Paul P. Tak, Peter C. Taylor, Ferdinand C. Breedveld, Tom J. M. Smeets, Mohamed R. Daha, Philip M. Kluin, A. Edo Meinders, and Ravinder N. Maini 1077

The mechanism by which anti-TNFα MAb therapy exerts its effect in patients with RA has not yet been defined. This study evaluated the role of anti-TNFα in synovial inflammation and found that its anti-inflammatory effect is, in part, dependent on the reduction in cytokine-inducible vascular adhesion molecules and consequent reduction in cell traffic in the joints.

Treatment of RA with antibody to TNFα has been shown to result in significant improvements in all clinical and laboratory parameters. The present study demonstrates a marked reduction in the circulating levels of leukocyte adhesion molecules, with a concomitant increase in circulating lymphocyte counts, suggesting that at least part of the beneficial effect of anti-TNFα may be due to reduced adhesion and subsequent trafficking of inflammatory cells to the arthritic joints.

G. V. Campion, M. E. Lebsack, J. Lookabaugh, G. Gordon, M. Catalano, and the IL-1Ra Arthritis Study Group 1092

This study is the first to use recombinant IL-1Ra in a large group of patients with RA. In a 7-week, randomized, double-blind study, different doses and dosing frequencies were administered by subcutaneous injection, and the effect on efficacy and safety variables of RA was assessed. The data suggest a potential role for the molecule in patients with RA, and indicate that further clinical trials are warranted.

Nancy J. Olsen, Raye H. Brooks, John J. Cush, Peter E. Lipsky, E.William St. Clair, Eric L. Matteson, Kenneth N. Gold, Grant W. Cannon, Christopher G. Jackson, W. Joseph McCune, David A. Fox, the Xoma RA Investigator Group, Betty Nelson, Todd Lorenz, and Vibeke Strand 1102

Biologic agents which deplete T cells may have efficacy in the treatment of rheumatoid arthritis. This study examined one such agent, a ricin-linked anti-CD45 murine monoclonal antibody, in a placebo-controlled, double-blind study with multiple drug doses.

Ali H. Hajeer, Jane Worthington, Alan J. Silman, and William E. R.Ollier 1109

The role of TNFα in RA is of major importance, particularly since anti-TNF monoclonal antibody therapy has already proved beneficial in the treatment of this disease. This study sought to more clearly define the association between important HLA subtypes and TNF microsatellites. A greater understanding of the genetics of TNFα will ultimately contribute to elucidation of its role in the disease process.

Laura C. Rall, Clifford J. Rosen, Gregory Dolnikowski, Wilburta J.Hartman, Nancy Lundgren, Leslie W. Abad, Charles A. Dinarello, and Ronenn Roubenoff 1115

This study explores for the first time the effects of inflammatory arthritis on protein metabolism. Accelerated protein breakdown, associated with the production of tumor necrosis factor α andglucagon, occurs in patients with RA and contributes to the cachexia of RA. Loss of body cell mass and body protein in RA may be an important contributor to the reduced functional status caused by RA and may be reversible with exercise or pharmacologic intervention.

Marc C. Hochberg, Donna L. Perlmutter, Thomas A. Medsger, Jr., Katherine Nguyen, Virginia Steen, Michael H. Weisman, Barbara White,and Fredrick M. Wigley 1125

Numerous case reports and case series have described patients who developed SSc after breast augmentation with either injections of liquid paraffin or silicone or placement of silicone gel-filled breast implants; however, it remains uncertain whether there is a causal association between the exposure and the development of SSc. The results of this multicenter case-control study involving more than 800patients with SSc and more than 2,500 age-, race- and sex-matched local controls fail to demonstrate a significant association between augmentation mammoplasty and increased odds of development of SSc. In combination with the findings of other recent studies, these results fail to support the hypothesis that augmentation mammoplasty is associated with an increased risk of development of definite connective tissue disease.

Eric L. Matteson, Mohammad I. Shbeeb, Tim G. McCarthy, Kenneth T.Calamia, Lester E. Mertz, and Jorg J. Goronzy 1132

There is no known effective treatment for SSc. It has been postulated that the T lymphocyte plays an important role in its pathogenesis. Modification of the T cell response with antithymocyte globulin may be a potentially promising therapy for SSc, but at a dosage of 10 mg/kg of body weight, it did not appear to be effective in improving the skin and pulmonary manifestations of this disease.

