bluuebunny/crossref_metadata_2025 huggingface dataset:
Magnetic resonance imaging in systemic lupus erythematosus patients without a history of neuropsychiatric lupus erythematosus
Authors: Jarek Mark J. , West Sterling G. , Baker Michael R. , Rak Kevin M.
Published: February 2007

Objective. To determine the prevalence of magnetic resonance imaging (MRI) lesions in systemic lupus erythematosus (SLE) patients without a history of neuropsychiatric symptoms and to correlate any MRI abnormalities with the patient's other disease manifestations or treatment.

Methods. Prospective study of 32 consecutive patients with SLE without a history of neuropsychiatric symptoms, from inpatient and outpatient rheumatology services, who underwent MRI scan during a 3‐year period.

Results. Five patients had MRI abnormalities consisting of white matter lesions or periventricular hyperintensities; this is similar to the prevalence of these abnormalities in the general population.

Conclusion. The prevalence of silent brain MRI abnormalities is not increased in SLE patients who do not have a history of neuropsychiatric manifestations.
Increased usage of vβ2 and vβ6 in rheumatoid synovial fluid t cells
Authors: Cooper Sheldon M. , Roessner Karen D. , Naito‐Hoopes Mikako , Howard Diantha B. , Gaur Lakshmi K. , Budd Ralph C.
Published: February 2007

Objective. To determine if the T cell antigen receptor Vβ usage of unstimulated rheumatoid arthritis (RA) synovial fluid (SF) T cells is biased compared with those in peripheral blood (PB).

Methods. Freshly isolated, matched synovial fluid and peripheral blood T cells were analyzed for Vβ gene expression using quantitative polymerase chain reaction (PCR) methods. Ten synovial fluid samples from the knees of 7 patients with RA were studied. The PCR assay used 26 Vβ primers with a constant region Cβ primer, and 2 Cα primers that co‐amplified a product that served as an internal standard. Cycle number and complementary DNA content were controlled to ensure the linear accumulation of PCR products. Labeled products were separated on 10% polyacrylamide gels and counted with a Betascope blot analyzer.

Results. There were consistent differences between the Vβ gene usage of SF and PB T cells directly isolated from patients with RA, regardless of HLA–DR haplotype. In all synovial specimens, Vβ2 was increased relative to the peripheral blood, while Vβ13.1 and Vβ13.2 were decreased. Vβ6 and Vβ21 were increased in 9 of the 10 synovial samples. Analyses of bilateral SF specimens from 2 subjects and serial specimens from the same knee of 1 subject revealed virtually identical patterns in each patient. The SF Vβ bias was not solely due to differences in the proportion of CD4+ and CD8+ cells, because the CD4:CD8 ratios in SF and PB were similar. However, Vβ gene usage of separated CD4+ and CD8+ synovial T cells showed that Vβ2 and Vβ6 were more highly expressed on CD4 cells.

Conclusion. Freshly isolated synovial T cells from inflamed (not end‐stage) knees of patients with RA have a remarkably consistent biased Vβ gene usage compared with PB T cells. Vβ2 and Vβ6 are uniformly increased, and this increase is primarily in CD4+ T cells. The same Vβ bias in the SF T cells of several RA patients suggests that shared antigens may be stimulating the T cell response.
Elevated expression of cd80 (b7/bb1) and other accessory molecules on synovial fluid mononuclear cell subsets in rheumatoid arthritis
Authors: Ranheim Erik A. , Kipps Thomas J.
Published: February 2007

Objective. To assess the expression of important accessory molecules such as CD80 (B7/BB1) and CD54 (intercellular adhesion molecule 1) on potential antigen‐presenting cells (APC) in the synovial fluid (SF) of patients with rheumatoid arthritis (RA).

Methods. The level of expression of various accessory molecules on T cells, monocytes, and CD5+ or CD5– B cells from RA SF was compared, by multiparameter flow cytometric analysis, with the expression on peripheral blood (PB) mononuclear cells from the same patients and from normal controls. The functional significance of increased expression of these accessory molecules was assessed by the ability of the different cell populations to stimulate T cells in the mixed lymphocyte reaction.

Results. Monocytes, T cells, and B cells isolated from the SF of inflamed joints of patients with RA expressed significantly higher levels of CD80 and CD54 than those from the PB of RA patients or normal controls. CD11b and CD11c expression also were increased on SF B cells, while SF monocytes exhibited enhanced levels of CD40. Further, we found that the elevated CD80 and CD54 levels in RA SF cells may enhance the capacity of these cells to act as stimulatory APC.

Conclusion. This is the first demonstration that specific cell subsets constitutively express increased levels of CD80 at a site of autoimmune pathology, which could potentially contribute to the initiation or maintenance of autoimmune disease.
Inhibition of human fibroblast adhesion by cartilage surface proteoglycans
Authors: Noyori Koji , Jasin Hugo E.
Published: February 2007

Objective. Recent studies from our laboratory have identified the nonaggregating, collagen‐binding proteoglycans, fibromodulin (FM) and decorin, and fibronectin (Fn) and albumin, noncovalently bound at the articular surface of cartilage. The present studies were designed to investigate the interactions between these cartilage macromolecules and the underlying collagen matrix and their role as a barrier to cell adhesion in intact articular cartilage.

Methods. Cell adhesion studies were carried out with human skin fibroblasts incubated on the articular surface of bovine cartilage explants and on collagencoated and/or Fn‐coated plastic surfaces. Interactions of collagen and Fn with either FM or decorin were studied by radioimmunoassay of the same surfaces, using specific antibodies.

