bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of glycosaminoglycan loss on chondrocyte viability: A study on porcine cartilage explants
Authors: Otsuki Shuhei , Brinson Diana C. , Creighton Lilo , Kinoshita Mitsuo , Sah Robert L. , D'Lima Darryl , Lotz Martin 
Published: March 2008

AbstractObjectiveLoss of glycosaminoglycan (GAG) is an early event in osteoarthritis. Recent findings showed increased cell death in arthritic cartilage and linkage with extracellular matrix degradation. The aim of this study was to analyze the direct effect of GAG loss on chondrocyte survival and cell death following mechanical injury.MethodsIn full‐thickness cartilage explants from porcine knee joints, GAG was depleted by digestion with chondroitinase ABC. Explants were subjected to single‐impact mechanical injury. Cell viability and the types of cell death were analyzed by Live/Dead cell assay, staining for active caspase 3, and sensitivity to caspase inhibitor.ResultsGAG depletion did not directly lead to increased cell death. In chondroitinase ABC–treated explants, but not in control explants, mechanical injury caused an immediate reduction in cell viability (from 84.6% to 71.0%); the reduction was prominent in the superficial zone. This immediate cell death was not inhibited by the pancaspase inhibitor Z‐VAD‐FMK, suggesting cell necrosis. During subsequent culture, viability in these explants decreased further, to 50.5% on day 3. The second wave of cell death was reduced by the addition of Z‐VAD‐FMK in chondroitinase ABC–treated explants and was also associated with activation of caspase 3, suggesting apoptotic mechanisms of cell death.ConclusionThese results indicate that GAG loss alone does not directly lead to chondrocyte death. In response to mechanical injury, there is an immediate induction of necrotic cell death that is seen only in GAG‐depleted explants and primarily in the superficial zone. During subsequent culture, cell death spreads via apoptotic mechanisms.
Increased cortisol relative to adrenocorticotropic hormone predicts improvement during anti–tumor necrosis factor therapy in rheumatoid arthritis
Authors: Straub Rainer H. , Pongratz Georg , Cutolo Maurizio , Wijbrandts Carla A. , Baeten Dominique , Fleck Martin , Atzeni Fabiola , Grunke Mathias , Kalden Joachim R. , Schölmerich Jürgen , Lorenz Hanns‐Martin , Tak Paul P. , Sarzi‐Puttini Piercarlo 
Published: March 2008

AbstractObjectiveSome patients with chronic inflammatory diseases such as rheumatoid arthritis (RA) improve rapidly from anti–tumor necrosis factor (anti‐TNF) therapy. No sensitive markers are available that might predict outcome of anti‐TNF therapy. We undertook this study to investigate the predictive value of hypothalamic–pituitary–adrenal (HPA) axis hormones for clinical improvement during anti‐TNF therapy.MethodsAn observational study in 23 RA patients was followed by a validation study in 38 RA patients. The patients receiving anti‐TNF antibodies had no glucocorticoid treatment, and we measured baseline serum levels of adrenocorticotropic hormone (ACTH) and cortisol. Improvement during anti‐TNF antibody treatment was judged by the Disease Activity Score in 28 joints (DAS28), and serum levels of cortisol were measured at followup.ResultsThe observational study demonstrated that improvement in the DAS28 correlated negatively with baseline serum levels of cortisol (R = −0.520, P = 0.011) and the cortisol:ACTH ratio (R = −0.700, P = 0.0002). In the longitudinal part of the study at followup, those patients with good improvement and initially low serum levels of cortisol demonstrated an increase of serum cortisol, in contrast to patients with little or no improvement. Findings in the observational study were supported by those in the validation study in a group of RA patients with less inflammation (correlation of improvement in the DAS28 with cortisol:ACTH ratio: R = –0.320, P = 0.025).ConclusionThis is the first study in a human chronic inflammatory disease to demonstrate that inflammation‐induced TNF interferes with HPA axis integrity, which is linked to the disease outcome. These findings position the HPA axis centrally in the vicious circle of perpetuation of chronic inflammation.
Association of interleukin‐23 receptor variants with ankylosing spondylitis
Authors: Rahman Proton , Inman Robert D. , Gladman Dafna D. , Reeve Jeff P. , Peddle Lynette , Maksymowych Walter P. 
Published: March 2008

