bluuebunny/crossref_metadata_2025 huggingface dataset:
Perceived physical and emotional trauma as precipitating events in fibromyalgia. Associations with health care seeking and disability status but not pain severity
Authors: Aaron Leslie A. , Bradley Laurence A. , Alarcón Graciela S. , Triana‐Alexander Mireya , Alexander Ronald W. , Martin Michelle Y. , Alberts Kristin R.
Published: February 2007

Objective. We examined relationships between perceived physical and emotional trauma that occur prior to, or that initiate, pain onset and health care seeking for fibromyalgia syndrome (FMS). We also assessed associations between perceived trauma and levels of health care usage, symptom severity, functional disability, and receipt of disability compensation among patients with FMS.

Methods. We evaluated these variables using interviews and standardized instruments in a consecutive series of FMS patients and community residents who met the American College of Rheumatology criteria for FMS but had not sought medical care (“nonpatients”).

Results. Emotional trauma was associated with status as an FMS patient independently of demographics, physical trauma, and sexual/physical abuse (P = 0.007). Among patients, emotional trauma was related to a high number of physician visits (P = 0.013), functional disability ratings (P = 0.012), and fatigue (P = 0.029), but physical trauma was associated with receipt of disability compensation (P = 0.019). Trauma history was not related to pain severity or pain thresholds.

Conclusion. Perception of physical trauma is a greater determinant of disability compensation for FMS than is perceived emotional trauma, symptom severity, or functional disability. Effort should be devoted to understanding the social and legal factors underlying this observation, as well as to reducing high health care usage among FMS patients with emotional trauma.
Relationship between biochemical markers of bone turnover and bone scintigraphic indices in assessment of Paget's disease activity
Authors: Alvarez Luisa , Peris Pilar , Pons Francisca , Guañabens Nuria , Herranz Ramón , Monegal Ana , Bedini José L. , Deulofeu Ramón , De Osaba M. Jesús Martínez , Munoz‐Gómez José , Ballesta Antonio M.
Published: February 2007

Objective. To evaluate the relationship between biochemical markers of bone turnover and bone scan indices of disease activity, as well as to analyze their variations based on skeletal involvement, in Paget's disease.

Methods. Serum samples were obtained from 51 patients with Paget's disease to determine the levels of total alkaline phosphatase (total AP), bone alkaline phosphatase (bone AP), propeptide carboxyterminal of type I procollagen (PICP), propeptide aminoterminal of type I procollagen (PINP), osteocalcin, tartrate‐resistant acid phosphatase, and telopeptide carboxyterminal of type I collagen. Urine samples were analyzed for levels of hydroxyproline (HYP), pyridinoline (PYR), deoxypyridinoline (DPYR), C‐terminal telopeptide of type I collagen (CTx), and N‐terminal telopeptide of type I collagen (NTx). In addition, 2 semiquantitative scintigraphic indices, disease activity (AI) and disease extent (EI), were obtained. Pagetic skeletal locations were evaluated individually, with special attention to skull involvement.

Results. All biochemical markers correlated with the AI and the EI. Serum PINP, bone AP, and total AP showed the highest proportions of increased values among the bone formation markers (94%, 82%, and 76%, respectively). Among the bone resorption markers, urinary NTx showed the highest proportion of increased values in patients with Paget's disease (96%), compared with PYR (69%), DPYR (71%), CTx (65%), and HYP (64%). In patients with mild disease activity, serum PINP was the marker with the highest proportion of increased values (71%). In contrast, serum PICP and urinary CTx were the most discriminative markers for skull involvement. Except for higher values for most of the biochemical markers of bone turnover in flat bones, no major differences in other skeletal locations were observed.

Conclusion. The determination of serum PINP as a marker of bone formation and urinary NTx as a marker of bone resorption provided the best biochemical profile to ascertain the extent and activity of Paget's disease. In patients with skull involvement, serum PICP and urinary CTx were shown to be the most discriminative markers.
Macrophage cathepsin L, a factor in the erosion of subchondral bone in rheumatoid arthritis
Authors: Iwata Yasuo , Mort John S. , Tateishi Hiroomi , Lee Eunice R.
Published: February 2007

Objective. To test the hypothesis that the proteinase cathepsin L is involved in the subchondral bone lesions found in chronic rheumatoid arthritis (RA).

Methods. The medial tibial plateaus from 4 control cases and 30 patients diagnosed as having end‐stage RA were examined immunochemically for cathepsin L.

Results. RA lesions include large groups of mononuclear cells, many of which are rich in cathepsin L. Since these mononuclear cells contained the CD68 glycoprotein and, in the electron microscope, displayed an irregular cell surface, cytoplasmic vacuoles, lysosomes, and phagosomes, they were identified as belonging to the macrophage family. The lesions were classified into 2 main patterns, both displaying these cathepsin L—rich cells, which, in at least 1 of the 2, were closely associated with bone degradation.

Conclusion. The cathepsin L—rich macrophages are sufficiently numerous to be considered a major factor in producing the erosion of subchondral bone found in chronic RA lesions.
Chronic meningitis with cranial neuropathies in Wegener's granulomatosis. Case report and review of the literature
Authors: Jinnah H. A. , Dixon Anne , Brat Daniel J. , Hellmann David B.
Published: February 2007

We report the case of a 41‐year‐old man with chronic meningitis and cranial neuropathies in whom leptomeningeal biopsy demonstrated Wegener's granu‐lomatosis. The literature on meningitis in this disease is reviewed. This case illustrates that Wegener's granulo‐matosis can cause chronic meningitis.
Immunogenetic similarities between patients with Felty's syndrome and those with clonal expansions of large granular lymphocytes in rheumatoid arthritis
Authors: Starkebaum Gordon , Loughran Thomas P. , Gaur Lakshmi K. , Davis Paul , Nepom Barbara S.
Published: February 2007

Objective. Patients with chronic clonal proliferation of large granular lymphocytes (LGL leukemia) often have splenomegaly, neutropenia, and rheumatoid arthritis (RA), thereby resembling the manifestations observed in patients with Felty's syndrome. The present study sought to determine whether patients with these disorders represent 2 distinct subsets of neutropenic RA.