Results. The present studies show that 1) Fn is immunologically detectable at the intact articular surface of cartilage; 2) fibroblast adhesion to Fn is inhibited by cartilage surface extract proteins and by purified FM, but not by purified decorin; 3) FM has binding affinity for Fn; 4) FM interferes with the binding of a monoclonal antibody specific for the cell‐binding domain of Fn; and 5) FM and decorin inhibit collagendependent fibroblast adhesion.

Conclusion. These results indicate that the small proteoglycans at the normal articular surface may act as a barrier to cell adhesion. Since protective cartilage surface proteins break down readily after the induction of acute arthritis in experimental animals, and in rheumatoid cartilage specimens, it is postulated that proteolytic degradation of the surface proteoglycans may be responsible for increasing cell adhesion to, and subsequent pannus invasion of, articular cartilage in inflammatory arthritis.
A new model for rheumatoid arthritis generated by engraftment of rheumatoid synovial tissue and normal human cartilage into scid mice
Authors: Geiler Thomas , Kriegsmann JÖUrg , Keyszer Gernot M. , Gay Renate E. , Gay Steffen
Published: February 2007

Objective. A new animal model was used to study the interaction between rheumatoid synovial cells and cartilage and to explore the cellular basis of rheumatoid joint destruction.

Methods. Fresh synovial tissue derived from patients with rheumatoid arthritis was implanted with normal human cartilage into SCID mice, either subcutaneously or under the renal capsule, for up to 304 days. The implants were analyzed by light and electron microscopy, as well as by immunohistochemistry and in situ hybridization.

Results. Human synovial tissue and cartilage implanted in SCID mice are maintained by the animals for up to 304 days. After 35 days, focal erosions occur at the site of attachment of synovial lining cells to the cartilage. After 105 days, a pannus‐like formation, consisting of proliferating synovial fibroblast‐like cells invading the cartilage, is observed. The fibroblast nature of these cells was supported by observation of only focal expression of the macrophage markers CD14 and CD68. Cells at the immediate site of cartilage destruction express messenger RNA for cathepsin L, whereas cathepsin D messenger RNA was detected in subsynovial regions away from the site of destruction. The human origin of the tissue involved in cartilage destruction was demonstrated using monoclonal antibodies to HLA‐ABC and human type IV collagen.

Conclusion. The present approach introduces a novel in vivo model of rheumatoid arthritis for the study of the molecular and cellular mechanisms of rheumatoid joint destruction at sites of synovial attachment to cartilage. In this model, the SCID mouse acts as a useful host for studying the properties of rheumatoid synovium in the absence of circulating human blood components.
Nucleosome‐restricted antibodies are detected before anti‐dsdna and/or antihistone antibodies in serum of mrl‐mp lpr/lpr and +/+ mice, and are present in kidney eluates of lupus mice with proteinuria
Authors: Amoura Zahir , Chabre Henri , Koutouzov Sophie , Lotton Chantal , Cabrespines Alban , Bach Jean‐Françlois , Jacob Laurent
Published: February 2007

Objective. To compare the humoral response to nucleosomes with the response to their individual components (double‐stranded DNA [dsDNA] and histones) and to assess the involvement of antinucleosome antibodies in immune deposits in the kidney of MRL mice.

Methods. We used enzyme‐linked immunosorbent assays of sera and kidney eluates for antibody activity against purified nucleosomes, dsDNA, and histones.

Results. Antinucleosome antibodies emerged before anti‐dsDNA and antihistone antibodies. A fraction of antinucleosome antibodies reacted exclusively with nucleosomes and not with their components, dsDNA and histones. These nucleosome‐restricted antibodies were detected in the proteinuric MRL mouse kidney eluate.

Conclusion. Our findings support the notion that nucleosomes play a major role in the emergence of antinuclear autoantibodies and that antinucleosome antibodies might be involved in the nephritogenic process in murine lupus.
Concentration of autoantibodies to native 60‐kd ro/ss‐a and denatured 52‐kd ro/ss‐a in eluates from the heart of a child who died with congenital complete heart block
Authors: Reichlin Morris , Brucato Antonio , Frank Mark B. , Maddison Peter J. , Mccubbin Victoria R. , Wolfson‐Reichlin Marianne , Lee Lela A.
Published: February 2007

Objective. To determine the serologic specificity of acid eluates from tissues of a child who died with congenital complete heart block (CCHB).

Methods. Tissues were extracted, acid eluted, and the IgG and antibody titers determined on the eluates by enzyme‐linked immunosorbent assay.

Results. Antibodies to native 60‐kd and denatured 52‐kd Ro/SS‐A were found to be enriched only in the heart eluate, and not in the eluates from brain, kidney, and skin.

Conclusion. These findings indicate a major role for anti–native 60‐kd Ro/SS‐A in the immunopathogenesis of CCHB.
Interleukin‐4 inhibits bone resorption through an effect on osteoclasts and proinflammatory cytokines in an ex vivo model of bone resorption in rheumatoid arthritis
Authors: Miossec Pierre , Chomarat Pascale , Dechanet Julie , Moreau Jean‐François , Roux Jean‐Paul , Delmas Pierre , Banchereau Jacques
Published: February 2007

Objective. To assess local bone resorption in the context of rheumatoid synovitis and its modulation by interleukin‐4 (IL‐4).

Methods. We developed an ex vivo model of bone resorption using juxtaarticular samples of bone obtained during joint surgery. We studied the histomorphometric parameters of bone resorption and the regulation of the production of IL‐6, leukemia inhibitory factor (LIF), and the collagen cross‐link pyridinoline, which is released during bone resorption in vivo.

Results. This was a sensitive and dynamic model of bone resorption. The bone samples produced high levels of pyridinoline and as much cytokine as synovium pieces obtained from the same joint. IL‐4 induced a 70% reduction of IL‐6 and LIF production by bone pieces and reduced pyridinoline levels. Histomorphometric studies performed on bone samples indicated a 35% increase in the mean total bone area after 7 days of treatment with IL‐4. More importantly, with IL‐4, osteoclasts were not detectable in the bone sections.

