Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 1694247 | Activated lymphocytes in the peripheral blood of patients with rheumatoid arthritis. | 1990 May | The peripheral blood and synovial fluid of patients with rheumatoid arthritis (RA), when compared to controls, has a higher proportion of mononuclear cells actively synthesizing DNA (S-phase cells). Such cells can be marked by radioautography after incubation with tritiated thymidine and can also be quantitated by the 4-h spontaneous in vitro uptake of tritiated thymidine. As our previous studies showed a marked and rapid decrease in this latter measure, in response to in vivo methotrexate, we suggested that the responsible cells may have a direct role in pathogenesis rather than merely reflecting the inflammation that is present. We have therefore tried to characterize them further. A mean of 46% of these autoradiography positive cells from the peripheral blood of patients with active RA bear CD3 markers and 61% Ia. On some occasions up to 25% stain for Leu M3 and 25% for Leu 7. None were esterase positive. Cell separation studies confirm that such cells were found in both T cell and non-T cell enriched populations. These cells, therefore, appear to be heterogeneous. A decreased number was seen in peripheral blood lymphocytes from patients who had received remittive therapy for over 4 months when compared to other patients with RA and this was associated with a lower 4-h spontaneous uptake of labelled thymidine. | |
| 2545638 | Methotrexate serum-level determinations during low-dose therapy of rheumatoid and psoriati | 1989 | In 29 patients, 21 suffering from psoriatic arthritis and eight patients suffering from rheumatoid arthritis, methotrexate serum-levels were determined by means of radioimmunoassay. The aim of the investigation was to recognize an eventual dependence of the serum level of methotrexate on the total cumulative dose and to test the possibility of a concomitant therapy control. Beside the determinations of the serum levels of methotrexate, clinical examinations and laboratory tests were done at regular intervals. The values obtained showed no significant increase during the course of therapy compared to the values at the beginning of the treatment. Likewise no correlation to the total cumulative dose, the clinical picture or to the occurrence of side-effects could be found. Nor could any relationship between the changing of laboratory parameters and the methotrexate serum-levels be observed. No differences appeared in the methotrexate serum-levels during therapy of either rheumatoid or psoriatic arthritis patients. In conclusion it seems impossible to monitor a low-dose methotrexate therapy by continuous determinations of the serum levels of the drug. | |
| 2123816 | Severe rheumatoid arthritis: current options in drug therapy. | 1990 Dec | Therapeutic advances have been made in rheumatoid arthritis (RA), but patients (and sometimes physicians) may become frustrated at the apparent lack of breakthrough treatments. The latest advances in the treatment of severe RA are discussed, along with what investigators are using experimentally both in combination with other drugs and alone to treat RA now and, possibly, in the future. These agents include methotrexate, cyclosporine, gamma-interferon, and omega-3 fatty acids. | |
| 2287944 | Methotrexate: mechanism of action in rheumatoid arthritis. | 1990 Dec | Most studies of immune function in rheumatoid arthritis (RA) patients treated with methotrexate (MTX) show only marginal effects on humoral or cellular immune responses. These include measurements of lymphocyte subsets, proliferative responses to mitogens, immunoglobulin production, rheumatoid factor and immune complexes. The mechanism of action of MTX in RA might be more antiinflammatory than immunosuppressive. This is supported by the rapid clinical response to drug treatment and by data from in vitro and animal studies. The inhibition of interleukin-1 (IL-1) activity or other inflammatory cytokines by MTX may play an important role in the antiinflammatory effect of MTX. MTX effects in RA are not fully understood and further studies are needed to clarify its mechanism of action. MTX has crucial effects on the cascade of events initiated by some cytokines (IL-1, IL-6, tumor necrosis factor), which plays a major role in RA and other inflammatory diseases. | |
| 3487652 | Methotrexate toxicity in a patient receiving trimethoprim-sulfamethoxazole. | 1986 Apr | A 61-year-old patient with rheumatoid arthritis receiving treatment with methotrexate developed bone marrow hypoplasia after treatment with trimethoprim-sulfamethoxazole. The bone marrow recovered after stopping methotrexate. | |
