Faye, Sherry Ann (1988) Investigations on plasma cholinesterase in man and animals using succinylcholine as the substrate. PhD thesis, University of Leeds.
Abstract
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.
Metadata
Supervisors: | Evans, Robert |
---|---|
Awarding institution: | University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > Institute of Molecular Medicine (LIMM) (Leeds) > Section of Pathology (Leeds) > Pathology (Leeds) |
Identification Number/EthosID: | uk.bl.ethos.513933 |
Depositing User: | Ethos Import |
Date Deposited: | 16 Feb 2010 08:36 |
Last Modified: | 07 Mar 2014 10:27 |
Open Archives Initiative ID (OAI ID): | oai:etheses.whiterose.ac.uk:228 |
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