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Gout: HELP
Articles from Georgia
Based on 17 articles published since 2008
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These are the 17 published articles about Gout that originated from Georgia during 2008-2019.
 
+ Citations + Abstracts
1 Review Treatment of acute gout: a systematic review. 2014

Khanna, Puja P / Gladue, Heather S / Singh, Manjit K / FitzGerald, John D / Bae, Sangmee / Prakash, Shraddha / Kaldas, Marian / Gogia, Maneesh / Berrocal, Veronica / Townsend, Whitney / Terkeltaub, Robert / Khanna, Dinesh. ·Division of Rheumatology, University of Michigan, 300 North Ingalls, 7D13, Ann Arbor, MI 48109-5422. Electronic address: pkhanna@umich.edu. · Emory University, Atlanta, GA. · Rochester General Health System, Rochester, NY. · David Geffen School of Medicine, UCLA, Los Angeles, CA. · Division of Rheumatology, University of Michigan, 300 North Ingalls, 7D13, Ann Arbor, MI 48109-5422. · Division of Rheumatology, University of Michigan, 300 North Ingalls, 7D13, Ann Arbor, MI 48109-5422; Taubman Health Science Library, University of Michigan, 300 North Ingalls, 7D13, Ann Arbor, MI 48109-5422. · VAMC/UCSD, La Jolla, CA. ·Semin Arthritis Rheum · Pubmed #24650777.

ABSTRACT: OBJECTIVE: Acute gout is traditionally treated with NSAIDs, corticosteroids, and colchicine; however, subjects have multiple comorbidities that limit the use of some conventional therapies. We systematically reviewed the published data on the pharmacologic and non-pharmacologic agents used for the treatment of acute gouty arthritis. METHODS: A systematic search was performed using PubMed and Cochrane database through May 2013. We included only randomized controlled trials (RCTs) that included NSAIDs, corticosteroids, colchicine, adrenocorticotropic hormone (ACTH), interleukin-1 (IL-1) inhibitors, topical ice, or herbal supplements. RESULTS: Thirty articles were selected for systematic review. The results show that NSAIDs and COX-2 inhibitors are effective agents for the treatment of acute gout attacks. Systemic corticosteroids have similar efficacy to therapeutic doses of NSAIDs, with studies supporting oral and intramuscular use. ACTH is suggested to be efficacious in acute gout. Oral colchicine demonstrated to be effective, with low-dose colchicine demonstrating a comparable tolerability profile as placebo and a significantly lower side effect profile to high-dose colchicine. The IL-1β inhibitory antibody, canakinumab, was effective for the treatment of acute attacks in subjects refractory to and in those with contraindications to NSAIDs and/or colchicine. However, rilonacept was demonstrated to be not as effective, and there are no RCTs for the use of anakinra. CONCLUSION: NSAIDs, COX-2 selective inhibitors, corticosteroids, colchicine, ACTH, and canakinumab have evidence to suggest efficacy in treatment of acute gout.

2 Review Safety and efficacy of allopurinol in chronic kidney disease. 2013

Thurston, Maria Miller / Phillips, Beth Bryles / Bourg, Catherine A. ·Mercer University College of Pharmacy, Atlanta, GA, USA. ·Ann Pharmacother · Pubmed #24259601.

ABSTRACT: OBJECTIVE: To review the evidence surrounding the use of allopurinol in chronic kidney disease (CKD) and discuss safety and efficacy considerations of such use. DATA SOURCES: A literature search was conducted through MEDLINE (1950-July 2013), PubMed (1965-July 2013), and International Pharmaceutical Abstracts (1970-July 2013) using the search terms allopurinol and kidney or renal. In addition, reference citations from publications identified were reviewed. STUDY SELECTION AND DATA EXTRACTION: All articles in English identified from the data sources were evaluated for inclusion. DATA SYNTHESIS: Gout management with allopurinol in patients with CKD can be challenging because of the risk of adverse events and uncertain efficacy. Not all gout treatment guidelines provide recommendations for allopurinol use specifically in patients with CKD. Literature regarding the safety and efficacy of dosing allopurinol in CKD has shown inconsistent results and is based primarily on retrospective, case cohort or observational data. Some trials have demonstrated an increased risk of allopurinol-induced adverse reactions in patients with CKD, whereas others have not confirmed renal insufficiency as a risk factor. More CKD patients achieved a target uric acid level in studies where the allopurinol dose was titrated to effect as compared with those studies in which patients were given renally adjusted or untitrated allopurinol doses. CONCLUSIONS: Studies evaluating allopurinol use in patients with CKD have reported inconsistent findings relative to safety and efficacy. Providers should be aware of the potential risk of allopurinol hypersensitivity syndrome as well as the need for reducing the initiation dose and gradual titration of allopurinol to safely achieve a target serum urate level in this population.

