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ID PMID Title PublicationDate abstract
17534211 [Anaerobic sternocostoclavicular septic arthritis: a case report]. 2007 May Septic arthirtis of the sternocostoclavicular joint is exceptional and usually occurs in immunodeficient subjects. The clinical presentation may be misleading, a rheumatoid disease often being suggested. We report a case of secondary joint infection caused by anaerobic bacteria and discuss the diagnostic problems involved as well as the disease course and the therapeutic options proposed in the literature. The diagnosis calls upon computed tomography and magnetic resonance imaging, leading to joint needle aspiration. Appropriate imaging enables an assessment of the anatomic damage and is useful for guiding surgical treatment under adapted antibiotic coverage.
17243489 Drug evaluation: the C5a receptor antagonist PMX-53. 2006 Dec Peptech is developing PMX-53, a complement C5a inhibitor for the potential treatment of inflammatory disorders, including rheumatoid arthritis and psoriasis. Phase Ib/IIa clinical trials have been completed for both indications.
17921185 Efficacy and safety of the selective co-stimulation modulator abatacept following 2 years 2008 Apr OBJECTIVE: To evaluate the safety and efficacy of abatacept during 2 years of the ATTAIN (Abatacept Trial in Treatment of Anti-TNF INadequate responders) trial in patients with rheumatoid arthritis. METHODS: Patients completing the 6-month, double-blind period were eligible to enter the long-term extension; patients received abatacept approximately 10 mg/kg, plus disease-modifying antirheumatic drugs. Safety and efficacy (American College of Rheumatology (ACR) criteria responses, DAS28 (C-reactive protein), HAQ-DI, SF-36, Medical Outcomes Study Sleep Problems Index, fatigue VAS) were assessed through 2 years. RESULTS: 317 patients (218 from the abatacept and 99 from the placebo group) entered and 222 (70%) completed 18 months of long-term extension treatment. The incidence and type of adverse events were consistent between the double-blind and cumulative (double-blind plus long-term extension) periods. Rates of serious adverse events were 25.6 and 23.4 per 100 patient-years in the double-blind versus cumulative period. At 6 months and 2 years, using non-responder analyses, ACR responses in abatacept-treated patients were: ACR 20, 59.4% and 56.2%; ACR 50, 23.5% and 33.2%; ACR 70, 11.5% and 16.1%; HAQ-DI responses were 54.4% and 47.9%. At 6 months and 2 years, using post-hoc as-observed analyses, the percentage of patients (95% confidence interval) achieving DAS28 (C-reactive protein) low disease activity score (< or = 3.2) and DAS28 (C-reactive protein)-defined remission (< 2.6) increased from 18.3% (13.0, 23.5) to 32.0% (24.6, 39.4) and 11.1% (6.8, 15.3) to 20.3% (13.9, 26.6). Clinically meaningful improvements in SF-36, pain, fatigue and sleep problems were also maintained throughout the 2 years of abatacept treatment. CONCLUSION: No unique safety observations were reported during open-label exposure. Improvements in the signs and symptoms of rheumatoid arthritis, physical function and health-related quality of life observed after 6 months, were maintained throughout the 2 years in this population with difficult-to-treat disease. TRIAL REGISTRATION NUMBER: NCT00124982.
