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

ID PMID Title PublicationDate abstract
9663484 Modulation of angiogenic vascular endothelial growth factor by tumor necrosis factor alpha 1998 Jul OBJECTIVE: To investigate the regulation of expression of the angiogenic cytokine vascular endothelial growth factor (VEGF) in rheumatoid arthritis (RA), in order to determine whether new blood vessel formation could be a potential therapeutic target in RA. METHODS: Dissociated RA synovial membrane cells were cultured in the presence of cytokine inhibitors, or under hypoxic conditions. Serum VEGF levels were serially measured in RA patients enrolled in clinical trials of anti-tumor necrosis factor alpha (anti-TNFalpha) monoclonal antibody treatment. RESULTS: Combined neutralization of TNFalpha and interleukin-1 (IL-1) in RA synovial membrane cultures reduced VEGF release by 45% (P < 0.05 versus control), although blockade of either TNFalpha or IL-1 activities alone resulted in only small inhibitory effects. In addition, release of VEGF from RA synovial membrane cells was selectively up-regulated by hypoxia. Serum VEGF levels were significantly elevated in RA patients relative to control subjects, and correlated with disease activity. Treatment of RA patients with anti-TNFalpha significantly decreased serum VEGF, and this effect was enhanced by cotreatment with methotrexate. CONCLUSION: Inhibition of TNFalpha and IL-1 activity in vivo could reduce the drive to new blood vessel formation, and hence pannus mass, adding to other therapeutic effects of anti-TNFalpha therapy in RA.
10399790 Echocardiographic findings and 24-h electrocardiographic Holter monitoring in patients wit 1999 Echocardiographic examination and 24-h electrocardiographic Holter monitoring were carried out on 35 patients with nodular rheumatoid arthritis (RA) and 35 with non-nodular RA, who were matched with the nodular RA group regarding age, sex and BSA. A further 35 patients with osteoarthrosis and spondyloarthrosis matched, with both RA groups, constituted a control group. Patients with a history of myocardial infarction, hypertension, rheumatic fever and diabetes were excluded from the study. Cardiac involvement, evaluated using echo-Doppler cardiography, 24-h electrocardiographic Holter monitoring and ECG at rest, occurred in 25 (71.9%) patients with nodular RA and in 15 (42.9%) with non-nodular RA in comparison to 8 (22.9%) control group patients (P < 0.0002). Holter electrocardiographic monitoring over 24 h did not present any essential differences in frequency of rhythm disorders between the examined groups and the control group. However, it revealed more patients with 1-mm ST depression in the nodular RA group than in the non-nodular and control groups. Echocardiographic examination revealed more cases of valvular heart abnormalities, especially those of mitral insufficiency, in nodular RA patients than in non-nodular and control patients. Both a mitral valve prolapse and a pericardial effusion were noted in 8.6% of nodular RA patients. Patients with nodular RA were noted to have a bigger aortic root diameter, but smaller ejection fraction, mean velocity of circumferential fibre shortening and fractional shortening in comparison to non-nodular and to control group patients.
11085796 Skewed T-cell receptor variable gene usage in the synovium of early and chronic rheumatoid 2000 Nov OBJECTIVE: Autoreactive T cells may contribute to the pathogenesis of rheumatoid arthritis (RA). We studied the T-cell receptor (TCR) V-gene repertoire in the blood and synovium of early and chronic RA patients using polymerase chain reaction-enzyme-linked immunosorbent assay to evaluate possible differences between these patient groups. RESULTS: Over-represented TCR V genes were observed in the synovium, but not in the blood of all RA patients (n = 38). The number of over-represented V genes was higher in the synovium of chronic RA patients (n = 31) than in that of early RA patients (n = 7). The V-gene profile was different among patients, and similar in the two knees for patients with bilateral synovitis (n = 5). The clonal composition of over-represented TCR BV genes in a patient with early RA and a patient with chronic RA was further studied by CDR3 region sequence analysis. A high level of clonal diversity was found in the joints and the blood of the early RA patient, suggesting a polyclonal T-cell expansion. In the chronic RA patient, predominant clonal expansions were observed in the blood and synovium, and some expanded clones were still present 2 yr later. CONCLUSIONS: The observation of similar T-cell populations in both joints in patients with bilateral synovitis and the persistence of clonally expanded T cells for more than 2 yr in the joints of a chronic RA patient may indicate a pathogenic role for these cells in the disease process.