Jaume Candell-Riera, Lluis Armadans-Gil, Carmen-PilarSimeon, Joan Castell-Conesa, Vicent Fonollosa-Pla, HerminioGarcia-del-Castillo, Josep Vaque-Rafart, MiquelVilardell, and Jordi Soler-Soler 1138

Although cardiac abnormalities in diffuse SSc have been documented individual investigations, a comprehensive evaluation of cardiac involvement in limited SSc has not previously been available. This study using noninvasive monitoring techniques found a significant prevalence of cardiac abnormalities in patients with limited SSc.

C. Michael Stein, S. Bobo Tanner, Joseph A. Awad, L. Jackson Roberts, II, and Jason D. Morrow 1146

This work provides evidence that free radical-mediated tissue injury is increased in scleroderma and provides a biologic marker of in vivolipid peroxidation that can be used to study the extent of free radical-mediated tissue damage in different subsets of scleroderma. This marker will allow the rational selection of patients for future studies of antioxidant therapy and provides a measure that can be followed during antioxidant therapy to demonstrate that such therapy decreases lipid peroxidation in these patients. In future studies, the clinical efficacy, or lack of efficacy, of antioxidant therapy in scleroderma will therefore be interpretable with the information provided by this marker--that the antioxidant therapy has effectively decreased lipid peroxidation.

Frank C. Arnett, John D. Reveille, Rose Goldstein, K. Michael Pollard,Kimberly Leaird, Edwin A. Smith, E. Carwile LeRoy, and Marvin J.Fritzler 1151

Among 335 SSc patients, autoantibodies to nucleolar fibrillarin were found in 8%, and their presence correlated with cardiac, renal, and gut involvement. This autoantibody response also was strongly associated with the HLA-DRB1*1302, DQB1*0604 haplotype, as well as several other HLA-DQB1 alleles. Antifibrillarin is thus a marker for severe SSc and is associated with a unique HLA haplotype.

Mohamed Hebbar, Jean-Michel Gillot, Eric Hachulla, Philippe Lassalle,Pierre-Yves Hatron, Bernard Devulder, and Anne Janin 1161

This study suggests a role for endothelial E-selectin, tumor necrosis factor α, and mast cells in the very early stages of systemic sclerosis. Moreover, these parameters could allow the early detection of systemic sclerosis in patients presenting only with Raynaud's phenomenon and abnormal nailfold capillaroscopy.

Christian Jorgensen, Marie-Christine Legouffe, Pascal Perney, JolietteCoste, Barbara Tissot, Christiane Segarra, Christophe Bologna,Laurent Bourrat, Bernard Combe, Francois Blanc, and Jacques Sany 1166

A 19% prevalence of chronic HCV infection was observed in patients presenting with sicca symptoms. These patients also had an increased frequency of neurologic symptoms and were seronegative for SS-A and SS-B antigens. HCV RNA was detected in the saliva of the HCV-positive patients, suggesting a tropism of HCV for the salivary gland.

Eric Rich, Edward W. Hook, III, Graciela S. Alarcon, and Larry W.Moreland 1172

This study suggests that a nongonococcal genital infection can trigger joint and tendon inflammation of mild intensity more often than usually thought. Moreover, the asymptomatic nature of the underlying genital infection is highlighted. The results of this study may enhance clinician awareness regarding the presence of an occult genital infectious process in patients who exhibit features of reactive arthritis.

Susan Manzi, Joan E. Rairie, A. Betts Carpenter, Robert H. Kelly,Santhi P. Jagarlapudi, Susan M. Sereika, Thomas A. Medsger, Jr.,and Rosalind Ramsey-Goldman 1178

Conventional serum complement measurements (C3 and C4) do not always accurately reflect complement activation and thus may be inadequate indicators of current, or predictors of future, disease activity inpatients with SLE. This study provides evidence that activation products of C3 and C4, such as C4d and Bb, are more sensitive markers. In addition, the presence of C3d in urine was better than C3, plasmaC4d, Bb, C5b-9, or serum anti-dsDNA antibody in distinguishing patients with and those without acute lupus nephritis. These laboratory measurements of complement activation may be helpful adjuncts in monitoring disease activity in patients with SLE.

