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Biomedical subjects

P W Howie

Publications and source records attributed to P W Howie.

At least 55 records · Page 3Linked to original sources

Prolactin response to low dose sulpiride.

1 Prolactin levels in response to sulpiride were studied in healthy volunteers. 2 Oral doses of 1 mg-50 mg sulpiride or placebo were given. 3 A 3 mg sulpiride dose produced similar levels to those achieved with both 10 mg and 50 mg. 4 Circadian effects were studied showing no significant differences in the prolactin response to sulpiride. 5 Acute or chronic responses showed an attenuation with chronic sulpiride treatment to 50% of the peak levels attained with acute treatment. 6 These results indicate that sulpiride retains its potent ability to produce prolactin release even at the low doses studied here.

Adolescent↗

Induction of transient hyperprolactinaemia in neonatal rats by direct or maternal treatment with the dopamine receptor blocker, sulpiride.

Prolactin was measured in the plasma of neonatal rats after iv and ip injection of the dopamine receptor blocking drug sulpiride, and after its ip injection to neonatal rats' nursing mothers. The sulpiride dose PRL response relationship in 10-25 day old neonatal rats was similar to that found in lactating rats, with a threshold sensitivity around 29 nmol sulpiride/kg body weight and a maximal response at about 2.9 mumol/kg. Absolute levels of PRL in the neonate (both peak and increment-over-basal) were, however, 90% lower than in adults. Treatment of lactating mothers with a maximally stimulatory dose of sulpiride (2.9 mumol/kg) twice daily for 4 days resulted in small but highly significant increases in neonatal PRL on days 1 and 2 but complete loss of response by day 4. These data demonstrate that there is a close similarity between the responses of maternal and neonatal rats to sulpiride and that transfer of the drug to the neonate via milk can induce neonatal hyperprolactinaemia. The subsequent loss of the neonatal PRL response on chronic exposure to sulpiride may indicate a degree of disturbance of hypothalamic dopaminergic mechanisms. In the clinical situation this would suggest that doses of dopamine receptor-blocking drugs used to enhance maternal milk production should be carefully chosen.

Animals↗

Diminution in energy expenditure during lactation.

Energy expenditure at rest and in response to a meal and to an infusion of noradrenaline was measured in 12 lactating women and compared with that in seven bottle feeding women and seven non-pregnant, non-lactating controls. The energy response of the lactating women was remeasured after lactation stopped. During lactation the resting metabolic rate was unaltered but there was a reduced response to infusion of noradrenaline and to a meal, which increased to normal control values after lactation stopped. Such reductions in expenditure were not found in women who had been bottle feeding and were tested at a similar six to eight weeks post partum. These findings suggest that metabolic efficiency is enhanced in lactating women, who may not need to increase energy intake to the extent suggested by current recommended dietary allowances.

Adult↗

Anticoagulants in pregnancy.

Thromboembolic disorders are still a serious problem in pregnancy and anticoagulants have an important part to play in both treatment and prevention. Warfarin is the most convenient drug to give but can cause maternal and fetal bleeding problems, especially during late pregnancy and delivery. There are also small risks of embryopathy from warfarin in early pregnancy but these may have been overstated. Heparin, which has to be given parenterally, does not cross the placental barrier but can still cause bleeding problems in pregnancy. Full intravenous heparin is only suitable for short-term use, and subcutaneous heparin has been introduced for long-term therapy. This regimen is a useful advance but long-term use still has problems of bruising and maternal bone demineralization. The standard treatment of acute thromboembolic events in pregnancy is continuous intravenous heparin followed by either subcutaneous heparin or warfarin, the latter being changed at 36 weeks gestation. In the prophylaxis of thromboembolism, the trend is towards a more selective approach, anticoagulants being given during pregnancy to those at highest risk and during labour and the puerperium to all with a previous history of thromboembolism. Anticoagulants during pregnancy are necessary in patients with artificial heart valves and, because subcutaneous heparin is not sufficient, warfarin should be used until 36 weeks followed by continuous intravenous heparin until delivery. No method of anticoagulation during pregnancy is entirely free of risk and all management policies must be based on an estimate of risk-benefit ratio in individual patients.

Anticoagulants↗

Sulpiride and the potentiation of progestogen only contraception.

