益赛普联合甲氨蝶呤治疗对类风湿关节炎临床及炎性细胞因子的影响

目的 研究类风湿关节炎（RA）患者益赛普（ETA）联合甲氨蝶呤（MTX）治疗后,临床表现及血清肿瘤坏死因子α（TNF-α）、白细胞介素-6（IL-6）、干扰素-γ（IFN-γ）浓度的变化.方法 选取活动性RA患者25例和正常人18例作为研究对象,研究期间患者均给予甲氨蝶呤10 mg每周1次口服,以及益赛普25 mg每周2次,皮下注射.治疗前及治疗后第6周收集患者血清,检测其TNF-α,IFN-γ、IL-6浓度,并记录肿胀关节数、压痛关节数、疾病活动性评分（DAS）、健康评估问卷评分（HAQ）、血沉（ESR）、C反应蛋白（CRP）和类风湿因子（RF）等,同时收集正常人血清检测上述指标.结果 RA组患者血清IL-6、TNF-α和IFN-γ浓度明显高于正常对照组（P分别＜0.01、0.05、0.05）.治疗后患者DAS28评分降低（P＜0.01）,HAQ、ESR、CRP、肿胀及压痛关节数也明显好转（P＜0.01）,血清RF、IL-6和TNF-α浓度也明显下降（P分别＜0.05,0.01,0.05）,治疗后血清IFN-γ浓度较前下降,但无显著性差异.结论 血清IL-6、TNF-α和IFN-γ浓度增高以及ESR、CRP、RF增加可作为RA病情活动指标.益赛普和甲氨蝶呤联合治疗能快速缓解患者关节炎症,并改善关节功能.     

甲氨蝶呤联合环磷酰胺治疗类风湿关节炎随机单盲对照临床研究

目的 评价甲氨蝶呤(MTX)联合环磷酰胺(CTX)及单独应用MTX、单独应用CTX治疗类风湿关节炎(RA)的疗效和安全性.方法 本研究为随机、单盲、对照的临床试验.符合纳入及排除标准的RA患者随机分为单用MTX(10～15 mg/周)、单用CTX(400 mg/2～3周)及MTX联合CTX治疗组(MTX10～15 mg/周+CTX 400 mg/2～3周).疗程24周,在基线、6、12、24周进行疗效及安全性评估.以美国风湿病学会(ACR)疗效评价指标ACR20为主要疗效指标,ACR50、ACR70、欧洲抗风湿联盟(EULAR)疗效指标、疼痛目视模拟测试表(VAS)评分、患者对自身健康状况的总体评估(PGA)、医生总体评价、压痛关节数(TJC)、压痛关节指数(TJI)、肿胀关节数(SJC)、肿胀关节指数(SJI)、健康评估问卷(HAQ)为次要疗效指标.结果 在第24周,MTX+CTX组达ACR20改善的患者比例(81%)高于MTX组(56%)及CTX组(35%),差异有统计学意义(P＜0.05).24周时MTX+CTX组达ACR50改善的患者比例高于CTX组(P＜0.05).与MTX组之间差异无统计学意义(P＞0.05).在第24周,MTX+CTX组达到EULAR有效的患者比例(77%)高于MTX组(48%)及CTX组(35%),差异有统计学意义(P＜0.05).24周时MTX+CTX组在TJC/TJI、SJC/SJI疼痛VAS评分、ESR的改善程度高于MTX组(P＜0.05).在压痛关节数脂数、肿胀关节数/指数、疼痛VAS评分、PGA、医生总体评价、HAQ、ESR的改善程度高于CTX组(P＜0.05).3组之间不良反应发生率差异无统计学意义.结论 MTX联合CTX治疗能显著改善RA的症状、体征和实验室炎性指标,疗效优于单用MTX及单用CTX.两者联合治疗安全耐受性好,与单用MTX及单用CTX相比,并不增加不良反应的发生率.     

