Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 2784139 | Immunomodulation by low-dose methotrexate. I. Methotrexate selectively inhibits Lyt-2+ cel | 1989 Mar 15 | We have studied the effect of methotrexate in murine acute graft vs host (GvH) disease at concentrations analogous to those used in human rheumatoid arthritis. The GvH reaction was induced by i.v. injection of parental spleen cells into a normal F1 recipient. The acute suppression of T cell function in GvH mice was prevented by methotrexate given orally for 10 days at 1.0 or 0.5 mg/kg but not at 0.25 mg/kg. T cell mitogen response and IL-2 secretion that were inhibited in GvH mice were restored by methotrexate. Protection from immunosuppression in drug-treated GvH mice lasted at least 3 wk after drug dosing was stopped. The mechanism of the protective effect appears to be a preferential inhibition of donor and host Lyt-2+ Ts cell proliferation. In mixing experiments we found that methotrexate inhibited Ts function in GvH mice. By dual fluorescence labeling we showed that the engraftment of donor Lyt-2+ cells was prevented by drug treatment. This was not true of donor L3T4+ cells which were clearly present in the spleens of GvH mice after methotrexate treatment. These donor L3T4 cells were functional in that they induced the production of anti-DNA autoantibodies in the methotrexate-treated GvH mice. | |
| 7858571 | [Rheumatoid arthritis and neoplasms]. | 1994 Dec 15 | The relationships between rheumatoid arthritis and malignant disease have been a focus of controversy for many years. The body of available data supports a relative decrease in the overall rate of occurrence of cancer, in particular of the colon, with no significant impact on mortality. However, increases have been demonstrated in the relative risks of lymphoma and, to a lesser degree, leukemia. The concomitant occurrence of rheumatoid arthritis and multiple myeloma seems fortuitous, with a relative risk of approximately 2. The effect of treatments, including methotrexate, remains unproven to date. | |
| 7732162 | Refractory rheumatoid arthritis. Therapeutic options. | 1995 Feb | Because rheumatoid arthritis rarely remits, refractory disease is common. Attention should be paid to aggravating comorbid conditions. Pharmacologic options currently available include cyclosporin, high-dose methotrexate, combination second-line agents, and creative use of corticosteroids. The available literature is reviewed in this article and the potential risks and benefits of the various options are discussed. | |
| 8846541 | Rheumatoid arthritis: new trends in therapy. | 1995 Sep | Recently, definite progress has been made in the pharmacotherapy of rheumatoid arthritis (RA). Since progression of joint damage is greatest during the first years of the disease, aggressive treatment nowadays is usually started early. RA has been considered to be a T cell driven disease, but therapies directed at eliminating T cells have not been consistently successful. Recent data indicate that macrophages may play an important role in the pathogenesis, and disease suppression has been demonstrated by antibodies against macrophage-derived cytokines. An important development in the treatment of RA has been the introduction of sulphasalazine and methotrexate, which are probably more effective than gold, D-penicillamine or hydroxychloroquine. The drug survival curve of the former drugs is better than that of the latter and their faster mode of action means that titration of these drugs towards optimal efficacy is easier. Due to these developments, the establishment of relevant measures for monitoring joint destruction and inflammatory mass are mandatory. | |
| 8293012 | [Malignant lymphoma in rheumatoid arthritis treated by low doses of methotrexate]. | 1993 Mar | The authors report a case of non-Hodgkin's malignant lymphoma which developed in a patient under low-dose methotrexate for rheumatoid arthritis. Although rheumatoid arthritis without immunosuppressive therapy may be associated with an increased incidence of malignant lymphoma, the immunosuppressive effects of methotrexate may further promote the development of malignant lymphoma. | |