Methods. Prospective cohort study of outpatients attending clinics in university and private hospitals and in offices of private practice physicians. Twenty‐two patients with Felty's syndrome and 22 patients with LGL leukemia, 10 of whom had RA, were studied. HLA genotyping was performed on peripheral blood mononuclear leukocyte genomic DNA.

Results. Nineteen of the 22 patients with Felty's syndrome (86%) were DR4 positive. Nine of the 10 patients with LGL leukemia plus RA were also DR4 positive. In contrast, only 4 of the 12 patients with LGL leukemia without RA (33%) were DR4 positive, a frequency that was within the normal range.

Conclusion. The finding of an equally high prevalence of DR4 in patients with Felty's syndrome and in those with LGL leukemia plus RA suggests that both disorders have a similar immunogenetic basis and are parts of a single disease process rather than 2 separate disorders.
Past use of oral contraceptives and the risk of developing systemic lupus erythematosus
Authors: Sanchez‐Guerrero Jorge , Karlson Elizabeth W. , Liang Matthew H. , Hunter David J. , Speizer Frank E. , Colditz Graham A.
Published: February 2007

Objective. To examine the relationship between past use of oral contraceptives (OCs) and development of systemic lupus erythematosus (SLE).

Methods. Prospective cohort study of 121,645 women who were followed up every 2 years between 1976 and 1990 as part of the Nurses' Health Study. Women were classified as never users or past users of OCs based on self‐report. Incidence of SLE was defined by 1) strict American College of Rheumatology (ACR) classification criteria (⩾4 ACR criteria), 2) ⩾4 ACR criteria and any physician's diagnosis, 3) ⩾4 ACR criteria and diagnosis by an ACR‐certified rheumatologist, 4) ⩾3 ACR criteria, or 5) diagnosis by a physician even if the patient did not meet the ACR criteria.

Results. Compared with never users of OCs, and after adjusting for age and ever use of postmenopausal hormones, the relative risk (95% confidence interval [95% CI]) for the incidence of SLE in the women who had definite cases of SLE (⩾4 ACR criteria) (n = 99) was 1.4 (0.9–2.1) for past users of OCs. Using the most stringent case definition (ACR criteria plus a diagnosis of SLE by an ACR member) (n = 58), the relative risk for past users compared with never users was 1.9 (95% CI 1.1–3.3). No relationship was observed between duration of OC use or time since first use and the risk of developing SLE.

Conclusion. Past use of OCs was associated with a slightly increased risk of developing SLE. The decision to use hormonal contraception must be individualized, but the small absolute risk observed for the development of SLE in white women should not be a dominant factor in the decision.
Decreased T cell response to anti‐CD2 in systemic lupus erythematosus and reversal by anti‐CD28. Evidence for Impaired T Cell‐Accessory Cell Interaction
Authors: Horwitz David A. , Tang Fu Lin , Stimmler Mary M. , Oki Alan , Gray J. Dixon
Published: February 2007

Objective. To assess the ability of T cells from patients with systemic lupus erythematosus (SLE) to respond to a mitogenic combination of anti‐CD2 monoclonal antibodies (MAb), and to learn the molecular basis of the documented defect.

Methods. Peripheral blood mononuclear cell (PBMC) populations from individuals with SLE and paired controls were stimulated in vitro with anti‐CD2, and the proliferative response was compared with that evoked by stimulation with phytohemagglutinin (PHA) and anti‐CD3. Surface markers on lymphocyte populations were assessed by flow cytometry after staining with specific MAb.

Results. The proliferative response to anti‐CD2 was decreased to a greater extent than was the response to anti‐CD3 or PHA in SLE patients. This defect was found in approximately one‐half of the patients examined, was not associated with disease activity, and was maintained upon repeated testing. Since either mono‐cytes or resting B cells can serve as accessory cells for T cells following activation by anti‐CD2, we examined the T cell response after depletion of adherent cells. In approximately two‐thirds of the individuals with a decreased response, depletion of monocytes or substitution of monocytes with allogeneic, resting B cells from normal donors corrected the defect. The addition to PBMC of anti‐CD28, but not of a neutralizing antibody to interleukin‐10, largely reversed the anti‐CD2 proliferative defect. Significantly fewer CD8+ T cells expressed CD28 in SLE, and this defect was also documented, to a lesser extent, in CD4+ cells.

Conclusion. This study provides evidence that some functional T cell defects in SLE may be due, at least in part, to decreased CD28‐mediated costimula‐tory activity following the interaction of T cells with conventional accessory cells.
Prevention of murine collagen‐induced arthritis in the knee and ipsilateral paw by local expression of human interleukin‐1 receptor antagonist protein in the knee
Authors: Bakker Andrew C. , Joosten Leo A. B. , Arntz Onno J. , Helsen Monique M. A. , Bendele Alison M. , van de Loo Fons A. J. , van den Berg Wim B.
Published: February 2007

Objective. To determine the efficacy of local human interleukin‐1 receptor antagonist (HuIL‐1Ra) gene therapy in murine collagen‐induced arthritis (CIA).