类风湿关节炎患者关节腔注射曲安奈德联合甲氨喋呤治疗前后滑膜超声表现的变化

目的 超声检测曲安奈德联合甲氨喋呤关节腔注射前后类风湿关节炎(RA)患者滑膜的变化,并进一步明确滑膜超声影像学变化对于RA诊断及治疗的意义.方法 选择以膝关节炎症状入院的RA患者222例,超声检测患者膝关节滑膜厚度及关节积液量,然后以曲安奈德(1ml:10 mg)及甲氨喋呤(1 ml:10mg)分别注入关节腔内,同时原口服药物方案行非甾体类抗炎药(NSAIDs)及缓解病情抗风湿药物(DMARDs)治疗,分别于注射后第7天和第14天再次行上述治疗,同时行膝关节滑膜超声检查,观察注射关节的疼痛指数、肿胀指数、压痛指数和晨僵时间.此后第2个月和6个月末再次行膝关节滑膜超声检查,并记录上述指标.结果 与治疗前比较,治疗第7天、第14天及第2和第6个月末,患者膝关节滑膜厚度及关节积液量均明显下降,关节疼痛指数、肿胀指数、压痛指数、关节晨僵时间均明显减少(P＜0.01或P＜0.05),滑膜厚度及关节积液与关节疼痛指数、肿胀指数、压痛指数均分别呈正相关(P＜0.05).结论 滑膜超声改变可作为评估RA患者曲安奈德联合甲氨喋呤关节腔注射治疗疗效观察指标之一.     

活动期类风湿关节炎患者血清基质金属蛋白酶一3及其组织抑制剂一1水平的检测和意义

目的研究活动期类风湿关节炎(rheumatoid arthritis,RA)患者血清基质金属蛋白酶一3(matrix metalloproteinase 3,MMP-3)、金属蛋白酶组织抑制剂一1(tissue inhibitors of metalloproteinase 1,TIMP-1)的水平及其相关影响因素,探讨MMP-3及TIMP-1在RA的作用机制.方法选择41例初诊活动期RA患者和30名正常健康志愿者,以酶联免疫吸附试验(ELISA)分别检测血清MMP-3及TIMP-1水平,计算MMP-3/TIMP-1,同时测定关节功能、X线、关节肿胀数(SJC)、血沉(ESR)、类风湿因子(RF)、C反应蛋白(CRP)等相关实验室指标.结果活动期RA患者血清MMP-3、TIMP-1明显增高(P＜0.01),且以MMP-3增高更为显著,MMP-3/TIMP-1较正常组亦增高(P＜0.05).不同关节功能分级时,上述指标差异无统计学意义(P＞0.05),而不同X线分期时,各指标差异有统计学意义(P＜0.01或P＜0.05).MMP-3、MMP-3/TIMP-1与SJC(P＜0.01)、CRP(P＜0.01)、ESR(P＜0.05)呈正相关,二者与年龄、病程、晨僵时间、RF无明显相关性(P＞0.05).结论 MMP-3、TIMP-1在RA血清中高水平存在,二者比例失衡导致RA发生.MMP-3、MMP-3/TIMP-1的高低可作为反映病情活动及预后的指标,阻断MMP-3高水平有可能成为治疗RA的新途径一.     

