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ID PMID Title PublicationDate abstract
12730513 Glucose-6-phosphate isomerase is not a specific autoantigen in rheumatoid arthritis. 2003 Aug OBJECTIVE: To test the hypothesis that glucose-6-phosphate isomerase (GPI) is a novel autoantigen in RA. METHODS: Eighty-eight serum samples from 23 patients with rheumatoid arthritis (RA), 25 with Sjögren's syndrome, 20 with systemic lupus erythematosus and 20 healthy controls were tested by enzyme-linked immunosorbent assay (ELISA) using a commercially available, partially purified rabbit GPI as antigen. Beside each duplicate well containing antigen (10 micro g/ml), uncoated blocked duplicate wells (phosphate-buffered saline only) were included as controls for non-specific binding for every serum tested. We also examined antibodies binding to various polypeptides in the GPI preparation by immunoblotting in 73 of the sera. RESULTS: By ELISA, binding levels were low and there was no difference between serum from patients with RA, other rheumatic diseases and normal controls. By immunoblotting, antibodies binding to the GPI polypeptide were present in 70-80% of all groups tested. In addition, we showed that another polypeptide identified as phosphoglucomutase was also present in the preparation and reacted with human immunoglobulins. CONCLUSION: Our findings suggest that GPI is not a specific autoantigen in RA.
12900849 ANCA-positive crescentic glomerulonephritis associated with minocycline therapy. 2003 Aug Minocycline is an oral antibiotic widely used for the long-term treatment of acne and rheumatoid arthritis. A few patients develop antineutrophil cytoplasmic antibodies (ANCAs) during minocycline therapy. In this report, the authors describe a case of severe pauci-immune crescentic and necrotizing glomerulonephritis associated with positive cytoplasmic ANCA (C-ANCA) titers and proteinase 3 (PR3) levels after minocycline therapy. Discontinuation of minocycline and initiation of immunosuppressive treatment resulted in improvement of renal function and decline in C-ANCA titers and PR3 levels. A high degree of suspicion, testing for ANCA titers, prompt discontinuation of the drug, and initiation of immunosuppressive treatment are crucial to the diagnosis and treatment of drug-induced ANCA-associated glomerulonephritis.
12003375 Biological modifier therapy for the treatment of rheumatoid arthritis. 2002 Apr The recent elucidation of pathogenic processes involving tumor necrosis factor alpha and interleukin-1beta in the pathogenesis and persistence of rheumatoid arthritis led to the development of biological modifier agents that have had significant impact on disease severity and progression. These agents--etanercept, infliximab, and anakinra--produce a dramatic reduction in RA disease activity with relatively low toxicity compared with currently available disease-modifying antirheumatic drugs. The main prohibition to their broader utilization is cost. The success of these agents underscores the investigative approaches to the pathogenesis of RA and the appropriate design of pharmaceutical agents to target specific proinflammatory molecules.
15473120 What really matters: an inquiry into the relative importance of dimensions of informal car 2004 Sep OBJECTIVE: Prevailing measures of subjective caregiver burden either have no overall summary score or do not consider the relative importance caregivers attach to different dimensions of burden. Our aim was to assess which dimensions informal caregivers perceive as being important to their overall burden from care giving. DESIGN: Cross-sectional. SUBJECTS: Data were pooled from two Dutch samples of primary informal caregivers covering a wide range of chronic care-giving situations: caregivers for stroke survivors (n = 196) and caregivers for individuals with rheumatoid arthritis (RA) (n = 131). MAIN MEASURES: Subjective burden of care giving was assessed using the Caregiver Reaction Assessment (CRA) and the Self-Rated Burden scale (SRB). RESULTS: In the total sample four of the five dimensions of the CRA were found to contribute to the overall subjective burden experienced by informal caregivers. In the individual stroke and RA samples only two of the five dimensions emerged as relevant. SRB scores were significantly higher for caregivers of stroke patients, but no differences were found for the five dimensions of the CRA between the two samples. CONCLUSIONS: The dimensions of CRA are not equally important to the overall subjective burden of informal caregivers. To assess overall subjective burden, a measure based on a caregiver's own assessment of burden such as SRB needs to be used in addition to prevailing measures.
