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Biomedical subjects

D R London

Publications and source records attributed to D R London.

At least 55 records · Page 3Linked to original sources
PubMed1977

Recurrent breast cancer treated with the antioestrogen tamoxifen: correlation between hormonal changes and clinical course.

Forty-five post-menopausal women with recurrent breast cancer were treated with the antioestrogen, tamoxifen, 20 mg twice daily. Clinical assessment after 12 weeks indicated that 18 (40%) showed some remission. Gonadotrophins were suppressed within two weeks to relatively constant concentrations within the post-menopausal range, responses to luteinising hormone-releasing hormone (LH-RH) did not change, and androgen concentrations remained within the normal range in all patients. Oestradiol concentrations rose steadily only in women in whom treatment failed. Serum prolactin concentrations were raised in 18 out of the 44 (41%) patients in whom they were measured; 13 of these did not respond to treatment. Treatment did not change the average prolactin concentration when this was within the normal range, but it significantly reduced prolactin concentrations in hyperprolactinaemic patients--within two weeks (P less than 0-01) in those who responded well and by six weeks (P less than 0-05) in those who showed no remission. Among patients with normal prolactin values the release of prolactin after thyrotrophin-releasing hormone was significantly greater in those with no remission than in those who responded to tamoxifen. Responses in those with hyperprolactinaemia were reduced to about half the control values, and again this change occurred faster in those who were successfully treated. Patients therefore seem to have a better chance of responding to anti-oestrogen treatment if prolactin secretion is low.

Androgens↗
PubMed1977

Suppression of basal insulin secretion by adrenalin in normal man and in patients with insulinomas.

Basal insulin secretion has been thought to be via a different mechanism from stimulated insulin secretion, partly because it is not similarly suppressed by adrenalin. However, adrenalin normally causes hyperglycaemia, but if it is infused while the plasma glucose is kept constant there is marked suppression of insulin secretion. Sympathetic stimulation modulates basal insulin secretion, and alpha adrenergic blockade impaired the suppression of insulin secretion in response to hypoglycaemia. Four of five benign insulinomas had marked suppression of insulin secretion by adrenalin, but one malignant and one benign insulionoma had little suppression. Both had a raised proportion of their basal plasma insulin as proinsulin, and the impaired suppression of secretion by adrenalin probably signified an undifferentiated tumour.

Adenoma, Islet Cell↗
PubMed1977

Hormonal effects of tamoxifen in oligospermic men.

The hormonal effects of tamoxifen (10 mg daily for 6 months) have been studied in nine men with oligospermia. Basal concentrations of serum LH (1-7 +/- 0-1 (S.E.M.) i.u./l) increased to a maximum of 4-1 +/- 1-3 i.u./l (P less than 0-001) after 6 months, and FSH rose from 4-9 +/- 1-0 to a maximum of 7-7 +/- 1-3 i.u./l after 4 months of treatment (P less than 0-01). The response to luteinizing hormone releasing hormone (LH-RH) was studied at monthly intervals. Sums of increments of serum LH increased from 35 +/- 4 to 92 +/- 17 i.u./l at 4 months (P less than 0-001) and of FSH from 14 +/- 3-4 to 23 +/- 3-5 i.u./l at 4 months (P less than 0-01). Basal serum androgens rose from 25 +/- 2-7 to 38 +/- 2-4 nmol/l after 4 months of treatment (P less than 0-05), and serum oestradiol-17beta increased from 185 +/- 25 to 631 +/- 90 pmol/l by 6 months (P less than 0-001). No significant changes occurred in sperm counts. Five normal men acted as controls: they were given tamoxifen for 1 week. No significant changes were observed in serum LH, FSH or release of these hormones following administration of LH-RH. Serum androgens and oestrogens however, increased significantly by day 4 of treatment (P less than 0-05).

Androgens↗
PubMed1976

Modification by sex steroids of LHRH response in the polycystic ovary syndrome.

Exogenously administered oestradiol or progesterone was found to induce augmentation of LH and FSH release in response to LHRH administration in patients with the polycystic ovary (PCO) syndrome. The effect of oestradiol upon LH release in the patients was significantly less than the augmented release induced in normal women (P less than 0-02). In contrast, progesterone induced a significantly greater LH release in PCO patients than normal women studied during the early follicular phase (P less than 0-001) but less than that in normal women studied during the mid-follicular phase of the cycle (P less than 0-01). The effects on FSH release in the PCO patients were less marked but similar to those in normal women with comparable basal steroid levels. The results suggest that both oestradiol and progesterone can modify the hypothalamic-pituitary axis in the PCO syndrome in a manner similar to that observed in normal women and a failure of these 'positive feedback' mechanisms does not appear to be the cause of the ovulatory deficiency in this syndrome.

Clinical Trials as Topic↗
PubMed1976

The control of gonadotrophin release in women with hyperprolactinaemic amenorrhoea: effect of oestrogen and progesterone on the LH and FSH response to LHRH.

