Rheumatoid Arthritis: Mur E

De Zordo T, Mlekusch SP, Feuchtner GM, Mur E, Schirmer M, Klauser AS. · Department of Radiology II, Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria. · Eur J Radiol. · Pubmed #17768022 No free full text.

Abstract: The purpose of this review is to describe the spectrum of sonographic findings in rheumatic diseases with respect to the diagnostic potential using US contrast media which prove activity or inactivity in synovial tissue where new treatment regimes target. Synovial activity can be found in non-erosive and erosive forms of primary and secondary osteoarthritis, and in inflammatory forms of joint diseases like rheumatoid arthritis and peripheral manifestations of spondyloarthritis including, ankylosing spondylitis, Reiter's syndrome, psoriatic arthritis and enteropathic arthritis. It can also be present in metabolic and endocrine forms of arthritis, in connective tissue arthropathies like systemic lupus erythematosus or scleroderma and in infectious arthritis. Ultrasound should be used as first-line imaging modality in suspected early cases of RA and other forms of arthritis, whereas contrast-enhanced ultrasound (CEUS) can further enable for sensitive assessment of vascularity which correlates with disease activity.

Klauser AS, Moriggl B, Duftner C, Smekal V, Pallwein L, Mur E, Schirmer M. · Universitätsklinik für Radiodiagnostik, Klinische Abteilung für Radiodiagnostik II, Medizinische Universität Innsbruck, Anichstrasse 35, 6020 Innsbruck, Osterreich. · Radiologe. · Pubmed #16715223 No free full text.

Abstract: High-frequency sonography enables excellent detection of early erosions and synovial proliferations. Power Doppler sonography (PDUS) allows for an improved characterization of articular and peritendinous augmented volume, because detection of hypervascularity correlates with inflammatory activity and further is helpful in differentiation from effusion and inactive pannus. The use of contrast media improves the sensitivity of vascularity detection, because they allow for a delineation of vessels at the microvascular level. This is of increased interest, as the development of new therapeutic options targeting the microvascular level calls for earlier diagnosis and optimal assessment of disease activity. Because of good availability, cost effectiveness, and patient acceptance, sonography facilitates early diagnosis of synovial proliferations and erosions as well as therapy follow-up.

Jank S, Haase S, Strobl H, Michels H, Häfner R, Missmann M, Bodner G, Mur E, Schroeder D. · Medical University of Innsbruck, Innsbruck, Austria. · Arthritis Rheum. · Pubmed #17330295 links to  free full text

Abstract: OBJECTIVE: To evaluate whether there are any correlations between the clinical parameters of temporomandibular joint (TMJ) arthritis and pathologic ultrasound (US) findings of the TMJ in patients with juvenile idiopathic arthritis (JIA). METHODS: We conducted prospective clinical and US investigations of the TMJs of 48 patients with JIA. The US investigation was performed by a 12-MHz high-resolution transducer, which was positioned parallel to the ramus of the mandible overlying the zygomatic arch in a closed-mouth position and maximum open-mouth position. RESULTS: Patients with > or = 5 peripheral affected joints showed significantly more sonographically diagnosed destructive changes in the TMJ than did patients with <5 affected joints. There was no significance between the number of affected peripheral joints and disc dislocation in the closed-mouth position. In the maximum open-mouth position, there was a significant correlation between the number of affected peripheral joints and disc dislocation. Patients with a JIA duration >23 months had a significantly higher rate of disc dislocation and destructive changes. Patients with a JIA duration >60 months had a significantly higher rate of destructive changes of the TMJ than patients with a disease duration <60 months, but no statistical significance was found concerning disc dislocation. CONCLUSION: The significant correlation between pathologic sonographic findings, duration of JIA, and the number of affected peripheral joints make the technique interesting for use as a diagnostic screening method.

Kullich WC, Mur E, Aglas F, Niksic F, Czerwenka C. · Ludwig Boltzmann Institute for Rehabilitation of Internal Diseases, Saalfelden, Austria. · Clin Exp Rheumatol. · Pubmed #16762150 No free full text.

