Lipid profiles and cardiovascular disease in the Whickham area with particular reference to thyroid failure.
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Biomedical subjects
Publications and source records attributed to R Hall.
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A survey in a general practice in the North-East of England in 1963 detected thyroglobulin antibodies in 16.2% of women and 4.3% of men. High titres of antibodies were found in 4.6% of women and 1.6% of men. Forty six subjects with thyroglobulin antibodies (from an original total of fifty-two) were studied in 1972 and forty of these were studied further in 1975. These subjects were compared with a group of age- and sex-matched controls from the original survey. Three of the subjects had developed overt hypothyroidism by 1975 and a raised serum thyroid-stimulating hormone (TSH) concentration was found more frequently in euthyroid subjects peviously found to be antibody positive. There was a striking difference in the antibody studies in that only 26% of the previously antibody positive subjects had thyroglobulin antibodies in 1972 and 30% in 1975. A raised serum TSH concentration was found to correlate with cytoplasmic a-tibodies and particularly with the combination of cytoplasmic and thyroglobulin antibodies.
Thyroid-stimulating immunoglobulins (TSI) have been detected by receptor assay in the sera of 43% of patients with ophthalmic Graves' disease. Comparison of the receptor assay studies with thyroid function tests indicated that in several patients the antibodies detected by receptor assay were biologically inactive. In other patients, thyroid function appeared to be under TSI control with hyperthyroidism prevented by autoimmune destruction of the thyroid.
Ten endocrinologically normal men with secondary sexual impotence were given 500 microng LHRH subcutaneously every 8 h. After 4 weeks treatment the LH response to 500 microng LHRH was reduced from a peak of 35.7+/-5.2 to 16.8+/-3.5 mu/ml (P less than 0.01) and the FSH response from 4.2+/-0.93 to 2.39+/-0.4 mu/ml (P greater than 0.01). Circulating total testosterone, oestradiol, prolactin and sex hormone binding globulin showed no significant changes. Whether this inability of the pituitary to maintain it s response to LHRH is peculiar to impotent men requires further study.
A comparative study of the outcome of surgical treatment for thyrotoxicosis was carried out in two countries with dissimilar dietary iodine levels. In the area with a high iodine level (Iceland) the prevalence of post-operative hypothyroidism was five times lower, but recurrent hyperthyroidism was five times higher, than in the area with lower iodine levels (northeast Scotland). The total morbidity reached comparable levels in the two samples. The prevalence of positive thyroid antibody tests and serum thyrotrophin levels was lower and the functional capacity of the thyroid remnant higher in the area with the higher dietary iodine intake. The study provides further evidence that there are important regional differences in the prevalence of factors known to influence the response to surgical treatment of thyrotoxicosis which should be taken into account when planning treatment services.
A comparative study was made of thyroid function in samples of 'well' subjects, from separate geographical areas with dissimilar dietary iodine levels. In the area with the higher iodine level, Iceland, the prevalence of positive thyroid antibody tests and serum thyrotrophin levels were lower, while the capacity of the thyroid to respond to exogenous thyrotrophin was higher than in NE Scotland, an area with lower iodine levels. In contrast the prevalence of positive tests for another organ-specific antibody, gastric parietal cell antibody, was higher in Iceland. These observations are consistent with the reported differences in the incidence rates for thyrotoxicosis and gastric carcinoma in the areas studied. The results are in agreement with our findings in two groups of post-thyroidectomy patients from the same populations. This study provides support for the view that differences in the prevalence of constitutional and environmental factors in different populations contribute to the variation in reported outcome of treatment for thyroid disease.
Social anxiety was found to be the most common complaint in a sample of psychiatric patients reporting social interaction difficulties. High social anxiety was shown to be associated with impairments to social behaviour in socially anxious psychiatric patients and non-psychiatric volunteers. A comparison was made of systematic desensitization and a form of social skills training in the treatment of social interaction difficulties associated with high social anxiety. This indicated that while both therapies were effective in the reduction of social anxiety, the training programme was the more effective in reducing problem behaviour, but desensitization appeared to lead to a wider generalization of improvement as indicated by increases in social participation.
