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ID PMID Title PublicationDate abstract
10666175 The existence of geographical clusters of cases of inflammatory polyarthritis in a primary 2000 Feb OBJECTIVES: To determine whether there is any evidence that there are spatial clusters of rheumatoid arthritis in particular, and inflammatory arthritis in general. METHODS: Setting was a population based incidence register of inflammatory arthritis: the Norfolk Arthritis Register (NOAR). All cases identified between 1990-1995 were mapped to place of residence. Statistical evidence of clustering was determined by calculating Poisson probabilities in putative areas. RESULTS: Three clusters were identified including one small area (population 85) where five unrelated cases developed during this time period. There was no obvious greater disease homogeneity within clusters and no common environmental factors were identified. CONCLUSION: Rare clusters of inflammatory polyarthritis do occur. Their significance and cause remain to be elucidated.
10606363 Extent of inflammation predicts cardiovascular disease and overall mortality in seropositi 1999 Dec OBJECTIVE: To identify predictors for cardiovascular disease (CVD) and for overall survival in patients with rheumatoid arthritis (RA) followed from disease onset. METHODS: A retrospective cohort of patients with seropositive RA and disease onset between 1974 and 1978 (n = 211) was followed up at the end of 1995. Potential predictors for CVD, as measured by "the first cardiovascular event," and for overall survival were registered. The predictors were identified by extended Cox regression models. RESULTS: In simple Cox regression analysis, male sex, higher age at disease onset, HLA-B27, high disease activity, corticosteroid treatment early in disease, and hypertension significantly increased risk of cardiovascular event. Higher educational level, extensive disease modifying antirheumatic drug (DMARD) treatment, and corticosteroids > or =1 yr before event decreased the risk. In multiple Cox regression analysis, male sex, high age at disease onset, hypertension, higher haptoglobin level at disease onset, and corticosteroid treatment early in disease increased risk of CVD. In a multiple model comprising only patients with CVD, corticosteroids delayed the event. A high last registered erythrocyte sedimentation rate (ESR) value before event increased CVD risk, in particular when early in disease progression. Decreased life span was predicted by higher age at disease onset, male sex, low education level, high disease activity, hypertension, and CVD. HLA-B27 was associated with decreased life span, as was early, but not extensive corticosteroid treatment. DMARD treatment was associated with decreased mortality risk, as was the presence of joint prosthesis. In multiple regression, male sex, higher age at disease onset, atlantoaxial subluxation early in disease, hypertension, and cardiovascular event increased mortality. A high last registered ESR value before event or death added to that risk. CONCLUSION: The study emphasizes the importance of inflammation as an important risk indicator for CVD and mortality in RA. The positive impact of disease activity reducing treatment on CVD risk and survival is suggested.
11394555 Distress and disease status among patients with rheumatoid arthritis: roles of coping styl 2001 Spring Previous research has shown that social support can have a beneficial impact on coping processes and psychological adjustment in patients with rheumatoid arthritis (RA). The association of individual coping styles and perceived responses from others to one's pain episodes with patients 'distress and disease status over time was investigated. The sample consisted of 42 middle-aged patients with RA who were predominantly White (98%), female (64%), and married (88%). Participants completed surveys and their rheumatologist completed clinical assessments of patient disease status at 2 time points over a 9-month period. Although punishing responses from others (e.g., getting irritated or angry when the patient is in pain) were perceived as relatively infrequent, they were associated with a patient coping style of focusing on and venting of negative emotion as well as elevated negative affect (NA). Findings also indicated that those who perceived punishing responses from close others and coped by venting negative emotions reported increased NA over time and were rated by their rheumatologist as having more severe RA disease status over time. Implications for psychosocial intervention and directions for future research are discussed.
