Search PubMed⌕ Search

Biomedical subjects

D L Healy

Publications and source records attributed to D L Healy.

At least 145 records · Page 8Linked to original sources
PubMed1984

Pulsatile progesterone secretion: its relevance to clinical evaluation of corpus luteum function.

Pulsatile progesterone (P) secretory patterns were characterized in rhesus macaques (n = 13) during the midluteal phase (cycle days 18 to 20) of the normal ovarian/menstrual cycle. Sixty high-amplitude (greater than 1 ng/ml) P pulses were observed during a total of 169 hours of sampling. Typically, P pulses had an ultradian periodicity of 2 hours and were independent of detectable luteinizing hormone (LH) and prolactin (PRL) pulses in 70% of instances. LH pulses were associated with a concomitant P and PRL pulse in 100% to 80% of occasions, respectively. Pulsatile P release was augmented by exogenous cynomolgus monkey LH and suppressed by administration of a gonadotropin-releasing hormone antagonist. Two individuals with apparently normal ovulation and once daily plasma P concentrations within the normal range demonstrated a nonpulsatile P profile. These findings encourage clinical investigations to characterize pulsatile P secretion in normal women and patients in whom corpus luteum dysfunction is suspected.

Animals↗
PubMed1984

The clinical significance of endometrial prolactin.

Prolactin (PRL) is produced not only by the anterior pituitary gland but also by human endometrium. That decidual stromal cells secrete PRL from day 22 of the menstrual cycle is demonstrated by: 1) nett accumulation of PRL during in vitro culture; 2) PRL accumulation is prevented by inhibitors of protein synthesis; and 3) identification of PRL mRNA within endometrial decidua. Endometrial PRL is biologically and immunologically equipotent with pituitary PRL and its amino acid sequence is very similar. In human pregnancy, decidual PRL binds to receptors on the fetal chorion and amnion and thereby passes into amniotic fluid in high concentration. Three putative functions of uterine PRL are suggested from current studies: a) a PRL receptor defect is present in the chorion laeve of patients with pregnancies complicated by chronic polyhydramnios and this deficiency in chorionic receptors for endometrial PRL may result in the development of excessive amniotic fluid; b) decidual PRL may modulate prostaglandin synthesis not only within the endometrium prior to menstruation, but also within the chorion and amnion to allow labour to proceed in a timely manner; and c) amniotic fluid PRL may pass into the fetal tracheo-bronchial system to promote surfactant production. Unlike pituitary PRL with distant target organs, decidual PRL appears to have paracrine or cybernetic functions in the human uterus, placental membranes and the fetus.

Decidua↗
PubMed1983

The thymus-adrenal connection: thymosin has corticotropin-releasing activity in primates.

Endotoxin-free thymosin fraction 5 elevated corticotropin, beta-endorphin, and cortisol in a dose- and time-dependent fashion when administered intravenously to prepubertal cynomolgus monkeys. Two synthetic component peptides of thymosin fraction 5 had no acute effects on pituitary function, suggesting that some other peptides in thymosin fraction 5 were responsible for its corticotropin-releasing activity. In agreement with these observations, total thymectomy of juvenile macaques was associated with decreases in plasma cortisol, corticotropin, and beta-endorphin. These findings indicate that the prepubertal primate thymus contains corticotropin-releasing activity that may contribute to a physiological immunoregulatory circuit between the developing immunological and pituitary-adrenal systems.

Adrenocorticotropic Hormone↗
PubMed1983

Induction of menstruation by an antiprogesterone steroid (RU 486) in primates: site of action, dose-response relationships, and hormonal effects.

The antiprogesterone compound RU 486 (17 beta-hydroxy-11 beta-[4-dimethylaminophenyl]-17 alpha-[ 1-propynyl]estra-4,9-dien-3-one; Roussel-Uclaf, Paris, France) was used to induce menstruation in a randomized controlled trial. Castrated adult female cynomolgus monkeys (n = 17) received sequential subcutaneous Silastic capsules of estradiol or progesterone over a 49-day regimen which stimulated the steroidal milieu of the fertile ovarian/menstrual cycle. RU 486 was injected at 10.0, 1.0 to 3.0, or 0.1 mg/kg from days 31 to 34 of this protocol. At all concentrations tested, menstruation followed RU 486 injection within 48 hours and persisted through 72 hours. No bleeding followed placebo injections. All monkeys that menstruated after RU 486 administration also manifested vaginal bleeding after removal of exogenous steroid treatments. No changes in daily serum follicle-stimulating hormone, luteinizing hormone, prolactin, or serum and urinary free cortisol accompanied RU 486 treatment. We conclude that (1) RU 486 promptly induces menstruation by a local action upon the endometrium; (2) familiar endometrial proliferation and withdrawal bleeding can redevelop after exposure to this compound; (3) no effects of RU 486 on serum cortisol or pituitary gonadotropins were noted; and (4) extensive combination therapy with estrogen and progesterone causes mild hyperprolactinemia.

