bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phenotypic characterization of osteoblasts from the sclerotic zones of osteoarthritic subchondral bone
Authors: Sanchez Christelle , Deberg Michelle A. , Bellahcène Akeila , Castronovo Vincent , Msika Philippe , Delcour J. P. , Crielaard J. M. , Henrotin Yves E. 
Published: January 2008

AbstractObjectiveTo determine the phenotype of osteoblasts from the sclerotic zones of human osteoarthritic (OA) subchondral bone.MethodsHuman osteoblasts were isolated from sclerotic or nonsclerotic areas of subchondral bone and cultured for 14 days in monolayer. The expression of 14 genes was investigated by real‐time reverse transcription–polymerase chain reaction. The activities of alkaline phosphatase (AP) and transglutaminases (TGases) were quantified by enzymatic assays. C‐terminal type I procollagen propeptide (CPI), interleukin‐1β (IL‐1β), IL‐6, IL‐8, transforming growth factor β1 (TGFβ1), osteocalcin (OC), and osteopontin (OPN) were assayed in the culture medium by immunoassay.ResultsGene expression levels of matrix metalloproteinase 13, COL1A1 and COL1A2, OPN, tissue‐nonspecific AP, OC, vascular endothelial growth factor, ANKH, TGase 2, factor XIIIA, and dentin matrix protein 1 were significantly up‐regulated in sclerotic osteoblasts compared with nonsclerotic osteoblasts. In contrast, parathyroid hormone receptor gene expression was depressed in sclerotic osteoblasts, but bone sialoprotein levels were unchanged. The activities of AP and TGases were increased in sclerotic osteoblasts, while matrix mineralization, revealed by alizarin red staining, was decreased. In parallel, protein synthesis of CPI, OC, OPN, IL‐6, IL‐8, and TGFβ1 was significantly higher in sclerotic osteoblasts than in nonsclerotic osteoblasts, while IL‐1β production was similar in both groups.ConclusionThese findings contribute to a better understanding of the mechanisms involved in subchondral bone sclerosis and identify osteoblasts with an altered phenotype as a potential target for future OA therapies.
The HLA–DRB1 shared epitope is associated with susceptibility to rheumatoid arthritis in African Americans through European genetic admixture
Authors: Hughes Laura B. , Morrison Dahliann , Kelley James M. , Padilla Miguel A. , Vaughan L. Kelly , Westfall Andrew O. , Dwivedi Harshit , Mikuls Ted R. , Holers V. Michael , Parrish Lezlie A. , Alarcón Graciela S. , Conn Doyt L. , Jonas Beth L. , Callahan Leigh F. , Smith Edwin A. , Gilkeson Gary S. , Howard George , Moreland Larry W. , Patterson Nick , Reich David , Bridges S. Louis 
Published: January 2008

AbstractObjectiveTo determine whether shared epitope (SE)–containing HLA–DRB1 alleles are associated with rheumatoid arthritis (RA) in African Americans and whether their presence is associated with higher degrees of global (genome‐wide) genetic admixture from the European population.MethodsIn this multicenter cohort study, African Americans with early RA and matched control subjects were analyzed. In addition to measurement of serum anti–cyclic citrullinated peptide (anti‐CCP) antibodies and HLA–DRB1 genotyping, a panel of >1,200 ancestry‐informative markers was analyzed in patients with RA and control subjects, to estimate the proportion of European ancestry.ResultsThe frequency of SE‐containing HLA–DRB1 alleles was 25.2% in African American patients with RA versus 13.6% in control subjects (P = 0.00005). Of 321 patients with RA, 42.1% had at least 1 SE‐containing allele, compared with 25.3% of 166 control subjects (P = 0.0004). The mean estimated percent European ancestry was associated with SE‐containing HLA–DRB1 alleles in African Americans, regardless of disease status (RA or control). As reported in RA patients of European ancestry, there was a significant association of the SE with the presence of the anti‐CCP antibody: 86 (48.9%) of 176 patients with anti‐CCP antibody–positive RA had at least 1 SE allele, compared with 36 (32.7%) of 110 patients with anti‐CCP antibody–negative RA (P = 0.01, by chi‐square test).ConclusionHLA–DRB1 alleles containing the SE are strongly associated with susceptibility to RA in African Americans. The absolute contribution is less than that reported in RA among populations of European ancestry, in which ∼50–70% of patients have at least 1 SE allele. As in Europeans with RA, the SE association was strongest in the subset of African American patients with anti‐CCP antibodies. The finding of a higher degree of European ancestry among African Americans with SE alleles suggests that a genetic risk factor for RA was introduced into the African American population through admixture, thus making these individuals more susceptible to subsequent environmental or unknown factors that trigger the disease.
Serum type I interferon activity is dependent on maternal diagnosis in anti‐SSA/Ro–positive mothers of children with neonatal lupus
Authors: Niewold Timothy B. , Rivera Tania L. , Buyon Jill P. , Crow Mary K. 
Published: January 2008