18383383 Differential expression of vasoactive intestinal peptide and its functional receptors in h 2008 Apr OBJECTIVE: Vasoactive intestinal peptide (VIP) has shown potent antiinflammatory effects in murine arthritis and ex vivo in human rheumatoid arthritis (RA) synovial cells. To investigate the potential endogenous participation of this system in the pathogenesis of RA, we analyzed the expression and regulation of VIP and its functional receptors in human fibroblast-like synoviocytes (FLS) from patients with osteoarthritis (OA) and patients with RA. METHODS: The expression of VIP was studied by reverse transcription-polymerase chain reaction (RT-PCR), enzyme immunoassay, and immunofluorescence in cultured FLS, and by immunohistochemical analysis in synovial tissue. The expression and function of the potential VIP receptors in FLS were studied by RT-PCR, determination of intracellular cAMP production, cell membrane adenylate cyclase (AC) activity, and interleukin-6, CCL2, and CXCL8 production in response to VIP or specific agonists and antagonists. RESULTS: VIP expression was detected in human FLS at the messenger RNA and protein levels, and it was significantly decreased in RA FLS compared with OA FLS. VIP receptor type 1 (VPAC1) was the dominant AC-coupled receptor in OA FLS, in contrast with RA FLS, in which VPAC2 was dominant. Tumor necrosis factor alpha-treated OA FLS reproduced the VIP and VPAC receptor expression pattern of RA FLS. The antagonistic effects of VIP on FLS proinflammatory factor production were reproduced by VPAC1- and VPAC2-specific agonists in OA FLS and RA FLS, respectively. CONCLUSION: VIP expression is down-regulated in RA and in tumor necrosis factor alpha-treated FLS, suggesting that down-regulation of this endogenous antiinflammatory factor may contribute to the pathogenesis of RA. In RA FLS, VPAC2 mediates the antiinflammatory effects of VIP, suggesting that VPAC2 agonists may be an alternative to VIP as antiinflammatory agents.
17696277 Effects of low-dose prednisolone on endothelial function, atherosclerosis, and traditional 2007 Sep OBJECTIVE: To determine the influence of low-dose prednisolone on atherosclerosis, endothelial function, and risk factors for atherosclerosis in patients with early rheumatoid arthritis (RA). METHODS: At start of the first disease modifying antirheumatic drug, 67 patients with early, active RA were randomized to either 7.5 mg prednisolone daily (n = 34) or no prednisolone (n = 33). In the prednisolone group, 21 were treated for 2 years and 13 continuously. After a mean of 5 years intima-media thickness (IMT) and calculated intima-media area (cIMa) of the carotid arteries were determined by B-mode ultrasound. Endothelial function was determined by flow-mediated dilatation (FMD) of the brachial artery. RESULTS: IMT [median (interquartile range) 0.675 mm (0.58-0.82) vs 0.673 mm (0.0.62-0.80)], cIMa [13.7 mm2 (11.45-20.37) vs 14.1 mm2 (12.34-17.38)], prevalence of atherosclerotic plaques (82.3% vs 81.9%), and endothelial function [FMD% (mean +/- SD) 3.88% +/- 2.8 vs 3.74% +/- 2.9] did not differ between patients treated with and those not treated with prednisolone. There were no differences in lumen diameter of carotid arteries, or levels of lipoproteins, glucose, and blood pressure. Patients treated for at least 4 years (and currently treated) with prednisolone had a trend to higher systolic blood pressure (157 +/- 29 mm Hg) compared with untreated patients (141 +/- 28 mm Hg; p = 0.06) and had higher cholesterol levels (5.6 mmol/L +/- 1.39 vs 4.9 +/- 28; p = 0.03). In the whole cohort, age and HDL were independently associated with IMT; age, HDL, and blood pressure with cIMa; and age and serum creatinine with presence of atherosclerotic plaques. CONCLUSION: Low-dose prednisolone did not influence endothelial function and atherosclerosis in patients with RA. However, total cholesterol was higher in patients treated with prednisolone.
16583484 Mycobacterium marinum arthritis mimicking rheumatoid arthritis. 2006 Apr Mycobacterium marinum is an atypical mycobacterium found in salt and fresh water. M. marinum infection occurs following skin trauma in fresh or salt water and usually presents as a localized granuloma or sporotrichotic lymphangitis. It rarely affects the musculoskeletal system. We describe a patient who presented with subcutaneous nodules and an inflammatory arthritis that was thought to be rheumatoid arthritis, and was treated as such with corticosteroids, methotrexate, and anti-tumor necrosis factor-alpha therapy, with worsening of his arthritis.
