bluuebunny/crossref_metadata_2025_split huggingface dataset:
Premature aging of the immune system in children with juvenile idiopathic arthritis
Authors: Prelog Martina , Schwarzenbrunner Nora , Sailer‐Höck Michaela , Kern Hannelore , Klein‐Franke Andreas , Ausserlechner Michael J. , Koppelstaetter Christian , Brunner Andrea , Duftner Christina , Dejaco Christian , Strasak Alexander M. , Müller Thomas , Zimmerhackl Lothar Bernd , Brunner Jürgen 
Published: June 2008

AbstractObjectiveJuvenile idiopathic arthritis (JIA) is an autoimmune disease of the young. The pathogenesis is not completely understood. Premature aging, associated thymic involution, and compensatory autoproliferation could play important roles in the pathogenesis of autoimmunity. We undertook this study to determine whether patients with JIA demonstrate premature immunosenescence.MethodsTo test this hypothesis, we measured 3 indicators of aging: the percentages and total counts of peripheral blood naive T cells, the frequency of T cell receptor excision circles (TRECs) in naive T cells, and telomeric erosion and Ki‐67 expression as estimates of the replicative history of homeostatic proliferation.ResultsJIA patients showed an accelerated loss of CD4+,CD45RA+,CD62L+ naive T cells with advancing age and a compensatory increase in the number of CD4+,CD45RO+ memory T cells. JIA patients demonstrated a significantly decreased frequency of TRECs in CD4+,CD45RA+ naive T cells compared with age‐matched healthy donors (P = 0.002). TREC numbers correlated with age only in healthy donors (P = 0.0001). Telomeric erosion in CD4+,CD45RA+ naive T cells was increased in JIA patients (P = 0.01). The percentages of Ki‐67–positive CD4+,CD45RA+ naive T cells were increased in JIA patients (P = 0.001) and correlated with disease duration (P = 0.003), which was also an independent factor contributing to telomeric erosion (P = 0.04).ConclusionOur findings suggest that age‐inappropriate T cell senescence and disturbed T cell homeostasis may contribute to the development of JIA. In patients with JIA, dysfunction in the ability to reconstitute the T cell compartment should be considered when exploring new therapeutic strategies.
Inflammation‐associated insulin resistance: Differential effects in rheumatoid arthritis and systemic lupus erythematosus define potential mechanisms
Authors: Chung Cecilia P. , Oeser Annette , Solus Joseph F. , Gebretsadik Tebeb , Shintani Ayumi , Avalos Ingrid , Sokka Tuulikki , Raggi Paolo , Pincus Theodore , Stein C. Michael 
Published: June 2008

AbstractObjectiveInsulin resistance is increased by inflammation, but the mechanisms are unclear. The present study was undertaken to test the hypothesis that decreased insulin sensitivity is differentially associated with mediators of inflammation by studying 2 chronic inflammatory diseases of different pathogenesis, systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).MethodsWe measured fasting insulin, glucose, and lipid levels, erythrocyte sedimentation rate (ESR), C‐reactive protein (CRP), interleukin‐6 (IL‐6), tumor necrosis factor α (TNFα), and coronary artery calcification in 103 patients with SLE and in 124 patients with RA. Insulin sensitivity was measured using the homeostasis model assessment (HOMA) index.ResultsThe HOMA value was higher in RA patients (median 2.05 [interquartile range (IQR) 1.05–3.54]) than in SLE patients (1.40 [0.78–2.59]) (P = 0.007). CRP and ESR did not differ significantly in RA and SLE patients. Body mass index (BMI) was significantly correlated with the HOMA index in both RA (ρ = 0.20) and SLE (ρ = 0.54), independently of age, sex, race, and current use of corticosteroids. In RA patients, the HOMA index was also significantly positively correlated with IL‐6 (ρ = 0.63), TNFα (ρ = 0.50), CRP (ρ = 0.29), ESR (ρ = 0.26), coronary calcification (ρ = 0.26), and Disease Activity Score in 28 joints (ρ = 0.21); associations adjusted for age, sex, race, BMI, and current use of corticosteroids remained significant (P < 0.05). In SLE patients, the HOMA index was also significantly correlated with ESR (ρ = 0.35) and CRP (ρ = 0.25), but not with other variables. The association between the ESR and the HOMA value in patients with SLE remained significant after adjustment for confounding covariates (P = 0.008). In multivariable models, the major contributing factors to the HOMA index were the BMI in SLE patients, and IL‐6 and TNFα levels in RA patients.ConclusionThe pathogenesis of insulin resistance and its contribution to atherogenesis varies in different inflammatory settings.
The PTPN22 620W allele confers susceptibility to systemic sclerosis: Findings of a large case–control study of European Caucasians and a meta‐analysis
Authors: Dieudé P. , Guedj M. , Wipff J. , Avouac J. , Hachulla E. , Diot E. , Granel B. , Sibilia J. , Cabane J. , Meyer O. , Mouthon L. , Kahan A. , Boileau C. , Allanore Y. 
Published: June 2008

