Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 8625558 | Markedly elevated serum MMP-9 (gelatinase B) levels in rheumatoid arthritis: a potentially | 1996 Feb | In an attempt to find a potentially useful serum marker in rheumatoid arthritis (RA) which reflects underlying pathogenic mechanisms, we measured the circulating levels of matrix-degrading metalloproteinase-9 (MMP-9), also termed gelatinase B, in sera and synovial fluid (SF) from patients with RA and also quantitated the deposition and local synthesis of MMP-9 in RA synovium. Clinical samples, subjected to gelatin substrate zymography, antigenic immunoassay, and a quantitative substrate degradation assay, revealed elevated 92- and 72-kDa proenzyme forms of MMP-9 and MMP-2 in RA sera and SF compared with healthy controls. Immunostaining on fresh RA synovial specimens revealed MMP-9 within vascular walls in fibroblast-like cells and macrophages; mRNA synthesis was detected using reverse transcriptase in situ PCR. In summary, MMP-9 levels are substantially elevated in the sera and SF from patients with RA. The RA synovium is a source of this MMP-9 production, with abundant mRNA and protein observed within several different type of rheumatoid synovial cells. | |
| 7940330 | [The sex- and age-related characteristics of the x-ray changes in rheumatoid arthritis]. | 1994 | To investigate sex- and age-specific features of radiographic abnormalities in rheumatoid arthritis (RA) patients, radiographic signs in hands and feet were assessed using Steinbroker criteria. A score system from 0 to 3 was also introduced to evaluate every radiographic feature: osteoporosis, cysts, joint space narrowing and erosions. Radiographic indices of every joint group, whole hand and metatarsophalangeal joints were calculated. Using the regression analysis, the implication of 3 factors (age at the disease onset, disease duration and sex) in joint involvement was estimated in 56 males and 50 females with RA. Age subgroups entered patients who at the disease onset were under 50 (38 males and 27 females), over 50 (18 males and 23 females). Neither sex nor age at the disease onset affected Steinbroker stage in hands, whereas the influence of the male sex on radiographic stage in feet was essential. Radiographic indices for joints of the hand were different in sex and age subgroups. A multiple regression analysis revealed a significant effect of age at the disease onset on the involvement of metacarpophalangeal and wrist joints and hand on the whole. Wrist involvement was related to the female sex. Radiographic feet indices were more significant in young males. | |
| 8685225 | Epstein-Barr virus and lymphoproliferation in methotrexate-treated rheumatoid arthritis. | 1996 Mar | Generalized lymphadenopathy developed in a 60-year-old female receiving methotrexate and prednisone for treatment of rheumatoid arthritis. Histologic examination of an enlarged right axillary lymph node revealed effacement of normal architecture by a polymorphic population of lymphocytes. The recognition that the patient was medically immunosuppressed and the similarity of lymph node histology to that of a polymorphic post-transplantation lymphoid proliferation led to suspicion that the adenopathy might represent an immunosuppression-related lymphoid proliferation. This possibility was supported by regression of the adenopathy on discontinuation of methotrexate, despite continued corticosteroid therapy, which is an outcome reminiscent of the remissions observed with reduction of immunosuppressive therapy in post-transplantation lymphoproliferative disorders. Subsequent ancillary laboratory studies of lymph node tissue included genetic probe analysis, which revealed a monoclonal population of B-lymphocytes containing clonal Epstein-Barr virus DNA. In situ hybridization studies performed on lymph node tissue revealed expression of Epstein-Barr virus-encoded RNA 1 transcripts, and immunohistochemical studies revealed expression of Epstein-Barr virus latent membrane protein 1. These ancillary studies confirmed the similarity to post-transplantation lymphoproliferative disorder. Although immunosuppression-related lymphoproliferative disorders share features with malignant lymphoma, the possibility of resolution in situations in which immunosuppression can be reversed provides a distinction from true malignancy and is of profound importance in therapeutic decision making. | |
| 1491385 | The effects of methotrexate on interleukin 1 in patients with rheumatoid arthritis. | 1992 Nov | The effect of methotrexate (MTX) treatment on patients with rheumatoid arthritis on interleukin 1 (IL-1) was evaluated. Eight patients received a weekly MTX dose of 7.5 mg for 6 weeks; none received concomitant corticosteroids. Peripheral blood was obtained 1 day before and 1 day after their weekly MTX dose at Week 1 and 6, isolated monocytes stimulated ex vivo with 1 mg/ml zymosan for 18 h and IL-1 measured by bioassay. Serum and plasma IL-1 levels were measured by immunoassay. Four patients manifested a sharp decrease in IL-1 production 6 weeks after MTX administration associated with a decrease in the number of painful but not swollen joints. No effect on blood levels was observed. Our results suggest that MTX may affect IL-1 production and IL-1 mediated events in some patients. | |
