随机盲法、阳性药对照评价前列地尔注射液治疗糖尿病下肢动脉闭塞症有效性和安全性多中心临床研究

摘要：目的：观察2种前列地尔注射液在治疗糖尿病下肢动脉闭塞症的等效性和安全性。方法 采用随机盲法、阳性药平行对照、多中心临床研究。试验组使用A 药(海南碧凯药业有限公司),对照组使用已上市B 药(北京泰德制药有限公司)。疗程均为14 d。结果 本试验共有8家医院参与,随机入组235 例受试者。对照组入选117人,试验组118 人。主要疗效指标中踝肱比值,全分析集（full analysis set,FAS）人群组内比较两组治疗14 d 后踝肱比值均较基线时有所提高,且有统计学意义。组间比较：治疗14 d 后对照组提高0.09;试验组提高0.10,两组间无统计学意义,符合方案集（per-protocol set,PPS）人群结果趋势和FAS 一致。两组治疗14 d 后静息痛均较基线时有所下降,且有统计学意义,组间比较无统计学差异,PPS 人群结果趋势和FAS 一致。最大无痛行走距离在两组间无统计学意义,PPS 结果和FAS 一致。全部不良事件发生率对照组为19.33％;试验组为17.65%。相关不良事件对照组10.08%;试验组为8.4%。差别无统计学意义。结论 临床验证表明,2 种前列地尔注射液在治疗慢性下肢动脉闭塞性疾病的过程中,表现出相同的疗效和安全性。 关键词：     

前列地尔联合疏血通注射液治疗下肢动脉硬化闭塞症疗效观察

目的观察前列地尔联合疏血通注射液治疗下肢动脉硬化闭塞症的疗效及安全性。方法64例下肢动脉硬化闭塞症患者按随机数字表法随机分为观察组和对照组,各32例。对照组在常规治疗基础上给予疏血通注射液治疗。观察组给予前列地尔联合疏血通注射液治疗,疗程均为2周。观察2组患者用药后间歇性跛行、麻木等症状改善状况以及不良反应发生情况。结果观察组患者治疗总有效率为81.25%,明显高于对照组（50.00%）（P〈0.01）,治疗期间均未出现严重不良反应。结论前列地尔联合疏血通注射液治疗下肢动脉硬化闭塞症疗效显著,无明显不良反应,值得临床推广应用。     

纤溶酶联合前列地尔治疗下肢动脉硬化闭塞症的临床观察

目的观察纤溶酶与前列地尔联合治疗下肢动脉硬化闭塞症疗效。方法将124例下肢动脉硬化闭塞症患者随机分为治疗组、对照组。治疗组静脉滴注纤溶酶与前列地尔,对照组应用马来酸桂哌齐特,疗程共2周。观察治疗前后症状缓解情况。结果联合治疗组疗效优于对照组,明显改善下肢动脉硬化闭塞。结论纤溶酶联合前列地尔治疗下肢动脉硬化闭塞症是治疗下肢血管病变的有效方法之一。     

参附注射液联合前列地尔在老年下肢动脉硬化闭塞症治疗中的疗效观察

目的观察参附注射液联合前列地尔在老年下肢动脉硬化闭塞症治疗中的疗效。方法 46例患者随机分为两组,治疗组在常规治疗基础上给予参附注射液联合前列地尔,对照组给予前列地尔联合常规治疗,14天为1个疗程。结果 1个疗程后治疗组有效率83.3%,对照组有效率63.6%,两组疗效比较有显著差异(P<0.05)。结论参附注射液联合前列地尔治疗明显优于前列地尔治疗组,能有效改善下肢动脉硬化闭塞症状。     

前列地尔治疗动脉硬化闭塞症下肢溃疡45例疗效观察

动脉硬化闭塞症是临床上常见的一组病症,随着生活水平的提高,其在我国的发病率有逐年增加的趋势.在肢体长期慢性缺血后,会出现坏疽和溃疡,是临床上难治的病症.2005年3月至2008年3月我们共收治动脉硬化闭塞症下肢溃疡患者45例,应用前列地尔(商品名:凯时,北京泰德制药有限公司生产)对其进行治疗,对治疗效果进行了临床观察,结果显示疗效果满意.现报告如下.     