9402858 Small fragments of cartilage oligomeric matrix protein in synovial fluid and serum as mark 1997 Nov We determined the tissue distribution of cartilage oligomeric matrix protein (COMP) in man and evaluated COMP in synovial fluid (SF) and serum. COMP was purified from human articular cartilage. Polyclonal antibodies were used to detect COMP in tissue cryosections and protein extracts. COMP was determined quantitatively and qualitatively in SF and serum by competitive enzyme-linked immunosorbent assay and immunoblotting. Knee joint SF was taken from nine cadaveric and six living controls, 52 patients with osteoarthritis (OA), 85 patients with rheumatoid arthritis (RA) and 60 patients with other forms of inflammatory arthritis. The degradative potential of SF on native COMP was tested in vitro. The highest concentrations of COMP were measured in articular cartilage and meniscus, the lowest in rib and trachea. Compared with controls, the concentrations of COMP in SF and serum were elevated in 36 and 50% of the patients. A total of 84% of patients with RA and 60% of patients with other forms of inflammatory arthritis showed significant amounts of low-molecular-weight COMP fragments (50-70 kDa) in SF. In contrast, SF fragments were present in only 21% of the OA patients. Furthermore, 13% of SF taken from patients with RA or other forms of inflammatory arthritis were able to degrade COMP in vitro. Using inhibitors, the involvement of serine proteinases could be demonstrated in only 8% of the cases. Based on these results, the absolute levels of COMP in SF and serum, and its fragmentation pattern in SF, seem to be promising as markers of joint tissue metabolism.
11762936 Elevated levels of small, low-density lipoprotein with high affinity for arterial matrix c 2001 Dec OBJECTIVE: This work studied the presence of inflammatory and atherogenic lipoprotein markers that could explain the high incidence of cardiovascular disease (CVD) reported in rheumatoid arthritis (RA) patients. METHODS: Inflammatory markers were 1) soluble adhesion molecules (intercellular adhesion molecule [ICAM] and vascular cell adhesion molecule [VCAM]), 2) C-reactive protein (CRP), 3) fibrinogen (Fb), 4) cytokines (interferon-gamma [IFNgamma], tumor necrosis factor alpha [TNFalpha]), and 5) secretory group IIA phospholipase A2 (sPLA2-IIA). Atherogenic lipoprotein markers were 1) the size distribution of plasma lipoprotein subclasses, and 2) the binding affinity of low-density lipoprotein (LDL) to chondroitin 6-sulfate glycosaminoglycan (GAG). RESULTS: RA patients (n = 31) and matched controls (n = 28) had similar plasma concentrations of total cholesterol, triglycerides, Apo B, Apo A-I, very low-density lipoprotein, intermediate-density lipoprotein, and high-density lipoprotein (HDL). RA patients had significantly higher plasma levels of sPLA2-IIA, ICAM, CRP, Fb, TNFalpha, and IFNgamma compared with controls. RA patients also had significantly higher levels of small, dense LDL-1 (P < 0.05) and lower levels of small HDL-2 particles (P < 0.001) compared with controls. In addition, LDL from RA patients had a significantly higher binding affinity (Kd) to GAG (mean +/- SD Kd 204+/-22.4 nM Apo B) than did LDL from control subjects (Kd 312+/-36 nM Apo B) (P < 0.05). This Kd value showed a significant negative correlation with the plasma levels of LDL-1 (r = -0.566, P < or = 0.004). In RA patients, a significant positive correlation was obtained between sPLA2-IIA and CRP, ICAM, and LDL-1. HDL-2 showed a negative correlation with sPLA2-IIA. CONCLUSION: These atherogenic lipoprotein factors combined with the presence of chronic inflammation may contribute to the high CVD-related mortality in RA patients.
11557652 Reduced expression of CD44 on monocytes and neutrophils in systemic lupus erythematosus: r 2001 Oct BACKGROUND: Increased numbers of apoptotic neutrophils, and impaired monocyte/macrophage clearance of apoptotic cells, have been demonstrated in systemic lupus erythematosus (SLE). CD44 is implicated in the clearance of apoptotic neutrophils. OBJECTIVE: To determine the expression of CD44 on peripheral blood monocytes and neutrophils in SLE, and examine the relations with disease activity and numbers of circulating apoptotic neutrophils. METHODS: Peripheral blood was sampled from 31 patients with SLE, 19 healthy normal subjects, and 19 patients with rheumatoid arthritis (RA). Monocyte and neutrophil density of surface CD44 expression was determined by immunofluorescence labelling and flow cytometry, and results expressed as mean channel fluorescence (MCF) values. Neutrophil apoptosis was measured by morphology in 15 patients with SLE, nine with RA, and six normal subjects. RESULTS: Monocyte CD44 expression was significantly lower in SLE (median MCF 4.71) than in healthy normal subjects (median MCF 5.61) and controls with RA (median MCF 5.39). Neutrophil CD44 expression was also significantly lower in SLE (median MCF 1.95) than in healthy normal subjects (median MCF 2.37) and controls with RA (median MCF 2.60). Monocyte, but not neutrophil, CD44 expression correlated negatively with the percentage of apoptotic neutrophils. There was no significant correlation of monocyte or neutrophil CD44 expression in SLE with disease activity or damage. CONCLUSIONS: Monocyte and neutrophil CD44 expression is reduced in SLE, and this may contribute to the impaired recognition and clearance of apoptotic neutrophils by monocyte derived macrophages.