Methods. DBA/1 mice were immunized against bovine type II collagen. Before the onset of arthritis, NIH/3T3 fibroblasts transfected with pMFG‐IRAP were transplanted into the knee cavity. Normal NIH/3T3 cells served as controls. Paws were evaluated macroscopically for redness, swelling, and deformities during the course of arthritis. Swelling of the knee joints was measured by external gamma counting of 99mtechnetium accumulation in the joint. Paws and knee joints were dissected and processed for histologic studies to evaluate inflammation and cartilage destruction.

Results. The NIH/3T3 fibroblasts survived in the joint cavity of DBA mice for at least 7 days. The transduced cells expressed immunoreactive and bioactive HuIL‐1Ra in the knee joint, and produced sufficient amounts to block the effect of 1 ng of recombinant murine IL‐1α on chondrocyte proteoglycan synthesis. The onset of CIA was almost completely prevented in knee joints containing HuIL‐1Ra‐producing cells, whereas joints containing normal cells showed severe inflammation and destruction of cartilage. Moreover, onset of CIA in the draining joints (ipsilateral paws) of the HuIL‐1Ra gene‐bearing knees was also prevented.

Conclusion. Local production of HuIL‐1Ra in the knee was able to ameliorate the effects of IL‐1 on cartilage and could prevent the onset of CIA not only in that knee, but also in the “draining” paw. This indicates the feasibility of gene transfer as a therapeutic approach to modulating arthritis.
Acute calcific tendinitis of the hip. Case report with magnetic resonance imaging findings
Authors: Chow Henry Y. , Recht Michael P. , Schils Jean , Calabrese Leonard H.
Published: February 2007

The clinical presentation of acute calcific tendinitis can be quite dramatic. This report describes a patient with this entity who had calcification in an unusual area, accompanied by abnormalities seen on radiography and magnetic resonance imaging. Clinical aspects of acute calcific tendinitis are also reviewed. With recognition of this entity, treatment can be initiated promptly, with dramatic resolution.
Bone morphogenetic protein 2 stimulates articular cartilage proteoglycan synthesis in vivo but does not counteract interleukin‐1α effects on proteoglycan synthesis and content
Authors: Glansbeek Harrie L. , van Beuningen Henk M. , Vitters Elly L. , van der Kraan Peter M. , van den Berg Wim B. , Morris Elisabeth A.
Published: February 2007

Objective. To study the effect of bone morphogenetic protein 2 (BMP‐2) on articular cartilage proteoglycan (PG) synthesis in vivo and to investigate whether BMP‐2 is able to counteract the effects of interleukin‐1 (IL‐1) on articular cartilage PG synthesis and content.

Methods. BMP‐2 alone or in combination with IL‐1α was injected into murine knee joints. PG synthesis was measured by 35S‐sulfate incorporation using an ex vivo method or autoradiography. Cartilage PG content was analyzed by measuring Safranin O staining intensity on histologic sections.

Results. BMP‐2 appeared to be a potent stimulator of articular cartilage PG synthesis in vivo. However, BMP‐2 was not able to counteract the deleterious effects of IL‐1α on articular cartilage PG synthesis and content. In addition, intraarticular injections of BMP‐2 induced chondrophytes.

Conclusion. Although BMP‐2 is a very potent stimulator of cartilage PG synthesis in vivo, the therapeutic applications of BMP‐2 are limited due to the inability of BMP‐2 to counteract the effects of IL‐1 and the induction of chondrophytes.
The transcriptional activator Sp1, a novel autoantigen
Authors: Spain Tammy A. , Sun Ren , Gradzka Margaret , Lin Su‐Fang , Craft Joseph , Miller George
Published: February 2007

Objective. To identify one nuclear autoantigenic protein within a complex of DNA binding proteins that bind to GC‐rich sequences in Epstein‐Barr virus and cellular DNA, and to describe the clinical characteristics of patients whose sera contained autoantibodies to this novel autoantigen.

Methods. Antibodies to autoantigen Sp1 were initially measured by an electrophoretic mobility shift assay to detect DNA binding proteins. Nuclear extracts and purified Sp1 protein were used in these assays. Recognition of the autoantigen by autoimmune sera was confirmed by immunoprecipitation and immunoblotting.

Results. The autoantigen was identified as Sp1. Anti‐Sp1 was detected in sera from 8 (3%) of 230 patients. These sera contained antinuclear antibodies, but lacked antibodies to double‐stranded DNA or to several extractable nuclear antigens. The patients whose sera contained antibodies to Sp1 were white women with fatigue, arthritis, Raynaud's phenomenon, malar rash, and photosensitivity.

Conclusion. Sp1 is the first described example of an RNA polymerase II transcription activator as an autoantigen. The presence of Sp1 autoantibodies is associated with undifferentiated connective tissue disease.
Human cartilage glycoprotein‐39 as a candidate autoantigen in rheumatoid arthritis
Authors: Verheijden Gijs F. M. , Rijnders Antonius W. M. , Bos Ebo , Coenen‐De Roo Christina J. J. , van Staveren Catherina J. , Miltenburg André M. M. , Meijerink Jan H. , Elewaut Dirk , de Keyser Filip , Veys Eric , Boots Annemieke M. H.
Published: February 2007

Objective. To identify a cartilage‐derived autoantigen that is relevant to the rheumatoid arthritis (RA) disease process.

