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γ-Glutamyl transpeptidase (GGTP) activity in normal amniotic fluids and corresponding maternal sera obtained at various gestational periods was measured. The ontogenic pattern of enzyme activity in amniotic fluid is very similar to alpha fetoprotein (AFP). However, the levels of these two proteins behaved differently in corresponding maternal sera. Also, in amniotic fluids obtained from pregnancies with neural tube defects (NTD), only AFP concentration was abnormally high whereas GGTP activity was normal.

A newborn infant had an unusual reversible complication caused by light therapy for hyperbilirubinemia. A dark grey-brown color of the skin, urine, and serum developed on the fifth day, after 24 hours of light therapy. Serum bilirubin (direct and total), SGOT, and LDH were elevated. The infant recovered, and bilirubin and enzymes returned to normal after a period of three weeks. A possible pathologic mechanism for this complication is suggested.

Summary A patient with galactosemia presenting with bilateral pedal gangrene and ascites is presented. The cause of gangrene is obscure, but it may be presumed to be due to sepsis associated with multiple small venous and capillary thromboses.

13 short children aged 7-13 years who had a retarded bone age and low hair zinc concentration (under 140 micrograms/g) were treated with oral zinc supplements for a year. There was a significant increase in the growth rate in the children whose hair zinc concentration increased. Growth hormone, testosterone and somatomedin C also increased after oral zinc supplementation. Data from 755 short healthy children who have attended our Growth Clinic are presented which describe their hair and serum zinc concentration at different ages. The data indicate a decline in hair zinc concentration after birth with a gradual increase at age 4-6 years, finally reaching adult normal levels after adolescence.

Using atomic absorption spectrophotometry, we have assayed zinc and copper concentrations in the hair of children with typical achondroplasia, familial short stature, or constitutional growth delay, and of unaffected parents of achondroplastic children and healthy adults of similar age and sex as the parents (Table). Specimens consisted of the terminal 2 to 3 inches of hair, obtained from the posterior scalp. Duplicate 60 to 80 mg hair specimens were digested in concentrated nitric:perchloric (3:1) acid mixture. The results are the mean of at least two determinations per specimen. The achondroplastic children were all confirmed as typical examples by physical examination and radiographs of skull, spine, long bones, and pelvis. Several of the parents were noted to have white flecks in their fingernails, which has been reported to be associated with zinc deficiency. The data indicate significantly reduced zinc and increased copper values, and reduced zinc:copper ratio, in the hair of parents and children with achondroplasia.

A 14-year-old girl and a 13-year-old boy were found to be growth hormone deficient by insulin-arginine stimulation tests, and were also found to be zinc deficient. When oral zinc replacement was given, they both had a significant increase in growth rate which continued for at least 2 years, and subsequent growth hormone tests were normal.

This rare syndrome is characterized by short stature, sparse, fine scalp hair, a pear-shaped nose, long philtrum, normal intelligence, and cone-shaped epi physes of the phalanges with deformities of the fingers.

Premature infants have a lower selenium concentration in serum than full-term infants and children. The selenium concentration goes down quickly in infants treated for respiratory distress syndrome without supplementation. One premature infant with bronchopulmonary dysplasia had persistently low concentrations of selenium. Vitamin E supplements did not affect the serum selenium concentration in healthy premature infants. Supplementation with 3 µg/kg of selenium in parenteral fluids prevented the fall in the concentration seen in other infants not supplemented. Premature infants and especially those treated withoxygen may warrant selenium supplementation to the parenteral nutrition solution. Vitamin E supplements alone are apparently not sufficient to prevent selenium deficiency and potential oxygen toxicity.

Zinc levels were measured in hair and serum of boys with constitutional growth delay and familial short status and in several boys before and after oral administration of methyltestosterone. These results show the following: (1) zinc levels in boys beyond stage 3 of genital development are significantly higher than in stage 1 and 2; (2) there is a linear relationship between zinc levels and serum testosterone concentration (up to 250 ng/dL); and (3) methyltestosterone administration raised the zinc concentration in serum and hair, especially in boys with constitutional growth delay. Therefore, increased endogenous production or exogenous supply of testosterone are associated with increased zinc levels. We speculate that the relative testosterone deficiency and hypogonadotropism seen in constitutional growth delay may result in decreased zinc levels, which in turn could cause a further delay in the appearance of secondary sexual characteristics and greater growth retardation.

