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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
9127856 Photodynamic laser therapy for rheumatoid arthritis. Cell culture studies and animal exper 1997 The introduction of arthroscopic techniques has improved the surgical therapy of rheumatoid arthritis. The additional application of the holmium:yttrium aluminum garnet (Ho:YAG) laser likewise holds great promise by providing complete hemorrhagic control. Unfortunately, a minimally invasive solution for use in smaller joints has not yet emerged. The present study describes the possible treatment of these joints by means of photodynamic laser therapy. Cell culture studies with human synovial fibroblasts obtained from patients with rheumatoid arthritis have demonstrated a cytotoxic effect after administration of Photosan-3 as a photosensitizer and subsequent laser irradiation at 630 nm. for the in vivo studies, IgG-induced arthritis in rabbits, which is histologically consistent with the proliferative phase of rheumatoid arthritis, was used as the animal model. The histologic picture following photodynamic laser therapy with Photosan-3 revealed complete synovial destruction which also extended to the border of the subjacent joint capsule. In contrast, bradytrophic structures, e.g. cartilage. menisci, and ligaments, remained unchanged at both the macroscopic and microscopic levels. Therefore, photodynamic laser therapy can be considered a new method in the surgical treatment of inflammatory disease of the synovial membrane. It has the advantage of being minimally invasive, while offering a high degree of efficacy and selectivity.
9177916 Oxidative burst of neutrophils in patients with rheumatoid arthritis: influence of various 1997 May OBJECTIVE: Toxic oxygen products are believed to be implicated in tissue damage in some complex-mediated diseases such as rheumatoid arthritis. In the present study we compared the superoxide (O2) production of polymorphonuclear leukocytes (PMNs) in 21 patients with rheumatoid arthritis (RA) with that of 9 healthy controls, examining the effect of different stimulants and cytokines on the oxidative burst (OB). Since many drugs used in the treatment of RA may alter O2 metabolism, the effects of antirheumatic medication were also studied. METHODS: Generation of superoxide anions was analysed by a flow cytometric method, using the fluorochrome dihydro-rhodamine. As stimulants for OB, we used N-formyl-methionyl-leucyl-phenylalanine (fMLP), which acts via a membrane receptor, and phorbol-myristate acetate (PMA), which acts in a membrane receptor-independent manner. As preactivating substances, TNF-alpha, G-CSF and GM-CSF were applied. RESULTS: In RA patients under treatment with antirheumatic medication, fMLP-induced OB (+/- cytokines) was significantly reduced, while O2 production after stimulation with PMA was similar compared to controls. GM-CSF showed the highest level of preactivation in controls, whereas in RA patients TNF-alpha proved to be most potent. In both controls and RA patients, a combination of GM-CSF or G-CSF with TNF-alpha further enhanced OB. No correlation between OB and clinical data or treatment could be established in RA patients. CONCLUSIONS: There is a reduced cytokine priming capacity for OB in RA patients under antirheumatic medication in spite of the presence of an intact enzyme system of OB. Antirheumatic medication combining multiple drugs capable of decreasing OB might effectively modulate oxidative metabolism.
9668731 A comparison of IgM rheumatoid factor by nephelometry and latex methods: clinical and labo 1998 Apr OBJECTIVES: To study the comparative performance characteristics of nephelometric and IgM latex rheumatoid factor (RF) with regard to diagnosis, to determine the level of test result that most accurately classifies patients as having rheumatoid arthritis (RA) versus noninflammatory rheumatic disorders, to develop mathematic and graphic conversion tools, and to determine the usefulness of serial nephelometric RF factors test in assessing change in clinical status. METHODS: Sera and clinical measurements were obtained from 576 rheumatic disease patients during routine clinic visits and were analyzed by latex and nephelometric methods. RESULTS: Nephelometric and latex methods were highly correlated (0.872) and generally equivalent in their ability to discriminate between RA and noninflammatory conditions. Serial measures of RF were correlated with changes in clinical activity, but were much less effective in this respect than erythrocyte sedimentation rate or C-reactive protein. CONCLUSION: Both tests yield equivalent results. Mathematic and graphic models will allow conversion between tests so that clinicians can use either or both methods effectively. RF is modestly correlated with changes in clinical activity and therefore is not a useful measure to follow clinical improvement or worsening.
