急性胰腺炎患者血脂和载脂蛋白水平的初步观察

本文测定了２３例急性胰腺炎（ＡＰ）患者和２３例健康对照组的血清甘油三酯（ＴＧ）与胆固醇（ＴＣ）、高密度脂蛋白胆固醇（ＨＤＬ－Ｃ）、低密度脂蛋白胆固醇（ＬＤＬ－Ｃ）、极低密度脂蛋白胆固醇（ＶＬＤＬ－Ｃ）和载脂蛋白（Ａｐｏｓ）ＡⅠ、Ｂ１００、ＣⅡ、ＣⅢ。结果表明与对照组比较，ＡＰ患者的ＴＧ（Ｐ＜０．０１）、ＬＤＬ－Ｃ（Ｐ＜０．０５）和ＡｐｏＢ１００（Ｐ＜０．０１）明显增高；与治疗前相比较，ＡＰ患者用大承气汤为基本方的中西医结合治疗措施治疗后的ＴＧ、ＬＤＬ－Ｃ和ＡｐｏＢ１００未能降低（Ｐ＞０．０５）。提示ＡＰ患者存在脂质和Ａｐｏｓ的异常，特点是高ＴＧ及ＬＤＬ－Ｃ增高，ＡｐｏＢ１００明显增高。     

透析患者脂蛋白A增高意义的探讨

本对５０例维持性血液透析（ＨＤ）患和３８例持续性非卧床腹膜透析（ＣＡＰＤ）患脂蛋白Ａ（Ｌｐ（ａ））及其他血脂进行测定，并以５０例正常人作对照，结果Ｌｐ（ａ）分别为０．５２±０．３３ｇ／Ｌ，０．７７４±０．３５４ｇ／Ｌ，均显高于对照组０．２７０±０．２５６ｇ／Ｌ（Ｐ〈０．０１）。两透析组患的甘油三酯（ＴＧ）、高密度脂蛋白胆固醇（ＨＤＬ－ｃｈ）低密度脂蛋白胆固醇（ＬＤＬ－ｃｈ），载脂蛋白Ａ－     

Ⅱ型糖尿病患者血清Ⅳ型胶原水平的变化及意义

目的　探讨Ⅱ型糖尿病患者血清Ⅳ型胶原（ ＣⅣ） 的变化及其与糖尿病肾损害可能的关系和作用。方法　采用放射免疫法对８４ 例Ⅱ型糖尿病患者及４５ 例正常人血清 ＣⅣ水平进行检测。结果　糖尿病（ Ｄ Ｍ） 患者血清 ＣⅣ水平［（１０５ ．４８ ±１８ ．０９）μｇ／ Ｌ］ 明显高于对照组［（８９ ．２０ ±９ ．７０）μｇ／ Ｌ, Ｐ ＜ ００１］ ;微量及大量白蛋白尿期患者［（１０６ ．４６ ±１８ ．５９）μｇ／ Ｌ,（１２０ ．９０ ±１５ ．５４）μｇ／ Ｌ］ 较对照组显著增高（ Ｐ ＜ ００１ , Ｐ＜ ０００１） ; Ｄ Ｍ 各组间血清 ＣⅣ水平差异显著,随着２４ 小时尿白蛋白 排泄量（ Ｕ Ａ Ｅ） 的增加及病程的延长,血清 ＣⅣ水平递增,病程超过５ 年者 显著高于病程短于５ 年者;血清 ＣⅣ与血尿素氮（ Ｂ Ｕ Ｎ） 、肌酐（ Ｃｒ） 、２４ 小 时 Ｕ Ａ Ｅ 及尿 Ｎ乙酰β氨基葡萄糖苷酶（ Ｎ Ａ Ｇ） 均呈显著正相关,与病程、空腹血糖（ Ｆ Ｂ Ｇ） 亦呈高度正相关。结论　 Ｄ Ｍ 存在着胶原代谢的异常。血清 ＣⅣ水平随 Ｄ Ｎ 的严重程度而明显增高。血清 ＣⅣ可作为 Ｄ Ｎ 早期诊断的敏感指标     

