Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 8346572 | [Methotrexate therapy of rheumatoid arthritis. An open observation study of 110 patients w | 1993 Jul 26 | Effects and side-effects of treating patients with rheumatoid arthritis with methotrexate given as weekly pulse-treatment are examined in an open observation study. One hundred and ten consecutive patients with active rheumatoid arthritis entered the study. Six criteria of remission were registered as effect variables. Median length of treatment at the time of investigation was 17.8 months. At this point, 34 patients were in complete remission, with a median effect score of five point five out of six possible points. Twenty-nine were in partial remission and 47 (42.7%) had not improved. The median effect score for all patients was three point 6 (95% confidence limits (2-4). Methotrexate treatment was stopped in 24 patients, in 15 of these because of a combination of side-effects and lack of therapeutic response. Prednisone treatment could be discontinued in 20 out of 57 patients during the course of methotrexate treatment. Side-effects were registered in 67 cases (62.7%), and led to treatment being discontinued in 21 cases. Nearly half the side-effects consisted of dyspepsia and rises in amino-transferase levels (48 of 67 patients). Consistently raised amino-transferase levels were found in five cases, all returned to normal after methotrexate was stopped. Serious side-effect were registered in four cases, consisting of two cases of short-term pancytopenia following overdosage and two cases of severe hypoxia following methotrexate-induced alveolitis. | |
| 8535649 | Efficacy of methotrexate in rheumatoid arthritis. | 1995 Nov | Methotrexate (MTX), an antifolate agent, has been used in the treatment of rheumatoid arthritis (RA) for over two decades. Open clinical studies and short-term, randomized, placebo-controlled studies demonstrate the efficacy of MTX in active RA. Long-term prospective studies, including two of over 7 yr duration, report a sustained response and a corticosteroid-sparing effect. Comparative studies demonstrate superior efficacy to auranofin, azathioprine and cyclosporin A. A highly favourable retention rate with the drug has been noted in large studies from academic and community-based practices. Radiographic studies suggest a slowing of radiographic progression with the compound. MTX has become an accepted and widely used treatment for active RA. | |
| 7797960 | Fibrous stabilization of the rheumatoid wrist. | 1995 Apr | 19 patients (mean age 59.8 years) underwent fibrous stabilization of the wrist for rheumatoid arthritis. 17 patients were reviewed after a mean follow up of 24.5 months (range 13-40 months). There were four excellent, 11 good, and two poor results according to modified Koka and D'Arcy (1989) criteria. The poor results were due to deep infection in one patient and an unbalanced wrist due to ruptured radial extensors in another. The pre-operative range of wrist movement was an important determinant of the frequency of radio-carpal and/or mid-carpal fusion and the final post-operative range of movement. | |
| 8856528 | A modified dorsal approach to the wrist for arthrodesis of the non-rheumatoid wrist. An an | 1996 Aug | Fourteen cadaveric wrists were dissected to investigate a modified dorsal approach that involved osteotomy of the small and dorsal tubercles without opening the third compartment. This approach could be safely made with good exposure of the dorsum of the wrist. The mean normal angle formed by the extensor pollicis longus tendon at the level of the dorsal tubercle was 144 degrees. An approach that involves division of the third compartment may lead to effective lengthening of the extensor pollicis longus musculotendinous unit by 8 to 17 mm with corresponding decrease in the tension generated by its contraction. The modified approach permits restoration of the normal alignment of the extensor pollicis longus tendon, and may be useful for performing arthrodesis of the non-rheumatoid wrist in young manual workers. | |
