ST段抬高心肌梗死应用国产西罗莫司洗脱支架与金属裸支架的对比研究

目的评估在ST段抬高心肌梗死(STEMI)患者应用国产西罗莫司洗脱支架的安全性和有效性。方法将1年内连续入选STEMI的患者随机分为国产西罗莫司洗脱(火鸟)支架组或金属裸支架(BMS)组。对所有患者连续临床随访6个月,术后6个月常规行冠状动脉造影。试验主要终点是术后6个月靶病变区晚期管腔丢失(LLL),次要终点包括支架内血栓发生率和主要心脏不良事件(MACE)。结果试验前6个月共入选85例患者。国产西罗莫司(火鸟)支架组42例,平均年龄58·1岁。BMS组43例,平均年龄59·8岁。两组6个月血管造影随访率分别为47·6%和44·2%。6个月随访结果显示,国产西罗莫司(火鸟)支架组死亡率、靶血管重建率(TVR)和MACE分别为2·4%,0%和2·4%,BMS组相应为4·7%,31·6%和25·6%(P<0·05)。BMS组有1例发生支架内亚急性血栓。定量冠状动脉造影结果显示,国产西罗莫司(火鸟)支架组支架内平均LLL为0·18mm,BMS组为0·72mm。结论与BMS比较,国产西罗莫司(火鸟)支架能够有效降低STEMI患者6个月死亡率、TVR和MACE发生率,其急性或亚急性支架血栓发生率低。     

西罗莫司洗脱支架防止冠脉支架内再狭窄的研究进展

冠脉内支架置入术目前在临床上广泛应用 ,但内膜增生造成 10 %～ 6 0 % [1] 病人支架内再狭窄 (In StentRestenosis,ISR)。ISR限制了该技术远期的疗效 ,日益成为重要的临床问题。大量实验资料表明西罗莫司 (Sirolimus)能抑制细胞周期 ,减少新生内膜的形成。通过聚合物涂层支架释放西罗莫司可能有效防止ISR。1　西罗莫司西罗莫司 (雷帕霉素 ,Rapamycin)是从吸水性链霉菌 (streptomyceshygroscopicus)发酵液中提取出来的一种大环内脂类化合物 ,西罗莫司于 1975年被发现 ,最初作为低毒性抗真菌的抗生素 ,由于其免疫毒性作为免疫抑制剂进…     

佐他莫司和西罗莫司支架在老年冠心病患者介入治疗中的对比研究

目的 比较佐他莫司支架和西罗莫司支架治疗老年冠心病的临床效果. 方法回顾性分析2006年8月至2007年5月我院对635例老年冠心病患者连续支架植入治疗的临床资料.其中植入佐他莫司(佐他莫司组)支架334例,西罗莫司(西罗莫司组)支架301例.比较两组治疗成功率、主要心脏不良事件等临床情况,并进行对比分析. 结果两组基线临床特点佐他莫司组高脂血症和左主干病变少于西罗莫司组,佐他莫司组再狭窄病变、支架长度、支架最大释放压和后扩张比率均小于西罗莫司组.两组介入成功率均为100%.主要心脏不良事件发生率与佐他莫司组比较(分别为4.5%(15例)与4.3%(13例)],差异无统计学意义,其中心原性死亡、非致死性心肌梗死和靶血管重建率两组比较,差异无统计学意义.支架内血栓发生率佐他莫司组和西罗莫司组分别为0.3%(1例)和0.7%(2例),差异无统计学意义.早期、晚期支架内血栓发生率两组比较,差异无统计学意义.7个月随访,佐他莫司组和两罗莫司组支架内和血管段再狭窄率[分别为5.9%(4/68)和3.5%(3/36),7.4%(5/65)和4.7%(4/86)]比较,差异无统计学意义.但支架内和血管段的晚期丢失佐他莫司组均大于西罗莫司组,分别为(0.48±0.12)mm与(0.24±0.09)mm和(0.44±0.13)mm与(0.26±0.09)mm,均P< 0.01. 结论7个月随访结果证实,佐他莫司和西罗莫司支架对于老年冠心病患者具有相似的疗效.     