| 1319485 | Demonstration of cytomegalovirus (CMV) DNA and anti-CMV response in the synovial membrane | 1992 May | One hundred forty-seven synovial membranes were investigated for the presence of human cytomegalovirus (CMV). In 11 of 83 synovial membranes of patients with rheumatoid arthritis (RA), but only in 2 of 64 synovial membranes from patients with other joint disorders, CMV-DNA could be detected by the polymerase chain reaction (PCR) technique (p less than 0.05). In contrast, the percentage of seropositive patients was not significantly different between the 2 groups of patients and no blood sample from any patient tested revealed the presence of CMV by PCR. Only in patients with RA and CMV positive synovial membranes was the titer of CMV specific antibodies in the synovia higher than in the serum. Thus, the local presence of CMV in the synovial membrane and associated local antiviral responses might participate in the pathogenesis of synovitis in a minority of patients with RA. | |
| 1398358 | Talonavicular arthrodesis in the rheumatoid foot. | 1992 Jul | Arthrodesis of the talonavicular joint with a cylindrical dowel was performed in 19 feet in 17 rheumatoid patients with arthritic destruction of the talonavicular joint, but without fixed hindfoot deformity. Osseous union was achieved in 12 feet, but all patients experienced pain relief and no foot showed progressive valgus deformity of the hindfoot during follow-up. Staple fixation seemed to promote osseous union. The procedure, easy to perform and requiring only 6 weeks of immobilization, may, in the absence of fixed hindfoot deformity, supersede triple arthrodesis in rheumatoid patients with hindfoot arthritis. | |
| 1526694 | Endocrine control of inflammation: rheumatoid arthritis double-blind, crossover clinical t | 1992 | A dysfunction in the endocrine control system for inflammation in rheumatoid arthritis serves as the theoretical basis for chronic inflammation in the study design described. Eighteen patients with rheumatoid arthritis, who acted as their own controls, were brought to a minimum symptom state through conventional means, trained, and allowed to control subsequent flares by a patient-initiated, flare-response prednisone regimen. The six-month trial was double-blind with a crossover at midpoint. While continuing stable non-steroidal anti-inflammatory and disease modifying antirheumatic drug therapies, the patients averaged additional 57% and 75% reductions from baseline in tender joint count and total pain score, respectively, on the prednisone therapy. The prednisone therapy was differentiated by improvement from that of a placebo by six of the nine parameters evaluated. The adverse events were no more frequent with prednisone than with placebo use. The efficacy of prednisone was increased threefold while reducing consumption by 40% when compared to the predecessor 5-mg prednisone/day clinical trial. | |
| 8619094 | Oncogenes in rheumatoid arthritis. | 1995 Aug | The evolving knowledge of the actions and interactions of (proto)oncogenes in cancer has deeply influenced the understanding of other nonmalignant diseases. In RA, the longstanding pathohistologic evidence of transformed-appearing synovial cells at the site of bone and cartilage attachment and joint destruction can now be explained in terms of alterations of cell regulation, cell cycle, and apoptotically triggered cell death. The detection of upregulated oncogenes and their gene products at these sites supported the hypothesis of an aberrant synovial cell type invading the joint. Interestingly, there are hints that this transformation of synovial cells may require more than one activated oncogene. A model was introduced by Carson and Ribero in 1993. In this model, a primary stimulus affects the cell and leads to the enhanced transcription of an oncogene (i.e., c-myc). A second stimulus activates other oncogenes and determines if this cell (i.e., a synovial fibroblast) proliferates (marked by the presence of bcl-2 mRNA) or undergoes apoptosis (marked by fas mRNA and Fas expression at the cell surface). This co-upregulation might explain why some investigators could not detect a significant upregulation of oncogenes in cultured synovial fibroblasts devoid of their normal milieu. Based on the results of the specific activity of Fas and perforin and recent data from our laboratory, we have modified Carson's model to include these data. As there exists an established retroviral model in which the tax sequence of the HTLV retrovirus initiates central oncogene transcription similar to those activated in RA, the retroviral particles, which do not resemble any other known retrovirus but are detectable in the synovial fluid, might well be an important stimulus in the pathogenesis of RA. To simplify the puzzling events of oncogene interactions in RA, we have summarized the data and propose that an oncogene network acts as a pathogenic mechanism in the synoviocytes of the rheumatoid joint. Similar to the "cytokine network" regulating the T-cell-dependent pathway, the "oncogene network" is presumably the major T-cell-independent pathway in RA (Fig. 4). | |
