Frederick Wolfe, Janice Anderson, Deborah Harkness, Robert M.Bennett, Xavier J. Caro, Don L. Goldenberg, I. Jon Russell, and Muhammad B. Yunus 1560

This study shows that the yearly cost for service utilization among patients with fibromyalgia averages $2,274. Fibromyalgia patients have high lifetime and current rates of utilization of all types of medical services. Compared with patients with other rheumatic conditions, they more frequently report symptoms and comorbid or associated conditions,and their symptom reporting is linked to service utilization and, to a lesser extent, functional disability and global disease severity.

Frederick Wolfe, Janice Anderson, Deborah Harkness, Robert M.Bennett, Xavier J. Caro, Don L. Goldenberg, I. Jon Russell, and Muhammad B. Yunus 1571

Fibromyalgia is among the most common musculoskeletal disorders seen by rheumatologists and generalists. This 7-year study of fibromyalgia shows that outcomes do not change over time in patients with established symptoms who are seen in rheumatology clinics, and that initial assessment results are predictive of final results.

Jolanda Cibere, John Sibley, and May Haga 1580

The incidence of malignancy was determined in 862 patients with RA and compared with that of the general provincial population of Saskatchewan. Colorectal cancer was reduced by half, which may be related to long-term NSAID use. The risk of hemopoietic cancers was increased, due to a significant increase in leukemia. Nevertheless, the overall malignancy rate was reduced in this RA cohort.

Marcos Bosi Ferraz, Andreas Maetzel, and Claire Bombardier 1587

Increasing use of economic evaluations to assess the effectiveness of interventions and their costs in the health care sector prompted this review of all economic evaluations published in the field of rheumatology over the last 3 decades. This study analyzes the basic methodologic issues relevant to the conduct of these evaluations. Future economic evaluations in rheumatology will need to conform more closely to accepted standards if they are to be widely used for decision making.

Jeffrey N. Katz, Jane Barrett, Matthew H. Liang, Anne M. Bacon, Herbert Kaplan, Raphael I. Kieval, Stephen M. Lindsey, W. Neal Roberts, Daniel M. Sheff, Robert T. Spencer, Arthur L. Weaver, and John A. Baron 1594

Medicare physician claims are used increasingly to study practice patterns and treatment outcomes in the outpatient setting. The validity of these analyses hinges upon the accuracy of administrative data in identifying diagnoses and procedures. This study evaluates the accuracy of Medicare physician claims for select rheumatic disorders and shows that the claims data are indeed accurate for rheumatoid arthritis, systemic lupus erythematosus, and aspiration and injection procedures, supporting the use of Medicare physician claims data in the study of these conditions and interventions. Medicare physician claims data should not be used to study fibromyalgia, and must be interpreted with caution in studies of anatomic site-specific osteoarthritis.

E. M. Tan, T. E. W. Feltkamp, J. S. Smolen, B. Butcher, R. Dawkins, M. J. Fritzler, T. Gordon, J. A. Hardin, J. R. Kalden, R. G. Lahita, R. N. Maini, J. S. McDougal, N. F. Rothfield, R. J. Smeenk, Y. Takasaki, A. Wiik, M. R. Wilson, and J. A. Koziol 1601

Some "healthy" individuals are known to have positive test results for antinuclear antibodies by the indirect immunofluorescence assay. The present multi-institutional study, sponsored by the International Union of Immunological Societies, was designed to address the significance of this finding. Readings using cutoff dilutions of serum at 1:40 and 1:160 are recommended, since judicious interpretation of the results can be used to exclude or confirm certain diseases.

Woodruff Emlen and Laurie O'Neill 1612

Measurement of ANA is a critical part of the diagnostic armamentarium of the rheumatologist. This study compared the methodologies of different ELISAs and immunofluorescent detection of ANA. The results showed significant differences between the ELISA ANA kits. Moreover, some ELISAs gave results that were significantly different from those using immunofluorescent ANA. In order to interpret the ANA test appropriately, clinicians must be familiar with the specific methodology being used.

Thomas A. Goodman, Peter A. Merkel, Gary Perlmutter, Mittie Kelleher Doyle, Stephen M. Krane, and Richard P. Polisson 1619

Heterotopic ossification is an important cause of acute arthritis in the critically ill patient. Rheumatologists need to be able to recognize heterotopic ossification in patients at risk, and they need to understand the natural history of heterotopic ossification so they can treat affected patients appropriately.

Chengsen Xue, Tomoko Hasunuma, Hiroshi Asahara, Weihong Yin, Toshiro Maeda, Koushi Fujisawa, Yi Dong, Takayuki Sumida, and Kusuki Nishioka 1628

This study demonstrates the modulation of the expression and transcriptional activity of HOX4C, one of the homeobox genes, by bFGF. Since the homeodomain protein promotes primitive mesenchyme proliferation during embryogenesis, the specific expression of HOX4C on rheumatoid fibroblasts suggests that it is involved in the hyperplasia of rheumatoid synovium. The activation of this transcriptional factor by bFGF should provide a better understanding of the pathogenic effect of bFGF in rheumatoid arthritis.

