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ID PMID Title PublicationDate abstract
11046059 Fibrin(ogen)-induced expression of ICAM-1 and chemokines in human synovial fibroblasts. 2000 Nov 1 It has long been recognized that in most inflamed arthritic joints the coagulation system is activated, leading to the local generation of fibrin, and it has long been hypothesized that the local fibrin deposition promotes inflammation and tissue destruction. However, only recently has the direct effect of fibrin on the inflammatory process been seriously investigated, and specific roles assigned to fibrin or its products as mediators of the inflammatory process. Although fibrin and/or fibrinogen (fibrin(ogen)) is abundantly present in inflamed tissues and joints rich in fibroblastic cells, no significant data on fibrin(ogen)-induced gene expression by fibroblasts have been published. We now demonstrate that coculture of human synovial fibroblasts with fibrin(ogen) results in the up-regulation of ICAM-1 as well as increased production of the chemokines IL-8 and growth-related oncogene-alpha. Increased ICAM-1 expression was fibrin(ogen) dose-dependent and was demonstrated by ELISA, flow cytometry, and functional adhesion assays. Levels of ICAM-1 induced by fibrin(ogen) were comparable to those that could be induced by cytokine stimulation. Fibrin(ogen) stimulation of ICAM-1 could be suppressed by pyrrolidinedithiocarbamate, an inhibitor of NF-kappaB activation. Chemokine production was induced by fibrin(ogen) in cell culture supernatants >100-fold as compared with controls. Thus, through its activation of synovial fibroblasts, fibrin(ogen) deposition may promote the recruitment (via chemokines) and retention (via adhesion molecules) of lymphocytes within the arthritic joint.
10646484 Leflunomide, mycophenolic acid and matrix metalloproteinase inhibitors. 1999 Nov Leflunomide inhibits dihydro-orotate dehydrogenase with secondary effects on interleukin 2, transforming growth factor alpha and antibody production. Published data show that it is effective at 10-25 mg/day. Leflunomide's side-effects include gastrointestinal toxicity, a low incidence of alopecia, elevated liver function test abnormalities and weight loss. Mycophenolate mofetil inhibits inosine monophosphate dehydrogenase with secondary decreases on guanine nucleotides, DNA synthesis and inhibition of natural killer cell activity. At 1 or 2 g daily it is effective clinically, although it has little effect on erythrocyte sedimentation rate. Incidences of toxicity obtained from transplantation experience are principally gastrointestinal but also include a probable increase in viral infections, some myelosuppression and occasional cholestasis or pancreatitis. Matrix metalloproteinase inhibitors (MMPIs) are a diverse group of enzymes that are rapidly induced by inflammatory mediators. Some MMPIs are effective in rheumatoid arthritis. Their toxicities include gastrointestinal toxicity, sun sensitivity and rare systemic lupus erythematosus-like syndromes.
11371662 Tolerability and pharmacokinetics of the collagenase-selective inhibitor Trocade in patien 2001 May OBJECTIVES: The purpose of this study was to assess the tolerability and multiple-dose pharmacokinetics of Trocade in rheumatoid arthritis patients. METHODS: Forty-eight patients entered this double-blind, placebo-controlled, multiple ascending dose study. Patients received Trocade (25, 50, 100 or 150 mg) or placebo once daily for 28 days. Tolerability was assessed daily. Plasma pharmacokinetics was assessed on days 1 and 28. Trough blood samples were collected weekly. RESULTS: Trocade was well tolerated, with no differences in the adverse event profile compared with placebo. There were no relevant changes in laboratory parameters, vital signs or 12-lead ECG recordings. Plasma concentration profiles showed that Trocade was rapidly absorbed and most was eliminated within 24 h. The area under the plasma concentration-time curve and the maximum plasma concentration reached increased with dose, but this increase was not proportional to dose. No relevant accumulation was seen. CONCLUSIONS: Trocade was well tolerated for the 28-day study period. From exposure data, doses of 100 and 150 mg were expected to yield plasma levels associated with efficacy, and from trough concentrations the doses of 25 and 50 mg were also expected to be efficacious.
