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T R Mikuls

Brian W Coburn, T Craig Cheetham, Nazia Rashid, John M Chang, Gerald D Levy, Artak Kerimian, Kimberly J Low, David T Redden, S Louis Bridges, Kenneth G Saag, Jeffrey R Curtis, Ted R Mikuls
BACKGROUND: Despite the availability of effective therapies, most gout patients achieve suboptimal treatment outcomes. Current best practices suggest gradual dose-escalation of urate lowering therapy and serial serum urate (sUA) measurement to achieve sUA<6.0mg/dl. However, this strategy is not routinely used. Here we present the study design rationale and development for a pharmacist-led intervention to promote sUA goal attainment. METHODS: To overcome barriers in achieving optimal outcomes, we planned and implemented the Randomized Evaluation of an Ambulatory Care Pharmacist-Led Intervention to Optimize Urate Lowering Pathways (RAmP-UP) study...
September 2016: Contemporary Clinical Trials
Lauren Lange, Geoffrey M Thiele, Courtney McCracken, Gabriel Wang, Lori A Ponder, Sheila T Angeles-Han, Kelly A Rouster-Stevens, Aimee O Hersh, Larry B Vogler, John F Bohnsack, Shelly Abramowicz, Ted R Mikuls, Sampath Prahalad
BACKGROUND: The association between rheumatoid arthritis (RA) and periodontitis is well established. Some children with juvenile idiopathic arthritis (JIA) phenotypically resemble adults with RA, characterized by the presence of anti-cyclic citrullinated peptide (CCP) antibodies. We sought to investigate an association between CCP-positive JIA and symptoms of periodontitis and antibodies to oral microbiota. METHODS: Antibodies to oral pathogens Porphyromonas gingivalis, Prevotella intermedia, and Fusobacterium nucleatum were measured using ELISA in 71 children with CCP-positive JIA and 74 children with CCP-negative JIA...
2016: Pediatric Rheumatology Online Journal
R S Redman, G S Kerr, J B Payne, T R Mikuls, J Huang, H R Sayles, K L Becker, E S Nylén
Serum procalcitonin (ProCT) is elevated in response to bacterial infections, whereas high sensitivity C-reactive protein (hsCRP) is a nonspecific inflammatory marker that is increased by excess adipose tissue. We examined the efficacy of ProCT and hsCRP as biomarkers of periodontitis in the saliva and serum of patients with arthritis, which is characterized by variable levels of systemic inflammation that potentially can confound the interpretation of inflammatory biomarkers. Blood and unstimulated whole saliva were collected from 33 patients with rheumatoid arthritis (RA) and 50 with osteoarthritis (OA)...
2016: Biotechnic & Histochemistry: Official Publication of the Biological Stain Commission
Marc A Sintek, Christopher T Sparrow, Ted R Mikuls, Kathryn J Lindley, Richard G Bach, Howard I Kurz, Eric Novak, Jasvindar Singh
OBJECTIVE: To investigate repeat revascularisation outcomes in patients with rheumatoid arthritis(RA) after percutaneous coronary intervention (PCI). METHODS: We performed a single-centre, retrospective matched cohort study of patients with RA matched to non-RA patients post PCI. Primary endpoints were time to target lesion revascularisation (TLR) and target vessel revascularisation (TVR) analysed by Cox proportional hazard shared frailty models. RESULTS: A total of 228 lesions (143 patients) were identified in the RA cohort and matched to 677 control lesions (541 patients)...
March 2016: Heart: Official Journal of the British Cardiac Society
Derrick T Antoniak, Michael J Duryee, Ted R Mikuls, Geoffrey M Thiele, Daniel R Anderson
Inflammation is widely accepted to play a major role in atherosclerosis and other cardiovascular diseases. However, the exact mechanism(s) by which inflammation exerts its pathogenic effect remains poorly understood. A number of oxidatively modified proteins have been associated with cardiovascular disease. Recently, attention has been given to the oxidative compound of malondialdehyde and acetaldehyde, two reactive aldehydes known to covalently bind and adduct macromolecules. These products have been shown to form stable malondialdehyde-acetaldehyde (MAA) adducts that are reactive and induce immune responses...
