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Williams P.L.,Derriford Hospital | Coote J.M.,Royal Devon and Exeter Foundation NHS Trust | Watkinson A.F.,Royal Devon and Exeter Foundation NHS Trust
CardioVascular and Interventional Radiology | Year: 2011

Uterine leiomyomata, or fibroids, although benign, cause debilitating symptoms in many women. Symptoms are often nonspecific and may be the presenting complaint in a number of other conditions. Furthermore, because the presence of fibroids may be coincident with other symptomatic conditions that result in similar complaints, there may be diagnostic difficulty and consequent difficulty in planning therapeutic strategy. Uterine artery embolization (UAE) is a safe and effective treatment for symptomatic fibroids and is increasingly being performed. Magnetic resonance imaging (MRI) evaluation before and after treatment is routine practice with the potential to significantly alter management in up to a fifth of patients. It is well recognized that significant incidental findings may be demonstrated during imaging investigations, and in particular that abnormalities that are not directly related to the clinical question may be overlooked. Radiologists evaluating pre-UAE MRI studies must be aware of the MRI appearances of gynecological pathologies that may cause similar symptoms or that may affect the success or complication rates of UAE, and they must also be wary of "satisfaction of search," reviewing imaging thoroughly so that relevant other pathologies are not missed. We demonstrate the appearances of coincidental pathologies found on pre-UAE MRI, with the potential to change patient management. © Springer Science+Business Media, LLC and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) 2011.

MacKinnon A.C.,Queens Medical Research Institute | Gibbons M.A.,Royal Devon and Exeter Foundation NHS Trust | Farnworth S.L.,Queens Medical Research Institute | Leffler H.,Lund University | And 8 more authors.
American Journal of Respiratory and Critical Care Medicine | Year: 2012

Rationale: Idiopathic pulmonary fibrosis (IPF) is a chronic dysregulated response to alveolar epithelial injury with differentiation of epithelial cells and fibroblasts into matrix-secreting myofibroblasts resulting in lung scaring. The prognosis is poor and there are no effective therapies or reliable biomarkers.Galectin-3 is a β-galactoside binding lectin that is highly expressed in fibrotic tissue of diverse etiologies. Objectives: To examine the role of galectin-3 in pulmonary fibrosis. Methods: We used genetic deletion and pharmacologic inhibition in well-characterizedmurinemodels of lung fibrosis. Further mechanistic studieswere performed in vitro and on samples from patientswith IPF. Measurements and Main Results: Transforming growth factor (TGF)-β and bleomycin-induced lung fibrosis was dramatically reduced in mice deficient in galectin-3, manifest by reduced TGF-β1-induced EMT and myofibroblast activation and collagen production. Galectin-3 reduced phosphorylation and nuclear translocation of β-catenin but had no effect on Smad2/3 phosphorylation. A novel inhibitor of galectin-3, TD139, blocked TGF-β-induced β-catenin activation in vitro and in vivo and attenuated the late-stage progression of lung fibrosis after bleomycin. There was increased expression of galectin-3 in the bronchoalveolar lavage fluid and serum from patients with stable IPF compared with nonspecific interstitial pneumonitis and controls, which rose sharply during an acute exacerbation suggesting that galectin-3 may be a marker of active fibrosis in IPF and that strategies that block galectin-3maybe effective in treating acute fibrotic exacerbations of IPF. Conclusions: This study identifies galectin-3 as an important regulator of lung fibrosis and provides a proof of principle for galectin-3 inhibition as a potential novel therapeutic strategy for IPF. Copyright © 2012 by the American Thoracic Society.

Telford R.J.,Royal Devon and Exeter Foundation NHS Trust
Anaesthesia and Intensive Care Medicine | Year: 2013

Peripheral arterial surgery is challenging; operations are frequently long and associated with insidious blood loss. Because of the high incidence of comorbidities these patients are a high-risk group with a high incidence of morbidity and mortality. They key to successful outcome is meticulous attention to detail by all those professions involved in their care. © 2013 Elsevier Ltd. All rights reserved.

Rice G.I.,University of Manchester | Forte G.M.A.,University of Manchester | Szynkiewicz M.,University of Manchester | Chase D.S.,University of Manchester | And 53 more authors.
The Lancet Neurology | Year: 2013

Background: Aicardi-Goutières syndrome (AGS) is an inflammatory disorder caused by mutations in any of six genes (TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, and ADAR). The disease is severe and effective treatments are urgently needed. We investigated the status of interferon-related biomarkers in patients with AGS with a view to future use in diagnosis and clinical trials. Methods: In this case-control study, samples were collected prospectively from patients with mutation-proven AGS. The expression of six interferon-stimulated genes (ISGs) was measured by quantitative PCR, and the median fold change, when compared with the median of healthy controls, was used to create an interferon score for each patient. Scores higher than the mean of controls plus two SD (>2·466) were designated as positive. Additionally, we collated historical data for interferon activity, measured with a viral cytopathic assay, in CSF and serum from mutation-positive patients with AGS. We also undertook neutralisation assays of interferon activity in serum, and looked for the presence of autoantibodies against a panel of interferon proteins. Findings: 74 (90%) of 82 patients had a positive interferon score (median 12·90, IQR 6·14-20·41) compared with two (7%) of 29 controls (median 0·93, IQR 0·57-1·30). Of the eight patients with a negative interferon score, seven had mutations in RNASEH2B (seven [27%] of all 26 patients with mutations in this gene). Repeat sampling in 16 patients was consistent for the presence or absence of an interferon signature on 39 of 41 occasions. Interferon activity (tested in 147 patients) was negatively correlated with age (CSF, r=-0·604; serum, r=-0·289), and was higher in CSF than in serum in 104 of 136 paired samples. Neutralisation assays suggested that measurable antiviral activity was related to interferon α production. We did not record significantly increased concentrations of autoantibodies to interferon subtypes in patients with AGS, or an association between the presence of autoantibodies and interferon score or serum interferon activity. Interpretation: AGS is consistently associated with an interferon signature, which is apparently sustained over time and can thus be used to differentiate patients with AGS from controls. If future studies show that interferon status is a reactive biomarker, the measurement of an interferon score might prove useful in the assessment of treatment efficacy in clinical trials. Funding: European Union's Seventh Framework Programme; European Research Council. © 2013 Elsevier Ltd.

Gosling O.E.,Musgrove Park Hospital | Morgan-Hughes G.,South West Cardiothoracic Center | Bellenger N.G.,Royal Devon and Exeter Foundation NHS Trust
Clinical Medicine, Journal of the Royal College of Physicians of London | Year: 2014

Symptomatic cardiovascular disease is one of the leading causes of hospital admissions in the UK; along with emergency attendances, over 100,000 patients are investigated using treadmill testing via rapid access chest pain clinics each year. With the introduction of new technologies, clinicians have a wide choice of investigations including nuclear perfusion scanning, dobutamine stress echocardiography, cardiac computed tomography and stress cardiac magnetic resonance imaging. These imaging modalities have their strengths and weaknesses, which depend not only on the pre-test likelihood of significant coronary artery disease but also the clinical characteristics of the patient. This article will review the differing imaging modalities, the patient experience, accuracy, prognostic data and future prospects for cardiac computed tomography and magnetic resonance imaging. © Royal College of Physicians 2014. All rights reserved.

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