 |
|
|
 |
71 PLASMA ENDOTHELIN-1 (ET) AND ANTIPHOSPHOLIPID ANTIBODIES IN SLE AND PAPS Jan Schulz, Peter Cernacek, Joseph Ragaz, Costa Makridis (St.Mary's Hospital, Montreal, Royal Victoria Hospital, Montreal) The potent vasoconstricting peptide ET was suggested as a marker of arterial but not venous thrombotic events in patients with antiphospholipid syndrome (APS). We measured plasma ET, anti beta2-glycoprotein I and anticardiolipin IgG & IgM antibodies in patients with primary APS (n=13), SLE (n=19), and with CNS thrombosis of non-immune origin (n=6. Their respective values were compared to controls (n=12). RESULTS: On average, ET was markedly increased in all 3 groups (PAPS: 4.6 fold, SLE: 5.8 fold, CNS: 5.9 fold). However, despite this trend, the increase did not achieve statistical significance. There was no difference in ET plasma levels among patients with SLE and PAPS with or without thrombotic events. On the other hand, all four antiphospholipid antibodies, although showing heterogenous values, were significantly increased in both PAPS and in SLE but not in CNS thrombosis. Anti beta 2-IgM levels were significantly higher in PAPS patients with vascular events compared to PAPS patients without vascular events. Conclusions: 1. Although plasma ET is markedly increased in some patients with SLE and PAPS, this elevation is not specific for thrombotic events. 2. Anti beta 2-IgM appears to be a marker of vascular events in patients with PAPS. 72 BONE & JOINT REFERRAL-CONSULTATION MADE EASY Steven M. Edworthy, Elisia Teixeira, Garrett Wobst, Jennifer Talavera, Alim Devani, Matt Low, Lucille Worone, Kristopher Dawson, Richard Hu (Rheumatology Division, Bone & Joint Telematics , Orthopaedics Division - University of Calgary) INTRODUCTION: Referrals have been identified as a particularly problematic area for primary care practitioners in the context of MSK health. Solutions for the identified problem were found through an action research approach. Demand for MSK health care is extremely high. Supply of services is limited leading to a need for prioritizing. A two phase project was undertaken in 2002 and 2003. An electronic approach, utilizing a secure Internet environment, was envisioned as a method that would permit ongoing dialogue between referral office and consultant office, an Electronic Referral System (ERS). MATERIALS & METHODS: An action research approach of qualitative research was chosen for this two-phase project. This methodology allows assessment of the general situation, identification of the problem, and development of the solution with direct interaction by the involved individuals of the different stakeholders, such as general practitioners, rheumatologists, orthopaedic surgeons, sports medicine, physiotherapists and MSK specialists. Specifications for the Electronic Referral System were defined, based on comments from focus groups, office visits, and detailed analysis of the Bone & Joint patient needs. Development plans were evaluated for an alpha version of the application in an iterative cycle of "story boarding", resulting in useful information for future scheduling discussions, including an approach to wait lists. A software development company was hired to undertake the technical aspects of the site development with attention to security issues as well as the need to comply with Health Level Standards accepted at international level (HL7 standards for data exchange). Visits to offices of general practitioners, rheumatologists and orthopaedic surgeons were undertaken throughout the project with the perspective of assuring that their needs were met. RESULTS: An alpha version of the ERS was the result of the first phase of the project. A Beta version demonstrates the current the status of this web-application, which is ready to be used by the interested health care professionals. The changes incorporated in the Beta version drew upon a list of more than 100 items identified through the action research process. CONCLUSIONS: Preliminary results of test-trials of this web-based application undertaken at referring physicians and consulting physicians' sites have shown that it can meet the referring-needs expectations of the Bone and Joint group. It is seen as a tool to properly assess the referred patient's priority of assessment, and to provide a channel for prompt delivery of the specialist's recommendations and impressions, in their consultation letter. Accountability is also identified as a benefit for all parties involved in the referring process. 73 SUCCESSFUL TREATMENT OF CHRONIC REFRACTORY POLYMYOSITIS WITH ANTITHYMOCYTE GLOBULIN: A CASE REPORT Achal Vaidya, John Cowdery (University of Iowa Roy J. and Lucille A. Carver College of Medicine and VA Medical Center, Iowa City, IA) Polymyositis is an autoimmune inflammatory myopathy characterized by infiltration of the muscles by CD8+ T lymphocytes. Traditional treatment includes corticosteroids, intravenous gammaglobulin (IVIG) and immunosuppressive agents like azathioprine, methotrexate, cyclophosphamide or cyclosporine. Some cases are resistant to these treatment modalities. We describe a young woman with severe, recalcitrant polymyositis who was successfully treated with rabbit antithymocyte globulin (ATG). She presented with a creatine kinase (CK) level of greater than 10,000 with classical muscle weakness and electromyogram and muscle biopsy findings of polymyositis. She initially responded to the combination of corticosteroids and IVIG followed by treatment with methotrexate and cyclosporine. After 2 years, myositis recurred and did not fully respond to a repeat of this regimen. After 6 weeks, the CK remained >4000 and was slowly rising despite continuing treatment with prednisone, methotrexate 25 mg weekly and cyclosporine 7mg/kg/day. She was then treated with ATG at 1.3 mg/kg/day intravenously for 10 days. The dose was titrated to maintain a lymphocyte count of at least 100/mm3. She also received prophylactic trimethoprim-sulfamethoxazole and acyclovir. ATG therapy was well tolerated. Within 10 days, her CK began to fall, and she experienced improvement in muscle strength. At her last follow up, 7 months following the ATG, she had minimal residual weakness, CK level was 203 and she had been tapered off steroids. She remains on methotrexate and cyclosporine. ATG may be considered as a therapeutic option in refractory polymyositis. The mechanism of action in this setting is unknown. It is possible that this treatment may target the IL-2 independent effector/cytotoxic T lymphocytes that may mediate muscle inflammation. Clearly, more studies are indicated to validate this observation. 