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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
9569999 The effects of non-steroidal anti-inflammatory drugs on the disposition of methotrexate in 1998 Apr We have studied the pharmacokinetics of methotrexate in patients with rheumatoid arthritis concurrently taking the most commonly used non-steroidal anti-inflammatory drugs (NSAIDs), aspirin, diclofenac, naproxen, indomethacin, and ibuprofen. The area under the curve, the total systemic clearance, the distribution volume, and the half-life of methotrexate in patients receiving concurrent NSAID therapy did not change significantly (at p < 0.05). Concurrent treatment with NSAIDs resulted in increased inter-patient variability of methotrexate concentration, possibly as a result of biochemical interactions; however, it does not appear clinically relevant. The data suggest that the NSAIDs do not significantly affect the disposition of methotrexate, contrary to some of the earlier reports.
9159412 Synovial mononuclear cells consist with T cells which produce high levels of tumor necrosi 1997 To determine whether synovial mononuclear cells include a population of tumor necrosis factor alpha-producing T cells, we measured tumor necrosis alpha levels in culture supernatants of synovial mononuclear cells by ELISA and analyzed tumor necrosis alpha mRNA-positive cell frequencies. There were no significant differences in the spontaneous levels of TNF alpha between synovial mononuclear cells and peripheral mononuclear cells. The frequency of tumor necrosis factor alpha mRNA-positive cells in synovial mononuclear cells was higher than that of peripheral mononuclear cells. When stimulated with a superantigen, mononuclear cells from the synovial fluid of rheumatoid arthritis patients showed higher levels of tumor necrosis factor alpha production (1,035 +/- 817 pg/ml) than did mononuclear cells from their peripheral blood (236 +/- 180 pg/ml). In addition, we observed that a few T cell clones were resistant to superantigenic restimulation in vitro. We conclude that when these types of T cells persist in the synovium, they play a role in the development of rheumatoid arthritis via a mechanism involving tumor necrosis factor alpha production.
10751010 Update on genetic risk factors for systemic lupus erythematosus and rheumatoid arthritis. 2000 Mar The results of twin and family studies clearly implicate an important role for genetic factors in the etiology of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). However, the complex nature of these diseases has hampered progress in defining the genetic determinants. Recent advances in molecular genetic and statistical methodology offer new hope to overcome these challenges. This review highlights recent efforts to identify genetic risk factors for SLE and RA using allele sharing and other linkage methods. In spite of striking differences between these studies, some agreement in terms of the regions providing evidence of linkage also exists. Thus, together these studies highlight regions of the genome that are likely to contain SLE and RA susceptibility genes. In addition, the results of these studies, in conjunction with progress in other complex human diseases, suggest several important considerations for future studies.
9667615 Vitronectin expression in rheumatoid arthritic synovia--inhibition of plasmin generation b 1998 Jun The plasmin-generating system controls, to a great extent, the degree of connective tissue destruction as well as fibrin deposition two contributors to the pathogenesis generated in diseases such as rheumatoid arthritis. Vitronectin, an adhesive blood glycoprotein, has the potential to modulate this system by its known capacity to interact with plasminogen activator inhibitor-1, plasminogen activators, the urokinase plasminogen activator receptor, and plasminogen. The net effect of these interactions, in terms of plasmin generation, is not known as yet. In the present study, we have investigated the possible expression and role of vitronectin in rheumatoid arthritic synovia. Analysis of synovial frozen sections by immunofluorescence showed the presence of vitronectin in the 13 cases studied. In situ hybridization analysis demonstrated the presence of vitronectin mRNA in cells present in areas rich in infiltrating inflammatory cells. The adherent population of the rheumatoid arthritic synovial cells was isolated and found to synthesize and secrete vitronectin into the medium (seven of 10 isolates), as assessed by metabolic labelling and immunoprecipitation. Plasmin-generating activity was detected in the adherent synovial cells, and this activity was increased by antibodies to vitronectin. Our findings show, for the first time, that vitronectin can be endogenously produced in a pathophysiological system where it can inhibit the generation of plasmin.
