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ID PMID Title PublicationDate abstract
11778659 The dual association between lymphoma and autoimmunity. 2001 Jul Autoimmune rheumatic diseases and lymphocytic malignancies are related and this association is bidirectional. Lymphomas occur more frequently in the course of autoimmune disease and autoimmune rheumatic manifestations occur in the course of lymphocytic malignancies. An increased incidence of malignant lymphocytic diseases is present in patients with rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, and autoimmune thyroid disease. Descriptions of lymphocytic malignancies among other autoimmune rheumatic disease have been published. In some patients, the malignant disease is diagnosed months or years before the appearance of the rheumatic disease.
9362599 A problem-based education program for patients with rheumatoid arthritis: evaluation after 1997 Oct OBJECTIVE: To develop and evaluate the effect of a new arthritis education program based on a previous study. METHODS: One hundred individuals with established rheumatoid arthritis randomized to an intervention group or a control group completed self-report questionnaires. RESULTS: Three months after the education program the patients in the intervention group had increased their knowledge about their disease. They reported increased practice of exercise and joint protection and reduction of disability and pain. After 12 months, increased knowledge and practice of joint protection was maintained. However, there was no longer any difference between the intervention group and the control group regarding reported pain, disability, and practice of exercise. At both intervals the individuals in the intervention group reported an increased ability to handle their pain and a reduction of problems with their disease. The control group remained stable except for a slight increase in pain. CONCLUSION: A structured patient education program had positive impact for 3 months, and some improvements were maintained for 12 months. We suggest that patient education should become an integrated part of the total management of rheumatoid arthritis.
11826737 [Expectations of patients with rheumatism from new therapies]. 2001 Dec The expectation of patients with rheumatism concerning newly developed therapies are described on the basis of the experience of the patients' self-help movement. Most important are the wishes of the patients for healing and for treatment which is safe and without adverse effects. The measures necessary for better implementation of research results in the treatment of patients are described.
11502618 Lymphoma in a patient with rheumatoid arthritis receiving methotrexate treatment: successf 2001 Sep A 55 year old man with chronic lymphocytic leukaemia (CLL) and rheumatoid arthritis (RA), treated for four years with methotrexate (MTX), who developed a B cell non-Hodgkin's lymphoma (B-NHL), is described. The tumour was localised to the shoulder and axillary lymph nodes, and positive for Epstein-Barr viral antigens. After failure of radiation and chemotherapy, a complete remission was achieved with a combination of antibody treatment (rituximab) and EPOCH. The development of a second malignancy in a patient with RA receiving MTX has not been described before. The summation of T cell deficiencies induced by MTX, CLL, and RA may all have contributed to the development of the B-NHL.
11508425 Production of cytokines, vascular endothelial growth factor, matrix metalloproteinases, an 2001 Aug OBJECTIVE: To investigate the role of proinflammatory cytokines, vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMPs), and tissue inhibitor of metalloproteinases 1 (TIMP-1) in the destruction of tendons by tenosynovium in rheumatoid arthritis (RA). METHODS: Synovial specimens were obtained from encapsulating tenosynovium (n = 17), invasive tenosynovium (n = 13), and wrist joints (n = 17) in 18 RA patients undergoing wrist extensor tenosynovectomy. Synovial membrane cells were dissociated from connective tissue by enzyme digestion and cultured in vitro for 48 hours, and harvested supernatants were assayed for the cytokines tumor necrosis factor alpha (TNFalpha) and interleukin-6 (IL-6), VEGF, MMPs 1, 2, 3, and 13, and TIMP-1 by enzyme-linked immunosorbent assay. Gelatin zymography was performed to demonstrate enzyme activity. Statistical analysis was performed using Student's paired 2-tailed t-tests for parametric data and the Wilcoxon signed rank test for nonparametric data. RESULTS: MMP-1 and MMP-13 levels were approximately 2.5-fold higher in invasive tenosynovium compared with encapsulating tenosynovium. Levels of MMP-2 were approximately 1.5-fold higher in invasive tenosynovium compared with both encapsulating tenosynovium and wrist joint synovium. MMP-13 (P = 0.009) and IL-6 (P = 0.03) levels were significantly lower in encapsulating tenosynovium compared with wrist joint synovium. Levels of VEGF, TIMP-1, TNFalpha, and MMP-3 were similar in all synovial sample groups. Zymography demonstrated enzyme activity in all synovium samples from all 9 patients assessed. CONCLUSION: Tenosynovium produces proinflammatory cytokines and proteolytic enzymes that are important in the tissue degradation seen in RA. Increased production of the enzymes MMP-1, MMP-2, and MMP-13 by invasive tenosynovium suggests a possible explanation for the worse prognosis and increased rupture rate associated with invasive tenosynovitis in RA. Production of VEGF by tenosynovium suggests that angiogenesis may have a role in tenosynovial proliferation and invasion of tendons.
