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ID PMID Title PublicationDate abstract
10090157 Immunohistochemical localization of somatostatin receptor sst2A in human rheumatoid synovi 1999 Mar OBJECTIVE: To identify the somatostatin receptor-expressing cells in rheumatoid synovium using a recently developed antiserum directed against the somatostatin receptor subtype 2A (sst2A). METHODS: We carried out immunohistochemical studies of synovial biopsies from 7 patients with rheumatoid arthritis (RA) and one non-RA patient, using a rabbit polyclonal antiserum directed against sst2A and monoclonal antibodies directed against phenotypic markers. RESULTS: SSt2A was expressed by the endothelial cells of the synovial venules but also by a subset of synovial macrophages. CONCLUSION: The identification of somatostatin receptors on macrophages, which are thought to be important effector cells in RA, may offer mechanistic insights into the potential therapeutic effect of somatostatin (analogs) in RA.
9415727 Total knee arthroplasty in the young rheumatoid patient. 1997 Sep Thirty-four total knee arthroplasties were performed for severe rheumatoid arthritis in 25 patients younger than 45 years. All patients were available for follow-up evaluation at an average of 7.2 years. According to the Knee Society scoring system, the knee score improved from an average of 21 points preoperatively to 85 points at follow-up (p < 0.001). The average functional score improved from 23 points to 87 points (p < 0.001). Average range of motion improved from 71 degrees to 93 degrees (p < 0.001). Nonprogressive radiolucencies less than 1-mm thick were observed in 6 knees. One knee was revised for severe polyethylene wear; another case was revised for chronic patellar dislocation. Actuarial survivorship analysis estimates a 97% survivorship after 5 years and 90% after after 10 years. In young rheumatoid patients, total knee arthroplasty can therefore be considered as a reliable procedure, with satisfactory results during at least the first 5 to 10 postoperative years.
10366113 Lack of efficacy of oral bovine type II collagen added to existing therapy in rheumatoid a 1999 Jun OBJECTIVE: To investigate the efficacy of oral type II collagen (CII) in the treatment of rheumatoid arthritis (RA), when added to existing therapy. METHODS: Patients with active RA (n = 190) were randomized into a 6-month, double-blind, placebo-controlled trial. Patients continued to take their current arthritis medications. Patients received either placebo or bovine CII, 0.1 mg/day for 1 month, then 0.5 mg/day for 5 months. RESULTS: There were no significant differences between the baseline characteristics of either group. The primary response parameter was the American College of Rheumatology (ACR) preliminary definition of improvement in RA (ACR 20). There was no statistically significant difference in the ACR 20 after 6 months (20.0% of placebo patients; 16.84% of bovine CII patients). There were significant differences in several clinical variables after treatment, all favoring the placebo group. CONCLUSION: Oral solubilized bovine CII, added to existing therapy, did not improve disease activity in patients with RA.
10685623 Effectiveness of rehabilitation in arthritis. 1999 If rehabilitation aims to improve function, the demonstration of its effectiveness requires functional assessment, rather than the standard clinical and laboratory tests beloved of many rheumatologists. Medical interventions are not often evaluated for their contribution to improved function, and this omission must be addressed in the future. The evidence, where it is available, supports a multidisciplinary approach, but increasingly stresses the importance of partnership with the patient, passing back to them the responsibility for maintaining their own exercise programmes and involvement in activities. However, the provision of background support appears to be essential to continued independence. Evidence for the various interventions is reviewed.
10550219 Suppression of collagen-induced arthritis by oral or nasal administration of type II colla 1999 Nov We directly compared the effects of oral and nasal administration of collagen type II (CII) on disease progression, cytokine production and T cell responses in DBA/1 mice. Lymphocytes were assayed for proliferation and cytokine production and cell lines established. T cells from fed or nasally treated groups proliferated significantly less and produced markedly less IFN-gamma than the non-fed immunized group 10 days after immunization and prior to onset of arthritis. T cell lines established from fed or nasally treated mice showed a pattern of cytokine production involving IL-4, IL-10 and TGF-beta, whereas T cell lines from the control group produced more IFN-gamma and IL-2. Suppression of clinical measures of arthritis was equivalent in the nasal and orally treated groups. Animals were then tested for IFN-gamma production 70 days after a booster immunization at a time when disease was apparent. Mucosally treated animals secreted less IFN-gamma as compared to controls, even at this late time point. Suppression of collagen induced arthritis (CIA) by nasal treatment of mice with CII was associated with diminished levels of TNF-alpha and IL-6 mRNA expression in the joints of tolerized mice, two cytokines known to be involved in the inflammatory and pathological process of CIA. These results demonstrate the induction of antigen specific Th2 and TGF-beta secreting regulatory cells following both oral and nasal treatment, which is associated with suppression of local inflammation in the joints and decreased Th1 type responses in the periphery throughout the course of the illness.