10648021 The effect of rheumatoid arthritis on the quality of life of primary caregivers. 2000 Jan OBJECTIVE: Rheumatoid arthritis (RA) is a chronic and disabling disease frequently leading to physical and psychological dependence, with considerable economic consequences. Responsibility for care of the patient is taken on by a member of the family called the primary caregiver. Studies of caregivers of patients with RA are scarce. A better understanding of the caregiver's situation could provide interventions that reduce the burden and postpone institutionalization of people with arthritis disability. Our objective was to assess the effect of RA on the quality of life of primary caregivers. METHODS: Sixty-two patients from the rheumatic disease outpatient clinic and their respective caregivers were interviewed. Demographic and clinical data were recorded. Health and psychological status were measured using the Health Assessment Questionnaire (HAQ), Medical Outcomes Survey Short Form 36 (SF-36), Self-Reporting Questionnaire (SRQ-20), and a numerical pain rating scale. Burden of disease on the caregiver was assessed by the Caregiver Burden scale (CB scale). RESULTS: The majority of caregivers were women (82.3%), married (59.7%), mean (SD) age of 39.7 (15.7) years, with children/son (32.7%) or spouse (24.2%), with low education level and low income. Thirty-seven percent displayed psychoemotional disturbance measured by SRQ-20. Emotional aspect and mental health (by SF-36) were the most affected. The mean (SD) score of total burden experienced was 1.82 (0.59). The quality of relationship between caregivers and patients and SF-36 mental health of caregivers were important predictors of burden. CONCLUSION: Caregivers of patients with RA show high prevalence of psychological disturbance. The quality of the relationship between caregivers and patients and the mental health of the caregiver are important predictors of the burden of disease.
10543278 Myofibroblasts and S-100 protein positive cells in idiopathic pulmonary fibrosis and rheum 1999 Sep The aim of this study was to investigate whether idiopathic pulmonary fibrosis (IPF) can be distinguished from rheumatoid arthritis (RA)-associated interstitial pneumonia (RA-IP) by means of quantitatively assessing myofibroblasts and S-100 protein positive dendritic cells. Seven patients with IPF and twelve with RA, in whom the pathological findings were consistent with usual interstitial pneumonia (UIP) were studied. Antibodies to vimentin, alpha-smooth muscle actin (alpha-SMA) and S-100 protein were used for immunohistochemical studies performed using the streptavidin/biotin/peroxidase complex method, applied to dewaxed sections from each case. In fibrosis of RA-IP, appearance of both vimentin- and alpha-SMA-positive cells, namely myofibroblasts, was widely observed, together with the pathological patterns of honeycombing, UIP and bronchiolitis obliterans-organizing pneumonia (BOOP). Fibrosis, in cases of chronic IPF, was found to be characterized mainly by vimentin-positive but alpha-SMA-negative fibroblasts. Pulmonary tissues from RA-IP patients especially when associated with a BOOP pattern, contained many cells positive for S-100 protein. However, such cells were generally hard to find in cases of IPF. These findings suggests that idiopathic pulmonary fibrosis and rheumatoid arthritis-associated interstitial pneumonia can be differentiated from each other, to some extent, based on the appearance of myofibroblasts and the presence of S-100-positive dendritic cells.
10534549 Rheumatic disorders developed after hepatitis B vaccination. 1999 Oct OBJECTIVE: To obtain an overview of rheumatic disorders occurring after hepatitis B vaccination. METHODS: A questionnaire was sent to rheumatology departments in nine French hospitals. Criteria for entry were rheumatic complaints of 1 week's duration or more, occurrence during the 2 months following hepatitis B vaccination, no previously diagnosed rheumatic disease and no other explanation for the complaints. RESULTS: Twenty-two patients were included. The observed disorders were as follows: rheumatoid arthritis for six patients; exacerbation of a previously non-diagnosed systemic lupus erythematosus for two; post-vaccinal arthritis for five; polyarthralgia-myalgia for four; suspected or biopsy-proved vasculitis for three; miscellaneous for two. CONCLUSIONS: Hepatitis B vaccine might be followed by various rheumatic conditions and might trigger the onset of underlying inflammatory or autoimmune rheumatic diseases. However, a causal relationship between hepatitis B vaccination and the observed rheumatic manifestations cannot be easily established. Further epidemiological studies are needed to establish whether hepatitis B vaccination is associated or not with an incidence of rheumatic disorders higher than normal.