CAT-SCRATCH fever is usually a nonbacterial regional lymphadenitis that occurs one or two weeks after a scratch by a cat. The course is variable and may last for a few weeks to months. The etiology...

Interest in human nutrition has been gaining rapidly in recent years. From the youngest child and oldest man, from the earliest grade school student to the most sophisticated graduate student, from the politician to the scientist, from the pulpit and at the autopsy table, we are all being bombarded with modern suggestions, theories, and recommendations that will improve human nutrition and prolong good health and life. While the food industry continues to advise the public, scientists lament the lack of nutrition education in medical schools. Parenteral Nutrition At the Maimonides Medical Center Symposium on Nutrition of the Fetus, Infant, and Child, 1973 (Brooklyn, NY, May 1973), Gilbert Forbes, MD (University of Rochester) proposed the goddess "Nutrix" for our consideration. Worship of this goddess by scientists, by millions of Americans, and by advertisers has resulted in a religion based upon faith rather than facts. How we eat and what we order

17 children between 5 and 15 years of age received mazindol for one year (2 mg daily). Their height was carefully evaluated by 2 physicians at 6 month intervals, and they were observed for the following year without any therapy. In each case, the growth rate slowed during mazindol administration (0.6 in/yr) compared to the previous year (1.5 in/yr). Assays of growth hormone during mazindol administration demonstrated reduced responses to insulin hypoglycemia and arginine (2 patients) and exercise (3 patients). It seems likely that mazindol reduces growth by increasing nor-epinephrine in the ventromedial nucleus of the hypothalamus, and it is interesting that increasing dopamine in that nucleus stimulates growth hormone release.

Perinatal stress may induce a surge of hormonal responses which includes the thyroid hormones. Information is inadequate with regard to the surge of thyroid hormones at the time of delivery as it relates to the type of CS. We studied 33 motherinfant pairs who had elective (E) or primary (P) CS. The infants studied had (x) gestational age of 38.0 wk. All thyroid hormone measurements made on venous cord blood obtained immediately after delivery on two CS groups follow (X±SEM): The following is comparative serum TSH concentrations (X±SEM) of subgroups of infants who underwent CS delivery with and without preceeding labor: The data suggest that labor may suppress TSH and the events surrounding the primary CS stimulates this surge at the time of delivery. The mechanism operative is not clear and needs further study.

A pituitary evaluation was carried out in a 12-year-old girl who had early puberty, short stature, optic nerve hypoplasia, and agenesis of the corpus callosum. Her growth hormone (GH) response to insulin-induced hypoglycemia and arginine infusion was blunted. Basal and stimulated levels of prolactin were elevated. The association of GH deficiency and hyperprolactinemia suggests a disruption of the dopaminergic modulation of these hormones. The facial features seen in our patient, such as hypertelorism, V-shaped frontal hairline, and cleft nose and upper lip, are enough to justify the diagnosis of median cleft face (MCF) syndrome. However, the optic nerve hypoplasia and the GH deficiency are characteristics of septo-optic dysplasia, and, to our knowledge, they have never been described in patients with MCF syndrome. Our case fulfills the diagnostic criteria of both, representing a link between both ends of this spectrum.

Zn deficiency has been reported in infants with BD and in children born with achondroplasia. 304 families were studied comparing parental age, Zn nutritional status and infant weight at the time of birth. There is a statistically significant correlation (p < .01) between infant hair Zn and maternal age at time of birth. The decrease in infant hair Zn seen with teenage (14-20) and elder mothers (31-40) may be related to the incidence of increased BD which occurs in these groups. Infant hair Zn was lowest in the heaviest infants and in a group with BD made up of porencephaly, anencephaly and microcephaly as the presenting sign (N=4; Zn=134±10). The heavier children may represent the infants of potential diabetic mothers (who have more BD). Placental Zn was 18-19 ug/g and did not correlate well with maternal or infant hair Zn. Finally, diet did not explain parental Zn status since paired deficiencies did not occur. Therefore, an association between Zn levels, high-risk age groups and those children with BD is apparent.