11246660 Disease course in systemic lupus erythematosus: changes in health status, disease activity 2001 Feb OBJECTIVE: To examine changes in health status, disease activity, and organ damage after 2 years and to study possible disease variables predicting change in health status, disease activity, and organ damage at followup in systemic lupus erythematosus (SLE). Second, to compare changes in health status in patients with SLE to that of matched patients with rheumatoid arthritis (RA) and matched healthy controls. METHODS: A 2 year longitudinal observational study, measuring health status (Short-Form 36. visual analog scale for pain and fatigue, modified Health Assessment Questionnaire, patient global assessment of disease activity), disease activity, and organ damage in 87 patients with SLE. Health status measures in SLE were compared to 65 matched RA patients selected from the Oslo RA register and to 77 matched healthy controls from the population register. RESULTS: On a group level the SLE patients showed stable health status measures and disease activity scores 2 years after baseline, but organ damage scores increased significantly. Increase in organ damage was significantly and independently predicted by baseline scores of disease activity and organ damage, health status, and disease activity by the respective baseline scores. Changes in health status measures over 2 years were similar in SLE, RA, and healthy controls. CONCLUSION: Our 2 year longitudinal observational SLE study showed a stable course of health status and disease activity, whereas organ damage increased. Disease activity and organ damage at baseline predicted the latter. Our results indicate the value of careful monitoring of disease activity over time in SLE and individually tailored treatment guided by the predictors of course and outcome.
10774456 New horizons in the treatment of autoimmune diseases: immunoablation and stem cell transpl 2000 The prevalence of autoimmune diseases (ADs) in Western countries is estimated to be from 3-7%, and the treatment of severe, relapsing/refractory cases is still not satisfactory. The concept of utilizing intense immunosuppression followed by allogeneic or even autologous hemolymphopoietic stem cells (HSCs) to treat AD is based on encouraging results in experimental animals and from serendipitous cases of patients with both ADs and malignancies who were allotransplanted for the latter. However, rare unexpected relapses despite donor immune engraftment have been reported following HSC transplantation for AD. Autologous transplantation is a more feasible procedure with lower toxicity than allogeneic transplantation. This article analyzes the experimental basis for stem cell transplantation in AD and discusses the most important clinical results of both allogeneic and autologous HSC transplants.
10189055 Tachykinin receptors on human monocytes: their involvement in rheumatoid arthritis. 1998 Jun Three types of tachykinin receptors, namely NK1, NK2 and NK3, are known to preferentially interact with substance P (SP), neurokinin A (NKA) and neurokinin B (NKB), respectively. Experimental evidence indicates that SP and NKA modulate the activity of inflammatory and immune cells, including mononuclear ones. This study evaluated the effects of mammalian tachykinins and selective tachykinin agonists and antagonists on human monocytes isolated from healthy donors: SP, NKA and NKB all evoked a dose-dependent superoxide anion (O2-) production and the NK2 selective agonist [beta-Ala8]-NKA(4-10) induced a full response. The NK3 selective agonist senktide was inactive, while the NK1 selective agonists septide and [Sar9Met(O2)11]SP displayed some effects. These results indicate that NK2 and also some NK1 receptors are present in monocytes isolated from healthy donors. The role of tachykinin receptor activation in rheumatoid arthritis was also investigated, by measuring O2- production and TNF-alpha mRNA expression in monocytes isolated from rheumatoid patients. Tachykinins enhanced the expression of this cytokine in both control and rheumatoid monocytes and NK2 receptor stimulation was shown to trigger an enhanced respiratory burst in monocytes from rheumatoid patients. In conclusion, these results indicate that NK2 and NK1 receptors are present on human monocytes, the former being preferentially involved in rheumatoid arthritis.
