甲氨蝶呤与柳氮磺吡啶治疗强直性脊柱炎的临床对比研究

目的：对甲氨蝶呤（methotrexate，MTX）和柳氯磺吡啶（sulfasalazine，SSZ）治疗强直性脊柱炎（ankylosing spondylitis，AS）的临床疗效进行长期对比观察，以评价两种药物治疗AS的有效性及安全性。方法：住院治疗的AS患者120例随机分为两组各60例，分别采用SSZ（SSZ组）、MTX（MTX组）治疗，两组患者年龄、性别、病程及病情相匹配，均选择一种非甾体类抗炎药作为基础疗法。随访3年的临床资料．包括症状体征、BathAS活动指数（BASDAI）、Bath AS功能指数（BASFI）、血沉和C反应蛋白等化验检查及不良反应。结果：两组患者随访第1、2、3年与入院时比较，腰骶痛明显减轻（P〈0．05）。晨僵时间显著缩短（P〈0．05），BASDAI和BASFI明显降低（P〈0．05），炎性指标血沉和C反应蛋白显著下降（P〈0．05）；而随访各阶段两组间差异均无统计学意义．不良反应以胃肠道反应和白细胞减少为主，胃肠道反应MTX组（5％）明显低于SSZ组（12％）（P〈0．05），白细胞减少两组间差异无统计学意义；随访所有病例无造血系统障碍发生。结论：MTX和SSZ治疗AS疗效相近。MTX不良反应较少，患者易耐受。采用MTX治疗AS有更多的优越性，其更长期的疗效及安全性有待进一步观察。     

美沙拉嗪及SASP治疗溃疡性结肠炎的临床疗效比较

目的 探讨并比较美沙拉嗪与柳氮磺吡啶两组药物在治疗活动期轻度与中度溃疡性结肠炎的临床疗效与副作用.方法 将我院自2009年12月至2011年6月期间收治活动性轻度或中度溃疡性结肠炎患者72例随机分成美沙拉嗪治疗组(观察组)38例和柳氮磺吡啶治疗组(对照组)34例,两组均连续治疗56 d,观察两组患者的临床症状、各生化指标、结肠镜下黏膜状况以及副作用情况.结果 通过56 d的治疗,观察组患者的病情出现明显改善,观察组的总有效率明显高于对照组,两组比较差异显著(P＜0.05),具有统计学意义.观察组与对照组患者在治疗后第56天时其腹痛、腹泻、脓血便、黏膜充血水肿、糜烂出血、溃疡以及血管模糊等情况均出现改善,两组患者均表现出腹痛减轻以及大便次数与脓血减少,内镜下黏膜的外观良好.两组患者在第56天时结肠黏膜组织学分值均较治疗前显著下降(P＜ 0.05),具有统计学意义.两组患者的副作用发生率之间比较差异显著(P＜0.01),具有统计学意义.上述副作用均在治疗过程中给予及时对症处理,均未对治疗过程产生影响.结论 采用美沙拉嗪对于活动期轻度与中度溃疡性结肠炎疾病的治疗方面具有令人满意的临床疗效,其临床疗效明显优于柳氮磺吡啶治疗组,而且应用美沙拉嗪治疗的副作用明显减少,值得临床上广泛推广并应用.     

血浆置换联合甲氨蝶呤、柳氮磺胺吡啶治疗重症类风湿关节炎30例

目的:评价血浆置换联合甲氨蝶呤(MTX)、柳氮磺胺吡啶(SSZ)与单纯甲氨蝶呤、柳氮磺胺吡啶治疗重症类风湿关节炎的疗效与安全性。方法:本研究采用随机对照方法,入选患者71例,随机分组,试验组32例,对照组39例。试验组血浆置换同时口服甲氨蝶呤及柳氮磺胺吡啶;对照组口服同等剂量的甲氨蝶呤及柳氮磺胺吡啶。试验组及对照组均在治疗后第1、12、24周评价疗效。疗效评价采用美国风湿病学会(ACR)疗效评价指标ACR20、ACR50、ACR70。结果:试验组及对照组治疗后第1周达到ACR20分别为34%和7.7%;治疗后第12周达到ACR20分别为75%和51%、达到ACR50分别为47%和26%;治疗后第24周达到ACR20分别为90%和74%、达到ACR50分别为62%和36%、达到ACR70分别为30%和10%。试验组及对照组出现不良反应共9例,对症治疗好转。结论:血浆置换联合甲氨蝶呤、柳氮磺胺吡啶治疗重症RA疗效显著,明显优于单纯甲氨蝶呤、柳氮磺胺吡啶,且起效快、副作用小,安全性好。     