18812430 Variation of immunological response in methotrexate-induced pneumonitis. 2008 Nov OBJECTIVES: To assess the variation of peripheral blood and bronchoalveolar lavage (BAL) inflammatory cell counts and lung biopsy findings with the degree of exposure to MTX therapy. METHODS: Fifty-six (16 males; 40 females) reported cases of MTX-induced pneumonitis (MTX-P) on low-dose MTX (5-30 mg) were identified from a literature search and classified using Searles and McKendry's criteria. The median cumulative dose was 300 mg and this was used to categorize patients into low and high MTX-exposure groups and 6 months was used to divide patients into early- and late-onset MTX-P groups. RESULTS: Neutrophil counts in the peripheral blood and BAL were significantly raised in the low MTX-exposure group compared with the high MTX-exposure group (P = 0.018 and 0.038, respectively). There were similar findings when early-onset was compared with late-onset group. Lymphocytes in BAL were significantly higher in the high MTX-exposure group compared with low-dose cumulative group (P = 0.007). There were 6 (11%) recorded deaths and all were in the low MTX-exposure group. Early-onset/low MTX-exposure groups had a high prevalence of lung fibrosis. CONCLUSIONS: This is the first study to describe the variation of immunological responses in MTX-P with the degree of exposure to MTX. Our findings suggest that MTX-P can be divided into two groups: type 1 MTX-P that occurs early, predominated by neutrophils, lung fibrosis and has a high mortality; and type 2 MTX-P that occurs late, predominated by lymphocytes, has less lung fibrosis and low mortality.
17892041 [The gamma-linolenic acid (GLA)--the therapeutic value]. 2007 The essential fatty acid deficiency (EFA) gives rise to many pathologic states and may predispose for certain disease development. One of the most frequently deficient EFA is gamma-linolenic acid. The gamma-linolenic acid supplementation brings some hopeful effects in treatment of diabetic neuropathy, eczema, cyclic mastalgia, rheumatoid arthritis, osteoporosis and ADHD. Many double blind trials have been performed for defective assessment of GLA efficiency. Some of them have proved statistically significant efficacy, the others have led to some doubts. There is a necessity to perform more trials. The gamma-linolenic acid is completely safe, non-toxic, and non-cancerogenic substance. It can be an interesting alternative for supporting treatment.
17170052 Investigation of genetic variation across the protein tyrosine phosphatase gene in patient 2007 May OBJECTIVE: To investigate single-nucleotide polymorphisms (SNPs) across the PTPN22 gene region in a UK cohort of patients with rheumatoid arthritis (RA), to look for evidence of disease associations independent of the well-characterised R620W variant (rs2476601). METHODS: 951 RA cases in the UK satisfying American Rheumatism Association (ARA) criteria and 448 population controls were genotyped for 11 SNPs across the PTPN22 gene region using the Sequenom MassArray MassEXTEND technology. Allele, genotype and estimated haplotype frequencies of cases and controls were compared. RESULTS: In addition to the R620W (rs2476601) SNP, three SNPs were associated with RA in this study. The sole haplotype on which the associated T allele of R620W occurred was associated with RA; no other haplotypes showed a significant difference in frequencies between RA cases and controls. CONCLUSION: In contrast with a study of American patients with RA no evidence of association with PTPN22 independent of the well-characterised R620W variant was found, suggesting that in these patients this variant alone explains the association with the PTPN22 gene.
