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ID PMID Title PublicationDate abstract
11027115 Leflunomide for rheumatoid arthritis. 2000 Jul Disease-modifying antirheumatic drugs (DMARDs) are given to patients with rheumatoid arthritis (RA) to prevent synovitis, slow destruction of articular cartilage and bone, preserve function and control systemic manifestations of the disease. Recognition that irreversible joint damage often occurs early in RA has led to much prompter use of DMARDs, with sulfasalazine or methotrexate commonly considered the treatment of first choice. Leflunomide (Arava-Aventis) is a new DMARD, licensed for the treatment of adults with active RA. The manufacturer claims that leflunomide has "comparable efficacy to methotrexate and sulphasalazine", with a "faster onset of action", and an "acceptable tolerability profile". Here, we consider the place of leflunomide in the management of patients with RA.
11884115 Long-term results of digital arthrodesis with the Harrison-Nicolle peg. 2001 Dec This study determined the long-term success of digital arthrodesis with the Harrison-Nicolle peg. We reviewed 90 digital joints in 60 patients fused with the peg between 1986 and 1998 at a mean follow-up of 6 (range 2-11) years. The prime indication for surgery was rheumatoid arthritis. The early complication rate was 8%. At 1 month 89% of joints were pain-free and stable. In the long-term follow up, 96% of the joints were pain-free and stable, with the original angle of fusion. 85% achieved bony fusion, with no clinical difference between bony and fibrous fusion. Overall there was a significantly higher complication rate in the distal interphalangeal joint. We conclude that, with the exception of the distal interphalangeal joint, the Harrison-Nicolle peg is extremely effective for digital arthrodesis in the rheumatoid patient.
9090763 How useful are bone turnover markers in rheumatoid arthritis? Influence of disease activit 1997 Mar Rheumatoid arthritis is associated with osteopenia possibly related to increased bone resorption. Until recently, the markers used to evaluate bone turnover lacked specificity, and as a result studies were difficult to interpret. OBJECTIVES: To study bone remodeling in patients with rheumatoid arthritis, with special attention to the effects of corticosteroid therapy. PATIENTS AND METHODS: Forty-eight patients (36 women and 12 men) with a mean age of 54.6 +/- 11.6 years and a mean disease duration of 11 +/- 9 years were studied. Thirty-nine patients (81%) had positive tests for rheumatoid factors, and 21 (43.7%) were under corticosteroid therapy, with a mean treatment duration of 4.5 +/- 2.9 years and a mean daily dosage of 9.4 +/- 2.5 mg prednisone. A group of age- and sex-matched controls was also studied. Serum levels of procollagen Type I C-terminal propeptide (PINP), procollagen Type I N-terminal propeptide (PINP), and procollagen type I C-terminal telopeptide (ICTP) were determined in all patients and controls. The first two markers reflect bone formation and the last bone resorption. Other tests performed in each patient were the erythrocyte sedimentation rate, serum C-reactive protein, serum total alkaline phosphatase, serum osteocalcin, 24-hour urinary hydroxyproline excretion, and calcium/creatinine ratio in a morning urine sample. Several clinical parameters were used to evaluate disease activity and severity in the rheumatoid arthritis patients. RESULTS: ICTP levels were significantly elevated in the patients as compared with the controls (6.6 +/- 3.9 ng/ml versus 3.1 +/- 1.2 ng/ml, P = 0.0001), whereas no significant differences were found for PICP or PINP. Similar results were found when the analysis was confined to nonsteroid-medicated patients. Conversely, PICP levels were higher in steroid-medicated patients than in controls (P = 0.0132) and were correlated with steroid therapy duration (r = 0.436). ICTP levels were correlated with age (r = 0.3), Lee's index (r = 0.585), the Health Assessment Questionnaire score (r = 0.391), and the erythrocyte sedimentation rate (r = 0.442). Urinary hydroxyproline excretion was elevated in 41.6% of the patients. CONCLUSION: Our data suggest that rheumatoid arthritis is associated with increased bone resorption, and that steroid therapy further accelerates bone remodeling in this disease.
