A controlled study of postoperative radiotherapy for patients with completely resected nonsmall cell lung carcinoma. Groupe d'Etude et de Traitement des Cancers Bronchiques.

BACKGROUND: Postoperative radiotherapy is commonly used to treat patients with completely resected nonsmall cell lung carcinoma, but its effect on overall survival has not been established. METHODS: After undergoing complete surgical resection, 728 patients with non-small cell lung carcinoma (221 Stage I, 180 Stage II, and 327 Stage III) were randomized to receive either postoperative radiotherapy at a total dose of 60 gray or observation only . The main end point was overall survival. RESULTS: At the reference date, 218 of 355 patients in the control group had died and 262 of 373 in the radiotherapy group had died. Five-year overall survival was 43% for the control group and 30% for the radiotherapy group (P = 0.002, log rank test; relative risk [RR]: 1.33; 95% confidence interval [CI]: 1.11-1.59). This result was not modified by adjustment for potential prognostic factors. The excess mortality rate for the radiotherapy group was due to an excess of intercurrent deaths (P = 0.0001; RR: 3.47; the 5-year intercurrent death rate was 8% for the control group and 31% for the radiotherapy group). Radiotherapy had no significant effect on local recurrence (RR: 0.85; 95% CI: 0.64-1.14) and no effect on metastasis (RR: 1.06; 95% CI: 0.85-1.31). The rate of non-cancer-related death increased with the dose per fraction delivered.     

Chronic prenatal exposure to phenobarbital and long-term behavior effects on mice offspring

Objective: To assess the impact of chronic prenatal exposure to phenobarbital on long-term behavior in mice offspring.

Methods: Twenty-eight C3H/He mice were randomized to receive diet chow containing either a daily therapeutic dose of phenobarbital (2.5?mg in 10-g chow) or a placebo for 1 week before mating and throughout gestation. Offspring from eight litters of each treatment group were evaluated using motor function, arousal/motivation, anxiety-provoking and cognition tasks.

Results: No significant differences between groups were found in duration of gestation, litter size and birth weights. Fewer counts in a locomotor chamber were observed in phenobarbital-exposed offspring (524?±?31 vs. 688?±?54 for 60?min, p <?0.02; 4174?±?229 vs. 5230?±?406 for 22?h, p <?0.05). Initial reactions to a startle were more apparent among phenobarbital-exposed offspring (p <?0.03). Impaired co-ordination of hindlimbs was observed in the phenobarbital-exposed offspring during the wire maneuver (p <?0.001). Fewer entries into the mirrored chamber were observed after phenobarbital exposure (2.1 vs. 4.5; p <?0.05). Exposure to phenobarbital was not found to affect responses to learning and memory tasks (homing, tube runway, water runway, Morris maze).

Conclusion: Although cognition was unaffected by prenatal exposure to phenobarbital, subtle effects on locomotor activity, hindlimb co-ordination and responses to anxiety-provoking conditions require human correlation.     

Phase III comparative study of high-dose cisplatin versus a combination of paclitaxel and cisplatin in patients with advanced non-small-cell lung cancer.

PURPOSE: New effective chemotherapy is needed to improve the outcome of patients with advanced non-small-cell lung cancer (NSCLC). Paclitaxel administered as a single agent or in combination with cisplatin has been shown to be a potentially new useful agent for the treatment of NSCLC. PATIENTS AND METHODS: Between January 1995 and April 1996, 414 patients with stage IIIB or IV NSCLC were randomized to received either a control arm of high-dose cisplatin (100 mg/m(2)) or a combination of paclitaxel (175 mg/m(2), 3-hour infusion) and cisplatin (80 mg/m(2)) every 21 days. RESULTS: Compared with the cisplatin-only arm, there was a 9% improvement (95% confidence interval, 0% to 19%) in overall response rate for the paclitaxel/cisplatin arm (17% v 26%, respectively; P=.028). Median time to progression was 2.7 and 4.1 months in the control and paclitaxel/cisplatin arm, respectively (P=.026). The study, however, failed to show a significant improvement in median survival for the paclitaxel/cisplatin arm (8.6 months in the control arm v 8.1 months in the paclitaxel/cisplatin arm, P=.862). There was more hematotoxicity, peripheral neuropathy, and arthralgia/myalgia on the paclitaxel/cisplatin arm, whereas the high-dose cisplatin arm produced more ototoxicity, nausea, vomiting, and nephrotoxicity. Quality of life (QOL) was similar overall between the two arms. CONCLUSION: This large randomized phase III trial failed to show a significant improvement in survival for the paclitaxel/cisplatin combination compared with high-dose cisplatin in patients with advanced NSCLC. However, the paclitaxel/cisplatin combination did produce a better clinical response, resulting in an increased time to progression while providing a similar QOL.     

