TNFα和VEGF在激素性股骨头坏死中的变化

[目的]通过应用马血清、激素作用新西兰兔，诱导激素性股骨头坏死动物模型。分析TNFα、VEGF在激素性股骨头坏死中的作用。[方法]将20只健康新西兰兔随机分成2组，每组10只。A组为模型组。每只用马血清10ml／kg。经兔耳缘静脉注射。间隔2周，按5ml／kg剂量连续2d注射马血清各1次。间隔2周后，注射醋酸泼尼松龙。按7．5mg／kg腹腔注射3次。B组：正常对照组。动物注射激素5周后，采血，应用ELISA法测血清中TNF-α浓度。处死模型组，标本进行常规组织病理学检查，免疫组化分析股骨头VEGF的表达。[结果]模型组兔血清TNF-α浓度明显高于正常组（P〈0．01）。组织病理学检查显示：部分血管栓塞。骨髓腔内造血组织明显减少。免疫组化结果显示：骨细胞及骨髓组织VEGF表达明显减少。[结论]血清中TNF-α浓度升高及股骨头骨髓组织VEGF表达减少可能是激素性股骨头坏死发生的重要因素。     

血管内皮细胞生长因子促进激素性股骨头坏死修复

[目的]探讨应用血管内皮细胞生长因子治疗激素性股骨头坏死的方法。[方法]新西兰兔30只，22只兔耳缘静脉注射马血清，臀肌注射醋酸泼尼松龙，制造激素性股骨头坏死动物模型。动物随机分为3组：A组：VEGF治疗组，B组：对照组，C组：正常对照组。治疗组骨穿刺针行经皮注射血管内皮细胞生长因子脂质体至股骨头。于治疗后5周，采用影像学方法观察股骨头结构变化，病理组织学观察股骨头骨组织、骨髓造血组织及血管的变化。[结果]VEGF治疗组，X线及CT检查显示：模型股骨头结构变清晰，骨质破坏明显修复；HE染色结果：VEGF治疗组可见软骨细胞修复性增生，骨髓腔造血组织出现增生，栓塞的血管旁边出现新生的血管。[结论]VEGF治疗股骨头坏死能促进新血管生成及骨修复。     

恒古骨伤愈合剂对激素性坏死股骨头内VEGF基因表达的影响

目的：研究中药恒古骨伤愈合剂对兔坏死股骨头内VEGF基因表达的影响。方法：成年新西兰大白兔分为4组：A组（空白对照组），B组（正常兔服用恒古骨伤愈合剂），C组（造模后不喂恒古骨伤愈合剂），D组（造模后喂恒古骨伤愈合剂），每组24只。以大肠杆菌内毒素（LPS）（10μg／kg体重）间隔24h静注2次加甲基强的松龙（MPS）肌注3次制作兔股骨头坏死模型后，B组和D组用恒古骨伤愈合剂，A组和C组用等量生理盐水，按计算出的药量灌胃，1次／2d。于喂药至第4、8、12周时取股骨头行免疫组化、原位杂交并提取总RNA行实时荧光定量PCR，动态观察兔股骨头内VEGF基因表达的变化特点。结果：喂药至第4、8周时，比较D组与C组股骨头内VEGF基因表达量的差别无统计学意义。喂药至第12周时，D组与C组股骨头内VEGF基因表达量的差别具有统计学意义（P=0．042〈0．05）。B组与A组比较差别无统计学意义。结论：LPS加MPS制作的兔股骨头坏死模型中股骨头内VEGF基因表达受抑制。中药恒古骨伤愈合剂可促进坏死股骨头内源性VEGF基因的表达，以用药时间长者效果明显。恒古骨伤愈合剂对正常兔股骨头内VEGF基因的表达无影响。     