11048947 Cartilage degradation by stimulated human neutrophils: reactive oxygen species decrease ma 2000 Aug BACKGROUND: Although neutrophilic granulocytes clearly contribute to cartilage degradation in rheumatic diseases, it is unclear if reactive oxygen species (ROS) or proteolytic enzymes are the most important components in cartilage degradation and how they interact. RESULTS: Neutrophils were stimulated by chemicals conferring a different degree of ROS formation and enzyme release. Supernatants of neutrophils were incubated with thin slices of pig articular cartilage. Supernatants of cartilage were assayed by NMR spectroscopy, MALDI-TOF mass spectrometry and relevant biochemical methods. Stimulation conditions of neutrophils correlated well with the extent of cartilage degradation. Due to the release of different enzymes, cartilage degradation could be best monitored by NMR since mainly low-mass degradation products were formed. Astonishingly, the suppression of the formation of ROS resulted in decreased cartilage degradation. CONCLUSION: ROS formed by neutrophils are not directly involved in cartilage degradation but influence the activity of proteolytic enzymes, which are the main effectors of cartilage degradation.
9195503 Back to the future: the pyramids of rheumatoid arthritis. 1997 Jun The management treatment pyramid, treatment target and treatment pyramids provide a framework for RA management and treatment. This model brings back the traditional pyramid, which was widely accepted, and adapts it to our newer understanding of RA treatment. It provides a focus for care, as well as the flexibility to apply selective treatments to different temperaments of disease. We hope that these models will fill the void left by the abandonment of the traditional pyramid. We certainly need a model to refocus the patient and physician to the importance of RA and bring "order out of chaos". With our current knowledge, resources, and drugs, we could be making a far greater impact on this serious, expensive, and crippling disease. We must re-excite and re-educate the public, the patient, and the profession to the remarkable progress we have made with incurable but very treatable arthritis.
11355216 What's new in rheumatoid arthritis? An evidenced based review. 2001 Apr BACKGROUND: Rheumatoid arthritis (RA) is the most common inflammatory arthritis and has been associated with significant functional impairment and a shortened life expectancy. Fortunately, over the past 10 years, there has been a significant change in its management, which has resulted in improved outcomes for RA patients. OBJECTIVE: To critically appraise the recent evidence which affects the contemporary management of RA. DISCUSSION: The bulk of recent evidence suggests that disease modifying anti-rheumatic drugs (DMARDs) should be commenced early and continued indefinitely in RA patients. Single DMARD therapy may be sufficient in some patients but combinations, particularly those which include methotrexate, improve symptomatic and radiological outcomes. The use of newer therapies, including leflunomide and tumour necrosis factor-alpha blocking drugs, promise to further improve these outcomes.
10403278 Synovial Epstein-Barr virus infection increases the risk of rheumatoid arthritis in indivi 1999 Jul OBJECTIVE: To investigate the presence of the Epstein-Barr virus (EBV) in rheumatoid arthritis (RA) synovium and its correlation with the HLA genotype in an attempt to elucidate the role of EBV in the pathogenesis of RA. METHODS: EBV DNA/RNA was investigated by polymerase chain reaction (PCR) analysis of synovial tissue from 84 patients with RA and from 81 patients with non-RA arthritis (controls) and was correlated with the patients' HLA genotype. RESULTS: EBV DNA and EBV-encoded RNA 1 transcripts were significantly more frequently present in synovial tissue from the RA patients (29 of 84) than in that from the non-RA patient controls (8 of 81). EBV DNA-positive individuals had a 5.47 times higher risk of presenting with RA than did EBV DNA-negative individuals. In HLA-DRB1*0401,0404,0405,0408-positive or shared epitope-positive patients, the risk was further increased (odds ratio for EBV and HLA-DR4 approximately 41, for EBV and the shared epitope approximately 15) compared with those who lacked both EBV DNA and RA-linked HLA genotypes. CONCLUSION: EBV seems to function as an environmental risk factor for RA, particularly in patients with the RA-linked HLA-DRB1 alleles.
9108401 Oligoclonal CD4+ CD57+ T-cell expansions contribute to the imbalanced T-cell receptor repe 1997 Apr 15 A peculiar feature of rheumatoid arthritis patients is that they carry clonally expanded CD4+ and CD8+ cells in the peripheral blood. While the distortion of the repertoire of CD8+ cells has been ascribed to the increase of CD8+ CD57+ large granular lymphocytes, often detected in these patients, the mechanism responsible for the clonal expansion of CD4+ cells remains unexplained. Here, we report that CD4+ CD57+ cells, that in healthy individuals represent a small subset of peripheral CD4+ lymphocytes, are significantly expanded in the peripheral blood of a considerable percentage of rheumatoid arthritis patients. Furthermore, the expansion of these lymphocytes appears to correlate with the presence of rheumatoid factor. The molecular analysis of the T-cell receptor variable beta segments expressed by the CD4+ CD57+ cells enriched in rheumatoid arthritis patients showed that they use restricted repertoires, that partially overlap with those of their CD4- CD57+ counterpart. The structural feature of the receptor ligand expressed by these cells revealed that their expansion is most likely mediated by strong antigenic pressures. However, since we also found that CD4+ CD57+ and CD4- CD57+ cells can share the same clonal specificity, it is likely that their selection is not mediated by conventional major histocompatibility complex restricted mechanisms. Thus, while our data demonstrate that CD4+ CD57+ cells play an important role in establishing the imbalance of the CD4+ cell repertoire observed in rheumatoid arthritis patients, they also suggest that these cells have common features with mouse CD4+ CD8- NK1.1+/T cells.
