Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
7586985 Serum soluble interleukin-2 receptor levels in rheumatoid arthritis: effect of methotrexat 1995 Jul The aim of this study was to assess the correlations of the serum soluble interleukin 2 receptor (sIL-2R) concentrations with disease activity parameters and response to treatment with second line drugs in patients with rheumatoid arthritis (RA). Sixty-seven patients with active disease completed a 24-week, open, randomized study of methotrexate (MTX) versus sulphasalazine (SSZ) or hydroxychloroquine (HCQ). Serum sIL-2R levels were evaluated before entry and after 24 weeks by ELISA. Serum sIL-2R were significantly higher in RA patients than in controls (P = 0.0001) and correlated significantly only with erythrocyte sedimentation rate (P = 0.03) and with Chronic Arthritis Systemic Index (P = 0.01) at study entry. No correlation was found between serum sIL-2R and other laboratory and clinical indices of disease activity. After 24 weeks of treatment no differences in serum sIL-2R in comparison with basal levels were found in either responding or in non-responding patients, although the mean reduction of sIL-2R was more marked in the MTX-treated cohort than in the HCQ and SSZ-treated groups. These data suggest that in RA the measurement of sIL-2R should be used with caution as an isolated index of disease activity and that it is not a useful marker of response to treatment with second line drugs.
1449401 Quality of life in multiple sclerosis. Comparison with inflammatory bowel disease and rheu 1992 Dec Multiple sclerosis (MS) and other chronic illnesses can drastically decrease quality of life (QOL), but there has been little systematic study of QOL in patients with chronic medical diseases. We analyzed QOL in 68 patients with MS, 164 patients with inflammatory bowel disease, and 75 patients with rheumatoid arthritis. The previously validated test instrument was a standardized interview consisting of 41 questions clustered in four subscales: functional and economic scale, social and recreational scale, affect and life in general scale, and medical problems scale. Patients were included in the study if they had a definite medical diagnosis and disease duration of 10 years or longer. In the patients with MS, Kurtzke's Expanded Disability Status Scale correlated strongly only with the medical problems score. Of Kurtzke's Functional System Scales, only the visual Functional System Scores was correlated with total QOL and subscale scores, suggesting that vision is strongly related to QOL. Duration of MS was unrelated to QOL scores. There were significant differences between patients with MS, inflammatory bowel disease, and rheumatoid arthritis on the subscale and total QOL scores. Results suggested that QOL was best in the inflammatory bowel disease group and worst in the MS group. Numerous statistically significant differences on individual questions were evident, suggesting that unique clinical profiles differentially characterize these diseases. Assessments of QOL are a meaningful addition to impairment scales, such as Kurtzke's Expanded Disability Status Scale. Furthermore, QOL scores may meaningfully measure the impact of a chronic medical disease, such as MS, compare the impacts of different diseases, and assess the effects of therapeutic intervention.
8517076 [Ultrasound diagnosis of joints and tendons in the body periphery in inflammatory rheumati 1993 Mar Possibilities and limits of ultrasound-presentation of the tendons and of the joints in the periphery of the body are shown by way of examples of normal and pathological conditions in the area of the hand and the foot. The margin of erroneous analysis, particularly in the field of ultrasound-diagnostics, of damages of the tendon itself are discussed in detail The article concludes with a critical assessment of the clinical relevance concerning the therapeutic consequences.
8976641 An open study of pentoxyfylline and thalidomide as adjuvant therapy in the treatment of rh 1996 Nov OBJECTIVE: Dysregulation of tumour necrosis factor alpha (TNF alpha) production is thought to be important in rheumatoid arthritis. Since pentoxifylline and thalidomide inhibit endotoxin induced TNF production in vitro, these drugs were tested in an open study in rheumatoid arthritis patients to assess toxicity, the effect on TNF production, and the antiarthritic effects. METHODS: 12 patients with active rheumatoid arthritis were treated with 1200 mg pentoxifylline and 100 mg thalidomide a day during 12 weeks. In addition, TNF production was assessed by ex vivo whole blood cultures stimulated with endotoxin. RESULTS: Adverse events such as xerostomia, drowsiness, and constipation occurred in almost all patients, which led to discontinuation in three. The drugs halved the TNF production capacity during treatment (ANOVA, P < 0.03) whereas production capacity of interleukin (IL) 6, IL-10, and IL-12 was not affected. Of the nine patients who completed the study, five fulfilled the ACR-20% response criteria after 12 weeks of treatment. CONCLUSIONS: Although pentoxifylline/thalidomide reduced the production capacity of TNF, the benefit/side effects ratio was poor due to multiple adverse effects, while clinical observation suggests limited efficacy.
