Manchester, United Kingdom
Manchester, United Kingdom

Time filter

Source Type

Eyden B.,Christie NHS Foundation Trust | Curry A.,Central Manchester Foundation Trust | Wang G.,Christie NHS Foundation Trust | Wang G.,Zhejiang University
Journal of Cellular and Molecular Medicine | Year: 2011

The free spindled cells of the lamina propria of the gut have been reported as showing fibroblastic, smooth-muscle and myofibroblastic differentiation. A precise understanding of the differentiation of these cells is essential for appreciating their functions, and this paper addresses this question using ultrastructural analysis. Histologically normal samples from different areas of the gastrointestinal tract were studied. Both subepithelial stromal cells, lying immediately beneath the basal lamina, and the deeper interstitial stromal cells, were studied. Subepithelial and interstitial cells had comparable features, reinforcing the idea that these formed a single reticulum of cells. Two major cell types were identified. Some were smooth-muscle cells, on the basis of abundant myofilaments with focal densities, glycogen, an irregular cell surface, focal lamina and multiple attachment plaques alternating with plasmalemmal caveolae. Some cells had a lesser expression of these markers, especially of myofilaments, and were regarded as poorly differentiated smooth-muscle cells and descriptively referred to as 'myoid'. Other cells were fibroblastic to judge by prominent rough endoplasmic reticulum, an absence of myofilaments and lamina, but presence of focal adhesions. The fibronexus junctions of true myofibroblasts were not seen. The study emphasises that the smooth-muscle actin immunoreactivity in this anatomical site resides in smooth-muscle cells and not in myofibroblasts, a view consistent with earlier ultrastructural and immunostaining results. The recognition that these cells are showing smooth-muscle or fibroblastic but not true myofibroblastic differentiation should inform our understanding of the function of these cells. © 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.


A shortcut review was carried out to establish if CXR had sufficient sensitivity to rule out significant thoracic injury in haemodynamically stable, paediatric patients with a significant mechanism of trauma. No studies were found that directly answered the three-part question, but 13 studies were found which were considered relevant. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. The clinical bottom line is that important thoracic injuries may not be clinically apparent and that CT scans have a significantly higher sensitivity than CXR in detecting such injuries. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.


Cooper K.,Central Manchester Foundation Trust
Nursing Times | Year: 2013

Enhanced recovery uses evidence-based interventions to improve the perioperative care of patients undergoing major surgery. Due to the relative lack of research into patient experience, Central Manchester Foundation Trust distributed a questionnaire to measure the experience of patients cared for on a colorectal ER pathway. Overall, results were favourable, and described good pain management and high-quality care provided by the enhanced recovery team. This article describes how the results will be used to shape services in the future.


Gibreel T.M.,University of Manchester | Dodgson A.R.,University of Manchester | Dodgson A.R.,Central Manchester Foundation Trust | Cheesbrough J.,Royal Preston Hospital | And 3 more authors.
Journal of Antimicrobial Chemotherapy | Year: 2012

Objectives: Multilocus sequence typing (MLST) has been used to characterize diverse pathogens, including uropathogenic Escherichia coli (UPEC). There has been significant interest in the contribution of the O25b:H4-ST131 lineage to UPEC disease, as these isolates are often highly virulent and exhibit multidrug resistance. To reveal the wider impact of sequence type (ST) 131, we have examined its contribution to the overall population structure of UPEC isolates that were not selected on the basis of virulence or antibiotic resistance. Methods: Three hundred UPEC isolates were recovered from community and hospital urine samples examined by clinical microbiology laboratories in the Northwest region of England in June 2007 and June 2009. They were characterized by susceptibility profiling, MLST and virulence gene PCR. PFGE was used to examine isolates from key clones. Results: The most common lineage was ST73 (16.6%) followed by ST131 (13.3%), ST69 (9%), ST95 (6.3%), ST10 (4.3%) and ST127 (3.6%). ST131 isolates were significantly more likely to exhibit high levels of antibiotic resistance (35% being CTX-M-15 PCR positive) and those of ST127 were the most widely susceptible but carried the highest number of virulence genes. Only when the CTX-M-15-O25b-positive strains were examined was a high level of virulence observed for ST131 isolates. PFGE indicated ongoing local evolution in ST131. Conclusions: ST131 isolates are well established in the wider UPEC population. This clone is still evolving and we further support suggestions that it represents a real threat to health. We suggest that ST127 is a recently emerged, community-associated, virulent clone that warrants further study. © The Author 2011. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.