AbstractObjectiveTo determine whether genetic variants of the PTPN22 gene, including the R620W (1858C>T) missense single‐nucleotide polymorphism (SNP), are associated with systemic sclerosis (SSc). Since PTPN22 is involved in multiple autoimmune diseases, we also examined the occurrence of a concomitant autoimmune disease. We then conducted a meta‐analysis of the most recent studies of SSc in order to verify the association or lack of association between the PTPN22 1858C>T variant and SSc.MethodsSeven PTPN22 SNPs were analyzed in a French Caucasian cohort of 659 SSc patients and 504 healthy controls. All SSc patient sera were tested for the presence of autoantibodies against topoisomerase I (anti–topo I) and for anticentromere antibodies (ACAs).ResultsThe co‐occurrence of an autoimmune disease was observed in 22% of the 416 SSc patients who were exhaustively screened. In 33 of the 416 patients (8%), the concomitant autoimmune disease was known to be associated with PTPN22 1858T; these patients were excluded prior to analysis. No association was detected for any of the SNPs tested. PTPN22 haplotype analysis identified a strong association between SSc and the presence of a risk haplotype carrying the 1858T allele (P = 1.52 × 10–7) and a protective haplotype carrying the 1858C allele (P = 2.20 × 10–16) in our French Caucasian population. The meta‐analysis provided evidence that the PTPN22 1858T allele is involved in the genetic susceptibility to SSc in Caucasian (P = 8.39 × 10–3, OR 1.08 [95% CI 1.02–1.15]) and mixed (P = 3.11 × 10–3, OR 1.09 [95% CI 1.04–1.16]) populations, particularly in the anti–topo I–positive subset.ConclusionOur results indicate that PTPN22, a shared genetic factor of multiple autoimmune diseases, also contributes to the genetic background of SSc.
Lack of association of functional CTLA4 polymorphisms with juvenile idiopathic arthritis
Authors: Prahalad Sampath , Bohnsack John F. , Whiting April , Clifford Bronte , Jorde Lynn B. , Guthery Stephen L. , Thompson Susan D. , Glass David N. , Bamshad Michael J. 
Published: June 2008

AbstractObjectiveJuvenile idiopathic arthritis (JIA) is an autoimmune disorder mediated by Th1 immune responses. CTLA‐4, expressed on the T cell surface, plays a negative role in regulating T cell activation. Single‐nucleotide polymorphisms (SNPs) in CTLA4 have been implicated in susceptibility to several autoimmune disorders, including JIA. This study was undertaken to test 3 functional CTLA4 variants for association with JIA.MethodsFamilies of 531 children with JIA were genotyped for SNPs located in the promoter region (C−318T), exon 1 (A49G), and the 3′‐untranslated region (CT60) of CTLA4 by polymerase chain reaction amplification and digestion. Family Based Association Testing (FBAT) was used to test CTLA4 SNPs and haplotypes for association with JIA. A second independent cohort of >300 children with JIA and >500 controls were genotyped for case–control analyses. Case–control analyses of the combined cohorts, as well as meta‐analyses of published association studies of CTLA4 and JIA, were performed.ResultsThere were no deviations of transmission of any of the CTLA4 variants to children with JIA, or JIA subtypes, determined by FBAT. No significant associations between CTLA4 C−318T or A49G SNPs and JIA were found in 650 JIA cases and 350 controls. Similarly, no significant associations with CT60 variants were found in >800 JIA cases and >500 controls. The meta‐analysis also failed to confirm an association between JIA and CTLA4 variants.ConclusionThese results suggest that C−318T, A49G, CT60, and haplotypes tagged by these CTLA4 SNPs are not associated with JIA or major JIA subtypes.
Risk factors for cardiovascular complications following total joint replacement surgery
Authors: Basilico Frederick C. , Sweeney Gerard , Losina Elena , Gaydos James , Skoniecki Debra , Wright Elizabeth A. , Katz Jeffrey N. 
Published: June 2008

