Journal ArticleImmunohorizons · March 26, 2025
MK-6194, an interleukin-2 mutein designed to selectively activate regulatory T cells (Tregs), was evaluated for safety, pharmacokinetics (PK), immunogenicity, and pharmacodynamics in healthy participants. In a single ascending dose trial (N = 56), particip ...
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Journal ArticleMod Rheumatol · February 28, 2022
OBJECTIVES: Evaluate the efficacy and safety of the Janus kinase-1 inhibitor filgotinib in Japanese patients with rheumatoid arthritis (RA) and inadequate response to methotrexate (MTX). METHODS: Data from 147 Japanese patients in FINCH 1, a 52-week global ...
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Journal ArticleMod Rheumatol · February 28, 2022
OBJECTIVES: To evaluate the efficacy and safety of filgotinib for Japanese patients with rheumatoid arthritis (RA) and limited or no prior methotrexate (MTX) exposure. METHODS: Data up to 24 weeks were analysed for 71 Japanese patients from a 52-week globa ...
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Journal ArticleMod Rheumatol · January 5, 2022
OBJECTIVES: To evaluate efficacy and safety of filgotinib in Japanese RA patients who have failed or were intolerant to one or more biologic disease-modifying antirheumatic drugs (bDMARD) from the global FINCH 2 study (NCT02873936). METHODS: This subgroup ...
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Journal ArticleJ Rheumatol · August 2021
OBJECTIVE: The long-term safety and efficacy of filgotinib (from phase II studies), with or without methotrexate (MTX), for the treatment of patients with rheumatoid arthritis was assessed in DARWIN 3, a long-term, open-label extension study (ClinicalTrial ...
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Journal ArticleAnn Rheum Dis · July 2021
OBJECTIVE: To evaluate the efficacy and safety of the Janus kinase-1-preferential inhibitor filgotinib versus placebo or tumour necrosis factor-α inhibitor therapy in patients with active rheumatoid arthritis (RA) despite ongoing treatment with methotrexat ...
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Journal ArticleAnn Rheum Dis · June 2021
OBJECTIVES: To investigate efficacy and safety of the Janus kinase-1 inhibitor filgotinib in patients with active rheumatoid arthritis (RA) with limited or no prior methotrexate (MTX) exposure. METHODS: This 52-week, phase 3, multicentre, double-blind clin ...
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Journal ArticleThorax · January 2020
In this retrospective study of a randomised trial of simtuzumab in idiopathic pulmonary fibrosis (IPF), prodromal decline in forced vital capacity (FVC) was significantly associated with increased risk of mortality, respiratory and all-cause hospitalisatio ...
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Journal ArticleJ Am Soc Nephrol · October 2019
BACKGROUND: Apoptosis signal-regulating kinase 1 (ASK1) activation in glomerular and tubular cells resulting from oxidative stress may drive kidney disease progression. Findings in animal models identified selonsertib, a selective ASK1 inhibitor, as a pote ...
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Journal ArticleJAMA · July 23, 2019
IMPORTANCE: Patients with active rheumatoid arthritis (RA) despite treatment with biologic disease-modifying antirheumatic drug (bDMARD) therapy need treatment options. OBJECTIVE: To evaluate the effects of filgotinib vs placebo on the signs and symptoms o ...
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Journal ArticleAm J Respir Crit Care Med · July 15, 2019
Rationale: Several common and rare genetic variants have been associated with idiopathic pulmonary fibrosis, a progressive fibrotic condition that is localized to the lung. Objectives: To develop an integrated understanding of the rare and common variants ...
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Journal ArticleJCI Insight · October 4, 2018
Graft-versus-host disease (GVHD) is a major complication of hematopoietic stem cell transplantation (HCT). The tyrosine kinase SYK contributes to both acute and chronic GVHD development, making it an attractive target for GVHD prevention. Entospletinib (EN ...
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Journal ArticleEur Respir J · September 2018
We evaluated performance characteristics and estimated the minimal clinically important difference (MCID) of data-driven texture analysis (DTA), a high-resolution computed tomography (HRCT)-derived measurement of lung fibrosis, in subjects with idiopathic ...