Lipid peroxidation and antioxidant status in kidney and liver of rats treated with sulfasalazine

Sulfasalazine (SASP) is a drug commonly used in the treatment of inflammatory bowel diseases (IBD). In this study, the changes in endogenous antioxidant capacity and oxidative damage in liver and kidney of SASP-treated rats were investigated. Adult male Sprague–Dawley rats were orally given 0, 300, or 600 mg SASP/kg body weight for 14 days. One half of the animals in each group remained 14 additional days without SASP treatment. At the end of the experimental period, rats were euthanized and liver and kidney were removed. In both organs, the following stress markers were determined: reduced glutathione (GSH), oxidized glutathione (GSSG), glutathione reductase (GR), glutathione peroxidase (GPx), glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), and thiobarbituric acid-reactive substances (TBARS). Moreover, histological examination of kidneys showed phagolysosomes after 14 days of SASP withdrawal. A dropsical degeneration was also observed in renal tissue. Oral SASP administration induced a significant increase in TBARS levels in both liver and kidney. After 2 weeks without SASP administration, a recovery of these levels was noted. SOD activity was significantly reduced, while CAT activity significantly increased at 600 mg SASP/(kg day). In kidney, GPx activity significantly increased, while GST activity and GSH levels were significantly reduced at 600 mg SASP/(kg day). These results suggest that in male rats, oxidative damage can be a mechanism for nephro- and hepatotoxicity related with SASP treatment.     

国产5-氨基水杨酸肠溶片治疗溃疡性结肠炎多中心临床研究

目的　评价国产 5 氨基水杨酸 (5 ASA)肠溶片治疗溃疡性结肠炎 (UC)的疗效和安全性及该药的口服吸收情况。方法　采用多中心、随机、双盲、双模拟和对照方案 ,将 1 2 9例UC患者随机分为5 ASA肠溶片试验组 (6 5例 ,2 .4 g/d)和水杨酸偶氮磺胺吡啶 (SASP)对照组 (6 4例 ,4 .0g/d) ,疗程均为6周。治疗第 8天 ,随机抽取试验组 1 3例和对照组 1 2例UC患者血清 ,应用高效液相色谱分析法检测血清 5 ASA及其代谢产物Ac 5 ASA的稳态血药浓度。对两组患者治疗前后的临床症状、粪便检查和肠镜检查的情况进行比较 ,并记录治疗过程中的不良反应。结果　实际完成研究者 1 2 0例 (5 ASA组 6 1例 ,SASP组 5 9例 ) ,两组各有 4例失访 ,SASP组有 1例因严重胃肠道不良反应中途退出。 5 ASA肠溶片组和SASP组治疗UC的总有效率分别为 70 .0 5 %和 6 7.79% ,两组间差异无显著性 (P >0 .0 5 ) ,5 ASA肠溶片的完全缓解率明显高于SASP (2 9.5 1 %比 1 3.31 % ,P <0 .0 5 )。 5 ASA肠溶片组和SASP组的不良反应分别为 1 1 .4 8%和 2 3.33%。 5 ASA组和SASP组的血清 5 ASA浓度分别为 (0 .0 32± 0 .0 0 8) μg/ml和 (0 .0 4 1± 0 .0 0 5 ) μg/ml(P >0 .0 5 )。 结论　 5 ASA肠溶片治疗UC总有效率与SASP相仿 ,但对UC的完     

Serious complications of sulfasalazine

Whereas minor side effects of sulfasalazine are common, serious adverse reactions to this drug generally are considered rare. However, this report discusses three major complications of sulfasalazine that occurred within the past three years, one resulting in the death of a patient. As more patients with inflammatory bowel disease are being managed by physicians of various disciplines, it is important to become familiar with the potentially dangerous side effects of all medications prescribed. For this reason, a brief review of the pharmacology, clinical use, and toxicity of sulfasalazine is presented.     

