Notes: The Anmatjira Range and adjacent Reynolds Range, central Australia, comprise early Proterozoic metasediments and othogneisses that were affected by three, and possibly four, temporally distinct metamorphic events, M1–4, and deformation events, D1–4, in the period 1820–1590 Ma. The north-western portion of the range, around Mt Stafford, preserves the effects of ±1820 Ma M1-D1, and shows a spectacular lateral transition from muscovite + quartz-bearing schists to interlayered andalusite-bearing migmatites and two-pyroxene granofelses that reflect extremely low-pressure granulite facies conditions, over a distance of less than 10 km. Orthopyroxene + cordierite + garnet + K-feldspar + quartz-bearing gneisses occur at the highest grade, implying peak conditions of ±750°C and 2.5 ± 0.6 kbar. An anticlockwise P–T path for M1 is inferred from syn- to late-D1 sillimanite overprinting andalusite, petrogenetic grid considerations and quantitative estimates of metamorphic conditions for inferred overprinting assemblages. The effects of M1 have been variably overprinted to the south-east by a c. 1760 Ma M2–D2 event. Much of the central Anmatjira Range, around Ingellina Gap, comprises orthogneiss, deformed during D2, and metapelites that have M1 andalusite and K-feldspar overprinted by M2 sillimanite and muscovite. The south-eastern portion of the range, around Mt Weldon, comprises metasediments and orthogneisses that were completely recrystallized during M2–D2, with metapelitic gneisses characterized by spinel + sillimanite + K-feldspar + quartz-bearing assemblages that suggest peak M2 conditions of 〉750°C and 5.5 ± 1 kbar. Overprinting parageneses in metapelitic gneisses imply that D2 occurred during essentially isobaric cooling. A third granulite facies event, M3, affected rocks in the Reynolds Range, immediately to the south of the Anmatjira Range, at c. 1730 Ma. A possible fourth event, M4, with a minimum age of c. 1590 My affected both Ranges, but resulted in only minor overprinting of M1–3 assemblages. The superimposed effects of M1–4, mapped for the entire Anmatjira–Reynolds Range area, indicate that only minor or no dislocation of the regional geology occurred during any of the metamorphic and accompanying folding, events. Although the immediate cause of each of the metamorphic events involved advection, the ultimate causes were external to the metasediments and most probably external to the crust.

Notes: Objective To investigate the endocrine changes associated with spontaneous miscarriage after fetal heart activity has been demonstrated.Design Prospective study during the first trimester of pregnancy comparing the circulating levels of human chorionic gonadotrophin (hCG), Schwangerschaft protein 1 (SP-1), pregnancy-associated plasma protein A (PAPP-A), oestradiol (E2), and progesterone (P), and fetal growth (crown-rump length [CRL] and gestational sac volume [GSV]) in women who miscarried after the identification of fetal heart activity with those of normal singleton and twin pregnancies achieved following in vitro fertilisation (IVF) and embryo transfer (ET).Setting The Assisted Conception Unit of King's College Hospital, London.Subjects Nine women who miscarried after demonstration of fetal heart activity, 52 normal singleton and 22 normal twin pregnancies.Interventions Weekly blood tests and ultrasound assessments of CRL and GSV.Results Four fetuses (all singleton) died between 9 and 12 weeks gestation (Group 1), and seven (three singleton and two twin) died between 16 and 20 weeks gestation (Group 2). In Group 1, both fetal growth and placental function, as assessed by serial measurements of CRL and GSV, and of serum levels of PAPP-A, SP-1 and hCG respectively, were reduced before fetal death. In Group 2, while fetal growth was maintained in all but one case, placental function was reduced in 4 of 5 women.Conclusion These findings suggest that there may be a relationship between trophoblast dysfunction and some forms of miscarriage. Furthermore, the pattern of the reduction in the circulating levels of the placental proteins in later miscarriages suggests that the function of specific cell types may be impaired.