11725831 Successful treatment of patients with rheumatic disorders and acquired factor VIII inhibit 2001 Sep Acquired haemophilia associated with autoimmune disorders can be fatal and has been reported to be refractory to steroid therapy alone. We report two cases of female patients, aged 24 years and 54 years, with acquired haemophilia caused by factor VIII inhibitors. Underlying diseases were systemic lupus erythematosus in the 24-year-old patient and rheumatoid arthritis in the 54-year-old patient. Both conditions were nearly quiescent when the patients manifested haemorrhagic diathesis. In response to combination therapy with prednisolone and cyclophosphamide, coagulation abnormalities were resolved together with complete elimination of factor VIII inhibitors in both patients. Thus, combination therapy with alkylating agents may be recommended as initial therapy for the management of autoimmune patients with factor VIII inhibitors.
10394301 [Immobilized antigenic preparations with magnetic properties in the diagnosis and treatmen 1999 A procedure was first developed to prepare the immobilized granulated antigen agents (IGAA) based on collagens of types I, II, III, IgG, native DNA, RNA, cardiolipin, superoxide dismutase, and glutathione reductase. The agents were applied to both immunofluorescence and enzyme immunoassay to identify specific antibodies. IGAA were effective in early diagnosis, prognosis, and control of therapy for systemic lupus erythematosus, systemic sclerosis, rheumatoid arthritis due to their high capacity. These antigen agents were used in vitro and in vivo in hyperimmune laboratory animals as magnetic sorbents and exhibited high capacities and low traumatic properties for blood cells. IGAA may be regenerated, sterilized, and reused.
9592865 Treatment of DMARDs-resistant rheumatoid arthritis with minocycline: a local experience am 1998 We report a local experience with minocycline (100 mg b.i.d.) in treating Chinese patients with rheumatoid arthritis (RA) who were resistant to the conventional disease-modifying antirheumatic drug (DMARD) treatment. In contrast to a preliminary observation in seven patients with rheumatoid arthritis, minocycline was effective and safe in treating our patients when added to the previous, relatively ineffective DMARD regimen. The antirheumatic effect of minocycline was impressive early in the first month. Drug compliance was fair; all patients continued to receive the study drugs, with no obvious adverse drug reactions. The reason why minocycline showed dramatic effects in reducing disease activity remains to be determined; however, minocycline-associated immune modulation, as indicated in this study, may be one of the important mechanisms in its antiarthritic effects.
10813278 Serum C-reactive protein does not predict rheumatoid arthritis. 2000 May OBJECTIVE: Clinical rheumatoid arthritis (RA) is preceded by an immunological process. Our objective was to investigate C-reactive protein (CRP) for its prediction of RA. METHODS: A case-control study was nested within a Finnish cohort of 19,072 adults who had no arthritis and no history of the disease at the baseline examination conducted between 1973 and 1977. By late 1989, 124 had developed RA. Three controls for each incident case were individually matched for sex, age, and municipality. The CRP concentration was measured by a sensitive ELISA. RESULTS: No difference was noted in serum CRP levels between cases and controls. The odds ratios (95% confidence intervals) of RA in the quintiles of CRP were 1.0, 0.89 (0.45-1.76), 1.11 (0.59-2.08), 0.99 (0.51-1.91), and 0.95 (0.49-1.87). Similarly, there was no difference when the data were analyzed in strata of sex, age, rheumatoid factor (RF) status at baseline, and length of time from taking the specimens to the onset of clinical disease. CONCLUSION: Pre-rheumatoid immunological process as reflected in RF production is not associated with any marked inflammation or tissue injury heightening CRP.
9359924 Muscle strength in rheumatoid elbow: quantitative measurement and comparison to Larsen's X 1997 Oct Accurate assessment of elbow function is important to determine the total ability of the arm. The purpose of this study was to clarify the relationship between isometric muscle strength of the elbows of patients with rheumatoid arthritis (RA) and Larsen's X-ray evaluation. Fifty-six elbows of 45 RA patients aged 47 to 77 years (mean age, 63 years) were tested. Muscle strength was measured with an isometric torque-cell dynamometer. Test-retest reliability of the dynamometer was proven by measuring 12 elbows of 6 healthy young men. In RA patients, elbow flexion and extension strength decreased in proportion to increases in the severity of Larsen's grades from Grade 1 to 4. However, Grade 5 elbows had greater muscle strength than those in Grade 4. Forearm pronation and supination strength also decreased in proportion to increases in the severity of Larsen's grades from Grade 1 to 5. This quantitative study made it clear that the muscle strength of RA patients' elbows almost completely correlates to X-ray finding according to the grade of Larsen's evaluation based on X-rays. With regard to muscle strength of postoperative elbows, both flexion strength and supination strength after total elbow replacement (TER) were about two times greater than before TER, and after synovectomy it was as great as those in non-operative RA patients of Grade 2.