Methods. A DR4 (DRB1*0401) peptide binding motif was used for the selection of potential self reactive peptides within human cartilage glycoprotein‐39 (HC gp‐39), a protein that is differentially expressed at the site of chronic inflammation. Synthetic peptides accommodating the motif were tested for binding the RA‐associated DR4 (DRB1*0401) molecules. High‐affinity binders were then tested for their capacity to stimulate peripheral blood mononuclear cell responses in RA patients or healthy donors. To assess the arthritogenic nature of native HC gp‐39, the protein was injected into BALB/c mice.

Results. HC gp‐39‐derived motif‐based peptides were selectively recognized by peripheral blood T cells from RA patients. Injection of the intact protein into BALB/c mice resulted in immunity to HC gp‐39, which was found to be associated with the development of a chronic, relapsing arthritis. Moreover, inhalation of the protein led to tolerization of antigen‐specific T cells and to suppression of HC gp‐39‐induced arthritis.

Conclusion. These data indicate that HC gp‐39 is a target of the immune response in RA. Consequently, HC gp‐39 is a candidate for antigen‐specific immunotherapy.
Mycoplasma infection and rheumatoid arthritis. Analysis of their relationship using immunoblotting and an ultrasensitive polymerase chain reaction detection method
Authors: Hoffman Robert W. , O'Sullivan Frank X. , Schafermeyer Kim R. , Moore Terry L. , Roussell Deborah , Watson‐Mckown Robyn , Kim Mary F. , Wise Kim S.
Published: February 2007

Objective. To examine the relationship between infection with Mycoplasma and the development of rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA).

Methods. Immunoblotting of patient synovial fluid and sera on detergent‐phase membrane protein extracts of various Mycoplasma species was carried out to learn whether patients exhibited serologic evidence of previous exposure to mycoplasmas. Moreover, an ultrasensitive polymerase chain reaction (PCR) method was developed for assessing whether Mycoplasma DNA could be detected in synovial fluid from patients and controls.

Results. Immunoblotting provided serologic evidence of previous Mycoplasma exposure in patients and controls. The genus‐specific PCR detected known human Mycoplasma species and could reliably detect <5 copies of Mycoplasma hominis, Mycoplasma fermentans, or a molecular mimic control in synovial fluid. Repeat testing revealed no evidence of Mycoplasma DNA in patient synovial samples.

Conclusion. This study provided serologic evidence suggesting that, while previous exposure to Mycoplasma was common, there was no detectable persistence of Mycoplasma DNA in the synovial fluid or tissue of patients with RA or JRA.
Fibrosing alveolitis in systemic sclerosis. Indices of lung function in relation to extent of disease on computed tomography
Authors: Wells A. U. , Hansell D. M. , Rubens M. B. , King A. D. , Cramer D. , Black C. M. , du Bois R. M.
Published: February 2007

Objective. Thin‐section computed tomography (CT) provides a sensitive and reproducible method of quantifying the morphologic extent of disease in the clinical management of fibrosing alveolitis associated with systemic sclerosis (FASSc). The aim of this study was to determine which indices of lung function best reflect the extent of disease on CT in FASSc, and to determine the independent influences of smoking history, extent of fibrosing alveolitis, demographic features, and concurrent treatment upon functional impairment in FASSc.

Methods. Sixty‐four patients with FASSc were studied using CT and static and exercise lung function testing. Statistical relationships were determined by multiple regression analyses.

Results. Five patients with overt pulmonary hypertension were characterized by severe impairment in 3 indices of lung function: diffusing capacity for carbon monoxide (DLCO), DLCO adjusted for alveolar volume (KCO), and arterial partial pressure of oxygen. On multiple regression analysis, the major determinant of functional impairment was the extent of fibrosing alveolitis on CT. A history of smoking was independently associated with preservation of total lung capacity and depression of KCO, but did not otherwise influence functional‐morphologic correlations. The percent predicted DLCO correlated better with extent of disease on CT (r = −0.70) than did oxygen desaturation on exercise (r = 0.55), the physiologic component of the clinical‐radiographic‐physiologic score (CRP index) (r = 0.52), or other indices of lung function. Lung volume measures correlated poorly with disease extent on CT.

Conclusion. The percent predicted DLCO best reflects the extent of fibrosing alveolitis in FASSc, and therefore should be measured in routine evaluations. Exercise testing may also have a useful role in staging the severity of pulmonary fibrosis, but the CRP index offers no additional advantage over the DLCO and exercise testing.
Pregnancy in relapsing polychondritis. Twenty‐five pregnancies in eleven patients
Authors: Papo Thomas , Wechsler Bertrand , Bletry Olivier , Piette Anne‐Marie , Godeau Pierre , Piette Jean‐Charles
Published: February 2007

Objective. To determine maternal and fetal outcome in pregnant women with relapsing polychondritis (RP).

Methods. Retrospective review of 11 records selected from among those of 116 female RP (Michet's criteria) patients.

Results. In these 11 women, 25 pregnancies occurred after or concomitantly with the onset of RP. The mean (±SD) age at RP onset was 25 ± 5 years (range 15‐31). Therapeutic abortion was performed in 1 woman because of ongoing cyclophosphamide treatment. Disease flare occurred in 7 of 24 pregnancies, requiring treatment modification in 2 cases. RP was considered stable in 16 and asymptomatic in 1 of the 24. Treatment of RP was with nonsteroidal antiinflammatory drugs (2 of 24), steroids (13 of 24), dapsone (7 of 24), or plasma exchanges (1 of 24); no treatment was given in 8 of the 24 pregnancies. In 14 pregnancies, the course was uneventful. Ten pregnancies were complicated by ectopic nidation (n = 3), spontaneous abortion (n = 3), premature birth (n = 3), and premature rupture of membranes (n = 1). Eighteen normal children were born.

