A5090982455- Ocular Surface and Contact Lens
- Glaucoma and retinal disorders
- Pain Mechanisms and Treatments
- Botulinum Toxin and Related Neurological Disorders
- Retinal Diseases and Treatments
- Corneal surgery and disorders
- Advancements in Transdermal Drug Delivery
- Protease and Inhibitor Mechanisms
- Cardiovascular Disease and Adiposity
- Diabetic Foot Ulcer Assessment and Management
- Forensic Anthropology and Bioarchaeology Studies
- Systemic Sclerosis and Related Diseases
- Musculoskeletal pain and rehabilitation
- Parathyroid Disorders and Treatments
- Bee Products Chemical Analysis
- Paleopathology and ancient diseases
- Atherosclerosis and Cardiovascular Diseases
- Mast cells and histamine
- Lymphatic System and Diseases
- Spine and Intervertebral Disc Pathology
- Reproductive System and Pregnancy
- Cerebrovascular and Carotid Artery Diseases
- Sarcoma Diagnosis and Treatment
- Angiogenesis and VEGF in Cancer
- Adipose Tissue and Metabolism
University of Manchester
2013-2022
NIHR Wellcome Trust Southampton Clinical Research Facility
2015-2021
NIHR Manchester Biomedical Research Centre
2020
Manchester University NHS Foundation Trust
2019
Manchester Royal Infirmary
1996-2017
Wellcome Trust
2009-2017
Manchester Academic Health Science Centre
2014-2017
National Institute for Health Research
2017
LMC Diabetes & Endocrinology (Canada)
2001-2017
University of Babylon
2015
Background— Inflammation in adipose tissue has been implicated vascular dysfunction, but the local mechanisms by which this occurs are unknown. Methods and Results— Small arteries with without perivascular were taken from subcutaneous gluteal fat biopsy samples studied wire myography immunohistochemistry. We established that healthy around human small secretes factors influence vasodilation increasing nitric oxide bioavailability. However, obese subjects metabolic syndrome (waist...
Surrogate markers of diabetic neuropathy are being actively sought to facilitate the diagnosis, measure progression, and assess benefits therapeutic intervention in patients with neuropathy. We have quantified small nerve fiber pathological changes using technique intraepidermal (IENF) assessment novel vivo corneal confocal microscopy (CCM). Fifty-four stratified for neuropathy, neurological evaluation, neurophysiology, quantitative sensory testing, 15 control subjects were studied. They...
Abstract Following a previous description of nociceptive nerve fibre growth into usually aneural inner parts painful intervertebral disc (IVD), this study has investigated whether ingrowth IVD is stimulated by local production neurotrophins. Immunohistochemistry and in situ hybridization have been used to investigate expression the candidate neurotrophin, factor (NGF), its high‐ low‐affinity receptors trk‐A p75, respectively, excised for management low back pain. from patients with pain were...
Diabetic neuropathy is associated with increased morbidity and mortality. To date, limited data in subjects impaired glucose tolerance diabetes demonstrate nerve fiber repair after intervention. This may reflect a lack of efficacy the interventions but also difficulty tests currently deployed to adequately assess repair, particularly short-term studies. Corneal confocal microscopy (CCM) represents novel noninvasive means quantify damage repair. Fifteen type 1 diabetic patients undergoing...
OBJECTIVE Quantitative assessment of small fiber damage is key to the early diagnosis and progression or regression diabetic sensorimotor polyneuropathy (DSPN). Intraepidermal nerve density (IENFD) current gold standard, but corneal confocal microscopy (CCM), an in vivo ophthalmic imaging modality, has potential be a noninvasive objective image biomarker for identifying damage. The purpose this study was determine diagnostic performance CCM IENFD by using guidelines as reference standard....
The aim of this study was to investigate the effects bariatric surgery on small artery function and mechanisms underlying this.In lean healthy humans, perivascular adipose tissue (PVAT) exerts an anticontractile effect adjacent arteries, but is lost in obesity-associated conditions such as metabolic syndrome type II diabetes where there evidence adipocyte inflammation increased oxidative stress.Segments subcutaneous fat were harvested from severely obese individuals before (n = 20) 6 months...
Impaired glucose tolerance (IGT) represents one of the earliest stages dysregulation and is associated with macrovascular disease, retinopathy, microalbuminuria, but whether IGT causes neuropathy unclear.Thirty-seven subjects 20 age-matched control underwent a comprehensive evaluation by assessing symptoms, neurological deficits, nerve conduction studies, quantitative sensory testing, heart rate variability deep breathing (HRVdb), skin biopsy, corneal confocal microscopy (CCM).Subjects had...
Corneal confocal microscopy (CCM) is a rapid, non-invasive, reproducible technique that quantifies small nerve fibres. We have compared the diagnostic capability of CCM against range established measures damage in patients with diabetic neuropathy.In this cross sectional study, thirty subjects Type 1 diabetes without neuropathy (T1DM), one T1DM (DSPN) and twenty seven non-diabetic healthy control underwent detailed assessment neuropathic symptoms neurologic deficits, quantitative sensory...
Small cohort studies raise the hypothesis that corneal nerve abnormalities (including fibre length [CNFL]) are valid non-invasive imaging endpoints for diabetic sensorimotor polyneuropathy (DSP). We aimed to establish concurrent validity and diagnostic thresholds in a large of participants with without DSP. Nine hundred ninety-eight from five centres (516 type 1 diabetes 482 2 diabetes) underwent CNFL quantification clinical electrophysiological examination. AUC were derived validated...
