Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 7871335 | TCR1+ large granular lymphocyte proliferation in rheumatoid arthritis. | 1994 | The T gamma-lymphoproliferative syndrome is characterized by a proliferation of large granular lymphocytes (LGL). It is often associated with neutropenia, and in 30% of cases with rheumatoid arthritis (RA). Phenotypic analysis has demonstrated that in most cases of RA with T gamma-proliferative disease, the LGL represent T cells with a clonal rearrangement of the alpha/beta T cell receptor (TCR2). Here, three patients with gamma/delta TCR1+ LGL proliferation suffering from long-standing arthritis and neutropenia are described. The first patient with RA showed an expansion of a heterogeneous CD2+ CD16+ CD56- LGL population, of which 30% coexpressed TCR1 with V delta 1 rearrangement. The second patient with ankylosing spondylitis and RA was suffering from proliferation of TCR1+ (V gamma 9-, V delta 1-), CD2+ CD16- CD56- LGL with low coexpression of CD8. The third patient with RA was suffering from a proliferation of TCR1+ (V delta 1+, V gamma 9-) CD4- CD8- CD16- CD56- lymphocytes. On the basis of these unusual findings, the pathogenetic role of TCR1+ T cells in RA is discussed. | |
| 8278817 | Early, aggressive therapy for rheumatoid arthritis: concerns, descriptions, and estimate o | 1993 Oct | The past few years have witnessed changing perceptions about rheumatoid arthritis (RA); it is now considered a serious systemic disease that confers not only physical and social morbidity but also earlier mortality. The long-term outcome of sequential monotherapy based on the therapeutic pyramid has been disappointing. A review of prognostic factors, acute disease activity measures, functional measures, and the results of preliminary trials with combination therapy suggests that specific goals of treatment can be established and that logical, aggressive treatment in early disease can be accomplished. These goals should include prompt control and continuous reduction of the active joint count to < or = 4 and normalization of acute-phase reactants. The "graduated-step paradigm" of treatment designed with these goals in mind is described, and a retrospective series that gives an estimate of outcome with its use is reported. | |
| 8619097 | Eicosanoids in rheumatoid arthritis. | 1995 Aug | Eicosanoids are potent mediators in the cellular microenvironment. Eicosanoids have different effects depending on tissue or organ, the polyunsaturated fatty acid content of the diet of the individual, and the net effect of local microenvironmental factors--as eicosanoids, cytokines, and hormones modulate each others' effects through a complex, multilevel network of interactions. In general, eicosanoids have significant net proinflammatory effects. In RA, the net proinflammatory effects of the prostanoids is underscored by the effectiveness of the cyclooxygenase antagonists (NSAIDs), and recent data indicate a proinflammatory effect of the leukotrienes. Changes in the dietary polyunsaturated fatty acid composition to increased intake of marine n-3 fatty acids and/or dihomogamma-linolenic acid may favorably modulate eicosanoid synthesis towards less inflammatory or antiinflammatory eicosanoids and may ameliorate disease activity in RA. Recent advances in the biochemistry and molecular biology of the eicosanoid receptors and the synthetic pathways of eicosanoids will provide opportunities for advances in the therapeutics for RA, including selective cyclooxygenase (PGHS-2) antagonists, selective eicosanoid receptor antagonists and agonists, and selective inhibitors of PGH2 isomerases and enzymes of the 5-lipoxygenase pathway. | |
| 1455792 | [A new method for treating rheumatoid arthritis patients by electrophoresis using mefenami | 1992 Jul | The paper provides clinical and experimental reasoning for application of a new treatment for rheumatoid arthritis (RA) implying electrophoresis of an anti-inflammatory drug mefenamic acid from dimexide solution. Complete and partial responses registered in 125 patients, reached 75%. With the new method it is possible to relieve pain, correct immunity and stop inflammation. The best effect was shown in an inactive disease and in activity phases I and II in adjuvant use of the method. | |