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Journal ArticleJ Crohns Colitis · August 29, 2018
BACKGROUND AND AIMS: Matrix metalloproteinase-9 [MMP9] is implicated in the pathogenesis of ulcerative colitis [UC] via disruption of intestinal barrier integrity and function. A phase 2/3 combined trial was designed to examine the efficacy, safety, and ph ...
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Journal ArticleJ Crohns Colitis · August 29, 2018
BACKGROUND AND AIMS: Matrix metalloproteinase-9 [MMP9] is implicated in the pathogenesis of Crohn's disease and may serve as a potential biomarker. A phase 2 trial was conducted to examine the efficacy and safety of the anti-MMP9 antibody andecaliximab [GS ...
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Journal ArticleThorax · January 2018
BACKGROUND: Assessing functional impairment, therapeutic response and disease progression in patients with idiopathic pulmonary fibrosis (IPF) continues to be challenging. Hyperpolarized 129Xe MRI can address this gap through its unique capability to image ...
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Journal ArticleClin Ther · January 2018
PURPOSE: Andecaliximab (GS-5745) is a highly selective monoclonal antibody against matrix metalloproteinase-9 (MMP9), a proteolytic enzyme implicated in the pathogenesis of rheumatoid arthritis (RA). This study assessed the safety and pharmacokinetic (PK) ...
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Journal ArticleHealth Psychol · September 2017
OBJECTIVE: We evaluated the effect of the cortisol (CORT) to high sensitivity C-reactive protein (hsCRP) ratio on stress-induced negative affect (NA) reactivity and whether the association was moderated by depressive symptom severity and gender. The CORT/C ...
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Journal ArticleAnn Rheum Dis · June 2016
OBJECTIVES: To assess the efficacy and tolerability of lesinurad, an oral selective uric acid reabsorption inhibitor, in combination with allopurinol versus allopurinol alone in patients with gout and an inadequate response to allopurinol. METHODS: Patient ...
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Journal ArticleArthritis Rheumatol · October 2015
OBJECTIVE: Existing criteria for the classification of gout have suboptimal sensitivity and/or specificity, and were developed at a time when advanced imaging was not available. The current effort was undertaken to develop new classification criteria for g ...
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Journal ArticleAnn Rheum Dis · October 2015
OBJECTIVE: Existing criteria for the classification of gout have suboptimal sensitivity and/or specificity, and were developed at a time when advanced imaging was not available. The current effort was undertaken to develop new classification criteria for g ...
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Journal ArticleChest · October 2015
BACKGROUND: The National Heart, Lung, and Blood Institute-sponsored IPF Clinical Research Network (IPFnet) studies enrolled subjects with idiopathic pulmonary fibrosis (IPF) to evaluate drug therapies in treatment trials. An adjudication committee (AC) pro ...
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Journal ArticleJAMA · May 26, 2015
IMPORTANCE: Soy isoflavone supplements are used to treat several chronic diseases, although the data supporting their use are limited. Some data suggest that supplementation with soy isoflavone may be an effective treatment for patients with poor asthma co ...
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Journal ArticleBrain Behav Immun · February 2015
We examined whether the ratio of cortisol (CORT) to high-sensitivity C-reactive protein (hsCRP), an index that captures the integrity of homeostatic regulation between the hypothalamic-pituitary-adrenal (HPA) axis and inflammatory processes, is associated ...
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Journal ArticleJ Clin Rheumatol · December 2014
BACKGROUND: In clinical trials of pegloticase, a PEGylated uricase developed for treatment of gout refractory to conventional therapy, infusion-related reactions (IRs) were the second most frequent adverse event reported. OBJECTIVE: The objective of this s ...
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Journal ArticleJ Rheumatol · August 2014
OBJECTIVE: To evaluate the safety and efficacy of once-weekly subcutaneous rilonacept 160 mg for prevention of gout flares in patients initiating or continuing urate-lowering therapy (ULT). METHODS: This phase III study was conducted in the United States, ...
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Journal ArticleArthritis Res Ther · March 7, 2014
INTRODUCTION: Pegloticase, a PEGylated recombinant porcine uricase, is approved for treating refractory gout at a dose of 8 mg intravenous (IV) every 2 weeks. However, during phase 1 testing, pharmacokinetics supported less frequent dosing. Also, single do ...
