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ID PMID Title PublicationDate abstract
8630633 A long-term study to evaluate the safety and efficacy of meloxicam therapy in patients wit 1996 Apr Meloxicam is a new non-steroidal anti-inflammatory drug (NSAID), which has a higher activity against cyclooxygenase-2 (COX-2) than against cyclooxygenase-1 (COX-1), with potentially high anti-inflammatory and analgesic action. This study was designed to assess the long-term safety and efficacy of meloxicam 15 mg daily. Three hundred and fifty-seven patients (aged 19-84 yr, mean 56 yr) with rheumatoid arthritis (RA) received meloxicam 15 mg orally once daily, for up to 18 months. Sixty-six per cent of patients remained on therapy for 18 months. Mean global efficacy, assessed by each patient on a visual analogue scale (0 cm = excellent, 10 cm = useless), was 3.32 +/- 3.1 cm at the last study visit (all patients included) and 2.33 +/- 2.25 cm after 18 months. Health status, general condition, morning stiffness, grip strength of right hand, Ritchie joint index, pain in the morning and pain at night all improved significantly. Efficacy was maintained through the study. Only 11.4% of patients discontinued prematurely due to lack of efficacy. Mean global tolerance was good. Twenty-eight per cent of patients experienced gastrointestinal (GI) adverse events, 21% musculoskeletal system disorders, 18% skin disorders and 15% respiratory disorders. Only 13.7% of patients discontinued due to adverse events. Severe GI effects, such as perforation, ulcer and bleeding, occurred in only three patients (0.8%). Withdrawals due to GI adverse events occurred in 3.9% of patients. Meloxicam 15 mg once daily was effective and compared favourably with standard NSAIDs regarding tolerance when administered to patients with RA over an 18 month period.
8484675 Modified suprascapular nerve block with bupivacaine alone effectively controls chronic sho 1993 Mar Chronic shoulder pain is a common and disabling symptom in patients with rheumatoid arthritis (RA). It has been previously shown that a suprascapular nerve block (SSNB) using the standard mixture of bupivacaine and adrenaline (Ba) plus methylprednisolone (P), which is routinely used in pain clinics, results in a considerable improvement in pain relief and range of movement compared with conventional intra-articular steroid injections in such patients. A double blind study was carried out in 29 patients (58 shoulders) with RA to compare SSNB induced with Ba alone with that induced using the conventional mixture of Ba plus P. Highly significant improvements were noted in measures of pain, stiffness, and range of most movements for both treatments (up to three months) compared with baseline. Results favoured Ba alone; the differences between the two treatments reached statistical significance for stiffness (at 12 weeks) and active abduction (at one week). It is concluded that the addition of P to the SSNB mixture confers no benefit in these patients.
9014820 TNF-alpha-mediated expression of membrane-type matrix metalloproteinase in rheumatoid syno 1996 Dec Degradation of the extracellular matrix plays an important role in rheumatoid articular destruction. Rheumatoid synovial fibroblasts secrete a large amount of matrix-degrading metalloproteinases (MMPs), which initiate tissue damage by proteolytic degradation of collagens and proteoglycans. Cytokines, such as interleukin-1 alpha, -1 beta or tumour necrosis factor (TNF)-alpha, are potent inducers of MMPs in rheumatoid synovial fibroblasts, MMPs are synthesized and secreted as latent pro-enzymes and their activation is achieved by proteolytic cleavage or the propeptide domain at the N-terminus of the molecule. Thus, the interaction of the pro-enzymes with specific activators determines the enzymatic activity in the extracellular space. In the present study, we identified a novel mechanism for the activation of pro-MMP-2, which can be achieved through the interaction of the inflammatory cytokine, TNF-alpha, with synovial fibroblasts. Although MMP-2 is constitutively secreted by synovial fibroblasts as a pro-enzyme, stimulation of fibroblasts by TNF-alpha-induced secretion of MMP-2 in an active form. In support of this result, TNF-alpha stimulation-induced membrane-type matrix metalloproteinase (MT-MMP), a newly identified MMP-2-specific activator on synovial fibroblasts. Cycloheximide analysis demonstrated that protein synthesis may be required for TNF-alpha-mediated MT-MMP expression on synovial fibroblasts. Our results suggest that TNF-alpha induces MMP-2 activation in part by up-regulating MT-MMP expression, thus representing a new mechanism for cytokine-mediated articular destruction in rheumatoid arthritis (RA).