AbstractObjectiveThe type I interferon (IFN) pathway is activated in many patients with systemic lupus erythematosus (SLE), and high serum levels of IFN are associated with anti‐SSA/Ro autoantibodies. To investigate the clinical features associated with type I IFN production in vivo, we compared serum IFN activity in individuals with anti‐SSA/Ro antibodies who were asymptomatic with that in individuals with clinical manifestations of SLE or Sjögren's syndrome (SS).MethodsAntibody‐positive sera from 84 mothers of children with manifestations of neonatal lupus were studied for type I IFN activity, using a functional reporter cell assay. Maternal health status was characterized as asymptomatic, SS, SLE, pauci‐SLE, or pauci‐SS, based on a screening questionnaire, telephone interview, and review of medical records. The prefix “pauci‐” indicates symptoms insufficient for a formal classification of the disease.ResultsOnly 4% of asymptomatic mothers had high serum type I IFN activity, compared with 73% with pauci‐SLE (P = 5.7 × 10−5), 35% with SLE (P = 0.011), and 32% of patients with SS (P = 0.032). One of the 4 patients with pauci‐SS had high levels of IFN. The majority of patients for whom longitudinal data were available had stable type I IFN activity over time, and changes in IFN activity were not clearly accompanied by changes in the clinical diagnosis.ConclusionPatients with SLE, patients with pauci‐SLE, and patients with SS are more likely to have high serum IFN activity than asymptomatic individuals with SSA/Ro autoantibodies, suggesting that these autoantibodies are insufficient for activation of the type I IFN pathway, and that disease‐specific factors are important for type I IFN generation in vivo.
Treatment of Churg‐Strauss syndrome without poor‐prognosis factors: A multicenter, prospective, randomized, open‐label study of seventy‐two patients
Authors: Ribi Camillo , Cohen Pascal , Pagnoux Christian , Mahr Alfred , Arène Jean‐Pierre , Lauque Dominique , Puéchal Xavier , Letellier Philippe , Delaval Philippe , Cordier Jean‐François , Guillevin Loïc 
Published: January 2008

AbstractObjectiveTo assess the efficacy of systemic corticosteroids (CS) alone as first‐line treatment in patients with Churg‐Strauss syndrome (CSS) without poor‐prognosis factors, as defined by the Five‐Factors Score (FFS), and to compare the efficacy and safety of oral azathioprine (AZA) versus intravenous pulse cyclophosphamide (CYC) as adjuvant immunosuppressive therapy for treatment failure or relapse.MethodsThis multicenter, prospective, randomized, open‐label therapeutic trial included 72 patients with newly diagnosed CSS (FFS of 0) treated with CS alone. At treatment failure or relapse, patients were randomized to receive 6 months of oral AZA or 6 pulses of CYC. Analyses were performed according to an intent‐to‐treat strategy.ResultsThe mean ± SD followup was 56.2 ± 31.7 months. Among the 72 patients studied, 93% achieved remission with CS therapy alone, and 35% relapsed, mainly during the first year of treatment. Among the 19 patients randomized to additional immunosuppression because of treatment failure or relapse, 5 of 10 receiving AZA and 7 of 9 receiving pulse CYC achieved remission, but the difference was not statistically significant. Survival rates in all patients at 1 and 5 years were 100% and 97%, respectively. At the end of followup, 79% of the patients whose disease was in remission required low‐dose CS therapy, mainly to control respiratory disease. CS‐related adverse events were observed in 31% of the 72 patients.ConclusionIn CSS patients with an FFS of 0, survival was excellent, confirming the predictive value of the FFS in this disease. First‐line therapy with CS achieved remission in most patients, but relapses were common, and one‐third of them required additional immunosuppressive therapy. AZA or pulse CYC was fairly effective in treating CS‐resistant disease or major relapses. Over the long term, most patients continued to take oral CS, which might explain the high rate of CS‐related adverse events.
Antiinflammatory role of endomorphins in osteoarthritis, rheumatoid arthritis, and adjuvant‐induced polyarthritis
Authors: Straub Rainer H. , Wolff Christine , Fassold Alexander , Hofbauer Rafael , Chover‐Gonzalez Antonio , Richards Louise J. , Jessop David S. 
Published: January 2008