Conclusion. Pregnancy does not seem to modify the course of RP. Successful pregnancies may be achieved in women with RP. No RP was observed in the neonates.
The AIMS2‐SF. A short form of the arthritis impact measurement scales 2
Authors: Guillemin Francis , Coste Joel , Pouchot Jacques , Ghézail Marc , Bregeon Christian , Sany Jacques
Published: February 2007

Objective. To develop a short form of the Arthritis Impact Measurement Scales 2 (AIMS2) questionnaire, preserving content validity as the priority criterion.

Methods. A 2‐step reduction procedure was used: 1) Delphi technique, with 1 panel of patients and 1 panel of experts each selecting 1 set of items independently; and 2) nominal group technique, where members of both panels reached consensus on the final selection of items, using information derived from item analysis. Psychometric properties of the AIMS2‐Short Form (AIMS2‐SF) and AIMS2 were compared using data from a cohort of 127 rheumatoid arthritis patients who completed the AIMS2 twice prior to the initiation of methotrexate (MTX) treatment and 3 months post‐initiation of MTX treatment.

Results. The 2 panels reached consensus on a 26‐item AIMS2‐SF (54.4% reduction from the AIMS2). Factor analysis showed preservation of the 5‐component structure. Convergent validity (Physical and Symptom components with clinical variables: r = 0.24‐0.59), test‐retest reproducibility (intraclass correlation coefficient >0.7), and sensitivity to change at 3 months (standardized response mean 0.36‐0.8, except Social Interaction component [0.08]) were very close to the values for the original AIMS2.

Conclusion. The AIMS2‐SF is a shorter version of the AIMS2 (i.e., available in 2‐page format) and has psychometric properties similar to those of the AIMS2.
Association of rheumatoid arthritis with an amino acid allelic variation of the T cell receptor
Authors: Cornélis F. , Hardwick L. , Flipo R. M. , Martinez M. , Lasbleiz S. , Prud' Homme J. F. , Tran T. H. , Walsh S. , Delaye A. , Nicod A. , Loste M. N. , Lepage V. , Gibson K. , Pile K. , Djoulah S. , Danzé P. M. , Lioté F. , Charron D. , Weissenbach J. , Kuntz D. , Bardin T. , Wordsworth B. P.
Published: February 2007

Objective. To investigate allelic variations of T cell receptor residues for a contribution to rheumatoid arthritis (RA) susceptibility.

Methods. We conducted an RA case‐control study involving 1,579 northwest Europeans: 766 patients with erosive and rheumatoid factor‐positive disease and 813 control subjects. Productive changes of segments TCRAV6S1, TCRAV7S1, TCRAV8S1, TCRAV10S2, and TCRBV6S1, TCRBV6S7 were investigated by single‐strand conformation polymorphisms. The TCRAV8S1 association was confirmed by restriction fragment length polymorphism.

Results. In the systematic study (77 patients and 119 controls), an increase in 1 TCRAV8S1 genotype was found in the RA patients (P = 0.0004). This finding was replicated in 2 further populations, one from France (212 patients and 254 controls) and the other from Britain (477 patients and 440 controls), with a similar odds ratio (OR), which allowed pooling of the data and confirmation of the association (OR 1.3 [95% confidence interval 1.1‐1.7], P = 0.008).

Conclusion. These findings show evidence that TCRA is an RA susceptibility locus.
Effects of pulse methylprednisolone on inflammatory mediators in peripheral blood, synovial fluid, and synovial membrane in rheumatoid arthritis
Authors: Youssef Peter P. , Haynes David R. , Triantafillou Sophie , Parker Angela , Gamble Jenny R. , Roberts‐Thomson Peter J. , Ahern Michael J. , Smith Malcolm D.
Published: February 2007

Objective. To establish whether the clinical efficacy of pulse methylprednisolone (MP; 1,000 mg intravenously) is related to the modulation of proinflammatory cytokines within the peripheral blood, synovial membrane, or synovial fluid compartments.

Methods. Eighteen patients with active rheumatoid arthritis (RA) were studied. Peripheral blood (11 patients) and knee synovial fluid (9 patients, 10 knees) were obtained before and at 4 and 24 hours after MP therapy. Interleukin‐1β (IL‐1β), IL‐8, and tumor necrosis factor α (TNFα) were measured by enzyme‐linked immunosorbent assay and biologic assays; prostaglandin E2 (PGE2) was measured by competitive radioimmunoassay. In 10 patients, arthroscopically directed synovial biopsies were obtained before and at 24 hours after treatment, at disease relapse (4 patients), and after retreatment (1 patient). Membranes were stained by immunohistochemical techniques with monoclonal antibodies against TNFα, IL‐8, IL‐1β, and the IL‐1 receptor antagonist protein (IL‐1Ra).

Results. MP therapy was associated with a rapid (within 24 hours) and substantial decrease in the expression of TNFα in the lining and sublining regions of the synovial membrane, as well as substantial decreases in the levels of TNFα in serum and synovial fluid. There was also reduced IL‐8 expression in the synovial lining, as well as reduced synovial fluid IL‐8 levels. No effect on synovial membrane IL‐1β and IL‐1Ra or synovial fluid IL‐1β and PGE2 was found.

Conclusion. MP therapy rapidly reduces IL‐8 and TNFα levels in the synovial compartment, with cytokine changes in the serum and synovial fluid reflecting the changes in the synovial membrane. Alterations in TNFα expression in the synovial membrane correlated with clinical response to, and subsequent relapse after, MP therapy.
Clinical significance of antinuclear antibodies. Comparison of detection with immunofluorescence and enzyme‐linked immunosorbent assays
Authors: Emlen Woodruff , O'Neill Laurie
Published: February 2007

Objective. To compare the measurement of antinuclear antibodies (ANA) by immunofluorescence and by 6 different commercial enzyme‐linked immunosorbent assays (ELISAs) in clearly defined patient groups and serum samples.