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Journal ArticleArthritis Research and Therapy · March 7, 2014
Introduction: Pegloticase, a PEGylated recombinant porcine uricase, is approved for treating refractory gout at a dose of 8 mg intravenous (IV) every 2 weeks. However, during phase 1 testing, pharmacokinetics supported less frequent dosing. Also, single do ...
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Journal ArticleArthritis Res Ther · March 4, 2014
INTRODUCTION: The efficacy of pegloticase, a polyethylene glycol (PEG)-conjugated mammalian recombinant uricase, approved for chronic refractory gout, can be limited by the development of antibodies (Ab). Analyses from 2 replicate, 6-month, randomized cont ...
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Journal ArticleJ Rheumatol · March 2014
OBJECTIVE: To determine the extent to which participants at the Outcome Measures in Rheumatology (OMERACT) 11 meeting agree that instruments used in clinical trials to measure OMERACT core outcome domains in acute gout fulfill OMERACT filter requirements o ...
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Journal ArticleArthritis Care Res (Hoboken) · January 2014
OBJECTIVE: Tophi are strongly associated with structural damage in gout, and urate-lowering therapy reduces tophus size. Pegloticase leads to dramatic reductions in serum urate and subcutaneous tophi in treatment responders. The aim of this analysis was to ...
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Journal ArticleRespir Med · January 2014
BACKGROUND: Dyspnea is a hallmark symptom of idiopathic pulmonary fibrosis (IPF), and dyspnea induced physical activity limitation is a prominent driver of quality of life impairment among IPF patients. METHODS: We examined response data for the 21 physica ...
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Journal ArticlePediatrics · November 2013
The proven effectiveness of biologics and other immunomodulatory products in inflammatory rheumatic diseases has resulted in their widespread use as well as reports of potential short- and long-term complications such as infection and malignancy. These com ...
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Journal ArticleArthritis Res Ther · September 26, 2013
INTRODUCTION: Two replicate randomized, placebo-controlled six-month trials (RCTs) and an open-label treatment extension (OLE) comprised the pegloticase development program in patients with gout refractory to conventional therapy. In the RCTs, approximatel ...
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Journal ArticleAnn Rheum Dis · September 1, 2013
OBJECTIVE: To evaluate the long-term safety (up to 3 years) of treatment with pegloticase in patients with refractory chronic gout. METHODS: This open-label extension (OLE) study was conducted at 46 sites in the USA, Canada and Mexico. Patients completing ...
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Journal ArticleRespir Res · July 13, 2013
BACKGROUND: Acute exacerbation of idiopathic pulmonary fibrosis has become an important outcome measure in clinical trials. This study aimed to explore the concept of suspected acute exacerbation as an outcome measure. METHODS: Three investigators retrospe ...
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Journal ArticleJ Asthma Allergy · 2013
BACKGROUND: The CD14 C-159T single nucleotide polymorphism (SNP) has been investigated widely as a candidate genetic locus in patients with allergic disease. There are conflicting results for the association of the CD14 C-159T SNP with total serum immunogl ...
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Journal ArticleAnnals of the Rheumatic Diseases · 2013
Objective: To evaluate the long-term safety (up to 3 years) of treatment with pegloticase in patients with refractory chronic gout. Methods: This open-label extension (OLE) study was conducted at 46 sites in the USA, Canada and Mexico. Patients completing ...
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Journal ArticleAdv Chronic Kidney Dis · November 2012
Gout is a metabolic disorder of purine metabolism with primary manifestations of acute and chronic arthritis and tophus formation. The prevalence of gout appears to be increasing and may affect up to 8 million people in the United States. The development o ...
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Journal ArticleDrugs Today (Barc) · July 2012
Gout is a metabolic disorder of excess uric acid accumulation that manifests clinically as inflammatory arthritis, chronic arthropathy and the formation of deposits of uric acid known as tophi. A primary objective of gout management is to reduce the excess ...
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Journal ArticleAm J Respir Crit Care Med · March 15, 2012
RATIONALE: Gene expression profiling of airway epithelial and inflammatory cells can be used to identify genes involved in environmental asthma. METHODS: Airway epithelia and inflammatory cells were obtained via bronchial brush and bronchoalveolar lavage ( ...