1467535 Systemic lupus erythematosus. 1992 The reported change in the incidence of systemic lupus erythematosus (SLE) is mainly due to a greater awareness of the disease, and to the introduction of serological detection methods such as the LE cell assay and subsequently a variety of other antinuclear antibody assays. SLE is seldom preceded by rheumatoid arthritis, nor does SLE often develop in patients with rheumatoid arthritis. In a substantial proportion of our SLE patients, discoid LE occurred first. On analyzing the literature no evidence could be found that nowadays less severe SLE is diagnosed. Also, in the last three decades no change has been observed in the prevalence of clinical features in large groups of patients with SLE. These data indicate that there has been no change in the expression or prognosis of SLE in recent decades.
7763111 Lack of influence of non-inherited maternal HLA-DR alleles on susceptibility to rheumatoid 1995 Apr OBJECTIVE: To reproduce findings from previous reports that non-inherited maternal HLA class II antigens might contribute to rheumatoid arthritis (RA) susceptibility in the offspring. METHODS: Families were recruited from the Arthritis and Rheumatism Council's National Repository of RA families and HLA-DRB1 alleles were examined in these individuals and their first degree relatives using DNA typing methods. RESULTS: There was no evidence of an increase in either non-inherited maternal HLA-DR4 or the HLA-DRB1 shared epitope as a whole compared with the frequency expected using the non-inherited paternal antigens as controls. CONCLUSIONS: The numbers of probands who were shared epitope negative were small, but we are unable to confirm in these families the findings that non-inherited maternal HLA contributes an additional susceptibility factor to rheumatoid arthritis.
7794990 Relative contributions of spousal support and illness appraisals to depressed mood in arth 1995 Jun OBJECTIVE: To examine the ability of cognitive appraisals of illness and spousal support to modify depressed mood in arthritis patients. METHODS: Psychosocial data were collected from 64 married patients with rheumatoid arthritis (RA) within 2 years of diagnosis and at an 18-month followup. RESULTS: The interaction of challenge appraisals with positive support received from the spouse was related to changes in depression over time. There was an increase in depression as challenge appraisals increased when accompanied by greater receipt of positive support, whereas individuals who did not experience a sense of challenge in response to the diagnosis of RA had the lowest levels of residualized depression when they also received higher positive support from their spouses at the beginning of the study. CONCLUSION: The results are considered in terms of the cognitive-behavioral mediation model suggested by Kerns and associates concerning the relationship of chronic pain to depression and have implications for interventions aimed at arthritis patients and their spouses.
8849348 Nuclear factor-kappa B in rheumatoid synovium. Localization of p50 and p65. 1995 Dec OBJECTIVE: To identify the cells that express transcription factor NF-kappa B subunits p50 and p65 in synovial tissue from patients with rheumatoid arthritis (RA) and to correlate the distribution of p50 and p65 with CD14 (macrophage lipopolysaccharide receptor) and members of the AP-1 transcription factor family, Jun and Fos. METHODS: Immunohistochemistry was used to identify p50, p65, Jun and Fos in sections of synovial tissue from 13 patients with RA and 4 "normal" control subjects. Double staining for CD14 and each of the transcription factor subunits was performed. RESULTS: Subunits p50 and p65 were present in the nuclei of synovial cells in all 13 RA patients, with expression varying from rare cells to more than half of all cells. In most cases, nuclear p50 and p65 were present in approximately one-third of synovial lining cells and in a variable proportion of cells scattered throughout the sublining region, including the endothelium. The distributions of p50 and p65 were similar. Jun and Fos were present in the nuclei of a large proportion of synovial lining cells with significantly less expression elsewhere. In each case the Jun/Fos distribution was clearly different from the p50/p65 distribution, although there was significant overlap in many cases. Cells expressing CD14 were mostly Jun/Fos negative and were predominantly p50/p65 positive. There was negligible staining for p50 or p65 in the 4 normal control synovium samples. CONCLUSION: In most RA patients, the p50 and p65 subunits of NF-kappa B were present in the majority of CD14-positive cells within the lining and sublining regions and in a proportion of other cells throughout the synovium, including endothelial cells. NF-kappa B is likely to play an important role in the expression of macrophage-derived cytokines in rheumatoid synovium. Different but overlapping distributions of nuclear p50 and p65 versus Jun and Fos indicate separate or divergent mechanisms for the activation of NF-kappa B and the expression of AP-1 proteins in rheumatoid synovium.
