Biomedical subjects
Publications and source records attributed to T R Gunn.
We present the case of a patient with Noonan's syndrome and massive nonimmune hydrops fetalis in whom lymphangiography was performed in the neonatal period. This demonstrated generalised lymphatic dysplasia, and we suggest a mechanism by which the lymphatic abnormalities in Noonan's syndrome may arise.
Term infants with seizures and evidence of perinatal asphyxia were prospectively identified in 1 city and 2 time periods: 1978-1981 and 1991. Infants with multiple congenital abnormalities, hypocalcaemia or infection were excluded. Although there was little change in the overall incidence of neonatal seizures between 1978-1981 (1.9 per 1,000) and 1991 (1.78 per 1,000, N.S.) there was a marked reduction in small for dates infants with seizures: 8 of 19 infants in 1978-1981 compared to none of 16 in 1991 (p < 0.005). In contrast, infants > or = 41 weeks continued to show a markedly increased risk for asphyxia (relative risk 4.48, 95% CI: 1.7-12.3). The mechanism of this improved outcome for small for gestational age infants is unknown, but speculatively may be due to improved obstetric monitoring techniques allowing early identification of compromised infants.
The current recommendation for resuscitation of infants is to blow air into both the nose and mouth. We have observed that mothers cannot cover both the nose and mouth of their infants. We compared postmortem tracheal and esophageal air entry by using the nose, combined nose and mouth, and mouth routes in eight infants. Air entry into the trachea occurred at lower pressures (P < 0.05) via a nose mask than via a combined nose and mouth mask or via a mouth mask. Air entry into the trachea occurred at lower pressures (P < 0.05) via the nose route in the neutral and extended neck positions compared with the flexed position. We were unable to demonstrate an effect of the route of air entry on esophageal air entry. The findings indicate that the nasal route of air entry is more effective than the combined nose and mouth or mouth routes and that neck flexion impedes air entry. We recommend that parents are taught to blow air into their infants' noses if the infant stops breathing.
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AIMS: To test the hypothesis that external radiant heating might lead to significant fluctuations in superficial and core head temperatures in newborn infants. METHODS: In an observation group of 14 term infants nursed under a radiant heater, servo-controlled to the abdominal skin, changes in rectal, core head, and scalp temperatures with heater activation were examined. In a further intervention group of six infants the effect of a reflective head shield on the fluctuations of scalp temperature was also tested. RESULTS: In the observation group, when the heater had been off for 30 minutes, the rectal and scalp temperatures were 36.7 (SD 0.6) and 35.6 (0.6) degrees C, respectively, a difference of 1.2 (0.2) degrees C. After 30 minutes with the radiant heater on this fell to 0.2 (0.5) degrees C. The core head temperature, however, remained similar to the rectal temperature throughout. In the intervention group a reflective shield prevented the loss of the rectal-scalp gradient. CONCLUSION: Overhead heater activation is associated with loss of the core to scalp temperature gradient, but no change in core head temperature in term infants. The clinical relevance of this superficial heating in vulnerable infants warrants further study.
Nonshivering thermogenesis is not initiated when the fetal sheep is cooled in utero but appears to require the removal of an inhibitor of placental origin at birth. To test whether adenosine is such an inhibitor, we examined the effect of the adenosine antagonist theophylline on the initiation of nonshivering thermogenesis during sequential cooling, ventilation, and umbilical cord occlusion in utero. Theophylline (18 mg/kg bolus and 0.6 mg.kg-1.min-1 thereafter) was infused for 90 min before and 90 min after cord occlusion. Theophylline enhanced the nonshivering thermogenic free fatty acid (FFA) and glycerol responses before cord occlusion, raising FFA concentrations 99% to 415 +/- 60 mueq/l (P < 0.01) and glycerol levels 87% to 526 +/- 135 mumol/l (P < 0.05). These FFA (P < 0.001) and glycerol (P < 0.05) concentrations were significantly greater than the corresponding period during the birth-simulation control. Umbilical cord occlusion did not alter FFA levels but induced a 41% rise in glycerol concentrations to 774 +/- 203 mumol/l (P < 0.05). The increases in nonshivering thermogenic indexes after the administration of the adenosine-receptor antagonist suggest that the quiescent state of ovine fetal brown adipose tissue may result, in part, from the tonic inhibitory actions of adenosine and that a decrease in adenosine concentrations enhances nonshivering thermogenesis. However, the further rise after umbilical cord occlusion suggests that at least one other inhibitor of placental origin inhibits nonshivering thermogenesis before birth.
