bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting mortality in patients with rheumatoid arthritis
Authors: Wolfe Frederick , Michaud Kaleb , Gefeller Olaf , Choi Hyon K. 
Published: June 2003

AbstractObjectiveA number of different variables have been proposed as risk factors for mortality in patients with rheumatoid arthritis (RA), but limited prospective information on the magnitude of their effects is available. This study was undertaken to evaluate the relative predictive strength and usefulness of a wide range of variables on the risk of mortality in a large, long‐term, prospectively studied cohort of patients with RA.MethodsOver a 20‐year period of followup beginning in 1981, 1,387 consecutive RA patients were seen in a single clinic. A wide range of clinical and demographic assessments were recorded and entered into a computer database at the time of each clinical assessment. Assessment of predictive strength included determination of standardized and fourth‐versus‐first–quartile odds ratios (ORs), goodness‐of‐fit measures, and contributing fraction.ResultsThe Health Assessment Questionnaire (HAQ) disability index was the strongest clinical predictor of mortality. A 1‐SD change in the HAQ resulted in a much larger increase in the odds ratio for mortality compared with a 1‐SD change in global disease severity, the next most powerful predictor of mortality (OR 2.31 versus 1.83). Considering the contributing fraction, mortality would be reduced by 50% for the HAQ and by 33% for global disease severity if patients in the fourth quartile for these variables could be switched to the first quartile. Global disease severity, pain, depression, anxiety, and laboratory and radiographic features were significantly weaker predictors. Disease duration, nodules, and tender joint count were clinical variables that provided very little predictive information. In multivariable analyses, HAQ and other patient self‐report measures were significantly better predictors than were radiographic and laboratory variables. A single baseline observation provided the least information, with substantially increasing predictive ability associated with 1‐year, 2‐year, and all–time point followup observations (time‐varying covariates).ConclusionIn this large 20‐year study from routine clinical practice, the HAQ was the most powerful predictor of mortality, followed by other patient self‐report variables. Laboratory, radiographic, and physical examination data were substantially weaker in predicting mortality. We recommend that clinicians collect patient self‐report data, since they produce more useful clinical outcome information than other available clinical measures.
Delayed lupus onset in (NZB × NZW)F1 mice expressing a human C‐reactive protein transgene
Authors: Szalai Alexander J. , Weaver Casey T. , McCrory Mark A. , van Ginkel Frederik W. , Reiman Rachael M. , Kearney John F. , Marion Tony N. , Volanakis John E. 
Published: June 2003

AbstractObjectiveHuman C‐reactive protein (CRP) binds apoptotic cells and alters blood clearance of injected chromatin in mice. To test whether CRP participates in the pathogenesis of systemic lupus erythematosus (SLE), we examined disease development in lupus‐prone (NZB × NZW)F1 (NZB/NZW) mice expressing a human CRP transgene (hCRPtg/BW).MethodsMortality was monitored, proteinuria was determined by dipstick, and serum levels of human CRP and anti–double‐stranded DNA (anti‐dsDNA) were determined by enzyme‐linked immunosorbent assay in NZB/NZW and hCRPtg/BW mice. Thin sections of kidneys were analyzed by immunofluorescence microscopy to compare deposition of IgG, IgM, C3, and human CRP, and electron microscopy was used to reveal differences in ultrastructure. In situ hybridization was performed to detect human CRP messenger RNA expression.ResultsThe hCRPtg/BW mice had less proteinuria and longer survival than NZB/NZW mice. They also had lower IgM and higher IgG anti‐dsDNA titers than NZB/NZW mice, although the differences were transient and small. In hCRPtg/BW mice, accumulation of IgM and IgG in the renal glomeruli was delayed, reduced, and more mesangial than in NZB/NZW mice, while end‐stage accumulation of IgG, IgM, and C3 in the renal cortex was prevented. There was less glomerular podocyte fusion, basement membrane thickening, mesangial cell proliferation, and occlusion of capillary lumens in hCRPtg/BW mice, but dense deposits in the mesangium were increased. With disease progression in hCRPtg/BW mice, there was little rise in the plasma CRP level, but CRP in the kidneys became increasingly apparent due to local, disease‐independent, age‐related expression of the transgene.ConclusionIn hCRPtg/BW mice, CRP protects against SLE by increasing blood and mesangial clearance of immune complexes and by preventing their accumulation in the renal cortex.
Clinical responses to tumor necrosis factor α antagonists do not show a bimodal distribution: Data from the Stockholm Tumor Necrosis Factor α Followup Registry
Authors: van Vollenhoven Ronald F. , Klareskog Lars 
Published: June 2003