11761346 Predictors of improvement in a cognitive-behavioral intervention for women with rheumatoid 2001 Fall In this article we present a secondary analysis of data from a brief cognitive-behavioral intervention for women with rheumatoid arthritis that resulted in significant overall improvements in personal coping resources, pain coping behaviors, psychological well-being, and fatigue. Not every participant, however, improved during the intervention. Establishing predictors of improvement in brief interventions is important to optimize the cost-effective use of these resources. In search of predictors of improvement, we examined demographic and background variables, personal coping resources, pain coping behaviors, and social support. Both linear and quadratic effects were analyzed, comparing baseline measures to both immediate postintervention and 3-month follow-up outcomes using standardized indexes ofpredictors and criteria variables. After removing the effects of baseline scores on the outcomes index, significant predictors of improvement included length of time since diagnosis, personal coping resources, and maladaptive and adaptive pain coping behaviors. Both linear and quadratic effects were found, although this varied as a function of type of predictor.
10605168 [Metalloproteinase inhibition: therapeutic application in rheumatic diseases]. 1999 Jul PURPOSE: Matrix metalloproteinases (MMPs) play an important role in the degradation of articular cartilage in several diseases, including osteorthritis and rheumatoid arthritis. Aiming at developing new drugs with selective inhibiting action against enzyme damaging the extracellular matrix, research is mainly directed towards the: 1) development of new drugs with specific inhibitory effect on MMPs; 2) better understanding of the pharmacologic profile of drugs already used in the treatment of rheumatic diseases, in order to identify those having an inhibiting action on degradative enzymes. MATERIALS AND METHODS: The interaction between rifamycins and collagenase type XI were studied using a fluorogenic substrate MOCAc-Pro-Leu-Gly-Leu-A2pr(Dnp)-Ala-Arg-NH2. RESULTS: In our experimental conditions rifamycins showed a marked inhibition capacity with a IC50 ranging from 13 to 20.7 microM. This inhibition was reversible after extensive dialysis. CONCLUSIONS: Our results indicate that the effects of rifamycins in rheumatoid arthritis may correlate to the inhibitory activity of these molecules on collagenase activity.
10894267 Adenoviral mediated delivery of FAS ligand to arthritic joints causes extensive apoptosis 2000 May BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease where the synovial lining layer of the joint becomes thickened, hypercellular, and highly aggressive. Invading synovial tissue erodes cartilage and subchondral bone and leads to loss of joint function. FasL, a cell-surface molecule on activated T-cells interacts with its receptor, Fas, to induce apoptosis in target cells. We addressed the feasibility of using adenoviral gene transfer of FasL therapeutically to mediate apoptosis in arthritic joints similar in size to the small joints of the hands and feet that are the primary sites of RA in humans. METHODS: Adenoviral vectors were used to transfer FasL and LacZ cDNAs into human RA and rabbit synovial fibroblasts in culture where apoptosis was evaluated using MTT and TUNEL analyses. The ability of Ad.FasL to mediate synovial apoptosis in vivo was then addressed in an IL-1-induced arthritis model in the rabbit knee. RESULTS: In culture, delivery of FasL was found to efficiently induce apoptosis in both human RA and rabbit synovial fibroblasts. The ability of Ad.FasL to induce synovial apoptosis was then evaluated in rabbit knee joints. 24 h after intra-articular injection of 10(11) Ad.FasL particles, large regions of synovial tissue were observed histologically consisting primarily of fibrous matrix and cellular debris. TUNEL staining of corresponding sections was highly positive for fragmented DNA. Glycosaminoglycan (GAG) synthesis from cartilage shavings from treated joints suggests that Ad.FasL does not induce significant apoptosis in resident articular chondrocytes. CONCLUSIONS: Infection of human and rabbit synovial fibroblasts with Ad.FasL results in significant apoptotic cell death in vitro. Direct intra-articular injection of Ad.FasL in the arthritic rabbit knee results in extensive apoptosis in the synovium without affecting chondrocyte viability.
