Biomedical subjects
Publications and source records attributed to J Sheldon.
A pregnancy occurring in an untreated woman with active acromegaly is described, together with the clinical and biochemical responses to bromocriptine treatment. It is suggested that bromocriptine treatment need not necessarily be continued throughout such a pregnancy.
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The effects of amiodarone on thyroid function tests in 100 patients treated for 6 weeks to 8 years are reported. One patient became thyrotoxic and 10 developed latent or overt hypothyroidism. Twenty-five patients remained clinically euthyroid throughout, but had free thyroxine indices above the normal range. In these patients with apparently anomalous results, total tri-iodothyronine was normal in 19 cases and low in 1; conversely, free thyroxine was high in all 17 cases in which it was measured. Thyrotrophin releasing hormone (TRH) tests were abnormal in 4 of the 13 patients who had the test. Reverse tri-iodothyronine was significantly raised after 2 weeks amiodarone in 5 healthy subjects, but an equivalent amount of iodine in 9 healthy individuals did not significantly affect any of these tests. We believe that these changes are due in part to inhibition of peripheral conversion of thyroxine to tri-iodothyronine with diversion to reversed tri-iodothyronine. Thyroid function tests should be checked once or twice a year in all patients on maintenance amiodarone. Tests indicating hypothyroidism are likely to be clinically relevant, whereas levels of thyroxine suggesting thyrotoxicosis may be misleading and do not usually imply the need to discontinue treatment with the drug.
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Experiments were performed with rat pancreas to investigate optimum conditions for obtaining and preserving the pancreas for subsequent isolation of islets that were viable by both functional and morphological criteria. After only 30 min of warm ischaemia, the yield and viability of islets that could be isolated were poor. However, if the pancreas was removed and placed immediately in a cold bicarbonate-buffered medium, which was supplemented with HEPES to maintain the pH and Trasylol to inhibit proteolytic activity, then viable islets could be isolated consistently after over 8 hr of storage. These results demonstrate that even short periods of warm ischaemia will render the pancreas unsuitable for islet isolation. Once the pancreas is placed in a suitable cold medium, however, considerable delay may be permissible without adversely affecting the viability of the islets which can be obtained. The same conditions might prove to be applicable when human pancreas is obtained for the purpose of transplantation into diabetic subjects.
The regulation of insulin biosynthesis, and insulin and glucagon secretion have been investigated in a human islet cell adenoma, by incubation of tumour fragments. Both biosynthesis and secretion of insulin were strongly stimulated by incubation of islet tumour cells in the presence of increasing glucose concentrations in the range 2-8 mmol/1. However, 20 mM-glucose or 20 mM-glucose plus isobutyl methylxanthine (IBMX), both of which provide potent secretagogues for normal B cells, failed to stimulate proinsulin biosynthesis and secretion from the tumour cells. Overall rates of secretion, expressed as a proportion of total insulin content, were up to 20-fold higher than those expected for normal pancreatic tissue. Glucagon secretion from the tumour was stimulated by low glucose concentrations; normal A cells also respond in this way under these conditions. However, no stimulation of glucagon secretion occurred in the presence of IBMX. There was therefore a major alteration in the regulation both of insulin and glucagon secretion, in that release of neither hormone was stimulated by cyclic AMP. Ultrastructural examination showed the tumour to be rather heterogeneous. A and B cells with normal storage granule content and structure were seen, as well as a rather larger number of B cells containing some granules of atypical appearance. The insulin content of the tumour (13 i.u./g wet wt) was consistent with 6-8% of the tumour cells being B cells.
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Two cases are reported in which a remission of diabetes was sustained throughout pregnancy. This seemed to be due in part to improved beta-cell function consequent on restoration of normoglycaemia before pregnancy, and in part to an increase in insulin sensitivity during pregnancy, which in the first case disappeared very rapidly after delivery.
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