Browse

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

ID PMID Title PublicationDate abstract
11696842 Aortic valve aneurysm: a novel cardiac manifestation of rheumatoid arthritis? 2001 Nov This report describes a 51-year-old man with rheumatoid arthritis, coronary artery disease, left ventricular failure, and saccular aneurysm of the left coronary cusp of the aortic valve. Rheumatoid arthritis can involve the heart in several ways; however, aortic valve aneurysm in rheumatoid arthritis has not been reported before. Absence of vegetation, lack of a history of infective endocarditis, and the preservation of aortic valve function suggested that this saccular aneurysm was not a result of infective endocarditis. An intimal flap, which strongly suggests aortic dissection, was not observed. To our knowledge, this may be a novel cardiac manifestation of rheumatoid arthritis, and this is the first published report.
10429522 [Rheumatoid arthritis and the kidney. Pinpointing an aspect of confusing contours]. 1999 Jul In literature there are only a few papers about renal involvement in rheumatoid arthritis. The scarcity of reports is due to the difficulties of pinpointing this subject; in fact a bloody investigation like kidney biopsy is necessary to obtain an exact diagnosis. Moreover it is often clinically hard to distinguish renal injury provoked by rheumatoid arthritis from nephropathy caused by drugs, either non steroidal antiinflammatory drugs or disease modifying antirheumatic drugs. This topic is perhaps neglected because primary renal involvement in rheumatoid arthritis is not considered to influence the survival, with the exception of renal amyloidosis. Pathologic examination of kidney biopsy shows in order of frequency: mesangial nephritis, renal amyloidosis, membranous nephritis, focal proliferative nephritis, minimal nephritis, interstitial nephritis. Both immune complexes and antineutrophil cytoplasmic antibodies may play a pathogenetic role. The mesangial nephritis with IgA or IgM deposits is linked to high levels of rheumatoid factor of IgA or IgM class; it has been hypothesized that the ability of mesangium to remove circulating immune complexes provokes the mesangial damage. Moreover it has been observed that rheumatoid arthritis with renal involvement shows positivity for perinuclear antineutrophil cytoplasmic antibodies more frequently than rheumatoid arthritis without nephropathy. Also in the former cases the title of these autoantibodies is higher. The aim of this paper is to bring the terms of the problem into focus by the revision of the literature. Further and wider studies are necessary to obtain more available data.
9789970 Concordant message of different inflammatory markers in patients with rheumatoid arthritis 1998 The acute phase reaction is an unspecific response to inflammatory stimuli characterized by alterations in the concentration of several plasma proteins. It is of great clinical value to monitor the inflammatory state in patients with rheumatoid arthritis. The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are the assays most widely used to measure the acute phase response, but there are also several other inflammatory markers (e.g., fibrinogen, haptoglobin, alpha 1-acid glycoprotein, alpha 1-antitrypsin, interleukins (IL), serum amyloid component A (SAA)). We have studied the interrelationships between several of these markers (ESR, Haptoglobin, Fibrinogen, CRP, SAA and IL-6) in rheumatoid arthritis patients. There was a good correlation between all acute phase markers in serum (p < .01). We found especially strong correlations between S-CRP and SAA (p < .000001) and between ESR and P-fibrinogen (p = .000004). The strong correlation indicates that P-fibrinogen could be used instead of ESR in monitoring rheumatoid arthritis patients. This would increase the specificity of the examination as ESR may be influenced by several factors other than the inflammatory response. There were no significant correlations between acute phase markers in serum or plasma and clinical index.
9558183 Ambulatory activity as an objective and quantifiable measure of nonsteroidal therapy. 1998 Apr OBJECTIVE: To quantify any increase in short term spontaneous ambulatory activity resulting from the use of nonsteroidal antiinflammatory drugs (NSAID) in patients with rheumatoid arthritis (RA). METHODS: Double blind placebo controlled crossover study of 8 women with RA using conventional assessments and the Numact activity monitor. RESULTS: Patients' ambulatory activity was 50% greater during NSAID treatment compared to placebo treatment. Effect size calculated at 0.62, suggesting good sensitivity to change. The increased activity occurred late morning. CONCLUSION: Spontaneous ambulatory activity is an objective and relevant measure of disability.