AbstractObjectivePain sensitization and the related secretion of neuropeptides from sensory nerve terminals are proinflammatory in osteoarthritis (OA), rheumatoid arthritis (RA), and adjuvant‐induced polyarthritis. In contrast, endogenous opioids such as the recently discovered endomorphins (EMs) are antiinflammatory. However, the role of endogenous EMs such as EM‐1 and EM‐2 has never been investigated in OA and RA.MethodsWe established a highly sensitive radioimmunoassay to detect EM‐1 and EM‐2. In patients with RA and patients with OA, immunohistochemistry for EM‐1 and EM‐2 was performed, and double‐staining was used to identify EM‐positive cells. The effects of EM‐1 and EM‐2 on the secretion of interleukin‐6 (IL‐6) and IL‐8 from human synovial tissue were studied by tissue superfusion, and the therapeutic effects of EM‐1 were tested in a rat model of adjuvant‐induced polyarthritis.ResultsEM‐positive cells were located in the sublining area and vessel walls but were particularly evident in the highly inflamed lining area. Human macrophages, T cells, and fibroblasts stained positive for EMs. The synovial density of EM‐positive cells was higher in patients with OA than in those with RA. EM‐1 inhibited synovial secretion of IL‐6 in patients with RA and secretion of IL‐8 in patients with RA and those with OA (maximum 10−10M). EM‐2 inhibited IL‐8 secretion only from RA tissue (maximum 10−10M). In rats with adjuvant‐induced polyarthritis, thymus, spleen, and synovial tissue contained significantly more EM‐1 than was observed in controls. Rats with adjuvant‐induced polyarthritis benefited from EM‐1 treatment.ConclusionEM‐1 had antiinflammatory effects in patients with OA or RA and in a model of adjuvant‐induced polyarthritis. Local enhancement of EM‐1 might be an interesting therapeutic option in different forms of arthritis.
Relapse of hepatitis C virus–associated mixed cryoglobulinemia vasculitis in patients with sustained viral response
Authors: Landau Dan‐Avi , Saadoun David , Halfon Philippe , Martinot‐Peignoux Michelle , Marcellin Patrick , Fois Elena , Cacoub Patrice 
Published: January 2008

AbstractObjectiveTo investigate the clinical characteristics, outcomes, and results of hepatitis C virus (HCV) RNA analyses in a group of patients with HCV‐associated mixed cryoglobulinemia (MC) vasculitis who experienced a relapse of vasculitis despite achieving a sustained viral response to treatment with antiviral agents.MethodsHCV RNA testing was performed by the transcription‐mediated amplification (TMA) method in sera and cryoprecipitates (detection limit 2.5 IU/ml). HCV replication was assessed in peripheral blood mononuclear cells (PBMCs) by a modified real‐time polymerase chain reaction assay (detection limit 15 IU/106 cells).ResultsWe identified 8 patients with relapse of HCV‐MC vasculitis despite their having achieved a sustained viral response to treatment. Relapse appeared early after the end of treatment (mean ± SD 2.5 ± 3.5 months) and included mainly purpura (n = 7) and arthralgia (n = 5). Relapse was associated with an increase in serum cryoglobulin levels as compared with end‐of‐treatment levels (mean ± SD 0.3 ± 0.09 gm/liter and 0.08 ± 0.04 gm/liter, respectively; P < 0.01) and a decrease in C4 levels. In most patients, the relapse was brief, and the MC vasculitis manifestations subsided. A search for HCV RNA by TMA was negative in all patients tested (7 of 8 patients), both in sera and in cryoprecipitates. HCV replication was not found in PBMCs from any of the patients tested (6 of 8 patients). In 3 patients, the MC vasculitis symptoms persisted and were associated with elevated cryoglobulin levels. B cell lymphoma was diagnosed in 2 of these 3 patients.ConclusionRelapse of MC vasculitis does occur in a few patients with HCV infection, despite achieving a sustained viral response, and this relapse is not related to persistence of virus. Relapse is short‐lived and may be induced by the withdrawal of interferon alfa therapy. However, in patients with persistent MC vasculitis symptoms, a different underlying condition should be considered, especially B cell lymphoma.
Cost‐effectiveness of intensive exercise therapy directly following hospital discharge in patients with arthritis: Results of a randomized controlled clinical trial
Authors: Bulthuis Yvette , Mohammad Sabrina , Braakman‐Jansen Louise M. A. , Drossaers‐Bakker K. Wiepke , van de Laar Martin A. F. J. 
Published: January 2008