A progestogen (norethisterone) and a dopamine antagonist (sulpiride) were given alone and in combination to volunteers to examine their effects on excretion of ovarian steroids. Compared with non-treatment cycles (n = 15), contraception with a progestogen alone (n = 10) was associated with increased excretion of oestrone and partial suppression of excretion of pregnanediol, suggesting partial luteinization of unruptured follicles. By contrast, the combination of norethisterone and sulpiride (n = 9) suppressed both ovarian steroids to basal values, the suppression being even greater than with sulpiride alone (n = 5). These results suggest that a combination of a progestogen with a dopamine antagonist might have a role in contraception.

Adult↗

Do pregnancy complications contribute to neurodevelopmental disability?

In the Dundee Development Screening Programme all children born in Dundee in 1974 and 1975 were screened at intervals during infancy and childhood. The obstetric and neonatal antecedent factors in 300 of the 322 singleton children with neurodevelopmental disability (index group) were compared with those of the 600 children of normal development born immediately before and after each child with disability (control group). Low social class was associated with mental retardation, global delay, speech delay, and behavioural disorder, but not with cerebral palsy or motor delay. With the exception of cerebral palsy, strong associations were found between all categories of disability and severe hypertension, unclassified antepartum haemorrhage, and preterm uterine activity. Cerebral palsy was not associated with antepartum complications, but was with fetal tachycardia during labour. Our data suggest that neurodevelopmental disability may, in many cases, originate during pregnancy and delivery.

Birth Weight↗

Effect of an intranasal LHRH agonist on gonadotrophins and hot flushes in post-menopausal women.

Alterations in circulating gonadotrophins have been reported at the time of onset of menopausal flushes. In order to study this association D-SER(TBU)6-EA10-LHRH, a luteinizing hormone releasing hormone (LHRH) agonist was given intranasally at a dose of 200 micrograms twice daily to 12 post-menopausal women to study its effect on gonadotrophin secretion and hot flushes. Following an initial period of 3-5 days of increased gonadotrophin secretion, pituitary desensitization occurred, with a significant suppression of circulating LH and follicle-stimulating hormone (FSH) levels (P less than 0.001) and a reduction in gonadotrophin pulse amplitude (P less than 0.05). This was accompanied by a significant diminution of the pituitary's response to exogenous LHRH (P less than 0.05). However, no significant alteration in the incidence of hot flushes was observed on such therapy.

Administration, Intranasal↗

Pulsatile secretion of LH in relation to the resumption of ovarian activity post partum.

Changes in the pulsatile pattern of LH secretion in relation to the resumption of ovarian activity post partum have been studied in breast feeding mothers. Basal concentrations of LH were significantly lower than normal both when ovarian activity was completely suppressed and when there was evidence of some follicular development prior to the resumption of menstruation. Once menstruation resumed basal concentrations of LH were unchanged whether ovulation occurred or not. No difference in the frequency or amplitude of pulses in LH secretion could be found at any stage post partum in either breast or bottle feeding women. FSH levels remained constant throughout the post partum period while mean concentrations of prolactin fell as ovarian activity returned to normal. However, during the period of complete suppression of ovarian activity in breast feeding women, two patterns of pulsatile secretion of LH were observed. In 76% of observation periods, basal levels of LH were lower than normal and were characterized by low frequency and low amplitude pulses of LH. In contrast, in the remaining 24% of observation periods, basal levels and pulse amplitude and frequency of LH were similar to those in the follicular phase of normal menstrual cycles in these women. Individual women showed either or both of these patterns of secretion during the period of ovarian suppression post partum. The data suggests that the failure to maintain ovarian follicular development post partum in breast feeding women may be due to: (1) a direct block of LH action at ovarian level, perhaps by the high levels of prolactin associated with lactation and/or (2) an inability of the hypothalamic-pituitary axis-as a result of the suckling stimulus and/or prolactin-to maintain pulsatile secretion of LH in the face of the negative feedback effects of the increased oestrogen secretion resulting from the initiation of follicular development.

Adult↗

The prolactin response to suckling.

Changes in prolactin concentration during single suckling episodes in twenty breast-feeding women from four to 40 weeks post partum have been investigated. Basal prolactin concentration and the increase in prolactin secretion in response to single suckling episodes and amount of milk taken by the infant were both independent of time post partum until the introduction of supplementary feeds, when a significant decrease with time was apparent. Basal concentrations of prolactin were dependent upon the interval between suckling episodes, and the magnitude of the prolactin response varied with the time of day when suckling took place. The relationship between acute suckling episodes and the long term pattern of prolactin secretion over time post partum is discussed.

Breast Feeding↗

Obstetric management of preterm labour.

