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Biomedical subjects

D T Baird

Publications and source records attributed to D T Baird.

At least 109 records · Page 6Linked to original sources
PubMed1994

Restoration of fertility to oophorectomized sheep by ovarian autografts stored at -196 degrees C.

Cortical slices were prepared from the right ovaries of six lambs and either grafted directly to the ovarian pedicles of origin or cooled slowly to liquid nitrogen temperatures in medium containing dimethylsulphoxide. Three weeks later, the contra-lateral ovary was removed and replaced with frozen-thawed slices from the same animal. Two of the animals mated during their second oestrous cycle 3-4 months later and the remainder had at least one ovulatory cycle. The pregnancies reached full-term development, one lamb being derived from an ovulation in a fresh graft and the other from a frozen-thawed graft. None of the sheep had peripheral plasma concentrations of follicle stimulating hormone or luteinizing hormone consistently in the castrate range, and only one graft was devoid of follicles when the animals were slaughtered 9 months after the operations. Grafts with primordial follicles always contained developing follicles, which occasionally attained pre-ovulatory sizes of 7 mm in diameter. A corpus albicans was present in five grafts. Since all developing follicles had degenerated 1 week after grafting in an additional ewe, the large follicles in long-term grafts had presumably commenced growing after the operation. There were no obvious differences between fresh and frozen-thawed grafts in either appearance or weight, and all had apparently grown since implantation. Despite substantial depletion of primordial follicle numbers, the results indicated that frozen storage and replacement of a patient's own ovarian tissue might be practicable when fertility potential is threatened by chemotherapy/radiotherapy.

Animals↗
PubMed1994

Detection of dimeric inhibin throughout the human menstrual cycle by two-site enzyme immunoassay.

OBJECTIVE: We have developed and validated a two-site immunoassay for the measurement of dimeric inhibin in plasma and subsequently measured dimeric inhibin levels in plasma through the normal female menstrual cycle. DESIGN: Recombinant inhibin added to plasma samples was quantitatively recovered in both follicular and luteal phase, and serial dilutions of samples were tested for parallelism to similar dilutions of recombinant 32 kDa inhibin. Daily samples were assayed from four women through a menstrual cycle. PATIENTS: (a) Four groups of six women who (i) were in the follicular phase of a normal menstrual cycle, (ii) were in the luteal phase of a normal menstrual cycle, (iii) were post-menopausal and (iV) who had received hMG to induce superovulation. (b) Four healthy female volunteers aged 25-33. RESULTS: Post-menopausal women had less than 2 ng/l of inhibin whereas six women treated with hMG had dimeric inhibin concentrations up to 1125 ng/l. During the early follicular phase, at the time of onset of menstruation, extremely low levels of dimeric inhibin were found (3.4 ng/l (CI 2.2-5.0)) while in the late follicular phase, there was a marked increase in dimeric inhibin concentration. The concentration of dimeric inhibin was maximal (65.6 ng/l (CI 53.1-81.1)) in the mid-luteal phase. The overall pattern of dimeric inhibin concentration during the menstrual cycle was similar to that observed with previous inhibin assays although the magnitude of change was considerably greater. CONCLUSION: The human ovary, in particular the corpus luteum, secretes significant amounts of dimeric and therefore biologically active inhibin.

Adult↗
PubMed1994

Treatment with the gonadotrophin releasing hormone-agonist goserelin before hysterectomy for uterine fibroids.