3 Review Pegloticase: a novel agent for treatment-refractory gout. 2012

Shannon, Jennifer A / Cole, Sabrina W. ·Philadelphia College of Osteopathic Medicine, School of Pharmacy, Suwanee, GA, USA. jennifersh@pcom.edu ·Ann Pharmacother · Pubmed #22395256.

ABSTRACT: OBJECTIVE: To evaluate efficacy and safety of pegloticase, approved by the Food and Drug Administration in September 2010 for treatment of patients with chronic treatment-refractory gout. DATA SOURCES: Literature searches were conducted using PubMed (1948-January 2012), TOXLINE, International Pharmaceutical Abstracts (1970-January 2012), and Google Scholar using the terms pegloticase, puricase, PEG-uricase, gout, uricase, and Krystexxa. Results were limited to English-language publications. References from selected articles were reviewed to identify additional citations. STUDY SELECTION AND DATA EXTRACTION: Studies evaluating the pharmacology, pharmacokinetics, safety, and efficacy of pegloticase for the treatment of chronic treatment-refractory gout were included. DATA SYNTHESIS: Pegloticase represents a novel intravenous treatment option for patients who have chronic gout refractory to other available treatments. Pegloticase is a recombinant uricase and achieves therapeutic effects by catalyzing oxidation of uric acid to allantoin, resulting in decreased uric acid concentrations. Results of published trials demonstrate the ability of pegloticase to maintain uric acid concentrations below 7 mg/dL in patients with chronic gout. Data supporting reduction of gout flares are limited. Pegloticase is well tolerated but associated with gout flares and infusion reactions. Other adverse events include nausea, dizziness, and back pain. During Phase 3 trials, 2 patients in the pegloticase biweekly group and 1 in the monthly group experienced heart failure exacerbation; another patient in the monthly group experienced a nonfatal myocardial infarction. Providers should exercise caution before administering pegloticase to patients with cardiovascular disease. The cost burden and safety profile may limit its use in practice, in addition to limited data available to support decreases in patient-centered outcomes (eg, gouty attacks). CONCLUSIONS: Pegloticase is an effective option for patients with symptomatic gout for whom current uric acid-lowering therapies are ineffective or contraindicated.

4 Review Febuxostat for treatment of chronic gout. 2011

Gray, Charnelda L / Walters-Smith, Nafesa E. ·Clinical Pharmacy, Kaiser Permanente of Georgia, Atlanta 30305, USA. charnelda.l.gray@kp.org ·Am J Health Syst Pharm · Pubmed #21330679.

ABSTRACT: PURPOSE: The pharmacology, pharmacokinetics, clinical efficacy, and safety of febuxostat are reviewed. SUMMARY: Febuxostat is a novel non-purine selective inhibitor of xanthine oxidase for the management of hyperuricemia in patients with gout. The ability of febuxostat to decrease serum uric acid production through selective inhibition of enzyme xanthine oxidase has been established in short-term Phase II and III clinical trials and long-term open-label studies. Clinical studies have revealed that febuxostat lowers serum uric acid levels more potently than allopurinol while having minimal effects on other enzymes associated with purine and pyrimide metabolism. The most frequent adverse events reported in clinical trials with febuxostat were liver function abnormalities, nausea, arthralgias, and rash. More cardiovascular thromboembolic events occurred in randomized trials in patients treated with febuxostat. Although a causal relationship has not been established, patients should be monitored for signs and symptoms of myocardial infarction and stroke. Febuxostat is available as 40- and 80-mg tablets. The recommended starting dosage is 40 mg orally once daily. If serum uric acid concentrations are not less than 6 mg/dL after two weeks, the dosage can be increased to 80 mg orally once daily. Dosage adjustments are not needed in elderly patients or patients with mild or moderate renal or hepatic impairment. CONCLUSION: Febuxostat is efficacious as a second-line therapy in lowering serum uric acid levels in patients with gout. Febuxostat may be an alternative for patients with gout who are unable to take allopurinol due to hypersensitivity, intolerance, or lack of efficacy.

