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Auranofin.
Pub Date : 2020-02-07 DOI: 10.32388/rx9at4
W. Kean, L. Hart, W. Buchanan
It has been widely accepted for a number of years that chrysotherapy is a valuable therapeutic agent in the treatment of progressive rheumatoid disease. This therapeutic benefit has, to some extent, been offset by the potential toxicity associated with gold compounds. The development of a gold compound with a greater therapeutic to toxicity ratio would be of considerable interest and benefit, to both patients and physicians. Initial studies with auranofin suggested that this compound was a reliably absorbed agent and that its use would avoid regular gold thiol injections. Its initial therapeutic profile was considered to be similar to that of injectable gold compounds, but with a significantly greater safety margin. The further information that has accrued from the clinical studies reported so far would tend to support these early suggestions in that auranofin has compared very favourably with gold thiols and other disease-remittive agents and that the prevalence of side effects requiring withdrawal of therapy has been approximately 25-30 per cent less. In addition, the reasons for withdrawal have often been less potentially serious side effects, notably nephrotoxicity and haematological reactions. In a review of over 3000 patients treated with auranofin, compared to 465 patients treated with injectable gold, the frequency of withdrawal from studies due to inefficacy of auranofin was approximately two to three times higher than with the gold thiols. It would appear, therefore, that in those patients continuing on therapy, auranofin is similar to injectable gold, but that a higher proportion of patients will fail to get a response within three to six months to the therapy. This potential lack of therapeutic effect is offset by the increased safety margin. In time, it is possible that auranofin will be accepted for earlier treatment in the course of rheumatoid disease than perhaps would normally have been considered. The in vivo and in vitro studies of auranofin on its mechanism of action are of considerable interest. They provide theoretical and valuable information on the mechanism of action of gold compounds and the cellular functions and interactions which may be involved in the pathogenesis of rheumatoid disease. It is interesting to note that auranofin appears to be more potent and have different effects than gold thiols, despite the fact that in terms of clinical therapeutic profile the compounds are similar.(ABSTRACT TRUNCATED AT 400 WORDS)
多年来,热疗法已被广泛接受为治疗进行性类风湿疾病的一种有价值的治疗剂。在某种程度上,这种治疗益处被与金化合物相关的潜在毒性所抵消。开发一种具有更大治疗毒性比的金化合物对患者和医生来说都是相当有趣和有益的。对金萘芬的初步研究表明,这种化合物是一种可靠的吸收剂,使用它可以避免常规的金硫醇注射。其最初的治疗效果被认为与注射用金化合物相似,但安全性明显更高。迄今为止所报告的临床研究所积累的进一步资料倾向于支持这些早期的建议,因为与金硫醇和其他疾病缓解剂相比,金硫醚非常有利,而且需要停止治疗的副作用发生率大约减少了25- 30%。此外,停药的原因往往是潜在的严重副作用较少,特别是肾毒性和血液学反应。在对3000多名接受金葡聚糖治疗的患者进行的一项审查中,与接受注射金葡聚糖治疗的465名患者相比,因金葡聚糖无效而退出研究的频率大约是金硫醇治疗的2至3倍。因此,在那些继续接受治疗的患者中,金糠蛋白与注射金类似,但更高比例的患者在接受治疗的3至6个月内没有得到反应。这种潜在的治疗效果不足被增加的安全边际所抵消。随着时间的推移,在类风湿疾病的早期治疗中,金糠蛋白可能会被接受,而不是通常认为的那样。对金糠蛋白的体内和体外作用机制的研究引起了人们极大的兴趣。它们为金化合物的作用机制以及可能参与类风湿病发病机制的细胞功能和相互作用提供了理论和有价值的信息。有趣的是,尽管在临床治疗方面这两种化合物是相似的,但金硫醚似乎比金硫醇更有效,效果也不同。(摘要删节为400字)
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引用次数: 66
Antineutrophil cytoplasmic antibodies in primary Sjögren's syndrome: prevalence and clinical significance. 抗中性粒细胞胞浆抗体在原发性Sjögren综合征中的患病率及临床意义。
Pub Date : 1998-12-01 DOI: 10.1093/rheumatology/37.12.1287
J Font, M Ramos-Casals, R Cervera, X Bosch, E Mirapeix, M García-Carrasco, R M Morlà, M Ingelmo

Objective: To evaluate the prevalence of cytoplasmic (c) and perinuclear (p) antineutrophil cytoplasmic antibodies (ANCA) in patients with primary Sjogren's syndrome (SS), and to correlate the presence of ANCA with extraglandular and immunological manifestations related to SS.