血塞通联合前列地尔治疗下肢动脉硬化闭塞症35例

目的观察血塞通联合前列地尔治疗下肢动脉硬化闭塞症的临床疗效。方法将70例下肢动脉硬化闭塞症患者随机分为两组。对照组35例在常规治疗基础上予以前列地尔静脉滴注治疗,治疗组35例在对照组基础上加用血塞通静脉滴注治疗,均14d为1个疗程。比较两组患者治疗前后踝肱指数（ABI）及超敏C-反应蛋白（hs—CRP）的变化。结果治疗组总有效率为94．74％,明显高于对照组的84．21％（P〈0．05）。两组治疗后的ABI升高、hs—CRP降低,治疗组改善优于对照组（P〈0．05）。结论血塞通联合前列地尔治疗下肢动脉硬化闭塞症,可升高ABI、降低hs—CRP水平,有效改善患者症状,提高临床疗效。     

超声对前列地尔并罂粟碱治疗下肢动脉硬化闭塞症的临床疗效评价

目的通过超声对老年下肢动脉硬化闭塞症患者采用前列地尔与罂粟碱联合治疗前后的血流动力学参数对比,评价前列地尔联合罂粟碱治疗老年下肢动脉硬化闭塞症的疗效。方法下肢动脉硬化闭塞症患者45例,治疗前应用超声测量股、腘、胫前、胫后动脉的舒张期内径,观察血管壁回声强度、血管走行及腔内彩色血流分布,脉冲多普勒定量计算血流峰值速度及血流量。经前列地尔联合罂粟碱治疗后,应用超声观察上述指标的变化。结果治疗后股、腘、胫后、足背动脉的舒张期内径,血流峰值速度及血流量治疗后较治疗前均有明显改善,差异有统计学意义。结论前列地尔联合罂粟碱治疗老年下肢动脉硬化闭塞症临床效果好,值得推广。     

前列地尔治疗慢性肾小球肾炎32例疗效观察

目的：对比前列地尔（凯时）注射液（Lipo PEG1)治疗方案治疗与常规方案治疗原发性肾小球肾炎（CGN）的疗效。方法：对照组18例采用常规方案治疗，治疗组32例采用前列地尔（凯时）注射液方案治疗。结果：治疗组患尿蛋白总改善率，尿红细胞数总改善率，综合显效率及总有效率，分别为90．6％，81．25％，65．63％，87．50％，显高于对照组的77．78％，72．22％，50．00％，72．74％（P＜0．05，P＜0．01），而治疗组综合无效率，恶化率分别为6．25％，6．25％，显低于对照组的13．63％，13．63％（P＜0．05）。结论：前列地尔（凯时）注射液治疗方案治疗CGN治疗优于常规方案治疗。     

前列地尔注射液治疗糖尿病肾病效果分析

目的:评价前列地尔注射液(商品名:曼新妥)治疗糖尿病肾病的疗效及安全性。方法:采用随机对照研究方法,将2型糖尿病并肾病患者70例分为A、B两组,治疗21 d。并于治疗前、治疗后21 d观察24 h尿蛋白、血肌酐、内生肌酐清除率、血小板聚集、血浆黏度,并观察治疗过程中的不良反应。结果:A、B两组24 h尿蛋白、血肌酐、内生肌酐清除率、血小板聚集率、血浆黏度均明显下降(P<0.05或者P<0.01),但两组间比较差异无统计学意义(P>0.05),治疗过程中无明显的不良反应。结论:哈药集团生物工程有限公司生产的前列地尔注射液(曼新妥)治疗糖尿病肾病有效且安全,其有效性和安全性与北京泰德制药有限公司产前列地尔注射液(凯时)相近。     

前列地尔注射液与小剂量阿司匹林治疗糖尿病双下肢动脉血管病变效果观察

糖尿病下肢动脉病变的病理改变为动脉粥样硬化所致，研究表明，与非糖尿病人群相比，糖尿病人群中动脉粥样硬化的患病率较高，多累及双侧膝下血管，尤其膝以下的中小动脉，特别是足部动脉。近些年来，许多抗血小板聚集、抗血栓、扩张小动脉以及改善动脉舒张的药物在临床应用，获得较好的疗效。为观察前列地尔注射液（凯时）联合小剂量阿司匹林对糖尿病双下肢动脉血管病变的影响，我们采用上述方法治疗糖尿病双下肢动脉血管病变，并与丹参治疗作为对照，现将结果报道如下：     

