Leicester Royal Infirmary

About: Leicester Royal Infirmary is a healthcare organization based out in Leicester, United Kingdom. It is known for research contribution in the topics: Population & Carotid endarterectomy. The organization has 5300 authors who have published 6204 publications receiving 208464 citations.

Sensitivities of Human Monocytes and Epithelial Cells to Pneumolysin Are Different

Abstract: The Streptococcus pneumoniae pore-forming toxin, pneumolysin, is an important virulence factor in pneumococcal pneumonia. The effect of pneumolysin on human lung epithelial and monocyte cell viability was compared. Pneumolysin caused a dose-dependent loss of viability of human lung epithelial (A549 and L132) and monocyte (U937 and THP-1) cell lines. Analysis of the dose-response curves revealed similar log 50% inhibitory concentration (pIC(50)) values for A549, L132, and THP-1 of 0.12+/- 0.1, 0.02+/- 0.04, and 0.12+/- 0.13 hemolytic units (HU), respectively, but U937 cells showed a significantly greater pIC(50) of 0.42+/- 0.12 HU. Differentiation of A549 and L132 with phorbol ester or THP-1 with gamma interferon had no effect on their sensitivity to pneumolysin. However, a significant decrease in the potency of pneumolysin against U937 cells followed gamma interferon treatment. The Hill slopes of the inhibition curves were greater than unity, indicating that pneumolysin may act with positive cooperativity. Analysis of pneumolysin-treated THP-1 cells by electron microscopy revealed membrane lesions of between 100 and 200 nm in diameter.

The potential impact of using glycated haemoglobin as the preferred diagnostic tool for detecting Type 2 diabetes mellitus.

Abstract: Diabet. Med. 27, 762–769 (2010) Abstract Aims There are calls to simplify the diagnosis of Type 2 diabetes mellitus (T2DM) to reduce the burden of undiagnosed disease. Glycated haemoglobin (HbA1c) is therefore being considered as a preferred diagnostic tool to replace the need for an oral glucose tolerance test (OGTT), considered by many as cumbersome and inconvenient. The aim of this study was to examine the potential impact of the preferred use of HbA1c as a diagnostic tool on the prevalence and phenotype of T2DM. Methods Analysis of the Leicester Ethnic Atherosclerosis and Diabetes Risk (LEADER) cohort for previously undiagnosed individuals between 40 and 75 years of age who had OGTT, repeated if within the diabetes range, and HbA1c results. We compared the prevalence and phenotype of subjects with T2DM based on either HbA1c≥6.5% or OGTT using 1999 World Health Organization criteria. Results From the total population of 8696, we detected 291 (3.3%) with T2DM from using an OGTT, and 502 (5.8%) had HbA1c≥6.5%. Of those diagnosed with T2DM by OGTT, 93 (1.2%) had HbA1c <6.5% and therefore would not have been classified as having T2DM using proposed criteria. Using HbA1c criteria resulted in 304 (3.5%) additional cases of T2DM, approximately doubling the prevalence. Of these 304 additional people, 172 (56.7%) had impaired glucose tolerance/impaired fasting glycaemia according to 1999 World Health Organization criteria. Using HbA1c criteria there was an increase of 2.2- and 1.4-fold in south Asians and white Europeans detected, respectively. Conclusions Within this multi-ethnic cohort, we found that introducing HbA1c≥6.5% as the preferred diagnostic test to diagnose T2DM significantly increased numbers detected with T2DM; however, some people were no longer detected as having T2DM.

Guidelines for using quantitative magnetization transfer magnetic resonance imaging for monitoring treatment of multiple sclerosis

Abstract: Quantitative evaluation of brain magnetic resonance imaging (MRI) scans is now an accepted part of the trial of new putative treatments for multiple sclerosis (MS). However, conventional MRI is not pathologically specific, and it does not reveal the details of the pathological processes that underlie the progression of the disease. Magnetization transfer (MT) imaging is a relatively new quantitative technique that appears to offer some pathological specificity, and can be used to monitor the changes over time in both individual lesions and the central nervous system as a whole. This paper considers the case for incorporating MT imaging into new clinical trials, so that the utility of MT for monitoring the modification of MS progression by treatment can be assessed. Specific guidelines for implementing MT imaging as part of a large multicenter clinical trial are given, and practical considerations when planning such a trial are detailed. It is anticipated that MT imaging will be incorporated into many new trials in the near future.