Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study): a randomized, controlled trial

OBJECTIVE: Several treatment strategies have proven value in the amelioration of rheumatoid arthritis (RA), but the optimal strategy for preventing long-term joint damage and functional decline is unclear. We undertook this study to compare clinical and radiographic outcomes of 4 different treatment strategies, with intense monitoring in all patients. METHODS: In a multicenter, randomized clinical trial, 508 patients were allocated to 1 of 4 treatment strategies: sequential disease-modifying antirheumatic drug monotherapy (group 1), step-up combination therapy (group 2), initial combination therapy with tapered high-dose prednisone (group 3), and initial combination therapy with the tumor necrosis factor antagonist infliximab (group 4). Treatment adjustments were made every 3 months in an effort to obtain low disease activity (a Disease Activity Score in 44 joints of < or =2.4). RESULTS: Initial combination therapy including either prednisone (group 3) or infliximab (group 4) resulted in earlier functional improvement than did sequential monotherapy (group 1) and step-up combination therapy (group 2), with mean scores at 3 months on the Dutch version of the Health Assessment Questionnaire (D-HAQ) of 1.0 in groups 1 and 2 and 0.6 in groups 3 and 4 (P < 0.001). After 1 year, mean D-HAQ scores were 0.7 in groups 1 and 2 and 0.5 in groups 3 and 4 (P = 0.009). The median increases in total Sharp/Van der Heijde radiographic joint score were 2.0, 2.5, 1.0, and 0.5 in groups 1-4, respectively (P < 0.001). There were no significant differences in the number of adverse events and withdrawals between the groups. CONCLUSION: In patients with early RA, initial combination therapy including either prednisone or infliximab resulted in earlier functional improvement and less radiographic damage after 1 year than did sequential monotherapy or step-up combination therapy.     

Effect of gestational age on in-vitro responses of pregnant rat aorta

The hypothesis that the changes in vascular reactivity seen during pregnancy are determined by the gestational age was examined. Experiments were designed to investigate changes in vascular responses with progression of pregnancy. The contractile responses to potassium and phenylephrine (in the presence and absence of N(omega)-nitro-L- arginine methyl ester, a nitric oxide synthase inhibitor) and the relaxant responses to acetylcholine and sodium nitroprusside were measured in isolated aortic rings from pregnant rats at various stages of gestation and from non-pregnant female rats. Potassium-evoked contractile response was higher early in pregnancy and was decreased at term (P < 0.05). The contractile response to phenyllephrine was decreased and the relaxant response to acetylcholine was increased in early pregnancy (P < 0.05). Inhibition of nitric oxide synthase caused an increase in the contractile response to phenylephrine in all the groups, but the attenuation of the response in early pregnancy was maintained (P < 0.05). There was a small decrease in the maximal relaxant response to sodium nitroprusside at term (P < 0.05). It was concluded that the effects of pregnancy on the responses of rat aorta in vitro vary at different stages of gestation. Vascular resistance may be lowered by changes in vascular reactivity in early gestation and by a decrease in the contractile potential of the vasculature during the later stages.      

Transplantation hépatique de l’adulte: qui et quand greffer?

Introduction. -- The shortage of cadaveric organ donors imposes a severe limit to the number of liver transplantations. A selection is thus necessary among patients: should the sickest be selected, or those who supposedly have the best chance to survive and recover? Optimizing the timing of transplantation during the course of the disease (not too early, but not too late) is another issue.Current knowledge and key points. -- Suitable candidates for transplantation are patients suffering from an irreversible, symptomatic liver disease. The goals of therapy are: firstly, to favorably modify the natural outcome of the disease; and secondly, in an acceptable risk taking manner. Major criterias for indication in the most common liver diseases can be summerized as follows: a) for chronic parenchymal liver diseases, a Child-Pugh score of 9 or 10, or less if complications have already occurred, is a mandatory and often sufficient criterion; b) for cholestatic liver diseases, a serum bilirubin level higher than 100-150 μmol/L is generally required; c) apart from «small» hepatocellular carcinomas on cirrhotic parenchyma (less than three tumors of less than 5 cm in diameter), most cancers are considered contraindications; d) acute liver failure requires early referral to a liver transplant center for potential emergency indication.Future prospects and projects. -- In an organ shortage situation which is likely to perdure, early consultative contact between the patient and the liver transplant team will allow improvement in the access to transplantation procedure.

