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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
1430106 Disease severity in rheumatoid arthritis: relationships of plasma tumor necrosis factor-al 1992 Sep Rheumatoid arthritis is a complex inflammatory disease of unknown cause. Although various laboratory and clinical measurements are useful in managing these patients, there is a need for better tests to quantitatively assess disease activity. The purpose of this study was to investigate the association of certain immune and inflammation (I-I) parameters with four traditional disease severity measures and a functional measure in rheumatoid arthritis patients. A single set of patient blood samples was analyzed, and four traditional disease severity measures and patient functional statuses were determined from 64 consecutive outpatients with rheumatoid arthritis. Plasma tumor necrosis factor-alpha (TNF), soluble interleukin-2 receptor (sIL-2R), sCD4 and sCD8 (and the sCD4/sCD8 ratio), neopterin, and fibrin D-dimer were analyzed in relationship to Westergren erythrocyte sedimentation rate (ESR), physician assessment of disease activity, joint pain count, grip strength, and Arthritis Impact Measurement Scale (AIMS) scores. Rheumatoid arthritis patients had higher mean levels of all I-I measures (except sCD4) compared to healthy subjects. Initial significant correlations between TNF, sIL-2R, and D-dimer and several disease severity and functional measures were detected. When we controlled for the covariates age, gender, race, and medications, regression analyses indicated that, as a group, the I-I measures were significantly related to grip strength, physician disease severity rating, ESR, and total joint pain. When the predictive values of the I-I measures were tested controlling for the covariates and ESR, D-dimer was independently and significantly associated with variability in grip strength, physician disease severity, and AIMS physical disability, while TNF was associated with a significant amount of variability in total joint pain.(ABSTRACT TRUNCATED AT 250 WORDS)
8737724 The stimulation of mononuclear cells from patients with rheumatoid arthritis to degrade ar 1996 Mar OBJECTIVE: To study the modulation of mononuclear cell (MNC) activity in patients with rheumatoid arthritis (RA) by constituents released from human articular cartilage, which may be present in vivo during early events of the disease, when articular cartilage is not only mildly damaged. METHODS: In an attempt to stimulate RA MNC, cells were co-cultured with healthy or mildly damaged articular cartilage tissue. In addition, because of the reported cross-reactivity between cartilage constituents and mycobacterial heat-shock protein (hsp60), RA MNC sensitized with hsp60 were also co-cultured with cartilage tissue. Activation of the RA MNC was assessed by analysing the production of catabolic factors involved in joint damage. For this purpose culture supernatants of the treated RA MNC, comprising the catabolic factors, were added to freshly isolated articular cartilage explants. As a read out for catabolic activity, proteoglycan (PG) turnover by the explants was determined. RESULTS: Spontaneous activity of untreated RA MNC caused inhibition of PG synthesis and increased PG release upon addition of their culture supernatants to the cartilage explants. This MNC activity was not enhanced by the constituents released from healthy or mildly damaged cartilage tissue, whereas sensitization of RA MNC with hsp60 resulted in a 40% enhanced inhibition of PG synthesis. However, even under these pre-activated conditions no reactivity towards the cartilage constituents could be observed. CONCLUSION: Cartilage constituents released from mildly damaged cartilage tissue, as may be present during the early events of RA. do not modulate the catabolic activity of RA MNC.
8474062 Is there an interaction between low doses of corticosteroids and methotrexate in patients 1993 Feb A study of methotrexate (MTX) pharmacokinetics with and without prednisolone was performed in 33 patients with rheumatoid arthritis. Ten mg im MTX were given on Day 0; patients were divided into 3 groups of 11 persons: Group 1: no corticosteroid; Group 2: prednisolone 15 mg/day per os from D -3 on; Group 3: patients continuing longterm prednisolone treatment (15 mg/day). Groups 1 and 2 were randomized. MTX plasma concentrations were measured at T 0, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12 and 24 h using fluorescence polarization immunoassay (TDx Abbott). There was no difference between MTX pharmacokinetics of Groups 1 and 2. Area under the curve (AUC), Cmax and residual concentration at 24th h were higher, while total body and renal MTX clearances were lower in Group 3 vs Groups 1 and 2. Only the differences in AUC and total clearance were significant (p < 0.01 and p < 0.05). Tmax and terminal half-life did not differ. Our data suggest a possible influence of prednisolone on MTX pharmacokinetics in longstanding steroid treated patients. The pharmacological processes that might be involved are discussed.
