雷公藤多甙联合苯那普利和大黄素治疗IgA肾病的前瞻性临床研究

目的观察雷公藤多甙联合苯那普利和大黄素(三联疗法)对IgA肾病(IgAN)的临床疗效及肾组织病理改变的影响.方法经肾活检并结合临床确诊为原发性IgAN的患者24例,年龄14～55岁,尿蛋白≥1.0g/d,血肌酐(SCr)≤267μmol/L,肾活检病理Lee氏Ⅲ级以上.根据尿蛋白、SCr及肾病理配对分为治疗组(n=12)和对照组(n=12),治疗组接受雷公藤多甙、苯那普利和大黄素三联治疗,对照组接受强的松和苯那普利治疗.疗效分为缓解(尿蛋白＜0.4g/d,血浆白蛋白＞35.0g/L,SCr＜110μmol/L)、部分缓解(尿蛋白＞0.4g/d,但下降＞基础值的50%,肾功能稳定,SCr上升＜基础值的25%)及无效(尿蛋白＞1.0g/d,或SCr上升＞基础值的50%).治疗12个月后9例治疗组和4例对照组患者接受重复肾活检,利用Scion Image 4.02 β软件进行病理图像分析肾小球指数(GI)、肾小管间质慢性化病变指数(TI)以及间质血管病变指数(Ⅵ).结果治疗6个月时治疗组5例(42%)缓解,6例(50%)部分缓解,1例(8%)无效,对照组分别为2例(17%)、7例(58%)和3例(25%).治疗组尿蛋白下降快于对照组,治疗0、1、3、6、9、12个月时治疗组尿蛋白分别为(2.04±0.76)g/d、(0.76±0.45)g/d、(0.51±0.31)g/d、(0.57±0.31)g/d、(0.55±0.43)g/d、(0.81±1.09)g/d,对照组分别为(1.88±0.67)g/d、(1.43±0.74)g/d、(0.79±0.58)g/d、(0.68±0.34)g/d、(2.03±1.90)g/d、(1.27±1.45)g/d.治疗组6例肾功能不全患者治疗12个月后SCr保持稳定[(140.6±19.0)μmol/L vs(134.1±24.1)μmol/L,P＞0.05],对照组5例肾功能不全患者SCr无变化[(126.6±19.6)μmol/Lvs (129.5±26.6)μmol/L,P＞0.05].重复肾活检病理定量分析发现治疗组GI显著降低(0.314±0.054 vs 0.243±0.042,P＜0.05),对照组GI则增加(0.274±0.065 vs 0.304±0.056,P＞0.05).治疗组TI由0.183±0.112降至0.148±0.100(P＞0.05),对照组TI无明显改变(0.278±0.102 vs 0.273±0.141,P＞0.05).两组患者治疗后Ⅵ均下降,但无统计学差异.结论雷公藤多甙联合苯那普利及大黄素三联疗法能有效减少IgAN的蛋白尿、稳定肾功能并减轻肾脏纤维化病变.     

雷公藤多甙对糖尿病肾病蛋白尿的影响

目的 观察雷公藤多甙对糖尿病肾病患者蛋白尿的作用及安全性.方法 选取天津医科大学代谢病医院2008年4月至12月肾病科住院及门诊的81例2型糖尿病患者为研究对象,24 h尿蛋白定量≥1.0 g,血清肌酐(Scr)<265.2 μmol/L.随机分为4组,对照组(21例)应用常规荆量血管紧张素转换酶抑制剂(ACEI)或血管紧张素受体拮抗剂(ARB),治疗组在应用常规剂量ACEI或ARB基础上,分别给予雷公藤多甙20 mg/d(低剂量组)、30 mg/d(中剂量组)、40 mg/d(高剂量组)(每组各20例),疗程3个月,观察治疗前后24 h尿蛋白定量、肝肾功能及血常规变化.结果 治疗组与对照组24 h尿蛋白定量均减少.雷公藤多甙低剂量、中剂量、高剂量治疗组24 h尿蛋白分别由治疗前(2.7±0.9)g、(2.7±0.9)g、(2.8±0.9)g减少到治疗后(2.2±1.0)g、(2.1±0.9)g、(1.9±1.0)g(P均<0.01),下降率分别为17.8%、22.8%、30.4%;对照组24 h尿蛋白由治疗前(2.4±1.2)g减少为治疗后(2.0±0.9)g(P>0.05),下降率为16.3%.雷公藤多甙治疗前后肝肾功能及外周血象比较差异均无统计学意义(P>0.05).结论 在常规治疗基础上,加用雷公藤多甙可在一定程度上降低糖尿病肾病患者蛋白尿水平,且随雷公藤多甙用药剂量在一定范围内增加,24 h尿蛋白定量下降率增大,趋势检验有统计学意义(P<0.05),对患者的肝、肾功能及外周血象未见明显不良影响.     