| 8324932 | Antifolates in rheumatoid arthritis: a hypothetical mechanism of action. | 1993 Mar | The antifolates, methotrexate, aminopterin, 10-deazaaminopterin and sulfasalazine are clinically useful in the treatment of rheumatoid arthritis. Toxicity, rather than efficacy, appears to the the major factor limiting the usefulness of the classical antifolates (i.e., methotrexate and 10-deazaaminopterin). The fact that folate supplementation of methotrexate-treated rheumatoid arthritis patients reduces toxicity without altering efficacy also suggests that inhibition of the drug's target enzyme, dihydrofolate reductase, is not complete and not essential for efficacy. Since polyglutamates of methotrexate are direct inhibitors of thymidylate synthase and folate dependent enzymes of purine biosynthesis, the efficacy of this agent may involve blockade of these pathways. We hypothesize that blockage of aminoimidazole carboxamide ribotide transformylase, the folate dependent enzyme responsible for the insertion of carbon 2 into the purine ring, produces an immunosuppression mediated by secondary inhibition of adenosine deaminase, and S-adenosyl homocystein hydrolase by aminoimidazolecarboxamide metabolites. This mechanism of immunosuppression may explain the clinical effect of methotrexate, 10-deazaaminopterin, and possibly sulfasalazine. Since purine biosynthesis is a fundamental process, blockading this pathway may also decrease leukotriene production and interleukin-1 expression, which also could contribute to the efficacy of methotrexate. | |
| 1609238 | [Synovectomy in the realignment-stabilization of the rheumatoid wrist. Apropos of a series | 1992 Mar | The authors studied a series of 104 rheumatoid wrists, stages II, III or IV according modified Larsen's grading, treated between 1980-1988 by synovectomy realignment stabilization. The mean follow-up period was 5 years. The operation presents different steps which have an additive effect and must be associated in order long term clinical and radiological stability. They associated: extensor tendons and articular synovectomy stabilization of the distal radio ulnar complex by Sauve-Kapandji's operation, tendon transfert: the extensor carpis radialis longus is transferred on the extensor carpi radialis brevis the extensor carpi ulnaris is relocated with posterior annular dorsal ligament plasty. Results concerning relief of pain were very clear because the patients presented either complete relief of pain (73%) or only intermittent occasional pain. The overall active range of motion is nearly the same, when compared pre- and post-operative ratings. In general the patients who presented good pre-operative mobility usually improved them and the others preserved them. Larsen's radiological grading was modified by the authors to include instability's criteria in frontal and sagittal plane. Carpal height remained stable (75% less than or equal to 1 mm), ulnar deviation has never overreached 3 mm, radial deviation was not modified in 50% of cases. They found only 4 wrists presenting a stage II radiological grading with an evolution to the stage III and 12 of the stage III grading became stage IV. The instable type of the stage IV was stabilized by a surgical radiolunate arthrodesis. The stabilized type was nearly not modified. The different steps of operation (articular and tenosynovectomy, carpus stabilization and realignment with stabilization by stabilization of the radio ulnar complex joint using Sauve-Kapandji operation, tendons transfers and dorsal retinacular plasty) have an additive effect in achieving relief of pain with preservation of the pre-existing mobility. The stabilization of the radio ulnar complex by the Sauve-Kapandji operation constitutes a new approach in rheumatoid arthritis published by the author in 1985 and in our opinion appears to be simple and is very efficient in stabilizing wrist immediately, thus allowing early rehabilitation of these patients. Long term stability is affirmed by clinical and roentgenologic follow-up and globally a painless wrist, a preservation of the pre-operative motion and a stabilization in frontal and sagittal plane is obtained. | |
| 8670317 | A double-blind, placebo-controlled study of anti-CD5 immunoconjugate in patients with rheu | 1996 Jul | OBJECTIVE: To evaluate the efficacy of an anti-CD5 ricin-linked immunoconjugate (CD5-IC) in patients with rheumatoid arthritis (RA). METHODS: A total of 104 evaluable patients were enrolled in a multicenter, double-blind, multiple-dose, placebo-controlled study of CD5-IC. RESULTS: Treatment with CD5-IC in doses up to 8 mg/m2/day for 4 days in 1 month failed to produce marked or prolonged T cell depletion and was no more effective than placebo in ameliorating disease manifestations. An unexpectedly high placebo response was observed in 48% of the patients. Adverse events were correlated with the dose of CD5-IC, but the treatment was generally well-tolerated. CONCLUSION: At the doses used in this study, CD5-IC was ineffective for treating RA. | |
