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Gout: HELP
Articles by Fiona Marion Florence McQueen
Based on 53 articles published since 2008
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Between 2008 and 2019, F. McQueen wrote the following 53 articles about Gout.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Review Advanced Imaging in the Diagnosis of Gout and Other Crystal Arthropathies. 2018

Teh, James / McQueen, Fiona / Eshed, Iris / Plagou, Athena / Klauser, Andrea. ·Department of Radiology, Nuffield Orthopaedic Centre, Oxford University Hospitals NHS Trust, Oxford, United Kingdom. · Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand. · Department of Diagnostic Imaging, Sheba Medical Center, Tel Hashomer, Israel. · Department of Radiology, Private Institution of Ultrasonography, Athens, Greece. · Department of Radiology, Medical University of Innsbruck, Innsbruck, Austria. ·Semin Musculoskelet Radiol · Pubmed #29672810.

ABSTRACT: In recent years significant advances have been made in imaging techniques. Dual-energy computed tomography has revolutionized the ability to detect and quantify gout. The key ultrasound features of gout have been defined. Magnetic resonance imaging is an excellent modality for demonstrating the extent and severity of crystal arthropathies, but the findings may be nonspecific. This article summarizes the use of advanced imaging techniques in the diagnosis and assessment of gout and other crystal arthropathies.

2 Review Imaging in the crystal arthropathies. 2014

McQueen, Fiona M / Doyle, Anthony / Dalbeth, Nicola. ·Department of Molecular Medicine and Pathology, University of Auckland, 85 Park Road, Grafton, Auckland 1023, New Zealand; Auckland District Health Board, Department of Rheumatology, Greenlane Clinical Centre, 214 Green Lane West, Auckland 1051, New Zealand. Electronic address: f.mcqueen@auckland.ac.nz. · Department of Anatomy and Radiology, University of Auckland, 85 Park Road, Grafton, Auckland 1023, New Zealand; Auckland District Health Board, Department of Radiology, Auckland City Hospital, 2 Park Road, Grafton, Auckland 1023, New Zealand. · Auckland District Health Board, Department of Rheumatology, Greenlane Clinical Centre, 214 Green Lane West, Auckland 1051, New Zealand; Bone & Joint Research Group, Department of Medicine, University of Auckland, 85 Park Road, Grafton, Auckland 1023, New Zealand. ·Rheum Dis Clin North Am · Pubmed #24703345.

ABSTRACT: Imaging in the crystal arthropathies has undergone great advances in the past decade, with newer techniques having additional benefits for assisting diagnosis, predicting prognosis, and monitoring the treatment of these conditions. Three-dimensional digitized modalities such as computed tomography, dual-energy computed tomography, and magnetic resonance imaging (MRI) offer a multislice view of any anatomic region. Both ultrasonography and MRI reveal features of inflammation and joint damage in all crystal arthropathies, and can be used to monitor the inflammatory response to therapy. The type of imaging used needs to be adapted to the clinical question of relevance.

3 Review Outcome measures in acute gout: a systematic literature review. 2014

Dalbeth, Nicola / Zhong, Cathy S / Grainger, Rebecca / Khanna, Dinesh / Khanna, Puja P / Singh, Jasvinder A / McQueen, Fiona M / Taylor, William J. ·From the Department of Medicine, University of Auckland, Auckland; Department of Medicine, University of Otago, Wellington, New Zealand; Division of Rheumatology, University of Michigan, Ann Arbor, Michigan; and Birmingham Veterans Affairs Medical Center and University of Alabama at Birmingham, Birmingham, Alabama, USA. ·J Rheumatol · Pubmed #24334652.

ABSTRACT: OBJECTIVE: Five core domains have been endorsed by Outcome Measures in Rheumatology (OMERACT) for acute gout: pain, joint swelling, joint tenderness, patient global assessment, and activity limitation. We evaluated instruments for these domains according to the OMERACT filter: truth, feasibility, and discrimination. METHODS: A systematic search strategy for instruments used to measure the acute gout core domains was formulated. For each method, articles were assessed by 2 reviewers to summarize information according to the specific components of the OMERACT filter. RESULTS: Seventy-seven articles and abstracts met the inclusion criteria. Pain was most frequently reported (76 studies, 20 instruments). The pain instruments used most often were 100 mm visual analog scale (VAS) and 5-point Likert scale. Both methods have high feasibility, face and content validity, and within- and between-group discrimination. Four-point Likert scales assessing index joint swelling and tenderness have been used in numerous acute gout studies; these instruments are feasible, with high face and content validity, and show within- and between-group discrimination. Five-point Patient Global Assessment of Response to Treatment (PGART) scales are feasible and valid, and show within- and between-group discrimination. Measures of activity limitations were infrequently reported, and insufficient data were available to make definite assessments of the instruments for this domain. CONCLUSION: Many different instruments have been used to assess the acute gout core domains. Pain VAS and 5-point Likert scales, 4-point Likert scales of index joint swelling and tenderness and 5-point PGART instruments meet the criteria for the OMERACT filter.

4 Review Gout in 2013. Imaging, genetics and therapy: gout research continues apace. 2014

McQueen, Fiona M. ·Department of Molecular Medicine and Pathology, University of Auckland, PO Box 92019, Auckland 1023, New Zealand. ·Nat Rev Rheumatol · Pubmed #24275962.

ABSTRACT: In 2013, much progress has occurred in gout research. Imaging continues to help elucidate aspects of pathophysiology and now suggests that healing of erosions could occur when urate levels are reduced dramatically. New genetic loci associated with hyperuricaemia have been identified and management strategies for prophylaxis of gout flares continue to evolve.