Gastrointestinal symptoms associated with enteric-coated sulfasalazine (Azulfidine EN tablets)

Abstract

To investigate both the incidence and the dosage used to treat gastrointestinal (GI) symptoms associated with enteric-coated sulfasalazine (Azulfidine EN, AZL) in patients with rheumatoid arthritis (RA), we studied the clinical history of 153 RA patients, and any available data on GI symptoms that might have been associated with AZL. GI symptoms appeared in 64 (42.5%) of the 153 cases. There were 19 events of nausea, vomiting, or dyspepsia, 14 events each of epigastric discomfort and reduction or loss of appetite, 10 events of epigastric, stomach, or abdominal pain, 9 events of heartburn, 8 events of mouth ulcer, 3 events each of loss of taste and abdominal bloating or borborygmus, 2 events each of diarrhea or loose stools, hematemesis or melanemia, and gastric or esophageal ulcer, and 1 event of stomatitis. These results indicate that GI symptoms associated with AZL are usually mild and treatment can continue, with almost all cases responding to a reduction in dose or drug cessation. In some cases, a histamine receptor-2 blocker or proton pump inhibitor is also required.     

美沙拉嗪与柳氮磺吡啶比较治疗溃疡性结肠炎疗效与安全性的系统评价

目的系统评价美沙拉嗪与柳氮磺吡啶比较治疗溃疡性结肠炎的疗效和安全性。方法计算机检索PubMed(1966～2010.1)、Cochrane Library(1996～2010.1)、EMbase(1974～2010.1)、CNKI(1994～2010.1)、VIP(1989～2010.1)和CBM(1978～2010.1)数据库,按照纳入与排除标准选择文献、评价质量并提取资料后,采用RevMan 5.0软件进行Meta分析。结果共纳入16个RCT,其研究质量均为中等,合计1333例溃疡性结肠炎患者。Meta分析结果显示:在总有效率方面,美沙拉嗪治疗溃疡性结肠炎优于柳氮磺吡啶,两组差异有统计学意义[RR=1.10,95%CI(1.04,1.17),P<0.05];在完全缓解率和复发率方面,两组差异均无统计学意义[RR=1.82,95%CI(1.14,2.91),P<0.05;RR=0.86,95%CI(0.57,1.29),P>0.05];共有12个RCT报道了不良反应,美沙拉嗪组不良反应更少[RR=0.56,95%CI(0.42,0.73),P<0.05]。结论现有证据显示,美沙拉嗪治疗溃疡性结肠炎的疗效和安全性均优于柳氮磺吡啶。但由于纳入研究在方法学质量方面还存在一些不足之处,可能影响到结果的真实性,因此上述结论尚有待开展更多设计严谨,大样本、多中心的随机对照试验来确认。     

加味不换金正气散灌肠治疗溃疡性结肠炎临床疗效观察

目的：观察并评价不换金正气散灌肠治疗溃疡性结肠炎（Ulcerative Colitis,UC）的临床疗效。方法：采用随机对照试验（RCT）研究方法观察加味不换金正气散灌肠疗法对UC临床治疗效果。将60例患者随机平均分为2组,两组患者均在口服美沙拉嗪缓释片基础上,治疗组给予加味不换金正气散煎剂保留灌肠,每晚1次;对照组给予柳氮磺吡啶肠溶片保留灌肠,每晚1次;持续治疗8周。分别记录并比较两组的临床症状、粪常规、内镜下肠黏膜病变改善情况、临床缓解时间及不良反应。结果：完成试验者55例（治疗组28例,对照组27例）,不良反应发生率在治疗组和对照组中,差异无统计学意义。两组患者临床症状缓解、肠黏膜疗效比较、临床活动指数等方面治疗组均优于对照组（P〈0.01或P〈0.05）。结论：加味不换金正气散治疗溃疡性结肠炎有较好的临床疗效,而且能够显著修复肠道黏膜。