bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long‐term safety and maintenance of clinical improvement following treatment with anakinra (recombinant human interleukin‐1 receptor antagonist) in patients with rheumatoid arthritis: Extension phase of a randomized, double‐blind, placebo‐controlled trial
Authors: Nuki George , Bresnihan Barry , Bear Moraye B. , McCabe Dorothy 
Published: November 2002

AbstractObjectiveTo demonstrate the long‐term efficacy of anakinra, a human recombinant interleukin‐1 receptor antagonist, in patients with rheumatoid arthritis (RA), and to assess the long‐term safety of anakinra at different daily doses.MethodsThe efficacy and safety of anakinra were previously demonstrated in a double‐blind, placebo‐controlled, 24‐week evaluation in 472 patients with active RA. Of 345 patients who completed the placebo‐controlled phase of the study, 309 continued in a 52‐week, multicenter, double‐blind, parallel‐group extension phase of the study. Patients received subcutaneous injections of anakinra (30, 75, or 150 mg) once daily. Efficacy was assessed among the 309 patients for the first 24 weeks of the extension phase (48 weeks total therapy), using the American College of Rheumatology composite score (ACR20), its components, and radiographs of the hands and wrists. Safety was assessed in all 472 patients over the entire 52‐week extension phase (76 weeks total exposure).ResultsA total of 218 patients completed the extension phase. Of the 91 patients who withdrew prematurely, 46 did so following adverse events, and 26 withdrew because of lack of efficacy. Among patients receiving anakinra who entered the extension phase, the level of improvement was maintained for 48 weeks. The ACR20 response was 51% at week 24 and 46% at week 48, and this effect was consistent across all dose groups. The durability of the response to anakinra was further demonstrated in an evaluation of the sustained ACR20 response, which was similar during the first and second 24‐week periods (36% and 42%, respectively). At week 48, ACR50 and ACR70 responses were demonstrated in 18% and 3% of patients, respectively, who continued taking anakinra (all dose groups) and in 20% and 1% of patients, respectively, who were originally receiving placebo and then were randomized to all doses of anakinra. Anakinra was well tolerated for 76 weeks. The only side effects that appeared to be treatment‐related were skin reactions at the injection site. There was no evidence of decreased tolerance, an increased number of withdrawals, or an increased incidence of clinical complications associated with extended anakinra therapy.ConclusionThe clinical benefits of treatment with daily self‐administered subcutaneous injections of anakinra in a cohort of patients with active RA were maintained for up to 48 weeks. Anakinra was well tolerated over 76 weeks. These observations support the long‐term use of anakinra for the treatment of patients with RA.
Hematopoietic stem cell transplantation for severe and refractory lupus
Authors: Traynor Ann E. , Barr Walter G. , Rosa Robert M. , Rodriguez Julianne , Oyama Yu , Baker Steven , Brush Mary , Burt Richard K. 
Published: November 2002

AbstractObjectiveTo determine the safety and long‐term efficacy of immune ablation and autologous hematopoietic stem cell transplantation (HSCT) in severe systemic lupus erythematosus (SLE).MethodsFifteen patients with persistently active SLE after intravenous (IV) cyclophosphamide (CYC) therapy underwent HSCT. Stem cells were mobilized with CYC (2.0 gm/m2) and granulocyte colony‐stimulating factor (5 μg/kg/day). Lymphocytes were depleted from the graft by selection of CD34‐positive cells. The conditioning regimen used was CYC (200 mg/kg), antithymocyte globulin (90 mg/kg), and methylprednisolone (3 mg/kg). Outcome was evaluated by the SLE Disease Activity Index (SLEDAI), serum complement levels, serologic features, function of diseased organs, and immunosuppressive medication requirements.ResultsFifteen patients with persistent, severe SLE, 7 of whom were critically ill, were treated. No deaths occurred following treatment. The median followup after HSCT has been 36 months (range 12–66 months). All patients demonstrated a gradual, but marked, improvement. The SLEDAI score has declined to ≤5 in 12 patients. Complement and anti–double‐stranded DNA levels have normalized and marked improvements in end organ function have occurred in all subjects. Of the 12 patients followed up for >1 year after HSCT, 10 have discontinued immunosuppressive medications, and the prednisone dosage has been tapered to 15 mg/day in 1. Only 2 patients have demonstrated clinical evidence of recurrence of active lupus. One of these patients currently requires no immunosuppressive medication and has a normal performance status. The other patient is currently receiving IV CYC.ConclusionIn patients experiencing the persistence of organ‐threatening lupus following standard, aggressive therapy, HSCT may be performed safely, with marked improvement and sustained withdrawal of all immunosuppressive medication for most patients. A phase III randomized trial is warranted to determine the relative efficacy and durability of remission of HSCT compared with standard therapies.
Determinants and sequelae associated with utilization of acetaminophen versus traditional nonsteroidal antiinflammatory drugs in an elderly population
Authors: Rahme Elham , Pettitt Dan , LeLorier Jacques 
Published: November 2002