Methods. Serum samples were derived from 3 sources: 1) patients with a known clinical diagnosis of systemic lupus erythematosus (SLE) (group 1), 2) sera with known monospecific ANA reactivity (group 2), and 3) sera from consecutive patients for whom ANA testing had been ordered (group 3). Each of these sera was tested for the presence of ANA by immunofluorescence on HEp‐2 cells, and by using each of 6 commercially available ELISA ANA kits.

Results. In patients with known clinical SLE, 88% were ANA positive by immunofluorescence. Positivity with the different ELISAs ranged from 62% to 90%. While most ELISAs successfully detected antibodies to SS‐A, RNP, and Sm, there were significant differences between assays in the detection of anticentromere antibodies and anti‐DNA. Measurement of ANA in consecutive patients for whom an ANA test was requested showed that, generally, those assays with high sensitivity for detection of SLE had a high false‐positive rate, whereas those assays with a low false‐positive rate failed to identify some patients with a clinical diagnosis of SLE.

Conclusion. There are significant differences in the detection of ANA by immunofluorescence and different ELISA kits. Agreement between different assays is generally marginal. When ordering and interpreting an ANA test, the clinician must be familiar with the specific assay being used to measure ANA and the differences between the various ANA assays.
Trial of intravenous pulse cyclophosphamide and methylprednisolone in the treatment of severe systemic‐onset juvenile rheumatoid arthritis
Authors: Wallace Carol A. , Sherry David D.
Published: February 2007

Objective. Not uncommonly, some children with systemic‐onset juvenile rheumatoid arthritis (JRA) have persistently active disease with joint destruction and profound growth delay despite maximum treatment with known medications. Based on previous observations of improvement in synovitis following intravenous (IV) cyclophosphamide (CYC) and methylprednisolone (MP) treatments, a group of children with severe systemic‐onset JRA was treated in an attempt to control active synovitis and to allow tapering of corticosteroids.

Methods. Four patients with systemic‐onset JRA were continued on a daily regimen of nonsteroidal antiinflammatory agents and prednisone, with a weekly subcutaneous dose of methotrexate (1 mg/kg). In addition, 1 patient continued receiving sulfasalazine and 1 patient remained on a regimen of sulfasalazine and hydroxychloroquine. Patients received 6–10 monthly treatments of IV CYC (500–1,000 mg/m2) and MP (30 mg/kg; 1 gm maximum) accompanied by IV mesna and large amounts of IV fluids. Subsequent treatments were given once every 2–3 months.

Results. After 12–20 IV pulses of CYC, all patients showed improvement, and 3 achieved remission of disease. All were able to discontinue corticosteroid use and all had an increase in linear growth.

Conclusion. Monthly IV pulse CYC treatments can be useful to control disease in selected children with severe, destructive JRA.
Blood transfusion, smoking, and obesity as risk factors for the development of rheumatoid arthritis. Results from a primary care‐based incident case‐control study in Norfolk, England
Authors: Symmons Deborah P. M. , Bankhead Clare R. , Harrison Beverley J. , Brennan Paul , Silman Alan J. , Barrett Elizabeth M. , Scott David G. I.
Published: February 2007

Objective. To examine a range of demographic, social, and clinical risk factors for the development of rheumatoid arthritis (RA).

Results. The controls were of higher socioeconomic status than the cases. This was probably due to response bias. Having a body mass index ⩾30 was associated with an adjusted odds ratio (OR) of 3.74 for developing RA (95% confidence interval [95% CI] 1.14−12.27). RA was also associated with a history of blood transfusion (OR 4.83, 95% CI 1.29−18.07). Even after correcting for social class, a history of having ever smoked was associated with a higher risk of developing RA (OR 1.66, 95% CI 0.95−3.06). There was no difference between cases and controls in previous exposure to childhood infections, certain surgical procedures, or reproductive history variables.

Methods. Population‐based case‐control study in Norfolk, England, involving adult patients, ages 18–70, with an inflammatory polyarthritis of <12 months' duration who were recruited from the Norfolk Arthritis Register. Controls, matched for sex and date of birth, were selected from the primary care register of the Norwich Health Authority. Both cases and controls completed identical self‐administered questionnaires. Matched analysis of the 165 case‐control sets was conducted for the whole group and for the subset in which the cases satisfied the 1987 American College of Rheumatology criteria for RA.

Conclusion. RA has a number of potential environmental triggers, including smoking, obesity, and blood transfusion.
Oncostatin M stimulates monocyte chemoattractant protein‐1‐ and interleukin‐1‐induced matrix metalloproteinase‐1 production by human synovial fibroblasts in vitro
Authors: Langdon Carrie , Leith Jonathon , Richards Carl D. , Smith Frank
Published: February 2007

Objective. To measure levels of oncostatin M (OSM) in the synovial fluid of rheumatoid arthritis (RA) patients and to examine the activities of human OSM in the regulation of human synovial fibroblast (HSF) production of chemokines and matrix metalloproteinases (MMP‐1 and MMP‐3) in vitro.

Methods. We examined the levels of OSM in the synovial fluids of patients with arthritis by an enzymelinked immunosorbent assay (ELISA). ELISA of cell culture supernatants and Northern blots were used to assess responses of HSF to interleukin‐1α (IL‐1α), OSM, and other members of the IL‐6/leukemia inhibitory factor (IL‐6/LIF) family of cytokines.