5 Article NLRP3 inflammasome inhibitor OLT1177 suppresses joint inflammation in murine models of acute arthritis. 2018

Marchetti, Carlo / Swartzwelter, Benjamin / Koenders, Marije I / Azam, Tania / Tengesdal, Isak W / Powers, Nick / de Graaf, Dennis M / Dinarello, Charles A / Joosten, Leo A B. ·Department of Medicine, University of Colorado Denver, Aurora, CO, USA. · Department of Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands. · Department of Internal Medicine and Radboud Institute of Molecular Life Sciences (RIMLS), Radboud University Medical Center, Geert Grooteplein Zuid 8, 6525, GA, Nijmegen, The Netherlands. · Department of Medicine, University of Colorado Denver, Aurora, CO, USA. leo.joosten@radboudumc.nl. · Department of Internal Medicine and Radboud Institute of Molecular Life Sciences (RIMLS), Radboud University Medical Center, Geert Grooteplein Zuid 8, 6525, GA, Nijmegen, The Netherlands. leo.joosten@radboudumc.nl. ·Arthritis Res Ther · Pubmed #30075804.

ABSTRACT: BACKGROUND: Activation of the NLRP3 inflammasome in gout amplifies the inflammatory response and mediates further damage. In the current study, we assessed the therapeutic effect of OLT1177, an orally active NLRP3 inflammasome inhibitor that is safe in humans, in murine acute arthritis models. METHODS: Zymosan or monosodium urate (MSU) crystals were injected intra-articularly (i.a.) into mouse knee joints to induce reactive or gouty arthritis. Joint swelling, articular cell infiltration, and synovial cytokines were evaluated 25 hours and 4 hours following zymosan or MSU challenge, respectively. OLT1177 was administrated intraperitoneally by oral gavage or in the food by an OLT1177-enriched diet. RESULTS: OLT1177 reduced zymosan-induced joint swelling (p < 0.001), cell influx (p < 0.01), and synovial levels of interleukin (IL)-1β, IL-6, and chemokine (C-X-C motif) ligand 1 (CXCL1) (p < 0.05), respectively, when compared with vehicle-treated mice. Plasma OLT1177 levels correlated (p < 0.001) dose-dependently with reduction in joint inflammation. Treatment of mice with OLT1177 limited MSU crystal articular inflammation (p > 0.0001), which was associated with decreased synovial IL-1β, IL-6, myeloperoxidase, and CXCL1 levels (p < 0.01) compared with vehicle-treated mice. When administrated orally 1 hour after MSU challenge, OLT1177 reduced joint inflammation, processing of IL-1β, and synovial phosphorylated c-Jun N-terminal kinase compared with the vehicle group. Mice were fed an OLT1177-enriched diet for 3 weeks and then challenged i.a. with MSU crystals. Joint swelling, synovial IL-1β, and expression of Nlrp3 and Il1b were significantly reduced in synovial tissues in mice fed an OLT1177-enriched diet when compared with the standard diet group. CONCLUSIONS: Oral OLT1177 is highly effective in ameliorating reactive as well as gouty arthritis.

6 Article P2Y6 Receptor Antagonist MRS2578 Inhibits Neutrophil Activation and Aggregated Neutrophil Extracellular Trap Formation Induced by Gout-Associated Monosodium Urate Crystals. 2017

Sil, Payel / Hayes, Craig P / Reaves, Barbara J / Breen, Patrick / Quinn, Shannon / Sokolove, Jeremy / Rada, Balázs. ·Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA 30602. · Institute of Bioinformatics, University of Georgia, Athens, GA 30602. · Department of Computer Science, Franklin College of Arts and Sciences, University of Georgia, Athens, 30602 GA. · Stanford University School of Medicine, Stanford, CA 94305; and. · Internal Medicine and Rheumatology, VA Palo Alto Health Care System, Palo Alto, CA 94034. · Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA 30602; radab@uga.edu. ·J Immunol · Pubmed #27903742.

ABSTRACT: Human neutrophils (polymorphonuclear leukocytes [PMNs]) generate inflammatory responses within the joints of gout patients upon encountering monosodium urate (MSU) crystals. Neutrophil extracellular traps (NETs) are found abundantly in the synovial fluid of gout patients. The detailed mechanism of MSU crystal-induced NET formation remains unknown. Our goal was to shed light on possible roles of purinergic signaling and neutrophil migration in mediating NET formation induced by MSU crystals. Interaction of human neutrophils with MSU crystals was evaluated by high-throughput live imaging using confocal microscopy. We quantitated NET levels in gout synovial fluid supernatants and detected enzymatically active neutrophil primary granule enzymes, myeloperoxidase, and human neutrophil elastase. Suramin and PPADS, general P2Y receptor blockers, and MRS2578, an inhibitor of the purinergic P2Y6 receptor, blocked NET formation triggered by MSU crystals. AR-C25118925XX (P2Y2 antagonist) did not inhibit MSU crystal-stimulated NET release. Live imaging of PMNs showed that MRS2578 represses neutrophil migration and blocked characteristic formation of MSU crystal-NET aggregates called aggregated NETs. Interestingly, the store-operated calcium entry channel inhibitor (SK&F96365) also reduced MSU crystal-induced NET release. Our results indicate that the P2Y6/store-operated calcium entry/IL-8 axis is involved in MSU crystal-induced aggregated NET formation, but MRS2578 could have additional effects affecting PMN migration. The work presented in the present study could lead to a better understanding of gouty joint inflammation and help improve the treatment and care of gout patients.

