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Biomedical subjects

D T Baird

Publications and source records attributed to D T Baird.

At least 181 records · Page 10Linked to original sources
PubMed1989

Blood loss following induction of early abortion using mifepristone (RU 486) and a prostaglandin analogue (gemeprost).

The pattern and amount of blood loss following induction of therapeutic abortion using mifepristone (RU 486) and a prostaglandin E analogue (gemeprost) was studied in 222 women of less than 63 days amenorrhoea. A single oral dose of mifepristone (400, 500 or 600 mg) was followed 48 hours later by a half or 1 mg gemeprost vaginal pessary. Complete abortion occurred in 218 (98%) women without necessity for surgical evacuation of the uterus. Bleeding commonly occurred following administration of mifepristone and prior to prostaglandin administration. The median duration of bleeding following abortion was 13 days with a range of from 1 to 44 days. There was a wide individual variation in measured blood loss between women, from 14 to 512 ml, with a median loss of 74 ml. The amount of blood loss was independent of the dose of mifepristone or prostaglandin but was significantly correlated with gestation. These results confirm that the combination of mifepristone and gemeprost is a highly effective and safe method of inducing therapeutic abortion medically. As the amount of blood loss increases with increasing gestation, it is suggested that its use should be restricted to women with amenorrhoea less than or equal to 56 days.

Abortifacient Agents↗
PubMed1989

Induction of early abortion with mifepristone (RU486) and two different doses of prostaglandin pessary (gemeprost).

One-hundred-and-twenty women of less than 56 days amenorrhoea were treated with a single dose of 600 mg of mifepristone in combination with half or a whole 1 mg gemeprost vaginal pessary. Complete abortion was induced in 119 (99%) women and there were no continuing pregnancies. There were few gastro-intestinal side effects following prostaglandin. The smaller dose of prostaglandin caused significantly less severe pain. This study confirmed the effectiveness of mifepristone and prostaglandin for the induction of early abortion but suggests that more research should be carried out to determine the lowest effective doses of both drugs.

Abortifacient Agents↗
PubMed1989

FSH and the control of follicular growth.

During 70 days or so from the time of recruitment until just before the beginning of the cycle during which a follicle is destined to ovulate, folliculogenesis is a continuous process dependent on gonadotrophins but independent of the fluctuations in their concentrations occurring during this time. For follicle growth to continue beyond the 2-4 cell antral stage FSH concentrations must rise above a certain threshold level at the correct time. Once threshold levels are exceeded a single follicle becomes dominant suppressing FSH concentrations to subthreshold values. The period during which FSH concentrations are above threshold can be imagined as a gate through which a follicle must pass if it is to ovulate.

Animals↗
PubMed1989

Estrogenic action of tamoxifen in women treated with luteinizing hormone-releasing hormone agonists (goserelin)--lack of shrinkage of uterine fibroids.

Six premenopausal women with uterine fibroids were treated with a combination of tamoxifen, 20 mg/d, and goserelin, 3.6 mg every 28 days, for a total of 24 weeks. Results were compared with those from six women, matched for pretreatment uterine volume, who had been treated with goserelin alone. During combined therapy, plasma and urinary estrogen concentrations were significantly lower than during goserelin alone, whereas sex hormone binding globulin concentrations were significantly higher. Plasma luteinizing hormone and follicle stimulating hormone (FSH) concentrations were both suppressed, in contrast with results during goserelin alone when FSH levels remained within the pretreatment range. None of the women on combined therapy bled in response to the endocrine changes of the initial treatment cycle. Despite this profound pituitary-ovarian suppression, there was no significant change in uterine volume during combined therapy. These results suggest that tamoxifen is acting as an estrogen agonist in women rendered hypoestrogenic with luteinizing hormone-releasing hormone agonists.

Amenorrhea↗
PubMed1989

Glucose phosphate isomerase activity in mouse and human eggs and pre-embryos.

We have measured the activity of glucose phosphate isomerase (GPI-1) in 12 unfertilized human eggs and five human pre-embryos relative to the GPI-1 activity in C57BL/OlaWs mouse eggs. The GPI-1 activity in the human eggs was approximately 6 times that in the C57BL mouse eggs. This implies that human eggs have approximately twice the activity per unit volume of the C57BL mouse eggs but no more than certain other strains of mice. The activity in five human pre-embryos, the most advanced of which was an early blastocyst, was similar to that seen in the human eggs. No change in GPI-1 activity was seen in mouse pre-embryos up to 2 1/2 days (8- to 12-cell stage) but the activity had declined by 3 1/2 days (compacted morula and early blastocyst stages). It seems that high levels of GPI-1 activity are maintained during the early preimplantation development of both species.

