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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
12528999 Salvage of major joint prostheses in aggressive non-specific panniculitis. 2002 Oct Panniculitis is a relatively rare condition, which is usually treated non-operatively. We present a case of panniculitis causing an acute septicaemic episode and threatening the integrity of underlying joint prostheses. The situation was salvaged by radical debridement of the affected areas, and reconstruction using split-skin grafts. Considerations in the management of patients with this condition are discussed.
12522829 Magnitude and characteristics of arthritis and other rheumatic conditions on ambulatory me 2002 Dec 15 OBJECTIVE: To describe ambulatory medical care utilization, defined to exclude injury-related visits, for persons with arthritis and other rheumatic conditions. METHODS: National estimates, rates, and other characteristics of ambulatory care visits were calculated from a national sample of patient visits to physician offices and acute care hospital outpatient and emergency departments. RESULTS: An estimated 36.5 million ambulatory care visits were related to arthritis and other rheumatic conditions. Visit rates increased with age and, overall, were twice as high among women as men. Rates of visits by race varied by ambulatory care setting. Soft tissue disorders (9.3 million), osteoarthritis (7.1 million), nonspecific joint pain/effusion (7.0 million), and rheumatoid arthritis (3.9 million) were the most common diagnoses. CONCLUSIONS: Arthritis and other rheumatic conditions account for about as many ambulatory care visits as cardiovascular disease or essential hypertension. These visits serve as excellent opportunities to counsel patients regarding prevention messages for arthritis.
14969073 Methotrexate as the "anchor drug" for the treatment of early rheumatoid arthritis. 2003 Sep The two major advances over the 1990s in the treatment of rheumatoid arthritis (RA) were a shift in strategy from a "pyramid", in which disease modifying anti-rheumatic drugs (DMARDs) were deferred for several years, to the early aggressive use of DMARDs and widespread acceptance of methotrexate as the DMARD with the most long-term effectiveness and safety. Methotrexate courses are continued far longer than those of any other DMARD, an excellent indicator of greater effectiveness and safety. In one recent series, methotrexate was the first DMARD used in more than 80% of patients with RA. Studies which document the superiority of combinations of methotrexate with biological agents to methotrexate monotherapy select for only a minority of contemporary patients with RA who have severe disease activity and incomplete responses to methotrexate. In one locale, only 5% of patients met criteria for the Anti-Tumor Necrosis Factor Trial in RA with Concomitant Therapy (ATTRACT) trial and only 30% met the criteria for the Early Rheumatoid Arthritis (ERA) trial. In studies comparing methotrexate directly with biological agents, the biological agents have greater efficacy in patients with very severe disease, but the best results are seen in patients who take a combination of methotrexate and biologic agents. These data establish that methotrexate is the anchor drug and probably should be the first DMARD used in the majority of patients with RA at this time.
12930303 Adalimumab, a fully human anti-TNF-alpha monoclonal antibody, treatment does not influence 2003 Aug TNF-alpha is known to play an important role in UV-induced immunomodulation and photodamage. It plays a role in UVB-mediated induction of apoptosis and is a strong inducer of the c-Jun N-terminal kinase (JNK) pathway, which eventually leads to the loss of dermal collagen and elastin content. Recently chimeric anti-TNF-alpha has been introduced as a therapy for rheumatoid arthritis. The aim of the present study was to investigate the effect of anti-TNF-alpha treatment on UV-induced DNA damage, apoptosis, and induction of matrix metallo proteinases. Twelve patients with rheumatoid arthritis were included and irradiated with 2 MED broadband UVB before and after administration of 0.5 mg/kg anti-TNF-alpha monoclonal antibody. Twenty-four hours after irradiation biopsies were taken. Frozen and paraffin sections were stained for p53, c-Jun, phosphorylated c-Jun, sunburn cells and MMP-1. No significant changes were observed in the expression of p53 and sunburn cells and MMP-1 content after treatment with anti-TNF-alpha, whereas a slight but significant decrease in c-Jun and phosphorylated c-Jun expression was noted (P = 0.0250 and P = 0.0431, respectively). Our results showed no influence of anti-TNF-alpha on UV response at therapeutic doses in patients with rheumatoid arthritis.