10415055 Regulation of cytokines, cytokine inhibitors, and acute-phase proteins following anti-TNF- 1999 Aug 1 Treatment with a chimeric mAb to TNF-alpha has been shown to suppress inflammation and improve patient well-being in rheumatoid arthritis (RA), but the mechanisms of action of such treatment have not been fully explored. Here we show that in vivo administration of anti-TNF-alpha Ab, using a longitudinal analysis, results in the rapid down-regulation of a spectrum of cytokines, cytokine inhibitors, and acute-phase proteins. Marked diurnal variation in the serum levels of some of these were detected. These results were consistent with the concept of a cytokine-dependent cytokine cascade, and the degree of clinical benefit noted after anti-TNF-alpha therapy is probably due to the reduction in many proinflammatory mediators apart from TNF-alpha, such as IL-6, which reached normal levels within 24 h. Serum levels of cytokine inhibitors such as soluble p75 and p55 TNFR were reduced as was IL-1 receptor antagonist. Reductions in acute-phase proteins occurred after serum IL-6 fell and included serum amyloid A, haptoglobin, and fibrinogen. The latter reduction could be of importance, as it is a risk factor for atherosclerosis, which is augmented in RA patients.
9350293 Interleukin-10 response abnormalities in systemic lupus erythematosus. 1997 Oct It has been previously reported that the production of interleukin-6 (IL-6) is often enhanced in systemic lupus erythematosus (SLE). The authors examined the secretion of IL-6, tumour necrosis factor-alpha (TNF-alpha), granulocyte-macrophage colony-stimulating factor, IL-1 alpha and IL-4 by B cells and monocytes from lupus patients and compared this to the production in normal controls and in rheumatoid arthritis patients. IL-6 production was increased an average of 3.4-fold compared to that in normal subjects and 8.4-fold compared to rheumatoid arthritis patients. In SLE, a strongly positive correlation was found between the levels of IL-6 and TNF-alpha (R = 0.8987, P = 0.002). Since production of both IL-6 and TNF-alpha is regulated by IL-10, the enhancement of the production of these cytokines could reflect a defect in either IL-10 production or responsiveness. However, spontaneous production of IL-10 was enhanced in cultures of B cells and monocytes from lupus patients, compared to normal controls, the levels being increased 3.1- to 6-fold for monocytes and B cells, respectively. The finding of increased secretion of these cytokines implies an abnormality in IL-10-mediated suppression in SLE. To assess this possibility, the authors examined recombinant human IL-10-mediated suppression of IL-6 production by monocytes and B cells from lupus patients, compared to normal controls, and found that whereas IL-10 caused a concentration-dependent suppression of IL-6 production in normal B cells and monocytes, this suppression was deficient in B cells and monocytes from lupus patients. In SLE, it therefore appears that there may be an intrinsic defect in IL-10-induced suppression of cytokine synthesis. This could explain the increased levels of IL-10 and IL-6 found in this condition, and may also be responsible for the characteristic polyclonal B-cell activation that is seen.
11746532 Dynamic changes in cytokine levels in serum and synovial fluid following filtration leukoc 2001 We attempted to determine whether various cytokine levels in the serum and synovial fluid (SF) of rheumatoid arthritis (RA) patients are influenced by the performance of filtration leukocytapheresis (LCP). The filtration LCP procedure that used a Cellsorba column (LCP group: n=22; responder subgroup: n=17, non-responder subgroup: n=5) or sham apheresis (control group; n=7) was repeated three times at 1-week intervals. Serum (LCP group, n=22; control group, n=7) and SF (LCP group, n=6; control group, n=3) samples were collected before and after LCP. Levels of tumor necrosis factor alpha (TNFalpha), interleukins (IL-1 beta, IL-2, IL-6, IL-8, IL-10, and IL-15), granulocyte-macrophage colony-stimulating factor (GM-CSF), monocyte chemoattractant protein-1 (MCP-1), RANTES were measured by an enzyme-linked immunosorbent assay. Serum TNF alpha, IL-15, and RANTES were significantly reduced only in the LCP group. Serum IL-10 significantly increased only in the LCP group. In the LCP subgroup, serum IL-15, GM-CSF, and RANTES levels were reduced significantly, while serum IL-10 levels increased significantly only in the responder group after treatment. Serum TNF alpha levels were reduced significantly in both subgroups. Changes in serum IL-10 correlated positively with the improvement of patient's assessment of pain and global severity, and physician's assessment of global severity. These results indicate that the removal of leukocytes from the peripheral blood of RA patients provokes dynamic changes in some cytokine levels in the serum and/or synovial fluid. These changes may explain some of the mechanisms by which the articular symptoms are improved by filtration LCP.