应用血管内皮生长因子基因治疗股骨头缺血性坏死的实验研究

目的：通过建立犬股骨头缺血坏死模型，探讨应用脱蛋白骨复合转染血管内皮生长因子（vascular endothelial growth factor，VEGF）基因骨髓基质细胞植入治疗股骨头缺血坏死的可行性。方法：实验选取36只成年犬，随机分为3组，每组12只。A组为脱蛋白异体骨复合转染VEGF基因的自体骨髓基质细胞；B组为脱蛋白异体骨复合未转染基因的自体骨髓基质细胞；C组单纯植入脱蛋白骨材料。采用液氮冷冻法制作狗股骨头缺血坏死模型，将细胞骨材料复合物植入缺血坏死股骨头内。应用微循环灌注方法了解股骨头内的血运情况，组织形态学观察坏死股骨头的修复情况，免疫组化方法检测VEGF的表达，骨密度仪测定股骨头的骨密度。结果：A组4周后股骨头内有VEGF表达，12周后股骨头内有大量的树枝状血管生成，大量新骨形成，骨密度增高；B、C组均无VEGF基因表达，B组有部分新骨及血管生成，C组仅见少量类骨质形成，血管再生不明显。结论：利用脱蛋白骨复合转染VEGF基因的骨髓基质细胞可促进新骨形成与血管再生，有利于促进坏死骨的修复。     

阿魏酸钠对兔激素性股骨头坏死早期促血管生成影响的实验研究

目的探讨药物阿魏酸钠对于激素性股骨头坏死(SANFH)早期干预以及对于血管变化的影响,以达到预防或延缓股骨头坏死的目的。方法利用改良的马血清加甲强龙的方法成功制备兔激素性股骨头坏死早期的动物模型,56只动物随机zhi分为对照,模型和治疗三组。分别选取激素注射后2周、4周、8周、12周共4个时间点,每组随机处死四只动物进行股骨头大体观察、HE染色、VEGF免疫组化染色、透射电镜观察。分析每组各时间点相关指标的变化情况以及各组之间的差异。结果大体观察以及HE染色和透射电镜观察发现早期股骨头坏死动物模型建立成功,且治疗组与模型组相比股骨头坏死表现明显减轻,VEGF表达增强,两组差别有统计学意义(P0.05)。结论阿魏酸钠可以有效地you,治疗e were dividied into 3 groups延缓或降低股骨头坏死的发生。     

一氧化氮对激素性股骨头缺血坏死治疗的生化研究’

目的 分析一氧化氮(NO)在前凝血状况下诱导实验性激素性股骨头缺血坏死过程中的作用。方法 36只成年新西兰兔随机分为三组，A组(正常对照组)12只；B组(疾病模型组)12只，间隔三周于兔耳缘静脉注射马血清，共2次，每次10ml／kg。于第二次注射后2周，腹腔连续3d注射甲基强的松龙，共3次，每天1次，每次40mg／kg，建立激素性股骨头缺血坏死模型；C组(治疗组)12只，模型诱导方式同B组，模型复制成功后，将硝酸甘油作为一氧化氮外源供体，采用介入疗法，通过微泵导管直接注入双侧股骨头供血动脉内，持续泵注药液治疗2周。三组动物均于实验完成后行心内穿刺抽取全血标本，测定血小板α颗粒膜蛋白(GMP-140)，氧化型低密度脂蛋白(OX—LDL)，NO的血浆含量，而后处死，切取双侧股骨头行HE染色，光镜下观察病理改变，统计空骨陷窝率和软骨下区血管数，进行组间t检验。结果 A、C组血浆OX—LDL和GMP-140水平明显低于B组，而血浆NO水平明显高于B组。C组空骨陷窝率及软骨下区血管数虽未完全达到A组正常水平，但较B组有明显改变。结论 NO生成减少导致的OX—LDL合成增多是引发激素性股骨头缺血坏死过程中系统血管内凝血的重要环节，以一氧化氮供体作为药物，采用介入疗法治疗激素性股骨头缺血坏死，具有一定临床应用前景。     