11404723 [Observations on the increased serum levels of YKL-40 in patients with rheumatoid arthriti 2001 Jun BACKGROUND: This study aimed to evaluate the function of glycoprotein YKL-40 in patients with rheumatoid arthritis, erosive osteoarthrosis or coxitis. METHODS: Serum levels of glycoprotein YKL-40 were assayed using an ELISA method in 40 patients with active-phase rheumatoid arthritis and 20 patients suffering from erosive osteoarthrosis or coxitis. RESULTS: The mean values of YKL-40 were enhanced in all patients with rheumatoid arthritis and arthrosis with higher mean values in erosive osteoarthritis and coxitis (440 ng/ml) compared to rheumatoid arthritis (190 ng/ml). CONCLUSIONS: YKL 40 is a local prognostic marker of joint destruction.
11034691 Antimalarials for treating rheumatoid arthritis. 2000 OBJECTIVES: To assess the short-term efficacy and toxicity of antimalarials for the treatment of rheumatoid arthritis (RA). SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Group's trials register, the Cochrane Controlled Trials Register, Medline and Embase up to and including August 2000. We also carried out a handsearch of the reference lists of the trials retrieved from the electronic search. SELECTION CRITERIA: All randomized controlled trials (RCTs) and controlled clinical trials (CCTs) comparing antimalarials against placebo in patients with RA DATA COLLECTION AND ANALYSIS: Data abstraction was carried out independently by two reviewers. The same two reviewers using a validated checklist (Jadad 1996) assessed the methodological quality of the RCTs and CCTs. Rheumatoid arthritis outcome measures were extracted from the publications for the 6-month endpoint. The pooled analysis was performed using standardized mean differences for joint counts, pain and global assessments. Weighted mean differences were used for erythrocyte sedimentation rate (ESR). Toxicity was evaluated with pooled odds ratios for withdrawals. A chi-square test was used to assess heterogeneity among trials. Fixed effects models were used throughout. MAIN RESULTS: We found four trials, with 300 patients randomized to hydrochloroquine and 292 to placebo. Only trials evaluating hydroxychloroquine could be pooled in the analysis. A statistically significant benefit was observed when hydroxychloroquine was compared to placebo. The standardized mean differences for the various outcome measures ranged from -0.33 to -0.52, and were statistically significant. Statistically significant differences were also observed for ESR. Overall withdrawals and withdrawals due to lack of efficacy were significantly more frequent in the placebo group. No differences were observed in withdrawals due to toxicity. REVIEWER'S CONCLUSIONS: Hydroxychloroquine appears to be efficacious for the treatment of RA. Its overall effect appears to be moderate, but its low toxicity profile should be considered when treating patients with RA.
10700424 Immunogenetic differences between patients with familial and non-familial rheumatoid arthr 2000 Mar OBJECTIVE: To search for possible immunogenetic differencies between the patients with familial and non-familial rheumatoid arthritis (RA). METHODS: The study compared 129 familial RA patients with 217 non-familial patients for the frequencies of HLA-DR antigens including DR4 subtypes, DR4-DQB1*0301 and DR4-DQB1*0302 haplotypes and HLA-B27 antigen as well as the age of disease onset and existence of rheumatoid factor or joint erosions. RESULTS: Two major differences between familial and non-familial groups were found: firstly, familial RA patients had increased frequency of HLA-DR4 as compared with the non-familial RA group (68.2 v. 54.8%; p = 0.019). Secondly, the mean age at onset of RA was significantly lower in the familial than in the sporadic RA patients (42.0 v. 46.5 years; p = 0.0020) and the difference still remained when the DR4 positive and negative subgroups were compared separately. CONCLUSION: These results confirm the more prominent association with HLA-DR4 in familial than in the non-familial cases and suggest that accumulation of HLA risk genes may, at least partly, explain the familial occurrence of the disease. Other susceptibility genes may also be concentrated in multiplex case families as suggested by an earlier age at the onset of RA in both HLA-DR4 positive and negative familial patients.
