Institution
Royal Devon and Exeter Hospital
Healthcare•Exeter, United Kingdom•
About: Royal Devon and Exeter Hospital is a healthcare organization based out in Exeter, United Kingdom. It is known for research contribution in the topics: Population & Randomized controlled trial. The organization has 2282 authors who have published 2526 publications receiving 78866 citations. The organization is also known as: RD&E.
Papers published on a yearly basis
Papers
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TL;DR: The level and morphological distribution of cyclooxygenase (COX)‐1 and ‐2 in human prostates is assessed and any association with the Gleason grade of prostate cancer is determined.
Abstract: Objective To assess the level and morphological distribution of cyclooxygenase (COX)-1 and -2 in human prostates and to determine any association with the Gleason grade of prostate cancer.
Materials and methods The study comprised 30 samples from patients with benign prostatic hyperplasia (BPH) and 82 with prostate cancer. Immunohistochemistry was used to assess the expression of COX-1 and -2, and 13 samples were also assessed using immunoblotting (six BPH and seven cancers).
Results For both BPH and prostate cancer, COX-1 expression was primarily in the fibromuscular stroma, with variable weak cytoplasmic expression in glandular/neoplastic epithelial cells. In contrast, COX-2 expression differed markedly between BPH and cancer. In BPH there was membranous expression of COX-2 in luminal glandular cells and no stromal expression. In cancer the stromal expression of COX-2 was unaltered, but expression by tumour cells was significantly greater (P = 0.008), with a change in the staining pattern from membranous to cytoplasmic (P < 0.001). COX-2 expression was significantly higher in poorly differentiated than in well differentiated tumours (P < 0.001). These results were supported by immunoblotting, which showed similar levels of COX-1 in both BPH and cancer, but four times greater expression of COX-2 in cancer than in BPH.
Conclusion This is the first study to assess the co-expression of COX-1 and COX-2 proteins in benign and malignant human prostates, and showed the induction and significantly greater expression of COX-2 in cancer, which was also associated with tumour grade. The regular use of nonsteroidal anti-inflammatory drugs is associated with a reduced incidence of cancers. The present results provide the basis for a potential role for COX-2 inhibitors in the prevention and treatment of prostate cancer.
178 citations
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TL;DR: Mutations in the gene encoding tau tubulin kinase 2 (TTBK2) are identified as the cause of spinocerebellar ataxia type 11 and affected brain tissue showed substantial cerebellar degeneration and tau deposition, suggesting that TTBK2 is important in the tau cascade and in spinocesrebellary degeneration.
Abstract: The microtubule-associated protein tau ( encoded by MAPT) and several tau kinases have been implicated in neurodegeneration, but only MAPT has a proven role in disease. We identified mutations in the gene encoding tau tubulin kinase 2 ( TTBK2) as the cause of spinocerebellar ataxia type 11. Affected brain tissue showed substantial cerebellar degeneration and tau deposition. These data suggest that TTBK2 is important in the tau cascade and in spinocerebellar degeneration.
178 citations
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TL;DR: The antigenic profile of SAs revealed significant modification of astrocyte protein expression in chronic MS lesions and may allow the development of therapeutic strategies that prevent scar formation and promote tissue repair.
Abstract: Dense astrocytic scarring in chronic multiple sclerosis (MS) plaques produces an inhibitory environment which can impede tissue repair. Animal studies have shown that the antigenic phenotype of the most abundant cell type in the brain, the astrocyte, varies depending on astrocyte type and location. To identify the phenotype of scar astrocytes (SAs) in chronic lesions, markers of reactive astrocytes characterized in animal studies were investigated. To date these are the only established markers. Cerebral subventricular deep white matter from normal control, MS normal appearing white matter and lesions (acute, subacute and chronic) were examined by immunohistochemistry and immunoblotting. The antigenic profile of SAs revealed significant modification of astrocyte protein expression in chronic MS lesions. SAs express nestin, embryonic neural cell adhesion molecule, fibroblast growth factor receptor 4, epidermal growth factor receptor, nerve growth factor and a subpopulation of SAs also express basic fibroblast growth factor. These are in addition to the expected markers glial fibrillary acidic protein, vimentin, and the tenascins C and R. Therefore, an SA antigenic phenotype has now been defined. This knowledge may allow the development of therapeutic strategies that prevent scar formation and promote tissue repair.
