Chris J Taylor

Chris J Taylor
The University of Sheffield | Sheffield · Academic Unit of Child Health

MD, FRCP, FRCPCH, DCH

About

150
Publications
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Introduction

Publications

Publications (150)
Article
Full-text available
Cystic fibrosis results from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-dependent protein kinase A (PKA) and ATP-regulated chloride channel. Here, we demonstrate that nucleoside diphosphate kinase B (NDPK-B, NM23-H2) forms a functional complex with CFTR. In airway epithelia forskolin/IBMX significantly incre...
Article
Full-text available
Background: Zenpep (APT-1008) is a pancreatic enzyme product for the treatment of exocrine pancreatic insufficiency (EPI) associated with cystic fibrosis (CF). Methods: Zenpep and Kreon, both containing 25,000 lipase units, were compared in a randomised, double-blind, crossover, non-inferiority study for CF-associated EPI in patients aged ≥12yea...
Article
Objectives An investigational PEP (APT-1008, to be marketed in Europe as ENZEPI®) was compared to KREON® in the treatment of EPI associated with CF. Methods This was a randomized, double-blind, active-controlled, 2-arm crossover, multinational, multicentre study comparing APT-1008 (APT) to KREON in the treatment of EPI in patients ≥12 years of age...
Article
Purpose: To develop significance testing methodology applicable to spatially heterogeneous parametric maps of biophysical and physiological measurements arising from imaging studies. Theory: Heterogeneity can confound statistical analyses. Indexed distribution analysis (IDA) transforms a reference distribution, establishing correspondences acros...
Article
Objective: The transverse relaxation time (T2) in MR imaging has been identified as a potential biomarker of hyaline cartilage pathology. This study investigates whether MR assessments of T2 are comparable between 3-T scanners from three different vendors. Design: Twelve subjects with symptoms of knee osteoarthritis and one or more risk factors...
Article
Complete or incomplete intestinal obstruction by viscid faecal material in the terminal ileum and proximal colon - distal intestinal obstruction syndrome (DIOS) - is a common complication in cystic fibrosis. Estimates of prevalence range from 5 to 12 episodes per 1000 patients per year in children, with higher rates reported in adults. DIOS is main...
Article
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Cartilage thickness from MR images has been identified as a possible biomarker in knee osteoarthritis (OA) research. The ability to acquire MR data at multiple centers by using different vendors' scanners would facilitate patient recruitment and shorten the duration of OA trials. Several vendors manufacture 3T MR scanners, including Siemens, Philip...
Article
Post-natal screening allied with genetic mutation testing has altered our perception of cystic fibrosis (CF) as a clinical entity. Increasingly, infants identified through screening programmes have few or no symptoms or present with atypical forms of the disease. We review how the sweat test has evolved to be the gold standard for confirming the di...
Article
To determine whether regional changes in lung ventilation in a group of pediatric cystic fibrosis (CF) patients following a course of chest physiotherapy could be detected with (3)He MRI. The reproducibility of lung ventilation volume measurements obtained with (3)He lung magnetic resonance imaging (MRI) was established in a group of five children...
Article
Full-text available
A subset (approximately 3%-5%) of patients with cystic fibrosis (CF) develops severe liver disease with portal hypertension. To assess whether any of 9 polymorphisms in 5 candidate genes (alpha(1)-antitrypsin or alpha(1)-antiprotease [SERPINA1], angiotensin-converting enzyme [ACE], glutathione S-transferase [GSTP1], mannose-binding lectin 2 [MBL2],...
Article
When using tracer kinetic modeling to analyze dynamic contrast-enhanced MRI (DCE-MRI) it is necessary to identify an appropriate arterial input function (AIF). The measured AIF is often poorly sampled in both clinical and preclinical MR systems due to the initial rapid increase in contrast agent concentration and the subsequent large-scale signal c...
Article
Background: Reports linking high pancreatic enzyme dosages with bowel stricturing in children with cystic fibrosis (CF) led us to review our policy for pancreatic enzyme supplementation. Methods: Twenty-five prepubertal children with CF, aged 3–10 years, underwent a programme of pancreatin reduction. They were encouraged to decrease their enzyme in...