造血干细胞移植术后慢性肝脏移植物抗宿主病的危险因素

目的研究造血干细胞移植(HSCT)术后肝脏慢性移植物抗宿主病(cGVHD)的危险因素。方法回顾性分析2014年4月至2019年4月甘肃省第二人民医院收治的149例HSCT患者的一般资料,分析术后肝脏cGVHD发生情况,采用多因素logistic回归分析法分析HSCT术后并发肝脏cGVHD的独立影响因素。结果 149例HSCT患者中,患者术后发生肝脏cGVHD40例。多因素logistic回归分析显示,GVHD预防方案中加用ATG(OR=0.235,95%CI=0.113～0.490)、早期出现aGVHD(OR=2.089,95%CI=1.020～4.279)是HSCT患者术后肝脏cGVHD的独立影响因素(P0.05)。结论 HSCT术后肝脏cGVHD的发生与移植早期出现aGVHD有关,而早期GVHD预防方案中加用ATG能降低其发生率。     

西罗莫司对肝癌HepG2细胞的增殖及mTOR、HIF-1α的抑制作用

目的:观察西罗莫司对体外培养的肝癌HepG2细胞增殖及mTOR、HIF-1α基因的抑制作用,探讨以mTOR为靶点治疗肝癌可能的细胞内信号转导机制.方法:缺氧培养HepG2细胞,外源性给予不同浓度的西罗莫司(0.1-1000 nmol/L)刺激细胞24h, MTT法检测不同浓度药物对肝癌细胞增殖的影响.Western blot法检测药物刺激后HepG2细胞内mTOR和HIF-1α蛋白的表达.结果:西罗莫司可显著抑制肝癌细胞HepG2的增殖,其抑制率随药物浓度的增加而上升(均P<0.05).在西罗莫司的干预下,HepG2细胞中mTOR和HIF-1α蛋白的表达水平显著下降,实验组与对照组比较,差异有统计学意义(P<0.05).结论:在缺氧条件下,西罗莫司可通过mTOR信号转导途径下调肝癌HepG2细胞内HIF-1α蛋白表达,诱导细胞凋亡,这可能是西罗莫司发挥抗肿瘤效应的机制之一.     

国产与进口西罗莫司药物洗脱支架治疗冠心病临床疗效对比

目的评估国产西罗莫司药物洗脱冠状动脉(冠脉)支架在冠心病患者中应用的安全性及1年临床随访结果,并与同期应用进口药物洗脱支架(Cypher和Taxus)比较。方法与结果2003年5月至2004年6月,共计673例经冠脉造影证实的冠心病患者接受药物洗脱支架治疗,其中接受国产西罗莫司药物洗脱支架(Firebird,上海微创公司)224例,进口西罗莫司药物洗脱支架(Cypher,美国强生公司)246例,进口紫杉醇药物洗脱支架(Taxus,美国波士顿公司)203例。各组基础临床情况及造影特征均相似,尽管Firebird组患者平均每例置入支架数目较多且支架总长度较长,但其住院总费用仍显著低于其他两组。术后1年临床随访严重心脏不良事件(包括心源性死亡、非致命性心肌梗死和靶血管再次血运重建)发生率在Firebird组为9·0%、Cypher组为8·4%、Taxus组为11·2%,相互比较差异无统计学意义。造影证实Firebird组2例(0·9%)、Cypher组2例(0·9%)和Taxus组3例(1·6%)发生支架内血栓形成。结论国产西罗莫司药物洗脱冠脉支架治疗冠心病安全,其1年临床疗效与进口西罗莫司及紫杉醇药物洗脱冠脉支架相似。     