AIMS: To determine the galactopoietic response to recombinant human growth hormone (hGH) in mothers of premature infants with inadequate lactation. STUDY DESIGN: Prospective placebo-controlled, double-blind trial. SUBJECTS: Twenty healthy mothers on no concurrent medication, with infants born between 26 and 34 weeks' gestation with insufficient milk production for their infants' needs. INTERVENTIONS: Ten mothers received hGH, .2 IU/kg/day subcutaneously to a maximum of 16 IU/day, for 7 days, while 10 mothers received the same volume of placebo. One mother from each group withdrew from the study. OUTCOME MEASURES: Maternal milk production and plasma concentrations of insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), and growth hormone (GH) were determined before starting treatment and 1 day after stopping therapy. A nurse measured the amount of milk expressed (5 to 6 times daily) plus, if the infant was suckling, weighed the infant before and after feeding. RESULTS: The mothers were enrolled 35 +/- 26 days after birth; at this time the infants weighed 1.89 +/- .64 kg. Milk production in hGH-treated mothers increased from 139 +/- 49 mL/day to 175 +/- 46 mL/day after 7 days of treatment (a rise of 31%). Placebo-treated mothers showed no significant change from 93 +/- 50 mL/day to 102 +/- 69 mL/day (a rise of 7.6%, not significant). Milk production increased in all treated mothers but decreased in 4 of 9 placebo mothers. Plasma concentrations of IGF-1 and IGFBP-3 increased in hGH-treated mothers but not placebo-treated mothers; there was no change in plasma GH levels in either group. No adverse effects were seen with hGH treatment in the mothers or infants. CONCLUSIONS: hGH therapy in mothers with lactational insufficiency can improve breast milk volumes.
The rapid initiation of thermogenesis is crucial for the survival of newborn infants. At birth the fetus must adapt to cooling, increased oxygenation and separation from the placenta. An experimental approach in the chronically instrumental fetal sheep of 'simulated birth in utero' allowed the evaluation of each of these stimuli sequentially. Cooling stimulated shivering, cardiovascular and endocrine responses but not nonshivering thermogenesis (NST). Ventilation of the cooled fetus with oxygen caused only modest NST which was not altered by an infusion of triiodothyronine. Occluding the umbilical cord was followed by a rapid substantial rise in NST which was maintained until the placental circulation was re-established. Thus the placenta is secreting factors into the fetal circulation which inhibit the ability of the brown adipose tissue to respond to either hormonal or neural stimuli. Placental prostaglandin E2 and probably adenosine are tonic inhibitors of thermogenesis in utero. Effective thermogenesis after birth requires the combination of separation from the placental inhibitors of lipolysis, increased oxygenation from breathing and the stimulation of cutaneous cold receptors.
In infants under 6 months of age air normally enters the trachea by the nose because the tongue fills the oral cavity, and the oral route is open only when the infant is making muscular efforts such as crying or gasping. The present recommendation for infant resuscitation is for the resuscitator's mouth to cover the mouth and nose of the baby. We set out to test whether this recommendation is feasible. We measured the dimensions of the faces of 28 babies aged between 2 and 4 months (the age when resuscitation is most often needed) and of the mouths of 25 of their mothers. Only 2 mothers would have been able to cover with their mouths the nose and closed mouth of 2 babies (not their own). The mannequins often used to teach adults to resuscitate infants are misleading because they present a wide open mouth, thus implying that that is the preferred route. We recommend that the nasal route of air entry be taught to parents for resuscitation of babies who have stopped breathing.
We report on a family with an abnormality of 10p. The propositus has monosomy for the distal region of 10p and severe psychomotor delay, growth failure, congenital heart defect, multicystic kidney, grade V vesicoureteric reflux, and neurosensory hearing loss. The mother and the elder brother of the propositus carry a balanced reciprocal translocation (5q;10p)(q35.3;p12.3). A retarded and epileptic maternal aunt was found to have dup(10p). Study of the family history led to the successful obstetric management of a subsequent twin pregnancy in which an affected fetus with dup(10p) was identified and selectively terminated, while the other normal twin was delivered at term without problems.
