bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating endothelial cells as a marker of ongoing vascular disease in systemic sclerosis
Authors: Del Papa Nicoletta , Colombo Gualtiero , Fracchiolla Nicola , Moronetti Lorenza Mazzeo , Ingegnoli Francesca , Maglione Wanda , Comina Denise P. , Vitali Claudio , Fantini Flavio , Cortelezzi Agostino 
Published: April 2004

AbstractObjectiveCirculating endothelial cells (CECs) have been described in different conditions involving vascular injury. Vascular abnormalities play a key role in the pathogenesis of systemic sclerosis (SSc). The aim of this study was to search for the presence of CECs in patients with SSc and to evaluate their clinical associations and possible pathogenic role.MethodsThe study cohort included 46 patients with SSc and 40 healthy controls. Five‐parameter, 3‐color flow cytometry was performed with a FACScan. CECs were defined as CD45 negative, CD34 positive, and P1H12 positive, and activated CECs were defined as CD45 negative and P1H12 positive, CD62 positive, or CD106 positive. Progenitors were identified as CD34 positive and CD133 positive.ResultsTotal and activated CEC counts were significantly higher in SSc patients compared with healthy controls and were positively correlated with the disease activity score. With respect to visceral involvement, significant correlation was observed between the CEC number and the severity of pulmonary hypertension. High levels of endothelial progenitors were observed in patients with SSc, and the counts were higher in the early stages of disease.ConclusionThe presence of CECs in patients with SSc may represent direct evidence of endothelial disease and may be a promising new clinical marker for active SSc. Notably, the association between CECs and pulmonary hypertension and impaired carbon monoxide diffusing capacity was evident in patients with limited cutaneous SSc only, suggesting an important role for CECs in this disease subset with prominent vascular changes. Detection of circulating endothelial progenitors may represent a response to vascular ischemia in early SSc, as an attempt at revascularization.
Slowing of bone loss in patients with rheumatoid arthritis by long‐term high‐intensity exercise: Results of a randomized, controlled trial
Authors: de Jong Zuzana , Munneke Marten , Lems Willem F. , Zwinderman Aeilko H. , Kroon Herman M. , Pauwels Ernest K. J. , Jansen Annemarie , Ronday Karel H. , Dijkmans Ben A. C. , Breedveld Ferdinand C. , Vliet Vlieland Theodora P. M. , Hazes Johanna M. W. 
Published: April 2004

AbstractObjectivePatients with rheumatoid arthritis (RA) are more at risk for the development of osteoporosis and osteoporotic fractures than are their healthy peers. In this randomized, controlled, multicenter trial, the effectiveness of a 2‐year high‐intensity weight‐bearing exercise program (the Rheumatoid‐Arthritis‐Patients‐In‐Training [RAPIT] program) on bone mineral density (BMD) was compared with usual care physical therapy, and the exercise modalities associated with changes in BMD were determined.MethodsThree hundred nine patients with RA were assigned to an intervention group, either the RAPIT program or usual care physical therapy. The primary end points were BMD of the hip and spine. The exercise modalities examined were aerobic fitness, muscle strength, and, as a surrogate for those effects not directly measured by the RAPIT program, attendance rate.ResultsThe data on the 136 RAPIT participants and 145 usual care participants who completed the study were analyzed. The mean rate of decrease in hip BMD, but not in lumbar spine BMD, was smaller in patients participating in the RAPIT program when compared with that in the usual care group, with a mean decrease of 1.6% (95% confidence interval [95% CI] 0.8–2.5) over the first year and 0.5% (95% CI 1.1–2.0) over the second year. The change in hip BMD was significantly and independently associated with changes in both muscle strength (multivariate odds ratio [OR] 1.75, 95% CI 1.07–2.86) and aerobic fitness (OR 1.79, 95% CI 1.10–2.90), but not with the attendance rate (OR 1.00, 95% CI 0.99–1.00).ConclusionA long‐term high‐intensity weight‐bearing exercise program for RA patients is effective in slowing down the loss of BMD at the hip. The exercise modalities associated with this effect are muscle strength and aerobic fitness.
Association of the interleukin‐1 gene cluster with radiographic signs of osteoarthritis of the hip
Authors: Meulenbelt Ingrid , Seymour Albert B. , Nieuwland Marja , Huizinga Tom W. J. , van Duijn Cornelia M. , Slagboom P. Eline 
Published: April 2004

