Dose reduction for the management of indinavir-related toxicity in human immunodeficiency virus type 1-infected patients in Taiwan: clinical and pharmacokinetic assessment.

This study evaluated the feasibility of reducing the indinavir (IDV) dosage in Taiwanese patients receiving the standard IDV/ritonavir (RTV) dosage of 800/100 mg twice a day who had undetectable plasma human immunodeficiency virus type 1 (HIV-1) RNA but had developed IDV-related toxicities. After dosage reduction to IDV/RTV 600/100 mg twice a day, the dose-related toxicity decreased and plasma HIV RNA remained undetectable at 24 weeks post-switch in all patients. The maximal plasma concentration (Cmax) and area under the plasma concentration-time curve of IDV decreased significantly (median, 6.3 vs 4.3 microg/mL and 1892 vs 1292 microg.min/mL, p=0.01 and 0.001, respectively) but the minimal plasma concentration remained at a similar level (median, 1.0 vs 0.8 microg/mL, p=0.12). This study found that the reduction in the dosage of IDV in HIV-1 infected patients receiving the standard IDV/RTV regimen guided by therapeutic drug monitoring decreased the Cmax, dose-related toxicity and medical cost without compromising viral control.     

Inhibition of the ubiquitin-proteasome system: a new avenue for atherosclerosis.

BACKGROUND: The ubiquitin-proteasome system (UPS) is thought to be functionally active in atherosclerosis (AS) lesions. Aspirin was found to be a potent inhibitor of the UPS in some tumour studies; however, its effect on AS remains to be demonstrated in vivo. METHODS: New Zealand rabbits were placed on a normal diet (N) or on a normal diet with aspirin (NI) or on an atherogenic diet without (H) or with aspirin (HI) for 12 weeks. Proteasome activity, concentrations of plasma lipids and levels of peroxidation were determined. Ubiquitin/ubiquitin-conjugates (Ub), IkappaBalpha, phosphorylated IkappaB (pIkappaBalpha) and p65 were investigated by Western blotting or immunochemistry. RESULTS: Concentrations of plasma lipids and peroxidation levels were higher in H or HI vs. N or NI. Histological analysis showed that atheroma was increased in H. Ub and IkappaBalpha were mainly localised in subendothelium and media vascular smooth muscle cells. Western blots revealed that Ub, IkappaBalpha, and pIkappaBalpha were increased, whereas p65 was lower in HI vs. H. The activity of the 20S proteasome was functionally active in H vs. N, NI or HI, while the 26S proteasome was not affected in any of the groups. CONCLUSIONS: Aspirin can attenuate the pathogenesis of atheroma formation, the degradation of IkappaBalpha and pIkappaBalpha, and lower the expression of p65, indicating that its therapeutic effects on AS may be via inhibition of the UPS.     

大脑中动脉支架内血栓形成1例报告

支架内血栓形成是支架置入术后的一种常见并发症。术后血管内皮损伤、胶原组织暴露和作为异物的支架均为引发血栓形成的可能机制。不能及时识别处理则成为再狭窄的重要原因。我们报告1例发生在大脑中动脉（middle cerebral artery，MCA）支架内的血栓形成，探讨其识别处理过程和可能的机制。     

大鼠大脑中动脉闭塞后丘脑钙调磷酸酶含量与活性的研究

目的 揭示大脑中动脉闭塞(MCAO)后丘脑钙调磷酸酶(CaN)的时空变化规律，探讨CaN的作用机制。方法 制备大鼠大脑中动脉永久性闭塞模型，分别测定缺血后不同时间点病灶侧丘脑CaN的活性和含量。结果 缺血后24h始丘脑CaN的含量下降且不恢复；CaN的活性在缺血后2h和4h减弱，6h始恢复至正常水平。可见，CaN的活性与含量分离。结论 大脑中动脉闭塞后丘脑CaN活性独特的时间变化规律显示其参与介导继发性丘脑损伤，可能具有毒性作用。     

注意缺陷多动障碍儿童初始沙盘游戏对照研究

目的 探究注意缺陷多动障碍儿童初始沙盘游戏特征.方法 对29名注意缺陷多动障碍儿童和29名正常儿童进行沙盘游戏干预,对照分析两组儿童初始沙盘游戏主题及沙具使用情况.结果 注意缺陷多动障碍儿童沙盘游戏主题较正常儿童混乱无序,两组比较差异有统计学意义(χ2=22.58,P<0.00);两组儿童在沙具使用方面比较差异无统计学意义(均P>0.05).结论 注意缺陷多动障碍儿童沙盘游戏具有独特特征以及一定的临床诊断筛查价值.     

