaccinia/HSV recombinants can provide protection against HSV infection in mice and that these recombinants may provide an alternative approach in the development of a live virus vaccine against HSV.

表达单纯疱疹病毒(HSV)抗原的重组痘苗病毒已被测试作为预防单纯疱疹病毒感染的潜在活病毒疫苗。我们描述了三种牛痘病毒/HSV重组。第一个表达HSV-1糖蛋白D(痘苗/gD),第二个表达HSV-1糖蛋白B(痘苗/gB),第三个同时表达HSV-1糖蛋白D和流感A血凝素(痘苗/ hsv - gD/流感)。用牛痘/gD或牛痘/gB免疫的小鼠在体外产生了能够中和HSV的抗体,并对HSV的致死性和潜伏性感染都有保护作用。牛痘/gD免疫小鼠对HSV攻击的保护持续超过1年。牛痘/gD免疫小鼠对HSV的免疫应答可通过牛痘/gD加强接种而增强。然而,在牛痘/gD疫苗接种前,用表达非HSV基因的痘苗重组疫苗免疫的动物对HSV的免疫反应降低。在单独的实验中,构建了一种双价重组痘苗/HSVgD/流感病毒,并发现在免疫原性和对致命HSV攻击的保护作用方面与痘苗/gD单价重组痘苗/流感病毒相当。我们得出结论,痘苗/HSV重组体可以对小鼠的HSV感染提供保护,并且这些重组体可能为开发针对HSV的活病毒疫苗提供一种替代方法。
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引用次数: 12
期刊
Reviews of infectious diseases
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