18356179 Cost-effectiveness of abatacept in patients with moderately to severely active rheumatoid 2008 Apr OBJECTIVE: To assess cost-effectiveness of abatacept in patients with moderately to severely active RA and inadequate response to MTX. METHODS: We developed a simulation model to depict progression of disability [in terms of the HAQ Disability Index (HAQ-DI)] in women aged 55-64 yrs with moderately to severely active RA and inadequate response to MTX. At model entry, patients were assumed to receive either only MTX or MTX plus abatacept. Patients were then tracked from model entry until death. Future health-state utilities and medical-care costs (except study therapy) were estimated based on predicted values of the HAQ-DI. The model was estimated using data from a Phase III clinical trial of abatacept plus various secondary sources. Cost-effectiveness was expressed in terms of incremental cost (2006 US$) per quality-adjusted life-year (QALY) gained over alternatively 10 yrs and a lifetime. Costs and health effects were both discounted at 3% annually. RESULTS: Over 10 yrs, abatacept would yield 1.2 additional QALYs (undiscounted) per patient (4.6 vs 3.4 for MTX) at an incremental (discounted) cost of $51,426 ($103,601 vs $52,175, respectively); over a lifetime, corresponding figures were 2.0 QALYS (6.8 vs 4.8) and $67,757 ($147,853 vs $80,096). Cost-effectiveness was [mean (95% CI)] $47,910 ($44,641, $52,136) per QALY gained over 10 yrs and $43,041 ($39,070, $46,725) per QALY gained over a lifetime. Findings were robust in sensitivity analyses. CONCLUSION: Abatacept is cost-effective by current standards of medical practice in patients with moderately to severely active RA and inadequate response to MTX.
17870032 Qualitative assessments. 2007 Oct Current NHS policies emphasise the involvement of patients and place them centre stage in the evaluation of health care. The unique experiences and views that patients can bring to health service research can be understood as complementary to staff skills. Qualitative research methods in particular provide a distinctive approach to recording and interpreting patients' perceptions and opinions; these insights can be used when developing and evaluating new treatments and services.
17938276 Extracellular survivin up-regulates adhesion molecules on the surface of leukocytes changi 2008 Jan Rheumatoid arthritis (RA) is an autoimmune disease with joints as a principal target of inflammation. We have shown recently that the extracellular expression of the antiapoptotic protein survivin is associated with a destructive course of RA. Here, we address the potential impact of extracellular survivin on peripheral blood leukocytes (PBL). The binding of survivin to the surface of human PBL as well as the expression of adhesion molecules were assessed by FACS. The expression of adhesion molecules on leukocytes as a function of circulating survivin was analyzed in blood of 24 patients with RA and compared with eight healthy individuals. We show that extracellular survivin expresses immunomodulatory properties. It binds to the surface of the majority of granulocytes and a significant part of lymphocytes and monocytes inducing the activation of alpha-chains of beta-integrins and their ligand ICAM-1. Survivin-induced expression of alpha-chains of beta 2-integrins is regulated by p38 MAPK and PI-3K but not by the NF-kappaB signaling pathway. Clinical relevance of our findings is supported by the in vivo association of high circulating survivin levels with an increased expression of CD11c on monocytes and granulocytes in RA patients. The results of our study demonstrate that extracellular survivin affects the phenotype of leukocytes having a possible impact on homing of inflammatory cells during arthritis.
18838387 Functional expression of the chemokine receptor CCR7 on fibroblast-like synoviocytes. 2008 Dec OBJECTIVES: We have characterized the expression and the function of the chemokine receptor CCR7 on fibroblast-like synoviocytes (FLS) of patients with RA and OA and on dermal fibroblasts. METHODS: FLS were obtained after enzymatic digestion of synovial tissue (ST) of patients with RA and OA undergoing knee replacement surgery and taken into culture for chemokine receptor analysis by RT-PCR, flow cytometry and functional tests. Immunofluorescence for CCR7, fibroblast and T-cell markers was performed on ST of RA and OA patients. To study the response of FLS to CCR7 ligands and other chemokines, migration assays were performed in modified Boyden chambers. After stimulation of FLS with CCR7 ligands, the secretion of VEGF was evaluated by ELISA and Luminex. RESULTS: CCR7 is expressed on FLS of patients with RA and OA, but not on dermal fibroblasts. FLS migrated in response to the CCR7 ligands, CCL19 and CCL21. Stimulation of FLS with CCL19 resulted in a significantly increased secretion of VEGF of RA- and OA-FLS. CONCLUSION: Apart from the migration of FLS in response to CCL19 and CCL21, it was shown that activation of the CCR7 receptor on FLS results in an enhanced VEGF secretion. A considerable expression of CCR7 ligands in proximity to perivascular infiltrates has previously been described in inflamed synovial tissue of RA patients. Stimulation of FLS via CCR7 could thereby contribute to angiogenesis in the synovial tissue.