11955534 Methotrexate and mortality in patients with rheumatoid arthritis: a prospective study. 2002 Apr 6 BACKGROUND: Methotrexate is the most frequent choice of disease-modifying antirheumatic therapy for rheumatoid arthritis. Although results of studies have shown the efficacy of such drugs, including methotrexate, on rheumatoid arthritis morbidity measures, their effect on mortality in patients with the disease remains unknown. Our aim was to prospectively assess the effect on mortality of methotrexate in a cohort of patients with rheumatoid arthritis. METHODS: Our cohort included 1240 patients with rheumatoid arthritis seen at the Wichita Arthritis Center, an outpatient rheumatology facility. Patients' details were entered into a computerised database at the time of their first clinic visit. We also obtained and recorded demographic, clinical, laboratory, and self-reported data at each follow-up visit (average interval 3.5 months). We estimated the mortality hazard ratio of methotrexate with a marginal structural Cox proportional hazards model. FINDINGS: 191 individuals died during follow-up. Patients who began treatment with methotrexate (n=588) had worse prognostic factors for mortality. After adjustment for this confounding by indication, the mortality hazard ratio for methotrexate use compared with no methotrexate use was 0.4 (95% CI 0.2-0.8). Other conventional disease-modifying antirheumatic drugs did not have a significant effect on mortality. The hazard ratio of methotrexate use for cardiovascular death was 0.3 (0.2-0.7), whereas that for non-cardiovascular deaths was 0.6 (0.2-1.2). INTERPRETATION: Our data indicate that methotrexate may provide a substantial survival benefit, largely by reducing cardiovascular mortality. This survival benefit of methotrexate would set a standard against which new disease-modifying antirheumatic drugs could be compared.
12734886 The responsiveness of generic health status measures as assessed in patients with rheumato 2003 May OBJECTIVE: We used a variety of health status measures in 2 groups of patients with rheumatoid arthritis (RA) to assess both the smallest distinguishable difference and the relative responsiveness to change of these measures, when used in clinical practice. METHODS: Two groups of patients were studied. Group 1: 24 patients with stable RA tested on 2 occasions; Group 2: 60 patients receiving methotrexate tested before and 14 weeks after treatment with infliximab. Assessments were made with self-completed questionnaires: the modified Health Assessment Questionnaire, Medical Outcomes Study Short Form-36 [SF-36 (SF-6D)], EuroQol, and, in some, the standard gamble. Group 2 also had joint counts, and measures of erythrocyte sedimentation rate, C-reactive protein, and hemoglobin. RESULTS: The limits-of-agreement (Bland-Altman) approach had greater confidence intervals (CI) than did CI based on +/- 2 standard errors of the measurement. Improvement with infliximab could be determined with all measures, however, but the standard gamble seemed least responsive to change. CONCLUSION: The various measures had different degrees of responsiveness, but with all it was possible to show improvement in Group 2 compared to Group 1. There was a closer association of the patient centered measures of improvement with changes in pain score than with joint counts.
15717805 [Seroprevalence of Helicobacter pylori in rheumatoid arthritis and its relationship to pha 2004 Dec GOAL: To find out a serology prevalence of Helicobacter pylori (Hp) infection in patients suffering from rheumatoid arthritis (RA) and to investigate its relationship to pharmacotherapy modes. METHOD: To determine Hp IgG class and IgA class antibodies by ELISA method in hospitalised patients with active RA according to ACR criteria (1987). RESULTS: 137 patients with RA were examined--20 men, 117 women, an average age was 54.6 +/- 13.1, an average length of RA in these patients was 12.46 +/- 9.75, positive RF/LFT had 88% of patients. Hp ELISA IgG antibodies were confirmed in 57% (78/137) of patients with RA, Hp ELISA IgA antibodies were confirmed in 60% of examined patients (82/137), and IgG + IgA antibodies simultaneously were found in 51% (70/137) of examined patients. A comparison of basic demographic data, specific parameters of the disease, and clinical signs has not confirmed any differences between groups of Hp positive and Hp negative patients. Patients with both types of Hp antibodies (IgG + IgA) had more frequent signs of RA in other places than joints (p = 0.046). RA patients with anti-Hp IgG antibodies more frequently used anticoagulation drugs (p = 0.029) while patients with anti-Hp IgA antibodies more frequently used methotrexate (p = 0.01). CONCLUSIONS: Results point out more frequent incidence of Hp IgA antibodies in RA patients treated with methotrexate and more frequent incidence of both IgG and IgA antibodies in patients with RA signs in other places than joints.