5 Review New insights into an old disease: advanced imaging in the diagnosis and management of gout. 2013

McQueen, Fiona Marion / Reeves, Quentin / Dalbeth, Nicola. ·Department of Molecular Medicine and Pathology, University of Auckland, 85 Park Rd, Grafton, Auckland 1023, New Zealand. f.mcqueen@auckland.ac.nz ·Postgrad Med J · Pubmed #23112219.

ABSTRACT: Advanced imaging modalities including MRI, ultrasound (US), CT and dual energy CT have important applications in gout. While conventional radiography (X-ray) remains the most widely used form of imaging in the clinical setting and is helpful in revealing erosions in chronic gout, these new imaging tools can reveal joint damage and tophi at a much earlier stage. As all are multiplanar techniques, they can define the position and dimensions of tophi, with startling clarity, as well as the size and extent of bone erosions. US and MRI also reveal the severity of inflammation within and adjacent to the joint and can capture information about the composite, vascular nature of many tophaceous deposits. These features can be used as imaging outcome measures, to monitor responses to anti-inflammatory and urate lowering therapies. The new possibility that gout could be diagnosed using imaging, without aspirating the joint, is on the horizon. This review discusses the clinical and research applications of advanced imaging in gout with particular focus on diagnosis and monitoring of joint inflammation and damage.

6 Review Imaging in gout: insights into the pathological features of disease. 2012

Dalbeth, Nicola / Doyle, Anthony / McQueen, Fiona M. ·Auckland Rheumatology Imaging Group, University of Auckland, Grafton, Auckland, New Zealand. n.dalbeth@auckland.ac.nz ·Curr Opin Rheumatol · Pubmed #22301866.

ABSTRACT: PURPOSE OF REVIEW: Imaging has the potential to assess various pathological manifestations of gout, including monosodium urate (MSU) crystal deposition, tophus formation and cartilage, soft tissue, and bone pathology. This review discusses recent research examining the role of imaging to assess the manifestations of disease. RECENT FINDINGS: Various imaging techniques are used in the assessment of gout, including plain radiography, ultrasonography, conventional computed tomography (CT), dual energy computed tomography (DECT), and MRI. Potential roles for ultrasonography are MSU crystal detection, measurement of tophi, and assessment of disease complications. Ultrasonography may allow detection of MSU crystals in patients with hyperuricaemia, prior to development of clinically apparent gout. Conventional CT allows excellent visualization of tophi and bone erosion. DECT is a promising method of noninvasive MSU crystal detection. MRI allows assessment of tophi, synovial and soft tissue disease, and bone pathology. The relative absence of MRI bone marrow oedema in gout suggests that the mechanisms of bone erosion in gout are quite different from those in other erosive arthropathies. SUMMARY: Imaging modalities have provided important insights into the pathology of gout. The role of various imaging techniques in gout diagnosis, monitoring, and prediction of outcome is rapidly developing.

7 Review Mechanisms of joint damage in gout: evidence from cellular and imaging studies. 2012

McQueen, Fiona M / Chhana, Ashika / Dalbeth, Nicola. ·Department of Molecular Medicine and Pathology, University of Auckland, Park Road, Grafton, Auckland 1023, New Zealand. f.mcqueen@auckland.ac.nz ·Nat Rev Rheumatol · Pubmed #22231231.

ABSTRACT: The clinical course of gout is initially characterized by acute self-limited joint inflammation, but long-standing disease is often associated with chronic inflammation followed by the development of erosive joint damage, which can result in long-term functional impairment. Preventing joint damage is now a major focus of therapeutic intervention in gout. New light has been shed on the mechanisms leading to cartilage and bone damage in patients with this disease. Here, we discuss basic science studies focusing on the cellular immunology of bone and cartilage in gout and the effects of monosodium urate crystals on signaling pathways, cytokine release and the function of osteoclasts, osteoblasts and chondrocytes. We then explore the use of advanced imaging modalities (including MRI, ultrasonography, CT and dual-energy CT) to investigate pathology in gout, as they provide new ways to visualize joint tissues. These modalities vary in their ability to detect the various pathological features of gout and have different clinical applications. Imaging provides information about the inflammatory nature of the joint lesion, position and size of tophaceous deposits, and extent of bone and cartilage damage. Imaging is also increasingly being used to monitor the progression of joint damage and regression of tophi with effective urate-lowering therapy.

8 Review Imaging in gout--what can we learn from MRI, CT, DECT and US? 2011

McQueen, Fiona M / Doyle, Anthony / Dalbeth, Nicola. ·Department of Molecular Medicine and Pathology, Faculty of Medicine and Health Sciences, University of Auckland, 85 Park Road, Grafton, Auckland 1023, New Zealand. f.mcqueen@auckland.ac.nz ·Arthritis Res Ther · Pubmed #22085684.

ABSTRACT: There are many exciting new applications for advanced imaging in gout. These modalities employ multiplanar imaging and allow computerized three-dimensional rendering of bone and joints (including tophi) and have the advantage of electronic data storage for later retrieval. High-resolution computed tomography has been particularly helpful in exploring the pathology of gout by investigating the relationship between bone erosions and tophi. Magnetic resonance imaging and ultrasonography can image the inflammatory nature of gouty arthropathy, revealing synovial and soft tissue inflammation, and can provide information about the composition and vascularity of tophi. Dual-energy computerized tomography is a new modality that is able to identify tophi by their chemical composition and reveal even small occult tophaceous deposits. All modalities are being investigated for their potential roles in diagnosis and could have important clinical applications in the patient for whom aspiration of monosodium urate crystals from the joint is not possible. Imaging can also provide outcome measures, such as change in tophus volume, for monitoring the response to urate-lowering therapy and this is an important application in the clinical trial setting.

