目的:评价A型肉毒杆菌毒素(BTX-A)尿道外括约肌注射加巴氯芬口服治疗脊髓损伤后尿道外括约肌协同失调症(DESD)的临床效果。方法:尿流动力学检查证实脊髓损伤后DESD患者38例,男31例、女7例,平均年龄(36.5±17.8)岁。200 U BTX-A溶解...目的:评价A型肉毒杆菌毒素(BTX-A)尿道外括约肌注射加巴氯芬口服治疗脊髓损伤后尿道外括约肌协同失调症(DESD)的临床效果。方法:尿流动力学检查证实脊髓损伤后DESD患者38例,男31例、女7例,平均年龄(36.5±17.8)岁。200 U BTX-A溶解于8 ml生理盐水,使用尿道镜注射针分8点二平面注射于尿道外括约肌(1 ml/点)。术后第2日,随机选取12例患者(BTX-A+巴氯芬组)加服巴氯芬10 mg/次、3次/d,服用3个月,与另外26例患者作比较(BTX-A组)。4周后复查尿流动力学,随访2~9个月,比较治疗前后排尿症状、尿动力学检查结果的变化,并观察毒副作用。结果:治疗后1个月,膀胱贮尿和排尿功能有不同程度改善,最大尿流率、单次尿量、最大膀胱测压容积、膀胱顺应性增加,剩余尿量及充盈末逼尿肌压力下降,差异均有统计学意义(P<0.05)。BTX-A+巴氯芬组患者症状改善程度及膀胱顺应性明显优于单纯BTX-A组(P<0.05)。BTX-A+巴氯芬组有3例患者因出现神经系统不良反应而停药,其余患者无明显不良反应发生。结论:BTX-A注射加巴氯芬口服可以有效改善脊髓损伤后逼尿肌尿道外括约肌协同失调症患者的排尿障碍,长期疗效尚需进一步的随访观察。展开更多
BACKGROUND: Many methods have been attempted to repair nerves following spinal cord injury, including peripheral nerve transplantation, Schwann cell transplantation, olfactory ensheathing cell transplantation, and em...BACKGROUND: Many methods have been attempted to repair nerves following spinal cord injury, including peripheral nerve transplantation, Schwann cell transplantation, olfactory ensheathing cell transplantation, and embryonic neural tissue transplantation. However, there is a need for improved outcomes. OBJECTIVE: To investigate the repair feasibility for rat spinal cord injury using human neural stem cells (hNSCs) genetically modified by lentivirus to express neurotrophin-3. DESIGN, TIME AND SETTING: In vitro cell biological experiment and in vivo randomized, controlled genetic engineering experiment were performed at the Third Military Medical University of Chinese PLA and First People's Hospital of Yibin, China from March 2006 to December 2007. MATERIALS: A total of 64 adult, female, Wistar rats were used for the in vivo study. Of them, 48 rats were used to establish models of spinal cord hemisection, and were subsequently equally and randomly assigned to model, genetically modified hNSC, and normal hNSC groups. The remaining 16 rats served as normal controls. METHODS: hNSCs were in vitro genetically modified by lentivirus to secrete both green fluorescence protein and neurotrophin-3. Neurotrophin-3 expression was measured by Western blot. Genetically modified hNSC or normal hNSC suspension (5 × 10^5) was injected into the rat spinal cord following T10 spinal cord hemisection. A total of 5μL Dulbecco's-modified Eagle's medium was infused into the rat spinal cord in the model grop. Transgene expression and survival of transplanted hNSCs were determined by immunohistochemistry. Motor function was evaluated using the Basso, Beattie, and Bresnahan (BBB) scale. MAIN OUTCOME MEASURES: The following parameters were measured: expression of neurotrophin-3 produced by genetically modified hNSCs, transgene expression and survival of hNSCs in rats, motor function in rats. RESULTS: hNSCs were successfully genetically modified by lentivirus to stably express neurotrophin-3. The transplanted hNSCs primarily gathered at, or around, the injection site two weeks following transplantation, and gradually migrated towards the surrounding tissue. Transplanted hNSCs were observed 7.0-8.0 mm away from the injection site. In addition, hNSCs were observed 10 weeks after transplantation. At week 4, BBB locomotor scores were significantly greater in the genetically modified hNSC and normal hNSC groups, compared with the model group (P 〈 0.05), and scores were significantly greater in the genetically modified hNSC group compared with the normal hNSC group (P 〈 0.05). CONCLUSION: hNSCs were genetically modified with lentivirus to stably secrete neurotrophin-3. hNSCs improved motor function recovery in rats following spinal cord injury.展开更多
文摘BACKGROUND: Many methods have been attempted to repair nerves following spinal cord injury, including peripheral nerve transplantation, Schwann cell transplantation, olfactory ensheathing cell transplantation, and embryonic neural tissue transplantation. However, there is a need for improved outcomes. OBJECTIVE: To investigate the repair feasibility for rat spinal cord injury using human neural stem cells (hNSCs) genetically modified by lentivirus to express neurotrophin-3. DESIGN, TIME AND SETTING: In vitro cell biological experiment and in vivo randomized, controlled genetic engineering experiment were performed at the Third Military Medical University of Chinese PLA and First People's Hospital of Yibin, China from March 2006 to December 2007. MATERIALS: A total of 64 adult, female, Wistar rats were used for the in vivo study. Of them, 48 rats were used to establish models of spinal cord hemisection, and were subsequently equally and randomly assigned to model, genetically modified hNSC, and normal hNSC groups. The remaining 16 rats served as normal controls. METHODS: hNSCs were in vitro genetically modified by lentivirus to secrete both green fluorescence protein and neurotrophin-3. Neurotrophin-3 expression was measured by Western blot. Genetically modified hNSC or normal hNSC suspension (5 × 10^5) was injected into the rat spinal cord following T10 spinal cord hemisection. A total of 5μL Dulbecco's-modified Eagle's medium was infused into the rat spinal cord in the model grop. Transgene expression and survival of transplanted hNSCs were determined by immunohistochemistry. Motor function was evaluated using the Basso, Beattie, and Bresnahan (BBB) scale. MAIN OUTCOME MEASURES: The following parameters were measured: expression of neurotrophin-3 produced by genetically modified hNSCs, transgene expression and survival of hNSCs in rats, motor function in rats. RESULTS: hNSCs were successfully genetically modified by lentivirus to stably express neurotrophin-3. The transplanted hNSCs primarily gathered at, or around, the injection site two weeks following transplantation, and gradually migrated towards the surrounding tissue. Transplanted hNSCs were observed 7.0-8.0 mm away from the injection site. In addition, hNSCs were observed 10 weeks after transplantation. At week 4, BBB locomotor scores were significantly greater in the genetically modified hNSC and normal hNSC groups, compared with the model group (P 〈 0.05), and scores were significantly greater in the genetically modified hNSC group compared with the normal hNSC group (P 〈 0.05). CONCLUSION: hNSCs were genetically modified with lentivirus to stably secrete neurotrophin-3. hNSCs improved motor function recovery in rats following spinal cord injury.