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Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
12775925 Employment and chronic non-cancer pain: insights into work retention and loss. 2003 OBJECTIVES: To explore the work experiences of three individuals who have chronic non-cancer pain and to identify factors which may affect their ability to remain in employment. METHODS: Three cases were selected from a data set of six, to illustrate distinct employment history scenarios. All participants had a diagnosis of rheumatoid arthritis. Data was gathered using semi-structured, in-depth interviews that were audiotaped and later transcribed for qualitative, content analysis. Themes identified were those which related to employment experiences and appeared to be important factors influencing the retention of work. FINDINGS: Four main themes were identified: the nature of physical barriers to employment, autonomy at work, social networks, and the importance and motivation to remain in employment. CONCLUSION: These findings support existing research in relation to chronic pain and employment in general and expands upon the nature and importance of social support at work. It is suggested that the qualitative methodology illustrated here, which explores the perspectives of those still in employment (as well as those who have stopped working) may be a useful approach to investigating this important area of research.
14688071 Molecular genetic analyses of human NKG2C (KLRC2) gene deletion. 2004 Jan Human NKG2A, NKG2C and NKG2E genes are located on 12p13 in the NK gene complex. We recently identified deletion of NKG2C in a Japanese population. This study was performed to identify the breakpoint, and to examine the association of NKG2C deletion with susceptibility to rheumatoid arthritis and systemic lupus erythematosus. The location of the breakpoint was determined to be 1.5-1.8 kb telomeric from the 3' end of NKG2A by comparing sequences of the intergenic segments upstream and downstream of the NKG2C gene in the common haplotype with the intergenic sequence between NKG2A and NKG2E in the deletion haplotype. Based on this information, a genotyping system was developed. The frequency of NKG2C deletion haplotype was 20.2% in Japanese and 20.0% in Dutch populations. The frequency of homozygous deletion was 4.1% in Japanese and 3.8% in Dutch. Evidence for an association with rheumatic diseases was not detected. These results indicated that NKG2C deletion is commonly present in Japanese and Dutch, suggesting that NKG2C is not essential for survival and reproduction, and is not associated with rheumatic diseases.
14600805 Disseminated tuberculosis, pulmonary aspergillosis and cutaneous herpes simplex infection 2003 Dec CASE PRESENTATION: Despite chemoprophylaxis with isoniazid a 58-year-old Creole patient with mild rheumatoid arthritis developed disseminated tuberculosis, pulmonary aspergillosis and cutaneous herpes simplex infection during treatment with infliximab and methotrexate. TREATMENT: The patient received antituberculous drugs (ethambutol, isoniazid, pyrazinamide, rifampicin), amphotericin B, flucytosine, and valaciclovir, along with prolonged intensive care treatment and mechanical ventilation. CONCLUSIONS: The present case confirms that isoniazid prophylaxis (300 mg once daily, during 6 months) does not protect against the reactivation and dissemination of latent tuberculosis. It also shows that combined treatment with infliximab and methotrexate may induce severe immunosuppression with prolonged leukocytopenia and depressed cellular immunity, leading to multiple opportunistic infections. Extensive diagnostic testing, early start of antimicrobial therapy and enteral immunonutrition, and further infection prevention with selective decontamination of the digestive tract may have been the key to a good clinical outcome.
14505214 Proteus mirabilis and rheumatoid arthritis: no association with the disease. 2003 Sep Proteus mirabilis(PM) is implicated in different studies in the pathogenesis of rheumatoid arthritis (RA) because of the structural homogeneity of its haemolysin B precursor with EQRRAA sequences in DRB 1 haplotype. The aim of the study was to compare the levels of antibodies specific to PM in the sera of patients with RA and healthy controls in our population. Serum samples from 78 consecutive RA patients and 75 healthy controls were analysed for the presence of IgG isotype and total immunoglobulins (IgG+IgA+IgM) against PM using enzyme-linked immunosorbent assay (ELISA) with two kinds of antigen preparation, whole bacteria and SDS-lysed bacterial extract. There was no significant increase in the concentrations of anti- Proteus antibodies (APA) in patients with RA compared to healthy controls in our population, when SDS-lysed bacterial extract or whole bacteria were used as antigen. The APA levels did not correlate with serum CRP levels. Infection with P. mirabilis is found to have no pathological or aggravating role in RA.
