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Biomedical subjects

W M Hague

Publications and source records attributed to W M Hague.

At least 19 recordsLinked to original sources

Pulmonary alveolar proteinosis: two contrasting cases.

Pulmonary alveolar proteinosis is a rare condition characterized by the abnormal accumulation of surfactant-like material within the alveolar spaces and distal bronchioles. Two cases with contrasting modes of presentation, course, and response to therapeutic whole lung lavage are described. Both cases were in hypoxaemic respiratory failure at the time the definitive diagnosis was made, and in both cases the diagnosis was made by segmental bronchoalveolar lavage following negative open lung biopsy. In neither was an underlying causative organism or agent identified. In one case the alveolar proteinosis developed in late pregnancy, a presentation that is previously unreported. Clinical improvement in this case required repeated whole lung lavages and was accompanied by a trend towards normalization of the ratios of surfactant protein-A and surfactant protein-B to disaturated phospholipid, ratios which may be useful as prognostic indicators. The response to therapeutic lavage was markedly different in the two cases, and it is postulated that this may relate to the fact that alveolar proteinosis is a heterogeneous disease and that the course and response to treatment may relate in part to the specific composition of the abnormal proteinaceous fluid.

Adult↗

The placenta in maternal hyperhomocysteinaemia.

It is becoming increasingly apparent that mild or moderate hyperhomocysteinaemia may be associated with adverse perinatal complications and outcomes. The placental pathology in 14 pregnancies from 11 women diagnosed retrospectively to have hyperhomocysteinaemia, following a recent history of intrauterine fetal growth restriction, abruption or of thromboembolic disease, were reviewed. Most of the placental findings indicated abnormal placentation but these were not specific to maternal hyperhomocysteinaemia nor found in every placenta. Features observed included absence of trophoblast-induced physiological vascular changes, acute atherosis, intraluminal endovascular trophoblast in the third trimester, infarction, retroplacental haematoma formation and accelerated villous maturity. Uteroplacental vascular thrombosis was also seen. Three of the women had a subsequent pregnancy where they were treated empirically with folic acid, and these resulted in improved perinatal outcomes. The finding of placental pathology warrants investigation of the woman for hyperhomocysteinaemia. Further randomised controlled trials of folic acid supplementation in preventing pregnancy complications associated with hyperhomocysteinaemia should be conducted.

Adolescent↗

Calcium supplementation in nulliparous women for the prevention of pregnancy-induced hypertension, preeclampsia and preterm birth: an Australian randomized trial. FRACOG and the ACT Study Group.

A multicentre, randomized controlled double-blind trial in 5 maternity hospitals in Australia assessed the effect of a daily supplement of calcium (1.8g oral calcium or an oral placebo) taken daily until delivery, from less than 24 weeks' gestation, on the frequency of pregnancy-induced hypertension, preeclampsia and preterm birth (< 37 weeks' gestation) in 456 nulliparas with a singleton pregnancy. Treatment with calcium reduced the risk of preeclampsia (relative risk 0.44 [95% CI, 0.21-0.90], p = 0.02) and the risk of preterm birth (relative risk 0.44 [95% CI, 0.21-0.90], p = 0.02). No significant differences were seen between the 2 groups in the frequency of pregnancy-induced hypertension, although the study only had statistical power to detect large differences in this outcome. An updated systematic review of the 9 randomized trials of calcium supplementation in pregnancy shows a significant reduction in the risk of hypertension and preeclampsia although no effect on preterm birth. Calcium supplementation during pregnancy reduced the risk of preeclampsia and preterm birth in this nulliparous population. The available evidence for systematic review of all the randomized trials of calcium supplementation shows benefit in reducing the risk of hypertension and preeclampsia.

Adult↗

Postpartum thyroiditis.

Postpartum thyroiditis (PPT) is a syndrome of transient thyroid dysfunction occurring in the first postpartum year. A thyrotoxic phase may be brief and unnoticed before a more long-lasting hypothyroid phase occurs. The incidence is variably reported, ranging from 1.9% to 16.7%, perhaps reflecting racial or geographical differences in the distribution of genetic or environmental risk factors such as the titre of thyroid antibodies and the dietary intake of iodine. The syndrome is an autoimmune disorder, strongly associated with the presence of thyroid microsomal antibody in serum. The thyrotoxic phase may be distinguished from Graves' disease by the finding of low, rather than high, uptake of radioactive iodine or technetium in the thyroid. Screening may be valuable in women with other autoimmune disorders such as Type 1 diabetes mellitus. Treatment should be tailored to the symptoms. Significant thyrotoxic problems should be managed with beta-blocking agents, but severe hypothyroid symptoms should be treated with the short-term replacement thyroxine. A small proportion of affected women will remain permanently hypothyroid. There is also a significant risk of recurrent disease after a subsequent pregnancy.