| 8913008 | An international study on measuring social support: interactions and satisfaction. | 1996 Nov | Recently, a new instrument was developed to measure social support. It consists of two parts; the Social Support Questionnaire for Transactions (SSQT) and the Social Support Questionnaire for Satisfaction with the supportive transactions (SSQS). The SSQT measures the number of supportive interactions and has proved to have good psychometric properties. From the taxonomy that was used for the present study, it results that social support in general consists of two aspects. There are, on the one hand, actual supportive transactions and, on the other hand, the perception of being supported or the satisfaction with the social support provided. In the present study, two research questions were addressed. The first concerned the psychometric properties of the SSQS, measuring the individual's satisfaction with the supportive interactions provided. Secondly, the relative contribution of both supportive interactions (the SSQT) and the satisfaction with the support provided (the SSQS) were assessed, in explaining the level of health related quality of life outcome. The data of 744 rheumatoid arthritis (RA) patients from four different countries (116 French, 238 Norwegian, 98 Swedish and 292 Dutch patients) were used in the present study. At the entry of the study, all patients fulfilled four out of seven American Rheumatism Association (ARA) criteria and had a disease duration of 4 years or less. The results of the study indicate that the SSQS has good psychometric properties across countries. Cronbach's alpha for the emotional support scales was 0.80 or more, and for the instrumental support subscales around 0.60. The standardized regression coefficients demonstrated that, compared to supportive interactions, support satisfaction was more relevant in explaining health related quality of life measures, although it is recommended that the SSQT and SSQS be used to complement each other. | |
| 8838508 | Validity, reliability, and sensitivity to change of a French version of the arthritis impa | 1996 Jan | OBJECTIVE: To develop and validate a cross cultural version of the Arthritis Impact Measurement Scales 2 (AIMS2) to be used by French speaking populations. METHODS: A French version of the AIMS2 was obtained using back translation, committee review, and pretesting. The French AIMS2 was studied in 127 patients with rheumatoid arthritis (RA) about to receive therapy with methotrexate (MTX). Construct validity of the questionnaire was assessed by factor analysis. Convergent validity was evaluated by correlation coefficients with joint counts, pain assessment, and sedimentation rate. Reliability was assessed by test-retest procedure at a 10-day interval, Cronbach's coefficients of internal consistency, and within scale factor analyses. Sensitivity to change after 12 and 24 weeks of therapy with MTX was assessed with computation of standardized response means (SRM) and paired t test comparisons. RESULTS: Factor analyses of the French version clearly identified the same scales of the AIMS2, except for the walking and bending scale which loaded on several factors. Convergent validity of the physical and symptom components of the instrument was demonstrated by significant correlations with clinical and laboratory features. All the scales were reliable (intraclass correlation coefficients: 0.65 to 0.90; percentage of explained variance larger than 50% in all but one scale; Cronbach's alpha: 0.70 to 0.90). Sensitivity to change was demonstrated in 11 of the 12 scales (SRM: 0.30 to 0.77). Most of the improvement was noted by Week 12. CONCLUSIONS: This cross cultural adaptation of AIMS2 in French is valid, reliable, and responsive in patients with RA in whom MTX therapy is instituted. It would permit international comparison studies. This study provides evidence for construct validity and responsiveness of the original version of the AIMS2, not demonstrated previously. | |