14639556 Effects of arthritis exercise programs on functional fitness and perceived activities of d 2003 Nov OBJECTIVE: To ascertain the effectiveness of the National Arthritis Foundation (NAF) aquatic and on-land exercise programs on functional fitness and perceived ability to perform activities of daily living (ADL) measures in older adults with arthritis. DESIGN: The effects of aquatic and on-land exercise intervention programs were analyzed by repeated-measures analysis of variance by using a planned comparison approach with an independent 3 x 2 (group by test) design. omega(2) analyses were used to ascertain the relative treatment magnitude of each dependent variable. SETTING: Testing in an indoor track facility; exercise programs conducted in community settings. PARTICIPANTS: A volunteer sample of 30 men and women with arthritis (osteoarthritis, n=22; rheumatoid arthritis, n=8), randomly assigned into either an aquatic exercise (n=10), on-land exercise (n=10), or control group (n=10). INTERVENTION: Eight-week on-land and aquatic exercise program. MAIN OUTCOME MEASURES: Functional fitness, ADLs, and hand-held dynamometry measures assessed on a 1-day pretest and posttest session, before and after an 8-week exercise program. RESULTS: Aquatic and on-land exercise subjects showed significant improvements on 9 of 12 functional fitness, 3 of 4 ADLs, and 7 of 8 hand-held isometric strength tests after their respective exercise programs. No significant changes were found in any of these measures for the control group. CONCLUSION: Both NAF exercise programs appear to be effective in improving functional physical fitness and perceived ability to perform ADL measures in older adults with arthritis.
12203149 [Results of arthroscopic synovialectomy of the wrist]. 2002 May In the course of inflammatory rheumatic diseases, isolated synovialitis of the wrist and distal radioulnar joint can be found without simultaneous affection of the extensor tendons. It may be the only manifestation of the disease in the sense of monarthritis or one of few affected sites as in oligoarthritis. With modern medical treatment of disease-modifying drugs, this constellation seems to be more frequent. In this situation, we rather perform arthroscopic synovialectomy than open synovialectomy as long as form and function of the joint are maintained. The distal radioulnar joint may also be approached arthroscopically through the perforation of the TFCC, which is usually encountered. A clinical study was performed to evaluate the results of this procedure concerning function, relief of pain, progression of the disease, and risk of recurrence. Between 1995 and 2000, 22 patients (15 female, 7 male) with an average age of 50 years (range 16 to 74) were operated, in one case both wrists. 19 patients have been reexamined clinically and by X-ray after an average follow-up of 21 months (range 6 to 57 months), three by telephone interview. The results were evaluated according to the Mayo modified wrist score (pain, function, motion, and grip-strength related to the contralateral side) and compared to the preoperative values. In the case of bilateral affection, the score was not applied. Also, the patients' subjective evaluation of the results have been taken into account. Progression of the disease has been checked in the standard preoperative and postoperative X-rays of the wrist graded according to the Larsen scale. Special attention was paid to signs of recurrence. The wrist-score improved significantly from an average of 40 points preoperatively to 69 points postoperatively. Eleven patients estimated their wrists as absolutely good, nine as improved, two as unchanged compared to the preoperative situation. Nine patients reported no pain at all, eleven less pain than before and two no change. 17 patients have been satisfied with the procedure, five not. Radiographic progression of the disease from the preoperative status (Larsen stage 0 to III, exceptionally IV) to postoperative was found in three cases. In 19 cases there was no progression. Recurrence was noted in six cases after an average time of six months; a secondary procedure was necessary in two cases. Wrist motion improved in almost all patients from an average value of extension plus flexion of 83 degrees preoperatively to 99 degrees postoperatively. Conclusion. Arthroscopic synovialectomy of the wrist reduces pain and improves function in most cases. It also improves motion, which is an advantage to the open procedure. Patient acceptance of the procedure is high.
15158970 Cathepsin K inhibitor-polymer conjugates: potential drugs for the treatment of osteoporosi 2004 Jun 11 The role of the newly discovered cysteine protease, cathepsin K, in osteoporosis and rheumatoid arthritis is reviewed. The current development of cathepsin K inhibitors and their targeted delivery using synthetic polymer carriers are discussed. Future challenges and possible strategies to improve these delivery systems are addressed.
