Biomedical subjects
Publications and source records attributed to R D Milner.
Hypoglycin A(0.01--1.0 mmol/l) stimulated insulin release from pieces of rabbit pancreas in vitro in the presence or absence of extracellular glucose. The relevance of this finding to the hypoglycaemia of Jamaican vomiting sickness is discussed.
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Intraperitoneal transplantation of collagenase-digested, isogeneic, neonatal rat pancreatic tissue successfully reversed streptozotocin-induced diabetes in 77% of recipients. The low serum immunoreactive insulin, hyperglycaemia, glycosuria and weight loss, characteristic of the diabetic animal, were corrected and the reduced activities of hepatic glucokinase and pyruvate kinase, and the low glycogen concentration of the liver of diabetic rats were restored to normal. Forty-three per cent of the successfully transplanted rats became normoglycaemic within 1 month of transplantation whereas 57% took from 1 to 6 months to achieve normoglycaemia and displayed a mild glucose intolerance when subjected to a glucose load. The rats which had not become normoglycaemic 6 months after transplantation showed some amelioration of the diabetic state, as shown by increased serum immunoreactive insulin and hepatic glycogen concentration and a slow weight gain compared with diabetic controls.
Rat prolactin at a concentration of 50 ng/ml perfusion medium stimulated the production of somatomedin-like activity (SLA) from the perfused liver of normal rats. The effect was demonstrable in perfusions performed at 11.00 h in which rat prolactin caused a mean (+/- S.E.M.) increase in the uptake of [35S]sulphate into rat costal cartilage in vitro of 64 +/- 14% in comparison with controls, but at 15.00 h no effect was observed. No effect or rat prolactin on hypophysectomized rat liver was detectable at 11.00 h. Hypophysectomized and sham-operated rats were given five intravenous injections of 50 microgram rat prolactin or a similar volume of hormone solvent at 12 h intervals. Plasma somatomedin activity (SMA) and cartilage metabolism, measured by the uptake of radioactive sulphate and thymidine by costal cartilage in vitro, were similar in hypophysectomized animals given rat prolactin or hormone solvent. Sham-operated rats given rat prolactin showed a significant increase of plasma SMA and cartilage metabolism compared with control animals. The production of SLA by rat liver in response to rat prolactin may be related to the density of specific hepatic lactogenic receptors, since these are absent or present only in low numbers in hypophysectomized animals.
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A case of idiopathic arterial calcification is described in a dysmature infant dying of massive pulmonary haemorrhage on the fourth day after a gestation of 36 weeks. The mother had disseminated lupus erythematosis and lupus nephritis treated with large amounts of prednisolone. Unlike most of the previously recorded cases of idiopathic arterial calcification of infancy subintimal proliferation of fibrous tissue and involvement of the coronary arteries did not occur. It is suggested that this non-occlusive form of arterial calcification may be a distinct entity.
The work reviewed here illustrates how a therapeutic procedure, exchange transfusion of newborn infants, may be used to gather information which is both of practical value to infants treated in this way and also of value in the study of human neonatal physiology. The scientific deductions that can be drawn are weakened by the uncontrolled nature of the subjects available for study but this problem can be mitigated by changing one variable at a time between two groups of clinically similar infants undergoing transfusion and paying attention only to large changes in whatever is measured. In this way it has been possible to show that the glucose of ACD blood stimulates insulin and GH secretion and that the stimulation of insulin secretion is less, and that of GH more, if the transfusion is performed via the umbilical artery rather than via the vein. Arterial transfusions may be more stressful than venous ones since they are associated with greater growth hormone, ACTH and glucocorticoid release. Citrate, the other additive in ACD blood, causes a fall in ionised plasma calcium levels resulting in a stimulation of PTH secretion and mobilisation of calcium and phosphorus. Transfusion with heparinised blood is therefore preferred by some because normoglycaemia is preserved during and for three hours after transfusion, whereas post-transfusion hypoglycaemia may occur after ACD transfusion. However, heparin transfusion causes a marked rise in plasma FFA levels which may interfere with the binding of bilirubin by albumin. In either type of transfusion the side-effects may be minimised by feeding the baby afterwards, as soon as practicable. Thyroid hormones are washed out of the infant during transfusion but normal thyroid balance is restored quickly afterwards. The temperature of the donor blood does have thermal effects on the baby but these are less than might be expected due to the rapid equilibration of donor blood temperature with that of the room. The metabolic consequences of transfusion with cold blood are less than might be anticipated due in part to the glucose infusion that is part of an ACD transfusion.