AbstractObjectiveTo determine risk factors for cardiac complications following total joint replacement (TJR) surgery.MethodsWe performed a case–control study of patients who had undergone a primary or revision total knee or total hip replacement surgery. Cases consisted of those who received a TJR and experienced a cardiac complication during the surgical admission period (myocardial infarction [MI], congestive heart failure [CHF], unstable angina, arrhythmia, symptomatic hypotension, or pulmonary embolus). Controls consisted of those who received a TJR and did not experience a cardiac complication during the surgical admission period. Controls were matched to the cases for age at surgery, year of surgery, and surgeon. Case and control status and identification of potential risk factors were ascertained by review of medical records. Conditional logistic regression analysis was used to identify independent predictors of cardiac complications.ResultsThe sample included 209 cases and 209 controls. Factors associated with a higher risk of cardiac complications included a history of arrhythmia (adjusted odds ratio [OR] 2.6 [95% confidence interval (95% CI) 1.5–4.3]), a history of coronary artery disease, MI, CHF, or valvular heart disease (OR 1.6 [95% CI 0.9–2.6]), revision surgery (OR 2.2 [95% CI 1.2–3.9]), and bilateral surgery (adjusted OR 3.5 [95% CI 1.6–8.0]). Even though controls were matched for age (within age brackets), age was still associated with a higher risk of cardiac complications (OR 1.7 [95% CI 0.9–3.4]).ConclusionThis case–control study identified 2 new risk factors for cardiac complications following TJR: bilateral and revision surgery. The study also confirmed previously documented risk factors, including older age at surgery and a history of arrhythmia and of other cardiac problems. These findings should help clinicians anticipate and prevent cardiac complications following TJR surgery.
Sjögren's syndrome and localized nodular cutaneous amyloidosis: Coincidence or a distinct clinical entity?
Authors: Meijer Jiska M. , Schonland Stefan O. , Palladini Giovanni , Merlini Giampaolo , Hegenbart Ute , Ciocca Olga , Perfetti Vittorio , Leijsma Martha K. , Bootsma Hendrika , Hazenberg Bouke P. C. 
Published: June 2008

AbstractObjectiveTo report 8 patients with Sjögren's syndrome (SS) and localized nodular cutaneous amyloidosis and to examine serologic and immunohistologic findings that may link the 2 diseases.MethodsThe databases for 3 amyloidosis centers were searched for patients with localized nodular cutaneous amyloidosis and SS. Eight patients with this combination were identified, and clinical, serologic, and histologic parameters were retrospectively evaluated.ResultsAmong the 8 patients with a clinical diagnosis of SS, 6 fulfilled the American–European Consensus Group criteria for SS. All of the patients were women in whom SS had been diagnosed at a median age of 47 years (range 30–61 years) and amyloid had been diagnosed at a median age of 60 years (range 42–79 years). The presence of the immunoglobulin light chain type of amyloid (AL amyloid) was confirmed in 4 patients. In 3 of these 4 patients as well as 2 other patients, a light chain–restricted plasma cell population was observed near the amyloid deposits. Progression to systemic amyloidosis was not observed in any patient during a median followup of 3.5 years.ConclusionSS should be considered in patients with cutaneous amyloidosis. The combination of cutaneous amyloidosis and SS appears to be a distinct disease entity reflecting a particular and benign part of the polymorphic spectrum of lymphoproliferative diseases related to SS.
Age‐ and sex‐related patterns of serum interferon‐α activity in lupus families
Authors: Niewold Timothy B. , Adler Jeremy E. , Glenn Stuart B. , Lehman Thomas J. A. , Harley John B. , Crow Mary K. 
Published: June 2008