7 Article A pilot study of CXCL8 levels in crystal proven gout patients during allopurinol treatment and their association with cardiovascular disease. 2017

Kienhorst, Laura / Janssens, Hein / Radstake, Timothy / van Riel, Piet / Jacobs, Johannes / van Koolwijk, Elly / van Lochem, Ellen / Janssen, Matthijs. ·Department of Rheumatology, Rijnstate Hospital, PO Box 9555, 6800 Arnhem, TA, The Netherlands. Electronic address: l.b.e.kienhorst@umcutrecht.nl. · Department of Primary and Community Care, Radboud University Medical Center, PO Box 9101, 6500 Nijmegen, HB, The Netherlands; Department of Clinical Research, Rijnstate Hospital, PO Box 9555, 6800 Arnhem, TA, The Netherlands. · Department of Rheumatology and Clinical Immunology, Laboratory of Translational Immunology, PO Box 85500, 3508 Utrecht, GA, The Netherlands; Department of Immunology, University Medical Center Utrecht, PO Box 85500, 3508 Utrecht, GA, The Netherlands. · Scientific Institute for Quality of Healthcare, Radboud University Medical Center, PO Box 9101, 6500 Nijmegen, HB, The Netherlands. · Department of Rheumatology and Clinical Immunology, Laboratory of Translational Immunology, PO Box 85500, 3508 Utrecht, GA, The Netherlands. · Department of Medical Microbiology and Immunology, Rijnstate Hospital, PO Box 9555, 6800 Arnhem, TA, The Netherlands. · Department of Clinical Research, Rijnstate Hospital, PO Box 9555, 6800 Arnhem, TA, The Netherlands; Department of Medical Microbiology and Immunology, Rijnstate Hospital, PO Box 9555, 6800 Arnhem, TA, The Netherlands. · Department of Rheumatology, Rijnstate Hospital, PO Box 9555, 6800 Arnhem, TA, The Netherlands. ·Joint Bone Spine · Pubmed #27894951.

ABSTRACT: OBJECTIVES: Gout is associated with cardiovascular diseases, and systemic inflammation has a role in this. CXCL8 (interleukin-8) levels were increased in synovial fluid of gout patients, and in serum in gout patients irrespective of their disease activity. We hypothesized that the well-known cardiovascular protective effects of allopurinol could be related to effects of this drug on CXCL8 levels. METHODS: Patients with a crystal proven gout diagnosis, who newly started allopurinol treatment, were included in this prospective cohort study. After evaluation at baseline for cardiovascular diseases, tophi, uric acid, CRP and CXCL8 serum levels, patients were followed for changes in uric acid and CXCL8 levels. A subgroup analysis was performed in 10 patients with the longest follow-up period and at least 4 assessments of serum uric acid and CXCL8. RESULTS: Sixty patients were included, and patients known with cardiovascular diseases at baseline had significantly higher CXCL8 and uric acid levels (P<0.01). In the whole group, median CXCL8 levels had not decreased after a median (IQR) follow-up of 27 (12-44) weeks (P=0.66). In the subgroup analysis in 9 out of 10 patients, CXCL8 levels showed a slight decrease, sometimes after an initial increase after a median (IQR) follow-up of 51 (45-60) weeks. CONCLUSIONS: This pilot study indicates that higher CXCL8 levels were associated cardiovascular diseases in gout patients. Short-term use of allopurinol does not decrease CXCL8 levels in gout patients, but longer use possibly does. Further studies are warranted to establish the potential mechanisms of treatment and effects on CXCL8 levels.

