Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 8983319 | Methotrexate in the treatment of children with chronic arthritis--long-term observations o | 1996 Sep | In a study to investigate the efficacy and toxicity of long-term methotrexate (MTX) therapy in children with chronic arthritis, the medical records of 26 children (seven boys and 19 girls) with juvenile rheumatoid arthritis (JRA) were reviewed retrospectively. The patients received MTX therapy for a mean of three years (range, six months to six years). A clinically significant response occurred in 19 children (73.1%): remission in ten (38.5%) and improvement (25% reduction in the number of actively inflamed joints) in nine (34.6%). Concomitant prednisolone therapy was reduced in 13 out of 14 children (93%). Haemoglobin levels and erythrocyte sedimentation rates were statistically significantly improved over baseline after MTX therapy. Six (23%) children experienced toxic effects during MTX therapy. One patient discontinued the MTX treatment after 18 months because of jaundice and raised liver enzymes. It is concluded that the study confirms the efficacy, and acceptable toxicity profile, of MTX given over a period of several years to children with JRA. | |
| 7736958 | [Severe pneumonitis as a complication of low-dose methotrexate therapy in psoriasis-associ | 1995 Apr 28 | A 71-year-old woman with psoriasis-associated rheumatoid arthritis had for 15 months been treated with methotrexate (5 mg/week orally). Four weeks before admission she had developed dyspnoea and cough. On admission her axillary temperature was 38.2 degrees C, the white cell count was normal. Erythrocyte sedimentation rate (50/90 mm), lactate dehydrogenase activity (449 U/l) and the creatinine level (1.33 mg/dl) were all elevated. Blood gas analysis revealed partial respiratory impairment (pO2 52 mm Hg), and the chest X-ray demonstrated bilateral interstitial-alveolar changes. Despite antibiotics the temperature continued to rise, and on the 11th day a blood eosinophilia of 4% was noted. The bronchial mucosa was normal on bronchoscopy, and transbronchial biopsy showed only minor interstitial fibrosis, occasional macrophages and lymphocytes. Cultures of the lavage-fluid were negative. As methotrexate pneumonitis was suspected the drug was discontinued and prednisolone administered (50 mg daily for 3 days, gradually reducing over 7 days). The symptoms quickly improved, and blood gas analysis and the X-rays became normal. The patient was discharged symptom-free after 30 days. | |
| 1578459 | Low dose methotrexate treatment in adult Still's disease. | 1992 Mar | Six patients with adult Still's disease who had either failed to respond to or had adverse effects from previous therapy were given weekly low dose methotrexate (MTX) therapy. They were followed for 4-28 months (mean 14 +/- 9 months). At 12 months of therapy 3 patients were evaluated as having a complete response. One patient had a partial response to MTX after 7 months. Therapy was discontinued in 1 patient at 4 months due to flares of rash and arthralgias after each MTX administration. One patient failed to respond to therapy despite maximum dosage, but was able to reduce his corticosteroid dose. MTX may be a useful therapy to consider in patients with adult Still's disease who are resistant to conventional therapy and may allow a reduction in the concomitant dose of corticosteroids. | |
| 8526184 | [Type III polyglandular autoimmune syndrome. Report of a case]. | 1995 Sep | Type III polyglandular syndrome is defines as the association of insulin dependent Diabetes mellitus, thyroid gland affection (hyper or hypothyroidism) and a non endocrinological disease, rheumatological or not. Less common manifestations include pernicious anemia, vitiligo and alopecia. Circulating organ-specific auto antibodies are detected in blood smear and a lymphocyte infiltrate in the affected glands. We report a patient with insulin dependent Diabetes mellitus since the age of 3, who developed hypothyroidism at the age of 14 and severe rheumatoid arthritis at 16. Moderate anemia with positive auto antibodies against parital gastric cells was detected. Treatment with methotrexate and indomethacin was indicated with excellent results regarding her arthritis and after 2 weeks of treatment she began to walk normally again. | |
| 1455374 | [Pulse therapy with methylprednisolone and cyclophosphamide in systemic juvenile rheumatoi | 1992 | The treatment for systemic JRA is among actual problems of pediatric rheumatology. To evaluate the effectiveness of pulse therapy (PT) with methylprednisolone 25-30 mg/kg/day for 3 consecutive days combined with cyclophosphamide 0.4-0.5 g/sq. m body surface area (BSA) on the 3rd day, repeated quarterly for 12 months, 30 patients with systemic JRA were randomized into 3 groups: 1--those with disease duration (DD) less than 2 years receiving PT (n = 13), 2--with DD 2 years and more (n = 8) receiving PT, and 3--with DD less than 2 years receiving no PT. Children in all 3 groups received concomitant medication (one of nonsteroidal anti-inflammatory drugs, methotrexate 10 mg/sq. m BSA/week and oral steroids). A rapid and significant improvement, according to systemic and articular manifestations as well as laboratory indices occurred in the 1st group, in most of the measured parameters exceeded effects in the other two groups and gave the opportunity to avoid the administration of oral steroids or to give the lesser initial dose. Side effects were minor and completely reversible. | |
