酶酚酸酯对实验性自身免疫性脑脊髓炎大鼠神经功能的影响

目的观察酶酚酸酯(MMF)对实验性自身免疫性脑脊髓炎(EAE)大鼠神经功能改善及脑脊髓组织的影响。方法用豚鼠全脊髓匀浆和完全弗氏佐剂制成的完全抗原免疫Wistar大鼠,制备EAE大鼠模型,以生理盐水和完全弗氏佐剂注射的Wistar大鼠作为对照。对照组大鼠7只,造模成功且存活的大鼠为25只,随机分为MMF大剂量组（n=8只）,MMF小剂量组（n=8只）,模型组（n=9只）。连续给药14d,每天观察记录神经功能评分及体重变化,14d后HE染色观察脑、脊髓组织病理变化。结果EAE大鼠的造模成功率为72.1%。与对照组相比,各组EAE大鼠神经功能评分明显增加,体重明显下降(P＜0.01),脑脊髓组织病理学变化主要表现为血管周围有大量炎细胞浸润;与模型组相比,用MMF治疗后神经功能评分有所下降,体重增加,病理表现有不同程度的减轻,且大剂量MMF疗效优于小剂量MMF(P＜0.01)。结论MMF能改善EAE大鼠的症状,促进神经功能恢复,并具有剂量依赖性。     

霉酚酸酯与环磷酰胺冲击治疗狼疮性肾炎临床疗效的比较

目的 比较霉酚酸酯（ＭＭＦ）与间断性环磷酚胺静脉冲击疗法（ＣＴＸ）治疗狼疮肾炎（ＬＮ）的近期及远期疗效、不良反应及安全性。方法Ａ组：间断性环磷酞胺冲击疗法治疗３０例ＬＮ患者，平均随访（１８６５±６．１０）（６～２４）月． Ｂ组：ＭＭＦ联合激素治疗ＬＮ患者，平均随访（２１.８９±７. ４８）（６～４８）月．两组患者的病理类型、病情基本相似，但 Ｂ组（ＭＭＦ）绝大部分为皮质激素联合 ＣＴＸ治疗无效者，Ｂ组患者病程明显较Ａ组长。结果ＣＴＸ组、ＭＭＦ组治疗ＬＮ均能降低蛋白尿和血尿，改善肾功能及免疫指标，两组间差异无显著性意义。ＭＭＦ组患者的平均疗程较ＣＴＸ组明显延长，而疗效却基本相同 ．不良反应：ＭＭＦ组无肝功能受累、性腺抑制副反应，感染率为 １３．３％。ＣＴＸ组感染率为 ２３．３％．肝功能受累为 ２３.３％，性腺抑制为 ２８％．结论 ＣＴＸ、ＭＭＦ都能有效的控制狼疮肾炎，改善肾功能，两者无显著性差异．对病程长、激素联合ＣＴＸ无效及病情迁延者，经ＭＭＦ治疗后达到与ＣＴＸ组同样效果，而且副作用少，提示ＭＭＦ具有一定的优越性。     

Neurotoxicity of calcineurin inhibitors: impact and clinical management

Between 10 %–28 % of patients who receive the immunosuppressant cyclosporine (CsA) experience some form of neurotoxic adverse event. Both sensorial motoric functions may be adversely affected, and thus patients present with a wide range of neurological and psychiatrical disorders. Mild symptoms are common and include tremor, neuralgia, and peripheral neuropathy. Severe symptoms affect up to 5 % of patients and include psychoses, hallucinations, blindness, seizures, cerebellar ataxia, motoric weakness, or leukoencephalopathy. Tacrolimus is associated with similar neurotoxic adverse events. Neurotoxicity may result in serious complications for some patients, particularly recipients of orthotopic liver transplants. Factors that may promote the development of serious complications include advanced liver failure, hypertension, hypocholesterolemia, elevated CsA or tacrolimus blood levels, hypomagnesemia, and methylprednisolone. Occipital white matter appears to be uniquely susceptible to the neurotoxic effects of CsA; injury to both the major and minor vasculature may cause hypoperfusion or ischemia and local secondary toxicity in the white matter. Calcineurin inhibition by CsA and tacrolimus alters sympathetic outflow, which may play a role in the mediation of neurotoxic and hypertensive adverse events. The symptoms of CsA- and tacrolimus-associated neurotoxicity may be reversed in most patients by substantially reducing the dosage of immunosuppressant or discontinuing these drugs. However, some patients have experienced permanent or even fatal neurological damage even after dose reduction or discontinuation. CsA-sparing and tacrolimus-sparing drug regimens that use the immunosuppressant mycophenolate mofetil, which has no neurotoxic effects, may reduce the incidence and severity of neurotoxic adverse events while maintaining an adequate level of immunoisuppression. Received: 6 April 1999/Revised: 19 April 2000/Accepted: 5 June 2000     

肾移植术后吗替麦考酚酯替换硫唑嘌呤的临床分析

目的 :观察肾移植后吗替麦考酚酯 (MMF)替换硫唑嘌呤 (Aza)的安全性及其临床效果。方法 :回顾分析16例由Aza转换为MMF患者的临床资料。4例因肝功能损害而改用MMF,7例肾功能损害 ,5例应患者要求而换用MMF。结果 :4例肝功能损害者肝功能均恢复正常 ,7例肾功能损害者2例逆转 ,4例肌酐 (SCr)下降但未能恢复正常 ,1例继续恶化恢复血液透析。2例不良反应包括原有贫血明显加重 ,1例腹泻。结论 :Aza可以安全替换为MMF。因环孢素 (CsA)加Aza引起肝功能损害者 ,换用MMF ,减少CsA用量 ,肝功能可望恢复。MMF对部分慢性排斥反应可能有效     

