Biomedical subjects
Publications and source records attributed to R P Shearman.
The technique of transcervical chorion biopsy was evaluated in women about to undergo therapeutic termination of pregnancy. The trophoblast biopsy catheter (Portex) under real-time ultrasound guidance was the most reliable in obtaining chorionic villi. The overall success rate for chorion biopsy was 73% in the first 100 patients studied.
Sixty-eight women with pituitary tumours exhibiting gynaecological symptoms have been reviewed. Fifty-two tumours were prolactinomas while 6 were growth hormone secreting, 6 ACTH secreting, 1 was a large 'inert' adenoma and 3 were late-presenting craniopharyngiomas. Several of the prolactinomas exhibited unusual features including excessively high prolactin secretion, a wide spectrum of sensitivity to bromocriptine, rapid expansion in pregnancy, association with the empty sella syndrome and even a secondary malignancy. The behaviour of tumours secreting other hormones but presenting with gynaecological symptoms is described.
Detailed studies of a family with hyperinsulinemia are reported. The index patient, a 30-yr-old woman with polycystic ovary syndrome, presented with gestational diabetes which was completely resistant to insulin in the presence of severe endogenous hyperinsulinemia. Sensitivity to insulin was regained after delivery. Therapy with cyproterone acetate and ethinyl estradiol for hirsutism exacerbated the hyperinsulinemia toward the levels occurring in pregnancy, with a concomitant deterioration of glucose tolerance. Five other members of her family also were found to have hyperinsulinemia together with high concentrations of circulating C-peptide. Antibodies to insulin and to insulin receptors were not detected, insulin antagonists were not increased, and insulin degradation in the circulation was normal. Insulin extracted from the patient's serum was identical to normal insulin by the criteria of Sephadex chromatography, placental membrane insulin receptor binding, and stimulation of 2-deoxyglucose uptake in isolated rat adipocytes. Although [125I]insulin binding to erythrocytes of all family members and to the patient's placental membranes was markedly reduced, binding to fibroblast cultures from the patient was normal. Insulin-stimulated glucose transport in these fibroblasts also was normal, but there was a mild (20%) reduction in the concentration of cytochalasin B-binding sites in erythrocyte ghosts. Insulin resistance in this family may be due to a partial defect distal to the insulin receptor. This is asymptomatic unless metabolic stresses (pregnancy or steroid administration) are superimposed.
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Two hundred and thirty two women with diabetes complicating pregnancy were seen at a metropolitan teaching hospital during a 4-year period. Management during pregnancy in insulin dependent diabetics was directed towards strict metabolic control using conventional insulin regimens and diet. A similar programme was followed for women in whom screening revealed glucose intolerance. Control of maternal blood glucose levels, assessment of fetal maturity and modes of delivery were reviewed in an attempt to define factors which could predict optimal neonatal outcome. Patients with insulin dependent diabetes were less likely to have optimal metabolic control both during pregnancy and parturition than patients with gestational diabetes. Women with gestational, but not preexisting diabetes, demonstrated a close correlation between gestational age and parameters of fetal pulmonary maturity. A high rate of intervention to deliver infants in both groups (50%) was noted. These data indicate the need for meticulous care of women with insulin dependent diabetes during pregnancy.
Saline or triiodothyronine (T3) (50-1000 micrograms) was injected into the amniotic sac of 17 pregnant ewes under general anesthesia at 130 days gestation. Forty-eight h later, the lambs were delivered by hysterotomy. Cord plasma T3 and cortisol and amniotic fluid T3 were assayed, and the maturity of the fetal lung was assessed in terms of its pressure-volume response and its surfactant (lamellar body phospholipid) content. With the highest dose of T3, cord plasma T3 and cortisol were raised, and lung maturity was enhanced compared with saline-treated controls; the pressure-volume curve showed increased hysteresis on inflation and deflation, and the lung retained air on return to zero pressure. There was also an apparent, but not statistically significant, increase in the lamellar body phospholipid content of the lung. Irrespective of treatment, lungs which were more mature, in terms of their pressure-volume characteristics, tended to contain a higher proportion of lamellar body phospholipid relative to total phospholipid.
The outcome of pregnancy was reviewed in 232 women with diabetes (Group 1 = 72 Insulin Dependent Diabetes; Group 2 = 9 Non Insulin Dependent Diabetes and 151 Gestational Diabetes) seen at a major metropolitan teaching hospital in the 4 yr period 1978-1981 inclusive. The perinatal mortality was 5.6% and there was a high rate of congenital malformations (5.6% major, 7.7% minor) with no difference in incidence between the 2 groups. Infants of women whose pregnancies extended beyond 37 weeks of gestation had a reduced incidence and severity of respiratory distress syndrome. Measurement of amniotic fluid lamellar body phospholipid proved accurate in predicting this complication. Neonatal hypoglycaemia correlated with poor maternal blood glucose control in the third trimester and during parturition.
