bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronic arthritis aggravates vascular lesions in rabbits with atherosclerosis: A novel model of atherosclerosis associated with chronic inflammation
Authors: Largo Raquel , Sánchez‐Pernaute Olga , Marcos M. Esther , Moreno‐Rubio Juan , Aparicio César , Granado Rosario , Ortega Luis , Egido Jesús , Herrero‐Beaumont Gabriel 
Published: August 2008

AbstractObjectiveTo determine whether systemic inflammation induced by chronic antigen‐induced arthritis (AIA) accelerates vascular lesions in rabbits with atherosclerosis.MethodsTwo models of atherosclerosis and chronic AIA were combined. Atherosclerosis was induced by coupling a hyperlipemic diet with an endothelial lesion at the femoral arteries, while chronic AIA was induced by ovalbumin injection. Markers in sera and peripheral blood mononuclear cells (PBMCs) as well as vessels and synovial membranes from the rabbits with the double phenotype (both chronic AIA and atherosclerosis) were compared with those from rabbits with each disease alone.ResultsSerum levels of interleukin‐6, C‐reactive protein, and prostaglandin E2 increased in rabbits with both chronic AIA and atherosclerosis as compared with healthy animals or animals with either chronic AIA alone or atherosclerosis alone. NF‐κB binding and CCL2 and cyclooxygenase 2 (COX‐2) expression were higher in PBMCs from rabbits with both chronic AIA and atherosclerosis than in PBMCs from healthy rabbits. The intima‐media thickness ratio of femoral arteries was equally increased in rabbits with atherosclerosis alone and in rabbits with both chronic AIA and atherosclerosis, but the latter group showed a higher level of macrophage infiltration. Femoral CCL2 and COX‐2 expression was increased in rabbits with both chronic AIA and atherosclerosis as compared with rabbits with atherosclerosis alone. In the aortas, vascular lesions were found in 27% of rabbits with atherosclerosis alone and in 60% of rabbits with both chronic AIA and atherosclerosis. Rabbits with both chronic AIA and atherosclerosis exhibited more severe synovitis and higher synovial expression of CCL2 than did rabbits with chronic AIA alone.ConclusionThe onset of chronic AIA in animals with atherosclerosis resulted in the local and systemic up‐regulation of mediators of tissue inflammation and plaque instability associated with a higher incidence of aortic lesions. This model could represent a novel approach to the study of inflammation‐associated atherosclerosis.
Remission and rheumatoid arthritis: Data on patients receiving usual care in twenty‐four countries
Authors: Sokka Tuulikki , Hetland Merete Lund , Mäkinen Heidi , Kautiainen Hannu , Hørslev‐Petersen Kim , Luukkainen Reijo K. , Combe Bernard , Badsha Humeira , Drosos Alexandros A. , Devlin Joe , Ferraccioli Gianfranco , Morelli Alessia , Hoekstra Monique , Majdan Maria , Sadkiewicz Stefan , Belmonte Miguel , Holmqvist Ann‐Carin , Choy Ernest , Burmester Gerd R. , Tunc Recep , Dimić Aleksander , Nedović Jovan , Stanković Aleksandra , Bergman Martin , Toloza Sergio , Pincus Theodore ,   Questionnaires in Standard Monitoring of Patients With Rheumatoid Arthritis Group
Published: August 2008

AbstractObjectiveTo compare the performance of different definitions of remission in a large multinational cross‐sectional cohort of patients with rheumatoid arthritis (RA).MethodsThe Questionnaires in Standard Monitoring of Patients with RA (QUEST‐RA) database, which (as of January 2008) included 5,848 patients receiving usual care at 67 sites in 24 countries, was used for this study. Patients were clinically assessed by rheumatologists and completed a 4‐page self‐report questionnaire. The database was analyzed according to the following definitions of remission: American College of Rheumatology (ACR) definition, Disease Activity Score in 28 joints (DAS28), Clinical Disease Activity Index (CDAI), clinical remission assessed using 42 and 28 joints (Clin42 and Clin28), patient self‐report Routine Assessment of Patient Index Data 3 (RAPID3), and physician report of no disease activity (MD remission).ResultsThe overall remission rate was lowest using the ACR definition of remission (8.6%), followed by the Clin42 (10.6%), Clin28 (12.6%), CDAI (13.8%), MD remission (14.2%), and RAPID3 (14.3%); the rate of remission was highest when remission was defined using the DAS28 (19.6%). The difference between the highest and lowest remission rates was ≥15% in 10 countries, 5–14% in 7 countries, and <5% in 7 countries (the latter of which had generally low remission rates [<5.5%]). Regardless of the definition of remission, male sex, higher education, shorter disease duration, smaller number of comorbidities, and regular exercise were statistically significantly associated with remission.ConclusionThe use of different definitions of RA remission leads to different results with regard to remission rates, with considerable variation among countries and between sexes. Reported remission rates in clinical trials and clinical studies have to be interpreted in light of the definition of remission that has been used.
Tibial subchondral trabecular volumetric bone density in medial knee joint osteoarthritis using peripheral quantitative computed tomography technology
Authors: Bennell Kim L. , Creaby Mark W. , Wrigley Tim V. , Hunter David J. 
Published: August 2008

