Herpes simplex virus latency in the nervous system – a new model

Permissive herpes simplex virus (HSV) infection in tissue culture results in host cell destruction. Latent HSV infection in vivo occurs in neurons of peripheral sensory ganglia (PSG) and it therefore can not take place in neurons in which the virus has completed a lytic replication cycle similar to that present in vitro. Our hypothesis, based on experimental data and observations in humans, suggests that establishment of latent infection and reactivation of HSV-1 does not involve neuronal cell loss. Latency is established in neurons in which the virus does not replicate and is determined, in part, by the tissue levels of a herpes transactivating protein (Vmw65) that is a component of the viral tegument. We also suggest that reactivation of latent infection does not involve destruction of neurons and is due to replication of virus at the peripheral mucocutaneous tissues to where virus or viral DNA have been transported from the nervous tissue. Alternatively, reactivation is initiated in the PSG using a replication cycle which does not involve irreversible damage to neurons. This model explains the lack of damage to neurons which continue to serve as permanent reservoirs of latent virus for the entire life of the host.     

Discordance in HIV-1 viral loads and antiretroviral drug concentrations comparing semen and blood plasma

Objectives

For individuals not on antiretroviral therapy, the risk of heterosexual transmission of HIV appears negligible when blood plasma (BP) viral loads are <1500 HIV‐1 RNA copies/mL. It is not clear whether this observation can be extrapolated to individuals on highly active antiretroviral therapy (HAART). Because of differential tissue penetration, antiretroviral drug concentrations may be sufficient to maintain an undetectable viral load in the BP yet not achieve adequate levels to suppress HIV in the genital tract. Therefore, we wanted to correlate HIV viral loads and drug concentrations in semen plasma (SP) and BP.

Methods

Thirty‐three men were included. All were on combination antiretroviral therapy with an undetectable BP viral load for at least 1 year. Blood and semen samples were collected within 2 h of each other and tested for HIV RNA by the NucliSens QT (bioMerieux, St Laurent, QC, Canada) method; drug concentrations were determined by liquid chromatography tandem mass spectrometry.

Results

Two of the 33 patients (6.1%) with BP viral loads below detection had time‐matched HIV viral loads in SP ≥700 copies/mL. Both patients were on efavirenz, the SP concentrations of which were ≤10% of the levels in BP and well below the minimal therapeutic drug monitoring target concentration required to suppress HIV.

Conclusions

Because, at least in part, of poor drug penetration into the genital tract, an undetectable HIV viral load in the BP does not guarantee an undetectable viral load in semen. In view of this, caution should be taken in concluding that patients on HAART with suppressed viraemia are sexually non‐infectious.     

Oral Valganciclovir Is Noninferior to Intravenous Ganciclovir for the Treatment of Cytomegalovirus Disease in Solid Organ Transplant Recipients

Intravenous ganciclovir is the standard treatment for cytomegalovirus disease in solid organ transplant recipients. Oral valganciclovir is a more convenient alternative. In a randomized, international trial, recipients with cytomegalovirus disease were treated with either 900 mg oral valganciclovir or 5 mg/kg i.v. ganciclovir twice daily for 21 days, followed by 900 mg daily valganciclovir for 28 days. A total of 321 patients were evaluated (valganciclovir [n = 164]; i.v. ganciclovir [n = 157]). The success rate of viremia eradication at Day 21 was 45.1% for valganciclovir and 48.4% for ganciclovir (95% CI -14.0% to +8.0%), and at Day 49; 67.1% and 70.1%, respectively (p = NS). Treatment success, as assessed by investigators, was 77.4% versus 80.3% at Day 21 and 85.4% versus 84.1% at Day 49 (p = NS). Baseline viral loads were not different between groups and decreased exponentially with similar half-lives and median time to eradication (21 vs. 19 days, p = 0.076). Side-effects and discontinuations of assigned treatment (18 of 321 patients) were comparable. Oral valganciclovir shows comparable safety and is not inferior to i.v. ganciclovir for treatment of cytomegalovirus disease in organ transplant recipients and provides a simpler treatment strategy, but care should be taken in extrapolating to organ transplant recipients not properly represented in the present study.     