1613740 From aspirin to biologics: therapeutic implications for rheumatoid arthritis. 1992 Jan As effective antiinflammatory agents have been added to our armamentarium, 2 major treatment strategies for the treatment of rheumatoid arthritis have developed. The traditional pyramid strategy is based on initial, conservative measures, followed by more aggressive therapy as the disease progresses. The step-down bridge approach is an alternative, more aggressive strategy that favors earlier use of more potent agents. The longterm effects of disease modifying antirheumatic drugs (DMARD) and combination second line therapy on disease progression remain unclear. Advances in the development of more specific DMARD and in human recombinant proteins offer promising future therapies.
9183648 The role of VCAM-1 molecule in the pathogenesis of rheumatoid synovitis. 1996 Sep The present review focuses on the possible role of VCAM-1 expression on synovial fibroblast-like cells in the synovial lesion of rheumatoid arthritis (RA). The VCAM-1 expressing cells were mainly present in the synovial lining layer. The VCAM-1 expressing fibroblast-like cells also showed activity of uridine diphosphoglucose dehydrogenase, indicating that they are activated fibroblasts. VCAM-1 expressing T cells were also found in RA synovial fluids, where T lymphocytes show upregulation of alpha 4 beta 1 expression, and these T lymphocytes are able to bind to VCAM-1 in solid phase. Further experiments excluded the production of VCAM-1 protein in synovial fluid T lymphocytes and supported the idea that the soluble VCAM-1 was bound to the surface of synovial fluid T lymphocytes. We next planned to examine the effect of soluble VCAM-1 on T cell functions, by using recombinant soluble VCAM-1. The recombinant soluble VCAM-1 rendered synovial or peripheral T cells anergic to various stimuli. These findings imply that recombinant soluble VCAM-1 might be useful as a therapeutic tool to prevent abnormal immune response, since it binds to activated T lymphocytes with upregulation of alpha 4 beta 1, but not to resting T lymphocytes, and soluble VCAM-1 bound T lymphocytes become anergic.
10147238 Assessment of quality of life in rheumatoid arthritis: methods and implications. 1994 Apr During the last decade, self-report of health status and quality of life has gained increasing credibility and acceptance in studies of individuals with rheumatoid arthritis (RA). According to a number of reports, the new self-assessment instruments offer an excellent complement to the more traditional clinical outcome measurements. In the absence of a cure for RA and the use of potentially toxic drugs, quality-of-life assessment seems to have an important place in clinical drug trials. The most commonly used quality of life or health status instruments in studies of RA seem to perform well and give reliable and valid information. A common concern, however, with these instruments is that there appears to be a lack of questionnaires which allow satisfaction with various aspects of quality of life to be expressed. Many instruments focus on negative aspects of quality of life, although quality of life for most individuals is related to something positive. There is no perfect instrument applicable for all situations, but the selection of an instrument depends on the specific purpose of a particular study. Psychological interventions are more likely to affect people's emotions and well-being, whereas a drug intervention might more dramatically affect physical function. It appears, however, reasonable to assume that effects of drug intervention on quality of life should be measured with a longer perspective, such as after at least 6 months' observation. The field is still in a phase of methodological and theoretical development which is also reflected in the few numbers of published studies concerning the effect of drug interventions on quality of life of patients with RA.
8992000 Onset of rheumatoid arthritis after surgical treatment of Cushing's disease. 1995 Oct We describe a patient with Cushing's disease who, shortly after trans-sphenoidal surgical resection of an adrenocorticotropic hormone secreting pituitary microadenoma and specifically at the time of normalization of her serum cortisol level, developed a subacute episode of symmetric polyarticular synovitis. This episode lasted for one month; however, it did not resolve completely and progressed after 3.5 years of diffuse arthralgias and morning stiffness to seropositive and erosive rheumatoid arthritis (RA). Review of the literature revealed 3 additional patients with RA with a similar course. These patients may represent a natural illustration of the antiinflammatory effects of supraphysiological levels of endogenous glucocorticoids.
8627446 Accelerated nodulosis during methotrexate therapy for juvenile rheumatoid arthritis. 1996 May We describe two patients with rheumatoid factor-positive, polyarticular-onset juvenile rheumatoid arthritis in whom accelerated nodulosis developed during methotrexate therapy. Although they had only a few nodules at diagnosis, the nodules increased in number and size 3 to 4 months after the start of methotrexate therapy in both patients. The nodules regressed after withdrawal of methotrexate therapy in one patient and were arrested with the addition of hydroxychloroquine in the other. Physicians treating patients with methotrexate for juvenile rheumatoid arthritis must be aware of this extraarticular side effect.