| 7835015 | Prediction of radiographic damage in hands and feet in rheumatoid arthritis by clinical ev | 1994 Sep | Radiography of hands and feet is a standard measure of outcome in rheumatoid arthritis. We hypothesised that this radiological information can be reproduced by clinical evaluation. A rheumatologist examined 78 patients with rheumatoid arthritis and tried to predict the radiological Larsen score, for the proximal interphalangeal (PIP), metacarpophalangeal (MCP), wrist, ankle, and metatarsophalangeal (MTP) joints. Spearman correlation between clinical Larsen and X-ray Larsen was 0.79 for hands and 0.66 for feet. There was no significant difference in scores for PIP, MCP, wrists, or ankles, but MTP joints were underscored by clinical Larsen relative to X-ray Larsen (median of 20 vs 22 respectively, p = 0.04). Categorical data for index finger MCP joints showed significant proportional agreement of 37% (Kappa 0.24, p < 0.0001). In conclusion, the Larsen X-ray score can be predicted by clinical examination with surprising accuracy in the small hand joints but less so in the feet. Although the favourable agreement shown in this study does not make X-rays redundant, we suggest that clinical examination of the hands should be further refined and standardised as a measure of outcome. | |
| 8882026 | Bone alkaline phosphatase in rheumatoid arthritis: a longitudinal study. | 1996 Feb | OBJECTIVE: To determine whether the raised total alkaline phosphatase (TAP) found in patients with active rheumatoid arthritis (RA) is derived primarily from an increase of the bone or liver isoenzyme, and to evaluate the treatment effect of steroids and disease modifying antirheumatic drugs (DMARD) on bone alkaline phosphatase (BAP) in serial analyses. METHODS: 58 patients with RA were treated with the DMARD gold sodium thiomalate (n = 22), D-penicillamine (n = 18), or sulfasalazine (n = 18) over a 24 week period with regular assessment of disease activity and measurement of BAP using a newly developed specific double monoclonal radioimmunometric assay. RESULTS: In the RA group as a whole, BAP correlated with TAP at all time points (e.g., Week 0 rs = 0.50, p < 0.0001). In contrast, no correlation was found between the intraindividual change of BAP and TAP between Weeks 4 and 24. TAP was correlated with disease activity (assessed by plasma viscosity rs = 0.33, p < 0.02 for the whole RA group and rs = 0.48, p < 0.0002 for intraindividual change from Weeks 4 to 24). Similarly, gamma-glutamyltranspeptidase was correlated with disease activity (rs = 0.56, p < 0.0001, and rs = 0.50, p < 0.0001, respectively). In contrast, BAP was not correlated with disease activity. Low dose steroids and the 3 DMARD studied had no significant effect on the time course of BAP. CONCLUSION: In the majority of patients with active RA, any increase of TAP is not mirrored by an increase of BAP. This supports the hypothesis that inflammatory reactions result in an increase in the plasma concentration of the membrane bound enzymes of the hepatobiliary system, including gamma-glutamyltranspeptidase and the liver isoenzyme of alkaline phosphatase, which is likely to be responsible, at least in part, for the increase of TAP. Since BAP is not correlated with disease activity, BAP measurements are not useful in monitoring response to treatment. | |
| 1581373 | Observation of pain behavior in rheumatoid arthritis patients during physical examination. | 1992 Mar | This study examined the reliability and validity of a behavioral observation method for the assessment of arthritis pain in a clinical practice setting. Trained observers measured the occurrence of seven pain behaviors in a group of 61 rheumatoid arthritis patients undergoing physical examinations. These observations were compared with videotaped observations of the patients in a laboratory setting. Significant differences were found between the pain behavior frequencies observed during the examinations and those observed during videotaped sessions. Total pain behavior scores obtained in both settings were significantly correlated with patients' self-reports of pain and with disease activity measures. Pain behavior observed during the exams was significantly associated with patients' self-reports of anxiety and depression. | |
| 1598613 | Psychological aspects of rheumatic diseases. | 1992 Feb | Psychological problems in rheumatic diseases are common and influence the maintenance of symptoms and management. The psychological and psychosocial aspect of rheumatoid arthritis and systemic lupus erythematosus are briefly described. An approach to psychological management and the role of the psychiatrist in rheumatology are considered. In addition to appropriate and adequate treatment of concomitant psychological disorders with drugs, psychosocial interventions and the use of other forms of therapy such as self-help groups are also invaluable. | |
