Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 11402516 | [Large granular lymphocyte proliferations. Clinical and pathogenic aspects]. | 2001 May | INTRODUCTION: The clinical course, biological features, and recent data on the pathogenesis of large granular lymphocyte (LGL) leukemia are reviewed. CURRENT KNOWLEDGE AND KEY POINTS: Clonal diseases of LGL disorders can arise from a CD3+, CD57+ T-cell lineage, which are the most frequent, or from a CD3-, CD56+ NK-cell lineage. The diagnosis of LGL leukemia is suspected on the basis of a persistent excess of LGL, usually with neutropenia and splenomegaly. It is assessed by immunophenotypic and molecular studies of T-cell receptor clonality (southern blot, PCR). Association with autoimmune diseases (rheumatoid arthritis, erythroblastopenia, etc.) is a main feature of chronic LGL proliferation. Questions about a viral agent (HTLV1?), facilitation of clonal expansion by cytokines (IL-12, IL-15), and the defective Fas apoptotic pathway are discussed. Treatment of symptomatic LGL proliferations is based on immunosuppressive agents (principally methotrexate and cyclophosphamide). FUTURE PROSPECT AND PROJECTS: The epidemiology, prognosis factors, therapeutics and the pathogenesis of LGL leukemia are unknown. We proposed the creation of a French register of LGL expansions to explore these different aspects. | |
| 10517404 | Fatal bacterial endocarditis following aortic valve replacement in a patient being treated | 1999 Sep | A 41-year-old man being treated with methotrexate for psoriasis underwent aortic valve replacement. He subsequently developed fulminating bacterial endocarditis. Bacterial endocarditis occurs in 1-2% of cases after prosthetic valve replacement and has a high mortality. The long-term use of methotrexate and similar drugs is increasing in conditions such as psoriasis, rheumatoid arthritis and inflammatory bowel disease. Thus, more patients undergoing heart valve surgery will be taking these preparations for coexisting disease. As methotrexate increases the risk of infection, its perioperative use in these patients requires further evaluation. | |
| 11059096 | Low dose treatment with methotrexate-adverse drug reactions survey. | 2000 Jul | Antineoplastic drugs caused various and frequent adverse drug reactions (ADR) in connection with their pharmacodynamics. Methotrexate (MTX) ADRs are preferably gastrointestinal disorders and hepatotoxicity (hepatic enzyme abnormalities). The aim of this study was to detect and analyse ADR induced by low-dose MTX treatment in rheumatology. We observed 94 patients, 63 with rheumatoid arthritis and 31 with psoriatic arthritis. All patients were co-medicated with nonsteroidal anti-inflammatory drugs (NSAID) as Diclofenacum, Indomethacinum, Piroxicamum and 51% with glycocorticosteroides. During the follow-up study we collected 18 case-reports with ADR for 17% of the patients. From the patients with registered ADR, 11 was treated with standard dose of 7.5 mg MTX for a week and 7 patients received from 10 to 15 mg for a week. The distribution of the cases according patients' gender was 9 females and 7 males. Prevail individuals in age groups' 41-50 and over 61 years. The most frequent adverse drug reactions were leucopenia, trombocytopenia, skin reactions and gastrointestinal disorders as vomiting, melaena, epigastrial pain, etc. The primary risk connected with long therapy of low doses MTX is hepatotoxicity that diagnose and treatment are painful and expensive. As a result of the appearance of ADR in 5 patients the therapy with MTX was not changed, in two cases MTX is stopped timely or the dosage is changed and in the rest 11 patients MTX was excluded from the therapeutic scheme. | |
| 10423160 | Antirheumatic agents and leukocyte recruitment. New light on the mechanism of action of ox | 1999 Jul 15 | Most anti-inflammatory agents used in the treatment of joint diseases exert inhibitory effects on leukocyte infiltration. Methotrexate, a disease-modifying drug, and corticosteroids also inhibit leukocyte accumulation during inflammation. However, the mechanisms of action of these different compounds on leukocytes vary and in the case of non-steroidal anti-inflammatory drugs (NSAIDs) the mechanism(s) may be indirect. No current drug for inflammatory or degenerative joint disease has been proposed to act specifically by an inhibitory action on neutrophilic leukocytes. Oxaceprol is an amino acid derivative that has been used for several years for the treatment of osteoarthritis and rheumatoid arthritis, ameliorating pain and stiffness and showing