Conclusion. The inhibitory effect of IL‐4 on bone resorption extends our knowledge of its antiinflammatory properties and suggests that the inflammatory cytokine imbalance in rheumatoid synovium also contributes to defects in bone resorption in RA.
Relationship between α1‐antitrypsin inactivation and tumor necrosis factor α concentration in the synovial fluid of patients with rheumatoid arthritis
Authors: Chidwick Keith , Whichelow Catherine E. , Zhang Zhi , Fairburn Kevin , Sachs John A. , Blake David R. , Winyard Paul G.
Published: February 2007

Objective. To examine the relationship between α1‐antitrypsin (α1AT) specific activity and tumor necrosis factor α (TNFα) concentration in synovial fluid from 48 patients with rheumatoid arthritis.

Methods. The specific activity of α1AT was calculated from the measurement of α1AT concentration (by rocket immunoelectrophoresis) and elastase inhibitory capacity. TNFα was detected by enzyme‐linked immuno‐sorbent assay.

Results. TNFα concentrations correlated with the extent of α1AT inactivation.

Conclusion. Our findings are consistent with a role of elastase in TNFα release within the inflamed joint.
Doxycycline disrupts chondrocyte differentiation and inhibits cartilage matrix degradation
Authors: Cole Ada A. , Chubinskaya Susan , Luchene Lawrence J. , Chlebek Kim , Orth Michael W. , Greenwald Robert A. , Kuettner Klaus E. , Schmid Thomas M.
Published: February 2007

Objective. The effects of doxycycline were tested in an in vitro system in which the cartilages of embryonic avian tibias are completely degraded.

Methods. Tibias were cultured with 5, 20, or 40 μg/ml doxycycline. Control tibias were cultured without doxycycline. Conditioned media and tissue sections were examined for enzyme activity and matrix loss.

Results. Cartilages were not resorbed in the presence of doxycycline, whereas control cartilages were completely degraded. Collagen degradation was reduced in association with treatment with doxycycline at all doses studied. Higher concentrations of doxycycline reduced collagenase and gelatinase activity and prevented proteoglycan loss, cell death, and deposition of type X collagen in the cartilage matrix; in addition, treatment with doxycycline at higher concentrations caused increases in the length of the hypertrophic region.

Conclusion. The effects of doxycycline extend beyond inhibition of the proteolytic enzymes by stimulating cartilage growth and disrupting the terminal differentiation of chondrocytes.
Granzyme‐positive cytotoxic cells are specifically increased in early rheumatoid synovial tissue
Authors: Tak Paul P. , Kummer J. Alain , Hack C. Erik , Daha Mohamed R. , Smeets Tom J. M. , Erkelens G. Wilhelmina , Meinders A. Edo , Kluin Philip M. , Breedveld Ferdinand C.
Published: February 2007

Objective. To define the expression and the phenotype of granzyme (Gran) A and B positive cytotoxic cells in synovial tissue (ST) from patients with rheumatoid arthritis (RA) with respect to disease duration and activity.

Methods. Using antibodies against GranA and GranB, which serve as markers of activated natural killer (NK) cells and cytotoxic T lymphocytes, ST sections from 10 patients with early RA, 10 patients with longstanding RA, and 10 patients with osteoarthritis were examined. The phenotype of Gran+ cells was determined with double‐labeling techniques.

Results. Gran+ cells, the majority of which were NK cells, were found in ST from patients in all groups. Several of these cells did not express the surface markers CD16, CD56, and CD57. The highest ST expression of GranB was found in patients with early RA. In RA patients, there was a positive correlation of GranB expression with serum levels of acute‐phase reactants, but not with histologic scores for inflammation.

Conclusion. Gran+ cells are mainly NK cells, a substantial proportion of which do not express conventional NK cell surface markers. GranB expression is specifically increased in the synovial tissues of patients with RA of short duration.
Noninvasive imaging of e‐selectin expression by activated endothelium in urate crystal–induced arthritis
Authors: Chapman Peter T. , Jamar François , Harrison Andrew A. , Binns Richard M. , Peters A. Michael , Haskard Dorian O.
Published: February 2007

Objective. To assess the expression of the cytokine‐inducible endothelial leukocyte adhesion molecule E‐selectin during the evolution of urate crystal–induced arthritis, using a recently described radiolabeled monoclonal antibody (MAb) imaging technique.

Methods. Monosodium urate (MSU) crystals and saline alone were injected respectively into the right (inflamed) and left (control) knees of 3 young pigs. Four hours later, 111In‐labeled 1.2B6 F(ab')2 (anti–E‐selectin MAb) and 125I‐labeled MOPC 21 F(ab')2 (control MAb) were injected intravenously. Uptake of 1.2B6 in inflamed and control joints was assessed by scintigraphy 7 and 24 hours after intraarticular injection of MSU crystals. Immunohistochemistry studies and radioactivity counting of tissues were performed postmortem to confirm the observations from scintigraphy.

Results. MAb 1.2B6 F(ab')2 scintigraphic images of the knees revealed a significantly increased uptake in the right (inflamed) knee at 7 and 24 hours postinjection, particularly over the joint space. These in vivo images were consistent with E‐selectin expression in the inflamed tissue detected by immunohistochemistry and with radioactivity counts postmortem. The synovial localization ratio (inflamed:control synovium counts) was 25.4 ± 9.7 (mean ± SD) for the anti–E‐selectin MAb compared with 2.5 ± 0.9 for the control MAb (P < 0.05, by paired Student's t‐test).