December 2015: Free Radical Biology & Medicine
R M Sellers, J B Payne, F Yu, T D LeVan, C Walker, T R Mikuls
BACKGROUND AND OBJECTIVE: Periodontitis results from interplay between genetic and environmental factors. Single nucleotide polymorphisms (SNPs) in the coding region of the toll-like receptor 4 gene (TLR4) may be associated with periodontitis, although previous studies have been inconclusive. Moreover, the interaction between environmental factors, such as cigarette smoking (a major risk factor for periodontitis), and Porphyromonas gingivalis (a major periodontal pathogen) with the TLR4 coding region Asp299Gly SNP (rs4986790; a SNP associated with lipopolysaccharide-mediated inflammatory responses in periodontitis), have been largely ignored in previous reports...
April 2016: Journal of Periodontal Research
Y Yu, C D Koehn, Y Yue, S Li, G M Thiele, M P Hearth-Holmes, T R Mikuls, J R O'Dell, L W Klassen, Z Zhang, K Su
Neutrophil extracellular traps (NETs) are web-like structures released by activated neutrophils. Recent studies suggest that NETs play an active role in driving autoimmunity and tissue injury in diseases including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). The purpose of this study was to investigate if celastrol, a triterpenoid compound, can inhibit NET formation induced by inflammatory stimuli associated with RA and SLE. We found that celastrol can completely inhibit neutrophil oxidative burst and NET formation induced by tumor necrosis factor alpha (TNFα) with an IC50 of 0...
2015: Current Molecular Medicine
Dorothée Diogo, Lisa Bastarache, Katherine P Liao, Robert R Graham, Robert S Fulton, Jeffrey D Greenberg, Steve Eyre, John Bowes, Jing Cui, Annette Lee, Dimitrios A Pappas, Joel M Kremer, Anne Barton, Marieke J H Coenen, Barbara Franke, Lambertus A Kiemeney, Xavier Mariette, Corrine Richard-Miceli, Helena Canhão, João E Fonseca, Niek de Vries, Paul P Tak, J Bart A Crusius, Michael T Nurmohamed, Fina Kurreeman, Ted R Mikuls, Yukinori Okada, Eli A Stahl, David E Larson, Tracie L Deluca, Michelle O'Laughlin, Catrina C Fronick, Lucinda L Fulton, Roman Kosoy, Michael Ransom, Tushar R Bhangale, Ward Ortmann, Andrew Cagan, Vivian Gainer, Elizabeth W Karlson, Isaac Kohane, Shawn N Murphy, Javier Martin, Alexandra Zhernakova, Lars Klareskog, Leonid Padyukov, Jane Worthington, Elaine R Mardis, Michael F Seldin, Peter K Gregersen, Timothy Behrens, Soumya Raychaudhuri, Joshua C Denny, Robert M Plenge
Despite the success of genome-wide association studies (GWAS) in detecting a large number of loci for complex phenotypes such as rheumatoid arthritis (RA) susceptibility, the lack of information on the causal genes leaves important challenges to interpret GWAS results in the context of the disease biology. Here, we genetically fine-map the RA risk locus at 19p13 to define causal variants, and explore the pleiotropic effects of these same variants in other complex traits. First, we combined Immunochip dense genotyping (n = 23,092 case/control samples), Exomechip genotyping (n = 18,409 case/control samples) and targeted exon-sequencing (n = 2,236 case/controls samples) to demonstrate that three protein-coding variants in TYK2 (tyrosine kinase 2) independently protect against RA: P1104A (rs34536443, OR = 0...
2015: PloS One
Nazia Rashid, Brian W Coburn, Yi-Lin Wu, T Craig Cheetham, Jeffrey R Curtis, Kenneth G Saag, Ted R Mikuls
OBJECTIVE: To identify modifiable patient and provider factors associated with allopurinol adherence and the achievement of a serum urate acid (SUA) goal in gout. METHODS: We identified a retrospective cohort of patients with gout, newly treated with allopurinol. All patient data came from administrative datasets at a large integrated health delivery system. Patients were ≥ 18 years old at time of initial allopurinol dispensing, and had 12 months or more of membership and drug eligibility prior to the index date...
