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The n-3 polyunsaturated fatty acid (PUFA) status of the neonatal brain has been associated with cognitive capability in mice. Previously, transgenic mice expressing the Caenorhabditis elegans (C. elegans) n-3 fatty acid (FA) desaturase gene under the control of a lactation-induced mammary gland promoter were found to produce milk containing significantly elevated levels of alpha-linolenic (ALA) and eicosapentaenoic (EPA) acid. In this study, the preweaning growth rate and development of mouse pups consuming elevated n-3 PUFA milk produced by transgenic dams were evaluated using the Wahlsten observational test battery and the object novelty preference test. Brains were collected at weaning and analyzed for FA composition. Pups nursed on transgenic dams had earlier eye opening, higher visual placement scores, and 1.6-fold more docosahexaenoic acid (DHA) in their brains compared with pups raised on wildtype dams. There was no significant effect of milk treatment (transgenic versus control) on other developmental parameters or novelty preference behavior. The pups consuming the elevated n-3 PUFA transgenic milk had slower preweaning growth rates such that pups reared on wildtype dams producing control milk were heavier than pups reared on transgenic dams producing high n-3 PUFA milk by postnatal day 18. This transgenic model enables the provision of a high n-3 PUFA lactational environment independent of maternal diet or gestational FA status.

Extract: This communication reports the edevelopment of a sensitive, reproducible, and specific radioimmunoassay for luteinizing hormone (LH) in plasma and the application of this method to a cross-sectional survey of plasma LH concentrations in 243 infants, children, and adolescents with normal and abnormal growth and sexual development. One nanogram of Hartree purified human pituitary LH standard was immunologically equivalent to 13.7 mIU of the Second International Reference Preparation of Human Menopausal Gonadotropin. The lower limit of sensitivity of the assay varied between 0.025 and 0.05 ng/ml. Specimens of plasma containing

A new hypoglycemic syndrome: Fasting and reactive hypoglycemia, nomal growth and deficient plasma growth hormone (HGH)

Isoxsuprine (ISX) treatment of premature labor has been associated with diverse metabolic side effects including hypoglycemia. This study was designed to identify anatomic and biochemical changes associated with ISX exposure during pregnancy. 6 timed-pregnant rats received ISX at 2mg/Kg/day at 120, 96, 72, 48 and 24 hrs. prior to delivery. 4 timed-pregnant control rats received similarily timed saline placebo. 102 neonatal rats were analyzed within 12 hrs. of birth. The results showed: The data confirm a significant effect of prenatal ISX on total BW, liver glycogen, heart/BW, liver/BW and organ weights of heart, kidney and lung and suggest that decreased hepatic glycogen may be a factor in neonatal hypoglycemia. *=N **=P < 0.005

Pediatric house staff have routinely attended all cesarean section (CS) and high risk vaginal (HRV) deliveries at Pennsylvania Hospital, a tertiary care perinatal center. This study compared the need for resuscitation (Apgar < 6 at 1 minute) with the presence of risk factors and mode of delivery. High risk factors were defined as:Pregnancy < 36 weeks,meconium, breech presentation, multiple gestation, fetal distress, vaginal bleeding, chorioamnionitis and severe pre-eclampsia. Indications for CS regarded as low risk were: repeat, failure to progress and cephalopelvic disproportion. 2679 deliveries from Jan.-Sept. 1980 were analyzed with the following results: The data indicate that, in the absence of risk factors, the mode of delivery did not influence the need for resuscitation and that pediatric attendance at delivery should be based on the presence of risk factors rather than the mode of delivery.

Testicular damage associated with cyclophosphamide (CX) therapy of steroid-dependent nephrosis prompted assessment of 5 pubertal males, 15-18 yrs, to identify those who may have gonadal injury as a result of medication. 3 who had received CX for 4 months and 2 for a total of 9 and 10 months between the ages of 12-1/2 to 16 yrs (2-4 yrs before testing) received LRF, 100 ugm. Basal serum testosterone (T) values in 4 were within the normal range for age, mean 507 (400-900 ngm/ml) and one was low, 246. Responses to LRF in 3 with normal T showed higher basal levels of LH, mean 46.3 mIU/ml, and peaks to 101-119. Mean basal levels of FSH were 25.7 mIU/ml and had sustained elevation rather than a significant peak. 1 with normal T and 1 with low T had mean basal LH 18.5 mIU/ml and mean basal FSH 1.4. After LRF a 3-4 fold rise of LH and 8-10 fold rise of FSH occurred. The LRF test caused no untoward reactions and does identify those who require further evaluation of their gonadal status. These studies showed that testesin CX-treated males may be under higher LH and FSH stimulation to maintain normal T.

