A5080048059- Cardiac electrophysiology and arrhythmias
- Cardiac Arrhythmias and Treatments
- Cardiovascular Function and Risk Factors
- Cardiovascular Effects of Exercise
- Ion channel regulation and function
- Cardiomyopathy and Myosin Studies
- Cardiac pacing and defibrillation studies
- MicroRNA in disease regulation
- Cardiac Fibrosis and Remodeling
- Cardiac Imaging and Diagnostics
- Trauma, Hemostasis, Coagulopathy, Resuscitation
- Glaucoma and retinal disorders
- Congenital heart defects research
- Ocular Surface and Contact Lens
- Retinal Diseases and Treatments
- Receptor Mechanisms and Signaling
- Cardiac Valve Diseases and Treatments
- Blood transfusion and management
- Cardiovascular Disease and Adiposity
- Parkinson's Disease Mechanisms and Treatments
- Neurological disorders and treatments
- Botulinum Toxin and Related Neurological Disorders
- Advanced Neuroimaging Techniques and Applications
- Atrial Fibrillation Management and Outcomes
- Retinal Development and Disorders
University of Manchester
2014-2025
United States Army Medical Research and Development Command
2016-2021
Manchester Academic Health Science Centre
2015-2021
Atkins (United Kingdom)
2020
Manchester University NHS Foundation Trust
2019
University of Leeds
1971-2016
Cardiovascular Research Center
2016
Kagawa Prefectural College of Health Sciences
2016
University of California, San Francisco
2016
National Health Service
2015
OBJECTIVE Impaired glucose tolerance (IGT) through to type 2 diabetes is thought confer a continuum of risk for neuropathy. Identification subjects at high developing and, hence, worsening neuropathy would allow identification and stratification more aggressive management. RESEARCH DESIGN AND METHODS Thirty with IGT 17 age-matched control underwent an oral test, assessment neuropathic symptoms deficits, quantitative sensory testing, neurophysiology, skin biopsy, corneal confocal microscopy...
Abstract Cardiac arrhythmias and conduction disturbances are accompanied by structural remodelling of the specialised cardiomyocytes known collectively as cardiac system. Here, using contrast enhanced micro-computed tomography, we present, in attitudinally appropriate fashion, first 3-dimensional representations system within intact human heart. We show that cardiomyocyte orientation can be extracted from these datasets at spatial resolutions approaching single cell. These data commonly...
The study aimed to assess the impact on neuropathy of simultaneous pancreas and kidney transplantation (SPK) in individuals with type 1 diabetes. This longitudinal observational examined neuropathic symptoms, deficits, quantitative sensory testing, neurophysiology, corneal confocal microscopy skin biopsy results 32 healthy (non-diabetic) control participants, 29 diabetes severe diabetic peripheral [DPN] 36 after SPK. Following SPK, HbA1c, eGFR, triacylglycerols HDL improved significantly...
Abstract We have previously shown in rabbit that the pacemaker of heart (the sinus node) is widespread and matches wide distribution leading site within right atrium. There is, however, uncertainty about precise location human heart, its spatial relationships with surrounding atrial muscle. Therefore, aim current study was to investigate node tissue a series healthy hearts and, for one construct computer three‐dimensional anatomical model node, including likely orientation myocytes. A...
The function of the sino-atrial node (SAN), pacemaker heart, is known to decline with age, resulting in disease elderly. aim study was investigate effects ageing on SAN by characterizing electrophysiological changes and determining whether gene expression are involved. In young old rats, characterized anaesthetized animal, isolated heart right atrium using ECG action potential recordings; quantitative PCR. declined age as follows: intrinsic rate 18 ± 3%; corrected recovery time increased 43...
We investigated whether the T7 system of phage display could produce peptide libraries greater diversity than M13 due to differing processes lytic and filamentous morphogenesis. Using a bioinformatics-assisted computational approach, collections random sequences obtained from 12-mer library (X(12)) 7-mer disulfide-constrained (CX(7)C) were analyzed compared with populations New England BioLabs' Ph.D.-12 Ph.D.-C7C libraries. Based on this analysis, constructed have fewer amino acid biases,...
Background The cardiac conduction system consists of the sinus node, nodal extensions, atrioventricular ( AV ) penetrating bundle, bundle branches, and P urkinje fibers. Node‐like ring tissue also exists at junctions, right left rings unite retroaortic node. study aims were to (1) construct a 3‐dimensional anatomical model (2) map electrical activation in its action potential characteristics, (3) examine gene expression Methods Results Three‐dimensional reconstruction (based on magnetic...