10589369 Combination therapy with DMARDs and biological agents in collagen-induced arthritis. 1999 Nov There is increasing interest in the use of combination therapy for rheumatoid arthritis and in the possibility of combining the conventional drug approach with newer biological therapies. Animal models of arthritis provide important tools for evaluating novel forms of therapy and for eludicating mechanisms of drug action. In this paper, we review the results of our own research into combination therapy in collagen-induced arthritis using biological therapies such as anti-tumor necrosis factor alpha, anti-CD4, and anti-interleukin 12 monoclonal antibodies, and small molecular weight compounds such as cyclosporin and the phosphodiesterase IV (PDE IV) inhibitor rolipram.
10812492 Broadening of the T cell receptor spectrum among rheumatoid arthritis synovial cell-lines 2000 Mar OBJECTIVE: The aim of the study was to evaluate the T cell receptor (TCR) family usage in T cell-lines from subcutaneous nodules and synovium from patients with rheumatoid arthritis (RA), with specific reference to the duration of symptoms. In vitro adherence characteristics of nodular T cells was studied as well. METHODS: Monoclonal antibodies were used to determine the distribution of TCR families in T cell-lines from synovium of patients with early and long-standing RA, from rheumatoid nodules and control tissues. An in vitro binding assay with T cell-lines from 2 rheumatoid nodules was performed. RESULTS: In early RA synovium, a restricted TCR family usage was observed in 5 out of 8 patients, contrary to long-standing disease, peripheral blood, ileum and colon. In RA nodules, a similar degree of restriction was noted. Moreover, the same TCR family was overexpressed by T cell-lines from different nodules derived from the same patient. T cell-lines from rheumatoid nodules demonstrated a preferential in vitro adherence to rheumatoid synovium and rheumatoid nodules, while no binding was observed on skin or tonsil. CONCLUSION: The TCR spectrum among RA synovial cell-lines broadens in relation to the disease duration. The overexpression of the same TCR family in different rheumatoid nodules from the same patients, and the in vitro adherence of T cell-lines from rheumatoid nodules may be indicative for recirculation between the different disease manifestations in RA.
10589352 Pyramids to myriads: the combination conundrum in rheumatoid arthritis. 1999 Nov Rheumatoid arthritis continues to be a cause of significant morbidity and disability. Increased understanding of the immunopathogenesis of the disease, of its progression over time, and of patient characteristics which correlate with outcome, have allowed more appropriate therapy. However, currently available disease-modifying therapy fails to adequately control disease in many patients, and many combinations of these drugs have therefore been described. In this review, we critically evaluate the existing literature, identifying combinations for which reasonable evidence of efficacy exists, and highlighting important issues in interpreting such evidence as well as issues of drug monitoring in such patients.
11094430 Association of MHC and rheumatoid arthritis. Regulatory role of HLA class II molecules in 2000 Human leucocyte antigen (HLA) class II molecules have been shown to be associated with predisposition to rheumatoid arthritis (RA). We generated HLA-DR and DQ transgenic mice that lacked endogenous class II molecules to study the interaction between the DR and DQ molecules and define the immunologic mechanisms in rheumatoid arthritis. Using collagen-induced arthritis (CIA) as an experimental model for inflammatory polyarthritis, we show that both DQ and DR are involved in predisposition or resistance to arthritis. Our studies suggest that polymorphism in DQB1 genes may determine predisposition to RA while the DRB1 polymorphism may dictate severity/protection of the disease. These mice provide powerful tools to develop immunotherapeutic protocols.