不同类型冠心病的胰岛素抵抗及危险因素分析

目的：比较不同类型冠心病（ＣＨＤ）的胰岛素抵抗（ＩＲ）程度和分析ＣＨＤ的危险因素。方法：检测急性心肌梗死（ＡＭＩ）８１例,不稳定型心绞痛（ＵＡ）８２例,稳定型心绞痛（ＳＡ）８５例和对照组１２７例糖耐量、胰岛素（ＩＳ）和Ｃ肽（ＣＰ释放试验、空腹血脂等,并以餐后血糖（ＢＧ）、ＩＳ和ＣＰ及血压等１０个变量进行Ｌｏｇｉｓｔｉｃ回归分析。结果：ＵＡ组舒张压（ＤＰ）显著高于对照组（Ｐ〈０．０１）,ＳＡ组ＤＰ明显高于对照组（Ｐ〈０．０５）;ＵＡ组ＣＨ明显高于ＳＡ组和对照组（Ｐ〈０．０５）;ＡＭＩ组服糖后３ｈＢＧ、ＵＡ组２ｈ、３ｈＢＧ均明显高于对照组（Ｐ〈０．０５）;ＵＡ组１ｈＩＳ明显高于对照组（Ｐ〈０．０５）;ＡＭＩ组服糖后２ｈ、３ｈＣＰ／ＢＧ分别明显高于对照组和ＳＡ组（Ｐ〈０．０５）;３ｈＢＧ和ＤＰ被筛选为ＣＨＤ的独立危险     

氨甲酰血红蛋白在评价血液透析充分性中的意义

目的　评价氨甲酰血红蛋白（ Ｃａｒ Ｈｂ） 在血液透析（ Ｈ Ｄ） 充分性中的意义。方法　用高效液相色谱法测定正常对照组３６ 例,非透析慢性肾功能衰竭５１ 例和 Ｈ Ｄ 患者３０ 例 Ｃａｒ Ｈｂ 含量（ 以每克血红蛋白含氨甲酰缬氨酸微克数,μｇ Ｃ Ｖ／ｇ Ｈｂ 表示） 。 Ｈ Ｄ 组 Ｃａｒ Ｈｂ 含量与尿素清除指数（ Ｋｔ／ Ｖ） 、尿素降低率（ Ｕ Ｒ Ｒ） 、平均时间尿素浓度（ Ｔ Ａ Ｃｕｒｅａ） 和校正蛋白质分解率（ｎ Ｐ Ｃ Ｒ） 作相关分析。结果　与对照组（３００ ±６１） 比较, Ｈ Ｄ 组 Ｃａｒ Ｈｂ 含量（１０２５ ±２８９） 显著升高（ Ｐ＜ ００１） ,但显著低于非透析组（１３９９ ±５２０）（ Ｐ＜ ００１） ; Ｋｔ／ Ｖ≤１１ 组 Ｃａｒ Ｈｂ 显著高于 Ｋｔ／ Ｖ＞ １１ 组［（１３５０ ±３１０）ｖｓ．（８８６±１２０） , Ｐ＜ ００１］ ; Ｃａｒ Ｈｂ 与 Ｋｔ／ Ｖ, Ｕ Ｒ Ｒ 呈负相关,但与 Ｔ Ａ Ｃｕｒｅａ 正相关。当 Ｋｔ／ Ｖ＞ １１ ,ｎ Ｐ Ｃ Ｒ＜ １０ ｇ· Ｋｇ１·ｄ１ 组 Ｃａｒ Ｈｂ 显著高于ｎ Ｐ Ｃ Ｒ≥１０ ｇ· Ｋｇ１·ｄ１ 组［（９６５ ±８３）ｖｓ．（８１５ ±１０４） , Ｐ     