12610796 Lack of association between -384 and 114 IL-2 gene polymorphisms and rheumatoid arthritis. 2003 Mar OBJECTIVE: To investigate the association of 2 single nucleotide polymorphisms (SNP) at positions -384 and 114 in the human interleukin 2 (IL-2) gene with susceptibility to and severity of rheumatoid arthritis (RA). METHODS: Genotyping for these IL-2 variants was performed by a polymerase chain reaction restriction fragment length polymorphism method in 174 RA patients and 153 control individuals. RESULTS: No statistically significant differences were observed when the -384 and 114 IL-2 genotype distributions between RA patients and healthy controls were compared. In addition, no association was found between the IL-2 genotypes with any demographic and clinical variables tested. CONCLUSION: Our results provide no evidence for genetic association conferred by the -384 and 114 IL-2 SNP with respect to susceptibility and severity of RA.
15064442 Collagen-induced arthritis as a model for rheumatoid arthritis. 2004 Collagen-induced arthritis (CIA) is an animal model of rheumatoid arthritis (RA) that is widely used to address questions of disease pathogenesis and to validate therapeutic targets. Arthritis is normally induced in mice or rats by immunization with autologous or heterologous type II collagen in adjuvant. Susceptibility to collagen-induced arthritis is strongly associated with major histocompatibility complex class II genes, and the development of arthritis is accompanied by a robust T- and B-cell response to type II collagen. The chief pathological features of CIA include a proliferative synovitis with infiltration of polymorphonuclear and mononuclear cells, pannus formation, cartilage degradation, erosion of bone, and fibrosis. As in RA, pro-inflammatory cytokines, such as tumor necrosis factor alpha(TNFalpha) and interleukin (IL)-1beta, are abundantly expressed in the arthritic joints of mice with CIA, and blockade of these molecules results in a reduction of disease severity.
11952510 Effect of filtration leukocytapheresis therapy: modulation of white blood cell enzyme acti 2002 Apr We treated 12 patients with rheumatoid arthritis by filtration leukocytapheresis (FLCP) and evaluated its effect on leukocyte enzyme activities. We calculated the number of leukocytes removed and assessed the clinical response. We also evaluated the cellular enzyme activities of elastase and dipeptidylpeptidase IV (DPP IV). Out of 12 patients, 7 patients achieved 20% improvement for 4 weeks following FLCP. The FLCP treatment resulted in removal of 96% of granulocytes, 98% of monocytes, and 61% of lymphocytes. Granulocytes and monocytes with high elastase activity were effectively removed by FLCP. The elastase activity of granulocytes was increased 4 weeks after the last FLCP only in responders. On the other hand, the DPP IV activity of lymphocytes was low at 4 weeks after the last FLCP in responders. Modulation of leukocyte enzyme activities is one of the main effects of FLCP therapy and alteration of granulocytes, monocytes, and lymphocytes.
15557189 A novel mechanism for TNF-alpha regulation by p38 MAPK: involvement of NF-kappa B with imp 2004 Dec 1 TNF-alpha is a key factor in a variety of inflammatory diseases. This study examines the role of p38 MAPK in the regulation of TNF-alpha in primary human cells relevant to inflammation, e.g., macrophages and rheumatoid synovial cells. Using a dominant negative variant (D168A) of p38 MAPK and a kinase inhibitor, SB203580, we confirm in primary human macrophages that p38 MAPK regulates TNF-alpha production using a posttranscriptional mechanism requiring the 3' untranslated region of the gene. However, in LPS-activated primary human macrophages we also detect a second previously unidentified mechanism, the p38 MAPK modulation of TNF-alpha transcription. This is mediated through p38 MAPK regulation of NF-kappaB. Interestingly this mechanism was not observed in rheumatoid synovial cells. Importantly however, the dominant negative mutant of p38 MAPK, but not SB203580 was effective at inhibiting spontaneous TNF-alpha production in these ex vivo rheumatoid synovial cell cultures. These data indicate there are potential major differences in the role of p38 MAPK in inflammatory signaling that have a bearing on the use of this kinase as a target for therapy. These results indicate despite disappointing results with p38 MAPK inhibitors in the clinic, this kinase is a valid target in rheumatoid disease.