Résumé

Introduction. -- L'augmentation du nombre de transplantations hépatiques est limitée par l'insuffisance des ressources en donneurs. La nécessité impose donc un choix parmi les patients susceptibles de bénéficier de ce traitement -- les cas plus graves? ou ceux qui ont les meilleures chances de guérir? -- et une évaluation optimale du moment de la transplantation dans l'histoire de la maladie: ni trop tôt, ni trop tard.Actualités et points forts. -- La transplantation doit être réservée aux patients souffrant d'une affection hépatique irréversible et symptomatique. Elle doit, en règle générale et par ordre d'importance, d'une part modifier l'histoire naturelle de la maladie et, d'autre part, pour un risque minimal. Les critères majeurs d'indication peuvent être ainsi schématisés pour les hépatopathies les plus fréquentes: 1) pour les cirrhoses non choléstatiques, un score de Pugh-Child de 9-10, ou un score inférieur si des accidents évolutifs se sont déjà produits, est un critère nécessaire et souvent suffisant ; 2) pour les cirrhoses choléstatiques, un taux de bilirubine sérique supérieur à 100-150 μmol/L est un critère admis ; 3) si l'on excepte les «petits» carcinomes hépatocellulaires sur cirrhose (moins de trois nodules de moins de 5 cm), presque tous les cancers sont une contre-indication à la transplantation ; 4) l'insuffisance hépatique aiguë nécessite un transfert précoce en milieu spécialisé pour une éventuelle indication de transplantation en urgence.Perspectives et projets. -- Dans un contexte de pénurie qui risque de perdurer, l'amélioration des conditions d'accès à la transplantation nécessite qu'un avis consultatif puisse être pris précocement dans l'histoire naturelle de la maladie auprès des équipes en charge de la transplantation.     

美白牙膏去除牙齿外源性色斑的临床效果观察

目的：与仅含有0．321％氟化钠的牙膏相比,评价含有0．321％氟化钠及20％高清洁二氧化硅（HCS）的牙膏减少外源性牙色斑的效果,方法：采用双盲,分层,二单位平行观察的临床研究方法,根据Lobene色斑指数均数（色斑指数包括染色部位及染色程度）,性别,将158名年龄为18－65岁的研究对象平衡地分为两组,随机地分配使用试验或对照牙膏,于基线,第4周及第8周固定由一名检查者完成研究对象的色斑指数测定,结果：4周时,使用美白牙膏的研究对象较对照组的牙齿色斑面积减少17．4％,染色程度减少19．2％（P＜0．01）,8周时,使用美白牙膏的研究较对照组的牙齿色斑面积减少38．6％,染色程度减少39．6％（P＜0．01）,结论：与对照组牙膏相比,使用含有0．321％氟化钠及20％HCS的牙膏可以有效地减少外源性牙色斑。     

Infliximab and methotrexate as induction therapy in patients with early rheumatoid arthritis

OBJECTIVE: To evaluate the efficacy of infliximab plus methotrexate (MTX) as induction therapy in patients with early rheumatoid arthritis (RA). METHODS: Disease-modifying antirheumatic drug (DMARD)-naive patients with active, early RA who were included as group 4 of the BeSt study were initially treated with infliximab (3 mg/kg) in combination with MTX (25 mg/week). The Disease Activity Score (DAS) was measured every 3 months. In patients with persistent low disease activity (DAS 2.4, the infliximab dosage was increased (maximum 10 mg/kg), and they were subsequently switched to another DMARD. Except for intraarticular administration, corticosteroids were not permitted. Functional ability and the modified Sharp/van der Heijde score were determined after 2 years of therapy. RESULTS: Of the 120 patients, 67 responders (56%) had persistent low disease activity and discontinued infliximab after a median of 9.9 months, with a median MTX dosage of 10 mg/week after 2 years. Ten other patients experienced a disease flare after discontinuation and resumed infliximab after a median of 3.7 months. Thirteen patients did not achieve persistent low disease activity and received infliximab at various dosages. Treatment was unsuccessful in 30 patients. In the 67 responders, the progression of joint damage was lower than in the 30 patients in whom treatment failed. CONCLUSION: Fifty-six percent of patients with active early RA, initially treated with infliximab plus MTX, could discontinue infliximab after achieving a DAS of 相似文献   