9566675 Distribution of T cells and signs of T-cell activation in the rheumatoid joint: implicatio 1998 Mar A prerequisite for comparative histology of synovial tissue by means of biopsies is insight into the distribution of a marker under study. This investigation focuses on the variation in the presence of T cells and signs of T-cell activation within the rheumatoid joint. For this purpose, multiple slides from several pieces of synovial tissue from different parts of a joint were stained and scored for the expression of CD3, CD25, HLA-DR, Ki67 and interferon-gamma. The variation in scores for the presence of T cells and markers of activation was more pronounced in slides prepared from different pieces of tissue than in slides from one piece of tissue. Based on multiple analysis of variance, methods are suggested to establish a reliable overall score for the expression of a certain marker within a joint. Following validation, such methods may prove to be useful by allowing semiquantitative histology of synovial tissue for studies on arthritis.
10643697 Characterizing the quantitative genetic contribution to rheumatoid arthritis using data fr 2000 Jan OBJECTIVE: Twin concordance data for rheumatoid arthritis (RA) on their own provide only limited insight into the relative genetic and environmental contribution to the disease. We applied quantitative genetic methods to assess the heritability of RA and to examine for evidence of differences in the genetic contribution according to sex, age, and clinical disease characteristics. METHODS: Data were analyzed from 2 previously published nationwide studies of twins with RA conducted in Finland and the United Kingdom. Heritability was assessed by variance components analysis. Differences in the genetic contribution by sex, age, age at disease onset, and clinical characteristics were examined by stratification. The power of the twin study design to detect these differences was examined through simulation. RESULTS: The heritability of RA was 65% (95% confidence interval [95% CI] 50-77) in the Finnish data and 53% (95% CI 40-65) in the UK data. There was no significant difference in the strength of the genetic contribution according to sex, age, age at onset, or disease severity subgroup. Both study designs had power to detect a contribution of at least 40% from the common family environment, and a difference in the genetic contribution of at least 50% between subgroups. CONCLUSION: Genetic factors have a substantial contribution to RA in the population, accounting for approximately 60% of the variation in liability to disease. Although tempered by power considerations, there is no evidence in these twin data that the overall genetic contribution to RA differs by sex, age, age at disease onset, and disease severity.
10666177 Relation of glenohumeral and acromioclavicular joint destruction in rheumatoid shoulder. A 2000 Feb OBJECTIVES: To evaluate the relation of glenohumeral (GH) and acromioclavicular (AC) joint involvement in a cohort of 74 patients with seropositive and erosive rheumatoid arthritis (RA) followed up prospectively. METHODS: At the 15 year follow up radiographs of 148 shoulders were evaluated, and the grade of destruction of GH and AC joints were assessed by the Larsen method. One GH joint arthroplasty had been performed after 13 years of the disease onset and the preoperative radiograph was evaluated. RESULTS: Erosive involvement (Larsen grade >/= 2) was observed in 96 of 148 (65%) of the shoulders. Both GH and AC joints were affected in 62 of 148 (42%) shoulders. GH joint alone was involved in nine (6%) shoulders and only AC joint was affected in 25 (17%) shoulders. AC joint destruction correlated with the GH joint destruction, r=0.74 (95% confidence intervals (CI) 0.65 to 0.80 ). CONCLUSION: In RA AC joint is affected more often than the GH joint, but in half of the patients both joints are involved. This should be remembered when treating painful rheumatoid shoulder.
9783770 RheumaNet--a novel Internet-based rheumatology information network in Germany. 1998 Sep Knowledge transfer in medicine has traditionally been achieved through personal communication, the medical literature, conferences and continuous medical education. However, many of these methods of communication have the problem of currentness, and the latest knowledge is mostly transferred with a certain delay. In particular, chronic disease management is frequently burdened by missing, incomplete or delayed communication. We present the implementation of a novel, Internet-based information system (RheumaNet) to facilitate rapid communication and information transfer between the 21 German Multipurpose Arthritis Centres (MACs). Medical information, agendas, urgent notifications, guidelines, etc., can be exchanged easily via electronic mail, file transfer protocol or the World Wide Web. RheumaNet allows interactive on-line communication as a common platform for joint projects or remote consultation. It supports a set of 'core documentation' that has been used by all German MACs for several years. RheumaNet was used for the organization, on-line presentation and evaluation of the 1997 annual meeting of the German Rheumatology Society and is currently appointed to establish its public representation in the 'Web'. An on-line version of the 'Quality Assurance Textbook' of German rheumatology is achieved with database-derived 'dynamic' Web pages, allowing easy access to any information within it. Advances in the future include the development of on-line patient information bulletin boards, on-line questionnaires, the coordination of rehabilitation and educational tools for medical students, and professional training.