| 1994911 | Local infectious complications following large joint replacement in rheumatoid arthritis p | 1991 Feb | We performed a 10-year retrospective analysis of the frequency of local postoperative infectious complications in methotrexate (MTX)-treated rheumatoid arthritis patients who underwent total joint arthroplasty. Sixty patients, who had a total of 92 joint arthroplasties, were receiving MTX. A comparison group of 61 patients with a combined total of 110 total joint arthroplasties were not receiving MTX. The 2 groups were compared for the occurrence of local postoperative infectious complications and poor wound healing. Eight patients in the MTX group experienced a total of 8 complications (8.7% of procedures). In comparison, 5 patients in the non-MTX group experienced a total of 6 complications (5.5% of procedures), a difference that was not statistically significant (chi 2 = 0.816, P = 0.366). Statistical analysis of many other variables revealed none that could be identified as risk factors for postoperative complications. These results suggest that treatment in the perioperative period with weekly low-dose pulse MTX does not increase the risk of local postoperative infectious complications or poor wound healing in rheumatoid arthritis patients who undergo total joint arthroplasty. | |
| 2004398 | [Rheumatoid factor in rheumatoid arthritis in old age]. | 1991 Jan 25 | Rheumatoid factors (RF) detected by agglutination methods (latex fixation test, haemagglutination test) were found in a group of patients with rheumatoid arthritis which started in advanced age (RAVV) less frequently than in a group with RA in middle age (RAMV). The author describes the ELISA method for assessment of RF which makes it possible to estimate immunoglobulin classes RF (IgM-RF, IgA-RF, IgG-RF). By this method RF were detected in class IgM in 15% of patients and in some immunoglobulin classes in 20 per cent where are RF negative when assessed by agglutination methods. The ELISA method detects probably also so-called "hidden" RF. In the group of healthy subjects above 60 years at least one class of RF rises to 17.5%. On correlation with the clinical status an association was found with the degree of affection according to the functional score, with the presence of rheumatoid nodes and muscular affection in RA. Patients with RA treated with Methotrexate and Sulfasalazine tend to have declining IgG RF levels. | |
| 2679014 | Methotrexate in the treatment of rheumatoid arthritis. | 1989 Oct | Methotrexate is an effective agent for the treatment of rheumatoid arthritis. It is now widely prescribed for patients who have not tolerated or responded to gold compounds or penicillamine. Minor adverse reactions are common, and fatal pulmonary toxicity or cirrhosis can occur. The drug does not produce disease remissions, but continued administration helps reduce pain, stiffness and swelling. Within the past year, the Food and Drug Administration has approved methotrexate for use in treating rheumatoid arthritis. | |
| 2080488 | [Methotrexate. Pharmacology applied to the treatment of rheumatoid arthritis]. | 1990 Nov | Methotrexate (MTX) is used increasingly for the treatment of rheumatoid arthritis (RA). It is an antagonist of folic acid. For the low doses used in RA (less than 15 mg/week), MTX is completely and rapidly absorbed with an active process membrane transport. The frequent toxic effects of this drug (hepatotoxicity, hematologic or possible long-term oncogenicity) limit its widespread use. MTX is as effective in treating RA as the other second line drugs and always more rapidly effective, perhaps because of anti-inflammatory properties. MTX must at the present time be used only in severe RA, refractory to more than one classical slow acting drug. Despite this, it is an extremely promising new agent in the therapy of rheumatic diseases. | |
| 2790404 | Synovial and serum levels of methotrexate during methotrexate therapy of rheumatoid arthri | 1989 Oct | Methotrexate (MTX) levels were studied following intravenous MTX in both serum and synovial fluid (SF) of rheumatoid arthritis patients. Two hours after injection serum MTX levels were higher than those of SF. At 24 hours SF levels of MTX exceeded those of the serum, while at 72 hours both blood and SF concentrations were undetectable. The localization of parenteral MTX in the SF may have importance in the understanding of its mechanism and site of action in rheumatoid arthritis. | |
| 1859490 | Methotrexate versus azathioprine in the treatment of rheumatoid arthritis. A forty-eight-w | 1991 Aug | We conducted a double-blind, randomized trial comparing azathioprine (AZA) and methotrexate (MTX) in the treatment of patients with rheumatoid arthritis in whom parenteral gold and/or D-penicillamine treatment had been unsuccessful. Patients were randomly assigned to receive either AZA (100 mg daily) or oral MTX (7.5 mg weekly). After 8 weeks, the dosage was increased depending on the clinical improvement. Sixty-four patients were followed up for 48 weeks (33 AZA, 31 MTX). Comparison of values at week 24 with baseline values revealed significant improvement in 12 of 13 disease variables in the MTX group and in 6 of 13 in the AZA group. Comparison between the 2 treatment groups at 24 weeks, by area-under-the-curve analysis, showed significantly more improvement in the MTX group in terms of the swollen joint count, pain score, erythrocyte sedimentation rate, C-reactive protein level, hemoglobin level, thrombocyte level, and disease activity score. A significant overall clinical improvement (disease activity score) was found in 7 of 20 patients treated with AZA and 18 of 30 patients treated with MTX after 24 weeks of therapy, and in 6 of 12 AZA-treated patients and 19 of 25 MTX-treated patients after 48 weeks. The number of withdrawals due to side effects was significantly higher in the AZA group. After 48 weeks, only 12 patients from the AZA group (36%), but 25 from the MTX group (81%), were still using the initial drug. These results demonstrate MTX to be superior to AZA in the treatment of rheumatoid arthritis, with a more rapid clinical improvement which is sustained after 1 year, accompanied by a lower rate of serious adverse reactions. | |