Female↗

Subjects with polycystic ovaries without hyperandrogenaemia exhibit similar disturbances in insulin and lipid profiles as those with polycystic ovary syndrome.

Polycystic ovaries (PCO) are detected using ultrasonography in a proportion of women who do not have clinical symptoms of the polycystic ovary syndrome (PCOS). The aim of this study was to compare the metabolic and endocrine differences between women with such ultrasound-detected PCO and women with PCOS, and to relate these changes to clinical presentation with particular reference to cycle irregularity. A group of 118 women showing PCO on vaginal ultrasound scan was divided into those who had no hyperandrogenaemia (n = 21) and those who had increased androgens and a clinical presentation normally associated with PCOS (n = 97). These were compared with a reference group of 26 normal subjects. Glucose tolerance, lipid concentrations and endocrine profiles were compared between groups. Apart from higher concentrations of androgens in the PCOS group, there were no significant differences between the PCO and PCOS groups in either fasting and stimulated insulin and glucose or in concentrations of sex hormone-binding globulin, gonadotrophins and blood lipids or in ovarian volume. Both PCO and PCOS subjects with cycle irregularity had significantly higher concentrations of serum fasting and stimulated insulin independent of androgens and body mass index than those with normal cycles. It was concluded that: (i) PCO and PCOS patients have equivalent disturbances in relation to insulin and glucose metabolism as well as lipid and lipoprotein disturbances compared to reference subjects; (ii) higher serum insulin values are associated with menstrual irregularity in both groups; (iii) ultrasound evidence for PCO predicts similar metabolic sequelae to PCOS and can therefore be used for studies of the genetics and long term risks for this condition.

Androgens↗

Aspirin and prevention of preeclampsia. Position statement of the use of low-dose aspirin in pregnancy by the Australasian Society for the Study of Hypertension in Pregnancy.

1. A heterogeneous group of randomized trials have been conducted using low-dose aspirin to prevent preeclampsia. The results do not support widespread use of low-dose aspirin to prevent preeclampsia. 2. On the basis of existing literature, it is reasonable to use prophylactic low-dose aspirin from early pregnancy in the following groups: (i) Women with prior fetal loss after the first trimester, with placental insufficiency (ii) Women with severe fetal growth retardation in a preceding pregnancy either due to preeclampsia or unexplained (iii) Women with severe early-onset preeclampsia in a previous pregnancy necessitating delivery at or before 32 weeks' gestation. 3. On the basis of existing literature, it is recommended that aspirin not be used in the following groups: (i) Healthy nulliparous women (ii) Women with mild chronic hypertension (iii) Women with established preeclampsia. 4. The data are sufficient to support further trials in more homogeneous select subgroups of women considered at risk of developing preeclampsia.

Aspirin↗

Transient diabetes insipidus and acute fatty liver of pregnancy.

OBJECTIVE: To review the association of transient diabetes insipidus and acute fatty liver of pregnancy. DESIGN: A retrospective study. SETTING: Six women presenting with polyuria and polydipsia in the third trimester or in the immediate postpartum period, referred over a two and a half year period; five out of six were primigravida. All had raised liver transaminases and biopsy-proven acute fatty liver of pregnancy. Four out of six also had pre-eclampsia. SUBJECTS: Tertiary referral centre. MAIN OUTCOME MEASURES: There were no maternal deaths and only one fetal death. Desamino-cys-1-D-arg-8-vasopressin administration produced a reduction in urine output in all five women to whom it was administered. In all cases symptoms had resolved by the end of the fourth postpartum week. Three of the women have had subsequent pregnancies uncomplicated by either transient diabetes insipidus or acute fatty liver of pregnancy. CONCLUSIONS: The association of transient diabetes insipidus and acute fatty liver of pregnancy appears more common than previously recognised. Both may be part of the spectrum of pre-eclampsia.

Acute Disease↗

Premature menopause management.

Premature menopause is most commonly iatrogenic, but may be due to an autoimmune or other ovarian disorder, or it may be idiopathic. The diagnosis is established by a raised serum FSH. Fertility can only be reliably achieved using donor oocytes; otherwise oestrogen replacement therapy should be offered.