7783055 Characterization and regulation of CD69 expression on rheumatoid arthritis synovial fluid 1995 Mar OBJECTIVE: To study CD69+ synovial fluid (SF) T cells and the mechanisms regulating CD69 expression in rheumatoid arthritis (RA). METHODS: One or 2 color flow cytometry was used to determine CD69 and other surface markers. Cultures of SF T cells alone or mixed with autologous SF non-T cells were used for CD69 maintenance assays. RESULTS: SF T cells were enriched in CD69+. These cells were mainly CD3+, CD8+ and CD25-. CD69 was maintained on SF T cells cultured with SF non-T cells but not when the former were cultured alone or in the presence of different supernatants from RA SF T and non-T cells cultures with sustained CD69 expression. Pretreatment of T and non-T cells with anti-CD18 monoclonal antibody inhibited CD69 expression, while paraformaldehyde-"fixed" non-T cells effectively maintained it. CONCLUSION: SF T cells exhibit a phenotype with evidence of past and recent activation. Our studies demonstrate that most of the recently activated SF T cells are CD8+. We also found that continuous cell-to-cell interaction between T and non-T cells are responsible for the maintenance of this particular state of activation of SF T cells.
7551652 Therapeutic monoclonal antibodies. 1995 Aug Monoclonal antibodies have been used extensively over the last few years in clinical trials of rheumatoid arthritis (RA). Not only are they potential therapeutic agents, but they are also useful probes into the immunopathogenesis of RA. Anti-tumour necrosis factor alpha (TNF alpha) monoclonal antibodies have been shown to be clinically efficacious. Although they produced rapid disease amelioration, the duration of clinical improvement was limited to 4-6 weeks. Re-treatments were again effective but long-term studies are required to assess their therapeutic role in RA. So far, the therapeutic effects of lymphocyte-depleting antibodies have been disappointing. From the data, it is clear that synovial lymphocytes are more difficult to eliminate than peripheral blood lymphocytes and it is likely that in order to delete all synovial lymphocytes, high doses of depleting antibodies will be required which could lead to severe immunosuppression. Hence, lymphocyte depletion may not be a feasible therapeutic strategy. However, there are a number of clinical trials currently underway attempting to inhibit CD4 lymphocyte function by non-depleting antibodies. In animal models of RA, such antibodies have been shown to induce long-term disease remission. Another possibility is to combine several monoclonal antibodies in order to induce disease remission in RA. This strategy has been used in murine collagen-induced arthritis in which a combination of anti-CD4 and anti-TNF alpha monoclonal antibodies was shown to be synergistic.
7795855 Alignment of total knee arthroplasty: the relationship to radiolucency around the tibial c 1995 Apr Between January 1982 and July 1985, 122 cemented 'Accord' total knee replacements were performed. Out of this number, 21 were lost to follow-up because of death (in 16), revision (2) due to infection, and failure to attend (3). The post-operative alignment of 101 prostheses were compared to the incidence of radiolucencies around the tibial component at 5 years follow-up. The mechanical axis was used as a reference. The mean alignment was 0.99 degrees valgus with a standard deviation of 2.48 degrees. Some 72% of knees were within 3 degrees and 94% within 5 degrees of true alignment. Using two methods of assessing radiolucencies there was a non-significant relationship between the alignment and radiolucencies. The alignment tolerance with this prosthesis is, therefore, at least 5 degrees.
8105626 Adverse immune reactions to gold in rheumatoid arthritis: lack of skin reactivity. 1993 Jun Adverse immune reactions develop in up to 30% of patients treated with gold compounds. However, sensitization to gold(I) drugs is rarely demonstrated by in vivo or in vitro testing. Recent data from a mouse model provides evidence that gold(I) is oxidized to gold(III) before T cells are sensitized. To study the diagnostic value of skin tests, patch testing with various gold compounds - including gold(I) and gold(III) - was performed in 50 patients with rheumatoid arthritis treated with gold(I) drugs. Positive patch test reactions to either gold(I) or gold(III) compounds were not detected. In contrast, the lymphocyte transformation test (LTT) revealed a gold(III)-induced response in one of the 7 patients being tested. We conclude that patch testing fails to indicate T cell sensitization to gold(I) drugs in rheumatoid arthritis patients. The in vitro response to gold(III) obtained by LTT supports the hypothesis that biooxidation of gold(I) compounds may play a crucial role for sensitization.