AbstractObjectiveTo study the role of the interleukin‐1β gene (IL1B) and the IL‐1 receptor antagonist gene (IL1RN) in relation to the occurrence of radiographic osteoarthritis (ROA) in the hip, knee, and hand and disc degeneration of the spine.MethodsThe study population consisted of a random sample of 886 subjects (ages 55–65 years) from a population‐based cohort (the Rotterdam study). Two polymorphisms within IL1B (3953C>T and −511C>T) and one within IL1RN (the variable‐number tandem repeat [VNTR]) were analyzed and used in an association study of the occurrence of ROA. Haplotyping and simultaneous logistic regression analysis were performed to investigate whether the associations observed were independent.ResultsAssociations with a predisposition for hip ROA were observed for heterozygous and homozygous carriers of the rare IL1B allele −511T (crude odds ratio [OR] 1.8, 95% confidence interval [95% CI] 1.0–3.4 and OR 2.9, 95% CI 1.4–6.3, respectively) and of the IL1RN VNTR allele 2 (crude OR 2.0, 95% CI 1.1–3.4 and OR 3.3, 95% CI 1.4–7.8, respectively). An additive effect was observed for carriers of risk alleles of both polymorphisms, with a significant linear‐by‐linear association (P = 0.00022).ConclusionOur findings suggest that the IL‐1 gene cluster polymorphisms may play a significant role in the pathogenesis of OA of the hip.
Magnetic resonance imaging of wrist and finger joints in healthy subjects occasionally shows changes resembling erosions and synovitis as seen in rheumatoid arthritis
Authors: Ejbjerg Bo , Narvestad Eva , Rostrup Egill , Szkudlarek Marcin , Jacobsen Søren , Thomsen Henrik S. , Østergaard Mikkel 
Published: April 2004

AbstractObjectiveTo explore the presence of changes resembling rheumatoid arthritis erosions and synovitis in metacarpophalangeal (MCP) and wrist joints of healthy individuals on magnetic resonance imaging (MRI) and to compare the MRI findings with conventional radiographic, clinical, and biochemical findings.MethodsTwenty‐eight healthy individuals were studied. Contrast‐enhanced MRI and conventional radiography of the dominant wrist and second through fifth MCP joints were performed, coupled with standard clinical assessments and biochemical analyses. MR images were evaluated according to the latest OMERACT (Outcome Measures in Rheumatology Clinical Trials) recommendations with respect to synovitis, erosions, and bone marrow edema.ResultsConventional radiography revealed erosion‐like changes in 1 of 224 MCP joint bones (0.4%) and in 1 of 420 wrist joint bones (0.2%). MRI depicted low‐grade erosion‐like changes in 5 of 224 MCP joint bones (2.2%) and in 7 of 420 wrist joint bones (1.7%), but postcontrast enhancement within the lesion was detected in only 8.3% of these. MRI depicted low‐grade synovitis‐like changes in 10 of 112 MCP joints (8.9%) and in 8 of 84 assessed wrist areas (9.5%), while only minimal early synovial enhancement was detected by dynamic MRI. Three subjects had elevated serum levels of C‐reactive protein, and these subjects displayed 44.5% of the synovitis‐like changes and 41.7% of the erosion‐like changes. Bone marrow edema–like changes were not found in any joints.ConclusionChanges resembling mild synovitis or small bone erosions are occasionally found in the MCP and wrist joints of healthy controls. Signs of synovitis on dynamic MRI, enhancement within bone erosion–like changes, and signs of bone marrow edema appear rarely or are absent in healthy controls. These signs may thus prove to be very specific in the distinction between arthritic and normal joints.
Mediation of spontaneous knee osteoarthritis by progressive chondrocyte ATP depletion in Hartley guinea pigs
Authors: Johnson Kristen , Svensson Camilla I. , Etten Deborah Van , Ghosh Soumitra S. , Murphy Anne N. , Powell Henry C. , Terkeltaub Robert 
Published: April 2004