| 8706140 | Antirheumatic agents. I. Novel methotrexate derivatives bearing an indoline moiety. | 1996 Jul | Various novel methotrexate (MTX) derivatives bearing an indoline moiety were synthesized and tested for biological activities using human peripheral blood mononuclear cell (hPBMC) and human synovial cells (hSC) derived from patients with rheumatoid arthritis (RA). Compounds having potent activity in vitro were further evaluated using an adjuvant arthritis model in vivo. N-[1-(2,4-Diamino-6-pteridinylmethyl)indoline-5-carbonyl]-L-glutam ic acid 2f showed more potent activities than MTX in vitro and in vivo, and N-[1-(2,4-diamino-6-pteridinylmethyl)-indoline-5-carbonyl]-L-2-ami noadipic acid 2d exhibited fairly good activities in vitro and considerable activity in vivo. Compound 2d was, as expected, not sensitive to folyl-polyglutamate synthetase (FPGS) and did not undergo polyglutamation, a process which may be responsible for a side-effect during MTX therapy. | |
| 7635041 | Immunosuppressive drugs and their complications. | 1994 Sep 15 | Drugs that suppress the immune system are widely used. They are part of the treatment of patients with organ transplants, malignancy, and increasingly those with conditions such as psoriasis, rheumatoid arthritis, and liver and bowel disease in which inflammation is an aetiological factor. Because of the broadening indications for immunosuppressive drugs, and the prolonged survival in conditions for which they are being used, many patients on immunosuppression are now cared for in the community or seen in non-specialist hospitals, usually in close collaboration with a specialist. This article looks at five commonly used immunosuppressive drugs in turn (corticosteroids, cyclosporin, azathioprine, methotrexate, cyclophosphamide), discussing the main, non-infection, unwanted effects, ways to avoid them and what to do if problems arise. The management of infection is dealt with as a separate section. | |
| 8996859 | Antirheumatic agents. II. Novel methotrexate derivatives bearing an alkyl-substituted benz | 1996 Dec | Novel methotrexate (MTX) derivatives with either a mono- or dialkyl-substituted benzene ring were synthesized and initially tested for in vitro anti-proliferative activities using human peripheral blood mononuclear cells (hPBMC) derived from healthy volunteers and synovial cells (hSC) derived from patients with rheumatoid arthritis (RA). Compounds with potent activities were further evaluated in an in vivo adjuvant arthritis model. In comparison with MTX, a glutamate derivative 3a was more potent as a suppressor of the in vitro cell proliferation and the in vivo experimental arthritis, and a homoglutamate derivative, 3e, exhibited fairly good activities in vitro and considerable activity in vivo in a dose-dependent manner. As expected, 3e did not act as a substrate of folylpolyglutamate synthetase (FPGS), and thus did not undergo polyglutamation, which is thought to be responsible for side-effects that occur during MTX therapy. | |
| 7744295 | [Myocardiopathy diagnosed in utero in a mother with SS-A antibodies treated with plasmaphe | 1995 Mar | We report a 36 years old patient with Sjogren's syndrome, who during her second pregnancy, the product developed a miocardiopathy with complete heart block that was diagnosed in utero at 26 weeks of pregnancy. Simultaneously, laboratory data reported a SS-A/Ro titer of 1:50,000 with positive antiphospholipids antibodies. Patient was subjected three times to plasmapheresis with three blood volume exchange each time. During the procedures, we had monitor the product and no hemodinamic changes were observed. Unfortunately, 25 days later the patient reported absence of fetal movement and by ecosonography and Doppler was not observed fetal movement or cardiac function. This pregnancy ends in cesarea. The patient is in perfect clinical conditions under control using prednisone and methotrexate. | |
| 8823714 | Propionibacterium acnes isolated from sternal osteitis in a patient with SAPHO syndrome. | 1996 Jul | A woman presented with palmar pustulosis and deep chest pain in association with osteitic lesions in the lower part of the sternum. Propionibacterium acnes was isolated and grew in pure culture from 6 surgically obtained bone specimens. The patient received clindamycin treatment for 6 months. Synovitis in both her wrists persisted and, based on a clinical suspicion of seronegative rheumatoid arthritis, she was treated with intramuscular gold and methotrexate with no apparent benefit. Subsequently, she was diagnosed with SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, and osteomyelitis). Our patient provides further data on the potential association between P. acnes and SAPHO syndrome. | |