9673724 Diagnostic value of the multifrequency tympanometry in active rheumatoid arthritis. 1998 May We carried out a functional evaluation of the malleus-incus and incus-stapes joints in 37 patients with rheumatoid arthritis using multifrequency tympanometry. As a reference point, we calculated the resonance point using two different methods, and the results obtained were classified into two groups according to the phase of the disease: active, with clinical affection of the joint and with no medication; and inactive, asymptomatic. The results were compared with previously published criteria indicating normality, which underlined a significant correlation in the analysis of the resonance point between both groups, and which determined the value of multifrequency tympanometry in that stage and reactivation of the rheumatoid arthritis in active phase.
11808985 Is hypocomplementemia useful for diagnosing or predicting extra-articular manifestations i 2001 Dec OBJECTIVE: Serum CH50 and C4 levels are usually normal or elevated in rheumatoid arthritis (RA) but are classically decreased in patients with serious extra-articular manifestations (SEAMs) of the disease. The objective of this study was to evaluate whether complement assays are useful in diagnosing or predicting SEAMs of RA. METHODS: First, a cross-sectional study of 405 patients admitted for RA compared patients with and without hypocomplementemia. Then, a retrospective longitudinal design was used to investigate within-patient complement level variations overtime. RESULTS: In the univariate analysis, patients with low CH50 and C4 levels were more likely to have vasculitis and/or cryoglobulinemia than those with normal CH50 and C4 levels, and nodules were more common in the patients with low than with normal C4 levels. In a multivariate model based on symptoms, low C4 was associated with vasculitis and pleurisy and low CH50 with vasculitis. However, these associations were too weak to make CH50 and C4 determination useful for detecting SEAMs, and the within-subject variations in patients with SEAMs limited the predictive value of these assays. CONCLUSION: Hypocomplementemia is of limited usefulness for detecting or predicting SEAMs.
9818647 High serum prolactin levels in men with rheumatoid arthritis. 1998 Nov OBJECTIVE: High prolactin (PRL) levels have been reported in systemic lupus erythematosus, Reiter's syndrome, and psoriatic arthritis. However, results of PRL investigations in rheumatoid arthritis (RA) are contradictory. We evaluated the PRL status in men with RA and the possible effect on bone mineral density (BMD). METHODS: We studied 91 men with RA and 68 controls. PRL serum levels were analyzed under standardized conditions. Sex hormones (testosterone, androstenedione, and DHEAS) were also studied. BMD was analyzed at L2-L4 and the femoral neck by Hologic QDR1000. Comparative tests, linear correlations, and multiple regression analysis were performed. RESULTS: Serum PRL levels were significantly higher in men with RA (249+/-162 mU/l) than in controls (189+/-85 mU/l) (p=0.0015). High PRL levels were significantly correlated with the duration of RA (r=0.23; p=0.01) and with functional stage according to the Steinbrocker classification (r=0.24; p=0.01). High PRL concentrations were not correlated with the low levels of androgens observed in males with RA. Femoral BMD showed a negative correlation with PRL concentrations (r=0.20; p=0.04). Nevertheless, PRL was not a significant determinant of BMD. CONCLUSION: Men with RA have high serum PRL levels and concentrations increase with longer disease evolution and worse functional stage. Prolactin levels do not have a direct effect on BMD.
11561106 Successful treatment of rheumatoid arthritis is associated with a reduction in synovial me 2001 Sep OBJECTIVE: To investigate the change in synovial membrane cytokine content and cell adhesion molecule expression in sequential biopsies from the same knee joint of patients with rheumatoid arthritis, before and following anti-rheumatic drug treatment and to assess the relationship of these changes with clinical responses to the drug treatment. METHODS: A selected group of patients with rheumatoid arthritis, some of whom had achieved a disease remission based on American College of Rheumatology (ACR) criteria, were included in this study. Sequential synovial biopsies obtained before and throughout the treatment period were studied by immunohistochemical labelling techniques for the cellular content, production of a range of pro- and anti-inflammatory cytokines and the expression of cell adhesion molecules. The staining was quantitated using computer-assisted digital image analysis. RESULTS: There was a decrease in tumour necrosis factor-alpha (TNFalpha) and interleukin-1beta (IL-1beta) production in the synovial membrane lining and sublining of all patients who responded to treatment. The changes in IL-1 receptor antagonist production were variable. Paradoxically, there was a trend to decreased synovial membrane production of the anti-inflammatory cytokines, IL-10 and transforming growth factor-beta (TGFbeta), while IL-4 was not detectable in any of the synovial membrane biopsies. A significant reduction in the density and total amount of E-selectin expression in the synovial membrane was seen. Similarly, intercellular adhesion molecule-1 (ICAM-1) expression in the lining and sublining was decreased in those patients who had a significant clinical response to drug treatment or attained disease remission. There were no consistent or significant changes seen in the expression of other cell adhesion molecules in the synovial membranes of these patients. CONCLUSIONS: Successful drug treatment of rheumatoid arthritis patients is characterized at the synovial membrane level by a decrease in TNFalpha, IL-10 and TGFbeta production. Some (E-selectin and ICAM-1) but not all (P-selectin, VCAM-1, PECAM-1) cell adhesion molecules are modulated in patients who respond clinically to drug treatment. E-selectin and ICAM-1 may be important targets for the development of future drug treatments for rheumatoid arthritis.