Results. We detected variable levels of OSM antigen in 9 of 10 RA patient synovial fluids, but levels were not detectable in 9 of 10 osteoarthritis (OA) patient fluids. Upon examining the responses of HSF in culture, OSM stimulated monocyte chemoattractant protein 1 (MCP‐1), whereas RANTES secretion (regulated upon activation, normal T expressed and presumably secreted) was not altered by OSM alone. In IL‐1α induced cells, OSM costimulation further enhanced MCP‐1 release, but inhibited the release of RANTES and IL‐8. Other members of the IL‐6/LIF family of cytokines did not show these effects. OSM induced a small elevation of MMP‐1 production over 2 and 3 days of stimulation (2‐fold), and acted significantly to enhance IL‐1α‐induced production of MMP‐1 (to 8‐fold and 9‐fold at 48 and 72 hours, respectively). No effect of OSM was seen on MMP‐3 secretion, either alone or in IL‐1α‐costimulated cells.

Conclusion. These results suggest that OSM has potentially important functions in the modulation of chemokine and metalloproteinase production by synovial cells of the joint.
Antifibroproliferative effect of tenidap in chronic antigen‐induced arthritis
Authors: Sánchez‐Pernaute Olga , López‐Armada Maria José , Hernández Purificación , Palacios Itziar , Egido Jesüs , Herrero‐Beaumont Gabriel , Navarro Francisco , Martinez Javier
Published: February 2007

Objective. To determine whether tenidap regulates extracellular matrix metabolism in chronic arthritis.

Methods. Antigen arthritis was induced in the knees of 30 rabbits. Animals were distributed into 3 groups: untreated, tenidap‐treated, and diclofenactreated rabbits. Three weeks after disease induction, synovial membranes were extracted and processed for histopathologic examination and detection of type I collagen (CI) and fibronectin (FN) by immunoperoxidase. Simultaneously, we analyzed the in vitro effect of tenidap on healthy synovial cell (SC) proliferation, FN expression and synthesis, and expression of transforming growth factor β1 (TGFβ1) messenger RNA.

Results. Untreated animals showed synovial lining hyperplasia, cellular infiltration at the sublining, and increased deposition of matrix proteins. These findings were not apparent in tenidap‐treated rabbits, where CI and FN had the same distribution as in healthy synovial membranes. In vitro, tenidap inhibited SC proliferation (⩾25 μM) and down‐regulated the expression and synthesis of FN in a dose‐dependent manner (⩾1 μM). This antifibrotic effect was associated with a reduction of TGFβ1 message.

Conclusion. Tenidap down‐regulates the fibroproliferative changes typical of chronic arthritis, an effect that fits the profile of a disease‐modifying agent for rheumatoid arthritis.
A promoter polymorphism of tumor necrosis factor α associated with systemic lupus erythematosus in African‐Americans
Authors: Sullivan Kathleen E. , Wooten Candra , Schmeckpeper Barbara J. , Goldman Daniel , Petri Michelle A.
Published: February 2007

Objective. The polymorphic tumor necrosis factor α (TNFα) gene encodes a cytokine involved in inflammation, angiogenesis, and apoptosis. One polymorphic variant is associated with increased production of TNFα. This study examined the frequency of this polymorphic variant in African‐American patients with systemic lupus erythematosus (SLE) compared with controls.

Methods. We determined the gene frequency of the polymorphic variant of TNFα in an African‐ American SLE patient population and in a geographically matched African‐American control population.

Results. The gene frequency of the TNFα ‐308A polymorphism was higher in the African‐American SLE population than in the control population. This relationship was independent of major histocompatibility complex DR alleles.

Conclusion. The TNFα ‐308A polymorphism is associated with an increased risk of SLE in African‐ Americans.
Autoantibodies to human recombinant erythropoietin in patients with systemic lupus erythematosus. Correlation with anemia
Authors: Tzioufas Athanasios G. , Kokori Styliani I. , Petrovas Constantinos I. , Moutsopoulos Haralampos M.
Published: February 2007

Objective. To investigate the existence of circulating autoantibodies to erythropoietin (EPO) in sera from patients with systemic lupus erythematosus (SLE), and to correlate their presence with anemia and clinical activity.

Methods. Ninety‐two consecutive patients with SLE, 80 patients with rheumatoid arthritis, and 42 normal individuals were studied. The patients with SLE were categorized into 3 groups according to hemoglobin (Hgb) level: group A (45 patients with Hgb >12 gm/dl), group B (26 patients with Hgb 10.1–12 gm/dl), and group C (21 patients with Hgb ⩽10 gm/dl). In all patients with SLE, the disease activity was evaluated using the European Consensus Lupus Activity Measurement scale. Antibodies to EPO were detected using an enzyme‐linked immunosorbent assay and purified recombinant human EPO as antigen. The specificity of the method was evaluated with homologous and crossreactive inhibition assays.

Results. Antibodies to EPO were found in 15.2% of the SLE patient sera. The distribution of these antibodies among the 3 groups of SLE patients was as follows: 8.8% (4 of 45) from group A, 15.4% (4 of 26) from group B, and 28.6% (6 of 21) from group C. The prevalence of antibodies to EPO in patients with severe anemia (group C) was statistically significantly higher compared with patients without anemia (χ2 = 4.31, P < 0.05). Patients with antibodies to EPO had higher disease activity scores (P < 0.005) and lower levels of the C4 component of complement (P < 0.05) compared with patients without antibodies to EPO.

