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Biomedical subjects

D L Healy

Publications and source records attributed to D L Healy.

155 records · Page 9Linked to original sources

Characteristics of an antiluteinizing hormone isoantibody produced during gonadotropin induction of ovulation.

Production of an antihuman LH antibody was suspected in a woman with isolated LH deficiency who received human pituitary gonadotropin (hPG) to induce ovulation and who developed secondary drug failure associated with very high "serum LH' values. Binding of [125I]LH to various dilutions of the patient's serum was demonstrated by precipitation with polyethylene glycol or sheep antihuman immunoglobulin G (anti-IgG) but not by precipitation with sheep antihuman immunoglobulin M (anti-IgM). Unlabeled LH competitively displaced [125I]LH from a 1:200 final dilution of the patient's serum, and indicated a single class of binding sites with a binding affinity of 1.5 X 1011 M-1 and a binding capacity of 84 ng LH/ml serum. The isoantibody was reactive against antigenic determinants in hPG, LH, and hCG but not against human FSH. Further examination showed binding to the beta, but not the alpha, subunit of two LH preparations and to beta hCG. It is concluded that repeated administration of hPG to this patient with isolated LH deficiency evoked IgG isoantibody formation against the beta subunit of LH.

Adult↗

Increased prolactin and thyrotrophin secretion following oral metoclopramide: dose-response relationships.

Four normal men received 1, 5, 10 and 20 mg doses of oral metoclopramide, a dopamine receptor antagonist, or placebo to determine the effect of this drug on anterior pituitary hormone secretion. Increases in serum prolactin (PRL) occurred even after the 1 mg tablet (P less than 0.01) while maximal responses were observed 60 min after ingestion of the 20 mg tablet (mean 27.8 ng/ml; range 25.6-30.3 ng/ml). Serum PRL levels peaked 60-90 min after ingestion of any dose of metoclopramide and values remained significantly elevated (P less than 0.05) for up to 8h after the tablet. Increases in serum thyrotrophin (TSH) also occurred after the 10 and 20 mg doses of metoclopramide. Peak responses were seen at 120-180 min, with significant elevation (P less than 0.05) persisting from 60 to 240 min after ingestion. No consistent changes in serum FSH, LH or GH were observed and no side-effects were reported. It was concluded that metoclopramide elevated serum PRL and TSH. The threshold dose of metoclopramide required for these effects was different for the two hormones; their peak responses occurred at different times and the duration of the elevation was dissimilar, suggesting a mechanism other than the release of hypothalamic thyrotrophin-releasing hormone (TRH).

Adult↗

Pituitary autonomy in hyperprolactinemic secondary amenorrhea: results of hypothalamic-pituitary testing.

Twenty-seven women with secondary amenorrhea of greater than six months duration were subjected to multiple testing of hypothalamo-pituitary function. They were divided into normo-prolactinemic (Group 1 mean serum prolactin (PRL) 9.8 ng/ml; range 6.8 to 13.0 ng/ml; n=9) and hyperprolactinemic (Group 2 mean 37.5 ng/ml; range 19.2 to 93.7 ng/ml; n=18) groups on the basis of 4 weekly baseline determinations. Group 2 had significantly (P less than .05) lower serum LH and urinary pregnanediol levels than did Group 1; there was no statistical difference between the groups in serum FSH, T4, T3 or urinary estrogen measurements. Two women in Group 2 were found to have a pituitary chromophobe adenoma. Group 2 women showed no significant rises in serum PRL following stimulation tests with thyrotropin releasing hormone (TRH, 200 microng iv) and metoclopramide (10 mg orally), which caused significant responses in Group 1. The TSH response to TRH was, however, preserved in Group 2, while it was subnormal in Group 1 subjects. Both groups showed similar FSH and LH responses to luteinizing hormone-releasing hormone (LHRH, 25 microng iv). No significant suppression of serum PRL was seen in Group 2 patients given L-Dopa (500 mg orally),, which produced a significant response (P less than 0.05) in Group 1 subjects, while all patient showed marked reduction in serum PRL values following 2-bromo-alpha-ergocryptine (CB-154, 2.5 mg orally). When compared with other Group 2 members, the 2 cases with proven pituitary adenomata gave similar responses to the stimulation-inhibition tests and were not clearly distinguished on this basis. We conclude: 1. The pattern of PRL responses to dynamic tests, although of pathophysiological interest an autonomous pituitary lesions in patients with hyperprolactinemic secondary amenorrhea. 2. Such dynamic tests, although a pathophysiological interest, provide no clinical information additional to that provided by the mean basal serum PRL value. 3. In clinical practice, such dynamic tests should be confined to patients with mean serum PRL levels at around the upper limit of the normal range.

Adult↗

Angiogenesis: a new theory for endometriosis.

Excessive endometrial angiogenesis is proposed as an important mechanism in the pathogenesis of endometriosis. Evidence is reviewed for the hypothesis that the endometrium of women with endometriosis has an increased capacity to proliferate, implant and grow in the peritoneal cavity. Data is summarized indicating that the endometrium of patients with endometriosis shows enhanced endothelial cell proliferation. Results are also reviewed indicating that the cell adhesion molecule integrin alphavbeta3 is expressed in more blood vessels in the endometrium of women with endometriosis when compared with normal women. Taken together, these results provide evidence for increased endometrial angiogenesis in women with endometriosis when compared with normal subjects. Endometriosis is one of the family of angiogenic diseases. Other angiogenic diseases include solid tumours, rheumatoid arthritis, psoriasis and diabetic retanopathy. Excessive endometrial angiogenesis suggests novel new medical treatments for endometriosis aimed at the inhibition of angiogenesis.

Cell Division↗

Phytoestrogens and breast cancer in postmenopausal women: a case control study.

OBJECTIVE: To examine the association between isoflavones, androgens, and dietary composition and the risk of breast cancer in Australian postmenopausal women. DESIGN: Eighteen women with recently diagnosed breast cancer before surgery and 20 controls were recruited over a 12-month period. Both cases and controls were similarly assessed for urinary isoflavones, serum and urinary sex steroids, and dietary intake. RESULTS: Women with breast cancer had lower 24-h urinary daidzein compared with controls (cases: 31 [95% CI: 4, 234] nmol/day; controls: 427 [95% CI: 4, 234] nmol/day; p = 0.03), and there was a trend to lower urinary genistein excretion (cases: 25 [95% CI: 5, 132] nmol/day; controls: 155 [95% CI: 43, 550] nmol/day; p = 0.08). Total testosterone was higher in women with breast cancer compared with controls (cases: 1.3 [95% CI: 1.1, 1.5] nmol/L; controls: 1.0 [95% CI: 0.8, 1.11 nmol/L; p = 0.05). No significant differences were found for serum sex hormone binding globulin, free androgen index, dehydroepiandrosterone sulphate, estradiol and progesterone, or in urinary androgen metabolites, or in dietary intake with regard to fat, carbohydrate, protein, or fiber consumption between cases and controls. CONCLUSIONS: This preliminary study is the first report of low urinary daidzein and genistein in postmenopausal women with breast cancer. These findings are in keeping with the increasing observational data demonstrating a protective effect from phytoestrogens on breast cancer risk.

Breast Neoplasms↗