类风湿关节炎患者外周血辅助性T细胞9及白细胞介素-9的变化及临床意义

目的 观察类风湿关节炎(RA)患者外周血中辅助性T细胞9(Th9)及血清中白细胞介素(IL)-9的变化,探讨其与RA临床表现的相关性及其可能的免疫学发病机制.方法 收集36例RA患者和22名健康对照者,RA患者根据病情活动度不同分为病情重度活动组22例、病情中度活动组14例.流式细胞仪检测患者和健康对照者外周血中Th9细胞的变化;酶联免疫吸附试验(ELISA)检测RA患者及健康对照者血浆中IL-9等细胞因子的水平.采用t检验、Spearman相关分析进行统计学分析.结果 RA患者外周血中Th9比例显著高于健康对照组[分别为(0.99±0.50)％,(0.21±0.08)％,P＜0.01];RA患者重度活动组的Th9表达率显著高于中度活动组[分别为(1.18±0.52)％,(0.69±0.25)％,P＜0.01].RA患者外周血IL-9水平高于健康对照[分别为(1.06±0.42) pg/ml,(0.69±0.13) pg/ml,P＜0.01],重度活动组的RA患者IL-9水平[( 1.37±0.47) pg/ml]高于中度活动组[(0.94±0.30) pg/ml],差异有统计学意义(P＜0.05).RA患者外周血Th9的表达与疾病活动指数(DAS )28、红细胞沉降率(ESR)、C反应蛋白(CRP)、关节压痛数、关节肿胀数及类风湿因子(RF)滴度、IL-9的水平呈正相关;RA患者IL-9的水平与DAS28、ESR、关节压痛数、关节肿胀数呈正相关.结论 RA患者外周血Th9细胞比例及血浆中IL-9水平显著升高,且与疾病活动度及相关炎症指标明显相关,提示Th9及IL-9参与RA的发病及病情发展.     

我国类风湿关节炎患者羟氯喹使用的现状调查

目的 了解我国类风湿关节炎(RA)患者羟氯喹使用的现状及特点.方法 现场调查全国20家大型医院风湿科就诊的858例RA患者,记录患者的一般人口学特征、临床病情活动度、羟氯喹用药情况以及不良反应等.采用SPSS 20.0软件根据不同数据特点进行Mann-Whitney U检验、x2检验及回归分析等.结果 ①羟氯喹在我国RA患者中使用方案较规范,使用率为19.5％(167/858),64.7％(108/167)达到足疗程,77.8％(130/167)达到推荐剂量,94.6％(158/167)为联合用药,最常用的联合药物为甲氨蝶呤和来氟米特.②足疗程使用羟氯喹的RA患者多项疾病活动指标得到明显改善,包括晨僵时间(U=1 670.5,P＜0.05)、压痛关节数(U=1 380.5,P＜0.01)及肿胀关节数(U=67 974.5,P＜0.01)、患者视觉模拟评分(VAS)疼痛评分(U=2 086.0,P=0.01)、患者VAS疾病活动评分(U=2 181.5,P＜0.05)、医生VAS疾病活动评分(U=2 086.5,P＜0.05)、28个关节疾病活动指数(DAS28)评分(U=827.5,P＜0.01)、斯坦福健康评定量表(HAQ)评分(U=1 855.5,P＜0.01)、红细胞沉降率(U=1 231.0,P＜0.05).③羟氯喹总体不良反应发生率为5.4％(9/167),最常见眼部受累(包括眼底黄斑变性、眼前闪光、眼异物感)及过敏反应、发生率分别为1.8％(3/167)及1.2％(2/167).结论 在我国大型医院就诊的RA患者中有19.5％使用羟氯喹,其中94.6％为联合用药.羟氯喹足疗程使用疗效肯定,总体不良反应发生率低,无严重不良反应.     