| 8493588 | [Development of multiple subcutaneous nodules in a patient with rheumatoid arthritis durin | 1993 Feb | A 59-year-old woman with a 14 years' history of seropositive nodular rheumatoid arthritis (RA) who developed multiple subcutaneous nodules during methotrexate therapy was reported. Weekly pulse methotrexate therapy (5-7.5 mg) was initiated in June, 1990 for exacerbation of RA. By January 1991 (total dose of methotrexate: ca 240-310 mg), marked clinical and laboratory improvements were observed. However, subcutaneous which were present prior to methotrexate administration, increased in number and size. The excised nodules showed typical histological features of rheumatoid nodules. The subcutaneous were also characterized by their presence in atypical locations such as the extensor surfaces of finger joints and toes. Recent reports which describe development of subcutaneous nodules and vasculitic lesions in RA patients following methotrexate therapy indicate different pathogenetic mechanisms might be involved in articular disease and nodular lesions. | |
| 7810240 | Rheumatoid nodules located in the penis of a methotrexate-treated patient with rheumatoid | 1994 Sep | A case is reported in which a patient with a rheumatoid factor-negative rheumatoid arthritis developed rheumatoid nodules in the penis during treatment with methotrexate. The development of rheumatoid nodules in seronegative rheumatoid arthritis patients is extremely rare. An acceleration of rheumatoid nodules in methotrexate-treated rheumatoid arthritis patients is reported in literature. Regarding the case reported here, we propose a causal relationship between methotrexate-treatment and the development of rheumatoid nodules in our patient. Methotrexate should not be the preferential treatment for patients with rheumatoid arthritis developing rheumatoid nodules and suffering from vasculitis. | |
| 8846653 | Guidelines for the use of cyclosporine in rheumatoid arthritis. | 1995 Sep | Cyclosporine has now been tested in over 10 clinical trials in Rheumatoid Arthritis. These show that it provides clinically important benefit in 30-50% of patients with severe rheumatoid arthritis with an acceptable side-effect profile. It should be offered to patients who fail to (or only partially respond to methotrexate. The use of Cyclosporine in combination with other slow acting agents shows promise and should be tested at different points in the natural history of the disease. | |
| 8833050 | History of combination therapy of rheumatoid arthritis. | 1996 Mar | Faced with continued active rheumatoid arthritis (RA) despite conventional treatments, clinicians have added and combined whatever drugs were available to them, attempting to increase the benefits and minimize the adverse effects of treatment. First, combined antimalarial and gold salts therapy was favorably compared with antimalarial therapy in a large series of patients reported in 1963, but was cautioned against in 1966 because of concern about increasing toxicity. This concern discouraged subsequent publication of clinical experiences with combination therapies until 1982, when major benefits were reported in 17 patients treated with cyclophosphamide, azathioprine, and hydroxychloroquine. This report opened the door to numerous abstracts and publications during the 1980s, describing anecdotal series and poorly controlled clinical trials with various combinations of disease modifying antirheumatic drugs (DMARD), mostly with favorable results. During the past 5 or 6 years, a few, large, well controlled, randomized, double blind clinical trials with a balanced design have been published, but conclusive evidence of benefit from combinations of DMARD was lacking. Recent abstracts have suggested that triple therapy with methotrexate (MTX), hydroxychloroquine, and sulfasalazine produces additive benefits, and that the addition of cyclosporine, in patients who are poorly controlled by MTX, is more effective than continuing MTX alone. Only a few of the many possible permutations and combinations of drugs and doses have been evaluated, and confirmatory studies have not been done. Combination therapy of RA is only now starting to evolve, with most major milestones yet to be achieved. | |
| 7789498 | Association of histologically proven rheumatoid arthritis with pulmonary sarcoidosis. | 1995 Mar | The association of rheumatoid arthritis proven by means of synovial biopsy with pulmonary sarcoidosis proven by means of bronchial biopsy, occurred in a 58 year old woman. Corticosteroid therapy resulted in complete resolution of sarcoidosis but only slight improvement of the rheumatoid arthritis, which was secondarily treated with methotrexate with a successful outcome. Only two similar cases have been reported with simultaneous histological proofs of both diseases. | |