| 8499739 | [Use of intravenous immunoglobulins for immunomodulating therapy of inflammatory rheumatic | 1993 Apr | The use of immunosuppressive and long-acting antirheumatic drugs in the treatment of rheumatic diseases is often limited by their side effects. Therefore, it is urgent to search for drugs which are better tolerated and which are at least as effective. Several studies have been performed using intravenously administered immunoglobulins in rheumatoid arthritis patients and in small groups of patients suffering from other connective tissue diseases. The results demonstrate a rapid onset of clinical improvement in patients who respond to this treatment. The tolerance has been excellent so far. This therapy is immunomodulating, since it induces changes in B- and T-lymphocyte function, especially in immunoregulatory T-cell subpopulations. Future work should focus on the establishment of treatment schedules and on the definition of patient subgroups which might benefit most from intravenous immunoglobulin therapy. | |
| 8475665 | [Indications, problems and results of dynamic compression spondylodesis in rheumatic atlan | 1993 Jan | 37 patients suffering from rheumatoid atlanto-axial dislocation underwent operations with the dynamic compression spondylodesis from 1982 until 1990 at the Department of Neurosurgery of the University Hospital of Giessen and Essen. They were examined with an average of 2 years after the operation. The clinical and radiological follow up and the complications are reported. Because of the results the indication of the surgical treatment was modified. In the case of an extended peridental inflammatory pannus with osteolysis of the dens and vertical dislocation of the axis a occipito-cervical fusion is indicated. | |
| 9157087 | Polymorphism of HLA-DRB, -DQA1, and -DQB1 in rheumatoid arthritis in Asian Indians: associ | 1996 Mar | We investigated the DRB, DQA1, and DQB 1 polymorphism and haplotypes in sporadic and familial RA subjects of Asian Indian origin by PCR oligotyping using biotinylated SSOPs. Molecular subtyping of DRB 1*04 in RA patients showed strongest association with highest relative risk with DRB 1*0405, followed by DRBI*0401. A significant decreased frequency of DRBI*1502 was observed in patients compared to controls (chi 2 = 4.5). Among other alleles, DRBI*1001 was found to be significantly increased. A total of 73.3% of patients carried the shared sequence of the third HVR (67-74) of DRB1 domain compared to its presence in only 37.6% of controls. A significant number of patients carried DR4 haplotypes on DQBI*0302 (58%) as against DQBI*0301 which was present only on 10.5% of the haplotypes. When compared to controls, the difference was significant for the latter allele only. Few unique DRDQ haplotypes were observed in Asian Indians. Among DR-DQ haplotypes, DRB1*0401-DQB1*0302 gave the highest risk whereas DRB1*0403-DQB1*O301 was negatively associated. Alleles with negative charge at position 70 confer protection or are negatively associated with RA whereas among the associated alleles, glycine at position 86 resulted in higher risk than those with valine at this position. A heterogenous association of DQB1 alleles with DR4 subtypes, influencing susceptibility to RA, suggests the DQB locus is not primarily associated with RA and susceptibility lies in the sequence 67-74 of the DRB1 loci. | |
| 8676677 | Are both genetic and reproductive associations with rheumatoid arthritis linked to prolact | 1996 Jul 13 | The risk of rheumatoid arthritis (RA) seems to be associated with reduced fecundity and with breastfeeding; these apparently contradictory risk factors can be explained by their association with high prolactin concentrations. The only consistent genetic association with RA is for genes encoded in the HLA complex, particularly HLA DR4. We have identified some data indicating that the effects of breastfeeding and nulliparity are modified by HLA DR4 status, suggesting an interaction between genetic and reproductive risk factors in the aetiology of RA. The prolactin gene is in close proximity to the HLA region on the short arm of chromosome six. We therefore propose the hypothesis that the associations between DR4 and reproductive risk factors in RA are due to linkage disequilibrium between DR4 and an abnormally regulated prolactin gene polymorphism. | |