AbstractObjectiveInterferon‐α (IFNα) levels are elevated in many patients with systemic lupus erythematosus (SLE) and may play a primary role in its pathogenesis. The purpose of this study was to determine whether serum IFNα activity in SLE patients and their healthy first‐degree relatives is highest in early adulthood, when the incidence of SLE is greatest.MethodsSerum samples from 315 SLE patients, 359 healthy first‐degree relatives, and 141 healthy unrelated donors were measured for IFNα activity using a functional reporter cell assay. IFNα activity was analyzed in relation to age, and subgroups with high levels of IFNα activity were identified within the large data sets using a Mann‐Whitney sliding window segmentation algorithm. The significance of each subgrouping was ranked by Kruskal‐Wallis testing.ResultsAge was inversely correlated with IFNα activity in female SLE patients (r = –0.20, P = 0.001) as well as their healthy female first‐degree relatives (r = –0.16, P = 0.02). In male patients and their healthy male first‐degree relatives, there was no significant overall correlation between age and serum IFNα activity. The segmentation algorithm revealed significantly increased IFNα activity between the ages of 12 and 22 years in female SLE patients and between the ages of 16 and 29 years in male SLE patients. Both male and female healthy first‐degree relatives had significantly decreased IFNα activity after the age of 50 years.ConclusionSerum IFNα activity is higher in younger individuals in the SLE family cohorts, and this tendency is accentuated in affected individuals. This age‐related pattern of IFNα activity may contribute to the increased incidence of SLE in early adulthood, and interestingly, males and females had similar age‐related patterns of IFNα activity.
Modulation of RANKL and osteoprotegerin expression in synovial tissue from patients with rheumatoid arthritis in response to disease‐modifying antirheumatic drug treatment and correlation with radiologic outcome
Authors: Haynes David , Crotti Tania , Weedon Helen , Slavotinek John , Au Virginia , Coleman Mark , Roberts‐Thomson Peter J. , Ahern Michael , Smith Malcolm D. 
Published: June 2008

AbstractObjectiveTo demonstrate the effect of treatment with disease‐modifying agents on the expression of osteoprotegerin (OPG) and RANKL in the synovial tissue from rheumatoid arthritis (RA) patients and to correlate these changes with radiologic damage measured on sequential radiographs of the hands and feet.MethodsSynovial biopsy specimens were obtained at arthroscopy from 25 patients with active RA (16 of whom had a disease duration <12 months) before and at 3–6‐month intervals after starting treatment with a disease‐modifying agent. Immunohistologic analysis was performed using monoclonal antibodies to detect OPG and RANKL expression, with staining quantitated using computer‐assisted image analysis and semiquantitative analysis techniques. Serial radiographs of the hands and feet were analyzed independently by 2 radiologists and a rheumatologist using the van der Heide modification of the Sharp scoring method.ResultsThirteen patients achieved a low disease state as defined by a disease activity score <2.6 while 19 patients achieved an American College of Rheumatology response >20% after disease‐modifying antirheumatic drug (DMARD) treatment. Successful DMARD treatment resulted in an increase in OPG expression and a decrease in RANKL expression at the synovial tissue level, which correlated with a reduction in erosion scores measured on annual radiographs of the hands and feet.ConclusionSuccessful treatment‐induced modulation of OPG and RANKL expression at the synovial tissue level, resulting in a reduction in the RANKL:OPG ratio, is likely to have a significant impact on osteoclast formation and joint damage in patients with active RA.
Rheumatoid arthritis patients' perceptions of mutuality in conversations with spouses/partners and their links with psychological and physical health
Authors: Kasle Shelley , Wilhelm Mari S. , Zautra Alex J. 
Published: June 2008

