Adrenal Cortical Function in Children on Steroids

Adrenal cortical function was assessed in 20 children receiving 2·5 to 10 mg. prednisolone daily, by measuring plasma cortisol levels before and after the administration of the synthetic polypeptide β^1-24, tetracosactrin (Synacthen). 18 of the children were asthmatics, one had nephrosis, and one had dermatomyositis.Adrenal function was classified as (a) abnormal response to tetracosactrin, where basal plasma cortisol and post-tetracosactrin levels did not exceed 6 μg./100 ml.; (b) partial response, where there was a rise of 5-10 μg./100 ml. in plasma cortisol following tetracosactrin but the basal levels (< 10 μg./100 ml.) were below or only slightly above the lower normal limit; (c) normal response, where there was usually at least a doubling of the basal value and an incremental increase of at least 10 μg./100 ml. in the plasma cortisol concentrations following tetracosactrin.All 6 children receiving the higher dosage of 10 mg. prednisolone daily had abnormal adrenal function. 4 receiving the lower dosage of 2·5 mg./day had satisfactory adrenal reserve. Of the 10 children receiving the intermediate dosage of 5 mg. prednisolone daily, 2 had frankly abnormal adrenocortical function, 3 had poor adrenal reserve, and 5 produced good incremental values, though their baseline cortisol levels were low. At the 5 mg. prednisolone dose adrenocortical suppression was not correlated either with duration of therapy or with age.     

Does a single plasma phenylalanine predict quality of control in phenylketonuria?

A 1993 MRC working group on phenylketonuria suggested standardising blood phenylalanine measurements by taking blood samples at the same time each day. Since it is not known how representative of a 24 hour period a single phenylalanine concentration is, the aim of this study was to investigate the 24 hour variability of plasma phenylalanine in well controlled children with phenylketonuria. Sixteen subjects, 12 girls and four boys aged 1 to 18 years, had hourly venous blood samples collected for 13 hours between 09.00and 21.00 on one day. Serial skin puncture blood specimens were then collected at 24.00, 03.00, and 06.00 within the same 24 hour period. All food and drink was weighed. The median variation in plasma phenylalanine concentration was 155 µmol/l/day, with a minimum of 80 and a maximum of 280. The highest concentration occurred in the morning between 6.00 and 9.00 in 63% of subjects; the lowest occurred between midday and midnight in 94%. Concentrations < 100 µmol/l occurred in 46% of children below 11 years, three having concentrations < 30 µmol/l for two, six, and seven hours respectively. Three of five subjects had concentrations above the MRC guidelines for 24% of the period studied. Except in two subjects, the blood concentrations did not rise in response to phenylalanine consumption. However, the greater the quantity of protein substitute taken between waking and the 16.00 specimen, the larger the decrease in daytime phenylalanine concentration (r = −0.7030) (p < 0.005). There is therefore wide variability in phenylalanine concentrations in a 24 hour period in children with phenylketonuria which is not reflected in a single observation. Further study is needed to investigate the effects of timing of protein substitute on the stability of phenylalanine concentrations.

     

Haemoglobin Levels in Cardiff Children of Nursery School Age

A study of 1074 apparently healthy children aged 2 to 5 years revealed a wide range of haemoglobin, extending from 6·8 g/100 ml to 15·6 g/100 ml. The mean Hb was 12·3 g/100 ml, with only minor variations for age, sex, and season. A significant increase in the Hb followed iron administration if the initial Hb was less than 10·5 g/100 ml, but there was no rise in the mean value if the initial level exceeded 12·5 g/100 ml. Taking 10·5 g/100 ml as the level below which anaemia is deemed to exist, 5·2% of the total study population were anaemic, compared with 0·3% in private nurseries, 3·7% in local authority nurseries, and 15% of infants on admission into the care of residential nurseries.     