Plasma adrenocorticotrophin (ACTH) and glucocorticoid concentrations were measured during and for 3 hours after exchange transfusion in four groups of infants. Transfusion with ACD blood via the umbilical artery were performed on 10 infants of 35--40 weeks gestation and 11 infants of 27 to 33 weeks gestation. Ten transfusions via the umbilical vein were performed with ACD blood and 9 with heparin blood on infants of 32 to 41 weeks gestation. In all four types of transfusion there was a significant washing out of ACTH and glucocorticoids from the baby. An associated rise of plasma ACTH and glucocorticoid levels indicated increased secretion in the larger infants transfused with ACD blood via the umbilical artery. Equivocal results were obtained in the other groups. After all types of transfusion plasma glucocorticoid levels remained relatively constant for one hour and then doubled and then doubled in the second and third hour. The results suggest that (a) exchange transfusion via the umbilical artery is more stressful than that via the umbilical vein, (b) the glucocorticoid response of premature infants to exchange transfusion is similar to that of mature ifants, (c) an unspecified stimulus, which is not solely hypoglycaemia nor the metabolic reaction to a citrate load, results in a rise in plasma glucocorticoid levels 2-3 hours after all types of transfusion.
Serial measurements of crying vital capacity (CVC), expressed as ml/cm chest circumference, were made by reverse plethysmography during the first 2 weeks of life. Clinically normal babies born at term by elective caesarean section had a smaller mean CVC in the first 2 weeks of life compared with clinically normal term babies born vaginally. In contrast, no significant difference was shown between the mean CVC in term babies born vaginally and those born by urgent caesarean section. Clinically normal term babies born by caesarean section (elective and urgent) had a smaller mean percentage rise of CVC in the first 24 hours of life and a significant delayed rise of CVC from 24-48 hours compared with those born vaginally. Clinically normal preterm babies born vaginally had a smaller mean CVC in the first 2 weeks of life compared with term babies born vaginally, and were characterized by a significant rise of CVC from 5-10 days. Babies with hyaline membrane disease (HMD) had a smaller CVC in the first 2 weeks of life compared with clinically normal preterm babies. Babies of various gestational ages with transient tachypnoea (TT) had a smaller mean CVC in the first 2 weeks of life compared with clinically normal term babies, but a similar mean CVC in the first 72 hours of life compared with clinically normal preterm babies. At each postnatal age the mean CVC of babies with HMD was less than the corresponding mean in babies with TT. All babies with TT had a rise in CVC from 24-48 hours, whereas CVC fell in all babies with HMD except one during this period. CVC is a simple, safe, rapid, and noninvasive test of neonatal lung function, and is a valuable aid to other methods of assessing pulmonary function in the neonate with respiratory distress.
Alterations of head shape in preterm, small-for-dates, and term normal infants were studied by measuring occipitofrontal circumference (OFC), biparietal diameter (BPD), and occipitofrontal diameter (OFD) at intervals after birth. In 9 preterm infants born by elective caesarean section ther was a 5-2% reduction in BPD and 2-0% reduction in OFC at the age of 7 days. In 18 term infants born by elective caesarean section these changes were 2-4% and 0% respectively in BPD and OFC. In 25 preterm infants born by vertex vaginal delivery there was a significant fall in OFC of 0-7% at the age of 7 days and of 2-4% in BPD, but no significant change in OFD. In 19 small-for-dates infants born vaginally OFC increased 1-0% and OFD 2-7% at 7 days, but BPD decreased 2-5%. After the first week all three measurements increased in both groups of vaginal deliveries. The results show that shrinkage and biparietal flattening of the skull occur during the first week of life in preterm and term infants born by caesarean section and in preterm infants born vaginally. This fact should be borne in mind when comparing the measurements of an infant's head size with published norms.
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A retrospective study of 1423 liveborn breech deliveries occurring in one hospital from 1964 to 1973 inclusive showed that application of forceps to the aftercoming head of infants between 1 and 3 kg birth weight was associated with a significant reduction in neonatal mortality.