10913062 Spontaneous and cytokine regulated c-fos gene expression in rheumatoid synovial cells: res 2000 Aug OBJECTIVE: To study the effect of cytokines on the transactivation of the c-fos gene in relation to the contribution of overexpression of c-fos/AP-1 in rheumatoid joint destruction. METHODS: The promoter region (-447 to +109) of the human c-fos gene was integrated upstream of the chloramphenicol acetyltransferase (CAT) reporter gene, and the effect of cytokines on the expression of the c-fos gene was studied in the rheumatoid synovial cells of early (3-4) or late (14-18) passages, in the presence or absence of cytokines, by the transient transfection assay. RESULTS: Expression of c-fos gene was enhanced by tumour necrosis factor alpha (TNF alpha) and interleukin 6 (IL6) in the synovial cells of early passage, whereas it was not enhanced in the synovial cells of late passage. The c-fos gene expression was also enhanced by 13-O-tetradecanoyl phorbol-13-acetate (TPA) in early passage but was somewhat suppressed in the late passage. It was found that the c-fos gene and c-Fos protein were both increased in the synovial cells of late passage. Similarly, c-fos gene expression was also not increased by TPA or cytokine stimulation in the stable c-fos transformants (fos-pH8) or H-ras transformed NIH3T3 cells (NIH H-ras cells) that constitutively expressed c-fos genes. CONCLUSIONS: Although TNF alpha and IL6 augmented c-fos gene expression of rheumatoid synovial cells, transactivation of c-fos gene became resistant against cytokine stimulation under prolonged expression of c-fos gene, which may impart a tumour-like characteristic to rheumatoid synovial cells.
9196873 Association of DMA and DMB with RA in Japanese. 1997 Mar OBJECTIVE: The contribution of polymorphism of DMA and DMB alleles to the pathogenesis of Japanese RA was studied. The association of DM alleles with HLA-DRB1*0405 and *0802, which were positively and negatively susceptible to Japanese RA, respectively, is also discussed. METHODS: DMA and DMB typing was carried out in 91 Japanese RA patients and in 77 normal subjects by the PCR-RFLP (restriction fragment length polymorphism) method. HLA-DRB1*04 and *08 genotyping were carried out by the PCR-SSCP (single-stranded DNA conformation polymorphism) method. RESULTS: Allele frequencies of DMB*0101 and DMB*0102 were slightly higher (52.2% and 27.0%) and the allele frequency of DMB*0103 was slightly lower (25.8%) in RA, but these differences were not significant. The increase of DMB*0102 was due to a negative association with HLA-DRB1*0802 [p < 0.05, pc = not significant (NS)]. The decrease of DMB*0103 was due to a positive association with DRB1*0802 (p < 0.005, pc < 0.05). The increase of DMB*0101 was possibly due to a weak association with HLA-DRB1*0405, (p = NS). Positivity of rheumatoid factor did not affect the prevalence of DMA and DMB alleles. CONCLUSION: Association analysis among DMA, DMB and DRB1 (*0405 and *0802) indicate that slight increases or decreases in DMB*0101, DMB*0102 and DMB*0103 are not primary indicators but reflect an increase in HLA-DRB1* 0405 and a decrease in HLA-DRB1*0802 in Japanese RA.
9741317 Prevalence of rheumatoid arthritis in Italy: the Chiavari Study. 1998 May OBJECTIVE: To ascertain the prevalence of rheumatoid arthritis (RA) in an Italian general population. METHODS: The study was performed in the years 1991-92 in Chiavari, a small town located on the Ligurian coast, and involved 4456 subjects aged 16 years or more from four general practices. The subjects received a postal questionnaire developed to detect patients with current or past inflammatory joint diseases. The age and sex distribution of the sample were similar to those of the Italian population from the 1992 census. Patients reporting a history of joint swelling in at least a pair of symmetrical joints were reviewed by a rheumatologist. The clinical records of non-responders and responders who failed to attend the clinic were also reviewed. RESULTS: 3294 of 4456 (73.9%) subjects answered to the questionnaire. The mean (SD) age of the 3294 responders was 48.3 (19.3) years; 53.7% of them were female. Swelling in at least two symmetrical joints was reported by 230 subjects (7%). Among them, 11 patients fulfilling the 1987 ARA criteria for RA were identified. The prevalence of RA was 0.33% (95% CI 0.13, 0.53) in the general population, 0.13% (95% CI 0, 0.31) in men, and 0.51% (95% CI 0.18, 0.84) in women. CONCLUSIONS: These data are consistent with the results of three earlier studies published in the fifties in the Italian literature and confirm that the prevalence of RA is low in Italy and has remained unchanged in the last 40 years.