Methods: In a cross-sectional study, we included 82 consecutive patients (75 female and seven male; mean age 61 yr; range 33-87 yr) attending our unit. All patients fulfilled four or more of the diagnostic criteria for SS proposed by the European Community Study Group in 1993. Extraglandular manifestations such as arthralgia and/or arthritis, Raynaud's phenomenon, autoimmune thyroiditis, peripheral neuropathy, renal involvement and cutaneous vasculitis were also recorded. Serum samples were examined by indirect immunofluorescence (IIF) and by ELISA using as substrates myeloperoxidase (MPO) and proteinase 3 (PR3).

Results: ANCA were detected in nine (11%) patients: seven had pANCA and two an atypical pattern. These two atypical ANCA became cANCA when paraformaldehyde fixation was applied. ELISA findings showed that two patients had antibodies against MPO, and no patient had antibodies to PR3. The most common extraglandular manifestations in the ANCA-positive patients were articular involvement in six (66%) patients, peripheral neuropathy in five (55%), Raynaud's phenomenon in four (44%) and cutaneous vasculitis in four (44%). Of the four patients with cutaneous vasculitis and ANCA, two had a mononuclear inflammatory vascular disease (MIVD) in the biopsy specimen. When compared with patients without ANCA, those with these antibodies had a higher prevalence of cutaneous vasculitis (44% vs 8%, P = 0.01), Raynaud's phenomenon (44% vs 8%, P = 0.01) and peripheral neuropathy (55% vs 7%, P < 0.001).

Conclusion: ANCA positivity can be found in patients with primary SS and its detection is associated with the presence of clinical manifestations attributable to vascular involvement (cutaneous vasculitis, peripheral neuropathy and Raynaud's phenomenon).

目的:评估原发性干燥综合征(SS)患者胞浆(c)和核周(p)抗中性粒细胞胞浆抗体(ANCA)的患病率,并探讨ANCA的存在与SS相关的腺外和免疫表现之间的关系。方法:在一项横切面研究中,我们纳入了82例连续患者(75名女性和7名男性;平均年龄61岁;33-87岁,在我们部队服役。所有患者均符合1993年欧洲共同体研究小组提出的四项或以上的SS诊断标准。腺外表现如关节痛和/或关节炎、雷诺现象、自身免疫性甲状腺炎、周围神经病变、肾脏受累和皮肤血管炎也被记录。以骨髓过氧化物酶(MPO)和蛋白酶3 (PR3)为底物,采用间接免疫荧光(IIF)和酶联免疫吸附试验(ELISA)检测血清样品。结果:9例(11%)患者检测到ANCA,其中7例为pANCA, 2例为非典型。应用多聚甲醛固定后,这两种非典型ANCA变为cANCA。ELISA结果显示2例患者有MPO抗体,无PR3抗体。anca阳性患者最常见的腺外表现为6例(66%)的关节受累,5例(55%)的周围神经病变,4例(44%)的雷诺现象和4例(44%)的皮肤血管炎。在4例皮肤血管炎和ANCA患者中,2例活检标本显示单核炎症性血管疾病(MIVD)。与无ANCA的患者相比,有这些抗体的患者有更高的皮肤血管炎(44%比8%,P = 0.01)、雷诺现象(44%比8%,P = 0.01)和周围神经病变(55%比7%,P < 0.001)的患病率。结论:原发性SS患者可发现ANCA阳性,其检测与血管受累的临床表现(皮肤血管炎、周围神经病变、雷诺现象)有关。
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引用次数: 66
Digital gangrene and anticentromere antibodies without scleroderma. 无硬皮病的手指坏疽和抗着丝粒抗体。
Pub Date : 1998-12-01 DOI: 10.1093/rheumatology/37.12.1352
U Picillo, M R Marcialis, A Matarazzo, G Italiano, A Petti
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引用次数: 8
Unusual occurrence of acute low back pain in a patient with ruptured urachal cyst. 尿管囊肿破裂患者急性腰痛的罕见发生。
Pub Date : 1998-12-01 DOI: 10.1093/rheumatology/37.12.1354
A Ambrozic, S Praprotnik, B Rozman
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引用次数: 0
The relevance of large-vessel vascular disease and restricted ankle movement to the aetiology of leg ulceration in rheumatoid arthritis. 大血管疾病和踝关节受限与类风湿关节炎腿部溃疡病因的相关性
Pub Date : 1998-12-01 DOI: 10.1093/rheumatology/37.12.1295
E R McRorie, C V Ruckley, G Nuki