12705898 p21waf1/cip1 is down-regulated in conjunction with up-regulation of c-Fos in the lymphocyt 2003 Apr 25 Features characteristic to rheumatoid arthritis (RA) including synovial overgrowth and joint destruction are experimentally produced by augmenting c-fos gene expression. We show that cyclin dependent kinase inhibitor p21waf1/cip1, that inhibits cell proliferation, is down-regulated in conjunction with up-regulation of c-fos in the lymphocytes of patients with RA. As to the mechanism of down-regulation of p21waf1/cip1 gene expression, transfection studies in U937 cells showed that c-fos down-regulated phosphorylation and dimerization of signal transducers and activators of transcription (STAT) 1, thereby inhibiting interferon -induced transactivation of p21waf1/cip1. Phosphorylation of STAT1 was indeed decreased in the lymphocytes of patients with RA. Thus, under overexpression of c-fos gene, c-Fos inactivates STAT1 to down-regulate p21waf1/cip1 gene expression in the lymphocytes of patients with RA, and in this way may enhance proliferation of lymphocytes.
14593701 Rheumatoid arthritis: targeting the proliferative fibroblasts. 2003 Our flexible joints are synovial joints composed of bone, hyaline cartilage, synovial membrane, ligaments and tendons. Rheumatoid arthritis is a disease that affects multiple synovial joints and involves inflammation of the synovial membrane, often resulting in loss of function due to erosion of bone and cartilage. Inflammation is accompanied by an influx of immune-competent cells and by aberrant proliferation of resident fibroblast-like synoviocytes. Accretion of fibroblasts directly contributes to joint destruction, through enhanced production of matrix-degrading enzymes, and indirectly, through excessive release of cytokines that boost the immune system. Targeting the proliferative fibroblast could facilitate regeneration of synovial joints.
11842822 Patients chosen for treatment with cyclosporine because of severe rheumatoid arthritis are 2002 Feb OBJECTIVE: To determine whether patients with rheumatoid arthritis (RA) selected for treatment with cyclosporin A (CSA) because of severe disease are more likely to carry HLA-DRB1 alleles encoding the conserved "shared epitope" (SE) sequence. METHODS: The majority of patients (n = 178) were currently being treated with methotrexate (MTX), either alone or in combination with chloroquine and/or CSA. In about 30% of patients, treatment with CSA had been initiated because of limited response to MTX or MTX and chloroquine. Patients were treated as clinically indicated without knowledge of their HLA-DRB1 status. HLA-DRB1 typing was by a reverse dot blot method. RESULTS: Patients that had been treated with CSA were significantly more likely to carry an SE allele than patients not treated with CSA (81.5% vs 60.5%; OR 2.9, p = 0.006). Patients with 2 SE alleles were the most likely to have been treated with CSA. Results were still significant after correction for age, sex, and disease duration in a logistic regression model. There was no association between rheumatoid factor positivity and requirement for CSA therapy. Examination of individual SE alleles by multiple logistic regression analysis indicated that the strongest association was with presence of HLA-DRB1**0401 (p = 0.004). The DRB1*0401/*0404 genotype provided the greatest risk of requiring CSA treatment. Patients selected for CSA treatment had developed RA at a significantly earlier age than those not requiring CSA (44.4 vs 51.3 yrs; p = 0.004). CONCLUSION: Patients requiring treatment with CSA because of severe RA were significantly more likely to carry an SE allele than patients not requiring such treatment. CSA treated patients were also more likely to have had earlier age of disease onset. These data provide further evidence that bearing the SE (particularly 2 alleles) is associated with development of severe RA.