Tavakoli M.,University of Manchester | Quattrini C.,University of Manchester | Abbott C.,University of Manchester | Kallinikos P.,University of Manchester | And 6 more authors.
Diabetes Care | Year: 2010

OBJECTIVE - The accurate quantification of human diabetic neuropathy is important to define at-risk patients, anticipate deterioration, and assess new therapies. RESEARCH DESIGN AND METHODS - A total of 101 diabetic patients and 17 age-matched control subjects underwent neurological evaluation, neurophysiology tests, quantitative sensory testing, and evaluation of corneal sensation and corneal nerve morphology using corneal confocal microscopy (CCM). RESULTS - Corneal sensation decreased significantly (P = 0.0001) with increasing neuropathic severity and correlated with the neuropathy disability score (NDS) (r = 0.441, P < 0.0001). Corneal nerve fiber density (NFD) (P < 0.0001), nerve fiber length (NFL), (P < 0.0001), and nerve branch density (NBD) (P < 0.0001) decreased significantly with increasing neuropathic severity and correlated with NDS (NFD r = -0.475, P < 0.0001; NBD r = -0.511, P < 0.0001; and NFL r = -0.581, P < 0.0001). NBD and NFL demonstrated a significant and progressive reduction with worsening heat pain thresholds (P = 0.01). Receiver operating characteristic curve analysis for the diagnosis of neuropathy (NDS >3) defined an NFD of <27.8/mm 2 with a sensitivity of 0.82 (95% CI 0.68-0.92) and specificity of 0.52 (0.40-0.64) and for detecting patients at risk of foot ulceration (NDS >6) defined a NFD cutoff of <20.8/mm 2 with a sensitivity of 0.71 (0.42-0.92) and specificity of 0.64 (0.54-0.74). CONCLUSIONS - CCM is a noninvasive clinical technique that may be used to detect early nerve damage and stratify diabetic patients with increasing neuropathic severity. © 2010 by the American Diabetes Association.


Pritchard N.,Queensland University of Technology | Edwards K.,Queensland University of Technology | Russell A.W.,Princess Alexandra Hospital | Russell A.W.,University of Queensland | And 4 more authors.
Diabetes Care | Year: 2015

OBJECTIVE This study determined if deficits in corneal nerve fiber length (CNFL) assessed using corneal confocal microscopy (CCM) can predict future onset of diabetic peripheral neuropathy (DPN). RESEARCH DESIGN AND METHODS CNFL and a range of other baseline measures were compared between 90 nonneuropathic patients with type 1 diabetes who did or did not develop DPN after 4 years. The receiver operator characteristic (ROC) curve was used to determine the capability of single and combined measures of neuropathy to predict DPN. RESULTS DPN developed in 16 participants (18%) after 4 years. Factors predictive of 4-year incident DPN were lower CNFL (P = 0.041); longer duration of diabetes (P = 0.002); higher triglycerides (P = 0.023); retinopathy (higher on the Early Treatment of Diabetic Retinopathy Study scale) (P = 0.008); nephropathy (higher albumin-tocreatinine ratio) (P = 0.001); higher neuropathy disability score (P = 0.037); lower cold sensation (P = 0.001) and cold pain (P = 0.027) thresholds; higher warm sensation (P = 0.008), warm pain (P = 0.024), and vibration (P = 0.003) thresholds; impaired monofilament response (P = 0.003); and slower peroneal (P = 0.013) and sural (P = 0.002) nerve conduction velocity. CCM could predict the 4-year incident DPN with 63% sensitivity and 74% specificity for a CNFL threshold cutoff of 14.1 mm/mm2 (area under ROC curve = 0.66, P = 0.041). Combining neuropathymeasures did not improve predictive capability. CONCLUSIONS DPN can be predicted by various demographic, metabolic, and conventional neuropathy measures. The ability of CCM to predict DPN broadens the already impressive diagnostic capabilities of this novel ophthalmic marker. © 2015 by the American Diabetes Association.