11296388 [A case of drug-induced interstitial pneumonitis in rheumatoid arthritis treated with buci 2001 Jan We report a case of bucillamine-induced interstitial pneumonitis in a 57-year-old woman. Rheumatoid arthritis was diagnosed in May 1999, and she was treated with bucillamine from June 1999, with a favorable outcome. After complaining of cough, fever, and dyspnea in October, she was admitted to this hospital. Blood gas analysis showed severe hypoxemia. The chest CT revealed both bilateral diffuse ground-glass opacity along the bronchovascular bundles, and thickening of the interlobular septa. We suspected bucillamine-induced interstitial pneumonitis from the findings of the CT scan, BALF and TBLB, and also from the improvement of PaO2 after the withdrawal of bucillamine. We treated the patient with prednisolone, and a favorable response was noted. A lymphocyte stimulation test using bucillamine was positive. A video-assisted thoracic surgery lung biopsy showed findings compatible with acute interstitial pneumonia without the association of hyaline membrane formation. A focal fibrosis was also observed. We believe that this is the only reported case of pathologically proven bucillamine-induced interstitial pneumonitis, in which a surgical lung biopsy was performed.
9972962 Safety of self-injection of gold and methotrexate. 1999 Feb OBJECTIVE: We review our experience with safety, efficacy, and practicality of self-administration of gold and methotrexate (MTX) in 40 patients. METHODS: Between 1992 and 1995, 40 patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) followed in the drug monitoring clinics of the Mary Pack Arthritis Centre were taught to self-administer parenteral gold or MTX. Self-injection education was recommended to patients who were stable and improved taking parenteral gold or MTX, and who had not experienced serious side effects. Charts were reviewed to extract and analyze prospectively collected data regarding safety, efficacy, and compliance. RESULTS: Sixty-five percent of patients performed self-injection and 35% received injections at home from a partner. Side effects in the self-injection patients are similar to those observed in clinic patients receiving drug by nurse administration. One MTX treated patient required treatment for interstitial pneumonitis, which developed after 22 weeks on self-injection. Side effects of self-injection included superficial irritation at the injection site in 2 patients and dosing error in 2 patients with no adverse effects. Seventy percent of gold and MTX treated patients continued self-injection after a mean of 34 months. Patients surveyed for satisfaction identified time saving and convenience as major benefits. CONCLUSION: With basic instruction and close supervision, self-injection of antirheumatic drugs is safe in selected patients. Self-injection reduces utilization of health care services, and is convenient and time and cost-saving to the patient.
9384419 The long-term results of Charnley low-friction arthroplasty in young patients who have con 1997 Nov We present the long-term results of 226 Charnley low-friction arthroplasties that were performed with use of cement in 161 patients between 1966 and 1978. Forty-four patients (sixty hips) had congenital dislocation of the hip, fifty-four patients (sixty-six hips) had degenerative osteoarthrosis, and sixty-three patients (100 hips) had rheumatoid arthritis. There were 114 female patients and forty-seven male patients. The average age of the patients at the time of the operation was 31.7 years (range, seventeen to thirty-nine years). Sixty-five patients (40 per cent) had a bilateral hip replacement. Thirty-eight patients (24 per cent; fifty-five hips), twenty-seven of whom had juvenile-onset chronic rheumatoid arthritis, died during the follow-up period. The average duration of follow-up for the entire series until the time of death, revision of both components, or the latest evaluation was 236 months (19.7 years; range, twenty-four to 361 months). Survivorship analysis was performed with the Kaplan-Meier method. At twenty-five years, the survival of the femoral component (with 95 per cent confidence intervals) was 89 per cent (80 to 98 per cent) in the patients who had congenital dislocation of the hip, 85 per cent (77 to 93 per cent) in the patients who had rheumatoid arthritis, and 74 per cent (61 to 87 per cent) in the patients who had degenerative osteoarthrosis. The rate of survival of the acetabular component was lower: at twenty-five years, it was 58 per cent (42 to 74 per cent) in the patients who had congenital dislocation, 79 per cent (70 to 88 per cent) in the patients who had rheumatoid arthritis, and 59 per cent (41 to 77 per cent) in the patients who had degenerative osteoarthrosis. The forty-four patients (sixty hips) who had congenital dislocation had the highest rates of aseptic loosening (twenty-two hips; 37 per cent), migration (seventeen hips; 28 per cent), and revision (twenty-two hips; 37 per cent) of the acetabular