半量激素联合霉酚酸酯治疗扁桃体摘除术后ⅠgA肾病的疗效观察

目的：观察半量激素联合霉酚酸酯（MMF）治疗扁桃体摘除术后ⅠgA肾病的疗效及安全性。方法：选取我院经肾活检确诊ⅠgA肾病患者共207例，分为手术组及对照组，2组均给予半量激素联合MMF，随访时间为1a。观察2组蛋白尿水平、红细胞数量及血压、肾功能情况变化。结果：2组服药治疗3个月后，尿红细胞、尿蛋白定量均好转，且手术组优于对照组（P〈0．05）；手术组血压、内生肌酐清除率及对照组血压无明显变化，但对照组内生肌酐清除率下降（P〈0．05）。结论：半量激素联合MMF治疗扁桃体摘除术后ⅠgA肾病疗效肯定，对肾功能有保护作用。     

吗替麦考酚酯对重症急性胰腺炎血清细胞因子的影响

目的 探讨肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1β和可溶性细胞间黏附分子（sICAM-1）-1 在重症急性胰腺炎（SAP）早期的动态变化及意义,并观察吗替麦考酚酯（MMF）的干预性作用.方法 将104 只雄性Wistar 大鼠随机分成4 组：正常组（（n=8,仅开腹后即缝合）,假手术组（n=32,开腹后仅翻动胰腺并以钝器轻划胰腺组织5 次）,SAP 组（（n=32,逆行胰胆管注射牛黄胆酸钠以建立SAP 模型）,和MMF 组（（n=32,建立SAP 模型后1h 经尾静脉注射MMF 250 mg/kg）.术后3 h、6 h、12 h、24 h 各组分批处死大鼠,采用全自动生化分析仪检测血清淀粉酶（AMS）、血清C 反应蛋白（CRP）;常规HE 染色进行胰腺组织病理学评分;ELISA 法检测血清TNF-α、IL-1β和sICAM-1 的含量.结果 在各时间点,SAP 组的胰腺组织病理评分,血清AMS、CRP,以及TNF-α、IL-1β和sICAM-1 的含量均显著高于正常组、假手术组（均P＜0.05）;而MMF 组的上述数值均显著低于SAP 组（均P＜0.05）.结论 SAP 早期阶段细胞因子的变化与病情进展密切相关,MMF 可通过抑制细胞免疫及炎性细胞因子的产生,减轻炎症损伤反应.     

Rituximab therapy for childhood-onset systemic lupus erythematosus

OBJECTIVE: To describe the safety and efficacy of rituximab in the treatment of childhood-onset systemic lupus erythematosus (SLE). STUDY DESIGN: We conducted a French multicenter retrospective study of childhood-onset SLE treated with rituximab. RESULTS: Eleven girls with severe SLE, including 8 girls with class IV or V lupus nephritis, 2 girls with severe autoimmune cytopenia, and 1 girl with antiprothrombin antibody with severe hemorrhage, were treated with rituximab. The mean age at onset of rituximab treatment was 13.9 years. Patients received 2 to 12 intravenous infusions of rituximab (350-450 mg/m2/infusion), with corticosteroids. Six patients also received different standard immunosuppressive agents, including Cyclophosphamide (2 patients). Remission was achieved in 6 of 8 patients with lupus nephritis and in the 2 patients with autoimmune cytopenia. Steroid therapy was tapered in 5 patients who responded to treatment, and low-dose prednisone treatment was maintained in 1 patient. The mean follow-up period was 13.2 months (range, 6-26 months), and remission lasted in all who patients who responded to treatment, except 1 patient who was successfully retreated with a second course of rituximab. Anti-double-stranded DNA antibody levels decreased in 6 of 11 patients, and anticardiolipin antibody levels decreased in 3 of 4 patients. Severe adverse events developed in 5 patients. Effective depletion of peripheral blood B cells was observed in 7 of 8 patients who were examined, and this paralleled the remission. CONCLUSION: Rituximab may be an effective co-therapy; however, further investigations are required because severe adverse events occurred in 45% of the patients in this study.     

霉酚酸酯对大鼠角膜移植术后排斥反应的抑制

目的研究霉酚酸酯(MMF)对大鼠角膜移植术后临床参数变化的影响.方法建立大鼠穿透性角膜移植排斥反应的动物模型,观察MMF对大鼠角膜植片存活和各排斥反应临床指数的影响,并与阴性对照组和环胞霉素A(CsA)治疗组相比较.结果阴性对照组角膜植片平均存活时间为11.375±1.685天,CsA治疗组为18.625±1.598天,MMF治疗组为16.500±1.852天,CsA±MMF组为24.500±1.773天,均比阴性对照组显著延长(P＜0.05);阴性对照组排斥反应指数(RI)、浑浊、水肿三项临床指标明显高于各用药组(P＜0.05),但新生血管指数与MMF组、CsA组相比较,差异无显著性意义(P＞0.05).结论MMF对大鼠穿透性角膜移植排斥反应具有明显的抑制作用,显著地延长角膜植片的存活时间,降低角膜植片浑浊、水肿的程度.     