Conclusion. E‐selectin is expressed by synovial endothelium during the evolution of urate crystal–induced arthritis and can be detected noninvasively using a radiolabeled MAb. This E‐selectin imaging technique has considerable potential for the noninvasive assessment of endothelial activation in arthritis and other inflammatory rheumatic diseases.
Combined treatment with terbutaline and aminophylline inhibits experimental amyloidosis in mice
Authors: Brandwein Sydney R. , Sipe Jean D. , Cohen Alan S.
Published: February 2007

Objective. To investigate the effects of drugs known to elevate adenosine 3':5'‐cyclic monophosphate (cAMP) on experimental amyloidosis.

Methods. A β2‐agonist, terbutaline, and a phosphodiesterase inhibitor, aminophylline, were administered in combination in a mouse model of amyloidosis induced by inflammatory stimulation with silver nitrate. Amyloidosis was quantitated by radioimmunoassay for splenic amyloid A (AA) protein.

Results. At the doses selected, aminophylline/ terbutaline inhibited splenic amyloid deposition more potently than did colchicine, a known inhibitor of amyloidosis.

Conclusion. Drugs known to elevate cAMP inhibit experimental mouse AA amyloidosis.
Serum levels of collagenase, stromelysin‐1, and timp‐1
Authors: Manicourt Daniel‐Henri , Fujimoto Noboru , Obata Ken'Ichi , Thonar Eugene J.‐M. A.
Published: February 2007

Objective. To measure serum levels of collagenase (MMP‐1), stromelysin‐1 (MMP‐3), and tissue inhibitor of matrix metalloproteinases‐1 (TIMP‐1) in normal subjects and in patients with osteoarthritis (OA), and to assess how these correlate with biochemical and clinical indicators of disease activity in OA.

Methods. Specific immunoassays were used to measure MMPs, TIMP‐1, and antigenic keratan sulfate (KS). The total area of cartilage affected by the disease was measured (expressed as an articular index).

Results. In the normal population (n = 118), the serum concentration of MMP‐3, but not of MMP‐1 or TIMP‐1, increased with age and was approximately 2 times higher in males than in females. In the OA patients (n = 33), the serum levels of MMP‐3, but not of MMP‐1 or TIMP‐1, were significantly elevated and correlated strongly with the articular index but poorly with objective and subjective functional capacity scores as well as with serum levels of antigenic KS and systemic parameters of inflammation.

Conclusion. These findings illustrate the importance of matching patients and normal controls for age and sex in further studies of MMP‐3 and are consistent with the hypothesis that MMP‐3 might play an important role in the degradation of joint cartilage in OA. Further, serum levels of MMP‐3 may prove useful for monitoring therapy for OA.
Treatment‐free remission in severe systemic lupus erythematosus following synchronization of plasmapheresis with subsequent pulse cyclophosphamide
Authors: Euler Hans H. , Schroeder Johann O. , Harten Pontus , Zeuner Rainald A. , Gutschmidt Hans J.
Published: February 2007

Objective. To investigate the effect of an intensified treatment protocol synchronizing plasmapheresis with subsequent pulse cyclophosphamide for severe systemic lupus erythematosus (SLE).

Methods. A protocol of plasmapheresis (3 x 60 ml/kg) and subsequent high‐dose pulse cyclophosphamide (36 mg/kg) followed by 6 months of peroral immunosuppression was used to treat 14 patients with severe SLE.

Results. Rapid improvement was achieved in all patients. Immunosuppressants, including corticosteroids, were withdrawn at month 6 in 12 patients. Eight patients continued without treatment for a mean observation period of 5.6 years (46–91 months).

Conclusion. The results demonstrate that treatment‐free clinical remission can be achieved in some patients with severe SLE.
Outcome of polyarteritis nodosa and churg‐strauss syndrome
Authors: Abu‐Shakra Mahmoud , Smythe Hugh , Lewtas Jody , Badley Elizabeth , Weber Deborah , Keystone Edward
Published: February 2007

Objective. To compare outcome in patients with polyarteritis nodosa (PAN) and patients with Churg‐Strauss syndrome (CSS) followed up at a single center.

Methods. A retrospective data review of 13 patients with PAN and 12 patients with CSS who were followed up at a vasculitis clinic. Outcome measures included a global damage index, disability and pain dimensions of the Health Assessment Questionnaire, and mortality rate.

Results. Compared with patients with CSS, patients with PAN had a significantly higher mean damage index score (5.15 versus 2.42; P = 0.011), a higher disability score (1.09 versus 0.16; P = 0.007), and a higher pain score (1.04 versus 0.01; P = 0.017). Patients with PAN had more relapses (relative risk = 5.07; P < 0.000) and a higher mortality rate (31%) compared with patients with CSS (8%).

Conclusion. PAN and CSS differ in their morbidity and mortality; therefore, they should be considered as distinct clinical entities.
COLCHICINE TREATMENT OF AA AMYLOIDOSIS OF FAMILIAL MEDITERRANEAN FEVER
Authors: Livneh Avi , Zemer Deborah , Langevitz Pnina , Laor Arie , Sohar Ezra , Pras Mordechai
Published: February 2007

Objective. To elucidate factors possibly influencing the outcome of colchicine therapy in patients with amyloidosis of familial Mediterranean fever (FMF).

Methods. Retrospective analysis of data abstracted from the charts of all 68 FMF patients with amyloidosis who presented during the study period (1974–1992) with proteinuria (≥0.5 gm/24 hours) and creatinine values ≤2.5 mg/dl, received colchicine, and were followed up for ≥5 years.

