Search PubMed⌕ Search

Biomedical subjects

D T Baird

Publications and source records attributed to D T Baird.

At least 19 recordsLinked to original sources
PubMed1992

Mifepristone (RU 486) compared with high-dose estrogen and progestogen for emergency postcoital contraception.

BACKGROUND: Mifepristone (RU 486) is a synthetic steroid with potent antiprogestational and antiglucocorticoid properties that provides an effective medical method of inducing abortion in early pregnancy. Since progesterone is essential for implantation, we tested the use of mifepristone for emergency postcoital contraception. METHODS: We studied 800 women and adolescents requesting emergency postcoital contraception who had had unprotected intercourse within the preceding 72 hours. A total of 398 women and adolescents were randomly assigned to treatment with 100 micrograms of ethinyl estradiol and 1 mg of norgestrel, each given twice 12 hours apart (standard therapy), and 402 women and adolescents were randomly assigned to receive 600 mg of mifepristone. RESULTS: None of the women and adolescents who received mifepristone became pregnant, as compared with four of those who received standard therapy; the difference in failure rates between the two regimens was not statistically significant. The number of pregnancies in each group was significantly lower than the number expected according to calculations based on the day of the cycle during which intercourse had taken place (P less than 0.001). In many subjects the stage of the cycle as calculated by menstrual history was inconsistent with measurements of plasma progesterone or urinary pregnanediol excretion. The subjects treated with mifepristone reported less nausea (40 percent vs. 60 percent) and vomiting (3 percent vs. 17 percent) on the day of treatment, as well as lower rates of other side effects, than the subjects treated with the standard regimen, but they were more likely to have a delay in the onset of the next menstrual period (42 percent vs. 13 percent). CONCLUSIONS: Mifepristone is a highly effective postcoital contraceptive agent that, if used more widely, could help reduce the number of unplanned and unwanted pregnancies.

Adolescent↗
PubMed1992

Medical abortion.

Explore the source record for details and available documents.

Abortion, Induced↗
PubMed1992

A study of gemeprost alone, dilapan or mifepristone in combination with gemeprost for the termination of second trimester pregnancy.

It is well established that abortion can be induced successfully in midtrimester of pregnancy by gemeprost vaginal pessaries. A randomised study was carried out to determine the efficacy of mifepristone and dilapan in combination with gemeprost for second trimester termination between 12-18 weeks' gestation. A contemporary group of women treated with gemeprost alone was used as a control group. A single course of 4 x 1 mg gemeprost pessaries was administered every six hours. If abortion had not occurred after 24 hours, a further course of 5 x 1 mg pessaries was administered every three hours over the next 24 hours. In the first twenty hours after administration of gemeprost, 95%, 85% and 72% of women aborted in the mifepristone, dilapan and the control group, respectively. The median induction-abortion interval in the mifepristone group (6.6h) was significantly shorter than the other two groups and fewer pessaries were required to induce abortion. The incidence of diarrhoea and vomiting was lower in the mifepristone than the other two study groups. This study demonstrated the efficacy of mifepristone in combination with gemeprost and this regimen is associated with fewer gastrointestinal side effects.

Abortifacient Agents, Nonsteroidal↗
PubMed1992

What do women want during medical abortion?

A questionnaire study was carried out to investigate the needs of women undergoing a medical abortion induced by mifepristone in combination with either gemeprost pessaries or oral misoprostol. One-hundred-and-eighty women undergoing medical abortion of pregnancy of up to 63 days amenorrhoea were randomised to treatment in the sitting-room (treatment room) or in the ward. Overall, 77% and 69% treated in the sitting-room and ward, respectively, would have preferred treatment in the sitting-room. Fifty-four per cent did not wish their partner or friend to be present and 76% would prefer to stay in hospital following administration of prostaglandin. Ninety-five per cent of the patients would recommend this method of abortion to their friends. Women who received misoprostol required significantly less analgesia than women who were given 1 mg gemeprost as a vaginal pessary. The requirement for opiate analgesia was not influenced by parity, gestation of pregnancy, history of dysmenorrhoea or the dose of mifepristone. Almost 100% of the patients were satisfied with this method of treatment. This study indicates that the majority of women undergoing medical abortion prefer to be treated in a group, a method which is highly cost-effective.

Abortifacient Agents, Nonsteroidal↗
PubMed1992

A retrospective study of 932 second trimester terminations using gemeprost (16,16 dimethyl-trans delta 2 PGE1 methyl ester).