评价Ti-6Al-7Nb合金的细胞相容性及其组织相容性

目的:评价Ti-6Al-7Nb合金的细胞相容性和组织相容性。方法:实验于2006-05/10在解放军第四军医大学口腔生物学实验室完成。实验分组:①细胞毒性试验:按照GB/T16886.5-2003《医疗器械生物学评价》体外细胞毒性的试验方法进行。分为5组:Ti-6Al-7Nb合金组、Ti-6Al-4V合金组、纯钛组、纯铅组、空白对照组。将对数生长期的L-929细胞用胰蛋白酶消化后制备成浓度为1×107L-1的细胞悬液,接种于培养板,待细胞贴壁生长后弃去原培养液。磷酸盐缓冲液冲洗后分别加入4种金属材料的浸提液和空白对照组的DMEM培养液。培养1,3,5,7d在倒置相差显微镜下观察细胞形态。每孔加入MTT后继续培养,抽出浸提液,磷酸盐缓冲液冲洗后加入二甲基亚砜,在490nm波长下用酶联免疫检测仪上测定吸光度值(A值),计算细胞相对增殖率,相对增殖率=(实验组A值/空白对照组A值)×100%。相对增殖率为≥100%,80%￣99%,50%￣79%,30%￣49%,0￣29%时细胞毒性分别为0,1,2,3,4级。②急性溶血性试验:抽取新西兰兔血10mL,制成新鲜抗凝稀释兔血。将Ti-6Al-7Nb合金、Ti-6Al-4V合金各5g浸泡入10mL生理盐水的试管。阳性对照组及阴性对照组分别为10mL的蒸馏水及生理盐水。每个试管中加0.2mL稀释兔血,离心后取上清液,用分光光度计在波长为545nm波长下测吸光度值,计算溶血率,溶血率=(Dt-Dnc)/(Dpc-Dnc)×100%。Dt,Dnc,Dpc分别代表Ti-6Al-7Nb合金组或Ti-6Al-4V合金组、阴性对照组、阳性对照组的A值。③短期皮下埋植试验:在10只新西兰大白兔皮下至肌肉间制备皮囊植入材料。囊底至切口>10mm,两皮囊间相隔>10mm,使植入材料相互之间不接触。每只兔植入4种金属材料各1个。于术后1,4,12周麻醉后处死动物各3只,取材料周围组织行苏木精-伊红染色,观察炎性细胞数量及种类,使用电子测量尺Version1.0测量纤维包膜厚度。参照GB/T16175-1996中的评价标准确定组织反应程度,其反应程度主要通过试验区组织中炎性细胞数量及种类变化,纤维包膜形成与否及厚度变化评价。结果:①细胞毒性评价:3种钛金属材料浸泡7d时L-929细胞形态正常,生长近汇合,排列密集规则;纯铅组可见大量细胞死亡。浸泡7d时Ti-6Al-7Nb、Ti-6Al-4V、纯钛、纯铅相对增殖率分别为100%,97%,101%,9%。经过评价,Ti-6Al-7Nb合金和纯钛的细胞毒性为0级,Ti-6Al-4V合金为1级,纯铅为4级。②细胞相容性评价:Ti-6Al-7Nb合金组、Ti-6Al-4V合金组溶血率分别0.95%,1.08%,低于国家标准规定的5%界限,无明显的急性溶血性。③组织相容性评价:肉眼可见材料被纤维包膜包裹,3组钛金属周围包膜透明且较薄,纯铅组包膜较厚呈半透明乳白色。术后12周时3种钛金属材料周围炎性细胞密度较低,包膜致密且进一步变薄。纯铅组炎性细胞数量及包膜厚度均较3种钛金属为高,组织反应较重。Ti-6Al-7Nb合金和纯钛炎性细胞/组织反应程度均为Ⅰ级,Ti-6Al-4V合金分别为Ⅰ、Ⅱ级,纯铅分别为Ⅱ、Ⅲ级。结论:Ti-6Al-7Nb合金具有良好的细胞相容性和组织相容性,是一种理想的生物医用钛合金。     

还你自信，面对竞争—谈颌骨畸形的外科治疗

颌骨可以维持面部的外形，同时又可形成千姿百态的表情。但人的颌骨发育如果出现缺陷，造成脸部畸形，这在就业、求职竞争日趋激烈的今天，可能首先就输在起跑线上，失去参与竞争的本钱，患者可能由此而感到自卑、无助，甚至抱怨，严重时会造成心理障碍。颌骨畸形在人群中的发生率为1‰，多见于中学生和大学生。     

Three new asterosaponins from the starfish Culcita novaeguineae and their bioactivity

Bioassay-guided fractionation of the active n-BuOH extract of the starfish Culcita novaeguineae resulted in the isolation of three new sulfated steroidal glycosides （asterosaponins） 1, 2 and 3, as active compounds causing morphological abnormality of Pyricularia oryzae mycelia. Compounds 1-3 possess the same pentasaccharide moiety, beta-D-fucopyranosyl-（1→2）-alpha-L-arabinopyranosyl- （ 1 → 4 ）-[- beta-D- quinovopyranosyl- （ 1 →2 ） ]-beta-D-xylopyranosyl- （ 1 → 3 ）-beta-D-quinovopyranosyl, linked to C-6 of 3beta-sulfated steroidal aglycones and differ from each other in the side chains.     

The regulatory role of interleukin 2-responsive T lymphocytes on early and mature erythroid progenitor proliferation

To analyze the role of T lymphocytes in human erythropoiesis, we evaluated the effect of recombinant interleukin 2 (IL 2) on marrow CFU- E and BFU-E colony formation in vitro. IL 2 resulted in an increase in CFU-E and BFU-E colony numbers in a dose-dependent manner. This increase could be prevented by anti-Tac, a monoclonal antibody to the IL 2 receptor. Moreover, anti-Tac on its own resulted in an overall decrease in colony numbers. Depletion of marrow adherent cells did not alter the effect of either IL 2 or anti-Tac on colony growth. Following the removal of marrow T lymphocytes, CFU-E and BFU-E colony formation proceeded normally; however, the effects of IL 2 and anti-Tac were markedly diminished. Readdition of T lymphocytes to the cultures restored the IL 2 effect. Although T lymphocytes were not themselves essential for in vitro erythropoiesis, our studies suggest that IL 2 and IL 2-responsive T cells can regulate both early and mature stages of erythroid differentiation.