Article
Full-text available
Following homozygosity mapping in a single kindred, we identified nonsense and missense mutations in MYO5B, encoding type Vb myosin motor protein, in individuals with microvillus inclusion disease (MVID). MVID is characterized by lack of microvilli on the surface of enterocytes and occurrence of intracellular vacuolar structures containing microvil...
Article
Full-text available
Growth hormone (GH) stimulates linear growth and improves nitrogen balance in many catabolic states, including sepsis, and in malnutrition associated with chronic obstructive pulmonary disease. In children with cystic fibrosis (CF), these anabolic effects could aid survival and enhance suitability for transplantation. We assessed response to 0.49 I...
Article
Non-rigid registration finds a dense correspondence between a pair of images, so that analogous structures in the two images are aligned. While this is sufficient for atlas comparisons, in order for registration to be an aid to diagnosis, registrations need to be performed on a set of images. In this paper, we describe an objective function that ca...
Article
The objective was to measure the effect of 100% oxygen inhalation on T1 relaxation times in skeletal muscle. Healthy volunteers were scanned using three different MRI protocols while breathing medical air and 100% oxygen. Measurements of T1 were made from regions of interest (ROIs) within various skeletal muscle groups. Dynamic data of subjects bre...
Article
Full-text available
Cystic fibrosis results from mutations in the cystic fibrosis conductance regulator protein (CFTR), a cAMP/protein kinase A (PKA) and ATP-regulated Cl(-) channel. CFTR is increasingly recognized as a component of multiprotein complexes and although several inhibitory proteins to CFTR have been identified, protein complexes that stimulate CFTR funct...
Article
To investigate the occurrence of microsatellite instability (MSI) in paediatric Barrett's oesophagus (BE) with the aim of identifying a potential marker for patients at risk for developing dysplasia or adenocarcinoma at a later stage. Endoscopic oesophageal biopsies from 6 pediatric patients harbouring BE and 6 age-matched controls were retrospecti...
Article
Full-text available
This study assesses the feasibility of hyperpolarized 3-Helium MRI in children with cystic fibrosis (CF) and correlates the findings with standard clinical parameters based on chest radiograph (CXR) and pulmonary function tests (PFT). An uncontrolled, observational study in eighteen children with cystic fibrosis aged 5 - 17 years (median 12.1 years...
Article
With a combined gamma camera/CT imaging system, CT images are obtained which are inherently registered to the emission images and can be used for the attenuation correction of SPECT and for mapping the functional information from these nuclear medicine tomograms onto anatomy. The aim of this study was to evaluate the clinical impact of SPECT/CT usi...
Article
The application of molecular methods to gastro-intestinal diseases is giving insight into the way in which the resident intestinal microbiota interacts with the mucosal immune system. Using traditional culture techniques, the importance of mucosally-associated bacterial biofilms in maintaining mucosal integrity has been demonstrated in ways previou...
Article
Full-text available
There is great heterogeneity in the clinical manifestations of cystic fibrosis (CF). Some patients may have all the classical manifestations of CF from infancy and have a relatively poor prognosis, while others have much milder or even atypical disease manifestations and still carry mutations on each of the CFTR genes. It is important to distinguis...
Article
Disease phenotype in cystic fibrosis (CF) shows considerable heterogeneity. Atypical or mild mutations in the CFTR gene have been linked to late-onset pulmonary disease; however, few reports document the condition of the airway in infants and young children with apparent "mild" disease. Prognosis is uncertain in this group of patients and this, in...
Article
Full-text available
Flat adenomas of the colon and duodenum have been described as associating with familial adenomatous polyposis (FAP), its attenuated variant, and the so-called hereditary nonpolyposis colorectal cancer. There seem to be no report on the occurrence of flat adenomas in pediatric patients with family history of FAP. We are reporting 4 children from 2...
Article
The intestinal epithelium regulates the transport of nutrients, electrolytes and water. CFTR, which is present in abundance at the luminal membrane, is central to these processes. Dysfunction leads to impaired intestinal Cl− and fluid secretion while Na+ and Na+-linked nutrient absorption areenhanced.The resulting dehydration of luminal contents co...
