玻璃体内注射联合全身应用更昔洛韦治疗AIDS合并巨细胞病毒视网膜炎的临床疗效

目的　观察玻璃体内注射联合全身应用更昔洛韦治疗AIDS合并巨细胞病毒视网膜炎（cytomegalovirus retinitis,CMVR）的临床疗效。方法　收集2016年1月至2018年1月在广西医科大学第一附属医院收治的AIDS合并CMVR患者7例13眼。患者全身用药为更昔洛韦和膦甲酸钠注射液，更昔洛韦 5.0～7.5 mg·kg^-1，每天2次静脉滴注；成人每次给予膦甲酸钠3 g，每天3次静脉滴注；同时在局部玻璃体内注射更昔洛韦。治疗前后对比的指标有:最佳矫正视力、眼压、眼底照相情况、视觉诱发电位、眼电图和视网膜电图等检查；检测指标包括CD4+T细胞计数，血液、前房水、玻璃体CMV-DNA病毒载量等。通过检查结果辅助判断治疗效果。结果　6例患者治疗后最佳矫正视力为（0.72±0.83）logMAR，较治疗前（1.14±0.83）logMAR提高（P=0.001），其中1例患者经过全身和局部抗病毒治疗后视力不提高。患者治疗前后眼压均在正常范围内，治疗前为（13.62±3.04）mmHg（1 kPa=7.5 mmHg），治疗后为（12.77±2.89）mmHg，差异无统计学意义（P=0.119）。注药后患者眼底病变范围逐渐变小（P<0.05）。治疗1个月后，患者视觉诱发电位N2-P2振幅及眼电图光峰电位较治疗前升高（均为P<0.05），视觉诱发电位P2潜伏期和视网膜电图（明适应）a波及b波潜伏期和振幅治疗前后差异均无统计学意义（均为P>0.05）。3例患者治疗前血液中CMV-DNA病毒载量检测为阴性，1例患者2眼经过治疗后眼内液中CMV-DNA病毒载量检测为阴性。治疗前玻璃体CMV-DNA病毒载量均明显高于前房水，而前房水CMV-DNA病毒载量又明显高于血液（均为P<0.05），说明三个部位的CMV-DNA病毒载量从高到低的排列顺序为玻璃体>前房水>血液。治疗后玻璃体、前房水CMV-DNA病毒载量均低于治疗前，差异均有统计学意义（均为P<0.05）。治疗前后血液CMV-DNA病毒载量差异无统计学意义（P>0.05）。治疗前后CD4+T 细胞计数差异无统计学意义（P>0.05）。治疗前CD4+T细胞计数与眼内液、血液CMV-DNA病毒载量均呈负相关关系（均为P<0.05）；治疗过程中，CD4+T细胞计数与眼内液CMV-DNA病毒载量无相关关系（均为P>0.05），与血液CMV-DNA病毒载量呈负相关关系（P<0.05），但两者之间不存在直线回归关系（P>0.05）。治疗前及治疗过程中玻璃体CMV-DNA病毒载量与前房水CMV-DNA病毒载量均存在正相关关系（回归方程分别为:Y=20 178.973+0.165X，Y=171 849.77+0.168X，均为P<0.05）。所有患者术中和术后均未出现严重并发症。结论　静脉滴注抗病毒药物联合玻璃体内注射小剂量更昔洛韦是治疗AIDS合并CMVR安全有效的治疗方法。     

神经保护因子对巨细胞感染新生儿听力影响的研究

目的 探讨神经保护因子对巨细胞感染新生儿听力的影响。方法 收集78例先天性巨细胞感染的新生儿分为2组,均给予更昔洛韦进行治疗,研究组患者在上述治疗的基础上给予神经保护因子,比较2组患者的治疗效果。结果 2组患儿在出生后3 d听力筛选不通过率差异无统计学意义(P>0.05);患儿听力筛选不通过率在出生后6周研究组(5.1%)明显低于对照组(15.4%,P<0.05)。研究组患儿诱发电位检测V波的阈值在出生后3个月与6个月均明显低于对照组(P<0.05)。结论 在一定程度上神经保护因子能降低先天性巨细胞感染新生儿听力的损伤,对患儿的听觉系统有很好的保护作用,在临床上值得进行推广应用。     