瓜蒌皮注射液对动脉硬化闭塞症术后疗效观察

目的观察瓜蒌皮注射液对下肢动脉硬化闭塞症患者（ASO）球囊扩张＋支架植入术后的疗效观察。方法选取我院2006年至2010年行球囊扩张＋支架植入手术的ASO患者39例,随机分为治疗组20例（22条患肢）和对照组19例（20条患肢）。所有患者术后均予以抗凝扩管治疗,治疗组予以瓜萎皮注射液8ml加入生理盐水250ml中静滴,疗程为15d。观察术后3个月和6个月时患肢的临床症状、血管通畅率及踝肱指数。结果术后3个月和6个月时两组痛感、冷感、皮色、皮温、间歇性跛行、静息痛、溃疡、血管通畅、踝肱指数和截肢等方面比较差异有统计学意义（P〈0．05）。结论瓜萎皮注射液对ASO患者球囊扩张＋支架植入术后的临床症状及血管通畅情况的改善均起到一定作用。     

Bimodal effect of hypoxia in cancer: role of hypoxia inducible factor in apoptosis

The effects of the separate and combined application of hypoxia and antisense oligonucleotides (ASO) against hypoxia inducible factor 1alpha (HIF1A) on cancer cells were examined. Experiments were carried out on human ovarian carcinoma cells in four series: (1) control [Normoxia (5% CO2 in air), no treatment], (2) hypoxia (1% O2, 5% CO2, and 94% N2 for 48 h), (3) treatment with ASO targeted to HIF1A (48 h), and (4) combined action of hypoxia and ASO. After treatment, the following processes and factors were monitored: apoptosis, cellular metabolism and viability, expression of genes encoding HIF1A, von Hippel-Lindau tumor suppressor protein (VHL), and genes responsible for cell death induction and antiapoptotic defense (P53, BCL2, BAX, and caspases 9 and 3). Expression of caspase 9 and HIF1A protein was confirmed by Western blotting. Liposomes were used as a delivery system of HIF1A ASO. It was found that hypoxia alone significantly disturbed cellular metabolism, reducing the level of respiration by 50% when compared with control. Hypoxia induced apoptosis by upregulating the P53-, BAX-, and caspase-dependent cell death pathways, while activating cellular antiapoptotic defense by the overexpression of BCL2 protein. Both opposing effects were dependent on the overexpression of hypoxia inducible factor. We conclude that hypoxia induces a bimodal effect, simultaneously promoting cell death and activating cellular resistance. The downregulation of HIF1A promoted cell death induction and prevented activation of cellular defense by hypoxia. This suggests that HIF1A is a potential candidate for anticancer therapeutic targeting.     

Pro-inflammatory cytokine inhibition in the primate using microencapsulated antisense oligomers to NF-kappaB

PRIMARY OBJECTIVE: Antisense oligomers to NF-kappaB (ASO) were incorporated into albumin microspheres to determine if microcapsules containing ASO inhibit pro-inflammatory cytokines to a greater extent than comparable doses of ASO in solution. Phagocytosis of microcapsules and intracellular release of ASO in macrophages was evaluated. RESEARCH DESIGN: Comparable doses of microencapsulated ASO and ASO in solution were evaluated in non-human primates. METHODS: Blood was sampled and stimulated with Escherichia coli endotoxin ex vivo. TNF, IL-1 and IL-6 concentrations were compared for 72 hrs. The intracellular concentration of ASO was measured in macrophages in vitro to evaluate the difference in intracellular penetration of microencapsulated ASO. RESULTS: Microencapsulated ASO produced significantly greater cytokine inhibition at all time points compared to ASO in solution. There were no side effects to ASO in the baboons. Intracellular ASO concentration was 10 fold greater in macrophages using microencapsulation. CONCLUSIONS: Microencapsulated ASO to NF-kappaB is more effective than ASO in solution in pro-inflammatory cytokine inhibition in non-human primates.     

动静脉转流术应用在下肢动脉硬化闭塞症中的体会

目的：探讨动静脉转流术治疗下肢动脉硬化闭塞症，研究其技术操作及临床应用。方法：对6例患下肢动脉硬化闭塞症患者行腘动脉径后静脉转流术。结果：疗效优良5例，好转1例，术后只有一足趾截去。结论：此方法不易导致心衰，可挽救缺血肢体，以避免截肢，疗效满意。     