9333771 [Rheumatoid arthritis as a risk factor for development of multiple myeloma]. 1997 Mar 7 out of 154 patients with multiple myeloma (MM) with concomitant rheumatoid arthritis (RA) (5 persons) and Bechterev disease (BD) (2 persons) have been presented. There were 5 women and 2 men at age from 52 to 67 years. Four of them had joint's disease for 4, 5, 24 and 25 years prior to MM, and in the next there MM was diagnosed simultaneously with RA. Two patients are still living (50 and 55 months from the diagnosis of MM), the mean survival time of the five already dead was 34.5 months, and did not differ from the survival of patients with MM alone. The contribution of interleukin-6 (Il-6) and adhesion molecules ICAM-1, VCAM-1, CD44 in pathogenesis of both diseases are discussed.
11554102 [Rehabilitation in rheumatic diseases]. 2001 Sep 1 Rehabilitation of rheumatic diseases is a difficult subject because it deals with a chronic life-long illness. The necessary therapy has to adjust to the changing symptoms of pain and malfunction. In this article we introduce the various means of physical medicine required. It will be a life-long rehabilitation process with changing handicaps and disabilities. Improvement with nearly no functional deficits and no clinical symptoms but impairment and disability show how varied this group of patients is. There is no borderline between the acute and chronic stage. We need an interdisciplinary approach and specialised centres for the rehabilitation of rheumatoid diseases.
9462172 Autoantibodies predicting the outcome of rheumatoid arthritis: evaluation in two subsets o 1997 Nov OBJECTIVE: Autoantibodies such as rheumatoid factor (RF), antikeratin antibodies (AKA), antiperinuclear factor (APF), and anti-RA 33 antibodies are considered of value for the diagnosis of RA. The purpose of this study was to evaluate these autoantibodies as predictors of severe radiographic damage in rheumatoid arthritis (RA). PATIENTS AND METHODS: Eighty six patients with RA (70 women, 16 men) fulfilling 1987 ACR criteria were selected from a cohort of 469 patients followed up since the first year of RA onset because they could be divided in two groups according to the severity of the radiographic damage. These 86 patients had a mean (SD) disease duration of eight (four) years: 43 patients had severe radiographic damage (Larsen score > or = 2) and 43 had limited radiographic damage (Larsen score < 2). The two groups were matched by disease duration and sex. The following autoantibodies were looked for: RF, ANA, AKA, APF, and anti-RA 33 antibodies. In addition, HLA class II DR beta alleles and standard inflammatory parameters (erythrocyte sedimentation rate, C reactive protein) were determined. RESULTS: Patients with severe radiographic damage differed from those with limited radiographic damage in that they had higher RF (p = 0.01), APF (p < 0.02), and AKA (p = 0.001) titres. Stepwise regression analysis was done to calculate the odds ratios (OR) for each clinical and laboratory variable; only presence of cutaneous nodules (OR: 14.9; 95% CI: 7, 128), HLA DRB1*04 or DRB1*01 (OR: 7.53; 95% CI: 1.32, 42.9), AKA (OR: 3.11; 95%, CI: 0.58, 16.8), a high erythrocyte sedimentation rate (OR: 2.66; 95% CI: 0.60, 11.9), and a high C reactive protein value (OR: 7.4; 95% CI: 1.43, 38.1) were predictive of severe radiographic damage. CONCLUSION: These data suggest that the risk of severe radiographic damage in RA patients is higher when cutaneous nodules, HLA DRB1*04 or DRB1*01, and/or AKA are present. The other autoantibodies of diagnostic significance are of little help for predicting joint destruction.