9125255 Abnormal homocysteine metabolism in rheumatoid arthritis. 1997 Apr OBJECTIVE: To assess total homocysteine (tHcy) metabolism in patients with rheumatoid arthritis (RA). METHODS: Assessments were performed to determine the fasting levels of tHcy and the increase in tHcy in response to methionine (Met) challenge in blood samples from 28 patients with RA and 20 healthy age-matched control subjects. RESULTS: Fasting levels of tHcy were 33% higher in the RA patients than in the control subjects (mean +/- SD 11.7 +/- 1.5 nmoles/ml versus 8.8 +/- 1.1 nmoles/ml; P < 0.01). Four hours after Met challenge, the increase in plasma tHcy levels (delta tHcy) was higher in the RA patients (20.9 +/- 10.4 nmoles/ml) than in the control subjects (15.5 +/- 1.6 nmoles/ml) (P < 0.02). In a subgroup analysis, the delta tHcy in patients taking methotrexate (12.9 +/- 2.2 nmoles/ml) did not differ from that in the control group, while the delta tHcy in patients not taking methotrexate (25.3 +/- 1.7 nmoles/ml) was significantly higher (P < 0.0001). CONCLUSION: Elevated tHcy levels occur commonly in patients with RA, and may explain some of the increased cardiovascular mortality seen in such patients. Studies of the prevalence and mechanism of hyperhomocysteinemia in RA are warranted.
11327272 Foundations of the minimal clinically important difference for imaging. 2001 Apr This article develops a generic conceptual framework for defining and validating the concept of minimal clinically important difference. We propose 3 approaches. The first uses statistical descriptions of the population ("distribution based"), the second relies on experts ("opinion based"), and a third is based on sequential hypothesis formation and testing ("predictive/data driven based"). The first 2 approaches serve as proxies for the third, which is an experimentally driven approach, asking such questions as "What carries the least penalty?" or "What imparts the greatest gain?" As an experimental approach, it has the expected drawbacks, including the need for greater resources, and the need to tolerate trial and error en route, compared to the other 2 models.
10984140 Hydroxychloroquine ototoxicity in a patient with rheumatoid arthritis. 2000 We report a case of reversible sensorineural hearing loss due to hydroxychloroquine (HQ) treatment. The patient was a 34-year-old woman with 1 year of rheumatoid arthritis (RA). She developed reversible hearing loss after 5 months of HQ treatment. Sensorineural deafness has previously been reported with chloroquine treatment, but this is the first report of ototoxicity associated with HQ in RA.
11555390 T-cell receptor repertoire in human germinal centres. 2001 Sep A search for an antigen-driven expansion of T lymphocytes in the inflamed joints in rheumatoid arthritis (RA) patients have been going on for decades. We here analyzed the human germinal centre T-cell receptor (TCR) Vbeta gene usage with polymerase chain reaction (PCR) combined with sequence analysis, to address the question of clonality in tonsils and synovial tissue from RA patients. Our data show a large degree of TCR heterogeneity in both these histological structures. Furthermore, clonally related T cells were found within different closely located germinal centres indicating either an active T-cell migration between germinal centres (GC) or that a T-cell clone may seed more than one GC.