Results. At the end of the study period, kidney disease had worsened in 31 patients and remained stable in 22. Proteinuria had regressed in 15 patients. Deterioration was related to initial serum creatinine values ≥1.5 mg/dl (P ≤ 0.01) and to mean colchicine dosage ≤1.5 mg/day (P ≤ 0.001). The 3 groups were comparable in terms of initial urinary protein levels, duration of proteinuria, presence of hypertension, occurrence of febrile attacks, sex distribution, and proportion of non‐compliant patients.

Conclusion. The therapeutic dosage of colchicine for amyloidosis of FMF is >1.5 mg/day. This dosage is effective only in patients with initial serum creatinine levels <1.5 mg/dl.
Role of interleukin‐1, tumor necrosis factor α, and interleukin‐6 in cartilage proteoglycan metabolism and destruction effect of in situ blocking in murine antigen‐ and zymosan‐induced arthritis
Authors: Loo Fons A. J. Van De , Joosten Leo A. B. , Van Lent Peter L. E. M. , Arntz Onno J. , Van Den Berg Wim B.
Published: February 2007

Objective. To determine the involvement of interleukin‐1 (IL‐1), tumor necrosis factor (TNF), and IL‐6 in the cartilage pathology of murine antigen‐induced arthritis (AIA) and zymosan‐induced arthritis (ZIA).

Methods. Arthritis was induced by intraarticular injection of zymosan in naive mice or by subcutaneous injection of methylated bovine serum albumin in sensitized animals. Mini‐osmotic pumps releasing human recombinant IL‐1 receptor antagonist (IL‐1ra) protein were implanted intraperitoneally 2 days before arthritis induction, and neutralizing antibodies directed against murine IL‐1α, IL‐1β, TNFα, or IL‐6 were administered 1 day before. Proteoglycan (PG) synthesis and degradation were assessed in patellar cartilage.

Results. Murine IL‐1α and IL‐1β injected intraarticularly at doses of 0.1–100 ng suppressed chondrocyte PG synthesis. The highest dose of TNF tested (100 ng) decreased PG synthesis marginally. In contrast, the maximum dose of IL‐6 (1 μg) stimulated PG synthesis 2 days after injection. Treatment of AIA with neutralizing monoclonal antibodies against either TNFα or IL‐6 did not reduce either the PG degradation or the suppression of its synthesis. However, treatment with anti‐IL‐1 (α + β) polyclonal antibodies totally prevented PG suppression, although the initial breakdown of PG was unaffected. This effect was confirmed when IL‐1ra was administered in high doses. Moreover, treatment of ZIA with anti‐IL‐1 (α + β), but not with anti‐TNF, resulted in normal PG synthesis, confirming the key role played by IL‐1 in the inhibition of PG synthesis. Treatment of AIA with anti‐IL‐1 did not affect inflammation during the acute phase, but a significant reduction of ongoing inflammation was noted at day 7, and there was a marked reduction in the loss of cartilage PG.

Conclusion. The suppression of PG synthesis in both ZIA and AIA in mice is due to the combined local action of IL‐1 (α + β), and neither IL‐6 nor TNF is involved. Moreover, the normalization of PG synthesis brought about by blocking of IL‐1 ameliorates the cartilage damage associated with AIA.
Correlation of soluble adhesion molecules in the peripheral blood of scleroderma patients with their in situ expression and with disease activity
Authors: Gruschwitz Matthias S. , Hornstein Otto P. , Driesch Peter Von Den
Published: February 2007

Objective. To correlate serum levels of the soluble adhesion molecules intercellular adhesion molecule 1 (ICAM‐1), vascular cell adhesion molecule 1 (VCAM‐1), E‐selectin, and P‐selectin with (a) clinical disease activity and progression and (b) the in situ expression and distribution of these adhesion molecules in lesional skin, in patients with systemic sclerosis (SSc).

Methods. Serum samples from 12 SSc patients and 36 healthy controls were examined by enzymelinked immunosorbent assay. Immunohistologic staining was carried out on cryostat sections of lesional skin.

Results. Patients whose SSc was in the early inflammatory stage or who had prominent disease progression showed elevated serum levels of soluble adhesion molecules. Serum levels correlated positively with the expression of these molecules on endothelial cells and fibroblasts in lesional skin.

Conclusion. Serum levels of soluble ICAM‐1, VCAM‐1, P‐selectin, and, to a lesser degree, E‐selectin correlate well with their in situ activity and with clinical disease activity. These parameters therefore provide a useful tool for the characterization of disease stage, progression, and prognosis in SSc.
Antigen‐based heteropolymers: a potential therapy for binding and clearing autoantibodies via erythrocyte cr1
Authors: Ferguson Polly J. , Reist Craig J. , Martin Edward N. , Johnson Cyd , Greene Kirsten L. , Kuhn Susan , Niebur Joann , Emlen Woodruff , Taylor Ronald P.
Published: February 2007

Objective. To determine if complexes containing monoclonal antibodies to CR1 cross‐linked with antigen (antigen‐based heteropolymers [AHP]) can bind the corresponding autoantibody to primate erythrocyte CR1 and promote autoantibody clearance from the circulation.

Methods. AHP were constructed by cross‐linking double‐stranded DNA (dsDNA) to monoclonal antibodies to CR1. The ability of AHP to facilitate binding of human anti‐dsDNA antibodies to primate erythrocytes was studied in vitro using a variety of radioimmunoassays (including Farr assays), enzyme immunoassays, and fluorescence‐activated cell sorting. In addition, we used a monkey model to study in vivo the AHP‐mediated clearance of passively infused human anti‐dsDNA antibodies.

Results. Large amounts of lupus IgG anti‐dsDNA antibodies can be specifically bound to human erythrocytes via the complexes, and studies in 2 rhesus monkeys indicate that the erythrocyte‐bound antibodies are rapidly cleared from the circulation.