活血化瘀中药对激素性股骨头缺血坏死血管内皮生长因子表达的影响

目的:通过观察活血化瘀中药对激素性股骨头缺血坏死血管内皮生长因子(VEGF)的表达,探讨活血化瘀法防治激素性股骨头缺血坏死的作用机制。方法:30只成年新西兰大白兔采用抽签法随机分为2组,正常对照组5只和激素造模组25只。激素造模组每周2次臀肌注射7.5mg/kg醋酸氢化泼尼松,6周后从激素造模组中抽签随机抽取5只与正常对照组5只同时处死,观察组织病理学变化和VEGF表达。再将其余激素造模组动物(20只)采用抽签法随机分为治疗1、2组与对照1、2组,每组5只。治疗1、2组用桃红四物汤(当归、川芎、赤芍、桃仁、红花、生地)7ml/kg灌胃,每天1次,对照1、2组等量生理盐水灌胃。于10周后处死治疗1组和对照1组动物,13周后处死治疗2组和对照2组动物,检测VEGF表达。结果:造模后VEGF的表达明显增加,与正常对照组比较差异有显著性意义(P<0.01),但随时间推移,其表达越来越弱。与治疗组比较对照组的VEGF表达明显减弱,有统计学差异(P<0.001)。结论:活血化瘀中药间接地促进了VEGF的表达,可以有效地改善股骨头微循环障碍。     

激素性股骨头坏死过程中骨矿物盐的变化

目的：探讨骨矿物盐在激素性股骨头坏死发病过程中改变的意义。方法：选用50只健康成年新西兰大白兔,随机分为2组。激素造模组每周一次臀肌注射甲基强的松龙（辉瑞生物）4mg／kg,至第8周末停药,该组动物分别在四个不同时间段处死。正常对照组每周一次臀肌注射等量生理盐水,上述各组动物均肌内注射青霉素钠15万u／只,每周2次预防感染。各组分别于处理后的第2、4、8、10周测定股骨头及股骨颈的骨密度,并检测血清钙、磷水平,同时观察其体重、精神、毛发情况等一般指标变化。结果：与正常对照组比较,激素造模组动物造模1周后体重开始进行性下降,股骨颈骨密度从第2周开始、股骨头骨密度从第4周开始显著下降（P〈0．05,P〈O．01）,且激素造模组10周时股骨颈骨密度明显低于第8周时（火0．05）。与正常对照组比较,激素造模组血清钙、磷水平均从第2周开始即显著显著降低（火0．05,P〈O．01）,且激素造模组10周时血清钙水平明显低于第8周时（P〈0．05）。结论：本次实验发现,给予激素后,动物模型中的股骨头坏死迅速出现。激素性股骨头坏死与股骨头、颈骨密度降低及骨矿物盐平衡的破坏有关。     

介入治疗对兔VX2肝癌MMP-2/PCNA/VEGF表达的影响及其意义

目的：模拟不同方法介入治疗对兔VX2肝癌基质金属蛋白酶（MMP-2）、增殖细胞核抗原（PC-NA）、血管内皮生长因子（VEGF）表达的影响。方法：将VX2瘤细胞接种于40只新西兰大白兔肝左叶，建立VX2肝癌模型，随机分为4组，每组10只。介入治疗前MRI测量并记录肿瘤直径。经股动脉途径行肝固有动脉插管，分别注入生理盐水（对照组）、水化碘油（A组）、Ad-p53（B组）、Ad-p53＋水化碘油（C组）。术后1周处死动物，取肿瘤组织制作石蜡切片（HE）染色，镜下观察肿瘤组织坏死情况。免疫组化方法测定MMP-2／PCNA/VEGF的表达。结果：经肝动脉插管介入治疗1周后，A、B、C组肿瘤生长受到明显抑制，与对照组比较，P均〈0.05。单纯碘油栓塞后，肿瘤区的MMP-2、PCNA及VEGF的表达略有升高，与对照组相比P〉0.05；B组与C组的MMP-2、PCNA及VEGF的表达阳性率降低，与对照组相比，P均〈0.05；有转移的MMP-2、PCNA及VEGF的表达阳性率均高于无转移者（P〈0.05）；MMP-2与VEGF、PCNA之间之间有相关性（P〈0.05）。结论：碘油＋Ad-p53可抑制肿瘤的生长，抑制肿瘤新生血管形成，减少转移。MMP-2、PCNA、VEGF的增高预示着肿瘤的高转移、高增殖能力，肿瘤血管的高形成能力。     

联合检测血管内皮损伤标志物对糖尿病肾病早期诊断的价值

近年来，血栓调节蛋白（TM）、内皮素（ET）和血管内皮生长因子（VEGF）在糖尿病。肾病（DN）发生发展中的作用已引起广泛关注。目前国内外采用ELISA联合检测血浆TM、ET和VEGF对DN早期诊断研究甚少。我们应用联合检测血血浆TM、ET和VEGF水平可从不同病理改变和病理过程反映DN的。肾小球、肾上管及间质内皮损伤程度来早期诊断DN。     

