Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 7821884 | [Does methotrexate induce "rheumatoid nodules"? Case report and discussion of the literatu | 1994 Nov 20 | A 58-year-old woman with chronic polyarthritis rapidly developed a large number of rheumatic nodules under treatment with methotrexate. A comparison with other cases reported to date showed that the sudden onset of such nodules after initiation of treatment, and their disappearance again after discontinuation of the drug make the causal relationship highly likely. Although the predominantly anti-inflammatory actions of methotrexate control the chronic polyarthritis in almost all cases so far reported, they are unable to prevent the primarily immunological tissue necrosis (rheumatic nodules) and may even promote their development through the liberation of adenosine. Only in very rare cases does the severity or localisation of the nodules--e.g. vasculitis, pulmonary or cardial manifestation--necessitate the discontinuation of methotrexate. | |
| 1541321 | High dose oral methylprednisolone in patients with rheumatoid arthritis: pharmacokinetics | 1992 | A commercially available 1.0 g intravenous (i.v.) dosage formulation of methylprednisolone, as the sodium hemisuccinate salt (Solu Medrol, Upjohn) was administered both parenterally and orally (pulse steroid therapy) on separate occasions, to eight elderly (mean 65 y) patients with active rheumatoid arthritis. The relative oral bioavailability of the sterol was 69.2%. Elimination of methylprednisolone was prolonged when given orally; the mean residence times were 7.23 h and 3.94 h for oral and i.v. administrations, respectively. Clinical response to pulse steroid therapy was no different with respect to route of administration. There were no significant differences in standard clinical and laboratory assessments of disease activity when the two therapies were compared. Oral administration of methylprednisolone in patients requiring high-dose pulse steroid therapy is convenient and avoids the discomfort and inconvenience associated with i.v. administration. | |
| 7539350 | Idiotypes as markers for immunoglobulin genes contributing to the production of rheumatoid | 1994 Nov | Monoclonal antibodies have been produced that recognise conventionally defined cross-reactive idiotopes (CRI) expressed on rheumatoid factors. However, it is now evident that these "CRI" are markers for variable region sequences encoded by germline V gene segments and, therefore, that most of these reagents recognise isotypic epitopes rather than CRI. The implications of these findings for the identification and manipulation of auto-reactive B cell clones and the definition of regulatory idiotypic networks are discussed. | |
| 7983117 | Cemented revision Charnley low-friction arthroplasty in patients with rheumatoid arthritis | 1994 Nov | We assessed 41 patients with rheumatoid arthritis (47 hips) who had had revision hip arthroplasty, at an average follow-up of 7 years 4 months (2 to 19). The clinical results were excellent or satisfactory in 43 hips. Radiologically, 45 stems were secure. Fifteen sockets (36.6%) were radiologically loose. Three hips required rerevision. Socket failure is the predominant problem in rheumatoid patients after cemented revision arthroplasty. | |
| 8009067 | [Rheumatoid polyarthritis in the elderly--rhizomelic pseudopolyarthritis: what differences | 1993 | The authors have conducted a comparative retrospective study between polymyalgia rheumatic (N = 26) and rheumatoid arthritis in the elderly (N = 44), including HLA DRB1 genotype determination by PCR-RFLP analysis. No clinical nor biological differences were significant between the 2 groups of patients. However 70% of RA patients had one ore more susceptibility alleles (shared epitope hypothesis) and 50% in polymyalgia rheumatica. | |
| 7788172 | Sulphasalazine-induced autoimmune abnormalities in patients with rheumatic disease. | 1995 May | Sulphasalazine is a commonly used second line agent in rheumatoid arthritis (RA) and other inflammatory joint diseases and is reported to be one of the least toxic of this group of drugs. Recently a severe allergic reaction and cases of lupus-like disease have been described in patients with RA after treatment with sulphasalazine. We describe five patients, all with inflammatory arthropathy who developed cutaneous vasculitis, lupus-like disease or atypical serology after exposure to sulphasalazine. Three of four cases investigated were found to have the slow acetylator phenotype. These reactions can complicate the diagnosis and delay discontinuation of the drug. Moreover, present guidelines for the diagnosis of drug-induced lupus do not apply to the majority of patients with sulphasalazine-induced lupus. | |