8646438 Arthroscopic synovectomy in rheumatoid and psoriatic knee joint synovitis: long-term outco 1996 May A long-term prospective study was performed to evaluate the safety and long-term outcome of surgical arthroscopy (AS) for persistent rheumatoid (RA) and psoriatic (PsA) knee joint synovitis (KJS). Local signs of joint inflammation (tenderness, swelling, "ballottement') and range of motion (ROM) were scored and the sum, taken as a global outcome measure, was recorded in 17 RA and 18 PsA knees, both before and at follow-up periods of 2, 6, 12, 24 and 36 months after surgical AS (knee joint synovectomy; meniscal curettage, cartilage shaving or chondrectomy, according to the degree of cartilage damage). A survival analysis (Kaplan-Meier) of the long-term outcome of surgical AS treatment and of the predictive value of clinical parameters of knee joint involvement was also performed. No intra- or post-operative morbidity, pain worsening or loss of joint motion was observed and all patients were discharged within 48 h. Comparison of the parameters of knee joint evaluation showed a significant reduction of the signs of joint inflammation and a significant increase in the ROM in all follow-up periods. At 36 months, the survival curves showed a 61.2% cumulative probability of clinical remission and 72.8% of definite improvement. No significant differences in the prognostic importance of RA, compared to PsA diagnosis, were observed, although higher percentages of PsA compared to RA knees (86.3% and 45.7% respectively) reached the end point of clinical remission at 36 months. KJS duration, radiographic severity and cartilage damage were not predictors of poor long-term outcome of AS synovectomy. Surgical AS treatment for PsA knees with more advanced cartilage damage gave a better long-term outcome. A total of 50.7% of operated knees reached the end point of a KJS relapse at 36 months, the majority (82%) within the initial 18 months of follow-up. Our study indicates that AS synovectomy is a safe procedure requiring short hospitalization which, in combination with second-line medical treatment, can reduce local inflammation in RA and PsA KJS, and preserve knee joint ROM for up to 3 yr.
1429494 Backwashing procedure for on-line reuse of a plasma fractionator in cryofiltration. 1992 During membrane plasma fractionation therapy there are reported incidences of membrane plugging requiring the corrective actions of either filter replacement or backwashing (BW) in order to continue the treatment. In this preliminary study, a simple BW procedure to allow for on-line reuse of the filter (Asahi AP06M) during the treatment was evaluated to assess its efficacy and safety in cryofiltration (CF). Evaluations were carried out on two patients treated for rheumatoid arthritis. Seven tests, each using 1 L or 2 L warmed saline as a BW solution were performed to evaluate the decrease of the transmembrane pressure (TMP) between just before and after backwashing and TMP change during cryofiltration procedures between before and after backwashing. Sieving coefficients of total protein, albumin, immunoglobulins (G, M, A), fibrinogen, and rheumatoid factor were also calculated at 1,000 ml plasma volume processed. Results showed statistically significant decreases of TMP from 300 mm Hg to 70 mm Hg between just before and after both backwashing procedures, and that there were no significant changes in the TMP increase during the cryofiltration procedure between pre- and post-BW. The protein sievings were not significantly affected by BW. The use of a second liter for rinsing did not reduce the inlet pressure further suggesting that 1 L BW was adequate. The accumulated solutes did not affect significantly the effective mean pore size. The BW procedure did not affect the overall patient safety during therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
1451700 Scintigraphic evaluation of disease activity in rheumatoid arthritis: a comparison of tech 1992 Technetium-99m-labelled, non-specific, polyclonal, human immunoglobulin G (99mTc-hIG) has been used to quantify synovial inflammation in rheumatoid arthritis. A comparison was carried out between the scintigraphic results obtained with this tracer, 99mTc-hexamethylpropylene amine oxime-labelled white blood cells (99mTc-WBC) and 99mTc-albumin nanocolloids (99mTc-NC). Twenty patients affected by rheumatoid arthritis and suffering from clinically active synovitis were studied with 99mTc-hIG. The number and sites of the involved joints had been previously assessed on the basis of the presence of pain and/or swelling. A radiological examination had already been carried out on all the joints. Two days after the 99mTc-hIG scan, 10 patients (group 1) underwent 99mTc-WBC scintigraphy and the other 10 (group 2) underwent a 99mTc-NC scan. The results show that the results of 99mTc-hIG and 99mTc-NC scans are in agreement with clinical examinations in the majority of cases. However, a certain number of positive joint scans corresponding to negative clinical examinations was found. The numerical distribution of these results according to the radiological stages seems to show that 99mTc-hIG is more useful than 99mTc-NC in the initial phases of the disease. The 99mTc-WBC scan was negative in a consistent percentage of the joints previously assessed as clinically and 99mTc-hIG scan positive.