8035383 Radiographic measurement of hallux valgus in the rheumatoid arthritic foot. 1994 Apr OBJECTIVE: To develop a method which is objective and quantifiable, as well as reliable and valid for measuring the severity and progression of hallux valgus deformity (HVD). HVD is defined as an increase in the hallux abductus angle (HAA). METHODS: HAA drawn on plain anterioposterior radiographs of the foot was measured in 94 patients with rheumatoid arthritis. The intra and interrater reliability were analyzed. RESULTS: Findings were significant with interclass correlation coefficients ranging from 0.9 to 0.99. Detection of changes in HAA using this method were comparable to the judgment of a panel of experienced clinicians. CONCLUSION: This method is useful in detecting progression of HVD.
7682616 Beta 1 (CD29) integrin expression in rheumatoid synovial membranes: an immunohistologic st 1993 Feb Cellular attachment to, and migration into, tissues are critical aspects of the inflammatory process. Our studies were undertaken to examine the distribution of one of the families of adhesion molecules, the beta 1 integrins (VLA antigens), in inflamed rheumatoid synovial tissues. The distribution of lymphocyte subsets and the beta 1 integrins (beta 1, VLA-1, 2, 3, 4, 5) were studied in 10 rheumatoid synovial membranes using immunohistochemistry and monoclonal antibodies. The majority of lymphocytes stained positively for beta 1, VLA-3, VLA-4 and VLA-5. Intravascular mononuclear cells adherent to the endothelium appeared to generally express low levels of beta 1 when compared to those in the extravascular space, suggesting that lymphocytes may augment their expression of this molecule subsequent to their extravasation into the tissue. Cells in the synovial lining layer expressed beta 1, VLA-1, VLA-3 and and VLA-5. The endothelium of the synovial vasculature stained intensely for beta 1, VLA-1, VLA-3 and VLA-5 with more limited staining for VLA-2. The venules and capillaries in and around the subsynovial lymphocytic aggregates demonstrated the most intense vascular staining. We conclude that the beta 1 integrins are expressed by a variety of cells in the rheumatoid synovial membrane. The expression of beta 1 integrins may be subject to regulation by the inflammatory microenvironment thus contributing to a more adhesive environment into which inflammatory cells are more readily recruited and retained.
1394449 Suppression of chronic antigen-induced arthritis in rats by a monoclonal antibody against 1992 Oct 15 We have investigated a role for T cells in chronic antigen-induced arthritis in rats employing a monoclonal antibody (R73 mAb) against the T cell receptor alpha beta. Treatment with R73 mAb from the time of intra-articular antigenic challenge blocked completely the induction of chronic, but not acute ovalbumin-induced arthritis in sensitized rats. Histologically, treatment-controlled arthritic rats exhibited marked hyperplasia of synovial membrane with pronounced infiltration of inflammatory cells including alpha beta + T cells in the chronic phase of arthritis. In contrast, R73 mAb-treated rats had almost normal joint histology. Treatment with R73 mAb after onset of arthritis was also effective in suppressing the progression of chronic antigen-induced joint inflammation. The preventive and suppressive effects of the mAb on chronic antigen-induced arthritis were associated with marked depletion of alpha beta + T cells in peripheral blood. The DTH but not the humoral response to ovalbumin in sensitized rats was suppressed significantly by R73 mAb. Thus, alpha beta + T cells appear to have a central role in both induction and progression of chronic antigen-induced arthritis.
8463679 Patellofemoral complications of total knee replacement. 1993 Patellofemoral complications account for the majority of problems following total knee replacement. Many of these problems are technical, and attention to detail at the time of surgery can help avoid them. An understanding of the potential postoperative complications should help one to diagnose these early and prevent catastrophic problems.
8296635 Anti-lactoferrin antibodies in patients with rheumatoid arthritis with vasculitis. 1993 Anti-lactoferrin antibodies (anti-LF Ab) are more frequently found in patients with rheumatoid arthritis (RA) complicated by vasculitis when compared to patients with uncomplicated RA. Therefore the detection of anti-LF Ab in serum of patients with RA may be useful in the diagnosis of vasculitis in RA patients.