尿脱氧吡啶啉对评价肾病综合征患儿泼尼松治疗后骨吸收异常的价值及肾康灵的干预作用

目的：（1）通过观察肾病综合征（NS）患儿尿脱氧吡啶啉（DPD）排泄率的变化,探讨用尿脱氧吡啶啉来评价泼尼松治疗肾病综合征患儿骨吸收异常的价值。（2）观察肾病综合征患儿肾康灵治疗前后DPD排泄率的变化,探讨肾康灵治疗激素性骨质疏松的疗效。方法：（1）以30例NS患儿为研究对象,在足量泼尼松治疗前及治疗后6周分别留取尿标本检测尿DPD排泄率。（2）30例患儿在泼尼松足量治疗后6周随机分为治疗组、对照组。对照组继续足量泼尼松治疗,治疗组在对照组的基础上加用中药复方肾康灵冲剂口服治疗,2周后留取尿标本检测尿DPD排泄率。结果：泼尼松足量治疗6周后尿DPD排泄率明显高于激素治疗前（P〈0.01）。（2）泼尼松足量治疗8周后治疗组与对照组相比较,尿DPD排泄率明显降低,两者比较有统计学差异（P〈0.05）。结论：（1）泼尼松治疗肾病综合征的患儿尿DPD排泄增加,支持了激素可导致骨吸收增加的观点。（2）肾康灵能显著降低肾病综合征的患儿尿DPD的排泄,提示其治疗激素性骨质疏松有一定益处,其抗骨质疏松作用可能通过多个途径而实现。     

霉酚酸酯治疗弥漫增生性狼疮肾炎的临床观察

目的 :评估霉酚酸酯联合强的松治疗弥漫增生性狼疮肾炎的疗效及其安全性。方法 :4 6例患者随机分成 2组 ,治疗组口服霉酚酸酯加强的松 12个月 ;对照组静滴环磷酰胺加口服强的松 6个月 ,之后给予强的松和硫唑嘌呤 6个月。结果 :治疗组的 2 5个病人中的 80 %完全缓解 ,对照组中 76 %完全缓解 ,而治疗组、对照组病人部分缓解率分别为 17%和 14 %。每组各有 1个病人因副作用中断治疗 ,治疗过程中治疗组有 2 0 % ,对照组有 33%病人出现感染 (P =0 .2 9)。同时观察到仅对照组病人中出现闭经 (占病人中的 2 3% )、脱发 (19% )、白细胞减少 (10 % )及死亡(10 % )等副反应。治疗组、对照组复发率分别为 13%和 11%。结论 :对于弥漫增生性狼疮肾炎的治疗 ,霉酚酸酯和强的松联合治疗的方案与环磷酰胺和强的松治疗后序贯使用硫唑嘌呤的方案效果相同 ,而前者的副作用较少     

免疫吸附治疗狼疮性肾炎的临床观察

目的 观察免疫吸附治疗狼疮性肾炎的临床疗效.方法 选择2007年7月至2010年7月狼疮性肾炎患者29例,均有明显的血尿、尿蛋白每天＞2.0 g,血肌酐(306.28±0.12)μmol.其中14例狼疮性肾炎患者采用DNA280免疫吸附柱进行血液净化治疗,免疫吸附治疗2次,每次2 h,同时按疗程给与小剂量泼尼松(0.5 mg·kg-1·d-1)及间断环磷酰胺(6～8 g)静脉冲击治疗.另外15例患者应用传统治疗方法,给予大剂量的泼尼松(1 mg·kg-1·d-1)及间断环磷酰胺静脉冲击治疗作为对照组并进行比较.结果 免疫吸附治疗组患者好转率为79%,对照组好转率为56%,两组比较差异有统计学意义(P＜0.01).结论 免疫吸附能有效地控制狼疮性肾炎,明显改善狼疮性肾炎患者的肾功能.