AbstractObjectiveTo estimate the cost‐utility and cost‐effectiveness of a 3‐week intensive exercise training (IET) program directly following hospital discharge in patients with rheumatic diseases.MethodsPatients with arthritis who were admitted to the hospital because of a disease activity flare or for elective hip or knee arthroplasty were randomly assigned to either the IET group or usual care (UC) group. Followup lasted 1 year. Quality‐adjusted life years (QALYs) were derived from Short Form 6D scores and a visual analog scale (VAS) rating personal health. Function‐related outcome was measured using the Health Assessment Questionnaire, the McMaster Toronto Arthritis (MACTAR) Patient Preference Disability Questionnaire, and the Escola Paulista de Medicina Range of Motion scale (EPMROM). Costs were reported from a societal perspective. Differences in costs and incremental cost‐effectiveness ratios (ICERs) were estimated.ResultsData from 85 patients (50 IET and 35 UC) could be used for health‐economic analysis. VAS personal health–based QALYs were in favor of IET. Function‐related outcome showed statistically significant improvements in favor of IET over the first 6 months, according to the MACTAR (P < 0.05) and the EPMROM (P < 0.01). At 1‐year followup, IET was €718 less per patient. The ICER showed a reduction in mean total costs per QALY. In 70% of cases the intervention was cost‐saving.ConclusionIET results in better quality of life at lower costs after 1 year. Thus, IET is the dominant strategy compared with UC. This highlights the need for implementation of IET after hospital discharge in patients with arthritis.
The comparative one‐year performance of anti–tumor necrosis factor α drugs in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis: Results from a longitudinal, observational, multicenter study
Authors: Heiberg Marte Schrumpf , Koldingsnes Wenche , Mikkelsen Knut , Rødevand Erik , Kaufmann Cecilie , Mowinckel Petter , Kvien Tore K. 
Published: January 2008

AbstractObjectiveTo compare the 1‐year retention rates of anti–tumor necrosis factor α (anti‐TNFα) medications in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) with complementary analyses of the effect on health status.MethodsOur analyses comprised 847, 172, and 249 anti‐TNFα treatment courses in patients with RA, PsA, and AS, respectively. Crude drug survival was compared and hazard ratios (HRs) for treatment termination were calculated with adjustments for age, sex, investigator's global assessment, and concomitant methotrexate (MTX). Adjusted changes in health‐related quality of life (HRQOL) were compared among the groups.ResultsUnadjusted 1‐year retention rates were 65.4%, 77.3%, and 77.5% in the RA, PsA, and AS groups, respectively. The adjusted HRs for treatment termination were 0.76 (95% confidence interval [95% CI] 0.53–1.07) for PsA versus RA and 0.66 (95% CI 0.47–0.92) for AS versus RA. High baseline disease activity and female sex were significantly associated with premature treatment termination, whereas concomitant MTX was associated with better drug survival. However, the impact of MTX was apparent for RA and PsA, but not for AS in stratified analyses. The improvements in HRQOL were superior in patients with PsA and AS compared with RA.ConclusionOur results suggest that survival of anti‐TNFα treatment is superior in AS and PsA patients compared with RA patients. Larger improvements in HRQOL in patients with spondylarthritides may contribute to the differences in drug survival. Concomitant MTX was associated with better retention rates in RA and PsA patients, but not AS patients.
A followup study of antiphospholipid antibodies and associated neuropsychiatric manifestations in 137 children with systemic lupus erythematosus
Authors: Avčin Tadej , Benseler Susanne M. , Tyrrell Pascal N. , Čučnik Saša , Silverman Earl D. 
Published: January 2008

AbstractObjectiveTo determine the prevalence of anticardiolipin antibodies (aCL), anti–β2‐glycoprotein I (anti‐β2GPI) antibodies, and lupus anticoagulant (LAC) in a large cohort of children with systemic lupus erythematosus (SLE), and to evaluate the associations with neuropsychiatric manifestations.MethodsA single‐center retrospective cohort study with longitudinal followup of antiphospholipid antibodies (aPL) in 137 children with SLE (25 boys and 112 girls, mean age at diagnosis 13.0 years) was performed. Patients were followed up for a mean of 31 months.ResultsAt the time of diagnosis, 65% of the children were aCL positive, 41% had anti‐β2GPI antibodies, and 26% were LAC positive. Analysis of the association between presence of aPL and individual neuropsychiatric manifestations at diagnosis showed a statistically significant association of positive LAC with cerebrovascular disease (5 patients; P = 0.015). A persistently positive aCL was observed in 50%, anti‐β2GPI antibodies in 29%, and LAC in 16% of children over time. The prevalence of anti‐β2GPI antibodies, but not aCL and LAC, was found to be statistically significantly higher in children with neuropsychiatric disease compared with those without (P = 0.02). Comparison for specific neuropsychiatric manifestations showed a statistically significant association between a persistently positive LAC and chorea (2 patients; P = 0.02).ConclusionThe prevalence of anti‐β2GPI antibodies was found to be higher in the group of SLE patients with neuropsychiatric disease compared with those without. Our data suggest an association between LAC and cerebrovascular disease at the time of SLE diagnosis and chorea over the disease course, but not between aPL and other neuropsychiatric manifestations.
The prevalence of foot ulceration in patients with rheumatoid arthritis
Authors: Firth Jill , Hale Claire , Helliwell Philip , Hill Jackie , Nelson E. Andrea 
Published: January 2008

