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Biomedical subjects

I Z MacKenzie

Publications and source records attributed to I Z MacKenzie.

At least 73 records · Page 4Linked to original sources
PubMed1991

Severe limb abnormalities after chorion villus sampling at 56-66 days' gestation.

Among 289 pregnancies in which chorion villus sampling (CVS) was carried out at 56-66 days' gestation, 5 babies with severe limb abnormalities were subsequently identified. 4 had oromandibular-limb hypogenesis syndromes, and the other had a terminal transverse limb reduction defect. This high incidence raises the possibility that CVS was an aetiological factor for these developmental anomalies.

Abnormalities, Multiple↗
PubMed1991

Mid-trimester termination of pregnancy with 16,16-dimethyl-trans-delta 2 PGE1 vaginal pessaries: a comparison with intra- and extra-amniotic prostaglandin E2 administration.

PGE1 analogue (gemeprost) vaginal pessaries administered three hourly for three doses has been compared with a single extra- or intra-amniotic injection of PGE2 for mid-trimester termination of pregnancy in 450 women between 13 and 20 weeks gestation. The mean (SD) induction-abortion interval (IAI) in the vaginal pessary group of 19.5 (8.4) h was significantly longer than the respective intervals of 14.4 (9.3) and 16.1 (6.8) h in the patients treated extra- or intra-amniotically (P less than 0.001). Seventy-three percent treated with gemeprost aborted within 24 h of initial treatment compared with 84% and 87%, respectively in the extra- and intra-amniotic groups (P less than 0.05). Patients treated with gemeprost were more likely to need further prostaglandin treatment and had an increased incidence of gastrointestinal side effects. Despite these differences vaginal gemeprost pessaries provide a safe, effective, easy to administer method for midtrimester termination of pregnancy.

Abortifacient Agents, Nonsteroidal↗
PubMed1991

Prostaglandin metabolite levels during cervical ripening with a controlled-release hydrogel polymer prostaglandin E2 pessary.

Prostaglandin E and F metabolite (PGEM and PGFM) concentrations in peripheral plasma were assayed following the vaginal administration of a controlled release hydrogel polymer pessary designed to release 0.6 mg PGE2 per hour in vivo. A linear relationship between calculated PGE2 release from the pessary and PGEM levels was observed with a correlation coefficient of 0.78. A significant rise in PGEM levels occurred two hours following pessary administration, with significantly higher PGEM levels in patients delivering within the eight hour observation period compared with those delivering later. PGFM levels increased more slowly. The results suggest that PGE2 released by the pessary crosses the vaginal epithelium and may stimulate endogenous prostaglandin production. The controlled rise of metabolites in association with the polymer pessary suggest that it should provide greater control in labour induction than other vehicles we have studied, but this should be confirmed by clinical trials.

Administration, Intravaginal↗
PubMed1991

Transplacental passage of mifepristone and its influence on maternal and fetal steroid concentrations in the second trimester of pregnancy.

The maternal and fetal endocrine effects of the maternal administration of the anti-progestin mifepristone in mid-pregnancy have been investigated. Mifepristone and the metabolite RU 42,633 were detected in the fetal circulation and in the amniotic fluid 4, 24 and 48 h after oral ingestion. Maximum fetal plasma concentrations of mifepristone occurred 4 h after treatment indicating rapid placental transfer of the drug. No significant changes in progesterone, cortisol, oestradiol or aldosterone concentrations were detected in the maternal circulation after mifepristone treatment. No significant changes occurred in the fetal progesterone, oestradiol or cortisol concentrations, but a significant increase in fetal aldosterone occurred 4 and 24 h after treatment. The significance of these results is discussed in relation to the possible therapeutic uses of mifepristone for inducing labour.

Abortion, Induced↗
PubMed1991

The steroid hormonal milieu of the undisturbed human fetus and mother at 16-20 weeks gestation.

