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Biomedical subjects

D S Munro

Publications and source records attributed to D S Munro.

At least 55 records · Page 3Linked to original sources

Long-term effects of cyproterone acetate on the pituitary adrenal axis in adult women.

Function of the pituitary-adrenal axis was assessed in 16 adult female patients who had been taking cyproterone acetate for greater than 1 year. Some evidence of reduced basal cortisol output was seen in 25% of the patients, but plasma cortisol levels could be stimulated both by hypoglycaemia and by direct corticotrophin (ACTH) stimulation. The latter effect was confirmed by analysis of steroid excretion in urine although basal excreation rates indicated extensive adrenal suppression. These results suggest that cyproterone acetate does have some glucocorticoid activity which is able partially to suppress the pituitary--adrenal axis, but leaves it still responsive to stress.

Adult↗

Comparison of human and porcine thyroid membranes for radioreceptor assay of bovine thyrotrophin and thyrotrophin-binding inhibiting immunoglobulins.

A detailed comparison between the use of human and porcine thyroid membranes for the radioreceptor assay (RRA) of bovine TSH (bTSH) and thyrotrophin-binding inhibiting immunoglobulins (TBIIg) is reported. Bovine thyroid membranes were also investigated but were found to be far less satisfactory than either human or porcine thyroid membranes. The affinity constant (ka) of the interaction of bTSH with porcine thyroid membranes (Ka = 3.3 X 10(9) l/mol) measured b Scatchard analysis was higher than with human thyroid membranes (Ka = 2.1 X 10(8) l/mol). Porcine thyroid membranes were more sensitive for the assay of bTSH (detection limit 30 microunits, half-maximal inhibition 0.3 microunit) than human thyroid membranes (detection limit 200 microunits, half-maximal inhibition 7.4 mu.). Preincubation of membranes from either species with immunoglobulin rich in long-acting thyroid stimulator (LATS) inhibited the saturable binding of 125I-labelled TSH to a greater extent than did normal immunoglobulin. The binding of 125I-labelled TSH to porcine membranes was more sensitive to the inhibitory effect of LATS-immunoglobulin and was also less affected by normal immunoglobulin than was binding to human thyroid membranes. When assayed with each type of membrane preparation there was good correlation between the RRA of immunoglobulins prepared from patients with Grave's disease and from normal subjects (n = 18) (r = 0.85, P less than 0.001, n = 73). The incidence of positive TBIIg in untreated Grave's disease was greater for porcine than for human thyroid membranes.

Animals↗

Characteristics of thyrotrophin-stimulated cyclic AMP production in cultured human thyroid cells from thyrotoxic tissue and non-toxic goitres.

We have described a system for the maintenance in culture of isolated human thyroid cells from both thyrotoxic tissue and non-toxic goitres. The cells isolated from the two thyroid tissue types showed similar cyclic AMP response characteristics to TSH with large increases in intracellular and extracellular cyclic AMP after 20-min incubations. Maximal responses were obtained with 50 mu. TSH/ml and half-maximal responses at 1.0 mu. TSH/ml. With cell passage the cyclic AMP responses to TSH decreased in magnitude and sensitivity. As with other thyroid cultures, growth of the cells with TSH induced arrangement into follicular structures, whereas cells grown in the absence of TSH remained as a monolayer. Basal intracellular cyclic AMP levels were increased in a dose-related fashion in cells grown in the presence of graded concentrations of TSH and the maximal response to further additions of TSH was not greater than in control cultures.

Cells, Cultured↗

The effect of partial thyroidectomy for Graves' disease on serum long-acting thyroid stimulator protector (LATS-P).

The effect of partial thyroidectomy on serum LATS-P has been investigated in twenty-one consecutive patients. Before surgery, LATS-P was detectable in seventeen (81%) but 1 year after operation only five (24%) had activity. The activity did not fall immediately after surgery but declined progressively throughout the year. In no patient was an increase in activity demonstrated; nor did LATS-P appear in those patients who did not have activity before operation.

Adolescent↗

The prediction of relapse after drug treatment of Graves' disease by assay of long acting thyroid stimulator-protector (LATS-P).