AbstractObjectiveKnee osteoarthritis (OA) is an organ‐level failure of the joint involving pathologic changes in articular cartilage and bone. This cross‐sectional study compared apparent volumetric bone mineral density (vBMD) of proximal tibial subchondral trabecular bone in people with and without knee OA, using peripheral quantitative computed tomography (pQCT).MethodsSeventy‐five individuals with mild or moderate medial compartment knee OA and 41 asymptomatic controls were recruited. Peripheral QCT was used to measure vBMD of trabecular bone beneath medial and lateral tibiofemoral compartments at levels of 2% and 4% of tibial length, distal to the tibial plateau.ResultsThere was no significant difference in vBMD beneath the overall medial and lateral compartments between the 3 groups. However, in the affected medial compartment of those with moderate OA, lower vBMD was seen in the 2 posterior subregions compared with controls and those with mild knee OA, while higher vBMD was seen in the anteromedial subregion. Beneath the unaffected or lesser affected lateral compartment, significantly lower vBMD was seen at the 2% level in the anterior and lateral subregions of those with moderate disease. Volumetric BMD ratios showed relatively higher vBMD in the medial compartment compared with the lateral compartment, but these ratios were not influenced by disease status.ConclusionSubregional vBMD changes were evident beneath the medial and lateral compartments of those with moderate medial knee OA. Of import, the posterior subchondral trabecular regions of the medial tibial plateau have markedly lower vBMD.
Rho kinase–dependent CCL20 induced by dynamic compression of human chondrocytes
Authors: Haudenschild Dominik R. , Nguyen Bao , Chen Jianfen , D'Lima Darryl D. , Lotz Martin K. 
Published: August 2008

AbstractObjectiveMechanical stimulation of cartilage affects tissue homeostasis and chondrocyte function. The chondrocyte phenotype is dependent on cell shape, which is largely determined by the actin cytoskeleton. Reorganization of the actin cytoskeleton results from Rho GTPase activation. The purpose of this study was to examine the roles of both actin and Rho in mechanotransduction in chondrocytes.MethodsWe embedded human articular chondrocytes in 2 × 6–mm agarose discs at 5 × 106 cells/ml and subjected the discs to unconfined dynamic compression at 0.5 Hz. By comparing samples with and without dynamic compression, we identified Rho activation according to the GTP‐bound active RhoA measured in cell lysates. We identified rearrangements in filamentous actin structures using fluorescence‐labeled phalloidin and confocal microscopy of fixed samples. We identified altered gene expression using TaqMan quantitative reverse transcription–polymerase chain reaction analysis. We tested for a requirement for Rho signaling by performing the dynamic compression in the presence of Rho kinase inhibitors.ResultsRhoA activation occurred within 5–10 minutes of dynamic compression. Rho kinase–dependent actin reorganization occurred within 20 minutes after application of dynamic compression and was apparent as “punctate” F‐actin structures that were visible under confocal microscopy. We identified early‐phase mechanoresponsive genes (CCL20 and inducible nitric oxide synthase) that were highly up‐regulated within 1 hour of dynamic compression in a Rho kinase–dependent and actin‐dependent manner.ConclusionTogether, these results are the first demonstration that the Rho–Rho kinase pathway and actin cytoskeletal reorganization are required for changes in the expression of genes involved in human chondrocyte mechanotransduction.
The presentation and outcome of heart failure in patients with rheumatoid arthritis differs from that in the general population
Authors: Davis John M. , Roger Véronique L. , Crowson Cynthia S. , Kremers Hilal Maradit , Therneau Terry M. , Gabriel Sherine E. 
Published: August 2008

