他克莫司缓释胶囊与他克莫司胶囊的临床对照试验

目的 比较和评价首次肾移植受者使用他克莫司缓释胶囊和他克莫司胶囊治疗的安全性和有效性.方法 11家中心的241例肾移植受者随机分配为试验组(应用他克莫司缓释胶囊+吗替麦考酚酯+皮质激素)和对照组(应用他克莫司胶囊+吗替麦考酚酯+皮质激素),观察时间从移植当天至术后12周.试验组受试者每天上午一次性服用他克莫司缓释胶囊,对照组受试者每天早晚分2次服用他克莫司胶囊.两组试验药物的起始剂量均为0.1～0.15 mg·kg-1·d-1.分别在治疗前和治疗后第1、3、7、14、28、56和84 d各随访1次.对两组受者用药的有效性、安全性、依从性以及不良反应进行对比分析.结果 进入符合方案分析集者共223例,其中试验组111例,对照组112例.两组受者的平均年龄、性别、原发病的差异均无统计学意义,各有12例发生急性排斥反应.对照组和试验组分别有36例(32.1%)和37例(33.3%)发生与试验药物相关的不良反应.无受者连续3 d未按照方案服用药物.两组治疗后期较治疗前期的服药量均减少,且组内差异有统计学意义(P<0.05).治疗早期两组血他克莫司浓度较接近,从28 d开始,试验组血药浓度低于对照组,但差异无统计学意义.结论 从药物安全性、药物治疗的有效性、相关不良反应以及受者依从性各方面分析显示,每天1次的他可莫司缓释胶囊均非劣效于每天2次的他克莫司胶囊,在临床应用中,用他克莫司缓释胶囊代替他克莫司胶囊是切实可行的.

Abstract：

Objective To compare the efficacy and safety of twice-daily tacrolimus (Tacrolimus BID; Prograf) vs once-daily prolonged release tacrolimus (Tacrolimus QD; Advagraf), combined with steroids and mycophenolate mofetil in preventing acute rejection in De Novo renal transplantation patients. Methods 241 patients from 11 centers were randomized into two groups with 3 months observation period post-transplantation. Advagraf was administered as a single oral dose in the morning (initially 0. 1-0. 15 mg/kg every day) and Prograf was administered in two equal oral doses 12h apart (initially 0. 1-0. 15 mg/kg). Study visits were scheduled for days 1, 3, 7, 14, 28, 56, 84post-transplantion. The efficacy, safety, compliance and adverse effects were compared between two groups. Results Totally 223 patients completed the study. The two groups were comparable in age,gender and primary disease. There were 12 episodes of acute rejection in each group. There was no graft loss or patient death in both groups. The incidence of drug related adverse events was 32. 1 %and 33. 3% respectively in the control and experimental groups. Dosage was decreased in both groups and there was significant difference in each group. The trough level was similar at the initiate period.Twenty-eight days post-transplantation the trough level in the Advagraf group was lower than in the Prograf group. Conclusion Advagraf has the same efficacy, safety and drug related adverse effects as Prograf. It is practical and feasible for Advagraf substitute for Prograf in clinical practice.     

肾移植后因免疫抑制剂的不良反应转换应用咪唑立宾的效果

Objective To investigate the efficacy and safety of conversion therapy to mizoribine (MZR) for renal transplant patients who suffered MMF or Aza adverse reaction. Methods In 56 patients with adverse reactions at different time points after renal transplantation, there were 23 cases of pulmonary infection, 14 cases of bone marrow depression, 6 cases of hepatic functional lesion and 13 cases of diarrhea. The immunosuppressive protocols of these patients were changed to CNI + MZR + Pre when the adverse reaction occurred. During the follow-up period (11 to 53 months), the effect and adverse events of conversion treatment were observed. Results After conversion treatment, 1 of 23 patients with pulmonary infection was re-infected after 26 months and finally died of heart and lung function failure. In 14 patients with bone marrow depression, blood test returned to normal in 13cases. Six patients with hepatic functional lesion were administered hepatoprotection treatment and their liver function was restored without recurrence of impaired liver function. All 13 patients with diarrhea were relieved without recurrence. The serum creatinine was 123 ± 21.3 μmol/L and 119±18. 2 μmol/L before and after the conversion therapy respectively (P＞0. 05). During the follow-up period, all patients' graft function was good. The incidence of rejection was 1.7 % (1 case). Nine patients (16. 1 %) had a higher level of uric acid after conversion. One patient had finger and toe joint pain. The symptoms were relieved after symptomatic treatment. Conclusion There were high security and good effect of conversion therapy to MZR due to MMF or Aza adverse reaction. Besides, MZR conversion therapy for renal transplantation patients provided a new option for individual immunosuppression.     

