他克莫司对猪胸腺细胞表面抗原表达的影响

目的 探讨他克莫司（ＦＫ５０６）对猪胸腺细胞表面抗原表达的影响。方法 对５头猪按１ｍｇ／ｋｇ肌肉注射ＦＫ５０６２１ｄ，然后取猪胸腺制成细胞悬液，双色法间接免疫荧光染色后，以流式细胞仪检测。方法 ＦＫ５０６组的胸腺Ｔ淋巴细胞数较对照组显著降低（Ｐ〈０．００１），表面抗原阴性的前Ｔ淋巴细胞较对照组显著增高（Ｐ〈０．０１）；ＦＫ５０６组ＣＤ１＾－ＣＤ５＾－、ＣＤ２＾－ＣＤ５＾－和ＣＤ４＾－ＣＤ８＾－双阴     

老年患者施行肾移植的临床特点

目的 探讨老年患者肾移植的特点、影响移植效果的主要因素及提高移植成功率的措施。方法 对６４例年龄在６０岁以上的老年患者肾移植的资料进行总结。６４例中年龄最大者７３岁，平均６３．６岁。术后环孢素Ａ（ＣｓＡ）的起始量较一般患者低０．５～１．０ｍｇ．ｋｇ＾－１．ｄ＾－１，术后１年内的维持量较同期一般患者低０．２～３．０ｍｇ．ｋｇ＾－１．ｄ＾－１。结果 人、肾１年存活率均为８６．５％，３年存活率为７１．４     

肾移植术后肝功能异常患者用他克莫司替换环孢素A疗效的？…

目的 观察他克莫司（ＦＫ５０６）替换环孢素Ａ（ＣｓＡ）并联合应用霉酚酸酯（ＭＭＦ）及泼尼松（Ｐｒｅｄ）防治肾移植术后肝功能异常患者的有铲性一。方法 肾移植术后８例肝功能异常患者（男性５例，女性３例，平均３８．２３岁），用ＦＫ５０６替换ＣｓＡ治疗，停用ＣｓＡ２４ｈ后，开始给予ＦＫ５０６。ＦＫ５０６初始剂量根据患者体重、肝功能损害程度及术后时间确定，服药１周后，根据全血ＦＫ５０６谷值浓度调整剂量，使其     

肾移植术后应用FK506抗排斥治疗的临床研究

目的　观察ＦＫ５０６ 在肾移植术后抗排斥治疗的效果及副作用。　方法　对肾移植术后单独应用环孢素Ａ（ＣｓＡ）５０ 例和术后应用ＦＫ５０６ ５０ 例（ 术后２４ 小时应用ＦＫ５０６ ４０ 例,ＣｓＡ 中毒后改ＦＫ５０６ １０ 例）患者进行比较。　结果　ＣｓＡ 组发生急性排斥反应（ＡＲ）９ 例,发生率为１８ ％ ,逆转８ 例（８８ ％） ,肾功能在２ ～２６ 天恢复正常３８ 例（７６ ％） ,肺部感染２ 例,泌尿系感染１ 例,肾中毒２例,肝中毒３ 例,高血糖２ 例,腹泻１ 例,摘肾１ 例。ＦＫ５０６ 组ＡＲ４ 例均逆转,肾功能２～１３ 天恢复正常４０ 例（８０％ ）,高血糖１４ 例（２８％ ）,肾中毒２ 例,肝中毒１ 例,腹泻２２ 例（４４％ ）,１ 例因肺部感染、高血糖难以控制仍改用ＣｓＡ。应用ＣｓＡ 肝中毒的１０ 例患者改用ＦＫ５０６ 后肝功能７ ～１６ 天全部恢复正常。　结论　肾移植术后应用ＦＫ５０６ 安全有效,排斥率明显降低,副作用小,但对长期存活的影响及并发症还需进一步观察。     

肾移植患者术后早期应用霉酚酸酯的临床观察

目的 观察肾移植术后早期不同剂量霉酚酸酯（ＭＭＦ）与环孢素Ａ（ＣｓＡ）和泼尼松（Ｐｒｅｄ）联用预防急性排斥反应的效果及安全性。方法 将６４例肾移植患者分为３组,分别给予ＭＭＦ２．０ｇ／ｄ（Ａ组）、１．５ｇ／ｄ（Ｂ组）及Ａｚａ ５０～１００ｍｇ／ｄ（Ｃ组）,每组均联用ＣｓＡ及Ｐｒｅｄ（剂量相同）。观察肾移植术后６个月内急性排斥反应的发生率、移植肾功能及药物的副作用。结果 Ａ、Ｂ、Ｃ组急性排斥反应的发     