肿瘤浸润性淋巴细胞结合偶联半乳糖抗CD3单克隆抗体的肝脏靶向性研究

目的　探讨结合偶联半乳糖（ Ｇａｌａｃｔｏｓｅ , Ｇａｌ） 抗 Ｃ Ｄ３ 单克隆抗体（ Ａｎｔｉ Ｃ Ｄ３ Ｍｃ Ａｂ） 肿瘤浸润性淋巴细胞（ Ｔｕｍｏｒｉｎｆｉｌｔｒａｔｉｎｇ ｌｙｍｐｈｏｃｙｔｅｓ , Ｔ Ｉ Ｌ） 肝脏靶向性。 方法　本组把大鼠抗小鼠 Ｃ Ｄ 单克隆抗体和半乳糖偶联在一起,与３ Ｈ Ｔｄ Ｒ 标记 Ｔ Ｉ Ｌ结合后,从鼠尾静脉注入小鼠体内,在注射不同时间眼眶取血０５ ｍｌ,然后处死,切除肝、脾、肺,分别称重后进行放射性强度测定。 结果　结果显示：注射 Ｇａｌａｎｔｉ Ｃ Ｄ３ Ｍｃ Ａｂ Ｔ Ｉ Ｌ小鼠肝脏比注射单纯 Ｔ Ｉ Ｌ 的小鼠肝脏具有较高的放射性（ Ｐ＜ ００１） ,且该放射性持续较长一段时间,而脾、肺、血液内放射性强度差异无显著意义（ Ｐ＞ ００５ , Ｐ＞ ００５ , Ｐ＞ ００５） 。结论　该结果提示： Ｇａｌａｎｔｉ Ｃ Ｄ３ Ｍｃ Ａｂ Ｔ Ｉ Ｌ较单纯 Ｔ Ｉ Ｌ具有更好的肝脏靶向性。     

长春新碱对5肽胃泌素促人结肠癌细胞株SW480增殖的影响及其临床意义

目的　从细胞信号传导方面探讨长春新碱抑制胃泌素促人结肠癌细胞株ＳＷ４８０ 增殖的机理及临床意义。方法　采用噻唑氮蓝（ ＭＴＴ） 比色分析法、３Ｈ肌醇掺入法及Ｃａ２＋ 荧光测定技术和γ３２ＰＡＴＰ 掺入法，在体外观察长春新碱（ ＶＣＲ） 对５ 肽胃泌素（ＰＧ） 促人结肠癌细胞株ＳＷ４８０ 增殖的影响。结果　ＰＧ＋ ＶＣＲ 组的ＳＷ４８０ 细胞活细胞数降低，与对照组相比Ｐ＜ ０ ．０１ ，与ＰＧ 组相比 Ｐ＜ ０ ．０１ ； ＰＧ＋ ＶＣＲ 组细胞内三磷酸肌醇及Ｃａ２＋ 浓度降低，与ＰＧ 组相比 Ｐ＜０ ．０１ ，与对照组相比Ｐ＞ ０ ．０５ ； ＰＧ＋ ＶＣＲ 组膜蛋白激酶活性降低，与ＰＧ 组相比Ｐ＜ ０ ．０５ ，与对照组相比 Ｐ＞ ０ ．０５ 。结论　长春新碱可能通过肌醇脂质信号通路而影响胃泌素促人结肠癌细胞株ＳＷ４８０ 的增殖，从而为结肠癌的抗信息传导治疗提供了实验依据。     

氧自由基与精索静脉曲张不育关系的研究

测定２５例精索静脉曲张（ＶＣ）不育患者外周及精索静脉血浆和红细胞丙二醛（ＭＤＡ）、超氧化物歧化酶（ＳＯＤ）和全血谷胱甘肽过氧化物酶（ＧＳＨ－Ｐｘ）的含量，并与２０例有生育能力的左侧鞘膜积液和腹股沟疝者进行了比较研究。结果曲张精索静脉血浆ＭＤＡ和红细胞ＭＤＡ的含量不仅高于外周血而且明显高于对照组（Ｐ＜０．０５，Ｐ＜０．０１），但二者外周血氧自由基均无显著性差异（Ｐ＞０．０５）。曲张精索静脉ＧＳＨ－Ｐｘ和ＳＯＤ活性低于ＶＣ外周血和对照组（Ｐ＜０．０５，Ｐ＜０．０１）。说明ＶＣ时由于自由基的产生增加和清除不足直接导致睾丸间质细胞的代谢功能紊乱，同时也造成精子生成障碍。因此氧自由基可能是造成ＶＣ不育的原因之一     

