国产奥沙利铂联合氟尿嘧啶-甲酰四氢叶酸钙治疗晚期大肠癌的疗效观察

目的观察奥沙利铂联合氟尿嘧啶-甲酰四氢叶酸钙治疗晚期大肠癌的临床疗效及毒副反应。方法经病理或细胞学证实的Ⅲ期和Ⅳ期大肠癌患者21例,给予奥沙利铂135 mg/m2,d1静滴;甲酰四氢叶酸钙(CF)200 mg/m2,d1~5静滴,5-Fu 300 mg/m2,d1~5静滴。结果21例患者中,部分缓解7例,稳定8例,进展6例,总效率为33.3%。主要的毒副反应为消化道症状和感觉神经毒性,绝大多数患者耐受良好。结论奥沙利铂联合氟尿嘧啶-甲酰四氢叶酸钙治疗晚期大肠癌疗效确切,患者耐受良好,值得推广。     

奥沙利铂联合氟尿嘧啶-甲酰四氢叶酸钙治疗晚期胃癌的临床观察

目的:观察奥沙利铂联合氟尿嘧啶-甲酰四氢叶酸钙化疗方案治疗晚期胃癌的近期疗效和毒副反应。方法:奥沙利铂130mg/m2静脉滴注2h,第1天,甲酰四氢叶酸钙200mg/m2 5-氟尿嘧啶300mg/m2静滴4h,第1～5天。21d为1个周期,治疗3个周期后评定疗效。结果:共治疗22例,CR0例,PR7例,SD8例,PD7例,总有效率为32.7%。主要毒性反应是消化道反应,其次是神经毒性。结论:奥沙利铂联合氟尿嘧啶-甲酰四叶酸钙治疗晚期胃癌,能使肿块缩小,缓解症状,近期疗效好,毒副反应轻,多数病人能耐受。     

草酸铂联合替加氟及甲酰四氢叶酸钙治疗胃肠肿瘤的疗效观察

目的：观察草酸铂联合替加氟、甲酰四氢叶酸钙治疗晚期胃癌、肠癌的疗效。方法：草酸铂130mg/m2,静脉滴注,d1;甲酰四氢叶酸钙100mg/m2,静脉滴注,d1～5;替加氟20mg/kg,静脉滴注4～6h,d1～5,21d为1个周期。结果：本组患者中,CR1例,PR12例,SD14例,PD5例,总有效率为40.6%。初治有效率为45.4%,复治有效率为38.1%,胃癌与大肠癌有效率分别为41.7%和37.5%。主要不良反应为消化道反应及外周神经毒性。结论：草酸铂联合替加氟及甲酰四氢叶酸钙治疗方案疗效肯定,经济实用,毒性可耐受。     

奥沙利铂联合5-氟脲嘧啶、甲酰四氢叶酸钙治疗晚期大肠癌的疗效观察

目的 :观察奥沙利铂联合 5 -氟脲嘧啶、甲酰四氢叶酸钙对晚期大肠癌治疗近期疗效及延长生存期的应用价值。方法 :将 6 3例晚期大肠癌随机分为实验组和对照组 ,实验组采用奥沙利铂 130mg/m2 静滴 2h ,第 1天 ;加甲酰四氢叶酸钙 2 0 0mg/m2 +5 -氟脲嘧啶 4 0 0mg/m2 静滴 8h以上 ,第 1～ 5d ;对照组甲酰四氢叶酸钙2 0 0mg/m2 +5 -氟脲嘧啶 4 0 0mg/m2 静滴 8h以上 ,第 1～ 5d。结果 :实验组总有效率为 5 6 .3% ,中位无进展生存期为 10 .5月 ,中位生存期为 2 1.6月 ;对照组分别为 2 2 .6 % ,5 .8月及 13.7月 ,两组相比 ,差异有显著性 (P<0 .0 5 ) ,毒副反应两组相比 ,实验组的神经毒性反应高于对照组 (Q <0 .0 5 ) ,但在其他毒副反应方面 ,两组相比 ,差异无显著性 (P >0 .0 5 )。结论 :奥沙利铂联合 5 -氟脲嘧啶、甲酰四氢叶酸钙对晚期大肠癌治疗有明显疗效 ,能延长生存期 ,毒副反应多数病人能耐受。     