| 8952546 | Apoptosis in rheumatoid arthritis: p53 overexpression in rheumatoid arthritis synovium. | 1996 Dec | DNA damage induces p53 tumor suppressor gene expression and protein production, which in turn facilitates DNA repair or apoptosis. Wild-type p53 protein has a short half-life, so it is rarely detected in non-neoplastic tissue. Because DNA fragmentation is abundant in the intimal lining in rheumatoid arthritis (RA) synovial tissue (ST) using in situ end-labeling (Firestein GS, Yeo M, Zvaifler NJ: Apoptosis in rheumatoid arthritis synovium. J Clin Invest 1995, 96:1631-1638), we assessed ST p53 expression. Immunohistochemical analysis of fixed RA synovium using antibody PAb 1801 showed prominent p53 staining in the cytoplasm and nuclei of intimal lining cells. Noninflammatory and osteoarthritis (OA) ST had significantly less p53 in the lining. These data were confirmed by Western blot analysis of ST extracts, with abundant p53 found in RA compared with OA. p53 expression in cultured fibroblast-like synoviocytes (FLS) was then examined. Flow cytometry on permeabilized cells showed that RA FLS constitutively express p53 protein. Western blots showed that RA FLS expressed significantly more p53 than either OA FLS or dermal fibroblasts. Immunohistochemistry of FLS cultured in chamber slides localized the p53 to the cytoplasm of most resting FLS, with nuclear staining in only 10.7 +/- 2.4%. Exposure to hydrogen peroxide for increased nuclear staining to 70.7 +/- 12.8% after 8 hours (P = 0.003). These data indicate that p53 is overexpressed in RA ST in the intimal lining, which is the primary site of DNA damage, and is constitutively expressed by FLS. | |
| 8060766 | Adhesion molecules in the pathogenesis of rheumatoid arthritis. | 1994 May | The molecules on the cell surface that mediate inflammatory interactions between endothelial cells and leukocytes and of leukocytes with one another have been isolated and their fine structure elucidated. Early studies clearly indicated that the interactions mediated by these proteins are involved in the pathogenesis of rheumatoid arthritis. This article is a review of work published over the past year that has confirmed and expanded the role of adhesive proteins on vascular endothelium, leukocytes, and other synovial cells in the pathogenesis of rheumatoid arthritis. Moreover, the results of recent studies have suggested novel strategies for the development of agents for the treatment of rheumatoid arthritis. | |
| 8619101 | Antibiotic therapy for rheumatoid arthritis. Scientific and anecdotal appraisals. | 1995 Aug | Minocycline is arguably the most interesting new drug for rheumatoid arthritis since the development of methotrexate. Tetracycline compounds have long been used by rheumatologists who were considered mavericks by their peers, and recent controlled studies have demonstrated their antirheumatic activity. The reason that minocycline works is unclear, and their niche in the treatment of rheumatoid arthritis remains to be established. Nonetheless, it is clear that some patients with rheumatoid arthritis respond favorably to this form of treatment. | |
| 8016588 | Leukotrien B4-induced interleukin-1 beta in synovial cells from patients with rheumatoid a | 1994 | We examined the role of Leukotrien B4 (LTB4) in the production of Interleukin-1 beta (IL-1 beta) by rheumatoid synovial cells since a substantial amount of LTB4 has been detected in the synovial fluid from patients with rheumatoid arthritis. The production of IL-1 beta was augmented by LTB4 at concentrations of 10(-9) to 10(-8) M. Furthermore, LTB4 showed the additive effect on the IL-1 beta production with interferon-gamma but not with lipopolysaccharide. These results suggest that LTB4 in cooperation with certain cytokines might play a pivotal role in the IL-1 beta production by rheumatoid synovial cells in vivo. | |
| 1588730 | [Aberrant expression of adhesion molecules in rheumatoid arthritis]. | 1992 Mar | The regulation of lymphocyte migration to specific tissues is complex and involves lymphocyte-endothelial interactions at sites of extravasation. Adhesion molecules play a vital role in the migration of lymphocyte into and out of the tissues. Therefore, excessive induction of adhesion molecules on the vascular endothelium might result in the accumulation of lymphocytes in the rheumatoid synovium. The rheumatoid synovium exhibits functionally as well as morphologically altered synovial vessels, which are probably induced by inflammatory mediators. It should be pointed out that the immunocompetent cells confront various extracellular matrix after extravasation. The signalling through receptors for extracellular matrix modify the subsequent cellular responses against certain target tissues. Thus, interaction of immunocompetent cells with endothelium as well as extracellular matrix through adhesion molecules is critical for the pathogenesis of rheumatoid arthritis. | |