8 Article Macrophage-derived IL-1β enhances monosodium urate crystal-triggered NET formation. 2017

Sil, Payel / Wicklum, Haley / Surell, Chandler / Rada, Balázs. ·Department of Infectious Diseases, College of Veterinary Medicine, The University of Georgia, 501 D.W. Brooks Drive, Athens, GA, 30602, USA. · Department of Infectious Diseases, College of Veterinary Medicine, The University of Georgia, 501 D.W. Brooks Drive, Athens, GA, 30602, USA. radab@uga.edu. ·Inflamm Res · Pubmed #27853847.

ABSTRACT: OBJECTIVE AND DESIGN: Arthritic gout is caused by joint inflammation triggered by the damaging effects of monosodium uric acid (MSU) crystal accumulation in the synovial space. Neutrophils play a major role in mediating joint inflammation in gout. Along with neutrophils, other immune cells, such as macrophages, are present in inflamed joints and contribute to gout pathogenesis. Neutrophils form neutrophil extracellular traps (NETs) in response to MSU crystals. In the presence of MSU crystals, macrophages release IL-1β, a cytokine crucial to initiate gout pathogenesis and neutrophil recruitment. Our research investigated interactions between human macrophages and neutrophils in an in vitro model system and asked how macrophages affect NET formation stimulated by MSU crystals. MATERIALS OR SUBJECTS: Human neutrophils and PBMCs were isolated from peripheral blood of healthy volunteers. PBMCs were differentiated into macrophages in vitro using human M-CSF. TREATMENT: Human neutrophils were pretreated with macrophage-conditioned media, neutrophil-conditioned media, recombinant human IL-1β or anakinra prior to stimulation by MSU crystals. METHOD: Interaction of neutrophils with MSU crystals was evaluated by live imaging using confocal microscopy. The presence of myeloperoxidase (MPO) and neutrophil elastase (NE) was measured by ELISA. NET formation was quantitated by Sytox Orange-based extracellular DNA release assay and NE-DNA ELISA. AggNET formation was assessed by macroscopic evaluation. RESULTS: We found that crystal- and cell-free supernatants of macrophages stimulated with MSU crystals promote MSU crystal-stimulated NET formation in human neutrophils. This observation was confirmed by additional assays measuring the release of MPO, NE, and the enzymatic activity of NE. MSU crystal-induced NET formation remained unchanged when neutrophil supernatants were tested. IL-1β is a crucial cytokine orchestrating the onset of inflammation in gout and is known to be released in large amounts from macrophages following MSU crystal stimulation. We found that recombinant IL-1β strongly promoted MSU crystal-induced NET formation in human neutrophils. Interestingly, IL-1β alone did not induce any NET release. We also found that clinical grade anakinra, an IL-1 receptor blocker, strongly reduced the NETosis-enhancing effect of macrophage supernatants indicating that IL-1β is mainly responsible for this effect. CONCLUSIONS: Macrophage-derived IL-1β enhances MSU crystal-induced NET release in neutrophils. We identified a new mechanism by which macrophages and IL-1β affect neutrophil functions, and could contribute to the inflammatory conditions present in gout. Our results also revealed a new anti-inflammatory mechanism of anakinra.

9 Article Clinical Inquiry: How do clinical prediction rules compare with joint fluid analysis in diagnosing gout? 2016

Westerfield, Katie L / Mounsey, Anne / Nashelsky, Joan. ·Martin Army Community Hospital Family Medicine Residency Program, Fort Benning, GA, USA. · Department of Family Medicine, University of North Carolina, Chapel Hill, USA. · University of Iowa, Iowa City, IA, USA. ·J Fam Pract · Pubmed #28087872.

ABSTRACT: Clinical prediction rules effectively diagnose gout without joint fluid analysis. The American College of Rheumatology clinical prediction rules, the most accurate rules developed for research purposes, have a sensitivity of 92%, specificity of 89%, positive likelihood ratio of 8.36, and negative likelihood ratio of 0.09.

10 Article Coevolution of URAT1 and Uricase during Primate Evolution: Implications for Serum Urate Homeostasis and Gout. 2016

Tan, Philip K / Farrar, Jennifer E / Gaucher, Eric A / Miner, Jeffrey N. ·Biology Department, Ardea Biosciences, Inc, San Diego, CA ptphiltan@gmail.com eric.gaucher@biology.gatech.edu. · School of Biology, Georgia Institute of Technology. · School of Biology, Georgia Institute of Technology General Genomics, Atlanta, GA ptphiltan@gmail.com eric.gaucher@biology.gatech.edu. · Biology Department, Ardea Biosciences, Inc, San Diego, CA. ·Mol Biol Evol · Pubmed #27352852.

