Biomedical subjects
T R Gunn
Publications and source records attributed to T R Gunn.
Bed sharing as a risk factor for sudden infant death (cot death)
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Modulation of growth hormone secretion by thermogenically derived free fatty acids in the perinatal lamb.
To evaluate the hypothesis that the rapid fall in circulating GH concentrations at birth is secondary to the initiation of nonshivering thermogenesis and the consequent rise in FFA levels, a series of experiments was performed in late-gestation fetal sheep. By sequentially cooling the fetus by means of a coil placed around the fetal thorax, ventilating with oxygen via an exteriorized tracheostomy tube, and separating the fetus from the placenta by occluding the umbilical cord, nonshivering thermogenesis could be induced in utero. In the first protocol (n = 6) cooling alone had no effect on fetal plasma FFA levels, oxygenation elevated FFAs slightly from 64 +/- 7 mu Eq/liter to 183 +/- 29 mu Eq/liter, and cord occlusion caused a further marked rise (P less than 0.005) to 635 +/- 69 mu Eq/liter. Neither cooling nor ventilation affected fetal plasma GH concentrations which fell (P less than 0.001) from 160 +/- 17 ng/ml to 65 +/- 13 ng/ml upon cord occlusion. When the cord occluder was removed FFA levels fell (P less than 0.001) and GH concentrations rose (P less than 0.001) once more, and when the cord was again occluded FFA levels rose (P less than 0.001) and GH concentrations fell (P less than 0.001). In a second protocol nine fetuses were cooled, ventilated, and the umbilical cord occluded. Once more, plasma FFA levels rose (P less than 0.001) and GH concentrations fell (P less than 0.001); when thermogenesis was inhibited by the infusion of the adenosine agonist N6-(L-2-phenyl isopropyl)-adenosine, FFA levels fell from 725 +/- 88 mu Eq/liter to 265 +/- 56 mu Eq/liter and GH concentrations rose from 54 +/- 13 ng/ml to 323 +/- 73 ng/ml. In two further protocols the possibility that PIA was acting directly on GH secretion was excluded in six fetuses with low plasma FFA levels and in three fetuses with elevated plasma FFA levels secondary to a fatty acid emulsion infusion. These studies provide direct evidence that the pattern of change in plasma GH concentrations at birth in the sheep is determined in part by the rise in plasma FFAs of thermogenic origin.
Breast feeding preterm infants.
Breast feeding is the optimal way to feed infants but may be difficult in preterm infants. In a study of 43 mothers with 49 preterm infants admitted to a neonatal unit during a 10 week period-84% (36 of 43) wished to breast feed and 92% (33 of 36) of these mothers left hospital breast feeding. Their infants were from 30 to 36.5 weeks gestation, weighing a mean 2590 (SD 530) g and were in hospital 16 (11) days. Only three mothers who wished to breast feed failed to do so. The 10 bottle fed infants were smaller, younger and remained longer in hospital. The majority of mothers (88%) who were discharged breast feeding were still successfully breast feeding their preterm infants three months later. This is in marked contrast to a previous study of mothers, of full term infants, where there was a marked decrease in breast feeding by three months. The mothercraft teaching described is an effective method of providing preterm infants and their mothers with the advantages of breast feeding.
The acquisition of hepatitis B and hepatitis D in high risk preschool children.
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Fetal subdural hematoma before labor.
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Factors influencing the initiation of nonshivering thermogenesis.
The aim of this study was to observe the sequential effects of oxygenation, umbilical cord occlusion, and finally cooling on circulating catecholamines and nonshivering thermogenesis in fetal sheep. We studied five fetal sheep at 132 +/- 3 days' gestation. The fetuses were first ventilated with oxygen; PaO2 levels were maintained above 150 mm Hg, and by 60 minutes there was a significant rise in both plasma glycerol and free fatty acid levels. After umbilical cord occlusion there was a peak in plasma catecholamine and triiodothyronine levels but no significant increase in lipolysis. Cooling, by circulating cold water through a coil around the fetus, induced maximum lipolysis and temperature difference between brown fat and body core, when plasma catecholamine levels were falling. During this study the changes in plasma catecholamine levels did not correlate with the onset of nonshivering thermogenesis. Cutaneous cooling, which causes neurally mediated sympathetic stimulation of brown adipose tissue, is the major signal for the initiation of nonshivering thermogenesis and thus neonatal adaptation.
