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Biomedical subjects

D T Baird

Publications and source records attributed to D T Baird.

At least 253 records · Page 14Linked to original sources

Menstrual induction: surgery versus prostaglandins.

In most developed countries in which therapeutic abortions are legal, termination of pregnancy is performed at between 8 and 12 weeks of gestation. Because the complication rate after this procedure rises with increasing gestation, there would be many advantages in inducing abortion before the eighth week ('menstrual induction'). With the increasing availability of highly sensitive methods of detecting human chorionic gonadotropin, pregnancy can now be diagnosed as early as 10-14 days after conception. The uterus can be surgically evacuated safely and simply by suction aspiration under local anaesthesia. However, a safe and effective method of inducing abortion by medical means would be a useful and cheaper alternative. Of the potentially useful compounds, only derivatives of prostaglandins E and F administered by vaginal pessary have so far been shown to be effective. Although the rate of haemorrhage and infection is low, 10-30% of women experience moderate side-effects of pelvic pain, diarrhoea and/or vomiting. The possibilities are discussed of reducing the incidence of side-effects by different methods of release or using prostaglandins in combination with other compounds such as antigestogens which might lower the therapeutic threshold.

Abortion, Induced↗

Prostaglandins in the human uterus: an interaction between endometrium and myometrium.

The interaction between the prostaglandin production of the human endometrium and myometrium has been further investigated using intact pieces of endometrium in homogenates of myometrium. There was an increase in the production of 6 oxo PGF, alpha when these tissues were incubated together, whereas there was no change in the production of PGE, PGF2 alpha or 13, 14 dihydro 15 - keto PGF2 alpha. This endometrial - myometrial interaction could have important implications in the pathogenesis of menorrhagia.

6-Ketoprostaglandin F1 alpha↗

Prolonged follicular phase and depressed gonadotrophins following hysterectomy and corpus lute-ectomy in women with premenstrual tension syndrome.

In an attempt to obtain further information on the aetiology of premenstrual syndrome (PMS), the endocrine changes following enucleation of the corpus luteum in the mid-luteal phase of the cycle were studied in seven patients with PMS, and the results compared to details of seven control patients undergoing hysterectomy for menstrual problems. In the luteal phase, before surgery, the concentration of progesterone and FSH was lower, while that of oestradiol was slightly higher, in women with PMS. Following enucleation of the corpus luteum, follicular development and ovulation recommenced more slowly in women with PMS compared to controls (time to ovulation: 21 (range 18-24, vs 19(14-20) d, P less than 0.01). During the follicular phase there was no difference between the two groups in the concentration of oestradiol. The rise in concentration of FSH following enucleation was delayed in patients with PMS, and the serum FSH concentration was significantly lower during the late follicular phase of the cycle, but not during the mid follicular phase. The results suggest that these women with PMS have a more sensitive 'feed-back' than the controls, resulting in a lower preovulatory FSH level even though the oestradiol levels were not different. The results also suggest that the abnormalities described during the preoperative luteal phase are associated with the delay in the initial FSH rise.

Adult↗

Specific binding of gonadotrophin-releasing hormone and an agonist to human corpus luteum homogenates: characterization, properties, and luteal phase levels.

The binding of radiolabeled GnRH and GnRH agonist (GnRHA) was studied in homogenates of human luteal tissue using a polyethylene glycol precipitation technique. GnRHA binding to human luteal homogenates was dependent on pH, was inhibited by a number of divalent metal ions, and was of moderately high affinity (Ka = 3 X 10(7) M-1). Binding of both radiolabeled GnRH and GnRHA increased linearly with increasing homogenate concentration, and binding of either tracer was parallel with different corpus luteum (CL) homogenates. Moreover, similar concentrations of unlabeled GnRH or GnRHA blocked the binding of either tracer, indicating that both hormones bound to a common site. The rate of dissociation of bound ligand was very low at 0 C, but was extremely rapid at physiological temperatures (t1/2 = 2.5-3.5 min). Human luteal GnRHA-binding sites were partially solubilized by treatment with Triton X-100 and were sensitive to trypsin and pronase, but not hyaluronidase. GnRHA binding to homogenates of human CL obtained at each stage of the luteal phase varied markedly, with levels ranging from less than 20 to greater than 1600 pg/mg DNA for CL from the (midluteal) stage of the menstrual cycle. This variability could not be accounted for by assay irreproducibility, loss of binding activity during storage, or occupancy of binding sites by endogenous ligand. These observations may help to explain negative reports from other groups, which demonstrated little or no specific binding of GnRH to human luteal tissue and no effect of GnRH on steroidogenesis using dispersed human luteal cells in vitro. We conclude that human luteal homogenates possess specific, moderately high affinity binding sites for GnRH and its agonist analogs.