12528069 New directions in symptomatic therapy for patients with osteoarthritis and rheumatoid arth 2002 Dec The cyclooxygenase (COX)-2-selective nonsteroidal anti-inflammatory drugs (NSAIDs; coxibs) were developed in order to reduce upper gastrointestinal (GI) side effects associated with traditional nonselective NSAIDs. This article presents an overview of clinical trials showing the efficacy of coxibs for the treatment of patients with arthritis. In osteoarthritis trials, coxibs were more effective than placebo and similarly effective compared with standard doses of traditional NSAIDs. Some studies lasted up to a year and showed effectiveness of coxibs for long-term treatment of patients with osteoarthritis. There are currently few adequately powered trials comparing the efficacy of the 2 first-generation coxibs, celecoxib and rofecoxib. Of 2 head-to-head studies comparing the 2 agents, 1 indicated similar efficacy, whereas the other showed the superiority of rofecoxib at a dose of 25 mg daily compared with celecoxib at a dose of 200 mg daily. In studies enrolling patients with rheumatoid arthritis, coxibs also have shown efficacy superior to that of placebo and similar to that of traditional NSAIDs. There are no clinical trials comparing the efficacy of different coxibs for treatment of patients with rheumatoid arthritis. In endoscopic studies, the GI safety and tolerability profile of coxibs has been consistently superior to that of traditional NSAIDs. In large clinical outcome trials, at least 1 of the coxibs, rofecoxib, significantly reduced the risk of confirmed complicated upper GI events compared with the conventional NSAID naproxen. Both rofecoxib and celecoxib reduced the risk of confirmed clinical upper GI events compared with the nonselective NSAIDs naproxen and ibuprofen in patients with osteoarthritis and rheumatoid arthritis not taking low-dose aspirin. Therefore, coxibs provide effective relief of pain from osteoarthritis and rheumatoid arthritis, with efficacy that is comparable to traditional NSAIDs, but with a significantly lower incidence of GI complications.
15188326 Anxiety in rheumatoid arthritis. 2004 Jun 15 OBJECTIVE: To examine the level of anxiety experienced by individuals with rheumatoid arthritis (RA). METHODS: Data from 2 previous studies were used to compare the level of anxiety (measured by the State-Trait Anxiety Inventory) in the following 4 subgroups: a general RA sample, a general osteoarthritis sample, a sample with both RA and major depression, and a normative sample of age-equivalent, working adults. Canonical correlations were used to examine associations between measures of anxiety and measures of both stress and depression. The relationship between anxiety and duration of RA was also explored. RESULTS: The general RA sample had state anxiety levels that were comparable to the normative sample, although trait anxiety levels were significantly higher (P < 0.001). In addition, individuals with RA who also met criteria for depression exhibited significantly higher levels of both state anxiety (P < 0.0001) and trait anxiety (P < 0.0001) than was observed in the normative sample. Canonical correlations revealed that measures of anxiety were correlated with both measures of depression (r = 0.83) and measures of stress (r = 0.50). Anxiety was not found to be significantly related to RA disease duration. CONCLUSION: These findings demonstrated that individuals with RA, especially if concomitantly depressed, tend to exhibit levels of anxiety that are generally higher than a normative group of age-equivalent, working adults. The substantial canonical correlations between anxiety and both depression and stress revealed that anxiety shares variance with these more frequently studied variables in RA. However, anxiety was not found to be related to RA disease duration.
20217662 Developing a service for biologic therapies: a personal experience. 2003 Mar Tumour necrosis factor alpha (TNFalpha) has been identified in the pathogenesis of synovitis and joint destruction in rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA). Therefore selected targeting of pathogenic elements of disease is possible (Chu et al., 1991). TNFalpha is a pro-inflammatory cytokine (mediator) and the over-expression of mediators is considered to be responsible for the damage to articular cartilage in bones. Elevated levels of TNFalpha, correlating with disease activity, have been measured in the serum and synovial fluid of patients with rheumatic diseases and are therefore an ideal target for therapy (Mangge et al., 1995; Cope et al., 1992). The National Institute for Clinical Excellence (NICE) approved the use of two therapies; entanercept (Enbrel) and infliximab (Remicade) for use in patients with active RA in 2002 (NICE, 2002). Other biologic treatments including adalimumab (D2E7) and anakinra (Kineret) will also be available for use in the future. This paper explores the development of a service to provide these therapies to patients.