泌尿系统疾病

口服氯沙坦50mg/d,治疗8周;然后增至100mg/d,再治疗8周。A组18例16周均维持在50mg/d。B组137例有130例随访至试验终点。结果:A组尿蛋白<3.5g/24h者,治疗8周后尿蛋白较入选时下降(31.9±6.2)％,16周后下降(47.8±6.6)％,均P<0.001。B组患者尿蛋白≥     

雷公藤多甙防治大鼠血管球囊损伤后平滑肌细胞增殖的实验研究

目的观察不同剂量雷公藤多甙对颈动脉球囊损伤后大鼠血管平滑肌细胞增殖的影响,探讨其在再狭窄防治方面的作用。方法SD雄性大鼠32只,随机分为4组。取8只为正常组,其余24只以内皮剥脱法造模,随机分为模型组、雷公藤多甙小剂量组及大剂量组各8只。模型组术后予蒸馏水3mL/(kg·d)灌胃,小剂量组予雷公藤多甙30mg/(kg·d)灌胃,大剂量组予雷公藤多甙60mg/(kg·d)灌胃。于术前处死8只正常组大鼠,于术后2周处死各实验组动物。取材检测指标:HE染色观察管壁增生情况,计算机图像分析内、中膜厚度及其比值,免疫组化法检测增殖细胞核抗原(PCNA)、α-平滑肌肌动蛋白(α-SMA)表达水平。结果雷公藤小剂量组内膜、中膜厚度与内膜/中膜厚度值分别为(54.19±11.59)μm、(102.66±15.58)μm与0.55±0.18;雷公藤大剂量组各指标分别为(37.58±8.51)μm、(115.09±18.98)μm与0.33±0.08。抑制PCNA表达,升高α-SMA水平,并呈剂量正相关。结论雷公藤多甙能有效抑制血管损伤后内膜增生,对大鼠血管球囊损伤后的狭窄有一定的防治作用。     

他克莫司联合激素治疗Ⅴ型狼疮性肾炎的疗效

目的:前瞻性观察他克莫司(FK506)治疗Ⅴ型狼疮性肾炎(LN)的临床疗效及安全性.方法:利用FK506治疗11例尿蛋白＞2.0g/24h、肾功能正常、并经肾活检确诊的Ⅴ型LN患者.FK506起始剂量为0.1mg/(kg·d),同时口服强的松0.6 mg/(kg·d).疗效分为完全缓解(CR,指尿蛋白＜0.4g/24h,无活动性尿沉渣,血清白蛋白≥35g/L,SCr正常),部分缓解(PR,指尿蛋白定量0.4～2 g/24 h且尿蛋白下降超过基础值的50%,血清白蛋白≥30g/L,SCr正常)及无效(NR,指尿蛋白定量≥2 g/24 h;或血清白蛋白＜30g/L;或SCr升高超过基础值50%;或重复肾活检病理类型转为Ⅳ型LN).结果:11例患者接受FK506治疗3～15个月,无一例退出治疗.治疗3个月时2例(18.2%)患者获得完全缓解、5例(45.5%)获部分缓解.治疗6个月以上的10例患者中获得完全及部分缓解者均为4例(40%).达到完全或部分缓解的中位数治疗时间为3个月(1～7个月).FK506治疗3个月时,2例尿蛋白降至正常,5例降至＜2.0g/24h治疗6个月以上的10例患者中尿蛋白完全、部分缓解者均为4例.10例低蛋白血症患者在治疗3个月后即有7例血清白蛋白升至正常.血清抗核抗体及抗dsDNA抗体转阴或滴度显著下降,同时血清补体水平明显升高.治疗6个月后,8例患者行重复肾活检,肾组织狼疮活动性指数由4.8±2.38降至2.25±1.28(P＜0.05),肾小管-间质纤维化无明显加重.6例患者在治疗初期出现血肌酐可逆性升高,各有1例并发带状疱疹、腹泻和血压升高.结论:FK506联合小剂量强的松能有效降低Ⅴ型LN的蛋白尿、升高血清白蛋白.     