A retrospective study of 932 second trimester terminations between 12-27 weeks gestation was carried out to determine the efficacy of gemeprost for second trimester termination. A single course of 5 x 1 mg gemeprost pessaries was administered every three hours. If abortion had not occurred after the first course of pessaries, a further course of 5 x 1 mg pessaries was administered. Intravenous oxytocin was administered after 36 hours if abortion had not occurred. Eighty per cent and ninety five per cent of patients aborted within 24 and 48 hours respectively. Of the remaining 5 per cent of women, 3 per cent aborted with escalating doses of oxytocin. In the remaining 18 (2 per cent) women, the pregnancies were electively terminated with an alternative method. The median induction-abortion interval was 18.0 hours and 15.0 hours in nulliparous and parous women respectively (P less than 0.0001). The number of pessaries required to induce abortion was not influenced by parity. Significantly more parous women bled more than 500 ml. The incidence of pelvic sepsis (0.1 per cent) and cervical tear (0.1 per cent) was low. Twenty six per cent of women had diarrhoea and 23 per cent vomited following administration of prostaglandin. This study confirmed the efficacy of gemeprost for second trimester termination of pregnancy. This method of termination is safe, non-invasive, simple and has a low complication rate.

Abortion, Induced↗
PubMed1992

Effect of cyclofenil on hormonal dynamics, follicular development and cervical mucus in normal and oligomenorrhoeic women.

Cyclofenil is a triphenylethylene derivative, similar in structure to clomiphene citrate, which is used to induce ovulation in anovulatory women. The effects of cyclofenil on a group of 10 normal cyclic and 10 oligomenorrhoeic subjects were examined in a double blind controlled cross-over study. Both groups of women were administered either cyclofenil or, following a washout cycle, a placebo in two treatment cycles. Urinary oestrone and pregnanediol excretion were measured daily and ultrasound scans performed to assess follicular development. Frequent sampling of blood was performed on day 6 to study luteinizing hormone (LH) and follicle stimulating hormone (FSH) pulsatile release. Cervical mucus changes and sperm-cervical mucus interaction were studied after identification of the LH peak. There were no significant differences between cyclofenil and placebo cycles in the following: ovulation rates, daily urinary oestrone and pregnanediol excretion, the number or size of developing follicles, LH pulsatility (parameters studied: number of peaks, pulse interval, pulse amplitude, pulse area and mean nadir LH), mean FSH level on day 6, cervical mucus and sperm-cervical mucus interaction. In view of our inability to demonstrate an effect on any parameter of endocrine function in normal and oligomenorrhoeic women, these results throw doubt on the therapeutic value of cyclofenil in its present dosage and formulation.

Adult↗
PubMed1992

Potential role for medroxyprogesterone acetate as an adjunct to goserelin (Zoladex) in the medical management of uterine fibroids.

Twenty women with symptomatic uterine fibroids were treated with the luteinizing hormone-releasing hormone (LHRH) agonist goserelin (Zoladex) combined with medroxyprogesterone acetate (MPA) in an open pilot study comparing two protocols. Ten women received goserelin 3.6 mg monthly combined with oral MPA 15 mg daily for 6 months. The mean uterine volume (497 cm3) measured by ultrasound fell by only 18% after 3 months, with no further reduction at 6 months. The other 10 women received goserelin alone for the initial 3 months, followed by combined treatment for 3 months. The mean uterine volume (557 cm3) fell by 39% after 3 months with no significant regrowth by 6 months. At 6 months post-treatment, uterine volume had not returned to pretreatment size. MPA significantly reduced the frequency of vasomotor side-effects. There were no differences in plasma oestradiol, luteinizing hormone or follicle stimulating hormone concentrations between the protocols and good symptomatic relief was experienced by both groups. Two years after completion, three women in each group have requested surgical treatment. The results indicate that MPA may be a useful adjunct to LHRH analogues in women with fibroids, reducing side-effects and possibly prolonging the response, although positive effects on bone density have yet to be confirmed. The optimum regimen of administration remains to be clarified as the clinical results were the same with both protocols.

Adult↗
PubMed1992

Do women want a once-a-month pill?

The attitudes of women of reproductive age in Scotland, Romania and Slovenia to the idea of a contraceptive pill which is taken only once each month or only when menses are delayed was investigated. In all three centres, the great majority of women felt positive towards the idea of a once-a-month pill which inhibited ovulation and greater than 50% found a pill which inhibited or interfered with implantation an acceptable idea. Only 24% of women in Scotland were attracted to the idea of a pill which was taken only if menstruation was delayed by 1 or 2 days, that is a pill which would cause an abortion, while in contrast 58% of women in Slovenia and 80% in Romania thought that such a method of controlling fertility would be acceptable. Attitudes were not related to age, social class or marital status but were influenced by religious belief and in Scotland by a history of abortion. In countries where the availability of contraception is limited and abortion is common, women would seem to welcome another method of fertility regulation--even one which disrupts the very early stages of pregnancy.