Acute viral myocarditis A death associated with anaesthesia

The death of a 35-year-old woman in the immediate postoperative period as a result of undiagnosed acute viral myocarditis is described. The presentation, diagnosis and course of the disease is discussed. It is recommended that wider use to be made of routine electrocardiographs as a screening test.     

转人GM—CSF基因人膀胱癌细胞株的建立及体外生物学特性

经逆转录病毒载体将人GM-CSF基因导入人膀胱癌细胞株BIU-87细胞中,建立了转基因细胞株BIU/GM。经流式细胞仪行细胞DNA周期分析表明GM-CSF基因的导人及表达对BIU-87细胞的增长无影响。免疫荧光测定发现转GM-CSF基因及表达不能促进BIU-87细胞表面HLA-ABC、DR、DQ抗原的表达。转基因瘤细胞株经6000rad X射线照射灭活后,丧失增殖能力,逐步死亡,但能维持一定水平的GM-CSF分泌活性达两周以上。从而为制备灭活的转基因瘤苗提供了初步经验。     

慢性重症病毒性肝炎并发医院内曲霉菌感染

1976～1991年我院收治慢性重症病毒性肝炎并发曲霉菌感染15例,感染于住院后3～112天,<30天9例。以血性痰液、胸水、腹水、脑脊液为特点。多数周围血象白细胞不增高,中性粒细胞增高,IgG增高,曲霉菌( );感染后2～10天均死亡。感染前咽部检出白色念珠菌6例,滥用抗生素者占80％。     

高原地区小儿病毒性心肌炎T细胞亚群检测及临床意义

本文对２８例小儿病毒性心肌炎患者进行了Ｔ细胞检测，发现患儿外周血Ｔ细胞亚群有明显改变。提示：小儿病毒性心肌炎患者均有不同程度的一过性细胞免疫功能低下。而体液免疫功能正常，我们在临床给与一般治疗的同时，佐以胸腺因子治疗，明显改善症状，取得良好疗效。     

The comparative evaluation of cellular localization of viral antigens with microscopic changes in the ileum of cattle infected with bovine viral diarrhea

The correlation between microscopic changes with cellular localization of viral antigens was studied in the ileum of 16 cases infected with bovine viral diarrhea virus (BVDV). Microscopic lesions in the ileum included multifocal erosive and ulcerative ileitis, severe congestion and hemorrhage, crypt dilation and mucus engorgement, epithelial debris and leukocytes, lymphoid depletion of Peyer’s patches, herniation of mucosal epithelium into depleted Peyer’s patches, and fibrinoid vasculitis of submucosal vessels. BVDV antigen was detected by immunohistochemistry in macrophages, dendritic cells, smooth muscle cells, endothelial cells, epithelial cells of crypts, and mucosal epithelium, together with other mononuclear cells including lymphocytes, plasma cells, fibroblasts, and intramural ganglial cells. No consistent correlation between the presence of BVDV antigen and vascular lesions in the ileum was identified. The intensity and distribution of the immunoperoxidase stain in the ileum was graded as highly positive (18.7%), moderately positive (56.3%), and mildly positive (25%). In conclusion, the pattern and density of distribution and localization of BVDV antigen in the ileum was not consistently correlated with the severity of microscopic lesions.     

血清乙型肝炎病毒标志物不同表现模式及肝功能异常对肾移植受者存活率的影响

目的　探讨血清乙型肝炎病毒标志物不同表现模式对肾移植受者长期存活的影响。方法　对 62例血清乙型肝炎病毒标志物阳性者及 1 96例血清乙型肝炎病毒标志物全阴性者肾移植术后的肝功能、人肾均存活的存活率等指标进行随访和回顾性分析。结果　术后早期血清乙型肝炎病毒标志物阳性组与血清乙型肝炎病毒标志物阴性组比较 ,肝功能异常发生率的差异无显著性 (P >0 .0 5) ;术后中远期 ,HBsAg、HBeAg及抗 HBc阳性者的肝功能受损率明显高于血清乙型肝炎病毒标志物阴性组及HBsAg、抗 HBe、抗 HBc阳性者 (P <0 .0 5) ,其人肾均存活的存活率也最低 (P <0 .0 5)。结论　对HBsAg、抗 HBe及抗 HBc阳性者进行肾移植应慎重 ,而HBsAg、HBeAg及抗 HBc阳性者则不适宜接受肾移植