高迁移率族蛋白1及Toll样受体4在类风湿关节炎患者血清和外周血单个核细胞中的表达及意义

目的 通过研究高迁移率族蛋白(HMGB)1及Toll样受体(TLR)4在类风湿关节炎(RA)外周血单个核细胞(PBMC)和血清中的表达,探讨HMGB1的作用及其与疾病活动的关系.方法 选取活动期RA患者38例和非活动期RA患者36例及健康对照组26名.采用反转录-聚合酶链反应(RT-PCR)方法检测PBMC中HMGB1 mRNA的表达,酶联免疫吸附试验(ELISA)检测血清中HMGBI蛋白的表达.采用流式细胞术分析PBMC上TLR4的表达.结果 ①活动期RA组PBMC中HMGB1 mRNA相对表达量和血清中HMGB1蛋白水平均高于健康对照组和非活动期RA患者[分别为2.63与0.71.0.93和(10.2±1.2)与(7.5+1.8),(8.3±1.8)ng/ml,P＜0.01.②活动期RA患者CD14+单核细胞和CD3+淋巴细胞上TLR4蛋白相对表达量高于非活动期和健康对照组(P＜0.05或P＜0.01),非活动期患者高于健康对照组(P＜0.05或P＜0.01).③血清中HMGB1蛋白水平与红细胞沉降率(ESR)、C反应蛋白(CRP)、类风湿因子(RF)、关节压痛数、肿胀数及关节X线分期均呈正相关,亦与TLR4蛋白相对表达量呈正相关.结论 RA患者PBMC具有合成和分泌HMGB1蛋白的功能,并部分通过与TLR4结合激活炎症反应,加重骨质破坏.     

类风湿关节炎患者骨质疏松与骨侵蚀关系的研究

目的 探讨类风湿关节炎(RA)患者骨质疏松的发生情况及其与关节骨侵蚀及其他临床指标的相关性.方法 采用双能X线骨密度仪.测量111例RA患者和30名健康人腰椎和股骨区的骨密度(BMD),并同时测定手关节X线分期及其他各临床指标.结果 RA患者的骨量丢失较对照组明显,骨质疏松的患病率更高(P＜0.05),随关节骨侵蚀加重,各测定部位的BMD呈下降趋势,手关节病变Ⅲ期、Ⅳ组的BMD均明显低于对照组(P＜0.05).RA患者中骨质疏松组较非骨质疏松组病程更长(P＜0.05),手关节骨侵蚀更重(P＜0.05),关节功能更差(P＜0.05).服用糖皮质激素比例更高(P＜0.05).Logistic回归分析显示手关节骨侵蚀(OR=0.636,0.424～0.954,P=0.029)和糖皮质激素服用情况(OR=2.696,1.026～7.083,P=0.044)是与RA患者骨质疏松发生有显著相关的因素.结论 随手关节骨侵蚀加蕈RA患者BMD呈下降趋势,RA患者骨质疏松的发生是多因素的,主要与关节骨侵蚀和是否服用糖皮质激素等有关.     

血清白细胞介素-37水平与类风湿关节炎发病及病情进展的相关性

目的探讨血清白细胞介素(IL)-37水平与类风湿关节炎(RA)发病及病情进展的相关性。方法选择50例RA患者(观察组)和30例健康者(对照组),观察或检测治疗前后关节肿胀数、关节压痛数、关节炎活动度评分(DAS28)及血清C反应蛋白(CRP)、红细胞沉降率(ESR)、类风湿因子(RF)和IL-37水平及IL-37 mRNA表达,并与对照组进行分析,分析血清IL-37水平与以上各指标的相关性。结果观察组治疗前的关节肿胀数、关节压痛数和DAS28评分均高于对照组(P0.05),治疗后以上临床指标均显著改善(P0.05);观察组治疗前血清中CRP、ESR、RF水平均高于对照组(P0.05),治疗后这3项实验室指标明显降低(P0.05);观察组治疗前血清IL-37水平、IL-37 mRNA表达明显高于对照组(P0.05),治疗后明显较治疗前降低(P0.05),且血清IL-37水平与以上临床指标和实验室指标呈正相关(P0.05)。结论血清中IL-37与RA的发病及病情进展密切相关,其在RA病程进展过程中具有抑制炎症的作用。     