Animals↗
PubMed1989

A comparison of the effects on follicular development between clomiphene citrate, its two separate isomers and spontaneous cycles.

An investigation of the effects on follicular development of clomiphene citrate and its two isomers En clomiphene and Zu clomiphene given separately was carried out on 19 normally cycling women being treated with donor insemination. All women received clomiphene citrate in the first cycle and, following a washout control cycle, were treated with either En clomiphene or Zu clomiphene alone. The number of follicles present, follicular phase oestrogen secretion and luteal phase pregnanediol excretion were not significantly different when Zu clomiphene cycles were compared with control cycles, but were significantly increased in En clomiphene and clomiphene citrate cycles. It is concluded that the En isomer, which has largely antioestrogenic properties, is the isomer active in inducing follicular development. The oestrogenic properties of Zu isomer did not appear to protect it from the possibly detrimental effects on sperm-cervical mucus interaction observed in both isomers and in the combined preparation.

Adult↗
PubMed1989

Tamoxifen prolongs luteal phase in premenopausal women but has no effect on the size of uterine fibroids.

Tamoxifen (20 mg per day) was administered for at least 3 months to six premenopausal women with uterine fibromyomata. In all the women there was an increased variability in the length of the menstrual and ovarian cycle associated with a significant lengthening of the luteal phase (16.9 +/- 3.5 vs 12.5 +/- 1.5 days, mean +/- SD, P less than 0.02). The concentration of oestradiol and progesterone in plasma and their metabolites in urine (oestrone glucuronide and pregnanediol) increased reflecting multiple follicular development and ovulation. There was a significant rise in the concentration of FSH during the luteal phase of the cycle (8.0 +/- 2.9 vs 2.0 +/- 1.7 U/l, P less than 0.01). There was no change in the size of the uterine leiomyomata. These results demonstrate that the antioestrogen tamoxifen results in an increased secretion of gonadotrophins by antagonizing the effects of oestradiol at the hypothalamus and anterior pituitary. The lengthening of the luteal phase suggests oestradiol may play a role in the mechanism of luteal regression either locally or via feedback effect on gonadotrophins.

Estrone↗
PubMed1989

LHRH analogues and fibroids--potential for longer-term use.

Improved diagnosis has made drug treatment of uterine fibroids more of a reality. For long-term use, conclusions cannot yet be drawn on the merits of LHRH analogues administered alone or in sequence with other agents. However, such treatment enables preservation of reproductive function, whilst avoiding potential sequelae of surgical myomectomy.

Drug Therapy, Combination↗
PubMed1989

Changes in the plasma concentrations of inhibin throughout the normal sheep oestrous cycle and after the infusion of FSH.

A radioimmunoassay for inhibin was developed using a peptide containing the 1-26 amino acid sequence of the N-terminus of the alpha-chain of 32 kDa porcine inhibin as immunogen, and 125I-labelled tracer. Evaluation of this assay using Sephadex column chromatography, chromatoelectrophoresis and immunoblotting confirmed that it measured all forms of inhibin present in sheep follicular fluid and was suitable for measurement of inhibin in sheep plasma. There was no evidence of the presence of free alpha-subunit in either sheep follicular fluid or ovarian vein plasma. The concentration of inhibin in jugular plasma throughout the follicular and luteal phases of four ewes with ovarian autotransplants was measured. The ovarian secretion of inhibin and oestradiol were also measured simultaneously throughout the follicular phase in a spontaneous cycle and after infusion of NIH-oFSH-S14 at 10 micrograms/h for 48 h following premature luteal regression induced by prostaglandin. The results showed: (1) no change in the peripheral concentration of inhibin throughout the cycle except an increase related to the periovulatory increase in FSH and LH. (2) Following luteal regression, the concentration of FSH fell as the secretion rate of oestradiol increased. During this time there was no significant change in the peripheral concentration of inhibin or ovarian inhibin secretion rate. (3) Following the infusion of FSH there was a marked increase in the concentration of inhibin in both ovarian and peripheral plasma and an increase in ovarian inhibin secretion rate. (4) The calculated metabolic clearance rate of inhibin, 20.3 ml/min, is similar to that of FSH. We conclude that in the ewe the ovarian inhibin secretion rate is stimulated by FSH and, although inhibin may modulate the basal secretion of FSH, a change in its secretion does not account for the fall in FSH which occurs during the follicular phase of the sheep oestrous cycle.