9694052 Soluble intercellular adhesion molecule 1 in spondylarthropathies. 1998 The aim of the study was to evaluate the soluble form of intercellular adhesion molecule 1 (sICAM-1), a ligand of LFA-1, in the serum of patients with spondylarthropathies (SpA) and to look for a correlation with several inflammatory parameters. sICAM-1 levels were measured by ELISA in 25 SpA patients, 20 healthy controls and 20 patients with rheumatoid arthritis (RA). Results showed that sICAM-1 levels were increased (but not significantly) in SpA patients compared with controls; high levels (> 400 ng/ml) where found in 28% of SpA patients but in none of the RA or control groups. In SpA, correlations were found between sICAM-1 and erythrocyte sedimentation rate, C-reactive protein and interleukin 6, but not with tumour necrosis factor alapha or IgA. These correlations were absent in RA. In conclusion, these results suggest that sICAM-1 levels in SpA may reflect the acute phase of inflammation.
9324011 Rheumatoid arthritis and the risk of malignancy. 1997 Sep OBJECTIVE: To determine the relative risks of malignancy and of site-specific malignancies in patients with rheumatoid arthritis (RA). METHODS: In a prospective cohort study, 862 patients with RA (96% white) were enrolled from 1966 to 1974 and were followed up for up to 35 years (mean 17.4 years) at the University of Saskatchewan Rheumatic Disease Unit. All diagnoses of cancer were cross-referenced with the Provincial Cancer Registry. Expected cancer incidence rates were determined based on province of Saskatchewan population statistics matched to each study patient for age, sex, and calendar year. Standardized incidence ratios (SIRs) of the observed-to-expected cancer incidence and 95% confidence intervals (95% CI) were then calculated. RESULTS: A total of 136 cases of cancer were observed compared with 168 expected (SIR 0.80, P = 0.011 [95% CI 0.67-0.95]). The relative risk of colorectal malignancy was significantly reduced in the RA study population (SIR 0.52, P = 0.037 [95% CI 0.25-0.96]). A significant excess of leukemia was found (SIR 2.47, P = 0.026 [95% CI 1.12-4.69]), whereas the incidence rates for Hodgkin's disease and non-Hodgkin's lymphoma and all other site-specific malignancies were not found to be significantly different from general population rates. CONCLUSION: In our cohort of RA patients, colorectal cancer was detected in only half the expected number of patients. This risk reduction may be related to long-term nonsteroidal antiinflammatory drug (NSAID) use in RA, as has been suggested in several other studies of long-term NSAID use. An increased risk of leukemia was confirmed. This may be due to the persistent immune stimulation associated with RA itself, since other potential explanatory factors for increased leukemia were not apparent. Despite the excess of hemopoietic malignancy and despite treatment of RA with potentially oncogenic agents, the overall risk of malignancy was reduced in this RA cohort.
9352604 Radiosynoviorthesis with rhenium-186 in rheumatoid arthritis: a prospective study of three 1997 The aim of this study was to evaluate the efficiency of radiation synovectomy with rhenium-186 in rheumatoid arthritis. In this prospective, randomized trial we compared three different treatment regimens for shoulder, elbow, wrist, hip and ankle joints: group 1, injection of rhenium-186; group 2, injection of rhenium-186 in combination with triamcinolone hexacetonide; group 3, injection of triamcinolone hexacetonide alone. Each treatment group included 50 joints. Patients included in the study had to fulfil the following criteria: (1) they had to have a diagnosis of rheumatoid arthritis (ARA criteria 1988), (2) their disease-modifying drug had to be methotrexate, started at least 6 months prior to injection therapy and given for the entire study time, (3) their nonsteroidal anti-inflammatory drug had to be diclofenac given at a dose of 150 mg/day or less and (4) they were also given prednisolone at a dose of 7.5 mg/day or less. After 3 years of follow-up, 79 joints met these criteria, i.e. 71 joints were excluded from the study: 26 joints because the patients changed the disease-modifying drug (12 joints from group 1, 4 joints from group 2 and 10 joints from group 3); 45 joints because of recurrent synovitis and second-stage treatment (21 joints from group 1, 5 joints from group 2 and 19 joints from group 3). During the follow-up period, joints were assessed for pain, synovitis, joint motion and stage of radiological destruction. Best clinical results and slowest progression in radiological destruction were achieved with the combined injection of rhenium-186 and triamcinolone hexacetonide. Therefore, we recommend this treatment for articulosynovitis with the exception of severe forms, the latter because of the effective penetration range of rhenium-186.