Propranolol, a beta adrenergic blocking drug, is known to inhibit the thyrotropin (TSH) stimulation of adenosine-3',5'-monophosphate (cyclic AMP production in thyroid membranes but the mechansim of this inhibitory action is known. We have therefore investigated the influence of propranolol on the binding of 125I-labelled TSH to human thyroid membranes. Both d- and l-propranolol were found to enhance the binding of 125I-labelled TSH to thyroid membranes. The amount of label bound increased from about 30% in the absence of propranolol to about 60% in the presence of 3.3 x 10(-3)M propranolol. Scatchard analysis of the binding data indicated that propranolol increased the association constant of the thyrotropin-thyrotropin receptor interaction. Practolol, lithium carbonate, methimazole, and somatostatin had no effect on thyrotropin binding. This effect of propranolol appeared to be due to a direct reversible action of propranolol on the thyroid membranes and could be attributed to the membrane-disrupting properties of the drug rather than its beta-blocking activity. The increased TSH receptor occupancy which resulted from the increased association constant of the TSH-thyroid membrane interaction corresponded with a decrease in TSH-stimulated cyclic AMP formation. These data could indicate that propranolol reduced the efficiency of the receptor-adenylyl cyclase coupling system.
The relationship between the binding of thyrotrophin (TSH) to receptors and the production of cyclic AMP has been investigated using crude human thyroid membranes. Receptor binding was studied by use of 125I-labelled bovine TSH, which had been purified by adsorption to and elution from human thyroid membranes. This 125I-labelled material showed the same biological activity as the unlabelled hormone. Binding studies at equilibrium indicated that the association constant of the TSH-membrane interaction decreased as the amount of TSH bound increased. Kinetic data did not provide definite evidence that this was due to an effect of increasing receptor occupancy on the dissociation rate constant. Detectable stimulation by TSH of cyclic AMP production by the membranes was observed with as little as 30 micromicron. (1 ng) hormone. Increasing amounts of TSH over the range 0-250 micromicron caused increases in the production of cyclic AMP, proportional to the amount of hormone bound. With larger amounts of TSH, increasingly greater amounts of bound hormone were required to give corresponding increases in cyclic AMP formation, and addition of TSH in amounts greater than 16 millimicron resulted in progressive inhibition of cyclic AMP formation. Kinetic studies indicated that receptor binding was not rate-limiting in the stimulation of cyclic AMP production by TSH.
Thyroid-stimulating antibodies (TSAb) were found to inhibit the binding of labelled thyrotrophin (TSH) to thyroid membranes in a dose-dependent manner and this effect was localized in the Fab part of the TSAb molecule. Analysis of the binding data suggested that TSAb and TSH bound to the same receptor site. Production of cyclic AMP by the thyroid membranes was stimulated by TSAb and TSAb-Fab with a similar time course to that observed with TSH. Kinetic studies indicated that the binding of TSAb to the thyroid membranes was not rate-limiting in the process of stimulation of cyclic AMP production.
Correlations of activity and weight at three water temperatures, 20 degrees, 26 degrees, and 30 degrees C, were examined in the comet goldfish (Carassius auratus). For the 12 subjects general activity scores increased as water temperature increased. Heavier subjects were more active at low temperatures while lighter subjects were more active at higher temperatures.
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A syndrome comprising Addison's disease, renal microangiopathy and renal failure is described in two patients. The renal lesions manifested despite corticosteroid replacement therapy and were characterized by glomerular damage and thrombo-microangiopathic changes in afferent arterioles and intralobular arteries. Both patients died as a result of their renal disease.
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The programmed investigation unit (PIU) is a inpatient unit where a full range of investigational medicine can be organised. It provides the basic minimum nursing care and is suitable for ambulant patients who can care for themselves. Requests for admission to the PIU at the Royal Victoria Infirmary, Newcastle upon Tyne, come directly from clinical units, and the staff of these units perform some of the tests and remain responsible for the patient while she is in the unit. At present the unit caters only for female medical patients. The average waiting time for admission is three weeks, and because the unit now deals with most investigations the waiting time for admission to the female general medical wards has fallen considerably. The staff of the unit have gained expertise in diagnostic methods, while the nurses of general medical wards have been free to concentrate on nursing those patients who need it. Separating patients who need investigations from those on general medical wards seems a logical way of using resources and staff to best effect.
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