骨髓间充质干细胞移植对心肌梗死大鼠血管新生和内皮功能的影响

目的:通过检测血特异的内皮细胞标记物管性假血友病因子,观察骨髓间充质干细胞移植治疗急性心肌梗死后大鼠局部新生血管情况,并探讨内皮血管功能指标E-选择素与新生血管的关系。方法:实验于2005-09/2006-06在唐山工人医院中心实验室完成。①选用清洁级健康近交系SD大鼠40只,随机数字表法分为假手术组、模型对照组、干细胞移植组、细胞培养基组,10只/组。②另取1只大鼠用于骨髓间充质干细胞的提取。大鼠处死后无菌条件下分离股骨和胫骨,应用密度梯度法分离培养骨髓间充质干细胞。待细胞80%贴满培养瓶底时,用乙二胺四乙酸和胰蛋白酶混合消化传代。将50mg/L4,6-二脒-2-苯基吲哚加入第3代细胞培养基中,制成细胞悬液备用。③术前各组大鼠均行气管插管,建立急性心肌梗死模型,以远端供血区心肌组织颜色苍白、心电图检测Ⅱ导联ST段持续抬高为模型建立成功的标志。假手术组仅开胸予以前降支穿线但不结扎。④造模成功后1～3h,干细胞移植组用微量注射器吸取4,6-二脒-2-苯基吲哚标记好的第3代骨髓间充质干细胞悬液50μL,直接注入梗死区边缘心肌组织。细胞培养基组按干细胞移植组的方法于相同部位注射等量无血清DMEM低糖培养基(pH值为6.9),模型对照组仅制作心肌梗死模型不作其他处理,假手术组亦不作其他处理。⑤造模后2,4周各组处死半数大鼠,切取心脏组织,于梗死边缘区心肌组织制作切片,荧光显微镜下观察4,6-二脒-2-苯基吲哚标记的供体细胞。链霉亲和素免疫组化法检测心肌细胞中血管性假血友病因子评估新生血管情况,酶联免疫吸附法测定血清E-选择素含量,评估内皮功能。结果:40只大鼠均进入结果分析。①各组大鼠心脏标本4,6-二脒-2-苯基吲哚标记移植细胞存活状况:骨髓干细胞移植治疗后,荧光显微镜下可见成团和散在的DAPI阳性细胞,其余3组大鼠心脏标本中均未见荧光细胞。②各组大鼠血清E-选择素的检测:心肌梗死后2,4周模型对照组及细胞培养基组E-选择素明显增高,与假手术组比较差异显著[2周:(36.04±4.47),(34.10±2.04),(13.37±3.01)μg/L;4周:(33.02±4.78),(33.96±5.18),(13.94±2.87)μg/L,P<0.01],干细胞组移植组E-选择素较模型对照组明显降低[2周:(24.29±3.51),(36.04±4.47)μg/L;4周:(17.45±3.22),(33.02±4.78)μg/L,P<0.05]。③各组大鼠心肌组织血管性假血友病因子表达情况:链霉亲和素免疫组化法显示,造模后2周干细胞移植组心肌细胞血管性假血友病因子呈强阳性表达,模型对照组和细胞培养基组血管性假血友病因子表达减弱。造模后4周干细胞移植组心肌细胞血管性假血友病因子表达仍呈强阳性,模型对照组和细胞培养基组血管性假血友病因子表达有减弱趋势。结论:①移入的骨髓间充质干细胞存活。②骨髓干细胞移植治疗实验性大鼠心肌梗死模型后,可提高心肌细胞血管性假血友病因子水平,促进局部血管新生。③移植后心肌梗死大鼠血清中E-选择素的降低,可能与其参与血管新生有关,同时也提示骨髓干细胞移植不会诱发E-选择素增高而加重动脉硬化。     

中药桔丙酯联合降糖治疗对2型糖尿病患者甲襞微循环及血液流变学的影响

目的观察中药桔丙酯注射液联合降糖治疗对2型糖尿病甲襞微循环及血液流变学的影响,探讨其治疗机制.方法于2005-10/2006-08选择河北北方学院附属校医院、张家口市第一人民医院门诊及住院收治的2型糖尿病患者48例,为治疗组.应用注射用桔丙酯治疗,桔丙酯180 mg,次,1次,d,连用2周;健康志愿者30例为对照组.采用微循环显微镜,于治疗前后常规检查左手第4指甲襞第一排管袢,按田牛加权积分法对16项指标综合定量分析,判断疗效和甲襞微循环的变化.同时观察2型糖尿病患者治疗前后血液流变学各项指标的变化.结果①治疗组治疗前甲襞微循环及血液流变学各项指标均表现为不同程度的异常,治疗后甲襞微循环及血液流变学各项指标明显改善.甲襞微循环由治疗前的中、重度异常恢复到大致正常,治疗后总积分值低于治疗前(分别为1.52±0.69,4.52±0.82,t=3.96,P＜0.05).②血液流变学指标变化表明,血浆黏度、全血黏度、纤维蛋白原及红细胞电泳等各指标经桔丙酯治疗后均明显降低(P＜0 05).结论中药桔丙酯联合降糖治疗能够明显改善2型糖尿病患者血流变异常及微循环障碍.