普乐可复在肾移植中的临床应用

目的 研究普乐可复（ＦＫ５０６）对肾移植患者免疫抑制的疗效与安全性。方法 肾移植术后应用ＦＫ５０６免疫抑制治疗８２例,分为临床验证组４２例和切换治疗组４０例。结果 临床验证组有４０例（９５．２％）肾功能在１４ｄ内恢复正常,１例（２．４％）发生急性排斥反应,经治疗逆转。切换治疗组有２４例肝功能正常;３例移植肾发生急性肾小管坏死（ＡＴＮ）伴急性排斥反应,６例发生慢性排斥反应,４例发生难治性排斥反应,均     

肾移植术后并发原发性肝癌二例

例１，女性，４８岁。因慢性肾小球肾炎、尿毒症于１９９３年２月行同种异体肾移植术。手术顺利，肾功能恢复正常。术后长期服用环孢素Ａ（３ｍｇ·ｋｇ－１·ｄ－１）、硫唑嘌呤（７５ｍｇ／ｄ）及泼尼松（１５ｍｇ／ｄ）。１９９５年１２月ＣＴ示肝右叶大片低密度影，Ｂ...     

免疫抑制方案对肾移植并发慢性病毒性肝炎预后的影响

１９９１至１９９４年４月中山医科大学附一医院共完成１０１例肾移植。随访时间２８．６±９．６个月。术前供受者淋巴细胞毒性试验阴性。术中及术后２天，每日用甲基泼尼松龙（ＭＰ）０．２５～０．５ｇ，同时选用二联或三联免疫抑制方案。三联方案为泼尼松（Ｐｒｅｄ）、硫唑嘌呤（Ａｚａ）加环孢素Ａ（ＣｓＡ）；Ａｚａ于术前１天开始用１ｍｇ·ｋｇ－１·ｄ－１；Ｐｒｅｄ于术后第３天开始３０ｍｇ／ｄ，３个月后开始减量，一年后减为１０ｍｇ／ｄ；ＣｓＡ一般术后第３天开始５～８ｍｇ·ｋｇ－１·ｄ－１。二联方案为Ｐｒｅｄ加ＣｓＡ…     

肾移植术后应用他克莫司的临床观察

目的 观察他克莫司（ＦＫ５０６）作为免疫抑制剂的有效性和安全性。方法 将首次接受同种异体肾移植的３５例患者随机分为２组,一组给予他克莫司,硫唑嘌呤（或霉酚酸酯）和泼尼松（ＦＫ５０６组）,另一组给予环孢素Ａ、硫唑嘌呤（或霉酚酸酯）及泼尼松（ＣｓＡ组）,观察２个组的免疫抑制效果及药物的副作用。结果 ＣｓＡ组和ＦＫ５０６组的人／肾１年存活率分别为１００．０％／９３／３％和９５．０％／９５．０％;两组肝和     

胃肠道癌术后腹腔,静脉化疗所致毒性反应临床分析

对胃肠道癌术后２３例腹腔内化疗（腹腔组）与３２例静脉化疗（静脉组）所致的毒性反应比较分析２腹腔组给予ＤＤＰ３０￣６０ｍｇ／Ｍ＾２，５－ＦＵ１￣２ｇ／Ｍ＾２，加入１Ｌ生理盐水，通过药泵滴入腹腔。静脉组给予ＤＤＰ２０￣２５ｍｇ／Ｍ＾２，５－ＦＵ０．５￣０．７５ｇ／Ｍ＾２，部分病例加用ＭＭＣ２￣４ｍｇ／Ｍ＾２静注。结果显示，腹腔组出现腹胀较静脉组多，而恶心、呕吐，周围静脉炎，肝、肾功能异常，骨髓抑制等较     

普乐可复预防同种肾移植排斥反应的研究

目的 评价并比较新型免疫抑制普乐可复（ＦＫ５０６）对预防同种肾移植受者排斥反应的疗效及安全性。方法 随机将９８例肾移植受者分成２组。（１）ＦＫ５０６组（ｎ＝４０）;主要用药为ＦＫ５０６＋霉酚酸酯（ＭＭＦ）＋泼尼松（Ｐｒｅｄ）;（２）环孢素９Ａ（ＣｓＡ组）（ｎ＝５８）;主要用药为;ＣｓＡ＋ＭＭＦ＋Ｐｒｅｄ。结果 ２组受者平均随访时间为１２．５个月。     

尸体肾移植术后应用他克莫司的体会

目的：观察肾移植患者应用他克莫司（FK506）进行免疫抑制治疗的效果和副作用。方法：对肾移植术后应用FK506的64例患者的临床资料进行回顾性分析。结果：肾移植术后应用FK506,霉酚酸酯（MMF）及泼尼松的24例患者,术后未发生急性排斥反应;先用环孢素A,后因肝功能异常,急性排斥反应及慢性排斥反应而改用FK506的40例患者,大部分排斥缓解,肝功能改善;FK506的主要副作用有血糖升高（10．9％）和肾毒性（4．7％）,结论：FK506是一种强效的免疫抑制剂,其用量的个体差异很大。     

Effects of inhaled FK 506 on the suppression of acute rejection after lung transplantation: use of a rat orthotopic lung transplantation model.