9617167 [Pain analysis is vital in rheumatic diseases. Pain often causes much worry to patients]. 1998 May The article consists of a synthesis of a rheumatic pain symposium held at the annual meeting of the Swedish Medical Association in 1996. Various aspects of pain in rheumatic diseases were discussed, such as physiological, neurohumoral and neurogenic mechanisms, sensory stimulation treatment, differentiation of mechanical and inflammatory pain, quality enhancement by improved co-operation between primary and tertiary care facilities, pharmacological treatment with (centrally and peripherally acting) opioids, selective cyclo-oxygenase inhibitors, and NMDA (N-methyl-D-aspartate) receptor antagonists. For patients with rheumatic disorders exacerbated by pain problems, as for other patients, a pain diagnosis is of fundamental importance. This can be achieved by analysis of the social, psychological, physiological and medical factors contributing to the cause and degree of pain and to pain behaviour, and of the extent to which the pain may be nociceptive (i.e., inflammatory, mechanical, or ischaemic in origin), neurogenic or idiopathic. Pain analysis should be followed by individualised treatment focused on the patient's most crucial problems, thus enhancing the prospect of optimal treatment outcome.
9749298 [Prosthesis of the upper extremity]. 1998 May 30 In functional impairment of a joint due to pain and (or) limited mobility in which conservative measures are inadequate, an operation may be considered. The principal possibilities are arthrodesis and implantation of an artificial joint. Reasons to opt for a prosthesis are involvement of adjacent articulations (in rheumatoid arthritis) and preservation of mobility which, together with stability, is necessary for good articular function. The principal indications for implantation of an artificial joint in the upper extremity are rheumatoid arthritis and (to a lesser degree) osteoarthritis and posttraumatic impairments. The functional results of prostheses in the shoulder, elbow and wrist are good, but the proportion of complications is relatively large (compared with that in hip and knee prostheses) and follow-up so far has only been short.
11178119 Synovial stromal cells from rheumatoid arthritis patients attract monocytes by producing M 2001 Macrophages that accumulate in the synovium of rheumatoid arthritis patients play an important role in the pathogenesis of this inflammatory disease. However, the mechanism by which macrophages are attracted into the inflamed synovium and accumulate there has not been completely delineated. The results of this study show that rheumatoid arthritis synovial stromal cells produce the chemokines monocyte chemotactic protein-1 and IL-8, and these have the capacity to attract peripheral monocytes. These results suggest that one of the mechanisms by which macrophages accumulate in the inflamed synovium is by responding to the chemokines produced locally.
10220819 [Complications of colonic diverticular disease during rheumatoid polyarthritis: 7 cases]. 1999 Jan INTRODUCTION: Among the gastrointestinal adverse effects of nonsteroidal anti-inflammatory drugs (NSAID) and corticoids are mentioned complications of colonic diverticular disease. However, very few studies have described their consequences in rheumatoid arthritis. EXEGESIS: We report on seven patients who were admitted in our department between 1984 and 1997. All patients received corticoids and another antirheumatic drug (gold salts, hydroxychloroquine, immunosuppressive drugs); treatment also included NSAID in four cases. Two patients had a necrotizing vasculitis accompanying rheumatoid arthritis. Intestinal accompanying diseases were the following: one diverticulitis, three colonic perforations with pelviperitonitis, one colovesical fistula, one pelvic abscess, and one diverticular hemorrhage. All patients underwent surgery with positive results. CONCLUSION: Combination of the four following symptoms: fever, abdominal pain, diarrhea, and hemorrhage, can uncover a complication of colónic diverticular disease occurring in the course of rheumatoid arthritis. It should be investigated, even if no history of diverculosis may be evidenced.
11491501 Focal sialadenitis in patients with early synovitis. 2001 Jul OBJECTIVE: To investigate the frequency of sialadenitis on lip biopsy in patients with synovitis of recent onset (ES), and see how sialadenitis relates to clinical and laborator findings of ES. METHODS: Joint involvement, laboratory measures and biopsies of the minor salivary glands were evaluated in 10 ES patients. Diagnosis at a one-year follow-up exam was noted. RESULTS: Six ES patients (60%) had a positive lip biopsy (mononuclear cell focus score greater than 1). ES patients with a positive lip biopsy presented with oligoarthritis, while ES patients with a negative lip biopsy had a more polyarticular presentation. No differences in laboratory measures between patients with a positive and negative lip biopsy were present. Seven ES patients had a diagnosis of rheumatoid arthritis and three had undifferentiated arthritis at the end of one year. CONCLUSION: ES patients had a higher than expected frequency offocal sialadenitis.
