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Title: Trace element studies in motor neurone disease
Author: Mitchell, John Douglas
ISNI:       0000 0001 3411 9702
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 1990
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The first part of the thesis reviews previous literature relating to motor neurone disease (MND), the cause of which remains obscure more than 150 years after it was first described. Historical aspects are presented drawing attention to the early descriptions of different facets of the clinical picture of MND which preceded its crystallisation into a single disease entity in the teaching and writing of Charcot. Much of this early work depended on knowledge of the toxic effects of lead on the peripheral nervous system. The epidemiology, blood group and HLA associations, pathology, immunology and virology of MND are discussed. Physical factors are also reviewed as are previous biochemical studies of MND. Knowledge regarding lead and mercury in relation to MND is discussed in detail. An analysis of previous literature concerning trace elements in MND is then presented to introduce the experimental section. This concerns the measurement of trace elements in spinal cord, liver, bone and cerebrospinal fluid (CSF) in MND patients and reference subjects by neutron activation analysis. Increased cervical cord, liver and bone selenium concentrations were found in the MND patients. Manganese content was increased in cervical and thoracic cord but reduced in liver. Low CSF cobalt concentration were also found. All other elements measured were striking by their concordance between the two groups in both tissue and CSF samples. These findings of an apparent alteration in the distribution of selenium and manganese in MND suggested that free radical mechanisms might be implicated in the pathogenesis of MND. CSF parameters of free radical activity were therefore studied but no differences found between reference subjects and MND patients. These results are discussed both in relation to the trace element studies and recent work on the possible importance of xenobiotics in the aetiology of the disease. Other aspects of the biological importance of selenium and manganese are described and some consideration is given to the DNA hypothesis of Bradley. This hypothesis is difficult to verify experimentally. A cytogenetic approach studying the sensitivity of lymphocytes obtained from control subjects and MND patients to mitomicin-C and ethyl methanesulphonate is described. This work did not yield any collateral evidence to support this hypothesis. In conclusion an attempt is made to bring the results of all this work together and consider how they might lead to a clearer understanding of the cause of this tragic and enigmatic disease.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Biophysics