Conclusion. This methodology may allow for development of a new therapy to facilitate autoantibody clearance in autoimmune disease.
Serum cytokines in juvenile rheumatoid arthritis: correlation with conventional inflammation parameters and clinical subtypes
Authors: Mangge Harald , Kenzian Harald , Gallistl Siegfried , Neuwirth Gudrun , Liebmann Peter , Kaulfersch Wilhelm , Beaufort Friedrich , Muntean Wolfgang , Schauenstein Konrad
Published: February 2007

Objective. To examine the usefulness of determining extended serum cytokine profiles in patients with juvenile rheumatoid arthritis (JRA), for the purpose of improving differential diagnosis and monitoring disease activity.

Methods. In a 2‐year prospective study, serum levels of interleukin‐1β (IL‐1β), soluble IL‐2 receptor (sIL‐2R), IL‐6, IL‐8, tumor necrosis factor α (TNFα), and the p55 soluble TNF receptor (sTNFR) were repeatedly determined by enzyme‐linked immunosorbent assay in 40 patients with JRA, 13 patients with postinfectious arthropathies, and 30 healthy controls. The data were compared with conventional parameters of inflammation, such as C‐reactive protein (CRP), iron and hemoglobin levels, erythrocyte sedimentation rate (ESR), white blood cell (WBC) counts, and platelet counts. WBC subsets were analyzed by flow cytofluorometry.

Results. At the first visit and at the peak of inflammatory activity according to CRP levels and/or ESR, serum levels of sIL‐2R, IL‐6, and sTNFR in JRA patients correlated significantly with conventional inflammation indicators, whereas IL‐1β, IL‐8, and TNFα did not. No changes in leukocyte subset distribution were noted. Among the different clinical subtypes of JRA, sIL‐2R, IL‐6, and sTNFR values at the time of the initial visit showed a pattern similar to CRP, whereby patients with systemic disease exhibited by far the highest values. TNFα and IL‐1β were variably elevated in certain JRA subtypes. Patients with postinfectious arthropathies showed elevated levels of CRP, sIL‐2R, TNFα, and sTNFR, which did not differ significantly from levels in the various JRA subtypes with the exception of systemic disease. Detailed analysis of types I and II pauciarticular JRA revealed that levels of CRP, IL‐1β, and TNFα were elevated in patients with type I disease. While these parameters were invariably normal in patients with type II disease, sTNFR and sIL‐2R were still found to be significantly elevated. Followup studies suggested that persistently high sTNFR values are a better indicator of JRA activity than are measurements of other cytokines or CRP.

Conclusion. JRA is associated with significant and consistent changes in serum levels of inflammatory cytokines and soluble receptors. For the clinical monitoring of JRA, determination of levels of sTNFR, and to some extent sIL‐2R, may be particularly useful, since these determinations yield information about subtype and/or activity of disease that is not available from conventional parameters of inflammation.
A genetic association between juvenile rheumatoid arthritis and a novel interleukin‐1α polymorphism
Authors: Mcdowell Tarra L. , Symons Julian A. , Ploski Rafal , FØRre ØYstein , Duff Gordon W.
Published: February 2007

Objective. The genetic factors that predispose to the development of juvenile rheumatoid arthritis (JRA) and its complications are not completely understood. The cytokine interleukin‐1 (IL‐1) has been implicated in the pathogenesis of JRA and other inflammatory diseases. This study was performed to test whether polymorphisms of the IL‐1α gene might be associated with JRA.

Methods. We sequenced the 5' regulatory region (containing the promoter) of the human IL‐1α gene in 18 normal subjects. This revealed a C (IL‐1A1) to T (IL‐1A2) transition polymorphism at position ‐889. We studied the frequencies of both alleles in patients with JRA (n = 269) and controls (n = 99).

Results. An increased gene carriage of IL‐1A2 was found in patients with early‐onset, pauciarticular JRA (EOPA‐JRA; n = 103) compared with controls (0.66 versus 0.49; P = 0.01, odds ratio [OR] = 2.1). Within this subset of JRA, the association with IL‐1A2 was particularly strong in the patients in whom chronic iridocyclitis developed (n = 28) compared with those without chronic iridocyclitis (0.89 versus 0.57; P = 0.002, OR = 6.2). Within the group of EOPA‐JRA patients, IL‐1A2 was also associated with elevation of the erythrocyte sedimentation rate (P < 0.0025).

Conclusion. This is the first report of a cytokine gene association with JRA, and we conclude that IL‐1α itself, or a gene for which the IL‐1α polymorphism is a marker, may contribute to the pathogenesis of EOPA‐JRA and the ocular complications found in this group.
The prevalence of sexual abuse in women with fibromyalgia
Authors: Taylor Mary Lou , Trotter Dana R. , Csuka M. E.
Published: February 2007

Objective. To determine the prevalence of sexual abuse in women diagnosed as having fibromyalgia (FM) compared with controls.

Methods. A self‐administered questionnaire designed to obtain information regarding demographics, health care utilization, and history of sexual and physical abuse was completed by 40 women with FM and by 42 women who had no evidence of connective tissue disease or other major medical condition.

Results. Women with FM reported more physical symptoms and were significantly different on multiple indices of health compared with controls. Twenty‐six FM subjects (65%) reported sexual abuse, in comparison with 22 controls (52%). The prevalence and type of abuse were not significantly different between groups. Sexually abused FM subjects reported significantly more symptoms than did non‐sexually abused FM women, but did not differ in the number of symptoms for which they sought medical treatment.

Conclusion. Sexual abuse does not appear to be a specific factor in the etiology of FM, but is correlated with the number and severity of associated symptoms.
Sexual and physical abuse in women with fibromyalgia syndrome
Authors: Boisset‐Pioro Mathilde H. , Esdaile John M. , Fitzcharles Mary‐Ann
Published: February 2007

Objective. To determine the prevalence of sexual and physical abuse in female patients with fibromyalgia syndrome (FMS), as compared with rheumatic disease control patients.