Adult↗

Endogenous luteinizing hormone surge during superovulation induction with sequential use of clomiphene citrate and pulsatile human menopausal gonadotropin.

There is dispute as to whether an endogenous LH surge occurs in women during follicle stimulation with human menopausal gonadotropin (hMG) for in vitro fertilization (IVF). In this study, 12 consecutive normally cycling women with tubal infertility were treated with clomiphene citrate and hMG for ovulation induction and subsequent IVF. Beginning on the fifth day of clomiphene administration (150 mg daily for 5 days), 225 IU hMG were given daily sc in a pulsatile manner (28 IU/3 h). All women had an endogenous LH surge which started on the seventh to ninth day of hMG administration. The mean duration [25.5 +/- 1.0 (+/- sem) h] and the mean peak value (38.9 +/- 4.7 U/liter) of the LH surge were less than those in spontaneous cycles. However, luteinization of at least some of the follicles occurred, based on findings of supraphysiological levels of serum progesterone during the surge and subsequent increase in urinary pregnanediol levels (luteal phase). Preovulatory oocytes were recovered via laparoscopy 34-35 h after the onset of the surge, and these oocytes cleaved after IVF. One pregnancy was achieved after embryo transfer, which resulted in abortion. These results represent the first demonstration that an attenuated LH surge is obtained in normally cycling women during superovulation induction with sequential clomiphene/pulsatile hMG treatment.

Clomiphene↗

Ovulation rate and embryo survival in Damline ewes after treatment with bovine follicular fluid in the luteal phase of the oestrous cycle.

Treatment of Damline ewes with twice daily i.v. injections of bovine follicular fluid during the luteal phase for 10, 6 or 2 days before prostaglandin-induced luteolysis resulted in an increase in ovulation rate. This was associated with a large rebound increase in plasma concentrations of FSH after the last injection of bovine follicular fluid. While conception rate was not affected by bovine follicular fluid treatment, a higher percentage embryonic loss was observed between Days 3 and 34 of pregnancy in the 10-day treatment group only compared to controls. This reflected the increase in ovulation rate above the optimum for embryonic survival in this breed. The present results suggest that the increase in ovulation rate induced by bovine follicular fluid treatment in the luteal phase of the cycle before mating would result in a significant increase in the number of lambs born.

Animals↗

Suppression of luteal progesterone secretion in the stumptailed macaque by an antagonist analogue of luteinizing hormone releasing hormone.

The dependence of progesterone secretion from the corpus luteum on pituitary gonadotrophin was examined in the cyclic stumptaile macaque by studying the effects of a single s.c. injection of a potent LH releasing hormone (LHRH) antagonist, [N-Ac-D-Nal(2)1, D-pCl-Phe2, D-Trp3, D-hArg(Et2)6, D-Ala10] LHRH. A dose of 100 micrograms antagonist/kg administered on days 9/10 of the luteal phase in three monkeys caused a marked temporary suppression of serum concentrations of LH and progesterone during the following 32h but levels still remained detectable and after 2 days serum hormone concentrations returned to the normal luteal-phase range. When the same animals were treated with 300 micrograms antagonist/kg at the same period during a subsequent cycle, serum LH levels were close to or at the limits of detection of the bioassay for the next 48h and progesterone concentrations declined steadily, reaching non-detectable values by 48h. In two monkeys the progesterone levels remained suppressed and they menstruated prematurely; in the third monkey the progesterone concentration rose to just above baseline and menstruation occurred at the expected time. Administration of 300 micrograms antagonist/kg on days 6/7 of the luteal phase in a further three monkeys also suppressed progesterone concentrations but not to baseline values, and after 2 days a normal progesterone profile was regained. These results suggest that the corpus luteum of the stumptailed macaque is largely dependent on pituitary gonadotrophin support during the mid to late luteal phase.

Animals↗

Intra-uterine pressure in dysmenorrhea.