9 Review Methods of tophus assessment in clinical trials of chronic gout: a systematic literature review and pictorial reference guide. 2011

Dalbeth, Nicola / Schauer, Cameron / Macdonald, Patricia / Perez-Ruiz, Fernando / Schumacher, H Ralph / Hamburger, Steve / Choi, Hyon K / McQueen, Fiona M / Doyle, Anthony / Taylor, William J. ·Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Road, Grafton, Auckland, New Zealand. n.dalbeth@auckland.ac.nz ·Ann Rheum Dis · Pubmed #21216814.

ABSTRACT: OBJECTIVE: To identify methods of tophus measurement for gout studies, summarise the properties of these methods and compile a detailed pictorial reference guide to demonstrate the methods. METHODS: A systematic search strategy for methods of tophus measurement was formulated. For each method, papers were assessed by two reviewers to summarise information according to the specific components of the Outcomes Measures in Rheumatology (OMERACT) filter: feasibility, truth and discrimination. Detailed images were obtained to construct the reference guide. RESULTS: Eight methods of tophus measurement were identified: counting the total number of tophi, physical measurement using tape measure, physical measurement using Vernier callipers, digital photography, ultrasonography (US), MRI, CT and dual energy CT. Feasibility aspects of the methods are well documented. Physical measurement techniques are more feasible than advanced imaging methods, but do not allow for assessment of intra-articular tophi or for data storage and central reading. The truth aspect of the filter has been documented for many methods, particularly Vernier callipers, US, MRI and CT. Reliability of most methods has been reported as very good or excellent. Sensitivity to change has been reported for all methods except MRI and CT. CONCLUSION: A variety of methods of tophus assessment have been described for use in clinical trials of chronic gout. Physical measurement techniques (particularly the Vernier calliper method) and US measurement of tophus size appear to meet most aspects of the OMERACT filter.

10 Review The natural killer cell: a further innate mediator of gouty inflammation? 2010

Empson, Victoria G / McQueen, Fiona M / Dalbeth, Nicola. ·Bone Research Group, Department of Medicine, University of Auckland, Grafton, Auckland, New Zealand. ·Immunol Cell Biol · Pubmed #19935769.

ABSTRACT: Natural killer (NK) cells are vital effector cells of innate immunity because of their rapid cytotoxic and cytokine-producing responses to cell stress or infection. A distinguishing feature of NK cells is the ability to balance these signals with those of normal homeostasis through the expression of an array of inhibitory and activating receptors. Two functional subsets of NK cells exist: the more mature CD56(dim) population is potently cytotoxic, whereas CD56(bright) NK cells have low cytotoxicity but produce much greater amounts of cytokines, and express homing molecules for secondary lymphoid organs and sites of inflammation. NK cells have been identified as important modulatory cells in shaping adaptive immune responses by interacting with dendritic cells (DCs) and T cells. NK cells also interact with cells of the innate immune system such as monocytes and macrophages. This review outlines the biology of NK cells and the potential role of NK cells in modulating gouty inflammation.

11 Review Use of imaging to evaluate gout and other crystal deposition disorders. 2009

Dalbeth, Nicola / McQueen, Fiona M. ·University of Auckland, New Zealand. n.dalbeth@auckland.ac.nz ·Curr Opin Rheumatol · Pubmed #19339922.

ABSTRACT: PURPOSE OF REVIEW: This review summarizes recent advances in plain radiography and advanced imaging for gout, calcium pyrophosphate dihydrate crystal arthropathy and basic calcium phosphate crystal arthropathy. RECENT FINDINGS: Plain radiography has diagnostic utility in the crystal-induced arthropathies. A gout radiographic damage index has been recently validated. High-resolution ultrasonography may improve noninvasive diagnosis of the crystal-induced arthropathies, and allow monitoring of intra-articular tophi in clinical trials. Computed tomography provides excellent definition of tophi and bone erosion, and three-dimensional computed tomography assessment of tophus volume is a promising outcome measure in gout. Magnetic resonance imaging is also a reliable method for assessment of tophus size in gout, and has an important role in detection of complications of disease in clinical practice. Emerging imaging techniques include three-dimensional ultrasonography and dual-energy computed tomography. Advanced imaging modalities also offer new insights into the mechanisms of cartilage and bone damage in the crystal-induced arthropathies. SUMMARY: Plain radiography and advanced imaging techniques may assist with diagnosis, assessment of disease complications and monitoring of crystal-induced arthropathies. Further study of these techniques will provide significant improvement in patient care and further aid in the understanding of disease pathogenesis.

12 Article Dual-Energy CT of Urate Deposits in Costal Cartilage and Intervertebral Disks of Patients With Tophaceous Gout and Age-Matched Controls. 2016

Carr, Alexander / Doyle, Anthony J / Dalbeth, Nicola / Aati, Opetaia / McQueen, Fiona M. ·1 Department of Molecular Medicine and Pathology, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Rd, Grafton, Auckland, New Zealand. · 2 Department of Radiology, Auckland City Hospital, Auckland District Health Board, Auckland, New Zealand. · 3 Department of Medicine, Bone and Joint Research Group, University of Auckland, Auckland, New Zealand. · 4 Department of Rheumatology, Greenlane Clinical Centre, Auckland District Health Board, Auckland, New Zealand. ·AJR Am J Roentgenol · Pubmed #26958708.