外源性甲状腺素对心内直视术围术期心肌能量代谢酶的影响

目的 研究外源性甲状腺素（ＴＨ）对心内直视术围术期心肌能量代谢的影响。方法 将二尖瓣置换术（ＭＶＲ）患者随机分为用药组和对照组，术前４～７ｄ用药组服甲状腺片，对照组服安慰剂。检测术前、中、后心民酸脱氢酶（ＬＤＨ）、细胞色素氧化酶（ＣＣＯ）、琥珀酸脱氢酶（ＳＤＨ）、钙ＡＴＰ酶（Ｃａ＾２＋－ＡＴＰａｓｅ）活性的变化。结果 用药组ＳＤＨ、ＣＣＯ、Ｃａ＾２＋－ＡＴＰａｓｅ的活化比对照组增高（Ｐ〈０．００１     

门脉高压大鼠胃粘膜屏障功能的实验研究

为探讨门脉高压性胃病的发病机理，将Ｗｉｓｔａｒ大鼠４２只随机分为肝硬变组（ＬＣ组，ｎ＝１５）、门静脉狭窄组（ＰＶＳ组，ｎ＝１５）和假手术组（ＳＯ组，ｎ＝１２），以观察其血流动力学指标、胃壁结合粘液（ＧＰ）、胃粘膜内源性前列腺素Ｅ２（ＰＧＥ２）水平、胃基础泌酸量（ＢＡＳ）以及Ｈ＋返渗量（Ｈ＋ＢＤ）。结果：ＬＣ组及ＰＶＳ组大鼠内脏血流量较ＳＯ组明显增加（Ｐ＜０．００１），但胃粘膜却处于缺血状态；其ＧＰ和ＰＧＥ２含量也较ＳＯ组显著下降（Ｐ＜０．０１），其中ＬＣ组又较ＰＶＳ组更低（Ｐ＜０．０５）；ＢＡＳ３组间无差异，但ＬＣ组及ＰＶＳ组大鼠之Ｈ＋ＢＤ明显高于ＳＯ组（Ｐ＜０．００１），且以ＬＣ组最为显著。本实验结果提示：门静脉高压大鼠胃粘膜屏障功能遭到严重破坏，尤以肝硬变大鼠为甚；门脉高压性胃病的发生与胃粘膜屏障功能削弱有关；肝功能受损参与胃粘膜病变的发生。     

肾移植受者应用他克莫司治疗窗浓度的探讨

目的　寻求适合国人肾移植受者他克莫司 (FK5 0 6 )理想治疗窗浓度范围。方法　应用微粒子酶免疫分析法测定 5 8例肾移植患者口服FK5 0 6后 12h的血药谷浓度 ,并观察排斥反应的发生及药物的肾毒性。结果　FK5 0 6的血药浓度 ,术后 1个月为 (13.0± 2 .1) μg/L ,2～ 3个月为 (9.4±1.6 ) μg/L ,3个月以后为 (6 .5± 1.3) μg/L ,比较各时期全血FK5 0 6谷浓度 ,差异均有极显著性 (P <0 .0 1) ;术后发生急性排斥反应 3例次 ,肾毒性 4例次。结论　FK5 0 6具有良好的免疫抑制效果 ,其治疗窗浓度范围 ,术后第 1个月为 11～ 15 μg/L ,第 2～ 3个月为 8～ 11μg/L ;第 3个月后为 5～ 8μg/L ,此浓度范围既能达到满意的免疫抑制效果 ,又能减少FK5 0 6的肾毒性     

异基因造血干细胞移植治疗重型β珠蛋白生成障碍性贫血

目的 探讨异基因造血干细胞移植(allo-HSCT)治疗重型β珠蛋白生成障碍性贫血的临床疗效.方法 PesaroⅡ-Ⅲ度重型β珠蛋白生成障碍性贫血患者24例接受allo-HSCT治疗,其中男性18例,女性6例,患者年龄中位数为4岁(2～15岁).24例中,同胞供者23例,母亲供者1例;HLA 6个抗原全相合23例,5个抗原相合1例;骨髓混合外周血干细胞移植15例,脐带血移植9例.采用白消安+环磷酰胺+氟达拉滨的预处理方案.环孢素A(CsA)+甲氨蝶呤(MTX)+抗胸腺细胞球蛋白(ATG)+吗替麦考酚酯(MMF)联用预防移植物抗宿主病(GVHD).中位随访时间13个月(3～69个月).结果 移植后22例患者造血功能顺利恢复.至随访结束,无病存活21例;移植相关死亡1例(4.2%);移植物排斥反应2例(8.3%).21例的3年无病存活率为87.5%,3年总体存活率为91.7%.Ⅱ-Ⅳ度急性GVHD的累积发生率为16.7%,慢性GVHD的累积发生率为20.3%,广泛性慢性GVHD的发生率为5.0%.结论 异基因骨髓混合外周血干细胞移植治疗珠蛋白生成障碍性贫血可获得确切疗效,同时脐带血是珠蛋白生成障碍性贫血移植的重要干细胞来源.CsA+MTX+ATG+小剂量、短疗程MMF的方案可以有效地减少严重急性GVHD的发生,提高移植疗效.

