bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prolongation of the corrected QT interval in adult patients with anti‐Ro/SSA–positive connective tissue diseases
Authors: Lazzerini Pietro Enea , Acampa Maurizio , Guideri Francesca , Capecchi Pier Leopoldo , Campanella Valeria , Morozzi Gabriella , Galeazzi Mauro , Marcolongo Roberto , Laghi‐Pasini Franco 
Published: April 2004

AbstractObjectiveNewborns of mothers positive for anti‐Ro/SSA autoantibodies may develop a series of electrocardiographic (EKG) disturbances. Prolongation of the corrected QT (QTc) interval was recently reported in a significant proportion of children with maternally acquired anti‐Ro/SSA antibodies, with a concomitant disappearance of EKG abnormalities and acquired maternal autoantibodies during the first year, suggesting a direct, reversible electrophysiologic effect of anti‐Ro/SSA antibodies on the ventricular repolarization. On this basis, we investigated whether these antibodies may also affect cardiac repolarization in anti‐Ro/SSA–positive adult patients with connective tissue diseases.MethodsFifty‐seven patients with connective tissue diseases were selected: 31 had anti‐Ro/SSA antibodies and 26 did not (controls). In all subjects, we analyzed the QTc interval, heart rate variability, and signal‐averaged high‐resolution EKG recording.ResultsAnti‐Ro/SSA–positive patients showed a significant prolongation of the mean QTc interval compared with the controls (mean ± SD 445 ± 21 versus 419 ± 17 msec; P = 0.000005). Eighteen of the 31 anti‐Ro/SSA–positive patients (58%) and none of the 26 anti‐Ro/SSA–negative patients had QTc values above the upper limit of normal (440 msec). Both groups had a reduction in heart rate variability, with a prevalence for the sympathetic nervous system and a high incidence of ventricular late potentials; these values were not significantly different between the 2 groups.ConclusionAdult patients with anti‐Ro/SSA–positive connective tissue diseases showed a high prevalence of QTc interval prolongation. This feature, with the concomitant abnormalities in the autonomic tone and ventricular late excitability observed in all patients studied, suggests that anti‐Ro/SSA–positive patients may have a particularly high risk of developing life‐threatening arrhythmias.
Potential strategies to reduce medial compartment loading in patients with knee osteoarthritis of varying severity: Reduced walking speed
Authors: Mündermann Anne , Dyrby Chris O. , Hurwitz Debra E. , Sharma Leena , Andriacchi Thomas P. 
Published: April 2004

AbstractObjectiveTo determine whether reducing walking speed is a strategy used by patients with knee osteoarthritis (OA) of varying disease severity to reduce the maximum knee adduction moment.MethodsSelf‐selected walking speeds and maximum knee adduction moments of 44 patients with medial tibiofemoral OA of varying disease severity, as assessed by using the Kellgren/Lawrence grade, were compared with those of 44 asymptomatic control subjects matched for sex, age, height, and weight.ResultsDifferences in self‐selected normal walking speed explained only 8.9% of the variation in maximum knee adduction moment for the group of patients with knee OA. The severity of the disease influenced the adduction moment–walking speed relationship; the individual slopes of this relationship were significantly greater in patients with less severe OA than in asymptomatic matched control subjects. Self‐selected walking speed did not differ between patients with knee OA, regardless of the severity, and asymptomatic control subjects. However, knees with more‐severe OA had significantly greater adduction moments (mean ± SD 3.80 ± 0.89% body weight × height) and were in more varus alignment (6.0 ± 4.5°) than knees with less‐severe OA (2.94 ± 0.70% body weight × height; and 0.0 ± 2.9°, respectively).ConclusionPatients with less‐severe OA adapt a walking style that differs from that of patients with more‐severe OA and controls. This walking style is associated with the potential to reduce the adduction moment when walking at slower speeds and could be linked to decreased disease severity.
Augmented production of chemokines by the interaction of type II collagen–reactive T cells with rheumatoid synovial fibroblasts
Authors: Min Do‐June , Cho Mi‐La , Lee Sang‐Heon , Min So‐Youn , Kim Wan‐Uk , Min Jun‐Ki , Park Sung‐Hwan , Cho Chul‐Soo , Kim Ho‐Youn 
Published: April 2004