AbstractObjectiveBecause articular chondrocytes reside in a hypoxic milieu, anaerobic glycolysis is central in generating ATP to support chondrocyte matrix synthesis and viability, with mitochondrial oxidative phosphorylation possibly providing physiologic reserve ATP generation. Nitric oxide (NO) potently suppresses mitochondrial oxidative phosphorylation. Because enhanced cartilage NO generation occurs in osteoarthritis (OA), we systematically tested for mitochondrial dysfunction in the pathogenesis of OA.MethodsWe assessed chondrocytes for ATP depletion and for in situ changes in mitochondrial ultrastructure prior to and during the evolution of spontaneous knee OA in male Hartley guinea pigs, a model in which chondrocalcinosis also supervenes.ResultsSpontaneous NO release from knee cartilage samples in organ culture doubled between ages 2 months and 8 months as knee OA developed. Concomitantly, chondrocyte intracellular ATP levels declined by ∼50%, despite a lack of mitochondrial ultrastructure abnormalities in knee chondrocytes. As ATP depletion progressed with aging in knee chondrocytes, an increased ratio of lactate to pyruvate was observed, consistent with an adaptive augmentation of glycolysis to mitochondrial dysfunction. Furthermore, we observed progressive elevation of chondrocyte ATP‐scavenging nucleotide pyrophosphatase/phosphodiesterase (NPP) activity and extracellular levels of the NPP enzymatic end product inorganic pyrophosphate (PPi), which stimulate chondrocalcinosis.ConclusionProfound chondrocyte ATP depletion develops in association with heightened NO generation in guinea pig knee OA. Increased NPP activity and concordant increases in extracellular PPi, which are strongly associated with human aging‐associated degenerative arthropathy and directly stimulate chondrocalcinosis, may be primarily driven by chondrocyte ATP depletion. Our findings implicate a decreased mitochondrial bioenergetic reserve as a pathogenic factor in both degenerative arthropathy and chondrocalcinosis in aging.
Association of the major histocompatibility complex with response to infliximab therapy in rheumatoid arthritis patients
Authors: Martinez Alfonso , Salido Marina , Bonilla Gema , Pascual‐Salcedo Dora , Fernandez‐Arquero Miguel , de Miguel Sonia , Balsa Alejandro , de la Concha Emilio G. , Fernandez‐Gutierrez Benjamin 
Published: April 2004

AbstractObjectiveTo determine whether major histocompatibility complex (MHC) polymorphisms are associated with a good or poor response to infliximab therapy in patients with rheumatoid arthritis (RA).MethodsSeventy‐eight infliximab‐treated patients with RA were genotyped for HLA–DRB1, HLA–DQA1, HLA–DQB1, MHC class I chain–related gene A (MICA) transmembrane polymorphism alleles, and tumor necrosis factor a (TNFa), TNFb, TNFc, TNFd, TNFe, D6S273, HLA–B–associated transcript 2 (BAT2), and D6S2223 microsatellites. Chi‐square tests were performed to compare allele proportions between responder and nonresponder patients. A control sample of 342 healthy individuals was also included to detect linkage disequilibrium between pairs of markers.ResultsAmong responders, the frequency of the TNFa11;b4 minihaplotype was increased (41% versus 16% in nonresponders; P = 0.01) and that of the D6S273_3 allele was decreased (32% versus 56% in nonresponders; P = 0.04). The D6S273_4/BAT2_2 pair was much more frequently observed among responders (46% versus 11% in nonresponders; P = 0.001). When compared with controls, this pair of alleles was found to be associated only with the group of responder patients (46% in responders versus 17% in controls; P = 0.00002). Most of the time, these markers are present in a DRB1*0404/D6S273_4/BAT2_2/TNFa11;b4 context. No statistically significant differences were observed for MICA and D6S2223 polymorphisms and for shared epitope status.ConclusionThe data suggest that genetic determinants of response to infliximab therapy exist in the HLA complex.
A modified model of graft‐versus‐host–induced systemic sclerosis (scleroderma) exhibits all major aspects of the human disease
Authors: Ruzek Melanie C. , Jha Sharda , Ledbetter Steve , Richards Susan M. , Garman Richard D. 
Published: April 2004