ABSTRACT: Uric acid is the highly insoluble end-product of purine metabolism in humans. Serum levels exceeding the solubility threshold can trigger formation of urate crystals resulting in gouty arthritis. Uric acid is primarily excreted through the kidneys with 90% reabsorbed back into the bloodstream through the uric acid transporter URAT1. This reabsorption process is essential for the high serum uric acid levels found in humans. We discovered that URAT1 proteins from humans and baboons have higher affinity for uric acid compared with transporters from rats and mice. This difference in transport kinetics of URAT1 orthologs, along with inability of modern apes to oxidize uric acid due to loss of the uricase enzyme, prompted us to ask whether these events occurred concomitantly during primate evolution. Ancestral URAT1 sequences were computationally inferred and ancient transporters were resurrected and assayed, revealing that affinity for uric acid was increased during the evolution of primates. This molecular fine-tuning occurred between the origins of simians and their diversification into New- and Old-World monkey and ape lineages. Remarkably, it was driven in large-part by only a few amino acid replacements within the transporter. This alteration in primate URAT1 coincided with changes in uricase that greatly diminished the enzymatic activity and took place 27-77 Ma. These results suggest that the modifications to URAT1 transporters were potentially adaptive and that maintaining more constant, high levels of serum uric acid may have provided an advantage to our primate ancestors.

11 Article Multiplicative interaction of functional inflammasome genetic variants in determining the risk of gout. 2015

McKinney, Cushla / Stamp, Lisa K / Dalbeth, Nicola / Topless, Ruth K / Day, Richard O / Kannangara, Diluk Rw / Williams, Kenneth M / Janssen, Matthijs / Jansen, Timothy L / Joosten, Leo A / Radstake, Timothy R / Riches, Philip L / Tausche, Anne-Kathrin / Lioté, Frederic / So, Alexander / Merriman, Tony R. ·Department of Biochemistry, University of Otago, Box 56, Dunedin, 9054, New Zealand. cushla.mckinney@otago.ac.nz. · Department of Medicine, University of Otago, Christchurch, PO Box 4345, Christchurch, New Zealand. lisa.stamp@cdhb.govt.nz. · Department of Medicine, University of Auckland, Auckland, New Zealand. n.dalbeth@auckland.ac.nz. · Department of Biochemistry, University of Otago, Box 56, Dunedin, 9054, New Zealand. ruth.topless@otago.ac.nz. · School of Medical Sciences, University of New South Wales, Sydney, Australia. r.day@unsw.edu.au. · Department of Clinical Pharmacology & Toxicology, St Vincent's Hospital, Sydney, Australia. r.day@unsw.edu.au. · School of Medical Sciences, University of New South Wales, Sydney, Australia. r.kannangara@unsw.edu.au. · Department of Clinical Pharmacology & Toxicology, St Vincent's Hospital, Sydney, Australia. r.kannangara@unsw.edu.au. · School of Medical Sciences, University of New South Wales, Sydney, Australia. ken.williams@unsw.edu.au. · Department of Clinical Pharmacology & Toxicology, St Vincent's Hospital, Sydney, Australia. ken.williams@unsw.edu.au. · Department of Rheumatology, Rijnstate Hospital, Arnhem, The Netherlands. matthijs.janssen@rijnstate.nl. · Department of IQ HealthCare, VieCuri Medical Centre, Venlo, The Netherlands. tim.jansen@radboudumc.nl. · Scientific Institute of Quality in HealthCare, Radboud University Medical Centre, Nijmegen, The Netherlands. tim.jansen@radboudumc.nl. · Department of Internal Medicine and Radboud Institute of Molecular Life Science, Radboud University Medical Center, Nijmegen, The Netherlands. l.joosten@aig.umcn.nl. · Department of Rheumatology and Clinical Immunology, Laboratory of Translational Immunology, University Medical Centre Utrecht, PO Box 85500, 3508, GA, Utrecht, The Netherlands. tradstake73@googlemail.com. · Department of Immunology, University Medical Centre Utrecht, PO Box 85500, 3508, GA, Utrecht, The Netherlands. tradstake73@googlemail.com. · Rheumatic Diseases Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK. priches@staffmail.ed.ac.uk. · Department of Rheumatology, University Clinic Carl-Gustav-Carus", Dresden, Germany. anne-kathrin.tausche@uniklinikum-dresden.de. · INSERM, UMR-S 1132, Hospital Lariboisière, F-75010, Paris, France. frederic.liote@lrb.aphp.fr. · University Paris Diderot (UFR de Médecine), Sorbonne Paris Cité, F-75205, Paris, France. frederic.liote@lrb.aphp.fr. · DAL, Service of Rheumatology, Laboratory of Rheumatology, University of Lausanne, CHUV, Nestlé 05-5029, 1011, Lausanne, Switzerland. alexanderkai-lik.so@chuv.ch. · Department of Biochemistry, University of Otago, Box 56, Dunedin, 9054, New Zealand. tony.merriman@otago.ac.nz. ·Arthritis Res Ther · Pubmed #26462562.