In a study of fifty-two patients with Graves' disease followed for 1 year after stopping antithyroid drugs, a strong relationship has been found between serum LATS-P and relapse. In those with serum LATS-P activity on stopping therapy, twenty-one (88%) out of twenty-four relapsed. In those with no LATS-P activity on stopping antithyroid drugs only eight (29%) out of twenty-eight relapsed and in five LATS-P was detectable at relapse. The overall prevalence of positive assays for LATS-P at relapse (90%) was similar to that seen in untreated Graves' disease.

Adolescent↗

Long-acting thyroid stimulator (LATS) and long acting thyroid stimulator protector (LATS-P) in untreated thyrotoxicosis.

The prevalence of serum LATS and LATS-P in untreated Graves' disease has been studied in eighty-three patients with thyroid overactivity; twelve (14%) were found to have significant levels of LATs and LATS-P whilst fifty-nine (72%) had significant levels of LATS-P alone. Twelve (14%) had neither activity. There was a very wide range in both activities. LATS was invariably found in association with a significantly greater concentration of LATS-P. There was no correlation between LATS-P and thyroid mass, as estimated from scintiscanning, thyroidal radioiodine uptake at 4 and 48 h, total serum T4 and total serum T3. Neither LATS nor LATS-P were detected in eleven patients with toxic multinodular goitre nor four with solitary toxic adenoma.

Adolescent↗

Pericardial effusion in hypothyroidism.

Thirty-nine patients with untreated hypothyroidism have been examined using echocardiography for the presence of a pericardial effusion. Effusions were present in twelve patients who tended to be more severely hypothyroid. Plasma creatine phosphokinase and lactate dehydrogenase levels were higher in the presence of an effusion. Nine were reinvestigated during thyroxine replacement therapy and the effusions did not disappear until thyroid function tests had returned to normal. There were no specific electrocardiographic changes associated with the presence of an effusion which could be associated with a normal cardiac silhouette on a standard P.A. chest X-ray.

Creatine Kinase↗

Evidence that both long-acting thyroid stimulator and long-acting thyroid stimulator-protector stimulate the human thyroid gland.

Thyroid-stimulating immunoglobulins were prepared from two potent sera, one contained long-acting thyroid stimulator (LATS) and the other contained both LATS and LATS-protector (LATS-P). The potencies of the immunoglobulin G (IgG) preparations were estimated in the McKenzie assay. The accumulation of cyclic AMP in mouse thyroid lobes was stimulated only by LATS--IgG; LATS-P--IgG was inactive. In contrast, both LATS-IgG and LATS-P--IgG were equally effective in slices of human thyroid.

Animals↗

Effects of human thyroid-stimulating hormone and immunoglobulins on adenylate cyclase activity and the accumulation of cyclic AMP in human thyroid membranes and slices.

The activation of adenylate cyclase and the accumulation of cyclic AMP resulting from the action of human thyroid-stimulating hormone (TSH), long-acting thyroid stimulator (LATS) or LATS-protector (LATS-P) have been investigated in preparations of human thyroid membranes and slices. Human TSH significantly increased adenylate cyclase activity in membranes from non-toxic goitres whereas LATS and LATS-P had no consistent effect. However, pre-incubation of goitrous membranes with LATS--immunoglobulin G inhibited the effect of TSH on adenylate cyclase. When thyroid membranes were prepared from the glands of patients with Graves's disease neither TSH nor thyroid-stimulating immunoglobulins (TSIg) stimulated adenylate cyclase significantly. Whether from non-toxic goitres or thyrotoxic tissue, the concentration of TSH needed to induce half of the maximum response was lower in thyroid slices than in membranes. Both LATS and LATS-P significantly stimulated the accumulation of cyclic AMP in slices of goitrous tissue but thyrotoxic tissue slices did not respond. In goitrous slices, submaximum concentrations of TSH and TSIg caused additive responses in the accumulation of cyclic AMP but TSIg did not increase the maximum response to TSH.

Adenylyl Cyclases↗

Thyroid carcinoma and concurrent hyperthyroidism: a study of ten patients.

Ten patients with thyroid carcinoma and co-existing thyrotoxicosis have been studied. In six patients thyroid carcinoma was suspected before thyroidectomy. In three of the four patients in whom neoplasia was not suspected before operation, the lesion was a small papillary carcinoma. In only one of the eight patients in whom serum long acting thyroid stimulator (LATS) and long acting thyroid stimulator protector (LATSP) were assayed was detectable activity found, a low incidence. The possible role of hyperthyroidism in initiating thyroid malignancy is discussed.

Adult↗