Notes: Summary. The effects of subcutaneous oestradiol implants on ovarian activity were investigated in 14 ovulating premenopausal women. Treatment with either 100 mg or 150 mg oestradiol was combined with cyclical oral norethisterone from days 20 to 26 of the cycle to ensure regular withdrawal periods and prevent endometrial hyperplasia. Ovarian function was monitored by regular pelvic ultrasonography and urinalysis over a period of nine cycles. During the first three cycles after hormone implantation, follicular development continued in almost half the study group, but only one of the women in each treatment group showed signs of follicular rupture and luteinization. By the sixth cycle, over half the women given the lower dose of oestradiol were developing follicles, including a large functional cyst in one, but none of them ovulated. A further implant given early in the seventh cycle was associated with ovarian suppression in all cases. Both doses of implant elevated the excretion of oestrone-3-glucuronide compared to pretreatment. The contraceptive and therapeutic implications of these results are discussed.

Notes: Summary. Ovarian volumes have been determined by pelvic ultrasonography in 2246 apparently healthy postmenopausal women of whom 2221 were included in the statistical analysis. Factors associated with gonadal size have been identified, and reference ranges for derived indices have been determined for use (in association with criteria for abnormal morphology) in a screening programme for ovarian carcinoma. The right ovary was present in 98·9% of subjects and the left in 99 · 1 %. The mean (SD; range) of right and left ovarian volumes were 3·58 (1·40; 1·00–14.01) and 3·57 (1·37; 0·88–10·9) ml respectively. Significant predictors of ovarian volume were years since the menopause, weight, parity, age at menopause, a history of hormone replacement therapy, and previously diagnosed breast cancer. Abnormal ovarian volumes were assessed from a score equal to the (observed mean log volume (MLV) minus the predicted MLV)/0·327. A simplified nomogram has been prepared for routine clinical use. The relative abnormality of one ovary was assessed from a ratio score equal to loge (larger ovarian volume/smaller ovarian volume)/0·211 compared with the 99th centile for the Gaussian distribution.

Notes: Summary. Real-time ultrasound scanning of ovarian follicles was performed during 61 cycles in 22 infertile patients being treated with sequential injections of human menopausal gonadotrophin (hMG) and human chorionic gonadotrophin (hCG). Total 24-h urinary oestrogens were estimated (and in 13 cycles plasma oestradiol) but the amount of gonadotrophin given was based mainly on the ultrasound findings. A retrospective analysis of the results showed that there was a poor statistical correlation between the diameter of the largest follicle and the total urinary oestrogens (r= 0.39) and with the level of plasma oestradiol (r= 0.56), although similar clinical information was obtained by all methods. Ovulation was induced in 58 cycles when the leading follicle had a mean diameter of 20–25 mm (mean 21.3 mm); follicular rupture was observed in 57 cycles and in these cases there was biochemical evidence of luteinization (plasma progesterone 〉15 nmol/1; total urinary pregnanediol 〉8 μmol/24h). Three patients (three cycles) were not given hCG; one developed micropolycystic ovaries and two showed evidence of hyperstimulation (one follicle 〉25 mm diameter, three or more follicles 20–25 mm diameter). Twelve patients became pregnant, all with single fetuses. Subsequently one aborted, one had an ectopic pregnancy, three gave birth to normal babies at term and seven pregnancies are continuing. Real-time ultrasound scanning of ovarian follicles is a simple, practical method for monitoring follicular growth during the administration of hMG and predicting the response to hCG.