ABSTRACT: OBJECTIVE: The purpose of this study was to investigate whether monosodium urate (MSU) deposits could be identified within the abdomen and axial skeleton of patients with tophaceous gout using dual-energy CT (DECT). CONCLUSION: DECT of the abdomen, chest wall, and spine revealed extensive MSU deposits in costal cartilages and, to a lesser extent, intervertebral disks in the male patients with gout in our study. These were quantified volumetrically. However, age-matched control subjects showed similar deposits, indicating this was not a disease-specific finding. Thus, MSU deposition in the axial skeleton may be physiologic in middle-aged men.

13 Article Path Analysis Identifies Receptor Activator of Nuclear Factor-κB Ligand, Osteoprotegerin, and Sclerostin as Potential Mediators of the Tophus-bone Erosion Relationship in Gout. 2016

Chhana, Ashika / Aati, Opetaia / Gamble, Gregory D / Callon, Karen E / Doyle, Anthony J / Roger, Mark / McQueen, Fiona M / Horne, Anne / Reid, Ian R / Cornish, Jillian / Dalbeth, Nicola. ·From the Bone and Joint Research Group, the Department of Medicine, the Department of Anatomy with Radiology, and the Department of Molecular Medicine and Pathology, University of Auckland; and the Department of Radiology, Auckland District Health Board, Auckland, New Zealand.A. Chhana, PhD, Bone and Joint Research Group, Department of Medicine, University of Auckland; O. Aati, MHSc, Bone and Joint Research Group, Department of Medicine, University of Auckland; G.D. Gamble, MSc, Bone and Joint Research Group, Department of Medicine, University of Auckland; K.E. Callon, BSc, Bone and Joint Research Group, Department of Medicine, University of Auckland; A. Horne, MBChB, Bone and Joint Research Group, Department of Medicine, University of Auckland; I.R. Reid, MBChB, MD, FRACP, Bone and Joint Research Group, Department of Medicine, University of Auckland; J. Cornish, PhD, Bone and Joint Research Group, Department of Medicine, University of Auckland; N. Dalbeth, MBChB, MD, FRACP, Bone and Joint Research Group, Department of Medicine, University of Auckland; A.J. Doyle, MBChB, Department of Anatomy with Radiology, University of Auckland, and Department of Radiology, Auckland District Health Board; M. Roger, MBChB, Department of Radiology, Auckland District Health Board; F.M. McQueen, MD, FRACP, Department of Molecular Medicine and Pathology, University of Auckland. ·J Rheumatol · Pubmed #26773114.

ABSTRACT: OBJECTIVE: To determine the relationship between tophus, erosion and bone remodeling factors in gout. METHODS: Computed tomography bone erosion and circulating bone factors were measured in adults with tophaceous gout. Multiple regression modeling and path analysis were used to determine predictors of erosion. RESULTS: Tophus number, Māori or Pacific ethnicity, creatinine, receptor activator of nuclear factor-κB ligand (RANKL), osteoprotegerin (OPG), and sclerostin were independently associated with erosion. Path analysis showed a direct effect of tophus number on erosion, partially mediated through OPG, RANKL, and sclerostin. CONCLUSION: Tophus number is strongly associated with bone erosion in gout. Circulating RANKL, OPG, and sclerostin are potential mediators of tophus-related erosion.

14 Article Gout on CT of the feet: A symmetric arthropathy. 2016

Doyle, Anthony J / Dalbeth, Nicola / McQueen, Fiona / Boyer, Lucinda / Dong, Jing / Rome, Keith / Frecklington, Mike. ·Radiology, Auckland City Hospital, Auckland, New Zealand. · Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand. · Rheumatology and Molecular Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand. · Department of Podiatry, School of Rehabilitation and Occupation Studies, Faculty of Health and Environmental Sciences, AUT University, Auckland, New Zealand. ·J Med Imaging Radiat Oncol · Pubmed #26631920.

ABSTRACT: INTRODUCTION: The aim of this study was to assess the distribution of bone erosions in the feet of patients with gout using CT and thereby to test the hypothesis that gout is an asymmetric arthropathy. METHODS: CT scans of both feet were obtained from 25 patients with chronic gout. CT scans were scored for bone erosion using a semi-quantitative method based on the rheumatoid arthritis MRI scoring system (RAMRIS). CT bone erosion was assessed at 22 bones in each foot (total 1,100 bones) by two independent radiologists. Symmetry was assessed by two methods: (i) comparing right and left foot scores for each patient; and (ii) calculating the proportion of paired joints with or without erosions. RESULTS: Observer agreement was excellent (intra-class correlation coefficient 0.92). In the group overall, the difference in scores between the feet was not significant (Student's t-test P = 0.8). In 17 of 25 patients, the difference in erosion scores between the two feet was less than the inter-observer difference. In 24 of 25 patients, the proportion of paired joints was greater than 0.5, indicating symmetric disease. CONCLUSIONS: Erosive disease from gout is, in fact, a symmetric process in our patient group. This finding is contrary to the established view of gout as an asymmetric arthritis and lends new insight into the behaviour of this common disease.