Animals↗
PubMed1983

Serum follicle-stimulating hormone, luteinizing hormone, and prolactin during the induction of ovulation with exogenous gonadotropin.

To examine the gonadotropic milieu presiding over recruitment and selection of a dominant follicle during gonadotropin induction of ovulation, four patients were studied over nine cycles of human pituitary gonadotropin (hPG) therapy. These hypogonadotropic subjects received a routine schedule of hPG injections monitored by daily urinary estrogen and pregnanediol determinations. Serum FSH, LH, and PRL profiles were measured in daily morning blood samples throughout each menstrual cycle. hPG therapy produced markedly abnormal gonadotropin patterns. Mean serum FSH levels were above the upper limit of the normal serum FSH range and no early or midfollicular FSH peaks occurred. The FSH-LH ratio was abnormally high for 8 days before ovulation. Progressive and marked elevations of serum PRL developed during hPG treatment. A bimodal luteal phase serum PRL profile appeared with peak values of 40.7 +/- 5.6 ng/ml (mean +/- SE) 1 day and 42.0 +/- 3.0 ng/ml 9 days after the LH peak. We conclude that: 1) Current gonadotropin treatment regimens to induce ovulation produce radioimmunoassayable serum FSH, LH, and PRL profiles which are qualitatively and quantitatively abnormal, and 2) Excessive FSH levels and the elevated FSH-LH ratio orchestrate aberrant folliculogenesis and result in the clinical problems of multiple ovulation and hyperstimulation.

Adult↗
PubMed1983

Chronic idiopathic polyhydramnios: evidence for a defect in the chorion laeve receptor for lactogenic hormones.

Binding of human GH (hGH) to the lactogenic receptor of human chorion laeve has been compared in membrane preparations from normal pregnancies and those complicated by chronic idiopathic polyhydramnios. Specific binding of [125I]hGH was significantly lower (mean +/- SE, 1.64 +/- 0.28%; n = 5) in chronic idiopathic polyhydramnios than in normal pregnancies (2.93 +/- 0.4%; n = 16). Scatchard analysis data were consistent with a reduced lactogenic hormone receptor concentration being the explanation for this reduced hGH binding. By contrast, the specific binding of [125I]insulin to its receptor was unchanged when chorion laeve from hydramniotic pregnancies (7.29 +/- 1.98%; n = 4) was compared with that from normal pregnancies (8.63 +/- 1.35%; n = 7). We conclude that a lactogenic hormone receptor defect exists in the chorion laeve of pregnancies complicated by chronic idiopathic polyhydramnios. Such impaired binding for PRL may explain the development of excessive amniotic fluid volumes, which is characteristic of this complication of pregnancy.

Chorion↗
PubMed1983

Pituitary and adrenal responses to the anti-progesterone and anti-glucocorticoid steroid RU 486 in primates.

RU 486 is a synthetic steroid with anti-progesterone and anti-glucocorticoid properties. While studying its acute effects on pituitary hormone secretion in cynomolgus monkeys, we found that RU 486 inhibited PRL secretion induced by an estrogen-progesterone synergy (P less than 0.025). By contrast, plasma levels of ACTH, arginine vasopressin and cortisol increased following RU 486 administration (P less than 0.05). Plasma FSH, LH, GH and TSH were unaffected by RU 486 treatment. Our findings suggest potential diagnostic and therapeutic applications of RU 486.

Adrenal Glands↗
PubMed1983

A method of thymectomy in macaques.

The aim of this study was to develop an operation for total thymectomy suitable for nonhuman primates. The thymus was removed from 24 macaque monkeys from fetal to adult life by a cervicothoracotomy and blunt gauze dissection. Mean wet weight of the thymus rose from 150 mg (range 50-250 mg) in fetal animals to 2.5 gm (range 0.3-4.2 gm) in prepubertal monkeys. Nonhuman primate thymic weight fell steadily and uniformly with age by over 300% when plotted as a function of body weight. This surgical technique appears to be a valid method of total thymectomy in macaque monkeys.

Age Factors↗
PubMed1982

Rotational delivery of the fetus: Kielland's forceps and two other methods compared.

A retrospective comparison was undertaken of 552 cases in which Kielland's forceps were used for rotation and delivery, 95 cases in which other forceps were used for rotation and delivery, and 160 cases in which manual rotation and forceps were used. There was no significant difference in maternal or fetal morbidity between the three groups, regardless of whether the indication for delivery was delay in the second stage of labour or fetal distress. When Kielland's forceps were used by junior staff, significantly more vaginal and cervical lacerations and primary postpartum haemorrhage occurred, but there was no increase in fetal morbidity.

