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Biomedical subjects

R H Mortimer

Publications and source records attributed to R H Mortimer.

54 records · Page 3Linked to original sources
PubMed1986

Hypothyroidism and Graves' disease after mantle irradiation: a follow up study.

Fifty of 66 patients whose thyroid function had previously been assessed 7-139 months after irradiation for Hodgkin's disease were re-evaluated 35 +/- 3 months later. They could be divided into three groups: those whose thyroid function had been normal in the first study (N = 26), those who had had asymptomatic impaired thyroid reserve (N = 19), and those in whom evidence of Graves' disease had developed (N = 5). The 26 patients who had been euthyroid when first studied had developed significant increases in mean thyroid-stimulating hormone (TSH) levels (basal and following thyrotrophin releasing hormone) without changes in mean free thyroxine index (FTI). In three of these patients, each studied within six years of irradiation, basal TSH had risen to hypothyroid levels. There were no significant changes in mean FTI or basal and peak TSH in 19 patients who had demonstrated impaired thyroid reserve in the first study. The cumulative incidence of impaired thyroid reserve in the total cohort is now 30/66 (45%) but only one of these 30 has developed clinical hypothyroidism. Five patients developed evidence of Graves' disease. Two patients with thyrotoxicosis and one with euthyroid Graves' disease were found in the initial study. On re-evaluation, a third patient had developed frank thyrotoxicosis and another euthyroid Graves' disease, giving a cumulative incidence of Graves' disease of 5/66 (7%). Three of these five were HLA-DR3 and three had measurable thyrotrophin binding inhibiting immunoglobulins. We conclude that impaired thyroid reserve continues to develop within six years of mantle irradiation in adults but once established appears to remain stable.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1984

Plasma cortisol delivery from oral cortisol and cortisone acetate: relative bioavailability.

Plasma cortisol levels were measured before and for 6 h after the intravenous injection of 50 mg cortisol as sodium succinate and oral administration of 50 mg cortisol and 50 mg cortisone acetate in 10 subjects with primary or secondary adrenal failure and in two normal volunteers. Peak cortisol levels of 1518 +/- 190 nmol 1(-1) (mean +/- s.e. mean) and 739 +/- 74 nmol 1(-1) were found 1.46 +/- 0.25 and 1.79 +/- 0.16 h after oral cortisol and cortisone acetate respectively. The relative bioavailability of oral cortisol and cortisone acetate varied widely (cortisol 26-91%, mean 54 +/- 6.9%, cortisone acetate 21-95%, mean 44 +/- 6.5%) but despite this wide variation there was, in individual subjects, a highly significant correlation between the bioavailability of the two steroids (r = 0.870, P less than 0.001). This suggests that the wide interindividual variations in plasma cortisol levels seen after oral cortisone acetate are not related to variations in bioconversion of cortisone.

Administration, Oral↗
PubMed1982

A comparison of serum thyroglobulin measurements and whole body 131I scanning in the management of treated differentiated thyroid carcinoma.

Serum thyroglobulin levels were measured by a sensitive radioimmunoassay in 76 patients whose differentiated thyroid carcinoma had been treated by surgery with or without subsequent administration of radioactive iodine (131I). Examination of the results of 105 concomitant whole body 131I scan results and serum thyroglobulin levels showed a high degree (83.8%) of concordance between these two techniques. A significant correlation (r = 0.670, p less than 0.001) was found between serum thyroglobulin levels and quantitative 131I uptake in the neck and/or metastases in 42 patients in whom this was measured. Although a high degree of congruence was found between the results of 131I scans and the presence or absence of circulating thyroglobulin, 13 patients with negative scans using conventional doses of 131I had measurable levels of thyroglobulin. Eight of these patients had or subsequently developed evidence of residual thyroid tissue or metastatic carcinoma. The measurement of serum thyroglobulin levels in patients previously treated for differentiated carcinoma offers a more convenient and more sensitive method of detecting residual normal or neoplastic thyroid tissue than does whole body scanning in 131I.

Carcinoma↗
PubMed1978

Pituitary response to bolus and continuous intravenous infusion of luteinizing hormone-releasing factor in normal women and women with polycystic ovarian syndrome.

Plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels were measured in response to luteinizing hormone-releasing factor (LRF), given as a 100 microgram intravenous bolus and/or as a 4 hour infusion of 0.2 microgram per minute to 27 normal menstruating women and 15 women with the polycystic ovarian syndrome (PCOS). In PCOS, LH response to bolus LRF was significantly greater than those of normal women at days 1 to 4 and 8 to 10 of the cycle, whereas FSH responses were similar in all women studied. Continuous LRF infusion resulted in a biphasic LH release pattern. In normal women, the early phase was low until days 12 to 14 of the normal cycle, whereas the second phase rose progressively from the early follicular to the periovulatory period. In PCOS, the early phase was relatively large and qualitatively resembled the normal periovulatory pattern. The increased pituitary LH response to LRF in PCOS is associated with a relatively large early releasable LH pool and a low FSH response.

Adolescent↗
PubMed1978

Endocrine tests in phenotypic children with bilateral impalpable testes can reliably predict "congenital" anorchism.

Congenital anorchism is a rare condition. Bilateral impa-pable undescended testes are relatively common by comparison. Surgical exploration has been regarded as the final arbiter between anorchism and bilateral cryptorchism. Exploration has not proved completely reliable in making this differentiation. Endocrine studies, particularly the human chorionic gonadotropin (HCG) stimulation test together with measurements of basal plasma gonadotropins, can reliably exclude "functioning" testicular tissue. Eleven fully evaluated and operated cases support this contention. In the specific clinical setting of a normal phenotypic male child with a 46XY karyotype and no müllerian structures palpable on rectal examination, nonfunctioning testes on endocrine testing means congenital anorchism and surgical confirmation is unnecessary. In contradistinction, a positive HCG test would appear to mandate through and extensive surgical exploration.

Child↗
PubMed1977

Failure of methyclothiazide to lower home blood pressure level in "essential" hypertensive and normotensive young men, despite significant plasma volume contraction.

Home blood pressure measurements were used to assess the effect of methyclothiazide in young essential hypertensive and normotensive males. Although plasma volume was reduced by approximately 10 percent, blood pressure was not reduced in either group. The lack of effect on blood pressure was probably not attributable to dosage employed, as doubling the dose (5 to 10 mg) in the normal subjects (who were equilibrated on constant diet) did not significantly increase changes in plasma volume, plasma renin activity, aldosterone excretion, urine sodium or blood pressure. The higher dose did result in greater changes in plasma potassium and uric acid. Homeostatic mechanisms which limit the volume mediated and other antihypertensive effects of methyclothiazide apparently achieved complete compensation in these young males. This suggests that thiazide diuretics may not be the drug of first choice in the treatment of hypertension in young adults. Further studies with other diuretics are clearly necessary before the significance of these findings can be fully assessed.

Adolescent↗
PubMed1976

Correlation between integrated LH and FSH levels and the response to luteinizing hormone relasing factor (LRF).

Integrated blood plasma levels of LH and FSH and their response to the iv administration of 100 mug synthetic LRF were studied in 29 normal subjects, 12 women with Stein-Leventhal syndrome, 8 subjects with primary gonadal failure, 7 women with Sheehan's syndrome, 20 subjects with pituitary tumors, 10 subjects with idiopathic gonadotropin deficiency and 5 subjects with hypothalamic tumors. Within each group there was considerable variation in the response of LH and FSH levels to LRF. In each group there was a statistically significant positive correlation between basal integrated gonadotropin levels and the response of the levels to LRF. Both within groups and between groups, the best indicator of the response to LRF was the basal levels of FSH and LH. In subjects with hypogonadotropic hypogonadism there was no significant difference in mean basal LH levels and mean response to LRF between patients with primarily pituitary disease (pituitary tumors or Sheehan's syndrome) and conditions which might represent hypothalamic disease (hypothalamic tumors or idiopathic gonadotropin deficiency). The response to an acute, single, injection of LRF appears to more directly reflect basal gonadotropin levels rather than disease category.

Adolescent↗
PubMedDate not supplied

Uptake of L-triiodothyronine sulphate by human choriocarcinoma cell line, JAr.