Abortion, Induced↗
PubMed1992

Inhibition of ovulation by low-dose mifepristone (RU 486).

Mifepristone (RU 486) is a potent antigestagen and antiglucocorticoid which when given at a dose of 25-600 mg disrupts folliculogenesis, inhibits ovulation and induces menses in healthy women. This study reports the effects of much lower doses of mifepristone than used previously, given for the duration of a complete menstrual cycle. Healthy female volunteers (n = 11) with regular menstrual cycles were given mifepristone at a daily dose of 5 mg (n = 6) or 2 mg (n = 5) for 30 days, beginning immediately after an ovulatory placebo cycle. Mifepristone prevented menstruation for the duration of the treatment period, with recurrence of menses 15-29 days after replacement of mifepristone with placebo. Daily mifepristone given in either 5 mg or 2 mg doses inhibited ovulation, as indicated by the lack of a rise in urinary pregnanediol excretion. The excretion of oestrone glucuronide in urine rose during treatment, suggesting ovarian follicular development. Inhibition of ovulation appeared to result from a failure of the positive feedback effect of oestradiol on the hypothalamo-pituitary axis, as no surges of luteinizing hormone were seen despite pre-ovulatory levels of oestrone glucuronide being measured during exposure to mifepristone. The cycle immediately following treatment was shorter than the pre-treatment cycle, with lower peak levels of pregnanediol glucuronide, suggesting an inadequate luteal phase. Recovery from the effects of mifepristone treatment was more rapid after 2 mg than after 5 mg and one subject conceived in the immediate post-treatment phase, indicating adequate ovulation and luteinization.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Mediation of gonadotrophin-stimulated growth and differentiation of human granulosa cells by adenosine-3',5'-monophosphate: one molecule, two messages.

OBJECTIVE: To determine how the second messenger adenosine-3',5'-monophosphate (cyclic AMP) is able to mediate divergent actions of FSH and LH on granulosa cell growth and differentiation in human ovaries. DESIGN: Human granulosa cells were cultured for 96 hours in serum-free medium 199 containing increasing doses of either FSH, LH or dibutyryl cyclic AMP. Extra and intra-cellular cyclic AMP levels were determined by radioimmunoassay. Tritiated thymidine uptake and cell number were measured as indices of cell growth, and spent medium was assayed for steroids (oestradiol and progesterone) to reflect differentiation. PATIENTS: 'Mature' granulosa cells were aspirated from preovulatory follicles in the ovaries of clomiphene-stimulated patients undergoing laparoscopic sterilization; 'luteinized' granulosa cells were aspirated from periovulatory follicles in the ovaries of gonadotrophin-stimulated in-vitro fertilization patients. RESULTS: LH consistently inhibited, whereas FSH maintained or stimulated, basal granulosa cell numbers. Steroidogenesis was dose-dependently increased by both gonadotrophins, with LH having the significantly greater effect over the entire dose-response range (1-100 micrograms/l). LH also induced significantly more cyclic AMP production than FSH, both intra and extra-cellularly, providing a basis for differential post-receptor signalling via a common second messenger. Addition of dibutyryl cyclic AMP, at low concentrations (10-250 mumol/l) to the cultured cells in the absence of gonadotrophins mimicked FSH effects with stimulation/maintenance of cell numbers and moderate steroidogenesis. High concentrations of dibutyryl cyclic AMP (500-1000 mumol/l) caused a significant inhibition of cell numbers together with maximal steroidogenesis, simulating LH action. CONCLUSIONS: These results suggest that granulosa cell maturation in the follicular phase of the menstrual cycle (controlled by FSH) is associated with a low cyclic AMP tone that favours cell growth and expression of aromatase activity in the developing preovulatory follicle. During the early luteal phase (dominated by LH), the intracellular cycle AMP tone increases to allow maximal progesterone production and inhibition of cell growth in the corpus luteum. Thereby one second messenger can mediate divergent gonadotrophic effects on granulosa cell growth and differentiation in the human ovary.

Adult↗
PubMed1992

Induction of abortion with mifepristone and misoprostol in early pregnancy.