7847295 Cognitive assessment in primary biliary cirrhosis: a case-control study. 1995 Feb OBJECTIVES: Primary biliary cirrhosis (PBC) patients frequently complain of fatigue and loss of memory. The aim of this study was to evaluate the mental performance and the neuropsychological assessment in patients with PBC. METHODS: A case-control study was performed that included 36 PBC patients (34 female, two male, mean age 55 yrs, 11 with stage II, 16 with stage III, and nine with stage IV disease) and 36 sex and age-matched controls with rheumatoid arthritis. A preliminary routine neurological examination failed to show any abnormality in each patient, including signs of encephalopathy. A battery of neuropsychological tests was administered to each subject, including: the Global Deterioration Scale; the Mini Mental State Examination; Buschke test; Gatterer's test; the Wechsler Memory Scale; the Blessed-Roth memory test; and the Clifton Assessment Schedule. RESULTS: The overall score for each test was not statistically different in PBC patients compared with rheumatoid arthritis patients, except for the Global Deterioration Scale and the Clifton Assessment Schedule; the performance was significantly poorer for these measures in PBC patients compared with rheumatoid arthritis patients. In both groups no correlation was found between the score of each test and age and/or duration of the disease. However, in the PBC group the score of BR was negatively correlated with the histological stage (p < 0.0025). CONCLUSION: The global mental status is not altered in PBC, but early changes in orientation and in personal memory are present in cirrhotic stage.
1299461 Change and status in quality of life in patients with rheumatoid arthritis. 1992 Oct Current status in quality of life and deterioration retrospectively attributed to the disease by patients with rheumatoid arthritis (RA) were examined. The study group included 169 female and 53 male patients with probable (n = 70), definite (n = 127) and classical RA (n = 25). In a cross-sectional postal survey the participants self-rated their quality of life according to a generic self-assessment package tailored in part for this study. Shortened parallel ratings by significant others were also performed. The impact of RA on quality of life was pervasive. Heaviest intrusion emerged within the physical life sphere and the behavioural and activity domain, followed by the impact on global life satisfaction and habits. Material, psychological and social life domains were less disrupted. In spite of the pervasive discomfort attributed to the illness, quality of life status was mostly rated as being 'rather good' to 'good'. There was a consistent pattern: the better off currently, the less disturbance from the disease perceived. Higher age and longer duration of RA were significantly correlated to a lower status. In addition, individuals still working rated a higher quality of life and less intrusion of the disease. Self-ratings were corroborated by ratings of significant others. While there was an agreement on the level of the negative impact of the disease, the patients rated their current situation more positively than did significant others. The dual assessment of quality of life status and change appears reasonable and informative as regards rheumatoid arthritis.
7665927 Study of interleukin-2 receptor in schistosomiasis mansoni and its analogous changes in co 1995 Aug An enzyme linked immunosorbent assay was used to quantify soluble interleukin-2 receptor (sIL-2R) in the serum of patients with different stages of S. mansoni infection, rheumatoid arthritis, systemic lupus erythematosus (SLE) and schistosomal arthropathy. The results demonstrated significant higher level of sIL-2R in different patient groups compared to the control group. The highest level of sIL-2R was recorded in hepatosplenic schistosomiasis complicated with ascites. The difference was statistically significant compared to other groups. There was no significant difference in sIL-2R regarding rheumatoid arthritis and SLE. Schistosomal arthropathy group showed significant higher level of sIL-2R compared to rheumatoid arthritis, SLE and early S. mansoni infection while the difference was insignificant compared to hepatosplenic schistosomiasis without ascites.
8016584 Prevalence of cervical spine subluxations and dislocations in a community-based rheumatoid 1994 The prevalence of rheumatoid cervical spine subluxations was studied by plain radiography in a population of 13,000 adults with 98 out of 103 detected cases of rheumatoid arthritis. Anterior atlantoaxial subluxation (AAS) of 4 mm or more was found in 33% of the cases and vertical dislocation in 14% or 27% depending on the diagnostic method. Lateral, posterior and subaxial subluxations were found in 14%, 2% and 21% respectively. These figures agree with former findings in clinical populations. One patient had been operated on for subaxial subluxation. Anterior AAS of 9 mm or more was found in four cases, subaxial subluxation of more than 4 mm in one case and a combination of anterior AAS of 6-9 mm and vertical dislocation in six cases. If these limits are taken as indications for surgery, as recommended earlier, about 10% of the RA patients should be operated, an unrealistic figure. It is concluded that intolerable pain or cervical myelopathy, and not the plain radiological findings alone, are indications for surgery. Most cases are treated by conservative methods.