good gastrointestinal safety, particularly in comparison with NSAIDs. Recent experimental studies have shown that oxaceprol does not inhibit the synthesis of prostaglandins in vitro, but markedly inhibits neutrophil infiltration into the joints of rats with adjuvant arthritis. These results support earlier screening data showing inhibition by oxaceprol of leukocyte infiltration into sites of acute inflammation. In studies on surgical ischemia reperfusion in hamsters in vivo, oxaceprol was an effective inhibitor of leukocyte adhesion and extravasation. It is proposed that oxaceprol represents a therapeutic agent for degenerative and inflammatory joint diseases, which acts predominantly by inhibiting leukocyte adhesion and migration. | |
| 9567207 | Update on clinical trials in the rheumatic diseases. | 1998 Mar | Therapeutic trials in rheumatoid arthritis (RA), osteoarthritis, seronegative spondyloarthopathies, back pain, systemic lupus erythematosus, and systemic sclerosis are reviewed. For RA, minocycline has been proven effective in some subsets of RA, whereas tumor necrosis factor receptor IgG fusion protein appears quite effective for treating the symptoms of RA in a more resistant group. The latter trial illustrates the importance of tumor necrosis factor in RA. Also, the triple combination of hydroxychloroquine, sulfasalazine, and methotrexate is very effective even in resistant RA. In osteoarthritis, the effects of nonsteroidal anti-inflammatory drugs, intra-articular steroids, and biologics are reviewed, with generally nondifferentiable nonsteroidal anti-inflammatory drug effects and some short-term intra-articular effects of new biologics. Sulfasalazine is moderately effective for ankylosing spondylitis and psoriatic arthritis, although the large placebo response in the latter makes it more difficult to show responses. Trials in the treatment of back pain are beginning to be published, with a large cohort study over 1 year favoring surgery for early relief of pain in both sciatica and lumbar stenosis, but not showing a clear advantage in functional outcome at 1 year. Finally, early reports show the ability of dihydroepiandrosterone to decrease steroid use in systemic lupus erythematosus, whereas Relaxin appears to be effective in decreasing skin involvement in systemic sclerosis. These trials demonstrate in numerous ways the need to consider the elements of good trial design when testing therapeutic modalities in the rheumatic diseases. These key elements include 1) careful patient definition and selection; 2) removal of bias (requiring blinding, randomization, prospective studies, and often, placebo); 3) use of well-defined outcomes; and 4) careful analytic techniques. | |
| 10984137 | Atypical methotrexate dermatitis and vasculitis in a patient with ankylosing spondylitis. | 2000 | Reports of histologically proven low-dose methotrexate (MTX)-induced vasculitis are uncommon and mostly found for patients with rheumatoid arthritis. Herein we present a patient with ankylosing spondylitis who developed large atypical erythematopurpuric cutaneous lesions after the second oral dose of 7.5 mg MTX therapy. The histological findings of a cutaneous lesion were consistent with vasculitis. The skin lesions regressed significantly after the discontinuation of MTX therapy. As the clinical picture of the patient's rheumatological condition became progressively severe, prednisolone therapy was initiated 8 days later and the skin rash resolved completely in a couple of weeks. | |
| 11757271 | [Autoimmune neutropenias]. | 2001 Sep 15 | Primary auto-immune neutropenia (AIN) is usually described in children. Secondary AIN occurs in collagen vascular diseases such as rheumatoid arthritis and (Felty's syndrome), Gougerot-Sjogren syndrome, and systemic lupus erythematosus. Some cases of other immune cytopenia (idiopathic thrombocytopenic purpura, Evans's syndrome) or lymphoproliferative disorders (large granular lymphocyte leukemia, malignant lymphoma) may be associated with AIN. Some cases of primary AIN occur, especially in children. The diagnosis of AIN depends on the demonstration of autoantibodies directed against neutrophil-specific antigens like CD16. The availability of granulocyte-colony stimulating factor for the treatment of AIN has been a major advance. In some cases, immunosuppressive therapy using prednisone, methotrexate, cyclosporine A must be added, especially in cases of secondary AIN. | |