Abstract：

Objective To investigate the effect of allgeneic hematopoietic stem cell transplantation (allo-HSCT) for β-thalassemia major. Methods Twenty-four β-thalassemia major patients with median age of 4 years (range: 2～15 years), 18 boys and 6 girls, received allo-HSCT.They were classified into class Ⅱ-Ⅲ according to Pesaro thalassemia classification. Twenty-three transplantations were from sibling donor and 1 was from mother, either HLA-identical (n = 23) or HLA-mismatched (5/6) (n = 1). Fifteen patients received bone marrow transplantation (BMT) plus peripheral blood stem cell transplantation (PBSCT), and 9 were subjected to umbilical cord blood transplantation (UCBT). The conditioning regimen consisted of busalphan, cyclophosphamide,fludarabine, plus hydroxyurea before transplantation. Graft-versus-host disease (GVHD) prophylaxis included CsA, methotrexate, antilymphpcute globulin, and mycophenolate mofetil. The median follow-up period was 13 months (range: 3～69). Results Of 24 patients, there were 21 cases (87. 5 %) of disease-free survival, 1 (4. 2 %) transplantation-related death, and 2 cases (8. 3 %) of rejection. Three-year overall survival and disease-free survival rate was 91.7 % and 87. 5 %respectively. The cumulative incidence of grade Ⅱ -Ⅳ acute GVHD and chronic GVHD was 16. 7 %and 20. 3 %, particularly cumulative extensive chronic GVHD was 5. 0 %. Conclusion The sibling donor BMT plus PBSCT is an effective and safe way to treat β-thalassemia major. Cord blood is an important source of hematopoietic stem cells for HSCT. The protocol GVHD prophylaxis of CsA,MTX, ATG with a low-dose and short course of MMF can effectively reduce the incidence of severe acute GVHD, improve the outcome of thalassemia transplantation.     

Six weeks of continuous intravenous cyclosporine and short-course methotrexate as prophylaxis for acute graft-versus-host disease after allogeneic bone marrow transplantation

The feasibility and toxicity of six-week continuous intravenous 3 mg/kg/day cyclosporine (CsA) treatment in conjunction with a short course of methotrexate (MTX) was studied in 69 consecutive patients after HLA genotypically identical bone marrow transplantation. In light of the uncertain efficacy of prolonged oral CsA immunoprophylaxis in preventing de novo chronic graft-versus-host disease (GVHD). CsA treatment was terminated three months after BMT. Sixty-one (88%) patients received the full intravenous regimen and no patient exclusions were necessary due to intolerable adverse effects. Weekly median blood CsA concentrations ranged between 820 ng/ml in the first and 648 ng/ml in the sixth week of treatment. No significant correlation existed between blood CsA concentrations and CsA dosages. Major adverse effects of the regimen included hypertension in 36%, acute nephrotoxicity in 36%, acute hepatotoxicity in 41%, and central nervous system toxicity in 4% of the patients. Since hepatotoxicity occurred predominantly in the early posttransplant period (median onset day 9), the relatively high incidence of this untoward effect might have been additionally caused by MTX and/or the preparative regimen. Blood CsA concentrations and CsA dosages did not significantly correlate with serum creatinine or total and conjugated bilirubin levels. In addition, blood CsA and serum creatinine levels did not differ between hypertensive and normotensive patients. Acute GVHD developed in 16% of the patients. Median CsA doses and blood CsA concentrations were identical for each week after BMT for patients contracting acute GVHD as compared with those without acute GVHD. In 55 patients surviving without acute or secondary chronic GVHD, the cumulative probability of de novo chronic GVHD after termination of CsA treatment was 13%. In conclusion, this regimen was tolerable and provided constant blood CsA concentrations for six posttransplant weeks that were not adversely influenced by the development of acute GVHD. Restriction of CsA treatment to the first three months after BMT appeared not to increase the risk of de novo chronic GVHD, which challenges regimens employing oral CsA immunoprophylaxis for 6-12 months after BMT.     