15 Article A comparative MRI study of cartilage damage in gout versus rheumatoid arthritis. 2015

Popovich, Ivor / Lee, Arier C L / Doyle, Anthony / McHaffie, Alexandra / Clarke, Andrew / Reeves, Quentin / Dalbeth, Nicola / McQueen, Fiona M. ·Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand. · Department of Epidemiology and Biostatistics, Tamaki Campus, University of Auckland, Auckland, New Zealand. · Department of Radiology, Auckland District Health Board, Auckland City Hospital, Auckland, New Zealand. · Bone & Joint Research Group, Department of Medicine, University of Auckland, Auckland, New Zealand. · Department of Rheumatology, Auckland District Health Board, Greenlane Clinical Centre, Auckland, New Zealand. ·J Med Imaging Radiat Oncol · Pubmed #25908527.

ABSTRACT: INTRODUCTION: Magnetic resonance imaging (MRI) is useful for detecting joint inflammation and damage in the inflammatory arthropathies. This study aimed to investigate MRI cartilage damage and its associations with joint inflammation in patients with gout compared with a group with rheumatoid arthritis (RA). METHODS: Forty patients with gout and 38 with seropositive RA underwent 3T-MRI of the wrist with assessment of cartilage damage at six carpal sites, using established scoring systems. Synovitis and bone oedema (BME) were graded according to Rheumatoid Arthritis MRI Scoring System criteria. Cartilage damage was compared between the groups adjusting for synovitis and disease duration using logistic regression analysis. RESULTS: Compared with RA, there were fewer sites of cartilage damage and lower total damage scores in the gout group (P = 0.02 and 0.003), adjusting for their longer disease duration and lesser degree of synovitis. Cartilage damage was strongly associated with synovitis in both conditions (R = 0.59, P < 0.0001 and R = 0.52, P = 0.0045 respectively) and highly correlated with BME in RA (R = 0.69, P < 0.0001) but not in gout (R = 0.095, P = 0.56). CONCLUSIONS: Cartilage damage is less severe in gout than in RA, with fewer sites affected and lower overall scores. It is associated with synovitis in both diseases, likely indicating an effect of pro-inflammatory cytokine production on cartilage integrity. However, the strong association between cartilage damage and BME observed in RA was not identified in gout. This emphasizes differences in the underlying pathophysiology of joint damage in these two conditions.

16 Article Urate crystal deposition in asymptomatic hyperuricaemia and symptomatic gout: a dual energy CT study. 2015

Dalbeth, Nicola / House, Meaghan E / Aati, Opetaia / Tan, Paul / Franklin, Christopher / Horne, Anne / Gamble, Gregory D / Stamp, Lisa K / Doyle, Anthony J / McQueen, Fiona M. ·Faculty of Medical and Health Sciences, Department of Medicine, Bone and Joint Research Group, University of Auckland, Auckland, New Zealand. · Department of Medicine, University of Otago, Christchurch, New Zealand. · Faculty of Medical and Health Sciences, Department of Anatomy with Radiology, University of Auckland, Auckland, New Zealand. · Faculty of Medical and Health Sciences, Department of Molecular Medicine, University of Auckland, Auckland, New Zealand. ·Ann Rheum Dis · Pubmed #25637002.

ABSTRACT: BACKGROUND: The aim of this study was to compare the frequency and volume of dual energy CT (DECT) urate deposits in people with asymptomatic hyperuricaemia and symptomatic gout. METHODS: We analysed DECT scans of the feet from asymptomatic individuals with serum urate ≥540 µmol/L (n=25) and those with crystal proven gout without clinically apparent tophi (n=33). RESULTS: DECT urate deposits were observed in 6/25 (24%) participants with asymptomatic hyperuricaemia, 11/14 (79%) with early gout (predefined as disease duration ≤3 years) and 16/19 (84%) with late gout (p<0.001). DECT urate deposition was observed in both joints and tendons in the asymptomatic hyperuricaemia group, but significantly less frequently than in those with gout (p≤0.001 for both joint and tendon sites). The volume of urate deposition was also significantly lower in those with asymptomatic hyperuricaemia, compared with the early and the late gout groups (p<0.01 for both comparisons). Similar urate volumes were observed in the early and late gout groups. CONCLUSIONS: Although subclinical urate deposition can occur in people with asymptomatic hyperuricaemia, these deposits occur more frequently and at higher volumes in those with symptomatic gout. These data suggest that a threshold of urate crystal volume may be required before symptomatic disease occurs.

17 Article Relationship between structural joint damage and urate deposition in gout: a plain radiography and dual-energy CT study. 2015

Dalbeth, Nicola / Aati, Opetaia / Kalluru, Ramanamma / Gamble, Gregory D / Horne, Anne / Doyle, Anthony J / McQueen, Fiona M. ·Bone and Joint Research Group, Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand. · Department of Anatomy with Radiology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand. · Department of Molecular Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand. ·Ann Rheum Dis · Pubmed #24521739.

ABSTRACT: OBJECTIVES: The aim of this work was to examine the relationship between joint damage and monosodium urate (MSU) crystal deposition in gout. METHODS: Plain radiographs and dual-energy CT (DECT) scans of the feet were prospectively obtained from 92 people with tophaceous gout. Subcutaneous tophus count was recorded. The ten metatarsophalangeal joints were scored on plain radiography for Sharp-van der Heijde erosion and joint space narrowing (JSN) scores, and presence of spur, osteophyte, periosteal new bone and sclerosis (920 total joints). DECT scans were analysed for the presence of MSU crystal deposition at the same joints. RESULTS: DECT MSU crystal deposition was more frequently observed in joints with erosion (OR (95% CI) 8.5 (5.5 to 13.1)), JSN (4.2 (2.7 to 6.7%)), spur (7.9 (4.9 to 12.8)), osteophyte (3.9 (2.5 to 6.0)), periosteal new bone (7.0 (4.0 to 12.2)) and sclerosis (6.9 (4.6 to 10.2)), p<0.0001 for all. A strong linear relationship was observed in the frequency of joints affected by MSU crystals with radiographic erosion score (p<0.0001). The number of joints at each site with MSU crystal deposition correlated with all features of radiographic joint damage (r>0.88, p<0.05 for all). In linear regression models, the relationship between MSU crystal deposition and all radiographic changes except JSN and osteophytes persisted after adjusting for subcutaneous tophus count, serum urate concentration and disease duration. CONCLUSIONS: MSU crystals are frequently present in joints affected by radiographic damage in gout. These findings support the concept that MSU crystals interact with articular tissues to influence the development of structural joint damage in this disease.