OBJECTIVE: To investigate the effect of the gonadotrophin releasing hormone (GnRH)-agonist goserelin, given by monthly subcutaneous injection for three months prior to total abdominal hysterectomy for uterine leiomyomata, on the pre-operative symptoms, difficulty of operation and operative blood loss. DESIGN: Randomised placebo-controlled study. SETTING: Patients were recruited from the gynaecological outpatient departments from hospitals in Edinburgh, Glasgow and Newcastle. SUBJECTS: Seventy-one premenopausal women with uterine leiomyomata who were on the waiting list for hysterectomy. INTERVENTIONS: After the presence of leiomyomata was confirmed using ultrasonography, the women were randomised to receive either the GnRH-agonist goserelin by monthly subcutaneous injection or a sham injection for three months prior to operation. At the monthly visits, patients were asked about treatment related symptoms, fibroid related symptoms, and their bleeding patterns. Blood was taken for haematological assessment. MAIN OUTCOME MEASURES: Haemoglobin concentrations at recruitment, at operation and post-operatively, pre-operative symptoms, operative difficulty and blood loss and post-operative complications. RESULTS: Treatment with goserelin induced amenorrhoea in over 80% of the women, and this was associated with a significant rise in haemoglobin level. At the time of operation, fibroid related symptoms were less in the goserelin group than in the placebo group. The hysterectomy was technically easier and the median (range) operative blood loss was significantly lower in the goserelin group compared with the placebo group (187 (60-600) ml vs 308 (118-1000) ml respectively; P < 0.05, Wilcoxon signed rank test). There was no difference between the two groups in the duration of hospital stay or the frequency of post-operative complications. The fibroids were smaller at the time of operation in the goserelin group, and more women treated with goserelin were able to have their operations through a transverse incision. CONCLUSIONS: This study demonstrates the benefits of goserelin in women having total abdominal hysterectomy for uterine leiomyomata.

Adult↗
PubMed1994

Attitudes of women to fetal tissue research.

The use of human fetal tissue for scientific research has enormous potential but is subject to government legislation. In the United Kingdom the Polkinghorne Committee's guidelines were accepted by the Department of Health in 1990. These guidelines set out to protect women undergoing termination of pregnancy from exploitation but in so doing may significantly restrict potential research. Although the committee took evidence from a wide variety of experts they did not seek the views of the general public. We asked 108 women about to have a therapeutic abortion; 167 women who had had a pregnancy terminated in the past, and 419 women who had never had an abortion, their views on research using human fetal tissue. Regardless of their past experiences the women were overwhelmingly in favour of research using fetal tissue (94 per cent). They made little distinction between basic research and research with obvious clinical relevance and supported the concept of using transplanted fetal tissue for the treatment of adult disease such as Parkinsonism. Women about to undergo an abortion were significantly more likely (p < 0.001) to approve of all types of research including that aimed at improving methods of abortion and research using live fetuses in utero.

Aborted Fetus↗
PubMed1994

First meiotic division abnormalities in human oocytes: mechanism of trisomy formation.

Trisomy is the single most frequent type of chromosome abnormality in humans and has considerable impact on many aspects of human pathology. It arises most commonly through "nondisjunction" at maternal meiosis I, but the underlying mechanism of formation remains obscure. Analysis of 100 haploid oocytes at second meiotic metaphase shows that the only type of chromosome abnormality compatible with trisomy formation after fertilisation is the presence of single chromatids in addition to, or replacing, whole chromosomes. The mechanism resulting in the presence of single chromatids is considered to be precocious division of univalents or dyads at first meiotic anaphase.

Adult↗
PubMed1994

Differential regulation of cholesterol side-chain cleavage (P450scc) and aromatase (P450arom) enzyme mRNA expression by gonadotrophins and cyclic AMP in human granulosa cells.

The co-ordinated biosynthesis of progesterone and oestradiol in the human ovary is critical for reproductive cyclicity and eventual pregnancy. The crucial regulatory enzymes for progesterone and oestradiol biosynthesis in granulosa cells are the cholesterol side-chain cleavage (P450scc) and aromatase (P450arom) enzymes respectively. We utilized the cDNA sequences encoding P450arom and P450scc to examine the roles of FSH and LH, and their intracellular second messenger, cyclic AMP (cAMP), in regulating steroidogenic gene expression. Mature granulosa cells (aspirated before the onset of the endogenous LH surge) and granulosa lutein cells (obtained after an ovulatory dose of human chorionic gonadotrophin) were cultured for 4 days with FSH, LH or dibutyryl cAMP (dbcAMP). After the period of culture, total RNA was extracted from granulosa cells and Northern analyses were performed utilizing 32P-labelled cDNAs encoding P450arom and P450scc. Spent culture media were analysed for steroid and cAMP content. Both FSH and LH strongly stimulated P450arom mRNA expression and oestradiol production in mature granulosa cells. On the other hand, P450scc mRNA expression and progesterone biosynthesis were weakly induced by FSH; maximal synthesis occurred only in the presence of LH. With both gonadotrophins at equivalent concentrations, LH generated a 30-fold higher level of cAMP than FSH. Furthermore, the differential effects of FSH and LH on P450 mRNA expression were reproduced by the presence of low and high concentrations of dbcAMP respectively. LH (and high levels of dbcAMP) increased P450arom mRNA expression in mature granulosa cells but inhibited its accumulation in granulosa lutein cells. In contrast, it stimulated P450scc mRNA expression and progesterone synthesis in both mature granulosa and granulosa lutein cells. Therefore, FSH/low cAMP levels stimulated P450arom gene expression and oestradiol production, while LH/high cAMP levels maximally induced P450scc gene expression and function, in a development-related manner consistent with steroid production in vivo. These findings support the hypothesis that one set of genes (like P450arom) in human granulosa cells is regulated by FSH/low cAMP levels and another (like P450scc) by LH/high cAMP levels.