| 19078457 | Pneumocystis carinii pneumonia prophylaxis in patients with rheumatic diseases undergoing | 2000 Apr | Pneumocystis carini (PCP) has been recognized as a cause of pneumonia in immuocompromised patients, most notably in AIDS patients, but also in those receiving immunosuppressive therapy for a variety of other conditions, including malignancy, having an organ transplant, connective tissue diseases, and vasculitic syndromes. In non-HIV PCP patients, presentations may be more dramatic than in HIV-related PCP and the mortality may be higher, thus emphasizing the need to identify and provide prophylaxis for those at highest risk for PCP. The incidence of PCP varies in different rheumatic disorders, with the highest rated noted in Wegener's granulomatosis and the lowest noted in rheumatoid arthritis. Prophylactic regimens should be used in patients with Wegener's granulomatosis taking cyclophosphamide and daily corticosteroids and in other rheumatic disease patients who are treated with this regimen, such as in PAN, microscopic polyarteritis, or severe systemic lupus erythematosus. Prophylaxis should be strongly considered in patients taking prolonged, high doses of daily corticosteroids (>40mg/day for > 3 months) with a second immunosuppressive agent other than cyclophosphamide, such as methotrexate, for example, as in PM/DM and in alternative regimens for Wegener's granulomatosis. Emerging data suggest the utility of CD4 counts as a method to distinguish those at highest risk for PCP to selectively apply prophylactic therapy. TMP-SMX is the usual first choice for prohpylaxis. | |
| 9361160 | Methotrexate hepatotoxicity. | 1997 Nov | Hepatoxicity is a major adverse reaction that can occur during methotrexate treatment of the rheumatic diseases. The pathologic lesions are nonspecific and the pathogenesis is poorly understood. Early studies in psoriasis clearly established a relationship between hepatic injury and several risk factors, particularly alcohol use. Methotrexate hepatoxicity occurs less frequently in rheumatoid arthritis than previously reported in psoriasis patients. Consequently, the American College of Rheumatology guidelines for methotrexate monitoring do not recommend baseline and surveillance liver biopsies in low-risk patients. These guidelines seem to be useful and cost-effective. | |
| 9137391 | [Respiratory function surveillance during prolonged treatment with low-dose methotrexate]. | 1997 Mar 22 | Long-term low-dose methotrexate (MTX) has a proven beneficial effect in patients with rheumatoid arthritis; the main drawback being the risk of interstitial pneumonia. Although estimations have varied, in our recent prospective analysis we observed 4 cases among 124 receiving MTX for rheumatological disorders, i.e. a risk rate of 3.2% Age, sex, disease duration, administration route and daily or cumulative dose do not appear to affect risk, but recent work suggest that renal failure, concomitent use of nonsteroid anti-inflammatory drugs, smoking, past pulmonary history or radiographic anomalies as well as recent withdrawal of corticosteroids are risk factors. Pulmonary function tests can be used to detect acute disorders and regular testing has been proposed to help predicted pulmonary complications in patients receiving long-term MTX. Unfortunately, minimal variations observed to date, for example in forced vital capacity or expiratory volume, do not appear to occur prior to clinical manifestations and may be due to normal aging processes or the pathological effect of the rheumatoid disease itself. In addition, due to the proven efficacy of MTX, randomized trials against a control group not given MTX would be ethically unacceptable. We are thus still unable to predict development of secondary pulmonary complications to long-term low-dose MTX. We therefore recommend testing pulmonary function at treatment onset to establish a reference for subsequent tests performed in case of clinical manifestations during MTX therapy. Patients should be counselled to consult in case of pulmonary symptoms in order to allow diagnosis as early as possible. The most recent data also would suggest that MTX may induce infraclinical alterations of pulmonary function although their significance remains to be clarified. | |