| 8358983 | Intestinal absorption in patients with rheumatoid arthritis treated with methotrexate. | 1993 Jun | Twelve patients with rheumatoid arthritis treated for at least 12 months with methotrexate and 11 matched rheumatoid arthritis controls underwent a standard d-xylose absorption test. No patients had any pre-existing clinical of biochemical evidence of malabsorption. No significant difference was observed in the 1 hour plasma d-xylose estimation between methotrexate treated patients and controls. The 2 to 5 hour urinary excretion ratio, however, was significantly lower in the methotrexate-treated group compared with controls indicating a minor degree of malabsorption. Six of the methotrexate treated patients and 5 of the controls underwent endoscopic duodenal biopsy but neither group demonstrated any significant histological changes. In conclusion, methotrexate therapy in patients with rheumatoid arthritis produces mild intestinal malabsorption. | |
| 8833043 | The rationale for combination therapy of rheumatoid arthritis based on pathophysiology. | 1996 Mar | Rheumatoid arthritis begins with activation of a few cells within joints. The initial process is most likely caused by presentation of an antigen or superantigen by specific HLA-DR glycoproteins to receptive lymphocytes, perhaps accompanied by retroviral activation of synoviocytes and macrophages. After this initial activation process, many different components of host immune, inflammatory, and proliferative responses are activated as well. These include: B cell proliferation, proteolytic enzyme biosynthesis, cytokine expression, activation of kinin, complement, clotting and fibrinolytic pathways, prostaglandin and leukotriene production generation of oxygen free radicals and nitric oxide, and proliferation of synoviocytes (pannocytes)/chondrocytes and their gene products. At some point after the initial stimulus, the rheumatoid synovitis may become self-sustaining, without a need for the initial inciting protein or virus. In consideration of the multiple activated pathways that become operational, it is appropriate to consider therapies that attack more than one pathway. This is the rationale for combination therapy. In practice it does not imply using 2 agents directed against the same pathway (e.g., 2 different nonsteroidal antiinflammatory drugs) but rather agents (e.g., methotrexate and cyclosporine) that have proven in vitro/in vivo to suppress different components of the immune/inflammatory/proliferative lesion. Thus, since many data suggest that irrevocable destruction of joints begins relatively early in the disease process, it is appropriate to begin substantial combination therapy early as well. | |
| 1598500 | A prospective analysis of liver biopsies in rheumatoid arthritis patients receiving long t | 1992 | Baseline and sequential liver biopsies were performed in ten patients with rheumatoid arthritis (RA) treated with methotrexate (MTX) for more than 4 years. Liver biopsies were performed in all patients before the initiation of MTX therapy and were repeated after reaching a cumulative dose of 1500 mg or more. In four patients a third biopsy was performed 3 years after the first one. No significant worsening of hepatic architecture was found in any of our patients after 4 to 7 1/2 years of MTX therapy. No correlations between histologic findings and various clinical or pharmacological variables could be found. Our results suggested that prolonged MTX administration in RA patients did not cause severe hepatic abnormalities. | |
| 8927885 | [Therapy of rheumatoid arthritis (chronic polyarthritis)]. | 1996 Sep 10 | A continuous and systematic monitoring of disease activity provides the basis for the therapeutic management of rheumatoid arthritis patients. This helps to individually tailor medication and to correctly time physiotherapy, ergotherapy, surgery, and rehabilitative measures. NSAID are the drugs of choice for symptomatic therapy. The dosage is adjusted to the circadian rhythm of the patient's complaints. Systemic glucocorticoids are very efficacious to control inflammation; however, caution is required in their long-term usage. Preventive measures to limit bone loss are mandatory. Disease-modifying antirheumatic drugs (DMARD) are prescribed early, at the time of diagnosis. The choice of sulfasalazine, antimalaric drugs, methotrexate or parenteral gold is based on the clinical presentation, the degree of systemic inflammation and on prognostic parameters. Treatment with DMARD has to be continued for years. If complete remission is achieved, lasting for at least six months, the dosage can be gradually reduced and finally stopped. At late stages of disease, residual joint pain is often due to secondary osteoarthritis. | |