| 7528280 | FK506, an immunosuppressant, partially inhibits interleukin 6 production by adherent rheum | 1994 Sep | OBJECTIVE: To investigate the effect of a new immunosuppressant, FK506, on interleukin 6 (IL-6) production by freshly prepared rheumatoid synovial cells. METHODS: Rheumatoid synovial cells were isolated from synovial tissue of patients with rheumatoid arthritis (RA) by using collagenase and DNase treatment. The surface phenotypes of the cells were analyzed by 2-color fluorescent analysis with FACScan. The levels of IL-6 in supernatant of cultured synovial cells were measured by enzyme immunoassay. RESULTS: The synovial cells used were mainly composed 32 +/- 1% of HLA-DR+/LeuM3+ cells and 53 +/- 6% of HLA-DR-/LeuM3-cells. These synovial cells spontaneously produced a large amount of IL-6 in culture. This spontaneous production of IL-6 was significantly inhibited by FK506 at the concentration of 10(-8) to 10(-6) M in a dose dependent manner. In the preincubation study, FK506 required more than 12 h to inhibit IL-6 production by synovial cells. CONCLUSION: These results suggest that FK506 may be beneficial for patients with RA via inhibiting IL-6 production in inflammatory joints. | |
| 8692565 | [Arthrodesis of the rheumatoid wrist]. | 1996 Apr | In rheumatoid wrists surgical procedures are not indicated before non surgical measures have failed to restore comfortable function or even severe instability and joint disorganisation have developed. Primarily synovectomies and stabilisation measures have to be done. Arthrodesis of the rheumatoid wrist is not indicated as often. In case arthrodesis is required in the rheumatoid wrist quality of bones and soft tissues should be taken carefully into consideration. The arthrodesis of the wrist according to Mannerfelt has been proven as a simple and safe method. | |
| 7551665 | Health economics as an aspect of health outcome: basic principles and application in rheum | 1995 Aug | Health economic evaluation comprises the systematic appraisal of the costs, the benefits and the relative economic efficiency of different medical interventions. The first section of this paper outlines the techniques of economic analysis and how they relate to the efficient use of health resources. This is followed by a review of the health economics of rheumatoid arthritis as a model for the wider application of health economics in the field of rheumatology. | |
| 7552079 | Gene therapy of rheumatoid arthritis via cytokine regulation: future perspectives. | 1995 Apr | Following many years of research using isolated human tissues and animal models, sufficient knowledge concerning rheumatoid arthritis has accumulated so that novel immunotherapies have been proposed. Biological agents are being tested in clinical trials and include antibodies to T cells and cytokines. Currently the most promising of these is intravenously administered neutralizing anti-TNF antibody. In order to establish disease modification, however, therapy needs to be delivered continuously over the long term. The prospect of delivering cytokine inhibitors as genetic material (naked DNA), viruses or in engineered autologous cells is considered as one option for achieving this goal. We compare two strategies, firstly, using immobile cells such as fibroblasts, myoblasts or keratinocytes, and secondly, the migratory cells of the immune system. The former provides a reservoir of systemic delivery of the therapeutic protein whereas the latter provides targeted delivery determined by the antigen specificity of the immune cells. Early validation has begun in animal models of rheumatoid arthritis. | |
| 9014586 | Hydroxyl radical generation by rheumatoid blood and knee joint synovial fluid. | 1996 Dec | OBJECTIVE: To demonstrate directly that highly reactive hydroxyl radicals (OH.) can be generated in patients with rheumatoid arthritis and contribute to joint damage, and to examine the ability of blood to cause OH. generation. METHODS: The sensitive and specific technique of hydroxylation of aromatic compounds (salicylate and phenylalanine) was used to measure OH.. Synovial fluid and blood from patients with active rheumatoid arthritis were aspirated and immediately added to tubes containing salicylate and phenylalanine as detectors of OH., or to tubes containing saline as a control. Levels of specific products of attack of OH. upon salicylate (2,3- and 2,5-dihydroxybenzoates) and phenylalanine (ortho- and meta-tyrosines) were measured by high performance liquid chromatography. RESULTS: Synovial fluid samples aspirated into saline never contained ortho- or meta-tyrosines or 2,3-dihydroxybenzoate. Of 53 patients examined, synovial fluid and blood from 36 caused formation of ortho- and meta-tyrosines when aspirated