AbstractObjectiveAcetaminophen is recommended as initial therapy for patients with arthritis, particularly those at increased risk of nonsteroidal antiinflammatory drug (NSAID)–induced gastrointestinal (GI) side effects. However, higher doses of acetaminophen inhibit prostaglandin synthesis and have been associated with GI events. This study was undertaken to compare the observed and adjusted rates of GI events (hospitalizations, ulcers, dyspepsia, GI prophylaxis) occurring with higher versus lower doses of acetaminophen.MethodsThis was a retrospective cohort study of subjects ages ≥65 years who received a prescription for acetaminophen or NSAID between 1994 and 1996. Pharmaceutical and medical records were reviewed for 1 year of historical data prior to the index prescription of acetaminophen or non‐aspirin NSAID. Risk factors for GI events were identified based on the historical data. To further control for bias, patients were categorized by propensity score (the likelihood of receiving acetaminophen, given defined risk factor values). Records were then reviewed for the duration of the index prescription or 30 days, whichever was less, to generate data on the occurrence of GI events. Determinants of acetaminophen utilization were identified using logistic regression, and rates of GI events for each therapy were examined using Poisson regression analyses, controlling for duration of exposure, individual risk factors, and propensity scores.ResultsThe study included 26,978 patients in the NSAID cohort and 21,207 in the acetaminophen cohort. Determinants of acetaminophen utilization compared with NSAIDs (odds ratio [95% confidence interval]) included recent hospitalization (8.6 [7.7–9.5]), concomitant anticoagulation therapy (3.2 [2.7–3.8]), age >85 years (2.3 [2.1–2.4]), and history of prior GI events, especially those requiring hospitalization (14.6 [11.7–18.7]). Unadjusted rates of GI hospitalization, ulcer, and dyspepsia were higher for patients in the acetaminophen cohort than for those in the NSAID cohort. The occurrence of GI events in acetaminophen‐treated patients was dose dependent, with rate ratios (compared with high‐dose NSAIDs and adjusted for risk susceptibility) ranging from 0.6 (95% confidence interval 0.5–0.7) for ≤650 mg/day to 1.0 (0.9–1.1) for >3,250 mg/day.ConclusionIn this cohort, acetaminophen utilization is more common in patients at higher risk of GI events. After adjustment for risk susceptibility, patients receiving higher doses of acetaminophen have higher rates of GI events compared with those receiving lower doses.
Increase in expression of receptor activator of nuclear factor κB at sites of bone erosion correlates with progression of inflammation in evolving collagen‐induced arthritis
Authors: Lubberts Erik , Oppers‐Walgreen Birgitte , Pettit Allison R. , Van Den Bersselaar Liduine , Joosten Leo A. B. , Goldring Steven R. , Gravallese Ellen M. , Van Den Berg Wim B. 
Published: November 2002