Autonomic and somatic denervation is well established in Parkinson's disease (PD).Objectives(1) To determine whether corneal confocal microscopy (CCM) can non-invasively demonstrate small nerve fiber damage PD. (2) identify relationships between parameters, intraepidermal density (IENFD) clinical features of PD.MethodsTwenty-six PD patients 26 controls underwent CCM both eyes. 24/26 10/26 skin biopsies from the dorsa feet. assessment parasympathetic function [deep breathing heart rate...
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...
Muscle weakness and atrophy of the lower limbs may develop in patients with diabetes, increasing their risk falls. The underlying basis these abnormalities has not been fully explained. aim this study was to objectively quantify muscle strength size type 2 diabetes mellitus (T2DM) relation severity neuropathy, intramuscular noncontractile tissue (IMNCT), vitamin D deficiency.
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...
Purpose: Sarcoidosis frequently is complicated by small nerve fiber loss (SNFL), which can be quantified using corneal confocal microscopy (CCM). Prior studies suggest that the innate repair receptor agonist cibinetide reverses loss. This phase 2b, 28-day, randomized trial of 64 subjects with sarcoid-associated SNFL and neuropathic pain assessed effect on area (CNFA) regenerating intraepidermal fibers (GAP-43+) as surrogate endpoints for disease modification, severity, functional capacity...
OBJECTIVE To assess the diagnostic utility of corneal confocal microscopy (CCM) for diabetic peripheral neuropathy (DPN) and risk factors nerve loss. RESEARCH DESIGN AND METHODS A total 490 participants, including 72 healthy control subjects, 149 with type 1 diabetes, 269 2 underwent detailed assessment CCM in relation to factors. RESULTS Corneal fiber density (CNFD) (P < 0.0001 P 0.0001), branch (CNBD) length (CNFL) = 0.02) were significantly lower patients diabetes compared...
An improved immunohistochemical method has been used to assess neovascularization within the vulnerable 'shoulder' regions of atherosclerotic plaques from carotid arteries. A combination monoclonal antibodies (CD31, CD34, +/- von Willebrand factor) was shown be far more effective than conventional techniques in demonstrating extensive vascularizations and cap late-stage plaques. Such sites were microfocal, often appearing as a plexus both large small vessels which occupied significant...
Immunohistochemical staining for mast cell tryptase and chymase was used to examine the distribution, activation, tryptase/chymase phenotype of cells (MCs) in 250 samples atherosclerotic lesions (type I VI) human carotid arteries. Dual immunolocalization histochemical techniques were identify associations MCs with macrophages, smooth muscle cells, extracellular matrix components. Whereas normal arteries contained very few within intima, showed increased MC numbers variable focal...
Tryptase and chymase immunolocalization techniques have been used to examine the distribution, activation, tryptase/chymase phenotype of mast cells (MCs) in 107 endometrial specimens that represented every day human menstrual cycle. MCs were identified endometrium all stages cycle; similar MC numbers observed for functionalis, basalis, muscularis. Extensive activation/degranulation, as judged by extracellular tryptase, was a common feature functionalis sampled just prior during menstruation....
OBJECTIVE—To assess the relevance of vascular endothelial growth factor (VEGF) in maintenance peripheral nerve integrity diabetic neuropathy we have assessed expression VEGF and intra-epidermal fiber density (IENFD) skin biopsy samples from patients. RESEARCH DESIGN AND METHODS—Fifty-three patients 12 nondiabetic control subjects underwent neurological evaluation, electrophysiology, quantitative sensory, autonomic function testing. Dermal blood flow responses were evaluated with laser...
Impaired rate-dependent depression (RDD) of the Hoffman reflex is associated with reduced dorsal spinal cord potassium chloride cotransporter expression and impaired γ-aminobutyric acid type A receptor function, indicative inhibitory dysfunction. We have investigated pathogenesis RDD in diabetic rodents exhibiting features painful neuropathy translational potential this marker dysfunction human neuropathy. allodynia were present 1 2 rats but not diabetes receiving insulin supplementation...
Abstract BACKGROUND Diabetic peripheral neuropathy (DPN) can lead to foot ulceration and amputation. There are currently no disease-modifying therapies for DPN. The aim of this study was determine if hypertension contributes DPN in patients with type 1 diabetes mellitus (T1DM). METHODS Subjects T1DM (n = 70) controls 78) underwent a comprehensive assessment RESULTS Hypertension present 40 70 subjects 20 78 controls. associated abnormal nerve conduction parameters (P 0.03 <0.001),...
OBJECTIVE Corneal nerve fiber length (CNFL) represents a biomarker for diabetic distal symmetric polyneuropathy (DSP). We aimed to determine the reference distribution of annual CNFL change, prevalence abnormal change in diabetes, and its associated clinical variables. RESEARCH DESIGN AND METHODS examined 590 participants with diabetes (399 type 1 [T1D] 191 2 [T2D]) 204 control patients without at least year follow-up classified them according rapid corneal loss (RCNFL) if was below 5th...
Calcification has been examined in 250 samples of atherosclerotic lesions (types II to VI) human carotid arteries using von Kossa and haematoxylin staining. Early calcification described as 'stippling' was first noted stage III specimens, with intermediate solid calcifications becoming increasingly prominent within advanced plaques, especially stages Vb VI. Although the relative frequencies stippling, large calcified deposits varied between plaques same stage, prevalent sites were recognized...