bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased proliferation of human synovial mesenchymal stem cells with autologous human serum: Comparisons with bone marrow mesenchymal stem cells and with fetal bovine serum
Authors: Nimura Akimoto , Muneta Takeshi , Koga Hideyuki , Mochizuki Tomoyuki , Suzuki Koji , Makino Hatsune , Umezawa Akihiro , Sekiya Ichiro 
Published: January 2008

AbstractObjectiveSynovial mesenchymal stem cells (MSCs) are a promising cell source for cartilage regeneration due to their high chondrogenic potential. For clinical safety, autologous human serum should be used instead of fetal bovine serum (FBS). We undertook this study to compare the 2 types of serum for their enhancement of the proliferation and chondrogenic potentials of synovial MSCs and to investigate the mechanisms of the differences. Since effectiveness of the sera might depend on the origin of the MSCs, we also examined bone marrow MSCs.MethodsSynovium, bone marrow, and peripheral blood were obtained from 18 donors. Synovial and bone marrow MSCs were cultured with autologous human serum or FBS and analyzed. In addition, rabbit synovial MSCs cultured with autologous serum or FBS were transplanted into full‐thickness cartilage defects of the knees of the same rabbits.ResultsHuman synovial MSCs expanded more in human serum than in FBS, and the opposite results were obtained with bone marrow MSCs. Hierarchical clustering analysis showed that the cell source, rather than the type of serum, affected the gene expression profile. Human serum contained high levels of platelet‐derived growth factor (PDGF), synovial MSCs expressed higher levels of PDGF receptor α than did bone marrow MSCs, and neutralizing PDGF decreased the proliferation of synovial MSCs with autologous human serum. Although the in vitro chondrogenic potential of human synovial MSCs was affected by the serum source, the in vivo chondrogenic potential of rabbit synovial MSCs was similar in autologous serum and FBS groups.ConclusionAutologous serum predominates in increasing the proliferation of synovial MSCs with chondrogenic potential through PDGF signaling.
Cathepsin K deficiency partially inhibits, but does not prevent, bone destruction in human tumor necrosis factor–transgenic mice
Authors: Schurigt Uta , Hummel Klaus M. , Petrow Peter K. , Gajda Mieczyslaw , Stöckigt Renate , Middel Peter , Zwerina Jochen , Janik Tobias , Bernhardt Ricardo , Schüler Susann , Scharnweber Dieter , Beckmann Felix , Saftig Paul , Kollias George , Schett Georg , Wiederanders Bernd , Bräuer Rolf 
Published: January 2008

AbstractObjectiveCathepsin K is believed to have an eminent role in the pathologic resorption of bone. However, several studies have shown that other proteinases also participate in this process. In order to clarify the contribution of cathepsin K to the destruction of arthritic bone, we applied the human tumor necrosis factor (hTNF)–transgenic mouse model, in which severe polyarthritis characterized by strong osteoclast‐mediated bone destruction develops spontaneously.MethodsArthritis was evaluated in hTNF‐transgenic mice that were either wild‐type for cathepsin K (CK+/+), heterozygous for cathepsin K (CK+/−), or deficient in cathepsin K (CK−/−). Arthritic knee joints were prepared for standard histologic assessment aimed at establishing a semiquantitative score for joint destruction and quantification of the area of bone erosion. Additionally, microfocal computed tomography was performed to visualize bone destruction in mice with the different CK genotypes. CK+/+ and CK−/− osteoclasts were generated in vitro, and their proteinase expression profiles were compared by complementary DNA array analysis, real‐time polymerase chain reaction, and activity assays.ResultsAlthough the area of bone erosion was significantly reduced in hTNF‐transgenic CK−/− mice, the absence of cathepsin K did not completely protect against inflammatory bone lesions. Several matrix metalloproteinases (MMPs) and cathepsins were expressed by in vitro–generated CK−/− osteoclasts, without marked differences from CK+/+ osteoclasts. MMP activity was detected in CK−/− osteoclasts, and MMP‐14 was localized by immunohistochemistry in inflammatory bone erosions in hTNF‐transgenic CK−/− mice, suggesting MMPs as potential contributors to bone destruction. Additionally, we detected a reduction in osteoclast formation in cathepsin K–deficient mice, both in vitro and in vivo.ConclusionThe results of our experiments raise doubts about a crucial role of cathepsin K in arthritic bone destruction.
Persistent association of nailfold capillaroscopy changes and skin involvement over thirty‐six months with duration of untreated disease in patients with juvenile dermatomyositis
Authors: Christen‐Zaech Stéphanie , Seshadri Roopa , Sundberg Joyce , Paller Amy S. , Pachman Lauren M. 
Published: January 2008