AbstractObjectiveTo study the distribution of clinical responses to treatment with the tumor necrosis factor α (TNFα) antagonists etanercept and infliximab, and in particular, to determine whether there is a biologically meaningful distinction between responders and nonresponders.MethodsAmong patients in the Stockholm TNFα Followup Registry, we analyzed the clinical responses to etanercept and infliximab, using the American College of Rheumatology (ACR) core set of outcome measures. For each parameter, the absolute change (value at baseline − current value) and the percentage change ([absolute change]/[value at baseline] × 100) from baseline were calculated. The results were plotted as histograms and inspected visually, and the distributions were statistically compared with computer‐generated normal distributions.ResultsAbsolute and relative changes in outcomes on the ACR core set of measures in 406 patients receiving etanercept or infliximab were studied. All but a few of these analyses yielded normal or somewhat skewed distributions. The statistical analyses did not detect any non‐normal distributions, and visually, the distributions did not appear to be bimodal.ConclusionThe clinical response to TNFα blockade displays a normal or skewed, but not bimodal, distribution. The frequently encountered perception that a clear distinction can be made between responders and nonresponders is not borne out. These relatively straightforward findings imply that the biologic mechanisms determining responsiveness to TNFα blockade are multifactorial and may also have important implications for regulatory guidelines pertaining to treatment with these biologic agents.
High mobility group box chromosomal protein 1, a DNA binding cytokine, induces arthritis
Authors: Pullerits Rille , Jonsson Ing‐Marie , Verdrengh Margareta , Bokarewa Maria , Andersson Ulf , Erlandsson‐Harris Helena , Tarkowski Andrej 
Published: June 2003

AbstractObjectiveTo examine the potential role of high mobility group box chromosomal protein 1 (HMGB‐1) in the pathogenesis of arthritis.MethodsMice were injected intraarticularly with 1 μg or 5 μg of HMGB‐1. Joints were dissected on days 4, 7, and 28 after injection and were evaluated histopathologically and immunohistochemically. To investigate the importance of different white blood cell populations for the development of arthritis, in vivo cell depletion procedures were performed. In addition, spleen cells were cultured in the presence of HMGB‐1, and nuclear factor κB (NF‐κB) activation was detected by electrophoretic mobility shift assay.ResultsInjection of recombinant HMGB‐1 (rHMGB‐1) into different mouse strains resulted in an overall frequency of arthritis in 80% of the animals. The inflammation was characterized by mild to moderate synovitis and lasted for at least 28 days. The majority of cells found in the inflamed synovium were Mac‐1+ macrophages, whereas only a few CD4+ lymphocytes were detected. Pannus formation was observed in some cases 7 and 28 days after HMGB‐1 injection. No significant differences were found with respect to incidence and severity of arthritis between mice depleted of monocytes, granulocytes, or lacking T/B lymphocytes. However, combined removal of monocytes and neutrophils resulted in a 43% lower incidence of arthritis. Mice rendered deficient in the interleukin‐1 (IL‐1) receptor did not develop inflammation upon challenge with HMGB‐1. In vitro data corroborate this finding, showing that rHMGB‐1 activated NF‐κB, a major pathway leading to IL‐1 production.ConclusionOur results indicate that HMGB‐1 is not a mere expression of inflammatory responses, but on its own, it triggers joint inflammation by activating macrophages and inducing production of IL‐1 via NF‐κB activation.
Broad‐spectrum matrix metalloproteinase inhibitor marimastat–induced musculoskeletal side effects in rats
Authors: Renkiewicz Richard , Qiu Luping , Lesch Charles , Sun Xin , Devalaraja Radhika , Cody Theresa , Kaldjian Eric , Welgus Howard , Baragi Vijaykumar 
Published: June 2003