AbstractObjectiveTo compare the clinical presentation, management, and outcome of heart failure in patients with rheumatoid arthritis (RA) compared with non‐RA patients.MethodsWe conducted a community‐based cohort study in the setting of Olmsted County, Minnesota, from 1979 to 2000. One hundred three patients with RA and 852 non‐RA patients with incident heart failure (physician diagnosed and Framingham criteria validated) were compared. Age‐ and sex‐adjusted rates/frequencies and multivariable logistic regression models were used to compare the clinical features and mortality of heart failure following its onset in the 2 groups of patients.ResultsThe patients with RA were more often female and less frequently were obese, were hypertensive, or had ischemic heart disease. Patients with RA and heart failure had fewer typical symptoms and signs and were less likely to undergo echocardiography compared with non‐RA patients. After adjusting for differences, the patients with RA and heart failure were more likely to have preserved ejection fraction (≥50%). Mortality at 1 year following heart failure was higher in patients with RA compared with non‐RA patients (35% versus 19%; multivariable hazard ratio 1.89, 95% confidence interval 1.26–2.84).ConclusionBoth the clinical presentation and the outcome of heart failure differ significantly between patients with and those without RA from the same population. Among patients with RA, the presentation of heart failure is more subtle, myocardial function is more likely preserved, while mortality from heart failure is significantly higher. These findings emphasize the importance of more vigilant screening of patients with RA for early signs of heart failure and may represent important insights into the biologic mechanisms underlying heart failure in RA.
The antioxidant resveratrol protects against chondrocyte apoptosis via effects on mitochondrial polarization and ATP production
Authors: Dave Mandar , Attur Mukundan , Palmer Glyn , Al‐Mussawir Hayf E. , Kennish Lauren , Patel Jyoti , Abramson Steven B. 
Published: August 2008

AbstractObjectiveTo determine the effects of the antioxidant resveratrol on the functions of human chondrocytes in osteoarthritis (OA).MethodsChondrocytes and cartilage explants were isolated from OA patients undergoing knee replacement surgery. Effects of resveratrol in the presence or absence of interleukin‐1β (IL‐1β) stimulation were assessed by measurement of prostaglandin E2(PGE2) and leukotriene B4(LTB4) synthesis, cyclooxygenase (COX) activity, matrix metalloproteinase (MMP) expression, and proteoglycan production. To explore the mechanisms of action of resveratrol, its effects on mitochondrial function and apoptosis were examined by assessing mitochondrial membrane potential, ATP levels, cytochrome c release, and annexin V staining.ResultsResveratrol inhibited both spontaneous and IL‐1β–induced PGE2production by >20% (P< 0.05) and by 80% (P< 0.001), respectively; similarly, LTB4production was reduced by >50% (P< 0.05). The production of PGE2was inhibited via a 70–90% suppression of COX‐2 expression and enzyme activity (P< 0.05). Resveratrol also promoted anabolic effects in OA explant cultures, by elevating proteoglycan synthesis and decreasing production of MMPs 1, 3, and 13. Pretreatment of OA chondrocytes with resveratrol blocked mitochondrial membrane depolarization, loss of mitochondrial biomass, and IL‐1β–induced ATP depletion. Similarly, IL‐1β–mediated induction of the apoptotic markers cytochrome c and annexin V was also inhibited by resveratrol. Exogenous addition of PGE2abolished the protective effects of resveratrol on mitochondrial membrane integrity, ATP levels, expression of apoptotic markers, and DNA fragmentation.ConclusionResveratrol protects against IL‐1β–induced catabolic effects and prevents chondrocyte apoptosis via its inhibition of mitochondrial membrane depolarization and ATP depletion. These beneficial effects of resveratrol are due, in part, to its capacity to inhibit COX‐2–derived PGE2synthesis. Resveratrol may therefore protect against oxidant injury and apoptosis, which are main features of progressive OA.
Reduction of plasma urate levels following treatment with multiple doses of pegloticase (polyethylene glycol–conjugated uricase) in patients with treatment‐failure gout: Results of a phase II randomized study
Authors: Sundy John S. , Becker Michael A. , Baraf Herbert S. B. , Barkhuizen Andre , Moreland Larry W. , Huang William , Waltrip Royce W. , Maroli Allan N. , Horowitz Zeb ,   Pegloticase Phase 2 Study Investigators
Published: August 2008

