Sanshiro Hashimoto, Morteza Setareh, Robert L. Ochs, and Martin Lotz 1749

This study shows that a subpopulation of chondrocytes expresses Fas and is susceptible to Fas-induced apoptosis. In normal cartilage, Fas-expressing cells are located predominantly in the superficial and midzones; in osteoarthritic cartilage, cells in the deep zone are also Fas positive. Fas ligand is not expressed by chondrocytes. These findings indicate that Fas-mediated chondrocyte apoptosis may contribute to cartilage degradation in arthritis.

Stephen L. Myers, Kenneth D. Brandt, Brian O'Connor, William R. Widmer, and Marjorie Albrecht 1756

This study used dorsal root ganglionectomy followed by transection of the anterior cruciate ligament to create a model of neuropathic arthropathy in dogs. Formation of new periosteal bone on the distal femur and tibia, though not seen in dogs that have undergone anterior cruciate ligament resection alone, was seen in this neuropathic arthropathy model. These results indicate that interruption of sensory input from the limb may affect the regulation of osteogenesis in the mechanically unstable joint.

I. Meulenbelt, C. Bijkerk, S. C. M. de Wildt, H. S. Miedema, H. A. Valkenburg, F. C. Breedveld, H. A. P. Pols, J. M. Te Koppele, V. F. G. Sloos, A. Hofman, P. E. Slagboom, and C. M. van Duijn 1760

In this study, radiographically evident hip OA in men was found to be associated with the CRTM gene locus, but not with the CRTL1 gene. Identification of genes affecting OA in the population may provide a molecular basis for a better understanding of the mechanisms underlying OA and its joint- and sex-specific characteristics and may enable further subclassification of OA patients.

Keld Ostergaard, Jorgen Petersen, Claus B. Andersen, Klaus Bendtzen, and Donald M. Salter 1766

OA is the world's most common joint disease and a major cause of chronic disability. Much data regarding the histopathology of OA is based on a histologic/histochemical grading system developed in 1971. The present study assessed this grading system and showed that its reproducibility and validity were inadequate. It is hoped that this finding will prompt discussion about the relevance and reliability of methods presently used in research on cartilage in general and OA in particular.

David L. Boyle, Zuoning Han, Joni L. Rutter, Constance E. Brinckerhoff, and Gary S. Firestein 1772

Adenosine receptor stimulation decreases collagenase gene expression in interleukin-1-stimulated synoviocytes. The results of the present studies demonstrate that this is the result of a decrease in collagenase mRNA half-life. This finding could lead to a novel therapeutic target for arthritis.

Ian Gotis-Graham, Philip J. Hogg, and H. Patrick McNeil 1780

This study shows that thrombospondin 1, a recently recognized proteinase inhibitor, is present in synovial tissue. In rheumatoid synovium, thrombospondin 1 expression correlates with the numbers of elastase- and cathepsin G-positive cells. Taken together with the known in vitro finding that thrombospondin 1 inhibits elastase and cathepsin G, these results indicate that thrombospondin 1 may act as an inhibitor of these enzymes in rheumatoid synovium.

Zhinan Yin, Jurgen Braun, Lucia Neure, Peihua Wu, Lanzhen Liu, Ulrich Eggens, and Joachim Sieper 1788

This study gives important information about the cytokine pattern and its regulation in the joints of patients with reactive arthritis. The results of this study should help to clarify the pathogenesis of reactive arthritis and might also lead to new treatment strategies.

F. C. Hall, M. A. Brown, D. E. Weeks, S. Walsh, A. Nicod, S. Butcher, L. J. Andrews, and B. P. Wordsworth 1798

In RA, T lymphocytes infiltrate synovium and are believed to be involved in initiation and probably also maintenance of disease. If T cells of certain specificities could be identified as pathogenic in RA, specific biologic therapeutic agents could be designed, obviating the need for the current immunosuppressive disease-modifying drugs. This study explored the possibility that genes encoding the T cell receptor α or β chain predispose to disease, and revealed no significant evidence that these genes play a major role in susceptibility.

Frank Jung, Gunter Neuer, and Friedlinde A. Bautz 1803

A high proportion of ANA found in sera from children with pauciarticular-onset JRA are directed against the high mobility group nucleosomal proteins, HMG-1, HMG-2, and HMG-17. This study demonstrates that the linker region of the HMG-1/2 box domains is a focal point for autoimmune responses in pauciarticular JRA patients, suggesting that a lysine-rich octapeptide constitutes an important autoantigenic epitope in the etiology of JRA.

H. Michael Belmont, David Levartovsky, Archana Goel, Ashok Amin, Ralph Giorno, John Rediske, Mary Louise Skovron, and Steven B. Abramson 1810

NO production is increased in patients with SLE, and 2 potential sources of excessive NO are activated endothelial cells and keratinocytes via up-regulated inducible nitric oxide synthase. This study provides insights into the mechanisms of vascular injury in SLE, and identifies endothelial cells and NO as potential targets of future, novel therapies for exacerbated SLE.

J. P. Mattei, D. Bendahan, M. Erkintalo, J. R. Harle, P. J. Weiller, H. Roux, and P. J. Cozzone 1817

P-31 MRS is a noninvasive technique that allows evaluation of muscle inflammation through the study of muscle energetics. This technique was used to study a group of patients with PMR, and no evidence of muscle energetics abnormalities was found.