17937475 Upregulation of kallistatin expression in rheumatoid joints. 2007 Nov OBJECTIVE: Previous studies demonstrated suppression of rat ankle arthritis by local injection of kallistatin gene, a negative regulator of angiogenesis. We analyzed circulating levels, synovial concentrations, and tissue localizations of kallistatin in patients with rheumatoid arthritis (RA). METHODS: Paired plasma and joint fluid samples were simultaneously obtained from 24 patients with RA and 14 with osteoarthritis (OA). Synovial tissues from 5 patients with RA and 5 with OA were obtained during surgery. Fibroblast-like synoviocytes (FLS) and mononuclear cells (MNC) were prepared. ELISA was used to measure kallistatin levels of plasma, joint fluid, cell lysate, and synovium homogenate extract. Synovial tissues were subjected to Western blot and immunohistochemical staining. In addition, the tissue kallikrein (TK) levels of plasma and joint fluid samples were also measured by the ELISA. RESULTS: Circulating and synovial levels of kallistatin and TK were elevated in patients with RA. The immunohistochemical assay exhibited stainings of kallistatin on both infiltrating MNC and FLS. Intracellular kallistatin levels were significantly elevated in MNC and FLS from patients with RA. CONCLUSION: Elevated kallistatin levels were demonstrated in patients with RA, particularly in synovial tissues, FLS, and MNC. This report is the first to demonstrate upregulation of kallistatin expression in rheumatoid joints.
18690048 Channel regulation by extracellular redox protein. 2007 Nov The most widely studied stimuli for ion channel activation are changes in membrane voltage and binding of a chemical ligand in a pocket of the channel protein. While modulation by redox potential has also been appreciated our study shows previously unrecognised channel activation via electron donation from the extracellular redox protein thioredoxin (TRX).(1) The ion channel type involved is a member of the Transient Receptor Potential (TRP) family. Activation by TRX led us to consider the relevance of TRP channels to the inflammatory condition of rheumatoid arthritis, where functions of ion channels are relatively unknown and TRX concentrations are high. TRP channel activation was found to be inhibitory for secretion of matrix metalloproteinases, suggesting activation by TRX may have a protective role against disease. Here we expand on our original article and discuss the potential wider implications of the findings in terms of concepts for channel activation and relevance to other ion channel types and systems.
17805984 Angiogenesis as a therapeutic target in arthritis: learning the lessons of the colorectal 2007 The idea of a therapeutic modality aimed at 'starving' a tissue of blood vessels, and consequentially of oxygen and nutrients, was born from the concept that blood vessel formation (angiogenesis) is central to the progression and maintenance of diseases which involve tissue expansion/invasion. In the first instance, solid malignancies were the target for anti-angiogenic treatments, with colorectal cancer being the first disease for which an angiogenesis inhibitor--anti-vascular endothelial growth factor antibody bevacizumab--was approved in 2004. Our understanding of the pathogenesis of rheumatoid arthritis (RA) has lead to many parallels being drawn between this chronic inflammatory disease and solid tumours, in that both involve tissue expansion, invasion, expression of cytokines and growth factors and areas of hypoxia/hypoperfusion. As a result, angiogenesis blockade has been touted as a possible treatment for RA. The lessons learnt during the progression of eventually successful therapies such as bevacizumab should undoubtedly guide us in the future development of comparable treatments for RA.
16404496 Tuberculous peritonitis in a patient with rheumatoid arthritis treated with adalimumab. 2007 Mar We present a case of tuberculous peritonitis in a 71-year-old woman with long-standing rheumatoid arthritis treated with adalimumab, and we review the association between antitumor necrosis factor therapy and tuberculosis. Our case illustrates that the index of suspicion of tuberculosis in these patients, even with atypical clinical features, must be very high, and underscores the need of tuberculosis screening before therapy is started.