15172046 The use of anakinra, an interleukin-1 receptor antagonist, in the treatment of rheumatoid 2004 May Interleukin-1 (IL-1) is a primary cytokine that is involved in the pathogenesis of rheumatoid arthritis; it contributes to inflammation and joint destruction. Anakinra (Kineret) is an IL-1 receptor antagonist that blocks the biologic activity of IL-1. It was approved by the U.S. Food and Drug Administration (FDA) for the treatment of rheumatoid arthritis in 2001. Anakinra is safe and effective in the treatment of rheumatoid arthritis, both as monotherapy and in combination with other disease-modifying antirheumatic drugs. This article reviews the preclinical, clinical, and postmarketing data on the safety and efficacy of anakinra in the treatment of rheumatoid arthritis and focuses on the pivotal clinical trials that led to FDA approval.
16134816 Apoptosis as a mechanism of autoimmune inflammation in human knee joint. 2004 Dec Apoptosis in the cartilage and synovial membrane of the knee joint in patients with rheumatoid arthritis was studied using the immunocytochemical TUNEL method. The degree of apoptosis correlated with the duration of inflammation. The process predominated in the chondroblast population, lymphocytic infiltration, and synovial membrane fibroblasts.
15794195 Clinical and radiological disease-course in a Swedish DMARD-treated early RA-inception coh 2004 OBJECTIVES: Disease-modifying anti-rheumatic drugs (DMARDs) decrease clinical signs and symptoms in rheumatoid arthritis (RA). However, radiographic changes sometimes continue to accrue despite effective suppression of clinical symptoms by therapy. The objective of this study was to identify whether successful clinical disease-control in a Swedish early RA-inception cohort of patients led to an attenuation of radiological progression. PATIENTS AND METHODS: We analysed clinical data and radiographs of 95 patients who were on a stable treatment regimen [methotrexate (MTX), sulfasalazine (SSZ), oral gold (AUR)] or who had changed between different DMARDs during the 2-year observation period [multiple therapy failures (mTF)]. Radiographs were quantified using the modified Larsen score and 'X-Ray RheumaCoach' software. RESULTS: Clinical measures improved markedly (p <0.001) from baseline to year 2 under AUR, MTX, and SSZ therapy but not in the mTF group. Similar levels of disease control were seen for each DMARD. During this period, patients treated with AUR had a deltaLarsen score (+ 14.5+/-1.3) similar to mTF patients (+ 15.8+/-1.1) but greater than patients on MTX (+8.6+/-0.8) or SSZ (+9.1+/-0.8). CONCLUSIONS: This study confirms that radiological progression occurs despite a clinically acceptable disease control, but also shows that, given the same degree of clinical disease control, radiological progression can be different for different DMARDs.
15077061 [Methotrexate for treatment of rheumatoid arthritis]. 2004 Feb 27 Rheumatoid arthritis (RA) is a common chronic inflammatory and destructive arthropathy that cannot be cured and that has substantial personal, social and economic costs. Methotrexate is a well-known folate analogue, and is the most frequently applied drug for the disease to modify antirheumatic therapy in patients with rheumatoid arthritis. Although results of studies have shown the efficacy of such drugs as methotrexate on rheumatoid arthritis, activity measures and their effect on mortality in patients with the disease remain unknown. The current therapeutic approach to rheumatoid arthritis consists of administration of anti-inflammatory, immunomodulating, and immunosuppressive drugs. Immunomodulating drugs, as opposed to non-steroid anti-inflammatory drugs, which only reduce the signs of inflammation, are capable of gradually checking the course of the disease. However, they do not prevent the slow but progressive destruction of joints. The prominent role of proinflammatory cytokines and growth factors in the pathogenesis of RA has been documented. Recent studies have demonstrated the efficacy of anticytokine treatment. Infliximab is a chimeric monoclonal antibody capable of neutralizing human TNF alpha. A number of clinical trials for the treatment of rheumatoid arthritis with infliximab indicated that TNF alpha blockade was effective and well tolerated, with excellent results occurring at 3 and 10 mg/kg in combination with methotrexate. Treatment of RA patients with the combination of infliximab and methotrexate also prevented radiographic evidence of progression of joint damage. If its clinical efficacy is sustainable and its safety confirmed over the long term, infliximab may become an essential agent of choice for the treatment of RA.