Growth hormone deficiency has been reported in 10-20% of Russell-Silver dwarfs. Two siblings with all the classical features of Russell-Silver Syndrome were low in growth hormone (insulinarginine stimulation test), and blood and hair zinc (Zn). They received 50 mg elemental Zn orally each day for 2 months and 50 mg weekly for 4 more months. Growth hormone and Zn determinations were repeated at 6 months: It appears there is a direct relationship between the growth hormone response and Zn nutritional status. We have data indicating that growth hormone therapy increases hair Zn and decreases urinary Zn in children with growth hormone deficiency. These two children provide new data indicating that there are patients whose growth hormone production is affected by their Zn nutritional status.

Concentration of zinc in hair and serum of children with short stature (familial or constitutional) was measured by atomic absorption spectrophotometry. Some of them were treated with methyltestosterone (MT), 10 mg. daily. Our Zn values were similar to those reported for normal children. Nevertheless, children receiving MT had higher Zn levels than the children without medication. Since Zn deficiency is associated with growth retardation, these results raise the question of whether increased Zn retention may be one of the mechanisms by which androgens accelerate growth. We were unable to find any significant difference between the Zn levels from children with familial short stature and those from children with constitutional growth delay.

Concentration of zinc (Zn) in hair, urine and serum were measured by atomic absorption spectrophotometry in one 14-month old girl with typical features of Fetal Alcohol Syndrome (FAS) (peculiar facies, congenital malformations, pre and post natal growth deficiency). She was born to an alcoholic woman who continued drinking heavily throughout her pregnancy. Zinc level was low in hair (66 μg/g) and urine (266.8 μg/g of creatinine) but normal in serum(95 μg%), reflecting probable chronic depletion of Zn. (Normal values are: hair 193 ± 18 μg/g, serum 75-160 μg%, urine 400-600 μg/g.) It has been shown that the offspring of Zn-deficient rats have marked growth retardation and high incidence of congenital malformation, some of which are similar to those seen in FAS. Alcoholic patients have been found to lose increased amounts of zinc in urine. Therefore, it is tempting to speculate that congenital Zn deficiency plays an important role in the pathogenesis of this syndrome.

Since there is a relationship between prostaglandin metabolism, Se and glutathione peroxidase (GSH-PX), and diabetics are reported to have low levels of Se and prostacyclin, we have wondered whether some of the problems which occur in IDM (cardiomyopathy and persistent fetal circulation) might be related to Se deficiency. We studied Se in whole blood of IDM (within 1-2 days after birth) and their mothers. The IDM had a birth weight (mean±SD) of 3857±1075 gm, gestational age of 37.8±1.5 wks, 1 and 5 minute Apgar scores of 7.3±2.7 and 8.8±1.7 respectively. Correlation between the maternal and infants' blood Se concentration in IDM group was not significant. Comparison between IDM, normal full term newborn (NB) infants, and the mother of IDM follows: This preliminary study did not find unusually low Se in whole blood of IDM or their mothers, but because of the potential importance of Se in IDM, a larger study is still indicated.

We have shown in laboratory animals that GH stimulates several mitochondrial processes like protein synthesis, bulk-protein turnover, levels of eytochromes and enzymes, and respiratory activity. We have presently studied respiratory activity (RA) in white cells (WC) and thymidine uptake in LY of children before and after GH therapy. RA (ngm of O2/mg protein or/μg DNA) was measured in WC. prepared by layering whole blood on metrizoate-dextran medium, with a Clark-Oxygen electrode in Krebs-Ringer solution containing glucose. There is significant correlation (r =0.8) between percent increase in respiration due to GH therapy for 1 month and height Rain after 4-8 months of therapy in 16 children. This correlation may have significance in the early prediction of growth-promoting effect during therapy. LY, isolated by layering whole blood over Lymphoprep, showed an increase in WBC, LY count and rosette forming LY in 11-12 children but showed a decrease in 5-6 children. There is a significant decrease in thymidine uptake by unstimulated LY in all 12 children. Therefore, stimulation index (uptake with stimulation by phytohemagglutinim/uptake without stimulation) increased. These results suggest that GH therapy may reduce basal rate of DNA synthesis in LY.

