Background: Fatigue is a major complaint of multiple sclerosis (MS) patients. However, little is known about its pathophysiological mechanisms. Evidence from chronic fatigue syndrome and studies on sickness behaviour ...Background: Fatigue is a major complaint of multiple sclerosis (MS) patients. However, little is known about its pathophysiological mechanisms. Evidence from chronic fatigue syndrome and studies on sickness behaviour suggest that immune and neuroendocrine factors may play a causative role in the development of fatigue. Methods: We compared whole blood stimulatory capacity for pro-(TNFα ,IFNγ ) and anti-inflamma-tory cytokines (IL- 10) as well as hypothalamo-pituitary-adrenal (HPA) axis function in 15 MS patients with marked fatigue and 15 patients without fatigue as determined by the Fatigue Severity Scale (FSS). Results: Proinflammatory cytokines were significantly higher (TNFα : 478.9 v 228.2 pg/ml, p = 0.01; IFNγ : 57.6 v 27.8 pg/ml; p = 0.01) in MS patients with fatigue. Furthermore, TNFα values significantly correlated with daytime sleepiness as measured by the Epworth Sleepiness Scale (r = 0.64, p = 0.001). Controlling for disease activity (as measured by the Cambridge Multiple Sclerosis Basic Score), disease duration, Expanded Disability Status Scale, and depression further increased the correlation of cytokine production and fatigue. HPA axis activity was not related to fatigue but was modestly correlated with cognitive impairment. Conclusion: Our data suggest that fatigue in MS is at least partially mediated through activation of proinflammatory cytokines. In line with earlier findings, HPA axis dysfunction seems not to be relevant in MS fatigue pathogenesis but appears to be linked to cognitive impairment. Our findings suggest that increased levels of inflammatory cytokines may be involved in MS fatigue. Investigation of cytokine profiles may increase the understanding of fatigue pathogenesis in MS.展开更多
目的评价健脾理气抑瘤方联合细胞因子介导的杀伤细胞（cytokine-induced killer,CIK）治疗晚期肝细胞癌（hepatocellular carcinoma,HCC）的临床疗效。方法自2011年1月—2014年1月共纳入60例晚期HCC患者,根据是否愿意服用健脾理气抑瘤方...目的评价健脾理气抑瘤方联合细胞因子介导的杀伤细胞（cytokine-induced killer,CIK）治疗晚期肝细胞癌（hepatocellular carcinoma,HCC）的临床疗效。方法自2011年1月—2014年1月共纳入60例晚期HCC患者,根据是否愿意服用健脾理气抑瘤方,分为治疗组和对照组,每组30例。两组均给予CIK细胞治疗：CIK细胞1~3×10~9个/次,第1~3天进行静脉滴注,每天1次;同时治疗组予健脾理气抑瘤方汤剂,对照组予辨证中药汤剂,两组均接受2周期以上的治疗。观察两组患者的疾病控制率（disease control rate,DCR）、疾病进展时间（time to progress,TTP）、总生存期（overall su rvival,OS）、体能状态评分（performance status scale,PS）、Child-Pugh评分及不良反应,并作亚组分析。结果截至2014年5月31日,两组所有患者均达到临床终点。治疗组TTP为3.5个月（95%CI 3.30~4.10）,优于对照组2.5个月（95%CI 2.32~2.68）,差异有统计学意义（P〈0.05）;治疗组和对照组DCR分别为36.7%和30.0%,OS为5.2个月（95%CI 4.53~5.87）和4.6个月（95%CI 4.06~5.14）,差异均无统计学意义（P〉0.05）。治疗组治疗后PS[（1.60±0.10）分]低于治疗前[（1.80±0.09）分],差异有统计学意义（P〈0.05）。在PS 0~1、2分和Child-Pugh评分为A级时,治疗组TTP均长于对照组（P〈0.05）。治疗期间两组患者未见明显不良反应。结论健脾理气抑瘤方联合CIK细胞较辨证中药治疗组可延长患者TTP及改善体力状态评分,且在体力状态评分0~2分或Child-Pugh评分为A级的情况下,可能是晚期HCC患者的更优治疗方案。展开更多
文摘Background: Fatigue is a major complaint of multiple sclerosis (MS) patients. However, little is known about its pathophysiological mechanisms. Evidence from chronic fatigue syndrome and studies on sickness behaviour suggest that immune and neuroendocrine factors may play a causative role in the development of fatigue. Methods: We compared whole blood stimulatory capacity for pro-(TNFα ,IFNγ ) and anti-inflamma-tory cytokines (IL- 10) as well as hypothalamo-pituitary-adrenal (HPA) axis function in 15 MS patients with marked fatigue and 15 patients without fatigue as determined by the Fatigue Severity Scale (FSS). Results: Proinflammatory cytokines were significantly higher (TNFα : 478.9 v 228.2 pg/ml, p = 0.01; IFNγ : 57.6 v 27.8 pg/ml; p = 0.01) in MS patients with fatigue. Furthermore, TNFα values significantly correlated with daytime sleepiness as measured by the Epworth Sleepiness Scale (r = 0.64, p = 0.001). Controlling for disease activity (as measured by the Cambridge Multiple Sclerosis Basic Score), disease duration, Expanded Disability Status Scale, and depression further increased the correlation of cytokine production and fatigue. HPA axis activity was not related to fatigue but was modestly correlated with cognitive impairment. Conclusion: Our data suggest that fatigue in MS is at least partially mediated through activation of proinflammatory cytokines. In line with earlier findings, HPA axis dysfunction seems not to be relevant in MS fatigue pathogenesis but appears to be linked to cognitive impairment. Our findings suggest that increased levels of inflammatory cytokines may be involved in MS fatigue. Investigation of cytokine profiles may increase the understanding of fatigue pathogenesis in MS.
文摘目的评价健脾理气抑瘤方联合细胞因子介导的杀伤细胞（cytokine-induced killer,CIK）治疗晚期肝细胞癌（hepatocellular carcinoma,HCC）的临床疗效。方法自2011年1月—2014年1月共纳入60例晚期HCC患者,根据是否愿意服用健脾理气抑瘤方,分为治疗组和对照组,每组30例。两组均给予CIK细胞治疗：CIK细胞1~3×10~9个/次,第1~3天进行静脉滴注,每天1次;同时治疗组予健脾理气抑瘤方汤剂,对照组予辨证中药汤剂,两组均接受2周期以上的治疗。观察两组患者的疾病控制率（disease control rate,DCR）、疾病进展时间（time to progress,TTP）、总生存期（overall su rvival,OS）、体能状态评分（performance status scale,PS）、Child-Pugh评分及不良反应,并作亚组分析。结果截至2014年5月31日,两组所有患者均达到临床终点。治疗组TTP为3.5个月（95%CI 3.30~4.10）,优于对照组2.5个月（95%CI 2.32~2.68）,差异有统计学意义（P〈0.05）;治疗组和对照组DCR分别为36.7%和30.0%,OS为5.2个月（95%CI 4.53~5.87）和4.6个月（95%CI 4.06~5.14）,差异均无统计学意义（P〉0.05）。治疗组治疗后PS[（1.60±0.10）分]低于治疗前[（1.80±0.09）分],差异有统计学意义（P〈0.05）。在PS 0~1、2分和Child-Pugh评分为A级时,治疗组TTP均长于对照组（P〈0.05）。治疗期间两组患者未见明显不良反应。结论健脾理气抑瘤方联合CIK细胞较辨证中药治疗组可延长患者TTP及改善体力状态评分,且在体力状态评分0~2分或Child-Pugh评分为A级的情况下,可能是晚期HCC患者的更优治疗方案。