18 Article Digital tomosynthesis for bone erosion scoring in gout: comparison with plain radiography and computed tomography. 2014

Dalbeth, Nicola / Gao, Angela / Roger, Mark / Doyle, Anthony J / McQueen, Fiona M. ·Auckland Rheumatology Imaging Group, University of Auckland, Auckland, New Zealand. n.dalbeth@auckland.ac.nz. · Auckland Rheumatology Imaging Group, University of Auckland, Auckland, New Zealand. ·Rheumatology (Oxford) · Pubmed #24972842.

ABSTRACT: -- No abstract --

19 Article Interactions between tenocytes and monosodium urate monohydrate crystals: implications for tendon involvement in gout. 2014

Chhana, Ashika / Callon, Karen E / Dray, Michael / Pool, Bregina / Naot, Dorit / Gamble, Greg D / Coleman, Brendan / McCarthy, Geraldine / McQueen, Fiona M / Cornish, Jillian / Dalbeth, Nicola. ·Bone & Joint Research Group, Department of Medicine, University of Auckland, Auckland, New Zealand. · Department of Histology, Waikato Hospital, Hamilton, New Zealand. · Department of Orthopaedic Surgery, Middlemore Hospital, Auckland, New Zealand. · Department of Rheumatology, Mater Misericordiae University Hospital, Dublin, Ireland. · Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand. ·Ann Rheum Dis · Pubmed #24709860.

ABSTRACT: OBJECTIVES: Advanced imaging studies have demonstrated that urate deposition in periarticular structures, such as tendons, is common in gout. The aim of this study was to investigate the effects of monosodium urate monohydrate (MSU) crystals on tenocyte viability and function. METHODS: The histological appearance of tendons in joints affected by advanced gout was examined using light microscopy. In vitro, colorimetric assays and flow cytometry were used to assess cell viability in primary rat and primary human tenocytes cultured with MSU crystals. Real-time PCR was used to determine changes in the relative mRNA expression levels of tendon-related genes, and Sirius red staining was used to measure changes in collagen deposition in primary rat tenocytes. RESULTS: In joint samples from patients with gout, MSU crystals were identified within the tendon, adjacent to and invading into tendon, and at the enthesis. MSU crystals reduced tenocyte viability in a dose-dependent manner. MSU crystals decreased the mRNA expression of tendon collagens, matrix proteins and degradative enzymes and reduced collagen protein deposition by tenocytes. CONCLUSIONS: These data indicate that MSU crystals directly interact with tenocytes to reduce cell viability and function. These interactions may contribute to tendon damage in people with advanced gout.

20 Article Zoledronate for prevention of bone erosion in tophaceous gout: a randomised, double-blind, placebo-controlled trial. 2014

Dalbeth, Nicola / Aati, Opetaia / Gamble, Gregory D / Horne, Anne / House, Meaghan E / Roger, Mark / Doyle, Anthony J / Chhana, Ashika / McQueen, Fiona M / Reid, Ian R. ·Department of Medicine, University of Auckland, , Auckland, New Zealand. ·Ann Rheum Dis · Pubmed #24442886.

ABSTRACT: OBJECTIVES: The osteoclast has been implicated in development of bone erosion in gout. The aim of this study was to determine whether zoledronate, a potent antiosteoclast drug, influences bone erosion in people with tophaceous gout. METHODS: This was a 2-year, randomised, double-blind, placebo-controlled trial of 100 people with tophaceous gout. Participants were randomised to annual administration of 5 mg intravenous zoledronate or placebo. The primary endpoint was change in the foot CT bone erosion score from baseline. Secondary endpoint was change in plain radiographic damage scores. Other endpoints were change in bone mineral density (BMD), bone turnover markers and the OMERACT-endorsed core domains for chronic gout studies. RESULTS: There was no change in CT erosion scores over 2 years, and no difference between the two treatment groups at Year 1 or 2 (p(treat)=0.10, p(time)=0.47, p(treat*time)=0.23). Similarly, there was no change in plain radiographic scores over 2 years, and no difference between the two groups at Year 1 or 2. By contrast, zoledronate increased spine, neck of femur, total hip and total body BMD. Zoledronate therapy also reduced the bone turnover markers P1NP and β-CTX compared with placebo. There was no difference between treatment groups in OMERACT-endorsed core domains. CONCLUSIONS: Despite improvements in BMD and suppression of bone turnover markers, antiosteoclast therapy with zoledronate did not influence bone erosion in people with tophaceous gout. These findings suggest a disconnect between responses in the healthy skeleton and at sites of focal bone erosion in tophaceous gout.