AbstractObjectiveTo determine the impact of type II collagen (CII)–reactive T cells on the production of chemokines in the joints of patients with rheumatoid arthritis (RA).MethodsT cell proliferative responses to bovine CII were assayed in synovial fluid (SF) mononuclear cells and peripheral blood mononuclear cells. CII‐stimulated T cells were cocultured with fibroblast‐like synoviocytes (FLS). The expression of interleukin‐8 (IL‐8), monocyte chemoattractant protein 1 (MCP‐1), and macrophage inflammatory protein 1α (MIP‐1α) in the sera, SF, and supernatant of the CII‐stimulated T cells and FLS coculture was measured by enzyme‐linked immunosorbent assays.ResultsThe levels of IL‐8, MCP‐1, and MIP‐1α in SF were significantly higher than those in paired sera of RA patients. IL‐8, MCP‐1, and MIP‐1α levels in SF were strongly correlated with T cell responses to CII. When FLS were cocultured with CII‐stimulated T cells, the production of IL‐8, MCP‐1, and MIP‐1α was significantly increased. This increase correlated well with the T cell proliferative response to CII. Chemokine production by coculture of CII‐stimulated T cells and FLS was mediated mainly by direct cell–cell contact through CD40 ligand–CD40 engagement.ConclusionOur data indicate that the presence of CII‐reactive T cells in RA joints can increase the production of chemokines such as IL‐8, MCP‐1, and MIP‐1α through interaction with FLS. This chemokine production is mediated by cell–cell contact, including CD40 ligand–CD40 engagement. These results suggest that CII‐reactive T cells play a crucial role in the amplification and perpetuation of the inflammatory process in the rheumatoid synovium.
Inhibition of antigen‐presenting cell function and stimulation of human peripheral blood mononuclear cells to express an antiinflammatory cytokine profile by the stress protein BiP: Relevance to the treatment of inflammatory arthritis
Authors: Corrigall Valerie M. , Bodman‐Smith Mark D. , Brunst Melanie , Cornell Hannah , Panayi Gabriel S. 
Published: April 2004

AbstractObjectiveThe stress protein and endoplasmic reticulum chaperone, immunoglobulin binding protein (BiP), is an autoantigen in rheumatoid arthritis (RA). Stress proteins, however, may have extracellular functions, mediated via cell surface receptors, that may include immunomodulatory functions. We sought to determine whether cell‐free BiP is present in the synovial fluid (SF) of patients with RA and to further investigate the possible extracellular antiinflammatory and immunomodulatory properties of BiP in peripheral blood mononuclear cells (PBMCs) in vitro.MethodsThe presence of BiP in SF was established by Western blotting. PBMCs were stimulated with exogenous recombinant human BiP, and cytokine production and cell proliferation were measured in the presence and absence of cell signaling inhibitors or neutralizing anti–interleukin‐10 (anti–IL‐10) monoclonal antibody. Cytokine levels were quantified by enzyme‐linked immunosorbent assay, cell proliferation by tritiated thymidine uptake, and cell surface molecule expression by flow cytometry.ResultsPBMCs responded to BiP with secretion of an antiinflammatory profile of cytokines. Although BiP stimulated the early production of tumor necrosis factor α (TNFα), the major cytokine induced was IL‐10. Soluble TNF receptor II and IL‐1 receptor antagonist secretion was also increased. Addition of SB203580, the MAPK p38 pathway inhibitor, partially inhibited the production of IL‐10 and TNFα, whereas they were unaffected by the MAPK ERK‐1/2 inhibitor PD98059. BiP also inhibited the recall antigen response by PBMCs to tuberculin purified protein derivative. Further investigation showed that incubation of monocytes in the presence of either BiP or IL‐10 down‐regulated CD86 and HLA–DR expression. The effect observed with IL‐10 was transient compared with the long‐lasting reduction induced by BiP.ConclusionExtracellular BiP may stimulate immunomodulatory and antiinflammatory pathways, which are only partly due to the production of IL‐10. These properties may be of relevance for the treatment of diseases such as RA.
Inefficacy of infliximab in primary Sjögren's syndrome: Results of the randomized, controlled trial of remicade in primary Sjögren's syndrome (TRIPSS)
Authors: Mariette Xavier , Ravaud Philippe , Steinfeld Serge , Baron Gabriel , Goetz Joelle , Hachulla Eric , Combe Bernard , Puéchal Xavier , Pennec Yvon , Sauvezie Bernard , Perdriger Aleth , Hayem Gilles , Janin Anne , Sibilia Jean 
Published: April 2004