Methods. Eighty‐three female FMS patients and 161 consecutive female rheumatology (non‐FMS) control patients answered a standardized confidential questionnaire recording previous sexual and physical abuse, drug and alcohol abuse, and eating disorders. Demographic information was collected on age, education, economic status, and cultural group.

Results. Overall abuse was greater in FMS patients than in control patients (53% versus 42%; P not significant). Significant differences were observed for lifetime sexual abuse (17% versus 6%), physical abuse (18% versus 4%), combined physical and sexual abuse (17% versus 5%), and drug abuse (16% versus 3%). There was a trend toward a higher incidence of childhood sexual abuse (37% versus 22%) and of eating disorders (10% versus 3%) in the FMS patient group.

Conclusion. A high frequency of sexual abuse was identified both in control patients and in FMS patients. A statistical association was demonstrated between FMS and the frequency and severity of sexual abuse, and the frequency of physical abuse and drug abuse. These results raise the possibility that abuse may have an effect upon the expression and perpetuation of FMS in adult life.
Renal biopsy findings and clinicopathologic correlations in rheumatoid arthritis
Authors: Helin Heikki J. , Korpela Markku M. , Mustonen Jukka T. , Pasternack Amos I.
Published: February 2007

Objective.To evaluate renal biopsy findings and clinicopathologic correlations in patients with rheumatoid arthritis (RA).

Methods.Retrospective study of renal biopsy specimens from 110 RA patients in whom the clinical renal disease was probably due to RA itself and/or to antirheumatic therapy.

Results.The most common histopathologic finding was mesangial glomerulonephritis (GN) (n = 40), followed by amyloidosis (n = 33), membranous GN (n = 19), focal proliferative GN (n = 4), minimal‐change nephropathy (n = 3), and acute interstitial nephritis (n = 1). Amyloidosis was the most common finding in patients with the nephrotic syndrome. In patients with isolated proteinuria, amyloidosis, membranous GN, and mesangial GN were almost equally common. Although mesangial GN was found in almost two‐thirds of the RA patients with hematuria (with or without proteinuria), there still remained a 1 in 5 chance that the biopsy would reveal membranous GN or amyloidosis. Membranous GN was closely related to gold or D‐penicillamine therapies, whereas mesangial GN probably related to RA itself.

Conclusion.The renal morphologic lesion in RA patients with isolated proteinuria and those with hematuria cannot be accurately predicted on the basis of clinical symptoms and signs. Biopsy is thus useful in differential diagnosis, assessment of prognosis, and decision‐making with regard to treatment.
Reduced red blood cell deformability in patients with rheumatoid vasculitis improvement after in vitro treatment with dipyridamole
Authors: Lau C. S. , Saniabadi A. R. , Belch J. J. F.
Published: February 2007

Objective. To assess red blood cell deformability (RCD) in patients with rheumatoid arthritis (RA) without extraarticular manifestations and in RA with vasculitic complications (RV), and to assess whether in vitro dipyridamole improves RCD.

Methods. An improved filtration technique was used to measure RCD in 15 patients with RA, 18 patients with RV, and 20 age‐ and sex‐matched normal control subjects. Washed erythrocytes suspended in buffer, at 5% hematocrit, were filtered through 4.7 μ Nuclepore Hemafil PC membranes. The initial steadystate relative filtration pressure (iRFP) was used as an index to assess RCD. A lower iRFP value reflects increased deformability, a higher value reflects a decrease. For each sample, 2 cell suspensions were prepared, one blank (control) and one containing 5 μM dipyridamole.

Results. The mean iRFP values of cells obtained from patients with RV were significantly higher than those of cells obtained from normal controls. There were no appreciable differences in iRFP between RA patients and normal controls. When the erythrocytes were pretreated in vitro with 5 μM dipyridamole before filtration, their deformability improved markedly (iRFP values were reduced) in all study subjects, compared with untreated cells.

Conclusion. RCD is reduced in patients with RV, and treatment with dipyridamole may be beneficial if reduced RCD contributes to impaired microvascular perfusion.
Synovial tissue response to treatment with campath‐1h
Authors: Ruderman Eric M. , Weinblatt Michael E. , Thurmond Linda M. , Pinkus Geraldine S. , Gravallese Ellen M.
Published: February 2007

Objective. Therapeutic trials in rheumatoid arthritis with the monoclonal antibody Campath‐1H have demonstrated recurrent clinical synovitis in some patients, despite profound depletion of circulating lymphocytes. This study was undertaken to examine the cellular infiltrates in synovial tissue at a time of persistent peripheral lymphopenia.

Methods. Immunohistochemical staining of synovial tissue and peripheral blood lymphocyte phenotyping.

Results. Synovial tissues from 2 patients with recurrent synovitis after Campath‐1H therapy contained significant T lymphocytic infiltrates at a time when circulating T lymphocytes were markedly depleted.

Conclusion. These results demonstrate that peripheral blood analysis may not accurately reflect the synovial tissue response to monoclonal antibody therapy.
Pseudoseptic inflammatory knee effusion caused by phagocytosis of sickled erythrocytes after fracture into the knee joint
Authors: Mann Delani , Schumacher H. Ralph
Published: February 2007

A 57‐year‐old black man with sickle cell disease was admitted to the hospital because of a painful crisis. After a fall with a fracture into the right knee joint, he developed an acutely painful, swollen knee. Synovial fluid from the right knee showed leukocyte counts of up to 154,000/mm3 and was negative for urate and calcium pyrophosphate dihydrate crystals. Gram stains and cultures were negative. Some sickled red cells were seen by light microscopy; electron microscopy revealed crystal‐like arrays of sickled hemoglobin tactoids in erythrocytes which were enfolded and phagocytized by the cells of the synovial fluid. We suggest that this phagocytosis of sickled red cells is the likely cause for the otherwise unexplained inflammation.
The total costs of drug therapy for rheumatoid arthritis
Authors: Prashker Mark J. , Meenan Robert F.
Published: February 2007

Objective. We created a model to estimate the total medication costs of treating patients with rheumatoid arthritis with 6 second‐line agents for the first 6 months of treatment.