171 citations
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Dresden University of Technology1, VU University Medical Center2, University of Nottingham3, Astellas Pharma4, University of São Paulo5, University of Regensburg6, University Hospital Heidelberg7, Utrecht University8, Royal Devon and Exeter Hospital9, Clalit Health Services10, University of California, San Diego11, St. John's University12, King's College London13, Kyushu University14, University of Giessen15, Cochrane Collaboration16, Osaka University17, University of London18, Ninewells Hospital19, University of New South Wales20, St George's Hospital21, Boston Children's Hospital22, Paul Sabatier University23, Jikei University School of Medicine24, University Medical Center Groningen25, Karolinska University Hospital26, University of Kiel27, Ludwig Maximilian University of Munich28, Nottingham University Hospitals NHS Trust29
TL;DR: Consensus was achieved to include clinical signs, symptoms, long‐term control of flares and quality of life into the core set of outcome domains for atopic eczema trials, and the HOME initiative strongly recommends including and reporting these core outcome domains as primary or secondary endpoints in all future atopic ecology trials.
Abstract: The use of nonstandardized and inadequately validated outcome measures in atopic eczema trials is a major obstacle to practising evidence-based dermatology. The Harmonising Outcome Measures for Eczema (HOME) initiative is an international multiprofessional group dedicated to atopic eczema outcomes research. In June 2011, the HOME initiative conducted a consensus study involving 43 individuals from 10 countries, representing different stakeholders (patients, clinicians, methodologists, pharmaceutical industry) to determine core outcome domains for atopic eczema trials, to define quality criteria for atopic eczema outcome measures and to prioritize topics for atopic eczema outcomes research. Delegates were given evidence-based information, followed by structured group discussion and anonymous consensus voting. Consensus was achieved to include clinical signs, symptoms, long-term control of flares and quality of life into the core set of outcome domains for atopic eczema trials. The HOME initiative strongly recommends including and reporting these core outcome domains as primary or secondary endpoints in all future atopic eczema trials. Measures of these core outcome domains need to be valid, sensitive to change and feasible. Prioritized topics of the HOME initiative are the identification/development of the most appropriate instruments for the four core outcome domains. HOME is open to anyone with an interest in atopic eczema outcomes research.
169 citations
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TL;DR: Comparing patients with frequent and those with infrequent symptoms, there was no difference in QT or QTc dispersion either off treatment or during therapy with beta-blocking agents.
Abstract: It has been suggested that QT dispersion recorded on the surface electrocardiogram may be a predictor of arrhythmic events in patients with congenital QT prolongation. To evaluate this, 9 patients (6 female, mean age 17.6 years) with congenital long QT syndromes, all of whom had syncope and documented torsades de pointes, were studied. Patients were studied off treatment and during therapy with β-blocking agents. Three patients were also studied after left stellate ganglionectomy. An age-matched control group was also studied. Good quality 12-lead electrocardiograms were recorded from all patients. For each lead, QT and RR intervals were measured, and QTc value was calculated. QT and QTc dispersions were calculated for each patient.
Patients had a significantly longer mean QT interval compared with that of the control group (450 ± 100 vs 359 ± 63 ms; p = 0.015) at similar mean RR intervals (736 ± 231 vs 783 ± 289 ms), with a longer mean QTc value (0.53 ± 0.08 vs 0.41 ± 0.02 s12; p = 0.004). Patients also had longer QT and QTc dispersions compared with those of the control group (110 ± 45 vs 43 ± 12 ms [p = 0.004], and 0.108 ± 0.03 vs 0.05 ± 0.02 s12 [p = 0.002], respectively). QT and QTc dispersions on and off β-blocking agents were not significantly different. Comparing patients with frequent and those with infrequent symptoms, there was no difference in QT or QTc dispersion either off treatment or during therapy with β-blocking agents. There was an increase in mean QT interval and QTc value in patients with frequent symptoms on β-blocking agents. On β-blocking agents, patients with frequent symptoms had a significantly longer mean QTc value compared with that of those with infrequent symptoms. There was no change in QT or QTc dispersion, mean QT or RR interval, or mean QTc value after left stellate ganglionectomy.
QT-interval dispersion is observed in patients with congenital long QT syndromes; however, the degree of dispersion is not related to the severity of symptoms, nor influenced by treatment with β-blocking agents.
168 citations
Authors
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Name | H-index | Papers | Citations |
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Andrew T. Hattersley | 146 | 768 | 106949 |
Timothy M. Frayling | 133 | 500 | 100344 |
Gordon D.O. Lowe | 105 | 560 | 44327 |
Rod S Taylor | 104 | 524 | 39332 |
Sian Ellard | 97 | 636 | 36847 |
Zoltán Kutalik | 90 | 321 | 42901 |
Michael N. Weedon | 87 | 201 | 60701 |
Masud Husain | 81 | 398 | 25682 |
David Melzer | 80 | 328 | 33458 |
Jonathan Mill | 78 | 301 | 36343 |
A. John Camm | 76 | 368 | 49804 |
David Silver | 74 | 227 | 81103 |
Jason D. Warren | 73 | 384 | 20588 |
Nicholas J. Talbot | 71 | 240 | 29205 |
Andrew R. Wood | 70 | 214 | 36203 |