March 2015: Journal of Rheumatology
Debbie T Lim, Amy C Cannella, Kaleb D Michaud, Ted R Mikuls
Although patients with rheumatoid arthritis (RA) are recognized to be disproportionately impacted by cardiovascular disease (CVD), effective approaches of primary and secondary CVD prevention have not been well defined in this population. Given their robust disease-modifying potential and effects on both pro-inflammatory and pro-atherogenic pathways, there has been substantial speculation that biologic treatments may serve as a means of providing highly effective RA disease control while simultaneously reducing CVD risk in this high risk group...
November 2014: Current Rheumatology Reports
Lisa A Davis, Emily Whitfield, Grant W Cannon, Roger K Wolff, Dannette S Johnson, Andreas M Reimold, Gail S Kerr, J Steuart Richards, Ted R Mikuls, Liron Caplan
OBJECTIVE: RA patients have an increased risk of cardiovascular (CV) disease, although the mechanisms are unclear. As RA and CV disease may be associated through lipid profiles, we examined whether single nucleotide polymorphisms (SNPs) associated with RA susceptibility were associated with low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglyceride (TG) levels in RA subjects. METHODS: Patients (n = 763) enrolled in the Veterans Affairs RA registry who were not on hydroxymethylglutaryl-CoA reductase inhibitor were genotyped for human leukocyte antigen shared epitope (HLA-DRB1-SE) and SNPs in the following genes: CTLA-4 (cytotoxic T-lymphocyte antigen 4), IL-10, PTPN22 (protein tyrosine phosphatase, non-receptor type 22), REL (c-Rel), STAT4 (signal transducer and activator of transcription protein), TNF- and TRAF1 (TNF receptor-associated factor 1)...
June 2014: Rheumatology
J R Curtis, S Yang, N M Patkar, L Chen, J A Singh, G W Cannon, T R Mikuls, E Delzell, K G Saag, M M Safford, S DuVall, K Alexander, P Napalkov, Kevin L Winthrop, M J Burton, A Kamauu, J W Baddley
OBJECTIVE: The comparative risk of infection associated with non-anti-tumor necrosis factor (anti-TNF) biologic agents is not well established. Our objective was to compare risk for hospitalized infections between anti-TNF and non-anti-TNF biologic agents in US veterans with rheumatoid arthritis (RA). METHODS: Using 1998-2011 data from the US Veterans Health Administration, we studied RA patients initiating rituximab, abatacept, or anti-TNF therapy. Exposure was based upon days supplied (injections) or usual dosing intervals (infusions)...
July 2014: Arthritis Care & Research
L A Davis, B Polk, A Mann, R K Wolff, G S Kerr, A M Reimold, G W Cannon, T R Mikuls, L Caplan
OBJECTIVES: Methotrexate (MTX) is the cornerstone medication in the treatment of rheumatoid arthritis (RA). We examined whether single nucleotide polymorphisms (SNPs) in enzymes of the folic acid pathway (folylpoly-gamma-glutamate synthetase [FPGS], gamma-glutamyl hydrolase [GGH], and methylenetetrahydrofolate reductase [MTHFR]) associate with significant adverse events (SigAE). METHODS: Patients (n=319) enrolled in the Veterans Affairs RA (VARA) registry taking MTX were genotyped for HLA-DRB1-SE and the following SNPs: FPGS (rs7033913, rs10760503, rs10106), GGH (12548933, rs7010484, rs4617146, rs719235, rs11988534), MTHFR (rs1801131, rs1801133)...
May 2014: Clinical and Experimental Rheumatology
Anand Dusad, Michael J Duryee, Anita T Shaw, Lynell W Klassen, Daniel R Anderson, Dong Wang, Ke Ren, Ellen M Gravallese, James R O'Dell, Ted R Mikuls, Geoffrey M Thiele
Joint damage in rheumatoid arthritis (RA) is characterized by cartilage and bone loss resulting in pain, deformity, and loss of joint function. Anti-citrullinated protein antibody (ACPA) has been implicated in RA pathogenesis and predicts radiographical joint damage and clinical severity. Therefore, the purpose of this study was to assess bone loss by micro-CT, histological joint damage, and ACPA levels using a mouse model of RA. Arthritis was induced by immunizing DBA/1 mice with autologous citrullinated type II mouse collagen (CIT-CII) weekly for 4 weeks...