儿童乙肝病毒相关性膜性肾病

病史摘要 病史患者男性,13岁,因"反复水肿,大量蛋白尿5年"入院.其病史摘要如下:①1999-03-25出现咳嗽伴发热(最高38.7°C),无痰,同时出现颜面部水肿,当地医院检查尿蛋白3 ,镜检红细胞 ,乙肝标志物HBsAg( ),HBcAb( ),HBeAb( ),给予抗感染治疗后无明显好转,同年4月给予强的松50 mg/d(服用1个月,后每周减量5mg,共用5个月)、雷公藤多甙30 mg/d(约1个月)及环磷酰胺0.5g治疗,水肿及尿检无改善;②1999-10-29来我院儿科住院,查尿蛋白1.2 g/24h,尿沉渣红细胞37万/ml(多形型),肾功能正常(SCr43μmol/L).     

中等量蛋白尿IgA肾病的治疗

目的 探讨皮质类固醇激素和环磷酰胺（CTX）治疗中等量蛋白尿（1.5g-3.5g/d)IgA肾病的疗效、副作用及影响疗效的因素。方法 将64例患者分为三组,分别使用强的松^ ,共一年;环磷酰胺苯那普利、雷公藤多甙三种药物进行治疗观察。并观察血、尿常规、肝、肾功能、血脂、24h尿蛋白排泄率、24h肌酐清除率及副作用等。结果 用激素加环磷酰胺组可显著降低平均尿蛋白水平,苯钠普利和雷公藤多甙组平均尿蛋白水平降低不明显;激素加环磷酰胺治疗有效率为68．2％,比使用苯那普利组患者的50％高,显著高于雷公藤多甙组患者（35％）（P＜0．05）。有感、肝损害、消化道反应等副作用,但治疗后出现三组总的副作用发生率无明显差异。结论 对于中等量蛋白尿IgA肾病患者,长疗程的激素结合环磷酰胺治疗,可以明显降低尿蛋白排泄率、提高治疗有效率且可延缓肾功能衰竭,但在治疗中应注意副作用。     

培哚普利对血压正常的早期糖尿病肾病患者微量白蛋白尿的疗效观察

目的观察培哚普利对血压正常的早期糖尿病肾病患者的白蛋白尿的疗效和对肾功能的保护作用.方法糖尿病患者52例,其尿白蛋白排泄率(AER)均在20～200 μg/min之间,所有患者经控制饮食、口服降糖药物及(或)采用胰岛素治疗使血糖控制在可接受水平(尚可,即空腹血糖<7.0 mmol/L,餐后2 h血糖<10.0 mmol/L),随机分成两组,A组为对照组,25例,在控制血糖基础上加用安慰剂治疗;B组为治疗组,27例,在控制血糖基础上加用培哚普利治疗.培哚普利剂量为4 mg/d.两组患者在治疗前及治疗后3、6、12、18个月复查空腹血糖(FBG)、餐后2 h血糖(PBG)、糖化血红蛋白A1C(HbA1C)和AER等.结果 A组在12、18个月时AER分别为(52.3±8.6) μg/min和(60.5±9.0) μg/min,二者与治疗前的(44.2±6.8)μg/min相比有显著升高(P＜0.05).B组用培哚普利治疗后3、6、12、18个月时AER分别为(20.3±5.6) μg/min、(22.1±6.1) μg/min、(21.3±5.9) μg/min和(20.8±5.7) μg/min,均明显低于同期A组水平(P值均<0.05),与治疗前的(45.3±7.6) μg/min相比,差异亦有显著性(P值均<0.05).结论培哚普利对血压正常的伴有微量白蛋白尿的早期糖尿病肾病患者减少尿蛋白和保护肾功能有良好效果.     

苯那普利对糖尿病肾病UALB、TGF-β1、CⅣ和LAM影响

目的 评价苯那普利对糖尿病肾病(DN)的临床疗效,并探讨相应作用机制.方法 采用随机对照研究,观察苯那普利治疗前后DN患者24 h平均尿微量白蛋白排泄量以及尿转化生长因子β1(TGF-β1)、层黏连蛋白(LAM)和Ⅳ型胶原(CⅣ)的变化.结果 苯那普利治疗6月后,患者24 h尿微量白蛋白平均排泄量为(0.044±0.034) g,尿TGF-β1为(1.48±0.59) μg/L,LAM为(22.74±23.26 )μg/L量,CⅣ浓度为(13.47±10.94) μg/L量,均较治疗前有显著降低(P＜0.05),而对照组则较基线值明显升高(P＜0.05).结论 苯那普利可以有效降低血压、抑制肾脏TGF-β1、LAM及CⅣ的表达、显著减少DN患者尿蛋白的排出,从而发挥其肾脏保护作用.     