11444091 Ultrasound measurements at the proximal phalanges in male patients with psoriatic arthriti 2001 Bone ultrasound parameters at the proximal phalanges of the hands were measured in 55 male patients with psoriatic arthritis (PA) (39 with peripheral radiologic involvement and 16 with axial involvement), comparing the findings with those in 16 rheumatoid arthritis (RA) patients, 20 ankylosing spondylitis (AS) patients and 55 age- and sex-matched normal controls. Mean values of amplitude-dependent speed of sound (Ad-SoS) and ultrasound bone profile score (UBPS) were significantly lower in RA (p < 0.001 and p < 1 x 10(-5)) and PA (p < 0.03 and p < 1 x 10(-6)) patients than in controls, while there was no statistically significant difference between AS patients and healthy subjects. Ultrasound parameters showed a significant negative correlation with age in all groups. In each patient group ultrasound values were unrelated either to disease duration or to inflammatory indices such as erythrocyte sedimentation rate and C-reactive protein. Moreover no significant differences were observed between ultrasound parameters of the dominant and the nondominant hand. PA patients with and without axial radiologic changes did not show any differences in ultrasound parameters. However, PA subjects with peripheral involvement only had significantly higher Ad-SoS (p < 0.04) and UBPS (p < 0.04) values than RA patients. PA patients with axial lesions had significantly lower (p < 0.04 and p < 0.01) ultrasound values than AS patients. These findings suggest that PA ultrasound techniques performed at the peripheral level are of value to speculate on bone involvement, although we think that ultrasound measurements cannot yet be recommended for monitoring bone involvement in these patients.
11032097 Defining COX-2 inhibitors. 2000 Oct Arachidonic acid metabolism is governed by 2 isoforms of cyclooxygenase (COX), the constitutively expressed COX-1 and the inducible COX-2. Antiinflammatory, analgesic, and antipyretic effects of nonsteroidal antiinflammatory drugs (NSAID) are explained by the capacity of these agents to inhibit COX-2, whereas the serious gastrointestinal side effects are caused by inhibitors of COX-1. The first of a new class of COX inhibitors, the COX-2 specific inhibitors, has just been approved for the treatment of osteoarthritis (OA) and rheumatoid arthritis (RA). As the clinical outcomes of specific COX-2 inhibitors are considerably different than those of NSAID, it is essential for the clinician to understand the basis of classification of those new, effective, and safer therapeutic agents for the treatment of OA and RA.
10822685 [The effect of combined therapy on the ortofen concentration of the blood plasma and synov 1999 Jul A pharmacologic investigation confirmed the possibility of deliberate correction of pharmacological properties of the nonsteroidal anti-inflammatory preparation orthophen in a clinical setting by combining it with those drugs (cimetidin and cocarboxylase) capable of inhibiting elimination of orthophen from the body. In consequence, the level of the drug gets elevated not only in blood plasma but also in the synovial fluid of those joints affected by inflammation, which fact secures high efficiency of the antiinflammatory therapy.
11642502 Potential for cytokine and product manipulation to improve the results of autologous stem 2001 Oct The eradication of autoreactive T cells by high dose therapy and stem cell transplantation and the resultant alterations in the immunologic network, thymic reeducation, and peripheral tolerance provide treatment mechanisms for autoimmune and inflammatory diseases. One outcome of autologous stem cell transplantation is a significant decrease in the CD4:CD8 ratio due to a loss in CD4+ cells and a depression in T cell function. Mechanistically, the loss of T cell function is associated with an increased frequency of circulating monocytes, their expression of Fas ligand (FasL), and a high frequency of apoptotic CD4+ T cells. This suggests that activated Fas+ CD4+ lymphocytes interact with FasL+ monocytes. resulting in apoptosis, preferential deletion of CD4+ T cells, an inversion in the CD4:CD8 ratio, and depressed T cell function. These observations suggest the potential for immune regulation using stem cell manipulation or posttransplant cytokine administration as therapeutic strategies for autoimmune/inflammatory diseases.