7697251 Low-dose methotrexate may cause air trapping in patients with rheumatoid arthritis. 1995 Apr Both rheumatoid arthritis (RA) and methotrexate (MTX) are reported to be associated with the development of pulmonary disease. To determine whether MTX enhanced the risk of developing abnormalities in pulmonary function in patients with RA, we prospectively studied 31 subjects (12 male, 19 female) with the diagnosis of classic RA for an average period of 4.4 yr (range, 1 to 5 yr). Each subject was placed on low-dose weekly MTX (mean 17 mg, range 2.5 to 40) for control of RA symptoms. Other medications included non-steroidal anti-inflammatory agents and prednisone if required for control of arthritis symptoms. No other immunosuppressive therapy was used. Each subject was evaluated by pulmonary function tests (PFT) and chest X-ray initially, and at 1, 2, 3.5, and 5 yr. Chest X-rays obtained initially and at the end of the study period were found to be normal. The percent predicted values for initial PFTs in the study group were within the normal range. From the beginning to the end of the observation period, the following mean changes in lung function were observed: 1.9% increase in TLC, 5.1% increase in residual volume (RV), 1.8% increase in FVC, 0.71% decrease in FEV1, 14.7% improvement in alveolar-arterial oxygen (A-aO2) difference, and a 12.7% increase in single-breath diffusing capacity (DLCO). To determine whether MTX (average dose, weekly dose, or cumulative dose) was significantly related to changes in pulmonary function, we used multivariate techniques to control for the initial measure of lung function while assessing the relationship between MTX and the subsequent measures of lung function.(ABSTRACT TRUNCATED AT 250 WORDS)
7656460 Shortening of life span and causes of excess mortality in a population-based series of sub 1995 Mar OBJECTIVES: To obtain information on the shortening of the life span and the causes of excess death in a population-based series of subjects with rheumatoid arthritis (RA). METHODS: The study included all 1666 subjects who had died in Finland in 1989 and were entitled under the nationwide sickness insurance scheme to receive specially reimbursed medication for RA. Demographic data on the Finnish population and sickness insurance statistics were used as the basis for computations. RESULTS: The life span in subjects with RA was shortened by 15-20% from the date of onset of illness. The determinants of excess mortality could be studied in females. About 40% of the excess deaths were due to cardiovascular causes, 30% to infections, 15% to amyloidosis, and the remaining 15% to diverse causes. CONCLUSION: This data provides an enlightened basis for understanding mortality associated with RA.
8997925 The structure of an instrument for assessing the effects of assistive devices and altered 1996 Oct OBJECTIVE: To use Rasch analysis to transform the ordinal score from a newly developed instrument, the Evaluation of Daily Activities Questionnaire (EDAQ), in order to obtain unidimensional linear measures; to analyze whether items change in difficulty with interventions; and to follow changes in subjects' degree of ability. METHODS: Twenty-one women with rheumatoid arthritis rated their perceived difficulty without and with assistive devices or altered working methods using the EDAQ; the EDAQ consists of 102 items of daily activities, divided into 11 dimensions. RESULTS: All items in the EDAQ could be structured into an acceptable model from "hard" to "easy" with the subjects overall measures ranging from "more able" to "less able." Forty-one items showed a significant reduction of difficulty with interventions. For some items results indicated that easier initial difficulty led to greater effect of interventions. In general, difficulty without assistive devices could not predict difficulty with interventions. Twenty women demonstrated a significant increase in activities of daily living (ADL) ability after interventions. CONCLUSION: The EDAQ analyzed with the Rasch model, demonstrated a hierarchical order of difficulty in 102 items showing that it was possible to evaluate the effect of using assistive devices or altered working methods.
8898482 Lack of expression of c-myc oncogene in peripheral blood mononuclear cells of patients wit 1996 Sep We looked for the expression of c-myc oncogene, one of the genes that enhance apoptosis, in 11 patients with active rheumatoid arthritis (RA) along with five patients with osteoarthritis (OA) knee as disease controls and six healthy volunteers. A dot-blot assay using a probe specific for c-myc oncogene was performed on total RNA obtained from peripheral blood mononuclear cells. There was no expression in patients with active RA and healthy volunteers. One patient with OA expressed c-myc. Lack of expression of c-myc suggests that in active RA circulating lymphocytes are not in the replicative phase despite ongoing disease activity.