Matthew A. Brown, Kevin D. Pile, L. Gail Kennedy, Duncan Campbell, Lee Andrew, Ruth March,Jane L. Shatford, Daniel E. Weeks, Andrei Calin, and B. Paul Wordsworth 588

AS is a common and highly familial rheumatic disease whose etiology is incompletely defined. This study provides evidence that susceptibility to AS is coded for both by genes lying within and genes lying outside the major histocompatibility complex. Defining these genes may result in improved diagnosis and treatment of this condition.

Ruty Mehrian, Francisco P. Quismorio, Jr., Gideon Strassmann, Mary M. Stimmler, David A. Horwitz, Rodanthi C. Kitridou, W. James Gauderman, John Morrison, Chaim Brautbar, and Chaim O. Jacob 596

It is clear that in SLE, genetic and environmental factors interact to cause the development and propagation of disease. The nature of the genes involved in human SLE is largely still unknown. This article presents evidence of the involvement of certain genes associated with programmed cell death in the genetic predisposition to developing SLE.

Saeed Fatanejad, Michele Bennett, Javid Moslehi, and Joe Craft 603

Antinuclear antibodies (ANA) are found in virtually all patients with systemic lupus erythematosus (SLE). These antibodies are frequently grouped in linked sets, which suggests that they are selected by self antigens. This study shows that grouping of autoantibodies against native small nuclear RNP particles, a major target of ANA, is a direct result of organization of these antigens, and loss of this organization results in loss of grouping of antibodies. These findings support the hypothesis that intact particles are specifically targeted by the humoral immune response in SLE.

Claus H. Nielsen, Jens Moller Rasmussen, Anne Voss, Peter Junker, and R. Graham Q. Leslie 613

Activated polymorphonuclear cells (PMN) play a central role in immune complex-induced vasculitis. This study demonstrates that erythrocytes from patients with SLE are defective in preventing deposition of soluble immune complexes on circulating PMN and, thereby, have a reduced capacity to protect against immune complex-induced PMN activation.

Markus Kaiser, Cornelia M. Weyand, Johannes Bjornsson, and Jorg J. Goronzy 623

Many clinical complications of giant cell arteritis are related to vasoocclusion. This study shows that intimal hyperplasia in inflamedtemporal arteries correlates with tissue expression of the growth factors PDGF-A and PDGF-B. The major PDGF-producing cells are macrophages that accumulate at the media-intima border but do not infiltrate into the newly formed intimal tissue.

Fons A. J. van de Loo, Onno J. Arntz, Frank H. J. van Enckevort, Peter L. E. M. van Lent, and Wim B. van den Berg 634

In this murine model of arthritis, joint inflammation was shown to be independent of IL-1 and NO, whereas both mediators played a major role in cartilage destruction. Previously it was shown that IL-1 was responsible for the suppression of proteoglycan synthesis. The present study demonstrates that NO mediates this IL-1 effect on chondrocytes and causes these cells to become unresponsive to their essential anabolic factor, insulin-like growth factor 1.

Joyce B. J. van Meurs, Peter L. E. M. van Lent, Irwin I. Singer, Ellen K. Bayne, Fons A. J. van de Loo, and Wim B.van den Berg 647

This study indicates that expression of matrix metalloproteinase-induced neoepitopes in articular cartilage is regulated by IL-1 together with as-yet-unknown factors. Although metalloproteinases don't seem to be involved in early proteoglycan degradation during antigen-induced arthritis, their expression correlates with areas of severe cartilage damage.

Hideo Hashimoto, Masato Tanaka, Takashi Suda, Tetsuya Tomita,Kenji Hayashida, Eiji Takeuchi, Motoharu Kaneko, Hiroshi Takano,Shigekazu Nagata, and Takahiro Ochi 657

This study demonstrates that synovial fluid lymphocytes from RA patients express FasL, and that soluble FasL accumulates in the inflamed joints. Membrane-bound FasL was able to induce apoptosis in RA and OA synovial cells, but naturally processed soluble FasL was not. Cleavage of membrane-bound FasL may regulate the Fas-mediated apoptosis of synovial cells.

Peter P. Youssef, Maarten Kraan, Ferdinand Breedveld, Barry Bresnihan, Nicola Cassidy, Gaye Cunnane, Paul Emery, Oliver FitzGerald, David Kane, Staffan Lindblad, Richard Reece, Douglas Veale, and Paul P.Tak 663

In this study of inflammation in the rheumatoid synovium, most immunohistologic parameters of inflammation in arthroscopically selected synovial biopsy samples were found to be similar to those in samples obtained blindly from the suprapatellar pouch by needle biopsy. However, measurements in samples from the suprapatellar pouch may underestimate the intensity of macrophage infiltration. Thus, in studies that require quantification of synovial macrophage populations, multiple tissue samples should be selected from different areas within a joint, especially from sites more adjacent to the cartilage-pannus junction.

Fredrick M. Wigley, Joseph H. Korn, M. E. Csuka, Thomas A. Medsger, Jr., Naomi F. Rothfield, Michael Ellman, Richard Martin, David H. Collier, Arthur Weinstein, Daniel E. Furst, Sergio A. Jimenez, Maureen D. Mayes, Peter A. Merkel, Barry Gruber, Lee Kaufman, John Varga, Patrice Bell, John Kern, Pran Marrott, Barbara White, Robert W. Simms, Andree C. Phillips, and James R. Seibold 670

Intravenous iloprost has been shown to be effective in the treatment of Raynaud's phenomenon secondary to scleroderma, but the intravenous method of administration is inconvenient for long-term use. In this multicenter, double-blind, randomized, placebo-controlled study, the efficacy of oral iloprost was investigated. Oral iloprost at a dosage of 50 [gm]g twice daily for six weeks was not shown to be more efficacious than placebo in the treatment of Raynaud's phenomenon in patients with scleroderma.

