Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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8523336 | Combination drug therapy of seropositive rheumatoid arthritis. | 1995 Sep | OBJECTIVE: To determine the longterm morbidity and mortality in a cohort of 169 patients with seropositive rheumatoid arthritis (RA) treated by a single rheumatologist with remittive agents used in combination. The effectiveness of a regimen combining pulse oral methotrexate, azathioprine and an antimalarial drug (MAH) was examined in detail. METHODS: All outpatient visits by patients followed for at least one year and up to 18 years (mean 7 years) were abstracted. Remittive antirheumatic drugs were used in combination to achieve progressive improvement. Univariate and multivariate analyses of the differences between first and last visit results in 9 process or outcome variables were calculated for the entire cohort, for those patients receiving or not receiving MAH at last visit, and for those patients taking methotrexate but not in combination with both azathioprine and an antimalarial. The numbers of patients in remission (Lansbury articular index zero), and near remission (articular index < 6) were determined for each of these groups. A survival curve was calculated. RESULTS: The entire patient cohort showed improvement in every variable except hemoglobin at the time of the last visit (p < 0.0004). On multivariate analysis MAH patients were improved only in American Rheumatism Association functional class compared to the other groups (p < 0.0001). Remission and near remission rates overall were 43 and 61%; for MAH patients 45 and 69% (p = n.s.). Survival was no different from that of the general population. Herpes zoster (17 patients) and second attacks of varicella (2 patients) were the most striking side effects. Prednisone use was reduced from 34 to 19% of patients and the mean daily dose was lowered from 9.3 to 5.9 mg. CONCLUSION: Combination therapy with multiple antirheumatic agents successfully controlled joint inflammation in 167 of 169 patients with seropositive RA; complete remission was achieved in 43% of patients. Survival of this patient cohort did not differ from that of the general population. | |
1602345 | Capacitively coupled electrical field in the treatment of a leg fracture after total knee | 1992 | Electrical stimulation has been used as treatment for nonunions of fractures since the early 1950s, with a reported success rate of 80-85%. We report a case of nonunion of a tibial fracture below a revised total knee prosthesis treated with a capacitively coupled electrical field. After 3 months of treatment, consolidation of this difficult fracture was evident with abundant callus formation. | |
7656342 | Assessing the activity of rheumatoid arthritis. | 1995 May | Disease activity in rheumatoid arthritis is not easily measured. The validity of current measures has been reviewed. Recent international efforts have resulted in consensus over a minimum (WHO/ILAR) core set of endpoints in RA trials: pain, patient and physician (assessor) global assessment, physical disability, swollen joint count, tender joint count, acute phase reactants; and for studies of one or more years' duration: radiographs of joints. The near future will hopefully see validation of new measures, also in terrains not currently covered by the core set. | |
1636052 | Membrane-associated phospholipase A2 detected by a radioimmunoassay is a sensitive marker | 1992 Jun | To investigate the clinical significance of membrane-associated phospholipase A2 (M-PLA2) measured by a radioimmunoassay(RIA) in rheumatoid arthritis, we examined serum M-PLA2 concentrations in 16 patients with rheumatoid arthritis. All showed elevated levels of serum M-PLA2. On the other hand, serum concentrations of C-reactive protein (CRP) and IL-6 were increased in 13 (81.3%) and 14 (87.5%) of 16 patients, respectively. The serum concentrations of M-PLA2 were significantly correlated with those of CRP. These results indicate that M-PLA2 is an acute phase reactant and a sensitive and useful marker of inflammation in rheumatoid arthritis. | |