Rustamov O.,University of Manchester | Smith A.,Central Manchester Foundation Trust | Roberts S.A.,University of Manchester | Yates A.P.,Central Manchester Foundation Trust | And 4 more authors.
Human Reproduction | Year: 2012

STUDY QUESTIONWhat is the variability of anti-Müllerian hormone (AMH) concentration in repeat samples from the same individual when using the Gen II assay and how do values compare to Gen I [Diagnostic Systems Ltd (DSL)] assay results? SUMMARY ANSWERThe Gen II AMH assay displayed appreciable variability, which can be explained by sample instability. WHAT IS KNOWN ALREADYAMH is the primary predictor of ovarian performance and is used to tailor gonadatrophin dosage in cycles of IVF/ICSI and in other routine clinical settings. Thus, a robust, reproducible and sensitive method for AMH analysis is of paramount importance. The Beckman Coulter Gen II ELISA for AMH was introduced to replace earlier DSL and Immunotech assays. The performance of the Gen II assay has not previously been studied in a clinical setting. STUDY DESIGN, SIZE AND DURATIONWe studied an unselected group of 5007 women referred for fertility problems between 1 September 2008 and 25 October 2011; AMH was measured initially using the DSL AMH ELISA and subsequently using the Gen II assay. AMH values in the two assays were compared using a regression model in log(AMH) with a quadratic adjustment for age. Additionally, women (n=330) in whom AMH had been determined in different samples using both the DSL and Gen II assays (paired samples) identified and the difference in AMH levels between the DSL and Gen II assays was estimated using the age-adjusted regression analysis. A subset of 313 women had repeated AMH determinations (n=646 samples) using the DSL assay and 87 women had repeated AMH determinations using the Gen II assay (n=177 samples) were identified. A mixed effects model in log(AMH) was utilized to estimate the sample-to-sample (within-subject) coefficients of variation of AMH, adjusting for age. Laboratory experiments including sample stability at room temperature, linearity of dilution and storage conditions used anonymized samples. MAIN RESULTS AND THE ROLE OF CHANCEIn clinical practice, Gen II AMH values were ∼20 lower than those generated using the DSL assay instead of the 40 increase predicted by the kit manufacturer. Both assays displayed high within-subject variability (Gen II assay CV 59, DSL assay CV 32). In the laboratory, AMH levels in serum from 48 subjects incubated at RT for up to 7 days increased progressively in the majority of samples (58 increase overall). Pre-dilution of serum prior to assay, gave AMH levels up to twice that found in the corresponding neat sample. Pre-mixing of serum with assay buffer prior to addition to the microtitre plate gave higher readings (72 overall) compared with sequential addition. Storage at-20°C for 5 days increased AMH levels by 23 compared with fresh samples. The statistical significance of results was assessed where appropriate. LIMITATIONS, REASONS FOR CAUTIONThe analysis of AMH levels is a retrospective study and therefore we cannot entirely rule out the existence of differences in referral practices or changes in the two populations. WIDER IMPLICATIONS OF THE FINDINGSOur data suggests that AMH may not be stable under some storage or assay conditions and this may be more pronounced with the Gen II assay. The published conversion factors between the Gen II and DSL assays appear to be inappropriate for routine clinical practice. Further studies are urgently required to confirm our observations and to determine the cause of the apparent instability. In the meantime, caution should be exercised in the interpretation of AMH levels in the clinical setting. CONFLICT OF INTEREST/STUDY FUNDINGS. Roberts is supported by the NIHR Manchester Biomedical Research Centre. © 2012 The Author.