| 8535646 | The antirheumatic agents sulphasalazine and methotrexate share an anti-inflammatory mechan | 1995 Nov | Increasingly, methotrexate (MTX) and sulphasalazine (SASP) are used initially for second-line therapy of rheumatoid arthritis (RA). Although SASP and MTX are commonly used, the mechanism(s) by which these drugs control the inflammation that characterizes RA have remained obscure. Results from my laboratory indicate that these agents share a mode of action; the anti-inflammatory effects of both SASP and MTX are due, in both in vitro and in vivo studies, to their capacity to enhance adenosine release at inflamed sites. This mode of action suggests that the development of agents that directly alter adenosine metabolism may lead to new, more effective and safer antirheumatic drugs than those currently available. | |
| 8020670 | Interstitial pneumonitis after low-dose methotrexate therapy in primary biliary cirrhosis. | 1994 Jul | Interstitial pneumonitis is an uncommon complication of low-dose methotrexate therapy in patients with psoriasis but occurs in 3%-5% of patients with rheumatoid arthritis. We found a higher incidence of interstitial pneumonitis in patients with primary biliary cirrhosis (14%) and describe its clinical manifestations, treatment, and possible etiology. Blood tests, arterial blood gas determinations, chest radiographs, bronchoscopy, tear production, autoantibody tests, and serum immunoglobulin levels were obtained in six women who developed interstitial pneumonitis while receiving methotrexate in a double-blind prospective trial of methotrexate vs. colchicine in 87 patients with primary biliary cirrhosis. Six of 43 patients (14%) who received methotrexate compared with no patients receiving colchicine developed interstitial pneumonitis 19-61 weeks after starting treatment. The pneumonitis was characterized by dyspnea, hypoxemia, and bilateral lung infiltrates, all of which responded within 24 hours to the administration of intravenous glucocorticoids. There was no correlation between the pneumonitis and pre-existing lung disease, the severity of the primary biliary cirrhosis, the titer of antimitochondrial antibody, or other diseases associated with primary biliary cirrhosis. Patients with primary biliary cirrhosis receiving low-dose methotrexate (15 mg/wk) are more susceptible to interstitial pneumonitis than patients with psoriasis or rheumatoid arthritis. The pneumonitis appears to be a hypersensitivity reaction and responds rapidly to intravenous glucocorticoid therapy. | |
| 9138387 | [Acute methotrexate poisoning: apropos of 16 cases reported to the Paris Poison Control Ce | 1996 Sep | 16 cases of acute methotrexate (MTX) poisoning were reported to the Paris Poison Control Centre and 62 others were published between 1974 and 1995. Until 1992, MTX was mainly prescribed for neoplastic diseases. Clinical features involve acute renal failure, pancytopenia, and cutaneous or mucous injury. These cases emphasise major risk factors responsible for misuse and overdosage. Since 1992, MTX has been increasingly used in rheumatological or pulmonary diseases (rheumatoid arthritis, steroid-dependent asthma). Most of the overdosages were due to a medical misuse (in the dosage regimen or a misunderstanding of the prescription by nurse, pharmacist or patient). All patients had a bone marrow suppression. The treatment is based especially on early administration of folinic acid rescue. | |
| 7598502 | Targets for antiinflammatory drugs. | 1995 | Aspirin-like nonsteroidal antiinflammatory agents, corticosteroids, and methotrexate are the mainstays of therapy in rheumatoid arthritis and other inflammatory diseases. It is now clear that these agents share at least one characteristic: All of these agents diminish the adhesive interactions required for the accumulation of white blood cells at an inflamed site. We discuss the biochemical and functional mechanisms by which these drugs alter the inflammatory response, and the potential for development of new antiinflammatory agents based upon these pharmacological actions. | |
| 7791153 | The effects of food on methotrexate absorption. | 1995 Apr | OBJECTIVE: To determine the effects of food on methotrexate (MTX) absorption in patients receiving MTX for the treatment of rheumatoid arthritis (RA). METHODS: Standard pharmacokinetic variables were determined in patients with RA after their usual maintenance dose of MTX, under fasting conditions and after they ate a standard breakfast. RESULTS: No significant differences in area under the serum concentration versus time curve, maximal MTX concentration after dosing (Cmax), time to Cmax), bioavailability, urinary MTX, renal clearance of MTX, or creatinine clearance were observed between the 2 dosing conditions. CONCLUSION: We observed no significant effect of food on MTX absorption or bioavailability. Patients may consume MTX without regard to meals. | |