1412417 HLA antigens in Tlingit Indians with rheumatoid arthritis. 1992 Aug HLA-DR4 has been described in association with rheumatoid arthritis (RA) in multiple populations. We have studied HLA antigens in Alaskan Tlingit Indians. HLA-DR4 was decreased in the RA group (n = 32) compared with controls (n = 62) (6% vs 21% p = 0.07). The predominant DR4 allele observed was DRB1*0403 (Dw13.1). The most striking observation in these studies was a marked predominance of the DRB1*1402 allele encoding Dw16 (DRw14). This allele was present in 91% of RA cases, but was also highly prevalent in controls (80%, OR = 2.4 p = 0.20). DRB1*1402 only was observed in 47% of cases and 31% of controls. The DRB3*0101 (DRw52), and the DQA*0501 and DQB*0301 alleles encoding a subset of DQw3 were associated with DRB1*1402 in cases and in controls. HLA-Bw62 was increased in RA cases (28%) compared with controls (8%) (OR = 4.5, p = 0.01, corrected p = ns).
8369890 HLA associations in subjects with rheumatoid arthritis and bronchiectasis but not with oth 1993 Sep We have examined HLA-DR, DQA and DQB variants in 72 controls, 153 subjects with RA without extra-articular features and in subjects with the rheumatoid pulmonary complications of interstitial fibrosis (23) peripheral airways disease (13) and in 41 subjects with RA and bronchiectasis. Subjects with RA alone showed the expected association with HLA-DR4 (79%) but those with RA and co-existent pulmonary fibrosis were less likely to be DR4 positive (61%). No other HLA-DR variants were significantly increased in the different disease groups. HLA-DQB1*0501 which types serologically as DQw1 was increased in subjects with RA and peripheral airways disease as compared to rheumatoid subjects with normal lung function, but these differences were not statistically significant. DQB1*0601 was increased in subjects with bronchiectasis with or without RA (but only significantly so in RA-BR subjects) DQB1*0301, DQB1*0201 and DQA1*0501 frequencies were also increased in subjects with RA and bronchiectasis as compared to those with RA alone.
1642655 Autoradiographic localization and analysis of endothelin-1 binding sites in human synovial 1992 Aug OBJECTIVE: To determine the localization of endothelin binding sites and immunoreactivity in human synovial tissues. METHODS: Quantitative in vitro autoradiographic and immunohistochemical techniques were used to localize and characterize 125I-labeled endothelin-1 (125I-ET-1) binding sites and endothelin-like immunoreactivity in sections of rheumatoid, osteoarthritic, and normal synovium. RESULTS: Specific 125I-ET-1-binding sites, characteristic of the ETA receptor, were localized to the media of synovial blood vessels in all 3 groups. No difference was found in vascular binding site density in rheumatoid and osteoarthritic synovium. Endothelin-like immunoreactivity was localized to endothelial cells in blood vessels displaying 125I-ET-1 binding sites. CONCLUSION: We conclude that endothelin may act locally, modulating synovial perfusion and exacerbating hypoxia in chronic arthritis.
7488277 Which outcome measures should be used in rheumatoid arthritis clinical trials? Clinical an 1995 Nov OBJECTIVE: To determine the discriminant validity of the core set of outcome measures proposed by the American College of Rheumatology (ACR) and the Outcome Measures in Clinical Trials (OMERACT) conference committee to be used in clinical trials of rheumatoid arthritis (RA). METHODS: Utilizing data from a multicenter randomized double-blind clinical trial of low-dose cyclosporine and placebo in RA, we estimated the relative efficiency (RE) of measures to detect a treatment effect (relative to tender joint count, which was assigned a value of 1). Four pain measures (10-cm visual analog scale [VAS], 5-point categorical scale, Health Assessment Questionnaire [HAQ] pain index, Arthritis Impact Measurement Scales [AIMS] pain score) and 3 quality-of-life measures (Problem Elicitation Technique [PET], HAQ, AIMS) were compared. RESULTS: Physician and patient global measures were the most responsive instruments, although neither was statistically superior to tender joint count. Swollen joint count, grip strength, pain measured on a 10-cm VAS, and functional status as measured by the PET and HAQ were all of intermediate responsiveness. Morning stiffness, 5-point pain scale, and erythrocyte sedimentation rate were the least responsive instruments. CONCLUSION: This study provides further evidence to support the core set of outcome measures proposed by the ACR and OMERACT:
8334715 The experience and management of pain in rheumatological disorders. 1993 Jun A case for studying the psychological aspects of pain is made through a discussion of the problems resulting from investigations of the so-called rheumatoid personality. Following a review of the current theory about pain mechanisms, proposals are made about the best ways of measuring pain in the rheumatological disorders. Later sections tackle issues about the many meanings of pain. Discussion particularly focuses on expectations about pain, on lay beliefs about the rheumatic diseases and on beliefs about pain control. Recommendations are made about the ways in which some of these psychological features might profitably be incorporated into the management of clinical pain.