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Journal ArticleArthritis Rheum · March 2012
OBJECTIVE: To evaluate the interleukin-1 inhibitor rilonacept (Interleukin-1 Trap) for prevention of gout flares occurring in the first few months following initiation of urate-lowering therapy. METHODS: In this double-blind study, adult patients with hype ...
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Journal ArticleHospital Medicine Clinics · January 1, 2012
Gout is an inflammatory arthritis resulting from the deposition of monosodium urate crystals in joints and soft tissues. This article discusses the definitions and epidemiology of acute gout. History and examination, diagnosis, management, prognosis, perfo ...
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Journal ArticleJ Appl Physiol (1985) · September 2011
Effect of laboratory exposure to O₃ (220 ppb) and filtered air (FA) on respiratory physiology were evaluated at two time points (acute and 1 day postexposure) in healthy cohort (n = 138, 18-35 yr, 40% women) comprised mainly of Caucasian (60%) and African ...
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Journal ArticleJAMA · August 17, 2011
CONTEXT: Patients with chronic disabling gout refractory to conventional urate-lowering therapy need timely treatment to control disease manifestations related to tissue urate crystal deposition. Pegloticase, monomethoxypoly(ethylene glycol)-conjugated mam ...
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Journal ArticleJ Med Econ · 2011
OBJECTIVE: Joint pain and swelling during gout flares may lead to considerable morbidity and disability, having an impact on patient work productivity and social participation. The objective of this study was to assess how gout flares affect these activiti ...
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Journal ArticleN Engl J Med · August 12, 2010
BACKGROUND: Sildenafil, a phosphodiesterase-5 inhibitor, may preferentially improve blood flow to well-ventilated regions of the lung in patients with advanced idiopathic pulmonary fibrosis, which could result in improvements in gas exchange. We tested the ...
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Journal ArticleProc Natl Acad Sci U S A · August 10, 2010
A high plasma urate concentration (PUA), related to loss of urate oxidase in evolution, is postulated to protect humans from oxidative injury. This hypothesis has broad clinical relevance, but support rests largely on in vitro data and epidemiologic associ ...
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Journal ArticleCurr Opin Rheumatol · March 2010
PURPOSE OF REVIEW: To summarize new knowledge on approved and emerging drugs used to treat hyperuricemia or the clinical manifestations of gout. RECENT FINDINGS: Results of several clinical trials provide new data on the efficacy and safety of the approved ...
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Journal ArticlePolitical Representation · January 1, 2010
Certainly, gentlemen, it ought to be the happiness and glory of a representative to live in the strictest union, the closest correspondence, and the most unreserved communication with his constituents. Their wishes ought to have great weight with him; thei ...
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Journal ArticleAnn Rheum Dis · October 2009
BACKGROUND: Recent studies suggest that blockade of the NLRP3 (cryopyrin) inflammasome interleukin 1beta (IL1beta) pathway may offer a new treatment strategy for gout. OBJECTIVE: To explore the potential utility of rilonacept (IL1 Trap) in patients with ch ...
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Journal ArticleJ Rheumatol · May 2009
OBJECTIVE: The relationship between self-reported quality of life and disability and disease severity was evaluated in subjects with treatment-failure gout (n = 110) in a prospective, 52-week, observational study. METHODS: Subjects had symptomatic crystal- ...
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Journal ArticleN Engl J Med · April 9, 2009
BACKGROUND: Gastroesophageal reflux is common among patients with asthma but often causes mild or no symptoms. It is not known whether treatment of gastroesophageal reflux with proton-pump inhibitors in patients who have poorly controlled asthma without sy ...
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Journal ArticleArthritis Rheum · September 2008
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OBJECTIVE: To 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. METHODS: Forty-one patients w ...
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Journal ArticleJ Allergy Clin Immunol · July 2008
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BACKGROUND: Exhaled breath condensate (EBC) pH and exhaled nitric oxide (FeNO) have been proposed as markers of asthma severity. EBC pH values below 6.5 have been associated with asthma exacerbations. Protonation of airway nitrite occurs at low pH and may ...