| 9314611 | Clinical pharmacokinetics of diclofenac. Therapeutic insights and pitfalls. | 1997 Sep | Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID) of the phenylacetic acid class. When given orally the absorption of diclofenac is rapid and complete. Diclofenac binds extensively to plasma albumin. The area under the plasma concentration-time curve (AUC) of diclofenac is proportional to the dose for oral doses between 25 to 150 mg. Substantial concentrations of drug are attained in synovial fluid, which is the proposed site of action for NSAIDs. Concentration-effect relationships have been established for total bound, unbound and synovial fluid diclofenac concentrations. Diclofenac is eliminated following biotransformation to glucoroconjugated and sulphate metabolites which are excreted in urine, very little drug is eliminated unchanged. The excretion of conjugates may be related to renal function. Conjugate accumulation occurs in end-stage renal disease; however, no accumulation is apparent upon comparison of young and elderly individuals. Dosage adjustments for the elderly, children or for patients with various disease states (such as hepatic disease or rheumatoid arthritis) may not be required. Significant drug interactions have been demonstrated for aspirin (acetylsalicylic acid), lithium, digoxin, methotrexate, cyclosporin, cholestyramine and colestipol. | |
| 10503652 | Evaluation of recent clinical trials in lupus. | 1999 Sep | Clinical trials in lupus pose many challenges, ranging from small numbers of subjects to endpoints that are difficult to quantify. Improved standardization of both design and appropriate endpoints is necessary. Recent trials have been small in number, with few randomized controlled trials. These trials have evaluated therapies such as methotrexate, cyclosporine A, bromocriptine, immunoadsorption columns, and hydroxychloroquine withdrawal. With the advent of improved techniques as well as newer therapeutic agents, options for the treatment of lupus should begin to grow over the next several years in a fashion similar to that which has been seen in rheumatoid arthritis. | |
| 9703150 | Thrombocytopenia after a single test dose of methotrexate. | 1998 Aug | Low dose methotrexate (MTX) can cause numerous gastrointestinal, pulmonary, central nervous system, and hematologic toxicities. Risk factors include folate deficiency, decreased renal function, older age, increased mean corpuscular volume or concomitant use of trimethoprim-sulphamethoxazole, probenecid, or nonsteroidal antiinflammatory drugs (NSAIDs). We describe a case of isolated thrombocytopenia after a single oral dose of MTX in a 36-year-old woman with sarcoidosis. She had rheumatoid arthritis and her only other medications included NSAIDs. One week after her first oral dose of 7.5 mg MTX, diffuse petechiae developed on her chest, abdomen, and extremities; she had a platelet count of 25,000/mm3. Nine days after discontinuation of both MTX and the NSAID, her platelet count increased to 189,000/mm3. | |
| 9924204 | An overview of rheumatological research in the European Union. | 1998 Nov | OBJECTIVES: To evaluate the distribution and scope of papers published by authors from the European Union (EU) in rheumatological journals and the impact of rheumatological research in the EU in comparison with that produced elsewhere. METHODS: Papers published during the year 1995 in the 17 rheumatological journals screened by ISI were considered. The journal impact factor (IF) was noted. All key words, both those reported by the authors and those attributed by ISI, were identified and their frequency was calculated using a special purpose program. RESULTS: 2331 papers were published in the rheumatological literature during 1995. Of them, 1316 (56.5%) came from the EU (29.4% from the UK, 17.4% from France, 11.5% from Germany, and 10.8% from Italy) and 544 (23.3%) from the USA. The mean IF of EU papers was approximately 2 in comparison with 3.5 for the USA and 2.4 for other countries. In 1995, 2680 key words attributed by the authors and 5651 attributed by ISI appeared in the rheumatological literature. Less than a quarter of them was cited more than twice. The leading key words were rheumatoid arthritis for diseases and methotrexate for drugs. CONCLUSIONS: Bibliometric findings are useful to follow research trends. These data show the relevance of EU rheumatological research and the high scientific production of small countries. Dispersion of key words should be avoided and journal editors should promote their standardisation. | |