| 7779126 | Use of magnetic resonance imaging and positron emission tomography in the assessment of sy | 1995 Jun | OBJECTIVE: To measure the anatomic and physiologic changes in the synovium of patients with active rheumatoid arthritis (RA) before and after the initiation of treatment with low-dose systemic glucocorticoids and methotrexate (MTX). METHODS: Two patients with RA with active synovitis involving the carpus were evaluated by imaging parameters at baseline and again after 14 weeks (of treatment with low-dose prednisone and MTX). Standard clinical parameters, laboratory measurements, and contrast-enhanced magnetic resonance imaging (MRI) (synovial volume estimate) and positron emission tomography (PET) with 18F-fluoro-2-deoxyglucose (18-FDG) (synovial metabolism estimate) were performed. RESULTS: Compared with baseline, standard clinical parameters (i.e., joint count, joint index, morning stiffness, global assessments of arthritis activity, and erythrocyte sedimentation rate) improved dramatically in both patients after treatment with low-dose prednisone and MTX. In concert with this trend, the synovial volume of the affected wrist was reduced by 60%, and 76% and the metabolism of 18-FDG was reduced by 66% and 69% in the 2 patients. CONCLUSION: These preliminary observations indicate that a volumetric estimate of inflamed synovium (using contrast-enhanced MRI) and quantification of synovial deoxyglucose metabolism (using PET) are technically feasible and, in the 2 reported cases, correlate well with standard outcome measures. These imaging modalities may provide new objective parameters to determine RA disease activity and effectiveness of antirheumatic medications; however, the potential clinical utility of these measures remains to be defined. | |
| 8747444 | Cilioretinal artery occlusion in sickle cell trait and rheumatoid arthritis. | 1995 | BACKGROUND: Although once thought to be a benign condition, retinal vascular occlusive disease and proliferative retinopathy can occur with sickle cell trait (hemoglobin AS) when additional systemic diseases or trauma are present. METHODS: The authors discuss the ophthalmologic evaluation and clinical course of a 49-year-old woman with sickle cell trait and rheumatoid arthritis who presented with a cilioretinal artery occlusion. RESULTS: The patient's laboratory evaluation showed both a high rheumatoid factor titer and a mild hypergammaglobulinemia, causing increased serum viscosity. The high level of sickle hemoglobin-42.3% (range in trait, 22%-46%)-increased serum viscosity, and lower cilioretinal artery perfusion pressure relative to the central retinal artery resulted in cilioretinal artery occlusion. CONCLUSIONS: Isolated cilioretinal artery occlusions carry a good prognosis, and this patient recovered 20/20 visual acuity in the affected eye. The association between sickle cell trait and rheumatoid arthritis resulting in retinal vascular occlusive disease has not been reported previously. The presence of retinal vascular occlusion in sickle cell trait necessitates a medical evaluation for additional systemic diseases. | |
| 7941789 | [The psychosomatic aspects and results of rheumatoid arthritis and fibromyalgia]. | 1994 | The results of an empirical study on psychosomatic aspects of rheumatoid arthritis (RA) and fibromyalgia syndrome (FMS) are presented and discussed in the setting of previous concepts about rheumatoid arthritis. The patients investigated in the two disease groups represent an unselected population with regard to psychological abnormalities (from two internistic rheumatism outpatient clinics); the results can thus be considered to be representative and permit the following conclusions to be drawn: RA is not a psychosomatic disease in the strict sense; however, psychological factors must be adjudged to have a disease-modifying influence. FMS may be classified within the group of psychosomatic diseases, although it should be regarded as the final stage of a wide variety of different processes within the biological, psychological and social sphere. | |
| 7562776 | Anterior dissection of popliteal cyst causing anterior compartment syndrome. | 1995 Jul | Dissection and rupture of popliteal cysts occur commonly. We describe a case of a 13-year-old girl with polyarticular juvenile rheumatoid arthritis who presented with anterior tibial swelling and dropped foot. She was found to have dissecting popliteal cyst resulting in anterior compartment syndrome. | |