Aromatase↗
PubMed1993

A model for follicle selection and the determination of ovulation rate in the ewe.

A model for folliculogenesis is proposed that is based as far as possible on a knowledge of physiological, rather than anatomical, changes taking place during follicle development. The model is therefore functional, rather than descriptive, and consists of five classes of follicles that have been defined by their dependency and sensitivity to gonadotrophins. These classes are: primordial, committed, gonadotrophin-responsive, gonadotrophin-dependent and ovulatory. The model is an attempt to encourage discussion and to promote the integration of morphological models of folliculogenesis with recent advances in the molecular endocrinology of the ovarian follicle. Two hypotheses for the mechanisms that determine ovulation rate are developed in light of the model. In the first, multiple ovulation results when the viability of gonadotropin-dependent follicles is enhanced. In the second, multiple ovulation is caused by increasing the number of gonadotrophin-responsive follicles available for further development; this results from the increasing rate of folliculogenesis and the throughput of follicles. The final section of this paper examines how these two hypothetical mechanisms, which are not mutually exclusive, appear to account for most of the known genetical and environmental effects on ovulation rate of sheep. In particular, the effects of nutrition, genotype, exogenous gonadotrophins, immunity to both oestrogens and androgens, and immunity to inhibin are discussed.

Animal Nutritional Physiological Phenomena↗
PubMed1993

Antigestogens.

Antigestogens are compounds which inhibit the synthesis of progesterone or antagonise its biological action. The progesterone antagonist mifepristone (RU 486) binds with high affinity to progesterone receptors throughout the body, blocking the action of endogenous progesterone. In the last 10 years it has been demonstrated that mifepristone, in combination with a suitable prostaglandin, is a safe, effective alternative to vacuum aspiration for termination of pregnancy in the first two months. Preliminary trials suggest that antigestogens may be useful true contraceptives by inhibiting ovulation or by preventing implantation as once a month pills and postcoital agents. In late pregnancy, by sensitising the uterus to prostaglandins and by promoting cervical dilatation, they may induce labour and facilitate lactation. In non-pregnant women mifepristone may have application in the treatment of hormone-dependent conditions such as endometriosis, fibromyomata, meningioma and breast cancer. The availability of hormone antagonists to oestrogens, androgens and progesterone offers the possibility of new methods of regulating reproductive function in health and disease.

Abortion, Induced↗
PubMed1993

The effects of mifepristone (RU486) on prostaglandin dehydrogenase in decidual and chorionic tissue in early pregnancy.

Prostaglandin dehydrogenase is the main inactivating enzyme for prostaglandins and therefore controls local levels of prostaglandins. Since there is some evidence that the expression of this enzyme is under progesterone control it is reasonable that one of the effects of antiprogestin is to reduce the concentration of this enzyme and thus increase the effective concentration of prostaglandin within tissue. We have investigated the amount of enzyme activity within decidua and chorionic villi from women receiving the antigestagen mifepristone (RU486) 12, 24 and 36 h prior to surgical abortion, and examined the effect on tissue concentrations of prostaglandin dehydrogenase. Women receiving mifepristone in all groups had a significant reduction in concentration of prostaglandin dehydrogenase enzyme in decidual tissue. There was also a marked reduction in prostaglandin dehydrogenase in decidual cells following RU486, as demonstrated by immunochemical methods. At this stage of pregnancy, prostaglandin dehydrogenase was present in abundance in cytotrophoblast cells of chorionic villi but virtually absent from syncytiotrophoblast. In chorionic villi after RU486 administration in vivo, there were no obvious differences in prostaglandin dehydrogenase distribution or reactivity in the majority of cases.

