Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 3409645 | Sexual dysfunction among patients with arthritis. | 1988 Mar | The relationship of arthritis and sexual dysfunction was investigated among 169 patients with rheumatoid arthritis, osteoarthritis and spondyloarthropathy, 130 of whom were pair-matched to controls. Assessments of marital happiness and depressed mood were also made using the CES-D and the Azrin Marital Happiness Scale (AMHS). Sexual dysfunctions were found to be common among patients and controls, the majority in both groups reporting one or more dysfunctions. Impotence was more common among male patients than controls and was found to be associated with co-morbidity and the taking of methotrexate. Depressed mood was more common among patients and was associated with certain sexual difficulties, but not with impotence. Marital unhappiness, as indicated by AMHS scores, was not associated with arthritis but was associated with sexual dysfunction, sexual dissatisfaction and being female. | |
| 3668846 | Influence of concomitant aspirin or prednisone on methotrexate synovial fluid concentratio | 1987 Oct | Methotrexate (MTX) is currently being used in the treatment of patients with rheumatoid arthritis. The purpose of this study was to investigate the effect of two classes of drugs, steroids and salicylates, on MTX synovial fluid concentrations. A novel canine model of monoarticular inflammation was used, in which each animal served as its own control with both inflamed and normal knees in the same animal. After the 6-week immunization process, animals in each group received either no drug (control), prednisone or aspirin (low dose and high dose) for 1 week before MTX. On the day of the study, each animal was given i.v. MTX, and serial serum and synovial fluid samples were obtained. Laboratory, histologic and clinical observations supported the presence of monoarticular inflammation. The end-of-infusion synovial MTX concentration in inflamed knees was significantly greater than in normal knees (P less than .05), but, 2 hr after the end of infusion, they were not different. The end-of-infusion ratio of synovial fluid MTX concentration to serum MTX concentration (both total and unbound) was significantly lower in the prednisone group than in the other treatment groups (P less than .05). The end-of-infusion ratio of the MTX synovial concentration in the inflamed knee compared with the normal knee at 2 hr was significantly lower in the prednisone group than in the other three treatment groups (P less than .05). These results have therapeutic implications for the use of MTX in treating rheumatoid arthritis. | |
| 1973354 | The in vitro effects of methotrexate on peripheral blood mononuclear cells. Modulation by | 1990 Jul | The mode of action of low-dose methotrexate (MTX) in rheumatoid arthritis (RA) is unclear. The effects of MTX are mediated primarily through inhibition of dihydrofolate reductase, resulting in a dose-dependent inhibition of purine and pyrimidine synthesis. Other folate-dependent metabolic pathways might be secondarily affected. One such pathway is the regeneration of methionine from homocysteine, with subsequent formation of the methyl donor S-adenosylmethionine (SAM) and polyamines, which are important in cell-mediated immune reactions. To assess whether MTX inhibits SAM and polyamine synthesis in lymphocytes, pokeweed mitogen-stimulated mononuclear cells from healthy donors were incubated with MTX. This resulted in decreased proliferation and IgG, IgM, and IgM rheumatoid factor synthesis. However, addition of folinic acid, methionine, SAM, or spermidine resulted in reversal of the MTX-mediated inhibition. These data suggest that MTX inhibits the folate-dependent pathway of methionine regeneration, thereby inhibiting SAM and polyamine synthesis. Since RA lymphocytes have increased concentrations of polyamines, the beneficial effects of MTX in RA may be related to its potential ability to reduce polyamine synthesis. | |