11579712 A sensitive assay for the measurement of serum chondroitin sulfate 3B3(-) epitope levels i 2001 Sep OBJECTIVE: To develop a sensitive assay to quantitate serum 3B3(-) levels in patients with rheumatoid arthritis (RA) and osteoarthritis (OA) as well as levels in control sera. METHODS: An enzyme-linked immunosorbent assay (ELISA) was developed using the monoclonal antibody (MAb) 3B3 to detect a chondroitin sulfate (CS) epitope in the sera and synovial fluid (SF) of RA and OA patients. Keratan sulfate levels were measured in the same biological fluids using the 5D4 monoclonal antibody. RESULTS: The detection limit for our 3B3(-) assay was 2 micrograms/L. Most OA sera sample curves run on the 3B3 assay were parallel (87.5%) to the standard curve and detectable (90.0%). RA sera sample curves were 87.1% detectable and 85.2% parallel. The 3B3(-) epitope was detectable in 60% of control sera and of these 66.7% of sample curves were parallel to the standard curve. All RA and OA SF had detectable quantities of 3B3(-). For the 3B3 assay, the OA and RA sera levels were significantly higher than for control sera (P = 0.03, P = 0.04 respectively). We found a significant correlation in a subset of paired OA sera and SF 3B3(-) concentrations. No correlation was found between age, joint activity scores, HAQ and CRP in RA patients and sera 3B3(-) and 5D4 levels. CONCLUSION: We have validated this assay for the quantification of 3B3(-) epitope in RA and OA serum. Levels of this epitope are significantly higher in sera from RA and OA patients than controls. 3B3(-) levels in RA sera were found to correlate with disease duration.
11093434 Neurotransmitter modulation of interleukin 6 (IL-6) and IL-8 secretion of synovial fibrobl 2000 Nov OBJECTIVE: The sensory nervous system with the 2 neurotransmitters substance P (SP) and calcitonin gene related peptide (CGRP) is proinflammatory in experimental models of arthritis. The role of the sympathetic nervous system with norepinephrine (NE), adenosine, beta-endorphin, and methionine enkephalin (MENK) is not clearly understood. We studied the influence of these neurotransmitters on secretion of interleukin 6 (IL-6) and IL-8 in primary cultures of synovial fibroblasts of patients with rheumatoid arthritis (RA) compared to osteoarthritis (OA). METHODS: Fibroblasts were isolated using fresh synovial tissue of 5 patients with RA and 5 with OA who underwent knee joint replacement surgery. Modulation of spontaneous secretion of IL-6 and IL-8 was investigated in vitro using the neurotransmitters noted above. RESULTS: In RA fibroblasts, CGRP increased IL-6 and IL-8 secretion at 10(-10) to 10(-8) M (p at least < 0.01), which was not observed in OA fibroblasts. SP had no effect on either cytokine in RA fibroblasts but stimulated IL-8 secretion at 10(-8) M in OA fibroblasts (p < 0.01). In RA fibroblasts, adenosine and NE inhibited secretion of both cytokines at low concentrations (10(-8) M; p < 0.01). However, in OA fibroblasts there was a NE induced increase of IL-8 and IL-6 secretion at 10(-7) and 10(-6) M (p < 0.01), but no inhibition at lower concentrations (10(-8) M; p = NS). In RA fibroblasts, beta-endorphin and MENK inhibited IL-8 secretion at 10(-9) to 10(-7) M (p < 0.01), whereas in OA fibroblasts the dose response curve was shifted to lower concentrations (10(-12) M, 10(-11) M; p < 0.01). CONCLUSION: In OA fibroblasts, the sympathetic neurotransmitters were stimulatory at higher concentrations. CGRP was the most potent stimulatory neurotransmitter in RA fibroblasts whereas the sympathetic adenosine, NE, beta-endorphin, and MENK were inhibitory. This indicates a dualism of action of sympathetic and sensory neurotransmitters, with inhibitory and stimulatory effects on cytokine secretion of RA fibroblasts.
