Royal London Hospital

About: Royal London Hospital is a healthcare organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Medicine. The organization has 4854 authors who have published 5081 publications receiving 168207 citations. The organization is also known as: London Infirmary & London Hospital.

Effects of sevoflurane on dopamine, glutamate and aspartate release in an in vitro model of cerebral ischaemia

Abstract: Release of excitatory amino acids and dopamine plays a central role in neuronal damage after cerebral ischaemia. In the present study, we used an in vitro model of ischaemia to investigate the effects of sevoflurane on dopamine, glutamate and aspartate efflux from rat corticostriatal slices. Slices were superfused with artificial cerebrospinal fluid at 34∞C and episodes of ‘ischaemia’ were mimicked by removal of oxygen and reduction in glucose concentration from 4 to 2 mmol litre ‐1 for <30 min. Dopamine efflux was monitored in situ by voltammetry while glutamate and aspartate concentrations in samples of the superfusate were measured by HPLC with fluorescence detection. Neurotransmitter outflow from slices was measured in the absence or presence of sevoflurane (4%). After induction of ischaemia in control slices, there was a mean (SEM) delay of 166 (7) s (n=5) before sudden efflux of dopamine which reached a maximum extracellular concentration of 77.0 (15.2) mmol litre ‐1 . Sevoflurane (4%) reduced the rate of dopamine efflux during ischaemia (6.90 (1.5) and 4.73 (1.76) mmol litre ‐1 s ‐1 in controls and sevoflurane-treated slices, respectively; P<0.05), without affecting its onset or magnitude. Excitatory amino acid efflux was much slower. Ischaemia-induced glutamate efflux had not reached maximum after 30 min of ischaemia. Basal (pre-ischaemic) glutamate and aspartate efflux per slice was 94.8 (24.8) and 69.3 (31.5) nmol litre ‐1 superfusate (n=4) and was not significantly reduced by 4% sevoflurane. Ischaemia greatly increased glutamate and aspartate efflux (to a maximum of 919 (244)% and 974 (489)% of control, respectively). However, ischaemiainduced efflux of both glutamate and aspartate was significantly reduced by 4% sevoflurane (P<0.001 for glutamate, P<0.01 for aspartate). In summary, sevoflurane may owe part of its reported neuroprotective effect to a reduction of ischaemia-induced efflux of excitatory amino acids and, to a lesser extent, dopamine.

A qualitative study exploring the factors influencing admission to hospital from the emergency department

Abstract: Objective The number of emergency admissions to hospital in England and Wales has risen sharply in recent years and is a matter of concern to clinicians, policy makers and patients alike. However, the factors that influence this decision are poorly understood. We aimed to ascertain how non-clinical factors can affect hospital admission rates. Method We conducted semistructured interviews with 21 participants from three acute hospital trusts. Participants included 11 emergency department (ED) doctors, 3 ED nurses, 3 managers and 4 inpatient doctors. A range of seniority was represented among these roles. Interview questions were developed from key themes identified in a theoretical framework developed by the authors to explain admission decision-making. Interviews were recorded, transcribed and analysed by two independent researchers using framework analysis. Findings Departmental factors such as busyness, time of day and levels of senior support were identified as non-clinical influences on a decision to admit rather than discharge patients. The 4-hour waiting time target, while overall seen as positive, was described as influencing decisions around patient admission, independent of clinical need. Factors external to the hospital such as a patient’s social support and community follow-up were universally considered powerful influences on admission. Lastly, the culture within the ED was described as having a strong influence (either negatively or positively) on the decision to admit patients. Conclusion Multiple factors were identified which go some way to explaining marked variation in admission rates observed between different EDs. Many of these factors require further inquiry through quantitative research in order to understand their influence further.

The phagocytic capacity of neurones

Abstract: Phagocytosis is defined as the ingestion of particulates over 0.5 microm in diameter and is associated with cells of the immune system such as macrophages or monocytes. Neurones are not generally recognized to be phagocytic. Using light, confocal, time-lapse and electron microscopy, we carried out a wide range of in-vitro and in-vivo experiments to examine the phagocytic capacity of different neuronal cell types. We demonstrated phagocytosis of material by neurones, including cell debris and synthetic particles up to 2.8 microm in diameter. We showed phagocytosis in different neuronal types, and demonstrated that debris can be transported from neurite extremities to cell bodies and persist within neurones. Flow cytometry analysis demonstrated the lack of certain complement receptors on neurones but the presence of others, including integrin receptors known to mediate macrophage phagocytosis, indicating that a restricted set of phagocytosis receptors may mediate this process. Neuronal phagocytosis occurs in vitro and in vivo, and we propose that this is a more widespread and significant process than previously recognized. Neuronal phagocytosis may explain certain inclusions in neurones during disease, cell-to-cell spread of disease, neuronal death during disease progression and provide a potential mechanism for therapeutic intervention through the delivery of particulate drug carriers.

Clouston hidrotic ectodermal dysplasia (HED): genetic homogeneity, presence of a founder effect in the French Canadian population and fine genetic mapping.

Abstract: HED is an autosomal dominant skin disorder that is particularly common in the French Canadian population of south-west Quebec. We previously mapped the HED gene to the pericentromeric region of chromosome 13q using linkage analysis in eight French Canadian families. In this study, we extend our genetic analysis to include a multiethnic group of 29 families with 10 polymorphic markers spanning 5.1 cM in the candidate region. Two-point linkage analysis strongly suggests absence of genetic heterogeneity in HED in four families of French, Spanish, African and Malaysian origins. Multipoint linkage analysis in all 29 families generated a peak lod score of 53.5 at D13S1835 with a 1 lod unit support interval spanning 1.8 cM. Recombination mapping placed the HED gene in a 2.4 cM region flanked by D13S1828 proximally and D13S1830 distally. We next show evidence for a strong founder effect in families of French Canadian origin thereby representing the first example of a founder disease in the south-west part of the province of Quebec. Significant association was found between HED in these families and all markers analysed (Fisher's exact test, P < 0.001). Complete allelic association was detected at D13S1828, D13S1827, D13S1835, D13S141 and D13S175 (P(excess) = 1) spanning 1.3 cM. A major haplotype including all 10 associated alleles was present on 65% of affected chromosomes. This haplotype most likely represents the founder haplotype that introduced the HED mutation into the French Canadian population. Luria-Delbruck equations and multipoint likelihood linkage disequilibrium analysis positioned the gene at the D13S1828 locus (likely range estimate: 1.75 cM) and 0.58 cM telomeric to this marker (support interval: 3.27 cM) respectively.

Laboratory Evaluation of the DCA 2000 Clinic HbA1c Immunoassay Analyser

Abstract: The DCA 2000 clinical analyser for the measurement of haemoglobin A1c was evaluated for analytical quality. The analyser, which utilises inhibition of latex agglutination immunoassay, demonstrated good within-batch (1.9-3.1% CV) and between-batch (2.2% CV) imprecision, and was not affected by haemoglobin concentration. The analyser was linear throughout the analytical range, and was found to correlate well with agar electroendosmosis (r = 0.93), affinity chromatography (r = 0.97), HPLC (r = 0.90) and EIA (r = 0.98). The analyser was found to give reliable analytical results, and with its ease of use, will provide the diabetologist with HbA1c results in the clinic; although an analysis time of 9 min will limit sample throughput.