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.

Modular extracorporeal life support for multiorgan failure patients

Abstract: Adults receiving respiratory Extracorporeal Membrane Oxygenation (ECMO) have 66% survival. Nonsurvivors develop multisystem organ failure (MSOF). Once hepatic failure develops, death usually follows shortly. Serum bilirubin > 300 micromol/l predicted death with 87.8% sensitivity and 90.3% specificity in 41 adults who received ECMO in our institution during 1998 and 1999. No patients survive with a peak bilirubin > 400 micromol/l. The Molecular Adsorbent Recirculating System (MARS) is a cell-free extracorporeal liver support device; we hypothesized that using MARS in adult respiratory ECMO patients with a bilirubin >300 micromol/l could improve survival in MSOF. The MARS was used in five such patients aged 19-56 who developed liver failure secondary to a respiratory illness. Mean peak bilirubin was 529 micromol/l and the lowest peak bilirubin was 436 micromol/l. Patients received between 1 and 8 MARS treatments, mean reduction in serum bilirubin for each patient ranging between 30 and 162 micromol/l. Two of five patients survived (40%), survivors showing the greatest reduction in serum bilirubin in response to MARS. All patients would have been expected to die according to our previous experience. We believe that MARS may prove a useful therapy for patients with MSOF.

Powerful identification of cis-regulatory SNPs in human primary monocytes using allele-specific gene expression.

Abstract: A large number of genome-wide association studies have been performed during the past five years to identify associations between SNPs and human complex diseases and traits. The assignment of a functional role for the identified disease-associated SNP is not straight-forward. Genome-wide expression quantitative trait locus (eQTL) analysis is frequently used as the initial step to define a function while allele-specific gene expression (ASE) analysis has not yet gained a wide-spread use in disease mapping studies. We compared the power to identify cis-acting regulatory SNPs (cis-rSNPs) by genome-wide allele-specific gene expression (ASE) analysis with that of traditional expression quantitative trait locus (eQTL) mapping. Our study included 395 healthy blood donors for whom global gene expression profiles in circulating monocytes were determined by Illumina BeadArrays. ASE was assessed in a subset of these monocytes from 188 donors by quantitative genotyping of mRNA using a genome-wide panel of SNP markers. The performance of the two methods for detecting cis-rSNPs was evaluated by comparing associations between SNP genotypes and gene expression levels in sample sets of varying size. We found that up to 8-fold more samples are required for eQTL mapping to reach the same statistical power as that obtained by ASE analysis for the same rSNPs. The performance of ASE is insensitive to SNPs with low minor allele frequencies and detects a larger number of significantly associated rSNPs using the same sample size as eQTL mapping. An unequivocal conclusion from our comparison is that ASE analysis is more sensitive for detecting cis-rSNPs than standard eQTL mapping. Our study shows the potential of ASE mapping in tissue samples and primary cells which are difficult to obtain in large numbers.

Cerebral blood flow response to neural activation after acute ischemic stroke: a failure of myogenic regulation?

Abstract: We tested two hypotheses: (1) neurovascular coupling is impaired after acute ischemic stroke, (2) subcomponent analysis of cerebral blood flow velocity can reveal significant differences between acute ischemic stroke and healthy controls. This was explored through the comparison of nineteen acute ischemic stroke patients with healthy controls. Recordings of cerebral blood flow velocity, blood pressure and end-tidal CO2 were obtained during 60s of passive elbow flexion. Cerebral blood flow velocity changes were decomposed into standardized subcomponents describing the contributions of blood pressure (VBP), resistance area product (VRAP) and critical closing pressure (VCrCP). The passive paradigm led to a bilateral cerebral blood flow velocity increase in both groups, but in acute ischemic stroke the magnitude of change was significantly lower. Blood pressure increases were shown to be an important contributor to cerebral blood flow velocity response throughout the paradigm in both groups, with no significant difference between groups. The VCrCP contribution was not different between groups or hemispheres; its continuous rise during activation indicating a vasodilatory effect. On the other hand, the VRAP contribution showed significant differences (p = 0.03), thus suggesting myogenic impairment in acute ischemic stroke. Cerebral blood flow velocity responses to passive elbow flexion suggest an impairment of neurovascular coupling in acute ischemic stroke. Subcomponent analysis suggests an impairment of the myogenic pathways, giving a greater insight into the different mechanisms contributing to neurovascular coupling. Further research is needed to assess the clinical value of subcomponent analysis of neurovascular coupling and the natural history of such changes following acute ischemic stroke.