8669235 A 3-year follow-up of temporomandibular disorders in rheumatoid arthritis and ankylosing s 1996 Feb Sixteen individuals with rheumatoid arthritis (RA) and 19 individuals with ankylosing spondylitis (AS) participated in this 3-year follow-up study. The individuals in each disease group were allocated to an experimental group (E group) and a comparison group (C group). They were investigated by questionnaire, clinical examination of the stomatognathic system, and laboratory tests. The individuals of the two E groups had performed a physical training program of the stomatognathic system during 3 weeks. After 3 years most of the patients in the E groups reported an unaltered or decreased severity of symptoms and signs from the stomatognathic system compared with the initial status. The clinical dysfunction score according to Helkimo (CDS) was lower in the RA group, and the mouth opening capacity was larger than before training. In the AS group there was no long-term change in the CDS but an increase of mouth opening capacity. The general inflammatory disease process in the RA group showed an increased activity during this follow-up period as assessed by erythrocyte sedimentation rate. This study suggests that local physical training of the stomatognathic system has a positive effect in individuals with RA.
8498123 [Present possibilities and perspectives in rheumato-orthopedics]. 1993 After a brief introduction the author expands on specific problems in patients with rheumatoid arthritis and indications of rheumo-orthopaedic operations. He gives an account of the main objectives of these operations, i.e. prevention of deformities and correction of existing deformities, restoration or improvement of mobility and at least palliative influencing of pain. In the subsequent part the author discusses pre- and postoperative care. In the main part of the paper the author deals with his own rheumo-orthopaedic operations with emphasis on preventive and curative operations (synovectomies). As to reconstruction operations, he mentions resections in different anatomical areas, arthrodeses. He emphasizes in particular arthroplasties--from hemiarthroplasties to articular prostheses, so-called total endoprostheses. In the present paper the author analyzes in detail modern concepts, in particular in total endoprostheses of the hip joint, knee and minor joints of the hand.
8992007 How to evaluate measuring methods in the case of non-defined external validity. 1995 Oct In the clinical routine of chronic diseases, a new measurement has to be compared to an established criterion to see whether there is agreement on assessing disease progress. Because of the nonexistence of established criteria for rheumatoid arthritis the evaluation of grading systems for radiological assessment needs an alternative approach. Using the measurement error as a measure for repeatability and rater agreement in comparison to the progress of the grading score might be a solution to this dilemma.
1596701 An examination of the role of female hormones and pregnancy as risk factors for rheumatoid 1992 Jun While being female is known to increase the risk of developing rheumatoid arthritis approximately threefold, this study, by making use of a male control group, suggests that female sex hormones per se are unlikely to be the main cause of this discrepancy. Apart from the teens, when rheumatoid disease is extremely rare in males, the female/male incidence ratio remains almost constant throughout the adult age range, in spite of the reduction in endogenous oestrogen levels at the menopause. Pregnancy is known to ameliorate RA, but this study found that it was also the most common identifiable event preceding the onset of RA in women of childbearing age (22%), which may explain the apparent protective role of oral contraceptives in this age group.
8866589 Pleural fluid interferon-gamma and tumour necrosis factor-alpha in tuberculous and rheumat 1996 Aug Tuberculous and rheumatoid pleural effusions show features suggesting a strong local cellular immune response. Pleural fluid (Pf) from patients with tuberculosis, rheumatoid arthritis (RA) and other diseases were compared with respect to interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha). Immunoassays were used to determine Pf-IFN-gamma and Pf-TNF-alpha in 102 patients, including 11 with RA, 31 with verified tuberculosis, 23 with suspected tuberculosis, 11 with pneumonia, 14 with lung cancer and 12 with congestive heart failure. Measurable Pf-IFN-gamma occurred exclusively in patients with verified (median 1.8 ng x mL-1; 95% confidence interval (95% CI) 0.63-4.0 ng x mL-1) or suspected (0.37 ng x mL-1; 95%CI 0-0.7 ng x mL-1) tuberculosis. The highest median Pf-IFN-gamma was observed in those patients who showed a positive pleural fluid culture for Mycobacterium tuberculosis. In pleural effusions due to other diseases, including RA, IFN-gamma was undetectable. The highest Pf-TNF-alpha occurred in verified tuberculosis (median 198 ng x L-1; 95% CI 169-222 ng x L-1) and RA (210 ng x L-1; 95% CI 147-231 ng x L-1). Pleural fluid interferon-gamma is a highly useful marker for diagnosing tuberculous pleurisy. Although tuberculous and rheumatoid pleural effusions share several biochemical features, they are strikingly different with respect to interferon-gamma.