9825203 Early deaths with thrombolytic therapy for acute myocardial infarction in corticosteroid-d 1998 Nov Intravenous thrombolytic therapy has become standard treatment for acute myocardial infarction (AMI). We describe three patients with long-standing seropositive rheumatoid arthritis (RA) on chronic corticosteroid therapy who experienced very early (1-6 h) mortality after the use of intravenous thrombolytic therapy for the treatment of AMI. All three patients likely experienced electromechanical dissociation (EMD). Their charts were evaluated in depth, and the literature was reviewed in regard to possible etiopathologic mechanisms. Within 1-6 h of apparently successful thrombolytic therapy for AMI, these three patients experienced sudden and profound bradycardia and hypotension and could not be resuscitated. The potential occurrence of EMD in all three patients raises the possibility of accelerated myocardial rupture, as EMD is one of the clinical hallmarks of this condition. As suggested by the three clustered cases, this heretofore undescribed association between sudden unexpected cardiac death and thrombolytic therapy for AMI in patients with seropositive, corticosteroid-dependent RA suggests that further study and observation are needed. This deleterious association, if verified, has important implications for the treatment of AMI in patients who have RA and are corticosteroid dependent.
9776418 Analysis of renal pathology and drug history in 158 Japanese patients with rheumatoid arth 1998 Sep To clarify the characteristics of renal pathology and its correlation with disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA), renal biopsy findings from 158 Japanese RA patients with urinary abnormalities and/or renal dysfunction were analyzed retrospectively in the period between 1979 and 1996. Urologic abnormality and urinary tract infection were ruled out in all patients. Light and immunofluorescence (IF) microscopy were performed in all patients. Mesangial proliferative glomerulonephritis (MesPGN) was diagnosed in 54 patients, membranous nephropathy (MN) in 49, and secondary amyloidosis (AM) in 30. Renal dysfunction was more frequent in patients with AM (22/30) than in patients without (40/128). Forty of 49 MN patients developed renal disorders during DMARDs therapy. The prevalence of DMARD-related MN increased during the period of observation. The fact that DMARDs are of very frequent use in recent Japanese RA patients may reflect the prevalence of MN in this study. Two thirds of patients with MesPGN developed renal disorders when no DMARDs were used. One half of 54 MesPGN patients demonstrated IgA glomerulonephritis (GN) by IF. The prevalence of primary renal diseases in Japan may reflect the frequency of IgA GN in Japanese RA patients. Furthermore, diffuse thinning of the glomerular basement membrane (GBM) was observed in 30 of 81 patients with electron microscopy. RA itself may underlie the pathogenesis of GBM thinning, and drugs used for RA treatment may also accelerate the development of this lesion. In conclusion, although MesPGN, MN, and AM may be relatively more common, IgA GN and GBM thinning also were other frequent entities in Japanese RA patients. No correlation was observed between DMARDs and renal disorders excepting MN.
9497911 Target effector role of vascular endothelium in the inflammatory response: insights from t 1997 Oct Rheumatoid arthritis (RA) is characterised by chronic joint inflammation and infiltration by cells from the blood, especially activated T cells and macrophages, together with formation of new blood vessels. The overgrowth of the synovial lesion results eventually in destruction of cartilage and bone. Cytokines play a major role in RA, both in systemic inflammatory processes, such as induction of acute phase protein synthesis, and in the stimulation of new blood vessel development and recruitment of leucocytes to developing lesions. The focus for the interplay of many cytokines is the endothelium, the lining layer of the vasculature. This is the primary target for circulating mediators, and it controls the traffic of cells and molecules from the bloodstream into underlying tissues. Targeting the action of individual cytokines--for example, using antibody against tumour necrosis factor alpha (TNF alpha), has been shown to be very effective in the treatment of RA. Blockade of TNF alpha activity results in deactivation of the endothelium, manifested as reduced expression of adhesion molecules and chemoattractant cytokines, leading to diminished trafficking of inflammatory cells to synovial joints. In addition anti-TNF alpha decreases circulating levels of the potent angiogenic cytokine VEGF, suggesting that new blood vessel formation, and hence the supply of nutrients to the growing synovial lesion, is also affected. These observations lend further support to the hypothesis that interruption of a component of the cytokine network in RA may modulate disease progression, and point the way towards the development of new therapeutic strategies for the treatment of chronic inflammatory disease states.