9306870 Radiographic patterns and response to corticosteroid hip injection. 1997 Aug OBJECTIVES: A prospective, open study of corticosteroid hip injection (CHI) was performed to determine if different radiological patterns of arthritis vary in their response. METHODS: Forty five patients (15 with rheumatoid arthritis, 27 with osteoarthritis, and three with anklyosing spondylitis) underwent hip injection with 80 mg methylprednisolone and lignocaine under x ray control. Outcome was assessed at two, 12, and 26 weeks for pain, range of hip movement, and graded functional questionnaire. Patients estimated their pain in four components, night pain, rest pain, weight bearing, and referred pain, each measured by 10 cm visual analogue score and summed to give a total score out of 40 cm. Hip radiographs were evaluated blindly for pattern and severity of arthritis, as well as for progression between 0 and 26 weeks. RESULTS: Median total pain score decreased from 29 cm at baseline to 22 cm at two weeks (p = 0.0001), 24 cm at 12 weeks (p = 0.03), but had returned nearly to baseline by 26 weeks (25 cm, p = 0.3). Greatest improvement was seen for night pain. Mean range of internal rotation increased from 16 to 28 degrees at two weeks (p = 0.03) and 21 degrees at 12 weeks (p = 0.06). Functional ability did not change. Hips with an atrophic pattern of arthritis on plain radiography gained negligible pain relief at two weeks compared with hips with a hypertrophic or mixed bone response (p = 0.04). The degree of pain relief was similar in patients with OA and RA, and was not influenced by radiographic severity or by the direction of migration of the femoral head. CONCLUSION: Pain and internal rotation improve for up to 12 weeks after CHI. CHI offers a useful and safe therapeutic option for patients with hip arthritis, with the exception of those with a purely atrophic radiological pattern.
9121017 [Long-term clinical results with a new surgical method for the fragile valvular annulus]. 1997 Mar We performed prosthetic valve replacement with skirt in 11 patients for the fragile valvular annulus. Subjects included 6 patients with active infective endocarditis involving aortic root abscess, 2 patients with systemic disease requiring steroid treatment, and 3 patients with hemolysis or perivalvular leakage. Operative procedure in 11 patients was performed aortic valve replacement with Dacron or Xenomedica skirt attached to the prosthetic ring. One patient died of heart failure during perioperative period. 2 patients died of arrhythmia, heart failure in late postoperative period. The event free rate was 77.1% since 5 years after operation. We conclude that prosthetic valve replacement with skirt is useful to tha fragile valvular annulus.
10422542 Arthrotec: the evidence speaks for itself. 1999 This article examines the most recently published scientific literature on arthritis therapy options and available mucosal-protective agents. Emphasis is placed on the risks of current nonsteroidal anti-inflammatory drug (NSAID) therapy, the options for reducing such risks, and the published information that either supports or refutes current thinking in these areas. A comprehensive evaluation is made of clinical data related to the use of Arthrotec (diclofenac/misoprostol) in the treatment of arthritis. A recent meta-analysis of the prophylaxis of NSAID-associated upper gastrointestinal complications is reviewed. The results of this meta-analysis should help to consolidate much of the current scientific literature on the safe and effective treatment of arthritis.
11669153 Removal of hyaline articular cartilage reduces lymphocyte infiltration and activation in r 2001 Oct OBJECTIVE: To analyze the effect of removal of hyaline articular cartilage on synovial membrane pathology in chronic arthritis. METHODS: Synovial membrane samples were obtained from patients with rheumatoid arthritis or ankylosing spondylitis in association with total hip arthroplasty, either primary or revision surgery. Synovial membrane histopathology was assessed by immunochemical staining and morphometry. RESULTS: CD68 positive macrophages were common in revision synovial membranes. In contrast, T lymphocytes were much more common in primary rheumatoid synovial membranes (p < 0.001). Many T lymphocytes in primary synovial membrane were HLA-D/DR positive (p < 0.001) and interleukin 2 receptor (IL-2R) positive (p < 0.001) and contained interferon-gamma(IFN-gamma; p < 0.001) and tumor necrosis factor-beta (TNF-beta; p < 0.001). In contrast, revision synovial membranes from patients with chronic arthritis contained only a few HLA-D/DR positive T cells and practically no IL-2R, IFN-gamma, or TNF-beta positive activated T lymphocytes. CONCLUSION: The components of hyaline articular cartilage may be the source of autoantigen responsible for perpetuation of chronic arthritides.