Methods. Drug costs were obtained from a survey of pharmacies; monitoring costs were calculated from utilization information obtained in a survey of rheumatologists; toxicity costs were obtained using decision trees to represent the evaluation and treatment of potential toxicities. Monitoring and toxicity costs were estimated using costs from the Boston University Medical Center or, for hospitalizations, using appropriate diagnosis‐related group categories. The sum of the 3 components determined the total medication costs.

Results. The least expensive medication was penicillamine, at $10.62/week, and the most expensive was injectable gold, at $30.89/week. In terms of monitoring costs, methotrexate had the highest costs associated with necessary laboratory tests and office visits. Hydroxychloroquine had the lowest monitoring costs for office visits, and oral gold had the lowest for laboratory costs. Hematologic toxicities were the largest component of toxicity costs for all 6 medications, and renal toxicities were costly for patients taking oral gold, penicillamine, and injectable gold. Total medication costs revealed oral gold as the least expensive medication and injectable gold as the most expensive. The combination of monitoring and toxicity costs accounted for more than 60% of the total costs for all medications except injectable gold. In all cases, the cost of treating toxicities was the smallest of the 3 components.

Conclusion. When calculating the costs of drug therapy, it is important to consider not only the price of the drug, but also the costs of monitoring and treating the toxicities that might occur. Failure to do so will result in underestimating the true costs of treatment with these medications.
The determinants of walking velocity in the elderly
Authors: Chang Rowland W. , Dunlop Dorothy , Gibbs James , Hughes Susan
Published: February 2007

Objective. To determine predictors of walking velocity in the elderly.

Methods. Five hundred thirty‐two persons from 3 cohorts of elderly persons (retirement community, ambulatory care medical clinic, or chronically homebound population) performed a 10‐foot (for the homebound subjects) or 50‐foot (for all other subjects) walk time test and underwent a standardized interview, chart review, and clinical examination. The 73 independent variables that were evaluated included demographic, musculoskeletal, neurologic, psychologic, and other comorbidity items. Least‐squares and least‐absolute‐deviation regression tree analyses were performed to determine the strongest predictive factors associated with walking velocity.

Results. Sampling cohort (homebound versus non‐homebound), quadriceps strength, hip flexion strength, lumbosacral spine impairment, lower joint impairment, and education were found to be associated with walking velocity. Joint pain measures were not associated with walking velocity.

Conclusion. Muscle strength variables are better predictors of walking velocity than are joint pain variables. Thus, clinical trials and observational studies using walking velocity as an outcome need to take into consideration the influence of muscle strength on this outcome variable.
Lyme arthritis in european children and adolescents
Authors: Huppertz Hans‐Iko , Karch Helge , Suschke Hans‐Joachim , DÖRing Eva , Ganser Gerd , Thon Angelika , Bentas Wassilios ,   Pediatric Rheumatology Collaborative Group
Published: February 2007

Objective. To evaluate and describe Lyme arthritis in European children and adolescents.

Methods. This was a prospective multicenter study. The diagnosis of Lyme arthritis required the exclusion of other diseases and positive findings on serology for IgG antibodies to Borrelia burgdorferi. Enzyme‐linked immunosorbent assay, immunoblotting, and polymerase chain reaction techniques to identify infection by B burgdorferi were used.

Results. Among 62 children and adolescents with Lyme arthritis, only 1 had a preceding erythema migrans. Arthritis was episodic in 62% and was chronic at onset in 18%. The most common manifestation was monarthritis of the knee. Joint involvement in patients with oligoarthritis was predominantly unilateral or symmetric. Arthralgia was very rare. Treatment with 1 or 2 courses of different antibiotics resulted in disappearance of the arthritis in 77% of the patients.

Conclusion. The clinical presentation of Lyme arthritis in children is different from that in adults. The calculated incidence of Lyme arthritis in persons under the age of 17 years (4/100,000) exceeds previous estimations.
Epidemiology of polymyalgia rheumatica in olmsted county, minnesota, 1970–1991
Authors: Salvarani Carlo , Gabriel Sherine E. , Michael O'Fallon W. , Hunder Gene G.
Published: February 2007

Objective. To determine the incidence, prevalence, and survival of polymyalgia rheumatica (PMR) over a 22‐year period in Olmsted County, Minnesota.

Methods. Using the unified record system at the Mayo Clinic for the Olmsted County population, we reviewed all medical records with a diagnosis of PMR from 1970 through 1991.

Results. There were 245 (173 female; 72 male) incidence cases of PMR between 1970 and 1991. The average annual age‐ and sex‐adjusted incidence of PMR per 100,000 population ≥ 50 years was 52.5 (95% confidence interval [CI] 45.9–59.2), with a significantly higher incidence in females (61.7; 95% CI 52.3–71.2) than in males (39.9; 95% CI 30.7–49.2). The incidence varied over the period of observation, but no significant trends were found. The prevalence of PMR among persons ≥ 50 years on January 1, 1992 was 6/1,000. There was a small but significantly increased survival rate among male PMR patients compared with the general population.

Conclusion. Our data demonstrate that PMR is a common nonfatal disease in the elderly, the incidence and clinical manifestations of which have varied but remained relatively stable over the last 2 decades.