AbstractObjectiveThe receptor activator of nuclear factor κB (RANK)/RANK ligand (RANKL) pathway is critical in osteoclastogenesis and bone resorption and has been implicated in the process of focal bone erosion in arthritis. This study was undertaken to identify in vivo the hitherto‐unknown origin and localization of RANK‐expressing osteoclast precursor cells at sites of bone erosion in arthritis.MethodsDBA‐1 mice were immunized with bovine type II collagen/Freund's complete adjuvant and were given an intraperitoneal booster injection of type II collagen on day 21. Arthritis was monitored visually, and joint pathology was examined histologically. RANK and RANKL expression were analyzed using specific immunohistochemistry, and tartrate‐resistant acid phosphatase (TRAP) staining was performed. In addition, TRAP and cathepsin K messenger RNA expression were analyzed by in situ hybridization.ResultsA marked increase in the number of cells expressing RANK correlated with the progression of synovial inflammation and clinical disease severity in evolving collagen‐induced arthritis (CIA). Interestingly, RANK expression demonstrated a gradient pattern with increased numbers of RANK‐positive cells within the synovial infiltrate in areas closer to periosteum and cortical bone. Cells expressing RANK included cells in synovial tissue, bone lining cells on the surface of trabecular bone at sites of erosion, and cells in periosteal areas adjacent to synovial inflammation. In areas where RANK‐positive cells were abundant, TRAP‐positive, multinucleated osteoclast‐like cells were also present at sites of focal bone erosion, suggesting differentiation of synovially derived RANK‐positive osteoclast precursor cells into osteoclasts. In addition, TRAP– and cathepsin K–double‐positive osteoclast‐like cells were detected on the synovial side of cortical bone at sites of early and advanced cortical bone erosion. Sites of RANK expression also correlated well with sites of RANKL expression, and there was a close correlation of the temporal expression of the receptor–ligand pair.ConclusionCells expressing RANK increased in abundance with the progression of arthritis in evolving CIA, and sites of RANK‐expressing cells correlated with sites of TRAP‐positive, multinucleated osteoclast‐like cells as well as with sites of RANKL expression. These data support the hypothesis that the RANK/RANKL pathway plays an important role in the process of bone erosion in CIA.
Dehydroepiandrosterone treatment of women with mild‐to‐moderate systemic lupus erythematosus: A multicenter randomized, double‐blind, placebo‐controlled trial
Authors: Chang Deh‐Ming , Lan Joung‐Liang , Lin Hsiao‐Yi , Luo Shue‐Fen 
Published: November 2002

AbstractObjectiveTo evaluate the efficacy and tolerability of dehydroepiandrosterone (DHEA) at a dosage of 200 mg/day in adult women with active systemic lupus erythematosus (SLE).MethodsIn a multicenter randomized, double‐blind, placebo‐controlled trial, 120 adult women with active SLE received oral DHEA (200 mg/day; n = 61) or placebo (n = 59) for 24 weeks. The primary end point was the mean change from baseline in the Systemic Lupus Activity Measure (SLAM) score at 24 weeks of therapy. Secondary end points included time to first flare, change in SLE Disease Activity Index (SLEDAI) score, and physician's and patient's global assessment scores at week 24.ResultsThe two groups were well balanced for baseline characteristics. Mean reductions in SLAM scores from baseline were similar and were not statistically significantly different between treatment groups (DHEA −2.6 ± 3.4 versus placebo −2.0 ± 3.8, mean ± SD). The number of patients with flares was decreased by 16% in the DHEA group (18.3% of DHEA‐treated patients versus 33.9% of placebo‐treated patients; P = 0.044, based on time to first flare). The mean change in the patient's global assessment was statistically significant between the two groups (DHEA −5.5 versus placebo 5.4; P = 0.005). The number of patients with serious adverse events, most of which were related to SLE flare, was significantly lower in DHEA‐treated patients compared with placebo‐treated patients (P = 0.010). Expected hormonal effects, including increased testosterone levels and increased incidence of acne, were observed. No life‐threatening reactions or serious safety issues were identified during this study.ConclusionThe overall results confirm that DHEA treatment was well‐tolerated, significantly reduced the number of SLE flares, and improved patient's global assessment of disease activity.
The relative prevalence of disease symptoms for ill persons: evidence from Benin
Authors: Muller Christophe 
Published: November 2002

AbstractIn developing countries, the usual modelling of the correlates of health problems is not a good fit for the health phenomena encountered and the available data. Indeed, three common situations occur: (a) it is often the observed symptoms that are used to determine medical interventions instead of specific disease diagnostics or general health indicators; (b) the ill persons described by the data are often affected by multiple health problems; and (c) the correlates of the full spectrum of all symptoms need to be considered together. In this paper, these issues are dealt with by proposing a statistical approach based on competing scores of symptoms that explain their relative prevalence among the observed ill persons.Using multinomial logit models, the relative prevalence of four symptoms was estimated for four age classes of ill persons in Benin. Socio‐demographic characteristics, household equipment and consumption behaviour are shown to influence the relative prevalence of symptoms and therefore could be used to decide what treatment to use. Moreover, living standards and economic activities are important and the pattern of symptoms among poor or agricultural ill persons differs from that of the rich or the non‐peasants. The proposed method can be used to assist the definition of target groups and to guide the allocation of scarce resources in poor countries. Copyright © 2000 John Wiley & Sons, Ltd.
NMR assignments of selected bacterial carotenoids
Authors: Lutnaes Bjart Frode , Krane Jostein , Liaaen‐Jensen Synnøve 
Published: November 2002

