Churchill Hospital

About: Churchill Hospital is a healthcare organization based out in Oxford, United Kingdom. It is known for research contribution in the topics: Population & Transplantation. The organization has 3548 authors who have published 5357 publications receiving 304275 citations.

Etomidate in the management of hypercortisolaemia in Cushing's syndrome: a review.

Abstract: This review addresses the practical usage of intravenous etomidate as a medical therapy in Cushing's syndrome. We reviewed the relevant literature, using search terms 'etomidate', 'Cushing's syndrome', 'adrenocortical hyperfunction', 'drug therapy' and 'hypercortisolaemia' in a series of public databases. There is a paucity of large randomised controlled trials, and data on its use rely only on small series, case study reports and international consensus guideline recommendations. Based on these, etomidate is an effective parenteral medication for the management of endogenous hypercortisolaemia, particularly in cases with significant biochemical disturbance, sepsis and other serious complications such as severe psychosis, as well as in preoperative instability. We suggest treatment protocols for the safe and effective use of etomidate in Cushing's syndrome.

A genome-wide metabolic QTL analysis in Europeans implicates two loci shaped by recent positive selection.

Abstract: We have performed a metabolite quantitative trait locus (mQTL) study of the 1H nuclear magnetic resonance spectroscopy (1H NMR) metabolome in humans, building on recent targeted knowledge of genetic drivers of metabolic regulation. Urine and plasma samples were collected from two cohorts of individuals of European descent, with one cohort comprised of female twins donating samples longitudinally. Sample metabolite concentrations were quantified by 1H NMR and tested for association with genome-wide single-nucleotide polymorphisms (SNPs). Four metabolites' concentrations exhibited significant, replicable association with SNP variation (8.6×10−11

DNA glycosylases involved in base excision repair may be associated with cancer risk in BRCA1 and BRCA2 mutation carriers

Abstract: Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p<0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.16), p = 2.7 × 10(-3)) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95%CI: 1.03-1.21, p = 4.8 × 10(-3)). DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/2 mutation carriers and should be more comprehensively studied.

A Phase Ib trial of CA4P (combretastatin A-4 phosphate), carboplatin, and paclitaxel in patients with advanced cancer

Abstract: A Phase Ib trial of CA4P (combretastatin A-4 phosphate), carboplatin, and paclitaxel in patients with advanced cancer

Rathke's cleft cysts.

Abstract: Rathke's cleft cysts (RCCs) are benign, sellar and/or suprasellar lesions originating from the remnants of Rathke's pouch. Although a common finding in routine autopsies (12-33% of normal pituitary glands), symptomatic cases are rare and comprise 5-15% of all surgically resected sellar lesions. Small, asymptomatic RCC do not require surgical intervention, and their natural history is not clear. In series of nonoperated presumed RCCs, 26-94% did not progress during follow-up periods up to 9 years. In symptomatic ones, surgery is indicated, aiming to drain the cyst content and safely remove as much of the capsule as possible. Following surgical intervention, headaches and visual field defects improve or resolve in a significant number of patients (40-100% and 33-100%, respectively) and partial hypopituitarism recovers in 14-50%. Data on relapse rates published in the last 15 years are based on variable follow-up periods and show wide variation (between 0% and 33%). The lowest relapse rates have been described in reports with relatively short mean observation periods (<3 years), whereas in those with longer follow-up the relapse rates increase. Most of the relapses occur within 5-6 years, suggesting that follow-up is required for at least 5 years after surgery. Risk factors for relapse include the presence of squamous metaplasia in the cyst wall, cyst size and the presence of inflammation. Long-term sufficiently powered studies aiming to clarify the natural history of asymptomatic RCCs and of those relapsing postoperatively are required.