15552508 Benefit/risk of therapies for rheumatoid arthritis: underestimation of the "side effects" 2004 Sep Most physicians are familiar with the side effects or risks of drugs used to treat rheumatoid arthritis (RA), but relatively less familiar with the "side effects" or risks associated with RA itself RA is not thought to have the same potential severity as a cardiovascular or neoplastic disease by most physicians, the public, or even some rheumatologists, although relative rates of predicted mortality in some patients with RA are in the range of some people with coronary artery disease or Hodgkin's disease. Many reasons may be identified to explain why the risks of RA have been underestimated: RA does not lead to acute life-threatening situations; population-based data have suggested that most people who meet criteria for RA have a mild or self-limited process; acute attributed causes of death in people with RA are superficially similar to those in the general population; clinical trials have suggested many therapies that are efficacious over a period of 3-12 months; few long-term longitudinal studies were performed prior to the 1980s; medical recommendations made during the 1950s-1980s suggested that simple therapies were adequate for most patients; and quantitative information concerning patient status is generally not included in standard rheumatology care. As more information has emerged concerning severe long-term outcomes in the "natural history" of RA (as treated prior to the 1990s), new strategies of aggressive intervention have been developed. Furthermore, basic research has led to new therapies. It appears that the benefit/risk ratio of therapies for RA has increased substantially over the last two decades, and the outlook for patients with RA is much better at this time than in previous years.
11954011 The prevalence and impact of managed care for persons with rheumatoid arthritis in 1994 an 2002 Apr 15 OBJECTIVES: To estimate the proportion of persons with rheumatoid arthritis (RA) in managed care and fee-for-service settings in 1994 and 1999, to ascertain whether there are differences in utilization between persons in the 2 systems of care in the 2 years, and to determine whether 1994 managed care status or change between 1994 and 1999 in managed care status affects outcomes. METHODS: The present study uses data from the University of California, San Francisco RA Panel Study, in which 310 patients with RA from a random sample of Northern California rheumatologists were interviewed annually between 1994 and 1999 using a structured survey instrument. We use linear and logistic regression to compare the health care utilization and outcomes of persons in managed care and fee-for-service after adjusting for differences in demographic and health characteristics. RESULTS: The proportion of respondents in managed care increased from 60% to 79% between 1994 and 1999, including an increase from 37% to 68% among persons eligible for Medicare and an increase from 74% to 92% among persons ineligible for Medicare. With the exception of physical therapy visits in 1999, patients with RA in managed care did not report significantly different utilization of any service for RA than those in fee-for-service in either 1994 and 1999, including hospital admissions and joint replacement surgery. Managed care status in 1994, and change in managed care status between 1994 and 1999, were not associated with significantly different outcomes in 1999. CONCLUSION: Despite the growth in the proportion of patients with RA in managed care, those in managed care did not differ from those in fee-for-service settings in utilization or outcomes.
