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Investigations on plasma cholinesterase in man and animals using succinylcholine as the substrate

Faye, Sherry Ann (1988) Investigations on plasma cholinesterase in man and animals using succinylcholine as the substrate. PhD thesis, University of Leeds.

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A simple, precise "reaction rate" assay for plasma cholinesterase based on a succiny1choline substrate has been developed. It's ability to define individuals at risk of succiny1choline sensitivity and identify those who had experienced apnoea was superior to the previously best available assay. However it was not able to identify abnormal forms of cholinesterase which could hydrolyze conventional assay substrates but not succinylcholine. It was-concluded that if these forms exist their numbers are small. The failure to identify such cholinesterase types may have been because'the substrate concentration chosen for the assay was higher than that found"pharnacologically. However investigation of the kinetics of the succiny1choline-cholinesterase interaction showed that this was not the case. The assay was applied to the assessment of liver dysfunction and compared to three established methods was superior. All assays identified patients with severe liver disease but the succinylcholine-based one identified more patients with moderate/mild disease. The assay was also used to investigate the clinical observation that children require a higher dose of succiny1choline for muscle relaxation than adults. Infants were found to have higher succiny1choline activities than adults which is compatible with their relative resistance to the drug. Finally cholinesterase measurements were made, using a range of substrates including succinylcholine, in a variety of animal species. Results show that only when succiny1choline is used as the substrate for'the assay of cholinesterase does enzyme activity correlate with tolerance to it's muscle relaxant properties. The choice of procedure for the analysis of any biochemical variable depends on a number of criteria including ease of assay, precision, accuracy and cost; however the primary consideration should be the ability of the method to provide clinically useful information. Based on all these criteria, in particular the latter, succiny1choline must be considered as the substrate of choice.

Item Type: Thesis (PhD)
Academic Units: The University of Leeds > Faculty of Medicine and Health (Leeds) > Institute of Molecular Medicine (LIMM) (Leeds) > Section of Pathology (Leeds) > Pathology (Leeds)
Depositing User: Ethos Import
Date Deposited: 16 Feb 2010 08:36
Last Modified: 07 Mar 2014 10:27
URI: http://etheses.whiterose.ac.uk/id/eprint/228

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