Abstract：

Objective immunoadsorption treatment of lupus nephritis clinical efficacy. Methods from July 2007 to July 2010 29 patients with lupus nephritis, have significant hematuria, urinary protein per day＞ 2.0 g, serum creatinine (306.28 ± 0.12) μmol. 14 patients with lupus nephritis were treated with DNA280 immunosorbent column and blood purification therapy, immunoadsorption therapy 2 times 2 h, while treatment given by a small dose of prednisone (0.5 mg·kg-1·d-1) and intermittent cyclophosphamide (CTX, 6-8 g) intravenous pulse therapy. Another 15 patients were treated with conventional therapy, high dose of prednisone (1 mg · kg-1 · d-1) and CTX intermittent intravenous pulse therapy as a control group and compared. Results improved in patients treated with immunoadsorption was 78.57% in the control group improvement was 56.25% (P ＜ 0.01). Conclusion The adsorption can effectively control the immune lupus nephritis, lupus nephritis significantly improved renal function.     

Observations on quadruple immunosuppression maintenance therapy using rapamycin, low-dose cyclosporine, mycophenolate mofetil, and prednisone following ATG induction

INTRODUCTION: We prospectively evaluated an immunosuppressive regimen consisting of rapamycin (Rapa), low-dose cyclosporine (CsA), low-dose mycophenolate mofetil (MMF), and prednisone (group 1) versus a regimen of CsA, MMF, and prednisone (group 2) in mismatched living related donor (LRD) and living unrelated donor (LUD) kidney transplantation. METHODS: Group 1 included 24 transplant recipients of eight mismatched LRD and 16 LUD, treated with Rapa, low-dose MMF, CsA, and prednisone. Group 2 included 53 transplant recipients (25 LRD, 27 LUD, and one cadaveric donor), treated with MMF, CsA, and prednisone. All patients in group 1 received a single bolus of rabbit-anti-human T-lymphocyte immune serum (ATG-Fresenius 4 to 6 mg/kg). In group 2, patients received either a single ATG or an extended ATG course (3 to 5 days postoperatively). RESULTS: Acute rejection occurred in one patient in group 1 (4.2%) and in five patients (9.4%) in group 2, all of which resulted in graft loss. Serum creatinine was not significantly different between the two groups. CONCLUSION: The immunosuppressive protocol of Rapa, CsA, MMF, and prednisone with single-bolus induction ATG achieves excellent immunosuppression and graft survival with no apparent risks in the short and intermediate term.     

阿奇霉素对大鼠阿霉素肾病的干预作用

目的 通过观察阿奇霉素对阿霉素肾病大鼠血、尿生化指标、肾脏组织病理以及细胞间黏附因子1（ICAM-1）、nephrin与podocalyxin在肾组织表达的影响,探讨其在大鼠阿霉素肾病中的干预作用。 方法 建立大鼠阿霉素肾病模型,分为阿奇霉素治疗组、泼尼松治疗组、联合治疗组、模型组及正常对照组。监测实验0、4、8周24 h尿蛋白量（24 h-up）及血生化指标动态变化,计算内生肌酐清除率（Ccr）。观察肾组织病理形态学改变。免疫组化SP法观察肾组织中ICAM-1、nephrin、podocalyxin的表达。 结果 实验4周时尿蛋白及白蛋白指标均达到肾病模型要求,提示模型制作成功。实验8周,与模型组相比,各治疗组大鼠的各项观察指标均有不同程度改善,24 h-up、胆固醇、Scr显著降低（P < 0.05）,总蛋白、Alb及Ccr（除外C组）有所增加（P < 0.05）,肾组织病理改变减轻,肾脏病理积分及细胞外基质/肾小球面积比值降低（P < 0.01）,肾小球及肾小管ICAM-1表达减少（P < 0.01）,nephrin、podocalyxin表达增高。综合比较,其中联合治疗组疗效最好。 结论 阿奇霉素对阿霉素肾病大鼠的干预有类似于泼尼松样的治疗作用,但其对早期肾功能的保护作用逊于泼尼松,而二者联合应用可起到协同治疗的作用,其药效明显优于两药的单独应用。     

Phase III study of mitoxantrone plus low dose prednisone versus low dose prednisone alone in patients with asymptomatic hormone refractory prostate cancer