The oral administration of Clonidine, (C) a selective Alpha-Adrenergic agonist has been shown to increase growth hormone(GH) secretion in children and has been proposed as one of the reliable tests of GH reserve. The effects of chronic administra tion of C on growth have not yet been reported. We have now evaluated the effects of C administration on the rate of growth (RG) and somatomedin C (SM-C) levels in normal prepubertal children with short stature. Ten children (4-9y) with normal RG and normal GH reserve as assessed by the C test and SM-C determination were the subjects of this study. C was administer ed orally to these children as a single dose (0.15mg/m2/body surface area) every night during a 6-month period. Height, weight and blood pressure were measured. Plasma SM-C was determined before and one week after the last C dose. No side effects were observed during the 6-month period. The administration of C during that period produced a significant increase in the RG and SM-C levels. We conclude that C-administration could be used as an alternative treatment modality for normal children with short stature

• A mildly obese 15-year-old boy had short stature with rounded facies and short, stubby hands and toes. He had the fully expressed syndrome of pseudohypoparathyroidism but was the only member of his family who had all the somatic characteristics of this disease. The serum parathyroid hormone level was substantially elevated. Urinary excretion of cyclic adenosine monophosphate and phosphate failed to increase following intravenous infusion of parathyroid hormone. However, he did not have hypocalcemia. The present entity is probably a transient form of pseudohypoparathyroidism with partial responsiveness of skeletal adenyl cyclase to parathyroid hormone. ( Am J Dis Child 129:1092-1095, 1975)

504 EARLY PUBERTY IN KLINEFELTER SYNDROME DUE TO A CHORIONIC GONADOTROPIN (hCG)-PRODUCING TUMO

1153 OBESITY IN CHILDREN. RELATIONSHIP BETWEEN ZINC (ZN) TRIGLYCERIDE (TG) AND TESTOSTERONE (T)

76 children (age 2-l6) with bronchial asthma received pyridoxlne (200 mg) daily or placebo in a double-blind study. Each day their parents completed data sheets assessing their symptoms and other medications. Each month they were examined by their allergist and provided vith new sheets and modication. Duration of the study vas 5 months. There were no significant differences in the 2 groups at the outset, but by the second month the pyridoxine group had significantly (p < 0.02) less asthma attacks, and less bronchodilator medicine vas being used. Significant differences in wheezing, tightness in chest, breathing difficulty and cough medicine were also seen. We had previously reported (SPR, 1972) significant abnormality in excretion of xanthurenic and kynurenic acid before and after oral tryptophane loading which returned toward normal with oral pyridoxine therapy. These and other studies suggest that asthmatic children have a relative Increase in serotonin and decrease in epinephrine production which are at least partially reversible with pyridoxine therapy.

GH has been shown to sensitize the adrenal glands to ACTH, probably by increasing the activity of the mitochondrial 11-hydroxylase. In kidney cell culture, stimulation of 1α -hydroxylase, another mitochondrial enzyme, could be induced by GH. We are presenting the long term effect (6 months) of GH replacement (0.1u/k IM three times per week) on 25 (OH) Vit D and 1,25 (OH)2Vit D levels in 12 GH-deficient children (table). The acute responsiveness (3h) of the same metabolites to the PTH administration (250u IV) was also evaluated before and after GH therapy in three children. There was not significant increase of 1,25 (OH)2D3 before GH. However, 6 months after GH therapy the PTH administration induced a 3-fold increase in the 1,25 (OH)2D3 levels, suggesting that GH exerts its effect predominantly in the kidney mitochondria by increasing the sensitivity of the 1α -hydroxylase to PTH.

