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ID PMID Title PublicationDate abstract
9751088 Should improvement in rheumatoid arthritis clinical trials be defined as fifty percent or 1998 Sep OBJECTIVE: To determine whether improvement of more than 20% in core set parameters should be required before patients are characterized as improved in rheumatoid arthritis (RA) clinical trials. METHODS: Data from 6 RA trials were reanalyzed to evaluate the discriminant validity (ability to differentiate active treatment from control) of 4 proposed definitions of improvement: the current American College of Rheumatology (ACR) definition (a 20% threshold for core set parameters [ACR 201), a 50% threshold (ACR 50), a 70% threshold (ACR 70), and an ordinal definition in which a patient could be classified in any of 3 categories (unimproved, ACR 20, or ACR 50). To evaluate the discriminant validity of these 4 definitions of improvement, we characterized each patient in each trial as improved or not, based on each definition, and computed a chi-square value differentiating the active treatment group from the control group, with the corresponding P value. RESULTS: With an increase in the threshold for improvement, the percentage of placebo-treated patients who were classified as experiencing response dropped dramatically in all trials, as did the percentage of patients receiving active therapy (second-line drug, combination therapy, tumor necrosis factor p75-Fc fusion protein) who were classified as experiencing response. Generally, the drop in active treatment response rates was greater than the drop in placebo response rates, leaving the difference between the 2 groups less at the higher thresholds. Therefore, chi-square values fell as the threshold for response was raised. The ordinal definition of improvement yielded chi-square values similar to those obtained using ACR 20 alone. CONCLUSION: Adopting a definition of efficacy in RA trials that requires 50% or 70% improvement in core set parameters would likely compromise statistical power and make it more difficult to distinguish between 2 treatments with different efficacy. ACR 20 should continue to be the primary measure of efficacy in RA trials, with higher thresholds for improvement being determined and reported as secondary efficacy measures.
9224241 Management of the rheumatoid hindfoot with special reference to talonavicular arthrodesis. 1997 Jul In the patient with rheumatoid arthritis, involvement of the hindfoot is common. If conservative management fails, surgical treatment should be considered before the development of a fixed deformity. In patients with isolated talonavicular disease, arthrodesis of this joint provides excellent pain relief and seems to prevent future deformity.
11937987 Aspects of the radiological evaluation of rheumatoid arthritis. 2001 Dec This paper gives an overview of several aspects of the radiographic evaluation of rheumatoid arthritis (RA). Radiographs give important information about the structural damage caused by RA. On a group level, the natural progression follows a rather linear cause, but on an individual patient level, this can vary widely. Feet are often affected earlier and to a larger extent than hands. Both hands and feet give a good overall impression of the damage in the large joints and are sufficient to monitor the patient. It is recommended to take annual films of hands and feet to monitor patients. Several scoring methods are available for application in clinical trials. Most widely used are the Sharp and Larsen methods with their modifications. For use in clinical practice the SENS method is more feasible. Several drugs are capable of retarding radiographic progression. However, it is difficult to compare results across trials and these difficulties are elaborated.
11817017 Anterior ischaemic optic neuropathy in patient with rheumatoid arthritis--case report. 2001 This case report presents a patient with long-lasting rheumatoid arthritis (RA) of fourth clinical grade, having ocular complications. RA was diagnosed according to current modified ARA criteria from 1987. Upon admission to the Department of Ophthalmology clinical examination revealed anterior ischaemic optic neuropathy (AION), which is not characteristic manifestation of RA in the eye. The occurrence of AION in patients with RA has been explained in literature as a secondary manifestation of hypertension in these patients or, by the presence of other connective tissue disease apart from RA (for example, MCTD--mixed connective tissue disease). Both mentioned causes were excluded in our case, as well as any other condition that could lead to AION. Therefore, we had concluded that AION presented a late complication of RA.
11469487 Markers for work disability in rheumatoid arthritis. 2001 Jul Work disability is common in rheumatoid arthritis (RA), and accounts for a large fraction of its costs. People with RA who are work disabled have more joint involvement, radiographic damage, and/or laboratory abnormalities than people who are working. However, analysis of predictive and associative markers in 15 studies of work disability indicate that the demographic variables, such as age, occupation, level of education, and duration of disease, as well as functional status in activities of daily living (ADL) identified on a patient questionnaire, appear to identify work status more than physiological variables. Work disability results from complex interactions of a medical disease, demographic variables, social conditions, and government policies. Some patients with RA are work disabled before they see a rheumatologist. Improved work disability outcomes in RA will require attention to social, economic, and political issues, and wider physician and public education concerning RA, in addition to improved medical management of disease.