10334681 The therapeutic response to D-penicillamine in rheumatoid arthritis: influence of glutathi 1999 Jan OBJECTIVES: To investigate whether the therapeutic response of rheumatoid arthritis (RA) patients to D-penicillamine is associated with polymorphisms in genes of the glutathione S-transferase (GST) supergene family. METHODS: Disease activity in 81 patients with RA treated with D-penicillamine monotherapy was assessed using the Stoke Index, a validated index of disease activity, prior to treatment and at 6 months. GST typing was performed using a polymerase chain reaction-based approach and a logistic regression model was used to investigate any possible association between the therapeutic response to D-penicillamine and the GST genotype. RESULTS: A poor therapeutic response was associated with the GSTM1 null genotype [odds ratio (OR) 3.94], and in particular with the GSTM1*0/GSTM3*A haplotype (OR 7.63). CONCLUSIONS: Our results suggest that GST polymorphisms may influence the response to D-penicillamine in RA, and that patients in possession of the GSTM1*0/GSTM3*A haplotype are significantly less likely to show a beneficial response to the drug.
9255114 A comparison of the prevalence of rheumatoid arthritis and other rheumatic diseases amongs 1997 Jul The impact of environmental factors on the causation of rheumatoid arthritis (RA) is thought to be considerable. We explored this by comparing the prevalence of RA amongst Pakistanis living in England, where it is relatively high amongst ethnic English, and in Pakistan. The frequency of other rheumatic diseases was also compared. Information on 2056 adult Pakistanis in England and 4232 in Pakistan was obtained by house-to-house surveys using identical protocols. Positive respondents were examined by the same two clinicians in both countries. Rheumatic complaints increased with age and were more common in females in both communities. The standardized morbidity ratio (SMR) (95% CI) of RA in England was 2.1 (1.1-3.1) compared with Pakistan, a difference that was entirely attributable to females. The SMR (95% CI) for women was 3.0 (0.4-5.6) and for men 0.86 (-0.84 to 2.56). In Pakistan, there was a trend to more reporting of some but not all rheumatic complaints amongst the affluent segment of the population. This was increasingly apparent amongst those resident in England and the possibility of an impact of easier ascertainment amongst the more educated cannot be discounted. Low back pain was significantly more common in England. Furthermore, the colder climate was frequently invoked as a cause of more symptoms in England. Thus, several factors may have influenced the observation that RA is more common amongst Pakistanis in England compared with Pakistan. An environmental factor cannot be excluded. However, the frequency of non-specific musculoskeletal pain was similar. The regions of Pakistan from which the two populations were derived were also different and immunogenetic heterogeneity might also have contributed to the difference in RA prevalence.
11196546 Incidence of elbow involvement in rheumatoid arthritis. A 15 year endpoint study. 2001 Jan OBJECTIVE: To evaluate the incidence of involvement and cause of destruction of humeroulnar (HU) and humeroradial (HR) joints in a prospectively followed cohort of 74 patients with seropositive and erosive rheumatoid arthritis (RA). METHODS: At the 15 year followup standard anteroposterior and lateral radiographs of 148 elbow joints were evaluated, and the grade of destruction was assessed by the Larsen method. RESULTS: Erosive involvement (Larsen grade 2) was observed in 75/148 (51%) elbows in 45/74 (61%) patients; 30 patients had bilateral and 15 unilateral involvement. The incidence of mild erosions (Larsen grade 2) was 49/148 (33%), and severe erosions (Larsen 3-5) 26/148 (18%). The 13 most severely involved (Larsen grade 4-5) joints were seen in 8 (11%) patients. Erosions were most often observed on the capitellum (64 joints) and the lateral epicondyle (58 joints) of the humerus (AP view) or on the olecranon of the ulna (52 joints). The Larsen score (0-100) for peripheral joints correlated significantly with the elbow joint Larsen grade on both sides: right, r = 0.53 (95% CI 0.34 to 0.68); left, r = 0.53 (95% CI 0.34 to 0.68). CONCLUSION: After 15 years more than half of the elbows and almost 2 of 3 patients with RA showed definite involvement of the elbow joint. Erosions were most often located on the capitellum and the lateral epicondyle of the humerus or the olecranon of the ulna. Severe destruction was most often bilateral.
