Treatment of hepatitis B and C after liver transplantation. Part 2, hepatitis C

Abstract End-stage liver disease caused by the hepatitis C virus is a major indication for liver transplantation. However, recurrence of hepatitis in the graft is a major issue. HCV re-infection after transplantation is almost constant, and recent data confirm that it significantly impairs patient and graft survival. Factors that may influence disease severity and consequent progression of HCV graft injury remain unclear. Chronic HCV infection develops in 60%–80% of patients, and 6%–28% ultimately progress to cirrhosis within 5 years. Pre-transplantation antiviral treatment is not easily related to poor tolerance. Attempts to administer prophylactic post-transplantation antiviral treatment are under evaluation but are limited by antiviral drug side effects. Treatment of established graft lesions with interferon or ribavirin as single agents has been disappointing. Combination therapy gave promising results, with sustained virological response in 25% of patients, but indications, modality and duration of treatment should be assessed.     

冠心病患者血栓前状态分子标志物的变化

观察冠心病患者凝血、纤溶指标的变化 ,以探讨凝血系统的变化与冠心病发病的关系。采用酶联免疫吸附双抗体夹心法检测 10 0例冠心病患者血浆D 二聚体、血小板α颗粒膜蛋白 14 0及血管性血友病因子含量 ,并与4 4例健康人比较。结果发现 ,冠心病患者血浆D 二聚体、血小板α颗粒膜蛋白 14 0和血管性血友病因子明显升高 ,与对照组比较差异显著 (P <0 .0 1) ,且急性心肌梗死患者各指标变化明显高于陈旧性心肌梗死、不稳定型心绞痛和稳定型心绞痛患者 (P <0 .0 1) ,其中不稳定型心绞痛患者血浆血小板α颗粒膜蛋白 14 0明显高于稳定型心绞痛患者 (P <0 .0 5 )。冠心病患者血小板α颗粒膜蛋白 14 0、血管性血友病因子及D 二聚体水平之间呈明显的正相关性(P <0 .0 5 )。结果提示 ,冠心病患者存在明显的高凝状态 ,表现为继发性纤溶亢进 ,血小板活性增加及血管内皮细胞损伤 ,且与冠心病患者的病情变化有一定关系。     

Treatment of hepatitis B and C after liver transplantation. Part 1, hepatitis B

Abstract The outcome of OLT for HBV-related liver disease is dependent on the prevention of allograft re-infection. Over the past decade, major advances have been made in the management of HBV transplant candidates. The advent of long-term hepatitis B immune globulin (HBIG) administration as a prophylaxis against HBV recurrence, and the introduction of new antiviral agents against HBV infection, such as lamivudine (LAM), were a major breakthrough in the management of these patients. Results of OLT for HBV infection are similar to those achieved with other indications. Pre-OLT antiviral treatment such as LAM can suppress HBV replication before OLT and thus decrease the risk of re-infection of the graft. Combination prophylaxis with LAM and HBIG after transplantation highly effectively reduces the rate of HBV re-infection, even in HBV replicative cirrhotic, patients. The optimal HBIG protocol in the LAM era is yet to be defined: dosing of HBIG, routes of administration, and possibility of stopping HBIG. Several antiviral drugs have been developed for the management of HBV infection on the graft, so outcome is currently good.     

Ultrastructural pathology and cytochemical investigations of l-2-chloropropionic acid-induced neurointoxication of the rat cerebellum

The objectives of the studies described were to assess the ultrastructural neuropathology, blood-brain barrier (BBB) integrity and calcium status of the cerebellum of rats following a single dose of 750 mg · kg^–1 l-2-chloropropionic acid (l-2-CPA). The first indications of intoxication appeared at 36 h when condensation of many granule cells associated with Purkinje cell degeneration and marked astroglial swelling were observed. Some electron-lucent granule cells were also noted lying amongst these condensed forms. Condensed granule cells had swollen, electron-lucent mitochondria, dilated Golgi apparatus and nuclear crenation. Occasionally, areas of granule cell necrosis were also present at this time. Granule cell condensation probably represents a preliminary and irreversible stage in an excitotoxic process that leads to necrosis. At 48 and 72 h, most granule cells were necrotic, and occasionally, extravasation of both erythrocytes and leucocytes into the expanded extravascular space was observed. Evaluation of the BBB by ultrastructural cytochemical visualisation of horseradish peroxidase injected i.v. 2 min before killing by perfusion fixation showed substantial leakage. At 36 h post-dose, ultrastructural calcium localisation using oxalate/pyroantimonate precipitation demonstrated a substantial increase in calcium pyroantimonate precipitate in mitochondria and other membranous cytoplasmic organelles (especially the Golgi apparatus) in condensed granule cells, but with little in their nuclei. However, their immediate neighbours (of ostensibly normal ultrastructural appearances) contained greater amounts of intranuclear precipitate. Swollen astroglial cells (especially the Bergmann glia) contained considerable quantities of precipitate. A possible excitotoxic mechanism via l-2-CPA-induced NMDA receptor agonism leading to overwhelming calcium influx and disruption of cellular calcium homeostasis is proposed. Received: 8 May 1996 / Revised: 1 September 1996 / Accepted: 11 September 1996     