| 10761014 | Large Granular Lymphocyte Leukemia. | 1998 Jan | BACKGROUND: Clonal diseases of large granular lymphocyte (LGL) disorders can arise from a CD3+ T-cell lineage or from a CD3- NK-cell lineage. CD3+ LGL leukemia is the most frequent form of LGL leukemia and is a distinct entity by FAB and REAL classifications. METHODS: The clinical course, biological features, and recent data on pathogenesis of CD3+ LGL leukemia are reviewed. The spectrum of differential diagnosis is described. RESULTS: T-LGL leukemia affects elderly people. Approximately 60% of patients are symptomatic; recurrent infections secondary to chronic neutropenia, anemia, and rheumatoid arthritis are the main clinical features. The most common phenotype is CD3+, CD8+, CD57+. Clonality is detected by clonal rearrangement of the T-cell receptor gene. Clinical and molecular remission can be obtained with oral low-dose methotrexate. Serologic findings show frequent reactivity to the BA21 epitope of HTLV-I env p21e, suggesting that a cellular or retroviral protein with homology to BA21 may be important in pathogenesis. Clonal expansion may be facilitated by IL-12 and IL-15 lymphokines. Constitutive expression of Fas ligand by leukemic LGLs support the hypothesis that leukemic cells arise from antigen-activated cytotoxic T cells. Leukemic LGLs express a multidrug-resistance phenotype that could partly explain the chemoresistance observed in aggressive cases. CONCLUSIONS: CD3+ LGL leukemia is a distinct lymphoproliferative T-cell disorder with specific clinicobiological aspects. The clinical spectrum of LGL proliferations is wide and immunophenotypic, and genotypic studies are needed to establish the diagnosis. | |
| 11589364 | Anti-inflammatory effects of methotrexate on reversed passive Arthus reactions in rats. | 2000 May | The anti-inflammatory effects of methotrexate (MTX), an anti-rheumatic drug for treating rheumatoid arthritis, on acute inflammation were studied by using Arthus reactions induced in the pleural cavity and dorsal skin of rats. The effects were compared with those of dexamethasone (DEX), a synthetic analog of adrenocortical steroid, and of ketoprofen (KET), a nonsteroidal anti-inflammatory agent. In reversed passive Arthus (RPA) reactions induced in the pleural cavity by an anti-bovine-albumin serum, DEX significantly suppressed both neutrophil accumulation and plasma exudation at the sites of injection of an antibody, whereas MTX and KET had no effect. In the RPA reaction induced in the dorsal skin by an anti-ovalbumin serum, all three drugs inhibited exudation to the same level. However, DEX and MTX suppressed neutrophil accumulation, whereas KET did not. We found that the oral administration of MTX for 3 days significantly inhibited both neutrophil accumulation and exudation in the RPA reaction in the dorsal skin, suggesting that MTX is an effective anti-inflammatory agent. However, the manifestation of these anti-inflammatory effects might be restricted by differences in the inflammation models in rats. | |
| 11602464 | Lymphomas complicating Sjögren's syndrome and hepatitis C virus infection may share a com | 2001 Nov | BACKGROUND: The occurrence of B cell non-Hodgkin's lymphoma is a complication of Sjögren's syndrome (SS) and, at least in some countries, of chronic hepatitis C virus (HCV) infection. Lymphomas occurring in both diseases share a number of characteristics: predominance of low grade, marginal zone histological type, frequency of mucosal localisation, possible transformation into a large B cell lymphoma, association with asymptomatic low level cryoglobulinaemia, absence of virus within lymphoma cells, but localisation of lymphomas in organs where the chronic viral infection is active in patients with HCV and where the autoimmune disease is active in patients with SS. HYPOTHESIS: It is proposed that in both diseases the first event of lymphomagenesis is the chronic stimulation at the site of the disease of polyclonal B cells secreting rheumatoid factor (RF). Then, that these RF B cells may become monoclonal and disseminate in other organs. The monoclonal secreted RF complexed with polyclonal IgG may cryoprecipitate. The following step would be a chromosomal abnormality (for example, trisomy 3 or bcl-2 translocation) which would confer to these cells a low grade B cell lymphoma comportment. A last event (for example, a mutation of p53) might transform this low grade B cell lymphoma into a high grade, large B cell lymphoma. The non-random utilisation of VH and VL by SS associated lymphoma B cells and the recent demonstration that these lymphoma B cells may display RF activity support the hypothesis that these lymphomas grow through an autoantigen driven process. CONCLUSION: The best preventive treatment of lymphoproliferations occurring in SS probably consists in decreasing the hyperactivation of autoreactive B cells when it is present, allowing the use of immunosuppressive drugs such as methotrexate or even tumour necrosis factor alpha antagonists, which in theory could favour other types of lymphoproliferation. | |