into solutions containing phenylalanine. Repeated sampling from three "positive" patients showed consistent evidence of these hydroxylation products. Similarly, of 22 patients examined, synovial fluid and blood from 18 caused formation of 2,3- and 2,5-dihydroxybenzoates when aspirated into salicylate solutions. Further evidence for the role of OH. was provided by inhibition of the hydroxylation by the specific OH. scavengers mannitol and sodium formate. CONCLUSIONS: Aspirated knee joint fluids and blood from rheumatoid arthritis patients can generate OH., consistent with current views on the importance of this radical as a cytotoxic agent in rheumatoid disease. The ability of body fluids to cause OH. formation is not correlated with simple laboratory indices of disease activity, but is reproducible on sequential sampling from the same patients. The mechanism and significance of the phenomenon in rheumatoid arthritis pathology remain to be established. | |
| 7827961 | Fibronectin and lymphocytes in inflammatory tissue. Studies of blood and synovial fluid ly | 1994 Jul | Lymphocytes infiltrating tissues under chronic inflammatory conditions are often surrounded by deposits of fibronectin. We have studied the possibility that this reflects capacity of lymphocytes to synthesize fibronectin and compared lymphocytes from blood and synovial fluid with respect to fibronectin interactions. In vitro activated blood lymphocytes exhibited synthesis of a fibronectin-like molecule. Synovial fluid cells appeared to synthesize the same high molecular weight component spontaneously. Activated blood lymphocytes have cell surface fibronectin and surface components of lower molecular weight which could be immunoprecipitated with anti-fibronectin antibodies as well as by insolubilized collagen. Synovial fluid cells showed cell surface fibronectin as revealed by immunocytochemical detection but seemed to lack or have relatively small amounts of the low-molecular weight fibronectin-like surface components. Synovial fluid T cells from arthritis patients showed adhesion to fibronectin. Immunocytochemistry demonstrated presence of alpha 4 and alpha 5 beta 1 integrins at the surface of the synovial fluid T cells and RGD and LDV peptides inhibited adhesion of the cells to fibronectin. Noteworthy, a portion of synovial fluid cells with lymphocyte markers also bound to plastic. Blood lymphocytes from the same arthritis patients displayed relatively poor or negligible adhesion to fibronectin unless activated to blast transformation and did not attach to plastic. Taken together these results suggest that activated lymphocytes from blood and synovial fluid may use fibronectin of exogenous or endogenous origin when interacting with tissues during inflammatory processes. Furthermore, the presence at the lymphocyte surface of components of different molecular weight precipitated by anti-fibronectin antibodies suggests that fibronectin or its fragments can bind to the lymphocyte surface. | |
| 8778986 | Cost evaluation of novel therapeutics in rheumatoid arthritis (CENTRA): a decision analysi | 1996 Apr | This study was performed to evaluate the potential costs of a hypothetical novel biological agent (BIO) as a therapy for rheumatoid arthritis (RA), compared with oral methotrexate (MTX) and intramuscular gold (IMG). A decision analysis model was used to compare the total costs of treating a cohort of 10,000 RA patients with each agent for 6 months. Total costs included direct costs and indirect costs. Baseline estimates were subjected to sensitivity analysis. Total costs per person were: MTX, $5,430; IMG, $6,725; BIO, $9,411. In sensitivity analysis, the primary cost drivers for MTX and IMG were the indirect costs of RA and monitoring costs. In contrast, total costs of the BIO were driven predominantly by medication costs. Sensitivity analysis showed, even when efficacy and safety were optimized, costs for the BIO still substantially exceeded those of MTX and IMG. Medication costs will be an important consideration in the development of novel BIOs for RA. | |
| 8752517 | [Clinical and immunological study of airway disease in collagen vascular disease]. | 1995 Dec | We studied the clinical and immunological characteristics of patients with bronchiolar diseases associated with collagen vascular disease (15 patients with rheumatoid arthritis and 1 primary Sjögren's syndrome). Histological examinations showed that 9 patients had follicular bronchiolitis and 7 had bronchiolitis obliterans. Follicular bronchiolitis was characterized by hyperplasia of bronchus-associated lymphoid tissue, and immunohistochemical studies revealed that the pattern of distribution of T cells and B cells in bronchus-associated lymphoid tissue from patients with follicular bronchiolitis was similar to that in diffuse panbronchiolitis, which may be used as a representative model of chronic respiratory infection. In addition, bacterial cultures of sputum samples were positive in 44% of patients with follicular bronchiolitis and in 71% of patients with bronchiolitis obliterans. These results suggest that antigen stimulation is involved in the development of bronchiolar diseases associated with collagen vascular disease. | |