7932409 | The Sa system: a novel antigen-antibody system specific for rheumatoid arthritis. | 1994 Jun | OBJECTIVE: To describe a novel autoimmune system (Sa/anti-Sa) specific for rheumatoid arthritis (RA). METHODS: Antibodies were detected in immunoblots using human spleen and placenta extracts as antigens. Sera from 482 patients with various rheumatic diseases as well as from healthy controls were evaluated to define the disease associations of anti-Sa antibodies. RESULTS: Sera from 88 of 206 (42.7%) unselected patients with RA recognized specific protein bands (the Sa antigen) in immunoblots of spleen or placenta extracts, including 9 of 31 (29%) patients seen in the first few months after disease onset. Anti-Sa antibodies were found both in rheumatoid factor (RF) negative (17/63 or 27%) and in RF positive patients with RA (71/143 or 50%). They were nevertheless absent in RF positive patients with other connective tissue diseases (0/39). Antibodies to Sa were essentially found in sera from patients with RA (specificity 98.9%) being found only in 3 patients whose arthritides did not fulfill the ACR criteria. The positive predictive value of anti-Sa antibodies for RA was 96.7%, while its negative predictive value was 69.8%. Anti-Sa antibodies were predominantly of the IgG isotype, with titers varying from 1/50 to > 1/1000. The Sa antigen was characterized as a poorly soluble protein that is present in normal human tissues and that is distinct from all previously described RA associated autoimmune systems. CONCLUSION: Anti-Sa antibodies are a novel serological marker highly specific for RA. Since anti-Sa antibodies occur independently of RF, they can be used as an additional diagnostic tool. The molecular nature of the Sa antigen as well as its potential pathogenic role in a significant proportion of patients with chronic articular inflammation of the rheumatoid variety merit further definition. | |
7945479 | Somatostatin receptor imaging. The presence of somatostatin receptors in rheumatoid arthri | 1994 Oct | OBJECTIVE: To investigate the in vivo and in vitro expression of somatostatin receptors (SS-R) on synovial membranes of patients with rheumatoid arthritis (RA). METHODS: The joints of 14 consecutive patients with active RA, 4 patients with severe osteoarthritis (OA), and 30 control patients were studied. The somatostatin analog [111In-DTPA-D-Phe1]-octreotide was used for in vivo SS-R scintigraphy, and the somatostatin analog [125I-Tyr3]-octreotide for in vitro SS-R autoradiography. RESULTS: Seventy-six percent (220 of 290) of the painful joints and 76% (207 of 274) of the swollen joints of the patients with RA were visualized by SS-R scintigraphy. The degree of pain and swelling correlated well with positive scintigraphy findings in the joints (P < 0.0001). In 2 of the RA patients who underwent scintigraphy, as well as in 4 of 5 other patients, in vitro studies of the synovial membranes showed the presence of specific SS-R. In patients with OA, uptake of radioactivity in the affected joints was significantly lower than that in patients with RA. None of the joints of the control patients demonstrated uptake of radioactivity. CONCLUSION: SS-R are present in the synovial tissue of patients with active RA, as demonstrated by both in vivo and in vitro techniques. The potential value of SS-R scintigraphy in the clinical evaluation of patients with active RA is presently unknown. | |
8378855 | [The diagnostic significance of neutrophil adhesive reactions in rheumatoid arthritis]. | 1993 | Literature and original data on 97 RA patients concerning the diagnosis of rheumatoid vasculitis (RV) are presented. Study was made of CIC, rheumatoid factor, migration profiles of skin fenestra, IgG- and C3b-dependent adherence of peripheral blood neutrophils. The latter was found when elevated to relate to RV symptoms which was confirmed by skin biopsy. Feasibility of using the results of the study for RV diagnosis is discussed. | |
8346462 | [Cause of death in autopsied RA patients]. | 1993 Jun | A mortality study was performed based on the data of Annual of the Pathological Autopsy Cases in Japan in 1985-1989. The average life span of the RA patients, revealing 66.5 years in male and 64.6 years in female, was shorter than that of general population in Japan. Of 1,246 autopsied RA cases, the most common causes of death were infections (26.6%), respiratory diseases including interstitial lung disease (17.5%) and amyloidosis (12.5%). Amyloidosis was common among RA cases (25.2%), and it was suggested that RA was the most important underlying disorder of the secondary amyloidosis: in 1985 to 1989, 316 cases of 515 secondary amyloidosis (61.4%) were associated with RA. | |