Abortion, Induced↗
PubMed1993

The effect of dose of mifepristone and gestation on the efficacy of medical abortion with mifepristone and misoprostol.

Although it has been demonstrated that a combination of mifepristone and a prostaglandin is an effective method of inducing abortion in early pregnancy, the optimum dose of the antigestogen is unknown. Women (n = 220) requesting abortion in early pregnancy (< or = 63 days amenorrhoea) were randomized to receive a single dose of either 600 or 200 mg mifepristone followed 48 h later by a single dose of 600 micrograms misoprostol by mouth. The percentage of women who had a complete abortion (93.6% confidence interval 90.4-95.5%) was identical in the two groups. There was no significant difference in the number of women who passed the fetus within 4 h of receiving the prostaglandin (64 versus 74%), the days of bleeding (14.6 +/- 1.1 versus 15.3 +/- 0.9) nor in the onset of the next period (39.7 +/- 1.3 versus 36.7 +/- 1.3) respectively between the groups receiving 200 or 600 mg mifepristone. However, the complete abortion rate was significantly higher in women < or = 49 days compared to women 50-63 days amenorrhoea (97.5 versus 89.1% respectively; P < 0.02). There was no difference in any of the other parameters at different weeks of gestation. We conclude: (i) that the recommended dose of mifepristone could be reduced from 600 to 200 mg without loss of clinical efficacy, (ii) that the combination of mifepristone and 600 micrograms misoprostol is a highly effective alternative to vacuum aspiration for inducing abortion in women < 50 days amenorrhoea and (iii) at gestation > 56 days, this combination may result in too many incomplete abortions to be clinically acceptable.

Abortion, Induced↗
PubMed1993

Expression of messenger ribonucleic acid for inhibin subunits and ovarian secretion of inhibin and estradiol at various stages of the sheep estrous cycle.

The relationship between expression of inhibin mRNA and ovarian secretion of estradiol (E2) and immunoactive inhibin was investigated at midluteal phase and throughout the follicular phase of the sheep estrous cycle. At laparotomy, timed samples of ovarian blood were collected and ovaries were removed from 39 Scottish Blackface ewes (ovulation rate 1.3 +/- 0.1) on Day 10 of the luteal phase or 24, 48, 60, 72, or 84 h after injection of cloprostenol (PG; 100 micrograms) on Days 10-12. Ovaries were removed and fixed for in situ hybridization using 35S-labeled antisense riboprobes transcribed from inhibin alpha, beta A, and beta B cDNAs. LH, E2, and inhibin concentrations were determined by RIA. On the basis of peripheral LH levels and the presence of estrogen-active follicles (E-A; > or = 3 mm in diameter secreting > 1 ng/min E2) or recent ovulations, animals were grouped as follows: presurge (24 or 48 h post-PG; LH < 5 ng/ml; n = 7), midsurge (with E-A; LH > 5 ng/ml; n = 6), late surge (large follicle not E-A; LH > 5 ng/ml; n = 4), postsurge (large follicle not E-A; LH < 5 ng/ml; n = 7), and postovulation (n = 10). As expected, E2 secretion by the "active" ovary (containing preovulatory follicle) tended to increase with follicular development such that secretion was maximal at midsurge and then declined. E2 secretion by the "inactive" ovary was low at all stages. Immunoactive inhibin, in contrast, was secreted in substantial quantities by both ovaries, although secretion from active ovaries was higher at all stages (p < 0.05). Effects of stage on secretion were not significant, but immunoactive inhibin secretion from active ovaries was high in postsurge animals when E2 secretion was very low. Hybridization for inhibin mRNA was specific for granulosa cells of antral follicles. While most sheep in the luteal (4 of 5), presurge (2 of 3), and midsurge groups (5 of 5) had at least one inhibin-positive large follicle (expressing both alpha- and beta-subunit mRNA), none were present between the LH surge and ovulation (late and postsurge groups). Inhibin mRNA was undetectable in midcycle CL, but 4 of 10 recent ovulations hybridized weakly with the alpha probe and one very weakly with the beta A probe. The mean number of inhibin-positive large follicles per animal (in those having at least one) was 1.3 +/- 0.15 (n = 15 ewes).(ABSTRACT TRUNCATED AT 400 WORDS)

Activins↗
PubMed1993

The relationship between peripheral immunoactive inhibin, human chorionic gonadotrophin, oestradiol and progesterone during human pregnancy.