Extraction, Obstetrical↗
PubMed1980

A normal cumulative conception rate after human pituitary gonadotropin.

Forty consecutive women were treated with human pituitary gonadotropin to induce ovulation. Thirty-seven patients (93%) ovulated and thirty (75%) conceived on at least one occasion. The cumulative conception rate for the series equaled that of the general population. Women with a past history of anorexia nervosa had the shortest average time to pregnancy. Of patients who did not conceive, four represented failures of patient selection in that they withdrew from treatment for a variety of psychiatric and social reasons, and six represented failures of treatment, not becoming pregnant despite the induction of ovulation. It is concluded that realistic goals for a contemporary human gonadotropin program include induction of ovulation in all patients and a cumulative conception rate equal to that of the general community.

Anovulation↗
PubMed1980

Prolactin in human milk: correlation with lactose, total protein, and alpha-lactalbumin levels.

To determine whether prolactin (PRL) could be conclusively demonstrated in human milk, samples from nine puerperal women were examined by radioimmunoassay techniques. Recovery of 78 +/- 5% (mean +/- SE) PRL added to eight milk samples and mean recoveries of 83, 92, and 92% of PRL after 1, 2, and 3 h incubation at 21 degrees C indicated that quantitative recovery was possible. PRL immunoreactivity was not lost by dialysis for 96 h. Serial dilution of milk samples before and after dialysis gave inhibition curves parallel to PRL standards. Milk PRL concentrations were high for the first 3 days after birth, with a peak mean value of 157 +/- 18 ng/ml (SE) on the third day. Milk PRL levels then fell sharply to a mean of 24 ng/ml 13 days after delivery. Milk PRL concentrations showed a significant negative correlation (P less than 0.001) with milk lactose (r = -0.59) and positive correlations (P less than 0.01) with total milk protein (r = 0.49) and alpha lactalbumin (r = 0.33) estimations. We conclude that i) PRL is a normal constituent of human milk, ii) high concentrations of PRL are present in human milk for the first 3 days postpartum but subsequently fall rapidly, and iii) milk PRL levels correlate significantly with milk lactose, total protein, and alpha-lactalbumin values.

Female↗
PubMed1980

The presence of lactogen receptors in human chorion laeve.

Lactogen receptors have been identified in human chorion laeve and possibly placenta but not other periplacental tissues. The receptors show the same hormonal specificity, and similar binding parameters (affinity 0.47 x 10(9) l/m, capacity 175 fmol3/mg) to lactogen receptors in mammary gland and liver. The presence of these receptors, suggests they may play a role in mediating an action(s) of amniotic fluid prolactn in chorion laeve, such as osmoregulation.

Chorion↗
PubMed1979

Long-term cimetidine does not alter serum prolactin.

The effect of repeated cimetidine ingestion on serum prolactin values was studied prospectively in 17 men with proven duodenal ulcers. These patients received 400 mg of cimetidine twice daily for 12 weeks but showed no alteration in their mean serum prolactin levels. Cimetidine-induced hyperprolactinaemia is not the explanation for the development of gynaecomastia in men exposed to this drug.

Administration, Oral↗
PubMed1978

Hypothesis: placental membranes produce prolactin.

Orthodox views for the origin of the high concentration of prolactin (PRL) present in amniotic fluid suggest it is derived from maternal or fetal serum. However, the data on which these conclusions are based can also be interpreted to indicate that this hormone may be a product of placental or periplacental tissues. Trophoblast or amnion do not appear to produce PRL, while PRL synthesis by decidua-chorion is suggested from experiments in the rhesus monkey and by in vitro incubation of human tissue. Production of PRL by an extrapituitary cell is not without precedent and would be a simple explanation for high amniotic fluid PRL concentrations. Moreover, decidual-chorionic PRL would be strategically placed to mediate local functions of this hormone such as osmoregulation and myometrial inhibition.

Amniotic Fluid↗
PubMed1978

An hypothesis for high multiple pregnancies after clomiphene.

A triplet and a quadruplet pregnancy following induction of ovulation with clomiphene are described; in each patient secondary amenorrhoea followed oral contraceptive use and several anovulatory or inadequate menstrual cycles had occurred on initial clomiphene therapy. Conception occurred in the first cycle after increasing drug dosage or the addition of human chorionic gonadotrophin (HCG) to the treatment regimen. We suggest, in explanation of these pregnancies, that repeated suboptimal stimulation of the ovaries as a result of clomiphene therapy develops several follicles to a critical stage; a subsequent greater ovulatory stimulus allows for synchronous development of several large follicles and multiple ovulation.

Adult↗