Hyperlactataemia during intravenous feeding in childhood

A recently introduced synthetic amino acid preparation, Aminoplex 5, appeared suitable for use in intravenous feeding in childhood because it has a low sodium concentration and high caloric value, achieved by using sorbitol and ethanol. The effects of a 2-hour infusion of Aminoplex 5 at 5 ml or 10 ml/kg per hr on the concentrations of several blood metabolites and hormones were investigated in 8 children. All the children showed a rise in blood lactate concentration (range of increase 0·23 to 6·72 mmol/l.) and lactate/pyruvate ratio (range of increase 2·5 to 18·0) and a small consistent fall in blood acetoacetate concentration. The effects were dose related. Free blood fructose was shown in 7 children after Aminoplex 5, the only exception being a preterm infant. No significant changes were found in plasma insulin or growth hormone concentrations. We suggest that the use of this preparation should be accompanied by frequent estimations of blood lactate or acid-base status.     

Clinical Pharmacology of Gentamicin in the Newborn Infant

Newborn infants with suspected bacterial infection were treated with intramuscular gentamicin. Serum levels of the drug were measured 1 hour after the first dose, immediately before the second dose, and immediately before and 1 hour after a dose given on the third day.On a low dosage regimen (1 mg/kg every 8 hours) 9 of 17 infants had serum gentamicin levels below the required minimum level of 1 μg/ml immediately before the second dose, and 5 of 19 infants had similarly low levels on the third day. On a high dosage regimen (3 mg/kg initially, then 2 mg/kg every 8 hours) 2 of 10 infants had preinjection serum gentamicin levels below 1 μg/ml on the first day, and 3 out of 16 had similar levels on the third day. The mean (± SE) serum gentamicin level on the high dosage regimen was 5·0 ± 0·5 μg/ml 1 hour after the first injection, 1·9 ± 0·4 μg/ml just before the second injection, and on the third day 1·9 ± 0·3 μg/ml just before an injection and 5·1 ± 0·5 μg/ml 1 hour after injection. The highest serum gentamicin level recorded in any of the 40 infants studied was 8·2 μg/ml.On the first day of treatment with the low dose regimen, a mean of 21% (range 9-68%) of the injected dose was recovered from the urine; and on the third or fourth day a mean of 44% (range 17-76%) of the gentamicin injected on that day was recovered.In 4 infants who died tissue gentamicin levels were measured in the liver, lungs, heart, kidneys, and brain, the highest concentration being in the kidney with low levels in the heart, liver, and brain, while levels in the lungs were intermediate. Neonatal renal and pulmonary infections are thus likely to be suitably treated with gentamicin.Bacteriological studies confirmed the effectiveness of gentamicin in the treatment of neonatal infection, but a dosage regimen derived by extrapolation from older children frequently resulted in inadequate serum levels, and a higher dosage regimen giving more satisfactory results was therefore defined.     

Role of Counterregulatory Hormones for Glucose Metabolism in Children and Adolescents with Type 1 Diabetes

To elucidate the mechanism of insulin resistance due to insulin counterregulatory hormones (ICRHs) and evaluate ICRH secretion kinetics, ICRH concentrations were measured and correlated with blood glucose levels in 28 type 1 diabetic patients. Blood glucose was measured before bedtime. Early morning urine samples were collected the next morning before insulin injection and breakfast. Fasting blood glucose, cortisol, glucagon and HbA1c levels were measured. Growth hormone (GH), adrenaline, cortisol and C-peptide levels in morning urine samples were measured; SD scores were calculated for urine GH. The laboratory values (mean ± SD) were as follows; HbA1c of 8.1% ± 1.4%; pre-bedtime glucose of 203 ± 105 mg/dl; fasting blood glucose of 145 ± 87 mg/dl; serum cortisol of 21.6 ± 5.5 µg/dl; plasma glucagon of 98 ± 41 pg/ml; urinary GH, 27.2 ± 13.0 ng/gCr; urinary cortisol of 238 ± 197 ng/gCr; and urinary Adrenaline of 22.9 ± 21.0 ng/gCr. The mean urinary GH SD score was increased (+1.01 ± 0.70; p=0.000); the mean plasma glucagon lebel (98 ± 41 pg/ml) was not. Fasting blood glucose was positively correlated with plasma glucagon (R=0.378, p=0.0471) and negatively correlated with urinary cortisol (R=–0.476, p=0.010). Urinary adrenaline correlated positively with urinary GH (R=0.470, p=0.013) and urinary cortisol (R=0.522, p=0.004). In type 1 diabetes, GH, glucagon and cortisol hypersecretion may contribute to insulin resistance, but the mechanism remains unclear.     