BACKGROUND: FK 506 inhalant was recently developed for localized administration. We investigated its effects on acute lung allograft rejection and compared its efficacy with that of intramuscular administration of FK 506. METHODS: Rats (n = 123) with orthotopic left lung transplantation were divided into 9 groups. Six groups inhaled FK 506 (5 puffs, 10 puffs or 20 puffs per day), or were given intramuscular administration of FK 506 (0.05, 0.1 or 1.0 mg/kg/day). The other groups included rats receiving an isograft, rats with an untreated allograft, and a placebo group. All groups (n = 6 each) were monitored for 14 days post-operatively as an end-point and graft survival time was determined. The remaining animals were killed 4 days after transplantation. The histologic grade of rejection was determined for all groups (n = 6 each). With both (n = 3 each) inhalation therapy and intramuscular administration of FK 506, which showed similar degrees of effectiveness, both blood FK 506 concentration and cytokine expression in the graft and spleen were evaluated. RESULTS: FK 506 inhalation therapy extended allograft survival time and reduced histologic rejection on Day 4 in all groups. Graft survival time and histologic rejection scores at a dose of 10 puffs/day were comparable to those with 0.1 mg/kg/day of intramuscular FK 506. Trough concentrations of FK 506 in blood were detectable with 0.1 mg/kg/day of intramuscular FK 506, but not with 10 puffs/day. The messenger RNA expression levels of interferon-gamma in the lung allograft was suppressed significantly at a dose of 10 puffs/day. CONCLUSIONS: FK 506 inhalant enhances acute lung allograft survival with lower blood concentrations than when using comparable intramuscular administration.     

环孢素A和他克莫司在高危肾移植患者中的应用比较

目的　比较高危肾移植患者术后应用环孢素 A(CsA)和他克莫司(FK506)的疗效和安全性。方法　将58例高危肾移植患者随机分为CsA组(30例)和FK506组(28 例),观察肾移植后 1年内两组的急性排斥发生率和药物逆转率、药物毒副作用及感染发生情况。结果　 FK506组和 CsA组的人/肾存活率分别为100%/100%和93.3%/86.7%;急性排斥反应发生率分别为14.3%和16.7%;抗排斥治疗的逆转率分别为100%和60%。FK506组药物毒副作用也较 CsA组小。结论　在高危肾移植患者的免疫抑制治疗中FK506应为首选。     

Clinical and Histopathologic Examination of Renal Allografts Treated with Tacrolimus (FK506) for at Least One Year

Background : We clinically and pathologically analyzed renal allografts from 19 renal transplant patients treated with tacrolimus (FK506) for more than 1 year.
Methods : Twenty-six renal allograft biopsy specimens from 19 renal transplant patients who underwent transplantations between 1991 and 1 993 were evaluated. Thirteen biopsies were performed from stable functioning renal allografts with informed consent (nonepisode biopsy) and the other 13 were from dysfunctional renal allografts with a clinical indication for biopsy (episode biopsy).
Results : The main pathologic diagnoses (some overlap) were acute rejection (AR; n = 4), chronic rejection (CR;n = 5), AR + CR(n=4), recurrent IgA nephropathy (n = 5), normal findings (n = 2), minimal-type chronic FK506 nephropathy (n = 9), and mild-type FK506 nephropathy (n = 11). Of the nonepisode biopsies, 7 and 4 biopsies showed minimal-type and mild-type chronic FK506 nephropathy, respectively. Chronic FK506 nephropathy consisted of rough and foamy tubular vacuolization (5 biopsies), arteriolopathy (angio-degeneration of the arteriolar wall; 20 biopsies), focal segmental glomerulosclerosis (4 biopsies) and the striped form of interstitial fibrosis (11 biopsies). The serum creatinine levels of patients in the mild-type chronic FK506 nephropathy group, which included 7 episode biopsies, were statistically higher than those in the minimum-type chronic FK506-nephropathy group (P < 0.001).
Conclusions : This study demonstrates that chronic FK506 nephropathy consists primarily of arteriolopathy manifesting as insudative hyalinosis of the arteriolar wall, and suggests that mild-type chronic FK506 nephropathy is a condition which may lead to deterioration of renal allograft function.     