Abstract Bradyarrhythmias are an important cause of mortality in heart failure and previous studies indicate a mechanistic role for electrical remodelling the key pacemaking ion channel HCN4 this process. Here we show that, mouse model which there is sinus bradycardia, upregulation microRNA (miR-370-3p), downregulation pacemaker channel, HCN4, corresponding ionic current, I f , node. In vitro, exogenous miR-370-3p inhibits mRNA causes protein, bradycardia isolated vivo, intraperitoneal...
Abstract Accurately quantifying the progression of diabetic peripheral neuropathy is key to identify individuals who will progress foot ulceration and power clinical intervention trials. We have undertaken detailed phenotyping assess longitudinal utility different measures in patients with diabetes. Nineteen diabetes (age 52.5 ± 14.7 years, duration 26.0 13.8 years) 19 healthy controls underwent assessment symptoms signs neuropathy, quantitative sensory testing, autonomic nerve function,...
High-resolution digitized cardiac anatomical data sets are in huge demand clinical, basic research and computational settings. They can be leveraged to evaluate intricate structural changes disease pathology, such as myocardial infarction (MI), which is one of the most common causes heart failure death. Advancements high-resolution imaging techniques this field our laboratory have led vast improvements understanding cardiovascular anatomy, especially conduction system (CCS) responsible for...
Tuberous sclerosis is a well-defined clinical entity characterized by triad of epilepsy, mental retardation, and adenoma sebaceum, with excellent descriptions elsewhere (Critchley Earl, I932; Lagos Gomez, I967).The principal ocular manifesta- tions comprise retinal tumours two morphological types (van der Hoeve, 1920, 192I).Elevated mulberry-like are found characteristically in the posterior pole where they may resemble drusen disc.Each tumour appears as whitish-grey glistening mass, studded...
Background The sinus node (SN) is the primary pacemaker of heart. SN myocytes possess distinctive action potential morphology with spontaneous diastolic depolarization because a unique expression ion channels and Ca 2+ ‐handling proteins. MicroRNAs (miRs) inhibit gene expression. role miRs in controlling genes responsible for human pacemaking conduction has not been explored. aim this study was to determine miR profile as compared that non‐pacemaker atrial muscle. Methods Results muscle...
Introduction The sinus node (SN) is the main pacemaker site of heart, located in upper right atrium at junction superior vena cava and atrium. precise morphology SN human heart remains relatively unclear especially microscopical anatomy hearts aged obese individuals. In this study, histology with surrounding atrial (RA) muscle was analyzed from young non-obese, impacts aging obesity on fibrosis, apoptosis cellular hypertrophy were investigated RA. Moreover, impact P wave ECG also to...
Heart failure is a major killer worldwide. Atrioventricular conduction block common in heart failure; it associated with worse outcomes and can lead to syncope bradycardic death. We examine the effect of on anatomical ion channel remodelling rabbit atrioventricular junction (AVJ). was induced New Zealand rabbits by disruption aortic valve banding abdominal aorta resulting volume pressure overload. Laser micro-dissection real-time polymerase chain reaction (RT-PCR) were employed investigate...
Background: KCNMA1 encodes the α-subunit of large-conductance Ca 2+ -activated K + channel, 1.1, and lies within a linkage interval for atrial fibrillation (AF). Insights into cardiac functions 1.1 are limited, has not been investigated as an AF candidate gene. Methods: The gene was sequenced in 118 patients with familial AF. role normal structure function evaluated humans, mice, zebrafish, fly. A novel variant functionally characterized. Results: complex identified 1 kindred To evaluate...
Denaturing high performance liquid chromatography (DHPLC) using ion-pairing reverse phase (IPRPC) columns is a technique for the screening of gene mutations. In order to evaluate potential utility this assay method in clinical laboratory setting, we subjected PCR products 73 CF patients known bear CFTR mutations analytic technique. We used thermal denaturation profile parameters specified by MELT program tool, made available Stanford University. Using strategy, determined an initial...
Heart block is associated with pulmonary hypertension, and the aim of study was to test hypothesis that heart result a change in ion channel transcriptome atrioventricular (AV) node.The most commonly used animal model monocrotaline-injected rat, used. The functional consequences monocrotaline injection were determined by echocardiography, ECG recording, electrophysiological experiments on Langendorff-perfused isolated AV node. measured quantitative PCR, biophysically detailed computer...