9741311 Serum androgen-anabolic hormones and the risk of rheumatoid arthritis. 1998 May OBJECTIVE: It has been hypothesised, mainly on the basis of indirect evidence, that low serum concentrations of androgen-anabolic hormones would play a causal part in the aetiology of rheumatoid arthritis (RA). METHODS: A case-control study was nested with a Finnish cohort of 19,072 adults who had neither arthritis nor a history of it at the baseline examination during 1973-1977. Pre-illness serum specimens for the assay of testosterone and dehydroepiandrosterone sulphate (DHEAS) were available from 116 cases who had developed RA by late 1989. Three controls per each incident case were individually matched for sex, age, and municipality. RESULTS: The mean testosterone concentration was 1.4 nmol/l in those 84 women who developed RA and 1.4 nmol/l in their controls; the corresponding figures for DHEAS were 5.2 mumol/l and 5.5 mumol/l, respectively. Mean testosterone concentration in the 32 male cases was 26.1 nmol/l and 26.4 nmol/l in their controls; the corresponding figures for DHEAS were 11.2 mumol/l and 10.1 mumol/l, respectively. Analysis by subgroups (rheumatoid factor positive and negative disease, pre-menopausal and postmenopausal women) and by hormone distributions showed no differences. CONCLUSION: The findings are not in line with the contention that low concentrations of testosterone and DHEAS play a part in the aetiology of RA.
9313396 Do people with rheumatoid arthritis develop illness-related schemas? 1997 Apr OBJECTIVE: To assess, using both qualitative/inductive and quantitative data, whether people with rheumatoid arthritis (RA) have schemas related to arthritis. METHODS: Themes identified from interview and focus group transcripts were used to develop 1) questionnaire items, and 2) statements participants were asked to recall during home interviews. Two hundred one people with RA completed questionnaires and recall tasks of the type used in cognitive research, followed 10 days later by another recall assessment by telephone. RESULTS: Qualitative methods, item-level questionnaire data, and category-level recall data yielded convergent results supporting 4 final categories: mastery, support, loss of independence, and depression. Regression analyses indicated that category of earlier recollections predicted subsequent recollections assessed via phone. CONCLUSIONS: Results from widely different methods offer at least partial support for arthritis schemas and suggest that the concepts identified are meaningful to patients as well as to researchers.
10584964 Elbow revision arthroplasty in the situation of bone loss using an unlinked long-stem pros 1999 Nov The results of 16 first-revision operations using an unlinked cemented long-stem elbow arthroplasty in the situation of major bone loss are presented. Fifteen patients with a mean age of 62 years and longstanding polyarthritis were monitored for a mean period of 31 months (range, 6-62 months). Seven revision arthroplasties showed a good result and 7 a fair result with improvement of function and pain. Two patients with postoperative instability requiring further surgery had a poor result, with one infected prosthesis and one elbow with persistent instability and ulnar nerve hypersensitivity. Using a visual analog scale, patients documented good pain relief, good subjective independence, and a high level of satisfaction. In the follow-up SF-36 health survey, patients scored low physical function but good mental function. These results show that in the absence of infection and instability, revision elbow arthroplasty, even in the situation of major bone loss, can be a successful treatment option using this unlinked cemented long-stem system.
10334679 Glomerular and tubular proteinuria as markers of nephropathy in rheumatoid arthritis. 1999 Jan OBJECTIVE: We examined the prevalence of nephropathy in unselected patients with rheumatoid arthritis (RA) by measurement of marker proteins for glomerular and tubular damage in urine. METHODS: A highly sensitive immunoluminometric assay was used to measure albumin, immunoglobulin G and alpha1-microglobulin in 24 h urines of 44 RA patients and a control group of 46 patients with generalized osteoarthritis (OA). RESULTS: Fifty-five per cent of RA patients were found to have proteinuria as a symptom of renal disease. Drug therapy or vasculitis were identified as possible reasons for proteinuria in only 25% of these patients; in most patients (75%), no reason for proteinuria was found. Tubular and mixed proteinuria were more frequent than glomerular proteinuria. Only 15% of the control group exhibited mild proteinuria, which was attributable to nephrotoxic factors. The renal function of RA patients and the control group did not differ significantly. CONCLUSIONS: Proteinuria is a frequent symptom of nephropathy in RA. Screening for renal disease in RA should not only include creatinine measurement and dipstick examination of urine, but also more sensitive methods to detect tubular and glomerular proteinuria as a marker of tubular and early stages of glomerular damage.