7754805 | Rheumatoid arthritis and bone mineral density in elderly women. The Study of Osteoporotic | 1995 Feb | Previous studies have suggested that women with rheumatoid arthritis (RA) have decreased bone mineral density (BMD) in both the appendicular and axial skeleton. The purpose of this investigation was to determine the association of RA and BMD from a community-based sample of ambulatory Caucasian women age 65 and over. BMD was measured by dual-energy X-ray absorptiometry (DXA) at the hip and lumbar spine and by single photon absorptiometry (SPA) at the distal radius and calcaneus. Study subjects included 120 postmenopausal women with RA who were further classified according to corticosteroid use, i.e., never users, current users, and ex-users, and 7966 age-similar controls. Elderly women with RA had a lower age-adjusted bone density of the distal radius, calcaneus, hip, and lumbar spine. Women with RA who were current users of steroids had the lowest BMD at both appendicular sites and at the hip, but those who never used steroids also had a significantly decreased BMD at all sites. The BMD of women with RA who had never used steroids remained significantly decreased at the distal radius, calcaneus, and hip after adjustment for age, BMD determinants, and functional outcomes of RA. Functional outcomes of RA largely accounted for the lower BMD of women who were currently using steroids. Women with RA have lower appendicular and axial bone mass that is not attributable to the use of steroids. Those currently taking steroids have even lower appendicular and axial bone mass that may reflect their poorer functional outcome and is likely to increase the risk of fractures.(ABSTRACT TRUNCATED AT 250 WORDS) | |
1348220 | Sulfasalazine-induced pulmonary disease. | 1992 Apr | We report the findings in two patients with sulfasalazine-induced pulmonary disease. The first patient developed pulmonary interstitial fibrosis after more than 4 yr of treatment for Crohn's disease. Pulmonary symptoms and chest roentgenographic and pulmonary function abnormalities gradually reversed after stopping the drug. No specific treatment was given. The second patient, who had rheumatoid arthritis without pulmonary disease, received the drug for 1 yr without experiencing any problems. Readministration seven months later resulted in the development of an acute interstitial pulmonary disease. Discontinuing the drug and treatment with corticosteroids produced rapid improvement. We discuss these patients in relation to other reports of sulfasalazine-induced pulmonary toxicity, highlighting their atypical features. | |
1358037 | Circulating cytokine levels in patients with rheumatoid arthritis: results of a double bli | 1992 Aug | Interleukin 1 (IL-1), IL-6, and tumour necrosis factor (TNF) alpha are pleiotropic cytokines produced predominantly by macrophages which have been implicated in the pathogenesis of rheumatoid arthritis (RA). Sulphasalazine has been shown to have disease modifying properties and to inhibit the production of cytokines in vitro. To evaluate the effect of sulphasalazine on cytokine production in vivo, serum cytokine levels were measured in a group of patients with RA entered into a randomised controlled trial. Serum levels of IL-1 alpha, IL-1 beta, IL-6, and TNF alpha were measured at baseline and at two monthly intervals for six months in 17 patients receiving sulphasalazine and in 22 patients treated with placebo. The two groups of patients had a similar age and sex distribution, had had RA for less than a year, had no joint erosions, and had not been treated previously with any other disease modifying drugs. In the 39 patients studied IL-1 alpha was detected (> 0.1 ng/ml) at baseline in 14 patients (median 0.24 ng/ml), IL-1 beta in 25 patients (median 1.0 ng/ml), TNF alpha in 27 patients (median 1.2 ng/ml), and IL-6 in 33 patients (median 0.44 ng/ml). In the group treated with sulphasalazine there was a progressive and significant decline in serum IL-1 alpha, IL-1 beta, and TNF alpha levels over the six month period (median levels at six months were < 0.1, 0.12, and 0.44 ng/ml respectively). Interleukin 6 levels were significantly reduced only at the four month time point (median level of 0.23 ng/ml). These reductions were associated with improvements in clinical and laboratory measures of disease activity. In contrast patients receiving the placebo showed no changes in serum cytokine levels and no improvement in clinical and laboratory indices of disease activity. These results suggest that sulphasalazine may exert its disease modifying effect partly by suppressing cytokine production in vivo. | |
