Phase I study of high-dose cytosine arabinoside and etoposide in patients with advanced malignancies

Summary Cytosine arabinsodie (ara-C) and etoposide (VP-16) display synergy in the laboratory. Twenty-six patients participated in a phase I study of high-dose ara-C in combination with VP-16. The dose of VP-16 was held constant at 50 mg/m² as an intermittent infusion over 33 h; escalating doses of ara-C were given as infusions during hours 9–12 and 21–24. Myelosuppression was the dose-limiting toxicity and occurred with doses considerably less than those expected from studies of the two drugs as single agents. The suggested initial doses for phase II trials with this schedule are 750 mg/m²×2 doses of ara-C and 50 mg/m² of VP-16. Nonhematologic toxicity was minimal; therefore, further dose escalation is feasible in patients in whom myelosuppression is acceptable.Supported in part by grants from the National Cancer Institute (CA-12197 and CA-09422) and the American Cancer Society CF-85-182     

散结消肿贴中大黄重楼提取工艺优选研究

目的：优选散结消肿贴中大黄、重楼的渗漉提取工艺。方法：以总固体物得率和总蒽醌得率为指标，用正交实验优选。结果：工艺中影响最大的因素是乙醇浓度，其次是乙醇用量，浸泡时间影响较小。最佳工艺条件为乙醇浓度65％，乙醇用量8倍量。浸泡时间24h。结论：渗漉法操作简单，成份破坏少，用优选所得条件进行提取，总蒽醌和总固体物得率均较高，优选结果可用于散结消肿贴中大黄、重楼的提取。     

膳食黑米皮抑制高脂诱导的家兔动脉粥样硬化形成及其机制的初步探讨

目的 探讨膳食黑米皮对高脂诱导的家兔动脉粥样硬化形成的影响及其作用机制。方法 24只雄性新西兰大耳白家兔,按体重随机分为3组,分别饲以正常基础饲料、高脂饲料(含96％基础饲料、0.5％胆固醇、3.5％猪油)、黑米皮饲料(含 91％基础饲料、0.5％胆固醇、3.5％猪油、5％黑米皮),实验期为 60d。用图像分析法测定各组家兔主动脉脂质斑块面积,并分析家兔氧化与抗氧化状态。结果 黑米皮实验家兔的主动脉壁斑块面积较高脂组低66%(P<0.001);黑米皮组实验家兔的主动脉壁8-ohdG含量和血清及主动脉壁中MDA水平也低于高脂组(P<0.05 );而红细胞及主动脉壁中SOD水平和血清α-生育酚含量在两个处理组之间差异无显著性。结论 膳食黑米皮可以抑制高脂诱导的家兔动脉粥样硬化形成,其机制可能与之降低机体氧化应激水平及过氧化脂质生成有关。     

肿瘤抑制因子PTEN蛋白在自发性高血压大鼠主动脉平滑肌中的表达

目的：研究PTEN蛋白在雄性自发性高血压大鼠及SD大鼠主动脉中的表达。方法：取18周龄和26周龄雄性自发性高血压大鼠及同龄雄性SD大鼠主动脉石蜡包埋切片，免疫组织化学观察PTEN在主动脉平滑肌细胞中的表达。结果：SD大鼠主动脉平滑肌细胞中存在PTEN阳怀免疫反应产物。自发性高血压大鼠主动脉平滑肌细胞也存在PTEN阳性免疫反应产物，但免疫反应产物的染色强度明显低于SD大鼠。结论：SD大鼠主动脉平滑肌细胞PTEN高表达，自发性高血压大鼠主动脉平滑肌细胞PTEN表达呈下降趋势。提示PTEN可能在自发性高血压大鼠主动脉平滑肌细胞重塑过程中发挥作用。     