Animals↗
PubMed1989

The binding of steroids to myometrium and leiomyomata (fibroids) in women treated with the gonadotrophin-releasing hormone agonist Zoladex (ICI 118630).

Since uterine leiomyomata (fibroids) are not found in conditions where oestradiol is either absent or present only in low concentrations, oestradiol is considered to be an important factor in the control of fibroid growth. To investigate whether this is due to a direct effect on the tissue, oestradiol and progestogen receptors were measured in tissue removed at hysterectomy from 12 normally cycling women and 13 women who had received the gonadotrophin-releasing hormone (GnRH) agonist Zoladex (ICI 118630) as a subcutaneous depot given at monthly intervals for 3 months preoperatively and a third group of three women who had received the antioestrogen tamoxifen (20 mg daily) for 3 months before surgery. Both unoccupied oestradiol receptors (measured by separating bound from free hormone with dextran-coated charcoal; DCC) and 'total' receptor populations (as measured by an enzyme immunoassay) were measured in each fibroid and adjoining myometrium. There was significantly more binding of both oestradiol and progestogen to fibroid than to myometrium in both the control (P less than 0.01) and agonist-treated groups (P less than 0.05). Oestradiol binding to fibroids in women treated with Zoladex exceeded that in the normally cycling women (P less than 0.05) which in turn exceeded that in the tamoxifen-treated group (P less than 0.05). However, the binding of progestogen, measured by DCC showed the reverse trend. These results may be explained by the low circulating oestradiol concentration in the GnRH agonist-treated women leading to low receptor occupancy.

Buserelin↗
PubMed1989

Episodic secretion of inhibin into the ovarian vein during the follicular phase of the oestrous cycle in the ewe.

Changes in the plasma concentration of inhibin were measured by radioimmunoassay in ovarian venous blood collected at 10-min intervals for 5-h periods between 16 and 21 h and 40 and 45 h after cloprostenol-induced luteal regression in six Finn-Merino sheep. Episodes of inhibin secretion occurred with an interpulse interval of 66 +/- 5 min in both stages of the follicular phase. These changes in inhibin were unrelated to pulses of LH or oestradiol. There was no relationship with plasma concentrations of FSH, which did not change in a pulsatile manner. These results suggest that the release of inhibin by the preovulatory follicle(s) occurs in a pulsatile manner and is under local control by unknown factors.

Animals↗
PubMed1989

Episodic ovarian inhibin secretion is not due to LH pulses in anoestrous ewes.

In sheep, secretion of oestradiol by the ovary is stimulated by pulses of LH but the factors controlling ovarian inhibin secretion are not well understood. We have investigated the effect of a single injection of LH on the ovarian secretion of inhibin. Six anoestrous Finn-Merino ewes which had one ovary autotransplanted to a site in the neck had jugular and timed ovarian venous blood samples collected at 10-min intervals for a total of 5 h. The secretion rates of both inhibin (1-3 ng/min) and oestradiol (0.5-8 ng/min) were similar to those observed during the breeding season indicating significant follicular development in these animals. After injection of 2.5 micrograms NIH-LH-S25 intravenously the concentration of LH in plasma rose from a baseline of 1.8 +/- 0.1 (S.E.M.) microgram/l to a peak of 3.9 +/- 0.3 micrograms/l (P less than 0.01). This LH pulse stimulated a corresponding increase (P less than 0.01) in oestradiol secretion from a basal level of 0.9 +/- 0.2 ng/min to a peak of 4.6 +/- 0.6 ng/min that occurred within 30 min of injection. Although inhibin secretion was episodic in nature, increases were not related to either exogenous or endogenous LH pulses. We conclude that, in contrast to oestradiol, the secretion of inhibin by the ovary is not controlled acutely by changes in plasma levels of LH during anoestrus.

Anestrus↗
PubMed1989

Source of ovarian inhibin secretion during the oestrous cycle of the sheep.