甲酰四氢叶酸钙与5-氟脲嘧啶联合用药治疗胃肠道恶性肿瘤

目的：观察中剂量甲酰四氢叶酸钙（CF）与5-氟脲嘧啶（5-Fu)联合用药治疗胃肠道恶性肿瘤的疗效。方法：甲酰四氢叶酸钙（CF）200mg/m^2,与5-氟脲嘧啶（5-Fu)600mg/m^2,分别静脉滴注。结果：54例胃肠道恶性肿瘤CR8例,PR27例总有效率64.8%。结论：甲酰四氢叶酸钙作为生物调节剂与5-氟脲嘧啶联合用药疗效较单一用药提高疗效2.2倍,毒副反应主要为胃肠道、造血系统,与单一用药反应相差无几。     

以草酸铂联合甲酰四氢叶酸及氟尿嘧啶为二线方案治疗晚期大肠癌的疗效

目的　研究国产草酸铂联合甲酰四氢叶酸、氟尿嘧啶治疗对甲酰四氢叶酸、氟尿嘧啶耐药的晚期大肠癌的临床疗效。方法　 30例患者给予国产草酸铂 130mg/m2 ,静脉滴注 3h ,第 1天 ,甲酰四氢叶酸 2 0 0mg/m2 ,静脉滴注 2h ,第 1～ 5天 ,氟尿嘧啶 5 0 0mg/m2 ,静脉滴注 6h ,第 1～ 5天 ,每 3周重复 ,3个周期后评价疗效。结果　所有患者可评价疗效 ,无CR病例 ,PR 9例 ,SD 14例 ,PD 7例 ,总有效率为 30 % ,毒副作用主要为消化道反应、神经毒性和骨髓抑制。结论　国产草酸铂联合甲酰四氢叶酸和氟尿嘧啶治疗对甲酰四氢叶酸、氟尿嘧啶耐药的晚期大肠癌疗效较好、其毒副反应是可以耐受的。     

紫杉醇联合5-氟尿嘧啶/甲酰四氢叶酸钙治疗21例晚期胃癌的疗效观察

观察紫杉醇加5-氟尿嘧彤甲酰四氢叶酸钙联合方案治疗晚期胃癌的近期疗效及不良反应。结果认为紫杉醇和5-氟尿嘧彤甲酰四氢叶酸钙治疗晚期胃癌有效,且毒副反应可以耐受。     

奥沙利铂合用甲酰四氢叶酸钙和5氟脲嘧啶治疗胃肠道肿瘤的疗效观察

目的：观察奥沙利铂联合甲酰四氢叶酸钙和5-氟脲嘧啶(OXA-LV5Fu)治疗胃肠道肿瘤的疗效及不良反应。方法：奥沙利铂(OXA)130mg／m^2,静脉滴注,第1日;甲酰四氢叶酸钙(LV)200mg／m^2,静脉滴注2小时,第1-5日;5-氟脲嘧啶(5-Fu)40mg／m^2,静脉缓慢滴注6-8小时,第1-5日。每21日为一疗程,进行4个疗程后判定疗效。结果：观察23例,总有效率(CR PR)47、8％(11／23)。主要不良反应为轻度的血液学毒性、胃肠道反应和外周感觉神经异常。结论：该方案治疗胃肠道肿瘤,疗效高,毒性小。     