更昔洛韦与病毒唑治疗小儿水痘的疗效比较

目的:探讨更昔洛韦与病毒唑治疗小儿水痘的临床疗效。方法:将120例水痘患儿随机分为两组,更昔洛韦 组、病毒唑组各60例。更昔洛韦组给予更昔洛韦5mg/(kg·d)静滴,每日1次治疗;病毒唑组给予病毒唑10mg/ (kg·d)静滴,每日1次治疗。两组均计数退热时间及皮疹结痂时间,同时观察药物的毒副作用。结果:更昔洛韦 组平均退热时间为(2.61±0.47)d,明显少于病毒唑组(3.7±0.38)d(P<0.05);皮疹结痂时间,更昔洛韦组为 (3.24±0.27)d,明显少于病毒唑组(4.3±0.31)d(P<0.05)。两组药物治疗过程中无明显毒副作用。结论:更昔 洛韦治疗小儿水痘疗效显著,明显优于病毒唑。     

更昔洛韦眼用凝胶和阿昔洛韦滴眼液治疗病毒性角膜炎疗效对比

目的：探讨病毒性角膜炎应用更昔洛韦眼用凝胶的疗效。

方法：随机选择2013-05/2014-10我院收治的84例101眼病毒性角膜炎患者作为研究对象,随机分为更昔洛韦组和对照组,分别给予更昔洛韦眼用凝胶和阿昔洛韦滴眼液治疗,2wk后观察疗效。

结果：两组患者治疗后较治疗前病毒性角膜炎各症状(畏光、流泪、疼痛、异物感)及各体征(睫状充血、角膜上皮缺损、角膜基质水肿、角膜荧光素染色)评分均有显著改善,更昔洛韦组改善更为明显(P<0.05); 更昔洛韦组有效率(92.9%)明显高于对照组(59.5%),差异有统计学意义(P<0.05); 两组患者不良反应无统计学差异(P>0.05),更昔洛韦组复发率明显低于对照组(P<0.05)。

结论：更昔洛韦眼用凝胶是一种安全有效的抗病毒滴眼液,治疗病毒性角膜炎疗效确切,值得临床中推广应用。     

Gene therapy for high grade gliomas

High grade gliomas in adults are devastating diseases, with very poor survival despite their lack of distant metastases. Local treatments, such as surgical resection and stereotactic radiosurgery, have been most successful, whereas systemic therapy (for example, chemotherapy and immunotherapy) have been rather disappointing. Several gene therapy systems have been successful in controlling or eradicating these tumours in animal models and are now being tested as a logical addition to current clinical management. This review describes the gene therapy clinical protocols that have been completed or that are ongoing for human gliomas. These include the prodrug activating system, herpes simplex thymidine kinase (HSVtk)/ganciclovir (GCV), utilising either retrovirus vector producer cells or adenovirus vectors; adenovirus mediated p53 gene transfer; adenovirus mediated IFN-β gene transfer and oncolytic herpes virus and adenovirus vectors. To date, all of the clinical studies have used direct injection of the vector into the glioma. The Phase I clinical studies have demonstrated low to moderate toxicity and variable levels of gene transfer and in some cases anti-tumour effect. Future directions will rely upon improvements in gene delivery as well as gene therapies and combinations of gene therapy with other treatment modalities.     

Clinical Evaluation of Intravitreal Injection of Ganciclovir in Refractory Corneal Endotheliitis

ABSTRACT

Purpose: To evaluate the efficacy and safety of intravitreal ganciclovir (GCV) injection in refractory endotheliitis.