The safety and efficacy of acute graft‐versus‐host disease prophylaxis with a higher target blood concentration of cyclosporine around 500 ng/mL

Cyclosporine (CsA) is the most widely used immunosuppressive agent for the prevention of acute graft‐versus‐host disease (GVHD). In a previous report, the incidence of acute GVHD was decreased by increasing the target blood concentration of CsA during a continuous infusion from 300 to 500 ng/mL without excessive toxicities. To confirm these results, we retrospectively analyzed 69 patients who received a continuous infusion of CsA at a higher target CsA level between 450 and 550 ng/mL (CsA500 group) and compared the clinical outcome with 29 patients who received CsA with a lower target concentration between 250 and 350 ng/mL (CsA300 group). The target concentration was determined based on the status of background diseases. Multivariate analysis revealed that the incidence of grade III‐IV acute GVHD was significantly lower in the CsA500 group, although the incidence of grade II‐IV acute GVHD was not different. Toxicities were equivalently observed between the two groups. Concomitant administration of voriconazole or itraconazole and higher hematocrit were identified as independent significant factors for higher concentration/dose ratio of CsA. The average dose of CsA to maintain CsA level around 500 ng/mL was higher compared with the previous study (3.4 mg/kg vs. 2.7 mg/kg at three wk), probably due to the difference in measuring method of CsA concentration. We conclude that continuous infusion of CsA with a target level between 450 and 550 ng/mL is a feasible and effective GVHD prophylaxis, but caution should be paid for the difference in measuring method.     

他克莫司对肾移植后糖代谢的影响及其控制

目的：制定他克莫司（PK506）治疗窗浓度,并控制肾移植后糖尿病（PTDM）的发生和发展。方法：对肾移植术后用PK506为基础的免疫抑制剂治疗的20例受者,进行回顾性研究,结果：20例患者随访1年,4例发展为糖尿病,发生率为20％,患者发病前4－8周都经受较高FK506浓度（20－28μg/L）作用,经降低泼尼松（Pred)用量、结合胰岛素替代治疗效果不佳,后经调整FK506浓度为：第1个月5－15μg/L,第2个月起5－10μg/L。2例血糖完全恢复正常,另2例因急性并发症转换为环孢素A（CsA)治疗。治疗期间无1例出现急性排斥和血肌酐升高。结论FK506具有强效免疫抑制作用,可防止急性排斥发生,在使用FK506期间,一旦发生PTDM,可通过减少Pred用量降低FK506浓度,同时使用胰岛素控制其发生、发展。如出现急性并发症,可将FK506转换为CsA。     