9455968 Rheumatoid arthritis in the elderly: is it a different disease? 1997 Dec 29 Controversy has surrounded the question of whether rheumatoid arthritis (RA) afflicting the elderly is a different disease than RA in younger patients. Resolution of this complex question requires careful consideration of the pathogenesis of the disease and its diagnosis and prognosis. Meaningful analysis of these factors optimally derives from a critical review of all relevant medical literature (i.e., an evidence-based approach); however, methodologic inconsistencies and other difficulties with the literature on this subject largely preclude definitive interpretation. This review examines the evidence concerning various aspects of RA in the elderly population.
10685794 Cells expressing dendritic cell markers are present in the rheumatoid nodule. 2000 Feb OBJECTIVE: To determine if dendritic antigen-presenting cells (DC) are present in rheumatoid nodules, as has been reported in the synovial lesions of rheumatoid arthritis. METHODS: Nodules (n = 14) were examined with monoclonal antibodies (Mab) recognizing the DC differentiation/activation markers CD83, CMRF44, and CMRF56 and an antibody recognizing the CD1a antigen present on epithelial tissue associated DC. Results. Cells expressing CMRF44 were common in rheumatoid nodules, comprising 22% of nucleated cells versus 13% in synovial membranes (n = 10). Cells positive for CD1a (5%) and CD83 (2%) were less common. A majority (86%) of CMRF44 positive cells were also positive for the macrophage marker CD14. This left a significant minority of putative DC that were single stained with CMRF44. CONCLUSION: Cells bearing DC markers are as frequent in the rheumatoid nodule as in the synovial lesions. A majority are "indeterminate" cells that are CD14 positive but a proportion are single stained putative DC. The lack of lymphoid collections containing DC and T and B lymphocytes in the nodule suggests that local presentation of antigen may not occur in the rheumatoid nodule, as is thought to be the case in synovial membranes containing lymphoid follicles. This difference could potentially be explained by different states of activation, and differentiation of DC within the 2 lesions.
9135914 Rehabilitation advances in the treatment of arthritis and musculoskeletal disease. 1997 Mar The current literature is reviewed related to three disease processes commonly encountered by the physiatrist, rheumatologist, and internist in clinical practice, including osteoarthritis, rheumatoid arthritis, and osteoporosis. These diseases often have effects beyond the pathology that has an impact on the individual's function and integration into society. Emphasis is on the specific rehabilitative approach to the individual.
10225742 Theoretical background of effect mechanism by extracorporeal immunomodulation. 1997 Aug Therapeutic plasmapheresis has usually been applied to diseases with unknown causes. Clear analysis of the mechanism of the effect that apheresis has on diseases derived from unknown causes has not been completed. The effect of leukocytapheresis on ulcerative colitis (UC) or rheumatoid arthritis (RA) also lacks clear analysis, but removal of 10(10) adhesive cells resulted in the suppression of both acute and chronic inflammatory reactions. The number of cells removed was not unreasonable for efficacy. A quite acceptable explanation is that the cells activated in the inflammatory lesions are more adhesive than nonactivated cells. However, only a few minutes of contact with the surface of the device can activate blood immune cells. All of the apheresis therapies, not only leukocytapheresis, should be evaluated for their efficacies, excluding the effects of contact activation. According to results presently available, the suppressive effect of leukocytapheresis on RA or UC is through to depend upon the removal of activated inflammation related cells that might transfer inflammatory signals. It may be that those cells removed are bound because of cell stimulation caused by microorganisms or foreign bodies.