| 8608352 | Absence of correlation between IL-1 alpha intron 6 polymorphism and rheumatoid arthritis. | 1995 Dec | Several studies have implicated interleukin 1 alpha (IL-1 alpha) in the pathogenesis of rheumatoid arthritis (RA). We analysed IL-1 alpha intron 6 polymorphism in relation to RA (50 patients with RA and 50 healthy controls). The study of a healthy control population confirmed the existence of the different alleles with a frequency similar to that in the Caucasian populations of northern England. Allele and genotype distributions did not differ significantly between the normal and RA populations, although the allele corresponding to 8 repeats was over-represented in the RA population (8 and 14% in the healthy and RA populations respectively). This suggests that IL-1 alpha intron 6 polymorphism could be part of a complex process involving other unidentified genetic factors in the pathogenesis of RA. | |
| 7817772 | Impaired interleukin-8-dependent chemotaxis by synovial fluid polymorphonuclear leukocytes | 1994 Aug | The accumulation of polymorphonuclear leukocytes (PMN) in synovial fluid is a common feature of rheumatoid arthritis (RA). We studied the chemotactic response of PMN obtained from the synovial fluid and from the peripheral blood of patients with RA using a modified Boyden's method, in which interleukin-8 (IL-8) or N-formyl-methionyl-leucyl-phenylalanine (FMLP) was used as a chemotactic agent. The IL-8-induced response of peripheral blood PMN from 15 patients with RA did not differ from that of 15 healthy controls. A decreased chemotactic response to IL-8 was, however, observed in PMN from the synovial fluid of 12 patients with RA compared with peripheral blood cells of the same individual. This defective chemotactic ability of PMN was inversely correlated with the number of infiltrating cells in the synovial fluid. We also obtained similar results with FMLP. These results indicate that the chemotactic ability of PMN may be reduced after migrating to the synovial fluid. | |
| 8147131 | [Present and future therapeutic strategies in rheumatoid arthritis]. | 1993 Nov | The triad of inflammation, immunoproliferation and synovial hyperplasia is recognized in the pathogenesis of rheumatoid arthritis, however, the sequence of events remains as highly controversial as ever. The "RA pyramid" was established on the assumption that inflammation is at the top with the destructive processes as sequelae. The moderate successes achieved by conservative therapy with regard to long-term outcome cast doubt on this hypothesis. Inhibitors of prostaglandin synthesis have not been and are not disease modifying. Do substances which influence the endothelial adhesion molecules or leucocyte adhesion receptors (leumedines) promise to be more successful? Do the empirically developed disease modifying antirheumatic drugs (Gold parenteral, MTX) have to be administered earlier? Unfortunately, there is a need for a differential diagnosis which is prognostically valid with regard to the dynamics and aggressiveness of rheumatoid arthritis. Moreover, a pharmacological basis for optimally founded combination strategies is also lacking. Presently, the emphasis of research is directed at the regulation of dysfunctional immune systems. Immunosuppressives (cyclosporin A), cytokine antagonists, receptor antagonists and soluble cytokine receptors (IL-1, IL-6, TNF-alpha), antibodies against lymphocyte subgroups (CD4, CD7) or against cytokines and their receptors are part of the arsenal for the medium term. Too little is still known about the role of protective cytokines (TGF-beta, IL-4, gamma-INF). Currently, however, it is prognosticated that these targeted therapies will only succeed in RA subgroups or only in intelligent combinations. More attractive alternative are strategic therapy modalities which intervene very early in the pathological process, such as the modulation of antigen presentation (MHC blocking peptides, T-cell receptor antagonists, T-cell vaccination) or the induction of tolerance against autoantigens through the oral administration of antigens (collagen II, HSP's, OM-8980). If the center of the pathological process, however, is found in the synovial proliferation of tumor-like cell clusters, then there are only a few years at the beginning of the disease when there is a real chance to impede destruction. In this case, aggressive induction therapy can be the only key to success. In the future, specifically active cytostatics (inhibitors of angiogenesis) will have to be developed and clinical trials conducted on adjuvant therapies with substances which strengthen bone and cartilage, making them more resistant to aggressive cell clusters (bisphosphonates, calcitonins, metalloproteinase- or collagenase-inhibitors). |