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Journal ArticleHum Mol Genet · July 1, 2008
Asthma is a multifactorial disease, in which the intricate interplay between genetic and environmental factors underlies the overall phenotype of the disease. Using a genome-wide scan for linkage in a population comprising of Danish families, we identified ...
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Journal ArticleClin Exp Allergy · March 2008
BACKGROUND: Asthma is a clinically heterogeneous disease caused by a complex interaction between genetic susceptibility and diverse environmental factors. In common with other complex diseases the lack of a standardized scheme to evaluate the phenotypic va ...
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Journal ArticleCurr Opin Rheumatol · March 2008
PURPOSE OF REVIEW: The purpose of this review is to discuss the defining characteristics of refractory gout and the pharmacological management of this problem. RECENT FINDINGS: Refractory gout refers to those patients who have ongoing symptoms of active di ...
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Journal ArticleJ Allergy Clin Immunol · February 2008
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BACKGROUND: Asthma is a significant cause of morbidity and mortality for African Americans. Fraction of exhaled nitric oxide (FeNO) levels are increased in patients with asthma, and airway levels of nitric oxide metabolites regulate airway inflammation and ...
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Journal ArticleEur Respir J · December 2007
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Age-related declines in forced expiratory volume in one second are accelerated in smokers. Smoking is associated with decreased exhaled nitric oxide fraction (F(eNO)). The aim of the present study was to determine the impact of age on F(eNO) in otherwise h ...
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Journal ArticleCurr Rheumatol Rep · June 2007
Featured Publication
Successful management of chronic gout depends on reducing body pools of urate. The benchmark of success is to maintain serum urate levels at less than 6 mg/dL using therapies such as probenecid or allopurinol. In a subset of patients with gout, these medic ...
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Journal ArticleHum Genet · March 2007
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Quantitative phenotypes correlated with a complex disorder offer increased power to detect linkage in comparison to affected-unaffected classifications. Asthma is a complex disorder characterized by periods of bronchial obstruction and increased bronchial ...
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Journal ArticleArthritis Rheum · March 2007
Featured Publication
OBJECTIVE: To evaluate the efficacy, immunogenicity, and tolerability of intravenous (IV) PEGylated recombinant mammalian urate oxidase (PEG-uricase) for the treatment of severe gout. METHODS: Single infusions of PEG-uricase (at doses ranging from 0.5 mg t ...
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Journal ArticleCurr Opin Rheumatol · May 2006
PURPOSE OF REVIEW: This review addresses recent concerns about the cardiovascular safety of nonsteroidal anti-inflammatory drugs, the disease-modifying role of these drugs in ankylosing spondylitis, and their use in the understudied pediatric population. R ...
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Journal ArticleEur J Hum Genet · March 2006
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Asthma is a complex disease and the intricate interplay between genetic and environmental factors underlies the overall phenotype of the disease. Families with at least two siblings with asthma were collected from Europe, Australia and the US. A genome sca ...
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Journal ArticleJ Endotoxin Res · 2006
BACKGROUND: Inhalation of environmental endotoxin is important in the pathogenesis of asthma and other environmental airway diseases. Inhaled airway challenge using lipopolysaccharide in humans has been performed for over 20 years to assess the airway resp ...
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Journal ArticleArthritis Res Ther · 2006
Featured Publication
PEG-modified recombinant mammalian urate oxidase (PEG-uricase) is being developed as a treatment for patients with chronic gout who are intolerant of, or refractory to, available therapy for controlling hyperuricemia. In an open-label phase I trial, single ...
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Journal ArticleArthritis Research and Therapy · December 2, 2005
PEG-modified recombinant mammalian urate oxidase (PEG-uricase) is being developed as a treatment for patients with chronic gout who are intolerant of, or refractory to, available therapy for controlling hyperuricemia. In an open-label phase I trial, single ...
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Journal ArticleConsultant · August 1, 2005
Early treatment with disease-modifying anti-rheumatic drugs (DMARDs)-alone or in combination-can prevent joint damage and minimize disability. Until recently, the DMARDs used predominantly in patients with rheumatoid arthritis had been methotrexate, sulfas ...