| 10844522 | Inhibition of cyclin A gene expression in human B cells by an immunosuppressant mizoribine | 2000 Jun | Mizoribine has been shown to have beneficial effects in the treatment of rheumatoid arthritis and lupus nephritis, in which abnormal B cell functions are involved. Previous studies demonstrated that mizoribine directly suppresses the function of human B cells. The current study explored in detail the mechanism of the suppression of human B cell responses by mizoribine at the molecular level. Highly purified peripheral blood B cells obtained from normal healthy individuals were stimulated with Staphylococcus aureus Cowan I (SAC) plus IL-2 in the presence or absence of mizoribine or methotrexate for 48 h to 72 h. The expression of cyclin A mRNA was determined by semiquantitative reverse transcriptase-polymerase chain reaction followed by Southern hybridization. Although at pharmacologically attainable concentrations both mizoribine and methotrexate suppressed the production of IgM of SAC-activated B cells, mizoribine, but not methotrexate, decreased the expression of cyclin A protein as well as mRNA in B cells stimulated with SAC + IL-2. Of note, mizoribine facilitated the degradation of cyclin A mRNA in the presence of actinomycin D, indicating that mizoribine shortens the stability of cyclin A mRNA. The results indicate that mizoribine suppresses the expression of cyclin A mRNA in human B cells by down-regulating its stability, and thus down-regulates their responses. | |
| 9051055 | Methotrexate management of immune-mediated cochleovestibular disorders. | 1997 Feb | Immune-mediated cochleovestibular disorders continue to present a management challenge to the otolaryngologist. The traditional treatment of these disorders, corticosteroids and/or cyclophosphamide (Cytoxan), has been associated with serious and occasionally life-threatening complications. In this study we report our experience in treating 25 patients with immune-mediated cochleovestibular disorders with methotrexate, a less toxic immunosuppressive agent that has been used extensively in patients with rheumatoid arthritis. Mean duration of treatment was 12.9 months, and adverse reactions were acceptable and reversible. Hearing improved in 69.6% of patients, and vestibular symptoms subsided or improved in 80% of patients. The results of this study suggest that methotrexate treatment is effective in a substantial number of patients with immune-mediated cochleovestibular disorders and has acceptable adverse reactions. A prospective, randomized study is needed to compare the efficacy of methotrexate with that of other immunosuppressive agents. | |
| 11014343 | The antiinflammatory drug sulfasalazine inhibits tumor necrosis factor alpha expression in | 2000 Sep | OBJECTIVE: Sulfasalazine (SSZ) is a commonly used drug in the treatment of inflammatory diseases such as rheumatoid arthritis and Crohn's disease. In both diseases, the proinflammatory cytokine tumor necrosis factor alpha (TNFalpha) plays a prominent role. In these studies, we investigated the mechanism by which SSZ inhibits TNFalpha expression in macrophages and macrophage-like cell lines. METHODS: Monocyte-derived macrophages and several macrophage-like cell lines were exposed to SSZ in vitro, and the effect on TNFalpha expression was monitored by reverse transcriptase-polymerase chain reaction and Western blot analysis. In addition, the effects of SSZ in vivo were examined by intraperitoneally injecting mice with SSZ, after which peritoneal cells were harvested and examined using various staining methods. RESULTS: Preincubation of macrophages with SSZ, but not with methotrexate, inhibited lipopolysaccharide (LPS)-induced TNFalpha expression. Inhibition of TNFalpha expression by SSZ coincided with the induction of apoptosis, as judged by the appearance of morphologic changes typical of apoptosis, such as nuclear condensation and fragmentation. Induction of apoptosis by SSZ was confirmed by TUNEL analysis and by the detection of cleaved U1-70K, a substrate of caspase 3. Intraperitoneal injections of SSZ in mice resulted in the induction of apoptosis of peritoneal cells within a few hours. SSZ-induced cleavage of the U1-70K protein was inhibited by Zn2+ and by specific inhibitors of caspases 3 and 8, but not caspases 1 and 9. Interestingly, the reduced expression of LPS-induced TNFalpha in the presence of SSZ was restored by inhibition of caspase 8. CONCLUSION: Inhibition of TNFalpha expression in macrophages by SSZ is due to the induction of apoptosis and involves the activation of caspase 8. |