华东制药产他克莫司在临床肾移植中的应用

目的 评估中美华东制药有限公司生产的他克莫司胶囊(赛氏Tac胶囊)在临床肾移植中应用的有效性及安全性.方法 采取多中心、随机开放性、前瞻性临床研究,按照入选标准和排除标准,来自9个移植中心的共计65例肾移植受者入选.人选受者的年龄为(36.53±5.71)岁,8例为亲属活体供肾,供肾冷缺血时间为(4.08±5.43)h,热缺血时间为(3.90±2.15)min,供、受者HLA抗原错配数为(2.1±0.8)个.受者肾移植后采用赛氏Tac胶囊+吗替麦考酚酯+皮质激素预防排斥反应,移植后48 h内给药,Tac的起始剂量为0.1～0.15 mg·kg-1·d-1,术后60 d内维持血Tac浓度谷值在8～12μg/L,之后维持在5～10μg/L,直至观察终点(术后12周).监测12周的治疗结果,并进行有效性和安全性的评价.主要有效性终点为发生经病理证实的急性排斥反应,次要有效性终点为移植肾或受者的存活情况以及肾功能(以血清肌酐水平评价).安全性评价指标为研究期间发生的感染、肝功能损害、高血压、高血脂、糖尿病、多毛或痤疮等不良反应.结果术后第1、2、4、8和12周的Tac用量分别为(6.54±1.69)、(6.39±1.45)、(6.73±1.25)、(6.25±1.02)和(6.03±1.16)mg,对应的血药浓度谷值分别为(8.24±2.09)、(9.39±1.35)、(9.93±1.87)、(7.23±1.16)和(6.43±1.26)μg/L.观察期内经活检证实的急性排斥反应发生率为12.3%(8/65),6例经冲击治疗逆转,移植肾存活率为96.9%(63/65).研究期内受者的肺部感染发生率为7.6%,肝功能异常发生率为7.7%,高血压发生率为7.7%,高血脂发生率为4.6%,糖尿病发生率为4.6%.结论 赛氏Tac胶囊用于肾移植受者是安全、有效的.

Abstract：

Objective To demonstrate the efficacy and safety of Hangzhou tacrolimus capsule(Saishi Tac capsule, Hangzhou Zhongmei Huadong Pharmaceutical Co. Ltd, China) in Chinese kidney transplant recipients. Methods Multicenter, randomized open-labeled, prospective controlled clinical trial was performed in de novo Chinese kidney transplant recipients. According to including and excluding criterions, 65 kidney recipients from 9 transplant centers were enrolled. The mean age of recipients was (36.53 ± 5.71 ) years, and 8 received living donor transplantion. The time of cold ischemia and warm ischemia was (4.08 ± 5.43) h and (3.90 ± 2.15) min respectively. The number of mismatched HLA was (2.1 ± 0.8). The recipients accepted Saishi Tac capsule + mycophenolate steroid 60 days, followed by 5-10 μg/L until the terminal observation time point (12 weeks after transplantation). The efficacy and safety were estimated during the period. The primary efficacy endpoint of the study was the incidence of biopsy-confirmed acute rejection. Graft survival and renal function (evaluated by serum creatinine) were the secondary endpoints. Safety was assessed by monitoring laboratory parameters and adverse events reported over the course of the study, such as infection, hepatic damage, hypertension, hyperlipema, diabetes mellitus and other adverse affairs.Results The dose of Tac at 1 st, 2nd, 4th and 8th week postoperation was (6.54 ± 1.69), (6.39 ±1.45),(6.73± 1.25), (6.25 ± 1.02) and (6.03 ± 1.16) mg, corresponding values to the C0 were (8.24±2.09),(9.39± 1.35),(9.93± 1.87),(7.23± 1.16) and (6.43± 1.26) μg/L. During 12weeks of follow-up, the incidence of biopsy-confirmed acute rejection was 12.3% (8/65), among which 6 cases were reversed by implosive therapy. The survival rate of graft kidney was 96.9% (63/65). The incidence of hypertension and hepatic damage was both 7.7% and morbidity of lung infection was 7.6%. There were 3 patients (4.6%) complicated with hyperlipema and diabetes mellitus respectively. Conclusion During the first 3 months of treatment Saishi Tac capsule was safe and effective to Chinese kidney transplant recipients.     

钙离子在胰腺炎发生发展中的作用

随着人们生活水平及医疗水平的不断提高,胰腺疾病的发病率和检出率也在逐年增加,尤其是急、慢性胰腺炎和糖尿病,对人们的健康造成了极大的危害。当前胰腺炎主要病因以胆道疾病和酒精性因素为主,不过近年来缺血性损伤、代谢异常、Oddi括约肌功能障碍、药物以及胰腺手术、创伤所致胰腺炎的发病率也有逐渐上升的趋势。     

消渴丸致低血糖昏迷一例

低血糖是降糖治疗最常见的严重并发症。“消渴丸”是以中药黄芪、生地黄、天花粉等和优降糖为主要成分的中成药。因其优降糖含量较少(每丸含0.25毫克)，故很少发生低血糖。我们收治一例因服用消渴丸引起低血糖昏迷的患，报道如下。     