14528524 Prevalence of rheumatic symptoms, rheumatoid arthritis, ankylosing spondylitis, and gout i 2003 Oct OBJECTIVE: To carry out a cross-sectional survey on prevalence of musculoskeletal symptoms, rheumatoid arthritis (RA), ankylosing spondylitis (AS), and gout. METHODS: In Shanghai, 4 communities comprising 7603 inhabitants over 15 years of age in an urban population were randomly selected from 13 communities. Interviews were conducted from September 1997 to March 1998 by trained physicians using the COPCORD Core Questionnaire. Physical and radiographic examinations and serologic tests were carried out when required to classify categories of rheumatic diseases. The diagnoses of RA, systemic lupus erythematosus (SLE), and gout were based on American Rheumatism Association criteria. The diagnosis of AS strictly followed the modified New York criteria of 1984. Crude prevalence rates were standardized according to a standard Chinese population for age and sex structure. RESULTS: A total of 6584 adults (3394 women, 3190 men) were interviewed, and response rate was 86.6%. The age and sex standardized prevalence rate of rheumatic symptoms at any site amounted to 13.3% (95% CI 12.5-14.1%). Symptoms occurred more frequently in the following sites: knee 7.0% (95% CI 6.4-7.6%), lower back 5.6% (95% CI 5.0-6.2%), shoulder 4.7% (95% CI 4.2-5.2%), and neck 2.4% (95% CI 2.0-2.8%). Women complained of rheumatic symptoms more frequently than men. The standardized rates of RA, AS, gout, symptomatic knee osteoarthritis, and soft tissue rheumatism were 0.28% (95% CI 0.15-0.41%), 0.11% (95% CI 0.03-0.19%), 0.22% (95% CI 0.11-0.33%), 4.1% (95% CI 3.6-4.6%), and 3.4% (95% CI 3.0-3.8%), respectively. Two cases of SLE, one case of dermatomyositis, and one case of systemic sclerosis were found. CONCLUSION: Compared with rates in European and Western countries the prevalence rates of RA, AS, and gout are low in Shanghai, China, although the prevalence rates of rheumatic symptoms are high.
13680139 Cost-effectiveness analysis of NSAIDs, NSAIDs with concomitant therapy to prevent gastroin 2005 Jan The objective was to assess the cost-effectiveness of nonsteroidal anti-inflammatory agents (NSAIDs), NSAIDs with concomitant therapy to prevent gastrointestinal (GI) toxicity, and cyclooxygenase-2 specific inhibitors (COX-2) in the treatment of rheumatoid arthritis (RA). Markov (state-transition) models were used to simulate a cohort taking disease-modifying antirheumatic drugs, low dose steroid, and one of the following strategies: (1) NSAIDs without prophylaxis, (2) NSAIDs with misoprostol, (3) NSAIDs with proton-pump inhibitor (PPI), or (4) COX-2. Costs were measured in 1999 US dollars and health effects are expressed as quality-adjusted life years (QALYs). COX-2 was the most cost-effective strategy for preventing GI toxicity. The incremental cost/effectiveness (C/E) ratio between COX-2 and no prophylaxis was 56,751 dollar/QALY. Although COX-2 are the best option (among the strategies analyzed) to prevent GI toxicity, the incremental C/E ratio between COX-2 and no prophylaxis is higher than 50,000 dollar/QALY.
15334432 Differences between participants and nonparticipants in an exercise trial for adults with 2004 Aug 15 OBJECTIVE: To investigate the generalizability of the results of a randomized controlled trial on the effectiveness of long-term, high-intensity exercises in the rheumatoid arthritis patients in training (RAPIT) trial by comparing the characteristics of the participants with the nonparticipants. METHODS: Participants and nonparticipants were mailed questionnaires on sociodemographic characteristics, health status, reasons not to participate, and attitudes toward intensive exercise. RESULTS: The questionnaires from 892 (75%) nonparticipants and 299 (97%) participants were collected. The nonparticipants were slightly older, more often male, and had longer disease duration than the participants. The nonparticipants perceived their disease as more serious, used fewer disease-modifying antirheumatic drugs, had a lower level of education, and a more negative attitude toward intensive exercise. CONCLUSION: The results of the RAPIT trial might not be generalizable to the entire target population. To promote participation in long-term, high-intensity exercises, health professionals should more actively discuss the potential benefits of exercise with their RA patients while taking into consideration specific factors related to participation.