OBJECTIVE: The objective was to establish the likelihood that antenatal upper urinary tract dilatation identified after 28 weeks of gestation will progress to significant postnatal uropathy. STUDY DESIGN: In 5 years, 3856 fetuses had ultrasonography after 28 weeks of gestation when the mothers were first seen in advanced pregnancy for delivery appointments or for other obstetric indications. Fetuses with urinary tract anomalies had ultrasonographic surveillance after 6 days and 6 weeks of life with further evaluation as necessary. RESULTS: Renal tract anomalies were identified in 313 fetuses, and 55 infants had significant renal tract abnormalities. There were 7 deaths; 2 infants were anephric and 5 with hydronephrosis had lethal congenital abnormalities. Dilatation of the upper urinary tract was identified in 7.7% of the fetuses (298/3856) but was transient in 216 of them (72%). Follow-up of children with transient renal pelvis dilatation found only one with a history of urinary tract infection. Obstruction occurred in 23 infants (6.0/1000) and 16 required surgical correction. Vesicoureteric reflux was identified in 14 infants (3.6/1000) and resolved by age 2 years in 64%. Unilateral multicystic renal dysplasia occurred in 8 and posterior urethral valves occurred in 3 infants. CONCLUSION: Antenatal ultrasonography after 28 weeks' gestation identified significant renal tract abnormalities with a frequency of 14.3 per 1000 births, permitting early treatment of the asymptomatic newborn and reducing later renal damage.
At the time of birth, many rapid metabolic changes occur including the initiation of nonshivering thermogenesis and a rapid fall in growth hormone concentrations. To evaluate the interaction between these events 5 fetal sheep were studied at 135-144 days' gestation. The fetuses were first cooled 2.22 +/- 0.19 degrees C by circulating cold water through a coil placed around the fetal thorax and then ventilated with oxygen through an exteriorized tracheostomy tube to raise fetal arterial PO2 above 67.5 +/- 14.1 Torr. An hour later the beta adrenergic agonist isoproterenol was infused intravenously for 90 min. The fetuses were then separated from the placenta by occluding the umbilical cord. After 60 min the cooling and then the isoproterenol infusion were stopped and the responses monitored. Basal plasma free fatty acid (FFA 35 +/- 5 microEq L-1) and growth hormone (GH 141 +/- 12 ng mL-1) concentrations were not significantly altered by cooling alone, but oxygenation modestly increased plasma FFA to 237 +/- 55 microEq L-1 (P < 0.01) while GH concentrations fell to 58 +/- 27 ng mL-1 (P < 0.05). Isoproterenol administration did not significantly affect either FFA or GH concentrations. Occlusion of the umbilical cord caused a rapid nearly threefold increase in plasma FFA concentrations to 903 +/- 71 microEq L-1 (P < 0.01) and a fall in the same proportions in GH concentrations to 16 +/- 2 ng mL-1 (P < 0.005). Maximal fetal oxygen consumption was 24.2 +/- 4.4 mL kg-1 min-1. Cessation of cooling induced a significant fall in plasma FFA to 480 +/- 58 microEq L-1 (P < 0.01) and rise in GH concentrations to 46 +/- 5 ng mL-1 (P < 0.01). Following the withdrawal of isoproterenol, the fall in plasma FFA and rise in GH concentrations continued while the fetal oxygen uptake fell to 6.4 +/- 1.7 mliter kg-1 mL-1 (P < 0.01). During the study the variation in plasma GH was inversely correlated with changes in FFA concentrations (R = 0.77, P < 0.001). This study confirms that the major factors initiating nonshivering thermogenesis at birth are: sympathetic stimulation from cutaneous cooling, which was not significantly enhanced by isoproterenol; adequate oxygenation; and removal of placental inhibitor(s). The findings are in agreement with a causal relationship between the initiation of nonshivering thermogenesis and consequent rise in FFA concentrations and the rapid fall in circulating GH concentrations after birth in the lamb, independent of beta adrenergic stimulation.