PURPOSE: We compared median time to treatment failure of men with asymptomatic, hormone refractory, progressive prostate cancer treated with mitoxantrone plus prednisone versus prednisone alone. MATERIALS AND METHODS: In a multicenter phase III trial 120 men with asymptomatic, progressive, hormone refractory prostate cancer were randomly assigned to treatment with mitoxantrone and prednisone or prednisone alone. Patients received 12 mg./m. mitoxantrone intravenously once every 3 weeks for 6 cycles and 5 mg. prednisone twice daily with or without mitoxantrone. Time to treatment failure was assessed as an aggregate end point comprised of time to disease progression, time to toxicity or death, or time to initiation of alternate therapy. RESULTS: Median followup was 21.8 months. Median time to treatment failure and median time to progression were the same: time to treatment failure and time to progression in the mitoxantrone and prednisone group was 8.1 months compared to 4.1 months in the prednisone alone group (p = 0.017 versus p = 0.018). More patients (27 or 48%) treated with mitoxantrone and prednisone achieved a 50% or greater reduction in prostate specific antigen levels than those who received only prednisone (15 or 24%, p = 0.007). There was no significant difference in median survival between the 2 groups, which was 23 and 19 months, respectively. Death was mainly attributable to disease progression. CONCLUSIONS: Patients with hormone refractory prostate cancer who are asymptomatic but had progressive disease had a significantly higher response rate when treated with mitoxantrone and prednisone as demonstrated by the 50% or greater decrease in prostate specific antigen compared to treatment with prednisone alone. Time to treatment failure was significantly prolonged in the chemotherapy treated group but survival rates were not different.     

Comparison of Sirolimus vs. Mycophenolate Mofetil on Surgical Complications and Wound Healing in Adult Kidney Transplantation

Mycophenolate mofetil (MMF) and sirolimus impair wound healing. We compared sirolimus vs. MMF to determine the relative impact on surgical complications and wound healing in adult kidney transplant recipients. This retrospective, single center study of 235 adult kidney transplants performed between 1 January 2000 and 31 January 2002 identified 158 adult, kidney-only recipients treated with tacrolimus and prednisone, from which two groups were defined: group 1 (n = 84) received MMF, group 2 (n = 74) received sirolimus. The incidence of fluid collections, wound problems, dehiscence, and urine leak were compared. A multivariate stepwise logistical regression analysis was performed to identify risk factors. The overall incidence of complications was 21.5%, with rates significantly lower in group 1 (2.4%) vs. group 2 (43.2%, p < 0.0001). Regression analysis showed only sirolimus (p < 0.001) and hypo-albuminemia (p = 0.006) to independently correlate with complication occurrence. In subanalyses, lymphoceles correlated only with sirolimus (p = 0.003), while other wound problems also correlated with higher body mass index (p = 0.067). The use of sirolimus, tacrolimus and prednisone was associated with a greater incidence of lymphoceles, non-lymphocele perinephric fluid collections and other consequences of poor wound healing, as compared to contemporary patients treated with MMF, tacrolimus and prednisone.     

Coadministration of either cyclosporine or steroids with humanized monoclonal antibodies against CD80 and CD86 successfully prolong allograft survival after life supporting renal transplantation in cynomolgus monkeys