11693266 Elevated levels of vascular endothelial growth factor in the sera of patients with rheumat 2001 Sep 7 To evaluate vascular endothelial growth factor (VEGF) levels in relation to disease activity in rheumatoid arthritis (RA), VEGF in the serum of 155 patients with RA and 75 healthy control subjects was quantified by our highly sensitive enzyme-linked immunosorbent assay. VEGF levels were found to correlate with the articular index (AI) and Lansbury's activity index (LI). Patients with RA had a mean serum VEGF concentration of 153.5+/-111.8 pg/ml, which was significantly higher than control subjects (104.8+/-65.7 pg/ml; P<0.01). VEGF concentration was elevated significantly according to disease progression as expressed by stages I to IV and correlated with AI (r=0.530, P<0.0001) and LI (r=0.688, P<0.0001) in stages I and II as well as with the conventional erythrocyte sedimentation rate or serum C-reactive protein concentration. Serum VEGF levels may therefore be valuable as a marker of disease activity in patients with early RA, and this cytokine may play a significant role in the pathophysiology of RA.
10923523 [Rheumatoid arthritis synoviocyte hyperplasia and expression of fas and bcl-2 genes]. 1998 Mar OBJECTIVE: To determine whether apoptosis occurs in the proliferative synovial tissue and cells from patients with rheumatoid arthritis (RA). METHODS: In situ hybridization was carried out by using labeled RNA probes of fas, fasL, and bcl-2 synthesized by in vitro transcription. Apoptosis was examined by DNA electrophoresis and flow cytometry. RESULTS: fas mRNAs were expressed in 6 of 7 patients with RA. bcl-2 mRNAs were positive in 5 of 7 patients with RA. fasL mRNAs were not detectable in all the patients. bcl-2 mRNAs were always coexpressed with fas in RA synovial lining cells. The positive rates of fas and bcl-2 expression in RA synovial tissues were significantly higher than those of patients with osteoarthritis (OA) and normal synovial tissues (P < 0.05). Immunochemistry staining showed that Fas and Bcl-2 proteins were expressed in the synovial lining cells. Nucleic DNA extracted from the synovial tissues of 6 patients with RA, 4 patients with OA and 2 normal controls. Agarose gel electrophoresis demonstrated that DNA ladders occurred in only one OA synovial tissue. The spontaneous apoptosis in cultured synoviocytes from patients with RA and OA was lower as analyzed by immunofluorescence staining and flow cytometry. CONCLUSION: The phenomena of apoptosis in RA synoviocytes was not significant and overexpression of bcl-2 perhaps inhibited apoptosis in these cells, leading to hyperplasia of RA synoviocytes.
9061174 Comparison of results of different types of knee arthroplasties. 1997 We summarise our experience gained with knee arthroplasties over 18 years. Between 1976 and 1994 1103 knee arthroplasties (1044 primary cases, 59 revisions) were performed at the Orthopaedic Department of the National Institute of Rheumatology and Physiotherapy in Budapest, Hungary. The diagnoses were osteoarthritis (OA) in 50.9%, rheumatoid arthritis (RA) in 40.7% and other causes in 8.4%. The average age of the patients at the time of the operation was 57.6 years (range 14-81 years). The types of primary implant were as follows: 60 constrained (hinge) prostheses, 876 unconstrained (sledge) prostheses, 108 semiconstrained (total condylar) prostheses. The mean follow-up period was 11.4 years for the hinge-type prostheses, 10.3 years for the unconstrained prostheses and 1.6 years for the semiconstrained prostheses. Reviewing the 59 revision cases, we conclude that complications with the constrained prostheses reached 17.8% and, most presented within the 1st year. Because of this high complication rate, the use of hinge prostheses has been reduced in this department to only selected cases. After sledge prosthesis implantation most of the complications (overall 5.3%) appeared after 1 year in aseptic circumstances. Given the short follow-up period of the semi-constrained total condylar knee replacement, apart from one infection in a patient with rheumatoid arthritis no other complication has been recorded. Summarising these data, it can be concluded that on average the knee function, using a standardised scoring system, improved from 38% to over 80% by introducing the semiconstrained total condylar knee prosthesis.