AbstractObjectiveMutuality, measured as subjects' perceptions of responsiveness in conversations with their spouse/partners, is linked with women's psychological health. Our objectives were to examine physical and psychological health outcomes of married/partnered patients with rheumatoid arthritis (RA) in relation to their perceptions of their own responsiveness (self‐mutuality), their partner's responsiveness (partner‐mutuality), and combined responsiveness (overall mutuality), and to examine potential sex differences in the links between mutuality and depressive symptoms.MethodsSymptoms of depression and anxiety, physical disability, and arthritis impact reported by RA patients were examined in correlation matrices with their perceptions of overall mutuality, partner‐mutuality, and self‐mutuality in conversations with spouses/partners in the whole sample (n = 148) and separately for men (n = 34) and women (n = 114). Sex moderation of the links between mutuality and depression was tested in hierarchical regressions.ResultsIn the whole sample and among women, all mutuality measures had significant inverse correlations with all health outcomes. In men, physical disability was unrelated to mutuality measures, but otherwise correlations approximated those in the whole sample and for women. Sex (being female) interacted with self‐mutuality, but not overall or partner‐mutuality, in predicting fewer depressive symptoms.ConclusionRA patients' perceptions of mutuality in conversations with spouses/partners predicted better health across a spectrum of outcomes. Overall mutuality and partner‐mutuality predicted fewer depressive symptoms for both men and women, but self‐mutuality appeared more important for women than for men. The clinical relevance of findings and their implications for behavioral interventions with RA patients are discussed.
Identifying the clinical domains of fibromyalgia: Contributions from clinician and patient delphi exercises
Authors: Mease Phillip J. , Arnold Lesley M. , Crofford Leslie J. , Williams David A. , Russell I. Jon , Humphrey Louise , Abetz Linda , Martin Susan A. 
Published: June 2008

AbstractObjectiveIn evaluating the effectiveness of fibromyalgia (FM) therapies, it is important to assess the impact of those therapies on the full array of domains considered important by both clinicians and patients. The objective of this research was to identify and prioritize the key clinically relevant and important domains impacted by FM that should be evaluated by outcome assessment instruments used in FM clinical trials, and to approach consensus among clinicians and patients on the priority of those domains to be assessed in clinical care and research.MethodsGroup consensus was achieved using the Delphi method, a structured process of consensus building via questionnaires together with systematic and controlled opinion feedback. The Delphi exercises involved 23 clinicians with expertise in FM and 100 patients with FM as defined by American College of Rheumatology criteria.ResultsThe Delphi exercise revealed that the domains ranked most highly by patients were similar to the domain rankings by clinicians. Pain was consistently ranked highest by both panels. Fatigue, impact on sleep, health‐related quality of life, comorbid depression, and cognitive difficulty were also ranked highly. Stiffness was ranked highly by patients but not clinicians. In contrast, side effects was important to clinicians but was not identified as important in the patient Delphi exercise.ConclusionThe clinician and patient Delphi exercises identified and ranked key domains that need to be assessed in FM research. Based on these results, a conceptual framework for measuring patient‐reported outcomes is proposed.
Trends in physician‐diagnosed osteoarthritis incidence in an administrative database in British Columbia, Canada, 1996–1997 through 2003–2004
Authors: Kopec Jacek A. , Rahman M. Mushfiqur , Sayre Eric C. , Cibere Jolanda , Flanagan William M. , Aghajanian Jaafar , Anis Aslam H. , Jordan Joanne M. , Badley Elizabeth M. 
Published: June 2008

AbstractObjectivePrevalence of osteoarthritis (OA) is expected to increase due to population aging. However, there is little information on the trends in the incidence of OA over time. The purpose of this study was to describe changes in physician‐diagnosed OA incidence rates between 1996–1997 and 2003–2004 in British Columbia (BC), Canada.MethodsWe used data on all visits to health professionals and hospital admissions covered by the Medical Services Plan of BC (population ∼4 million) for the fiscal years 1991–1992 through 2003–2004. Rates were standardized to the BC population in 2000. We used 2 definitions of OA: 1) at least 1 visit or hospitalization with a diagnostic code for OA, and 2) at least 2 visits or 1 hospitalization with a code for OA. Incidence rates were calculated with a 5‐year run‐in period to exclude prevalent cases.ResultsBetween 1996–1997 and 2003–2004, crude incidence rates of OA based on definition 1 increased from 10.5 to 12.2 per 1,000 in men and from 13.9 to 17.4 per 1,000 in women. The age‐standardized rates did not change in men and increased from 14.7 to 16.7 per 1,000 in women. Incidence rates based on definition 2 were almost 50% lower, but the trends were similar.ConclusionWe observed an increase in the incidence of OA in both men and women due to population aging and an additional increase in women beyond the effect of aging. These trends have important implications for public health and provision of health services to this very large group of patients.