| 7881833 | Increased IL-1 receptor antagonist (IL-1ra) production and decreased IL-1 beta/IL-1ra rati | 1995 Jan | In order to investigate the possible role of IL-1 receptor antagonist (IL-1ra) in patients with rheumatoid arthritis (RA), this study was undertaken to measure the amounts of IL-1ra and interleukin-1 beta (IL-1 beta) protein produced by mononuclear cells (MNC) and to investigate the relationship between production of these cytokines and clinical parameters. The MNC were cultured for 24 h and the supernatants were measured for IL-1ra and IL-1 beta by ELISA kits. MNC from peripheral blood (PB) and synovial fluid of RA patients produced significantly higher amounts of IL-1ra than normal PBMNC (P < 0.01 and P < 0.05, respectively). When the IL-1 beta/IL-1ra ratio was calculated, IL-1 beta/IL-1ra ratios of RA PBMNC were significantly lower than those of normal PBMNC (P < 0.001). The IL-1 beta/IL-1ra ratio of RA PBMNC was significantly higher in active RA patients than in RA patients in remission (P < 0.02). The amounts of IL-1ra produced by stimulated RA PBMNC positively correlated with the joint score (P < 0.05), serum CRP levels (P < 0.05) and the amounts of IL-1 beta produced (P < 0.01). The amounts of IL-1ra produced by unstimulated RA PBMNC did not correlate with any of the clinical parameters studied. Gold sodium thiomalate (GST), but not auranofin, increased IL-1ra production in vitro.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 8282254 | Prevalence of Helicobacter pylori infection and its effect on symptoms and non-steroidal a | 1993 Dec | Non-steroidal anti-inflammatory drugs (NSAIDs) and Helicobacter (H pylori) are both associated with an increased risk of peptic ulceration and gastropathy. It is not known, however, if there is an interaction between these two agents, and thus whether or not screening for H pylori before NSAID treatment is of value. The aim of this study was to find out if H pylori potentiates the damaging effects of NSAIDs. Fifty two patients with rheumatoid arthritis requiring longterm NSAID treatment were studied. Dyspeptic symptoms were assessed according to a standardised questionnaire. Gastroscopy was performed after a one week washout period during which NSAIDs were discontinued. Gastric and duodenal mucosal damage was graded endoscopically. H pylori was identified by biopsy urease test and by histological tests. Investigations were repeated after one month's treatment with an NSAID. Patients with H pylori infection (n = 26) had a higher dyspeptic symptom score (p < 0.05). One patient with duodenal ulcer (H pylori +ve) and two with endoscopic gastritis (both H pylori +ve) were excluded from further study. Forty two subjects completed the study. After treatment there was a rise in the gastric damage score both in the H pylori +ve (p = 0.06) and the H pylori -ve (p < 0.005) groups. There was no difference in the extent of increase in grade or the final grade at the end of the treatment period between the H pylori +ve and -ve patients. It is concluded that H pylori infection is associated with increased dyspeptic symptoms in patients receiving NSAIDs but that it does not potentiate NSAID gastropathy. | |
| 8693201 | [Rheumatoid arthritis and ankylosing spondylitis]. | 1995 | A case of a patient having ankylosing spondylitis of 16 years duration is presented. Eight years ago developed a clinical picture with symptoms which completely fulfill criteria for diagnosing rheumatoid arthritis with exception of rheumatoid factor. As a conclusion we can say that in our patient there have been developed ankylosing spondylitis and rheumatoid arthritis as a coexistence of two diseases. | |
| 1390968 | Validation of the NIH activity record: a quantitative measure of life activities. | 1992 Jun | This article reports the results of the validation of a life activity record. We devised a self-administered daily log (the NIH Activity Record, ACTRE), for persons with rheumatoid arthritis (RA), which recorded specific daily activities over a 24-hour period and identified the level of physical effort for each task. In addition, each activity was assigned a level of pain, fatigue, difficulty, competence, meaningfulness and enjoyment. Twenty-one persons with RA completed the log. They underwent an articular examination (AI) (Ritchie Articular Index) as well as completed the following self-reports: Psychosocial Adjustment to Illness Scale (PAIS); The Feeling Tone Checklist (FTC), a measure of fatigue; The Modified Health Assessment Questionnaire (ALI); and the Pain and Disability Index (PDI). Significant correlations were found between fatigue measured by ACTRE and FTC (p = 0.028); pain measured by ACTRE, PDI (p = 0.002), and (p = 0.01) and the visual analog scale in the ALI (p = 0.0002). Pain experienced while performing self-care measured by ACTRE correlated with AI (p = 0.001) and ALI (p = 0.0013). Difficulty with self-care activities on the ACTRE correlated with difficulty (p = 0.007) and pain (p = 0.012) on the ALI. The ACTRE is a valid measure of symptoms and perceptions that can be quantified, and is unique in that it identifies specific daily activities likely to produce them. | |