HLA单倍相合造血干细胞移植治疗恶性血液病的临床研究

目的 探讨人类白细胞抗原(HLA)单倍相合造血干细胞移植(HSCT)治疗恶性血液病的疗效和主要并发症.方法 对2004年7月至2006年12月第三军医大学附属新桥医院收治的35例恶性血液病患者进行HLA单倍相合亲缘供者HSCT.采用延长、强化联合免疫抑制促进植入、抗胸腺细胞球蛋白(ATG)加强预防移植物抗宿主病(GVHD)、粒细胞集落刺激因子(G-CSF)动员的骨髓(BM)加外周血干细胞(PBSC)混合移植方案.结果 所有患者均重建供者造血.18例(51.4%)发生急性GVHD(aGVHD),其中Ⅰ度8例,Ⅱ度5例,Ⅲ度3例,Ⅳ度2例,Ⅱ～Ⅳ度aGVHD累积发生率为28.6%.12例(34.3%)发生慢性CVHD(cGVHD),均为局限性.23例患者存活,总存活率为65.7%,2年无病存活率(DFS)为62.9%.12例患者死亡,7例死于复发,5例死于移植相关合并症,其中肺部感染2例,Ⅳ度GVHD 2例,巨细胞病毒(CMV)感染1例.结论 随着预处理方案、GVHD预防方案及移植物成分的优化,HLA单倍相合造血干细胞移植的疗效明显改善,已成为治疗恶性血液病的重要方法.     

间充质干细胞治疗糖皮质激素耐药性慢性移植物抗宿主病临床疗效观察

目的 探讨间充质干细胞(MSC)治疗糖皮质激素(激素)耐药性慢性移植物抗宿主病(cGVHD)的疗效及作用机制.方法 12例激素耐药性cGVHD患者在原有免疫抑制剂基础上联合MSC治疗.12例患者共接受24例次MSC输注,17例次MSC来自第二方,7例次来源于第三方,其中1例输注1次、10例输注2次、1例输注3次.首次输注细胞量1.0(0.4～2.1)×106/kg,第2次输注1.2(0.8～1.9)×106/kg,末次输注细胞量为1.1×106/kg.5例接受2例不同供者MSC输注.并分别于MSC治疗前、治疗后4周应用流式细胞仪检测患者外周血CD+3、CD+4、CD+8、CD+19、CD+4CD+25、FOXF3+、FOXP3+CD+4及FOXP3+CD+25淋巴细胞亚群比例.结果 12例患者接受MSC输注后3例获得完全缓解(CR)、6例获得部分缓解(PR),总有效率(CR+PR)为75%(9/12).3例CB患者在MSc治疗471(372～731)d后停用免疫抑制剂,随访129(100～292)d cGVHD无复发;6例PR患者在MSC治疗64(60～79)d后开始进入免疫抑制剂减量阶段,目前除1例继发舌瘤致死外,其他患者应用小剂量免疫抑制剂维持治疗随访中位生存时间1152(795～1914)d病情仍稳定并存活.3例无效患者中,1例疾病稳定患者目前仍需联合三种免疫抑制剂治疗,另2例疾病进展患者分别于输注MSC8个月及10个月后死于白血病复发及肺脏cGVHD.输注MSC后12例患者CD4/CD8比例及调节性T细胞均显著升高,B细胞无明显改变.结论 第二方或第三方来源的Msc对于治疗激素耐药性cGVHD具有一定疗效,其作用机制可能与提高CD4/CD8比例及诱导调节性T细胞形成有关.     