11881821 HLA DMA and DMB show no association with rheumatoid arthritis in US Caucasians. 2001 Oct HLA DM is a heterodimeric molecule functioning in normal antigen presentation; it is encoded by adjacent HLA-region loci, HLA DMA and DMB, located between DP and DQ. Some previous studies have suggested that HLA susceptibility to rheumatoid arthritis (RA) is associated with certain DMA and DMB alleles. Our aim was to examine whether this association is also present in US Caucasians. We studied 288 US Caucasian subjects with rheumatoid arthritis and 263 US Caucasian control subjects. DMA and DMB typing was achieved by PCR amplification followed by sequence-specific oligonucleotide hybridization and by PCR-restriction fragment length polymorphism. There was no frequency difference for DMA alleles or DMB alleles between RA and control subjects, indicating no association. Neither was a difference apparent when data were analysed in subgroups based on shared-epitope DRB1, on the rheumatoid factor test, on radiographic changes of RA, or on sex. DRB1-DQB1-DMB analyses for linkage disequilibrium showed that the DRB1*0401-DQB1*0301 haplotype had the DMB*0103 allele more often than DMB*0101 (estimated haplotype frequencies 0.08 and 0.039 in RA, respectively). In contrast, the DRB1 *0401-DQB1 *0302 haplotype usually had the DMB*0101 allele (haplotype frequency 0.084 compared to 0.01 for DMB*0103). Thus, neither HLA DMA nor DMB was associated with RA in this population, and not all shared-epitope-bearing haplotypes had the same DMB allele distribution.
10464558 No significant effects of sodium aurothiomalate on haem metabolism and mixed function oxyg 1999 Jul OBJECTIVE: Animal studies suggest that gold compounds impair haem synthesis and increase haem degradation and, as a result, reduce activity of the hepatic haemoproteins cytochromes P-450. The aim of this study was to investigate whether intramuscular gold exerts similar effects in patients with rheumatoid arthritis (RA). METHODS: Urinary porphyrin and precursor excretion, erythrocyte protoporphyrin, and antipyrine clearance, were measured in 6 patients with RA before and 10 weeks after commencement of intramuscular gold. RESULTS: Parameters of haem metabolism were unaffected by gold. While antipyrine clearance was not statistically changed after gold treatment, in 3 of the patients there was an average decrease in antipyrine clearance of 23%. CONCLUSION: Further studies examining RA patients at different time points are required to investigate further the possibility of reduced hepatic drug metabolising activity during prolonged treatment with gold.
9153546 Polymorphism of the HLA-DMA and DMB genes in rheumatoid arthritis. 1997 May OBJECTIVE: To determine whether the HLA-DMA and DMB genes, whose encoded molecules are involved in HLA class II-restricted antigen presentation, contribute to the genetic susceptibility to rheumatoid arthritis (RA). METHODS: One hundred ninety-one RA patients, 147 control subjects, and 218 HLA-DRB1 genotype-matched control subjects were oligotyped for DMA and DMB genes. RESULTS: DMA*0103 and DMB*0104 were significantly increased in the RA patients compared with the randomly selected and the matched controls, thus indicating a direct influence of the DM genes. After stratification of the patients and matched controls according to DRB1 genotypes, only DMA*0103 was increased in the RA patients with DRB1*01, as well as in the patients negative for the RA-susceptibility DR alleles. CONCLUSION: Our results suggest that DMA*0103 could play an additional role in the genetic susceptibility to RA.