Leg ulceration in rheumatoid arthritis (RA) without systemic vasculitis is a difficult clinical problem and a common cause of morbidity. We have assessed venous function, arterial pressures and range of ankle movement in 23 RA patients with a leg ulcer and compared the results with those in the non-ulcerated contralateral limb and in 25 RA patients matched for age and duration of arthritis. We found evidence of venous insufficiency in RA ulcer patients compared to disease controls. Ankle movement was more restricted in the ulcerated limb compared to the non-ulcerated contralateral leg. There was no difference in large-vessel arterial function between groups. These findings have implications for therapy and rates of healing.

无系统性血管炎的类风湿性关节炎(RA)的腿部溃疡是一个困难的临床问题,也是发病率的常见原因。我们评估了23例腿部溃疡的RA患者的静脉功能、动脉压力和踝关节活动范围,并将结果与未溃疡的对侧肢体和25例年龄和关节炎持续时间相匹配的RA患者进行了比较。与疾病对照组相比,我们发现RA溃疡患者静脉功能不全的证据。与未溃烂的对侧腿相比,溃烂肢体的踝关节活动更受限制。各组大血管功能无明显差异。这些发现对治疗和治愈率具有启示意义。
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引用次数: 30
Successful treatment with antithymocyte globulin and cyclosporin A of a severe aplastic anaemia associated with an eosinophilic fasciitis. 抗胸腺细胞球蛋白和环孢素A成功治疗与嗜酸性筋膜炎相关的严重再生障碍性贫血。
Pub Date : 1998-12-01 DOI: 10.1093/rheumatology/37.12.1358
B Bonnotte, B Chauffert, D Caillot, F Martin, B Lorcerie
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引用次数: 30
Infection with an unenveloped DNA virus (TTV) associated with non-A to G hepatitis in patients with rheumatoid arthritis. 类风湿性关节炎患者感染无包膜DNA病毒(TTV)与非a型到G型肝炎相关。
Pub Date : 1998-12-01 DOI: 10.1093/rheumatology/37.12.1361
D Hirata, N Kaneko, M Iwamoto, T Yoshio, H Okazaki, A Mimori, J Masuyama, S Minota
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引用次数: 12
The Heberden Oration 1997. Treatment of rheumatoid arthritis: from symptomatic relief to potential cure. 希伯登演说,1997。类风湿关节炎的治疗:从症状缓解到潜在治愈。
Pub Date : 1998-12-01 DOI: 10.1093/rheumatology/37.12.1265
P M Brooks
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引用次数: 8
GB virus C in systemic medium- and small-vessel necrotizing vasculitides. GB病毒C在全身中小血管坏死性血管中的作用。
Pub Date : 1998-12-01 DOI: 10.1093/rheumatology/37.12.1292
A Servant, M Bogard, C Delaugerre, P Cohen, P Dény, L Guillevin

Background: Vasculitides are diseases of unknown origin in the majority of cases, but sometimes are the consequence of viral infections; for instance, hepatitis B virus (HBV)-related polyarteritis nodosa (PAN) or hepatitis C virus (HCV)-associated cryoglobulinaemia.

Objective: To investigate the role of hepatitis G or GB virus C (GBV-C) in various forms of medium- and small-vessel vasculitides.

Design: Retrospective analyses of sera.

Setting: Tertiary care hospital in Bobigny, France.

Patients: Fifty-six vasculitides: 19 HBV-PAN, 10 PAN without HBV infection, 11 microscopic polyangiitis (MPA), seven Churg-Strauss syndrome (CSS) and nine Wegener's granulomatosis (WG). Every sample was collected before treatment.

Measurements: GBV-C RNA was detected using a reverse transcription-polymerase chain reaction assay with primers derived from the conserved GBV-C helicase and NS5a regions.

