更昔洛韦滴眼剂治疗单疱病毒角膜炎137例临床研究

用双盲法对比观察０．１％更昔洛韦与０．１％阿蚶洛韦滴眼剂治疗单疱病毒角膜炎１３７例的疗效。两者疗效相近,总治愈率为８６．５％（更昔洛韦）和９０．０％（阿昔洛韦）,统计学处理差异无显著性。结果表明更昔洛韦滴眼剂是治疗单疱病毒角膜炎有效而安全的药物。     

更昔洛韦对小鼠单纯疱疹病毒性急性脑损伤的保护作用

目的探讨更昔洛韦(GCV)对单纯疱疹病毒(HSV)性急性脑损伤的保护作用及其机制。方法建立小鼠HSV急性脑损伤模型,比较GCV治疗前后小鼠生存状况、死亡率和电镜下脑组织结构变化;接种病毒后d7处死小鼠,通过荧光定量FCR检测脑组织中HSV-ⅠDNA的拷贝数。结果电镜下感染模型组小鼠脑细胞胞浆水肿明显.核仁固缩,核内结构破坏,多数线粒体呈空泡样改变,核仁内可见病毒颗粒内脊破坏、髓鞘严重松解、破坏。GCV治疗后小鼠症状明显好转,体质量增加理想,死亡率明显降低,脑组织病理损害明显减轻,小鼠脑组织中HSV-ⅠDNA拷贝数也显著低于模型组。结论GCV能有效抑制HSV-Ⅰ复制,减轻临床症状、脑组织损伤,降低小鼠HSV急性脑损伤的死亡率。     

紫外分光光度法测定更昔洛韦滴眼液的含量

目的:建立更昔洛韦滴眼液含量的测定方法。方法:采用紫外分光光度法测定更昔洛韦的含量。结果:更昔洛韦在4~16μg/ml浓度范围内与吸收度有良好的线性关系,回归方程为A=0.0531 7C 0.010 4,r=0.999 9;平均回收率为99.83%,RSD为0.45%(n=5)。结论:该方法简便、快速、准确,适用于医院制剂的快速分析。     

Ganciclovir treatment in Ménétrier's disease

A 2-y-old girl with severe edema, oliguria and hypoalbuminemia caused by protein-losing gastritis was diagnosed with cytomegalovirus-associated Ménétrier's disease. After almost two weeks, during which the patient required repeated albumin transfusions, she was treated with intravenous ganciclovir. Within five days her condition had improved, and no additional albumin replacement was needed. Complete recovery was observed after several weeks. CONCLUSION: In patients with severe Ménétrier's disease, a course of ganciclovir treatment may be of benefit and should be considered.     

Adenovirus/Herpes Simplex-Thymidine Kinase/Ganciclovir Complex: Preliminary Results of a Phase I trial in Patients with Recurrent Malignant Gliomas

The management of patients with glioblastoma remains challenging with an average survival of 32-56 weeks. We report on a clinical trial of patients with recurrent glioblastoma treated with adenovirus/herpex simplex-thymidine kinase/ganciclovir (ADV/HSV-tk/GC). Entry criteria for this study included: recurrent malignant glioma after surgical resection and conventional radiation therapy. At the time of recurrence, computerized volumetric resection of the tumor was performed and the ADV/HSV-tk complex was injected in the tumor bed. GC was administered 24 h after surgery (10 mg/kg/day) for 7 days. Patients were divided into 3 ADV/HSV-tk dose-escalating cohorts. Adenoviral vector shedding, and local or systemic toxicity did not occur in this study. Magnetic resonance imaging showed lack of increased brain edema in the treated patients. Histological examination of the 5 patients that had repeated surgery after gene therapy treatment showed lack of tissue toxicity. Additionally, PCR for HSV-tk was negative in the brain 3 months after injection. The patients' Karnofsky score was maintained > or = 70 in 8/10 patients (80%) and 5/9 patients (55%) 3 and 6 months respectively, after gene therapy. Ten of 11 patients survived > or = 52 weeks from diagnosis with an average survival of 112.3 weeks. One patient is still alive 248 weeks from diagnosis. These data show that the ADV/HSV-tk/GC complex at the dose used in this study is safe. Additional dose escalation is currently in progress.     