西罗莫司经利阿诺定受体2途径诱导血管内皮细胞钙超载

目的观察西罗莫司造成血管内皮钙超载引起细胞损伤并探讨其相关机制。方法在西罗莫司处理和利阿诺定稳定利阿诺定受体通道的情况下,采用MTT法检测人脐静脉内皮细胞(HUVEC)细胞存活率,HE染色观察细胞形态,一氧化氮(NO)检测试剂盒测定培养液NO含量,Ca2+敏感的荧光染料Fluo-3 AM标记胞质Ca2+,分别采用流式细胞仪分析和激光共聚焦显微镜观察细胞内Ca2+水平,JC-1荧光探针检测线粒体膜电位,Annexin VFITC/PI染色法检测细胞凋亡率。结果西罗莫司能降低细胞存活率(P0.01)。西罗莫司500 nmol/L刺激24 h后,HE染色发现细胞肿胀,核固缩、核碎裂及胞浆空泡;NO含量降低,细胞内Ca2+含量增高,线粒体膜电位降低,细胞凋亡率增加(P均0.01)。与西罗莫司500 nmol/L组相比,利阿诺定50μmol/L干预组细胞存活率明显增加(P0.01),细胞内Ca2+含量降低(P0.05),细胞培养液NO含量由28.33±4.18μmol/L增至47.03±3.87μmol/L(P0.01),线粒体膜电位水平由0.24±0.03增至0.45±0.04(P0.01),细胞凋亡率由43.3%±2.0%降至30.7%±0.9%(P0.01)。结论西罗莫司可能通过内质网利阿诺定受体途径增加细胞内Ca2+水平,造成钙超载和线粒体损害,继而引起细胞凋亡。     

非清髓异基因造血干细胞移植治疗恶性血液病临床分析

目的:观察非清髓异基因造血干细胞移植(NST)治疗恶性血液病的疗效及并发症的处理。方法:对33例恶性血液病患者施行NST并随访观察。预处理方案应用氟达拉滨30mg.m-2.d-1(-7～-2d),马利兰4mg.kg-1.d-1(-6～-5d),环磷酰胺350mg.m-2.d-1(-3～-2d),HLA不全相合者加用抗淋巴细胞球蛋白(ALG)750mg/d(-2～-1d)。移植物抗宿主病(GVHD)预防应用环孢素A(CsA)和骁悉(MMF)。应用美司那、大量水化、碱化尿液预防出血性膀胱炎。应用凯时(前列腺素E1)预防肝静脉闭塞病(VOD)。结果:全部患者均成功植入,造血重建速度快。中性粒细胞0.5×109/L的中位时间是+13(+10～+16)d,血小板20×109/L的中位时间是+12(+9～+25)d。3例患者在+100d左右出现间质性肺炎,血CMV-DNA阳性,应用更昔洛维抗病毒等治疗后均痊愈。17例患者发生急性移植物抗宿主病(aGVHD)(51.5%),Ⅰ度患者10例(30.3%),Ⅱ度患者5例(15.2%),Ⅲ度患者2例(6.06%)。有20例患者出现慢性移植物抗宿主病(cGVHD)(64.5%),其中局限型15例(48.4%),广泛型5例(16.1%)。有3例患者出现VOD(9.1%),5例患者出现出血性膀胱炎(15.2%),经积极治疗均有效控制。中位随访37(2.5～58.0)个月,现存活24例(72.7%),9例死亡(27.3%),5例疾病复发(15.2%)。9例死亡患者中7例死于GVHD,2例死于疾病复发。结论:NST植入可靠,造血重建快,复发率低,移植相关并发症感染、出血性膀胱炎、VOD发生率低,治疗安全、有效。但GVHD发生率较高,是导致死亡的主要原因。     

A high risk of life-threatening infectious complications in mycophenolate mofetil treatment for acute or chronic graft-versus-host disease

We describe herein the clinical courses and outcomes of 26 patients who received oral mycophenolate mofetil (MMF) for the treatment of steroid-resistant refractory or steroid-dependent acute or chronic graft-versus-host disease (GVHD) in a single institution. In most cases, 1,500 mg/day of MMF is a median dose (range 500–3,000 mg/day) and administered for 116.5 days (range 9–584 days) along with calcineurin inhibitors and steroids. Although 20 patients (77%) showed rapid improvement of GVHD symptoms, of 15 patients, 13 (87%) showed acute GVHD; of 11 patients, 7 (64%) showed chronic GVHD; most patients (54%) experienced infection during MMF administration, including 5 cases with life-threatening infection. Positive cytomegalovirus (CMV) antigenemia was also observed in 19 patients (73%), but no patients developed CMV infection. Within the median follow-up of 12.5 months (range 0.5–67 months), 10 patients (39%) died. This small study demonstrates that MMF offers an alternative tool for rescuing steroid-refractory or steroid-dependent GVHD, but increases the risk of developing life-threatening infection.     