无环鸟苷亲脂性前体药物脂质体的制备及体外抗病毒活性(英文)

本文通过将无环鸟苷(acyclovir,简称ACV)2’位羟基分别与月桂酰氯或棕榈酰氯进行酯化反应,制得亲脂性前体药物无环鸟苷月桂酸酯和无环鸟苷棕榈酸酯(分别简称为C₁₂-ACV和C₁₆-ACV),使脂质体包封率从ACV的29.9%提高到C₁₂-ACV的95.6%和C₁₆-ACV的97.1%;漏泄实验表明在4℃透析60h后,一半以上的ACV从脂质体中漏泄,而C₁₂-ACV和C₁₆-ACV的滞留率分别为70%和80%;体外抗疱疹病毒的试验中,在最低试验浓度0.044μmol/L时,ACV不显示抗病毒活性,而C₁₆-ACV脂质体抑制细胞病变率达75%,说明前体药物通过与脂质体脂膜的结合增加了药物的进入细胞能力,从而提高了ACV的抗病毒能力。     

Tubulointerstitial nephritis caused by the antiviral agent foscarnet

The antiviral agent foscarnet has long been used in our unit to treat cytomegalovirus (CMV) infections in renal transplant patients. The clinical effect has been convincing and, apart from changes in serum calcium levels, very few side effects have been noted. We have, however, observed a nephrotoxic reaction in a series of patients with initially good renal function who therefore received high doses of foscarnet. Transplant biopsies performed in five of those patients revealed degenerative changes in the tubular epithelial cells as well as tubular calcium deposits and an infiltration of the interstitium by mixed mononuclear and polymorphonuclear leucocytes. Renal insufficiency was accompanied by high fever. After withdrawal of the drug, the temperature rapidly normalized, whereas serum creatinine continued to rise for about 3 days and then fell back towards previous levels. We conclude that transplant biopsies are of great value in distinguishing between a foscarnet nephrotoxic effect and CMV nephritis, various forms of rejection, and other causes of impaired renal function.     

大鼠创伤性肠粘连模型的制备及黄厚排气颗粒对其粘连程度的影响

为筛选出操作方法简便，结果稳定可控的大鼠创伤性肠粘连模型，观察中药复方黄厚排气颗粒对其粘连程度的影响，选用SD大鼠，手术造成肠粘连模型，用中药复方2．5、5．0、10．0g/kg连续治疗7d后观察肠粘连程度。结果表明，以盲肠型动物模型的制备较为理想，手术易于操作，结果稳定可控。用中药复方治疗后模型动物的肠粘连程度得到明显改善。提示黄厚排气颗粒对术后肠粘连有一定的预防作用。     

养阴清热、宣痹通络法治疗类风湿性关节炎的临床研究

目的 观察清络通痹颗粒治疗类风湿性关节炎阴虚络热证的临床疗效。方法 将118例患者随机分为清络通痹颗粒治疗组63例和雷公藤多甙片对照组55例，观察用药前后主要症状、体征和实验室检测指标的变化。结果 治疗组的临床治愈率为9．52％，临床治愈显效率为38．10％，总有效率为90．48％，疗效明显优于对照组的0％、20％、83．64％（P＜0．05）；治疗组的类风湿因子滴度、血沉、C反应蛋白、免疫球蛋白也明显降低，与对照组相比差异显著（P＜0．05或P＜0．01）。结论 清络通痹颗粒具有抗炎镇痛、调节免疫紊乱等作用，从而达到控制病情的治疗效果。     

青天葵抗甲、乙型流感病毒作用研究

目的研究青天葵在体外抗甲、乙型流感病毒株作用。方法选用狗肾细胞培养法考察青天葵不同极性部位对甲型(FM1)、乙型(昆40B)流感病毒的作用。结果青天葵水溶性部位对甲型流感病毒FM1有抑制作用。结论青天葵具有体外抗甲型流感病毒作用。     

慢性乙型肝炎患者抗病毒治疗后生存质量评估

目的了解慢性乙型肝炎（CHB）患者生存质量（QOL）状况,并通过抗病毒治疗对其QOL进行干预.方法采用横断面调查,选择2003年至2004年期间武汉大学人民医院感染科212例慢性乙型肝炎患者及健康人群185例,分别以健康状况问卷（SF-36）、医学应对问卷以及肝病特质问卷进行调查.结果与健康对照组比较,CHB患者除情感职能（RE）外,其他维度得分均明显低于健康对照者（P＜0.05）.CHB患者QOL与年龄、肝病特质问卷得分以及医学应对问卷中的屈服、面对因子分显著负相关（P＜0.01）.虽然不同抗病毒治疗方案对CHB患者QOL的影响差异无统计学意义,但完全应答组与无应答组比较,两组除社会功能（SF）（P＜0.05）以外其他维度的得分差异均有统计学意义（P＜0.01）;部分应答组与无应答组比较,仅RE、躯体疼痛（BP）及一般健康状况（GH）维度的得分差异有统计学意义（P＜0.05）.结论CHB患者QOL多个纬度均有受损.有效的抗病毒治疗能提高患者的QOL.