| 8967183 | [Indicators of work incapacity in the first year of chronic polyarthritis]. | 1996 Jul | Already in the early phase of rheumatoid arthritis (RA) sick-leave (SL) frequently indicates a severe handicap with respect to work capacity. However, the significance of demographic, disease and work characteristics for SL are not known in early RA. Therefore, the indicators of SL (defied as the history of SL as certified by a physician) were sought in a cross-sectional multicenter study of early RA (< or = 1 year duration). One-hundred-and-thirty-four employed consecutive outpatients fulfilled > or = 4 of 7 ARA 1987 criteria of RA: 85 females (63%), age 50 years (median), disease duration 7 months (median). At the time of the examination 74 of the 134 patients (55%) were on SL because of RA (dependent dichotomous variable of the analyses). In order to identify the most important indicators of SL all variables with p < or = 0.10 in univariate analyses were entered into a multivariate logistic regression (stepwise forward analysis, p < or = 0.10). Parameters included in two different regression models (somatic variable and depression, job characteristics, respectively) were analyzed together in order to find the final model (p < or = 0.05). The following variables were included in the final logistic regression model of SL (p < or = 0.05): higher values of age, pain, and number of swollen joints, frequent overhead work, frequent pressure of time at work. Other indicators of SL in univariate analyses (p < or = 0.10) were not included in the model: male sex, low functional capacity, walking time, control over the pace and activities of work, occupational qualification, elevated ESR and depression. Significant indicators of SL are work conditions, disease activity, pain and age. Thus interventions focusing on the amelioration of the work capacity and thereby on the reduction of SL should concentrate on both the control of the disease and the improvement of the work conditions. | |
| 8814061 | Increased responsiveness of rheumatoid factor-producing B cells in seronegative and seropo | 1996 Sep | OBJECTIVE: To compare the frequencies and responsiveness of rheumatoid factor (RF)-producing B cells in the peripheral blood of patients with seronegative and seropositive rheumatoid arthritis (RA). METHODS: Frequencies of IgM+, IgG+, and RF+ B cells were determined by limiting-dilution analysis of purified peripheral blood B cells from 6 patients with seropositive RA, 8 patients with seronegative RA, and 7 normal controls. B cell help was provided by cloned T helper cells, which were stimulated by either anti-CD3 or the bacterial superantigen staphylococcal enterotoxin D (SED). IgM and IgG antibodies and RF in culture supernatants were detected by enzyme-linked immunosorbent assay. RESULTS: In the presence of anti-CD3-stimulated T helper cells, 2-10% of B cells from normal individuals secreted IgM and IgG antibodies. The frequency of RF+ B cells was low and ranged from 1:182 to 1:885 (RF+: IgM+) B cells. In patients with seropositive RA, the numbers of Ig-producing B cells were reduced by a factor of 2, while the fraction of RF+ B cell precursors was expanded by more than 50-fold (7-20% of IgM+ B cells; P = 0.004). Patients with seronegative RA had higher frequencies of RF-producing B cells (1.5-6% of IgM+ B cells) than normal individuals (P = 0.002), but not to the same extent as seropositive patients (P = 0.002). Stimulation of B cells using SED preferentially induced RF+ B cells in normal controls and in patients with seronegative and seropositive RA. CONCLUSION: B cell precursors with the potential to secrete RF were detectable in high frequencies in normal individuals and in patients with seropositive and seronegative RA. In all donors, these B cells could be stimulated with the bacterial superantigen SED. In normal individuals, RF+ B cells remained nonresponsive to help provided by anti-CD3-activated T cells, but were responsive in RA patients. Seronegative and seropositive RA form a continuous spectrum of disease, with a higher number of RF-secreting B cells in the seropositive patients. | |