15576213 Arthrodesis of the thumb metacarpophalangeal joint using a cannulated screw and threaded w 2004 Nov We describe a technique of arthrodesis of the thumb metacarpophalangeal joint that we performed in 26 patients. Indications for surgery were instability (6 patients), chronic instability with secondary degenerative joint disease (6), osteoarthritis (6), inflammatory arthritis (7), and paralytic boutonniere (1). The technique uses the cup-and-cone method of decortication and positioning with the internal fixation using a 3.0-mm partially threaded cannulated screw and threaded washer (Synthes, Paoli, PA). Twenty-five of 26 joints had clinical and radiographic fusion. Average time to radiographic fusion for 24 patients (1 nonunion, 1 patient without x-rays until 4 months) was 10 weeks. Long-term follow-up evaluation was available for 20 patients and averaged 32 months (range, 21-44 months). All 20 had stable radiographic fusion with maintenance of the fusion angle. There were no infections and no need for hardware removal. Our results indicate that this technique for arthrodesis of the thumb metacarpophalangeal joint is effective and reliable, is accomplished easily, and has a low incidence of complications.
12210507 Preliminary observations on the influence of rheumatoid alpha-1-acid glycoprotein on colla 2002 Aug This study investigates the effect of alpha(1)-acid glycoprotein (AGP) isolated from both normal and rheumatoid plasma on type II collagen fibril formation. Rheumatoid samples were obtained over 2 years from two patients with early arthritis. The glycosylation of each sample was analysed to establish any correlation with fibrillogenesis. Rheumatoid AGP displays increased fucosylation compared to normal AGP. In both patients the fucosylation dipped after 1 year, then rose again over year 2. It is proposed that year 1 corresponds to the acute phase of the disease and the onset of chronic inflammation after this time produces a subsequent increase in fucosylation. Rheumatoid AGP influences type II collagen fibrillogenesis. Native fibrils were produced but with differences in the rate and extent of fibrillogenesis depending on AGP concentration and fucosylation. Low concentrations produced a decrease in fibrillogenesis rate and fibril diameter. High concentrations produced fibrils at a rate and diameter dependent on fucosylation. Highly fucosylated AGP produced narrow fibrils slowly, whereas poorly fucosylated AGP produced thicker fibrils more quickly. We propose that differences in glycosylation (especially fucosylation) of AGP are responsible for differences in collagen fibrillogenesis and this phenomenon may contribute to the exacerbation of cartilage destruction in rheumatoid arthritis.
14763244 Identification of masqueraders of autoimmune disease in the office. 2003 Nov There are several rheumatologic and autoimmune disorders that can masquerade as allergic disease. Identification of these conditions in an office setting can be a challenge for the practicing allergist-immunologist. These conditions include rheumatoid and juvenile arthritis, Sjogren's syndrome, systemic lupus erythematosus, Behcet's and antiphospholipid syndromes, systemic sclerosis, vasculitis, sarcoidosis, chronic fatigue syndrome, and fibromyalgia. The article will address these topics and include clinical uses of immunologic tests for diagnosis.
15513678 Quantitative assessment of periarticular osteopenia in patients with early rheumatoid arth 2004 BACKGROUND: Involvement of the metacarpophalangeal (MP) joints is one of the major problems in patients with rheumatoid arthritis (RA). Although several data about the cumulative influence of steroid intake on bone are available, the course of demineralisation in RA has not been described by quantitative methods until now. PATIENTS AND METHODS: Computed tomography (CT) sections of 96 MP joints in 12 RA patients and of 32 MP joints in four age-matched healthy controls were investigated. Patients were classified according to Steinbrocker. Densitometric evaluation of subchondral bone density was performed by CT osteoabsorptiometry (CT-OAM). Quantitative CT-OAM was used to evaluate mineralisation of the articular surfaces in MP joints. RESULTS: In the distal articular surface of MP joints, the number of density maxima was reduced from 3 to 2.1+/-0.3, 1.9+/-0.5 and 1.3+/-0.3 in RA patients with early, mild to moderate, and severe disease, respectively. Means of calcium concentrations were 633.4+/-35. 3 mg Ca2+/mL, 518.9+/-56.2 mg Ca2+/mL, 497.7+/-23.8 mg Ca2+/mL and 455.1+/-28.6 mg Ca2+/mL for controls and RA patients with early, mild to moderate, and severe RA, respectively. Mineralisation of the distal articular surface was significantly reduced in all groups of RA patients [probability (p) = 0.005]. Regarding the number of density maxima, no differences were detected in the proximal articular surface of normal and RA fingers. However, mineralisation of the proximal articular surface was significantly reduced in all groups of RA patients (p = 0.004). Means of calcium concentrations of the proximal articular surface were 494.1+/-48.5 mg Ca2+/mL, 413.0+/-16.2 mg Ca2+/mL, 406.0+/-51.4 mg Ca2+/mL, 390,4+/-41.1 mg Ca2+/mL for controls and RA patients with early, mild to moderate, and severe RA, respectively. CONCLUSION: Patients with early and untreated RA show loss of mineralisation and altered morphology of the MP joints of the hand, even before corticosteroid therapy. CT-OAM provides evidence for an early alteration of functional anatomy in MP joints.