Five-hour Oral Glucose Tolerance Test in Obese Children

Concentrations of blood glucose, plasma free fatty acids, and plasma glycerol during a 5-hour oral glucose tolerance test on 46 obese children are reported.Seven children had unequivocally impaired glucose tolerance. However in the group as a whole, there was a delay in return of blood glucose to baseline levels after oral glucose, 27 children (60%) having a blood glucose concentration greater than 110 mg/100 ml at 2 hours. It was concluded that some degree of glucose intolerance is common in childhood obesity. No relation was seen among the following: impairment of glucose tolerance and age, degree or duration of obesity, or family history of diabetes.Fasting plasma free fatty acids and glycerol concentrations were high (mean ± 1SD, 1030 ± 221 μEq/litre FFA and 121 ± 44 μmol/l. glycerol). For all children, concentrations of FFA and glycerol decreased during the first hour after glucose, though minimal levels were not reached until 90-120 minutes (mean ± 1SD, 395 ± 170 μEq/litre FFA, 77 ± 24 μmol/l. glycerol). For those children (27) who had raised blood glucose at 2 hours, there was a positive correlation between fasting plasma glycerol concentration and glucose tolerance sum, suggesting that impaired glucose tolerance was associated with increased basal lipolysis.     

Effect of Human Growth Hormone Treatment for 1 to 7 Years on Growth of 100 Children,with Growth Hormone Deficiency,Low Birthweight,Inherited Smallness,Turner's Syndrome,and Other Complaints

(1) Human growth hormone (HGH) has been given for one whole year or longer to 100 patients, aged 1·5 to 19 years, participating in the Medical Research Council Clinical Trial of HGH. Each patient was measured 3-monthly for a control year before treatment, and the majority for a control year after the first treatment year. All measurements were made by one anthropometrist. Radiographic measurements of widths of bone, muscle, and fat in calf and upper arm were made. Methods and standards for assessing the significance of a given height acceleration are presented.(2) The characteristics at diagnosis are given of 35 patients with isolated GH deficiency or hyposomatotrophism (HS), 18 with craniopharyngiomas and other CNS lesions, 3 with multiple trophic hormone deficiency, 18 with low birthweight short stature, 4 with hereditary smallness and/or delay in growth, 4 with psychosocial short stature, 1 with high resting HGH and low somatomedin, 6 with Turner''s syndrome, and 11 with other diagnoses.(3) 29 of the 35 HS patients were boys and 13 had an abnormally small penis and ill-developed scrotum. Only 2 were sibs. Parents averaged 40th centile for height. 4 children developed growth-suppressing antibodies, and had to cease treatment. The mean standard deviation score (SDS) for height at diagnosis was -4·7, range -2·6 to -7·3. Bone age SDS averaged -3·2, range -0·8 to -5·7. Skinfold SDS averaged +0·91. Limb muscle width SDS averaged about -3·0. GH peak in insulin hypoglycaemia averaged 4·7 ± 0·7 μU/ml, range 1 to 13.(4) A category of partial growth hormone deficiency is defined as patients with GH peaks of 7-20 μU/ml inclusive and height velocity SDS in the year before treatment between -1 and -2. Total HS patients have GH peaks of 1 to 6 μU/ml inclusive and height velocity SDS of < -2. Partial HS patients are accelerated by HGH and should be treated; but their average acceleration is below that of total HS patients.(5) There was a highly significant relation (r = -0·64) between blood GH peak level and pretreatment height velocity in the HS patients.(6) The LBW patients were 10 boys and 7 girls; all the boys had normal genitalia. The average height SDS at diagnosis was -3·7; parents'' height centile averaged 50th, bone age SDS -1·8, skinfold SDS -0·9. GH peaks were all above 30     

URINARY PHENYLALANINE EXCRETION IN HYPERPHENYL-ALANINEMIC CHILDREN

24-hour phenylalanine loading tests were done in 5 children with persistent hyperphenyl-alaninemia off diet. The urinary excretion of phenylalanine were compared to the excretion after loading of phenylketonuric children on diet. Serum phenylalanine of children with persistent hyperphenylalaninemia returned to preloading levels (285 μmol/l) within 24 hours. These children, however, excreted phenylalanine during phenylalanine loading in lesser quantities than patients with phenylketonuria on diet. Serum phenylalanine of phenylketonuric children on diet attained preloading levels (300 μmol/l) approximately 14 days after loading. Thus, the present data do not support the hypothesis that hyperphenylalaninemic patients are phenylketonurics protected by increased urinary excretion of phenylalanine.     