前瞻性比较普乐可复与环磷酰胺诱导治疗Ⅴ型伴Ⅳ型狼疮性肾炎的疗效

目的前瞻性比较普乐可复(FK506)与环磷酰胺(CTX)联合激素诱导治疗Ⅴ型合并Ⅳ型(Ⅴ+Ⅳ型)狼疮性肾炎LN)的临床疗效.方法经肾活检诊断为Ⅴ+Ⅳ型活动性、女性LN患者37例,平均年龄(30.0±9.8)岁,尿蛋白定量≥2.0 g/d,血清白蛋白＜3.0 g/dl,随机分为两组,分别给予口服FK506[FK506组,n=19,起始剂量0.1mg/(kg·d)]或CTX静脉冲击治疗(CTX组,n=18)(0.5～1.0g/m2 BSA,1/月×6月),同时口服泼尼松[起始剂量0.6 mg/(kg·d)],其中17例接受甲基泼尼松龙静脉冲击治疗.主要评价指标为治疗6个月完全缓解率(CR,定义为尿蛋白定量＜0.4 g/24h,尿红细胞正常范围,无管型尿及白细胞尿,血清白蛋白≥3.5 g/dl,SCr正常或上升不超过正常范围15%,无肾外狼疮活动),次要观察指标为治疗6个月部分缓解率(PR)和有效率(CR+PR).结果(1)临床疗效有31例患者完成6个月诱导期治疗,其中FK506组15例,CTX组16例;6例退出治疗,CTX组2例,FK506组4例.FK506组4例患者获得CR(26.7%),10例患者PR(66.7%),而CTX组仅1例CR(6.3%)、7例PR(43.8%).FK506组治疗有效率明显高于CTX组(93.3% vs 50%,P=0.015).两组患者治疗后SLE-DAI、血清白蛋白、补体较前有显著改善,但血尿及抗dsDNA抗体的阳性率无明显改变;FK506组平均尿蛋白较治疗前显著减少,而CTX组较治疗前无明显下降;(2)FK506剂量浓度与不良反应FK506诱导治疗剂量在0.086～0.091 mg/(kg·d),平均谷浓度水平为6.6～8.1 ng/ml.4例获得CR的患者FK506浓度在6.9～10.2 ng/ml,10例PR患者血药浓度平均为(8.1±3.3)ng/ml.在此剂量下治疗6个月,未见肾小管间质损害.FK506组不良反应的发生率(肝酶升高、上消化道不适、白细胞减少、感染、脱发、月经紊乱等)低于CTX组,尤其是月经紊乱的发生率显著低于CTX组(5.6% vs 38.9%,P=0.041);虽然血压升高、糖代谢异常等并发症高于CTX组,但两组间无统计学差异.结论FK506诱导治疗Ⅴ型合并Ⅳ型病变的LN疗效明显优于CTX治疗,不良反应小.     

肿瘤病人弓形虫感染分析

在肿瘤的发生和发展进程中 ,多伴有免疫功能低下或缺陷 ,从而极易遭受各种感染。弓形虫是机会感染因子 ,当患者免疫功能受损时 ,易于感染 ,还会使隐性感染激活 ,引起低热不退、淋巴结肿和脑神经系统的反应 ,此现象尚未引起临床医师的重视。近年来 ,我们对 4 0 9例肿瘤病人进行了弓形虫感染及弓形虫病的分析观察 ,报告如下 :1　材料与方法1 1　材料　 30 4例病人血清取自江西省肿瘤医院住院或门诊病人 ,随机抽样后低温保存待检 ,10 5例取自其他医院送检样品 ,有急性症状者随到随检 ,以便及时做病原学检测。1 2　弓形虫病诊断方法1 2 1　免疫…     

A patient with rectal ulcer with severe stenosis presenting with perforated peritonitis

We report a patient with rectal ulcer with severe stenosis, who underwent urgent surgical treatment for perforated peritonitis. The 54-year-old man suddenly developed cramping abdominal pain and fever while hospitalized, with signs of peritoneal irritation. An emergency laparotomy was performed, and severe stenosis of the rectum and a perforated lesion on the oral side approximately 10 cm distant from the stenosis were found, with massive abdominal purulent fluid. He was treated by rectosigmoid colon resection with transverse colon loop colostomy. Histopathologically, the stenosis was caused by ulceration extending to all muscular layers of the rectum, with inflammatory changes. Benign rectal stenosis is so rare that differential diagnosis from malignancy may be difficult when there are inflammatory changes in the surrounding tissues. However, it is necessary to keep in mind the likelihood of this disease in differentiation from rectal cancer. Received: December 21, 1998 / Accepted: May 28, 1999     