| 8386767 | Rheumatoid arthritis with monoclonal IgE rheumatoid factor. | 1993 Mar | We studied a patient with rheumatoid arthritis (RA) and a high titer of IgE that could be attributed to a mono or oligoclonal expansion of IgE+ B lymphocytes. These IgE had no specificity for known allergens but bound to a panel of self (including Fc fragment of IgG) and exogenous antigens, displaying properties typical of polyspecific antibodies. We concluded that (1) RA can be associated with increased amounts of polyspecific IgE antibodies; (2) clonal excess populations of B cells are not a unique feature of malignant lymphoma, but may occur in autoimmune diseases in the form of a benign oligoclonal B cell proliferation. | |
| 8882022 | Treatment of rheumatoid arthritis by immunization with mononuclear white blood cells: resu | 1996 Feb | OBJECTIVE: To determine if immunization with alloantigenic blood mononuclear cells (MNC) in active rheumatoid arthritis (RA) can result in objective and subjective improvement in RA. METHODS: Eleven patients meeting American College of Rheumatology criteria for RA were treated in an open label trial by immunization with allogeneic MNC obtained from donors screened for infectious agents according to American Association of Blood Banks guidelines. MNC (30-250 x 10(6) cells) were given at 6 week intervals. Half the MNC (vol 2 ml) were injected intravenously and half in 4 divided doses subcutaneously (sq, 0.5 ml each). Disease activity assessments were done before entry and at immunotherapy visits thereafter. These included physician global assessment of disease activity, patient global assessment of pain, arthritis impact measurement scales (AIMS), swollen joint count, erythrocyte sedimentation rate (ESR), and/or C-reactive protein (CRP). RESULTS: Statistically significant improvement was noted in all clinical variables measured when pretreatment data were compared to those obtained at the time of injection number 3. MNC dose related improvement was found when the total number of cells given in the first 2 injections were compared to percentage improvement in patient assessment of pain (r = 0.71, p < 0.02), AIMS (r = 0.60, p = 0.05), and improvement in the means of all variables measured (r = 0.70, p < 0.03). When all variables were averaged, 6 of 11 patients experienced > 20% and 3 of 11 experienced > or = 40% improvement. The only side effects noted were transient local pain and swelling at the sq injection sites. CONCLUSION: MNC immunization may represent a suitable and safe alternative to drug treatment for selected patients with RA. Statistically significant improvement was found in all variables and several of these were cell dose related. A placebo controlled randomized trial immunizing with a standardized number of cells will address efficacy of this biological treatment approach. | |
| 1588737 | [Immunological and serological tests useful for diagnosis of rheumatoid arthritis]. | 1992 Mar | There are four areas of laboratory medicine engaged in the diagnosis of rheumatoid arthritis. They are serological tests for diagnosis of infection, tests for autoantibodies, analysis of serum proteins and lymphocyte function tests, including surface markers. In these areas except for diagnosis of infection, marked development has been achieved in the recent ten years. Enumerating roughly, I like to point out quantitative tests of rheumatoid factor, precise examinations for antinuclear antibodies, recent method for electrophoresis of serum protein and monoclonal antibodies for lymphocyte surface markers. Diagnosis of rheumatoid arthritis has became more precise and reliable by using these laboratory tests. In addition, effective tools are available to approach pathogenesis of rheumatoid arthritis through management of RA patients. An outline of these recent laboratory tests, useful for diagnosis of rheumatoid arthritis is presented. | |
| 7768058 | Cyclosporin in rheumatoid arthritis. | 1994 Nov | Rheumatoid arthritis is present in a population which is heterogeneous both clinically and immunologically. A variety of cells including lymphocytes, macrophages and fibroblasts play important roles in its pathogenesis, but the T cell appears to be a common thread throughout the disease process. Treatments aimed at reducing these lymphocytes mechanically and specifically result in a good clinical response in many patients. The mechanism of action of cyclosporin A (CyA) in inhibiting T lymphocytes presents a more specific form of therapy. The effects of CyA on the activity of RA have mainly been investigated in patients with active, refractory long-term disease. The data obtained in these trials suggest that CyA is not only a symptomatic treatment for RA but can also be considered a DMARD. The potential benefits of CyA on the one hand and its potential toxicity on the other indicate that a careful assessment should be made of its use in patients with early active RA. |