Early albumin infusion to infants at risk for respiratory distress

In a randomized prospective study, 100 high-risk infants (selected on the basis of a cord serum protein level of 4·6 g/100 ml or less, gestational age under 37 weeks, birthweight 2500 g or less, and/or arterial pH below 7·25) received 8 ml/kg of either 25% salt-poor albumin or 5% dextrose in water before the age of 2 hours. All infants were then managed supportively with warmth, appropriate oxygen supplementation, isotonic fluid infusion, and close monitoring, without further administration of colloid or hypertonic alkali solutions over the first 4 hours of life.     

Plasma 17-hydroxyprogesterone in newborn infants with congenital adrenal hyperplasia and in infants with normal adrenal function

Plasma 17-hydroxyprogesterone (17-OHP) was estimated in 9 infants aged 6 to 12 days with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. Raised plasma 17-OHP values, ranging from 3·4 to 25·0 μg/100 ml were found. 50 infants aged 10 hours to 15 days with normal adrenal function were also studied. One infant with galactosaemia had 17-OHP levels of 1·8 and 2·4 μg/100 ml, and a further 3 infants aged 15 hours to 3 days had 17-OHP levels between 1·1 and 2·1 μg/100 ml. In the remaining infants, plasma 17-OHP was less than 1·0 μg/100 ml. It therefore appears that estimation of plasma 17-OHP provides a useful method for confirming the diagnosis of CAH during the newborn period.     

Family Social Status and Dietary Adherence of Patients with Phenylketonuria

Objective

There are several problems associated to the management of patients with phenylketonuria (PKU). Social status could be one of the affecting factors on dietary adherence in these patients. The aim of this study was to evaluate family social status and dietary adherence of PKU patients in Iranian population.

Methods

In a cross-sectional study, we studied 105 Iranian PKU patients (born 1984 to 2010), treated and followed at Mofid Children''s Hospital, Tehran. Social status was defined by number of children in family, number of affected children in family, maternal and paternal education, marital and employment status of the parents. Age at diagnosis and duration of treatment were also recorded. Mean plasma phenylalanine level was considered as a sign of dietary adherence in PKU patients and was calculated considering the phenylalanine measurements throughout at least one year.

Findings

Mean plasma phenylalanine concentration was 5.9±3.6 mg/dl in patients <12 years old and 13.1±3.9 mg/dl in patients >12 years old. Blood phenylalanine concentrations in 47.6% of patients were in normal age-related reference range. There was a significant association between divorced and unemployed parents, and higher levels of blood phenylalanine concentration (P=0.02 and P=0.03 respectively). There was a significant positive correlation between number of affected children in the family (r=0.43, P<0.001), age at diagnosis (r=0.2, P=0.03), treatment duration (r=0.7, P=<0.001) and blood phenylalanine concentrations. There was no significant relation between parental education, family size and dietary adherence.

Conclusion

Social status affects dietary adherence to some extent. We suggest exploring care-givers dietary knowledge as the next step to improve dietary compliance in these patients.     

Phenylketonuria masked by low protein feeds.

Two patients with phenylketonuria (PKU) requiring treatment were fed on low protein milks. Both had blood phenylalanine levels below 1200 micronmol/l (20mg/100 ml) until given a phenylalanine challenge. Phenylalanine content of mature breast milk may provide intakes similar to those used in treating PKU. Diagnosis of PKU is unlikely to be missed if screening is carried out on the sixth or seventh day of life because of higher phenylalanine in breast milk during the first week. Interpretation of screening tests requires knowledge of the infants'' feeds and a blood phenylalanine above 360 micronmol/l (6 mg/100 ml) in the absence of tyrosinaemia requires careful investigation.     