AbstractObjectiveDiffuse systemic sclerosis (SSc; scleroderma) is a debilitating disease characterized by excessive dermal fibrosis with later progression to internal organs. In addition to the fibrotic component, major aspects of the disease include vascular or circulatory involvement and immune dysregulation evidenced by inflammatory cells in affected tissues and production of autoantibodies. Many animal models resembling this disease have been studied, including genetic models in mice and chickens, challenge with chemicals such as bleomycin or vinyl chloride to induce fibrosis, and models of graft‐versus‐host (GVH)–induced disease using certain strains of mice with differences in minor histocompatibility loci. The present studies were undertaken to determine if alteration of the induction of GVH‐induced scleroderma could result in a model that more fully represented the human condition.MethodsDisease was induced by injection of spleen cells from B10.D2 mice into BALB/c mice deficient in mature T and B cells (recombination‐activating gene 2 targeted). Dermal thickening, collagen deposition, vasoconstriction, and parameters of immunity were analyzed.ResultsSimilar to the human disease, this modified GVH model of SSc demonstrated evidence of dermal thickening, particularly in the extremities, progressive fibrosis of internal organs, vasoconstriction and altered expression of vascularity markers in skin and internal organs, early immune activation, inflammation in skin and internal organs, and autoantibody generation.ConclusionThis modified model of GVH‐induced SSc exhibits all major components of human disease and is likely to contribute to better understanding of the disease mechanisms and, ultimately, improved treatments for patients.
A functional haplotype of the PADI4 gene associated with rheumatoid arthritis in a Japanese population is not associated in a United Kingdom population
Authors: Barton Anne , Bowes John , Eyre Stephen , Spreckley Kristian , Hinks Anne , John Sally , Worthington Jane 
Published: April 2004

AbstractObjectiveIn the era of postgenomic research, linkage‐ and association‐based strategies are beginning to reveal novel complex disease genes. Using such an approach, a functional haplotype of the peptidylarginine deiminase 4 gene (PADI4) has recently been identified as a gene conferring susceptibility to rheumatoid arthritis (RA) in a Japanese population. In the present study, we investigated the association of single‐nucleotide polymorphisms (SNPs) in the PADI4 gene with RA in a UK population.MethodsAssociation with 4 exonic SNPs (padi4_89*G/A, padi4_90*T/C, padi4_92*G/C, and padi4_104*T/C), mapping to the PADI4 gene and defining a haplotype previously reported to be associated with RA, was investigated. Genotyping was performed using 5′ allelic discrimination assays. Estimated haplotypes were generated using the expectation‐maximization algorithm, and frequencies of the SNPs and haplotypes were compared between unrelated Caucasian RA patients from the UK (n = 839) and population controls (n = 481).ResultsAllele frequencies for the 4 SNPs in the UK population were similar to those reported in the Japanese control population, but none of these was associated with RA. As in the Japanese population, the SNPs in the UK population defined 2 major haplotypes, but neither was associated with RA (P = 0.79).ConclusionA PADI4 susceptibility haplotype associated with RA in a Japanese population is not associated with RA in a UK population. Other genes involved in the citrullinating pathway remain strong candidate RA‐susceptibility genes and require further investigation.
Mortality and causes of death in primary Sjögren's syndrome: A prospective cohort study
Authors: Theander Elke , Manthorpe Rolf , Jacobsson Lennart T. H. 
Published: April 2004

AbstractObjectiveThis study was undertaken to analyze standardized mortality ratios (SMRs) and causes and predictors of death in primary Sjögren's syndrome (SS) diagnosed according to 3 different classification criteria sets (the Copenhagen criteria, the European criteria, and the American‐European consensus criteria (AECC).MethodsA linked registry study using information from the Malmö Primary SS Registry combined with the Swedish Cause‐of‐Death Registry was performed, and SMRs were calculated. Kaplan‐Meier survival curves and log rank tests were used to compare survival probability between subgroups of patients with primary SS. Cox regression analysis was used to study the predictive value of various laboratory findings at the time of diagnosis.ResultsFour hundred eighty‐four patients with a median followup of 7 years (range 1 month to 17 years 11 months) were included. The SMR for those fulfilling the AECC (n = 265) was 1.17 (95% confidence interval [95% CI] 0.81–1.63). Thirty‐four deaths occurred in this group of patients. Excess mortality was found only for lymphoproliferative malignancy (cause‐specific SMR 7.89 [95% CI 2.89–17.18]), corresponding to 2.53 excess deaths per 1,000 person‐years at risk. In those not fulfilling the AECC (n = 219), 14 deaths occurred, the SMR was 0.71 (95% CI 0.39–1.20), and no excess mortality due to any specific cause was found. Hypocomplementemia, defined as C3 and/or C4 values in the lowest quartile of the SS patients' values at the time of diagnosis, was a significant predictor of death, mainly due to lymphoproliferative malignancy.ConclusionNo increased all‐cause mortality could be detected for patients with primary SS compared with the general population. When subgroups of primary SS were compared, excess mortality due to lymphoproliferative malignancy was found in patients fulfilling the AECC, the strongest predictor for unfavorable outcome being low C3 and/or C4 levels at the time of diagnosis.
Systemic lupus erythematosus in three ethnic groups. XVIII. Factors predictive of poor compliance with study visits
Authors: Uribe América G. , Alarcón Graciela S. , Sanchez Martha L. , McGwin Gerald , Sandoval Robert , Fessler Barri J. , Bastian Holly M. , Friedman Alan W. , Baethge Bruce A. , Reveille John D. ,   For the Lumina Study Group
Published: April 2004