9184785 Occupational therapy for patients with chronic diseases: CVA, rheumatoid arthritis and pro 1997 May A substantial proportion of the patients treated by occupational therapists have a chronic disease. The aim of this study was to describe the outlines of occupational therapy treatment for three specific groups of chronic diseases: progressive neurological diseases, cerebrovascular accident and rheumatoid arthritis. A total of 143 therapists, working in 49 occupational therapy departments in The Netherlands, were asked to complete a standard registration from based on the ICIDH. This form consisted of three sections: (a) patient characteristics, (b) occupational therapy diagnosis and treatment goals in terms of ICIDH and (c) treatment characteristics. The present study concerns 507 patients: 102 had progressive neurological diseases (PND), 338 had a CVA and 67 had rheumatoid arthritis (RA). Our results showed that each patient group was characterized by a specific treatment approach. Especially at the level of treatment programmes substantial differences between groups were observed. Besides the clear differences, similarities in approaches were found between the PND and RA group, e.g. total time spent on therapy differed largely between the PND and RA patients (both averages 6 h) and the CVA patients (average 14 h).
10953913 Gene therapy of autoimmune diseases with vectors encoding regulatory cytokines or inflamma 2000 Jul Gene therapy offers advantages for the immunotherapeutic delivery of cytokines or their inhibitors. After gene transfer, these mediators are produced at relatively constant, non-toxic levels and sometimes in a tissue-specific manner, obviating limitations of protein administration. Therapy with viral or nonviral vectors is effective in several animal models of autoimmunity including Type 1 diabetes mellitus (DM), experimental allergic encephalomyelitis (EAE), systemic lupus erythematosus (SLE), colitis, thyroiditis and various forms of arthritis. Genes encoding transforming growth factor beta, interleukin-4 (IL-4) and IL-10 are most frequently protective. Autoimmune/ inflammatory diseases are associated with excessive production of inflammatory cytokines such as IL-1, IL-12, tumor necrosis factor alpha (TNFalpha) and interferon gamma (IFNgamma). Vectors encoding inhibitors of these cytokines, such as IL-1 receptor antagonist, soluble IL-1 receptors, IL-12p40, soluble TNFalpha receptors or IFNgamma-receptor/IgG-Fc fusion proteins are protective in models of either arthritis, Type 1 DM, SLE or EAE. We use intramuscular injection of naked plasmid DNA for cytokine or anticytokine therapy. Muscle tissue is accessible, expression is usually more persistent than elsewhere, transfection efficiency can be increased by low-voltage in vivo electroporation, vector administration is simple and the method is inexpensive. Plasmids do not induce neutralizing immunity allowing repeated administration, and are suitable for the treatment of chronic immunological diseases.
9489812 A randomized controlled trial to evaluate the efficacy of community based physical therapy 1998 Feb OBJECTIVE: To evaluate the short term efficacy of a community based physical therapy (PT) program for people with rheumatoid arthritis (RA) through a single blind randomized controlled trial. METHODS: Adults with active RA were referred by their physician for community based PT. Participants were randomized to either an immediate intervention group [experimental group (EG)] or a wait list control group (CG). The intervention was a standardized program of education and exercise consisting of at least 4 visits or 3 h of PT over 6 weeks. Baseline, 6, and 12 week assessments were by a blinded independent assessor. The primary outcome instrument was the Stanford Arthritis Self-Efficacy Scale (SES) and secondary outcome measures included the ACREU Rheumatoid Arthritis Knowledge Questionnaire (KQ) and visual analog scale for pain (VAS). Duration of morning stiffness, grip strength, and tender joint count were also collected at each assessment. Outcome analysis was conducted using analysis of variance. RESULTS: Of 150 eligible and randomized participants, 127 completed the study according to protocol. Baseline analysis showed no differences between the EG and CG for demographics, disease status, or other characteristics. At the 6 week assessment, primary outcome analysis for those who completed the protocol identified a mean change (improvement) of 13.5% in the EG and 5.8% in the CG, representing a 7.7% difference in change scores between the 2 groups [F(1,121) = 6.03; p = 0.015]. A statistically significant difference in change scores was also identified for the KQ [F(1,120) = 6.67; p = 0.011], but not for the VAS. Disease status measures did not change, except for duration of morning stiffness, which improved by 68.8 min in the EG and 8.3 min in the CG (F(1,121) = 4.50; p = 0.036]. CONCLUSION: Four hours of a community based PT intervention delivered over 6 weeks significantly improved self-efficacy, disease management knowledge and morning stiffness in people with RA.