Abstract: OBJECTIVE: To determine the effects of the disease modifying antirheumatic drug (DMARD) leflunomide on the expression of the matrix metalloproteinase MMP-1 (collagenase) and the activity of MMP-9 that are believed to play a major role in cartilage destruction associated with inflammation in patients with rheumatoid arthritis (RA). Serum concentrations of cartilage oligomeric matrix protein (COMP) should offer promise for monitoring tissue degradation in the RA joints during a 6-month therapy with leflunomide. METHODS: Thirty-six patients with RA meeting the ACR-criteria were recruited for the study in a multicentre trial. A dose of 20 mg leflunomide/day (after a 3-day 100 mg/day loading dose), an isoxazole derivate and inhibitor of the "de novo" pyrimidine synthesis, was administered for a study period of 6 months. MMP-1, the activity of MMP-9 and COMP values were measured in serum by enzyme immuno assay. The very sensitive acute phase protein serum amyloid A (SAA) was also determined by EIA. The measurements were performed before and after 3 and 6 months of leflunomide therapy. RESULTS: High levels of active MMP-9, COMP and SAA were detected in the sera of the patients with RA prior to the start of the leflunomide therapy compared to normal control sera. A significant reduction of the MMP-9 activity levels was seen after 3 months immunomodulation with leflunomide and was maintained after 6 months (p < 0.01). The degradation marker COMP and the inflammation marker SAA decreased significantly after 6 months (p < 0.04, respectively p < 0.01). There was also an insignificant tendency of MMP-1 reduction in serum after 6 months. CONCLUSION: This study demonstrated that a DMARD therapy with leflunomide can cause positive effects on cartilage degradation and inflammation achieving reductions in the acute phase protein SAA, the enzymatic attack of MMPs and the loss of the cartilage matrix component COMP.

Mur E, Hartig F, Eibl G, Schirmer M. · Department of Internal Medicine, Innsbruck University Hospital, Austria. · J Rheumatol. · Pubmed #11950006 No free full text.

Abstract: OBJECTIVE: To evaluate safety and clinical efficacy of a plant extract from the pentacyclic chemotype of Uncaria tomentosa (UT) in patients with active rheumatoid arthritis (RA). METHODS: Forty patients undergoing sulfasalazine or hydroxychloroquine treatment were enrolled in a randomized 52 week, 2 phase study. During the first phase (24 weeks, double blind, placebo controlled), patients were treated with UT extract or placebo. In the second phase (28 weeks) all patients received the plant extract. RESULTS: Twenty-four weeks of treatment with the UT extract resulted in a reduction of the number of painful joints compared to placebo (by 53.2% vs 24.1%; p = 0.044). Patients receiving the UT extract only during the second phase experienced a reduction in the number of painful (p = 0.003) and swollen joints (p = 0.007) and the Ritchie Index (p = 0.004) compared to the values after 24 weeks of placebo. Only minor side effects were observed. CONCLUSION: This small preliminary study demonstrates relative safety and modest benefit to the tender joint count of a highly purified extract from the pentacyclic chemotype of UT in patients with active RA taking sulfasalazine or hydroxychloroquine.

Yocum DE, Allard S, Cohen SB, Emery P, Flipo RM, Goobar J, Jayawardena S, Job-Deslandre C, Jubb RW, Krüger K, Lopes Vaz A, Manger B, Mur E, Nygaard H, Weiner SM, Rainer F, Sack MR, Schiff MH, Schnitzer TJ, Trigg LB, Whatmough I, Schmidt AG. · Arizona Arthritis Center, University of Arizona, Tucson, Arizona, USA. · Rheumatology (Oxford). · Pubmed #10725065 links to  free full text

Abstract: OBJECTIVE: To compare the safety, tolerability and efficacy of the new oral microemulsion formulation of cyclosporin A (CyA; Sandimmun Neoral) and the original CyA formulation (Sandimmun), in patients with severe active rheumatoid arthritis (RA), over a 12-month period. METHODS: In this double-blind, multicentre study, patients were randomized to treatment with Neoral or Sandimmun, starting with 2.5 mg/kg/day, with dose adjustments after 4 weeks. Primary efficacy criteria included patients' assessment of disease activity. Pharmacokinetic and safety assessments were performed at regular intervals. RESULTS: Compared with Sandimmun, Neoral showed a consistent trend towards greater clinical efficacy from week 12 onwards, including a significant difference in patients' assessment of disease activity at the study end-points. A significantly lower increase in dose from baseline was observed with Neoral at week 24. Pharmacokinetic assessments at week 24 showed increased absorption and decreased variability with Neoral. No differences in safety were found between treatment groups. CONCLUSION: These observations indicate that Neoral is as safe and at least as effective as Sandimmun and have important implications for patient management given the increasing role for CyA in the treatment of severe, active RA.

Lüth P, Herold M, Mur E. · Klinische Abteilung für Allgemeine Innere Medizin, Medizinische Universität Innsbruck, Innsbruck, Osterreich. · Wien Med Wochenschr. · Pubmed #15999628 No free full text.

Abstract: This study was designed to analyze reasons why rheumatologists prescribed coxibs instead of non-selective NSAIDs in the treatment of rheumatoid arthritis in Austria. A simple questionnaire was distributed among interested doctors of internal or orthopedic medicine in medical practices treating patients with rheumatic diseases. 730 patients with rheumatoid arthritis could be included in this study. The argument most often mentioned was the low incidence of gastrointestinal side-effects followed by analgesic effectiveness compared with non-selective NSAIDs. Easy to use, age of patients and general tolerability were further reasons for the decision to prescribe rofecoxib.