1628165 The effect of non-steroidal anti-inflammatory drugs on faecal flora and bacterial antibody 1992 Jul The faecal flora and bacterial antibody levels of 22 patients with active rheumatoid arthritis (RA) were compared with those of 26 patients with osteoarthritis (OA) undergoing comparable treatment with non-steroidal anti-inflammatory drugs (NSAIDs), and a further 22 patients with OA who were not receiving NSAIDs. Faecal counts of Clostridium perfringens were significantly higher in the RA patient group and in those OA patients receiving NSAIDs, compared with those OA patients not taking NSAIDs (P = 0.032, P = 0.0004 respectively). Total aerobic and anaerobic counts were, however, identical in all three groups. Levels of serum IgA antibody to the alpha toxin of Cl. perfringens were higher in the RA group and in the OA group taking NSAIDs than in OA patients not taking NSAIDs (P = 0.011, P = 0.055). Serum IgG antibody to alpha toxin was higher in the RA group than in OA patients both on and off NSAIDs (P = 0.019, P = 0.0072) and also a group of normal controls (P = 0.032). These results suggest that the increased faecal counts of Cl. perfringens together with the associated increased antibody levels seen in this and previous studies are more likely to result from NSAID therapy used to treat the disease than from a disease specific change in bowel flora.
8951506 Leflunomide, a novel immunomodulating drug, inhibits homotypic adhesion of peripheral bloo 1996 Nov OBJECTIVE AND DESIGN: A novel immunomodulating drug, leflunomide has been shown recently to be effective and well tolerated in patients suffering from rheumatoid arthritis (RA). The present study evaluated the effect of the drug on cell adhesion in RA. MATERIAL AND TREATMENT: Peripheral blood and synovial fluid mononuclear cells were obtained from a clinical trial, undertaken primarily to evaluate the efficacy and pharmacokinetic profile of multiple-dose pulsing leflunomide therapy in RA patients. PB MNC and corresponding synovial fluid (SF) MNC for in vitro homotypic aggregation (HA) assay were obtained from healthy volunteers and RA patients with active disease not treated with leflunomide in vivo. METHODS: Expression of activation antigens (CD25, CD54, CD69, CD71, HLA-DR) on peripheral blood mononuclear cells (PB MNC), as well as ex vivo ability of cells to aggregate spontaneously were determined in patients before entering into the clinical trial and at the end of 6 months treatment. HA was measured by aggregation in vitro. Data were compared by Student's t-test. RESULTS: There was a decreased expression of activation antigens and decreased spontaneous MNC clustering after leflunomide therapy. We found in the in vitro study that HA of PB and SF MNC was mainly mediated through beta 2-integrin molecules. The active metabolite of leflunomide, A77 1726, effectively suppressed both spontaneous and phorbol-ester (PMA)-induced HA. Disruption of cell aggregates by A77 1726 was dose-dependent and, most likely, unrelated to the quantitative modulation of integrin receptors. CONCLUSIONS: Results from this study support the idea that leflunomide elicits its immunomodulatory action, at least partially, by modulating the adhesion process.
7774099 A prospective study of the long-term efficacy and toxicity of low-dose methotrexate in rhe 1995 Jan OBJECTIVE: To determine the long-term efficacy and safety of weekly low-dose methotrexate (MTX) in rheumatoid arthritis (RA). METHODS: Fifty-one patients receiving MTX for RA were prospectively studied over a mean treatment period of 36 months. Standard clinical and laboratory measures of disease activity were assessed by the same investigator at baseline, and at 3, 6, 12, 24 and 36 months. RESULTS: The overall probability of continuing to take MTX was 80.3% at 12 months, 74.5% at 24 months, and 70.5% at 36 months. Of the 36 patients who completed 36 months of therapy, a significant improvement was noted compared to baseline in all of the clinical disease variables and acute phase reactants, with a steroid-sparing effect. There were no significant differences in these parameters between the 36-month visit and the 24- or 12-month visit. Adverse events occurred frequently (80.3%), but only 15.6% of the patients discontinued MTX permanently. Four patients (7.9%) withdrew due to a lack of efficacy. CONCLUSION: Our findings indicate that MTX remains effective over 36 months of therapy, with an acceptable toxicity profile.