AbstractObjectiveRecent studies have shown that a nonsynonymous single‐nucleotide polymorphism (SNP) (Arg381Gln; rs11209026) in the interleukin‐23 receptor (IL‐23R) gene on chromosome 1p31 is associated with Crohn's disease and psoriasis. Given the clinical and immunologic overlap between ankylosing spondylitis (AS) and these diseases, and the potential function of this candidate SNP, this study was undertaken to examine the association of IL‐23R variants with AS in multiple Canadian populations.MethodsWe examined 3 cohorts of AS patients from established rheumatic disease centers in Canada. The majority of AS patients were Caucasians of northern European descent, and all patients satisfied the modified New York classification criteria for AS or for juvenile spondylarthritis. We examined 424 AS probands and 401 controls from Alberta, 251 AS probands and 122 controls from Toronto, and 121 AS probands and 219 controls from Newfoundland. Ten IL‐23R SNPs were genotyped, 9 of which were incorporated in the haplotype analysis. Allele and haplotype associations were calculated using the WHAP software package.Pvalues for haplotype associations were calculated using a permutation test.ResultsThe primary SNP of interest in a previous study of inflammatory bowel disease (IBD) (Arg381Gln; rs11209026) was found to be protective against AS in the Newfoundland population (P= 0.04) and in the Toronto population (P= 0.04) in single‐marker univariate analysis. The strongest association, however, was with SNP rs11465804 (P= 0.007 for the Newfoundland population andP= 0.0007 for the Toronto population). A 3‐marker sliding window omnibus test revealed a significant association with markers rs10489629, rs2201841, and rs11465804 in both the Newfoundland population (P= 0.04) and the Alberta population (P= 0.034). Our results were independent of the IBD and psoriasis status of the AS patients.ConclusionThis concurrent analysis of 3 distinct AS populations and their regional controls demonstrates a disease association with the IL‐23R locus and implicates the same polymorphisms associated with IBD and psoriasis.
Genetic association of vasoactive intestinal peptide receptor with rheumatoid arthritis: Altered expression and signal in immune cells
Authors: Delgado Mario , Robledo Gema , Rueda Blanca , Varela Nieves , O'Valle Francisco , Hernandez‐Cortes Pedro , Caro Marta , Orozco Gisela , Gonzalez‐Rey Elena , Martin Javier 
Published: March 2008

AbstractObjectiveVasoactive intestinal peptide (VIP) has been shown to be one of the endogenous factors involved in the maintenance of immune tolerance. Administration of VIP ameliorates clinical signs in various experimental autoimmune disorders. This study was undertaken to investigate whether the exacerbated inflammatory autoimmune response in rheumatoid arthritis (RA) might result directly from altered expression and/or signaling of VIP receptors in immune cells.MethodsThe effect of specific agonists of different VIP receptors on collagen‐induced arthritis in mice was investigated by clinical and histologic assessment and measurement of cytokine and chemokine production. Expression of VIP receptor type 1 (VPAC1) in synovial cells and monocytes from RA patients was determined by flow cytometry. Potential associations of VPAC1 genetic polymorphisms with RA susceptibility were investigated.ResultsA VPAC1 agonist was very efficient in the treatment of experimental arthritis, and deficient expression of VPAC1 in immune cells of RA patients was associated with the predominant proinflammatory Th1 milieu found in this disease. Immune cells derived from RA patients were less responsive to VIP signaling than were cells from healthy individuals and showed reduced VIP‐mediated immunosuppressive activity, rendering leukocytes and synovial cells more proinflammatory in RA. A significant association between multiple‐marker haplotypes of VPAC1 and susceptibility to RA was found, suggesting that the reduced VPAC1 expression in RA‐derived immune cells is associated with the described VPAC1 genetic polymorphism.ConclusionThese findings are highly relevant to the understanding of RA pathogenesis. They suggest that VIP signaling through VPAC1 is critical to maintaining immune tolerance in RA. In addition, the results indicate that VPAC1 may be a novel therapeutic target in RA.
Changes in surgical loads and economic burden of hip and knee replacements in the US: 1997–2004
Authors: Kim Sunny 
Published: March 2008