Reversible umbilical cord occlusion: effects on thermogenesis in utero.
The initiation of thermogenesis at birth is an important adaptation for survival. We examined the sequential effects of cooling, increased oxygenation, and repeated episodes of umbilical cord occlusion on nonshivering thermogenesis in six fetal sheep at 139 to 145 d of gestation. The fetal sheep were cooled by circulating cold water through a coil placed around the trunk for 4 h. The fetal core temperature fell 2.47 +/- 0.24 degrees C in the first 60 min of cooling with minimal changes in plasma FFA and glycerol levels. After fetal arterial O2 tension was increased above 6.65 kPa by ventilation, fetal temperature and thermogenic indices rose significantly in 60 min. After occlusion of the umbilical cord by a reversible occluder cuff, plasma FFA levels rapidly increased to 635 +/- 69 muEq/L (p less than 0.005) by 30 min, fetal temperature increased a further 0.96 +/- 0.20 degrees C (p less than 0.001) and fetal O2 consumption peaked at 25.3 +/- 4.9 mL.min-1.kg-1. Release of cord occlusion caused a rapid fall in FFA to 149 +/- 23 muEq/L (p less than 0.005) and a fall in fetal core temperature of 0.90 +/- 0.13 degrees C (p less than 0.001) in 30 min. After irreversibly snaring the umbilical cord, the plasma FFA rose to 611 +/- 83 muEq/L (p less than 0.005) and the fetal temperature rose 0.78 +/- 0.09 degrees C (p less than 0.02). The effects on thermogenesis of interrupting and reestablishing placental flow are rapid and reversible and suggest the presence of placental inhibitors of brown adipose tissue thermogenesis.
Prenatal cranial haemorrhages in 47 Pacific Islander infants: is traditional massage the cause?
Intracranial haemorrhage is usually a very rare occurrence in the fetus before the onset of labour but we have identified major, mostly subdural, prenatal intracranial haemorrhages in 47 infants of immigrant Pacific Islander parentage. Forty-four infants have been stillborn and the numbers from 1983 to 1986 were sufficient to account for the stillbirth rate for Pacific Islanders in Auckland being approximately 60% higher than rates for Europeans or Maoris. Two of three liveborn infants survived with neurological sequelae. Similar haemorrhages may be the cause of a congenital hydrocephalus in Pacific Islanders. A bleeding disorder can be excluded in most cases, as can trauma from accidents or assaults. Trauma during attempts at cephalic version of breech presentations by traditional methods could explain why 53% of deliveries were breech and other pathological and clinical features. Advice at antenatal clinics about possible dangers of traditional massage has coincided with a reduction in the incidence of haemorrhages since 1986.
Quality of outcome and cost in an obstetric and neonatal service.
A review has been made of the outcome and efficiency of the obstetric and neonatal service, St Helen's Hospital, Auckland. In the last seven years there has been a 33% fall in perinatal mortality rates to 5.88 per 1000 births in 1987. The average perinatal death rate for Maori infants was low, 4.81 per 1000 compared to 7.43 per 1000 for Europeans over this period. There has been a 38% increase in births to 3597 a year while the total hospital staffing has only risen 9%. Thus the ratio of births to staff has increased by 26.6% to 15.6. The cost per infant delivered in constant dollars has fallen 18.7% in the same period to $2432. The postnatal bed occupancy was 101% in 1987 and the average day stay fell to 5.7 days. An extra 61 full time staff would be needed to reduce the workload to that of 1981 and the staff is now unable to give the family focused holistic care that is needed.
The safety and immunogenicity of a recombinant hepatitis B vaccine in neonates.
A study to evaluate the safety and immunogenicity of a yeast derived recombinant DNA hepatitis B vaccine (Engerix-B) was conducted in healthy newborn infants born to low risk European mothers negative for hepatitis B surface antigen (HBsAg). The vaccination schedule using 20 micrograms doses was administered intramuscularly at 0, 1 and 6 months. The seroconversion rate was 99% (90 of 91 infants). The geometric mean titer of antibody to hepatitis B was 1259 mIU/mL one month after the third dose of vaccine. Possible side effects reported by the mothers were minor and uncommon. This vaccine is highly immunogenic and safe for use in infants.