OBJECTIVE: The objective of this study was to investigate serial changes in the plasma concentration of inhibin in both the very early days of pregnancy following implantation and in late pregnancy. The timing of the changes in inhibin concentration relative to changes in the concentrations of other hormones of pregnancy was also investigated. DESIGN: Serial observations of the peripheral concentrations of inhibin and other hormones in two groups of healthy volunteers in (a) early pregnancy and (b) late pregnancy. PATIENTS: (a) Four healthy women recruited on cessation of contraception prior to conception. (b) Nine healthy women recruited at the antenatal clinic. MEASUREMENTS: In the early pregnancy subjects, the concentrations of inhibin, progesterone, oestradiol and hCG were measured in plasma samples obtained three times per week from day 8 to day 10 of each menstrual cycle until 11 weeks after the last menstrual period in the conception cycle. In the late pregnancy subjects, plasma samples were obtained at 4-week intervals from 12 weeks until term. RESULTS: The concentration of inhibin, progesterone and oestradiol in conception cycles were similar to those in the preceding cycles until the mid/to late-luteal phase of the cycle when hCG was first measureable. By day 12 of the luteal phase the concentration of inhibin was significantly higher in the pregnancy cycle than in the non-pregnancy cycle (P < 0.05) and progressively increased after the time of the missed menstrual period. The concentration of inhibin reached a peak (513.0 U/l, CI 442.1-595.3) by day 47 when the concentration of hCG was maximal. In early pregnancy the concentration of inhibin was correlated with that of hCG (r = 0.361; P < 0.01) as well as progesterone (r = 0.584, P < 0.001) and oestradiol (r = 0.602, P < 0.001). After 12 weeks there was no significant correlation between hCG and inhibin although significant correlations persisted with progesterone (r = 0.553, P < 0.001) and oestradiol (r = 0.361, P < 0.01). CONCLUSIONS: The corpus luteum makes a significant contribution to the production of inhibin in early pregnancy while after 12 weeks the placenta is the major source.

Adult↗
PubMed1993

Abnormal twenty-four hour pattern of pulsatile luteinizing hormone secretion and the response to naloxone in women with hyperprolactinaemic amenorrhoea.

OBJECTIVE: Hyperprolactinaemic amenorrhoea is associated with disturbances of pulsatile gonadotrophin secretion. The underlying mechanism remains unclear and the aim of this study was to investigate the 24-hour secretory pattern of gonadotrophins in women with hyperprolactinaemic amenorrhoea. The effect of opioid blockade using naloxone infusion on LH secretory pattern was also studied. DESIGN: The secretory patterns of LH, FSH, PRL and their responses to naloxone infusion were studied by serial blood samples collected at 10-minute intervals for 24 hours. On the following day, naloxone was infused at a dose of 1.6 mg per hour for 4 hours. PATIENTS: Eight women with hyperprolactinaemic amenorrhoea, two women hyperprolactinaemic but with normal ovarian cycles, and nine control subjects in the early follicular phase of menstrual cycle. MEASUREMENTS: Concentrations of LH, FSH and PRL were measured in plasma samples obtained at 10-minute intervals for 24 hours. In one woman, concentrations of urinary oestrone glucuronide were measured daily during treatment with pulsatile GnRH. RESULTS: The number of LH pulses per 24 hours was significantly fewer in women with hyperprolactinaemic amenorrhoea than in those with hyperprolactinaemia with normal cycles or control subjects (mean +/- SEM 4.5 +/- 2.4 vs 13.5 +/- 2.5 vs 17.3 +/- 0.8, P < 0.001). The magnitude of each episode of secretion was significantly higher in the hyperprolactinaemic amenorrhoeic women (P < 0.05) so the overall mean concentrations of LH throughout the 24-hour period was similar in the three groups (5.2 +/- 1.1, 4.8 +/- 0.8 and 5.2 +/- 0.4 U/l respectively). In women with hyperprolactinaemic amenorrhoea there was no significant change in the pattern of LH secretion during sleep in contrast to the control women in whom there was a slowing in the LH pulse frequency during the night. There was no significant change in the mean concentrations of LH, FSH and PRL during the naloxone infusion. There were also no significant changes in the LH pulse frequency in response to naloxone infusion when compared with an equivalent period of time in the previous 24 hours. In one hyperprolactinaemic amenorrhoeic woman, follicular development, ovulation and pregnancy were induced when gonadotrophin releasing hormone (GnRH) was infused in a pulsatile manner at a dose of 5 micrograms every 90 minutes. CONCLUSIONS: The suppression of normal ovarian cycles in women with hyperprolactinaemic amenorrhoea is due to a significant reduction in frequency of LH (GnRH) secretion which is not due to an increase in hypothalamic opioid activity. As normal ovarian cycles can occur or be induced by exogenous GnRH in hyperprolactinaemia, it is unlikely that a high level of prolactin by itself inhibits follicular development and ovulation.