Article
Full-text available
In the past eight years magnetic resonance imaging has been used to detect fetal abnormalities in utero at many centres around the world. An increasing number of published papers have shown improved diagnostic accuracy with in utero magnetic resonance imaging compared with obstetric ultrasonography, the current reference standard. This is particula...
Article
To investigate regional airways obstruction in patients with cystic fibrosis (CF) with quantitative analysis of dynamic hyperpolarized (HP) (3)He MRI. Dynamic radial projection MRI of HP (3)He gas was used to study respiratory dynamics in a group of eight children with CF. Signal kinetics in a total of seven regions of interest (ROIs; three in each...
Article
Oxygen-enhanced MR imaging has been demonstrated in a number of recent studies as a potential method to visualize regional ventilation in the lung. A quantitative pixel-by-pixel analysis is hampered by motion and volume change due to breathing. In this study, image registration via active shape modeling is shown to produce significant improvements...
Conference Paper
Full-text available
The non-rigid registration of a group of images shares a common feature with building a model of a group of images: a dense, consistent correspondence across the group. Image registration aims to find the correspondence, while modelling requires it. This paper presents the theoretical framework required to unify these two areas, providing a groupwi...
Conference Paper
Full-text available
Osteoarthritis (OA) involves changes in the composition and ultimately the loss of cartilage from articulating joints. MRI has the ability to non-invasively probe the compositional integrity of cartilage, thereby potentially identifying diseased cartilage before loss occurs. In this study we have developed a technique to compare local changes in si...
Conference Paper
Full-text available
Oxygen enhanced MR imaging of the lung is a promising technique for monitoring a range of pulmonary diseases but regional analysis is hampered by lung motion and volume changes due to breathing. We have developed an image registration method to improve the quantitative regional analysis of both static and dynamic oxygen-enhanced pulmonary MRI. Imag...
Article
Changes in intestinal transport in cystic fibrosis (CF) include both defective Cl(-) secretion and alterations in absorption. This study focused on the effects of CF on the active re-absorption of bile acids in the ileum of normal and transgenic CF mice. Taurocholic acid absorption was monitored as changes in short-circuit current (SCC) in intact a...
Article
This document describes methods of building models of shape and appearance, and how such models can be used to interpret images
Article
Intestinal transport is disturbed in cystic fibrosis (CF), with both defective Cl- secretion and changes in absorption being reported. We have examined the effects of the disease on Na(+)-dependent glucose absorption by the small intestine. Active glucose absorption was monitored as changes in short-circuit current (SCC) in intact and stripped inte...
Article
Statistical shape models are used widely as a basis for segmenting and interpreting images. A major drawback of the approach is the need, during training, to establish a dense correspondence across a training set of segmented shapes. We show that model construction can be treated as an optimisation problem, automating the process and guaranteeing t...
Conference Paper
Full-text available
This paper introduces a novel groupwise data-driven algorithm for non-rigid registration. The motivation behind the algorithm is to enable the analysis of groups of registered images; to this end, the algorithm automatically constructs a low-dimensional, common representation of the warp fields. We demonstrate the algorithm on an example set of 2D...
Article
Objectives Thromboembolism is a significant cause of morbidity and mortality in patients with inflammatory bowel disease (IBD). Plasma total homocysteine (tHcy) is a risk factor for vascular disease and has been implicated as a mediator of thromboembolic events in adults with IBD. The authors studied the link between tHcy and IBD in children, in wh...
Article
Thromboembolism is a significant cause of morbidity and mortality in patients with inflammatory bowel disease (IBD). Plasma total homocysteine (tHcy) is a risk factor for vascular disease and has been implicated as a mediator of thromboembolic events in adults with IBD. The authors studied the link between tHcy and IBD in children, in whom associat...
Article
Normal growth patterns are seen throughout the first decade in children with cystic fibrosis (CF). Growth in the second decade is, however, less satisfactory and may reflect pubertal delay. This study was performed to assess the extent of pubertal delay, to examine factors that influence the timing and magnitude of the pubertal growth spurt, and to...
Article
We extend recent work on building 3D statistical shape models, automatically, from sets of training shapes and describe an application in shape analysis. Using an existing measure of model quality, based on a minimum description length criterion, and an existing method of surface re-parameterisation, we introduce a new approach to model optimisatio...