7747147 Mortality from cancer in patients with rheumatoid arthritis. 1995 Data in nationwide Finnish registers were used to study the relationship between rheumatoid arthritis (RA) and site-specific cancers as a cause of death. The study included in all 1,666 subjects who had died in 1989 and who were entitled, under the nationwide sickness insurance scheme, to specially reimbursed medication because of RA. There were 277 deaths from malignancies. The proportion of such deaths in relation to all deaths declined with the duration of RA (p < 0.05). There was an excess of hematopoietic malignancies, particularly in males (p < 0.05). Deaths due to these malignancies, in relation to all cancer deaths, accumulated in long-lasting RA (p < 0.05). This suggests that hematopoietic malignancies arise as a complication of either RA or its treatment and to some degree argues against the notion of a shared etiological agent for these diseases.
7594511 Elevated Th1- or Th0-like cytokine mRNA in peripheral circulation of patients with rheumat 1995 Nov 15 The current studies examined whether cytokine patterns indicative of an imbalance in Th1 and Th2 cells could be identified in PBMC of patients with active rheumatoid arthritis (RA). To investigate this possibility, a reproducible PCR technique to assess cytokine mRNA levels in PBMC was employed that minimized in vitro manipulation of the cells. Seven of 14 RA patients had increased mRNA levels for IL-2, 5/14 for IFN-gamma, 3/14 for IL-4, and 4/14 for the IL-2R alpha-chain, compared with normal donors. Whereas 4 patients had elevated mRNA for IL-2 and IFN-gamma, indicative of an increase in activated Th1 or Th0 cells, 1 of 14 patients expressed low levels of IL-2 and IFN-gamma and high levels of IL-4 mRNA. Seven RA patients were treated with a mAb to ICAM-1 (CD54). To determine whether changes in cytokine mRNA levels might be associated with and/or account for the anti-inflammatory effect of anti-ICAM-1 mAb therapy, changes in cytokine mRNA levels were assessed and correlated with clinical improvement. Anti-ICAM-1 mAb administration was followed by a prompt and transient increase of IFN-gamma mRNA. Elevation of IFN-gamma mRNA expression throughout the treatment period reflected a temporary increase in the number of circulating CD3+CD4+ T cells, suggestive of altered circulatory patterns of activated Th1-like cells and was related to clinical efficacy. The results indicate that elevated cytokine mRNA levels characteristic for Th1 cells can be detected in the PBMC in active RA and, furthermore, that anti-ICAM-1 mAb may be beneficial in RA by altering the recruitment of activated Th1-like cells into the synovium. This assumption further strengthens the hypothesis of a significant contribution of Th1-like cells to the pathogenesis of RA.
8650656 [Disease-modifying drugs in rheumatoid arthritis. Duration of treatment and reasons for wi 1996 Mar 20 Duration of treatment and the reasons for discontinuing medication were studied in 360 patients with rheumatoid arthritis who had received in all 710 prescriptions for disease modifying antirheumatic drugs. The most frequently prescribed drugs were methotrexate, gold thiomalate, auranofin and sulphasalazine. Median duration of treatment ranged from 165 days (chlorambucil) to 341 days (methotrexate). The most common reason for discontinuing treatment with hydroxychloroquine was insufficient effect. The other drugs were most often discontinued because of adverse reactions. The probability of continued therapy with methotrexate after two years was 23% (Kaplan-Meier survival analysis), which is low compared with results from similar studies performed in other countries. This discrepancy may be due to differences both in local practices as regards monitoring of drug therapy and guidelines for conducting checks.
1614569 [Good 10-year results following cemented total knee arthroplasty]. 1992 Jun 20 The results of primary total knee arthroplasty in patients with a follow-up of 4-10 years are presented. The study population consisted of osteoarthritis as well as rheumatoid arthritis patients. Both groups were analyzed separately for postoperative pain reduction at rest and during activity, as well as for improvement of some daily activities (walking distance, stair climbing). Pain reduction at rest and during activity was maintained during the follow-up period of 4-10 years. The walking distance and the ability to climb stairs improved during the first few postoperative years, but declined in the later postoperative years. Survival curve analysis of the total knee arthroplasty showed good results for osteoarthritis as well as rheumatoid arthritis (estimated probability of survival of the prosthesis at 10 years' follow-up was 94%).
8992008 Future opportunities using technical advantages in picture processing and data transfer. 1995 Oct In recent years there have been many significant developments in the ability to process radiographic pictures and transfer the images from one location to another, and we can now examine the application of computers in the radiographic evaluation of rheumatoid arthritis. Image management and communication systems can assist in providing better health care while lowering costs. Although this work is still in its infancy, the rapid growth in both hardware capability and software techniques will soon make these techniques available to physicians everywhere. The expanding capability in the commercial world is being embraced by the radiology department, and will soon allow rheumatologists to access images at greater distances, and do more with the images which become available.