基于4-氨基-5-甲酰基-8,10-二去氮杂四氢叶酸二乙酯侧链的水解反应条件优化

目的：改进经典抗叶酸类药物关键中间体4-氨基-5-甲酰基-8,10-二去氮杂四氢叶酸二乙酯侧链的水解条件。方法：以经典叶酸拮抗剂侧链N-(4-氨基苯甲酰)-L-谷氨酸二乙酯(1)为反应原料,尝试了氢氧化钠（NaOH）和氢氧化钾（KOH）2种碱催化、20~180 min 5种反应时间和0.175~1 mol/L 3种碱浓度的反应条件,用高效液相色谱法检测目标产物和副产物,最终确定副产物为单酯水解产物以及酰胺键水解产物,并以此为依据完成了4-氨基-5-甲酰基-8,10-二去氮杂四氢叶酸二乙酯(5)水解条件的优化。结果:改进后的4-氨基-5-甲酰基-8,10-二去氮杂四氢叶酸二乙酯侧链的水解条件为0.3 mol/L KOH溶液中室温条件反应60 min,在该反应条件下,水解反应收率为95.6%。反应产物通过磁共振氢谱（1H nuclear magnetic resonance,1H NMR）、磁共振碳谱（13C nuclear magnetic resonance,13C NMR）和电喷雾飞行时间质谱（electrospray ionization time of flight mass spectrometry,ESI-MS）分析鉴定后结构正确,并通过高效液相色谱法确定其纯度为96%。新的水解反应条件避免了副产物的生成,提高了反应收率。结论：利用新的水解条件可以简便、高效地完成4-氨基-5-甲酰基-8,10-二去氮杂四氢叶酸二乙酯的水解反应,该条件对经典叶酸拮抗剂的合成和生产工艺的改进也有重要的意义。     

甲氨喋呤、四氢叶酸和米非司酮联合治疗剖宫产术后瘢痕部位妊娠的临床疗效观察

目的:探讨甲氨蝶呤不同途径给药联合四氢叶酸和米非司酮治疗剖宫产术后瘢痕部位妊娠的临床效果。方法:将30例确诊为剖宫产术后瘢痕部位妊娠的患者随机分为甲乙两组,甲组15例MTX150mg静脉点滴,乙组MTX50mg单次肌肉注射给药,两组均给予米非司酮50mg口服,2次/d,连服3d,甲酰四氢叶酸钙6mg肌注。通过超声及血β-hCG的变化动态观察疗效。结果:甲组治疗成功14例,成功率93.33%,乙组治疗成功12,成功率80%,静脉给药相对于肌肉注射疗效更优。结论:MTX联合米非司酮,四氢叶酸治疗剖宫产瘢痕部位妊娠取得满意的疗效,用药安全,简便,适用于剖宫产瘢痕部位妊娠保守治疗的临床应用。     

炮制对天南星毒性成分草酸钙针晶及凝集素蛋白含量的影响

目的 探究天南星炮制前后内源性毒性成分的含量变化,建立天南星毒性控制指标检测方法.方法 采用HPLC法对35批天南星炮制前后草酸钙含量进行测定,色谱柱为Megres C18(250 mm×4.6 mm,5μm),流动相为0.5％磷酸水溶液,流速0.8 mL·min-1,检测波长220 nm,柱温25℃;采用Wester...     

血浆钙离子浓度对血小板聚集的影响

目的 探讨血浆钙离子浓度对血小板聚集检验结果的影响.方法 采集健康志愿者静脉血标本(n=42),添加不同量的氯化钙,采用血浆比浊法进行血小板聚集率检测.结果 血浆Ca2+浓度在2.1-0.12mmol/l时,二磷酸腺苷(ADP)和花生四烯酸(AA)诱导的血小板聚集率分别为(75.9±10.4)％-(51.8±9.6)％和(83.7±13.9)％-(64.4±12.2)％,血小板聚集率随Ca2+浓度的降低而降低;血浆Ca2+浓度在2.1-33.66mmol/L时,ADP和AA诱导的血小板聚集率分别为(75.9±10.4)％-(94.7士4.8)％和(83.7士13.9)％-(93.2±5.5)％,随Ca2+浓度的增高而增高;Ca2+浓度为39.00mml/L时,血小板聚集率明显降低[ADP和AA诱导的血小板聚集率分别为(9.1±5.3)％和(11.1±4.5)％,均P＜0.01].结论 钙离子浓度波动对血小板聚集检验结果有明显影响.低于生理钙浓度(2.1mmol/L血小板聚集率随Ca2+浓度的降低而降低,高于生理钙浓度血小板聚集率随Ca2+浓度的增高而增高;血钙过高(≥39.0mmol/L)抑制血小板聚集.     

The attenuative effect of purified protein derivative sensitization on T helper 2 reaction and eosinophil infiltration of the lung in ovalbumin sensitized mice

OBJECTIVE To identify the effects of tuberculin purified protein derivative (PPD) sensitization on attenuating pulmonary T helper 2 (Th2) reaction and eosinophil infiltration in ovalbumin sensitized mice, and to search for the possibility of its clinical use in the management of asthma in a new way.