| 8895143 | Association of specific amino acid sequence of HLA-DR with rheumatoid arthritis in Koreans | 1996 Oct | OBJECTIVE: To analyze the association of susceptibility epitopes and alleles of HLA-DRB1 with rheumatoid arthritis (RA) in Koreans. METHODS: We performed HLA-DRB1 epitope typing in 61 patients and 82 controls using polymerase chain reaction (PCR) oligonucleotide hybridization, and HLA-DR4, DR1, and DR8 alleles were characterized by PCR single strand conformation polymorphism (SSCP). RESULTS: The frequency of HLA-DR4 was significantly increased in patients with RA compared with controls (61 vs 29%; RR = 3.7, p < 0.0001). Epitope analysis revealed that susceptibility sequences in Korean patients with RA were 70QRRA74A (52 vs 21%; RR = 4.2, p < 0.0001) and 70QKRA74A (10 vs 1%; RR = 8.8, p < 0.05). The frequency of patients carrying either QRRAA or QKRAA at the 70-74 position on the HLA-DR beta 1 molecule was significantly increased compared with controls (57 vs 22%; RR = 4.8, p < 0.0001). Genotypical analysis showed that DRB1*0405 and *0401 were the DR4 alleles associated with RA in Koreans (RR = 9.4, p < 0.00005; RR = 8.8, p < 0.05, respectively). No significant differences were noted for other alleles including DRB1*0404 and DRB1*0101. QRRAA epitope typing was considered to have some diagnostic value for early RA. CONCLUSION: Our observation indicates that a shared sequence 70QR(K)RA74A, especially in HLA-DR4 subtypes, is strongly associated with RA in the Korean population. Additionally, the importance of DRB1*0405 in the pathogenesis of RA in East Asian ethnic groups was confirmed. These data suggest that not only the specific amino acid sequences but also the whole structure of the HLA-DR beta 1 molecule are important with regard to susceptibility to RA. | |
| 8368016 | [Therapy of rheumatoid arthritis with azathioprine--results of an open long-term study of | 1993 May | In an open study 528 patients affected with rheumatoid-arthritis were treated with azathioprine, then observed for a period of at least 4 years and assessed according to Steinbrocker's therapeutic criteria. In 178 of them (33.7%) the therapy was still effective even after that time, which corresponds to grade I and II according to Steinbrocker. The therapy was cancelled in 211 patients due to ineffectiveness and in 85 patients due to side-effects. The side-effects are represented in detail. Owing to the favorable relationship between benefit and risk, azathioprine proves to be a means of first choice in all cases with a high process activity and an unfavorable prognosis. | |
| 8239756 | Neuropathology of the brainstem and spinal cord in end stage rheumatoid arthritis: implica | 1993 Sep | OBJECTIVE: To study the detailed histopathological changes in the brainstem and spinal cord in nine patients with severe end stage rheumatoid arthritis, all with clinical myelopathy and craniocervical compression. METHODS: At necropsy the sites of bony pathology were related exactly to cord segments and histological changes, and correlated with clinical and radiological findings. RESULTS: Cranial nerve and brainstem pathology was rare. In addition to the obvious craniocervical compression, there were widespread subaxial changes in the spinal cord. Pathology was localised primarily to the dorsal white matter and there was no evidence of vasculitis or ischaemic changes. CONCLUSIONS: Myelopathy in rheumatoid arthritis is probably caused by the effects of compression, stretch, and movement, not ischaemia. The additional subaxial compression may be an important component in the clinical picture, and may explain why craniocervical decompression alone may not alleviate neurological signs. | |