| 2784965 | Antiproliferative effects of methotrexate on peripheral blood mononuclear cells. | 1989 Apr | Methotrexate was added to cultured mononuclear cells from the peripheral blood of normal individuals and patients with rheumatoid arthritis (RA) to study the drug's effects on mononuclear cell proliferation and antibody synthesis. In the presence of methotrexate, marked antiproliferative effects (to levels less than 15% of baseline) were seen with 3H-deoxyuridine, but not with 3H-thymidine, as the marker of cell division. This difference was not due to altered kinetics of proliferation or the presence of salvage nucleotides in the culture medium. The absence of suppression of antibody production preactivated by pokeweed mitogen in vitro and the low levels of suppression of spontaneous IgM rheumatoid factor production by blood mononuclear cells from RA patients suggested a relative resistance of activated cells to the effects of methotrexate. The effects of methotrexate on both cell proliferation and antibody synthesis were completely reversed by the addition of high concentrations of exogenous folinic acid. The results suggest that methotrexate has effects on immunocompetent cells that may contribute to the efficacy of this drug in the treatment of RA and other autoimmune diseases. | |
| 3120583 | Current modalities in arthritic diseases. | 1987 Oct 30 | Little progress has been made in identifying the etiologies of the major rheumatologic diseases, which substantially limits our ability to identify truly disease-modifying treatments. Despite this constraint, major advances in the suppression of the signs and symptoms of these diseases have been made. Second-line drugs such as methotrexate have gained wide acceptance among rheumatologists and may supplant gold as the major therapy for rapidly advancing rheumatoid arthritis. The nonsteroidal anti-inflammatory drugs (NSAIDs), however, remain the first line of treatment for arthritic conditions. In recent years, much has been learned about how the NSAIDs suppress the inflammation and pain of arthritis. Even here, however, several inconsistencies exist with our current understanding. New findings in neurobiology may shed light on some of these puzzling features. Although the number of NSAIDs currently available seems a bit overwhelming, rationale exists for their continued development. Many patients do not have a response to some or all of these agents, with noncompliance because of gastrointestinal intolerance being among the probable causes. New compounds that offer improved safety in this regard are greatly needed. | |
| 1986675 | Methotrexate-induced asthma. | 1991 Jan | A patient with rheumatoid arthritis developed pulmonary symptoms and function test abnormalities consistent with asthma during methotrexate therapy. Assessments of airway responsiveness to methacholine during therapy revealed airway hyperreactivity that reverted to normal when the methotrexate was stopped. An extension of the methotrexate dosage interval from 7 to 10 days resulted in an abolition of the asthma, which remained in remission despite a return to a weekly cycle after a 3-month period of 10-day cycles. | |
| 3223742 | Multicentric reticulohistiocytosis. | 1988 Oct | This is a short report on the first case of a multicentric reticulohistiocytosis diagnosed at Middle Road Hospital in 1987. He presented with multiple reddish brown papules and nodules but without arthritis. Systemic review did not show any associated malignancies. Treatment with methotrexate has not been useful. Multicentric Reticulohistiocytosis is a proliferative histiocytic disorder that is benign. It is characterised by a dermatoarthritis, extensive red nodule and a rheumatoid-like arthritis. Histologically, multinucleated giant cells in ground glass cytoplasma and mononuclear histiocytes form the granulomatous infiltrate that invades the dermis, mucosa, synovium and others--bone, plasma, pericardium etc. | |
| 1678395 | Low-dose weekly methotrexate for unusual neutrophilic vascular reactions: cutaneous polyar | 1991 Jun | Low-dose weekly methotrexate therapy has been used to treat patients with psoriasis for more than 20 years. This regimen has also been used to treat rheumatoid arthritis, inflammatory bowel disease, primary sclerosing cholangitis, and corticosteroid-dependent asthma. We report two patients with Behçet's disease with cutaneous neutrophilic vascular reactions and three with cutaneous polyarteritis nodosa who responded dramatically to low-dose weekly methotrexate therapy. | |
| 3229029 | The effect of in vivo and in vitro methotrexate on lymphocyte proliferation as measured by | 1988 Oct | In several studies methotrexate therapy of patients with rheumatoid arthritis has not been found to depress the lymphocyte response to mitogens measured by the uptake of tritiated thymidine. We have postulated two effects of methotrexate on stimulated lymphocytes in vitro: a decrease in cell proliferation, but also a relative increase in thymidine uptake reflecting a specific decrease in the intracellular thymidine pool. The increased incorporation of tritiated guanosine by mitogen-stimulated lymphocytes was found to be markedly depressed by methotrexate (1 x 10(-7) M) in vitro whereas the incorporation of thymidine was often unchanged. Thymidine uptake of lymphocytes may not be an appropriate measure of stimulation in the presence of methotrexate. | |