7966058 | Immunization of patients with rheumatoid arthritis against influenza: a study of vaccine s | 1994 Jul | OBJECTIVE: To address the issues of immunogenicity and local and systemic reactions to vaccination with influenza vaccine in patients with rheumatoid arthritis (RA). METHODS: One hundred and twenty-six patients with RA were stratified into 3 groups: (1) those with a history of vaccination with influenza vaccine within 24 months who were receiving usual therapy for RA, (2) those receiving usual therapy for RA but without prior vaccine, and (3) those receiving immunosuppressive medication or prednisone > or = 7.5 mg/day, irrespective of their prior immunization status. Within each group, patients were randomized to receive vaccine or placebo. A group of age matched, healthy controls were also vaccinated. RESULTS: During a one month followup period, adverse reactions occurred with equal frequency among patients with RA and healthy controls. Similar significant increases in titers to the vaccine were seen in all groups of patients with arthritis and in the controls. CONCLUSION: The potential increase in susceptibility to influenza and death from respiratory illness in patients with RA and the demonstrated safety and immunogenicity of influenza vaccine should require the inclusion of patients with RA in standard immunization programs. | |
7734477 | Therapeutic exercise in rheumatoid arthritis. | 1994 Dec | Although about 80% of individuals with rheumatoid arthritis [RA] are functionally independent on any given occasion [1], substantial functional disability is often observed over time in the average patient [2]. One important goal in rehabilitation of individuals with RA is the prevention of functional decline, and therapeutic exercise is frequently used for this purpose. The target population for therapeutic exercise consists mainly of functionally independent persons with RA [3]. For these individuals, aerobic exercise seems superior to nonaerobic methods of exercise [4]. Likewise, dynamic exercise, requiring muscle work during joint motion, appears to be superior to static or isometric exercises [5]. | |
8088070 | Antibodies to 65Kd heat-shock protein were elevated in rheumatoid arthritis. | 1994 Jun | Antibodies to 65Kd heat-shock protein (hsp) of mycobacterium leprae were measured by enzyme-linked immunosorbent assay (ELISA) in the three immunoglobulin classes in paired sera and synovial fluids of patients with rheumatoid arthritis (RA). Titers of anti-hsp antibody were expressed by optical density (OD) values for sera or indexes (OD values divided by amounts of immunoglobulin in each class) for synovial fluids and for their paired sera. Indexes of anti-hsp antibody were higher in synovial fluids than those in sera at 15/18 for IgG, 17/18 for IgA and 16/18 for IgM class. These results suggest the participation of anti-hsp antibodies to synovitis in RA. | |
7797962 | Distal ulnar instability following wrist arthrodesis in men. | 1995 Apr | 11 male patients with rheumatoid arthritis and 14 with osteoarthritis had total arthrodesis of the wrist. All patients with rheumatoid arthritis and ten (71%) of those with osteoarthritis had distal ulnar excision, two of the latter as a secondary procedure for impingement. Seven patients with osteoarthritis and none of the rheumatoid patients developed painful instability of the distal end of the ulna following excision. It is suggested that, in male patients with rheumatoid arthritis, distal ulnar excision with wrist arthrodesis produces excellent results with no complications. However, in male patients with osteoarthritis attempts should be made to avoid excessive shortening and ulnar impingement. If distal ulnar surgery is required, a procedure that does not affect the stability of the distal radio-ulnar joint should be performed rather than distal ulnar excision. | |
8424833 | HLA-DR4 subtypes in New Zealand Polynesians. Predominance of Dw13 in the healthy populatio | 1993 Jan | OBJECTIVE: To analyze HLA-DR4 alleles in New Zealand Polynesians with rheumatoid arthritis (RA). METHODS: Thirty Polynesians and 30 Caucasians with RA, as well as 65 Polynesian and 60 Caucasian healthy blood donors, were DR4 subtyped using the polymerase chain reaction and sequence-specific oligonucleotide probes. RESULTS: The frequency of DR4 (DRB1*04) was increased in both Polynesian (P < 0.001) and Caucasian (P < 0.005) RA patients compared with race-matched controls. Dw4 (DRB1*0401) was detected in 15 of 30 Caucasian patients but only 2 of 30 Polynesian patients (P < 0.001). In Polynesians, RA was associated with Dw15 (DRB1*0405), which was present in 11 of 30 patients and 3 of 65 controls (P < 0.001). Dw13 (DRB1*0403) was the most frequent DR4 allele in healthy Polynesians, but was not significantly associated with RA. CONCLUSION: The predominance of the Dw13 subtype in Polynesians may explain in part the low prevalence of RA in this population. The association of Dw15 with RA in Polynesians supports the hypothesis that the third hypervariable region of DR beta determines susceptibility to RA. | |