The endocrine control of the onset of thermogenesis at birth.
The experimental studies in the fetal sheep demonstrate that the central hypothalamic mechanisms for responding to a cold stress have differentiated well before birth. There are several major determinants of the initiation of maximal thermogenesis at birth. These are cutaneous cooling, oxygenation and separation from the placenta. Firstly the stimulation of cutaneous cold receptors regulates sympathetic nervous system activity, primarily local noradrenaline release from sympathetic nerve termini to the brown adipocyte adrenoreceptors. Circulating catecholamines, the euthyroid state and other hormones also play a role. Secondly an increase in oxygen delivery to brown adipose tissue through increased oxygen content and increased blood flow is required. Finally, our observations suggest that separation from the placenta is necessary for maximal nonshivering thermogenesis. The effects on thermogenesis of interrupting and reestablishing placental flow are rapid and reversible. Umbilical cord occlusion is the signal for a rapid increase in thermogenesis, while the release of cord occlusion is followed by an equally rapid fall in thermogenesis. This strongly suggests the presence of a placental inhibitor of brown adipose tissue thermogenesis. The problem of the regulation of growth and recruitment of brown adipose tissue in the fetus despite the lack of thermal stress in utero may be resolved by this evidence for an inhibitory factor of thermogenesis produced by the placenta. The withdrawal of the inhibitor at birth by separation from the placenta will allow the rapid initiation of thermogenesis in response to sympathetic nervous system stimulation of the brown adipose tissue.
Upper airway measurements during inspiration and expiration in infants.
Accurate measurements of the upper airway of the infant are important but are difficult to obtain reliably because of the normal variation that occurs during respiration. X-ray films of the lateral upper airway were obtained during inspiration and expiration in healthy infants, by using as a timing device a respiration monitor which was wired to the x-ray machine and was attached to the abdominal wall of the infant. Cephalometric measurements were made of 44 "normal" full-term neonates and 29 infants at 6 weeks of age. Despite significant differences in head circumference between the sexes, only the nasion to sella length was significantly longer in the boys (P less than .01). The lateral upper airway measurements were independent of weight, head circumference, and sex in the neonates and infants at 6 weeks of age but were significantly smaller during inspiration than expiration (P less than .01). The measurements progressively increased from the middle to the posterior airway space at both ages. The middle airway space behind the caudal end of the hard palate was smaller during inspiration at 6 weeks of age compared to the neonate (P less than .01). During expiration, the posterior airway space was larger at 6 weeks compared to the neonate (P less than .01). The method described in this report enables reliable roentgenographic measurements to be made of the upper airway of the infant; normal values for the changes during inspiration and expiration are provided. This may assist in the evaluation of infants with suspected upper airway obstruction.
Umbilical cord occlusion but not increased plasma T3 or norepinephrine stimulate brown adipose tissue thermogenesis in the fetal sheep.
Nonshivering thermogenesis is normally inactive in utero but increases with supplemental oxygenation and again after occlusion of the umbilical cord. To test the hypothesis that brown fat responses are triggered by the surge in triiodothyronine (T3) which occurs at birth, we studied 7 fetal sheep at 132-143 days gestation. Fetuses were first cooled 2-3 degrees C by circulating cold water through an external coil in the amniotic fluid and then ventilated with oxygen in utero to raise arterial PO2 to 109 +/- 10 (SEM) mmHg. An hour later T3 was infused intravenously to elevate and maintain plasma levels at 39.8 +/- 6.1 nmol/l, some 40-50 times basal levels. Indices of brown heat production did not rise during the next 30 min. Following snaring of the umbilical cord, however, plasma free fatty acid levels increased 400% to 423 +/- 91 mEq/l, plasma glycerol rose 350% to 766 +/- 168 mmol/1, and the temperature difference between brown fat and body core widened to 0.59 +/- 0.13 degrees C during the next 30 min. Whole body oxygen consumption peaked at 23.1 +/- 2.8 ml.min-1.kg-1 body weight. These responses to cord occlusion were similar with and without T3 administration. Changes in plasma catecholamines during these experiments did not correlate with the onset of nonshivering thermogenesis. We conclude that the rise in T3 or the changes in plasma catecholamines which occurs at birth are not causally related to the onset of nonshivering thermogenesis.