AbstractObjectiveA major component of the economic burden associated with the treatment of arthritis relates to surgical joint replacements of the hips/knees. The purpose of this study was to describe the recent trend of hip/knee replacements and the associated economic burden.MethodsThe Nationwide Inpatient Survey from 1997 to 2004 was analyzed. The International Classification of Diseases, Ninth Revision, Clinical Modification procedure coding was used to identify joint replacement cases.ResultsDuring 2004, ∼225,900 (95% confidence interval [95% CI] 201,782–250,018) primary hip replacements and 431,485 (95% CI 397,454–465,516) primary knee replacements were performed. This was a 37% increase in primary hip replacements and a 53% increase in primary knee replacements compared with 2000. The number of primary replacement procedures increased equally for males and females; however, the number of procedures increased excessively among persons age 45–64 years. While Medicare remained the major source of payment (55.4% for primary hip replacements, 59.3% for primary knee replacements), private insurance payment experienced a steeper increase. In 2004, the national bill of hospital charges for hip/knee replacements was $26.0 billion, the hospital cost was $9.1 billion, and the amount of reimbursement was $7.2 billion (28% of hospital charges or 79% of hospital cost). Nearly 600,000 hip replacements and 1.4 million knee replacements will be performed in the year 2015.ConclusionThe number of joint replacement procedures performed is growing faster than ever. The health care community should consider and prepare for this upcoming demand of surgical loads and its associated economical burden.
Prescribing pattern of drugs in the treatment of osteoarthritis in italian general practice: The effect of rofecoxib withdrawal
Authors: Alacqua Marianna , Trifirò Gianluca , Cavagna Lorenzo , Caporali Roberto , Montecucco Carlo Maurizio , Moretti Salvatore , Tari Domenico Ugo , Galdo Mariella , Caputi Achille P. , Arcoraci Vincenzo 
Published: March 2008

AbstractObjectiveIn October 2004, rofecoxib was removed from the world market because of an increased risk of myocardial infarction. The aim of the present study was to compare the trend of nonsteroidal antiinflammatory drug (NSAID) use and other analgesics in osteoarthritis (OA) treatment before and after rofecoxib withdrawal in Italian general practice.MethodsFrom the Caserta‐1 Local Health Service database, 97 general practitioners were recruited. Prevalence and incidence of use of any study drug were calculated within 1 year before and after rofecoxib withdrawal.ResultsOne‐year prevalence of nonselective and preferential NSAID use did not change after rofecoxib withdrawal, whereas coxib use fell from 4.4% (95% confidence interval [95% CI] 4.2–4.5%) in the period before rofecoxib withdrawal (period I) to 1.6% (95% CI 1.5–1.7%) in the period after withdrawal (period II). Weak opioids were used in no more than 0.4% (95% CI 0.3–0.5%) in period II, after their introduction to reimbursement in December 2004. Also, 1‐year incidence of coxib decreased from 31.3 per 1,000 (95% CI 30.2–32.4%) in period I to 8.7 per 1,000 (95% CI 8.1–9.2%) in period II. The disappearance of rofecoxib was associated with replacement drugs such as newly marketed dexibuprofen and aceclofenac, whereas nimesulide use coincidentally decreased.ConclusionRofecoxib withdrawal has markedly changed the prescribing pattern of drugs that are used in OA‐related pain treatment, with a striking decrease of coxib use in Italian general practice. Education strategies addressed to health professionals should be planned to improve the management of pain treatment, particularly in degenerative joint diseases.
High titer of serum antiphospholipid antibody levels in adult Henoch‐Schönlein purpura and cutaneous leukocytoclastic angiitis
Authors: Kawakami Tamihiro , Yamazaki Masahide , Mizoguchi Masako , Soma Yoshinao 
Published: March 2008