AbstractObjectiveTo characterize the clinical and histopathologic changes in a rat model of broad‐spectrum matrix metalloproteinase (MMP)–induced musculoskeletal syndrome (MSS), and to facilitate research into the causes and treatments of MSS in humans.MethodsMale Lewis rats weighing 150–180 gm were administered 10–30 mg of the broad‐spectrum MMP inhibitor marimastat over a 2‐week period via surgically implanted subcutaneous osmotic pumps. The animals were monitored and scored for the onset and severity of MSS, using clinical and histologic parameters.ResultsMarimastat‐treated rats exhibited various clinical signs, including compromised ability to rest on their hind feet, high‐stepping gait, reluctance or inability to move, and hind paw swelling. Histologically, marimastat‐treated rat joints were characterized by soft tissue and bone changes, such as increased epiphyseal growth plate, synovial hyperplasia, and increased cellularity in the joint capsule and extracapsular ligaments. The severity of MSS, as judged by clinical criteria (2 blinded observers using 3 clinical parameters), paw volume, and histologic score, was nearly identical. The observed changes were indistinguishable from those reported for primate models and mimic MSS in humans.ConclusionThis simple and sensitive model of MSS is an attractive alternative for studying the pathology of MSS.
Asymmetric knee loading in advanced unilateral hip osteoarthritis
Authors: Shakoor Najia , Hurwitz Debra E. , Block Joel A. , Shott Susan , Case John P. 
Published: June 2003

AbstractObjectiveSubjects with unilateral end‐stage hip osteoarthritis (OA) who undergo total hip replacement (THR) preferentially require subsequent replacement of the contralateral knee compared with the ipsilateral knee. We investigated whether this nonrandom, preferential evolution of lower extremity OA from the hip to the contralateral knee joint may be related to asymmetries in dynamic joint loading at the knees, particularly the peak external knee adduction moment, which has been associated with the progression of knee OA.MethodsGait analysis was performed on 50 subjects who were preoperative for unilateral THR. Twenty‐two of these subjects were reevaluated postoperatively 10–23 months after undergoing successful THR. At each analysis, dynamic joint loads in the contralateral knee were compared with those in the ipsilateral knee.ResultsPrior to THR, the peak external knee adduction moment and peak medial compartment load were significantly higher in the contralateral knee. This asymmetry persisted after THR.ConclusionSubjects with unilateral end‐stage hip OA preferentially require subsequent replacement of the contralateral knee, as compared with the ipsilateral knee. Among patients with unilateral end‐stage hip OA, the contralateral knee is subjected to higher dynamic joint loads than is the ipsilateral knee, and this asymmetric loading persists long after subjects have undergone successful THR. Biomechanical factors appear to be involved in the multiarticular evolution of OA of the lower extremities.
Hsp70 prevents nitric oxide–induced apoptosis in articular chondrocytes
Authors: Terauchi Ryu , Takahashi Kenji A. , Arai Yuji , Ikeda Takumi , Ohashi Suzuyo , Imanishi Jiro , Mazda Osam , Kubo Toshikazu 
Published: June 2003

AbstractObjectiveTo deliver and overexpress the hsp70 gene in cultured chondrocytes to investigate its effect on nitric oxide (NO)–induced apoptosis of chondrocytes.MethodsPrimary chondrocyte cultures were established from rabbit joints. The cells were transduced with an empty adenovirus vector (Ax1w) or an adenovirus vector harboring the hsp70 E‐tag fusion gene (AxSHEwt). Apoptosis was induced by sodium nitroprusside (SNP) dihydrate, which generates NO, or by staurosporine, which is a proapoptotic agent dependent upon Bax or Bak protein. Cell viability and apoptosis induction were estimated by lactate dehydrogenase (LDH) assay, Hoechst 33342 staining, or the TUNEL method. To study Hsp70, cytochrome c, and caspase 3, Western blot analyses were performed.ResultsThe AxSHEwt‐transduced cells escaped apoptosis, as revealed by the LDH assay, Hoechst 33342 staining, and the TUNEL method. A massive amount of the tagged Hsp70 was demonstrated in the AxSHEwt‐transduced chondrocytes but not in control cells. Hsp70 did not affect the cytosolic cytochrome c level, but appeared to have obstructed the activation of caspase 3.ConclusionExperimentally overexpressed Hsp70 almost completely inhibited NO‐ or staurosporine‐induced apoptosis in primary chondrocytes.
Elevated levels of leukotriene B4 and leukotriene E4 in bronchoalveolar lavage fluid from patients with scleroderma lung disease
Authors: Kowal‐Bielecka Otylia , Distler Oliver , Kowal Krzysztof , Siergiejko Zenon , Chwiećko Justyna , Sulik Agnieszka , Gay Renate E. , Łukaszyk Anna Bodzenta , Gay Steffen , Sierakowski Stanisław 
Published: June 2003

