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Biomedical subjects

K J Thong

Publications and source records attributed to K J Thong.

At least 19 recordsLinked to original sources
PubMed1995

Metabolic regulation of androgen production by human thecal cells in vitro.

The association between hyperinsulinaemia and hyperandrogenism in many women with polycystic ovarian syndrome (PCOS) implies roles for insulin and insulin-like growth factors (IGFs) in the regulation of ovarian androgen production. The aim of the present study was to compare the abilities of insulin, IGF-I and IGF-II to stimulate androgen production by human thecal cells in vitro. Serum-free monolayer cell cultures were established from the ovaries of euandrogenic women undergoing hysterectomy with oophorectomy for non-ovarian indications. Androgen (androstenedione) production was determined after 4 days of culture in the presence of insulin or either of the IGFs (10-100 ng/ml), with and without a maximal stimulatory dose of luteinizing hormone (LH; 10 ng/ml). Interactions with inhibin (30 ng/ml), a putative paracrine regulator of ovarian androgen synthesis, were also tested. The three metabolic hormones exerted similar dose-related effects on androgen production (ED50 < or = 10 ng/ml), which were augmented 2- to 3-fold in the presence of LH and further increased several-fold by the additional presence of inhibin. No treatment with insulin or either IGF stimulated thecal cell growth, but all treatments caused striking morphological changes consistent with enhanced steroidogenesis. These results reveal potent regulatory effects of metabolic hormones on human thecal androgen synthesis, which imply (i) 'progonadotrophic' roles for insulin and IGF-I in regulating normal ovarian androgen production, (ii) a role for insulin in the aetiology of hyperandrogenism (both with and without hyperinsulinism) in PCOS and (iii) paracrine roles for granulosa-derived IGF-II and inhibin in regulating ovarian androgen production.

Adult↗
PubMed1995

Randomized trial of misoprostol and cervagem in combination with a reduced dose of mifepristone for induction of abortion.

Mifepristone (600 mg) in combination with a prostaglandin has been demonstrated to be a safe, acceptable alternative to vacuum aspiration for induction of abortion in the first 9 weeks of pregnancy. However, the efficacy and side-effects of different prostaglandins used in combination with mifepristone have not been assessed in a randomized trial. In this study, 800 women seeking an abortion at gestational age < or = 63 days amenorrhoea were randomized to receive either 0.5 mg gemeprost by vaginal pessary (group I) or 600 micrograms misoprostol (group II) by mouth approximately 48 h after taking 200 mg mifepristone by mouth. The side-effects and number of complete abortions were used as measures of efficacy. There was no significant difference in the rate of complete abortion between group I [96.7%; 95% confidence interval (CI) 94.9-98.5%, n = 391] and group II (94.6%; 95% CI 92.3-96.9, n = 386). It was not possible to assess the outcome with certainty in the remaining 23 women. However, there were significantly more ongoing pregnancies in the women who received misoprostol than in those who received gemeprost (nine versus one, P < 0.01) and in eight of these 10 women the gestation was > 49 days. Fewer women in group II required analgesia than in group I (48 versus 60%, P < 0.001) although the number requesting opiate was similar in each group (6.9 versus 5.2%, P > 0.4). The incidence of nausea and vomiting after misoprostol (47.8 and 21.9% respectively) was higher (P < 0.001) than after gemeprost (33.9 and 12% respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Abortifacient Agents, Nonsteroidal↗
PubMed1995

Failure of oestrogen induced luteinizing hormone surge in women treated with mifepristone (RU 486) every day for 30 days.

It has been demonstrated previously that administration of the antiprogestin mifepristone (RU 486; 1-5 mg daily) inhibits or delays both the pre-ovulatory luteinizing hormone (LH) surge and ovulation. To investigate this mechanism, dynamic tests of pituitary ovarian function were performed in six healthy women before and during the administration of mifepristone (2 mg daily for 30 days). On day 9 of the control and treatment cycles, samples of blood were collected every 15 min over 12 h for measurement of LH concentration. After 10 h, the responsiveness of the pituitary was tested by the i.v. injection of 10 micrograms of gonadotrophin-releasing hormone (GnRH). On day 10 of the control and treatment cycles, two patches releasing 200 micrograms/day of oestradiol were applied to skin on the abdomen for 3 days. Blood was collected at 24, 48, 59, 72, 81 and 96 h after application of the oestrogen patches for the measurement of gonadotrophin and ovarian hormone concentrations. Follicular development continued in all women during their treatment with mifepristone, and ovulation was suppressed (four women) or delayed (two women). There was no significant difference in the basal concentration of LH between the control and treatment cycles (mean +/- SE; 5.5 +/- 0.4 versus 7.7 +/- 0.4 IU/l respectively), or in the frequency (interpulse interval, 101 +/- 12 versus 105 +/- 13 min respectively) and the amplitude (2.1 +/- 0.4 versus 2.6 +/- 0.4 IU/l respectively) of LH pulses. The response to GnRH was similar. On day 10, the basal concentrations of LH, follicle-stimulating hormone (FSH), prolactin, oestradiol and progesterone and the diameter of the dominant follicle (15.7 +/- 1.8 versus 13.3 +/- 1.9 mm) were similar during control and treatment cycles. In control cycles, there were significant increases in the concentrations of LH and FSH within 72 h of application of the oestrogen patches. During treatment cycles, concentrations of FSH and LH remained low, and were significantly lower than the values observed during control cycles (P < 0.006). We conclude that the antiprogestin mifepristone disrupts ovulation by inhibiting the positive feedback effect of oestrogens and, hence, prevents or delays the generation of a pre-ovulatory LH surge.