Intra-uterine pressure recordings in normal and dysmenorrheic women during the menstrual period were analysed regarding amplitude, duration, frequency and peak area of contractions and the resting pressure. The activity of the myometrium showed large between subject variability and no significant difference was found, between the two groups in amplitude and duration of contractions or their frequency. However, there was a consistent difference in peak area at the onset of the menses (p less than 0.01) and there was also a significant decrease in peak area during the menses in the group with dysmenorrhea, with maximum uterine work being performed on the day when the pain was at its worst. The contribution of the pattern of contractility to the etiology of dysmenorrhea is discussed. Abnormal uterine activity as a cause of primary dysmenorrhea was first suggested in the 1930s and 1940s on the basis of intra-uterine pressure recordings (Moir, 1936; Woodbury et al., 1947). Since then, intra-uterine pressure has been measured in a number of studies using a micro-balloon (Lundström et al., 1976; Bygdeman et al., 1979). With the introduction of the highly sensitive micro-transducer catheter it has been possible to make accurate quantitative estimations (Akerlund et al., 1978; Ulmsten & Andersson, 1979) but, to our knowledge, no detailed analysis and quantification of intrauterine pressure recordings in primary dysmenorrhea has been reported. In this paper we publish the results of a study in which daily recordings obtained from women suffering from primary dysmenorrhea were compared with those from a group of women with very similar menstrual patterns but with minimal or no symptoms.

Adult↗

X-Y translocation. A case report.

A translocation of genetic material involving the long arm of the X chromosome and the heterochromatic portion of the Y chromosome is reported in a young woman. The phenotypic effect of this translocation and loss of almost half of the long arm of the X chromosome is described.

Adolescent↗

Effects of 17 beta-estradiol and progesterone on the levels of prostaglandins F2 alpha and E in human endometrium.

17 beta-estradiol and progesterone were administered to post-menopausal women to determine their effects in vivo on the capacity of human endometrium to synthesize prostaglandins (PGs) F2 alpha and E. Basal amounts of PGF2 alpha and PGE synthesized by endometrium exposed to 17 beta-estradiol and progesterone were significantly higher than the levels produced by endometrium exposed to 17 beta-estradiol alone (p less than 0.02 for both PGs). Levels found in the former endometrium were broadly comparable to levels in secretory endometrium and in the latter to amounts found in proliferative endometrium of spontaneous, ovulatory cycles.

Dinoprost↗

Prostaglandin production from homogenates of separated glandular epithelium and stroma from human endometrium.

The biosynthesis of prostaglandins by isolated epithelial glandular and stromal cells was studied after collagenase digestion of endometrium collected from women at various stages of the menstrual cycle. Homogenates of the separate cell types were incubated for 60 minutes with 2.08 micrograms 1(14)C arachidonic acid and the products separated by thin layer chromatography. Both glandular and stromal homogenates synthesised PGF2 alpha. More PGF2 alpha was synthesised by glandular epithelium separated from both proliferative and secretory endometrium than by stroma. The ratio of PGF2 alpha/PGE2 was greater in glands and stroma isolated from secretory than proliferative endometrium. Small but significant amounts of 6-keto-PGF1 alpha were produced by all cell types. These results suggest that the increased synthesis of PGF2 alpha from secretory endometrium is due, at least in part, to increased activity of cyclo-oxygenase enzyme in the glandular epithelium.

Arachidonic Acid↗

The relationship between menstrual blood loss and prostaglandin production in the human: evidence for increased availability of arachidonic acid in women suffering from menorrhagia.

In this study we have obtained endometrium and myometrium from women whose menstrual blood loss had been measured objectively. Samples of tissue were snap frozen in liquid nitrogen for the estimation of PG content and tissue was homogenized and incubated with and without added arachidonic acid. PGE, PGF2 alpha and 6-oxo PGF1 alpha were measured by gas chromatography - mass spectometry. We confirm that the F2 alpha/E2 ratio in the snap frozen samples was significantly lower in women with a high blood loss although this was not reflected in the production by incubated homogenates. Incubation of endometrial tissue with myometrium from the same patient and with a pool of myometrium showed that the source of myometrium was not important. This suggests that previous observations of increased 6 oxo F1 alpha production in incubations of endometrium and homologous myometrium from women with high MBL, resulted from differences in endometrium. When prostaglandin E and F production by endometrium is studied there is a significant inverse correlation between the percentage difference in production with and without added arachidonic acid and menstrual blood loss which suggests that women with high MBL have relatively high levels of available arachidonic acid in their endometrium.

Arachidonic Acid↗

Pulsatile release of LH and oestradiol during the periovulatory period in women.

Blood was collected every 8 h in five women from Day 10 of the menstrual cycle for 5-7 d for the measurement of LH, oestradiol and progesterone. In all women the LH surge started between 2400 and 0800 h before there was any significant decline in the concentration of oestradiol. In order to investigate the pulsatile secretion of LH and estradiol during the mid-cycle surge, blood samples were collected every 5 min for up to 5 h. Immediately before and during the LH surge there were numerous episodic pulses of LH with an interpulse interval (44 +/- 7 min) very similar to that observed in two women with hypergonadotrophic hypogonadism (48 min). The concentration of oestradiol fluctuated in a similar manner although it was not always possible to relate each pulse of oestradiol to a corresponding pulse of LH. The mid-cycle surge of LH is characterized by frequent pulses of high amplitude. These results are compatible with the view that the positive feedback effect of oestradiol is due not only to enhanced sensitivity of the anterior pituitary to LHRH but also to the high frequency of LHRH pulses released from the hypothalamus.