14672887 A randomised controlled trial of occupational therapy for people with early rheumatoid art 2004 Jan BACKGROUND: Occupational therapy (OT) aims at improving performance of daily living tasks, facilitating successful adjustments in lifestyle, and preventing losses of function. OBJECTIVE: To evaluate the effects of a pragmatic, comprehensive OT programme on self management and health status of people with early rheumatoid arthritis (RA) (<2.5 years). METHODS: A randomised, controlled "assessor blinded" trial was conducted with assessments made at entry, 6, 12, and 24 months. Main outcomes were AIMS2: physical function (PF), pain visual analogue scale (VAS), and Arthritis Self-Efficacy Scale (ASES). RESULTS: Groups had similar disease duration (9 months OT (n = 162) v 10 months control (n = 164)). The OT group received 7.57 (SD 3.04) hours of therapy. Self management significantly increased in the OT group. Otherwise, there were no significant differences in any outcome measures, or between groups, by ACR functional class: AIMS2: PF (F = 0.04; p = 0.96); pain VAS (F = 0.29; p = 0.74); total ASES score (F = 0.93; p = 0.39). CONCLUSIONS: OT improved self management but not health status in early RA. Functional ability remains reasonably good for many in the first five years, so preventive benefits of self management may not yet be apparent and longer follow up is needed. Although many considered the education and therapy useful, insufficient numbers in the OT group used self management sufficiently to make a difference. Behavioural approaches can improve adherence and, potentially, the long term benefits. Future research should evaluate OT as a complex intervention and develop programmes from a theoretical and evidence base.
12017858 [Coxarthritis]. 2002 Mar Coxarthritis is seen with specific and unspecific signs. The more specific signs are available in connection with clinical and laboratory findings, all the more certain is the result. Static and dynamic examinations are as necessary as a complete scanning of the dorsal side of the femoral head.
15022312 Investigation of susceptibility loci identified in the UK rheumatoid arthritis whole-genom 2004 Mar OBJECTIVE: A previous whole-genome scan (WGS) of 182 UK rheumatoid arthritis (RA) affected sibling pair (ASP) families suggested linkage to HLA and 11 other chromosome regions. Replication of such findings in an independent cohort can help to distinguish true linkages from false-positive linkages. Since RA is a heterogeneous disease, some loci may be linked only in subsets of patients. Thus, the aim of this study was to investigate in an additional set of RA ASP families linkage to regions showing deviation in expected allele-sharing ratios in the UK WGS and to perform subset analysis on the combined cohort. METHODS: Twenty loci were investigated for linkage in 217 Caucasian UK RA ASPs. Stratification analysis was performed on the combined cohort of 377 RA ASP families to account for sex, RA severity, and the shared epitope (SE). RESULTS: None of the regions of linkage identified in the initial WGS achieved statistical significance in the second cohort. In contrast, after stratification analysis, 14 regions showed nominal evidence of linkage (logarithm of odds score >0.8) in one or more subgroups. In particular, the strength of evidence for linkage to chromosome 16p was increased in subsets of ASPs with younger age at disease onset (LOD score 2.38) and for linkage to chromosome 6q in female-female ASPs (LOD score 2.31) and in ASPs in which both siblings had 2 copies of the SE (LOD score 3.03). CONCLUSION: These results support the evidence for heterogeneity of RA. This information will inform the future design of association-based investigations as the search for disease genes in the linked regions begins.