AbstractObjectiveTo determine the association of changes on nailfold capillaroscopy with clinical findings and genotype in children with juvenile dermatomyositis (DM), in order to identify potential differences in disease course over 36 months.MethodsAt diagnosis of juvenile DM in 61 children prior to the initiation of treatment, tumor necrosis factor α (TNFα) −308 allele and DQA1*0501 status was determined, juvenile DM Disease Activity Scores (DAS) were obtained, and nailfold capillaroscopy was performed. The disease course was monitored for 36 months. Variations within and between patients were assessed by regression analysis.ResultsAt diagnosis, shorter duration of untreated disease (P = 0.05) and a lower juvenile DM skin DAS (P = 0.035) were associated with a unicyclic disease course. Over 36 months, end‐row loop (ERL) regeneration was associated with lower skin DAS (P < 0.001) but not muscle DAS (P = 0.98); ERL regeneration and decreased bushy loops were associated with a shorter duration of untreated disease (P = 0.04 for both). At 36 months, increased ERL regeneration (P = 0.007) and improvement of skin DAS (P < 0.001) and muscle DAS (P = 0.025) were associated with a unicyclic disease course.ConclusionEarly treatment of juvenile DM may lead to a unicyclic disease course. The non‐unicyclic disease course usually involves continuing skin manifestations with persistent nailfold capillaroscopy changes. The correlation of nailfold capillaroscopy results with cutaneous but not with musculoskeletal signs of juvenile DM over a 36‐month period suggests that the cutaneous and muscle vasculopathies have different pathophysiologic mechanisms. These findings indicate that efforts to identify the optimal treatment of cutaneous features in juvenile DM require greater attention.
Association between treatment with central nervous system stimulants and Raynaud's syndrome in children: A retrospective case–control study of rheumatology patients
Authors: Goldman William , Seltzer Ryan , Reuman Peter 
Published: January 2008

AbstractObjectiveTo investigate whether central nervous system (CNS) stimulants used for the treatment of attention deficit hyperactivity disorder (ADHD) are associated with the development of Raynaud's syndrome (RS).MethodsA case–control design was used for this study. All patients seen in a pediatric rheumatology practice during a 5‐year period who had signs and symptoms of RS and met diagnostic criteria for RS as determined by pulse volume recording were studied as cases. Controls were randomly selected patients at the same clinic who did not have signs or symptoms of RS. They were matched to the cases for age, sex, and time of presentation. We tested for associations between various CNS medications and presence of RS. We also evaluated differences in laboratory test results between RS cases and matched controls.ResultsSixty‐four patients were enrolled in the study (32 cases with RS [23 female, 9 male] and 32 control patients). McNemar's test showed a significant association between the presence of RS and past or current use of ADHD stimulants (methylphenidate and dextroamphetamine) (χ2 = 5.00, P = 0.01). The use of other CNS medications was not found to be significantly associated with RS (χ2 = 1.33, P = 0.25 by McNemar's test). C‐reactive protein levels and erythrocyte sedimentation rates were significantly higher in controls than in cases.ConclusionThe results of this study indicate that there is a significant association between development of RS and therapy with CNS stimulants used for the treatment of ADHD. Although this was a small study, these findings provide preliminary evidence of an adverse effect of CNS stimulant medications in patients seen in rheumatology practice.
Immunosuppressive therapy in lupus‐ and mixed connective tissue disease–associated pulmonary arterial hypertension: A retrospective analysis of twenty‐three cases
Authors: Jais Xavier , Launay David , Yaici Azzedine , Le Pavec Jérôme , Tchérakian Colas , Sitbon Olivier , Simonneau Gérald , Humbert Marc 
Published: January 2008