ABSTRACT: INTRODUCTION: The acute gout flare results from a localised self-limiting innate immune response to monosodium urate (MSU) crystals deposited in joints in hyperuricaemic individuals. Activation of the caspase recruitment domain-containing protein 8 (CARD8) NOD-like receptor pyrin-containing 3 (NLRP3) inflammasome by MSU crystals and production of mature interleukin-1β (IL-1β) is central to acute gouty arthritis. However very little is known about genetic control of the innate immune response involved in acute gouty arthritis. Therefore our aim was to test functional single nucleotide polymorphism (SNP) variants in the toll-like receptor (TLR)-inflammasome-IL-1β axis for association with gout. METHODS: 1,494 gout cases of European and 863 gout cases of New Zealand (NZ) Polynesian (Māori and Pacific Island) ancestry were included. Gout was diagnosed by the 1977 ARA gout classification criteria. There were 1,030 Polynesian controls and 10,942 European controls including from the publicly-available Atherosclerosis Risk in Communities (ARIC) and Framingham Heart (FHS) studies. The ten SNPs were either genotyped by Sequenom MassArray or by Affymetrix SNP array or imputed in the ARIC and FHS datasets. Allelic association was done by logistic regression adjusting by age and sex with European and Polynesian data combined by meta-analysis. Sample sets were pooled for multiplicative interaction analysis, which was also adjusted by sample set. RESULTS: Eleven SNPs were tested in the TLR2, CD14, IL1B, CARD8, NLRP3, MYD88, P2RX7, DAPK1 and TNXIP genes. Nominally significant (P < 0.05) associations with gout were detected at CARD8 rs2043211 (OR = 1.12, P = 0.007), IL1B rs1143623 (OR = 1.10, P = 0.020) and CD14 rs2569190 (OR = 1.08; P = 0.036). There was significant multiplicative interaction between CARD8 and IL1B (P = 0.005), with the IL1B risk genotype amplifying the risk effect of CARD8. CONCLUSION: There is evidence for association of gout with functional variants in CARD8, IL1B and CD14. The gout-associated allele of IL1B increases expression of IL-1β - the multiplicative interaction with CARD8 would be consistent with a synergy of greater inflammasome activity (resulting from reduced CARD8) combined with higher levels of pre-IL-1β expression leading to increased production of mature IL-1β in gout.

12 Article Effects of Xanthine Oxidase Inhibition in Hyperuricemic Heart Failure Patients: The Xanthine Oxidase Inhibition for Hyperuricemic Heart Failure Patients (EXACT-HF) Study. 2015

Givertz, Michael M / Anstrom, Kevin J / Redfield, Margaret M / Deswal, Anita / Haddad, Haissam / Butler, Javed / Tang, W H Wilson / Dunlap, Mark E / LeWinter, Martin M / Mann, Douglas L / Felker, G Michael / O'Connor, Christopher M / Goldsmith, Steven R / Ofili, Elizabeth O / Saltzberg, Mitchell T / Margulies, Kenneth B / Cappola, Thomas P / Konstam, Marvin A / Semigran, Marc J / McNulty, Steven E / Lee, Kerry L / Shah, Monica R / Hernandez, Adrian F / Anonymous4280830. ·From Brigham and Women's Hospital, Harvard Medical School, Boston, MA (M.M.G.) · Duke University Medical Center, Durham, NC (K.J.A., G.M.F., C.M.O., S.E.M., K.L.L., A.F.H.) · Mayo Clinic, Rochester, MN (M.M.R.) · Michael E. DeBakey VA Medical Center, Baylor College of Medicine, Houston, TX (A.D.) · Ottawa Heart Institute, Ontario, Canada (H.H.) · Emory University, Atlanta, GA (J.B.) · Cleveland Clinic, OH (W.H.W.T.) · MetroHealth Campus of Case Western Reserve University, Cleveland, OH (M.E.D.) · University of Vermont, Burlington (M.M.L.) · Washington University, St. Louis, MO (D.L.M.) · Hennepin County Medical Center, Minneapolis, MN (S.R.G.) · Morehouse School of Medicine, Atlanta, GA (E.O.O.) · Christiana Care Health System, Newark, DE (M.T.S.) · University of Pennsylvania, Philadelphia (K.B.M., T.P.C.) · Tufts Medical Center, Boston, MA (M.A.K.) · Massachusetts General Hospital, Boston (M.J.S.) · and National Heart, Lung, and Blood Institute, Bethesda, MD (M.R.S.). ·Circulation · Pubmed #25986447.