移植物中不同种类和数量的细胞对异基因外周血造血干细胞移植后急性GVHD的影响

目的 探讨移植物中单个核细胞(MNC),CD34+细胞,T淋巴细胞(包括CD3+、CD3+CD4+、CD3+CD8+和CD4+CD25+),CD3 CD16+CD56+自然杀伤(NK)细胞,以及树突状细胞(DC)Ⅰ和Ⅱ型(DC1和DC2)的数量对人类白细胞抗原(HLA)相合的同胞异基因外周血造血干细胞移植(allo-PBSCT)后急性移植物抗宿主病(aGVHD)的影响.方法 选择65例接受HLA相合的同胞allo-PBSCT的患者进入研究.采用流式细胞术检测移植物中MNC,CD34+细胞,T淋巴细胞(CD3+、CD3+CD4+及CD3+CD8+)的数量,对其中31例患者进一步检测CD4+CD25+T淋巴细胞、CD3-CD16'C+D56+NK细胞及DC的数量.按患者的每公斤体重计算出输注的移植物中以上各细胞的数量.并根据上述细胞数量的中位数分别将患者分为高数量组(>中位数)和低数量组(≤中位数),比较各高数量和低数量组aGVHD的发生情况.结果 CD3+CD4+、CD3+CD8+T淋巴细胞高数量组和相应低数量组相比,Ⅱ～Ⅳ度aGVHD的累积发生率增加,但差异无统计学意义(P值分别为0.089和0.098);CD4+CD25+T淋巴细胞高数量组Ⅲ～Ⅳ度aGVHD的累积发生率显著低于相应低数量组(P<0.05);DC1高数量组总的aGVHD累积发生率显著高于相应低数量组(P<0.05),Ⅱ～Ⅳ度aGVHD累积发生率亦明显高于相应低数量组,但差异无统计学意义(P=0.069).MNC、CD34+细胞、CD3+T淋巴细胞、CD3-CD16+CD56+NK细胞及DC2高数量组与相应低数量组比较,总的及Ⅱ～Ⅳ度aGVHD的累积发生率差异均无统计学意义(P>0.05).结论 移植物中高数量的DCl增加总的aGVHD的累积发生率;而高数量的CD4+CD25+T淋巴细胞则减少Ⅲ～Ⅳ度aGVHD的累积发生率.     

Optimizing tacrolimus therapy in the maintenance of renal allografts: 12-month results

BACKGROUND: The determination of optimal tacrolimus (TAC) trough levels is needed to prevent adverse effects of calcineurin inhibitors. METHODS: Stable transplant recipients currently receiving cyclosporine (CsA) were assigned randomly (1:1:1) to continue CsA (target trough level of 50-250 ng/mL); or convert to "reduced" TAC (target trough level 3.0-5.9 ng/mL) or "standard" TAC (target trough level 6.0-8.9 ng/mL). RESULTS: At 12 months, there was a significant improvement in renal function in the reduced TAC versus CsA group with lower serum creatinine (P=0.004) and cystatin C (P<0.001), and higher estimated creatinine clearance (P=0.017). However, there were no statistically significant differences in any renal parameter in the standard TAC versus CsA group. Total and low-density lipoprotein cholesterol were significantly reduced in both TAC groups versus the CsA group (P<0.001). Patient and graft survival and episodes of biopsy-confirmed acute rejection were similar for all treatment groups, and no statistically significant differences were observed between groups in the incidence of new-onset diabetes or cardiac conditions, or in the prevalence of hyperglycemia, hypertension, or hyperlipidemia among patients who did not have these conditions at baseline. Alopecia developed more commonly among TAC-treated patients than CsA-treated patients (P<0.001). CONCLUSIONS: Compared with CsA continuation, conversion to reduced TAC target trough concentrations resulted in significantly improved renal function without increasing the risk of rejection. Conversion to TAC, regardless of target concentration, resulted in improved serum lipid profiles in kidney transplant recipients at 12 months.     

环孢素A血药浓度监测的临床意义

目的：探讨环孢素A(CsA)血药谷值浓度监测的临床意义。方法：对269例同种肾移植受者术后4081次CsA血药谷值浓度进行了分析。结果：随着移植肾存活时间的延长,CsA治疗浓度水平呈逐渐下降趋势。排斥反应发生时及排斥反应前两周内,CsA浓度不仅低下,而且有一持续约2周的显著下降过程,平均降幅达31％。术后一周内急性排斥反应的发生与CsA浓度关系不大。过高的CsA浓度则与肾中毒’反应有关。CsA治疗浓度与发生排斥反应时的浓度及肾中毒浓度均有一定程度的重叠。结论：认为术后CsA理想的治疗窗浓度应为：术后第1月内为300-450ng／ml,3月内为250～400ng／ml,半年内为200～350ng／ml,以后CsA浓度最好维持在150～250ng／ml。     

Randomized, International Study of Cyclosporine Microemulsion Absorption Profiling in Renal Transplantation with Basiliximab Immunoprophylaxis