The interrelations of steroid hormone levels in plasma and amniotic fluid from mothers and their undisturbed fetuses at early midgestation of human pregnancy have not been defined previously. We, therefore, studied 12 healthy mothers and their fetuses undergoing termination of pregnancy for social reasons at 16-20 weeks gestation. Fetal arterial and venous blood was obtained by direct vessel puncture through a fetoscope in the conscious sedated mothers immediately before termination of pregnancy. Simultaneously, maternal peripheral venous blood and amniotic fluid were collected. Aldosterone (Aldo), corticosterone (B), 11-deoxycorticosterone, progesterone (P), 17-hydroxyprogesterone (17OHP), 11-deoxycortisol, cortisol (F), and cortisone were simultaneously determined by specific RIA after extraction and chromatography. Positive fetal arterio-venous differences were found for F, B, and Aldo, whereas arteriovenous differences were negative for P and 17OHP. In amniotic fluid, six of the eight corticosteroids showed significantly lower levels during fetoscopy than during routine amniocentesis, as reported previously using the same analytical methods. The present study demonstrates that the undisturbed human fetus at 16-20 weeks gestation actively secretes the most important gluco- and mineralocorticoids, F, B, and Aldo, independent of the mother. P and 17OHP were shown to be primarily derived from placental production and supplied to the fetus as a source of F and Aldo biosynthesis. The fetoscopy procedure with premedication seemed to give rise to less stress to the fetus than routine amniocentesis without sedation. Fetoscopy is, therefore, an ideal method to study feto-maternal steroid interrelations in human pregnancy.

17-alpha-Hydroxyprogesterone↗
PubMed1990

The efficacy of oral Mifepristone (RU 38,486) with a prostaglandin E1 analog vaginal pessary for the termination of early pregnancy: complications and patient acceptability.

Outpatient terminations were performed on 100 ultrasonographically confirmed pregnancies of less than or equal to 63 days with a single oral dose of RU 38,486 (600 mg) and a single vaginal pessary of 16,16-dimethyl-trans-delta 2-prostaglandin E1 (1 mg) 48 hours later. Abortion occurred in all patients; in 95 it was complete, in four it was incomplete, and one resulted in a missed abortion. In 88% the abortion occurred within 4 hours of prostaglandin treatment. A total of 25% of patients had nausea and 15% vomited after RU 38,486 treatment. After prostaglandin-treatment, 13% vomited, 10% had diarrhea, and 23% required administration of an opiate analgesic agent. No patient was transfused and there was no genital tract trauma; one case of suspected pelvic infection occurred. If the need for termination arose again, 88% would elect to use the method again, 9% would not. The combination of the antiprogestin RU 38,486 and a vaginal prostaglandin pessary appears to offer a safe, efficient, acceptable nonsurgical outpatient method of termination. Further studies on dosage and treatment protocols would be justified.

Abortifacient Agents↗
PubMed1990

Early termination of pregnancy: medical induction with prostaglandins versus surgical aspiration under local anesthetic.

Termination of pregnancy at 4-8 weeks gestation in 1085 patients using either local prostaglandin instillation (n = 820) or uterine aspiration under local anesthetic (n = 265) have been analyzed. Morbidity for both methods was similar although the incidence of side-effects (0.4%) and the transfusion rate (0%) were lower after aspiration than the respective rates of 59% and 1.3% after prostaglandin treatment. However the rates of genital tract trauma (0.75%) and uterine sepsis (1.8%) after aspiration were higher than the respective rates of 0.3% and 0.9% after prostaglandin treatment. The major disadvantage of prostaglandin treatment was the rate of re-admission for evacuation (8.5%) compared with (0.9%) after aspiration, although patient acceptability for both techniques was similar. In view of the advantages, more widespread use of both methods of termination is indicated.

Abortion, Induced↗
PubMed1990

The concurrent in vitro and in vivo release of PGE2 from a controlled-release hydrogel polymer pessary for cervical ripening.

Twenty five patients booked for induction of labour, at 38 weeks or more gestation, were administered a controlled release vaginal polymer pessary containing 10 mg prostaglandin E2 (PGE2), designed to release 0.6 mg per hour in vivo. The release profile from the polymer was linear throughout the eight hour observation period with a correlation coefficient of 0.81, and regression slope of 0.93 mg/hr. with 95% confidence intervals of 0.63 mg/hr. to 1.23 mg/hr. This compared with a concomitant release profile in vitro which was uniform with time for the first five hours, but then continued at a decreasing rate with a correlation coefficient of 0.98. The relationship between PGE2 release and cervical score change was linear, with a correlation coefficient of 0.65. The results show that PGE2 release from the pessary in vivo is predictable, and suggest that the controlled release pessary offers the advantages of greater control of cervical ripening than alternative vehicles currently available.

Cervix Uteri↗
PubMed1990

The effect of RU 38,486 on progesterone and oestrogen receptor concentrations in the decidua and placenta in early pregnancy.

