Hamish Richardson

The University of Edinburgh, Edinburgh, SCT, United Kingdom

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Publications (6)71.25 Total impact

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    American Journal of Respiratory and Critical Care Medicine 02/2014; 189(4):500-1. · 11.04 Impact Factor
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    ABSTRACT: -18F-Sodium fluoride (18F-NaF) and 18F-fluorodeoxyglucose (18F-FDG) are promising novel biomarkers of disease activity in aortic stenosis. We compared 18F-NaF and 18F-FDG uptake with histological characterization of the aortic valve and assessed whether they predicted disease progression. -Thirty patients with aortic stenosis underwent combined positron emission and computed tomography (PET/CT) using 18F-NaF and 18F-FDG radiotracers. In 12 patients undergoing aortic valve replacement surgery (10 for each tracer), radiotracer uptake (mean TBR) was compared to CD68 (inflammation), alkaline phosphatase and osteocalcin (calcification) immunohistochemistry of the excised valve. In 18 patients (6 aortic sclerosis; 5 mild, 7 moderate), aortic valve CT calcium scoring was performed at baseline and after 1 year. Aortic valve 18F-NaF uptake correlated with both alkaline phosphatase (r=0.65, P=0.04) and osteocalcin (r=0.68, P=0.03) immunohistochemistry. There was no significant correlation between 18F-FDG uptake and CD68 staining (r=-0.43, P=0.22). After 1 year, aortic valve calcification increased from 314 (193-540) to 365 (207-934) Agatston units (P<0.01). Baseline 18F-NaF uptake correlated closely with the change in calcium score (r=0.66, P<0.01) and this improved further (r= 0.75, P<0.01) when 18F-NaF uptake overlying CT-defined macrocalcification was excluded. No significant correlation was noted between valvular 18F-FDG uptake and change in calcium score (r=-0.11, P=0.66). -18F-NaF uptake identifies active tissue calcification and predicts disease progression in patients with calcific aortic stenosis. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01358513.
    Circulation Cardiovascular Imaging 02/2014; · 5.80 Impact Factor
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    ABSTRACT: Rationale: Depletion of monocytes reduces lipopolysaccharide-induced lung inflammation in mice, suggesting monocytes as potential therapeutic targets in acute lung injury. Objectives: To investigate whether depletion of circulating blood monocytes has beneficial effects on markers of systemic and pulmonary inflammation in a human model of acute lung inflammation. Methods: Thirty healthy volunteers were enrolled in a randomized controlled trial. Volunteers inhaled lipopolysaccharide at baseline and were randomized to receive active mononuclear cell depletion by leukapheresis, or sham leukapheresis, in a double-blind fashion (15 volunteers per group). Serial blood counts were measured, bronchoalveolar lavage was performed at 9 hours, and [18F]fluorodeoxyglucose positron emission tomography at 24 hours. The primary end-point was the increment in circulating neutrophils at 8 hours. Measurements and Main Results: As expected, inhalation of lipopolysaccharide induced neutrophilia and an up-regulation of inflammatory mediators in the blood and lungs of all volunteers. There was no significant difference between the depletion and sham groups in the mean increment in blood neutrophil count at 8 hours (6.16 x109/L and 6.15 x109/L respectively, P=1.00). Furthermore, there were no significant differences in bronchoalveolar lavage neutrophils or protein, positron emission tomography-derived measures of global lung inflammation or cytokine levels in plasma or bronchoalveolar lavage supernatant between the study groups. No serious adverse events occurred, and no symptoms were significantly different between the groups. Conclusions: These findings do not support a role for circulating human monocytes in the early recruitment of neutrophils during lipopolysaccharide-mediated acute lung inflammation in humans.
    American Journal of Respiratory and Critical Care Medicine 04/2013; · 11.04 Impact Factor
