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T R Mikuls

S Timilsina, K Brittan, J R O'Dell, M Brophy, A Davis-Karim, A M Henrie, T Neogi, J Newcomb, P M Palevsky, M H Pillinger, D Pittman, T H Taylor, H Wu, T R Mikuls
BACKGROUND: Gout patients do not routinely achieve optimal outcomes related in part to suboptimal administration of urate lowering therapy (ULT) including first-line xanthine oxidase inhibitors allopurinol or febuxostat. Studies leading to the approval of febuxostat compared this agent to allopurinol in inappropriately low, fixed doses. We will compare allopurinol with febuxostat in gout using appropriately titrated doses of both agents and a "treat-to-target" strategy congruent with specialty guidelines...
May 2018: Contemporary Clinical Trials
Patrick R Wood, Evan Manning, Joshua F Baker, Bryant England, Lisa Davis, Grant W Cannon, Ted R Mikuls, Liron Caplan
AIM: To determine the scope of acute hypoglycemic effects for certain anti-rheumatic medications in a large retrospective observational study. METHODS: Patients enrolled in the Veterans Affairs Rheumatoid Arthritis (VARA) registry were selected who, during follow-up, initiated treatment with tumor necrosis factor inhibitors (TNFi's, including etanercept, adalimumab, infliximab, golimumab, or certolizumab), prednisone, or conventional disease-modifying anti-rheumatic drugs (DMARDs), and for whom proximate random blood glucose (RBG) measurements were available within a window 2-wk prior to, and 6 mo following, medication initiation...
February 15, 2018: World Journal of Diabetes
Michael J Duryee, Benjamin M Wiese, Jordan R Bowman, Jared D Vanlandingham, Lynell W Klassen, Geoffrey E Thiele, Carlos D Hunter, Daniel R Anderson, Ted R Mikuls, Geoffrey M Thiele
Precision-cut liver slices (PCLSs) provide a novel model for studies of alcoholic liver disease (ALD). This is relevant, as in vivo ethanol exposure does not appear to generate significant liver damage in ethanol-fed mice, except in the National Institute on Alcohol Abuse and Alcoholism binge model of ALD. Previous studies have shown that the two metabolites of ethanol consumption, malondialdhyde (MDA) and acetaldehyde (AA), combine to form MDA-AA (MAA) adducts, which have been correlated with the development and progression of ALD...
March 1, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
Jill A Poole, Ted R Mikuls, Michael J Duryee, Kristi J Warren, Todd A Wyatt, Amy J Nelson, Debra J Romberger, William W West, Geoffrey M Thiele
BACKGROUND: Agriculture organic dust exposures induce lung disease with lymphoid aggregates comprised of both T and B cells. The precise role of B cells in mediating lung inflammation is unknown, yet might be relevant given the emerging role of B cells in obstructive pulmonary disease and associated autoimmunity. METHODS: Using an established animal model, C57BL/6 wild-type (WT) and B-cell receptor (BCR) knock-out (KO) mice were repetitively treated with intranasal inhalation of swine confinement organic dust extract (ODE) daily for 3 weeks and lavage fluid, lung tissues, and serum were collected...
December 22, 2017: Respiratory Research
Bryant R England, Ted R Mikuls, Jeffrey R Curtis
No abstract text is available yet for this article.
February 2018: Arthritis & Rheumatology
R Bright, G M Thiele, J Manavis, T R Mikuls, J B Payne, P M Bartold
BACKGROUND AND OBJECTIVE: Postranslational modification of proteins can lead to the production of autoantibodies and loss of immune tolerance. This process has been hypothesised to be a critical factor in the pathogenesis of rheumatoid arthritis. The objective of this study was to demonstrate that inflamed human gingival tissue provides an extrasynovial source of malondialdehyde-acetaldehyde adducts, citrullinated and carbamylated proteins all of which are considered to be linked to the development of rheumatoid arthritis...
February 2018: Journal of Periodontal Research
Ted R Mikuls, Michael J Duryee, Rafid Rahman, Daniel R Anderson, Harlan R Sayles, Andrew Hollins, Kaleb Michaud, Frederick Wolfe, Geoffrey E Thiele, Jeremy Sokolove, William H Robinson, Nithya Lingampalli, Anthony P Nicholas, Geoffrey A Talmon, Kaihong Su, Matthew C Zimmerman, Lynell W Klassen, Geoffrey M Thiele
Objective: To characterize the expression of malondialdehdye-acetaldehyde (MAA) adducts and anti-MAA antibody in articular tissues and serum of patients with RA. Methods: Paired sera and SF were examined from 29 RA and 13 OA patients. Anti-MAA antibody, RF, ACPA and total immunoglobulin were quantified. SF-serum measures were compared within and between disease groups. The presence and co-localization of MAA, citrulline and select leukocyte antigens in RA and OA synovial tissues were examined using immunohistochemistry...
October 1, 2017: Rheumatology
Michael D George, Jon T Giles, Patricia P Katz, Bryant R England, Ted R Mikuls, Kaleb Michaud, Alexis R Ogdie-Beatty, Said Ibrahim, Grant W Cannon, Liron Caplan, Brian C Sauer, Joshua F Baker
OBJECTIVE: The C-reactive protein (CRP) level and erythrocyte sedimentation rate (ESR) are important disease activity biomarkers in rheumatoid arthritis (RA). This study aimed to determine to what extent obesity biases these biomarkers. METHODS: Body mass index (BMI) associations with CRP level and ESR were assessed in 2 RA cohorts: the cross-sectional Body Composition (BC) cohort (n = 451), including whole-body dual x-ray absorptiometry measures of fat mass index; and the longitudinal Veterans Affairs Rheumatoid Arthritis (VARA) registry (n = 1,652), using multivariable models stratified by sex...
December 2017: Arthritis Care & Research
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...
February 9, 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
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