11138340 Effects of estrogen on interleukin-6 production in rheumatoid fibroblast-like synoviocytes 2000 Nov OBJECTIVE: In view of the importance of estrogen and IL-6 in the pathogenesis of rheumatoid arthritis (RA), the effects of 17 beta-estradiol (E2) on interleukin (IL)-6 production in cultured rheumatoid fibroblast-like synoviocytes were investigated. METHODS: Cultured fibroblast-like synoviocytes obtained from RA joints were treated with the vehicle (control), as well as 10(-8) and 10(-6) M of E2, with or without IL-1 beta stimulation. After 72 hours of culture, the levels of IL-6 in supernatants were measured by ELISA. RESULTS: Treatment with 10(-8) and 10(-6) M of E2 had no effect on the constitutive production of IL-6 in cultured fibroblast-like synoviocytes. However, E2 increased IL-1 beta-induced IL-6 production in a dose-dependent manner, with a mean 12.5% increase with 10(-8) M of E2 (p = 0.048) and 33.4% with 10(-6) M (p < 0.0001) versus the control. CONCLUSION: Estrogen up-regulates IL-1 beta-induced IL-6 production in cultured fibroblast-like synoviocytes, possibly contributing to the enhancement of rheumatoid inflammation in synovial tissues.
11350845 Clinical and immunogenetic characteristics of European multicase rheumatoid arthritis fami 2001 Jun OBJECTIVE: To describe the characteristics of a new set of European families with affected sib pairs (ASP) collected by the European Consortium on Rheumatoid Arthritis Families (ECRAF) to replicate the results of our first genome scan. Potential gradients for disease severity in Europe and concordance within families were studied. PATIENTS AND METHODS: From 1996 to 1998 European white families with at least two affected siblings were enrolled in the study. Demographic (sex, age at onset), clinical data (rheumatoid factor (RF), disease duration, erosive disease, extra-articular features (EF)), and HLA-DRB1 oligotyping were analysed. RESULTS: 565 patients with rheumatoid arthritis (RA), belonging to 271 families including 319 affected sib pairs (ASP) were collected. Belgium, France, Italy, the Netherlands, Portugal, and Spain contributed 20, 96, 52, 24, 9, and 70 families, respectively. Sex (78% women), age at onset (mean 44 years), and RF positivity (79%) were similar among the countries. Differences were found in disease duration (11-18 years) and in the prevalence of erosive disease (70-93%), nodules (15-44%), subjective Sjögren's syndrome (5-38%), and EF (3-16%) (p<0.05 in all cases). A total of 22% RA sibs were shared epitope (SE) negative, whereas 47% and 30% carried one and two SE alleles respectively. Carriage of SE differed widely among countries (p<0.0001): no SE alleles (6-36%), one allele (43-60%), and two alleles (20-39%). SE encoding alleles were mainly DRB1*04 in the Netherlands and Belgium, whereas SE carriage was less common and evenly distributed between DRB1*01, *04, and *10 in Mediterranean countries. No concordance within families was found either in age/calendar year of onset (intraclass correlation coefficient <0.50) or in clinical and radiological features (kappa<0.22). CONCLUSIONS: The differences in RA characteristics between European countries and within families underline the heterogeneity of the disease. No clear cut gradient of disease severity was seen in Europe.