| 3580007 | Increase of dihydrofolate reductase in peripheral blood lymphocytes of rheumatoid arthriti | 1987 Apr | Because of a previously observed plateau of clinical response after long-term methotrexate (MTX) therapy for rheumatoid arthritis (RA), we investigated whether such treatment might lead to acquired resistance to the drug. We studied the activity of dihydrofolate reductase (DHFR) (the target enzyme of MTX) in peripheral blood mononuclear cells of 11 RA patients who had been treated with MTX for a median of 43 months. The enzyme levels were markedly increased compared with levels found in the cells of 6 RA patients treated with other slow-acting drugs. Quantitative dot-blot analysis of DNA from 7 of these patients showed no evidence of DHFR gene amplification. No correlation was observed between increased levels of DHFR and either response to therapy or to the weekly MTX dosage. Phytohemagglutinin-stimulated peripheral blood lymphocytes from 6 patients with increased levels of DHFR showed no evidence of MTX resistance in vitro. The increased DHFR levels may result from binding of MTX to the enzyme, which may block the normal degradation pathways; they do not appear to be a marker of impending drug resistance. | |
| 3572937 | Toxicity of methotrexate in rheumatoid arthritis. | 1987 Feb | Seventy-two patients with rheumatoid arthritis had been treated with pulse weekly oral methotrexate with a mean followup of one year. Minor side effects (oral ulcers, transient elevation of liver enzymes, nausea, vomiting) were present in 46 patients (63.8%), whereas major side effects (severe infection, cytopenia, respiratory failure, seizures, gastrointestinal bleeding) were present in 7 (9.7%), 2 of whom died. Patients with major side effects had shorter disease duration and increased frequency of extraarticular manifestations as compared to those with no side effects. No association between a particular clinical or genetic variable and occurrence of side effects to methotrexate was found. | |
| 2715941 | Pharmacokinetics of low-dose methotrexate in rheumatoid arthritis patients. | 1989 Feb | The pharmacokinetics and bioavailability of low-dose methotrexate (MTX) (10 mg/m2) were evaluated in 41 subjects who had definite or classical rheumatoid arthritis as defined by the American Rheumatism Association criteria. Subjects received 10 mg/m2 (to the nearest 2.5 mg) of MTX in a single oral dose and a single intravenous (iv) dose one week apart. Serum concentrations for this low-dose regimen were monitored using a radiochemical ligand binding assay. The results indicate the MTX is cleared from the plasma at a rate of 84.6 mL/min/m2. The terminal half-life was approximately 6 h. The volumes of distribution at steady state and for the central compartment were 22.2 and 13.5 L/m2, respectively. The mean residence time in the body, in the systemic circulation, and in the periphery were estimated to be 4.7, 3.0, and 1.7 h, respectively, with a peripheral single-pass mean transit time of 6.0 h and an intrinsic mean residence time in the periphery of 7.9 h. The mean absorption time was 1.2 h and the oral bioavailability was 0.70. The ratio of synovial fluid concentration to serum concentration 4 and 24 h after a dose was found to be approximately 1.0, indicating that at least within that time range serum and synovial fluid concentrations are approximately equal. Because of conflicting results and insufficient data from previous high-dose pharmacokinetic studies, it is difficult to say whether or not low-dose MTX pharmacokinetics differs from those of high-dose MTX. | |
| 1934868 | Homocysteine levels in patients with rheumatoid arthritis treated with low-dose methotrexa | 1991 Nov | Plasma homocysteine levels were determined in patients who participated in a randomized, double-blind placebo-controlled trial of folate supplementation (1 mg/day) during methotrexate therapy for rheumatoid arthritis. Plasma and red blood cell folate levels before methotrexate therapy were significantly negatively correlated with homocysteine levels. Homocysteine levels were not significantly correlated with the initial C1 index (an assay that measures the folate status of blood mononuclear cells) or the C1 index during methotrexate therapy. There was no significant difference in homocysteine levels between pretreatment and levels drawn at 3 or 6 months. Initial homocysteine levels were predictive of toxicities, such as gastrointestinal intolerance and elevations of liver enzymes in the placebo group. There was no significant correlation between occurrence of toxicity and initial homocysteine levels in the folic acid-supplemented group. Homocysteine levels were not predictive of the efficacy of methotrexate therapy. We conclude that plasma homocysteine levels are correlated with plasma and red blood cell folate levels before methotrexate therapy but is not correlated with folate status in blood mononuclear cells. | |