Congenital hydrocephalus secondary to prenatal intracranial haemorrhage.
A high incidence of intracranial haemorrhage in utero of uncertain aetiology has been previously identified as an important cause of stillbirth in infants of immigrant Pacific Islanders in New Zealand. Congenital hydrocephalus is now described as a consequence of intracranial haemorrhage in 2 stillborn Pacific Islander infants. A large intracerebral haemorrhage, hydrocephalus and hydrops in one infant was first recognized prenatally by ultrasonography and caused intrauterine death at 26 weeks' gestation. Severe hydrocephalus in the other infant was first identified just before labour at term but the pathological findings were of old intraventricular haemorrhage with narrowing of the aqueduct of Sylvius as a reaction to the haemorrhage. Prior intracranial haemorrhage may be the cause of an increased incidence of hydrocephalus in Pacific Islander stillbirths and of some otherwise unexplained cases of congenital hydrocephalus in other races.
Outcome after antenatal diagnosis of upper urinary tract dilatation by ultrasonography.
A prospective study was carried out during 1986 to find out the incidence of fetal renal tract anomalies in 3228 pregnant mothers delivered in one hospital. Ultrasound examination of the fetus was performed as part of the routine antenatal assessment at 16-20 weeks' gestation, and later examinations were done if there were obstetric indications. Fetuses with any degree of dilatation of the renal pelvis or other renal tract anomalies were followed up with serial ultrasound examinations in utero and then postnatally at 6 days and 6 weeks of age, or earlier if indicated. No renal tract anomalies were detected before 28 weeks' gestation, but of 761 fetuses examined later, 62 had dilatation of the renal pelvis not associated with overdistended bladders, and one fetus was anephric. After birth 10 of these infants (16%) were found to have pronounced renal tract abnormalities. Three who had associated serious congenital abnormalities died, five infants had obstruction of the pelviureteric junction, and two infants had vesicoureteric reflux. Antenatal ultrasonographic examination after 28 weeks identifed pronounced renal tract abnormalities in asymptomatic infants with a frequency of 9.2/1000 births (seven of 761) thus permitting early treatment and reducing the incidence of late complications.
Surface cooling rapidly induces coordinated activity in the upper and lower airway muscles of the fetal lamb in utero.
Stimulation of cutaneous thermoreceptors may be an important factor in the initiation of continuous breathing at birth. Maintenance of a patent airway is also important in the continuation of effective ventilation after birth, but whereas in the adult the principal pharyngeal dilator is the genioglossus muscle, in the fetus genioglossus phasic activity is not synchronous with that of the fetal diaphragm. To ascertain whether a cold stimulus that initiates continuous breathing would also induce synchronized inspiratory activity in the upper airway muscles of the fetus, we have cooled fetal lambs in utero and examined the response of the genioglossus and alae nasi muscles in relation to diaphragm activity. Deep regular breathing as recorded by diaphragmatic activity and tracheal pressure started within 1-102 s after cooling commenced and coordinated inspiratory activity was seen in the alae nasi within 2-356 s. Genioglossus activity became synchronized with that of the diaphragm within 11-356 s. Cooling was continued for 4 h but although in one fetus continuous breathing with associated inspiratory activity in the genioglossus and alae nasi muscles lasted throughout the 4-h period, in the others continuous breathing was not sustained and adaptation to the cold stimulus occurred after periods ranging from 27-218 min. The relationship between breathing, upper airway muscle activity, and sleep state passed through one or more different phases, including breathing through high voltage electrocortical activity, before the normal fetal pattern of episodic breathing restricted to the low voltage electrocortical state resumed.(ABSTRACT TRUNCATED AT 250 WORDS)
The prenatal ultrasonographic diagnosis of cardiomegaly due to tricuspid incompetence.
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