OBJECTIVE: To investigate the clinical efficacy of the combination of mifepristone and an orally active prostaglandin, misoprostol, for early medical termination. DESIGN: Women with amenorrhoea < or = 56 days were given 200 mg mifepristone. 48 h later, 600 micrograms misoprostol was given orally. SETTING: Medical Termination Unit, Simpson Memorial Maternity Pavilion, Edinburgh. SUBJECTS: 100 women requesting medical termination of pregnancy. INTERVENTIONS: Evacuation of uterus for incomplete abortion or on-going pregnancies. RESULTS: One woman had an incomplete abortion prior to administration of misoprostol. 92 (93%) out of 99 women had complete abortion following administration of misoprostol. There were three on-going pregnancies (3.0%, 95% confidence limits (CL) 0.6-8.6) and four incomplete abortions with this regimen (4.0%, 95% CL 1.1-10.0). 24% women vomited and 7% had diarrhoea following administration of misoprostol. 62% did not require any analgesia. CONCLUSIONS: The combination of misoprostol with mifepristone is inexpensive, simple, effective, noninvasive and an acceptable alternative to current regimens for medical termination.

Abortion, Induced↗
PubMed1992

Medical abortion in women of less than or equal to 56 days amenorrhoea: a comparison between gemeprost (a PGE1 analogue) alone and mifepristone and gemeprost.

OBJECTIVE: To determine the efficacy of a new dose regimen of vaginal gemeprost (1 mg every 6 h up to three doses) in induction of abortion in women less than or equal to 56 days gestation, and to compare this regimen with mifepristone (200-600 mg) followed 48 h later by a single dose of gemeprost (1 mg). DESIGN: Two separate protocols, with 50% of the subjects randomized to one or other protocol. SETTING: The Royal Infirmary of Edinburgh, Scotland, UK. SUBJECTS: 301 referred by their general practitioner or local family planning clinic, requesting termination of pregnancy at less than or equal to 56 days amenorrhoea. INTERVENTIONS: Ongoing pregnancies and incomplete abortions were terminated surgically. MAIN OUTCOME MEASURES: Number of complete abortions, analgesic requirements and bleeding pattern following treatment. RESULTS: Complete abortion occurred in 87% of women treated with gemeprost alone and 98% of women treated with mifepristone and gemeprost (P = 0.0004). Analgesic requirements were greater in the group treated with gemeprost alone, compared with the group treated with mifepristone and gemeprost (P = 0.0001). CONCLUSION: The new dose regimen of gemeprost can be used for early induced abortion, but the use of mifepristone and gemeprost has several advantages over the use of gemeprost alone.

Abortifacient Agents, Nonsteroidal↗
PubMed1992

Hormonal regulation of the growth and steroidogenic function of human granulosa cells.

The aim of this study was to assess development-related interactions between gonadotropins and insulin-like growth factor (IGF-I) on DNA synthesis and steroidogenesis in human granulosa cells. "Immature" granulosa cells were obtained from follicles during the late luteal phase or first half of the follicular phase; "mature" granulosa cells came from follicles during the second half of the follicular phase but before the midcycle LH surge; and granulosa-lutein cells were obtained as a by-product of in vitro fertilization. Granulosa cells were cultured for 96 h in serum-free medium 199 with and without LH or FSH, and in the presence and absence of IGF-I. The cell monolayers were then incubated with [3H]methyl thymidine to assess DNA synthesis. Spent culture medium was assayed for progesterone and estradiol content. Immature granulosa cells: Tritiated thymidine uptake in granulosa cell cultures from immature follicles were significantly increased by IGF-I. FSH was able to maintain or increase basal and IGF-I stimulated growth whereas LH had no effect. Basal progesterone production was low and not increased by either FSH or LH. However, treatment with FSH, but not LH, increased aromatase activity. Mature granulosa cells: IGF-I also stimulated thymidine uptake. However, whereas FSH either maintained or increased thymidine uptake by these cells, LH dose dependently suppressed thymidine uptake. This inhibitory action of LH was accentuated by the presence of IGF-I. Despite the inhibitory effect of LH on thymidine uptake, the gonadotropin markedly stimulated steroid production and the maximal steroidogenic response to LH was equivalent to 3-fold greater than that to FSH. Granulosa-lutein cells: Patterns of basal and IGF-I- and gonadotropin-stimulated steroid synthesis were similar to those observed for mature granulosa cells but steroid production rates were higher. Suppression of basal and IGF-I-stimulated thymidine uptake by LH was even more pronounced. These results suggest that the granulosa cell LH receptor, once expressed, negatively regulates cell growth and, simultaneously, positively regulates steroid synthesis. This development related event could be crucial to the mechanism whereby granulosa cells cease to divide and commence maximal rates of steroid synthesis in response to the LH surge.