腹腔镜在直肠癌保肛手术中的应用与评价

腹腔镜技术存结直肠恶性肿瘤手术中的应用．是结直肠肿瘤手术发生的重大变革之一．该文主要对腹腔镜技术在直肠癌保肛手术中应用的原则、病例选择、技术关键进行论述，并对腹腔镜直肠癌保肛手术的可行性、肿瘤根治性、短期疗效、远期疗效进行了评价．认为腹腔镜直肠癌根治手术术后生命质量、远期疗效、卫生经济学评价将是今后需要探讨的重要目标．     

Urinary excretion of 5-oxoproline (pyroglutamic aciduria) as an index of glycine insufficiency in normal man

1. The evidence is accumulating to suggest that glycine, the simplest amino acid, is conditionally essential in man. Benzoic acid, by conjugation with glycine to form hippuric acid, is known to deplete the free glycine pool of the body. Glycine is one substrate for the enzyme glutathione synthase (EC 6.3.2.3) and in the inborn error of metabolism in which glutathione synthase function is defective, increased quantities of 5-oxoproline are excreted in the urine. 2. An oral dose of 4-10 g sodium benzoate was given to six normal adults to deplete the metabolic pool of glycine, and the urinary excretion of 5-oxoproline was followed for 6 h. In five of the six, a significant increase in the urinary 5-oxoproline was seen within 3 h. 3. These findings show that 5-oxoprolinuria can result from limited glycine availability, and may provide a useful test for assessing glycine sufficiency in a range of physiological and pathological states.     

Cast-brace treatment of ankle sprains

Forty-two severely sprained ankles treated by a cast-brace have been reviewed. This method was devised to avoid the disadvantages of immobilization. Diagnosis was based on the history and clinical signs. Strain films were taken in 31 patients but it is submitted that this investigation may be misleading unless general anaesthesia is used. The results of the treatment by cast-brace compare favourably with those by other methods and it is considered that patients were able to return to sport in a shorter time.     

多柔比星肾病肾损伤早期核因子-κB和血管紧张素ⅠⅡ的表达及关系探讨

目的　探讨在多柔比星 (阿霉素 )肾病综合征 (NS)幼年大鼠肾损伤过程中核因子 (NF) κB和血管紧张素ATⅠ、ATⅡ的表达及其相关性。方法　 4周龄雄性Wistar大鼠单侧肾切除加腹腔注射阿霉素造成NS模型 ,分别以免疫组织化学和原位杂交检测ATⅠ、ATⅡ和NF κB。结果　肾病组随着病变时间的延长 ,NF κB和ATⅠ、ATⅡ表达的强度和部位均呈增强趋势 ,治疗组在相同时间点则两者都有不同程度下调 (P <0 .0 5 )。结论　在阿霉素肾病损伤过程中NF κB和ATⅠ、ATⅡ起着介导作用。     

Prediction of steady-state bioequivalence relationships using single dose data I-linear kinetics

Simulated data using a linear one- and two-compartment body model with different absorption characteristics were used to evaluate the ability of single dose bioavailability data to predict the relationships that exist at steady state. This was done by comparing the confidence intervals obtained from single and multiple dose data sets for the parameters of Tmax, Cmax, and area under the curve from time zero to infinity (AUC0-infinity). As a consequence of Tmax and Cmax decreasing and increasing from single to multiple dosing regimens, the confidence intervals for these parameters reflected these changes. The 90 per cent confidence interval expressed as a percentage of the reference mean increased or decreased for Tmax dependent upon the ratio of Ka test/Ka reference, and decreased for Cmax while the interval for AUC0-infinity exhibited no predictable pattern and appeared to be influenced by the amount of error in the data set. Alteration of either the dosing interval or the fraction absorbed did not affect the pattern of change in the confidence intervals for Tmax and Cmax, but the latter did result in a decrease in the interval for AUC0-infinity. Analysis of the confidence intervals for Tmax, Cmax and AUC0-infinity in bioequivalency studies for quinidine gluconate and procainamide hydrochloride following administration of single and multiple doses to different subjects appeared to be consistent with the patterns observed for the simulated data sets.