74 RESPONSIVENESS OF FOUR PERFORMANCE MEASURES USED TO EVALUATE OUTCOME FOLLOWING TOTAL HIP AND KNEE ARTHROPLASTY Deborah Kennedy, Paul Stratford, Jean Wessel, Jeffrey Gollish, D Penney (Orthopaedic and Arthritic Institute of Sunnybrook and Women's College Health Sciences Centre, Rehabilitation Department, Toronto, Ontario , McMaster University, Hamilton, Ontario, Orthopaedic and Arthritic Institute of Sunnybrook and Women's College Health Sciences Centre, Rehabilitation Department, Toronto, Ontario) PURPOSE: To examine the reliability and responsiveness of the six minute walk test (6MWT), a fast self-paced walk test (SPWT), the timed up and go test (TUG) and a stair performance measure (ST) in patients with osteoarthritis who subsequently underwent total hip (THA) or knee arthroplasty (TKA). Physical performance measures are used to evaluate change in patients undergoing THA or TKA, and yet there is little information on measurement properties such as responsiveness. METHODS: Subjects were 69 women and 81 men, age 63.7+/-10.7 years consecutively admitted for primary THA or TKA at a specialized, orthopaedic tertiary care facility. They were tested on the four performance measures pre-operatively, within two weeks post-operatively, and a median of 38 days after that. Nineteen subjects were tested at two additional times pre-operatively. Intraclass correlation coefficients (ICC) and standard errors of measurement (SEM) were used to examine the reliability of the pre-operative measures. The standardized response mean (SRM) was used to evaluate responsiveness. RESULTS: Reliability estimates were 0.89-0.90 except for the TUG (ICC=0.75). The SEMs were: 6MWT=41 m, SPWT=1.9 sec, TUG=1.3 sec, and ST=2.2 sec. All measures demonstrated a deterioration in performance at 2 weeks post-operatively (SRM=-0.9 to -1.7), but an improvement from baseline to 8 weeks post-operatively (SRM=0.8 to 2.0). The SRMs were greatest for ST and 6MWT. CONCLUSION: The test-retest reliability estimates of the 6MWT, ST and SPWT met the requisite standards for making decisions at the individual patient level. All of the measures were responsive to detecting deterioration and improvement in the early period following arthroplasty. 75 LEPTIN IS PRESENT IN SYNOVIUM OF EARLY ARTHRITIS BUT IS NOT INDUCED BY HYPOXIA Carol Hitchon, Miranda Ma, Keng Wong, Hani El-Gabalawy (University of Manitoba, Winnipeg, Manitoba) PURPOSE: Leptin regulates energy metabolism homeostasis as well as T cell responses and angiogenesis. Leptin deficient mice have reduced T cell proliferative responses and are partially protected from BSA induced arthritis. Leptin is upregulated by hypoxia via hypoxia inducible factor-1 (HIF1). We have previously shown that hypoxic conditions in RA synovium upregulate VEGF and SDF1 expression in synoviocytes. We therefore hypothesized that leptin may also be induced by hypoxic conditions in RA synovium and thus may contribute to the persistence of the synovitis. METHODS: Leptin levels were measured in serum (rheumatoid arthritis n=10, non-rheumatoid arthritis n=9) and synovial fluid (rheumatoid arthritis n=9, non-rheumatoid arthritis n=3). The duration of disease was less than 12 months for 18/27 (66%) patients. Clinical characteristics including joint counts, rheumatoid factor (RF), ESR, CRP and synovial fluid pO2 were recorded at the time of sampling. Synovial tissue was obtained by closed needle biopsy from patients with early inflammatory arthritis (n=5) or from patients with established RA or osteoarthritis (OA) at the time of joint arthroplasty. Tissue sections were stained for leptin expression using immunohistochemistry. Tissue explants were cultured with cobalt chloride (CoCl), which stabilizes HIF1 and simulates hypoxia. Fibroblast-like synovial cells (FLS) were cultured under hypoxic (1%O2), or normoxic conditions for up to 48 hours. Leptin levels were measured in serum, synovial fluid and culture supernatants using ELISA. RESULTS: Leptin levels in serum and synovial fluid were similar (20 vs 28 ng/ml p=ns). No differences in serum leptin levels were seen between early RA (n=9) or early undifferentiated arthritis (UA) (n=8) (20 ng/ml vs 18 ng/ml p=ns). No significant differences were seen in serum or synovial fluid leptin levels between early and late disease. There were no correlations with clinical parameters, including synovial pO2 levels. In synovium, leptin was detected in scattered cells of perivascular aggregates seen in highly inflamed tissues from 2 patients with early RA. One patient had low synovial fluid pO2 levels (pO2=24). Leptin expression in the synovial lining layer and endothelium was enhanced in tissue explants cultured with CoCl. Leptin was detected in the supernatants of cultured FLS by 24 hours (2.9 ng/ml), and increased at 48 hours (4.4ng/ml) p<0.01) but was not significantly induced by hypoxia (3.2 ng/ml vs 4.4 ng/ml p=ns). No differences were seen between cultured OA and RA FLS. CONCLUSIONS: Leptin levels in serum and synovial fluid do not distinguish different types of inflammatory arthritis and are not reflective of systemic inflammatory activity in rheumatoid arthritis. Leptin can be detected in inflamed synovium however, unlike human dermal fibroblasts, leptin is not enhanced in hypoxic synovial fibroblast cultures. |