肝胰肾联合移植的免疫抑制治疗

目的 介绍1例存活超过1年的肝胰肾联合移植患者术后免疫抑制治疗方法。方法对1例肝炎后肝硬化合并尿毒症、I型糖尿病、慢性胰腺炎患者施行原位背驮式肝、胰液空肠引流式胰、十二指肠及肾一期联合移植，采用二剂巴利昔单抗（舒莱）诱导，抗胸腺细胞球蛋白（ATG）、他克莫司（FK506）、吗替麦考酚酯（MMF）、泼尼松四联维持治疗。结果 术后移植肝脏及胰腺功能1周内逐渐恢复；肾功能延迟恢复，于术后第16天因消化道大出血致肾脏血流下降，切除移植肾脏，于原移植部位进行第2次肾移植，术后第3天肾功能恢复正常，未发生排斥反应。患者已健康存活超过1年，移植肝、胰、肾功能良好，生活自理。结论 肝胰肾联合移植术前后采用二剂舒莱诱导，同时用ATG、FK506、MMF及泼尼松作为免疫维持治疗安全有效，用药期间进行移植物功能、血药浓度及T细胞亚群（CD4^＋，CD4^＋）监测是防治排斥反应、感染及药物中毒的有效手段。     

转化生长因子-β1在他克莫司肾毒性中的作用

目的 观察转化生长因子(TGF)-β1在他克莫司大鼠肾毒性中的作用.方法 将SD大鼠24只随机分成对照组、CsA组、FK506组和FK506+Dil组,用药4周后建立起各组大鼠模型.观察各组大鼠的肾功能,应用免疫组织化学技术检测各组大鼠TGF-β1的表达.结果 FK506组大鼠的血肌酐值为(34.17±4.54)μmol/L,肌酐清除率为(0.58±0.39)ml·min-1·100g-1,与对照组比较差异有统计学意义(P<0.05).FK506组TGF-β1的阳性表达率均为100%(6/6),对照组TGF-β1的阳性表达率为16%(1/6),两者差异有统计学意义(P<0.05). 结论 TGF-β1可能介导了FK506引起的肾毒性.     

Rescue therapy with tacrolimus (FK 506) in renal transplant recipients -a Scandinavian multicenter analysis

Abstract All renal allograft recipients ( n = 32) in Sweden and Norway who were converted from cy-closporin(CyA)-based immunosuppression to FK 506 (tacrolimus) between October 1992 and June 1995 were analyzed retrospectively. The reasons for conversion were acute refractory rejection ( n = 21), chronic rejection ( n = 4), and suspected CyA toxicity ( n = 6); one patient was converted for psychological reasons. The mean time from transplantation to conversion was 29 (range 1–243) weeks and there was a mean follow-up of 46 (2–143) weeks. Overall graft survival was 59 %, with graft survival 52 % in patients converted because of acute rejection, 50 % in patients converted because of chronic rejection, and 83 % in patients converted because of CyA toxicity. There was no significant correlation between preconversion serum creatinine and outcome. Seventy-two percent of the patients had significant side effects during FK 506 treatment, the most frequent ones being neurological and gastrointestinal symptoms. These improved after dose reduction. Two patients became overimmunosup-pressed and developed lymphoma. One patient died of the primary kidney disease, hemolytic uraemic syndrome. We conclude that FK 506 therapy is able to salvage kidneys with acute refractory rejection and that it is an alternative in patients with CyA toxicity. However, the risk of overimmunosuppression must be considered.     

Skin allograft survival and analysis of renal parameters after FTY720 + tacrolimus treatment in mice

Calcineurin inhibitors such as cyclosporine (CsA) and tacrolimus (FK506) show similar efficacy to prevent rejection within the first year after organ transplantation. However, their use is limited by side effects, such as kidney damage, hypertension, new-onset diabetes, and hyperlipidemia. The consensus opinion suggests that compared with CsA, FK506 has fewer negative effects on blood pressure, serum lipids, and renal function. Nevertheless, FK506 use is associated with a higher incidence of posttransplantation diabetes mellitus. FTY720 is a new compound that has shown beneficial effects in animal models of rejection in transplantation, ischemia/reperfusion injury, autoimmune diseases, and tumor development. Our aim was to investigate whether FTY720 + tacrolimus association could provide additional immunosuppression without causing renal toxicity. FTY720 as a monotherapy or in association with FK506 was administered to C57BL/6 mice for 21 days to prevent skin graft rejection and to evaluate renal function and structure. Increased skin allograft survival in the FTY720 + FK506 group was associated with decreased cell numbers in the spleen, blood, and axillary lymph nodes. Changes in major histocompatibility complex (MHC) class II and intercellular adhesion molecule-1 (ICAM-1) expressions in splenocytes were also found in this group. The major effects already described for FK506 (diabetes) or FTY720 (lymphopenia) were observed after 21 days administration even when the drugs were associated. FTY720 associated with FK506 caused fewer changes in kidney structure, and blood glucose levels were lower than in FK506 monotherapy.