AbstractComplete 1H and 13C NMR assignments for selected carotenoids from purple and green phototropic bacteria are reported for the first time. Assignments are made for the all‐E isomers of OH‐rhodopin (1, 1,2,1′,2′‐tetrahydro‐ψ,ψ‐carotene‐1,1′‐diol), rhodovibrin (2, 1′‐methoxy‐3′,4′‐didehydro‐1,2,1′,2′‐tetrahydro‐ψ,ψ‐carotene‐1‐ol), anhydrorhodovibrin (3, 1‐methoxy‐3,4‐didehydro‐1,2‐dihydro‐ψ,ψ‐carotene), 2‐ketorhodovibrin (4, 1′‐hydroxy‐1‐methoxy‐3,4,3′,4′‐tetradehydro‐1,2, 1′,2′‐tetrahydro‐ψ,ψ‐carotene‐2‐one) and chlorobactene (5, ϕ,ψ‐carotene). Copyright © 2002 John Wiley & Sons, Ltd.
19F diffusion NMR analysis of enzyme–inhibitor binding
Authors: Derrick Tiffany S. , Lucas Laura H. , Dimicoli Jean‐Luc , Larive Cynthia K. 
Published: November 2002

AbstractNMR diffusion measurements are a useful tool for probing molecular interactions, especially ligand–protein binding, because the diffusion coefficient measured for the ligand can reflect the binding affinity. This technique is useful for determining relative affinities of multiple ligands and quantitating binding constants to a specific biomolecular target, such as an enzyme. In this work, binding of two TFA‐derivitized inhibitors to the enzyme elastase was measured by 19F pulsed field gradient NMR spectroscopy. The differing thermodynamic (Kd) and kinetic (chemical exchange) properties of the elastase inhibitors introduced unique challenges to the NMR diffusion analysis. Line broadening due to fast T2 relaxation, differential T1 relaxation on the diffusion time‐scale and chemical exchange severely compromised the spectral signal‐to‐noise ratio and forced the use of extensive signal averaging. The resultant experimental time caused inhibitor hydrolysis to occur on the time‐scale of the measurement. Modulation of resonance intensity in LED spectra measured as a function of the diffusion delay time was explored as a function of the population ratio of the free and bound ligands. The intensity modulation introduced by chemical exchange during the diffusion delay of the LED experiment can be removed by choosing a pulse sequence such as BPPLED that incorporates bipolar gradient pulse pairs separated by 180° pulses that refocus chemical shift evolution. Copyright © 2002 John Wiley & Sons, Ltd.
Computations on historic masonry structures
Authors: Lourenço Paulo B 
Published: November 2002

AbstractIs modelling and analysis of historical masonry structures necessary? Is the experimental behaviour of historical masonry constructions known? The answers seem to be ‘yes’, and substantial developments have occurred in recent decades in the challenging issues of conservation and restoration. A key issue is what type of analysis should be used. It seems that all methods are of interest, depending on the actual constraints of the engineering problem. In this paper, the possibilities of analysis of historic structures are addressed and a set of guidelines is proposed.
The novel antagonist 3‐CBW discriminates between kainate receptors expressed on neonatal rat motoneurones and those on dorsal root C‐fibres
Authors: More Julia C A , Troop Helen M , Jane David E 
Published: November 2002

The natural product willardiine is a selective AMPA receptor agonist. We report that an N3‐substituted analogue of willardiine, (S)‐3‐(4‐carboxybenzyl)willardiine (3‐CBW), antagonizes AMPA and kainate receptors expressed on motoneurones and dorsal root C‐fibres, respectively.
Reduction of the fast component of the dorsal root‐evoked ventral root potential (fDR‐VRP) has been used as a novel method to compare AMPA receptor antagonists. 3‐CBW, NBQX and GYKI53655 depressed the fDR‐VRP with IC50 values of 10.3±2.4, 0.214±0.043 and 4.03±0.31 μM, respectively. That 3‐CBW depressed the fDR‐VRP by acting at AMPA and not metabotropic glutamate receptors was demonstrated by the lack of effect of LY341495 (100 μM).
The Schild plot for antagonism of responses to (S)‐5‐fluorowillardiine on motoneurones by 3‐CBW had a slope of 1.11±0.13 giving a pA2 value of 4.48. The Schild plot for antagonism of kainate responses on the dorsal root by 3‐CBW had a slope of 1.05±0.05 giving a pA2 value of 4.96.
On neonatal rat motoneurones 3‐CBW (200 μM) almost completely abolished responses to AMPA while responses to NMDA, kainate and DHPG were 101.6±11.6%, 39.4±5.8% and 110.5±9.0% of control, respectively. 3‐CBW can therefore be used to isolate kainate receptor responses from those mediated by AMPA receptors.
3‐CBW antagonized kainate‐induced responses on dorsal root C‐fibres with a pA2 value of 4.96 whereas kainate receptor mediated responses (isolated by including GYKI53655 in the medium) on motoneurones were not completely blocked by 200 μM 3‐CBW, substantiating evidence that kainate receptors on neonatal rat motoneurones differ from those on dorsal root C‐fibres.