| 3033240 | Effect of low dose methotrexate on neutrophil chemotaxis induced by leukotriene B4 and com | 1987 Feb | When mediators of inflammation such as complement component C5a or leukotriene B4 are introduced into an air pouch created in mice, these mediators induce the migration of neutrophils into the air pouch. Pretreatment of mice with low doses of methotrexate inhibits leukotriene B4 or C5a induced neutrophil migration into the air pouch. Inhibition of neutrophil chemotaxis by methotrexate may, at least in part, account for the rapid onset of antiinflammatory activity that was observed in clinical trials with methotrexate in rheumatoid arthritis. | |
| 2784964 | The effects of methotrexate on the production and activity of interleukin-1. | 1989 Apr | To explore the possibility that the mechanism of action of methotrexate (MTX) in rheumatoid arthritis (RA) is related to modulation of interleukin-1 (IL-1), the effects of MTX on IL-1 production and activity were evaluated. Human peripheral blood mononuclear cells and murine peritoneal and splenic cells were stimulated by lipopolysaccharide to produce IL-1. No inhibition of IL-1 synthesis or secretion caused by MTX treatment could be demonstrated either in vitro or in vivo, in patients with RA or in mice treated with MTX. We did show, however, that MTX had an inhibitory effect on IL-1 activity in 2 assays that demonstrate 2 different functions of IL-1. In a 2-step assay using LBRM-33-1A5 (1A5) and CTLD cells, MTX inhibited the secretion of IL-2 by 1A5 lymphoma cells in response to phytohemagglutinin and IL-1. In an assay using D10.G4.1 (D10) cells, MTX inhibited IL-1-induced proliferation of the D10 T cell clone. No effect of the drug on IL-2 activity was observed. The results demonstrate that MTX is capable of inhibiting some IL-1 activities without affecting IL-1 production or secretion. We propose that the inhibition of IL-1 activity or IL-1-dependent events may be one of the mechanisms of action of MTX in RA. | |
| 2920054 | Reversal of neutropenia with methotrexate treatment in patients with Felty's syndrome. Cor | 1989 Feb | We evaluated the clinical and hematologic response to methotrexate (MTX) in 4 women with Felty's syndrome (FS) who had had neutropenia for 1-3 years. Since immune complexes or antineutrophil antibodies are implicated in the pathogenesis of the neutropenia of FS, we also measured both direct and indirect levels of neutrophil-reactive IgG. All 4 patients showed a prompt and dramatic increase in neutrophil counts within 1-2 months of starting MTX therapy. In 3 patients, the symptoms of arthritis also improved; in the fourth patient, arthritis worsened. Recurring infections ceased in 3 patients. Neutrophil-reactive IgG levels, which were elevated in all patients prior to treatment, decreased toward normal while the patients were receiving MTX therapy. We conclude that MTX is effective in treating the neutropenia of FS, in part by lowering neutrophil-reactive IgG. | |
| 2309509 | Severe reversible thrombocytopenia resulting from butoconazole cream. | 1990 Feb | A 54-year-old woman with a 19-year history of rheumatoid arthritis developed life-threatening thrombocytopenia one week after beginning butoconazole therapy for a vaginal yeast infection. This was complicated by upper gastrointestinal hemorrhage that probably resulted from ibuprofen and methotrexate therapy. Sepsis, myelophthisic anemias, and other potential etiologies were ruled out. Once stabilized, the patient was rechallenged with other medications without incident. These findings indicate that a potentially serious thrombocytopenia may result from the administration of butoconazole vaginal cream or in combination with methotrexate and/or ibuprofen. | |
| 1947892 | 20 years' experience with ketoprofen. | 1991 | Ketoprofen has emerged as a potent nonsteroidal anti-inflammatory drug. Its efficacy in the treatment of conditions such as rheumatoid arthritis and osteoarthritis has been demonstrated throughout nearly 20 years of clinical use. It has also been shown to be an effective analgesic. In comparative studies, ketoprofen appears to be at least as effective as other anti-inflammatory and analgesic agents. Because of its short half-life (approximately 1.5 hours) no dosage adjustment appears to be necessary in elderly patients unless there is concomitant renal insufficiency. Although rapidly eliminated from plasma, elimination from synovial fluid is delayed, so therapeutic concentrations can be