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Journal ArticleEnviron Health Perspect · May 2005
Featured Publication
Aerial emissions from a swine house at North Carolina State University's field laboratory were diluted to a level that could occur at varying distances downwind from a confined animal feeding operation (CAFO) both within and beyond the property line, and t ...
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Journal ArticleCurr Opin Allergy Clin Immunol · October 2004
Featured Publication
PURPOSE OF REVIEW: We review the role of bioaerosols in the pathogenesis of inflammatory airway disease. The focus is on recent discoveries in innate immune responses induced by common components of bioaerosols. RECENT FINDINGS: Common components of bioaer ...
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Journal ArticlePharmacogenetics · September 2004
BACKGROUND: Cysteinyl leukotrienes (CYSLTR) are potent biological mediators in the pathophysiology of asthma for which two receptors have been characterized, CYSLTR1 and CYSLTR2. The leukotriene modifying agents currently used to control bronchoconstrictio ...
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Journal ArticleJ Allergy Clin Immunol · February 2003
BACKGROUND: Previous estimates of the cost of allergic rhinitis predate the substantial increase in the use of second-generation antihistamines and intranasal corticosteroids. OBJECTIVE: We sought to update estimates of the direct costs of allergic rhiniti ...
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Journal ArticleCurr Rheumatol Rep · February 2001
The selective cyclooxygenase 2 (COX-2) inhibitors have emerged as an important option in the treatment of rheumatoid arthritis (RA). Rofecoxib and celecoxib, the selective COX-2 inhibitors currently available, have shown efficacy in reducing symptoms of RA ...
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Journal ArticleCurr Rheumatol Rep · October 2000
Upregulated adhesion molecule and cytokine expression on endothelial cells and infiltrating inflammatory cells occur in most vasculitis syndromes. These observations suggest that vasculitis is associated with pathologic activation of normal immune cell cyt ...
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Journal ArticleJ Immunol · February 15, 2000
The roles that thymus cytokines might play in regulating thymic atrophy are not known. Reversing thymic atrophy is important for immune reconstitution in adults. We have studied cytokine mRNA steady-state levels in 45 normal human (aged 3 days to 78 years) ...
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Journal ArticleJ Immunol · June 15, 1998
Human CD7 is an Ig superfamily molecule that is expressed on mature T and NK lymphocytes. Although in vitro studies have suggested a role for CD7 in lymphoid development and function, the exact function of CD7 in vivo has remained elusive. One patient has ...
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Journal ArticleArthritis Rheum · October 1997
OBJECTIVE: To describe the clinical, laboratory, radiologic, and histopathologic features of methotrexate (MTX)-induced lung injury in a combined cohort of selected patients with rheumatoid arthritis (RA) and all cases reported in the English-language lite ...
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Journal ArticleAnn Intern Med · September 1, 1997
BACKGROUND: Toxicity limits the use of methotrexate. OBJECTIVE: To identify risk factors for methotrexate-induced lung injury in patients with rheumatoid arthritis. DESIGN: Case-control study. SETTING: One private and five academic rheumatology practices. ...
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Journal ArticleArthritis Rheum · January 1996
This report describes a 30-year-old man who presented with an acute multisystem illness which was diagnosed as Rocky Mountain spotted fever (RMSF). Near the time of admission the patient was noted to have a newly developed aseptic monarticular arthritis of ...
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Journal ArticleJournal of Investigative Medicine · January 1, 1996
Human CD7 is a 40 kilodalton member of the immunoglobulin gene superfamily that is expressed early in natural killer and T lymphocyte development. Although CD7 involvement in lymphocyte activation has been suggested by numerous studies, the functional role ...
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Journal ArticleRheum Dis Clin North Am · November 1995
The pathogenesis of vasculitis syndromes is via a diverse array of mechanisms that disrupt vessel integrity and produce clinical signs and symptoms of tissue ischemia. In many patients with vasculitis, it is not possible to directly classify the syndrome a ...
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Journal ArticleJ Immunol · July 15, 1989
T cell epitopes residing within vaccine candidate peptides have been identified by delayed-type hypersensitivity (DTH) responses in mice. The recombinant sporozoite vaccine candidate, R32tet32, contains at least two T epitopes, one located within the repea ...
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