Sirolimus in combination with tacrolimus and corticosteroids for the treatment of resistant chronic graft-versus-host disease

Chronic graft-versus-host disease (cGVHD) remains a major cause of morbidity and mortality in haematopoietic transplant recipients. Sirolimus is a macrocyclic triene antibiotic with immunosuppressive, antifungal and antitumour properties, that has activity in the prevention and treatment of acute GVHD. We conducted a phase II trial of sirolimus combined with tacrolimus and methylprednisolone in patients with steroid-resistant cGVHD. Thirty-five patients who developed GVHD after day 100 post-transplant were studied. Six patients had a complete response and 16 a partial response with an overall response rate of 63%. Major adverse events related to the combination of tacrolimus and sirolimus were hyperlipidaemia, renal dysfunction and cytopenias. Four patients had thrombotic microangiopathy (TMA) and 27 (77%) had infectious complications. The median survival for the whole group was 15 months. A significantly better outcome was observed in patients with a platelet count > or = 100 x 10(9)/l, as well as in those with true chronic manifestations of GVHD compared to those with acute GVHD beyond day 100. Controlled trials comparing this approach with alternative strategies to determine which can best achieve the goal of GVHD-free survival are warranted.     

Infliximab for GVHD therapy in children

GVHD remains a significant complication of allogeneic hematopoietic stem cell transplantation. Tumor necrosis factor-alpha (TNF-alpha) is a major mediator of GVHD pathogenesis. Infliximab inhibits the binding of TNF-alpha with its cellular receptors and has been associated with encouraging responses in adults with severe GVHD. We retrospectively evaluated the efficacy and safety of infliximab 10 mg/kg i.v. once a week for a median of eight doses (range 1-162) in 24 children with steroid-resistant GVHD. The overall response rate in 22 evaluable children was 82% (12 CR+6 PR). Among those patients with acute GVHD, both skin and gastrointestinal involvement responded well to infliximab; however long-term outcome was poor. While infliximab may be useful to acutely control GVHD manifestations, GVHD recurs commonly upon discontinuation of infliximab. Within 100 days of the final infliximab dose, 77% of patients had bacterial infections, 32% had viral infections and 13.6% had probable or proven non-candidal invasive fungal infections. Infliximab appears to be well-tolerated and to have activity in steroid-resistant GVHD. Controlled studies to assess the pharmacokinetics and most effective dosing regimen of infliximab for the treatment of GVHD are warranted.     

Sirolimus,tacrolimus, and low-dose methotrexate for graft-versus-host disease prophylaxis in mismatched related donor or unrelated donor transplantation

We studied the feasibility and activity of adding sirolimus to tacrolimus and low-dose methotrexate as graft-versus-host disease (GVHD) prophylaxis in recipients of alternative donor transplants. Forty-one patients with hematologic malignancies were conditioned with cyclophosphamide and total body irradiation. Marrow stem cells were from an HLA-A, -B, and -DR compatible, unrelated donor (n = 26, 68%), from a 5 of 6 antigen-matched unrelated donor (n = 8, 20%), or from a 5 of 6 antigen-matched family member (n = 5, 12%). Therapeutic serum levels of sirolimus were attained in most patients. All evaluable patients engrafted. An absolute neutrophil count of 500/microL was achieved on day +18 (range, 11-32 days). Sustained platelet counts of more than 20 000/ microL were attained on day +29 (range, 14-98 days). Grades 0-I acute GVHD occurred in 75% of patients. Grades II, III, and IV acute GVHD occurred in 13%, 8%, and 5%, respectively (total grades II-IV GVHD, 26%). Median survival is 366 days (95% CI 185, not estimable) and actuarial survival at 1 year is 52%. Oral sirolimus is tolerable, adequate blood levels are achievable, and there is a low rate of acute GVHD compared with historical data in this high-risk population. This novel agent is worthy of further study in allogeneic transplantation.     

