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D T Baird

Publications and source records attributed to D T Baird.

At least 127 records · Page 7Linked to original sources
PubMed1993

The effect of mifepristone (RU486) on the immunohistochemical distribution of prostaglandin E and its metabolite in decidual and chorionic tissue in early pregnancy.

The widespread tissue distribution of prostaglandin dehydrogenase (PGDH), the main enzyme for the metabolism and deactivation of prostaglandin (PG), suggests that local effective levels of PG are controlled by catabolism. Previous reports have suggested that after the administration of mifepristone (RU486) in vivo, the levels of PGDH in uterine tissues fall, such results support earlier suggestions that PGDH is under progesterone control in reproductive tissues. In this study we have used immunohistochemistry to assess tissue concentrations of PGE and its main metabolite 13,14-dihydro-15-keto-PGE in chorionic villi and decidua from women treated with RU486 12, 24, and 36 h previously. In control villous tissue, PGE and 13,14-dihydro-15-keto-PGE2 (PGEM) are prominent in the syncytiotrophoblastic layer, whereas PGE stains only weakly in cytotrophoblasts, due to the presence of PGDH in this region; treatment with RU486 in vivo causes little change in distribution or intensity in villi. However, in decidua, staining for PGE2 was intense in the glands after RU486 and localized in the supranuclear region of the cells. Small blood vessels that were PGE negative and PGEM positive in the controls were PGE positive and PGEM negative in treated tissue. These findings show that PG stimulation by antiprogestin is by means of a direct effect on PGDH, and secondly, that the prominent rise in PGE in blood vessels may be a major mode of action of this steroid in causing abortion, as PGs may synergize with leukocyte chemotactic agents to stimulate neutrophil ingress and tissue destruction.

Chorionic Villi↗
PubMed1993

Follicular development and ovarian hormone secretion following passive immunization of ewes against inhibin or oestradiol.

Immunization against inhibin or oestradiol causes an increase in the peripheral plasma concentration of FSH. In this study we have investigated the effect of this post-immunization rise in FSH concentration on follicular development by means of real-time ultrasonography, in ewes in which an ovary and its vascular pedicle had been autotransplanted to a site in the neck. Groups of ewes on day 10 of the luteal phase of the oestrous cycle were injected with a single 10 ml i.v. bolus of plasma from normal ewes (control; n = 4), antiserum to the 1-26 peptide fragment of the N-terminus of the alpha chain of porcine inhibin (n = 5) or antiserum to oestradiol-17 beta (n = 4). The plasma concentration of FSH was unaffected by treatment in the control group but showed a significant (P < 0.001) rise following treatment in both immunized groups (inhibin-immunized 175% over 19h; oestradiol-immunized 138% over 22 h as a per cent of the original value). This rise in FSH concentration was accompanied by a significant (P < 0.001) rise in the total number of follicles > 2.0 mm per ovary in both immunized groups (inhibin-immunized 5.5 +/- 1.0 to 13.6 +/- 1.4; oestradiol-immunized 4.6 +/- 0.5 to 11.5 +/- 1.0).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Clinical use of mifepristone (RU 486).

Because progesterone is essential for the establishment and maintenance of pregnancy, it has long been recognized that a substance which antagonized the action of progesterone would have potential as an antifertility agent. Within 2 years of the synthesis of the progesterone antagonist RU 486 (mifepristone) it was demonstrated that bleeding and uterine contractions occurred following its administration in non-pregnant and pregnant women. Extensive trials over the last 10 years have established that a single dose of mifepristone followed 36-48 hours later by a prostaglandin, is an effective, safe alternative to vacuum aspiration for the termination of early pregnancy. Although this combination is licensed in France, China and the United Kingdom for induction of abortion, research is continuing to determine the minimum effective dose of mifepristone and type of prostaglandin which is associated with minimum side effects without loss of efficacy. In addition, studies to determine the acceptability of this type of medical abortion to women in different cultures and societies are required. The facilities necessary for medical termination differ from those for surgical abortion, although the requirements for access to emergency resuscitation and treatment of (rare) complications are similar for the two methods. Mifepristone is very effective in the management of prostaglandin-induced midtrimester abortion. By sensitizing the uterus to prostaglandin, the dose of prostaglandin can be reduced with a shortened prostaglandin-abortion interval. Administration of mifepristone in the early luteal phase of the cycle delays the development of a secretory endometrium. Preliminary studies suggest that it may be highly effective when given at this time as a post-coital contraceptive or 'once a month' pill. Although antigestagens offer great promise as agents to help regulate human fertility, their widespread use may be constrained more by religious and political factors, rather than by demonstration of clinical efficacy.

Abortifacient Agents, Nonsteroidal↗
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.

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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↗