10765932 Joint symmetry in early and late rheumatoid and psoriatic arthritis: comparison with a mat 2000 Apr OBJECTIVE: To establish a mathematical model to predict the probability of symmetry of joint involvement as a function of the number of joints involved and to compare expected with actual probabilities in psoriatic arthritis (PsA) and rheumatoid arthritis (RA) and in early and late disease. METHODS: Random involvement of joints was assumed, and the binomial theorem was used to give the frequency distribution of involved joints as a function of each joint count. Ten joint pairs were included: shoulder, elbow, wrist, metacarpophalangeal joints, proximal interphalangeal (PIP) joints of the hands, hip, knee, ankle, metatarsophalangeal joints, and PIP joints of the feet. Observed probabilities were obtained from subjects with early (duration < or =12 months) and late PsA and RA. RESULTS: The number of subjects in each of the disease subgroups was as follows: early PsA n = 33, late PsA n = 77, early RA n = 61, late RA n = 93. Observed probabilities of symmetry exceeded predicted probabilities for all disease subgroups. The median number of involved joints in each group was as follows: early PsA 4, late PsA 8, early RA 8, late RA 15 (chi2 = 95.3, 3 degrees of freedom, P = 0.0001, by Kruskal-Wallis test). After correcting for the discrepancy in the number of involved joints, no difference in joint symmetry was found between the groups (chi2 = 1.77, P = 0.62 by Friedman two-way analysis of variance). Similar results were obtained when individual hand and foot joints were analyzed separately. CONCLUSION: The pattern of joint involvement is often used to distinguish between rheumatoid and psoriatic arthritis. This study confirms that symmetry is largely a function of the total number of joints involved and that, in terms of joint pattern, differences between these disorders are more quantitative than qualitative. Both disorders have high absolute values of symmetry, particularly in the joints of the wrist and hand.
11708409 The effect of low dose methotrexate on bone density. 2001 Nov OBJECTIVE: High dose methotrexate (MTX) has been linked with bone loss in oncology patients. However, it is unclear whether longterm low dose MTX used in the treatment of inflammatory arthritis is associated with bone loss. We compared the effect of low dose MTX on bone density in prospectively recruited patients with rheumatoid arthritis (RA) and psoriasis/psoriatic arthritis (Ps/PsA). METHODS: Thirty RA patients and 30 Ps/PsA patients taking MTX were compared to controls not taking MTX (30 with RA, 27 Ps/PsA). Bone mineral density (BMD) of the radius, lumbar spine, trochanter, and femoral neck was measured using Lunar dual energy x-ray absorptiometry. Student t tests were used to detect differences in bone density (using Z scores) of the MTX group versus controls for both the RA and Ps/PsA groups. Analysis of covariance was used to examine for confounders including disease duration, disease activity, age, and sex. RESULTS: BMD of the radius/femoral neck/trochanter did not differ significantly between the MTX treated groups and controls when analyzed by Z scores. The mean difference between the MTX group and controls of the femoral neck was 0.040 (95% CI -0.40, 0.12) and 0.060 (95% CI -0.30, 0.15) for the RA and Ps/PsA groups, respectively. The absolute BMD of the lumbar spine (L2-L4) was higher in the RA MTX group than in controls. Analysis of covariance did not reveal an effect of study group on bone density. CONCLUSION: This study suggests that low dose MTX does not have a negative effect on bone density, at either cortical or trabecular sites.