High Incidence of Severe Acute Graft-Versus-Host Disease with Tacrolimus and Mycophenolate Mofetil in a Large Cohort of Related and Unrelated Allogeneic Transplantation Patients

Both acute and chronic graft-versus-host disease (GVHD) are major causes of morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplantation (AHSCT). The optimal pharmacological regimen for GVHD prophylaxis is unclear, but combinations of a calcineurin inhibitor (cyclosporin or tacrolimus [Tac]) and an antimetabolite (methotrexate or mycophenolate mofetil [MMF]) are typically used. We retrospectively evaluated the clinical outcomes of 414 consecutive patients who underwent AHSCT from sibling (SD) or unrelated donors (UD) with Tac/MMF combination, between January 2005 and August 2010. The median follow-up was 60 months. Less than one third of the patients received a reduced-intensity chemoregimen. The incidence of grades III and IV acute GVHD was 22.3% and 36.5% in SD and UD groups, respectively (P = .0007). The incidence of chronic GVHD was 47.1% and 52.7% in the SD and UD groups, respectively. Nonrelapse mortality (NRM) at 60 months was 33.3% and 46.5% in the SD and UD groups, respectively (P = .0016). The incidence of relapse was 22.4% for UD and 28.8% for SD. Five-year overall survival was 43% and 34% in the SD and UD groups, respectively (P = .0183). GVHD was the leading cause of death for the entire cohort. Multivariable analysis showed that 8/8 HLA match, patient's age < 60, and low-risk disease were associated with better survival. The use of Tac/MMF for GVHD prophylaxis was associated with a relatively high incidence of severe acute GVHD and NRM in AHSCT from sibling and unrelated donors.     

肝移植术后转换为以吗替麦考酚酯胶囊为主的免疫抑制方案的临床应用

目的探讨肝移植术后长期生存受者转换为以吗替麦考酚酯胶囊(商品名:骁悉)为主的免疫抑制方案的疗效及安全性。方法回顾性分析我中心肝移植术后长期生存受者中22例因钙神经蛋白抑制剂(calcineurin inhibitors,CNI)所致肝肾功能损害、高血压等原因转换为以吗替麦考酚酯胶囊为主的免疫抑制方案前后肝肾功能的改善情况及排斥反应和副作用的发生率。结果 8例受者因肾功能损害而转换为以吗替麦考酚酯胶囊为主的免疫抑制方案,其中7例(87.5%)在2个月内肾功能明显好转;4例肝功能损害,其中3例(75%)肝功能明显改善;9例受者逐渐减少CNI剂量,其中8例(88.9%)肝肾功能良好,未出现排斥反应,1例(4.5%)减量后6个月出现排斥反应,增加CNI剂量后治愈;1例因移植后高血压难以控制换用吗替麦考酚酯胶囊,其后监测血压在正常范围。1例(4.5%)换药后8个月出现白细胞减少,减少吗替麦考酚酯胶囊用量后白细胞恢复正常。结论肝移植术后长期应用CNI类药物发生肝肾功能损害、高血压等副作用时,转换为以吗替麦考酚酯胶囊为主的免疫抑制方案能有效控制排斥反应,改善毒副作用,且可为CNI的减量或停药提供机会。     

霉酚酸酯用于狼疮肾炎的循证治疗

目的探讨霉酚酸酯治疗增生性狼疮肾炎的最佳方案。方法计算机检索Cochrane图书馆(2005年第4期)、MEDLINE(1990~2006.12)、CMB(1980~2006.12)、CNKI(1979~2007.10)和中国循证医学/Cochrane中心数据库(2006年第2期),收集霉酚酸酯治疗增生性狼疮肾炎的系统评价、临床随机对照试验等,并对所获证据的质量进行评价。并将证据应用于临床实践。结果共纳入4篇系统评价和6篇高质量随机对照研究(A级证据)。高质量的临床证据表明霉酚酸酯联合激素用于诱导期及缓解期能有效治疗弥漫增殖型狼疮肾炎,与环磷酰胺相比毒副作用较少。结论据患者意愿,结合我们的经验与当前最佳临床证据,制定出霉酚酸酯起始用量为1000mg/d的治疗方案。对患者进行3个月的随访,未发现明显副作用。     

霉酚酸酯对不同病理类型原发性肾小球疾病的疗效分析

目的　分析霉酚酸酯 (MMF)治疗原发性肾小球疾病不同病理类型与临床疗效的关系 ,探讨MMF治疗原发性肾小球疾病的作用机制。方法　观察 2 0 0 0 - 0 2 2 0 0 3- 0 1中国医科大学附属第二医院住院或门诊的 4 8例原发性肾小球疾病患者应用MMF治疗的临床效果。结果　膜增殖性肾小球肾炎 (MsPGN)的显效率及有效率明显高于其他类型 ;MMF的治疗效果与原发性肾小球疾病的病程有关 ,病程在 1 5年以内应用MMF治疗者效果明显好于病程在 1 5年以上的应用者。结论　MMF对原发性肾小球疾病的疗效与病理类型及用药时机有关