Schroecksnadel K, Frick B, Kaser S, Wirleitner B, Ledochowski M, Mur E, Herold M, Fuchs D. · Institute of Medical Chemistry and Biochemistry, University of Innsbruck, Fritz Pregl Strasse 3, A-6020 Innsbruck, Austria. · Clin Chim Acta. · Pubmed #14637281 No free full text.

Abstract: BACKGROUND: Moderate hyperhomocysteinaemia related to folate deficiency has been described in patients with cardiovascular risk and also in patients with autoimmune diseases including rheumatoid arthritis (RA). METHODS: In 33 patients with RA, serum concentrations of homocysteine and cysteine, of B-vitamins folate and vitamin B(12), and of immune activation markers neopterin and soluble 75-kDa TNF-receptor (sTNF-R75) were measured. RESULTS: A significant proportion of patients presented with elevated homocysteine and cysteine concentrations in comparison to reference ranges of healthy control persons. Moderate hyperhomocysteinaemia coincided with decreased serum folate and with higher concentrations of sTNF-R75 and neopterin, but it was rather independent from methotrexate (MTX) therapy. CONCLUSIONS: The coincidence of higher homocysteine and lower folate concentrations with increased concentrations of immune activation markers in patients with RA suggests that immune activation could be involved in the development of hyperhomocysteinaemia.

Schroecksnadel K, Kaser S, Ledochowski M, Neurauter G, Mur E, Herold M, Fuchs D. · Institute of Medical Chemistry and Biochemistry, Leopold Franzens University of Innsbruck, Fritz Pregl Strasse 3, A-6020 Innsbruck, Austria. · J Rheumatol. · Pubmed #12966593 No free full text.

Abstract: OBJECTIVE: Activation of the enzyme indoleamine-(2,3)-dioxygenase (IDO) by interferon (IFN)-g leads to enhanced tryptophan conversion to kynurenine. In consequence of chronic immune activation, tryptophan availability is reduced, leading to inhibition of cell proliferation as protein synthesis is affected. Tryptophan deprivation due to IDO activation could therefore be effective in abrogating processes with high metabolic turnover, thus modulating cellular immune response. METHODS: Concentrations of tryptophan, kynurenine, and neopterin were measured by HPLC in the sera of 38 patients with rheumatoid arthritis (RA). The kynurenine:tryptophan ratios (kyn/trp) were calculated to estimate IDO activity. RESULTS: Tryptophan concentrations were lower in patients with RA (median, interquartile range: 44.95 microM, 40.31-49.95 microM) compared to healthy blood donors (62.62 microM, 57.27-74.61 microM; p < 0.001). Kynurenine in patients (1.86 microM, 1.54-2.31 microM) did not differ from controls (2.06 microM, 1.58-2.65 microM; NS). The kyn/trp ratio was higher in patients (42.39 mM/M, 37.02-48.60 mM/M) than in controls (31.72 mM/M; 27.95-35.03 mM/M; p < 0.001). Kynurenine concentrations (rs = 0.611; p < 0.001) and kyn/trp ratios (rs = 0.621; p < 0.001) correlated with neopterin concentrations, which indicate stimulated cellular immune response in patients with RA. CONCLUSIONS: The data point to a role of immune activation and Th1-type cytokine INF-g to induce elevated tryptophan degradation in patients with RA.

Gutweniger S, Kopp M, Mur E, Günther V. · Department of Psychiatry, University Hospital of Innsbruck, Austria. · Clin Exp Rheumatol. · Pubmed #10464550 No free full text.

Abstract: OBJECTIVE: Physical disabilities generally cause severe disturbances in a patient's body image perception. The aim of the present study was to investigate different aspects of body image, including sexual dissatisfaction, in women with rheumatoid arthritis (RA) in relation to their subjective impression of handicap. METHODS: Forty women with RA were investigated using a series of instruments: Strauss and Appelt's questionnaire for assessing one's body (1), the body perception scale of Paulus (2), and an interview focusing on appearance, worries about health and sickness, and sexual dissatisfaction. In addition, clinical parameters and the subjective extent of morning stiffness were documented, and patients with a high degree of morning stiffness were compared to patients with a low degree of morning stiffness. RESULTS: In contrast to patients with a low degree of morning stiffness, patients with a high degree of morning stiffness worried significantly more about their bodies (p < or = 0.05) and reported significantly more problems in sexuality (p < or = 0.05). CONCLUSION: Our results suggest that morning stiffness plays a very important role in how severely a woman feels herself to be handicapped. Severely handicapped women have to deal with anxieties about health and have sexual problems. Physicians should not shy away from addressing these issues and in severe cases psychological therapy should be initiated.