Lai, Kai-Sum

2018-09-13T16:01:29Z

2018-09-13T16:01:29Z

1962

The relatively small number of cases in this series, aggravated by the need for further division into subgroups, makes interpretation difficult. The situation is made worse by a number of factors as yet unknown, e.g., the effect of anaesthesia and duration of operation on the gastrin content, the rate of turnover of gastrin and the significance of a single estimate of extractable gastrin -like activity. Any comment on the above results must therefore be speculative.

There is now good experimental evidence indicating that vagal excitation stimulates acid gastric secretion by (a), causing release of gastrin, (b), sensitizing the parietal cells to various stimuli including gastrin, and (c), direct stimulation of the parietal cell. If one assumes that, under strong and possibly maximal vagal stimulation by insulin- induced hypoglycaemia direct stimulation of the parietal cells is responsible for a constant proportion of the acid output, then the remainder of the acid secretory response to insulin would be accounted for by the amount of gastrin liberated. Since, however, there is a positive correlation between the insulin- stimulated acid secretion and the total gastrin-like activity in the uncomplicated D.U.'s in this study, it would seem reasonable to assume that, in these cases, the amount of gastrin liberated into circulation is proportional to the total gastrin -like activity extractable from the stomach. This is assumed to be true also for D.U.'s with stenosis.

Hunt & Kay (1954) have suggested that the increase in parietal cell mass in D.U.'s with stenosis was a result of repeated distension of the stomach with consequent stimulation of the parietal cells. The data presented in Fig. 15 and 16 is compatible with this view. The cases with stenosis had more gastrin in the antral mucosa (and hence probably in the circulation) than the uncomplicated cases. The observation that cases with mild as well as severe stenosis had similar total gastrin -like activity could be explained by the possibility of operative intervention at different phases of progression of the disease, it being assumed that a considerable time lag exists between the increase in gastrin content (and production) and the associated growth in the parietal cell mass.

The results in Fig. 16 indicate that the insulin -stimulated secretion per secretory unit, represented by the ratio 'insulin- secretion test/ maximal histamine output', remained about the same despite increase in the total gastrin -like activity beyond a point at about the equivalent of 100 pg of the Standard. This might represent a plateau response to maximal or supramaximal levels of circulating gastrin.

The possible role of gastrin in the aetiology of duodenal ulceration has been suggested by Gillespie & Kay (1961) who showed that antrectomy alone led to healing of the duodenal ulcer in four patients. The Zollinger -Ellison syndrome provides an extreme example of possible effects of excessive gastrin (or gastrin -like substance) in circulation. The idea of gastrin possibly playing a role as a trophic hormone to the parietal cells has been summarized by Card (1962), who cited in support a case of Zollinger -Ellison syndrome of Dr. Bryan Alton when the 'maximal histamine output' of the patient progressively fell after partial resection of the pancreas and left adrenalectomy without any surgery on the stomach. The failure to demonstrate a correlation between the 'maximal histamine output' and gastrin -like activity in this present study does not support this idea but certainly does not exclude it, since apart from all the unknown factors mentioned above, this series could well have included cases with a large parietal cell mass to start with, irrespective of the gastrin content in the antrum.

The whole problem of the clinical significance of gastrin is obviously a dynamic one, a better approach to which would probably be the assay of gastrin in blood or urine, methods for which remain to be devised.

http://hdl.handle.net/1842/32444

The University of Edinburgh

Annexe Thesis Digitisation Project 2018 Block 20

Method of biological assay of Gastrin and its application to the study of human tissue

Thesis or Dissertation

Doctoral

PhD Doctor of Philosophy