component. The fifty-four patients (sixty-six hips) who had degenerative osteoarthrosis had the highest rates of aseptic loosening (seventeen hips; 26 per cent) and revision (eighteen hips; 27 per cent) of the femoral component as well as the highest rate of femoral endosteal lysis (thirteen hips; 20 per cent). The sixty-three patients (100 hips) who had rheumatoid arthritis had the lowest prevalences of loosening and revision of the acetabular component but the highest rates of trochanteric non-union (fifteen hips; 15 per cent) and mortality (twenty-seven patients; 43 per cent). The average rate of wear of the acetabular component for the entire series was 0.11 millimeter per year; the average rate for the revised components (0.19 millimeter per year) was higher than that for the surviving components (0.09 millimeter per year). This was a consistent finding in each of the three diagnostic groups, and an increased annual rate of wear was found to be significantly associated with increased rates of migration and revision of the acetabular component (p < 0.01 for both). The femoral component proved to be durable: the twenty-five-year rate of survival for the entire series was 81 per cent (95 per cent confidence interval, 76 to 87 per cent). The major factors that limited the longevity of the cemented total hip implants in the present study were wear, loosening, and revision of the acetabular component, for which the twenty-five-year probability of survival was 68 per cent (95 per cent confidence interval, 61 to 75 per cent).
11525560 Gene therapy for rheumatoid arthritis. 2001 Aug Gene therapy was initially conceived of as a means of replacing defective genes in monogenic disorders such as cystic fibrosis or hemophilia, but has rapidly progressed into areas of medicine that involve a wide range of diseases including cancer, neurodegenerative disorders and autoimmunity. Elucidation of some of the cellular and molecular mechanisms implicated in the pathogenesis of joint inflammation and cartilage and bone destruction in inflammatory joint diseases such as rheumatoid arthritis (RA) have revealed novel targets for gene therapy. Strategies include the inhibition of pro-inflammatory cytokines, blockade of cartilage-degrading enzymes, inhibition of synovial cell activation or apoptosis of synovial cells, and manipulation of the Th1-Th2 cytokine balance. Both viral and non-viral gene transfer vector systems have been used to deliver therapeutic genes systemically or directly to arthritic joints by ex vivo as well as in vivo administration. Animal models of RA have been essential not only for better understanding the mechanisms of RA but also in serving as basic experimental tools to evaluate candidate gene products with anti-arthritic properties and develop therapeutic strategies.
11426031 WHO Collaborating Centre consensus meeting on anti-cytokine therapy in rheumatoid arthriti 2001 Jun Severe adult rheumatoid arthritis is a cause of progressive disability and increased mortality across Europe. A cure for the disease remains elusive, but control of symptoms and maintenance of individual independence is possible. Anti-cytokine therapies offer a new approach to disease management. They are effective after the failure of full doses of methotrexate, and are at least as effective as methotrexate in retarding the progression of radiological changes. Until more is known about the long-term safety and efficacy of these drugs they should be reserved for patients with severe disease who are progressing despite adequate doses of methotrexate or other disease-modifying anti-rheumatic drugs. They should be continued until therapeutic failure or intolerance. A comprehensive health economic evaluation is needed to optimally direct the use of these drugs. This should be undertaken when long-term safety and efficacy studies are completed.
11557656 Prevention of symptomatic thrombosis with short term (low molecular weight) heparin in pat 2001 Oct The need for prevention of venous thromboembolism (VTE) after total hip or knee replacement is obvious. However, the optimal regimen to achieve this remains to be defined. In patients with rheumatoid arthritis (RA) long term coumarins may not be necessary owing to the use of non-steroidal anti-inflammatory drugs (NSAIDs). 103 patients in whom 151 surgical procedures were performed (55 hip and 96 knee prostheses) were treated only with short term subcutaneous heparin. NSAIDs were used daily in 85% of the patients, and they were continued after hospital discharge. Only one patient developed symptomatic deep venous thrombosis during one year follow up. Bleeding complications were seen in 20/151 (13%) of the surgical procedures, all clinically judged as minor, and recovery was not delayed except in one case. Short term (low molecular weight) heparin appears to be an adequate, simple, and safe method for prevention of symptomatic VTE in patients with RA after knee or hip replacement, though further studies are necessary to confirm these preliminary findings.