Robert R. Freedman and Maureen D. Mayes 1189

Case reports have suggested a genetic etiology for primary Raynaud's disease. The present controlled investigation revealed significant familial aggregation of the disease, whether assessed by questionnaire or by physical examination. These results provide further evidence for a role of genetics in primary Raynaud's disease.

Frederic Liote, Florence Prudhommeaux, CorinneSchiltz, Romuald Champy, Andre Herbelin, Esteban Ortiz-Bravo,and Thomas Bardin 1192

In an experimental model of monosodium urate crystal-induced acute inflammation in vivo, recombinant human TGFβ1 inhibited acute cellular responses and changes in the distribution of cells, particularly monocytes. This study suggests a role for TGFβ in the self-limitation of acute gouty inflammation.

Riccardo Meliconi, Lia Pulsatelli, Mariagrazia Uguccioni, CarloSalvarani, Pierluigi Macchioni, Cinzia Melchiorri, Maria CristinaFocherini, Luigi Frizziero, and Andrea Facchini 1199

This immunohistochemical study analyzes the characteristics of PMR synovitis and the phenotype of infiltrating mononuclear arthroscopic shoulder synovial biopsy tissues in untreated patients with active disease as well as in treated patients. Similarities to the inflammatory process observed in GCA were found. Although corticosteroids rapidly control the clinical manifestations of PMR, the inflammatory process may persist for a much longer time.

Richard A. Watts, Victoria A. Jolliffe, David M. Carruthers, MartinLockwood, and David G. I. Scott 1208

"Polyarteritis nodosa" has been used as a generic term for systemic vasculitis. Recent recognition of the different outcomes nodosa and microscopic polyangiitis makes it important for rheumatologists to be able to distinguish between the 2 conditions. This report describes the application of the American College of Rheumatology Criteria and Chapel Hill Consensus Conference definitions to unselected patients with systemic vasculitis and discusses the problems associated with these definitions/classification.

Eldad Ben-Chetrit, Jean-Michel Scherrmann, and Micha Levy 1213

Colchicine is the drug of choice for familial Mediterranean fever, which is a hereditary disease treated by rheumatologists. Furthermore, colchicine is widely used to treat various rheumatologic conditions, such as gout, Behcet's syndrome, and scleroderma. The results of the present study, which show colchicine to be compatible with breastfeeding, have practical implications for the use of this treatment by rheumatologists.

David D. Sherry, Carol A. Wallace, and Stuart J. Kahn 1218

This study investigated the extent to which adult rheumatologists treat children with rheumatic diseases, and their level of comfort in doing so. The data document the need for pediatric rheumatologists to support adult rheumatologists in the care of children, and to provide education during fellowship training as well as subsequent continuing medical education

Amato de Paulis, Isabella Marino, Anna Ciccarelli, Gennaro deCrescenzo, Monica Concardi, Laura Verga, Eloisa Arbustini, andGianni Marone 1222

In this study, human synovial mast cells were studied ultrastructurallyin situ and were analyzed biochemically, immunologically, and functionally in vitro and compared with mast cells from other organs. Synovial mast cells were found to differ from mast cells from other sites in a number of respects, raising the possibility that the local microenvironment influences mast cell phenotype. This experimental model could be used to identify pharmacologic agents that could selectively act on synovial mast cells.

Julie Olszewski, Joseph McDonnell, Karla Stevens, Denise Visco, and Vernon Moore 1234

Biochemical markers of cartilage degradation are important for evaluating normal tissue turnover, as well as for information on the pathology and treatment of the arthritides. The current report demonstrates that a matrix metalloproteinase-induced cleavage product of aggrecan, F(M/V)DIPEN341, is a marker of skeletal maturation and aging in cartilage from guinea pigs and rabbits. F(M/V)DIPEN cannot be used as a marker of pathologic cartilage degradation without accounting for its accumulation during physiologic tissue turnover.

Yong Zhang, Christel Gripenberg-Lerche, Karl-OveSoderstrom, Auli Toivanen, and Paavo Toivanen 1238

The value of antibiotic prophylaxis and treatment of reactive arthritis following infection by a variety of microorganisms has remained unresolved. This study indicates that early antibiotic treatment should be considered in patients with infections known to induce reactive arthritis. It is also apparent that antibiotic treatment of fully developed enterogenic arthritis remains ineffective.