10689120 The association of HLA-DM genes with rheumatoid arthritis in Eastern France. 2000 Mar In this study, the polymorphisms of the HLA DMA and DMB genes in patients with rheumatoid arthritis (RA) were examined.DMA and DMB typing was performed in 120 white RA patients from eastern France and 100 healthy controls, using PCR-SSO (sequence specific oligonucleotide probes) method for DMA determination and PCR-RFLP (restriction fragment length polymorphism) method for DMB typing. All patients and controls had been HLA DRB1* genotyped.DMA*0103 was found significantly increased in RA patients (RA vs. controls: 18.3% vs. 4%) (p(corr) = 0.004; OR: 5.39; CI: 1.67-19.23). A decreased frequency of DMA*0102 was also observed in the RA group (RA vs. controls: 18.3% vs. 31%), but not significantly. There were no differences in the prevalence of DMB alleles between RA and controls. The patients and the controls were then stratified according to the expression of the HLA DRB1* RA-linked alleles (DRB1*01 and *04) and this allowed us to find no linkage disequilibrium between DMA*0103 and DRB1*01 or *04 alleles. Finally, most DMA*0103 patients were positive for rheumatoid factors and had extraarticular involvement such as subcutaneous nodules. Thus, our results suggest that DMA*0103 could be an additional genetic factor for RA susceptibility in French whites.
11676333 Non-cirrhotic portal fibrosis in a patient with rheumatoid arthritis. 2001 Sep A 53-year-old man suffering from rheumatoid arthritis for 15 years presented with bleeding esophageal varices, hepatosplenomegaly and normal splenoportal venous axis. Liver biopsy revealed mild fibrosis, suggestive of non-cirrhotic portal fibrosis (NCPF). There are reports of the association of idiopathic portal hypertension, a condition similar to NCPF, with progressive systemic sclerosis, Hashimoto's thyroiditis and systemic lupus erythematosus.
10364915 Serum samples of patients with rheumatoid arthritis contain a specific autoantibody to "de 1999 Mar OBJECTIVE: To identify rheumatoid arthritis (RA) specific autoantibody and its antigen in the human osteoblast-like cell line, MG-63. METHODS: MG-63 cell extract was subjected to western blotting by using RA and normal serum samples as probes. The autoantigen was purified and its N-terminal sequence was determined by automated Edman degradation. The reactivity of denatured aldolase A was evaluated by immunoblotting. Screening by enzyme linked immunosorbent assay (ELISA) using the autoantibody was performed. RESULTS: 40 kDa protein was found only in the RA serum samples and it was identified as aldolase A. A polyclonal antibody for rabbit muscle aldolase A bound to the 40 kDa protein and reacted in preference with the denatured enzyme. Using ELISA for denatured rabbit aldolase A, the autoantibody was found in approximately 10% of RA patients, whereas it was not found in the other arthropathy and healthy adults. CONCLUSION: This 40 kDa anti-aldolase A autoantibody, which was identified only in serum samples of RA patients with severe bone erosion, could be related to a certain event that induces RA specific joint destructions.
9227167 Effect of disease modifying agents on the lipid profiles of patients with rheumatoid arthr 1997 Jun OBJECTIVE: To determine the effect of intramuscular gold and oral hydroxychloroquine (HCQ) on the lipid profile of patients with rheumatoid arthritis (RA). METHOD: A prospective randomised clinical trial of 12 months' duration was performed in 100 RA patients. Data on clinical and laboratory parameters of disease activity, and fasting serum lipid samples was collected at baseline and at three monthly intervals over one year. RESULTS: The expected second line response was seen with no significant difference in efficacy between the groups at 12 months. The HCQ group had a significant overall improvement in their lipid profile while there was a trend for lipid profiles in the gold group to worsen. CONCLUSIONS: HCQ is an effective second line agent that has beneficial effects on serum lipids. This should be taken into account when choosing a disease modifying anti-rheumatic drug in patients who suffer from RA and who have significant cardiovascular risk factors.
9572643 A 15-year exercise program for rheumatoid vasculitis. 1998 A rare case of rheumatoid vasculitis and responses to a 15-year supervised exercise program. This patient presented with significant impairment in mobility and physical work capacity. His exercise tolerance improved considerably and he benefited emotionally.
