Royal Devon and Exeter Hospital

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.

DPP-4 enzyme deficiency protects kidney from acute ischemia-reperfusion injury: role for remote intermittent bowel ischemia-reperfusion preconditioning.

Abstract: We analyzed the effects of acute ischemia-reperfusion (KIR) injury on the status of kidney function and architecture in dipeptidyl peptidase4-difficient (DPP4D) rats and the effect of remote small bowel ischemia-reperfusion (BIR) preconditioning. DPP4-deficient (DPP4D) and normal Fischer344 (F344) rats were divided into 6 groups: (1) sham-F344, (2) sham-DPP4D, (3) KIR-F344 (4) KIR-DPP4D, (5) DPP4D-KIR-extendin-9-39 and (6) BIR-KIR-F344. Blood creatinine and urea nitrogen levels and the urinary protein-to-creatinine ratio was higher in KIR-F344 rats than BIR-KIR-F344 or KIR-DPP4D rats 72 h after acute KIR. Conversely, the circulating glucagon-like peptide 1 (GLP-1) levels were higher in BIR-KIR-F344 and KIR-DPP4D than KIR-F344 rats after acute KIR. KIR-F344 rats showed greater inflammation, oxidative stress, apoptosis, DNA damage and kidney injury than other rat groups. Damage to the kidney architecture in KIR-F344 rats was greater than in BIR-KIR-F344 or KIR-DPP4D rats. Expression of antioxidant proteins and GLP-1 receptor was higher in kidneys from KIR-DPP4D and BIR-KIR-F344 than KIR-F344 rats, which suggests better intrinsic responses. We therefore suggest that elevated circulating GLP-1 levels due to DPP4 deficiency and BIR preconditioning protect kidney function and architecture during acute IR injury.

Genetic risk variants for brain disorders are enriched in cortical H3K27ac domains.

Abstract: Most variants associated with complex phenotypes in genome-wide association studies (GWAS) do not directly index coding changes affecting protein structure. Instead they are hypothesized to influence gene regulation, with common variants associated with disease being enriched in regulatory domains including enhancers and regions of open chromatin. There is interest, therefore, in using epigenomic annotation data to identify the specific regulatory mechanisms involved and prioritize risk variants. We quantified lysine H3K27 acetylation (H3K27ac) - a robust mark of active enhancers and promoters that is strongly correlated with gene expression and transcription factor binding – across the genome in entorhinal cortex samples using chromatin immunoprecipitation followed by highly parallel sequencing (ChIP-seq). H3K27ac peaks were called using high quality reads combined across all samples and formed the basis of partitioned heritability analysis using LD score regression along with publicly-available GWAS results for seven psychiatric and neurodegenerative traits. Heritability for all seven brain traits was significantly enriched in these H3K27ac peaks (enrichment ranging from 1.09–2.13) compared to regions of the genome containing other active regulatory and functional elements across multiple cell types and tissues. The strongest enrichments were for amyotrophic lateral sclerosis (ALS) (enrichment = 2.19; 95% CI = 2.12–2.27), autism (enrichment = 2.11; 95% CI = 2.05–2.16) and major depressive disorder (enrichment = 2.04; 95% CI = 1.92–2.16). Much lower enrichments were observed for 14 non-brain disorders, although we identified enrichment in cortical H3K27ac domains for body mass index (enrichment = 1.16; 95% CI = 1.13–1.19), ever smoked (enrichment = 2.07; 95% CI = 2.04–2.10), HDL (enrichment = 1.53; 95% CI = 1.45–1.62) and trigylcerides (enrichment = 1.33; 95% CI = 1.24–1.42). These results indicate that risk alleles for brain disorders are preferentially located in regions of regulatory/enhancer function in the cortex, further supporting the hypothesis that genetic variants for these phenotypes influence gene regulation in the brain.

Transport and temperature effects on measurement of serum and plasma potassium.

Abstract: Transport of blood samples from general practice to a central laboratory can result in spuriously high or low potassium concentrations. The importance of this phenomenon was studied in a general practice serving a population of 15,000 patients, 27 km from the pathology laboratory that routinely measured serum potassium. The design involved comparison of potassium levels between control serum (plain gel-separation serum tubes centrifuged in the surgery), routine serum (plain gel-separation tubes centrifuged in the laboratory) and routine plasma samples (lithium-heparin tubes centrifuged in the laboratory). Complete triple sets of data were obtained for 371 samples. Altman and Bland plots for the control serum vs routine serum samples showed a mean difference of +0.1 mmol/L with limits of agreement (+/- 2SD) +0.6 mmol/L, -0.4 mmol/L and for control serum vs routine plasma a mean difference of +0.2 mmol/L with limits of agreement +0.8 mmol/L, -0.4 mmol/L. There was a negative association between mean weekly routine plasma potassium levels with mean weekly temperatures achieved. Regression analysis indicated that both maximum temperature achieved and time to centrifugation significantly contributed to differences observed in the routine plasma samples, but not with the routine serum samples. For plasma samples exposed to high temperatures a clinically significant lowering of potassium concentrations can arise. These results confirm that spurious lowering of potassium concentrations occurs in plasma samples collected in a primary care setting. The preferred method is to centrifuge samples soon after venepuncture. Where this is not possible, collection into plain gel-separation tubes (serum) ensures less variation due to temperature and time to centrifugation than does collection into lithium-heparin tubes (plasma).

Frozen shoulder after simple arthroscopic shoulder procedures: What is the risk?

Abstract: Frozen shoulder is a recognised complication following simple arthroscopic shoulder procedures, but its exact incidence has not been reported. Our aim was to analyse a single-surgeon series of patients undergoing arthroscopic subacromial decompression (ASD; group 1) or ASD in combination with arthroscopic acromioclavicular joint (ACJ) excision (group 2), to establish the incidence of frozen shoulder post-operatively. Our secondary aim was to identify associated risk factors and to compare this cohort with a group of patients with primary frozen shoulder. We undertook a retrospective analysis of 200 consecutive procedures performed between August 2011 and November 2013. Group 1 included 96 procedures and group 2 104 procedures. Frozen shoulder was diagnosed post-operatively using the British Elbow and Shoulder Society criteria. A comparative group from the same institution involved 136 patients undergoing arthroscopic capsular release for primary idiopathic frozen shoulder. The incidence of frozen shoulder was 5.21% in group 1 and 5.71% in group 2. Age between 46 and 60 years (p = 0.002) and a previous idiopathic contralateral frozen shoulder (p < 0.001) were statistically significant risk factors for the development of secondary frozen shoulder. Comparison of baseline characteristics against the comparator groups showed no statistically significant differences for age, gender, diabetes and previous contralateral frozen shoulder. These results suggest that the risk of frozen shoulder following simple arthroscopic procedures is just over 5%, with no increased risk if the ACJ is also excised. Patients aged between 46 and 60 years and a previous history of frozen shoulder increase the relative risk of secondary frozen shoulder by 7.8 (95% confidence interval (CI) 2.1 to 28.3)and 18.5 (95% CI 7.4 to 46.3) respectively. Cite this article: Bone Joint J 2015; 97-B:963–6.