21 Article OMERACT endorsement of measures of outcome for studies of acute gout. 2014

Singh, Jasvinder A / Taylor, William J / Dalbeth, Nicola / Simon, Lee S / Sundy, John / Grainger, Rebecca / Alten, Rieke / March, Lyn / Strand, Vibeke / Wells, George / Khanna, Dinesh / McQueen, Fiona / Schlesinger, Naomi / Boonen, Annelies / Boers, Maarten / Saag, Kenneth G / Schumacher, H Ralph / Edwards, N Lawrence. ·From Birmingham Veterans Affairs Medical Center and University of Alabama at Birmingham, Birmingham, Alabama, USA; Department of Medicine, University of Otago, Wellington; Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand; SDG LLC, Cambridge, Massachusetts,; Duke University School of Medicine, Durham, North Carolina, USA, and Duke-National University of Singapore Graduate Medical School, Singapore; Schlosspark-Klinik Teaching Hospital of the Charité, University Medicine Berlin, Berlin, Germany; University of Sydney Institute of Bone and Joint Research and Department of Rheumatology, Royal North Shore Hospital, Sydney, Australia; Stanford University Division of Immunology and Rheumatology, Portolo Valley, California, USA; University of Ottawa, London, Ontario, Canada; University of Michigan Medical School, Ann Arbor, Michigan, USA; University of Auckland, Department of Molecular Medicine and Pathology, Grafton, Auckland, New Zealand; Rutgers-Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA; Maastricht University Medical Center, Division of Rheumatology, and Caphri Research Institute, University Maastricht; VU University Medical Center, Amsterdam, the Netherlands; University of Pennsylvania and Philadelphia Veterans Affairs Medical Center, Philadelphia, Pennsylvania; Department of Rheumatology, University of Florida, Gainsville, Florida, USA. ·J Rheumatol · Pubmed #24334651.

ABSTRACT: 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 of truth, discrimination, and feasibility; and where future research efforts need to be directed. METHODS: Results of a systematic literature review and analysis of individual-level data from recent clinical studies of acute gout were presented to OMERACT participants. The information was discussed in breakout groups, and opinion was defined by subsequent voting in a plenary session. Endorsement was defined as at least 70% of participants voting in agreement with the proposition (where the denominator excluded those participants who did not vote or who voted "don't know"). RESULTS: The following measures were endorsed for use in clinical trials of acute gout: (1) 5-point Likert scale and/or visual analog scale (0 to 100 mm) to measure pain; (2) 4-point Likert scale for joint swelling; (3) 4-point Likert scale for joint tenderness; and (4) 5-point Likert scale for patient global assessment of response to treatment. Measures for the activity limitations domain were not endorsed. CONCLUSION: Measures of pain, joint swelling, joint tenderness, and patient global assessment in acute gout were endorsed at OMERACT 11. These measures should now be used in clinical trials of acute gout.

22 Article Bone erosions in patients with chronic gouty arthropathy are associated with tophi but not bone oedema or synovitis: new insights from a 3 T MRI study. 2014

McQueen, Fiona M / Doyle, Anthony / Reeves, Quentin / Gao, Angela / Tsai, Amy / Gamble, Greg D / Curteis, Barbara / Williams, Megan / Dalbeth, Nicola. ·Department of Molecular Medicine and Pathology, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Rd, Grafton, Auckland 1023, New Zealand. f.mcqueen@auckland.ac.nz. ·Rheumatology (Oxford) · Pubmed #24080252.

ABSTRACT: OBJECTIVES: Bone erosion has been linked with tophus deposition in gout but the roles of osteitis (MRI bone oedema) and synovitis remain uncertain. Our aims in this prospective 3 T MRI study were to investigate the frequency of these features in gout and determine their relation to one another. METHODS: 3 T MRI scans of the wrist were obtained in 40 gout patients. Scans were scored independently by two radiologists for bone oedema, erosions, tophi and synovitis. Dual-energy CT (DECT) scans were scored for tophi in a subgroup of 10 patients. RESULTS: Interreader reliability was high for erosions and tophi [intraclass correlation coefficients (ICCs) 0.77 (95% CI 0.71, 0.87) and 0.71 (95% CI 0.52, 0.83)] and moderate for bone oedema [ICC = 0.60 (95% CI 0.36, 0.77)]. Compared with DECT, MRI had a specificity of 0.98 (95% CI 0.93, 0.99) and sensitivity of 0.63 (95% CI 0.48, 0.76) for tophi. Erosions were detected in 63% of patients and were strongly associated with tophi [odds ratio (OR) = 13.0 (95% CI 1.5, 113)]. In contrast, no association was found between erosions and bone oedema. Using concordant data, bone oedema was scored at 6/548 (1%) sites in 5/40 patients (12.5%) and was very mild (median carpal score = 1, maximum = 45). In logistic regression analysis across all joints nested within individuals, tophus, but not synovitis, was independently associated with erosion [OR = 156.5 (21.2, >999.9), P < 0.0001]. CONCLUSION: Erosions were strongly associated with tophi but not bone oedema or synovitis. MRI bone oedema was relatively uncommon and low grade. These findings highlight the unique nature of the osteopathology of gout.

23 Article Exploratory study of radiographic change in patients with tophaceous gout treated with intensive urate-lowering therapy. 2014

Dalbeth, Nicola / Doyle, Anthony J / McQueen, Fiona M / Sundy, John / Baraf, Herbert S B. ·University of Auckland, Auckland, New Zealand. ·Arthritis Care Res (Hoboken) · Pubmed #23836458.