9924208 Synovial mast cell responses during clinical improvement in early rheumatoid arthritis. 1998 Nov OBJECTIVES: To determine the synovial mast cell response in early rheumatoid arthritis (RA) during clinical improvement, and to examine for relations with clinical and histological parameters of disease activity. METHODS: Twenty two synovial samples were obtained from six patients with RA using needle arthroscopy. The mean disease duration at baseline was eight months, and two to three further samples were obtained over a mean follow up period of 15 months during which treatment initiated clinical improvement occurred. Sections were immunostained to detect MCT and MCTC mast cells and correlations were sought between clinical and histological data. RESULTS: The overall mean synovial mast cell density was 40.3 cells/mm2, with regional densities of 60.6 and 34.2 mast cells/mm2 in the superficial and deeper synovial layers respectively. The MCT subset predominated, outnumbering MCTC by 3:1. There was a significant correlation between the histological inflammation index and the MCT density, (r = 0.4, p < 0.05) but not the MCTC subset. The regional distribution and predominant subset of mast cells varied in individual patient's synovia over time, with a trend towards restriction of the mast cell response to the superficial synovium during clinical improvement. CONCLUSIONS: The mast cell response in early RA is characterised by substantial expansion of predominantly MCT mast cells that correlates with histological indices of inflammation. During clinical improvement, this expansion tended to become more superficial. Taken together with previous studies of long duration RA, which implicate MCTC cells in synovial damage and disease progression, these results suggest that MCT and MCTC mast cells may possess distinct functions in the spectrum of inflammatory events occurring during RA.
9549386 [Therapy of refractory rheumatoid arthritis. Cyclosporin and methotrexate combination]. 1998 Jan Rheumatoid arthritis (RA) is a chronic multisystemic disease affecting mainly the joints and characterised by a poor prognosis. In a four month open study we evaluated the efficacy and tolerability of a combination therapy in 14 patients with active and refractory RA (non responsive to MTX or CsA monotherapy). After three pulses of methyl-prednisolone (125 mg/die i.v. for 3 days), at day the 4 patients received methotrexate (MTX 15/mg/week p.os) and cyclosporine (CsA 3 mg/kg/day p.os). At the end of treatment period, patients had a statistically significant improvement in the tender-joint count (Ritchie Index) in the swollen-joint count and in the pain as recorded on a 100-mm visual-analogue scale. Following the criteria of the American College of Rheumatology for response to treatment in RA, 6 patients (60%) met these criteria, whereas 2 had a worsening. We could not detect any clear difference in serological parameters (ESR, CRP and Hb levels) between the beginning and the end of the therapy. A significant difference in the score of edema/joint effusion was documented at the RM analysis. Side-effects were not substantially increased as compared to MTX or CsA in single therapy. Combination therapy with CsA and MTX seems to be a safe and effective treatment for patients with active and refractory RA.
10875314 Compliance with drug therapy in rheumatoid arthritis. A longitudinal European study. 2000 OBJECTIVE: To delineate compliance with drug therapy in rheumatoid arthritis patients, determine specific characteristics of compliant and noncompliant patients, and look for changes in compliance over time. PATIENTS AND METHODS: A prospective European cohort study (EURIDISS) recruited 556 patients in four countries over three years. Compliance with drug dosages and dosing times was evaluated yearly using a questionnaire. RESULTS: Of the 556 patients, 429 (77.2%) were on drug therapy at all three evaluation time points. Use of steroids, nonsteroidal anti-inflammatory drugs, and second-line drugs varied significantly across countries. The compliance behavior was stable over time in 59.5% of them (35.7% of patients were consistently compliant and 23.8% consistently noncompliant); it was independent of disease duration and from the clinical features of the disease. Older patients and women were more likely to be compliant (odds ratios, 2.5 and 2, respectively). CONCLUSION: Compliance with drug therapy can be measured using two simple questions. Compliance is more closely dependent on individual behavior than on responses to specific features of rheumatoid arthritis.
10494495 Comparative study of self-rating pain scales in rheumatoid arthritis patients. 1999 Although progress has been made in the clinical metrology of pain in rheumatoid arthritis, much further work remains. The preferred methods of measurement remain debatable. In this longitudinal, open study, a comparison of eight self-rating pain scales has been conducted. A total of 124 patients entered the four-week study after completing a 3-7-day NSAID-free washout period. Patients were assigned to treatment with oxaprozin 1200 mg p.o. once daily with titration permitted between 600 mg and 1800 mg. Rescue analgesia with acetaminophen (paracetamol) 325 mg (maximum 2600 mg) was permitted. At the end of the washout and treatment period, patients completed eight self-administered pain rating scales. All pain measures detected clinically important and statistically significant improvements in pain. The pain scales differed in their degree of responsiveness. The Likert and visual analogue scales and their primary variations (continuous chromatic analogue and numerical scales) were more responsive than more complex measures. A positive correlation between initial pain rating and subsequent pain response was confirmed in this study. We conclude that, while pain is a subjective sensory phenomenon, its perceived severity can be evaluated using a variety of self-administered pain scales, all of which are capable of detecting improvements in health status following effective pharmacological intervention.