10796342 Dynamic exercise therapy for rheumatoid arthritis. 2000 OBJECTIVES: To assess the effects of dynamic exercise therapy in improving joint mobility, muscle strength, aerobic capacity and daily functioning in patients with rheumatoid arthritis (RA). In addition, possible unwanted effects such as an increase in pain, disease activity and radiological progression were studied. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal trials register, the Cochrane Controlled trials Register, Medline, Embase and SCISEARCH databases up to may 1997 in order to controlled trials on the effect of exercise therapy. SELECTION CRITERIA: Randomized trials on the effect of dynamic exercise therapy in RA patients with an exercise program fulfilling the following criteria: a) intensity level such that heart rates exceeded 60% of maximal heart rate during at least 20 minutes, b) exercise frequency of two session per week, and c) duration of intervention of greater than six weeks DATA COLLECTION AND ANALYSIS: Two blinded reviewers independently selected eligible studies, rated the methodological quality and extracted data. MAIN RESULTS: Six out of 30 identified controlled trials met the inclusion criteria. Four of the six included studies fulfilled at least seven out of 10 methodological criteria. Due to heterogeneity in outcome measures, data could not be pooled. The results suggest that dynamic exercise therapy is effective at increasing aerobic capacity and muscle strength. No detrimental effects on disease activity and pain were observed. The effects of dynamic exercise therapy on functional ability and radiological progression are unclear. REVIEWER'S CONCLUSIONS: Dynamic exercise therapy has a positive effect on physical capacity. Research on the long-term effect of dynamic exercise therapy on radiological progression and functional ability is needed.
11791646 Serum vascular endothelial growth factor in late rheumatoid arthritis. 2001 Nov OBJECTIVES: To investigate the serum levels of VEGF in patients with rheumatoid arthritis of long duration. METHODS: Serum VEGF levels were measured in 118 patients with long-standing rheumatoid arthritis according to the ACR criteria (mean duration 12 years). The disease activity score was evaluated by the method of van der Heijde et al. RESULTS: Serum levels of VEGF in patients with RA were significantly higher than in healthy controls. VEGF levels showed no correlation with CRP, SAA amyloid protein, or the disease activity score. CONCLUSIONS: Our findings suggest that, contrary to the results reported in patients with early onset RA, where VEGF appears to play an active part in joint inflammation, in long-standing RA elevated VEGF serum levels may be an independent marker although its significance remain to be established.
9690770 Could diet be used to reduce the risk of developing Alzheimer's disease? 1998 Apr Researchers have recently reported a possible inverse relationship between taking steroids or non-steroidal anti-inflammatory drugs, or both, and the development of Alzheimer's disease. In this article it is hypothesized that the reduction in the human body of the amount of available arachidonic acid, the precursor of inflammatory eicosanoids, by dietary methods might offer a path to prevention of Alzheimer's disease without resorting to drugs having potentially harmful side effects, and without inhibiting the production of highly important, non-inflammatory eicosanoids.
10728742 Clinical improvement as reflected in measures of function and health-related quality of li 2000 Mar OBJECTIVE: To examine correlations between clinical improvement as defined by the American College of Rheumatology (ACR) responder analysis and clinical improvement as determined by 4 function and/or health-related quality of life measures, and to estimate the sensitivity and relative efficiency of these measures compared with changes in the tender joint count in patients with rheumatoid arthritis (RA). METHODS: A 52-week, multicenter, double-blind controlled trial was conducted to compare treatment with leflunomide (n = 182), methotrexate (n = 180), or placebo (n = 118) in patients with active RA. ACR response rates and improvement in scores on the Health Assessment Questionnaire (HAQ), Problem Elicitation Technique (PET), and Medical Outcomes Survey Short Form 36 (SF-36) were compared in 438 of the patients. RESULTS: In comparing leflunomide with placebo, the patient global assessment, HAQ disability index, and SF-36 bodily pain scale were most responsive to treatment group differences. The modified HAQ (M-HAQ), PET Top 5, SF-36 physical component score, physician global assessment, pain intensity scale, and SF-36 physical functioning scale were more responsive to treatment group differences than was the tender joint count. In comparing methotrexate with placebo, the patient and physician global assessments were most responsive. These 2 measures, as well as the pain intensity scale and the C-reactive protein level, were more responsive to treatment group differences than was the tender joint count, while the SF-36 mental health component score was least responsive. A close correlation between changes in the M-HAQ and HAQ scores indicated that the M-HAQ was similarly responsive to change over time. Improvements in the PET, SF-36 physical component score, bodily pain, and physical functioning scales correlated with the ACR responder status. CONCLUSION: Both disease-specific and generic measures of function and health-related quality of life detect improvements in RA patients. Using both types of measures for evaluating therapies will identify discernible changes that are important to patients, and will facilitate comparisons across different disease states.