maintained in affected joints without necessitating frequent administration. The side effects of ketoprofen are similar to those of all NSAIDs, gastrointestinal disturbances being the most frequent. Evidence for the adverse effects of NSAIDs on cartilage is still limited. Drug interactions are similar to those of all NSAIDs, antacids, methotrexate and probenecid being particularly important. Ketoprofen is available in a wide range of formulations, each designed to provide appropriate therapy in specific clinical situations: oral capsules for short term therapy; sustained release forms for chronic therapy and once-daily administration; suppositories to avoid possible gastrointestinal disturbances in susceptible patients; intramuscular preparations for rapid action; and a gel formulation for topical treatment. In the future, research should determine whether ketoprofen and other NSAIDs have any disease-modifying effects on inflammatory conditions in addition to providing symptomatic relief. | |
| 2533001 | Discrepancy between 3H-thymidine uptake and cell cycle studies in stimulated lymphocyte cu | 1989 Nov | The mode of action of methotrexate (MTX) in rheumatoid arthritis (RA) is unknown. The hypothesis that its cytostatic effect may be involved has been questioned based on the evidence of several negative results, the most intriguing being its lack of effect on the Lymphoblastic Transformation Test (LTT) and other lymphoproliferations in cultures from patients' samples. Our study demonstrates that LTT evaluation by 3H-thymidine uptake, a standard method, is misleading when applied to MTX-treated cells. At in-vitro concentrations similar to those present in the red blood cells of RA patients, MTX produced an early block in the cell cycle without reducing the cellular uptake of 3H-thymidine. While the explanation of this discrepancy is still open to discussion, it is clear that future studies on the immunological status of RA patients on MTX should not use thymidine uptake for the measurement of the lymphocyte response to mitogens and various stimuli, but must rely on other methods for evaluating DNA synthesis. | |
| 1656898 | In vitro effects of methotrexate on peripheral blood monocytes: modulation by folinic acid | 1991 Sep | The mechanism of action of low dose methotrexate in rheumatoid arthritis has not been established. It has been shown to have an anti-inflammatory effect and to inhibit neutrophil chemotaxis, but the effect on monocytes has not been widely studied. Normal donor peripheral blood monocytes were incubated with methotrexate in vitro and their superoxide production, chemotaxis, and phagocytosis subsequently assessed. Additionally, the influence of different culture media, and of folinic acid, and the methyl donor S-adenosylmethionine, and spermidine on the methotrexate mediated effects were evaluated. It was found that methotrexate in low concentrations inhibited in vitro monocyte chemotaxis and superoxide production but only after prolonged incubation. This inhibition was augmented by incubation in medium containing a low methionine concentration and was abolished by folinic acid and S-adenosylmethionine, suggesting that methotrexate may interfere with specific methylation reactions. | |
| 1887157 | [The application of photopheresis in the therapy of cancerous and autoimmune diseases]. | 1991 May | Photopheresis is an extracorporeal form of immunotherapy, recently approved by the FDA for the treatment of cutaneous T-cell lymphoma. During photopheresis lymphocytes are collected from the patients by leukapheresis and after exposure to psoralens and UVA reinfused to the host. The reinfused cells induce an immunological reaction against the neoplastic cells that seems to be clone specific. 37 CTCL patients have been initially treated; 1/4 showed a complete remission, 1/4 did not answer to the therapy and 1/2 showed a clinical improvement without complete remission. The best responders were patients in erythrodermic stage, particularly when photopheresis had been started early. The association with methotrexate induced a complete clinical remission in the cases with a partial answer to photopheresis. The average survival of patients treated with photopheresis was around 50 weeks in comparison with the Mycosis Fungoides Study Group data reporting for the same type of patients a 30 weeks survival using conventional therapies. Photopheresis has been recently used in the rejection control after heart transplantation and in the treatment of AIDS and several autoimmune diseases as pemphigus, sclerodermia, rheumatoid arthritis, LES. The preliminary therapeutic results are very encouraging for a larger use of photopheresis in the treatment of T cell mediated diseases. | |