9883414 Long-term results of unconstrained Roper-Tuke total elbow arthroplasty in patients with rh 1998 Nov We evaluated the long-term results of 12 unconstrained Roper-Tuke total elbow replacements that were performed in 12 patients with rheumatoid arthritis from 1983 to 1989. The mean follow-up period was 9.5 years (range 8 to 13 years). We used the Ewald elbow-scoring system to chart results. This showed that the scores for the 12 elbows had improved from an average preoperative score of 39 points (range 17 to 72 points) to an average postoperative score of 80 points (range 45 to 97 points). The greatest improvements were in terms of pain relief, function, and range of motion. Eight elbows were free of pain by the end of follow-up. Average elbow flexion increased from 115 degrees before operation to 140 degrees after operation, and pronation and supination increased from 52 degrees to 61 degrees and 42 degrees to 71 degrees, respectively. Radiographs of the 12 elbows showed constant wear of the ulnar polyethylene with loosening of 2 ulnar components. Revision of the prosthesis was necessary in 2 elbows because of aseptic loosening. Complications included 1 subluxation, 1 supracondylar fracture, and 2 ulnar neuropathies. Despite some excellent clinical results with a follow-up of over 10 years, the authors no longer recommend the use of this kind of elbow prosthesis in patients with rheumatoid arthritis because of the high complication rate and the impossibility of adapting this implant in the event of bone loss. The authors propose a new classification of humeral bone loss that will allow for better planning of primary and revision total elbow arthroplasties.
9440132 The contribution of synovial fluid lipoproteins to the chronic synovitis of rheumatoid art 1997 Oct Lipids in the synovial fluid of patients with active rheumatoid arthritis are elevated compared to normal synovial fluid and that of other inflammatory arthropathies. Various assumptions about the role of these lipids have been made. This study offers evidence that these lipids may contribute to the synovitis in rheumatoid arthritis through participation in the arachidonic pathway within the joint space. Phospholipase A2 activity, phospholipids, prostaglandin E2, and leukotriene B4 have been correlated in the synovial fluid and plasma of untreated rheumatoid patients and compared with that of patients with osteoarthritis.
11438037 A follow-up to "Anti-cytokine therapy in chronic destructive arthritis" by Wim B van den B 2001 In recent years, the effectiveness of anti-TNF therapy in treating rheumatoid arthritis (RA) has become apparent. While trials of IL-1 receptor antagonist in RA have been encouraging, it clearly is more difficult to target two molecules (IL-1 alpha and beta) than one (TNF-alpha). In his review article, Professor Wim van den Berg argues that both TNF-alpha and IL-1 must be blocked in RA and that although TNF is clearly a potent inflammatory molecule, the dominant cytokine in the subsequent degradation of the joint tissue is IL-1. This commentary discusses his hypothesis in light of animal studies and the limitations of the conclusions that can be drawn from them. More broadly, it discusses the biology of TNF-alpha and IL-1 and suggests explanations of why TNF-alpha is a pivotal cytokine in this disease.
11817872 Cementless Lord total hip arthroplasty: cup loosening common after minimum 10-year follow- 2001 Dec We evaluated the clinical and radiographic results of 103 (88 patients) cementless Lord total hip arthroplasty after a mean follow-up period of 12.5 (10-16) years. 77 hips had arthrosis, 15 rheumatoid arthritis and 11 osteonecrosis. The preoperative mean Harris Hip Score improved from 47 (19-66) to 87 (62-99) at 5 years, but declined to 77 (56-97) at the final examination. The survivorship of the cup, using radiographically confirmed aseptic loosening as the end point, was 63% at 10 years and 45% at 15 years and the survivorship of the stem was 97% at 10 years and 96% at 15 years. The low figures of the cup may be due to insufficient contact between the smooth-surfaced threads of the cup and the acetabular bone. Thinner polyethylene, insufficient initial bone coverage, and larger femoral head diameter were significantly related to the occurrence of loosening. We can not recommend this smooth-surfaced threaded cup because of its high failure.