ABSTRACT: BACKGROUND: Oxidative stress may contribute to heart failure (HF) progression. Inhibiting xanthine oxidase in hyperuricemic HF patients may improve outcomes. METHODS AND RESULTS: We randomly assigned 253 patients with symptomatic HF, left ventricular ejection fraction ≤40%, and serum uric acid levels ≥9.5 mg/dL to receive allopurinol (target dose, 600 mg daily) or placebo in a double-blind, multicenter trial. The primary composite end point at 24 weeks was based on survival, worsening HF, and patient global assessment. Secondary end points included change in quality of life, submaximal exercise capacity, and left ventricular ejection fraction. Uric acid levels were significantly reduced with allopurinol in comparison with placebo (treatment difference, -4.2 [-4.9, -3.5] mg/dL and -3.5 [-4.2, -2.7] mg/dL at 12 and 24 weeks, respectively, both P<0.0001). At 24 weeks, there was no significant difference in clinical status between the allopurinol- and placebo-treated patients (worsened 45% versus 46%, unchanged 42% versus 34%, improved 13% versus 19%, respectively; P=0.68). At 12 and 24 weeks, there was no significant difference in change in Kansas City Cardiomyopathy Questionnaire scores or 6-minute walk distances between the 2 groups. At 24 weeks, left ventricular ejection fraction did not change in either group or between groups. Rash occurred more frequently with allopurinol (10% versus 2%, P=0.01), but there was no difference in serious adverse event rates between the groups (20% versus 15%, P=0.36). CONCLUSIONS: In high-risk HF patients with reduced ejection fraction and elevated uric acid levels, xanthine oxidase inhibition with allopurinol failed to improve clinical status, exercise capacity, quality of life, or left ventricular ejection fraction at 24 weeks. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00987415.

13 Article Pathology in practice. Mycotic dermatitis and gout in an American alligator. 2015

Ilha, Marcia R S / Rajeev, Sreekumari. ·Veterinary Diagnostic and Investigational Laboratory, College of Veterinary Medicine, University of Georgia, Tifton, GA 31793. ·J Am Vet Med Assoc · Pubmed #25719841.

ABSTRACT: -- No abstract --

14 Article Gout. 2010

Cayley, William E. ·University of Wisconsin Department of Family Medicine, UW Health Augusta Family Medicine Clinic, 207 West Lincoln, Augusta, Wisconsin, WI 54722, USA. bcayley@yahoo.com ·BMJ · Pubmed #21078757.

ABSTRACT: -- No abstract --

15 Minor Febuxostat for Asymptomatic Hyperuricemia in CKD. 2016

Mome, Ruth / Bakinde, Nicolas. ·Morehouse School of Medicine, Atlanta, Georgia. ·Am J Kidney Dis · Pubmed #27211367.

ABSTRACT: -- No abstract --

16 Minor Polyarticular Gout Flare Masquerading as Sepsis. 2015

Shah, Deep / Mohan, Gopi / Flueckiger, Peter / Corrigan, Frank / Conn, Doyt. ·Department of Medicine, Emory University School of Medicine, Atlanta, Ga. Electronic address: djshah@emory.edu. · Department of Medicine, Emory University School of Medicine, Atlanta, Ga. · Department of Medicine, Emory University School of Medicine, Atlanta, Ga; Department of Cardiology, Wake Forest School of Medicine, Winston-Salem, NC. · Department of Medicine, Emory University School of Medicine, Atlanta, Ga; Department of Cardiology, Emory University School of Medicine, Atlanta, Ga. · Department of Rheumatology, Emory University School of Medicine, Atlanta, Ga. ·Am J Med · Pubmed #25614957.

ABSTRACT: -- No abstract --

17 Minor Miliarial gout: a rare clinical presentation. 2014

Mireku, Kenyatta A / Burgy, Jessica R / Davis, Loretta S. ·Georgia Regents University, Augusta, Georgia. · Georgia Regents University, Augusta, Georgia. Electronic address: jburgy@gru.edu. ·J Am Acad Dermatol · Pubmed #24947704.

ABSTRACT: -- No abstract --