PHENYLKETONURIA: REDUCTION OF SERUM LEVELS OF PHENYLALANINE FOLLOWING ORAL ADMINISTRATION OF B-2 THIENYLALANINE

8 mentally retarded but otherwise healthy phenylketonuric individuals were given two oral loads of phenylalanine (100 mgm/Kg). One of these loads was accompanied by β-2-thienylalanine (20 mgm/Kg). Blood levels of phenylalanine in the 6 hours after the two phenylalanine loads were compared. β-2-thienylalanine reduced the levels of phenylalanine in every case. This suggests that if the phenylketonuric child were to take an appropriate amount of β-thienylalanine with meals, he might be able to eat more phenylalanine, and this would allow a considerably more liberal diet. As diet has been shown to be a dominant factor in the emotional climate of families of phenylketonuric children, this stress would be considerably reduced. Thus, the administration of β-thienylalanine might lead to a more normal social development of the patient.     

Comparison of dried milk preparations for babies on sale in 7 European countries: II. Folic acid,vitamin B6, thiamin,riboflavin, and vitamin E

Four vitamins of the B-complex—thiamin, riboflavin, vitamin B₆, and folate—were measured in 30 dried milk preparations for babies, representing products of manufacturers in 7 European countries. 7 of the preparations were also assayed for vitamin E. The milks varied widely in their B-vitamin composition. The content of riboflavin ranged from 2·8 to 11·2 μg/g, thiamin from 2·8 to 13·0, vitamin B₆ from 1·5 to 12·7, and folate from 0·03 to 1·12.Compared on a basis of equal solids content, all the preparations were considerably richer than mature human milk in thiamin and vitamin B₆, and most were similar to human milk in their content of riboflavin, though a few were markedly higher. With folate the findings were less reassuring. In 3 of the products the content was close to that in goat''s milk, which may cause folate-deficiency anaemia in infants. In a further 8 the content was less than 60% of that in human milk.The 7 products tested showed marked differences in vitamin E content. In 4, which contained cow''s milk fat only, the vitamin E content was 0·70-0·83 mg α-tocopherol equivalents/100 g as against 2·33 mg/100 g solids in human milk. The remaining 3 products contained vegetable oils and were considerably richer, with 4·77-10·21 mg/100 g.     

Urinary excretion of calcium and magnesium in children

Urine calcium excretion in healthy children was 2·38±0·66 (SD; no. = 52) mg/kg per 24 hr and urinary magnesium excretion was 2·82±0·79 (SD; no. = 23). The 24-hour urine calcium excretion could be predicted with reasonable confidence from the calcium/creatinine concentration ratio of the second urine specimen passed in the morning. In this specimen the urine calcium/creatinine concentration ratio was 0·14±0·06 (SD; no. = 60) mg/mg and the magnesium/creatinine concentration ratio was 0·21±0·10 (SD; no. = 29) mg/mg.The upper limit of the urine calcium excretion is taken to be 4 mg/kg per 24 hr and that of the calcium/creatinine concentration ratio in the second morning urine is 0·25 mg/mg. After a milk load of 700 ml/1·73 m² the urinary calcium/creatinine concentration ratio rose in the first two hours, but in no sample exceeded 0·25 mg/mg.     

Antibody persistence and Haemophilus influenzae type b carriage after infant immunisation with PRP-T

OB JECTIVES—To assess the persistence of serum Haemophilus influenzae type b antibodies and the prevalence of H influenzae type b carriage in a group of preschool age children previously vaccinated in infancy.
DESIGN—Names were randomly selected from immunisation records. Families were visited on five occasions over a period of 12 months and throat swabs were taken from all family members present, with blood obtained from children at the first and last visits.
RESULTS—One hundred and fifty three children at a median age of 3.6 years had a geometric mean titre (GMT) of 1.06 µg/ml (95% CI 0.80to 1.38). Eight per cent had an undetectable antibody concentration, received a booster dose of plain PRP vaccine, and responded with concentrations > 2 µg/ml. GMT at 4.5 years of age was 0.89 µg/ml (0.69 to 1.16). Twelve children who had been exposed to H influenzae had a GMT of 4.7 v 0.8 µg/ml for those without exposure.
CONCLUSIONS—Accelerated immunisation against H influenzae without a second year booster results in persistence of satisfactory serum concentrations of antibody to 4.5 years of age. In those with undetectable antibody, immunological memory may still be present.