Administration, Cutaneous↗
PubMed1995

Effect of daily low dose mifepristone on the ovarian cycle and on dynamics of follicle growth.

BACKGROUND AND OBJECTIVE: The antiprogestin mifepristone has been shown to disrupt folliculogenesis and endometrial maturation and, therefore, has the potential to be used as a novel form of contraception. The purpose of this study was to investigate further the effects of daily administration of a low dose of mifepristone (2mg) on the ovarian cycle and on the dynamics of follicle growth. SUBJECTS: Six healthy female volunteers were given 2mg mifepristone daily for 30 days following an ovulatory control cycle. MEASUREMENTS: Follicle growth was monitored with transvaginal ultrasonography and hormonal measurements in blood and urine were used to monitor effects on the ovarian cycle. In addition, concentrations of cortisol and ACTH in serum were measured to assess the effects of mifepristone on the pituitary-adrenal axis. RESULTS: Treatment with mifepristone retarded the follicular growth rate in all women (P = 0.01). Ovulation was inhibited in 4 of 6 subjects and appeared to be mediated through an effect on the hypothalamo-pituitary axis, as no surge of FSH or LH occurred. In these subjects the dominant follicle continued to grow and developed into a persistent follicle. In two cases the persistent follicle remained functional and ovulation occurred soon after stopping treatment. In the remaining two subjects, the dominant follicle developed into a non-functioning cyst ( > 30 mm) which persisted for one month after the end of the post-treatment cycle. In the two subjects who ovulated, the LH surge was delayed by 6 and 7 days but was followed by a luteal phase of normal length. There was no significant change in the concentration of ACTH or cortisol suggesting that treatment with mifepristone in this dose has little if any effect on the pituitary-adrenal axis. CONCLUSION: These findings add further evidence to support the contraceptive potential of mifepristone through effects on follicular development and on the menstrual cycle.

Adrenocorticotropic Hormone↗
PubMed1994

Decrease in human plasma gravidin levels after medical abortion.

The aim of this study was to determine if loss of pregnancy is associated with a decrease in plasma levels of gravidin, a phospholipase inhibitor thought to maintain pregnancy. Blood was taken from 28 women in the first trimester of pregnancy who had requested an abortion. The progesterone receptor antagonist, RU-486 was given on Day 0 for termination of pregnancy. Plasma gravidin levels were measured on day 0 and on day 2 just before the patients were given misoprostol, a prostaglandin E1 analogue (600 micrograms). In a small group of patients, plasma measurements were continued up to 42 days. By day 2, plasma gravidin levels had fallen significantly (100% to 94%, p = 0.010 in a paired t-test). Following treatment with prostaglandins and pregnancy loss, plasma gravidin levels continued to fall until day 14 when the non pregnant level was reached at 80% of the pregnant level. We conclude that a decrease in plasma gravidin levels is associated with loss of pregnancy. This may occur because progesterone action is blocked.

Abortion, Induced↗
PubMed1994

Lymphocyte subpopulations in early human pregnancy.

OBJECTIVE: To examine changes in lymphocyte subpopulations in early pregnancy using a methodologically appropriate study design that addresses previous sources of bias. METHODS: Thirty-seven healthy women without risk factors for human immunodeficiency virus (HIV) were reviewed when less than 9 weeks pregnant (median 51 days, range 44-61) and again at least 4 weeks following termination of pregnancy. No woman took the oral contraceptive pill. Blood was taken on each occasion at the same time of day under the same conditions of rest and food intake, transported immediately to the laboratory, and directly prepared for analysis. Lymphocyte surface markers were determined by staining with dual-colored, isotype-matched monoclonal antibody fluorescent conjugates, followed by whole blood lysis and subsequent flow cytometric analysis. RESULTS: Pregnancy was associated with a significant reduction in total lymphocytes (P < .0001) and also in CD4+ cells, whether expressed as a percentage of lymphocytes (P = .004), an absolute count (P = .0006), or a ratio (P = .01). Change was independent of the basal level except for lymphocytes, and almost all indices had significant correlations between pregnant and nonpregnant values. CONCLUSIONS: In this study design, each woman served as her own control and all factors remained constant except the pregnancy state. Early pregnancy causes a reduction in total lymphocytes of about 6% expressed as a percentage of total white cell count, and in CD4+ cells by 3% as a percentage of lymphocytes, or 100/mm3. We believe this fall can be accepted as definitive.

Adolescent↗
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

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↗
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↗
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↗