Article
Full-text available
The correspondence problem is of high relevance in the construction and use of statistical models. Statistical models are used for a variety of medical application, e.g. segmentation, registration and shape analysis. In this paper, we present comparative studies in three anatomical structures of four different correspondence establishing methods. T...
Article
A number of studies have suggested that the non-antimicrobial actions of macrolide antibiotics may be valuable in treating patients with cystic fibrosis. The use of long-term macrolide antibiotics for the management of CF patients colonised by Pseudomonas aeruginosa and progressive pulmonary disease was introduced into our clinic in 1997. A retrosp...
Article
Statistical shape models are widely used as a basis for segmenting and interpreting images. A majordrawback of this approach is the need to identify corresponding points across a training set of example shapeoutlines. In 2D, this can be achieved by `manual landmarking' but in 3D, this becomes impractical. By posingthe problem as one of minimising t...
Article
A pilot evaluation to assess the safety and possible benefits of TLC C-53, (prostaglandin E(1) associated with egg phosphatidylcholine liposomes) in acute respiratory exacerbations in children with cystic fibrosis (CF). Randomised, double-blind, placebo-controlled study in 20 P. aeruginosa colonised patients. All received intravenous antibiotics. S...
Article
Full-text available
We describe a method for automatically building statistical shape models from a training set of example boundaries/surfaces. These models show considerable promise as a basis for segmenting and interpreting images. One of the drawbacks of the approach is, however, the need to establish a set of dense correspondences between all members of a set of...
Conference Paper
Full-text available
We describe an automatic method for building optimal 3D statistical shape models from sets of training shapes. Although shape models show considerable promise as a basis for segmenting and interpreting images, a major drawback of the approach is the need to establish a dense correspondence across a training set of example shapes. It is important to...
Article
The pancreas secretes a bicarbonate-rich fluid containing digestive enzymes via the ampulla of Vater into the duodenum. Defective secretion leads to maldigestion of fat and protein with increased faecal losses. Cystic fibrosis (CF) is the major cause of pancreatic exocrine failure in childhood, whereas pancreatic insufficiency in adults is commonly...
Article
Full-text available
Pseudomonas aeruginosa colonizes and infects human tissues, although the mechanisms by which the organism evades the normal, predominantly neutrophilic, host defenses are unclear. Phenazine products of P. aeruginosa can induce death in Caenorhabditis elegans. We hypothesized that phenazines induce death of human neutrophils, and thus impair neutrop...
Article
Full-text available
Statistical shape models have been used widely as a basis for segmenting and interpreting images. A major drawback of the approach is the need to establish a set of dense correspondences across a training set of segmented shapes. By posing the problem as one of minimising the description length of the model, we develop an efficient method that auto...
Article
Ursodeoxycholic acid possesses choleretic and cytoprotective properties and in cystic fibrosis (CF) it is used to treat the hepatobiliary symptoms of the disease. This study investigated the effects of this bile acid on the transport function of the small intestine in normal and CF mice. The effects of ursodeoxycholic acid were monitored as changes...
Article
In vitro studies have shown that glibenclamide sensitivity is conferred upon Kir 1.1 K(+) channels when they are co-expressed with the cystic fibrosis transmembrane conductance regulator (CFTR). In rats, glibenclamide acts as a K(+)-sparing diuretic by a mechanism that involves blockade of Kir 1.1 channels in the distal nephron. To test whether int...
Conference Paper
Statistical shape models show considerable promise as a basis for segmenting and interpreting images. A major drawback of the approach is the need to establish a dense correspondence across a training set of segmented shapes. By posing the problem as one of minimising the description length of the model, we develop an efficient method that automati...
Conference Paper
Statistical shape models show considerable promise as a basis for segmenting and interpreting images. One of the drawbacks of the approach is, however, the need to establish a set of dense correspondences between examples of similar structures, across a training set of images. Often this is achieved by locating a set of ‘landmarks’ manually on each...
Article
Bile acids cause secretion throughout the intestinal tract and this process contributes to maintaining the fluidity of intestinal contents. In cystic fibrosis (CF) defective intestinal secretion can lead to excessive dehydration of the luminal contents and the development of clinical symptoms. This study was designed to investigate bile acid-induce...