9546471 Ankle arthroplasty for rheumatoid arthritis and osteoarthritis: prospective long-term stud 1998 Mar We performed 52 cemented ankle arthroplasties for painful osteoarthritis (OA) (25) or rheumatoid arthritis (RA) (27) using an ankle prosthesis with a near-anatomical design. We assessed the patients radiologically and clinically for up to 14 years using an ankle scoring system. The preoperative median scores were 29 for the OA group and 25 for the RA group and at ten years were 93.5 and 83, respectively. Six ankles in the OA group and five in the RA group required revision or arthrodesis. Survivorship analysis of the two groups showed no significant differences with 72.7% survival for the OA group and 75.5% for the RA group at 14 years.
9093776 Sleep disturbances, fibromyalgia and primary Sjögren's syndrome. 1997 Jan OBJECTIVE: To investigate the association and prevalence of sleep disturbances and fibromyalgia (FM) in a group of patients with primary Sjögren's syndrome (pSS). METHODS: Sixty-five patients with pSS were investigated. A 10-point Mini Sleep Questionnaire (MSQ) was completed focusing on sleep complaints. The same questionnaire was also used in three control groups: Group A-67 patients with rheumatoid arthritis. Group B-53 patients with rheumatoid arthritis (RA) and sicca symptoms; Group C-31 patients with osteoarthritis. All patients with pSS were also studied fro the presence of FM. RESULTS: Moderate or severe sleep disturbances were reported by 49 out of 65 pSS patients (75%). This frequency was significantly higher than that reported by patients in the three control groups (p < 0.001). FM was present in 36 out of 65 pSS patients (55%) and was associated with sleep disturbances. FM or sleep disturbances were not associated with any clinical or laboratory parameters. CONCLUSION: Our results suggest that sleep abnormalities and FM in pSS patients are frequent and their etiology might involve other mechanisms besides joint pain or sicca symptomatology.
9067521 Characteristics of synovial fluid effusion in collagen-induced arthritis (CIA) in the DA r 1997 Mar We have characterized the cellular content and some antibody reactivities in synovial fluid (SF) from DA rats with CIA. Since CIA is widely used as a model for RA, in which many studies concerning immune responses are performed on SF samples, we considered it important to describe the local, disease-causing immune reactions in CIA. At the peak of disease (day 22 after immunization), the major cell population in CIA SF was granulocytes (72%), but macrophages (17.9%), plasma cells (2.6%) and lymphocytes (7.7%) were also present. The CIA synovial membrane (SM) obtained at the same time was mainly infiltrated by monocytes, with granulocytes, lymphocytes and plasma cells also present. Cell populations in blood did not differ between arthritic and normal DA rats. Equally, high anti-collagen type II (CII) and rheumatoid factor (RF) levels could be detected both in SF and in sera. Notably, RF levels were also increased in normal DA rats. Moderate levels of anti-heat shock protein 65 kD (hsp) antibodies were recorded systemically in both normal and diseased animals. In conclusion, the cellular composition in SF and in SM are similar in rat CIA and in RA. The morphological differences between SF and SM that are characteristic for RA could also be demonstrated in CIA. The antibody data indicate systemic production of anti-CII and anti-hsp antibodies as well as RF, but they give no support for local production of these antibodies in the joints, which is the case in RA.
10052859 Can non-steroidal anti-inflammatory drugs act as metalloproteinase modulators? An in-vitro 1998 Dec The in-vitro effects of some non-steroidal anti-inflammatory drugs and some analgesic drugs on collagenase activity were studied by use of a self-quenched fluorogenic esapeptide as substrate. The increased fluorescence signal arising as a result of peptide cleavage by collagenase was recorded and related to the inhibitory potency of the drugs. The effective concentrations in collagenase modulation were also correlated with the levels of the drugs in the plasma and synovial fluids of patients receiving therapeutic doses. Six of the tested drugs, nimesulide, piroxicam, tolmetin, meloxicam, sulindac and sodium meclofenamate, inhibited enzyme activity with IC50 values (concentrations resulting in 50% inhibition) ranging from 1.9 to 28.2 microM and Ki (apparent inhibition constant) ranging from 0.83 to 21.8 microM. Much of the activity was restored after dialysis of the enzyme-drug complex, demonstrating the reversibility of the effect. Although these results indicate that some anti-inflammatory drugs could modulate enzymatic activity involved in the degradation of the extracellular matrix, their possible pharmacological involvement as collagenase inhibitors in collagen degradative diseases remains to be assessed by clinical studies.