ABSTRACT: 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 examine whether profound urate lowering can alter radiographic findings in gout. METHODS: Serial plain radiographs of the hands and feet were obtained from 8 patients with tophaceous gout treated with pegloticase. Radiographs were scored for erosion and joint space narrowing (JSN) according to the gout-modified Sharp/van der Heijde method. Scorers were blinded to each other's scores and to the clinical characteristics of the patients (including the clinical response to pegloticase). A detailed qualitative site-by-site analysis was undertaken to define additional changes observed from baseline. RESULTS: All patients experienced a profound urate-lowering response (serum urate level <1 mg/dl) during pegloticase treatment. For the entire group, the median total radiographic scores reduced from 69.25 (range 1.5-138) at baseline to 57.25 (range 1.5-110) at 12 months (P = 0.02). Median erosion scores reduced over 1 year (P = 0.008), but JSN scores did not change (P = 0.50). Further reductions were observed in total scores and erosion scores in 5 patients with 24-month followup films (one-way analysis of variance P = 0.009 for total score, 0.02 for erosion, and 0.95 for JSN). Qualitative site-by-site analysis identified regression of soft tissue masses, increased sclerosis, and filling in of erosions in the followup films. CONCLUSION: This exploratory study suggests that profound urate lowering can lead to improvement in structural damage, particularly bone erosion, in patients with tophaceous gout.

24 Article Lack of change in urate deposition by dual-energy computed tomography among clinically stable patients with long-standing tophaceous gout: a prospective longitudinal study. 2013

Rajan, Ashwin / Aati, Opetaia / Kalluru, Ramanamma / Gamble, Gregory D / Horne, Anne / Doyle, Anthony J / McQueen, Fiona M / Dalbeth, Nicola. · ·Arthritis Res Ther · Pubmed #24286500.

ABSTRACT: INTRODUCTION: Dual-energy computed tomography (DECT) has potential for monitoring urate deposition in patients with gout. The aim of this prospective longitudinal study was to analyse measurement error of DECT urate volume measurement in clinically stable patients with tophaceous gout. METHODS: Seventy-three patients with tophaceous gout on stable therapy attended study visits at baseline and twelve months. All patients had a comprehensive clinical assessment including serum urate testing and DECT scanning of both feet. Two readers analysed the DECT scans for the total urate volume in both feet. Analysis included inter-reader intraclass correlation coefficients (ICCs) and limits of agreement, and calculation of the smallest detectable change. RESULTS: Mean (standard deviation) serum urate concentration over the study period was 0.38 (0.09) mmol/L. Urate-lowering therapy was prescribed in 70 (96%) patients. The median (interquartile range) baseline DECT urate volume was 0.49 (0.16, 2.18) cm(3), and change in DECT urate volume was -0.01 (-0.40, 0.28) cm(3). Inter-reader ICCs were 1.00 for baseline DECT volumes and 0.93 for change values. Inter-reader bias (standard deviation) for baseline volumes was -0.18 (0.63) cm(3) and for change was -0.10 (0.93) cm(3). The smallest detectable change was 0.91 cm3. There were 47 (64%) patients with baseline DECT urate volumes <0.91 cm(3). Higher serum urate concentrations were observed in patients with increased DECT urate volumes above the smallest detectable change (P = 0.006). However, a relationship between changes in DECT urate volumes and serum urate concentrations was not observed in the entire group. CONCLUSIONS: In patients with tophaceous gout on stable conventional urate-lowering therapy the measurement error for DECT urate volume assessment is substantially greater than the median baseline DECT volume. Analysis of patients commencing or intensifying urate-lowering therapy should clarify the optimal use of DECT as a potential outcome measure in studies of chronic gout.

25 Article The effects of monosodium urate monohydrate crystals on chondrocyte viability and function: implications for development of cartilage damage in gout. 2013

Chhana, Ashika / Callon, Karen E / Pool, Bregina / Naot, Dorit / Gamble, Gregory D / Dray, Michael / Pitto, Rocco / Bentley, Jarome / McQueen, Fiona M / Cornish, Jillian / Dalbeth, Nicola. ·From the Bone and Joint Research Group, Department of Medicine and the Department of Orthopaedic Surgery, University of Auckland, Auckland; and the Department of Histology, Waikato Hospital, Hamilton, New Zealand. ·J Rheumatol · Pubmed #24187106.

ABSTRACT: OBJECTIVE: Cartilage damage is frequently observed in advanced destructive gout. The aim of our study was to investigate the effects of monosodium urate monohydrate (MSU) crystals on chondrocyte viability and function. METHODS: The alamarBlue assay and flow cytometry were used to assess the viability of primary human chondrocytes and cartilage explants following culture with MSU crystals. The number of dead chondrocytes in cartilage explants cultured with MSU crystals was quantified. Real-time PCR was used to determine changes in the relative mRNA expression levels of chondrocytic genes. The histological appearance of cartilage in joints affected by gout was also examined. RESULTS: MSU crystals rapidly reduced primary human chondrocyte and cartilage explant viability in a dose-dependent manner (p < 0.01 for both). Cartilage explants cultured with MSU crystals had a greater percentage of dead chondrocytes at the articular surface compared to untreated cartilage (p = 0.004). Relative mRNA expression of type II collagen and the cartilage matrix proteins aggrecan and versican was decreased in chondrocytes following culture with MSU crystals (p < 0.05 for all). However, expression of the degradative enzymes ADAMTS4 and ADAMTS5 was increased (p < 0.05 for both). In joints affected by gout, normal cartilage architecture was lost, with empty chondrocyte lacunae observed. CONCLUSION: MSU crystals have profound inhibitory effects on chondrocyte viability and function. Interactions between MSU crystals and chondrocytes may contribute to cartilage damage in gout through reduction of chondrocyte viability and promotion of a catabolic state.

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