AbstractObjectiveTo describe the response to first‐line immunosuppressive therapy with or without pulmonary vasodilators in pulmonary arterial hypertension (PAH) associated with systemic lupus erythematosus (SLE) or mixed connective tissue disease (MCTD).MethodsTwenty‐three consecutive patients with SLE‐ or MCTD‐associated PAH treated with first‐line immunosuppressive therapy either alone (n = 16) or in combination with pulmonary vasodilators (n = 7) were evaluated according to clinical and hemodynamic criteria before and after immunosuppressive therapy. Responders were defined as patients in New York Heart Association (NYHA) functional class I or II with hemodynamic improvement after the last pulse of cyclophosphamide.ResultsAmong the 16 patients treated with first‐line immunosuppressive therapy alone, 8 (50%) were responders. These patients had a significantly improved NYHA functional class, 6‐minute walking distance, and mean pulmonary artery pressure. Patients in NYHA functional class I or II and/or a cardiac index >3.1 liters/minute/m2 at baseline were more likely to benefit from immunosuppressive therapy. Six of the 8 nonresponders subsequently improved with pulmonary vasodilators. Among the 7 patients who were initially treated with immunosuppressive therapy and pulmonary vasodilators, 4 (57.1%) were responders.ConclusionPAH associated with SLE or MCTD may respond to a treatment combining cyclophosphamide and glucocorticoids. Patients who could benefit from this immunosuppressive therapy could be those who have less severe disease at baseline. For patients with more severe disease, pulmonary vasodilators should be started, possibly in combination with immunosuppressants. In any case, clinical and hemodynamic evaluations are mandatory to monitor the response and adapt the treatment. These retrospective and uncontrolled data need to be confirmed by randomized controlled trials.
AUF1, the regulator of tumor necrosis factor α messenger RNA decay, is targeted by autoantibodies of patients with systemic rheumatic diseases
Authors: Skriner Karl , Hueber Wolfgang , Süleymanoglu Erhan , Höfler Elisabeth , Krenn Veit , Smolen Josef , Steiner Günter 
Published: January 2008

AbstractObjectiveTo investigate which members of the heterogeneous nuclear RNP (hnRNP) family are targeted by autoantibodies from patients with systemic rheumatic diseases.MethodsUsing a semipurified preparation of natural hnRNP proteins, 365 sera from patients with rheumatic diseases and control subjects were screened by immunoblotting for the presence of autoantibodies. Bacterially expressed recombinant hnRNP D (AUF1) proteins were used for confirming the data obtained. Binding of RNA and autoantibody to AUF1 was investigated by gel retardation assays. Expression of AUF1 in cultivated cells and synovial tissue was analyzed by indirect immunofluorescence and immunohistochemistry.ResultsAutoantibodies to AUF1 proteins were detected in 33% of patients with systemic lupus erythematosus, 20% of patients with rheumatoid arthritis, 17% of patients with mixed connective tissue disease, and <10% of patients with other rheumatic disorders. Epitope mapping studies showed the autoantibodies to be directed to conformational epitopes in the N‐terminal RNA‐binding part of AUF1. However, autoantibody binding did not interfere with RNA binding as assessed by gel‐shift assays. Immunohistochemical studies revealed AUF1 to be expressed in the cytoplasm of RA synovial tissue as compared with nuclear staining in osteoarthritis and normal synovium, particularly in macrophages of the lining layer and in fibroblasts of the sublining areas.ConclusionThese data identify AUF1 proteins as novel autoantigens in SLE and related autoimmune disorders. Because AUF1 proteins are major components of messenger RNA stability complexes, our findings suggest that these complexes form a novel macromolecular target structure for autoantibodies in rheumatic autoimmune diseases.
Factors influencing surgeons' decisions in the indication for total joint replacement in hip osteoarthritis in real life
Authors: Maillefert Jean Francis , Roy Carine , Cadet Christian , Nizard Rémy , Berdah Laurent , Ravaud Philippe 
Published: January 2008