| 7939731 | The use of immunomodulators in early rheumatoid arthritis. | 1994 Jun | Immunomodulators represent a unique class of drugs that are not biologics, usually are isolated from nature, and have relatively specific noncytotoxic effects on the immune system. Although most slow-acting antirheumatic drugs (SAARDs) have effects on the immune system, these effects usually are not specific, often are cytotoxic, are not associated with specific cellular binding proteins, and their effect on immunity is difficult to correlate with their clinical effects. Most immunomodulators primarily affect T cells; because of their apparent role in rheumatoid arthritis (RA), studies of these agents are appropriate. Cyclosporine, the most widely tested of the immunomodulators, has shown significant efficacy in established RA in studies worldwide. However, only one study using cyclosporine has been performed in relatively early RA, in which the most positive effects might be expected. FK506 and rapamycin, agents similar to cyclosporine, are being tested in human transplantation; the only arthritis studies have been performed in animals. Tilomisole, imuthiol, and mycophenolate mofetil have been studied in limited RA trials, with positive effects. However, no trials have been conducted in early RA. Although promising, this class of drugs will require more studies to establish their efficacy and safety, especially in early RA. | |
| 7750888 | [Chronic polyarthritis--treatment with alternative medicine. How frequent is (self-) thera | 1995 Mar 10 | Between 1987 and 1992, we carried out an initial survey of 535, and second and third surveys of 552, patients with chronic polyarthritis, with the aim of obtaining information about paramedical and unconventional treatments and drugs used by those patients to self-treat their conditions. Some 32 to 64% had tried acupuncture, homeopathy and a number of obscure procedures (iridoscopy, cupping, and ozone treatment). Unconventional methods--use of vitamin E, enzymes, dietary measures--predominated. Over the years, the use of paramedical methods and drugs decreased, but the number of patients living on a diet (no pork, sausages or offal, but vegetarian food) remained constant. Attempts to separate the tares from the wheat, are reflected by the nomenclature: so-called unconventional therapies have the potential of becoming recognized forms of treatment. This appears to be the case with dietary measures and the use of vitamin E. | |
| 7492217 | Risk of vertebral fracture and relationship to bone mineral density in steroid treated rhe | 1995 Oct | OBJECTIVES: To determine the prevalence of vertebral fracture in postmenopausal women with steroid treated rheumatoid arthritis (RA), and whether the risk of vertebral fracture could be predicted from measurements of bone mineral density (BMD). METHODS: Vertebral deformities were defined from spine radiographs in 76 postmenopausal women with steroid treated RA (aged 50-79 years) and 347 age matched women from a population based group, using a morphometric technique. Lumbar spine (LS) BMD was measured by dual energy x ray absorptiometry. RESULTS: The odds ratio for vertebral fracture in the women with RA was 6.2 (95% confidence interval 3.2 to 12.3). The decrease in LS-BMD was less than expected for the observed prevalence of vertebral fracture and, among the women with RA, LS-BMD was not lower in those with vertebral fractures. CONCLUSIONS: We conclude that patients with steroid treated RA may have abnormal bone quality, and that LS-BMD cannot be used to predict the risk of vertebral fracture in these patients. | |
| 8259718 | [Nutrition as adjuvant therapy in chronic polyarthritis]. | 1993 Sep | In the literature many casual observations report an arthritogenic effect of individual nutrients. The discovery of eicosanoids derived from arachidonic acid (AA) as most relevant mediators of joint inflammation allowed to elaborate the basis for a dietary therapy of rheumatoid arthritis. With an average intake of 18 g/d linoleic acid in western societies, linoleic acid is not converted to AA, and plasma levels of AA depend on its dietary intake with meat or meat products. The amount of AA ingested with the diet correlates with the formation of proinflammatory eicosanoids. Additionally, AA levels can be lowered by the ingestion of fish oil fatty acids. In our experiment, we aimed to combine the effect of low AA intake with the known anti-inflammatory effect of fish oil fatty acids. Our results demonstrate that vegetarians have lower AA percentages in erythrocyte lipids compared to the control group. The lower AA levels in plasma lipids coincided with higher percentages of fish oil fatty acids after supplementation, resulting in lower formation of mediators of inflammation. Moreover, the vegetarian group experienced a more pronounced decrease of AA in erythrocyte lipids after supplementation with fish oil fatty acids. These effects are supposed to contribute to the more favorable clinical course and laboratory findings in patients with rheumatoid arthritis on a vegetarian diet. | |