Adult↗
PubMed1993

Induction of second trimester abortion with mifepristone and gemeprost.

OBJECTIVE: To determine the efficacy of a new regimen of the antiprogestogen mifepristone and gemeprost for midtrimester abortion. DESIGN: Prospective study. SETTING: Medical Termination Unit, Simpson Memorial Maternity Pavilion, Edinburgh. SUBJECTS: One hundred women undergoing midtrimester abortion. INTERVENTIONS: Women were pretreated with 200 mg mifepristone 36 h before prostaglandin; 1 mg gemeprost was administered every 6 h for the first 24 h. If abortion had not occurred, 1 mg gemeprost was administered 3 hourly over the next 12 h. MEASUREMENT AND MAIN RESULTS: Ninety-six percent and 99% women aborted within 24 h and 48 h, respectively. The median prostaglandin-abortion interval was significantly shorter in multigravidae compared to primigravida (6.6 vs 8.2 h, P < 0.01). The median number of gemeprost pessaries to induce abortion was only two and 47% of women required one pessary. The incidence of vomiting and diarrhoea was 31% and 5%, respectively. Eighty-four percent of women required intramuscular diamorphine for analgesia. Thirty-three percent of women required an evacuation of the uterus following abortion. CONCLUSIONS: The shortened induction-delivery interval following pretreatment with mifepristone makes it possible to conduct midtrimester abortion on a daycare basis.

Abortifacient Agents, Nonsteroidal↗
PubMed1993

Changes in the concentration of alpha-fetoprotein and placental hormones following two methods of medical abortion in early pregnancy.

OBJECTIVE: Measurement of alpha-fetoprotein (AFP) was used to investigate the occurrence of feto-maternal haemorrhage in women undergoing medical abortion. DESIGN: Three groups of women with amenorrhoea of 56 or less days were studied. A control and a mifepristone group had two blood samples taken 48 h apart. Women undergoing medical abortion with gemeprost had two blood samples taken 24 h apart. SETTING: Medical Termination Unit, Simpson Memorial Maternity Pavilion, Edinburgh. SUBJECTS: Three hundred and thirty-five women requesting abortion. INTERVENTIONS: Blood samples taken at 24 h or 48 h apart. MEASUREMENTS AND MAIN RESULTS: The rise in concentration of AFP in plasma was much higher (P = 0.01) in the two groups of women in whom abortion was induced by gemeprost or mifepristone than in control women. Whereas only 5% of women in the control group had a significant rise in AFP, 27% and 33% of women in the mifepristone and gemeprost groups, respectively, had a rise in AFP level which exceeded the 95th centile (> or = 38%). The concentration of hCG rose by 48 h in both control and mifepristone groups. Progesterone remained unchanged, and oestradiol decreased (P < 0.02) in the mifepristone group. By 24 h, there was a significant fall in the concentrations of hCG, progesterone and oestradiol in the group who had aborted after being given gemeprost. CONCLUSIONS: Anti-D prophylaxis must be administered to rhesus negative women to avoid rhesus iso-immunisation.

Abortifacient Agents, Nonsteroidal↗