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    ABSTRACT: With combined positron emission tomography and computed tomography (CT), we investigated coronary arterial uptake of 18F-sodium fluoride (18F-NaF) and 18F-fluorodeoxyglucose (18F-FDG) as markers of active plaque calcification and inflammation, respectively. The noninvasive assessment of coronary artery plaque biology would be a major advance particularly in the identification of vulnerable plaques, which are associated with specific pathological characteristics, including micro-calcification and inflammation. We prospectively recruited 119 volunteers (72 ± 8 years of age, 68% men) with and without aortic valve disease and measured their coronary calcium score and 18F-NaF and 18F-FDG uptake. Patients with a calcium score of 0 were used as control subjects and compared with those with calcific atherosclerosis (calcium score >0). Inter-observer repeatability of coronary 18F-NaF uptake measurements (maximum tissue/background ratio) was excellent (intra-class coefficient 0.99). Activity was higher in patients with coronary atherosclerosis (n = 106) versus control subjects (1.64 ± 0.49 vs. 1.23 ± 0.24; p = 0.003) and correlated with the calcium score (r = 0.652, p < 0.001), although 40% of those with scores >1,000 displayed normal uptake. Patients with increased coronary 18F-NaF activity (n = 40) had higher rates of prior cardiovascular events (p = 0.016) and angina (p = 0.023) and higher Framingham risk scores (p = 0.011). Quantification of coronary 18F-FDG uptake was hampered by myocardial activity and was not increased in patients with atherosclerosis versus control subjects (p = 0.498). 18F-NaF is a promising new approach for the assessment of coronary artery plaque biology. Prospective studies with clinical outcomes are now needed to assess whether coronary 18F-NaF uptake represents a novel marker of plaque vulnerability, recent plaque rupture, and future cardiovascular risk. (An Observational PET/CT Study Examining the Role of Active Valvular Calcification and Inflammation in Patients With Aortic Stenosis; NCT01358513).
    Journal of the American College of Cardiology 04/2012; 59(17):1539-48. · 14.09 Impact Factor
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    ABSTRACT: JAC, 59 (2012) 1539-1548. doi:10.1016/j.jacc.2011.12.037
    Journal of the American College of Cardiology 01/2012; 59(17):1539-1548. · 14.09 Impact Factor
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    ABSTRACT: The pathophysiology of aortic stenosis is incompletely understood, and the relative contributions of valvular calcification and inflammation to disease progression are unknown. Patients with aortic sclerosis and mild, moderate, and severe stenosis were compared prospectively with age- and sex-matched control subjects. Aortic valve severity was determined by echocardiography. Calcification and inflammation in the aortic valve were assessed by 18F-sodium fluoride (18F-NaF) and 18F-fluorodeoxyglucose (18F-FDG) uptake with the use of positron emission tomography. One hundred twenty-one subjects (20 controls; 20 aortic sclerosis; 25 mild, 33 moderate, and 23 severe aortic stenosis) were administered both 18F-NaF and 18F-FDG. Quantification of tracer uptake within the valve demonstrated excellent interobserver repeatability with no fixed or proportional biases and limits of agreement of ±0.21 (18F-NaF) and ±0.13 (18F-FDG) for maximum tissue-to-background ratios. Activity of both tracers was higher in patients with aortic stenosis than in control subjects (18F-NaF: 2.87±0.82 versus 1.55±0.17; 18F-FDG: 1.58±0.21 versus 1.30±0.13; both P<0.001). 18F-NaF uptake displayed a progressive rise with valve severity (r(2)=0.540, P<0.001), with a more modest increase observed for 18F-FDG (r(2)=0.218, P<0.001). Among patients with aortic stenosis, 91% had increased 18F-NaF uptake (>1.97), and 35% had increased 18F-FDG uptake (>1.63). A weak correlation between the activities of these tracers was observed (r(2)=0.174, P<0.001). Positron emission tomography is a novel, feasible, and repeatable approach to the evaluation of valvular calcification and inflammation in patients with aortic stenosis. The frequency and magnitude of increased tracer activity correlate with disease severity and are strongest for 18F-NaF. http://www.clinicaltrials.gov. Unique identifier: NCT01358513.
    Circulation 11/2011; 125(1):76-86. · 15.20 Impact Factor