Evaluation of atrial vulnerability with transoesophageal stimulation in patients with atrioventricular junctional: Comparison with patients with ventricular pre-excitation and with normal subjects

The aim of our work was to evaluate the inducibility of atrialfibrillation in a group of patients with atrioventricular junctionalreentrant tachycardia and to compare it with that of patientswith a Kent-type ventricular pre-excitation (Wolff-Parkinson-Whitesyndrome) and a control group. One hundred and twenty-five subjects were separated into groups.Group 1 comprised 49 Wolff-Parkinson-White patients, with amean age of 26.4, range 10.66 years; group 2, 51 patients withatrioventricular junctional reentrant tachycardia inducibleby transoesophageal atrial stimulation andlor clinically documented,with a mean age of 43.4, range 16–78 years; group 3, 25control subjects with a mean age of2.64, range 13–76 years. Each subject underwent atrial transoesophageal stimulation withthe following protocol: programmed atrial stimulation with 1and 2 stimuli during atrial pacing of 100. min^–1 and 150.min^–1; atrial stimulation for 10 s at a rate of 200–300–400–500–600.min^–1 with intervals of 10 s between stimulations, fivesuccessive ‘ramp-up’ atrial stimulations for 9 swith the rate increasing from 100 to 800. min^–1 with intervalsof 10 s between stimulations. The end point was the completionof the protocol or induction of sustained atrial fibrillation(>1 min). The chi-square test was used for statistical analysis. Our resultsshowed that in group 1 atrial fibrillation was induced in 27149patients (55.1%); this was sustained in 13149 (26.5%) and non-sustainedin 14149 (28.5%); in group 2, atrial fibrillation was inducedin 22151 patients (43.0%); it was sustained in 7151 (13.7%)and non-sustained in 15151 (29.4%); in group 3, sustained atrialfibrillation was not induced in any subject and in only onesubject was a non-sustained atrial fibrillation (4 s) induced. The chi-square test showed that group 2 vs group 1 were non-significant,while group 2 vs group 3 and group 1 vs group 3 were significant(P<0.003 and P<0.0007, respectively). Therefore group 2 patients showed a greater atrial vulnerabilityin comparison to the control subjects and a similar vulnerabilityto group 1 patients. It is possible that the greater atrialvulnerability in the patients of group 2 was due to the doublenodal pathway.     

Infection with Rhodococcus equi in a patient with sarcoidosis treated with corticosteroids

A 51-year-old female farmer was diagnosed as having sarcoidosis. During 4 years of observation, slow radiological progression was observed. Cough then developed, necessitating treatment with corticosteroids. After 28 months of continuous treatment with prednisolone in low doses (5-7.5 mg daily), she suffered fever episodes, recurrent haemoptyses, general malaise and loss of weight. A chest roentgenogram showed a left upper lobe infiltrate, which progressed and finally cavitated, and rib destruction. Despite efforts, including a thoracotomy, 22 months passed before a diagnosis could be made. Blood and sputum cultures and cultures from the destroyed rib showed growth of Rhodococcus equi, a common soil organism which can cause infections in foals and other animals. Treatment with rifampicin and erythromycin was successful. R. equi has been reported to cause infection in patients with neoplastic disease and/or immunosuppression, but the disease might be more common than is suggested by the sparse case reports in the literature, owing to lack of familiarity with the organism, which will tend to be overlooked as a contaminant.     

Treating patients with lupus with B-cell depletion

A new era in the treatment of systemic lupus erythematosus has dawned with the increasing introduction of monoclonal antibodies and other approaches, that target the key molecules involved in the pathogenesis of the disease. At present the ability to block the CD20 molecule on those B cells that carry this marker has proved the most effective way to treat patients resistant to conventional immunosuppressive drugs. However, these studies have all been open label and the results of double blind controlled studies are eagerly awaited.     

Severe hepatotoxicity with jaundice associated with paroxetine

Hepatotoxicity due to paroxetine, a selective serotonin reuptake inhibitor, is very rare, and to the best of our knowledge, only five cases of liver injury in association with paroxetine have previously been reported in the medical literature. We describe the clinical, biochemical, and pathological findings in a patient with paroxetine hepatotoxicity, which was reversed after withdrawal of the drug. The present case and the others previously reported suggest that hepatotoxicity should be taken into account as a rare complication, sometimes severe, that may occur with paroxetine.