门静脉注射白细胞介素-12治疗肝转移肿瘤的实验研究

目的　探讨通过门静脉系统局部应用白细胞介素 12 (IL 12 )对于肝转移肿瘤的治疗作用。方法　通过门静脉注射 2× 10 5个MCA 2 0 5肿瘤细胞建立小鼠肝转移肿瘤模型 ,同时脾脏被移植到皮下 ,作为反复多次向门静脉系统注射的途径。第 3～ 7天 ,0 1μgIL 12通过腹腔或脾脏注射 ,同时对照组中通过脾脏注射等体积的平衡盐水。第 2 1天检查肝转移肿瘤的情况。结果　在肝转移模型中 ,IL 12腹腔注射组和IL 12脾脏注射组的肝脏重量 (1 33± 0 0 8)g和 (1 2 9± 0 0 7)g明显小于对照组 (1 92± 0 17)g ,P <0 0 5 ,IL 12腹腔注射组和IL 12脾脏注射组的肝脏转移结节数目 (1 5 3± 0 5 8,0 6 0± 0 89)明显少于对照组 (18 2 5± 5 71,P <0 0 5 )。在IL 12脾脏注射组中 (n =6 ) ,3只小鼠的肝脏肿瘤完全消失。结论　通过门静脉系统局部应用IL 12是治疗肝转移肿瘤的有效方法。     

大鼠胰腺十二指肠移植的手术技巧

目的探讨建立大鼠胰腺十二指肠移植模型的手术技巧。方法不阻断体循环，采用双套管将供胰所带腹主动脉、门静脉分别与受鼠的左肾动、静脉进行套管吻合，尽量减轻对全身血流动力学的影响；同时行十二指肠空肠端侧吻合引流胰液，重建胰腺外分泌途径；围手术期注意补液、保暖及抗凝。结果100例手术中83例手术成功，术后移植胰腺具有内分泌功能，胰腺轻度充血水肿。结论该移植模型不阻断体循环且操作简单实用，其成功的关键在于手术操作及围手术期处理。     

持续不卧床腹膜透析患者的自我管理教育

目的探讨门诊腹膜透析患者自我管理教育的方法。方法对82例门诊腹膜透析患者进行自我管理教育,包括集体教育活动、讨论小组和个别指导等多种形式,责任护士随访评估。结果患者尿量、总液体清除量、肌酐清除率干预前后比较,差异有显著性意义（P〈0.05,P〈0.01）;干预前后患者睡眠质量及主观、客观生活质量显著提高,临床症状显著缓解（均P〈0.01）。结论以患者为中心的自我管理教育可提高门诊腹膜透析患者的生活质量。     

泰素蒂加顺铂治疗进展期NSCLC的临床研究

目的观察泰素蒂加顺铂方案治疗进展期非小细胞肺癌的临床疗效、毒副作用。方法收集可评价疗效的进展期非小细胞肺癌50例,以泰素蒂加顺铂方案进行化疗,泰素蒂75 mg/m2静脉滴注,第1天;顺铂25 mg/m2～30 mg/m2静脉滴注,第2天～第5天,每3周为一个周期,2～3周期后评价疗效和毒副反应并随访。结果50例患者中,总有效率为50.0 %,其中初治病例为53.1 %,复治病例为44.4 %,初复治病例间差异无显著性(P >0.05)。中位缓解期为5个月。中位生存期为9.5个月,1年生存率为61.0 %。毒副反应主要为骨髓抑制,白细胞下降达Ⅲ度、Ⅳ度者52.0 %,血小板下降达Ⅲ度、Ⅳ度者为14.0 %。血红蛋白下降不严重。其他毒副反应还有脱发、过敏反应、水钠潴留、静脉炎、末梢神经炎、口腔炎、腹泻等,但发生率均较低。结论泰素蒂加顺铂方案治疗进展期非小细胞肺癌,特别是复发病例,临床疗效比较满意,毒副反应能够耐受。辅以G蛳CSF可防治重度的骨髓抑制,有较好的临床应用价值。