1578448 | Functional disability in rheumatoid arthritis: two different models in early and establish | 1992 Mar | A hypothesis that the development of functional disability in rheumatoid arthritis (RA) would be more rapid at the beginning than in established disease was studied in a group of 82 patients with RA referred to the Rheumatology Unit of Nancy, France. The relationship between disease activity, articular destruction and functional disability indicated a significant interaction (moderating effect) of disease duration. Two different models are proposed to explain functional disability. A model for early RA (less than 5 years duration) includes biological activity, and a model for established disease (more than 5 years) includes disease duration, extraarticular lesions and radiographic damage. These models could be useful in designs of therapeutic trials. | |
7585180 | Marked amelioration of established collagen-induced arthritis by treatment with antibodies | 1995 Aug | CD23 is a low-affinity receptor for immunoglobulin E (IgE) expressed by a variety of haematopoietic cells. Proteolytic cleavage of the transmembrane receptor generates soluble forms, which can be detected in biological fluids. CD23 regulates many functional aspects of immune cells, both in its cell-associated and soluble forms. In view of the increased levels of CD23 in rheumatoid arthritis, we have studied the effect of neutralizing CD23 in type II collagen-induced arthritis in mice, a model for human rheumatoid arthritis. Successful disease modulation is achieved by treatment of arthritic DBA/1 mice with either polyclonal or monoclonal antibodies to mouse CD23. Treated mice show a dose-related amelioration of arthritis with significantly reduced clinical scores and number of affected paws. This improvement in clinical severity is confirmed by histological examination of the arthritic paws. A marked decrease in cellular infiltration of the synovial sublining layer and limited destruction of cartilage and bone is evident in animals treated with therapeutic doses of anti-CD23 antibody. These findings demonstrate the involvement of CD23 in a mouse model of human rheumatoid arthritis. | |
8085060 | [Clinical usefulness of rheumatoid factor in synovial fluid. Re-evaluation]. | 1993 Dec | The aim of this work is to analyze the usefulness of rheumatoid factor determination in synovial fluid. One hundred twenty nine patients (29 with rheumatoid arthritis), in whom rheumatoid factor was simultaneously determined in serum and synovial fluid, were retrospectively analyzed. Serum rheumatoid factor had a 48% sensitivity, 98% specificity, 88% positive predictive value and 87% negative predictive value for the diagnosis of rheumatoid arthritis. These numbers were 76, 79, 51 and 92% respectively for synovial fluid rheumatoid factor. In rheumatoid arthritis of less than one year of evolution, serum and synovial rheumatoid factor have a sensitivity of 15% and 62% respectively, a positive predictive value of 50 and 28% respectively and a negative predictive value of 90 and 94% respectively. It is thus concluded that the absence of rheumatoid factor in serum and synovial fluid in a patient with arthritis of less than one year of evolution, renders the diagnosis of rheumatoid arthritis very unlikely. Likewise the simultaneous presence of rheumatoid factor in both fluids has a high diagnostic certainty. Among other studied variables, leukocyte count, C3 and C4 levels in synovial fluid are the best discriminators within the different diagnostic groups. | |
8391953 | Metalloproteinase inhibitors as therapeutics. | 1993 Mar | Matrix metalloproteinases (MMPs) are a family of enzymes which contain zinc at their active site and can degrade most of the matrix macromolecules found in connective tissues. These MMPs are secreted by connective tissue cells and infiltrating leucocytes in response to inflammatory mediators. There is now widespread recognition that MMPs are the major class of proteinases responsible for the excessive degradation of cartilage that leads to joint dysfunction in rheumatoid arthritis. The properties of the MMPs are reviewed and a therapeutic role for synthetic, zinc-binding pseudopeptide MMP inhibitors in the treatment of arthritis is proposed. |