Adult↗

Changes in plasma levels of prolactin, in relation to those of FSH, oestradiol, androstenedione and progesterone around the preovulatory surge of LH in women.

Plasma samples were obtained at 8 hourly intervals around the preovulatory surge of LH in three groups of women with spontaneously ovulatory menstrual cycles, in order to clarify the hormonal events around the time of ovulation. In 21 of 25 women in whom samples were collected every 8 hours the start of the LH surge occurred between midnight and 0800. In 16 of these women the concentration of LH, FSH and progesterone was measured every 8 hours around the pre-ovulatory surge of LH. A progressive increase in progesterone started with the onset of the LH surge, with a transient fall after 32-40 h at a time coincident with that of ovulation. In 10 women oestradiol, androstenedione and prolactin were measured 8 hourly around the pre-ovulatory surge of LH beginning at 0800 h. Prolactin showed a sustained increase in levels beginning at the start of and lasting for the duration of the pre-ovulatory LH surge; oestradiol levels did not rise around this time, and declined by 24 h after the onset of the LH surge. These results suggest that (1) the pre-ovulatory LH surge begins between midnight and 0800 h in the majority of women, (2) luteinization of the granulosa cells within the pre-ovulatory follicle occurs in response to the LH surge, (3) the increase in prolactin at the time of the LH surge is not directly related to increasing levels of oestradiol but may be due to a decrease in hypothalamic inhibition of prolactin secretion which occurs coincident with the release of LHRH associated with the preovulatory LH surge.

Adult↗

The recovery of pre-ovulatory oocytes using a fixed schedule of ovulation induction and follicle aspiration.

Thirty-two volunteer women, scheduled for laparoscopy, were subjected to a fixed regimen of ovulation induction and ovarian follicle aspiration, following manipulation of the previous menstrual cycle with oral contraceptive pills or norethisterone. This allowed the time of oocyte recovery to be planned several weeks in advance. The recovery rate of mature oocytes (loosely dispersed cumulus) in the patients who had their cycles adjusted with norethisterone was comparable to that in a group of women treated in an embryo-transfer programme who were being individually monitored, although there was evidence from cleavage rates and concentration of sex steroids in follicular fluid that further follicular maturation could have occurred. It is suggested that a modification of this schedule could provide an acceptable recovery rate of pre-ovulatory oocytes for research purposes, and possibly by simplifying the monitoring technique could be applicable to a wider range of patients seeking embryo transfer.

Androgens↗

The use of 16,16-dimethyl-trans delta 2 prostaglandin E1 methyl ester (gemeprost) vaginal pessaries for the termination of pregnancy in the early second trimester. A comparison with extra-amniotic prostaglandin E2.

The use of gemeprost pessaries has been compared in an open randomized trial with the extra-amniotic infusion of prostaglandin E2 (PGE2) for the termination of pregnancy between 12 and 16 weeks gestation. The success rates were 77% and 79% for the pessary and infusion group respectively, and these rates were unaffected by parity. There was no significant difference in the cumulative abortion rate between the two groups, nor were there differences in the induction-abortion interval, nor in the time taken to the onset of pain or bleeding. However, women in the pessary group required significantly less analgesia than those in the infusion group. Side-effects, experienced both during treatment and during the 6 weeks after abortion, were similar in both groups. Gemeprost vaginal pessaries are an effective alternative to the extra-amniotic infusion of PGE2 for the termination of pregnancy in the early second trimester.

Abortion, Induced↗

Induction of ovulation with gonadotrophins--a ten year review.

We describe the outcome of induction of ovulation with gonadotrophins (HMG/HCG) in 46 patients treated over 138 cycles. Ovulation was induced in 88 per cent of cycles and there were 43 conceptions in 33 patients with a cumulative conception rate of 96 per cent. The incidence of multiple pregnancy was 36 per cent of those reaching a gestation of 13 weeks or more and accounted for all the second and third trimester foetal losses. Overall, 61 per cent of the patients have taken home at least one healthy child. Mild symptomatic ovarian hyperstimulation complicated 9.4 per cent of courses and was more frequent among patients with normal pretreatment oestrogen levels. We found continuous biochemical monitoring of follicular growth to be a poor predictor of multiple pregnancy or hyperstimulation. We discuss our local experience with reference to published reports from other centres and in relation to recent advances in management and consider the future role of this therapy.

Chorionic Gonadotropin↗