AbstractObjectiveTo determine the baseline factors predictive of poor compliance with study visits in a longitudinal multiethnic lupus cohort study.MethodsPatients with systemic lupus erythematosus (n = 344) representing a total of 2,069 potential study visits were studied. Of the participants, 24.4% were Hispanic, 43.3% African American, and 32.3% Caucasian. Noncompliance was defined as missing 2 or more study visits. For the purpose of these analyses, visits completed only by review of medical records were considered missing. Baseline socioeconomic–demographic, clinical, and psychosocial features between compliant and noncompliant patients were compared. Variables with P < 0.10 were then entered into a multivariable logistic regression analysis with compliance being the dependent variable.ResultsThere were 178 compliant and 166 noncompliant patients. Noncompliant patients were more likely to be young, unmarried, of African American ethnicity, live closer to the medical centers, and have longer disease duration and greater disease activity as assessed by the physician than the compliant patients. In the multivariable model, longer disease duration (P = 0.010), higher level of disease activity (P = 0.009), and shorter distance to travel to study visits (P = 0.046) were predictors of noncompliance; their odds ratios and confidence intervals were below 1.ConclusionsWe have identified baseline patient characteristics that may predict noncompliance with study visits (disease duration, disease activity, and distance to the medical center). This information will serve as the basis for developing interventions to curtail noncompliance. Our data may have applicability in other lupus cohort studies.
Giant cell arteritis without clinically evident vascular involvement in a defined population
Authors: Gonzalez‐Gay Miguel A. , Garcia‐Porrua Carlos , Amor‐Dorado Juan C. , Llorca Javier 
Published: April 2004

AbstractObjectivesTo examine the frequency and clinical presentation of biopsy‐proven giant cell arteritis (GCA) patients who do not exhibit overt clinical vascular manifestations. To assess whether differences exist between this group of patients and the rest of biopsy‐proven GCA patients.MethodsRetrospective study of biopsy‐proven GCA patients diagnosed from 1981 through 2001 at the single hospital for a well‐defined population of almost 250,000 people. Patients were considered as having no evident vascular involvement if cranial ischemic manifestations or other vascular complications of GCA were not present at the time of diagnosis or during at least 12 months' followup.ResultsBetween 1981 and 2001, 210 patients from the Lugo region of northwest Spain were diagnosed with biopsy‐proven GCA. Eleven patients did not show overt vascular manifestations of GCA. Nine of them presented with polymyalgia rheumatica (PMR) and another 2 fulfilled criteria for fever of unknown origin. Patients without clinically evident vascular involvement had a significantly longer delay to diagnosis than those with vascular manifestations. Also, PMR manifestations were more frequently observed in this group of patients.ConclusionsBiopsy‐proven GCA without clinically evident vascular involvement is not exceptional. Despite having a longer delay to diagnosis, these patients constitute a more benign subgroup of GCA.
Predictors of pain in children with established juvenile rheumatoid arthritis
Authors: Malleson Peter N. , Oen Kiem , Cabral David A. , Petty Ross E. , Rosenberg Alan M. , Cheang Mary 
Published: April 2004

AbstractObjectiveTo examine demographic and disease‐related variables that affect pain in a large cohort of patients with juvenile rheumatoid arthritis (JRA).MethodsSelection criteria were an onset of JRA ≥5 years prior to study and age ≥8 years at the time of the study. Pain was measured by a self‐administered 10‐cm visual analog scale. Possible explanatory variables studied included age at study, sex, race, onset subtype, active disease duration, active joint count, and physician's global assessment (PGA).ResultsIn a multiple regression model, active disease duration, PGA, and age at study were independent predictors explaining 22% of the variation in pain scores. Stratified analyses showed an effect of age in the 8–15‐year group, but not in older patients.ConclusionDisease‐related factors explain only a small proportion of the variation in pain scores. Age has an effect on pain scores only in younger patients. The role of other factors, including psychosocial factors, needs further study.