This study investigated uptake of triiodothyronine sulphate (T3S) and interactions between uptake of T3S and triiodothyronine (T3) using the human choriocarcinoma cell line (JAr) as a model of placental transport. Cells were incubated at 37 degrees C with 30 pM 125I-T3 for 2 min with unlabelled T3 (0-30 microM) or T3S (0-1 mM). Addition of an excess unlabelled T3 (30 microM) or T3S (1 mM) reduced the initial rate of 125I-T3 uptake by 69.3+/-3.6 per cent (P<0.0001) and 52.9+/-7.8 per cent (P<0.0001), respectively. The calculated Michaelis constant (Km) for T3 uptake was 0.378+/-0.133 microM (n = 3) with a corresponding maximum velocity (Vmax) of 15.4+/-6.9 pmol/min/mg protein. Uptake of 125I-T3 was inhibited in a dose-dependent way by the addition of unlabelled T3S (0-1 mM). The calculated inhibition constant (Ki) for the inhibition of 125I-T3 uptake by T3S was 121.8+/-35.2 microM (n = 6). Saturable uptake of 125I-T3S by JAr cells was negligible. The T3S preparation incubated with the cells contained about 0.1 per cent T3, sufficient to explain the apparent inhibition of 125I-T3 uptake by unlabelled T3S. These results suggest that, in contrast to T3 uptake in these cells, JAr cells do not have a saturable uptake mechanism for T3S, and that T3S does not interact with the T3 transporter in these cells.

Biological Transport↗
PubMedDate not supplied

Lack of membrane transport of l-thyroxine sulphate in the human choriocarcinoma cell line, JAr.

We examined uptake of l -thyroxine sulphate (T(4)S) and possible interactions between T(4)S and thyroxine (T(4)) uptake in the choriocarcinoma cell line JAr. Cells were incubated with 50 p m(125)I-T(4)S in the absence (total uptake) and in the presence (non-specific uptake) of 10 microm T(4)S. Cells were also incubated at 37 degrees C for 2 min with 50 p m(125)I-T(4)in the presence of an increasing amount of unlabelled T(4)(0-10 microm) or T(4)S (0-30 microm). There was negligible total uptake of(125)I-T(4)S (1.14+/-0. 05 fmol/mg cellular protein, mean+/-sem) and no specific uptake after 120 min incubation. Minor inhibition of(125)I-T(4)uptake by T(4)S could be explained entirely by a low level of residual T(4)(0. 2 per cent) in the T(4)S preparation. These findings indicate that T(4)S does not share the T(4)membrane transporter.

Biological Transport, Active↗
PubMedDate not supplied

Sodium iodide symporter (NIS) gene expression in human placenta.

The placenta must allow the passage of iodide from the maternal to the fetal circulation for synthesis of thyroxine by the fetal thyroid. The thyroid sodium iodide symporter (NIS) was cloned in 1996 and, although widely distributed among epithelial tissues, early studies failed to detect it in placenta. We demonstrated NIS mRNA in human placenta and in the human choriocarcinoma cell line, JAr. NIS protein was localized to trophoblasts, with a tendency to apical distribution, in sections of human placenta immunostained with a monoclonal antibody against hNIS. We conclude that NIS is expressed in placenta and may mediate placental iodide transport.

Antibodies, Monoclonal↗
PubMedDate not supplied

Computer assisted validation of binding assays for sex hormone binding globulin.

Accurate measurement of sex hormone binding globulin (SHBG) by 5 alpha-dihydrotestosterone (DHT) binding assays requires the establishment of acceptable upper and lower limits of labelled DHT binding and the use of optimal quantities of radioinert DHT to displace labelled DHT. A computer assisted binding assay for SHBG is described in which upper and lower binding limits are derived mathematically from analysis of labelled DHT binding to eight concentrations of SHBG in the range 25 to 400 nM. The optimal quantity of radioinert DHT for a given SHBG concentration is also derived from these binding curves. A computer program determines whether or not, in a given sample, the binding of labelled DHT falls within these established binding limits and also calculates the concentration of SHBG. This technique reduces the number of tubes required in an assay and provides rapid validation and calculation of results.

Adult↗