9973441 Integrin engagement regulates proliferation and collagenase expression of rheumatoid synov 1999 Feb 1 Growth of and metalloproteinase production by fibroblast-like synoviocytes (FLSs) in patients with rheumatoid arthritis (RA) contribute to cartilage and bone destruction associated with development of the expanding inflammatory tissue referred to as pannus. Increased levels of extracellular matrix (ECM) proteins in the pannus suggest that intracellular signals generated through integrin receptors might control these processes. We developed a cell culture system permitting accurate assessment of the effect of cell adhesion to various ECM proteins on FLS phenotype. We show that FLS proliferation to platelet-derived growth factor requires a second signal provided by adhesion to an ECM protein. Fibronectin, vitronectin, collagen, or laminin could provide the second signal and was similarly required for the proliferation of FLSs from RA or osteoarthritis patients. Adhesion to fibronectin, collagen, or Arg-Gly-Asp peptide down-regulated collagenase expression. Primarily alphav integrin receptors mediated this down-regulation upon adhesion to fibronectin. Loss of cell adhesion and TNF-alpha stimulation synergistically increased collagenase expression. Increased collagenase expression upon nonadherence was mimicked by treatment with cytochalasin B, suggesting that the loss of cytoskeletal structure associated with a change in cell shape mediates increased collagenase in nonadherent cells. Thus, although increased fibronectin in the lining layer in RA might be expected to inhibit collagenase expression, the change in cell shape associated with this multilayer structure might actually lead to increased collagenase expression.
9667617 Microscopic measurement of synovial membrane inflammation in rheumatoid arthritis: proposa 1998 Jun Previous studies have used various techniques for microscopic analysis of rheumatoid synovium, ranging from rapid analysis of limited areas of tissue to detailed quantification of extensive areas. The sensitivity and reproducibility of these methods have not been tested. This study sought to determine the minimum area of rheumatoid synovium needed to allow accurate microscopic analysis of synovial inflammation. Multiple synovial tissue samples were obtained from patients with rheumatoid arthritis at knee arthroplasty (n = 10), knee arthroscopy (n = 10) and by blind needle biopsy (n = 23). Lining layer thickness, sublining T-cell infiltration and vascularity were measured in all high-power fields (hpf) throughout every sample obtained from each patient. These complete measured results were compared with estimated results from limited numbers of hpf from each patient. It was observed that lining layer thickness estimated from as few as five readings from 3 samples/patient correlated significantly with the measured results obtained from as many as 85 readings/patient [Tau (T) = 0.70-0.94 for the three groups, all P < or = 0.005). Estimated measures of T-cell infiltration and vascularity derived from only 17 randomly selected hpf from 3 samples/patient (equivalent to 1 mm2) correlated significantly with the measured results obtained from up to 150 hpf/patient (T = 0.65-0.94, all P < or = 0.002). Quantitative analysis of inflammation in synovial tissue samples is both accurate and practical when restricted to an evaluation of a limited number of microscopic fields. It is proposed that lining layer thickness may be confidently quantified from five randomly selected readings from three tissue samples, and that sublining T-cell infiltration and vascularity may be quantified from 17 randomly selected hpf from the same samples.
9668730 The relationships of cognitive coping and pain control beliefs to pain and adjustment amon 1998 Apr OBJECTIVE: Ethnic groups may experience or report pain differently; thus, we compared ethnic differences on pain coping strategies and control beliefs, and the relationships of these variables to health status, among women with rheumatoid arthritis (RA). METHODS: Using a sample of 100 women (48 African-American, 52 Caucasian), we related pain coping strategies and control beliefs to pain severity, activity levels, and affective state, controlling for socioeconomics, behavioral impairment, and disease activity. RESULTS: Ethnic groups did not differ in pain severity or negative affect, but African-Americans were less physically active. African-Americans used more coping techniques involving diverting attention and praying/hoping; Caucasians used more coping techniques involving ignoring pain. The relationships of praying/hoping and reinterpreting pain to RA adjustment differed by ethnic group. In contrast, ignoring pain, coping statements, and stronger control beliefs predicted better health status, and diverting attention predicted more pain for all patients. CONCLUSION: There are ethnic differences in the use of coping strategies that should be acknowledged when helping RA patients cope with their disease, but control beliefs and several coping strategies predict pain and adjustment, regardless of ethnicity.
