Studies on immuno-reactive gastrin with special reference to rheumatoid arthritis

Rooney, Patrick Joseph (1975) Studies on immuno-reactive gastrin with special reference to rheumatoid arthritis. MD thesis, University of Glasgow.

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Abstract

The work presented in this thesis stems from the recurrent clinical problem of dyspepsia and peptic ulceration In patiants with rheumatoid arthritis. Little light on the aetiology of this problem has been thrown by previous investigators using clinical techniques such as radiology.gastric function studies and gastro-intestinal endoscopy. A new approach using the modern technology of radioimmunoassay of small peptide hormones has been applied and the resultant findings are the major aspect of this work. The first chapter deals extensively with the background to this work and includes detailed historical reviews of the incidence and possible aetiology of rheumatoid arthritis. In addition a detailed history of gastric function and of tests of gastric function are presented. Special emphasis is placed on those aspects known to influance gastrin secretion and action including the parietal cell functions of acid and intrinsic factor secretion. A shorter review of the background of pancreatic secretion and pancreatic endocrinology is also presented in view of its relevance to the work reported on immunoreactive secretin. The technique of radioimmunoassy of gastrin which is the central investigative tool used in this work is presented in considerable detail in Chapter 2. The background to the development of radioimmunoaassay and the limitations and advantages of the method are considered. Chapter 3 describes the results of the clinical significance of immunoreactive gastrin in rheumatoid arthritis. My original observation that immunoreactive gastrin is elevated in somo patients with rheumatoid arthritis is reported in detail. consideration is given to the extensive clinical and laboratory studices which this observation occasioned in an effort to uncover the aetiology of the phenomenon. It Is reported that the distribution of values of immunoreactive gastrin in normal subjects is log/norinal and the patients with rheumatoid arthritis seem to belon; to two distinct populations in respect to immunoreactive gastrin status. No Correlation could be found between this hypergastrinaemia and gastric acid output. Nor oould it be attributed to anti-inflammatory drug therapy. No othor clinical aspect of rheumatoid disease could be incriminated in this effect and it is of note that other chronic inflanmmtory arthritides failed to show a similar elevation of immunoreactive gastrin concentrations. In Chapter 5 further evidence ia presented that gastrin. may be implicated in the pathogenesis of ohronic inflammation. In rats the induction of adjuvant arthritis is shown to cause an elavation of immunoreactive gastrin. Some evidence is also prsented that the changes in hormone recorded by the immunoassay are biologically meaningful since a significant fall in gastric acid output in fistula rats was noted at the time of peak elevation of immunoroactive gastrin in intact animals. The unusual combination of ulcer healing and anti-inflarmatory actions of carbenoxolone sodiam induced me to use this drug therapeutically in patients with rheumatoid arthritis. chaptar 4 records the failure of this drug to benefit the inflammatory joint disease but also reports the original observation that this drug may act on peptic ulcer via its action on immunoreactive secretin. How this accords with the observations of other investisti; ators is considered in some detail. The close association in terms of gastric physiolosgy between gastrin and histamine is reviewed in Chapter 6, Histamine has long been associated with inflammation so that my implication of gastrin in inflammatory disease encouraged me to look at a possible role for aastrin in micro-circulatory responses. The results obtained using a dog model are oonaidered. There was no apparent effect of gastrin on this model which reflects well, the profound actions of histamine on blood vessels. The major changes in symptomatology of both inflammatory joint disease and peptic ulceration which occurs in pregnancy induced me to consider the role of gastrin in pregnancy. Chapter 7 reports important new information which indicates that a significant rise occurs in immunoreactive, gastrin towards the end of pregnancy and in the early puerperium.

Item Type: Thesis (MD)
Qualification Level: Doctoral
Additional Information: Adviser: Edward N McGirr
Keywords: Immunology
Date of Award: 1975
Depositing User: Enlighten Team
Unique ID: glathesis:1975-72071
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 24 May 2019 15:11
Last Modified: 24 May 2019 15:11
URI: http://theses.gla.ac.uk/id/eprint/72071

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