Notes: Intracellular oestrogen metabolism has been investigated in endometrial tissue from postmenopausal women receiving oestrogen therapy either alone or in combination with a progestogen. During oestrogen therapy alone, there was a 3·2 fold predominance of oestradiol over oestrone within the endometrial cell nucleus and the mean nuclear oestrogen receptor content was 1·40 pmol/mg DNA. The addition of norethisterone decreased the nuclear oestradiol/oestrone ratio to 1–4:1 by lowering the oestradiol mass. A concurrent reduction in the mean level of the nuclear oestrogen receptor to 0·58 pmol/mg DNA indicated a decrease in oestro-genic stimulation. The activity of oestradiol-17β dehydrogenase was significantly increased. There was a plasma excess of oestrone over oestradiol during oestrogen therapy alone and the oestrone/oestradiol ratio was not significantly altered following norethisterone administration. The ability of the endometrium to incorporate oestradiol selectively into the nucleus is discussed in relation to the risk of endometrial hyperplasia with unopposed oestrogen therapy. The profound biochemical changes induced by norethisterone help elucidate mechanisms whereby progestogens lower oestrogenic potency and thereby protect the endometrium against excessive stimulation.

Notes: The absorption, metabolism and clearance of oestradiol, oestrone and oestriol from the peripheral circulation were investigated in five postmenopausal women after the oral administration of Hormonin (oestradiol 600 μg, oestrone 1400 μg, oestriol 270 μg) daily for five consecutive days. In addition the concentrations of plasma oestrone-3-sulphate, oestrone-3-glucuronide, LH and FSH were determined in the same plasma samples. The maximum concentrations of each steroid in peripheral plasma and the time intervals during which the peak occurred after ingestion of the last tablet were:—oestrone (750 to 2116 pmol/1, 0·5 to 6·0 hours), oestradiol (246 to 813 pmol/1, 1 to 8 hours), oestriol (173 to 241 pmol/1, 5 to 12 hours), oestrone-3-glucuronide (32·2 to 78·8 nmol/1, 0·5 to 3·0 hours) and oestrone-3-sulphate (21·9 to 39·0 nmol/1, 1 to 7 hours). The mean factorial increases in the concentration of each compound during the first 12 hours post-treatment over the baseline values were:—oestrone (4·1); oestradiol (4·4); oestriol (1·7); oestrone-3-sulphate (2·6) and oestrone-3-glucuronide (8·1). After treatment, the concentration of plasma oestradiol remained significantly higher than the baseline values (p 〈0·025) for 24 hours and the values for each subject were within the normal range for premenopausal women. Moreover, there was a significant reduction (p 〈 0·025) in the level of circulating LH. It is concluded that the simultaneous administration of oestrone, oestradiol and oestriol, by mouth, to postmenopausal women is a good approach to maintaining an appropriate concentration of oestradiol in peripheral plasma.

Notes: The tissue concentrations of prostaglandin E2 (PGE2) were measured by radioimmunoassay in components of the umbilical cord. The levels were significantly higher in the walls of arteries than in non-vascular tissue from the umbilical cord. The highest values were found after emergency Caesarean sections and the lowest after induced labour ending in normal delivery. The use of forceps and the presence of fetal distress were both associated with significantly raised tissue concentrations of PGE2.

Notes: The concentrations of prostaglandins E2 and Fα were measured by radioimmunoassay in samples of endometrial tissue from 155 women. The results showed that the concentration of prostaglandin E2 (ng/100 mg of wet tissue; mean ± SD) in tissue from apparently healthy women with regular menstrual cycles was 79·3 ± 9·9 during the menstrual period. The level in the proliferative and early secretory phases fell to 11·8 ± 4·0 and 13·3± 8·3 respectively. During the late secretory phase there was a significant increase to 20·1±10·8. The corresponding values from patients with fibromyomata and without menorrhagia were similar. However, the concentration in tissue from patients with fibromyomata and menorrhagia was significantly higher (63·9 ±17·9) during the secretory phase of the uterine cycle. In addition, the amount was significantly higher in the groups with dysmenorrhoea (19 ·0 ± 4·5 proliferative; 68 · 0 ± 18 ·15 secretory) and irregular uterinbleeding (78·3 ± 59·0 proliferative; 87·4 ± 64·9 secretory). The mean concentration was higher in cases of endometriosis, and significantly elevated in endometrial carcinoma. The results for prostaglandin Fα showed a similar pattern, but the changes were less marked in patients with irregular dysfunctional bleeding. The findings are discussed.