11462065 Fibrosing alveolitis in patients with rheumatoid arthritis as assessed by high resolution 2001 Aug BACKGROUND: Fibrosing alveolitis (FA) is a common and serious complication of rheumatoid arthritis (RA). Before the availability of high resolution computed tomographic (HRCT) scanning, it was difficult to diagnose accurately without recourse to biopsy. Prospective studies have reported a prevalence of interstitial lung disease (ILD) of 19-44%. The term ILD used by these authors encompasses a variety of appearances on HRCT scans. This prospective study used HRCT scanning to determine the true prevalence of FA in hospital outpatients with RA, and to study associated clinical characteristics. METHODS: One hundred and fifty consecutive patients with RA were selected from a hospital outpatient department, irrespective of the presence or absence of chest disease. All underwent a detailed clinical assessment, chest HRCT scanning, and conventional chest radiography within 4 weeks of full pulmonary function tests. RESULTS: Seventy percent of patients were current or reformed cigarette smokers. Twenty eight (19%) had FA, most frequently of reticular pattern, and 12 of this group (43%) also had emphysematous bullae. None of the previously suggested risk factors for developing FA were confirmed. Fifty four percent of patients with HRCT evidence of FA had bilateral basal chest crackles, 82% had a reduced carbon monoxide transfer factor (TLCO), 14% had restrictive pulmonary function tests, and 14% had bilateral chest radiographic signs of FA. CONCLUSIONS: HRCT evidence of FA was present in 19% of hospital outpatients with RA. Abnormalities on chest examination or on full pulmonary function tests, even without restrictive changes or chest radiographic abnormalities, should prompt physicians to request a chest HRCT scan when investigating dyspnoea in patients with RA.
11155806 Correlation of IL-6 with the classical humoral disease activity parameters ESR and CRP and 2000 Rheumatoid arthritis (RA) is a systemic inflammatory disease with elevated levels of proinflammatory cytokines in peripheral blood, especially IL-6, but also IL-1 alpha and TNF alpha, for example, in different concentrations, depending on disease activity. A disturbed circadian rhythm of cortisol secretion and an overall elevated cortisol release in active RA, depending on disease activity, is known. The presented study examined correlations of IL-6 as the most important systemic mediator of the acute phase response in active RA with classical humoral disease activity parameters, such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), and with serum cortisol. We investigated 64 active RA patients, previously untreated with glucocorticoids. IL-6 was measured by ELISA from Pharmingen (San Diego), ESR by the method of Westergren and CRP by nephelometry (Behring Marburg, Germany). Cortisol was measured in 34 of these patients, using a fluorescence-polarization immunoassay (FPIA) from Abbott. We found correlations of IL-6 with CRP (p < 0.001, Spearman Rank Test, rs = 0.75), with ESR (p < 0.001, rs = 0.62) and with serum cortisol (p = 0.019, rs = 0.401). ESR and CRP correlate (p < 0.001, rs = 0.8) and cortisol also correlates with ESR (p = 0.002, rs = 0.52) and CRP (p < 0.001, rs = 0.57). IL-6 as an important systemic mediator of inflammation in RA correlates closely with CRP, as it induces its production, and with ESR. These three parameters correlate well with serum cortisol, which is increased in active RA, depending on disease activity. Thus, IL-6 is an important disease activity parameter in RA that is closely related to both the classical humoral disease activity and the HPA axis.