AbstractObjectiveTo evaluate factors influencing orthopedic surgeons' decision in daily practice to recommend or not recommend total hip arthroplasty (THA) in patients with hip osteoarthritis (OA).MethodsGeneral practitioners and rheumatologists were asked to prospectively include 1 patient with hip OA for whom a consultation with an orthopedic surgeon was planned to determine whether or not THA was indicated. The following variables were obtained: age, sex, occupational status, body mass index, comorbidities, duration of hip OA, patient's global assessment, Western Ontario and McMaster Universities Osteoarthritis Index pain and functioning subscale scores, New Zealand score, quality of life, and structural parameters on radiographs. The surgeon's decision was obtained by followup questionnaires. Statistical analysis evaluated potential predictors of the surgeon's decision (indication for THA within the next 6 months, yes or no) using univariate and multivariate analysis.ResultsA total of 558 patients were included (249 men, 300 women, mean age 68.4 years, mean disease duration 4.9 years). The surgeon's decision, available for 486 patients, was to prescribe THA in 60.7% of patients. On multivariate analysis, the variables related to the surgeon's decision were the presence or absence of severe cardiovascular disease, Short Form 12 physical subscale score, and amount of joint space narrowing.ConclusionWhile the amount of structural degradation is only slightly or not at all taken into account in numerous criteria and/or recommendations on indications for THA, it is an independent predictor of the surgeon's decision in daily practice. Such a discrepancy should be evaluated and understood in further studies.
Association of health‐related quality of life with dual use of prescription and over‐the‐counter nonsteroidal antiinflammatory drugs
Authors: Kovac Stacey H. , Saag Kenneth G. , Curtis Jeffrey R. , Allison Jeroan 
Published: January 2008

AbstractObjectiveInadequate prescription therapy pain management, lack of doctor‐patient communication about over‐the‐counter (OTC) medications, and easy accessibility of OTC medications may contribute to patients using more than 1 medication to manage pain. It is well established that taking multiple nonsteroidal antiinflammatory drugs (NSAIDs) can lead to serious gastrointestinal problems. Little is known about whether use of more than 1 NSAID (i.e., dual use) is related to patient self‐reported outcomes, specifically health‐related quality of life (HRQOL). We hypothesized that dual use of NSAIDs would be associated with reduced HRQOL.MethodsPatients from a managed care organization who filled ≥1 NSAID prescription over a 6‐month period were eligible for a telephone interview focusing on NSAID use, which included the Short Form 12 (SF‐12) Health Survey. Dual use was defined as taking 2 NSAIDs, either prescription or OTC, at least twice weekly during the past month. A multivariable linear regression model examined the association between dual use and the Physical Component Summary score (PCS‐12) from the SF‐12.ResultsDual use was associated with lower PCS‐12 scores indicating poorer HRQOL, after controlling for clinical and demographic factors.ConclusionPatients may self‐manage their pain to improve their daily activities by taking more than 1 NSAID. However, by attempting to obtain symptom relief, patients may be putting themselves at risk for complications. Providers are likely unaware of patients' risk. Future research should evaluate the causal factors contributing to dual use.
Performance of the polymyalgia rheumatica activity score for diagnosing disease flares
Authors: Binard Aymeric , de Bandt Michel , Berthelot Jean‐Marie , Saraux Alain ,   Inflammatory Joint Disease Working Group of the French Society for Rheumatology
Published: January 2008

AbstractObjectiveTo evaluate the effectiveness of the polymyalgia rheumatica activity score (PMR‐AS) in diagnosing disease flares.MethodsRheumatologists prospectively included 89 patients with PMR (mean ± SD age 74.6 ± 6.2 years, mean ± SD disease duration 1.6 ± 2.2 years). At each visit, the rheumatologist assessed disease activity using a visual analog scale (VAS) and recorded whether a disease flare was diagnosed and/or the glucocorticoid dose changed. Overall, 137 visits including 49 pairs (allowing intraindividual comparisons) were available; a disease flare was diagnosed at 32 visits. We evaluated statistical associations linking flare diagnosis to the PMR‐AS, each of its components (VAS, VAS for pain, C‐reactive protein, morning stiffness, and elevation of upper limbs), and changes in these parameters between 2 visits.ResultsAssociations with disease flare diagnosis were strongest for PMR‐AS scores ≥9.35 (agreement 92%, 95% confidence interval [95% CI] 85.8–95.7%, κ = 0.78; sensitivity 96.6%, 95% CI 80.4–99.8; specificity 90.7%, 95% CI 83.2–95.2) and for ΔPMR‐AS scores ≥6.6 (agreement 98%, 95% CI 88.0–99.9%, κ = 0.95; sensitivity 100%, 95% CI 74.7–100; specificity 97.1%, 95% CI 82.9–99.8). Other parameters showed weaker diagnostic performance.ConclusionThis study supplies new evidence that the PMR‐AS is useful for monitoring PMR activity in everyday practice and for managing glucocorticoid tapering. PMR activity changes seem even more relevant than absolute values.
Preliminary validation and clinical meaning of the cutaneous assessment tool in juvenile dermatomyositis
Authors: Huber Adam M. , Dugan Elizabeth M. , Lachenbruch Peter A. , Feldman Brian M. , Perez Maria D. , Zemel Lawrence S. , Lindsley Carol B. , Rennebohm Robert M. , Wallace Carol A. , Passo Murray H. , Reed Ann M. , Bowyer Suzanne L. , Ballinger Susan H. , Miller Frederick W. , Rider Lisa G. ,   Juvenile Dermatomyositis Disease Activity Collaborative Study Group
Published: January 2008