Forty-two women with hirsutism completed 12 months of treatment with cyproterone acetate and ethinyl oestradiol given in a reverse sequential regimen. A highly significant improvement was recorded in the whole group using the Ferriman and Gallwey scoring system. Ten patients recorded a poor response whereas 19 recorded a good or very good result. Patients from groups with polycystic ovarian disease and idiopathic hirsutism recorded equally beneficial responses. Fasting plasma triglycerides rose significantly after 12 months. Other lipids were largely unaffected although a small fall in high density lipoprotein-cholesterol was detected at mid-cycle. No other biochemical abnormalities were found. Circulating levels of testosterone and 17 hydroxyprogesterone were suppressed during treatment. Side-effects were not prominent. This appears to be a very useful medication for a clinical problem which hitherto has been difficult to treat.
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During the 5-year period 1977-1982, 57 patients below 35 years of age with secondary amenorrhea were assessed for hypergonadotropic (primary) ovarian failure. The histological findings within the ovaries as well as pertinent clinical and laboratory correlates are described. Nineteen had diagnostic ovarian biopsies performed. The importance of this technique is stressed. The ovaries of 14 patients showed absence of primordial follicles (true premature menopause); three others showed "resistant ovary syndrome" characterized by the presence of primordial follicles but little or no follicular development (including a case of galactosemia, in which the associated ovarian failure has been ascribed to follicular atresia). The remaining two revealed florid chronic perifollicular inflammatory reactions in the presence of both primordial and also developing follicles--one lymphoplasmacytic and the other granulomatous. The former has been previously suggested as evidence of an autoimmune process, but the latter has not hitherto been reported.
The overwhelming majority of girls presenting with primary amenorrhoea have aetiologies with their roots in disturbances of embryogenesis and/or the endocrinology of sexual differentiation. This review will deal with the fundamentals of embryology and endocrinology relevant to the subject and then discuss the findings in a group of one hundred and forty patients with primary amenorrhoea as they relate to these disturbances.
In the 1960s and 1970s a substantial body of data was published indicating an excess death rate, mainly related to a cluster of cardiovascular complications, in women who either were taking or had ever taken oral contraceptives. The epidemiological interpretation of these data has been seriously questioned, and many workers now think that the excess deaths in these women are almost entirely attributable to smoking. In addition, it is clear that the death rate from myocardial infarction in women in Australia, which has declined significantly in the last twelve years, is quite different from that seen in women in the United Kingdom, where the death rate from myocardial infarction continues to increases. The validity of basing warnings, contraindications and advice to patients regarding the use of oral contraceptives on data from different populations should be reconsidered.
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The pharmacokinetics of a dose of 50 microgram ethynyloestradiol administered orally was studied in fourteen centres. Absorption was rapid and the highest serum concentrations of total ethynyloestradiol were found in most subjects at 1 h and by 24 h concentrations were less than 250 pg/ml. Calculation of the half-lives for absorption, distribution and elimination showed wide variations between subjects, the half-life of elimination varying from 2.5 h to more than 30 h. Bioavailability as measured by the area under the serum ethynyloestradiol concentration-time curve also showed more than a ten-fold variation. Intra-centre differences in the various parameters measured were as large as the inter-centre differences.
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Sixty-nine patients with a convincing history of menorrhagia completed a 4-cycle double-blind randomized placebo-controlled crossover trial of mefenamic acid taken during menstruation. Only 30 of these patients demonstrated objective menorrhagia with a measured menstrual loss greater than 80 ml during the placebo cycles, but the remainder reported passing clots and/or using 2 pads at a time. Fourteen of these women (20%) had a loss of less than 35 ml while taking placebos. This raises serious questions about the establishment of menorrhagia based on history alone. Overall, there was a mean reduction of 28.1% in menstrual blood loss between placebo and mefenamic acid cycles (P less than .001). The greatest reduction recorded was 80%, and most of the large percentage reductions were seen in patients with high loss during placebo cycles. Significant reductions in blood loss (P less than .001) were seen in patients with ovulatory dysfunctional uterine bleeding and menorrhagia that developed after tubal interruption. There was also an indication based on small sample sizes that mefenamic acid reduced blood loss in women with anovulatory dysfunctional uterine bleeding, fibroids, intrauterine devices, and von Willebrand disease. No reduction was seen during the mefenamic acid cycle in the group with a loss of less than 35 ml during the placebo cycle. There was a significant shortening of duration of bleeding (P less than .003). Fifteen patients (21.7%) experienced no objective reduction in blood loss.
Peripheral plasma concentrations of 13, 14-dihydro-15-keto prostaglandin F2 alpha (PGFM) were measured in seven women having elective cervical encerclage in an otherwise normal pregnancy. Three of seven patients had a statistically significant elevation of PGFM levels at 60 minutes after commencement of surgery. On the basis that the majority of patients had no significant rise and that there was no objective evidence of uterine contractions post-operatively, the routine administration of prostaglandin inhibitory agents to patients having cervical encerclage cannot be recommended.