SERUM TRACE ELEMENTS AND CERULOPLASMIN (CP) CONCENTRATIONS ON MATERNAL AND CORD BLOOD AT DELIVERY

Gaucher disease (GD) is an autosomal recessive condition that presents in a variety of clinical forms, better known as adult, infantile and juvenile or Type 1, 2 and 3 GD respectively. A 22 month old greek female presented with history of progressive difficulties in breathing and swallowing and anemia plus splenomegaly noticed at the age of 3 months. She had normal growth and development, physical exam revealed a pale child with clinical picture of “Pseudobulbar palsy”, strabism, abdominal distention, hepatomegaly and massive splenomegaly. She had microcytic anemia, thrombocytopenia, increased acid phosphatase, foam cell in bone marrow aspiration and Erlenmeyer flask deformity of distal femurs. Her Hb electrophoresis, G-6-PD activity, RBC osmotic fragility ferritin, liver enzymes and chest x-ray were normal. There was a history of anemia and splenomegaly in her mother and maternal aunt. Her mother has been asymptomatic since 1981 when she underwent splenectomy. Glucosylceramide-β-glucosidase activity in leukocytes and skin fibroblasts was compatible with homozygote state in both, mother and child and heterozygote in the father. The findings in this family represents a rare compound heterozygote child with clinical manifestations of type 2 GD as result of a mating between a carrier of infantile GD and an homozygote of adult GD. Discrimination between izozymes for type 1 and 2 could have been interesting unfortunately cross reacting material to all 3 forms of the enzyme is commonly seen.

• We describe a premature female infant exposed in utero to danazol during the first trimester of pregnancy. She was first observed in the newborn period with marked degree virilization and clinical findings suggestive of salt-losing congenital adrenal hyperplasia. This was supported by the high plasma levels of 17α-hydroxyprogesterone and adrenocorticotropic hormone and low plasma cortisol level. Levels of testosterone, androstenedione, 11-deoxycortisol, and renin were also elevated. An excessive increase in the levels of 17α-hydroxyprogesterone and 11-deoxycortisol to corticotropin administration associated with impaired increase in plasma cortisol level strongly suggests a partial block in the 21-hydroxylation of 17α-hydroxyprogesterone. However, the high levels of 11-deoxycortisol also suggest a block of the steroid 11 β-monooxygenase. A year later she was found to have normal basal levels of the adrenal steroids and normal response to corticotropin administration, pointing out the transitory nature of these abnormalities. It may be hypothesized that danazol produced a transitory block of the steroid 21- and 11β-monooxygenases in this child. (Am J Dis Child1981;135:1032-1034)

To the Editor:— Aldosterone excretion in urine has been measured in few infants and newborns. The aim of this study was to determine serially normal aldosterone excretion during the newborn period and to see whether there was a relationship between the initial neonatal weight loss and aldosterone excretion. Four normal premature male infants were studied because of the relative ease of collecting 24-hour urine samples in males. Their birth weights ranged between 1,814 to 2,267 gm (4 to 5 lb) and their gestational ages were between 33 and 35 weeks. Three 24-hour urine samples were collected from each: (1) during the first 24 hours; (2) during the 24 hours when they had reached the lowest weight; and (3) during the 24 hours when the regained their birth weight. These infants were fed 5% dextrose in water at 4, 8, and 12 hours of age, and then were fed a milk

A case study details the clinical, biochemical, and roentgenographic findings in a diastrophic dwarf. The clinical findings were scoliosis and lordosis of the spine, club feet, cleft palate, dysplastic hips, and flexion contractures of knee joints and short extremities. Biochemical abnormalities observed were high cholesterol level, abnormal glucose tolerance, low growth hormone levels, and abnormal excretion of xanthurenic and kynurenic acids following tryptophan loading.

Oral glucose tolerance tests on 24 children with achondroplasia showed glucose intolerance in 16 of them. They were also found to have significantly elevated levels of plasma free fatty acids after an overnight fast, which rose still higher following human growth hormone administration. Plasma insulin levels were normal, but growth hormone levels were significantly below normal at 8 am, and tended to remain low during the day. These data are consistent with the concept that children with achondroplasia have a defect in peripheral glucose utilization.