AbstractObjectiveTo investigate a possible role of antiphospholipid (aPL) antibodies in adult Henoch‐Schönlein purpura (HSP) and cutaneous leukocytoclastic angiitis (CLA).MethodsWe reviewed the records of 30 HSP and 8 CLA adults with an initial cutaneous manifestation of palpable purpura on their lower extremities between 2003 and 2007. Eight microscopic polyangiitis (MPA) patients and 30 healthy persons were recruited as controls. Serum anticardiolipin (aCL), anti–phosphatidylserine‐prothrombin complex (anti‐PS/PT), and anti–β2‐glycoprotein I (anti‐β2GPI) antibody levels in HSP, CLA, MPA patients, and healthy controls were measured by enzyme‐linked immunosorbent assay.ResultsTwenty‐two HSP patients (73%) were positive for serum IgA aCL antibodies. Nineteen (63%) had IgA anti‐PS/PT antibodies and 4 (13%) had IgA anti‐β2GPI antibodies. IgA aCL and anti‐PS/PT antibodies showed a significant correlation (P = 0.007). Twenty (67%) HSP patients had IgM anti‐PS/PT antibodies and 6 (20%) had IgG anti‐PS/PT antibodies. Six (75%) CLA patients had IgM anti‐PS/PT antibodies and 2 (25%) had IgG anti‐PS/PT antibodies. In contrast, aPL antibodies were not found in any MPA patients or normal controls. Serum IgA aCL antibody levels in HSP patients showed a significant correlation with serum IgA and C‐reactive protein (CRP) levels (P = 0.030 and 0.039, respectively). A positive correlation between CRP and serum IgA anti‐PS/PT antibody levels was observed in HSP patients (P = 0.023). Serum IgA aCL antibody levels were also significantly associated with proteinuria according to urinalysis (P = 0.024).ConclusionSerum levels of IgA aCL and anti‐PS/PT antibodies were elevated in adult HSP, suggesting that serum IgA antibodies may play some role in adult HSP. IgA aCL and/or anti‐PS/PT antibodies could serve as markers for adult HSP and should be monitored as an indicator of adult HSP activity. Small‐vessel vasculitis could be dependently associated with the presence of IgM anti‐PS/PT antibodies. These findings suggest that aPL antibodies are closely related to the pathogenic factors that trigger the development of vasculitis.
Impaired arterial function associated with thinning of cortical bone in rheumatoid arthritis
Authors: Roldán José F. , Escalante Agustín , del Rincón Inmaculada 
Published: March 2008

AbstractObjectiveTo evaluate the association between peripheral arterial function and cortical bone thickness in rheumatoid arthritis (RA).MethodsIn a cross‐sectional study, we measured the combined cortical thickness (CCT) of the second metacarpal bone from hand radiographs, and the ankle‐to‐arm systolic blood pressure ratio, also known as ankle–brachial index (ABI), in RA patients. We evaluated the association between the 2 using multinomial logistic regression.ResultsWe obtained CCT and ABI measurements in 588 RA patients. The mean ± SD CCT was 3.62 ± 1.16 mm. The proportion of patients with ≥1 ABI value ≤0.9, indicating obstructed lower limb arteries, increased from 18 (9.2%) of 191 patients in the highest CCT tertile to 25 (12.5%) of 200 in the middle CCT tertile to 38 (19.2%) of 198 in the lowest CCT tertile (P for trend 0.005). We noted a similar pattern for ABI values >1.3, indicative of arterial incompressibility (frequencies in high, middle, and low CCT tertiles were 4.7%, 9.5%, and 19.9%, respectively; P for trend ≤0.001). These trends remained significant after multivariable adjustment for potential confounders. After adjustment for the manifestations of RA and cumulative glucocorticoid dose, the association between CCT and arterial obstruction remained significant, but that with arterial incompressibility weakened considerably.ConclusionThere is an association between metacarpal cortical bone thinning and obstruction or incompressibility of the peripheral arteries in RA. The association with incompressibility may be mediated by systemic inflammation and/or glucocorticoids, but that with obstruction is independent of a wide array of potential confounders. Clinicians should be alert to the possibility of impaired arterial function RA patients with thinned metacarpal cortical bone.
Prepared patients: Internet information seeking by new rheumatology patients
Authors: Hay M. Cameron , Cadigan R. Jean , Khanna Dinesh , Strathmann Cynthia , Lieber Eli , Altman Roy , McMahon Maureen , Kokhab Morris , Furst Daniel E. 
Published: March 2008