18311044 A case report of rheumatoid arthritis complicated with rapidly progressive interstitial pn 2008 Feb A 64-year-old woman had been treated with prednisolone (PSL) for interstitial pneumonia (IP) of unknown origin since 1988. The IP progressed gradually, however, and home oxygen therapy was instituted in 1993. In 2002, persistent arthritis of the hands appeared and diagnosis of rheumatoid arthritis (RA) was finally established based on radiological and pathological findings. Salazosulfapyridine was given with only partial effect. On October 2002, she was hospitalized because of back pain followed by dyspnea. Chest X-ray revealed multiple giant bullae on bilateral upper lung fields, accompanied by deterioration of IP. Methyl-prednisolone pulse therapy followed by 30 mg/day of PSL was instituted and the bullae were diminished with gradual improvement of IP and synovitis. On the 55th hospital day, she complained of chest oppression, and chest X-ray revealed a complication of pneumomediastinum. Since IP was still active and serum KL-6 remained high, 3 mg/day of tacrolimus was added to control IP further and to reduce the dosage of PSL which was recognized as one of the aggravation factors of pneumomediastinum. As a result, pneumomediastinum disappeared gradually along with amelioration of IP. PSL was successfully tapered to 15 mg/day by the 87th hospital day and the patient was discharged. Although the efficacy of tacrolimus on IP complicated with polymyositis / dermatomyositis and other autoimmune diseases has been reported, this case first suggests its efficacy on IP associated with RA.
18502096 A tribute to an outstanding immunologist - Ian Reay Mackay. 2008 Nov The 11th Australasian Autoimmunity Workshop was held in Melbourne, Australia from July 6-8, 2007 organized by the Monash University Autoimmunity Network. The workshops, founded by the late Kevin Lafferty, are a chance for Australasians interested in research into autoimmune disease to present and discuss their work. This workshop also was a chance to acknowledge Ian Mackay, a pioneer clinician-scientist who has made major contributions to our understanding of autoimmune diseases. Friends, colleagues and former students attended the Workshop and acknowledged Ian's expertise and mentorship. This edition of the Journal of Autoimmunity pays tribute to Ian Mackay. It features articles from attendees at the workshop, and contributions from some of Ian's past students and past and current collaborators.
18825587 Predictors of fatigue over 1 year among people with rheumatoid arthritis. 2008 Aug Fatigue is a systemic feeling of exhaustion that is a common symptom of many chronic illnesses, including the autoimmune inflammatory disease rheumatoid arthritis (RA). We examined predictors of levels of fatigue among people with RA using Leventhal's Common-Sense Model (CSM), which states that cognitive representations of an illness spur (or halt) people's efforts to cope and thereby influence outcomes of the illness. Our use of the CSM was designed in the light of evidence in the literature specific to fatigue in RA. Current fatigue was reported on a 100 mm visual analogue scale (with anchors "No fatigue" and "Unbearable fatigue") by 114 people (73.7% women) with RA at baseline and 1 year later. Baseline employment status, pain, impact of disability, sleep disruption frequency, depressed mood, perceptions of consequences, arthritis self-efficacy and attempts to cope by praying/hoping were also self-reported. Duration of RA and a haematological measure of systemic inflammation (erythrocyte sedimentation rate; ESR) were obtained from hospital records. Unexpectedly, RA duration did not predict fatigue after 1 year, although lower baseline inflammation did (controlling for baseline fatigue and other disease impact variables). This may be due to sampling flares of RA at baseline. Baseline perceptions that RA has severe consequences and is uncontrollable also predicted greater fatigue after 1 year but this relationship was not mediated by praying/hoping. Targeted psychological care to modify perceptions of severe consequences may therefore improve later fatigue for people with RA even when the condition is longstanding, but the mechanisms of any benefit require further investigation.