British Journal of Pharmacology (2002) 137, 1125–1133. doi:10.1038/sj.bjp.0704957
Unravelling mechanisms underlying ischaemic arrhythmias – the importance of models
Authors: Guppy L J , Walker M J A 
Published: November 2002

A new model of regional ischaemia using blood‐perfused isolated rat hearts is reported in this issue. This model has potential value in pharmacology to test the actions of drugs against the arrhythmias that arise early period (0–30 min) after induction of ischaemia. Unfortunately, the severity of arrhythmias in this new model is reduced, when compared to other models, in both the early and the late period (1–4 h) of coronary artery occlusion. This commentary compares the new model with previous models, and comments on the possible mechanisms of arrhythmias induced by ischaemia.British Journal of Pharmacology (2002) 137, 941–942. doi:10.1038/sj.bjp.0704976
La representación social de los derechos humanos en estudiantes universitarios argentinos
Authors: Roselli Néstor D. , Calvo Rafael A. , Spini Dario 
Published: November 2002

Esta investigación forma parte de un vasto estudio trans-nacional sobre el tema, llevado a cabo por Doise y colaboradores (1994, 1995, 1999) en la Universidad de Ginebra. Si bien los datos presentes (N:375) fueron recogidos con fines de una comparación internacional, ello no impide un análisis autónomo, por demás significativo. El cuestionario aplicado en esta ocasión es el mismo que se utilizó en los demás países involucrados en el referido estudio. También el análisis de los datos sigue de cerca el modelo desarrollado por los autores nombrados. De todos modos el análisis prescinde de referencias comparativas ajenas a la población relevada: estudiantes universitarios argentines.
Estructura social y personalidad en la obra de Ignacio Martín Baró
Authors: Sánchez Esteban , Trejo Zarahy 
Published: November 2002

Este artículo tiene como objetivo analizar la obra de Ignacio Martín Baró utilizando un marco teórico fundamental en la historia de la Psicología Social: el estudio de la Estructura Social y la Personalidad. Según J. S. House (1977), esta perspectiva tiene sus raíces en algunos de los grandes pensadores que inauguran la Sociología: Marx, Weber y Durkheim. Su principal característica sería la integración tanto en el nivel teórico como en el nivel empírico de elementos de estructura social y elementos psicológicos o de personalidad. La perspectiva psicosocial se caracterizaría por esta integración teórica y empírica. El análisis de la conducta humana y de la realidad social presente en la obra de Martín Baró comparte en gran medida estos principios. En el presente artículo se analizan el tratamiento que el autor da a aspectos como la violencia, la pobreza, las actitudes y a la propia definición de la Psicología Social. Finalmente, se señalan las notas características de la perspectiva de Martín Baró en relación con el estudio de la estructura social y la personalidad.
Solid‐state 13C‐NMR investigations of crosslinked structure modifications in elastomers during heating treatment
Authors: Buzaré Jean‐Yves , Silly G. , Emery J. , Boccaccio Guy , Rouault Eric 
Published: November 2002

AbstractThe chemical modifications occurring during the thermal degradation of sulfur‐cured natural rubber were investigated with 13C‐NMR. Samples of vulcanized rubbers were heat‐aged at 70°C under an air (oxidative) environment for 3, 7, and 21 days. Changes were analyzed by the measurement of the variations of the concentrations of different C–Sx–C crosslinked structures during the thermooxidative process through the intensity of the related NMR lines in the 10–70‐ppm range. © 2002 Wiley Periodicals, Inc. J Appl Polm Sci 87:3–8, 2003