AbstractObjectiveTo provide preliminary validation of the Cutaneous Assessment Tool (CAT), a new tool to assess cutaneous manifestations of juvenile dermatomyositis (DM), and to explore the clinical meaning of CAT scores.MethodsChildren with juvenile DM (n = 113) were assessed at baseline and 7–9 months later (n = 94). Internal consistency, redundancy, construct validity, and responsiveness of the CAT were examined. CAT scores corresponding to ordinal global assessments were determined.ResultsItem‐total correlations ranged from 0.27–0.67 for activity lesions present in ≥10% of patients; item‐domain and domain‐total correlations ranged from 0.25–0.99. Cronbach's alpha was 0.79 for the CAT activity score and 0.74 for the CAT damage score. As predicted, the CAT activity score correlated strongly with both global disease activity and skin disease activity and moderately with the Childhood Myositis Assessment Scale, whereas the CAT damage score correlated moderately with the physician global disease and skin disease damage scores. Median CAT activity scores of 1, 7, 13, 18, and 31 corresponded to absent, mild, moderate, severe, and extremely severe skin disease activity, respectively. Median CAT damage scores of 0, 1, 2, and 5 correlated with the same descriptions of damage (severe and extremely severe combined).ConclusionPreliminary validation of the CAT demonstrated good internal consistency, nonredundancy, good construct validity, and appropriate responsiveness. The CAT is a comprehensive, semiquantitative assessment tool for skin disease in juvenile DM.
Development and validation of a patient‐based disease activity score in rheumatoid arthritis that can be used in clinical trials and routine practice
Authors: Choy Ernest H. , Khoshaba Bernadette , Cooper Derek , MacGregor Alex , Scott David L. 
Published: January 2008

AbstractObjectiveAssessor‐based disease activity measures such as the Disease Activity Score in 28 joints (DAS28), although widely used in rheumatoid arthritis (RA), have high interobserver variability. We developed and validated a patient‐based disease activity score (PDAS) as an alternative assessment.MethodsPatients' assessments of swollen or tender joints, visual analog scales for pain and general health, the Health Assessment Questionnaire, and erythrocyte sedimentation rate (ESR) were used to develop the PDAS. In a developmental cohort (204 patients), regression analyses determined the best fit with the DAS28. A validation cohort (322 patients) subsequently evaluated criterion and construct validity against a range of outcome measures, including the Nottingham Health Profile (NHP) and Short Form 36 (SF‐36). Sensitivity to change was assessed in 56 patients after 6 months of treatment with disease‐modifying antirheumatic drugs or biologics.ResultsIn the developmental cohort, the PDAS with ESR (PDAS1) and without ESR (PDAS2) achieved excellent fit with the DAS28 (r = 0.88 and 0.74, respectively). In the validation cohort, the PDAS showed high criterion validity by correlation with the DAS28 (PDAS1: r = 0.89, PDAS2: r = 0.76). Construct validity was demonstrated by high correlations with a range of disease activity measures (r ≥ 0.45), whereas low correlations (r < 0.45) with mental and social components of the SF‐36 and NHP indicated divergent validity. The PDAS and DAS28 had similar sensitivity to change, determined using effect sizes (DAS28 = 1.03, PDAS1 = 1.02, PDAS2 = 0.77) or standardized response means (DAS28 = 0.79, PDAS1 = 0.77, PDAS2 = 0.73).ConclusionThe PDAS1 and PDAS2 are valid and sensitive tools to assess disease activity in RA. They appear suitable for clinical decision making, epidemiologic research, and clinical trials.