| 3199396 | Methotrexate kinetics in rheumatoid arthritis: is there an interaction with nonsteroidal a | 1988 Sep | Pharmacokinetic drug interaction between methotrexate (MTX) and nonsteroidal anti-inflammatory drugs (NSAID) has been implicated in several case reports of MTX related toxicity. We therefore studied the kinetics of low dose (15 mg) oral MTX with and without concomitant NSAID therapy after preliminary determination of the systemic bioavailability of commercial tablets. Fourteen patients with rheumatoid arthritis, age range 44-77 years, participated in paired kinetic studies performed 1-4 weeks apart. The Abbott TDx fluorescence polarization immunoassay was used to measure serum levels and urinary excretion of MTX over 72 h after a single dose. The mean systemic bioavailability was 73% for the 15 mg oral dose. Area under the serum concentration versus time curve for a 50 mg oral dose was 1.1-2.7 times that of the 15 mg oral dose indicating dose dependent absorption. Mean kinetic variables after oral MTX did not differ significantly with and without NSAID therapy despite apparent interactions in individual patients. Renal clearance of MTX correlated with creatinine clearance (r = 0.8, p less than 0.01). | |
| 2213774 | Lack of significant interaction between low dose methotrexate and ibuprofen or flurbiprofe | 1990 Aug | Low dose methotrexate (MTX) is widely used in the treatment of rheumatoid arthritis. Current product recommendations accompanying MTX preparations advise against concurrent usage of nonsteroidal antiinflammatory drugs (NSAID), and adverse pharmacokinetic interactions have been reported with this combination. Six patients who were receiving MTX were studied with both oral and parenteral MTX, 10-25 mg/dose, without NSAID and with ibuprofen (2400 mg/day) and flurbiprofen (300 mg/day) for 6 weekly doses. Serum MTX levels were obtained at frequent intervals. Serum was separated and MTX analyzed using a radioimmunoassay (RIA). There was no observable interaction between MTX and either ibuprofen or flurbiprofen, with respect to the area under the curve per unit dose, Cmax, Cmax/dose, Tmax, and serum half-life. The pharmacokinetic indices were not significantly influenced by the route of administration. | |
| 3741499 | The safety and efficacy of the use of methotrexate in long-term therapy for rheumatoid art | 1986 Jul | Twenty-nine patients participated in a prospective study of the safety and efficacy of oral methotrexate in the treatment of refractory rheumatoid arthritis. Patients received a mean dosage of 12.4 mg weekly over a mean duration of 29.1 months. All patients had liver biopsies at baseline, 2 years, and annually thereafter. Patients improved significantly by all clinical measures of efficacy after 1 month; maximum improvement tended to occur after approximately 6 months of therapy. Radiographs showed improvement of erosive disease in 7 of 11 patients measured. There was a significant reduction in mean prednisone dosage. Four patients required an increase in the dosage of methotrexate after prolonged therapy, because of declining clinical response. Toxicity was noted at some time in 26 of 29 patients (90%), but reactions universally became mild and tolerable after adjustment of the dosage. No significant hepatotoxicity was found in 60 sequential liver biopsies, although elevated transaminase levels were noted at some time in 20 of 29 patients (70%). | |
| 2387560 | [Pulmonary disease induced by methotrexate]. | 1990 Jun 1 | A 68-year-old man with rheumatoid arthritis developed methotrexate-induced lung disease. He presented with fever, cough, respiratory distress and pulmonary infiltrates, which were initially mistaken for pneumonia. Alertness to this rare and dangerous complication of methotrexate treatment will reduce possible damage and help maintain its place as a leading medication for rheumatoid arthritis. | |
| 2387814 | Early beneficial effects of low dose oral methotrexate in rheumatoid arthritis. | 1990 May | The effect of low dose methotrexate pulse therapy was studied in 21 patients with active rheumatoid arthritis. Three doses of oral methotrexate 2.5 mg at 12 hourly intervals weekly was administered to all the patients. Patients were followed up for clinical, radiological and serological evaluation. Significant reduction in the number of painful and swollen joints, decrease in the duration of morning stiffness, fall in the erythrocyte sedimentation rate, and improvement in global assessment were seen in 15 patients (71.4%) by the end of 16 weeks. Five patients (23.8%) complained of minor gastric discomfort. None of the patients discontinued the treatment because of any side effect. |