METHODS Sixty C57BL/6 mice were sensitized with PPD and then with ovalbumin and aluminum hydroxide, and randomized into 4 groups: ovalbumin (OVA), pre-PPD, post-PPD and control groups. Aerosol PPD were administered 3 h before or after ovalbumin challenge in the pre-PPD and post-PPD groups respectively, and control group received aerosol PPD only. IL-4, IL-5 expression was detected by immunocytochemistry in situ hybridization. Lung slides were stained with eosin and hemotoxylin, and pathological changes were observed.

RESULTS Ovalbumin aerosol inhalation caused a mixed inflammatory infiltration dominated by CD4+ T lymphocytes and eosinophils in the lung of sensitized mice. 87.5%-89.7% and 89.0%-89.2% of the CD4+ T lymphocytes were IL-4 mRNA+ and IL-5 mRNA+ respectively. 88.7%-91.2% of IL-4 mRNA+ cells and 89.8%-90.6% of IL-5 mRNA+ cells were CD4+ T lymphocytes in OVA group. Aerosol administration of PPD markedly suppressed IL-4 and IL-5 expression, and lung eosinophil infiltration. It was more effective in pre-PPD group. 76.6%-78.0% of IL-4 mRNA+ and 73.8%-79.7% of IL-5 mRNA+ cells were CD4+ and 78.1%-84.9% and 78.4%-85.3% of the CD4+ cells were IL-4 mRNA+ or IL-5 mRNA+ respectively in pre-PPD group, both were markedly lower than that of OVA group. CD4+ percentage of IL-4 mRNA+ and IL-5 mRNA+ cells were 80.7%-82.0% and 78.0%-83.9% in post-PPD group, which were markedly lower than that of OVA group.

CONCLUSIONS Sensitization with PPD by intraperitoneal injection and then challenged by PPD inhalation markedly suppressed IL-4, IL-5 expression and eosinophil infiltration, and attenuated pulmonary Th2 reaction in ovalbumin sensitized mice. This induces Th1 type reaction and inhibits Th2 cell differentiation. It may be beneficial for glucocorticoids dependent or resistant patients.

     

临床试验中纵向缺失数据不同处理策略统计性能的比较

目的：评估不同缺失值处理方法在不同缺失模式、缺失机制及缺失比例下双臂优效临床试验中的统计性能,筛选出相应的最优缺失值处理方式。方法：使用SAS 9.4 软件分别生成不同缺失模式（单调缺失或任意缺失）、缺失机制（完全随机缺失或随机缺失）以及不同缺失比例（0%～5%、5%～10%、10%～15%）的纵向模拟数据集,基于各模拟数据集分别使用不同缺失值处理策略进行疗效估计,并分别与完整数据集比较,以评价不同缺失值处理方式的统计性能。结果：当缺失比例＜5%时,任意缺失模式下不同缺失值处理方式所得效应估计值均较为接近,单调缺失模式下只有重复测量混合效应模型（MMRM）以及多重填补后协方差分析误差较小。当缺失比例＞5%时,不论缺失机制以及缺失模式,不同协方差矩阵结构的MMRM以及多重填补不同次数后协方差分析所得效应估计值与真实值之间仍最接近,且前者较后者更为稳定。而单一填补方式以及模式混合模型（PMM）随着缺失比例增加,其效应估计的误差也增加,尤其是单调缺失,当缺失比例为10%～15%时其误差最大。结论：不同缺失比例（0%～5%、5%～10%、10%～15%）,缺失模式（单调缺失或任意缺失）以及缺失机制（完全随机缺失或随机缺失）下,MMRM误差最小,提示MMRM是处理双臂优效性临床试验中纵向定量数据缺失的首选方案。     

Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy With Risedronate Therapy (VERT) Study Group.