11145851 Investigation of novel polymorphisms within the 3' region of the IL-6 gene in patients wit 2001 Jan 21 A highly polymorphic AT rich repeat exists in the 3' flanking region of the IL-6 gene. Using Genescan analysis we studied this region of the IL-6 gene in 55 normals and 95 patients with rheumatoid arthritis (RA). The influence of alleles on need for early major joint surgery in RA patients was assessed. We identified nine alleles of which, G8, G7 and G4 were the most common (37% vs 36% vs 13%). RA surgery patients had an increase in the frequency of G7 compared to non-surgery and control populations (46% vs 27% vs 34%, respectively) and a decrease in G8 (22% vs 46% vs 43%, respectively). RA patients homozygous for G8 had a lower ESR than those homozygous for G7 (23 mm/h vs 36 mm/h) although this was not significant. We have determined these alleles and their distribution in a normal and RA population. Initial findings suggest G8 may be associated with lower erythrocyte sedimentation rate (ESR) and less severe RA. Although trends in allele distribution were observed, further studies in larger cohorts are required.
10865685 Comparison of knowledge and psychological well-being between patients with a short disease 1999 Nov Patients with rheumatoid arthritis (RA) of short disease duration (i.e. < or = 1 year) compared with patients of longer disease duration (i.e. > or = 10 years) in terms of RA knowledge, symptoms of anxiety, symptoms of depression and disease acceptance. In addition, the predictors of psychological distress (i.e. symptoms of anxiety and depression) were examined. Data were collected by self-administered questionnaires. As expected, patients with more established disease were significantly older and had more physical dysfunction. However, there were no statistically significant differences on anxiety, depression, acceptance of illness, pain or knowledge about RA. The need for education regarding RA and its implications was expressed by all participants regardless of disease duration. Illness acceptance beliefs were identified as significant predictors of both anxiety and depression.
9770962 [Pulse therapy with prospidin and methotrexate: comparative efficacy in rheumatoid arthrit 1998 Efficiency of pulse-therapy with prospidin (500 mg for 5 days in hospital, 500-1000 mg for a month as maintenance) and methotrexate (30 mg a week i.v. in hospital, 7-10 mg a week as maintenance) was investigated in 93 patients with severe RA. The response to prospidin and methotrexate arose quickly (within 10-14 and 4-5 weeks, respectively) and occurred in 73 and 70% of patients, respectively. Withdrawal of the drug was caused by side effects of methotrexate (19.3%) and resistance to prospidin (23.2%).
10468411 Methotrexate and leflunomide: biochemical basis for combination therapy in the treatment o 1999 Aug OBJECTIVES: Methotrexate is currently one of the most widely prescribed disease-modifying antirheumatic drugs (DMARDs) for the treatment of rheumatoid arthritis (RA). Combination therapy of methotrexate with other DMARDs increases the clinical success of low-dose methotrexate treatment. Leflunomide is a new DMARD that may have a high potential for success in combination therapy with methotrexate. This review compares the mode of action of methotrexate and leflunomide and speculates on how this contributes to therapeutic efficacy in RA when these agents are used singly or in combination. METHODS: A literature review of the biochemical mechanisms considered to be the basis for the therapeutic efficacy of methotrexate and leflunomide in treating RA is presented. RESULTS: Low-dose methotrexate inhibits cytokine production, purine biosynthesis, and, in an animal model, causes the release of adenosine, a potent antiinflammatory agent. Leflunomide, through inhibition of de novo pyrimidine biosynthesis, can regulate lymphocyte proliferation. CONCLUSIONS: The biochemical mechanisms underlying the therapeutic efficacy of low-dose methotrexate and leflunomide in the treatment of RA are quite different. The potentially complementary mechanisms of action of these two effective DMARDs should provide a rationale for their use in combination therapy for patients whose condition no longer responds to methotrexate alone.
