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Title: Myasthenia gravis
Author: Simpson, John Alexander
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 1964
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The thesis is 72 publications describing the author's hypothesis of an autoimmune basis for myasthenia gravis (MG) and its validation. At the time of the first 24 papers many considered that MG was a syndrome rather than a disease entity, due to a biochemical disorder of the neuromuscular junction. Favoured models were a circulating 'curare-like' substance released from the thymus gland, or a pre-junctional abnormality, possibly causing release of small quanta of acetylcholine at the motor nerve terminals. Endplate receptor substance was speculative. The immunological role of the thymus was unknown and autoimmunity was a new concept in medicine. The therapeutic value of thymectomy was controversial. The controversy about thymectomy was resolved (papers 2,3) by re-analysing data separately for patients with a thymona and the conclusions have proved definitive. Papers based on the cases reviewed in that survey led to an autoimmune hypothesis with a thymic disorder causing production of antibodies with loss of tolerance to self-tissue, mainly but not exclusively at the motor endplates of muscle. The first recognition of many associated diseases and a re-interpretation of the relationship with thyroid disorders are described, with the first evidence for a genetic predilection with alternative expression. During the 35 years of this work the distinct nature of 'carcinomatous' myasthenia has been identified, and the non-immunological congenital myasthenias defined by other workers.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available