Decidual and placental concentrations of progesterone and oestrogen receptors in 15 women having medical terminations of pregnancy with a combination of the anti-progesterone steroid RU 38,486 and prostaglandin E1 analogue have been compared with 10 matched controls undergoing surgical aspiration of pregnancy. In the patients treated with RU 38,486, the mean (SD) decidual cytosolic and total progesterone receptor concentrations of 4.3 (5.6) and 7.6 (7.1) fmol/microgram DNA respectively were significantly lower than the levels of 18.5 (14.4) and 22.3 (17.4) fmol/microgram DNA in the control patients. Progesterone receptor concentrations in the placenta were very low in both groups. No significant change in oestrogen receptor concentrations occurred in the decidua or placenta after treatment with RU 38,486. These data indicate that there may be down-regulation of decidual progesterone receptor concentrations following RU 38,486 treatment.

Adult↗
PubMed1990

The placental transfer of mifepristone (RU 486) during the second trimester and its influence upon maternal and fetal steroid concentrations.

A double-blind, placebo-controlled study has assessed the maternal and fetal endocrine effects of the maternal administration of the anti-progestin mifepristone in mid-pregnancy. There were six women in each group. Four hours after oral administration of 600 mg mifepristone, the drug was detected in both maternal and fetal circulations and in the amniotic fluid. No significant changes in progesterone, cortisol, oestradiol, or aldosterone concentrations were detected in the maternal circulation after treatment with mifepristone or placebo. In women treated with mifepristone, the mean fetal aldosterone level was 1699 (SD 217) pmol/l which was significantly higher than the mean level of 999 (SD 84) pmol/l in the control group but no significant changes occurred in the fetal progesterone, oestradiol or cortisol concentrations. The significance of these results is discussed in relation to the possible therapeutic uses of mifepristone for inducing labour.

Aldosterone↗
PubMed1990

Prostaglandin induced cervical ripening under tocolytic cover in primiparae: results of a double blind placebo controlled trial.

In a double blind trial, 60 nulliparae with a modified Bishop score of less than or equal to 5 requiring induction of labour, received either 8 mg of salbutamol or an identical placebo orally, 30 min before vaginal administration of 2 mg prostaglandin E2 gel. Women in the salbutamol group experienced less uterine activity over the subsequent 12 h compared with those given placebo, and fewer (35%) commenced labour compared with the placebo group (62%). However, the change in cervical score was significantly less in the salbutamol group (mean 3.0, SD 3.1) than that in the placebo group (mean 5.8, SD 3.2), and the prostaglandin treatment to delivery time in the salbutamol group (mean 26.1 h, SD 6.49) was significantly longer than that in the placebo group (mean 19.3 h, SD 7.95). The first stage of labour lasted greater than 10 h in 11 women in the salbutamol group compared with five in the placebo group. Side effects attributable to salbutamol occurred in 10% of the treated women but in none of their fetuses and fetal outcome was satisfactory and similar in both groups. Our findings show that salbutamol can suppress prostaglandin-induced uterine activity during cervical ripening, which could be an advantage in induction of labour where a planned delivery is preferred. However, the poorer outcome of labour in salbutamol-treated women mitigates against this approach.

Administration, Intravaginal↗
PubMed1990

The effect of the anti-progestin mifepristone (RU 486) on plasma prostaglandin metabolite levels in early pregnancy and its influence on pregnancy termination.

The effect of a single dose of RU 486 (600mg) on prostaglandin metabolite levels has been studied over a 48 h period in 20 women undergoing medical termination of early pregnancy. The results were compared with controls of similar gestation who were treated surgically. The mean (SD) PGEM levels at 0 and 48 h in the RU 486 group were 13.7 (2.7) and 13.2 (2.2) pg/ml respectively, which was not significantly different from the values of 11.7 (1.1) and 11.3 (0.4) pg/ml measured in the control patients. Similarly the mean (SD) PGFM values of 22.3 (14.7) and 17.0 (7.2) pg/ml at 0 and 48 h were not significantly different from the corresponding control values of 21.9 (13.8) and 23.8 (7.2) pg/ml. In 10 of the study patients, there were no significant changes in PGEM and PGFM concentrations prior to and at 4, 24 and 48 h after RU 486 administration. Although all pregnancies were successfully terminated with the combination of RU 486 and subsequently a vaginal pessary containing PGE1, no stimulation of prostaglandin production could be demonstrated.