AbstractObjectiveThe leukotrienes are a family of arachidonic acid–derived lipid mediators with proinflammatory and profibrotic properties. The aim of this study was to analyze the role of leukotriene B4 (LTB4) and LTE4 in the pathogenesis of scleroderma lung disease (SLD).MethodsNineteen systemic sclerosis (SSc) patients with SLD, 11 SSc patients without SLD, and 10 healthy controls were studied. Bronchoalveolar lavage (BAL) fluid was obtained during routine bronchoscopy of the right middle lobe in all study subjects. Levels of LTB4 and LTE4 were measured using enzyme immunoassay kits.ResultsLevels of LTB4 and LTE4 were significantly higher in SSc patients with SLD (251 ± 170 pg/ml and 479 ± 301 pg/ml, respectively), than those in patients without SLD (114 ± 86 and 159 ± 149 pg/ml) and those in normal controls (86 ± 49 and 110 ± 67 pg/ml). In the total group of patients with SSc, levels of both leukotrienes correlated positively with the total number of cells in the BAL fluid and correlated negatively with the forced vital capacity. After intravenous pulse therapy with cyclophosphamide in 6 patients, there was a significant reduction in the concentration of LTB4 (from 380 ± 196 pg/ml to 155 ± 123 pg/ml) but no significant difference in the levels of LTE4 (from 697 ± 325 pg/ml to 418 ± 140 pg/ml).ConclusionOur findings show that LTB4 and LTE4 levels are elevated in SSc patients with SLD and correlate with parameters of inflammation in the lungs. These results indicate that leukotrienes may contribute to the pathogenesis of SLD and may represent a new therapeutic target.
Informed consent in a clinical trial of a novel treatment for rheumatoid arthritis
Authors: Criscione Lisa G. , Sugarman Jeremy , Sanders Linda , Pisetsky David S. , St.Clair E. William 
Published: June 2003

AbstractObjectiveTo evaluate the informed consent process for a clinical trial of intravenous doxycycline for rheumatoid arthritis.MethodsParticipants completed a self‐administered questionnaire about the consent process at baseline and 16 weeks following enrollment in a clinical trial.ResultsRespondents (n = 30) affirmed voluntary participation in the parent trial. Participants acknowledged hope and altruism as reasons for entering the trial more than expectation of personal benefit or outside influences. Many respondents did not understand randomization (14/30), placebos (15/30), or risks of study medications; 11/30 respondents believed that the study drug was completely safe.ConclusionRespondents generally understood the experimental nature of the trial and confirmed their participation was voluntary. However, gaps existed in participants understanding of trial design, raising the question of whether they were adequately informed about the research study prior to enrollment. Further education of potential participants in clinical trials may be required to achieve valid informed consent.
European Consensus Lupus Activity Measurement is sensitive to change in disease activity in childhood‐onset systemic lupus erythematosus
Authors: Brunner Hermine I. , Silverman Earl D. , Bombardier Claire , Feldman Brian M. 
Published: June 2003

AbstractObjectivesTo evaluate the European Consensus Lupus Activity Measurement (ECLAM) for responsiveness to change in disease activity when used in childhood‐onset systemic lupus erythematosus (cSLE). To confirm the construct validity and to characterize the measurement properties of the ECLAM by assessing its ability to predict damage and steroid requirements.MethodsThe disease courses of 66 newly diagnosed cSLE patients were reviewed. The ECLAM and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) were scored for all clinic visits and hospitalizations. Damage was assessed at the end of the followup period using the Systemic Lupus International Collaboration Clinics/American College of Rheumatology Damage Index. Disease activity at the time of diagnosis, 6 months after diagnosis, at the time of first flare, and 6 months after first flare was used to estimate responsiveness of the measures. Responsiveness was measured by the effect size, the effect size index, the standardized response mean, and the relative efficiency index (REI). The measurement properties of the ECLAM and SLEDAI over time were examined by comparing the ability of both measures to predict damage and oral steroid requirement.ResultsThe ECLAM and SLEDAI are both responsive to change in disease activity irrespective of the statistic used. The ECLAM is more sensitive than the SLEDAI using the REI (all >1.9). Cumulative disease activity as measured by the SLEDAI or the ECLAM are important predictors of damage. There are no statistically important differences between the 2 measures with regard to their ability to predict steroid requirements.ConclusionsThe ECLAM has construct validity in cSLE and, like the SLEDAI, is highly sensitive to clinically important change in disease activity. The ECLAM may be more responsive. The quantitative properties of the 2 measures are very similar. The SLEDAI likely remains the preferable disease activity measure for cSLE given its overall measurement properties and ease of use.
Changes in self‐efficacy and health status over 5 years: A longitudinal observational study of 306 patients with rheumatoid arthritis
Authors: Brekke Mette , Hjortdahl Per , Kvien Tore K. 
Published: June 2003