9831331 Cyclooxygenase selectivity and the risk of gastro-intestinal complications of various non- 1998 Oct Severe gastro-intestinal complications are a major cause of NSAID-induced deaths in cases of rheumatoid arthritis. We measured COX selectivity by using an intact cell assay system, and found that NS-398 is a highly COX-2-selective inhibitor. Meloxicam, etodolac and diclofenac also showed high COX-2 selectivity. Zaltoprofen, loxoprofen-SRS (active metabolite of loxoprofen), 6-MNA (active metabolite of nabumetone) and ibuprofen showed intermediate COX-2 selectivity. The lowest COX-2 selectivities, which means the highest COX-1 selectivities, were observed in indomethacin, aspirin, and oxaprozin. There appears to be a good relationship between our data and some clinical data of severe gastro-intestinal toxicity. The more a given NSAID is selective for COX-2, the safer it is for clinical use. In conclusion, to anticipate the safety of NSAIDs, we find that an intact cell assay system, using human cells for measurement of COX selectivity, may be more useful than using direct enzyme assay systems.
10464551 Relationship between serum RANTES levels and radiological progression in rheumatoid arthri 1999 Jul OBJECTIVE: The aim of this study was to evaluate the relationship between serum chemokines and the clinical and radiological response to a one-year course of methotrexate (MTX) in patients suffering from rheumatoid arthritis (RA). METHODS: Twenty out-patients suffering from active RA entered a one-year open prospective study on the effects of low dose MTX therapy. Plain radiographs of the hands and feet were taken at study entry and at the end of the follow-up, and were compared for the number of eroded joints. Serum levels of both C-X-C and C-C chemokines were obtained before the initation of MTX and after 6 and 12 months of treatment. RESULTS: The levels of serum RANTES before treatment were significantly higher in RA patients than in the controls and returned to normal levels after one year of treatment. Serum levels of the other chemokines were either in the normal range or undetectable. Twelve patients (60%) did not show any new eroded joints at the end of the follow-up period and were considered as radiological responders (RR). Serum levels of GRO-alpha and RANTES after 6 months of treatment were significantly higher among the patients with radiological progression than in RR patients. CONCLUSIONS: We observed high levels of serum RANTES in a series of RA patients during the active stage of the disease. MTX treatment significantly lowered the serum levels of RANTES, GRO-alpha and MCP-1. High levels of serum RANTES or GRO-alpha after 6 months of MTX treatment seem to be predictive of radiological erosions after one year.
11684100 Abnormal IgG galactosylation and arthritis in MRL-Fas(lpr) or MRL-FasL(gld) mice are under 2001 Oct 26 MRL mice bearing the lpr (Fas) or gld (Fas ligand) mutation, MRL-Fas(lpr) or MRL-FasL(gld), respectively, develop arthritis similar to rheumatoid arthritis, but C3H and C57BL/6 mice bearing such mutations do not. In MRL-Fas(lpr) mice, agalactosylated oligosaccharides in serum IgG increase significantly in comparison to MRL-+/+ mice without arthritis. In this study, an increased level of agalactosylation in IgG, as compared to MRL-+/+, was found in both MRL-Fas(lpr) and MRL-FasL(gld) mice. In contrast, the incidence of IgG without galactose was comparable among C3H-Fas(lpr), C3H-FasL(gld), and C3H-+/+ mice as well as between C57BL/6-Fas(lpr) and C57BL/6-+/+ mice. These results suggest that the increase in agalactosylated IgG and the development of arthritis in MRL-Fas(lpr) and MRL-FasL(gld) mice are controlled by the MRL genetic background.
11491502 A comparative study of outcome in myositis and other musculoskeletal disorders assessed us 2001 Jul OBJECTIVE: This study evaluated the comparative impact of myositis and other musculoskeletal disorders on general health using the Nottingham health profile (NHP) as a generic measure of health status. METHODS: A prospective observational study of 113 females with myositis, 142 females with rheumatoid arthritis, 45 females with spinal osteoporosis and 96 females with knee osteoarthritis. RESULTS: All mean NHP section scores were higher in myositis and other musculoskeletal disorders compared to population mean values. Section scores for energy and social isolation were high in myositis compared to all other disorders. Scores for physical disability in myositis were similar to RA. Pain scores were higher in RA and OA compared to myositis. Backwards linear regression models explained 26-42% of the variation in energy and social isolation scores. Emotion and physical section scores were the major determinants and the pattern was similar in all disorders. Disease duration and age had little effect. CONCLUSIONS: Myositis is not simply a disease with physical problems but has wide ranging effects on social and emotional well being. Until disease-specific instruments are available, a generic measure like the NHP can be used to assess problems other than muscle pain and loss of strength.