| 1307351 | Methotrexate: clinical and immunological effects in refractory rheumatoid arthritis. | 1992 Oct | Thirty five patients with refractory rheumatoid arthritis were given 7.5 mg of methotrexate (Mtx) every week. Eleven patients had to discontinue treatment either because of adverse effects or unresponsiveness. Twenty four patients showed clinical response and significant improvement in ESR and they continued Mtx for a mean of 25.24 months. Seven patients achieved clinical remission as defined by ARA criteria. Immunological parameeters including IgG, IgM, IgA, lymphocyte subsets (CD3+, CD4+, CD8+ and B), C3 and C4 however, did not show any change during this treatment in any of the groups upto 6 months. There was a significant fall in the erythrocyte sedimentation rate (ESR), c-reactive protein (CRP) and rheumatoid factor (RF) levels in responders only. | |
| 8151588 | The effect of methotrexate on ex vivo lipoxygenase metabolism in neutrophils from patients | 1994 Jan | OBJECTIVE: To examine the effect of methotrexate (MTX) administered in vivo on the production of the 5-lipoxygenase (5-LO) metabolites of arachidonic acid by neutrophils from subjects with rheumatoid arthritis. METHODS: Neutrophils were isolated from peripheral blood samples taken 12 h before and 12 h after the ingestion of an oral dose of MTX and stimulated in vitro by calcium ionophore A23187. Lipid extracts of cell suspensions were assayed for leukotriene B4 (LTB4), the all-trans isomers of LTB4, 20-hydroxy LTB4 and 5-hydroxyeicosatetraenoic acid by high pressure liquid chromatography. RESULTS: An increase in the production of all measured 5-LO metabolites was seen between the pre and postdose assessments. CONCLUSION: Our results do not support the putative inhibitory effect of MTX on 5-LO metabolism. | |
| 8460435 | [Pleuropulmonary manifestations of rheumatoid arthritis. A casuistic reminder]. | 1993 Mar 15 | A case of pleuropulmonary manifestations of rheumatoid arthritis (RA) in the form of persistent pleuritis and effusion in a 58 year old male patient with known RA is presented. The well-known pleuropulmonary complications of RA pleurisy, interstitial fibrosis, effusion, rheumatoid nodules and Caplan's syndrome can occur in sero-negative patients without primary articular symptoms and therefore pose difficult problems in differential diagnosis. These problems can be partially overcome by thoracoscopic visualization of the often characteristic changes of the parietal pleura: hyperemia, vasculitis and rheumatoid nodules and histochemical examination of the pleural liquid will show low glucose concentration, high protein concentration, elevated lactate-dehydrogenase concentration, acid pH and a characteristic cytomorphology with mononuclear and neutrophil leucocytes in typical cases. The pleuropulmonary manifestations can sometimes be successfully treated with a combination of NSAIDs and methotrexate. | |
| 8523366 | Radiographic progression in rheumatoid arthritis: results of 3 comparative trials. | 1995 Sep | In 3 clinical trials the effects of 6 different disease modifying antirheumatic drugs on radiographic progression were evaluated. Despite the wide range in disease duration of patients in the different studies, a statistically significant slowing of radiographic progression was found in those patients treated with aurothioglucose, sulfasalazine, and methotrexate compared to auranofin, hydroxychloroquine, and azathioprine, respectively. These drugs might therefore be considered as disease controlling antirheumatic drugs. | |
| 1294748 | Liver disease, erroneously attributed to methotrexate, in a patient with rheumatoid arthri | 1992 Dec | We describe a patient with rheumatoid arthritis and Felty's syndrome who developed evidence of hepatic dysfunction initially attributed to a short course of methotrexate therapy. He was subsequently found to have nodular regenerative hyperplasia. | |
| 7791154 | Influence of low doses of methotrexate on superoxide anion production by polymorphonuclear | 1995 Apr | OBJECTIVE: The mechanism of methotrexate (MTX) action in rheumatoid arthritis (RA) is unclear. We assessed the influence of MTX on neutrophil superoxide production evaluated by ferricytochrome c reduction. METHODS: Neutrophils were collected from MTX treated patients with RA (MTX-RA), patients with RA without medication (RA) and healthy donors, cocultured with MTX or MTX-RA serum. RESULTS: Polymorphonuclear leukocytes (PMN) from MTX-RA showed decreased superoxide production when compared with cells collected from patients with RA and controls. Control PMN superoxide production was inhibited (36%) by MTX-RA serum incubation. This reduction was accompanied by clinical improvement. MTX had no activity in the in vitro assays. CONCLUSION: MTX treatment may interfere with neutrophil superoxide production. |