AbstractObjectiveTo establish the prevalence of foot ulceration in patients with rheumatoid arthritis (RA) in secondary care.MethodsA postal survey of all patients with RA (n = 1,130) under the care of rheumatologists in Bradford, West Yorkshire, UK was performed. The prevalence data were validated through clinical examination, case‐note review, and contact with health professionals. The false‐negative rate was investigated in a subsample of patients (n = 70) who denied any history of ulceration.ResultsThe postal survey achieved a 78% response rate. Following validation, the point prevalence of foot ulceration was 3.39% and the overall prevalence was 9.73%. The false‐positive rate was initially high at 21.21%, but use of diagrammatic questionnaire data to exclude leg ulceration reduced the rate to 10.76%. The false‐negative rate was 11.76%. The most common sites for ulceration were the dorsal aspect of hammer toes, the metatarsal heads, and the metatarsophalangeal joint in patients with hallux abducto valgus, with 33% of patients reporting multiple sites of ulceration. Patients with open‐foot and healed‐foot ulceration had significantly longer RA disease duration, reported significantly greater use of special footwear, and had a higher prevalence of foot surgery than ulcer‐free patients.ConclusionFoot ulceration affects a significant proportion of patients with RA. Further work is needed to establish risk factors for foot ulceration in RA and to target foot health provision more effectively.
Clinical correlates of quality of life in systemic sclerosis measured with the World Health Organization Disability Assessment Schedule II
Authors: Hudson Marie , Thombs Brett D. , Steele Russell , Watterson Rita , Taillefer Suzanne , Baron Murray ,   Canadian Scleroderma Research Group
Published: January 2008

AbstractObjectiveTo identify the clinical characteristics of systemic sclerosis (SSc) that best correlate with the health‐related quality of life (HRQOL) of patients with SSc, using the World Health Organization Disability Assessment Schedule II (WHODAS II) as the measure of HRQOL.MethodsA cross‐sectional, multicenter study of 337 patients from the Canadian Scleroderma Research Group Registry was conducted. Patients were assessed through detailed clinical histories, medical examination, and the WHODAS II. Hierarchical multiple linear regression was used to assess the relationship between selected clinical variables and HRQOL.ResultsThe mean WHODAS II score was 23.7 (range 0–100), with the greatest impairments seen in the subscales measuring life activities, mobility, and participation in society. In multivariate analysis, significant predictors of the WHODAS II were skin scores, shortness of breath, number of gastrointestinal problems, fatigue, pain, and depression. The final model explained 61% of the variance in the WHODAS II scores.ConclusionThe clinical characteristics identified in this study as significant correlates of HRQOL in SSc should each be targets of intervention in order to improve the HRQOL of patients with this disease.
Communication about depression during rheumatoid arthritis patient visits
Authors: Sleath Betsy , Chewning Betty , de Vellis Brenda M. , Weinberger Morris , de Vellis Robert F. , Tudor Gail , Beard Ashley 
Published: January 2008

AbstractObjectiveTo examine whether rheumatologists and rheumatoid arthritis (RA) patients with depressive symptoms communicate about depression.MethodsThe data used in this study came from a randomized controlled trial to improve provider‐patient communication about patients' agendas. The current secondary analysis used data collected at baseline, before any intervention occurred. A total of 200 RA patients from 4 rheumatology clinics participated in the study. Patient medical visits were audiotape recorded and patients were interviewed after their medical visits. Physicians recorded patients' American College of Rheumatology (ACR) functional status after their visits.ResultsTwenty‐one (11%) patients were scored as having moderately severe to severe symptoms of depression. Patients who were rated by their physicians as having worse ACR functional status were more than twice as likely to have moderately severe to severe symptoms of depression (odds ratio 2.23, 95% confidence interval 1.1–4.6). Only 4 (19%) of the 21 patients who were scored as having moderately severe to severe symptoms of depression discussed depression during their medical visits, and patients initiated the discussion each time.ConclusionRheumatologists should consider assessing depressive symptoms among their patients, especially among those with worse functional status.