Female↗

HLA associations in patients with polycystic ovaries and in patients with congenital adrenal hyperplasia caused by 21-hydroxylase deficiency.

Ninety-nine Caucasian patients with ultrasonically detected polycystic ovaries (PCO) were typed for human leucocyte (HLA) antigens. Fifty patients with congenital adrenal hyperplasia (CAH) caused by 21-hydroxylase deficiency were similarly typed. Among the patients with PCO, there was a significant increase in the frequency of HLA DRW6 (P = 0.0027) compared with that found in a control population, which remained significant (P = 0.027) when corrected for the number of antigens tested. This difference was reduced, but remained significant (P = 0.006), when the patients with CAH and PCO were added. There was also a significant decrease in the frequency of HLA DR7 (P = 0.017) among the patients with PCO compared with a control population, but there was no distortion of the frequencies of HLA A, B or Cw antigens. Among the patients with CAH, previously well documented associations of HLA B14 and DR1 with non-classical disease were confirmed. The frequency of HLA Bw47 was increased among the whole group of CAH patients (P = 0.05) but was not increased among those with classical salt-wasting (SW) or simple virilizing (SV) disease. Family studies were performed in close female relatives of 16 of the PCO patients and 21 of the CAH patients but no evidence for genetic linkage between HLA and PCO status could be found. These data suggest that there is no significant component of disturbed adrenal steroid 21-hydroxylase activity to account for the PCO morphology, although there may be some other genetic factor, more proximal to the centromere on chromosome 6, affecting the development of polycystic ovaries.

Adrenal Hyperplasia, Congenital↗

The prevalence of polycystic ovaries in patients with congenital adrenal hyperplasia and their close relatives.

Seventy-seven female patients (36 adults and 41 children aged under 16 years) with congenital adrenal hyperplasia (CAH) were assessed using pelvic ultrasound, as well as with standard endocrine tests and HLA typing. Forty-six close female relatives were also tested for ovarian morphology using ultrasound after assessment of their heterozygous state using HLA typing. The association of CAH with ultrasonically detected polycystic ovaries (PCO) was confirmed in 30/36 (83%) adult patients, 4/10 (40%) postpubertal girls and 1/31 (3%) pre and peripubertal girls: in all, 35/46 (76%) postmenarcheal patients. Six out of nine (67%) pre-menopausal mothers of patients with PCO, and 8/10 (80%) sisters of patients with PCO also had PCO. The proportions of both CAH patients and heterozygote subjects with PCO were significantly greater than that found in a normal population (P less than 0.0001). The finding, however, of two homozygous non-CAH-affected adult sisters with PCO and, conversely, of 10 heterozygous adult relatives and of 12 postmenarcheal CAH patients with normal ovaries, indicates that the ovarian morphological change may be independent of the adrenal lesion.

Adolescent↗

Steroid responses to ACTH in women with polycystic ovaries.

Sixty-three women with ultrasonically detected polycystic ovaries (PCO) were investigated for a disorder of adrenal steroid biosynthesis. Serum was obtained before, and at 30 and 60 min after, the administration of 250 micrograms tetracosactrin, and assayed for 17 alpha-OH-progesterone, 21-deoxycortisol, 17 alpha-OH-pregnenolone and dehydroepiandrosterone by radioimmunoassay following paper chromatography. Results were compared with those in 11 women with normal ovaries, seven adult females with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD), and 15 women heterozygous for this defect. Although the basal-peak steroid concentration differences were significantly greater when ACTH tests were conducted between 1400 and 1700 h than between 0900 and 1000 h, absolute peak steroid concentrations were not different at either time of day. Four of 63 (6.4%) women with PCO had responses to ACTH characteristic of non-classical (late onset) 21OHD CAH, and about half the remainder had responses characteristic of 21OHD heterozygotes. There was no clear cut evidence for a deficiency in 3 beta-hydroxysteroid dehydrogenase activity in women with PCO.

17-alpha-Hydroxypregnenolone↗

Inappropriate ACTH concentrations in two patients with functioning adrenocortical carcinoma.

Two female patients with functioning adrenocortical carcinomas had plasma ACTH detectable by RIA at presentation. In both patients there was evidence for biological activity of ACTH. There was no evidence for an ectopic source of ACTH, nor for a pituitary tumour. Urinary steroid analysis showed patterns of multiple hormone secretion characteristic of adrenocortical carcinomas. The finding of detectable ACTH concentrations in a patient with Cushing's syndrome does not exclude the presence of an adrenocortical tumour.

Adrenal Gland Neoplasms↗