Abortion, Induced↗
PubMed1989

Transfer of prostaglandins to the fetus after prostaglandin E2 vaginal pessary administration.

The kinetics of prostaglandins instilled vaginally has been studied in the maternal and fetal circulations, with observation of changes in the stable prostaglandin E2 metabolite 11-deoxy-13,14-dihydro-15-keto-11 beta,16-cyclo-prostaglandin E2. After the administration of prostaglandin E2, 10 mg in a wax-based pessary, concentrations of prostaglandin E2 metabolite in the maternal circulation increased; concentrations in the fetal circulation were higher than those in control subjects. There was a positive correlation between levels found in the fetal and maternal circulations. The implications of these preliminary findings are discussed in relation to the consequences of the use of vaginally administered prostaglandin E2 for cervical ripening and labor induction.

Abortion, Induced↗
PubMed1989

Tocolysis during cervical ripening with vaginal PGE2.

Forty-two primigravidae with unripe cervices (modified Bishop score less than or equal to 5) were pretreated with 8 mg of oral salbutamol 30 min before vaginal administration of 5 mg of PGE2. The proportion of patients in established labour after treatment (19%) was markedly less than results reported previously and cervical improvement occurred in 86% of the non-labouring patients. The improved outcome of labour associated with the prior administration of PGE2 when the cervix is unripe, including reduced induction-to-delivery intervals and higher rates of vaginal delivery was maintained. Apart from some minor side-effects, there were no adverse effects noted as a direct consequence of the tocolytic; blood loss was not increased, although one patient suffered an intrapartum abruption. This approach allows a greater control of induced uterine activity and timing of delivery which may be of particular importance in women with suspected placental insufficiency.

Administration, Intravaginal↗
PubMed1989

Discrepancy between curettage and hysterectomy histology in patients with stage 1 uterine malignancy.

Histology reports of endometrial curettage and hysterectomy specimens were compared in patients with stage 1 uterine malignancy. In 63 of 117 (54%) the tumour grade or type reported in the curettage specimen differed from that described in the hysterectomy specimen; the grading was as likely to be more as less well differentiated at hysterectomy. The differences were not related to endometrial sampling technique or pre-operative intracavity radiotherapy. The results suggest that if decisions about patient management continue to be based on histological grading of tumours in endometrial curettage samples, unnecessary morbidity will be caused to some patients and inadequate treatment will be given to others.

Adenocarcinoma↗
PubMed1989

2308 second trimester terminations using extra-amniotic or intra-amniotic prostaglandin E2: an analysis of efficacy and complications.

A total of 2308 mid-trimester terminations using PGE2 extra-amniotically (1608) or intra-amniotically (700) has been analysed for efficacy and immediate and early morbidity. The mean induction-to-abortion intervals were similar for the two routes. Overall, 67% of the patients were in hospital for 1 night. Morbidity rates were similar for the two administration routes and were no higher than those reported for second trimester terminations using dilatation and evacuation. Minor side-effects of vomiting occurred in 1006 (44%) and diarrhoea in 320 (14%). Forty (1.7%) lost more than 500 ml of blood during termination and 13 (0.6%) were transfused. Major complications were extremely rare and genital tract trauma only occurred in 4 (0.17%) and proven pelvic infection in 2 (0.08%) patients. Thirty-three (1.4%) were readmitted and required a surgical evacuation of the uterus. Since long-term complications have been assessed for this method of termination and found to be infrequent, we see no reason to consider a change in methods for second trimester terminations.

Abortion, Induced↗
PubMed1988

A prospective self-controlled study of fertility after second-trimester prostaglandin-induced abortion.

One hundred forty women whose pregnancies were terminated in the second trimester with prostaglandins because of suspected fetal disease have been prospectively followed to assess their subsequent fertility. In six instances difficulties had been experienced in conceiving the pregnancy that was terminated. Since abortion 104 women have conceived, 97% within 24 months of abortion but in five instances after some delay. Only one woman had not succeeded in conceiving a wished-for pregnancy. There were no apparent differences in abortion management between those women readily conceiving and those in whom there was some delay, although termination because of chromosomal reasons or anatomic abnormalities was less commonly followed by another pregnancy as compared with those terminated for rubella or other viral infections. Reduced fertility after a late prostaglandin-induced abortion thus appears to be very infrequent.

Abortion, Induced↗