Successful treatment of refractory acute GVHD with mycophenolate mofetil after peripheral blood stem cell transplantation from the patient's one locus-mismatched mother

A 35-year-old male with chronic myeloid leukemia in the accelerated phase received a peripheral blood stem cell transplant from his HLA-DR-mismatched mother. Graft-versus-host disease (GVHD) prophylaxis was with short-term methotrexate and tacrolimus. After transplantation, grade II skin acute GVHD occurred and was unsuccessfully treated with bolus methylprednisolone administration. The acute GVHD progressed to grade III of the skin, gut and liver, and mycophenolate mofetil (MMF) was accordingly administered at a daily dose of 2 g. This treatment resulted in a dramatic improvement in the clinical features of the acute GVHD. The patient suffered from hemorrhagic cystitis and several episodes of cytomegalovirus antigenemia. MMF may be useful for steroid-resistant acute GVHD despite an increasing risk of viral infections.     

Sirolimus and tacrolimus as immune prophylaxis compared to cyclosporine with or without methotrexate in patients undergoing allogeneic haematopoietic stem cell transplantation for non-malignant disorders

For prevention of graft‐versus‐host disease (GVHD), treatment of 24 haematopoietic stem cell transplantation (HSCT) patients with sirolimus and tacrolimus was compared to treatment of matched controls with cyclosporine‐based regimens. The patients mainly had non‐malignant disorders. Two‐thirds of the donors were unrelated, and bone marrow was the most common source of stem cells. Rejection occurred in four patients in the sirolimus group and three in the control group. Donor chimerism for CD3, CD19 and CD33 was similar in the two groups. The cumulative incidence of grade II acute GVHD was 22% in the sirolimus patients and 17% in the controls (P = 0.78). No patients developed acute GVHD of grades III–IV. The cumulative incidence of chronic GVHD was 25% and 37% in the two groups, respectively (P = 0.40). Two patients in the sirolimus group developed Epstein–Barr virus lymphoma, and none in the controls. Side effects and toxicity were similar in the two groups. There was no transplant‐related mortality at 5 yr in the sirolimus group, as opposed to 8% in the controls (P = 0.47). Survival at 5 yr was 95% and 92%. Thus, sirolimus combined with tacrolimus is a promising immunosuppressive regimen in HSCT, also for non‐malignancies, and its efficacy should be confirmed in prospective clinical trials.     

The addition of sirolimus to the graft‐versus‐host disease prophylaxis regimen in reduced intensity allogeneic stem cell transplantation for lymphoma: a multicentre randomized trial

Inhibition of the mechanistic target of rapamycin (mTOR) pathway has clinical activity in lymphoma. The mTOR inhibitor sirolimus has been used in the prevention and treatment of graft‐versus‐host disease (GVHD) after allogeneic haematopoietic stem cell transplantation (HSCT). A retrospective study suggested that patients with lymphoma undergoing reduced intensity conditioning (RIC) HSCT who received sirolimus as part of their GVHD prophylaxis regimen had a lower rate of relapse. We therefore performed a multicentre randomized trial comparing tacrolimus, sirolimus and methotrexate to standard regimens in adult patients undergoing RIC HSCT for lymphoma in order to assess the possible benefit of sirolimus on HSCT outcome. 139 patients were randomized. There was no difference overall in 2‐year overall survival, progression‐free survival, relapse, non‐relapse mortality or chronic GVHD. However, the sirolimus‐containing arm had a significantly lower incidence of grade II‐IV acute GVHD (9% vs. 25%, P = 0·015), which was more marked for unrelated donor grafts. In conclusion, the addition of sirolimus for GVHD prophylaxis in RIC HSCT is associated with no increased overall toxicity and a lower risk of acute GVHD, although it does not improve survival; this regimen is an acceptable option for GVHD prevention in RIC HSCT. This trial is registered at clinicaltrials.gov (NCT00928018).     