类风湿关节炎患者血清中肿瘤坏死因子凋亡样微弱诱导剂和凋亡调节蛋白生存素水平的检测和意义

目的 检测类风湿关节炎(RA)患者血清中肿瘤坏死因子样凋亡微弱诱导剂(TWEAK)和凋亡调节蛋白生存素(survivin)的水平,以探讨其在RA中的意义.方法 采用酶联免疫吸附试验(ELISA)方法测定61例RA患者和35名健康对照组血清中TWEAK和survivin水平,同时测定RA患者关节功能、X线分期、关节压痛数和肿胀数、红细胞沉降率、类风湿因子、C反应蛋白等各项临床指标,进行相关性分析.结果 RA患者血清中TWEAK水平[(479±381)pg/ml]与健康对照组TWEAK水平[(421±87)pg/ml]差异无统计学意义.RA患者血清中survivin水平[(159±82)pg/ml]比对照组[(119±24)pg/ml]增高(P＜0.05),且血清gurvivin水平与RA患者关节X线分期呈正相关(r=0.29,P＜0.05).结论 血清TWEAK水平与RA的关系还需要更深入的研究.Survivin与关节侵蚀性相关,可能成为新的判断病情及治疗的新指标.     

青少年高血压的研究进展

随着人们生活和行为方式的改变,高血压发病明显呈年轻化趋势。在青少年时期识别高血压病高危人群有助于早期进行有效干预和治疗,降低未来高血压的发生率及其严重性。现试从青少年高血压的诊断、发病因素、特点、治疗策略等方面的研究进展作一综述。     

Morbidity in cardiovascular diseases in immigrants in Sweden

INTRODUCTION: Although immigration to Sweden has increased in the last few decades, the incidence rates of cardiovascular disease and coronary heart disease in immigrants are unknown. The aim of the present study is to estimate whether place of birth affects the incidence rates of cardiovascular disease and coronary heart disease. MATERIAL AND METHODS: The study was designed as a follow-up study on morbidity in cardiovascular disease and coronary heart disease between 1 January 1997 and 31 December 1998, including three and a half million persons with age range 35-64 years, of whom 550 000 were born abroad, from the database MigMed consisting of the whole Swedish population. Incidence rates and relative risks were estimated by indirect standardization and a proportional hazard model. RESULTS: The age-adjusted risk of coronary heart disease was higher in most foreign-born groups than in Swedes. For example, in nine of 12 male groups, the relative risks varied between 1.1 and 2.2, and in seven of 12 female groups, the relative risks varied between 1.4 and 2.5. When also adjusting for level of education and employment status, the risks were still high, but on a lower level. CONCLUSIONS: Foreign-born people possess an over-risk of cardiovascular or coronary heart disease(CVD/CHD) compared with Swedish-born persons, also when level of education and employment status are taken into account.     

C·肉毒杀鼠素(冻干剂)应用研究

目的为研究C·肉毒杀鼠索对杀灭达乌尔黄鼠(简称黄鼠)的大面积应用情况和对家畜、家禽的毒害作用,进行了C·肉毒杀鼠素的应用研究.方法大面积投毒采用ES-2药饵撒播机[1],间隔约80m进行条投.羊、鸡采用直接灌胃.结果大面积应用的灭鼠率为83.72%.对羊、鸡最高剂量分别为500万MLD、150万MLD,均未出现中毒现象.结论 C·肉毒杀鼠素是较为理想的草原大面积杀灭黄鼠的理想、首选药物.     

高龄老年高血压的临床研究进展

随着社会老龄化进程的加快,80岁以上高龄老人的绝对数量以及占总人口的比例均在增加,如何提高高龄老年高血压的防治水平备受关注。现试从高龄老年高血压的临床特点、治疗策略等方面的临床研究进展作一综述。     

中国老年性耳聋的研究与干预进展

老年性耳聋已成为影响我国老年人生活质量的最主要的慢性病之一。助听器是目前帮助听力损失的老年人克服交流障碍的主要手段。在我国,数字助听器已逐渐取代模拟助听器并且体现出了更好的效果。但是老年听力损失患者中使用助听器的比例仍然很小。人工耳蜗植入也已被应用在老年患者中。我国针对老年人的听力康复服务还有较长的路要走。     