AbstractObjectiveTo assess the efficacy of pegloticase in achieving and maintaining plasma urate levels of <6 mg/dl in gout patients in whom other treatments have failed, and to assess the pharmacokinetics and safety of pegloticase.MethodsForty‐one patients were randomized to undergo 12–14 weeks of treatment with pegloticase at 1 of 4 dosage levels: 4 mg every 2 weeks, 8 mg every 2 weeks, 8 mg every 4 weeks, or 12 mg every 4 weeks. Plasma uricase activity, plasma urate, and antipegloticase antibodies were measured, pharmacokinetic parameters were assessed, and adverse events were recorded.ResultsThe mean plasma urate level was reduced to ≤6 mg/dl within 6 hours in all dosage groups, and this was sustained throughout the treatment period in the 8 mg and 12 mg dosage groups. The most effective dosage was 8 mg every 2 weeks. Twenty‐six patients received all protocol doses. The percentage of the patients in whom the primary efficacy end point (plasma urate <6 mg/dl for 80% of the study period) was achieved ranged from 50% to 88%. Gout flares occurred in 88% of the patients. The majority of adverse events (excluding gout flare) were unrelated to treatment and were mild or moderate in severity. Infusion‐day adverse events were the most common reason for study withdrawal (12 of 15 withdrawals). There were no anaphylactic reactions. Antipegloticase antibody, present in 31 of 41 patients, was associated with reduced circulating half‐life of pegloticase in some patients.ConclusionPegloticase, administered in multiple doses, was effective in rapidly reducing and maintaining plasma urate levels at ≤6 mg/dl in most patients in whom conventional therapy had been unsuccessful due to lack of response, intolerability, or contraindication.
A systematic review on the effectiveness of treatment with antidepressants in fibromyalgia syndrome
Authors: Üçeyler Nurcan , Häuser Winfried , Sommer Claudia 
Published: August 2008

AbstractObjectiveTo systematically review the efficacy of treatment of fibromyalgia syndrome (FMS) with antidepressants.MethodsWe screened Medline, PsychINFO, SCOPUS, and the Cochrane Library databases (through October 2007) and the reference sections of original studies, meta‐analyses, and evidence‐based guidelines and recommendations on antidepressants in FMS. Randomized controlled trials (RCTs) on the treatment of FMS with antidepressants were analyzed. Inclusion criteria, study characteristics, quality, and all outcome measures were investigated.ResultsTwenty‐six of 167 studies were included. The main outcome variables reviewed were pain, fatigue, sleep, depressiveness, and quality of life. Amitriptyline, studied in 13 RCTs, was efficient in reducing pain with a moderate magnitude of benefit (pain reduction by a mean of 26%, improvement in quality of life by 30%). Selective serotonin reuptake inhibitors (SSRIs) were studied in 12 RCTs, which also showed positive results, except for 2 studies on citalopram and 1 on paroxetine. Three RCTs on the dual serotonin and noradrenaline reuptake inhibitors (SNRIs) duloxetine and milnacipran and 1 of the 2 RCTs using the monoamine oxidase inhibitor moclobemide reported a positive result. The longest study duration was 12 weeks.ConclusionAmitriptyline 25–50 mg/day reduces pain, fatigue, and depressiveness in patients with FMS and improves sleep and quality of life. Most SSRIs and the SNRIs duloxetine and milnacipran are probably also effective. Short‐term treatment of patients with FMS using amitriptyline or another of the antidepressants that were effective in RCTs can be recommended. Data on long‐term efficacy are lacking.
Efficacy and safety of infliximab in patients with ankylosing spondylitis over a two‐year period
Authors: Braun Jürgen , Deodhar Atul , Dijkmans Ben , Geusens Piet , Sieper Joachim , Williamson Paul , Xu Weichun , Visvanathan Sudha , Baker Daniel , Goldstein Neil , van der Heijde Désirée 
Published: August 2008