Matthew A. Brown, L. Gail Kennedy, Alex J. MacGregor, Chris Darke, Emma Duncan, Jane L. Shatford, Andrew Taylor, Andrei Calin, and Paul Wordsworth 1823

AS is a common rheumatologic disorder with a strong tendency to recur within families. This study documents the extent to which this recurrence is determined by genetic and environmental factors. The contribution of HLA-B27 to AS susceptibility is shown to be a minority of the overall genetic contribution, which has implications regarding the use of B27 testing in clinical practice.

Joel M. Kremer, Graciela S. Alarcon, Michael E. Weinblatt, Mari V. Kaymakcian, Maurizio Macaluso, Grant W. Cannon, William R. Palmer, John S. Sundy, E. William St. Clair, Ronald W. Alexander, G. J. Walker Smith, and Constantine A. Axiotis 1829

MTX-associated lung injury is the most common serious complication of this agent when used to treat patients with rheumatoid arthritis. The clinical, radiographic, laboratory, and histopathologic features of this reaction are described in the present report, and a current best practice approach is suggested for clinicans who must assess pulmonary symptoms in rheumatoid arthritis patients who are on a regimen of MTX.

Dennis McGonagle, Andrew Rawstron, Stephen Richards, John Isaacs, Howard Bird, Andrew Jack, Gareth Morgan, and Paul Emery 1838

This study demonstrates that in patients with longstanding active RA, G-CSF alone can mobilize hematopoietic progenitor cells in numbers suitable for harvesting. No flare in disease activity can be seen following this regimen. This approach obviates the need to use cyclophosphamide for stem cell mobilization, and allows the collection of hematopoietic progenitor cells (with the potential for autologous stem cell transplantation) to be conducted more safely.

C. Michael Stein, Theodore Pincus, David Yocum, Peter Tugwell, George Wells, Oscar Gluck, Gunnar Kraag, Helen Torley, John Tesser, Robert McKendry, and Raye H. Brooks, for the Methotrexate-Cyclosporine Combination Study Group 1843

Few combination therapies have proven efficacy in refractory RA, but one such combination that has been shown to be effective in a clinical trial is CSA-MTX. However, there have not been any long-term data on the efficacy and safety of this combination therapy given long term (beyond 6 months) in RA. The present report provides information regarding the efficacy and safety of CSA-MTX in RA patients treated for up to 48 weeks.

Carol A. Wallace and David D. Sherry 1852

Four children with severe systemic-onset JRA were aggressively and successfully treated with intravenous pulse cyclophosphamide and methylprednisolone monthly. This report presents another treatment strategy that can be helpful in selected children with severe, destructive JRA in whom all other treatments have been unsuccessful.

Mikkel Ostergaard, Michael Stoltenberg, Preben Lovgreen-Nielsen, Birgitte Volck, Claus Hjorth Jensen, and Ib Lorenzen 1856

This study compares synovial membrane and joint effusion volumes, determined by MRI, with macroscopic and microscopic synovial pathology in 17 RA and 25 OA knees. A significant correlation with synovial inflammation is reported, and this and other factors influencing the synovial membrane volumes are discussed. MRI-determined synovial membrane and effusion volumes may be sensitive predictors and/or markers of treatment outcome and disease activity in RA.

Katy Wong, Dafna D. Gladman, Janice Husted, Jennifer A. Long, and Vernon T. Farewell 1868

This is the first systematic study of mortality in psoriatic arthritis. The study looked at causes of death as well as risk of death in a cohort of 428 outpatients with psoriatic arthritis in comparison with the general population of Ontario. A 62% increased risk of death was observed. The results demonstrate that psoriatic arthritis is not a benign condition.

Sherine E. Gabriel, Jayasimha Sunku, Carlo Salvarani, W. Michael O'Fallon, and Gene G. Hunder 1873

Retrospective evaluation of a population-based cohort of patients with PMR revealed that adverse events associated with corticosteroid and NSAID therapy developed at a significantly higher rate than expected. Long-term use of these therapies to treat patients with PMR should be reevaluated, and safer therapeutic alternatives should be considered.

Avi Livneh, Pnina Langevitz, Deborah Zemer, Nurit Zaks, Salim Kees, Tzvi Lidar, Amiel Migdal, Shai Padeh, and Mordechai Pras 1879

This work proposes new sets of criteria that may facilitate and increase the reliability of the diagnosis of familial Mediterranean fever in patients who present with attacks of painful manifestations accompanied by fever. These new criteria sets have sensitivity and specificity of >95% and >97%, respectively.

Joseph V. Campellone, David Lacomis, Michael J. Giuliani, and Chester V. Oddis 1886

This study demonstrates that a minimally invasive technique of needle muscle biopsy offers a safe, convenient method of acquiring adequate tissue for the histopathologic diagnosis of inflammatory myopathy. This technique is considerably less expensive than open muscle biopsy and has a diagnostic yield comparable with that of more invasive forms of needle biopsy. Since this method is well-tolerated by patients and can be performed in an outpatient setting, clinical rheumatologists may wish to consider utilizing this diagnostic procedure as a primary technique in patients with suspected inflammatory myopathy.