| 2251435 | [Pneumopathy caused by methotrexate]. | 1990 | Methotrexate, an antifolate cytotoxic drug, is used in anticancer chemotherapy as well as an immuno suppressive in rheumatoid arthritis. It is responsible for numerous secondary effects, amongst which is a characteristic acute pneumonia known since 1969. This pneumonitis has been described in detail, up to the present time in 78 cases gathered in this review. The prevalence of this complication is estimated at around 7%. This pneumonia may occur whatever the age, indication for which methotrexate is prescribed, the route of administration of the product (including the intra-thecal route) and the dose. It includes dyspnoea, fever, (sometimes quite marked) and frequently an acute reversible respiratory failure. Radiologically the opacities are usually diffuse interstitial and symmetrical with a basal predominance with sometimes some confluence and occasionally a pleural reaction. In a small number of cases a transient mediastinal adenopathy has been described. Respiratory function tests show a rapidly developing restrictive syndrome accompanied by hypoxia and hypocapnia. Broncho-alveolar lavage is characterised by hypercellularity with a frank and apparently transitory lymphocytosis. Histologically the most frequent lesion sighted is an extensive acute granulomatous reaction with or without oedema. Most often the outcome is favourable (75% of cases). However 6 deaths due to respiratory failure have been reported. Even though there has not been any formal test, steroid therapy in high dosage seems to accelerate recovery. Progress to an irreversible pulmonary fibrosis is possible but rare. The mechanism of this drug related acute pneumonia is not known but would seem to resemble that of other granulomatosis. Besides this rapidly progressive pneumonitis, methotrexate is responsible for a very small number of cases of severe pulmonary oedema and of acute painful pleurisies. | |
| 1771651 | Trace analysis of methotrexate and 7-hydroxymethotrexate in human plasma and urine by a no | 1991 Nov | A new high-performance liquid chromatographic method for the quantitative determination of methotrexate (MTX) and its metabolite 7-hydroxymethotrexate (7-OHMTX) in blood plasma and urine was developed. The method utilized a solid-phase extraction procedure (Certify II cartridges) for the simultaneous isolation of MTX and 7-OHMTX. Chromatographic separation was achieved using a C18 reversed-phase column with isocratic elution. The eluent was irradiated with UV light of 254 nm, which converted MTX and 7-OHMTX by photolytic oxidation to fluorescent products. The limits of detection of MTX and 7-OHMTX in plasma were approximately 0.2 and 1 nmol/L, respectively. The intraday variability in the quantitation of MTX and 7-OHMTX was less than 8% down to 1 nmol/L and 4.6 nmol/L, respectively. Both MTX and 7-OHMTX could be detected in plasma from a patient being treated for rheumatoid arthritis 1 week after the last dose (10 mg orally). | |
| 2576330 | Drug interactions with non steroidal anti-inflammatory drugs (NSAIDs). | 1989 | Drug interactions occur when the pharmacologic profile of one drug is altered by the administration of another drug. These interactions may be due to changes in absorption, distribution, metabolism or excretion. NSAIDs are associated with drug interactions but only a proportion are clinically relevant. Many are due to displacement of a drug from its plasma protein binding sites by NSAIDs which are tightly protein-bound. They may not occur with all NSAIDs but might be selective: most NSAIDs do not have clinically important interactions with oral hypoglycemic agents whereas phenylbutazone, azaprozone & aspirin prolong their half-life. Similarly phenylbutazone and azaprozone prolong coumadin's half-life. Lithium clearance may be decreased by indomethacin, piroxicam, phenylbutazone and diclofenac. Methotrexate (MTX) may be displaced from its binding protein sites by NSAIDs. This is generally not clinically relevant with low doses of MTX as utilized in rheumatoid arthritis patients with normal renal function. NSAIDs also may reduce renal blood flow, tubular excretion of drugs & renal prostaglandin production and may attenuate the effect of anti-hypertensive drugs. Renal failure & hyperkalemia have been reported in patients receiving triamterene & indomethacin. The clinician should be aware of important drug-drug interactions prior to prescribing NSAIDs. Continued scrutiny of these effects are indicated to increase the safety profile. |