Adult↗
PubMed1992

Hormone production in vivo and in vitro from follicles at different stages of the oestrous cycle in the sheep.

This experiment was undertaken in order to investigate the production of inhibin, oestradiol and androstenedione by ovarian follicles at different stages of the oestrous cycle in sheep. 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 after the induction of luteal regression by an injection of 125 micrograms cloprostenol on day 10 of the luteal phase. Samples of jugular and ovarian venous blood were collected under anaesthesia and ovaries were then removed and all follicles larger than 3 mm diameter dissected out and incubated in medium for 2 h. After injection of cloprostenol, luteal regression occurred as indicated by a fall in the secretion rate of progesterone. The ovarian secretion rate of inhibin was similar at all stages of the follicular phase and during the luteal phase while, in contrast, the secretion rate of oestradiol was significantly (P less than 0.05) elevated in the group 24 h after injection of cloprostenol. There was good correlation between the in-vivo ovarian secretion rate and production rate during incubation in vitro for both inhibin (r = 0.57) and oestradiol (r = 0.60). When follicle diameter was compared with in-vitro hormone production there was good correlation for inhibin (r = 0.72) with larger follicles producing more inhibin, while the value for oestradiol was somewhat lower (r = 0.57) owing to the presence of large atretic follicles with low oestradiol production. Androstenedione production showed a lower correlation with follicle diameter (r = 0.39). When the four time periods were compared separately, there were significantly (P less than 0.05) more follicles with high in-vitro oestradiol production (greater than 90 fmol/min) in the group at 36 h than in the other three groups, while inhibin release in relation to follicle size was similar in the four groups. Large oestrogenic follicles were responsible for 90% of the total oestradiol production during culture while only providing 55% of the total inhibin production, with large non-oestrogenic and small follicles contributing 33% and 12% of inhibin production respectively. From the results of this study we conclude that while oestradiol is mainly produced by the large oestrogenic follicles, a considerable amount of inhibin is also produced by large non-oestrogenic and small follicles.(ABSTRACT TRUNCATED AT 400 WORDS)

Androstenedione↗
PubMed1992

The role of inhibin and oestradiol in the control of FSH secretion in the sheep.

The relative importance of inhibin and oestradiol in the control of FSH and LH secretion in the ewe was investigated by passive immunization in intact animals and by hormone replacement therapy following acute ovariectomy, in the same experiment. Mature Scottish Blackface ewes on day 10 of the luteal phase were allocated to nine groups of four to five animals. Four groups were ovariectomized and immediately treated with either progesterone alone or in combination with steroid-stripped ovine follicular fluid ('inhibin') and/or oestradiol. Three further groups of ewes were left intact and injected with antibodies to the 1-26 alpha peptide fragment of porcine inhibin and/or oestradiol-17 beta. Two groups of animals were either ovariectomized alone with no further treatment, or were left intact and treated with normal sheep plasma to act as controls. Blood samples were collected at 2 h intervals from 12 h before until 48 h after ovariectomy/immunization, and from 12 to 24 h after treatment, blood samples were collected at 10-min intervals. After ovariectomy there was a large rise in the peripheral concentration of LH (P less than 0.001) which was not affected by treatment with progesterone alone but was completely prevented by treatment with progesterone and oestradiol. Treatment with inhibin had no effect on this post-castrational rise in LH. In intact ewes, immunization against oestradiol, alone or in combination with inhibin, resulted in a rise in the concentration of LH, while immunization against inhibin had no effect on LH concentration. The peripheral concentration of FSH showed a significant (P less than 0.001) increase after ovariectomy which was not affected by treatment with progesterone alone. Treatment with inhibin or oestradiol alone caused a significant (P less than 0.01) reduction in this rise, while treatment with inhibin and oestradiol together completely prevented this post-castrational rise in FSH concentration. Passive immunization against inhibin or oestradiol alone resulted in a transitory (P less than 0.01) rise in the peripheral concentration of FSH, while immunization against the two hormones in combination resulted in a significantly (P less than 0.01) larger rise. During the 14-h period after treatment, the rise in the concentration of FSH in this combined immunization group was not significantly different from that seen in the control ovariectomized group. These results provide evidence that FSH secretion is under the control of both oestradiol and inhibin, while reinforcing the hypothesis that inhibin is not involved in the regulation of LH production, which is under the dual control of oestradiol and progesterone.

Animals↗