AbstractObjectiveThere is no effective treatment for patients with primary Sjögren's syndrome (SS). Since tumor necrosis factor α (TNFα) could be a key element in the pathogenesis of primary SS, we conducted a multicenter, randomized, double‐blind, placebo‐controlled trial to evaluate the effect of infliximab in primary SS.MethodsA total of 103 patients with primary SS were randomly assigned to receive infliximab infusions (5 mg/kg) or placebo at weeks 0, 2, and 6 and were followed up for 22 weeks. All patients fulfilled the new American‐European Consensus Group criteria for SS and had active disease as assessed by values >50 mm on 2 of 3 visual analog scales (VAS) (0–100 mm) that evaluated joint pain, fatigue, and buccal, ocular, skin, vaginal, or bronchial dryness. A favorable overall response was defined as the patient having ≥30% improvement between weeks 0 and 10 in the values on 2 of the 3 VAS. Secondary end points were values on each VAS separately, the number of tender and swollen joints, the basal salivary flow rate, results of the Schirmer test for lacrimal gland function, the focus score on labial salivary gland biopsy, the level of C‐reactive protein, and the erythrocyte sedimentation rate evaluated at weeks 0, 10, and 22, as well as quality of life evaluated by use of the generic Short Form 36 questionnaire administered at weeks 0, 10, and 22.ResultsAt week 10, 26.5% of patients receiving placebo and 27.8% of patients treated with infliximab had a favorable overall response (P = 0.89), and at week 22, 20.4% of the placebo group and 16.7% of the infliximab group had a favorable response (P = 0.62). In addition, the 2 groups did not differ in any of the secondary end points over the 22 weeks of the trial. Severe adverse events reported in the infliximab group did not differ from those observed in previous studies.ConclusionThis randomized, double‐blind, placebo‐controlled study of an anti‐TNF agent did not show any evidence of efficacy of infliximab in primary SS.
Early failures of total hip replacement: Effect of surgeon volume
Authors: Losina Elena , Barrett Jane , Mahomed Nizar N. , Baron John A. , Katz Jeffrey N. 
Published: April 2004

AbstractObjectiveTo determine whether provider volume is associated with early failures following total hip replacement (THR) requiring revision.MethodsClaims data were analyzed to follow a cohort of 57,488 Medicare beneficiaries who underwent elective primary THR in 1995–1996 in 3,044 hospitals in the US. Patients were followed through the end of 1999. Failure of primary THR was defined as a subsequent revision THR, as determined by International Classification of Diseases, Ninth Revision codes in hospital claims. Hospitals were stratified into 4 volume groups: low (<25 THRs/year), medium (26–50, 51–100 THRs/year), and high (>100 THRs/year). Low‐volume surgeons were defined as those surgeons performing <12 elective primary THRs annually in the Medicare population. Associations between the rates of revision and surgeon volume were determined by hazard ratios from a proportional hazard model, with adjustment for hospital volume, patient age, poverty status, sex, and comorbidities. We also examined whether the effect of surgeon volume on revision rates differed between the first 18 months postoperatively and later time periods.ResultsAmong 57,488 patients who had elective primary THR in 1995–1996, 2,537 (4.4%) had at least 1 revision THR by the end of 1999, with 1,437 (56.6%) of these revisions occurring within the first 18 months after the index primary THR. Median followup time was 47 months (range 0–54). Patients of high‐volume surgeons were less likely to have revision THRs than patients of low‐volume surgeons, regardless of hospital volume stratum. Further analysis revealed that the effect of surgeon volume on revisions was striking in the first 18 months after surgery but was not evident in the subsequent years.ConclusionPatients of low‐volume surgeons have higher rates of revision THR than patients of high‐volume surgeons, particularly within the first 18 months postoperatively. Referring clinicians should consider including surgeon volume among the factors influencing their choice of surgeon for elective THR.
A pilot study of the use of 2‐[18F]‐fluoro‐2‐deoxy‐D‐glucose–positron emission tomography to assess the distribution of activated lymphocytes in patients with systemic lupus erythematosus
Authors: Nowak Miroslawa , Carrasquillo Jorge A. , Yarboro Cheryl H. , Bacharach Steven L. , Whatley Millie , Valencia Xavier , Takada Kazuki , Brust Douglas G. , Illei Gabor G. 
Published: April 2004