10755623 HLA molecules, bacteria and autoimmunity. 2000 Apr It has been well established that many diseases are linked to HLA antigens. Two of the most interesting HLA associations may provide some insight into the pathogenesis of rheumatic inflammatory conditions. In ankylosing spondylitis (AS), 96% of patients possess HLA-B27, whilst the frequency of this marker in the general population is c. 8%. In rheumatoid arthritis (RA), >90% of patients possess either HLA-DR1 or some subtypes of HLA-DR4, whilst the frequency of this marker in the general population is c. 35%. The association between HLA-B27 and reactive arthritis (ReA) has also been well established. Furthermore, it has been shown that ReA is triggered by infection via the gastrointestinal tract due to Yersinia, Salmonella or Campylobacter spp. and in the genitourinary tract due to chlamydia. In a similar way, microbiological and immunological studies have revealed an association between Klebsiella pneumoniae in AS and Proteus mirabilis in RA. This article reviews the possible pathological implications of the associations between HLA-B27, K. pneumoniae and AS, as well as HLA-DR1/DR4, P. mirabilis and RA.
9676758 Comparison of the combined cortical thickness of the second metacarpal with Sharp's method 1998 Jul OBJECTIVE: To compare the correlation and specificity of the combined cortical thickness of the second metacarpal (CCT-MC) with Sharp's method (SM) for scoring joint erosions and joint space narrowing in rheumatoid arthritis (RA) and to compare the degree of interobserver agreement between the 2 methods. METHODS: Hand microradiographs of 22 women with RA, functional classes III and IV, were scored independently by 3 rheumatologists using the CCT-MC and the CCT of the middle phalanx and SM. RESULTS: (1) There was a highly significant correlation between the total SM score and the CCT-MC for the 3 observers (r = 0.61, p = 0.0026), but not between the CCT of the middle phalanx and SM (r = 0.15, p = 0.53). There was a lower degree of agreement between the observers for SM erosion scores compared to the CCT-MC (intraclass correlation 0.88 for the CCT-MC and 0.63 for the SM); (2) Both joint space narrowing and erosion scores correlated highly with the CCT-MC (r = -0.60, p = 0.004; and r = -0.51, p = 0.014, respectively); (3) CCT-MC measurements are more closely related to the inner (d) as opposed to the outer (D) diameter of the 2nd metacarpal; (4) The mean time to obtain the CCT-MC score was 3.43 min (SD = 1.38) versus 9.83 min (SD = 3.20) for SM (p = 0.0001); (5) the derivative, (D2-d2)/D2, was significantly correlated with SM (r = -0.72, p = 0.0002) and its erosion and joint space narrowing components (r = -0.63, p = 0.0019; and r = -0.71, p = 0.0002, respectively). CONCLUSION: The CCT-MC is a rapid, practical method with higher agreement among observers compared to SM and correlates highly with SM scores for joint damage in RA. CCT-MC appears to have a higher degree of specificity than other sites for CCT measurement. The CCT-MC is more closely related to the inner diameter than the outer diameter, which supports the notion that the principal site of accelerated bone loss due to RA in the hand occurs at the endosteal surface. The CCT-MC should be further assessed with respect to monitoring radiological progression in RA.
10203024 CTLA4 polymorphisms in Spanish patients with rheumatoid arthritis. 1999 Mar Cytotoxic T-lymphocyte antigen 4 (CTLA4) polymorphisms located in the promotor region at positions -318 (C/T) and in exon 1 (49 A/ G) were investigated in 138 Spanish patients (37 men and 101 women) with rheumatoid arthritis and in 305 ethnically-matched healthy controls. When the allelic and genotypic frequencies corresponding to the CTLA4 -318 position were compared, no significant differences between patients and controls were found. However, when the CTLA4 49 A/G polymorphism was analysed, a significant increase of A/G heterozygous individuals among female patients (48.5% vs. 33.8% in controls; P=0.008; OR=2.0) was observed. This increase was absent among males (37.8%, P=NS). Analysis of the CTLA4 49 polymorphism with respect to HLA-DRB1 typing demonstrated a significant increase of A/G heterozygosity in the HLA-DR3-positive patient group compared with HLA-DR3-negative patient group (14/19, 74% vs. 49/119, 41%; P=0.009, OR=4.0). The increase of A/G genotype among HLA-DR3-positive patients was found in both males (4/6, 67%) and females' (10/13, 77%), although statistical differences were only reached in the female group. These results provide new insight into this complex association, confirm previous data from other studies, and suggest that the CTLA4 gene could be involved in the pathogenesis of rheumatoid arthritis.