Exclusive elemental enteral diet in cortico-resistant and cortico-dependent forms of Crohn's disease

The aim of this study was to investigate the value of elemental diet in steroid-resistant and steroid-dependent Crohn's disease. Elemental diet (Vivonex HN, 39.4 +/- 9.2 kcal/kg/d) was delivered through a nasogastric tube at a constant rate. Twenty therapeutic periods lasting from 20 to 74 days (median, 32 days) were undertaken in 18 patients. Elemental diet was well tolerated. Mean values of hemoglobin, serum albumin, and serum transferrin increased significantly through the therapeutic period; body weight and anthropometric data did not change significantly. The short-term response to elemental diet was excellent in 11 cases, demonstrated by achievement of clinical remission and steroid withdrawal; six patients had an incomplete remission and remained slightly active or had to be maintained under low dose steroids; three patients did not respond to therapy and had to be operated upon. During the follow-up (6-30 months), 8 patients out of 17 had a relapse. Relapse was controlled by medical therapy in 5 cases and led to surgery in the 3 other cases. We conclude that elemental diet, as total parenteral nutrition, is an effective therapy of steroid-resistant and steroid-dependent Crohn's disease. However, elemental diet does not prevent relapse.     

Compared azathioprine efficacy in ulcerative colitis and in Crohn's disease

AIM: To compare the 6-month efficacy and tolerance of azathioprine in 68 patients with steroid-resistant or steroid-dependent chronic ulcerative colitis (n=30) or Crohn's disease (n=38).METHODS: Clinical remission was defined as a Crohn's Disease Activity Index<150 for Crohn's disease and number of non-bloody stools<=3/day for ulcerative colitis, associated with prednisone requirement<=10 mg/day.RESULTS: Seventy-three per cent of patients with ulcerative colitis had distal or left-sided colitis and 84% of patients with Crohn's disease had pancolitis. Azathioprine was discontinued early for side-effect in 8 (26.7%) patients with ulcerative colitis and in 8 (21.1%) patients with Crohn's disease (NS). In patients treated at least 6 months by azathioprine, clinical remission rates were 77.3% and 70% for chronic ulcerative colitis and Crohn's disease (NS). Complete corticosteroids weaning was obtained significantly more often in ulcerative colitis patients than in Crohn's disease patients (59.1% vs 30%; P<0.05).CONCLUSION: Azathioprine seems to be at least as effective and equally tolerated in steroid-resistant or steroid-dependent chronic ulcerative colitis or Crohn's disease patients.     

Use of sirolimus in patients with primary steroid-resistant nephrotic syndrome

Persistent nephrotic syndrome that does not respond to treatment may cause progression to kidney failure. We designed a therapeutic protocol with sirolimus for this group of patients. We conducted a prospective, interventional, time series, cohort study lasting 20 months. Thirteen patients were enrolled, with a mean age of 10 years (range: 8-18 years old) with steroid-resistant primary nephrotic syndrome and a histological diagnosis of focal and segmental glomerulosclerosis. We administered sirolimus 3.6mg/m2/day. The duration of this regimen was 12 months in responsive patients. The protocol's efficacy was assessed according to reduction of proteinuria (3 response levels: total, partial, or no response). Severity of histological renal damage and mean time from clinical diagnosis to protocol initiation were also assessed. Nine of 13 patients responded to the treatment with sirolimus, and mean progression time and the severity of histological renal damage influenced response to therapy. We believe that sirolimus is a valid treatment option in patients with steroid-resistant nephrotic syndrome, even though this regimen probably requires an earlier treatment.