闭塞性周围动脉粥样硬化患者血管内皮损伤的研究

目的:观察闭塞性周围动脉粥样硬化(ASO)患者的凝血和纤溶系统功能的变化,探讨ASO患者的内皮损伤机制。方法:选择ASO患者82例(患者组)和健康对照80例(对照组),采用流式细胞仪测定循环内皮细胞(CEC)和内皮祖细胞(EPCs)数量。采用酶联免疫吸附法测定凝血酶-抗凝血酶复合物(TAT)。采用血液凝固仪测定凝血因子Ⅶ活性(FⅦ:A)、纤维蛋白原(FIB)、vW因子抗原水平(vWF∶Ag)、组织型纤溶酶原激活物活性(t-PA∶A)及纤溶酶原活化抑制物活性(PAI∶A)水平。以vWF∶Ag参考范围上限(150%)作为医学决定水平,将患者组分为vWF∶Ag正常组(38例)和vWF∶Ag增高组(44例)。结果:患者组PAI∶A、FⅦ∶A、FIB、vWF∶Ag、TAT和CEC高于对照组,EPCs低于对照组,vWF∶Ag增高组的PAI∶A、FⅦ∶A和TAT均高于vWF∶Ag正常组,差异有统计学意义(均P<0.01);患者组vWF∶Ag与FⅦ∶A、PAI∶A、TAT均呈正相关(P<0.01)。结论:ASO患者存在较严重的血管内皮损伤,内皮细胞大量脱落,且损伤后的修复能力不足,其纤溶和凝血系统功能紊乱和血管内皮损伤程度相关。     

Pro-inflammatory cytokine inhibition in the primate using microencapsulated antisense oligomers to NF-κB

Primary objective: Antisense oligomers to NF-κB (ASO) were incorporated into albumin microspheres to determine if microcapsules containing ASO inhibit pro-inflammatory cytokines to a greater extent than comparable doses of ASO in solution. Phagocytosis of microcapsules and intracellular release of ASO in macrophages was evaluated.

Research design: Comparable doses of microencapsulated ASO and ASO in solution were evaluated in non-human primates.

Methods: Blood was sampled and stimulated with Escherichia coli endotoxin ex vivo. TNF, IL-1 and IL-6 concentrations were compared for 72?hrs. The intracellular concentration of ASO was measured in macrophages in vitro to evaluate the difference in intracellular penetration of microencapsulated ASO.

Results: Microencapsulated ASO produced significantly greater cytokine inhibition at all time points compared to ASO in solution. There were no side effects to ASO in the baboons. Intracellular ASO concentration was 10 fold greater in macrophages using microencapsulation.

Conclusions: Microencapsulated ASO to NF-κB is more effective than ASO in solution in pro-inflammatory cytokine inhibition in non-human primates.     

Transposition of the great arteries: operative outcome in the current era

AIMS: To assess the operative outcome, cardiac and neurodevelopmental sequelae in infants with transposition of the great arteries (TGA) undergoing the arterial switch operation (ASO). METHOD: Cross-sectional review of the 48 consecutive patients operated on in the calendar years 1995 and 1996 was undertaken to obtain recent cardiac, growth and neurodevelopmental parameters, and the mortality results were compared to the entire cohort of infants who underwent the ASO for definitive repair of TGA and double outlet right ventricle at Greenlane hospital between 1984 and 1998. RESULTS: Between January 1995 and December 1996, 48 patients underwent the ASO. 96% were alive, and 88% alive and free from reoperation or significant neurological sequelae at a mean followup interval of sixteen months. Six (13%) had important residual cardiac lesions, of which supra valvular pulmonary stenosis was the most common. Growth parameters at follow-up were normal, as was the neurodevelopmental progress of all but two survivors (96%). CONCLUSION: In the current era, the ASO is a relatively safe procedure with excellent cardiac and neurodevelopmental outcome in the majority of infants.     

心功能不全合并下肢动脉硬化闭塞症的危险因素及列线图模型的建立

目的 探讨心功能不全患者发生下肢动脉硬化闭塞症（ASO）的危险因素,构建及验证列线图风险预测模型。方法 选取心功能不全患者319例,依据下肢动脉彩超结果是否存在下肢动脉狭窄或闭塞分为ASO阳性组（161例）和ASO阴性组（158例）。收集患者性别、年龄、吸烟史、饮酒史、高血压史、美国纽约心脏病协会（NYHA）心功能分级...     

盐酸沙格雷酯和阿司匹林在下肢动脉硬化闭塞症中抗血小板的疗效观察

目的观察盐酸沙格雷酯和阿司匹林在下肢动脉硬化闭塞症中抗血小板的疗效。方法分别采用盐酸沙格雷酯和阿司匹林治疗,在治疗前后对两组患者的凝血酶原时间、血小板计数情况、肝功能、肾功能指标进行对比,分析两组治疗效果。结果对照组总的治疗有效率为33.3％治疗组治疗有效率为75.8％治疗前后血小板计数和SGPT的变化值最大,治疗组的血小板的聚结功能下降幅度要比对照组大。结论在下肢ASO患者治疗中可以将盐酸沙格雷酯当做血管扩张剂以及血小板祛聚药物使用,治疗效果理想,且安全性较高。