CsA,MTX,MMF联合ATG预防非亲缘供者外周血造血干细胞移植后GVHD的疗效观察

本研究旨在探讨非亲缘供者外周血造血干细胞移植(URD-PBSCT)后的移植物抗宿主病(GVHD)预防方法、疗效及其对患者生存、复发的影响。对我院HLA高分辨相合或1个位点不合URD-PBSCT患者33例的临床资料进行总结,主要比较了不同GVHD防治方法下的GVHD发生率、疾病的复发率及患者的生存率。GVHD防治方法:环孢素A(CsA)+短疗程甲氨喋呤(MTX)+霉酚酸酯(MMF)+抗胸腺细胞球蛋白(URD-ATG组),其中13例加用CD25单克隆抗体(URD-ATG+CD25组)。结果显示,移植后所有患者100%植入,造血重建顺利。URD-ATG+CD25组、URD-ATG组急性GVHD的发生率分别为23.07%、45%%,慢性GVHD的发生率分别为0和47.4%,后者均显著高于前者(p0.05);疾病的复发率分别为53.84%、15%,前者显著高于后者(p0.05)。根据移植前患者疾病状态(稳定、进展)分层分析显示,进展期疾病的复发率显著高于稳定期(p0.01),而URD-ATG+CD25组进展期疾病的复发率高达100%。URD-ATG+CD25组和URD-ATG组患者的1年总生存率(OS)分别为53.8%、75%;5年OS分别为38.5%、65%,URD-ATG组高于URD-ATG+CD25组(p0.05);同时移植前疾病进展期患者的生存率显著下降。结论:在HLA相合或1个位点不合的URD-PBSCT中采用CsA+MTX+MMF+ATG的GVHD防治措施是安全可行的,对于进展期患者可考虑进一步减少ATG用量以减少复发,提高存活。     

Switch from cyclosporine A to mycophenolate mofetil in nephrotic children

Nephrotoxicity is a well-known adverse effect of cyclosporine A (CyA) treatment in children with steroid-dependent (SD) and steroid-resistant (SR) nephrotic syndrome (NS). We analyzed nine children (age: 3.3–15.7 years, two girls) with SD or SR NS who experienced a significant decrease in their GFR under CyA treatment as measured by inulin clearance (C_IN). Mycophenolate mofetil (MMF) was introduced progressively until doses of 1 g/1.73 m² twice daily were reached. CyA treatment was stopped after introduction of MMF and oral steroids were reduced if possible. After a median follow up of 261 days, no adverse effects of MMF such as diarrhea or hematological anomalies occurred in our patients. After switching from CyA to MMF, those children with SD NS remained in remission without proteinuria and those with SR NS did not show any significant changes in their residual proteinuria. The serum protein level did not change significantly in any of the children analyzed. GFR increased from a mean of 76.9±4.8 to 119.9±5.9 mL/1.73 m² per min (P<0.001). Oral steroid treatment could be reduced from a median [range] prednisone dose of 0.85 [0.26–2.94] mg/kg/d pre-MMF to 0.29 [0–1.1] mg/kg per day (P=0.026), and blood pressure decreased moderately after CyA withdrawal, but the difference did not reach statistical significance. We conclude that a switch from CyA to MMF seems to be safe for children with SDNS and SRNS in terms of side effects as well as disease control, at least in the short term. Interruption of CyA treatment lead to rapid amelioration of kidney function in these children, often associated with steroid sparing, which may lead to additional benefit for growth velocity, blood pressure and physical appearance.     

注射用吗替麦考酚酯的细菌内毒素检查法可行性研究

目的:建立检查注射用吗替麦考酚酯(mycophenolate mofetil for injection,MMF)中细菌内毒素的方法。方法:按2005年版中国药典二部收载的细菌内毒素检查法的规定,用2个不同厂家的鲎试剂对 MMF 分别进行检查。结果:将 MMF 稀释到浓度为0.625 mg·mL~(-1)时,不干扰细菌内毒素试验,其细菌内毒素限值为0.4 EU·mg~(-1)。结论:MMF 可用细菌内毒素检查法控制热原,此法灵敏可靠,方便经济。     

Magnetoencephalographic recordings demonstrate attentional modulation of mismatch-related neural activity in human auditory cortex

It is widely agreed that the negative brain potential elicited at 150–200 ms by a deviant, less intense sound in a repetitive series can be modulated by attention. To investigate whether this modulation represents a genuine attention effect on the mismatch negativity (MMN) arising from auditory cortex or attention-related activity from another brain region, we recorded both the MMN and the mismatch magnetic field (MMF) elicited by such deviants in a dichotic listening task. Deviant tones in the attended ear elicited a sizable MMF that was well modeled as a dipolar source in auditory cortex. Both the MMN and MMF to unattended-ear deviants were highly attenuated. These findings support the view that the MMN/MMF elicited in auditory cortex by intensity deviants, and thus the underlying feature-analysis and mismatch-detection processes, are not strongly automatic but rather can be gated or suppressed if attention is strongly focused elsewhere.