11163096 Autoimmunity versus tolerance: analysis using transgenic mice. 2000 Dec On the basis of our extensive studies on collagen induced arthritis in HLA class II transgenic mice, we proposed a hypothesis to explain role of shared epitope in rheumatoid arthritis (RA) association. According to our hypothesis, complementation between both DQ and DR molecules is required for susceptibility or protection from disease. While certain DQ alleles predispose individuals to RA, DRB1 molecule can modulate disease by shaping T-cell repertoire in the thymus by providing self-peptides and presented by DQ molecules. Using A beta o.DQ8 transgenic mice, we tested ability of peptides derived from HV3 of DR molecules, implicated in RA positively or negatively, to activate T cells. While the peptides derived from RA susceptible DR molecule were poor binders and poor in activating T cells, the peptides derived from RA resistant DR molecules were high affinity binders and efficient T-cell activators. Our experiments suggest that high affinity DR peptides could induce tolerance to autoimmunity while the low affinity peptides could be permissive to autoimmunity. Using peptide from DRB1*0402 molecule, known to be associated with resistance to RA, prior to induction of collagen induced arthritis prevents the onset of disease. Thus, self-peptides derived from HLA molecules could potentially generate tolerance or autoimmunity depending on their binding affinity with HLA molecules.
10680086 Role of human parvovirus B19 in the pathogenesis of rheumatoid arthritis. 1999 Oct Rheumatoid arthritis (RA) is a chronic inflammatory disease of unknown origin. It has been speculated that infectious agents are responsible for triggering RA. Persistent infection with human parvovirus B19 and its induction of immunopathology are hypothesized to explain the initiation and perpetuation of the disease process.
9647250 Enhancing effect of IL-17 on IL-1-induced IL-6 and leukemia inhibitory factor production b 1998 Jul 1 IL-17 is a cytokine produced by CD4 T cells that activates the production of inflammatory mediators by synoviocytes. To study the contribution of soluble factors in the interaction between T cells and synoviocytes in rheumatoid arthritis (RA), we looked at the effect of IL-17 on these cells in the presence of cytokines classified as pro (IL-1)- and anti-inflammatory (IL-4, IL-13, IL-10). Both human rIL-1beta and rIL-17 induced IL-6 and leukemia inhibitory factor (LIF) production by synovial fibroblasts in a dose-dependent manner. After 7 days of culture, optimal concentrations of IL-1beta increased IL-6 (33-fold) and LIF (10-fold) production by synoviocytes, while IL-17 showed a lesser effect on IL-6 (17-fold) and LIF (4-fold) production. Using low concentrations of IL-17 and IL-1beta in combination, a synergistic effect was observed on the production of IL-6, whereas an additive effect was observed for LIF production. Production of biologically active IL-17 was demonstrated in RA synovium supernatants with the use of a blocking anti-IL-17 Ab. Both IL-4 and IL-13 had a modest stimulatory effect on IL-1- and IL-17-induced production of IL-6, but inhibited that of LIF. In contrast, IL-10 had a limited inhibitory effect on IL-6 production and no effect on that of LIF. These findings indicate that low levels of cytokines produced by monocytes (IL-1) and T cells (IL-17) can act together on synoviocytes. Thus, some RA synovium T cells producing IL-17 can activate mesenchymal cells leading to an increased proinflammatory pattern sensitive to Th2 cytokine regulation.
10606371 Role of opticare eye drop delivery system in patients with rheumatoid arthritis. 1999 Dec OBJECTIVE: To investigate the prevalence of keratoconjunctivitis sicca in 340 patients with rheumatoid arthritis undergoing outpatient followup, and to assess their ability to use artificial tears, and the role of an aid to dispensing drops, the Opticare. METHODS: Initial questionnaire given to 340 patients based on preliminary criteria for classification of Sjögren's syndrome. Thirty symptomatic patients were invited to undergo objective and subjective assessment of the ability to instill artificial tears with and without the Opticare. RESULTS: One hundred twenty-seven (37%) patients had had symptoms lasting at least 3 months at some time, and 85 (25%) were currently symptomatic. Many patients found difficulty using artificial tears due to problems aiming and squeezing the bottles as a result of impaired upper limb function. The Opticare statistically significantly improved the ability to squeeze out drops and get them in the eye. CONCLUSION: The Opticare device allows patients with functional impairment of the upper limb to instill artificial tears, resulting in less wastage of tears and increased independence and compliance.