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Gulati R.,Mayo Medical School | Raphael C.E.,NIHR Cardiovascular Biomedical Research Unit | Negoita M.,Medtronic Inc. | Pocock S.J.,London School of Hygiene and Tropical Medicine | Gersh B.J.,Mayo Medical School
Nature Reviews Cardiology | Year: 2016

Renal denervation has a chequered history. Dramatic reductions in blood pressure after denervation of the renal arteries were observed in early trials, but later trials in which denervation was tested against a sham procedure produced neutral results. Although a sound pathophysiological basis exists for interruption of the renal sympathetic nervous system as a treatment for hypertension, trial data to date are insufficient to support renal denervation as an established clinical therapy. In this Perspectives article, we summarize the currently available trial data, device development, and trials in progress, and provide recommendations for future trial design. © 2016 Macmillan Publishers Limited.

Watt V.,University of Sheffield | Chamberlain J.,University of Sheffield | Steiner T.,University of Sheffield | Francis S.,University of Sheffield | And 2 more authors.
Atherosclerosis | Year: 2011

TRAIL (tumour necrosis factor-related apoptosis inducing ligand) is most often reported to induce apoptosis in tumour cells. It is expressed in artery walls but its role and regulation in vascular pathologies is little studied.We aimed to measure the effect of genetic deletion of TRAIL on atherosclerosis in a mouse model. TRAIL was mainly expressed in endothelium, smooth muscle cells and macrophages within plaques. The absence of TRAIL in chow and in fat-fed mice led to greater lesion coverage in aortae (8 weeks, % area ± SEM), n= 7-8, 1.24 ± 0.2 (no TRAIL, chow diet) vs. 0.42 ± 0.1, p< 0.01 and 3.4 ± 0.8 (no TRAIL, Western diet) vs. 0.94 ± 0.2, p< 0.01 and larger, smooth muscle cell rich lesions at aortic roots than control mice (8 weeks, mean lesion area/total cross sectional area ± SEM, n= 7-8, 0.17 ± 0.01 (no TRAIL, chow diet) vs. 0.135 ± 0.006, p< 0.05 and 0.36 ± 0.03 (no TRAIL, Western diet) vs. 0.23 ± 0.02, p< 0.05) particularly at early time points. The larger early lesions appeared to be as a result of increased smooth muscle cells in lesions of TRAIL deficient, pro-atherosclerotic animals. We conclude that TRAIL attenuates plaque size at early stages of atherosclerosis. © 2011 Elsevier Ireland Ltd.

Bourke L.,Queen Mary, University of London | Kirkbride P.,Consultant Clinical Oncologist | Hooper R.,Queen Mary, University of London | Rosario A.J.,Foxhill Medical Center | And 3 more authors.
British Journal of Cancer | Year: 2013

In the 70 years following the first description of the benefits of surgical castration, despite advances in medical therapy e.g. cabazitaxel, enzalutamide, abiraterone, androgen deprivation therapy (ADT) remains the cornerstone of treatment for advanced prostate cancer. However, with increasing numbers of men undergoing PSA testing, the disease is being diagnosed earlier and the costs of ADT, with uncertain survival benefits and associated risks, have risen dramatically. Clinical studies of potent novel agents have shown survival benefits in advanced disease, but timing, risks and cost-effectiveness of treatment remain controversial. As new agents enter clinical practice, a comprehensive research strategy is essential to optimise benefits whilst minimising harm. © 2013 Cancer Research UK. All rights reserved.

Ellam T.J.,Sheffield Kidney Institute Sorby Wing | Ellam T.J.,NIHR Cardiovascular Biomedical Research Unit
Nephron - Clinical Practice | Year: 2011

Current guidelines illogically recommend that a different approach is taken to the correction for creatinine generation rate when estimating glomerular filtration rate (GFR) and when interpreting urine albumin:creatinine ratio (ACR). Age, gender and race are routinely used to adjust for predicted muscle mass in GFR estimation, even though estimated GFR is expressed per unit body surface area. Conversely, ACR is at most adjusted with the use of gender-specific classification thresholds. This difference is surprising since the proportional effect of muscle mass on serum and urine creatinine is identical. Failure to adjust for creatinine generation rate compromises ACR, potentially adversely affecting management decisions and mislabelling individuals as having/not having CKD. A greater ACR is also a marker of low muscle mass, which has confounding prognostic effects. Determination of the optimal method to adjust ACR for estimated muscle mass should improve its performance. Routine reporting of the resulting 'estimated albumin excretion rate', as for routine eGFR reporting, would remove the need for gender-specific thresholds. Copyright © 2011 S. Karger AG, Basel.

Objective: Among people with Marfan syndrome who have a typical aortic root aneurysm, dissection is a characteristic cause of premature death. To pre-empt Type A dissection, composite root replacement with a mechanical valve became the standard of care in the 1980s and 1990s. This is being superseded by valvesparing aortic root replacement to avoid lifelong anticoagulation. In 2004, a total root and valve-sparing procedure, personalised external aortic support, was introduced. We report here results among the first 30 recipients. Methods: From cross-sectional digital images, the patient's own aorta is modelled by computer aided design and a replica is made in thermoplastic by rapid prototyping. On this, a personalised support of a macroporous polymer mesh is manufactured. The mesh is positioned around the aorta, closely applied from the aortoventricular junction to beyond the brachiocephalic artery. The operation is performed with a beating heart and usually without cardiopulmonary bypass. Results: Between 2004 and 2011, 30 patients, median age 28 years (IQR 20-44) had this operation and have been prospectively followed for 1.4-8.8 years by February 2013. During a total of 133 patient-years there were no deaths or cerebrovascular, aortic or valve-related events. These early outcomes are better than published results for the more radical extirpative root replacement operations. Conclusions: The aortic valve, the root architecture, and the blood/endothelia interface are conserved. The perioperative burden is less and there has been freedom from aortic and valvular events. A prospective comparative study is planned.

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