| 7966059 | Outcome in patients with rheumatoid arthritis receiving prednisone compared to matched con | 1994 Jul | OBJECTIVE: To determine the longterm outcome including disease activity, mortality, and adverse events in patients with rheumatoid arthritis (RA) treated with prednisone. METHODS: A case-control study was performed, based on our cohort of 893 mostly Caucasian patients with adult onset RA, followed since 1966. Data collection was based on protocols and included single physician global assessment. Prednisone was started in 122 patients (85 women, 37 men) after 1966. All were matched for age, sex, disease duration, and global assessment to 122 controls from the same cohort who have never received prednisone. RESULTS: Mean disease duration before prednisone was 14.1 years. Mean duration of use was 6.9 years with a mean dose of 8.0 mg/day. Prednisone was eventually stopped in 34% of patients. Life expectancy and causes of death were similar in both groups. No differences in hemoglobin, erythrocyte sedimentation rate, global assessment, Lansbury index, functional class or Health Assessment Questionnaire (HAQ) disability index were seen between the 2 groups before or 5 years after starting prednisone. Ten years after starting prednisone, HAQ scores were similar but Lansbury and global assessment were worse in the prednisone treated group. As expected, adverse events, notably cataracts and fractures, were observed more often in the prednisone group. CONCLUSION: Case-control matching can only reduce, not eliminate, potential selection bias. Nonetheless, the lack of demonstrable longterm benefit with prednisone use in this and other studies is disconcerting. Caution and further studies are required before the more aggressive use of longterm prednisone therapy in RA is embraced. | |
| 8472412 | Rapidly progressive protrusio acetabuli in patients with rheumatoid arthritis. | 1993 Apr | Current literature suggests protrusio acetabuli in patients with rheumatoid arthritis progresses at a gradual rate of 2-3 mm per year. This report presents five patients with rheumatoid arthritis (RA) who experienced rapidly progressive protrusio. The period of rapid clinical progression averaged 40 days. During progression, medial protrusio increased an average of 7.5 mm, superior protrusio advanced 6.9 mm, femoral head width decreased 2.7 mm and center-edge angle increased 20.7 degrees. Axial protrusio occurred along an axis 137 degrees from vertical. A key clinical feature was an absence of significant hip symptoms before a marked increase in symptoms over a period of days to several weeks, resulting in a significant decrease in the patient's ambulatory capacity. Osteopenia was a consistent preexisting radiographic feature. The findings underscore the existence of rapidly progressive protrusio in the natural history of RA and its importance in the differential diagnosis of hip pain in patients with RA. Early recognition is important to minimize the potential complications of delayed surgical treatment. | |
| 8846543 | Aggressive therapy for rheumatoid arthritis. | 1995 Sep | Although valuable progress has been made in the study of the etiopathogenesis of rheumatoid arthritis, available treatments have up to now been unable to control severe and resistant cases. Different approaches have been tried in order to stop the articular and/or systemic features of this disease. The present report reviews these attempts which, unfortunately, have thus far failed to provide fully satisfactory solutions. | |
| 8670579 | A randomized trial of testosterone therapy in males with rheumatoid arthritis. | 1996 Jun | Thirty-five male patients, aged 34-79 yr, with definite rheumatoid arthritis (RA) were recruited from out-patient clinics and randomized to receive monthly injections of testosterone enanthate 250 mg or placebo as an adjunct therapy for 9 months. Endpoints included disease activity parameters and bone mineral density (BMD). At baseline, there were negative correlations between the ESR and serum testosterone (r = -0.42, P < 0.01) and BMD (hip, r = -0.65, P < 0.01). A total of 29.6% of all patients had at least one vertebral fracture, most having multiple fractures. Back pain, however, was not more prevalent in fracture patients (55% vs 50%). Disease activity was significantly higher in the fracture group (joint score P < 0.05, rheumatoid factor P < 0.01). Thirty patients completed the trial, 15 receiving testosterone and 15 receiving placebo. There were significant rises in serum testosterone, dihydrotestosterone and oestradiol in the treatment group. There was no significant effect of treatment on disease activity overall, five patients receiving testosterone underwent a "flare'. Differences in mean BMD following testosterone or placebo were non-significant (spine: +1.2% vs -1.1%; femur: -0.3% vs +0.3%). There was no suggestion of a positive effect of testosterone on disease activity in men with RA. |