15588689 Clinical trial outcome of anti-tumour necrosis factor alpha therapy in rheumatic arthritis 2004 Nov 21 Rheumatoid arthritis is a common debilitating disease. Chronic joint inflammation leads to irreversible joint damage. Disability is a common sequel, therefore it is a major healthcare burden. Treatment by convention disease modifying anti-rheumatic drugs improves symptoms and signs but does not improve long-term prognosis. Tumour necrosis factor alpha is a powerful pro-inflammatory cytokine. Blocking this cytokine by either monoclonal antibody or soluble receptor reduces inflammation, improves symptoms and significantly reduces joint damage. Tumour necrosis factor alpha antagonists are major breakthroughs in the treatment of rheumatoid arthritis. In the UK, they are approved for the treatment of rheumatoid arthritis in patients with active disease who have failed at least two disease modifying anti-rheumatic drugs.
12784423 OMERACT Rheumatoid Arthritis Magnetic Resonance Imaging Studies. Summary of OMERACT 6 MR I 2003 Jun Magnetic resonance image (MRI) scanning is a new method for imaging and quantifying joint inflammation and damage in rheumatoid arthritis (RA). Over the past 4 years, the OMERACT MR Imaging Group has been developing and testing the RA-MRI scoring system (RAMRIS) for use in RA. The OMERACT filter demands that an ideal outcome measure satisfy the elements of truth, discrimination, and feasibility. The RAMRIS as it currently stands incorporates measures of joint inflammation and damage including bone erosion, edema, and synovitis. Tendonitis has not been scored because of feasibility issues; joint space narrowing, reflecting cartilage damage, has also been excluded as reliability was low at the small joints of the hands. Anatomical coverage of the score is currently restricted to the wrists and hands but can provide a basis for a more comprehensive score. The MR measurement of synovitis correlates closely with histological evidence and work continues on validating MR erosions with reference to radiographic techniques. The RAMRIS has demonstrated good reliability for bone erosion and synovitis at the wrists and metacarpophalangeal joints subject to reader training, with slightly lower levels of reader agreement for bone edema. Reliability was less satisfactory in discriminating between 2 time points, and further work is required if the score is to be used to monitor change. Feasibility also needs to be considered for the practical application of the score, including the time taken for scanning and scoring, as well as cost and safety issues. The OMERACT RAMRIS provides a framework for scoring inflammation and damage in RA upon which further modifications can be built. It has been endorsed by the MRI working group and OMERACT 6 participants as useful for inclusion as an outcome measure in clinical trials.
15459671 Gene therapy for autoimmune diseases: quo vadis? 2004 Oct Biological therapies using antibodies and cytokines are becoming widespread for the treatment of chronic inflammatory autoimmune diseases. However, these treatments have several limitations - such as expense, the need for repeated injections and unwanted side-effects - that can be overcome by genetic delivery. This review summarizes the ingenuity, sophistication and variety of gene-therapy approaches that have been taken in the design of therapeutic molecules and vectors, the engineering of cells and the regulation of gene expression for the targeting of disease outcome. We focus our attention on multiple sclerosis, type 1 diabetes and rheumatoid arthritis.