AbstractObjectiveThe 2‐[18F]‐fluoro‐2‐deoxy‐D‐glucose–positron emission tomography (FDG‐PET) technique provides information on uptake and metabolism of glucose in various tissues. Compared with resting cells, activated lymphocytes take up radioactively labeled glucose analog at a higher rate, which makes it possible to identify lymphoid organs with higher concentrations of activated lymphocytes. This study was undertaken to compare the pattern of PET images and quantitative FDG uptake in lymphoid organs of patients with active systemic lupus erythematosus (SLE) versus patients with inactive SLE and to correlate these findings with peripheral blood lymphocyte phenotypes.MethodsTen patients with active SLE and 9 patients with inactive SLE were studied. FDG‐PET images were obtained from the inguinal region to above the ear, starting at 60 minutes after injection of FDG. Standardized uptake values using lean body mass were determined over areas of interest.ResultsBoth patients with active lupus and those with inactive lupus had increased FDG uptake in lymph nodes when compared with healthy volunteers, and there was no statistically significant difference between the 2 groups of lupus patients. Thymic uptake was demonstrated in 5 of 10 patients with active lupus compared with 0 of 9 patients with inactive disease. Three of the 5 patients with active SLE who were over 29 years of age had thymic uptake. Of the activation markers tested, only the CD3/CD71 population of cells was significantly different between the patient groups, with an increased percentage in the active disease group (P = 0.0247).ConclusionIncreased FDG uptake in lymph nodes of both patients with active SLE and patients with inactive SLE suggests that metabolic, and probably immunologic, activity is enhanced not only in active, but also in clinically quiescent, disease. The increased thymic uptake observed only in patients with active disease suggests that the thymus plays an important role during periods of disease activity.
Antibodies to microtubule‐associated protein 2 in patients with neuropsychiatric systemic lupus erythematosus
Authors: Williams Ralph C. , Sugiura Kazumitsu , Tan Eng M. 
Published: April 2004

AbstractObjectiveMicrotubule‐associated protein 2 (MAP‐2), a cellular protein restricted to neurons, is important in the control of cytoskeletal integrity and other neuronal functions. We undertook this study to examine the presence of autoantibodies to MAP‐2 in neuropsychiatric systemic lupus erythematosus (NPSLE).MethodsSera from 100 patients with SLE, 74 patients with other neurologic disorders and injuries (including cerebrovascular accidents, brain trauma, brain tumors, and demyelinating disorders), and 60 normal controls were examined both by enzyme immunoassays and by Western immunoblotting for autoantibodies to MAP‐2. Sera designated positive for antibodies to MAP‐2 were required to be positive in both assays.ResultsSeventeen percent of SLE patients had autoantibodies to MAP‐2, in contrast to 4% of neurologic injury/disease control patients (P = 0.028) and 1.7% of normal controls. In SLE, anti–MAP‐2 positivity in both assays was associated with neuropsychiatric symptoms in 76.5% of patients, whereas the absence of anti–MAP‐2 was associated with neuropsychiatric symptoms in 19.7% of patients (P = 0.0002). The neuropsychiatric symptoms in the former group included psychosis, seizure, neuropathy, and cerebritis.ConclusionAutoantibodies to MAP‐2, a neuron‐restricted cytoskeletal protein, appear to be another immune marker for NPSLE.
Cyclooxygenase 2–derived prostaglandin E2 production by corticotropin‐releasing hormone contributes to the activated cAMP response element binding protein content in rheumatoid arthritis synovial tissue
Authors: McEvoy Alice N. , Bresnihan Barry , FitzGerald Oliver , Murphy Evelyn P. 
Published: April 2004

AbstractObjectiveTo determine a mechanism by which corticotropin‐releasing hormone (CRH) promotes human inflammatory joint disease progression.MethodsAn ex vivo synovial tissue culture system was established to investigate the functional properties of CRH at peripheral sites of inflammation. CRH‐ and interleukin‐1β (IL‐1β)–induced prostaglandin E2 (PGE2) production from 10 fresh rheumatoid arthritis (RA) synovial tissue (ST) explants was quantified using a competitive enzyme‐linked immunosorbent assay. Modulation of PGE2 levels was further examined following selective and nonselective cyclooxygenase 2 (COX‐2) inhibition. Nuclear extracts were analyzed by electrophoretic mobility shift assays to determine functional cAMP response element binding protein (CREB) activity in response to CRH and PGE2 in isolated primary synovial cell populations. Western blot analysis measured levels of total and activated (phosphospecific) CREB/activating transcription factor (ATF) family members prior to and following stimulation.ResultsCRH, in a time‐ and dose‐dependent manner, significantly (P = 0.022) up‐regulated PGE2 production from 10 fresh RA ST explants. Costimulation of RA ST with CRH and IL‐1β significantly augmented (P = 0.036) the effects on PGE2 production additively over 24 hours. We demonstrated that selective COX‐2 inhibitors prevent the induction of PGE2 by both CRH and IL‐1β. Further, we provided evidence that CRH and PGE2 signal through the induction of CREB and phosphorylated CREB/ATF family members in RA ST and in isolated primary RA cell populations.ConclusionOur findings underscore the pathogenic role that CRH may play in modulating inflammatory joint disease and establish the CREB/ATF family of transcription factors as principal effector molecules of proinflammatory mediator action in RA.
Decreases in rates of hospitalizations for manifestations of severe rheumatoid arthritis, 1983–2001
Authors: Ward Michael M. 
Published: April 2004