器官保存液中聚乙二醇对人红细胞聚集性和血液流变学的影响

背景：聚乙二醇作为一种非渗透性大分子物质,在器官保存液中可发挥保护细胞膜、维护细胞骨架完整性、防止细胞水肿、抗脂质过氧化和免疫调节的作用。 目的：探讨器官保存液中的聚乙二醇对人红细胞聚集性和血液流变学的影响。 设计、时间及地点：对比观察实验,于2008-10在解放军第二军医大学附属长征医院器官移植科完成。 材料：抽取接受体格检查的6名健康志愿者的肘前静脉血。 方法：在抽取的新鲜血液中按5∶1的稀释比分别加入生理盐水、器官保存液及含不同相对分子质量、不同浓度聚乙二醇的多器官保存液,按加入液体的不同分为：生理盐水组、器官保存液组、不添加聚乙二醇的保存液组、20聚乙二醇1,10,30 g/L和35聚乙二醇1,10,30 g/L组。 主要观察指标：室温下通过魏氏法检测红细胞沉降率、自动血液流变仪检测血液流变学指标、光镜观察红细胞聚集的形态学改变,分析聚乙二醇对人红细胞聚集性和血液流变学的影响。 结果：不含胶体的保存液对红细胞聚集无影响,含低浓度聚乙二醇的保存液对红细胞聚集性和血液流变学的影响较小,器官保存液组、20聚乙二醇30 g/L,35聚乙二醇10 g/L和35聚乙二醇30 g/L的保存液则可显著加快红细胞沉降率,降低红细胞变形能力,引起红细胞明显聚集。 结论：器官保存液中的聚乙二醇可引起红细胞聚集,降低红细胞变形能力,其相对分子质量越大,浓度越高,促进红细胞聚集的作用越明显,对血液流变学的影响越大。     

肾移植供肾MDR1基因多态性对FK506肾毒性和血药浓度的影响

目的：观察肾移植术后供肾多药耐药基因（MDR1）外显子26及外显子21的基因型对他克莫司（FK506）急慢性肾毒性和血药浓度的影响。方法回顾51例肾移植术后常规使用FK506＋MMF＋Pred三联免疫抑制用药方案的患者资料。通过基因组测序检测肾移植供者MDR1 exon26和exon21的基因型,比较不同供肾基因型的患者FK506的用量、血药浓度及和肾毒性的差异。结果在术后1年时比较内生肌酐清除率时,在exon26中,TT型的内生肌酐清楚率明显低于CC型和CT型（P＜0.05）,在exon21中,低表达型（TT型）明显低于高表达型（GG/GT/GA/AT型）（P＜0.05）;在比较术后1个月内的移植肾急性肾中毒发生率时,exon21中低表达型明显高于高表达型（P＜0.05）。结论在保护移植肾功能,减少FK506的急慢性肾毒性上,exon26的CC/CT型和exon21的高表达型明显优于exon26的的TT型和低表达型。     

七例血钙正常无症状原发性甲状旁腺功能亢进的外科治疗

1临床资料 1．1一般资料 大连医科大学附属二院普外科2002年至2010年经手术治疗的7例血钙正常无症状原发性甲状旁腺功能亢进（normocalcemic asymptomatic primary hyperparathyroidism,NAPHPT）,均为首次手术,男2例,女5例,男女比为2：5,年龄35～68岁,3例〉50岁,4例〈50岁,无泌尿系结石、骨骼疼痛和高钙血症等典型原发性甲状旁腺功能亢进（PHPT）症状.     

依达拉奉对肝移植术后再灌注损伤的保护作用

目的探讨依达拉奉对肝移植患者肝功能恢复的影响。方法 2007年1月~2011年1月于本院施行异体原位肝移植手术、肾功正常的患者28例,随机分为2组,治疗组14例于肝移植术中门静脉开放前30 min予依达拉奉30 mg+生理盐水100 mL静脉滴注,术后每日静点上述剂量的依达拉奉2次/d,对照组14例则不使用依达拉奉。其余所有治疗2组均相同。定期监测肝功能,包括天门冬氨酸转氨酶(AST),丙氨酸转氨酶(ALT)及乳酸脱氢酶(LDH),总胆红素(TBIL)。结果 2组患者手术前肝功能指标无明显差异,术后1 d AST,ALT及LDH急剧升高,但治疗组升高幅度明显低于对照组;术后3 d有所下降;至术后7 d大幅回落,但仍高于正常;术后胆红素水平亦升高,以术后1 d为著,手术后7 d趋于正常。依达拉奉组治疗后,其酶学指标及胆红素水平下降情况显著优于对照组。结论依达拉奉作为一种新型的氧自由基清除剂,能更快速的改善肝移植患者的肝功能,在肝移植术后肝功能的恢复治疗中,有很好的治疗价值。