| 8948305 | Injectable gold compounds: an overview. | 1996 Nov | Injectable gold compounds have enjoyed widespread, but occasionally controversial, use in rheumatoid arthritis since the 1920s. This overview examines the data from controlled trials and longer-term observational studies. We conclude that gold is equivalent to other widely used second-line agents in terms of efficacy. Toxicity profiles are similar, apart from methotrexate. It is most efficacious and toxic in the first 2 yr of treatment. There appears to be a dose-response relationship for both efficacy and toxicity. Gold is one of the few agents that decreases the rate of progression of erosions (RR 0.38, 95% CI 0.23-064). Gold compounds, therefore, have a definite place in the rheumatologist's armamentarium, but further research is required to determine optimal monitoring regimes as well as the role of maintenance therapy and combination therapy. | |
| 8025760 | Opportunistic infection during treatment with low dose methotrexate. | 1994 Jul | Two patients receiving low dose methotrexate, one with rheumatoid arthritis and the other with pityriasis rubra pilaris, developed disseminated histoplasmosis and Mycobacterium avium intracellulare pneumonia, respectively. Twenty-three cases of opportunistic infection in patients receiving low dose methotrexate have been reported previously, with Pneumocystis carinii pneumonia being the most common infection (10 of 23, 43%). Patients receiving low dose methotrexate are at risk for opportunistic infection despite normal leukocyte counts. | |
| 7645110 | [Methotrexate treatment of patients with prednisolone dependent bronchial asthma]. | 1995 Aug 21 | In this review we went through eight placebo-controlled clinical trials of the folic acid antagonist methotrexate in the treatment of bronchial asthma. The studies, which differ in their methods and findings, are reviewed critically. Some studies seem to give documentation of methotrexate as an effective drug in reducing the corticosteroid requirements in patients with chronic corticosteroid-dependent asthma. Adverse effects are wellknown from the use of methotrexate in patients with rheumatoid arthritis and include nausea, diarrhoea, vomiting, transient increases in liver enzymes, alopecia and stomatitis. Rare but potentially life-threatening adverse effects are interstitial pneumonitis, opportunistic infections, bone marrow- and renal insufficiency. The role of methotrexate in patients with chronic corticosteroid-dependent asthma still needs to be clarified. Practical guide-lines in treating asthma patients with methotrexate are suggested. | |
| 8453317 | Methotrexate pneumonitis in bronchial asthma. | 1993 | Methotrexate pneumonitis is one of the most unpredictable and potentially serious adverse effects associated with the use of low-dose pulse methotrexate in treating rheumatoid arthritis. However, its occurrence in treating bronchial asthma has never been reported. A patient with steroid-dependent bronchial asthma developed interstitial pneumonitis during methotrexate therapy. Dyspnea, fever and oral ulcer occurred successively during the initial 4 months of intermittent low-dose methotrexate pulse therapy. Despite severe hypoxemia and interstitial infiltration in both lung fields, the lung lesions disappeared after treatment with corticosteroid and discontinuation of methotrexate therapy. In conclusion, methotrexate pneumonitis might develop after treatment. Once pneumonitis is suspected, methotrexate should be withdrawn. | |
| 8129775 | The effect of low-dose methotrexate on bone metabolism and histomorphometry in rats. | 1994 Feb | OBJECTIVE: To ascertain the effects of low-dose methotrexate (MTX) on bone metabolism and histomorphometry in rats. METHODS: Female Sprague-Dawley rats (6 months old, n = 42) were divided into the following 4 groups: intraperitoneal (IP) injections of MTX, with and without ovariectomy, and IP saline (controls), with and without ovariectomy. Injections were given for 16 weeks. The MTX dose was equivalent to a standard dose for rheumatoid arthritis in humans that would yield similar serum MTX levels (0.6 +/- 0.1 mumoles). RESULTS: Bone formation (assessed by serum alkaline phosphatase and osteocalcin levels and histomorphometry) was significantly lower in the MTX groups, and bone resorption (assessed by urinary hydroxyproline levels and histomorphometry) was increased in the MTX groups. Bone mass was significantly diminished in the MTX groups. CONCLUSION: Prolonged administration of low-dose MTX in rats causes significant osteopenia via suppression of osteoblast activity and stimulation of osteoclast recruitment, which results in increased bone resorption. |