12386945 The use of low-dose prednisone in the management of rheumatoid arthritis. 2001 Low doses of prednisone are safe and effective in the management of RA. Yet, some clinicians continue to manage their RA patients with glucocorticoid doses that are too high or avoid them altogether. Glucocorticoids in low doses have proven to be very effective in suppressing the inflammation associated with RA. In addition, there is good evidence that low doses of prednisolone retard bony erosions of RA. Potential side effects of low doses of glucocorticoids can be anticipated and avoided with prudent preventative measures and appropriate management. Therefore, prednisone should be initiated as early as possible in the treatment of RA usually with another DMARD. Treatment of the inflammation in RA should not exceed 10 mg/day and often may need to be given in daily divided doses (5 mg BID). Supplemental daily calcium at 800-1,000 mg/day and vitamin D at 400-800 units/day should always be initiated with treatment. Tapering of prednisone should be done slowly using 1 mg decrements every couple weeks to a month. One should not deem it a failure to hold the patient on the lowest effective dose of prednisone.
10664486 Gait analysis after ankle arthrodesis. 2000 Feb The purpose of this study was to employ a computerized motion analysis system to identify the effect of ankle arthrodesis on the three-dimensional kinematic behavior of the rear and fore foot during level walking. A three-segment rigid body model was used to describe the motion of the foot and ankle. The results demonstrated that sagittal plane motion of the hindfoot was significantly decreased in the foot of patients having had ankle arthrodesis compared to normal subjects. The kinematic data indicated a generalized stiffness of the hindfoot on the involved foot in the sagittal plane. Sagittal plane movement in the forefoot and transverse plane movements in the hindfoot and forefoot increased in patients compared to controls.
9249645 Outcome of specific COX-2 inhibition in rheumatoid arthritis. 1997 Jul We reviewed data suggesting the hypothesis that specific inhibition of the inducible isoform of cyclooxygenase, COX-2, would provide therapeutic benefit in patients with rheumatoid arthritis (RA) with less gastrointestinal toxicity and presented the results of a therapeutic trial to test this hypothesis. Various doses of the selective COX-2 inhibitor, celecoxib, or placebo were used to treat patients with RA in a 4 week, double blind, placebo controlled trial. Celecoxib provided significant improvement in patient global assessment, morning stiffness, and the number of painful and tender joints compared with placebo. In addition, the number of withdrawals in celecoxib treated patients was significantly less than in the placebo group. No significant adverse events and no difference in the total number of adverse events were noted between the placebo and celecoxib groups. At the doses employed, celecoxib inhibited only COX-2 and not COX-1. Specific COX-2 inhibition with celecoxib causes significant improvement in the signs and symptoms of RA.
9778227 Depression and the long-term risk of pain, fatigue, and disability in patients with rheuma 1998 Oct OBJECTIVE: To determine whether a previous episode of major depression leaves a "scar" that places previously depressed patients with rheumatoid arthritis (RA) at risk for experiencing high levels of pain, fatigue, and disability. METHODS: A cohort of 203 patients with RA was randomly selected from a national panel and interviewed by phone about pain, fatigue, depressive symptoms, disability, and history of major depression. RESULTS: Excluding patients who met the criteria for current major depression, patients with both a history of depression and many depressive symptoms at the time of the interview (dysphoria) reported more pain than those without current dysphoria, irrespective of whether they had a history of depression. Dysphoria alone was not reliably related to pain reports. CONCLUSION: An episode of major depression, even if it occurs prior to the onset of RA, leaves patients at risk for higher levels of pain when depressive symptoms persist, even years after the depressive episode.
9061536 Hand function following Silastic arthroplasty of the metacarpophalangeal joints in the rhe 1997 Feb Twenty-one consecutive rheumatoid patients (23 hands, 92 joints) who underwent Silastic metacarpophalangeal joint arthroplasty between 1989 and 1993 had the 33-task Baltimore quantitative upper extremity function test prior to surgery and then repeated at intervals from 6 weeks to 1 year for all 23 hands and 3 to 4 years for 14 of the hands. In addition all hands had goniometer measurement of active range of finger joint motion and ulnar drift at each assessment. The average preoperative score was 71 improving rapidly to 89 at 6 weeks, to 91 at 1 year and 92 at 3 to 4 years. Most improvement occurred in functions requiring pinch span or hook grip and could be attributed largely to correction of ulnar drift and the change of metacarpophalangeal arc of motion. These results confirm that the Silastic metacarpophalangeal joint arthroplasty significantly improves hand function and that the improvement is maintained over a 3- to 4-year period.