12209487 Relationship among the HLA-DRB1 shared epitope, smoking, and rheumatoid factor production 2002 Aug OBJECTIVE: Rheumatoid factor (RF) production in rheumatoid arthritis (RA) is generally associated with more severe disease. In some studies, RF production has been associated with carriage of HLA-DRB1 alleles encoding the RA-associated shared epitope (SE). Patients who smoke are also more likely to be RF positive. In this study, we investigated whether the association between RF production and smoking was influenced by carriage of the SE. METHODS: The smoking histories of 371 RA patients attending a hospital clinic were recorded. RF levels and SE status were determined for every patient, and the associations between the SE, smoking, and RF production were examined. HLA-DRB1 typing was performed using polymerase chain reaction. Results were analyzed using chi-square tests and logistic regression analysis. RESULTS: Patients who had ever smoked were significantly more likely to be RF positive than nonsmokers (odds ratio 2.2, P < 0.0001). This remained significant (P = 0.003) after correction for age, sex, and disease duration in a logistic regression model. An association was also found between RF positivity and carriage of the SE (P = 0.03, after correction for age, sex, and disease duration), but significance was reduced or lost after correction for previous or current smoking (P = 0.05 and 0.09, respectively). Examination of the major SE phenotypes in this RA population by multivariate logistic regression analysis revealed that only DRB1*0401 was associated with RF positivity, and that this was independent of the influence of smoking. CONCLUSION: Our data confirm that RF production in RA patients is associated with smoking. This does not appear to depend on an HLA-DR-restricted immune response. The association of the SE with RF positivity is primarily due to HLA-DRB1*0401. This appears to be independent of the association with smoking, although smoking further increases the likelihood of RF production in DRB1*0401 patients.
15638044 Follistatin-related protein gene (FRP) is expressed in the synovial tissues of rheumatoid 2004 Nov OBJECTIVE: To examine the expression level and function of follistatin-related protein gene (FRP, also referred to as FSTL1) in rheumatoid arthritis (RA), and possible association of its polymorphisms with genetic susceptibility to RA. METHODS: FRP mRNA expression levels in the synovial tissues from 10 patients with RA and 5 patients with OA were measured using real-time RT-PCR. Effects on the growth of synovial cells were evaluated by stably introducing FRP cDNA into a rheumatoid synovial cell line, E11. Screening of genomic DNA variations was done using DNA from 12 patients with RA and 12 healthy individuals by direct sequencing. Genotypes at the detected polymorphic sites were determined in 224 patients with RA and 220 healthy individuals using PCR-single strand conformation polymorphism. RESULTS: FRP mRNA was overexpressed in synovial tissues from RA patients by 2.3-fold as compared with those from OA. A rheumatoid synovial cell line (E11) transfected with FRP exhibited reduced proliferation, probably mediated by secreted FRP molecule. 16 genomic variations were identified, among which 4 were polymorphisms within the promoter region and exons, and the remainder were either rare variations or intronic polymorphisms. Genotyping of 4 polymorphic sites did not reveal statistically significant association with the susceptibility to RA. CONCLUSION: FRP mRNA is overexpressed in RA synovium, the product of which exerts inhibitory activity on synovial cell growth. Although new polymorphic sites were identified, they were not associated with susceptibility to RA, suggesting that overexpression of FRP is secondarily caused by synovial environment of RA.
15565336 The polymorphisms of Tim-1 promoter region are associated with rheumatoid arthritis in a K 2005 Jan It has been determined that the family of T-cell immunoglobulin domain and mucin domain (TIM) proteins is expressed on T cells. A member of the TIM family, TIM-1, is considered to be a membrane protein associated with the development of Th2-biased immune responses and selectively expressed on Th2 cells. We previously showed that the exon 4 variations of Tim-1 are associated with susceptibility to allergic diseases, as well as autoimmune diseases such as rheumatoid arthritis (RA). In this study, we assessed the association between genotype and allele frequencies of the Tim-1 gene promoter region, in both RA patients and the controls without RA, using polymerase chain reaction-restriction fragment length polymorphism and single-base extension methods. We further investigated the relationships among the genotypes of each polymorphism and C-reactive protein or rheumatoid factor levels in RA patients. The genotype and allele frequencies of the -1637A>G polymorphism in RA patients are significantly different from those in the non-RA controls (P=0.0004 and P=0.001, respectively). Our results strongly suggest that polymorphism in the Tim-1 promoter region might be associated with susceptibility to RA.