Sex Differences in Ethanol-induced Dopamine Release in Nucleus Accumbens and in Ethanol Consumption in Rats

In vivo microdialysis was used to examine changes in nucleus accumbens and striatal dopamine, dihydrophenylacetic acid (DO-PAC), and homovanillic acid (HVA) following acute administration of ethanol (0.0, 0.25, 0.5, 1.0, or 2.0 g/kg) in male and female Long-Evans rats. Following dialysis, rats were trained to bar-press for oral ethanol reinforcement. In nucleus accumbens, females showed significant increases in extracellular dopamine following 0.25 or 0.5 g/ kg ethanol, but did not show significant increases over baseline at the higher doses. Males showed slight increases in dopamine at the lower doses and decreased dopamine at 2.0 g/kg. In striatum, both sexes showed increased dopamine at the lower doses and decreased dopamine at 2.0 g/kg. There were slight increases in nucleus accumbens DOPAC and HVA at some doses in both sexes, but no changes in striatal metabolite levels. In addition to showing increased responsiveness to ethanol-induced mesolimbic dopamine stimulation, females consumed more ethanol than males during behavioral testing. The pattern of both greater ethanol-induced nucleus accumbens dopamine release and greater ethanol consumption in females supports the hypothesis that ethanol reward is mediated, at least in part, by the mesolimbic dopamine system.     

Epstein-Barr virus in malignancies in renal transplant recipients in Japan

A role for Epstein-Barr virus (EBV) in the development of malignancies including lymphomas, and carcinoma of the stomach, nasopharynx, thymus and salivary gland is suggested. It is indicated that EBV evokes polyclonal-B-cell-proliferative diseases in immunocompromised hosts, such as transplant patients, which results in monoclonal malignant lymphomas. The suppression of immune functions in these patients is thought to lead to incomplete elimination of the cells expressing EBV latent infection genes. To examine the etiological role of EBV in the development of malignancies following renal transplant in Japan, 42 malignancies in 1744 cases of renal transplant were studied for the presence and type of EBV. The polymerase chain reaction revealed that 5 malignancies were positive for EBV, all type A: 2 of 2 cases of non-Hodgkin's lymphoma (NHL), 2 of 8 cases of gastric adenocarcinoma of the common type, and 1 of 2 cases of gastric plasmacytoma. In situ hybridization revealed positive signals in the nucleus of tumor cells in 2 cases of NHL and 1 of plasmacytoma. Positive signals were found in the small lymphoid cells but not in the tumor cells in 2 cases of gastric carcinoma. On the basis of these findings, a role for EBV in the development of malignancies in renal transplant patients is unlikely except for lymphoid neoplasias.Abbreviations PCB polymerase chain reaction - EBV Epstein-Barr virus - NHL non-Hodgkin's lymphoma     

Dead in Bed Syndrome in Young Diabetic Patients in Norway

The incidence of unexplained deaths (‘dead in bed syndrome’) in Norwegian diabetic patients under the age of 40 was investigated during the period 1981–1990. During this 10-year period there were 240 deaths of all causes in the age group 0–39 years. Sixteen of these cases fulfilled the following criteria of the ‘dead in bed syndrome’: (1) patient found dead in an undisturbed bed; (2) patient observed to be in good health condition the day before; (3) no clinical evidence of late complications (except background retinopathy in two cases). Of the 16 cases ascertained, 10 were males and 6 females. The age range was 7–35 years, and the duration of diabetes varied between a few months and 26 years. Autopsy, performed in 13 cases, did not reveal any cause of death. Nine patients had been using insulin regimens with multiple daily doses. Twelve patients were reported as having had frequent episodes of hypoglycaemia, with nocturnal episodes in 10 cases. There was apparently an increasing incidence of unexplained deaths during the study period, with 12 of 16 cases occurring in the years 1988 to 1990.