10223089 Antibiotics for rheumatoid arthritis? Minocycline shows promise in some patients. 1999 Apr Rheumatoid arthritis is a painful, chronic disease that affects an estimated 2 million Americans. Although no single pharmacologic agent is completely effective against the disease, some patients have shown significant improvement when treated with minocycline. Dr Alarcón summarizes the outcomes of studies to date and offers her recommendations.
10614738 HLA polymorphisms and T cells in rheumatoid arthritis. 1999 A dense infiltrate of activated T cells, macrophages, and B cells in the synovial membrane is the cardinal pathological feature of rheumatoid arthritis (RA). Frequently, tissue infiltrating cells acquire a morphological organization reminiscent of secondary lymphoid tissue. The composition of the inflammatory lesions, the production of autoantibodies, and the association of disease risk with genes related to the HLA-D region have all been cited as evidence for a critical role of T cells in disease pathogenesis. Investigations on the precise role of HLA genes in RA have confirmed the importance of this genetic risk factor and have identified a consensus sequence within the HLA-DRBI genes. The observation that HLA polymorphisms are mostly associated with disease progression and severity and that a gene dose effect for HLA-DR genes is operational has challenged the simple model that HLA molecules select and present an arthritogenic antigen. Studies analyzing the repertoire of tissue infiltrating T cells have not been able to identify a dominant and common disease relevant T cell. The infiltrate is diverse in terms of T cell receptor gene usage but consistently includes clonally expanded populations. Recent evidence indicates that RA patients carry expanded CD4 clonotypes which are characterized by deficient CD28 expression and autoreactivity. These autoreactive CD4 T cells are not restricted to the joint, raising the possibility that rheumatoid synovitis is a manifestation of a systemic autoimmune disease. Support for this model has come from studies in T cell receptor (TCR) transgenic animals which develop inflammation of the synovial membrane stimulated by a T cell response to ubiquitously expressed self-MHC molecules. Antigens driving the chronic persistent immune response in RA may not be restricted to the joint but rather may be widely distributed, providing an explanation for the difficulties in identifying arthritogenic antigens directly or indirectly through the selection of joint infiltrating T cells.
11846054 Lower level of education in young adults with arthritis starting in the early adulthood. 2001 An appropriate education may lead to less work disability in patients with arthritis. The aim of the study was to determine the educational level in two groups of young adults with arthritis. Patients with juvenile arthritis ( JA, n=32) and patients with early adult onset of arthritis (EA, n=47) were examined with the Quality of Life Scale (QOLS) and a questionnaire concerning education and profession counselling. Comparisons with a reference group (n=95) from the general population were made. The EA group had lower level of education (p<0.01), compared to the reference group. Among the EA patients, 62% had not discussed their choice of occupation with anybody, compared to 19% in the JA group. The educational level was lower in patients with rheumatic disease starting in early adulthood. Educational issues and counselling should be focused on the care of young adults with arthritis.
9440144 Antiperinuclear factor--clinical, serological and genetic correlates in Israeli patients w 1997 The possible association between the presence of antiperinuclear factor (APF) and clinical and genetic parameters was investigated in 54 Israeli patients with rheumatoid arthritis (RA). Rheumatoid factor (RF) was detected in the sera of 43 patients (80%) and APF was positive in 33 (61%). No significant statistical differences were found in the presence of HLA-DR4 and/or DR1 between APF-positive and -negative patients. Furthermore, neither the Ritchie articular index nor the patient's functional class correlated with the presence of APF. The results of our study suggested that although Israeli patients have a different genetic background, the presence and behaviour of APF is similar to that of other Caucasian populations.