9728170 Operative hip arthroscopy. 1998 Aug Twenty patients underwent operative arthroscopic procedures of the hip joint. All procedures were performed with the patient in the supine position on a standard fracture table using fluoroscopy through three arthroscopic portals (anterolateral, anterior paratrochanteric, and posterior paratrochanteric). The initial indications were therapeutic in 16 patients: loose bodies in four, synovial chondromatosis in three, rheumatoid arthritis in five, ankylosing spondylitis in one, septic arthritis in one, avascular necrosis of femoral head in one, and primary osteoarthritis in one. In four patients who had unexplained hip pain, the initial indications were diagnostic: minimal synovial change was seen in two patients, a synovial chondromatosis was present in another, and a tear of the acetabular labrum and hypertrophy of ligament teres were present in a fourth patient. In one patient who had primary osteoarthritis, the insertion of the arthroscopic instrument into the hip joint failed because of profuse osteophytes along the acetabular rim. Twelve of the 19 patients showed significant improvement of the symptoms after the arthroscopic procedure, but seven patients had no benefit from the procedure. One patient had a postoperative reflex sympathetic dystrophy.
10374415 Anti-Sa antibody in Chinese rheumatoid arthritis. 1998 Mar OBJECTIVE: To test anti-Sa antibody in different autoimmune connective tissue diseases and analyze the relationship between Sa antibody and clinical manifestations and laboratory tests in rheumatoid arthritis. METHOD: Sa antigen was extracted from human placenta. Anti-Sa antibody was tested in 40 normal people and 478 connective tissue disease (CTD) patients using Western Blotting (WB). RESULTS: Sa antigen was a protein with molecular weights of 50 kD and 55 kD. Anti-Sa antibody was positive in 31.9% (61/191) rheumatoid arthritis (RA), 3.0% (2/67) Sjögren's syndrome (SS), 4.3% (2/46) systemic lupus erythmatosus (SLE) and 0% (0/66) Behcet's disease, 0% (0/60) polymyositis/dermatomyositis (PM/DM), 0% (0/66) other CTD and 0% (0/40) normal controls. Anti-Sa antibody was different from other auto-antibodies in RA. In rheumatoid arthritis its sensitivity, specificity, positive prediction rate, negative prediction rate were 31.9%, 98.6%, 93.8% and 68.5% respectively. Anti-Sa antibody positive patients were significantly different from anti-Sa antibody negative patients in moming stiffness, ESR, ANA and X-ray grade. CONCLUSION: Anti-Sa antibody was a new auto-antibody for the diagnosis of RA. Anti-Sa antibody positive patients seem to have more serious inflammation and more advanced disease process.
11060752 Metalloproteinase inhibitors: new opportunities for the treatment of rheumatoid arthritis 2000 Jul The clinical efficacy of anti-TNF-alpha therapies have highlighted the apparently central role that TNF-alpha plays in the pathology of rheumatoid arthritis, particularly the inflammatory component. Recent identification of a metalloproteinase from the metzincin superfamily responsible for the production of the soluble form of this cytokine, has generated a large amount of pharmaceutical interest and presents the prospect of a metalloproteinase inhibitor as an anti-inflammatory drug. However, the traditional focus of metzincin inhibitor research has been the identification of inhibitors of matrix metalloproteinases; enzymes associated with matrix destruction, a feature common to both rheumatoid arthritis and osteoarthritis. Inhibitors of this class of metalloproteinase are now in clinical evaluation in patients. This review summarises the current development status of metalloproteinase inhibitors in arthritic diseases and discusses some of the issues that have arisen during their progress to become clinical treatments for these diseases.
10652649 Investigational treatments in rheumatoid arthritis. 1999 Dec The active search for new treatment modalities of established rheumatoid arthritis have created a dynamic period for rheumatology. Both promising pharmaceutical products and targeted interventions with products of the biotechnology industry are being developed. Leflunomide and the selective blockade of the cytokine tumour necrosis factor (TNF) have recently been registered in several countries and others will follow. Like all new therapeutic strategies much remains to be learned about the optimal use of these therapies and their possible limitations. The success of these interventions have shown that a complex disease such as rheumatoid arthritis that is refractory to conventional treatment can be modulated by new therapeutic strategies. This experience has also resulted in further searches for new drugs that influence those pathogenetic pathways affected by the interventions found to be effective.