John H. Stone, Carl L. Millward, Jean L. Olson, William J. C. Amend, and Lindsey A. Criswell 678

Lupus nephritis is a leading cause of morbidity in SLE. A significant minority of SLE patients reach end-stage renal disease and undergo renal transplantation. The frequency with which lupus nephritis recurs in the transplanted kidney has not been well studied. This study documents recurrent lupus nephritis following 106 renal transplantation procedures, the largest single-center experience in the world.

Harald Roos, Marten Lauren, Torsten Adalberth, Ewa M. Roos, Kjell Jonsson, and L. Stefan Lohmander 687

This study represents the first long-term followup assessment of radiographic changes associated with OA in patients who underwent removal of a meniscus of the knee as compared with an age- and sex-matched, healthy knee control group. A high relative risk for radiographic tibiofemoral OA after meniscectomy was found in patients, suggesting that surgical open total meniscus removal following an isolated meniscus tear is a significant long-term risk factor for the development of tibiofemoral OA.

Dennis McGonagle, Wayne Gibbon, Philip O'Connor, Michael Green, Colin Pease, and Paul Emery 694

This is the first MRI study of new-onset knee synovitis using fat suppression techniques. Characteristic abnormalities were demonstrated in the entheseal regions in all patients with spondylarthropathy-associated knee swelling. This suggests that the primary abnormality in synovial joint involvement in spondylarthropathy is at the entheses. These results have implications for a unifying hypothesis on the classification of spondylarthropathy.

Pierre Duhaut, Micheline Berruyer, Laurent Pinede, Sylvie Demolombe-Rague, Robert Loire, Dominique Seydoux, Marc Dechavanne, Jacques Ninet, and Jean Pasquier, for the Groupe de Recherche sur L'Arterite a Cellules Geantes 701

The prevalence and role of aCL in the thrombotic complications of giant cell arteritis were assessed in this study comprising the largest prospective series of patients with giant cell arteritis, including biopsy-positive and -negative temporal arteritis and polymyalgia rheumatica. The results show that aCL are related to the vasculitis itself, and that they are no more prevalent in patients with polymyalgia rheumatica alone than in healthy controls. It appears that aCL are associated with, but not responsible for, the development of the thrombotic complications, which seem to be due to the inflammatory process affecting the arteries.

Lisa G. Rider, Rebecca C. Gurley, Janardan P. Pandey, Ignacio Garcia-de la Torre, Apostolos E. Kalovidouris, Terrance P. O'Hanlon, Lori A. Love, Raoul C. M. Hennekam, Lisa L. Baumbach, Hans E. Neville, Carlos A. Garcia, Jeffrey Klingman, Michael Gibbs, Michael H. Weisman, Ira N. Targoff, and Frederick W. Miller 710

The clinical, serologic and immunogenetic features of 16 families in which more than 1 first-degree relative developed an idiopathic inflammatory myopathy are reported. Although HLA-DRB1*0301 is a major genetic risk factor for both familial and sporadic IIM, homozygosity for DQA1 alleles is a distinctive risk factor for familial IIM. IIM should be considered in the differential diagnosis of familial muscle weakness.

Susan Ferry, Alan J. Silman, Tina Pritchard, Janet Keenan, and Peter Croft 720

In this population-based study, it was found that the presence of self-reported symptoms of carpal tunnel syndrome, i.e., pain, numbness, or tingling in the hand, was not a highly sensitive predictor of median nerve compression seen on nerve conduction testing. This result may have significance with regard to clinical decisions as to which patients should be referred for nerve conduction studies.

Fiona Donald and Michael M. Ward 725

Several laboratory tests can be used to monitor disease activity in patients with rheumatoid arthritis, systemic lupus erythematosus, and ANCA-associated vasculitis. This survey of the testing practices of 575 US rheumatologists indicates that laboratory tests are frequently used for this purpose, and that test results are most often used to confirm clinical impressions, rather than as independent guides for treatment.

Sultan A. Bahabri, Wafaa M. Suwairi, Ronald M. Laxer, Alexander Polinkovsky, Abdullah A. Dalaan, and Matthew L. Warman 730

This report delineates the clinical features of the autosomal recessive camptodactyly-arthropathy-coxa vara-pericarditis syndrome. Although the syndrome is rare, patients frequently present to the clinical rheumatologist because of unexplained joint swelling and deformity. The synovial hyperplasia seen on biopsy resembles that of rheumatoid arthritis, although CACP lacks the inflammatory cell infiltration typical of rheumatoid arthritis. Also of importance to clinicians is the demonstration of the application of molecular genetic approaches to the study of rare rheumatologic disorders, for which the number of patients may be limited.

Julian Thumboo and J. Desmond O'Duffy 736

This prospective cohort study showed no occurrence of significant patient-reported joint or soft tissue hemorrhage following 32 joint or soft tissue aspirations or injections in patients taking warfarin sodium (Coumadin). The risk of significant procedure-related hemorrhage was therefore [gt]10% by the ``rule of threes,'' while diagnostic information and therapeutic benefit were obtained in 53% (8 of 15) and 74% (17 of 23) of procedures, respectively. These results indicate that the risks of carefully performed joint and soft tissue aspirations or injections in patients taking warfarin sodium are low and that clinically useful diagnostic information can be obtained and a satisfactory therapeutic result achieved.