8591656 Innovative treatment approaches for rheumatoid arthritis. Issues in clinical trials of bio 1995 Nov Biological agents have pointed out directions for future research, although none yet are therapies to be employed in the clinic. To date we have administered them at pharmacological; even industrial-strength doses, without demonstrating the desired cell- or diseased-specific effects. There are many issues specific to the clinical development of biological agents which distinguish them from pharmaceutical products. Most are immunologically active; early trials are performed in patients with disease, rather than normal volunteers. This poses multiple challenges: access to an appropriate patient population, as well as effecting immunomodulation without interfering with normal immune surveillance. Species-specificity of the agent may limit the use of preclinical animal models, and the duration of toxicology studies. Immunogenicity may preclude regular re-administration, necessitating prolonged benefit after single or limited treatment courses. Parenteral administration requires more careful monitoring, limits access to the agent, is associated with more expense, and may contribute to the high observed placebo response following treatment with biological agents. Requirements, and our expectations, for clinical benefit are therefore higher with these products than with traditional pharmaceuticals. Despite a scientific rationale and the use of biological markers, it is unlikely that development of a biological agent for the treatment of a chronic auto-immune disease can progress significantly faster than for a traditional pharmaceutical product. It is therefore important, particularly in the treatment of chronic RA, to develop a careful and rational step-by-step clinical development programme and to define the goals of the therapy: anti-inflammatory or symptom modification versus disease modification. Some biological agents may be expensive but safe NSAIDs. Others may treat disease flares. After 'induction therapy', utilizing a biological agent, followed by 'maintenance therapy' with a traditional DMARD agent, we may envisage 'combination chemotherapy', employing multiple biological products targeting different specific immunological aspects of the disease. We must therefore develop biological agents utilizing rigorous clinical trial principles, and follow suggested guidelines.
7966063 The clinical and research significance of the erythrocyte sedimentation rate. 1994 Jul OBJECTIVES: To determine normal limits for erythrocyte sedimentation rate (ESR) in rheumatology clinics based on observations from patients with noninflammatory disorders (NID); to determine the proportion of patients with osteoarthritis (OA) excluded from clinical trials because of elevated ESR; to determine the proportion of patients with rheumatoid arthritis (RA) meeting ESR criteria for remission, clinical activity, and eligibility for clinical trials; and finally, to explain elevations of ESR in OA. METHODS: Cross sectional and longitudinal study of all rheumatic disease clinic outpatients with RA (N = 1,556, ESR = 12,683) and NID (N = 3,961, ESR = 5,706). RESULTS: For all NID the 90th, 95th percentiles were 33, 40 for women and 23, 31 for men. For patients with OA, 21.2% of women and 8.5% of men had ESR > or = 30 mm/h. ESR in women with OA but not men with OA or those with RA were significantly associated with body mass index. Twenty-nine (29.4) percent of men and 41.6% of women with RA satisfied the ESR remission criterion. When the active disease criterion was considered (ESR > or = 28 mm/h), only 54.5% of men and 62.6% of women, on the average, have active RA. CONCLUSION: The upper limit for normal ESR for women through age 60 is about 38 mm/h. A significant proportion of patients with RA with active disease will satisfy the ACR ESR criterion for remission, but only 54-63% of patients being treated in a rheumatology clinic will have active disease (ESR > or = 28 mm/h). Current use of the ESR as a criterion in clinical trials and remission criteria while based on wide clinical experience is contradictory and may not reflect actual data.
7543145 Samarium-153-EDTMP for palliation of ankylosing spondylitis, Paget's disease and rheumatoi 1995 Aug Samarium-153-EDTMP is an effective agent for palliation of widespread skeletal metastases because it concentrates in bone metastases which have an osteoblastic component. Similar concentration in areas of osteoblastic activity in ankylosing spondylitis, Paget's disease and rheumatoid arthritis suggests a possible new treatment approach. Three patients with ankylosing spondylitis, one patient with Paget's disease and one patient with rheumatoid arthritis were treated with 153Sm-EDTMP. Objective and subjective improvement was noted, especially in ankylosing spondylitis patients. Samarium-153-EDTMP has disease-modifying potential in ankylosing spondylitis and Paget's disease and has palliative value in resistant rheumatoid arthritis. Further trials to determine optimal dose, treatment scheduling, long-term disease-modifying potential and toxicity are needed.