AbstractObjectiveTo assess safety and efficacy of infliximab in patients with ankylosing spondylitis (AS) through 102 weeks.MethodsPatients (n = 279) with active AS were randomized to either group 1 (n = 78; placebo through week 24 and then infliximab 5 mg/kg from weeks 24 through 96) or group 2 (n = 201; infliximab 5 mg/kg through week 96). The primary efficacy end point at week 24 (≥20% improvement in the ASsessment in Ankylosing Spondylitis International Working Group criteria [ASAS20]) was assessed with an intent‐to‐treat analysis of observed data.ResultsMore patients in group 2 than group 1 achieved the ASAS20 response at week 24 (61.2% versus 19.2%; P < 0.001). By week 102, groups 1 and 2 were similar with regard to ASAS20 response (72.1% versus 73.9%); ASAS40 responses at week 102 were 45.9% versus 59.4%. No new safety issues were discerned.ConclusionInfliximab demonstrated sustained efficacy and safety over 2 years in this large cohort of patients with active AS.
Disease activity of rheumatoid arthritis during pregnancy: Results from a nationwide prospective study
Authors: de Man Yaël A. , Dolhain Radboud J. E. M. , van de Geijn Fleur E. , Willemsen Sten P. , Hazes Johanna M. W. 
Published: August 2008

AbstractObjectiveAccording to common knowledge and retrospective studies, approximately 75–90% of patients with rheumatoid arthritis (RA) will improve during pregnancy. Prospective data on disease activity during pregnancy are limited. Therefore, this study aimed to prospectively determine the disease activity during pregnancy in RA patients treated in an era of new treatment options.MethodsFor 84 RA patients (American College of Rheumatology criteria), a Disease Activity Score in 28 joints (DAS28) and medication use were obtained, before conception if possible, at each trimester of pregnancy and at 6, 12, and 26 weeks postpartum. Improvement and deterioration were determined by assessing changes in DAS28 and by applying the DAS28‐derived European League Against Rheumatism (EULAR) response criteria.ResultsDisease activity decreased with statistical significance (P = 0.035) during pregnancy and increased postpartum. In patients with at least moderate disease activity in the first trimester (n = 52), at least 48% had a moderate response during pregnancy according to EULAR‐defined response criteria. In patients with low disease activity in the first trimester (n = 32), disease activity was stable during pregnancy. Thirty‐nine percent of patients had at least a moderate flare postpartum according to reversed EULAR response criteria. Less medication was used during pregnancy compared with before conception and compared with postpartum.ConclusionThis study demonstrates that patients achieve remission during pregnancy and deteriorate postpartum, although less frequently than previously described.
Generalized vibratory deficits in osteoarthritis of the hip
Authors: Shakoor Najia , Lee Kristen J. , Fogg Louis F. , Block Joel A. 
Published: August 2008

AbstractObjectiveLower extremity sensory deficits, including reduced proprioception, joint kinesthesia, and, recently, vibratory sense, have been described in subjects with osteoarthritis (OA) of the knee. However, comparable deficits in OA of the hip have not previously been evaluated. Vibratory perception threshold (VPT) is a reliable measure used to assess sensory deficits and is amenable to testing multiple body sites. This study examined VPT at the upper and lower extremities of subjects with hip OA compared with subjects without hip OA.MethodsFourteen subjects with symptomatic and radiographic hip OA were compared with 13 age‐matched controls without hip OA. VPT was assessed using a biothesiometer. Five sites in the lower extremity and 1 site in the upper extremity (radial head) were evaluated and compared between OA and control subjects.ResultsVPT was significantly reduced at all 6 testing sites of the OA subjects compared with controls (P < 0.05 for all sites). VPT scores (mean ± SEM volts) for OA subjects and controls were as follows: first metatarsophalangeal joint (13.5 ± 1.4 versus 7.4 ± 0.7), medial malleolus (18.1 ± 2.6 versus 11.2 ± 1.7), lateral malleolus (20.9 ± 2.4 versus 10.6 ± 1.5), medial femoral condyle (22.8 ± 2.9 versus 12.6 ± 1.3), lateral femoral condyle (26.7 ± 2.6 versus 16.2 ± 1.9), and radial head (10.2 ± 0.8 versus 7.5 ± 0.6).ConclusionTo our knowledge, this is the first study to evaluate sensory deficits in hip OA and to demonstrate that there is vibratory sense loss at both the upper and lower extremities in these subjects compared with controls. The noted generalized deficits may have significant implications in the neuromechanical pathophysiology of OA.