The source of inhibin secretion by the ovary in the sheep at different stages of the oestrous cycle was investigated by in-vivo cannulation of the ovarian veins. Twenty-four Scottish Blackface ewes were allocated to four groups of six ewes, i.e. those operated on during the luteal phase (day 10), and those operated on during the follicular phase 24-30, 36 and 60 h following an injection of 125 micrograms cloprostenol on day 10 of the luteal phase. Samples of jugular and timed ovarian venous blood were collected under anaesthesia before and after enucleation of the corpus luteum. Ovaries were then removed and follicles dissected out. Following injection of cloprostenol, luteal regression occurred as indicated by a fall in the secretion of progesterone. The concentration of inhibin in jugular venous plasma and its ovarian secretion rate were similar at all stages of the follicular phase and during the luteal phase. In contrast, the secretion rate of oestradiol rose from 2.86 +/- 0.73 pmol/min during the luteal phase to 8.70 +/- 2.24 pmol/min 24 h after injection of cloprostenol (P less than 0.05). Following enucleation of the corpus luteum the secretion rate of progesterone fell from 809 +/- 270 pmol/min to 86 +/- 30 pmol/min (P less than 0.001). There was also a smaller, artifactual fall in the secretion rate of oestradiol following enucleation of the corpus luteum, which was of similar size to a fall seen in the secretion rate of inhibin. This resulted in a significant (P less than 0.001) fall in the ratio of progesterone to inhibin, while the oestradiol to inhibin ratio remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Passively immunizing ewes against inhibin during the luteal phase of the oestrous cycle raises the plasma concentration of FSH.

Passive immunization was used to investigate the importance of inhibin in the negative feedback loop regulating the production of FSH in sheep. An anti-serum raised to the 1-26 peptide fragment of the N-terminus of the alpha-chain of porcine inhibin was first shown to neutralize the suppressive effects of inhibin on the production of FSH by dispersed ovine pituitary cells in vitro. Groups of five mature Scottish Blackface ewes on day 8 of the luteal phase of the oestrous cycle were then injected with either 10 ml plasma from normal ewes (control) or 10 ml ovine inhibin antiserum. On day 10, luteal regression was induced by an i.m. injection of cloprostenol (100 micrograms), and ovulation rate determined 6 days later by laparoscopy. Peripheral plasma samples were collected throughout the experimental period. Following treatment, there was no change in the peripheral plasma concentration of LH in either group. Following injection of the inhibin antiserum, the concentration of FSH rose significantly (P less than 0.001) compared with the control group. The concentration of FSH rose from 1.42 +/- 0.06 to a maximum of 2.58 +/- 0.23 (S.E.M.) micrograms/l by 5.6 +/- 0.9 h, this maximum lasting 9.0 +/- 1.1 h. By 32.8 +/- 6.9 h, the concentration of FSH had returned to pretreatment levels, while the titre of free antibody in the plasma of treated ewes was still high. In the treated ewes, there were one single and four double ovulations compared with three single and two double ovulations in the control group, indicating that the inhibin immunization may have resulted in an increase in ovulation rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Superovulation with exogenous gonadotropins does not inhibit the luteinizing hormone surge.

The administration of human chorionic gonadotropin to women undergoing superovulation with exogenous gonadotropins was delayed in order to document the occurrence of a surge of luteinizing hormone (LH). An LH surge was seen to occur in 10 of 10 women receiving clomiphene citrate (CC) and pulsatile human menopausal gonadotropin (hMG); in 10 of 12 women treated with pulsatile hMG alone; and in 12 of 14 women treated with single daily injections of hMG without CC. The height of the surge was attenuated in all cycles and the timing of its onset was significantly earlier among women receiving single daily injections of hMG. Possible mechanisms for these findings are discussed.

Adult↗
PubMed1988

The effects of clomiphene citrate on the histology of human endometrium in regularly cycling women undergoing in vitro fertilization.

Thirty-six women with histories of regular cycles undergoing elective laparoscopic sterilization volunteered to participate in a research program of endometrial biopsy, oocyte donation, and in vitro fertilization (IVF). One half of the volunteers received 5 days of 150 mg of clomiphene citrate (CC) ending 5 days before human chorionic gonadotropin injection and 6.5 days before laparoscopy and biopsy. The control patients were treated identically, except they received no CC. CC cycles were more uniform in duration and follicular response better, enabling a prescheduled IVF regimen. Control cycles were complicated by poor follicular response or untimely endogenous surges of luteinizing hormone (LH). The mean urinary estrone glucuronide excretion per follicle was the same in each group, and there was no evidence of a luteal defect by either luteal phase length or urinary pregnanediol excretion. Although there were minor differences in mitotic rate and basal vacuolation of glandular epithelium in biopsies, no specific deleterious effect of CC could be seen.

Adult↗