The effect of the administration of oestradiol benzoate and of progesterone on the subsequent response to LHRH has been investigated in women with hyperprolactinaemia. There was an amplification in the release of LH in four out of ten patients and of FSH in one out of ten patients at 44 h after the administration of 2-5 mg oestradiol benzoate. The average amount of LH released before and after oestrogen did not change, but there was a significant decrease in the amount of FSH released. There was no correlation between the LH released and the oestradiol concentration in serum at the time of the LHRH tests but there was a negative correlation between the FSH released and the oestradiol concentration (r = 0-507;P less than 0-05). These results contrast with those obtained in normal subjects in the follicular phase of the cycle when there is a positive correlation of oestrogen concentrations and the amount of LH and FSH released. As in normal subjects, however, a significant suppression of basal FSH concentrations, persisting until 44 h, was produced by the oestrogen (P less than 0-01). Seven out of eleven patients showed an amplification of LH response and six out of eleven an FSH response 20 h after the administration of 25 mg progesterone. The mean amplifications are not significantly different from those of normal subjects tested in the early follicular phase of the cycle, but are significantly less than those tested in the mid follicular phase of the cycle (LH P less than 0-001; FSH P less than 0-01). This may be related to the serum concentrations of oestradiol which in patients with hyperprolactinaemia are significantly less than those found in the mid follicular phase of the cycle (P less than 0-05). These results indicate that in women with hyperprolactinaemia oestrogen negative feedback, necessary for cycle initiation, is normal: failure of ovulation may be related to failure of positive feedback to oestroen. Oestrogen-negative feedback is unopposed and this may explain the follicullar development and lack of oestrogen in the mid-follicular phase.

Amenorrhea↗
PubMed1976

Basal serum prolactin values and responses to the administration of thyrotrophin releasing hormone (TRH) in women with amenorrhoea.

Basal prolactin concentrations were measured in 77 patients presenting with amenorrhoea; 17 per cent were found to have hyperprolactinaemia. The release of prolactin in response to a standard dose of thyrotrophin releasing hormone for amenorrhoeic subjects with normal basal levels of prolactin was within the normal range. However, patients with hyperprolactinaemic amenorrhoea and no evidence of pituitary tumour were found to have a blunted response.

Amenorrhea↗
PubMed1976

Luteinizing release hormone tests in impotent diabetic males.

Assessment of pituitary-gonadal function was made in impotent diabetic males using luteinizing hormone-release hormone tests. Serum testosterone, sex-hormone-binding globulin capacity, and basal and incremental gonadotrophin concentrations in the impotent diabetics were similar to those in control diabetics, suggesting a primary neurologic rather than an endocrine defect as the cause of the impotence.

Adult↗
PubMed1975

An abnormality of oestrogen feedback in amenorrhoea-galactorrhoea.

Fourteen patients with amenorrhoea and hyperprolactin-anemia but no evidence of pituitary tumours were each given an intramuscular injection of 1 mg oestradiol benzoate. Thirteen patients failed to release luteinizing hormone in response to the oestrogen. This hypothalamic abnormality may help to explain the menstrual disturbances in subjects with hyperprolactinaemia.

Amenorrhea↗
PubMed1975

Incorporation of amino acids into protein from an intracellular pool of lymphocytes.

The nature of the precursor pool for protein synthesis in porcine lymphocytes has been investigated. Intracellular free glycine was found to be used in preference to its extracellular counterpart. It is suggested that a similar preference applies for all amino acids. However, with certain amino acids such as phenylalanine, this preference is difficult to demonstrate because of a rapid exchange occurring between intracellular and extracellular pools. A small portion of the intracellular phenylalanine pool was found not to exchange rapidly but this was not important in the maintenance of protein synthesis. A different type of compartmentation of the intracellular glycine pool was apparent, but this was less well defined. During the course of these investigations it was demonstrated that the nature of the incubation medium is an important consideration for enabling correct interpretation of kinetic experiments. To maintain what appeared to be a constant rate of protein synthesis, lymphocytes had to be incubated in a comprehensive culture medium (basal Eagle's medium without serum); a declining rate of synthesis was observed if a simple buffered salts medium (Krebs-Ringer bicarbonate buffer) was used.

Amino Acids↗
PubMed1975

The oestrogen provocation test: a method of assessing the hypothalamic-pituitary axis in patients with amenorrhoea.

The oestrogen feedback and gonadotrophin release in ten amenorrhoeic women were investigated, using intramuscular injection of 1 mg oestradiol benzoate. Serial estimations of serum oestradiol and gonadotrophins (LH and FSH) were made over a period of 72 h following the injection. Five patients demonstrated positive feedback release of LH to the oestrogen stimulus with elevated levels of LH significantly above baseline (P less than 0.001), which occurred between 48 and 72 h after the injection. Two of the five patients also demonstrated elevated FSH levels accompanying these LH peaks, The hypothalamic-pituitary axis was postulated to be intact in these five patients, and all ovulated on clomiphene. None of the remaining five subjects showed any increase in serum gonadotrophin levels in response to oestradiol and none ovulated on clomiphene when given a dose of up to 200 mg daily x5 days. This 'oestrogen provocation test" seems to be a useful means of evaluating the functional capacity of the hypothalamic-pituitary axis for gonadotrophin release and has proved useful in predicting responsiveness to clomiphene in amenorrhoeic women.

Adult↗