Conclusion. In this study, the presence of antibodies to EPO in the sera of SLE patients is demonstrated for the first time. The presence of these antibodies is associated with severe anemia and active disease.
Use of self‐report activities of daily living questionnaires in osteoarthritis
Authors: Brooks Raye H. , Callahan Leigh F. , Pincus Theodore
Published: February 2007

Self‐report activities of daily living (ADL) questionnaires and traditional observer‐reported physical measures were used to assess clinical status in a clinical trial involving patients with osteoarthritis (OA) of the knee. The observer‐reported measures included pain on active motion, pain on passive motion, joint tenderness, joint swelling, joint crepitus, walking time, and observer global assessment. Self‐report ADL questionnaires included scales to assess difficulty, dissatisfaction, and pain in eight activities of daily living, as well as a visual analog pain scale and patient global assessment. Significant correlations were seen between the observerreported physical measures and self‐report questionnaire measures, indicating that both types of measures detect similar information.

In comparisons made four weeks apart, changes in observer‐reported physical measures and self‐report questionnaire measures were also significantly correlated. Among the eight individual activities within the ADL scales, poorest status was reported for walking, and minimal problems were reported for the two activities involving use of the upper extremities, indicating criterion validity. Self‐report ADL questionnaire measures appeared as sensitive as traditional observer‐reported measures in detecting changes in clinical status over a four‐week period. Self‐reported ADL questionnaires appear valid, sensitive, and useful in assessment of clinical status in OA.
Assessing physical fitness of women with rheumatic disease
Authors: Burckhardt Carol S. , Clark Sharon R. , Nelson Donna L.
Published: February 2007

The feasibility, safety, and reliability of selected physical fitness tests were examined in a sample of 70 women between the ages of 20 and 59 with either rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), or fibrositis (FS). Three components of physical fitness were tested: flexibility of the lower back, muscle strength of the arms and legs, and cardiovascular endurance. A group of 40 women without rheumatic or other chronic disease was also tested using the same tests in order to control for modifications in the testing methods. Results showed that the women with rheumatic disease could complete the tests without adverse reactions. Overall, most of them had low to fair cardiovascular endurance and flexibility when compared to either the controls or known norms for women their age. The study concludes that women with three forms of rheumatic disease can safely complete a series of simple, clinically oriented physical fitness tests that are sensitive enough to distinguish several levels of physical fitness.
Health locus of control and well‐being in systemic lupus erythematosus
Authors: Pfeiffer Carol A. , Wetstone Scott L.
Published: February 2007

The health locus of control and well‐being of 53 lupus patients were compared to samples of healthy individuals and samples of those with other chronic diseases. The SLE sample had more negative affect, more positive affect, and a stronger belief in powerful others locus of control than healthy individuals. A subgroup of SLE patients who could predict their flares was identified. They had significantly more experience with the disease and a greater belief in internal health control. Disease duration and socioeconomic status explained significant amounts of variance in powerful‐others locus of control. The learned helplessness model was tested and the results suggested that symptoms impact on well‐being while disease duration and predictability of flares impact on health locus of control.
Dance‐based aerobic exercise for rheumatoid arthritis
Authors: Perlman Susan G. , Connell Karen J. , Clark Andrea , Robinson Marlena S. , Conlon Patricia , Gecht Maureen , Caldron Paul , Sinacore James M.
Published: February 2007

Reported here are the results of the first effort to examine the effects of a dance‐based aerobic exercise program for people with rheumatoid arthritis (RA). Forty‐three subjects with RA completed a 16‐week program that met twice weekly for 2 hours. One hour was devoted to exercise consisting of 15 to 20 minutes of warm‐ups, 20 to 30 minutes of dance‐based aerobic exercise, and 15 to 20 minutes of mat work for muscle strengthening and flexibility. The second hour was devoted to discussion that emphasized participant problem solving. The combined exercise/ problem‐solving discussion program was called EDUCIZE. Analyses of pretest to posttest changes indicated no deleterious effects on disease activity. In fact, physician‐assessed articular pain and swelling decreased significantly, as did 50‐foot walk time, pain, and depression. Participants reported significant improvement in lower extremity function. Changes in vigor and fatigue approached significance. Perceptions of general health as well as four of five quality of life indices improved significantly.

This study adds to the as yet limited literature that indicates that weight‐bearing vigorous exercise is beneficial for people with arthritis. Controlled studies to validate the findings of this study appear warranted. Also important for future research is investigation of the influence of the problem‐solving discussion component on program effects.
The impact of JRA on children, adolescents, and their families: Current research and implications for future studies
Authors: Quirk Mark E. , Young Martin H.
Published: February 2007

This arthicle focusses on the impact of Juvenile Rheumatoid Arthritis (JRA) on children, adolescents, and their families. Investigations reported in the literature that consider the etiologic role of psychopatho‐logy and JRA, psychologic adjustment/maladjustment of adolescents with JRA, family adaptation to chronic illness, and changes in the family that affect health outcomes and treatment compliance are critically reviewed. Methodologic and research design issues are discussed in relation to previous investigations, and implications for future research are presented.
Fatigue in rheumatoid arthritis: Conditions, strategies, and consequences
Authors: Tack Basia Belza
Published: February 2007

Fatigue is a frequent and debilitating problem for people with rheumatoid arthritis (RA). In this descriptive study a Fatigue Interview Schedule was administered to 20 patients with RA to elicit symptomspecific information. Qualitative analyses resulted in the identification of descriptors of fatigue, conditions under which fatigue occurs, an intricate repertoire of strategies used to prevent and manage fatigue, and the consequences of chronic fatigue.