Hankin D.,Central Manchester Foundation Trust
Foot & ankle specialist | Year: 2011

Early diagnosis, essential for timely appropriate treatment and reduction of complications, can be difficult. This article aims to give an overview of the role that different imaging modalities have to play in the diagnosis of osteomyelitis. Osteomyelitis is a heterogeneous disease in its pathophysiology, clinical presentation, and management. It infers inflammation of bone and marrow, whereas osteitis is inflammation of the bone only. Thus, a soft-tissue infection that reaches the bone surface but has not infected the marrow is osteitis and not osteomyelitis. Chronic osteomyelitis is divided into active and inactive forms. Newly appearing periosteal reaction or bone destruction within the chronic involucrum are indicators of activation. Imaging modalities represent different underlying pathophysiological processes that may be represented in differing types and differing phases of osteomyelitis. Sequential selection of appropriate imaging modalities requires a thorough understanding of the disease processes and the process by which each modality visualizes this dynamic disease process. Copyright © 2011 The Author(s)


Hennayake S.,Central Manchester Foundation Trust
Journal of Pediatric Urology | Year: 2010

Introduction: Two children presented with malignant hypertension due to complex reno-vascular malformations. The 7-min video shows the use of prone retroperitoneoscopy in both. Patient 1: A 6-year-old girl presented with convulsions and malignant hypertension. Captopril DMSA was suggestive of right renal artery stenosis. On formal angiography, the kidney was perfused by what appeared to be an arterio-venous malformation. The renal artery was hypoplastic and there were pulsatile vessels along the ureter due to the gonadal periureteric and gonadal inferior capsular collateral supply to the kidney. The kidney could be devascularized easily by controlling these. Patient 2: A 14-month-old boy presented with 6-month history of poor appetite, weight loss and irritability. Formal angiography showed acute obstruction of the main upper pole branch. The vessels to the upper pole could be clearly seen and controlled at surgery for partial right nephrectomy. He recovered with no urine leak or bleeding. Conclusion: Gravity kept the renal vessels under stretch allowing excellent two-hand dissection and the space was adequate for suture closure of a calyx in Case 2. The prone approach provides excellent exposure of the renal blood vessels, aorta and vena cava, and seems to be the most suitable for complex renal vascular malformations. © 2009 Journal of Pediatric Urology Company.


Gibreel T.M.,University of Manchester | Dodgson A.R.,University of Manchester | Dodgson A.R.,Central Manchester Foundation Trust | Cheesbrough J.,Royal Preston Hospital | And 3 more authors.
Journal of Clinical Microbiology | Year: 2012

Uropathogenic Escherichia coli (UPEC) is the predominant cause of urinary tract infection in both hospital and community settings. The recent emergence of multidrug-resistant clones like the O25b:H4-ST131 lineage represents a significant threat to health, and numerous studies have explored the virulence potential of these organisms. Members of the ST131 clone have been described as having variable carriage of key virulence factors, and it has been suggested that additional unidentified factors contribute to virulence. Here we demonstrated that ST131 isolates have high metabolic potential and biochemical profiles that distinguish them from isolates of many other sequence types (STs). A collection of 300 UPEC isolates recovered in 2007 and 2009 in the Northwest region of England were subjected to metabolic profiling using the Vitek2 Advanced Expert System (AES). Of the 47 tests carried out, 30 gave a positive result with at least one of the 300 isolates examined. ST131 isolates demonstrated significant association with eight tests, including those for peptidase, decarboxylase, and alkalinization activity. Metabolic activity also correlated with antibiotic susceptibility profiles, with resistant organisms displaying the highest metabolic potential. This is the first comprehensive study of metabolic potential in the ST131 lineage, and we suggest that high metabolic potential may have contributed to the fitness of members of the ST131 clone, which are able to exploit the available nutrients in both the intestinal and urinary tract environments. Copyright © 2012, American Society for Microbiology. All Rights Reserved.

Loading Central Manchester Foundation Trust collaborators
Loading Central Manchester Foundation Trust collaborators