AbstractObjectiveTo investigate to what extent and why new rheumatology patients access medical information online prior to first appointments and secondarily to ask whether they discuss information gained from the Internet with physicians.MethodsResearch was conducted in a teaching rheumatology clinic with a nonrandom sample of 120 English‐speaking adults presenting for first appointments in rheumatology. Quantitative and qualitative data were gained in pre‐ and postappointment patient surveys and interviews, including online information gathering prior to first appointment, demographics, health status, information usage in patient‐physician interactions, and satisfaction. Data were analyzed for significant relationships across variables and for qualitative insights into quantitative outcome measures.ResultsOf all patients, 87.5% looked up their symptoms or suspected condition prior to their first appointment and 62.5% of all patients sought that information on the Internet. Only 20% of online information seekers discussed that information with their physicians. Age and sex were significant predictors of Internet information seeking. Physician and patient appointment satisfaction was significantly higher when Internet information was discussed; however, most patients did not discuss their information seeking because they primarily feared being perceived as challenging their physician.ConclusionThe majority of patients research their conditions online prior to initial appointments, but are unlikely to discuss that research with physicians even though discussion is related to higher satisfaction. Physicians may want to consider strategies for enabling communication about online research.
Disability in valued life activities among individuals with systemic lupus erythematosus
Authors: Katz Patricia , Morris Anne , Trupin Laura , Yazdany Jinoos , Yelin Edward 
Published: March 2008

AbstractObjectiveTo identify the prevalence of disability in a wide range of valued life activities (VLAs) among individuals with systemic lupus erythematosus (SLE), 1‐year changes in such disability, and predictors of and changes in VLA disability.MethodsData were from 2 waves of a cohort of 829 individuals with SLE interviewed annually by telephone. VLA disability was assessed using a scale rating the difficulty of performing 21 activities. Scores were also calculated for subscales corresponding to obligatory, committed, and discretionary activities. Changes in VLA disability from baseline to 1‐year followup were assessed. Sociodemographic and disease status measures were examined as predictors of and changes in VLA disability using multiple regression analyses.ResultsAlmost half of the subjects were unable to perform ≥1 VLA at baseline. Almost all (91%) reported ≥1 VLA affected by SLE. One‐quarter of the subjects experienced a significant increase in the number of activities they were unable to perform; approximately half experienced significant increases in the number of activities affected and in difficulty scores. Proportions of individuals whose disability increased and whose disability decreased were roughly equivalent. Disease status measures accounted for 62–72% of the variation in VLA difficulty. More severe disease status was predictive of increases in VLA difficulty; few predictors of improvements were identified.ConclusionVLA disability was common, with more disability noted in committed and discretionary activities than in obligatory activities. Because VLA disability has been linked to psychological well‐being in previous studies, identification of factors that may protect against such disability is important.
Prognostic factors in short‐term disability due to musculoskeletal disorders
Authors: Abásolo Lydia , Carmona Loreto , Lajas Cristina , Candelas Gloria , Blanco Margarita , Loza Estibaliz , Hernández‐García César , Jover Juan A. 
Published: March 2008

AbstractObjectiveTo identify factors associated with poor outcome in temporary work disability (TWD) due to musculoskeletal disorders (MSDs).MethodsWe conducted a secondary data analysis of a 2‐year randomized controlled trial in which all patients with TWD due to MSDs in 3 health districts of Madrid (Spain) were included. Analyses refer to the patients in the intervention group. Primary outcome variables were duration of TWD and recurrence. Diagnoses, sociodemographic, work‐related administrative, and occupational factors were analyzed by Cox proportional hazards models.ResultsWe studied 3,311 patients with 4,424 TWD episodes. The following were independently associated with slower return to work: age (hazard ratio [HR] 0.99, 95% confidence interval [95% CI] 0.98–0.99), female sex (HR 0.84, 95% CI 0.78–0.90), married (HR 0.90, 95% CI 0.83–0.97), peripheral osteoarthritis (HR 0.77, 95% CI 0.6–0.9), sciatica (HR 0.59, 95% CI 0.54–0.65), self‐employment (HR 0.56, 95% CI 0.48–0.65), unemployment (HR 0.41, 95% CI 0.28–0.58), manual worker (HR 0.86, 95% CI 0.79–0.94), and work position covered during sick leave (HR 0.84, 95% CI 0.77–0.92). The factors that better predicted recurrence were peripheral osteoarthritis (HR 1.75, 95% CI 1.14–2.6), inflammatory diseases (HR 1.66, 95% CI 1.009–2.72), sciatica (HR 1.30, 95% CI 1.08–1.56), indefinite work contract (HR 1.43, 95% CI 1.14–1.75), frequent kneeling (HR 1.39, 95% CI 1.15–1.69), manual worker (HR 1.19, 95% CI 1.003–1.42), and duration of previous episodes (HR 1.003, 95% CI 1.001–1.005).ConclusionSociodemographic, work‐related administrative factors, diagnosis, and, to a lesser extent, occupational factors may explain the duration and recurrence of TWD related to MSD.