Article
1. Changes in proximal tubule function have been reported in cystic fibrosis patients. The aim of this study was to investigate proximal tubule function in the Cftr(tm2cam)deltaF508 cystic fibrosis (CF) mouse model. A range of techniques were used including renal clearance studies, in situ microperfusion, RT-PCR and whole-cell patch clamping. 2. Re...
Article
The incidence of inflammatory bowel disease in children in western countries may be rising. Since there is no prospective national data on the incidence of inflammatory bowel disease in the UK and Republic of Ireland (ROI), we undertook a prospective survey to determine this incidence. The incidence during 1998 and 1999 was 5.2/100,000 per year in...
Article
Aims To investigate the effects of age and disease states on the expression and activity of intestinal CYP3A4 in a paediatric population. Methods Duodenal biopsies and surgical sections were collected from 104 paediatric patients (age range 2 weeks to 17 years) and from 11 foetuses. An S9 fraction was prepared in each case. CYP3A4 expression was as...
Article
Full-text available
In intestinal biopsies from cystic fibrosis (CF) patients acetylcholine fails to elicit a chloride secretion response, and this observation can be explained by a defect in the Ca2+ signalling pathway in CF secretory cells. We tested the hypothesis that in CF intestine, the generation of an intracellular Ca2+ signal upon cholinergic stimulation is a...
Article
In intestinal biopsies from cystic fibrosis (CF) patients acetylcholine fails to elicit a chloride secretion response, and this observation can be explained by a defect in the Ca2+ signalling pathway in CF secretory cells. We tested the hypothesis that in CF intestine, the generation of an intracellular Ca2+ signal upon cholinergic stimulation is a...
Article
Full-text available
It has been suggested that CFTR Cl(-) channels in the renal inner medullary collecting duct may be involved in mediating increased renal salt excretion during extracellular fluid volume expansion. To investigate this hypothesis, in-vivo clearance experiments were performed comparing wild-type (WT) and DeltaF508-CFTR transgenic mice (cftr (tm2Cam))....
Article
Statistical shape models are used widely as a basis for segmenting and interpreting images. A major drawback of this approach is the need to identifying corresponding points across a training set of segmented shapes. By posing the problem as one of minimising the description length of the model, we describe an efficient method that automatically de...
Article
Full-text available
The aims of this study were to investigate (a) if renal Na(+) handling was normal in Cftr(tm2cam) delta F508 cystic fibrosis mice, (b) whether adaptation to dietary salt depletion was preserved and (c) whether Cftr(tm2cam) delta F508 mice exhibited enhanced amiloride-sensitive Na(+) absorption. In Na(+)-replete animals (maintained on a 0.32 % NaCl...
Article
Full-text available
The μ-opioid agonist loperamide is an antidiarrhoeal drug which inhibits intestinal motility and secretion. Its anti-absorptive effects are less well investigated, but may be mediated through calmodulin. We have investigated further the effect of loperamide on the intestinal Na+-dependent d-glucose transporter (SGLT1). Brush-border membrane vesicle...
Conference Paper
Full-text available
Osteoarthritis is the most common cause of disability in the developed world. One the most important features of the disease is the progressive thinning and eventual loss of articular cartilage which can be visualised using Magnetic Resonance (MR) imaging. A major goal of research in osteoarthritis is the discovery and development of drugs which pr...
Article
Sodium channel inhibitors block the enhanced Na+ reabsorption in cystic fibrosis (CF). Extracellular nucleotides facilitate Cl- secretion via Ca2+ gated Cl- channels. A combination of these effects may produce less viscid secretions in CF which are easier to expectorate. This study examined the effects of combining sodium channel blockers with urid...
Article
The expression of matrix metalloproteinases 1, 2, 3, and 9 was examined in biopsy specimens removed from adult and pediatric patients with ulcerative colitis and Crohn's disease. The aim of this study was to determine if the expression of these enzymes was altered between areas of actively inflamed vs. noninvolved mucosa in the same patient and bet...
Article
Full-text available
The ability of mouse colon to generate a secretory response to stimulation by 5-hydroxytryptamine (5-HT) was investigated in intact colonic sheets mounted in Ussing chambers. A preparation of intact isolated crypts was used to determine whether 5-HT action was associated with an elevation of cytosolic calcium levels, measured using the calcium-sens...