Results: GBV-C was detected in five of the 56 samples (8.9%): four patients with HBV-related PAN and one with MPA; three of these patients (two with HBV-PAN, one with MPA) had been transfused and two HBV-PAN were i.v. drug addicts. GBV-C was not found in CSS or in WG.

Conclusion: GBV-C infection was observed only in patients who had been transfused or who were addicts. This virus is unlikely to have a primary role in vasculitides.

背景:血管增生在大多数病例中是病因不明的疾病,但有时是病毒感染的结果;例如,乙型肝炎病毒(HBV)相关结节性多动脉炎(PAN)或丙型肝炎病毒(HCV)相关冷球蛋白血症。目的:探讨丙型肝炎或GB病毒C (GBV-C)在各种形式的中小血管中的作用。设计:血清回顾性分析。地点:法国博比尼的三级保健医院。患者:56例血管病变:HBV-PAN 19例,无HBV感染的PAN 10例,镜下多血管炎(MPA) 11例,Churg-Strauss综合征(CSS) 7例,Wegener肉芽肿病(WG) 9例。每个样品都在处理前采集。测量方法:采用逆转录聚合酶链反应法检测GBV-C RNA,引物来自GBV-C保守解旋酶和NS5a区域。结果:56例样本中有5例(8.9%)检测到GBV-C: 4例hbv相关PAN患者和1例MPA患者;其中3例患者(2例HBV-PAN, 1例MPA)曾输血,2例HBV-PAN为静脉吸毒者。在CSS和WG中没有发现GBV-C。结论:GBV-C感染仅发生在输血患者或依赖者中。这种病毒不太可能在血管分裂中起主要作用。
{"title":"GB virus C in systemic medium- and small-vessel necrotizing vasculitides.","authors":"A Servant,&nbsp;M Bogard,&nbsp;C Delaugerre,&nbsp;P Cohen,&nbsp;P Dény,&nbsp;L Guillevin","doi":"10.1093/rheumatology/37.12.1292","DOIUrl":"https://doi.org/10.1093/rheumatology/37.12.1292","url":null,"abstract":"<p><strong>Background: </strong>Vasculitides are diseases of unknown origin in the majority of cases, but sometimes are the consequence of viral infections; for instance, hepatitis B virus (HBV)-related polyarteritis nodosa (PAN) or hepatitis C virus (HCV)-associated cryoglobulinaemia.</p><p><strong>Objective: </strong>To investigate the role of hepatitis G or GB virus C (GBV-C) in various forms of medium- and small-vessel vasculitides.</p><p><strong>Design: </strong>Retrospective analyses of sera.</p><p><strong>Setting: </strong>Tertiary care hospital in Bobigny, France.</p><p><strong>Patients: </strong>Fifty-six vasculitides: 19 HBV-PAN, 10 PAN without HBV infection, 11 microscopic polyangiitis (MPA), seven Churg-Strauss syndrome (CSS) and nine Wegener's granulomatosis (WG). Every sample was collected before treatment.</p><p><strong>Measurements: </strong>GBV-C RNA was detected using a reverse transcription-polymerase chain reaction assay with primers derived from the conserved GBV-C helicase and NS5a regions.</p><p><strong>Results: </strong>GBV-C was detected in five of the 56 samples (8.9%): four patients with HBV-related PAN and one with MPA; three of these patients (two with HBV-PAN, one with MPA) had been transfused and two HBV-PAN were i.v. drug addicts. GBV-C was not found in CSS or in WG.</p><p><strong>Conclusion: </strong>GBV-C infection was observed only in patients who had been transfused or who were addicts. This virus is unlikely to have a primary role in vasculitides.</p>","PeriodicalId":9307,"journal":{"name":"British journal of rheumatology","volume":"37 12","pages":"1292-4"},"PeriodicalIF":0.0,"publicationDate":"1998-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/rheumatology/37.12.1292","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40728797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 15
Lumping or splitting autoimmune rheumatic disorders? Lessons from Sjögren's syndrome. 自身免疫性风湿病的集中或分裂?Sjögren综合症的教训。
Pub Date : 1998-12-01 DOI: 10.1093/rheumatology/37.12.1263
H M Moutsopoulos, M N Manoussakis
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引用次数: 15
期刊
British journal of rheumatology
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