AbstractObjectiveTo investigate changes in self‐efficacy and health status over 5 years in patients with rheumatoid arthritis (RA), the relationships between these changes, and the influence of baseline values on subsequent changes.Methods306 adult patients with RA, born in 1926 or later, were examined by questionnaire in 1994 and again in 1999. We analyzed data regarding pain (visual analogue scale [VAS], Arthritis Impact Measurement Scale [AIMS2] symptom scale, Short Form‐36 [SF‐36] pain scale), fatigue (VAS, SF‐36 vitality scale), mental distress (AIMS2 affect scale, SF‐36 mental health scale) and self‐efficacy (Arthritis Self‐Efficacy Scales for pain and for other symptoms).ResultsOn group level, all health status measures were numerically somewhat improved, and self‐efficacy slightly reduced. Changes in self‐efficacy and in corresponding health status measures were significantly correlated. For patients with above average educational level self‐efficacy for pain at baseline was positively correlated to improvement in pain measures. Good mental health at baseline was correlated to improvement in self‐efficacy for other symptoms, but only for patients with below average educational level.ConclusionBaseline self‐efficacy seems to influence future level of perceived pain and baseline mental health status seems to influence future self‐efficacy. These associations seem to be affected by level of education.
The effects of physician specialty and patient comorbidities on the use and discontinuation of coxibs
Authors: Patino Fausto G. , Allison Jeroan , Olivieri Jason , Mudano Amy , Juarez Lucia , Person Sharina , Mikuls Ted R. , Moreland Larry , Kovac Stacey H. , Saag Kenneth G. 
Published: June 2003

AbstractObjectiveTo examine the effects of physician specialty and comorbidities on cyclooxygenase 2–selective nonsteroidal antiinflammatory drugs (NSAIDs; coxibs) utilization.MethodsMedical records of 452 patients from a regional managed care organization with ≥3 consecutive NSAID prescriptions from June 1998 to April 2001 were abstracted. Multivariable adjusted associations between coxib initiation and discontinuation and patient and provider characteristics were examined.ResultsA total of 1,142 NSAID prescriptions were written over 9,398 total patient‐months of followup. Compared with patients seeing family or general practitioners, patients seeing rheumatologists (odds ratio [OR] 3.4, 95% confidence interval [95% CI] 2.1–5.7) and internists (OR 2.3, 95% CI 1.5–3.6) were significantly more likely to receive a coxib, as well as patients with a history of osteoarthritis (OR 2.6, 95% CI 1.7–3.8), gastrointestinal disease (OR 2.3, 95% CI 1.2–4.5), and congestive heart failure (OR 4.1, 95% CI 1.0–16.4). Although specialists were more likely than generalists to prescribe coxibs, only family or general practitioners were significantly more likely to selectively use coxibs among their patients with a history of gastrointestinal disease. Fifty‐four percent of NSAID prescriptions were discontinued, and coxibs were significantly less likely to be discontinued than were traditional NSAIDs (OR 0.6, 95% CI 0.5–0.8).ConclusionOur findings suggest significantly greater, but perhaps less selective use of coxibs among specialists, even after accounting for important covariates. The initiation and discontinuation of coxibs was influenced by physician specialty and by patient risk factors.
Vertebral deformities in 229 female patients with rheumatoid arthritis: Associations with clinical variables and bone mineral density
Authors: Ørstavik Ragnhild E. , Haugeberg Glenn , Uhlig Till , Falch Jan A. , Halse Johan I. , Høiseth Arne , Lilleås Finn , Kvien Tore K. 
Published: June 2003

AbstractObjectiveTo examine the occurrence of vertebral deformities in female patients with rheumatoid arthritis (RA), and the relationship between vertebral deformities and bone mineral density (BMD) and between vertebral deformities and clinical variables.MethodsLateral radiographs of the spine were obtained in 229 female patients with RA (mean age 63.4 years, range 51.4–73.6 years) recruited from a county RA register. Vertebral deformities were measured semiquantitatively by an experienced radiologist. A clinical examination including core measurements of disease activity and severity was performed, and BMD was measured at the spine (L2–L4) and hip.ResultsAccording to the statistical analysis, 49 patients were considered to have relevant vertebral deformities. The occurrence of vertebral deformities was independently associated with age, long‐term corticosteroid use, and previous nonvertebral fracture, as well as reduced BMD. Our results failed to show any independent relationship between vertebral deformities and the activity or severity of disease.ConclusionCorticosteroid use is an important marker of established osteoporosis in patients with RA. Additionally, there seems to be a consistent relationship between BMD and vertebral deformities in this patient group.