更昔洛韦对肾移植患者环孢菌素A药代动力学的影响

 目的：观察更昔洛韦对肾移植患者环孢菌素A药代动力学参数的影响,以促进临床合理用药,提高肾移植存活率。方法：分别对10例肾移植患者单用环孢菌素A与合用更昔洛韦后环孢菌素A的药代动力学参数进行研究和评价,采用荧光偏振免疫法测定各时刻环孢菌素A血中浓度,3P87程序拟合药代动力学参数,t检验比较组间差异。结果：合用更昔洛韦后,环孢菌素AKe,t_1/2（Ka）分别由单用组的（0.16±0.04）h^-1和（1.39±0.76）h降至（0.09±0.05）h^-1和（0.50±0.32）h（P＜0.05）,t_max由（3.67±0.77）h^-1减至（2.00±0.78）h^-1（P＜0.01）,t_1-2（Ke）由（4.08±1.85）h^-1增至（10.51±6.42）h^-1,峰浓度c_max平均升高27％。结论：更昔洛韦使肾移植患者对环孢菌素A的吸收显著加快,而使环孢菌素A在体内的消除减慢,对血中环孢菌素A的峰浓度也有一定影响,揭示临床调整用药方案。     

HSVtk/GCV自杀基因系统治疗小鼠腹水瘤的研究

目的:研究HSVtk/GCV系统对腹水瘤的治疗作用.方法:采用XTT、动物实验、透射电镜和流式细胞仪等方法.结果:HSVtk( )的P388tk细胞对GCV的敏感性约为其亲本P388细胞的37倍,且对其邻近的HSVtk(-)的P388细胞或S细胞具有旁观者效应,当P388tk细胞与P388细胞或S细胞混合培养,5μg/ml GCV处理后,P388tk细胞占混合细胞的10%,就可杀伤50%的混合细胞.动物实验中P388tk细胞或P388tk与P388细胞等量混合所致的荷瘤鼠在以CCV治疗后与对照组相比,肿瘤生长受到明显抑制,小鼠生存期明显延长;细胞死亡的机制与凋亡有关.结论:在体内和体外水平,HSVtk( )的P388tk细胞能被GCV有效杀伤,且对其邻近的HSVtk(-)的细胞产生旁观者效应.     

Cytomegalovirus prophylaxis with ganciclovir and cytomegalovirus immune globulin in liver and intestinal transplantation

Liver and intestinal transplant recipients at the University of Miami receive an intensive regimen of cytomegalovirus (CMV) prophylactic therapy consisting of a combination of CMV immune globulin intravenous (CMV-IGIV, CytoGam®) and ganciclovir. The 5-year experience with this regimen in liver transplant patients showed effective CMV prophylaxis in this patient population. The importance of an effective prophylactic strategy was underscored by higher observed rates of chronic rejection and post-transplant lymphoproliferative disorder (PTLD) in CMV-infected patients. The use of CMV-positive donors for intestinal transplants did not increase the incidence of CMV disease. Intestinal transplant recipients had improved survival rates, reflecting an aggressive policy of monitoring, immunosuppression, and CytoGam® plus ganciclovir prophylaxis.     

A review of antiviral therapies in the treatment of cytomegalovirus

ABSTRACT: Cytomegalovirus (CMV) is a member of the herpesvirus family that is very prevalent world wide based on serologic testing. In immunocompromised persons CMV produces high rates of morbidity and mortality. Congenital CMV is the leading infectious cause of fetal abnormalities in the United States. Infection of human immunodeficiency virus (HIV) seropositive persons or transplant patients with CMV can produce retinitis, encephalitis, pneumonitis, hepatitis, gastrointestinal ulcerations, and cutaneous lesions. Three intravenous therapies are available for CMV infections: ganciclovir; foscarnet and cidofovir. Most recently a fourth antiviral agent was approved for intravitreal injection. This drug, fomivirsen, is the first antisense oligonucleotide available for therapeutic use. A number of other antiviral drugs and vaccines are currently under study.