14969051 Biochemical markers of joint tissue turnover in early rheumatoid arthritis. 2003 Sep The progression of rheumatoid arthritis (RA), a disease characterized by synovitis, cartilage degradation and bone erosion, is highly variable from patient to patient. New specific biological markers reflecting quantitative and dynamic changes in joint tissue turnover have been recently developed and include assays for type II collagen synthesis and degradation and synovitis. Increasing evidence from prospective studies in early RA indicate that some of these markers may be useful to predict the progression and identify patients at risk for rapid joint damage, before any damage is detected by radiography. Although studies on their value in assessing the efficacy of treatments are still limited, preliminary data in early RA suggest that biological markers will play an important role in the development and the early monitoring of disease modifying antirheumatic drugs with respect to future radiographic progression.
12415588 Longterm predictors of anxiety and depressed mood in early rheumatoid arthritis: a 3 and 5 2002 Nov OBJECTIVE: Heightened levels of anxiety and depressed mood are known to be common consequences of rheumatoid arthritis (RA). We examined the role of stress vulnerability factors in the longterm course of anxiety and depressed mood in patients with early RA. Specifically, the role of personality characteristics (neuroticism, extraversion), physical and psychological stressors (clinical status, disease influence on daily life, major life events), and coping and social support at the time of diagnosis were studied to predict changes in anxiety and depressed mood 3 and 5 years later. METHODS: Anxiety and depressed mood, predicted from clinical and self-reported assessments of stress vulnerability factors at the time of diagnosis in 78 patients with RA were assessed again after 3 and 5 years. RESULTS: A worse clinical status, more neuroticism, and lower education level at the time of diagnosis were all significantly related to increased psychological distress at the 3 and 5 year followup. However, the personality characteristics of neuroticism proved to be the most consistent and effective predictor of anxiety and depressed mood after 3 and 5 years, irrespective of initial distress levels, biomedical factors, use of medication, and other stressors or vulnerability factors. CONCLUSION: Results indicate the prognostic value of personality characteristics for longterm susceptibility to distress in patients with early RA, and emphasize the importance of paying close attention to factors unrelated to RA when screening for patients at risk.
11814479 Fucosylation of alpha1-acid glycoprotein (orosomucoid) compared with traditional biochemic 2002 Mar BACKGROUND: Fucosylation of alpha1-acid glycoprotein (AGP, orosomucoid) has previously been found to be increased in patients with rheumatoid arthritis. Furthermore, the degree of fucosylation has been suggested to reflect disease activity. Therefore, we investigated the fucosylation of AGP in 131 patients (96 women and 35 men) with recent onset rheumatoid arthritis (RA). We compared the results with traditional biochemical markers of inflammation, i.e. plasma concentrations of AGP (P-AGP), and C-reactive protein (P-CRP). METHODS: AGP fucosylation measured with a novel lectin enzyme-linked immunosorbent assay (ELISA) was compared with a disease activity score (DAS28) and its components, and with P-AGP, and P-CRP at the time of diagnosis, and at a follow-up visit 1 year later. RESULTS: Both men and women with RA had increased AGP fucosylation compared to healthy individuals. We found a weak correlation between AGP fucosylation and DAS28 only in men. In men with initially increased AGP fucosylation, the level of fucosylation correlated with the change in DAS28 during the first year following diagnosis. CONCLUSION: We conclude that AGP fucosylation is not superior to traditional markers of disease activity in RA. However, AGP fucosylation may give some additional information to traditional biochemical markers on the disease progression in men.