In recent years the trends in the obstetric management of preterm labour have moved in the direction of more active policies with greater use of fetal heart monitoring and Caesarean section to avoid traumatic and asphyxial damage to the baby. Conservative management still has an important place, especially in association with extreme prematurity. Following initial enthusiasm, the use of tocolytic drugs and antenatal corticosteroids are going through a phase of re-evaluation and careful assessment is essential in individual cases to avoid their inappropriate use. Future developments in the obstetric management of preterm labour will depend upon careful evaluation studies which examine not only the short-term mortality statistics but also the long-term effects in respect of neurological and developmental handicap. This task is one of the major challenges for obstetricians to tackle over the next two decades.

Adrenal Cortex Hormones↗

Release of oxytocin and prolactin in response to suckling.

The oxytocin and prolactin responses to suckling were measured in 10 women in early (n = 5) and established lactation (n = 5). Oxytocin was released in a pulsatile manner during suckling in all women, but the response was not related to milk volume, prolactin response, or parity of the mother. In all 10 women plasma oxytocin concentrations increased three to 10 minutes before suckling began. In five women this occurred in response to the baby crying, in three it coincided with the baby becoming restless in expectation of the feed, while in two it corresponded with the mother preparing for the feed. There was no prolactin response to stimuli other than stimulation of the nipple associated with suckling. These results clearly indicate that the milk ejection reflex, with release of oxytocin, occurs in most women before the tactile stimulus of suckling. A second release of oxytocin follows in response to the suckling stimulus itself. Thus it is important that care is taken to protect breast feeding mothers from stress not only during suckling but also immediately before nursing, when conditioned releases of oxytocin will occur.

Breast Feeding↗

Factors affecting the duration of breast feeding: 1. Measurement of breast milk intake in the first week of life.

Test-weigh measurements of 24 h milk intake by babies in the immediate puerperium (days 1-9) were carried out in a group of 18 mothers and babies using an accurate electronic balance. Estimated milk intakes were then calculated on the basis of one, and of two consecutive, breast feeds. These estimates were then compared with the actual total intake to give a measurement of reliability. Significant positive correlations were found between both the one-feed and the two-feed estimated intake, and the measured 24 h intake. Accuracy increased from day 3 onwards. These results show that using an electronic balance an accurate estimate of 24 h milk intake during the first week of life can be obtained by using one or two test-weigh measurements. While this gives a minimally invasive and reliable method for estimating daily milk intake, it is not advocated as a routine procedure in postnatal wards.

Breast Feeding↗

Factors affecting the duration of breast feeding: 2. Early feeding practices and social class.

Breast milk intake by babies on the third and the sixth postpartum day was measured by a test-weigh procedure in a group of 47 mothers and babies. Women who gave the largest amount of breast milk to their babies on the third postpartum day continued to breast feed for longer than women who gave smaller amounts. These mothers also suckled most frequently, gave least additional fluid to their babies, and their infants regained their birth weight most rapidly. However, an increased early milk intake and duration of breast feeding were both associated with higher social class. These results suggest that, although practices in the initiation of breast feeding are relevant, factors in the background and environment of the mother are also of fundamental importance. Thus recent emphasis on the importance of breast-feeding practices in the immediate puerperium should not divert attention from the equally important task of establishing the optimum conditions for breast feeding in the home environment of mothers.

Body Weight↗

Fertility after childbirth: changes in serum gonadotrophin levels in bottle and breast feeding women.

Changes in basal serum gonadotrophin levels during the resumption of ovarian activity post partum have been studied longitudinally in breast and bottle feeding mothers. On the basis of urinary steroid levels, ovarian activity was classified as showing complete suppression, follicular activity only, deficient luteal phases or normal menstrual cycles. Complete suppression of ovarian activity during lactation was associated with normal levels of FSH but low levels of LH. The resumption of follicular development was not accompanied by any increase in levels of either LH or FSH when compared with the phase of complete suppression and this pattern persisted during menstrual cycles characterized by deficient luteal phase progesterone secretion. Basal LH levels did not rise to normal levels during lactation until the resumption of normal ovulatory cycles. FSH secretion remained at a level comparable with the follicular phase of normal ovulatory cycles throughout the post partum period. In mothers who did not breast feed, LH levels rose more rapidly than in breast feeding mothers and had returned to within normal limits by three weeks post partum. At 4 weeks post partum FSH levels were lower in bottle feeding mothers than in breast feeders probably in response to the early rise in oestrogen levels among bottle feeders. These results suggest that decreased LH but not FSH secretion may be important in maintaining infertility associated with breast feeding.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