BACKGROUND: Recent studies have shown some efficacy using monotherapy with monoclonal antibodies (mAb) against CD80 and CD86 receptors after life-supporting renal transplantation in non-human primates. Our study was designed to evaluate the efficacy of combinations of the same mAbs with either microemulsion cyclosporine (CsA) or steroids. METHODS: Unilateral renal transplantation was performed in 16 blood group-matched and MLR-mismatched cynomolgus monkeys that were assigned to four different treatment groups. All monkeys in groups I, II, and IV were treated with the combination of a CD80 (h1F1) and CD86 (h3D1) mAb given at 20 mg/kg each preoperatively, then 5 mg/kg at weekly intervals starting postoperative (po) day 0 until poday 56 (9 doses). In group I the animals (n=4) were treated with mAbs only. In group II (n=4) mAbs were combined with a CsA regimen adjusted daily to maintain target 24 hr trough levels of 150-300 ng/ml CsA for poday 0 to poday 56. In group III (n=4) the animals received CsA monotherapy according to the same regimen as group II. In group IV methylprednisone was administered at 2 mg/kg IV on poday 0-2, then at 0.5 mg/kg/day prednisone per gavage that was and tapered to 0.2 mg/kg/day on which they were maintained until poday 56. All animals were off all immunosuppressive treatment after poday 56 and were then followed until poday 119. RESULTS: The mean survival of groups I-IV was 74 (range 9-119 days), 113 (96-119 days), 39 (22-71 days), and 79 days (6 to 119), respectively. All animals in group I showed clinical evidence of acute severe rejection (fever, creatinine increase, anuria) within the first week posttransplant, including those that retained renal function until poday 119. Only one animal in group II had a moderate clinical rejection during the treatment period and three of four animals survived the intended follow-up period. All animals in group III had multiple biopsy proven or severe clinical rejection episodes within the first 21 days and only one animal survived beyond poday 40. Moderate or severe acute rejection was diagnosed in three of four animals of group IV within the first 28 days post transplant and only one animal survived until poday 119. CONCLUSION: Our data show that combining a calcineurin inhibitor or prednisone with mAbs designed to block costimulatory signals does not antagonize the immunosuppressive efficacy of these mAbs. In addition, combining CsA with mAbs directed against the CD80 and CD86 receptors significantly prolongs graft survival when compared to CsA monotherapy. Therefore clinical trials of humanized mAbs to CD80 and CD86 used in combination with conventional immunosuppression can be considered.     

Low-dose maintenance prednisone and antilymphoblast globulin for the treatment of acute rejection. A steroid-sparing approach to immunosuppressive therapy

The purpose of this prospective randomized trial was to evaluate an immunosuppressive protocol involving reduced maintenance and antirejection steroid dosages in cadaver renal transplantation. The study comprises 23 first cadaver graft recipients who experienced an acute rejection episode. All patients received an initial 14-day course of antilymphocyte globulin (ALG) and azathioprine 1.5 to 2.0 mg/kg/day. In 11 patients (group 1), a low maintenance dose of prednisone (30 mg/day) was administered and first rejection episodes were treated with a second 10-day course of ALG. The remaining 12 patients (group 2) received high maintenance doses of prednisone (2 mg/kg/day with tapering) and intravenous methylprednisolone (IVMP) for first rejection episodes. Subsequent rejections in both groups were treated with high doses of steroids. In group 1, all first rejection episodes were reversed with ALG alone, 6 patients experienced no subsequent rejection, and 10 patients currently have a functioning graft. In Group 2, the first rejection episode was reversed with IMVP alone in 10 patients; in two patients in whom IVMP therapy was unsuccessful, ALG was then administered, and subsequent rejection reversal was effected. In group 2, 4 patients experienced no subsequent rejection, and 9 patients currently have a functioning graft. Patients in group 1 received significantly lower (P less than .01) cumulative steroid doses in the first six months following transplantation, which resulted in a reduced number of major infections, as compared with patients in group 2. We conclude that the steroid-sparing regimen of low maintenance prednisone and ALG for first rejection is as effective immunologically as the established high steroid protocol.     

Immunosuppression without prednisone after liver transplantion is safe and associated with normal early graft function: preliminary results of a randomized study

Abstract Prednisone has been commonly considered the mainstay of immunosuppressive therapy after liver transplantation. Recent data suggest that prednisone withdrawal late after transplant reduces complications without affecting graft function. We report here the preliminary results of an open-label, randomized study aimed at investigating whether prednisone therapy can be completely avoided during the first 3 months after transplantation. Twenty-seven consecutive patients were randomized to receive double (group A: cyclosporine and azathioprine) or triple (group B: prednisone, cyclosporine, and azathioprine) immunosuppressive therapy after liver transplantation. Six patients died within the first 3 weeks in each group and were excluded from the calculations. The present results refer to 10 patients in group A and 11 in group B. The actuarial 1-year survival did not differ between the two groups (90.9 % vs 88.8 %). There were no differences with respect to infectious complications or episodes of histological acute graft rejections. Only one severe acute rejection occurred in group A and two in group B. During the first month after transplant, liver and kidney functions tended to be better in the group of patients treated without prednisone, although there were no differences in the mean cyclosporine blood levels. These data, though preliminary, indicate that early immunosuppression without the use of prednisone is safe and tends to be associated with improved liver and renal functions compared to conventional triple therapy.