AbstractObjectiveTo determine whether the rates of hospitalization for 4 manifestations of severe rheumatoid arthritis (RA), which are used as indicators of long‐term health outcomes, have changed from 1983 to 2001.MethodsData on all patients with RA who were hospitalized with rheumatoid vasculitis or to undergo splenectomy for Felty's syndrome, cervical spine fusion for myelopathy, or total knee arthroplasty at hospitals in California were abstracted from a state hospitalization database. Changes in rates of hospitalization from 1983 to 2001 were examined in this serial cross‐sectional study.ResultsRates of hospitalization for rheumatoid vasculitis and splenectomy in Felty's syndrome decreased progressively over time. The risk of hospitalization for rheumatoid vasculitis was one‐third lower in 1998–2001 than in 1983–1987. The risk of hospitalization for splenectomy in Felty's syndrome was 71% lower in 1998–2001 than in 1983–1987. There were no significant decreases in the rates of hospitalization for cervical spine surgery or total knee arthroplasty (primary and revision), although in 1998–2001 there was a reversal of the trend of increasing rates of total knee arthroplasty. The risk of hospitalization for primary total knee arthroplasty was significantly lower in 1998–2001 than in 1990–1993 (rate ratio 0.90, 95% confidence interval 0.86–0.95; P < 0.0001).ConclusionRates of hospitalization for rheumatoid vasculitis and splenectomy in Felty's syndrome have decreased over the past 19 years, and there has been a recent decrease in the rates of primary total knee arthroplasty in patients with RA. Although several factors may account for these decreases, these findings suggest that since the early 1980s, the long‐term health outcomes of patients with RA have improved.
Sustained improvement over two years in physical function, structural damage, and signs and symptoms among patients with rheumatoid arthritis treated with infliximab and methotrexate
Authors: Maini R. N. , Breedveld F. C. , Kalden J. R. , Smolen J. S. , Furst D. , Weisman M. H. , St.Clair E. W. , Keenan G. F. , van der Heijde D. , Marsters P. A. , Lipsky P. E. 
Published: April 2004

AbstractObjectiveTo evaluate the efficacy and safety of repeated administration of infliximab plus methotrexate (MTX) over a 2‐year period in patients with rheumatoid arthritis (RA) who previously experienced an incomplete response to MTX.MethodsFour hundred twenty‐eight patients were randomly assigned to receive MTX plus placebo or infliximab at a dose of 3 or 10 mg/kg plus MTX for 54 weeks, with an additional year of followup. The protocol was later amended to allow for continued treatment during the second year. Of 259 patients who entered the second year of treatment, 216 continued to receive infliximab plus MTX for 102 weeks. Ninety‐four of these 259 patients experienced a gap in therapy of >8 weeks before continuing therapy. Infusions were administered at weeks 0, 2, and 6, followed by treatment every 4 weeks or every 8 weeks (alternating with placebo infusions in the interim 4‐week visits) at a dose of 3 or 10 mg/kg for a total of 102 weeks (including the gap in therapy). For safety and efficacy assessments, data on the patients who were randomized to receive treatment, irrespective of whether treatment was administered for 102 weeks, were evaluated using all actual observations available. The efficacy measures included the Health Assessment Questionnaire (HAQ) (physical function), Short Form 36 health survey (SF‐36) (health‐related quality of life), total radiographic scores (structural damage), and the American College of Rheumatology 20% improvement criteria (ACR20) (signs and symptoms).ResultsThe infliximab plus MTX regimens resulted in significantly greater improvement in HAQ scores (P ≤ 0.006) and SF‐36 physical component summary scores (P ≤ 0.011) compared with the MTX‐only group. There also was stability in the SF‐36 mental component summary score among patients who received the infliximab plus MTX regimens. Median changes from baseline to week 102 in the total radiographic score were 4.25 for patients who received the MTX‐only regimen and 0.50 for patients who received the infliximab plus MTX regimen. The proportion of patients achieving an ACR20 response at week 102 varied from 40% to 48% for the infliximab plus MTX groups compared with 16% for the MTX‐only group.ConclusionThroughout 102 weeks of therapy, infliximab plus MTX provided significant, clinically relevant improvement in physical function and quality of life, accompanied by inhibition of progressive joint damage and sustained improvement in the signs and symptoms of RA among patients who previously had an incomplete response to MTX alone.