CONTEXT: Risedronate, a potent bisphosphonate, has been shown to be effective in the treatment of Paget disease of bone and other metabolic bone diseases but, to our knowledge, it has not been evaluated in the treatment of established postmenopausal osteoporosis. OBJECTIVE: To test the efficacy and safety of daily treatment with risedronate to reduce the risk of vertebral and other fractures in postmenopausal women with established osteoporosis. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled trial of 2458 ambulatory postmenopausal women younger than 85 years with at least 1 vertebral fracture at baseline who were enrolled at 1 of 110 centers in North America conducted between December 1993 and January 1998. INTERVENTIONS: Subjects were randomly assigned to receive oral treatment for 3 years with risedronate (2.5 or 5 mg/d) or placebo. All subjects received calcium, 1000 mg/d. Vitamin D (cholecalciferol, up to 500 IU/d) was provided if baseline levels of 25-hydroxyvitamin D were low. MAIN OUTCOME MEASURES: Incidence of new vertebral fractures as detected by quantitative and semiquantitative assessments of radiographs; incidence of radiographically confirmed nonvertebral fractures and change from baseline in bone mineral density as determined by dual x-ray absorptiometry. RESULTS: The 2.5 mg/d of risedronate arm was discontinued after 1 year; in the placebo and 5 mg/d of risedronate arms, 450 and 489 subjects, respectively, completed all 3 years of the trial. Treatment with 5 mg/d of risedronate, compared with placebo, decreased the cumulative incidence of new vertebral fractures by 41 % (95% confidence interval [CI], 18%-58%) over 3 years (11.3 % vs 16.3%; P= .003). A fracture reduction of 65% (95% CI, 38%-81 %) was observed after the first year (2.4% vs 6.4%; P<.001). The cumulative incidence of nonvertebral fractures over 3 years was reduced by 39% (95% CI, 6%-61 %) (5.2 % vs 8.4%; P = .02). Bone mineral density increased significantly compared with placebo at the lumbar spine (5.4% vs 1.1 %), femoral neck (1.6% vs -1.2%), femoral trochanter (3.3% vs -0.7%), and midshaft of the radius (0.2% vs -1.4%). Bone formed during risedronate treatment was histologically normal. The overall safety profile of risedronate, including gastrointestinal safety, was similar to that of placebo. CONCLUSIONS: These data suggest that risedronate therapy is effective and well tolerated in the treatment of women with established postmenopausal osteoporosis.     

非穿透性小梁手术治疗开角型青光眼的Meta分析

目的：对非穿透性小梁手术治疗开角型青光眼的疗效进行Meta分析。方法：检索MEDLINE和中国生物医学文献数据库，获得以往发表的相关论文。根据临床和统计标准进行合并分析，评价非穿透性小梁手术的降压效果。结果：总计有26篇文献纳入Meta分析。无需降压药物治疗而术后眼压控制良好患者的合并百分率：单纯深层巩膜切除术为71．3％[95％CI为56．2％～86．5％]，深层巩膜切除术联合胶原植入物为58．5％[95％CI为47．8％～69．2％]，深层巩膜切除术联合交键透明质酸植入物为62．0%[95％CI为51．0％～73．0％]，粘性小管切除术为69．7％[95%CI为50．5％～88．9％]。非穿透性小梁手术和小梁切除术的合并危险差为2％[95％CI为-8％0～12％]。结论：非穿透性小梁手术是药物难以控制的开角型青光眼的一种很好的治疗措施，治疗成功率超过60％，眼压控制效果和标准小梁切除术近似。但联合植入物的应用并没有显著改善治疗效果的意义。     

Experience with cardiac valve operations in Cape York Peninsula and the Torres Strait Islands, Australia