Methods: Retrospectively recruited 25 eyes with endotheliitis, proved by clinical manifestations, positive PCR for viral DNA and responded poor to topical and systemic antiviral medications. All patients received additional continued intravitreal GCV injections.

Results: Cytomegalovirus (CMV), varicella zoster virus (VZV), and herpes simplex virus (HSV) DNA were detected in 64.0%, 28.0%, and 8.0% of the eyes, respectively. Within 2 weeks after the last injection, 16/25 eyes recovered corneal clarity; active keratic precipitates (KPs) were eliminated in 21/25 eyes; intraocular pressure (IOP) was controlled in 12/15 eyes with elevated IOP on study entry. Best-corrected visual acuity increased at the last follow-up (p = 0.016). Clinical recurrence occurred in three patients. No complications were detected.

Conclusions: CMV endotheliitis was the main type of refractory endotheliitis. Despite its invasive nature, intravitreal GCV injection appears to be an effective method for refractory endotheliitis.     

Effect of individualized therapy for AIDS patients with cytomegalovirus retinitis in intravitreal ganciclovir injections

The effect of intravitreal ganciclovir injection combined with intravenous infusion on acquired immune deficiency syndrome (AIDS) patients with cytomegalovirus retinitis (CMVR) was investigated. A total of 32 eyes in 23 AIDS patients diagnosed as CMVR from 2017 to 2018 were included in the retrospective study. All patients underwent induction therapy by using intravenous drip of the anti-cytomegalovirus (CMV) agent ganciclovir (5 mg/kg q12h) combined with intravitreal ganciclovir injection (3 mg/time, 2 times/wk). The visual acuity, fundus photographs, lesion location, and number of intravitreal injections were observed preoperatively and postoperatively. Totally 14 eyes were cured during induction therapy. The number of injections [4.13 (2 to 6)] in CMVR patients with peripherally fundus lesions were significantly lower than those with central lesions [4.89 (2 to 6)]. The individualized therapy of intravitreal ganciclovir injections for AIDS patients with CMVR can effectively reduce the numbers of intravitreal injections.     

Interferon treatment with or without oral ganciclovir in HBeAg-negative chronic hepatitis B: a randomized study

The treatment of HBeAg-negative chronic hepatitis B with alpha interferon alone is unsatisfactory. We evaluated the efficacy of combined administration of interferon-a2a (IFN) with oral ganciclovir, a nucleoside analogue. Forty patients with hepatitis B virus (HBV)-DNA-positive/HBeAg-negative chronic hepatitis B, were randomized to receive 4.5 MU IFN thrice weekly, subcutaneously, alone or in combination with 3 g ganciclovir per os daily for 26 weeks and followed for 12 months after treatment. Mean serum HBV-DNA levels decreased by 4.0 log10 in the combination group (from 5 x 106 to 4.8 x 102 copies/ml) and by 2.2 log10 in the interferon group (from 8 x 106 to 4.8 x 104 copies/ml) by quantitative polymerase chain reaction (PCR). HBV-DNA became undetectable in 11 of 20 (55%) and in three of 20 (15%) patients in the two groups, respectively (P=0.02). The alanine aminotransferase levels became normal in all patients receiving combination therapy, compared to 75% of those in the interferon group. After cessation of therapy, HBV-DNA increased or reappeared in all patients with 85% also relapsing biochemically. One year after treatment, three patients in each group (15%) remained in sustained biochemical remission with very low serum HBV-DNA levels (median 15 700 copies/ml). We conclude that, in HBeAg-negative chronic hepatitis B, 6-month combination therapy with oral ganciclovir and IFN is associated with complete biochemical remission in all treated patients and a 4 log10 decrease in serum HBV-DNA levels. The end of treatment efficacy of this combination scheme is far super- ior to that of IFN monotherapy but sustained responses are few. Further studies are warranted to evaluate the efficacy of prolonged combination schemes with nucleoside analogues and IFN, compared to IFN monotherapy.