Glenfield Hospital

About: Glenfield Hospital is a healthcare organization based out in Leicester, United Kingdom. It is known for research contribution in the topics: Population & Extracorporeal membrane oxygenation. The organization has 1382 authors who have published 1812 publications receiving 99238 citations. The organization is also known as: Glenfield General Hospital.

Loss of functional BAP1 augments sensitivity to TRAIL in cancer cells

Abstract: Malignant mesothelioma (MM) is poorly responsive to systemic cytotoxic chemotherapy and invariably fatal. Here we describe a screen of 94 drugs in 15 exome-sequenced MM lines and the discovery of a subset defined by loss of function of the nuclear deubiquitinase BRCA associated protein-1 (BAP1) that demonstrate heightened sensitivity to TRAIL (tumour necrosis factor-related apoptosis-inducing ligand). This association is observed across human early passage MM cultures, mouse xenografts and human tumour explants. We demonstrate that BAP1 deubiquitinase activity and its association with ASXL1 to form the Polycomb repressive deubiquitinase complex (PR-DUB) impacts TRAIL sensitivity implicating transcriptional modulation as an underlying mechanism. Death receptor agonists are well-tolerated anti-cancer agents demonstrating limited therapeutic benefit in trials without a targeting biomarker. We identify BAP1 loss-of-function mutations, which are frequent in MM, as a potential genomic stratification tool for TRAIL sensitivity with immediate and actionable therapeutic implications.

Proton pump inhibitors and diarrhoea related to Clostridium difficile infection in hospitalised patients: a case-control study

Abstract: The incidence and disease severity of Clostridium difficile infection are rising There is increasing evidence of a potential association between proton-pump inhibitors (PPI) and C difficile infection We performed a case-control study to examine the relationship between PPI and polymerase chain reaction (PCR)-proven C difficile infection in 137 hospitalised patients in a tertiary hospital in Western Australia Only antibiotic exposure within 3 months prior to onset of diarrhoea was associated with PCR-proven C difficile infection (odds ratio 597, 95% confidence interval 240-148, P= 0001) A restricted analysis on those who had exposure to antibiotics within 3 months before the onset of diarrhoea did not change the negative association between PPI exposure and PCR-proven C difficile infection Long-term PPI usage and intensity of PPI exposure prior to onset of diarrhoea were not significantly associated with C difficile infection

A comparison of the shrinkage of commercial bone cements when mixed under vacuum

Abstract: The outcome of a cemented hip arthroplasty is partly dependent on the type of cement which is used. The production of an interface gap between the stem and the cement mantle as a result of shrinkage of the cement, may be a factor involved. Palacos R, Palacos LV (both with gentamicin), CMW 1, CMW 2, CMW Endurance (CMWE) and Simplex were prepared under vacuum and allowed to cure overnight in similar cylinders. The next day this volume was determined by the displacement of water. Shrinkage varied between 3.82% and 7.08% with CMWE having the lowest and Palacos LV the highest. This could be a factor to consider when choosing a cement for a shape-closed stem.

Evidence for the Involvement of Oxygen-Derived free Radicals in Ischaemia-Reperfusion Injury

Abstract: Six patients undergoing vascular reconstructive surgery were examined for evidence of oxygen-derived free radical (ORF) damage to the protein, immunoglobulin G (IgG). OFR damage was determined as an increase in the fluorescence (ex 360 nm em 454 nm) to ultraviolet absorption (280 nm) ratio of IgG, representing N-Formyl kynurenine and other as yet unidentified fluorophores. The IgG ratio was found to increase slightly during ischaemia and to undergo marked elevation upon reperfusion (275 +/- 405% baseline value at 40 min post-clamp; mean +/- sd). A high ratio was maintained post-reperfusion, even after 60 min reperfusion. Determination of thromboxane B2, (TXB2), leukotriene B4, (LTB4) and 6-keto prostaglandin F1 alpha, (PGF1a), revealed a decrease in their concentrations during ischaemia and a transient, marked increase on reperfusion. Only TXB2 concentrations were found to correlate with the IgG ratio (negative correlation, p < 0.05). No correlation was observed between von Willebrand antigen factor, a marker of endothelial cell damage and fluorescent IgG ratio. However, levels of the factor increased slightly during ischaemia and more sharply upon reperfusion. These preliminary results therefore suggest that a more likely source of the OFRs responsible for IgG damage is endothelial cell xanthine oxidase, rather than cyclo-oxygenase or lipoxygenase.

Antihypertensive therapy and orthostatic responses in elderly hospital in-patients

Abstract: The study aim was to determine the association between use of antihypertensive drugs and orthostatic hypotension on prolonged standing in an elderly in-patient population. Hospital in-patients aged > 60 years had manually and automatically determined blood pressure (BP) measurements recorded in the supine position. On standing a total of nine measurements were taken over 10 min, six measurements were taken using a mercury sphygmomanometer and three by an automatic monitor. Seventy-four patients of mean age 73 +/- 7 years were studied; 52 (70%) were taking > or = 1 antihypertensive drug and 22 (30%) none. On standing, manually determined systolic BP (SBP) fell to a similar extent in the group of patients taking antihypertensive therapy compared to those not taking such treatment (at 9 min standing: -6 +/- 16 vs -10 +/- 15 mm Hg, respectively) and the frequency of orthostatic hypotension (SBP fall > or = 20 mm Hg) was similar in both groups [at 9 min: 9 (17%) vs 5 (23%)]. Automatically determined measurements also revealed similar orthostatic SBP responses in both treated and non-treated groups (at 8 min: -3 +/- 18 vs -6 +/- 13 mm Hg, respectively) and a similar frequency of orthostatic hypotension. No significant change in standing compared to supine diastolic BP (DBP) measured manually or automatically was seen in either group. Even in the subgroup of patients taking > or = 2 antihypertensive drugs the orthostatichypotension. BP response and the frequency of orthostatic hypotension was similar to that in the non-treated group. In conclusion no association was found between use of antihypertensive therapy and orthostatic hypotension in an elderly in-patient population.