11899850 [Cytokines in rheumatoid arthritis. I. Proinflammatory cytokines]. 2001 Dec Proinflammatory cytokines play an important role in the pathogenesis of rheumatoid arthritis. It is why they became the targets for new therapies. In this review we describe their expression in synovial tissue, synovial fluid and in serum, and correlation with disease activity. Particular attention was paid to the possibilities of the alternative treatment strategies modifying the balance of cytokine network, in the rheumatoid arthritis patients, towards limiting their proinflammatory activity. Inhibiting the action of proinflammatory cytokines by using their specific inhibitors or anti-inflammatory cytokines have shown significant clinical benefits with mild side effects.
9632061 Expression and function of CD40 in rheumatoid arthritis synovium. 1998 Jun OBJECTIVE: To determine the involvement of CD40 in chronic activation of rheumatoid arthritis (RA) synovial monocytes. METHODS: CD40 expression on RA synovial monocytes was examined by immunostaining. Involvement of CD40 in tumor necrosis factor-alpha (TNF-alpha) secretion from RA synovial fluid mononuclear cells (SFMC) was examined by blocking with anti-CD40 antibody. RESULTS: CD40 was expressed on RA synovial monocytes. TNF-alpha secretion from RA SFMC was enhanced by CD40 ligand stimulation. Spontaneous secretion of TNF-alpha from RA SFMC was inhibited by anti-CD40 antibody. CONCLUSION: CD40 was involved in the activation of RA synovial monocytes that leads to TNF-alpha production.
9224242 Compression arthrodesis of the rheumatoid ankle and hindfoot. 1997 Jul The reported frequency of involvement of the rheumatoid ankle and hindfoot varies between 9% and 70%. Fusion of the ankle joint, the subtalar, talonavicular, or calcaneocuboidal joint (Chopart's joint) or all of them is the preferred method of treatment for severe rheumatoid involvement causing pain, instability, and/or severe deformity. Ankle arthroplasty is indicated rarely. Pantalar arthrodesis is performed more frequently than talonavicular fusion or ankle fusion. Reported rates of fusion after compression arthrodesis of the ankle joint vary from 65% to 90%, averaging 80% to 85%. Higher success rates of as high as 95% were obtained with internal lag screw fixation as proposed by Wagner. The result of various combinations of arthrodesis (n = 54) of the ankle joint, the subtalar joint, and Chopart's joint in 43 patients with rheumatoid arthritis operated on in a 10-year period from 1984 through 1993 are presented. In all cases internal fixation by lag screws according to Wagner was used with a modified lateral approach incorporating osteotomy of the distal fibula. The technique is described in detail. Solid fusion was obtained in 21% of the cases after 8 weeks, in 9% of the cases after 12 weeks, and in 92% of the cases after 16 weeks. In 8% (3 patients) revision because of delayed union or nonunion eventually led to bony fusion. Postoperative pain, walking capacity, gait, and the subjective outcome were assessed. Complications occurred in 16%, revision was performed in 11.6% of the cases; in all cases healing was obtained. Overall patient satisfaction was 93%.
10873966 Labour force participation among patients with rheumatoid arthritis. 2000 Jul OBJECTIVES: To assess work history and labour force participation among patients with rheumatoid arthritis (RA) in the Netherlands. METHODS: A random sample of 1056 patients with RA aged 16-59 years from 17 rheumatology practices in the Netherlands was examined. Data on disease status and outcome were obtained by a questionnaire including standardised instruments, such as the Rapid Assessment of Disease Activity in Rheumatology (RADAR) and RAND-36 questionnaires. Labour force participation was defined as having a paid job. RESULTS: Of the study group with a mean disease duration of 12 years, 35.7% held a paid job (men 56.7%; women 27.7%). When standardised for age, sex, and educational level, the labour force participation of patients with RA was 61.2% compared with 65.5% for the general population, which was not statistically significant. Disease duration of six years and more was negatively associated with labour force participation. CONCLUSIONS: After controlling for the confounding effects of age, sex, and education, the labour force participation of patients with RA in the Netherlands is only slightly lower than that of the general population.