Nineteen exchange transfusions were performed via the umbilical artery using blood preserved with acid-citrate and dextrose in 8 infants of 34-40 weeks gestation (larger infants) and 9 very small infants of 26-33 weeks gestational age. The plasma glucose rise which was similar in both groups stimulated insulin secretion from the larger infants but not the very small infants. No significant differences occurred between the groups in the fall in mean free fatty acid levels or increase in growth hormone secretion. Following transfusion there was a sharp rise in mean plasma insulin concentration in the larger infants and a smaller rise in the very small infants. A highly significant positive correlation was found between the maximum posttransfusion plasma insulin and the birth weight of the infants. Plasma glucose levels of less than 30 mg/100 ml occurred in 2 larger and 5 very small infants during the first 3 hours after transfusion. One infant of birth weight 0.98 kg received four transfusions; in 2 where he received ACD blood via the umbilical artery or vein, insulin secretion was not stimulated but in the other 2 in which glucagon or arginine was added to the ACD donor blood, insulin secretion was stimulated. Feeding practice should take account of the fact that although very small infants secret less insulin than larger infants during exchange transfusion they are more likely to become hypoglycaemic in the immediate posttransfusion period.
The changes in plasma thyroid hormone concentration were studied during exchange transfusion performed for haemolytic disease. 24 transfusions were performed using blood preserved with acid-citrate and dextrose and in 11 cases 10 or 50 mug glucagon was added to the donor blood. Plasma tri-iodothyronine (T3), thyroxine (T4), thyrotropin (TSH), thyroid hormone binding capacity, and free thyroxine index were measured in the donor blood and in the infant at the start and at intervals during the transfusion. Before transfusion the plasma TSH levels of the infants fell as postnatal age indreased and plasma T3 and T4 were correlated with one another. In 20 transfusions the mean infant/donor ratio of TSH was approximately 10, of T4 3, and of T3 2. During these transfusions there was a progressive fall in the infant's plasms TSH, T4, and T3 concentration. In 3 transfusions in which the donor plasma TSH was greater than that of the infant, plasma TSH levels rose during the transfusion and in 2 cases this was associated with a late rise in plasma T3 levels. The addition of glucagon to donor blood had no effect on thyroid hormone levels. It is concluded that erythroblastotic infants have normal thyroid function and that they became biochemically hypothyroid during transfusion. Acute changes in plasma thyroid hormone and glucagon concentration do not induce TSH responses by the neonatal pituitary during the period of the exchange transfusion.
The relation between fetal distress and the subsequent condition at birth was studied in 2791 pregnancies. Fetal distress was defined as a heart rate greater than 160 or less than 120/min between uterine contractions, with or without meconium-stained liquor. Infants of 28 to 42 weeks' gestational age were examined at 1 and 5 minutes after birth when the heart rate, respiration, and skin colour was recorded. Birth scores of 0, 1, or 2 were given respectively if respirations were absent, gasping, or regular; if the heart rate was undetectable, less than 100/min, or greater than 100/min; and if the colour was white, blue, or pink. Fetal distress was associated with low birth scores in infants at 1 and 5 minutes of age. Among those who had not suffered fetal distress a significantly greater proportion of preterm infants had low birth scores compared with term or post-term infants at 5 minutes of age. Infants did not score equally for colour, heart rate, and respiration at 1 and 5 minutes of age. Colour usually gave a birth score of 5 and heart rate was recordable when infants scored 0 for colour and respiration. The reduction in birth scores was greater in the presence of meconium-stained liquor and abnormal fetal heart rate than meconium-stained liquor alone; the latter being an early sign of fetal distress. Since fetal distress was not diagnosed by conventional methods in 93 term infants who probably suffered prenatal asphyxia, more sophisticated techniques are necessary for an accurate assessment of fetal condition during labour.
Plasma concentrations of calcium, phosphate, citrate, albumin, and parathyroid hormone (PTH) were measured during and after exchange transfusion of infants suffering from haemolytic disease using blood anticoagulated with acid-citrate and dextrose (ACD) or heparin. Pretransfusion plasma PTH and phosphate both correlated positively with postnatal age but not with each other. Transfusion with ACD blood caused a twelvefold rise in plasma citrate levels but no significant change in plasma calcium, phosphate, or PTH of the infant, despite the concentration of these substances being lower in the donor blood. The concentration of calcium, phosphate, and albumin was higher in heparinized than in ACD donor blood, and infants transfused with heparinized blood showed no change in the plasma concentration of any substance measured during transfusion. The addition of 50 mug glucagon to ACD donor blood had no effect on PTH secretion. 3 hours after transfusion there was a rise in the plasma PTH infants who had received ACD blood but not in those given heparinized blood. Transfusion with ACD blood caused a net loss of calcium, phosphate and albumin from the infant, whereas transfusion with heparin blood did not. Both types of transfusion caused a net loss of PTH but this was significantly greater in those given ACD blood. These results show that transfusion with ACD blood results in increased secretion of PTH, probably due to the fall in ionized calcium concentration caused by the citrate load.