A comparison of serum and plasma levels of vascular endothelial growth factor during the menstrual cycle in healthy female volunteers

Angiogenesis is the formation of new blood vessels from the existing vasculature, and is essential for the growth and metastasis of most solid tumours. One of the most important growth factors involved in the angiogenesis process is vascular endothelial growth factor. Vascular endothelial growth factor expression has been shown to be regulated by female hormones in breast cancer cell lines, and two previous authors have reported on cyclical variations in serum vascular endothelial growth factor concentrations with conflicting results. No work has been performed on variations in plasma levels of vascular endothelial growth factor during the menstrual cycle. We therefore conducted the first prospective trial to compare serum and plasma levels of vascular endothelial growth factor in healthy pre-menopausal volunteers. Twenty healthy pre-menopausal women were recruited and had blood samples taken over one menstrual cycle with an average of eight samples taken per patient. Plasma and serum samples were then analysed for sex hormones and vascular endothelial growth factor 165. Serum vascular endothelial growth factor levels were found to be significantly higher than plasma vascular endothelial growth factor levels (P<0.005). We found no significant difference between serum and plasma vascular endothelial growth factor in the luteal and follicular phases of the cycle. The majority of the measurements for plasma levels of vascular endothelial growth factor at all phases of the cycle were under the limit of detection of the vascular endothelial growth factor ELISA kit. We found no significant correlation between plasma or serum levels of vascular endothelial growth factor and either FSH, LH, Oestradiol or Progesterone levels. This study has demonstrated no difference in serum concentrations of vascular endothelial growth factor during the different phases of the menstrual cycle in a group of healthy volunteers. We also demonstrated no obvious difference in plasma concentrations of vascular endothelial growth factor between the phases of the cycle, but most of the measurements were below the level of accuracy reported by the ELISA kit manufacturer. With the sensitivity of this ELISA test, therefore, we must still regard the question of whether there is a variation in plasma concentrations of vascular endothelial growth factor throughout the menstrual cycle as unanswered

Factors associated with spontaneous stone passage in a contemporary cohort of patients presenting with acute ureteric colic. Results from the MIMIC Study (A Multi-centre cohort study evaluating the role of Inflammatory Markers in patients presenting with acute ureteric Colic)

Objectives There is conflicting data on the role of white blood cell count (WBC) and other inflammatory markers in spontaneous stone passage in patients with acute ureteric colic. The aim of the study was to assess the relationship of WBC and other routinely collected inflammatory and clinical markers including stone size, stone position and Medically Expulsive Therapy use (MET) with spontaneous stone passage (SSP) in a large contemporary cohort of patients with acute ureteric colic. Subjects and Methods Multi‐centre retrospective cohort study coordinated by the British Urology Researchers in Surgical Training (BURST) Research Collaborative at 71 secondary care hospitals across 4 countries (United Kingdom, Republic of Ireland, Australia and New Zealand). 4170 patients presented with acute ureteric colic and a computer tomography confirmed single ureteric stone. Our primary outcome measure was SSP as defined by the absence of need for intervention to assist stone passage. Multivariable mixed effects logistic regression was used to explore the relationship between key patient factors and SSP. Results 2518 patients were discharged with conservative management and had further follow up with a SSP rate of 74% (n = 1874/2518). Sepsis after discharge with conservative management was reported in 0.6% (n = 16/2518). On multivariable analysis neither WBC, Neutrophils or CRP were seen to predict SSP, with an adjusted OR of 0.97 [95% CI 0.91 to 1.04, p = 0.38], 1.06 [95% CI 0.99 to 1.13, p = 0.1] and 1.00 [95% CI 0.99 to 1.00, p = 0.17], respectively. Medical expulsive therapy (MET) also did not predict SSP [adjusted OR 1.11 [95% CI 0.76 to 1.61]). However, stone size and stone position were significant predictors. SSP for stones 7mm. For stones in the upper ureter the SSP rate was 52% [95% CI 48 to 56], middle ureter was 70% [95% CI 64 to 76], and lower ureter was 83% [95% CI 81 to 85]. Conclusion In contrast to the previously published literature, we found that in patients with acute ureteric colic who are discharged with initial conservative management, neither WBC, Neutrophil count or CRP help determine the likelihood of spontaneous stone passage. We also found no overall benefit from the use of MET. Stone size and position are important predictors and our findings represent the most comprehensive stone passage rates for each mm increase in stone size from a large contemporary cohort adjusting for key potential confounders. We anticipate that these data will aid clinicians managing patients with acute ureteric colic and help guide management decisions and the need for intervention

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Wet weather highway accident analysis and skid resistance data management system. Volume 2: user's manual. Final report.

Louisiana Transportation Research Center, Baton RougeFederal Highway Administration, Washington, D.C.Mode of access: Internet.Author corporate affiliation: Louisiana State University, Baton Rouge, Industrial Engineering DepartmentReport covers the period of 1 Feb 1990 - 30 June 1992Subject code: CDFSubject code: MSDSubject code: NCYS*CDFSubject code: XL