Increasing information suggests that absorption profiling may be superior to trough level monitoring for optimal concentration control of cyclosporine microemulsion (Neoral^TM) therapy, and that CsA exposure early post‐transplant may correlate significantly with reduced risk of acute graft rejection. This randomized, prospective, multicenter international concentration‐controlled study was conducted in 21 renal transplant centers in 8 countries to test and compare the clinical feasibility, functionality, accuracy, precision and prediction of rejection by cyclosporine microemulsion absorption profiling to conventional trough‐level drug monitoring. Primary or second renal allograft recipients treated with basiliximab, cyclosporine microemulsion and prednisone immunosuppression were randomized to two study groups in which cyclosporine microemulsion therapy was monitored using a multipointalgorithm or by trough levels. The two study arms were comparable in terms of baseline characteristics, treatment and clinical outcomes. Treatment failure, consisting of acute rejection, graft loss or death, occurred with equal incidence in the two groups (30% and 33%, respectively). Diagnostic feasibility, measured as the proportion of samples obtained within the designated time window, was marginally lower in area under the time‐concentration curve (AUC) than in trough groups, but the therapeutic accuracy and precision were comparable or superior in the AUC group. Cox regression analysis performed across study groups showed a highly significant correlation between the predicted probability of acute rejection and cyclosporine (CsA) exposure measured by AUC over the entire 12‐h dosage interval (AUC[0–12]) (p = 0.0068), AUC over the first 4 h of the 12‐h dosage interval (AUC[0–4]) (p = 0.0014) or 2 h post‐dose (C2) CsA level (p = 0.0027). Day 3 dose‐ and weight‐corrected C2 values (EMIT equivalent) separated patients into low (< 200 μg/L/mg/kg dose), intermediate (200–350 μg/L/mg/kg dose) and high absorber categories (> 350 μg/L/mg/kg dose), defining those at greatest risk. Within these categories, C2 values above approximately 1500 μg/L by day 3 post‐transplant were associated with the lowest predicted probability of rejection. Comparable analysis by Cox regression using C0 levels did notreach statistical significance. Absorption profiling is a feasible, accurate and precise method for monitoring cyclosporine microemulsion therapy in clinical practice and, as shown in the companion article, may be simplified by the use of single‐point C2 concentrations which accurately predict individual AUC[0–4] exposure levels. Both cyclosporine microemulsion relative absorption (i.e. dose‐ and weight‐corrected exposure) and CsA exposure (measured by predicted AUC or C2 levels) are closely correlated with the risk of rejection, and define patients at high and low risk of acute graft rejection. Trough (C0) levels are not closely correlated with either CsA exposure or rejection risk, and should not be considered reliable for monitoring cyclosporine microemulsion therapy.     

Relationship between pharmacokinetic parameters of cyclosporin and the incidence of acute rejection after heart transplantation

Despite two decades of use, there are limited data on the best way to monitor Cyclosporine (CsA) for heart transplantation. The aim of our study was to determine the relationships between pharmacokinetic parameters and clinical outcomes after heart transplantation and to evaluate the range of CsA trough levels provided the most effective protection against graft rejection. We retrospectively analyzed the clinical outcomes of all adult patients who received a heart transplant between January 1998 and February 2005. All had routine monitoring of CsA trough levels and scheduled endomyocardial biopsies. Rejection was defined as grade > or =3, based on International Society for Heart and Lung Transplantation (ISHLT) criteria. Follow-up period was 1 year. All patients were on CsA, corticosteroids, and azathioprine/mycophenolate mofetil with or without antilymphocyte induction (eight patients with basiliximab). Data were analyzed by unpaired Student t-test, Cox regression model, and ROC curve. Among 70 patients (60 men and 10 women) who entered the study, 34 (48.6%) had at least one acute rejection episode of grade > or =3 during the first posttransplant year. Mean CsA trough level (C(0)) measured at first week posttransplant was significantly lower in the rejection than the no-rejection group (125.17 +/- 56.9 ng/mL versus 169.33 +/- 48.27 ng/mL, P = .001). C(0) was the strongest predictor of acute graft rejection (P = .000, HR = .985.) The risk decreased by 1.5% for each unit increase of the C(0) value. ROC analysis showed that C(0) of 150 ng/mL provided the optimal cutoff. Patients with mean C(0) >150 ng/mL over the first week had less incidence of acute rejection than patients with levels <150 ng/mL (30.3% versus 64.9%) (P = .009, Cochran-Mantel-Haenszel test). In conclusion, our data suggest that in heart transplant patients it may be crucial to target early trough levels above 150 ng/mL during the first days postsurgery to avoid rejection.