January 2014: Immunologic Research
Stella Aslibekyan, Jin Sha, David T Redden, Larry W Moreland, James R O'Dell, Jeffrey R Curtis, Ted R Mikuls, Richard J Reynolds, Maria I Danila, S Louis Bridges
No abstract text is available yet for this article.
April 2014: Annals of the Rheumatic Diseases
Daniel R Anderson, Joseph T Poterucha, Ted R Mikuls, Michael J Duryee, Robert P Garvin, Lynell W Klassen, Scott W Shurmur, Geoffrey M Thiele
Biomarkers such as interleukin-6 (IL-6), soluble interleukin-6 receptor (sIL-6R), and high sensitive C-reactive protein (hsCRP) have been reported to be elevated in acute myocardial infarction (AMI). The aim of this study is to determine the relationship between these markers during AMI, as well as their relationship to clinical parameters in an effort to discern their predictive potential in cardiac events. Serum was collected from 73 patients with; AMI, stable coronary artery disease (CAD), and controls during cardiac catheterization...
June 2013: Cytokine
S Aslibekyan, E E Brown, R J Reynolds, D T Redden, S Morgan, J E Baggott, J Sha, L W Moreland, J R O'Dell, J R Curtis, T R Mikuls, S L Bridges, D K Arnett
Methotrexate (MTX) has emerged as first-line therapy for early moderate-to-severe rheumatoid arthritis (RA), but individual variation in treatment response remains unexplained. We tested the associations between 863 known pharmacogenetic variants and MTX response in 471 Treatment of Early Aggressive Rheumatoid Arthritis Trial participants with early RA. Efficacy and toxicity were modeled using multiple regression, adjusted for demographic and clinical covariates. Penalized regression models were used to test joint associations of markers and/or covariates with the outcomes...
February 2014: Pharmacogenomics Journal
Geoffrey M Thiele, Michael J Duryee, Anand Dusad, Carlos D Hunter, Jordan P Lacy, Daniel R Anderson, Dong Wang, James R O'Dell, Ted R Mikuls, Lynell W Klassen
INTRODUCTION: Citrullinated self-proteins are thought to be involved in the onset/progression of rheumatoid arthritis (RA). Numerous studies have been performed to look for the self-antigen that becomes citrullinated and induces RA. Importantly, these studies have been performed using citrullinated self-antigens injected into an animal model in the presence of a strong adjuvant in order to derive the response. However, to date no studies have been performed to determine if these phenotypes can be induced in the absence of an adjuvant...
August 2012: International Immunopharmacology
Ted R Mikuls, Brian T Fay, Kaleb Michaud, Harlan Sayles, Geoffrey M Thiele, Liron Caplan, Dannette Johnson, John S Richards, Gail S Kerr, Grant W Cannon, Andreas Reimold
OBJECTIVES: To examine the all-cause mortality rate and factors associated with mortality in US veteran men with RA. METHODS: Men with RA were enrolled and followed until death or censoring. Vital status was ascertained through systematic record review and standardized mortality ratios (SMRs) were calculated using US life tables for men. Multivariate Cox proportional hazards regression was used to examine the independent associations of patient factors including socio-demographics, comorbidity, measures of RA disease activity/severity and medication use with mortality...
January 2011: Rheumatology
Jie Zhang, David T Redden, Gerald McGwin, Leigh F Callahan, Edwin A Smith, Graciela S Alarcón, Larry W Moreland, Désirée M van der Heijde, Elizabeth E Brown, Donna K Arnett, Ted R Mikuls, S Louis Bridges
OBJECTIVE: To examine the association between baseline bone mineral density (BMD) and radiographic damage at 3 years of disease duration in a longitudinal cohort of African Americans with recent-onset rheumatoid arthritis (RA). METHODS: African American RA patients with a disease duration of <2 years (n = 141) were included in the study. All patients underwent baseline BMD measurements (femoral neck and/or lumbar spine) using dual x-ray absorptiometry. T scores were calculated using normative data from the general population of African Americans...
August 2010: Arthritis and Rheumatism
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