| 8162458 | Hyaluronan concentration in non-inflamed and rheumatoid synovium. | 1994 Jan | The concentration of hyaluronan was measured by a novel application of an ELISA technique, using biotinylated hyaluronan binding-region (HABr) derived from cartilage proteoglycan core-protein, to digested frozen sections of synovium. The relative extractability of hyaluronan, from sections of synovium by short-term washes in buffer, was assessed by the same method. The distribution of hyaluronan in adjacent sections was assessed histochemically using the biotinylated HABr and alkaline phosphatase-conjugated streptavidin. Hyaluronan concentrations were lower in rheumatoid synovium (0.71 +/- 0.10 mg/cm3; mean +/- S.E.M.) than in non-inflamed synovium (1.07 +/- 0.16 mg/cm3). However, the ratio of extractable or 'free' hyaluronan to non-extractable or 'bound' hyaluronan, was greatly increased in rheumatoid synovium, being 4.53 +/- 0.40 (mean +/- S.E.M.) compared with 1.87 +/- 0.42 in non-inflamed synovium. Histochemical staining showed hyaluronan to be concentrated in the lining layer of non-inflamed samples, whereas in rheumatoid synovium the stain was more uniformly distributed throughout the tissue. Although the total concentration of hyaluronan was not increased in rheumatoid synovium, the increased proportion of 'free', and therefore presumably mobile, hyaluronan molecules together with increased synovial bulk may contribute to the known increases in serum levels of hyaluronan in patients with RA. | |
| 8118983 | Systemic bone changes accompanying early rheumatoid arthritis in patients treated with non | 1994 Jan | Seventeen patients suffering from early rheumatoid disease (mean duration, 3.5 years) and treated with nonsteroidal antiinflammatory drugs alone had evidence of systemic bone changes. Transiliac bone biopsies, compared with age and gender-matched controls, demonstrated reduced bone volume and increased eroded surface. In addition, the metacarpal indices were reduced in the rheumatoid patients and correlated with the iliac crest bone volume. These changes, found distal from sites of synovitis, suggest that in this group of rheumatoid patients there were systemic changes of bone metabolism. No biochemical abnormalities of calcium homeostasis were found. Collectively, present observations may be a reflection of the rheumatoid disease process itself. | |
| 8843864 | High prevalence of serum apolipoprotein E4 isoprotein in rheumatoid arthritis patients wit | 1996 Oct | OBJECTIVE: To determine whether serum Apolipoprotein E (Apo E) type 4 isoprotein is a risk factor for the development of amyloidosis in patients with rheumatoid arthritis (RA). METHODS: Using isoelectric focusing, we studied Apo E phenotype expression and the corresponding allele frequencies (epsilon 2, epsilon 3, and epsilon 4) in 35 patients with RA and amyloidosis, 65 patients with RA and without amyloidosis, and 63 healthy controls. RESULTS: The Apo E3/4 phenotype was significantly more common in the group with amyloidosis (31.4%) than in the patients without amyloidosis (12.3%; P < 0.05) or in healthy controls (12.7%; P < 0.05). The frequency of the epsilon 4 allele was significantly greater in the group with amyloidosis (0.16) than in the patients without amyloidosis (0.07; P < 0.05) or in healthy controls (0.07; P < 0.05). CONCLUSION: The presence of Apo E4 isoprotein may be a risk factor for the development of amyloidosis in patients with RA. | |
| 1588746 | [Rehabilitation in rheumatoid arthritis]. | 1992 Mar | In the patient with rheumatoid arthritis, muscle weakness and joint contracture and deformity develop, despite the most carefully directed programs of medical care. At the acute phase of this disease, the immobilization or stabilization of arthritic joints is effective for the improvement of inflammation without risk of contracture. At the chronic phase, the patients should be carefully instructed as to the importance of the joint mobility exercise and muscle strengthening exercise. Finally, we must consider that patients with rheumatoid arthritis suffer not only from painful joints but also from psychological and socio-economical damage. |