15230148 [Significance of tumor necrosis factor (TNF-alpha) in rheumatoid arthritis]. 2004 Tumor necrosis factor (TNF alpha) plays a key role in the pathogenesis of rheumatoid arthritis (RA), where both cell-mediated and humoral immune responses contribute to the destruction of cartilage and inflammation of synovium. This article presents genetics, properties and mechanisms of action of TNF alpha in RA. In addition, results of experimental and clinical studies are summarized, showing that treatment with antagonists against TNF alpha proved to be beneficial to the patients with RA by modifying the course of disease, slowing its progress and reducing its symptoms.
14738910 Interleukin-18 induces serum amyloid A (SAA) protein production from rheumatoid synovial f 2004 Feb 13 Interleukin-18 (IL-18) is a novel proinflammatory cytokine that was recently found in synovial fluids and synovial tissues from patients with rheumatoid arthritis (RA). To investigate the role of IL-18 in rheumatoid synovitis, the levels of IL-18 and serum amyloid A (SAA) were measured in synovial fluids from 24 patients with rheumatoid arthritis (RA) and 13 patients with osteoarthritis (OA). The levels of IL-18 and SAA in the synovial fluids were elevated in RA patients. In contrast, the levels of IL-18 in synovial fluids from OA patients were significantly lower compared to those of RA patients. SAA was not detected in synovial fluids from OA patients. The expression of SAA mRNA in rheumatoid synovial cells was also examined. SAA4 mRNA, which was constitutively expressed by rheumatoid synovial cells, was not affected by IL-18 stimulation. Although acute phase SAA (A-SAA, SAA1 + 2) mRNA was not detected in unstimulated synovial cells, its expression was induced by IL-18 stimulation. By immunoblot, we demonstrated that IL-18 induced the SAA protein synthesis from rheumatoid synovial cells in a dose-dependent manner. These results indicate a novel role for IL-18 in rheumatoid inflammation through the synovial SAA production.
15581648 Menstrual cycle influences on pain and emotion in women with fibromyalgia. 2004 Nov OBJECTIVE: This study examined the influence of the menstrual cycle on pain and emotion in women with fibromyalgia (FM) as compared with women with rheumatoid arthritis (RA) and to healthy controls. METHODS: One hundred and twenty-five premenopausal women (21-45 years old) participated in this study (57 with FM, 20 with RA, and 48 controls). Pain and emotion assessments were conducted during the follicular and the luteal phases of the menstrual cycle. RESULTS: Women with FM experienced more pain, menstrual symptoms, and negative affect than did women with RA and the controls. All women reported less positive affect during the luteal phase, although this pattern was more pronounced in women with FM and RA than in controls. CONCLUSION: Although FM pain did not vary across the menstrual cycle, these results point to the importance of considering the lower level and cyclical nature of positive affect when studying women with chronic pain.
13680151 Fatal outcome of constrictive pericarditis in rheumatoid arthritis. 2003 Nov This is a report of a 39-year-old patient diagnosed with seropositive rheumatoid arthritis at the age of 17. The patient died 2 years after the onset of extra-articular cardiac symptoms. This case demonstrates the devastating course of progressive constrictive pericarditis under sole medical therapy and emphasizes the importance of early radical pericardectomy to avoid progression of disease and secondary complications with fatal outcome. Further, we discuss risk factors, diagnostic caveats, diagnostic tests and therapy of hemodynamically relevant contrictive pericarditis.
12634237 Regional differences in Finland in the prevalence of rheumatoid factor in the presence and 2003 Apr OBJECTIVES: To look for possible regional differences in the prevalence of rheumatoid factor (RF) in the presence and absence of arthritis. METHODS: The study covered a representative sample of the Finnish population aged 30 years or over, primarily comprising 8000 people, of whom 7217 participated in the field survey carried out in 1978-80. RF from serum samples from 7116 subjects was determined by the Waaler-Rose (sensitised sheep cell agglutination) test. Titres >or=32 were regarded as positive and titres >or=128 as strongly positive. Arthritis was diagnosed by a thorough clinical examination. RESULTS: In the absence of arthritis the prevalence of positive and strongly positive RF reactions was 2.1% and 1.0%, respectively. The lowest prevalence of strongly "false positive" RF occurred in south western Finland. After adjustment for age, sex, smoking, and coffee consumption the odds ratio of having a strongly "false positive" RF reaction in eastern Finland was 3.16 (95% confidence interval 1.29 to 7.72) and in northern Finland 2.94 (1.13 to 7.64) compared with south western Finland. The corresponding odds ratio of strongly RF positive arthritis in eastern Finland was 5.08 (1.41 to 18.27). CONCLUSION: Regional differences are found in the prevalence of a strongly positive RF reaction in the Finnish population. The findings are in accordance with recent results from another study concerning regional differences in the incidence of rheumatoid arthritis in Finland.