OBJECTIVE: To describe the outcome of valve surgery, for rheumatic heart disease (RHD) and non-RHD, in residents of Cape York Peninsula and the Torres Strait Islands referred to the Cairns Base Hospital specialist outreach service. DESIGN AND PARTICIPANTS: Retrospective review of medical records on all patients residing in the outreach area who had surgery for valvular heart disease between 1 January 1992 and 31 December 2004. MAIN OUTCOME MEASURES: Operation type and perioperative characteristics; 5- and 10-year survival rates; reoperation rates; complications. RESULTS: Forty-seven patients met the selection criteria; the median age was 40 years (range, 4-76 years); and 39 patients were Indigenous. RHD was the predominant cause of valve dysfunction (30/47 patients). Thirty-seven patients had valve replacements, six had valve repair and four had balloon valvotomy as the initial procedure. There were three bleeding complications, two episodes of operated valve endocarditis, and six embolic complications. There were nine valve-related deaths (six in the first 5 years). At 5 years, all seven patients who had had valve repair or balloon valvotomy were alive. Seven of the 47 patients required reoperation. Survival analysis showed freedom from valve-related deaths to be 83% (95% CI, 66%-92%) at 5 years and 61% (95% CI, 33%-80%) at 10 years. Freedom from reoperation at 5 years was 88% (95% CI, 71%-95%). Among the 30 patients with RHD, freedom from valve-related death was 80% (95% CI, 60%-92%) at 5 years and 52% (95% CI, 21%-75%) at 10 years. In patients with RHD, freedom from reoperation at 5 years was 87% (95% CI, 65%-96%). CONCLUSION: Valvular heart disease results in substantial morbidity and mortality, despite intervention. Efforts need to focus on prevention of rheumatic fever and closer follow-up.     

槲皮素、芦丁及葛根素抑制HDL氧化修饰作用的研究

目的研究槲皮素、芦丁及葛根素等抑制HDL氧化修饰的作用。方法按一次性密度梯度超速离心法分离人血清HDL,分别加5μmol／L槲皮素、芦丁及葛根素与HDL温育3h。然后利用Cu^2 介导体外氧化修饰脂蛋白的方法,观察HDL氧化修饰不同时间,其A234、REM、TBARS及蛋白质羰基的动力学改变,并与不加药物的对照组比较。结果Cu^2 介导氧化HDL修饰时,在2、4、6、8、12及24h后,其A234、REM、TBARS及蛋白质羰基含量均逐步增加;加入5．0μmol／L槲皮素、芦丁及葛根素的实验组,Cu^2 介导HDL的氧化修饰分别延迟2～4h、4h和2～4h。其A234、REM、TNAR及载脂蛋白羰基含量较对照组降低;槲皮素实验组分别降低24．2％～49．0％、3．0％～25．0％、7．9％～34．1％及28．3％～50．4％;芦丁实验组降低9．4％～42．0％、4．0％～20．7％、1．2％～26．8％及18．6％～64．6％;葛根素实验组载脂蛋白羰基含量较对照组降低14．1％～52．1％。而其A234、REM,TBARS虽有降低,但降低幅度不大。结论槲皮素及芦丁可显著抑制HDL的氧化修饰,而葛根索的抑制作用较小。     

异鼠李素及橙皮甙抑制HDL氧化修饰作用的研究

目的 研究异鼠李素及橙皮甙对高密度脂蛋白(HDL)氧化修饰的抑制作用.方法 按一次性密度梯度超速离心法分离人血清HDL,分别加入5.0 μmol/L异鼠李素及橙皮甙温育3 h,然后利用Cu2 介导体外氧化修饰脂蛋白的方法,观察HDL氧化修饰不同时间,其234 nm吸光度(A234)、相对电泳迁移率(REM)、硫代巴比妥酸反应物质(TBARS)及蛋白质羰基的动力学改变.结果 Cu2 介导HDL氧化修饰2、4、6、8、12及24 h后,其A234、REM、TBARS及蛋白质羰基含量均逐步增加;加入5.0 μmol/L 异鼠李素及橙皮甙的实验组,Cu2 介导HDL的氧化修饰分别延迟2～6 h和2～4 h;其A234、REM、TBARS及载脂蛋白羰基含量较对照组降低,异鼠李素实验组分别降低16.3%～46.9%、0.6%～25.2%、9.2%～28.4%及11.6%～45.2%;橙皮甙实验组降低1.5%～30.0%、1.4%～13.3%、6.6%～18.8%及14.4%～62.0%.结论 异鼠李素及橙皮甙可抑制Cu2 诱导的HDL的氧化修饰,且异鼠李素的抗氧化作用比橙皮甙强.     

火焰原子吸收法测定紫薯中的微量元素

目的测定紫薯中锌、铁、钙、铜、锰的含量。方法样品经微波消解,采用火焰原子吸收法测紫薯中微量元素的含量。结果该方法准确、可靠,相对偏差为0．108％～1．784％,回收率为98．5％～100-3％。结论紫薯中含有丰富的微量元素,钙和铁的含量较高,锰的含量较低。