Anne Roivainen, Jari Jalava, Laura Pirila, Tuomas Yli-Jama, Hannu Tiusanen, and Paavo Toivanen 1636

Rheumatoid pannus shows similarities with malignant tumors. The present study examined ras proto-oncogene activation as a possible mechanism for this phenomenon. The results revealed point mutations in codons 13 and 14 of the H-ras proto-oncogene in both arthritic and control synovial samples. The codon 14 mutations were most frequently observed in OA tissue, thus suggesting a role for these mutations in OA pathogenesis. The possible significance of this phenomenon remains to be clarified.

Mark J. Cantwell, Tinh Hua, Nathan J. Zvaifler, and Thomas J. Kipps 1644

This work demonstrates that due to deficient expression of the Fas ligand, there is ineffective clearance of activated lymphocytes in the diseased joints of patients with RA. This finding reveals potential new avenues of treatment for this disease.

Florina Moldovan, Jean-Pierre Pelletier, John Hambor, Jean-Marie Cloutier, and Johanne Martel-Pelletier 1653

Collagenase-3 is a recently discovered enzyme that is able to degrade type II collagen and is believed to be implicated in human osteoarthritis. This study shows a preferential localization of this enzyme within human arthritic cartilage, different from that found for collagenase-1 and possibly reflecting a different function between these 2 collagenases. Importantly, transforming growth factor β was found to cause a mimicking, in vitro, of the in situ distribution pattern of collagenase-3

Christine H. Le, A. Graham Nicolson, Alejandro Morales, and K. Lea Sewell 1662

This study investigates the feasibility of adenovirus-mediated gene transfer as a therapeutic approach in inflammatory arthritis. The effects of systemic and intraarticular blockade of TNFα, an important inflammatory component of rheumatoid synovitis, were studied using TNF inhibitor gene expression in collagen-induced rat arthritis.

Corinne Guingamp, Pascale Gegout-Pottie, Lionel Philippe, Bernard Terlain, Patrick Netter, and Pierre Gillet 1670

This study shows that MIA-induced OA in rats reproduces OA-like lesions, such as cartilage erosion and osteophytes, in a dose-responsive manner. High doses of MIA induce a secondary long-term loss of spontaneous mobility, reproducing clinical signs of human disease, accompanied by subchondral bone exposure and variations of proteoglycan metabolism. Both rat mobility and proteoglycan metabolism during the time course of this experimental OA could be useful indicators to evaluate the putative chondroprotective properties of various drugs, and the ability of imaging techniques to detect early osteoarthritic lesions.

M. Haubitz, P. Schulzeck, S. Schellong, M. Schulze, K. M. Koch, and R. Brunkhorst 1680

In this study, elevated plasma elastase levels were found in patients with active ANCA-associated pauci-immune vasculitis. This supports the theory that ANCA-induced granulocyte activation plays a pathogenetic role in this autoimmune disease. Complexed plasma elastase levels might complement ANCA as a marker of disease activity.

Shunichi Kumagai, Sugayo Kanagawa, Akio Morinobu, Masami Takada, Kishiko Nakamura, Susumu Sugai, Etsuko Maruya, and Hiroh Saji 1685

This work demonstrates a potential association of a new polymorphism of the TAP2 gene (codon 577: Met|adVal) with susceptibility to primary Sjogren's syndrome. It was also found that the new allele of the TAP2 gene (TAP2*Bky2) was strongly associated with SS-A autoantibody production. The mutation in TAP2 (Val577) may be involved is SS-A autoantibody production and could be a genetic factor that determines susceptibility to Sjogren's syndrome.

Kevin J. Griffith, Edward K. L. Chan, Chien-Cheng Lung, John C. Hamel, Xiaoying Guo, Kiyomitsu Miyachi, and Marvin J. Fritzler 1693

Autoantibodies directed against intracellular antigens are a serologic feature of systemic rheumatic diseases. The present study identifies a unique autoantigen in the Golgi complex that is targeted by autoantibodies in Sjogren's syndrome sera. Awareness of this new serologic marker may lead to a better understanding of the pathogenesis of Sjogren's syndrome.

Naoko Kanda, Tetsuya Tsuchida, and Kunihiko Tamaki 1703

Testosterone has been reported to suppress the development of SLE. Results of the present study demonstrated the in vitro effects of testosterone on the production of SLE-specific IgG anti-dsDNA antibodies in peripheral blood mononuclear cells from SLE patients. The findings provide important clarification of an immunoregulatory role for testosterone in human patients with SLE.