12904892 The SCID mouse model: novel therapeutic targets - lessons from gene transfer. 2003 Aug The hallmark of rheumatoid arthritis (RA) is progressive destruction of the joints, preceded and accompanied by synovial hyperplasia and chronic inflammation. Spontaneous and induced animal models of RA reflect predominantly the inflammatory aspects of the disease. To reproduce the destruction of cartilage and bone mediated by an activated synovium, it was desirable to develop models that allow the dissection of cellular and molecular components derived from human tissue. The SCID mouse co-implantation model of human RA focuses on RA synovial fibroblasts (RA-SF) and their role in cartilage destruction. The model has provided the best evidence that RA-SF contribute significantly to matrix degradation, even in the absence of human lymphocytes and macrophages, since highly purified RA-SF invade the co-implanted normal human cartilage. Moreover, it became clear that they maintained their aggressive phenotype over long periods of time, particularly at sites of invasion into the co-implanted human cartilage. Targeting different signaling molecules, cytokines and matrix-degrading enzymes by soluble receptors, antagonists or negative mutants in the SCID mouse model of RA has implicated many of them in the mechanisms leading to cartilage destruction. However, since inhibition of a single molecule or pathway is not sufficient to inhibit the aggressive behavior of RA-SF it appears necessary to co-express in the synoviocytes genes for two or even more antagonists of e.g. cytokines, matrix-degrading enzymes or molecules interfering specifically with signaling pathways involved in the apoptosis of RA-SF. Based on the recent observation that the L1 (line-1) endogenous retroviral element appears responsible for the cytokine- independent activation via the MAPK p38delta, the current understanding of disease pathogenesis suggests that both the cytokine-dependent as well as the cytokine-independent pathways of joint destruction must be inhibited. Modulation of both pathways by gene transfer approaches in the SCID mouse model is a feasible method aimed at identifying novel targets for the prevention of cartilage destruction in RA.
14872451 Translation and validation of Arthritis Impact Measurement Scales 2 into Chinese: CAIMS2. 2004 Feb 15 OBJECTIVE: To evaluate the validity, reliability, and cultural relevance of the Arthritis Impact Measurement Scales 2 (AIMS2) as a health assessment tool for Chinese-speaking patients with arthritis. METHODS: The cultural relevance, language equivalency, and content validity of the AIMS2, Chinese version (CAIMS2) were evaluated by an expert panel. Measurement performance was tested on 240 subjects (rheumatoid arthritis = 81, osteoarthritis = 77, healthy = 82). Subjects (n = 175) were retested within 2 weeks for testing of reliability. RESULTS: Three items were modified and 2 items were added, as suggested by the expert panel. Interitem reliability was satisfactory (intraclass correlation coefficient 0.8552-0.9594). Test-retest reliability of the CAIMS2 subscales ranged from 0.770 to 0.952 in subjects in whom the CAIMS2 was self administered. Significant score differences between patients with arthritis and healthy subjects were found in all 12 subscales, except for the support from family and friends and tension subscales. CAIMS2 subscale scores correlated with clinical and laboratory measures of disease activity and patients' perceived quality of life as measured using the Chinese version of the World Health Organization Quality of Life instrument. CONCLUSION: Empirical data support CAIMS2 is a valid and reliable health status measure for Chinese speaking patients with arthritis.