11302876 Treatment with cyclosporin switching to hydroxychloroquine in patients with rheumatoid art 2001 May OBJECTIVE: To investigate the therapeutic benefit of cyclosporin A (CSA) switching to hydroxychloroquine (HCQ) in patients with rheumatoid arthritis (RA). METHODS: Thirty four patients with RA who displayed residual inflammation and disability despite partial responses to prior maximal tolerated doses of methotrexate, were included. All were treated with a staged approach using CSA for 24 weeks to induce clinical improvement, followed by HCQ for 16 weeks to maintain the improvement. Seven ACR core set measures were evaluated every four to eight weeks. RESULTS: During a 40 week open trial, 27/34 patients completed the study. CSA treatment significantly reduced the tender joints score, swollen joints score, visual analogue pain scale, patient's or doctor's global assessment, patient's self assessed disability, and C reactive protein. Compared with the time of entry into the trial, patients who switched from CSA to HCQ still possessed significantly lower levels of most variables, determined at 28, 32, and 40 weeks. According to the ACR 20% improvement definition, 15/27 (56%) patients had improved at 24 weeks after CSA treatment, and 14/27 (52%) remained improved at 16 weeks after the change to HCQ. Frequent side effects, such as hypertrichosis, gastrointestinal trouble, and hypertension, were noted during CSA treatment, but most of these disappeared after switching to HCQ. The mean levels of blood pressure and serum creatinine were significantly increased during CSA treatment, but returned to normal after changing to HCQ. CONCLUSIONS: The data suggest that CSA switching to HCQ treatment may be an effective strategy for patients with RA partially responding to methotrexate, particularly those with toxicity due to CSA.
11005773 Systematic review of the cost effectiveness of prophylactic treatments in the prevention o 2000 Oct A systematic review on the cost effectiveness of prophylactic treatments of non-steroidal anti-inflammatory drug (NSAID) induced gastropathy in patients with osteoarthritis or rheumatoid arthritis was conducted. Two reviewers conducted the literature search and the review. Both full and partial economic evaluations published in English, Dutch, or German were included. The criteria list published in the textbook of Drummond was used to determine the quality of the economic evaluations. The methodological quality of three randomised controlled trials (RCTs) in which the economic evaluations obtained probability estimates of NSAID induced gastropathy and adverse events was assessed by a list of internal validity criteria. The conclusions were based on a rating system consisting of four levels of evidence. Ten economic evaluations were included; three were based on RCTs. All evaluations studied misoprostol as prophylactic treatment: in one evaluation misoprostol was studied as a fixed component in a combination with diclofenac (Arthrotec). All economic evaluations comprised analytical studies containing a decision tree. The three trials were of high methodological quality. Nine economic evaluations were considered high quality and one economic evaluation was considered of low methodological quality. There is strong evidence (level "A") that the use of misoprostol for the prevention of NSAID induced gastropathy is cost effective, and limited evidence (level "C") that the use of Arthrotec is cost effective. Although the levels of evidence used in this review are arbitrary, it is believed that a qualitative analysis is useful: quantitative analyses in this field are hampered by the heterogeneity of economic evaluations. Existing criteria to evaluate the methodological quality of economic evaluations may need refinement for use in systematic reviews.
9324014 Range of antinuclear antibodies in "healthy" individuals. 1997 Sep OBJECTIVE: To determine the range of antinuclear antibodies (ANA) in "healthy" individuals compared with that in patients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc; scleroderma), Sjögren's syndrome (SS), rheumatoid arthritis (RA), or soft tissue rheumatism (STR). METHODS: Fifteen international laboratories experienced in performing tests for ANA by indirect immunofluorescence participated in analyzing coded sera from healthy individuals and from patients in the 5 different disease groups described above. Except for the stipulation that HEp-2 cells should be used as substrate, each laboratory used its own in-house methodology so that the data might be expected to reflect the output of a cross-section of worldwide ANA reference laboratories. The sera were analyzed at 4 dilutions: 1:40, 1:80, 1:160, and 1:320. RESULTS: In healthy individuals, the frequency of ANA did not differ significantly across the 4 age subgroups spanning 20-60 years of age. This putatively normal population was ANA positive in 31.7% of individuals at 1:40 serum dilution, 13.3% at 1:80, 5.0% at 1:160, and 3.3% at 1:320. In comparison with the findings among the disease groups, a low cutoff point at 1:40 serum dilution (high sensitivity, low specificity) could have diagnostic value, since it would classify virtually all patients with SLE, SSc, or SS as ANA positive. Conversely, a high positive cutoff at 1:160 serum dilution (high specificity, low sensitivity) would be useful to confirm the presence of disease in only a portion of cases, but would be likely to exclude 95% of normal individuals. CONCLUSION: It is recommended that laboratories performing immunofluorescent ANA tests should report results at both the 1:40 and 1:160 dilutions, and should supply information on the percentage of normal individuals who are positive at these dilutions. A low-titer ANA is not necessarily insignificant and might depend on at least 4 specific factors. ANA assays can be a useful discriminant in recognizing certain disease conditions, but can create misunderstanding when the limitations are not fully appreciated.