     

Cord haemoglobin in low birthweight infants

Cord haemoglobin was measured in 349 low birthweight infants born after a pregnancy lasting 28 to 41 weeks inclusive. 82 babies were small-for-dates and were born after 36 weeks'' gestation; their Hb was not related to sex or duration of pregnancy, but there was a negative correlation with placental weight and placental weight/birthweight ratios. The mean Hb of small-for-dates babies (17·09±2·11 g/100 ml) was higher than for comparable normal babies (16·24±2·26 g/100 ml).In normal-for-dates females there was a linear relation between Hb and duration of pregnancy approximately expressed by: cord Hb (g/100 ml) = 7 + gestational age in lunar months. In males a plateau Hb of 16·22 g/100 ml was reached at 32 weeks.     

Congenital heart disease in maternal phenylketonuria: report from the Maternal PKU Collaborative Study

The frequency and types of congenital heart disease in offspring from pregnancies in women with hyperphenylalaninemia were examined in the international prospective Maternal Phenylketonuria Collaborative Study. Relationships of congenital heart disease in offspring to the basal blood phenylalanine level in the mother, metabolic control through diet during pregnancy, and phenylalanine hydroxylase mutations in mother and offspring were determined. The 416 offspring from 412 maternal phenylketonuria pregnancies that produced live births and 100 offspring from the 99 control pregnancies were included in this examination. Thirty-four of the 235 offspring (14%; 95% CI, 10.2 to 19.6%) from pregnancies in phenylketonuric women with a basal phenylalanine level > or = 900 microM (15 mg/dL) [normal blood phenylalanine < 120 microM (2 mg/dL)] and not in metabolic control [phenylalanine level < or = 600 microM (10 mg/dL)] by the eighth gestational week had congenital heart disease compared with one control offspring (1%) with congenital heart disease. One offspring among the 50 (2%) from mothers with non-phenylketonuria mild hyperphenylalaninemia also had congenital heart disease. Coarctation of the aorta and hypoplastic left heart syndrome were overrepresented compared with expected percentages among those with congenital heart disease in the general population. A basal maternal phenylalanine level > 1800 microM (30 mg/dL) significantly increased the risk for bearing a child with congenital heart disease (p = 0.003). Phenylalanine hydroxylase mutations in the mothers and offspring did not have an independent relationship to congenital heart disease but were related through the basal maternal phenylalanine levels. The data in this study indicate that a basal maternal phenylalanine level of 900 microM may be a threshold for congenital heart disease, that women with the most severe degree of phenylketonuria are at highest risk for bearing such a child, and that prevention of the congenital heart disease requires initiation of the low phenylalanine diet before conception or early in pregnancy with metabolic control no later than the eighth gestational week.     

Insulin Resistance during Puberty in Non-obese Japanese Children

We examined whether non-obese Japanese children without diabetes exhibited insulin resistance during puberty. The study subjects were 201 Japanese school students, consisting 95 males and 106 females, aged 11.5 ± 2.6 yr. None of the subjects were obese, with the mean percent of overweight being 0.7 ± 10.5%, or had diabetes at the time of the study. Overnight fasting plasma values of insulin (FIRI) and HOMA-R were measured, with concomitant measurement of the plasma glucose (FPG) levels. The mean FPG, FIRI and HOMA-R values were 89.6 ± 7.3 (70–109) mg/dl, 9.0 ± 3.6 (1.7–24.4) µU/ml and 2.0 ± 0.9 (0.3–5.2), respectively. The mean FIRI value was significantly higher in females than in males (8.3 ± 3.4 vs. 9.6 ± 3.7 µU/ml, p=0.0060). The FIRI and HOMA-R values of the pubertal students were significantly higher compared with those of the prepubertal students (FIRI, 10.0 ± 3.4 vs. 6.5 ± 2.8 µU/ml; HOMA-R, 2.3 ± 0.8 vs. 1.4 ± 0.7; p<0.0001 for both). Similar trends were observed between the two genders. The mean FIRI levels and HOMA-R values were positively correlated with age (FIRI, r=0.280, p<0.0001; HOMA-R, r=0.300, p<0.0001). In conclusion, we demonstrated that the FIRI and HOMA-R values were significantly associated with pubertal development in non-obese Japanese children without diabetes, consistent with the results of studies in white and black children.