Adenosine is released by the placenta into the fetal circulation and has potent antilipolytic properties in vitro. Nonshivering thermogenesis cannot be demonstrated by cooling fetal sheep in utero but can be induced by supplemental oxygenation and umbilical cord occlusion; this suggests the presence of inhibitor(s) of placental origin. To test whether circulating adenosine could be such an inhibitor, a series of experiments was carried out in nine fetal sheep at 136-145 d gestation. Birth was simulated in utero by sequentially cooling the fetus 2.49 +/- 0.23 degrees C with no change in the low levels of plasma FFA or glycerol; ventilating with O2 via an exteriorized tracheostomy tube and umbilical cord occlusion. Thermogenic indices rose markedly, and plasma FFA and glycerol concentrations peaked at 725 +/- 88 microEq/L (p < 0.01) and 771 +/- 154 mumol/L, (p < 0.001), respectively, O2 consumption rose to 20 +/- 2 mL/min/kg, and temperature increased 1.99 +/- 0.35 degrees C. The long-acting adenosine analog N6-(L-2-phenylisopropyl)-adenosine (PIA) was then infused (90 micrograms/kg bolus, then 300 micrograms/kg/h for 30 min); plasma FFA and glycerol decreased to 265 +/- 56 microEq/L (p < 0.003) and 477 +/- 102 mumol/L (p < 0.04), respectively; O2 consumption fell rapidly to 4.5 +/- 0.3 mL/min/kg (p < 0.01); temperature decreased 1.89 +/- 0.39 degrees C (p < 0.001); and fetal arterial BP decreased to 38 +/- 5 mm Hg (p < 0.004) in 30 min. A stepped dose-response study was performed in three fetal sheep.(ABSTRACT TRUNCATED AT 250 WORDS)
Upper airway measurements in nine infants considered to be at risk of upper airway insufficiency, six of whom presented after an apnoeic episode, were compared with measurements taken in two age groups of healthy infants. Paired, inspiratory and expiratory, lateral upper airway radiographs were obtained while the infants were awake and breathing quietly. The radiographs of all nine infants demonstrated narrowing in the oropharyngeal portion of the airway during inspiration and in six infants there was ballooning of the upper airway during expiration. Seven of the nine infants subsequently experienced recurrent apnoeic episodes which required vigorous stimulation to restore breathing. Experience suggests that respiratory phase timed radiographs are a useful adjunct to the evaluation of infants who are suspected of having upper airway dysfunction. They provide information regarding both the dimensions and compliance of the upper airway as well as the site of any restriction.
AIMS: To evaluate the persistence of hepatitis B surface antibodies (anti-HBs) after immunisation in early infancy. METHODS: The infants were born to low risk European mothers negative for hepatitis B surface antigen (HBsAg). All the children had received 3 doses of 20 micrograms of recombinant DNA hepatitis B vaccine. RESULTS: One month after the third dose all 92 infants were seropositive. The GMT was 1190 mIU/mL and all but one infant had seroprotective titres above 10 mIU/mL. Three years after the vaccination 91% (59 of 65) children who returned for testing still had measurable anti-HBs titres. The GMT was 32 mIU/mL but 26% (17 of 65) had titres less than 10 mIU/ml. Only one child had serologic evidence of contact with the hepatitis B virus but did not develop the disease. CONCLUSION: This vaccine is safe and effective for at least 3 years. The long term duration of protection from vaccination in early infancy requires further studies.
Significant nonshivering thermogenesis cannot be demonstrated in fetal sheep cooled in utero but can be induced by supplemental oxygenation and umbilical cord occlusion, which suggests the presence of inhibitor(s) of placental origin. To test the hypothesis that an ecosanoid could be such an inhibitor, we studied eight fetal sheep at 136-141 days gestation. Thermistors were placed in the fetal esophagus, a cooling tube was placed around the trunk, a tracheal cannula and carotid catheters were inserted, and a snare was placed loosely around the umbilical cord. After indomethacin infusion for 18 h, the fetuses were cooled by 2.13 +/- 0.13 degrees C by circulating cold water through the coil. Within 60 min plasma free fatty acid levels rose threefold to 245 +/- 82 mu eq/l (P < 0.01) and glycerol levels rose to 197 +/- 17 mumol/l (P < 0.01). Ventilation caused a further rise in thermogenic indexes, and fetal oxygen consumption rose to 19.9 +/- 1.2 ml.kg-1.min-1. In four fetuses we ceased cooling, which caused thermogenic indexes to fall and oxygen consumption to fall to 6.9 +/- 1.1 ml.kg-1.min-1. We continued to cool three fetuses and infused prostaglandin E2 into the fetuses for 60 min; thermogenic indexes and oxygen consumption fell rapidly on infusion and rose rapidly when infusion ceased. We suggest that placental prostaglandins inhibit brown adipose tissue thermogenesis before birth and that withdrawal after placental separation is one factor in the initiation of nonshivering thermogenesis at birth.
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