Bovine adrenal 20α-hydroxysteroid oxidoreductase has been measured in various age groups. Fetal ( 33-35 weeks gestation);newborn;calf(prepuberal) and adult The substrate 20α-hydroxyprogesterone was used under conditions favoring oxidation. Results are as nM of progesterone produced/gm. protein/ 4 hours. Highest levels were in prepuberal calves:228-250 units. The second highest but much lower was in newborns, 68-73 units. Fetal glands had no activity and adult glands were low, 2-7 units. The highest levels in prepuberal tissue suggests the oxidoreductase reduces progesterone and precludes it from further conversion and side chain cleavage to C-19 steroids. With adrenarche the activity drops probably accounting for rises of the adrenal C-19 steroids at this time. Such a system may also operate in the gonads and represent an additional mechanism for onset of puberty. Absence of this oxidoreductase in the fetus is consistent with the known high levels of C-19 steroids. It is to be noted that under the conditions employed, 17α, 20α - dihydroxyprogesterone as substrate did not undergo oxidation. All measurements of extracts were made by suitable derivatives on GLC chromatography.

Hypothyroxinemia (HT) has been implicated as a factor in the etiology of respiratory distress syndrome (RDS). To assess the importance of HT, we measured thyroxine (T4) by filter paper spot (FPS) in the first 5 days of life in premature infants (PI) with RDS, PI with illnesses other than RDS, well PI, sick term infants (TI) and well TI. FPT4 estimates, as ug/dl serum, were comparable to simultaneously obtained serum T4 values in each group. Mean FPT4 values were similar in PI with RDS and in PI with other illnesses and were lower than in well PI (p

Progression of CLT in T4 treated children has been poorly documented. The response of endogenous T4, T3 and TSH to withdrawal after 2 to 9 yrs of therapy in 6 children, 7-18 yrs, was studied with weekly levels for 4-20 wks. At Dx. of CLT 5 had hypothyroid values. Results indicated 3 patterns of response: 1) clinical and lab evidence of hypothyroidism in 6 wks, 2) increased TSH with normal T4 followed by return of goiter 8 wks off therapy, 3) clinical & chemical euthyroidism in 3 with no return of goiter 12-20 wks off therapy. This group demonstrated a reduction in agglutinating antibody (Ab) titers from initial levels. Two had hypothyroid lab data at dx. of CLT. Normal TSH, T4 & T3 occurred 3 wks after discontinuing therapy. A reduction in Ab titers with normal TSH accompanied euthyroidism. Hypothyroidism coincided with unchanged Ab. In contrast to adults treated for 10 yrs, with deterioration in thyroid function noted 6 wks off therapy (Papapetrou et al, Lancet, Nov.72), these studies indicated that the child may recover function after a period of replacement.

RADIOIMMUNOASSAY OF HUMAN CHOEIONIC GONADOTROPIN (HCG) AND ALPHA FETOPROTEIN (αFP) IN THE MANAGEMENT OF HEPATOBLASTOMA

Sixty-seven pregnant women at risk for fetal isoimmunization were followed prospectively from 6/78–6/84 and scored by nonstress testing (NST) (reactive =2, nonreactive =0), amniotic fluid Δ 450 (slope: increasing =2, stable =1, decreasing =0), and fetal ultrasound (U/S) (erythroblastosis fetalis: none =2, minimal-moderate =1, moderate-severe =0). Postnatally, the 67 infants (GA 36.6±3.1 wks, mean±SD, BW 2850±656 grams) were independently scored without knowledge of the maternal score (living =2, dead =0; treatment: none =2, phototherapy =1, exchange transfusion =0; problems of prematurity: none =2, mild =1, moderate-severe =0). The mothers and infants were each assigned a rank from 1–10 according to their scores. A sign test (non-parametric) between the maternal and infant scores revealed no significant difference indicating agreement between rankings. The chi square goodness of fit for the distribution of scores when grouped as 1/2/3, 4/5/6/7, and 8/9/10 also indicated no significant differences in rankings. The correlation coefficient for infants rank against maternal rank was .76 at p

Subjects with GD have elevated LH & FSH and achieve greater rise in both after LRF (Silver, Yen 1973). Estrogens exert inhibitory action on FSH & LH release (Yen et al 1972). To ascertain an effect of estrogen on LH and/or FSH to LRF in GD, 8 females 7-20 yrs, were studied; 4 XO, 1 XO/XY, constitutional delay, hypopituitarism, normal female. LRF, 50-100 ugm IV, was followed by 0.1 mgm EE daily 3-7 days, with 1-7 days off EE prior to second LRF test. In 3 young XO GD, 7 days EE decreased basal FSH (mean 17.6 mIU/ml before EE, 6.1 after EE) and the FSH peak to LRF (mean FSH peak 64.1 before EE, 16.1 after); LH was not significantly affected. With 3 days EE, a 7 yr. XO/XY had no change in LH, FSH responses. An older XO had an LH rise to LRF after 3 days EE, with a decreased FSH responsiveness. LH levels with LRF (after EE) were decreased in a normal female and constitutional delay. The younger child with GD lacks ovarian feedback mechanism and may have chronic endogenous secretion of LRF which induces pubertal LH response, as shown in these studies. LH & FSH responses to EE varied with age.

THE ROLE OF ADRENOCORTICOTROPHIC AND GROWTH HORMONE ON GLUCOCORTICOID SECRETION IN HYPOPITUITARY (HP) PATIENTS

There are many biochemical and clinical findings in patients with anorexia nervosa to suggest altered thyroid hormone activity but laboratory tests of thyroid gland function are generally normal or low normal. TSH, total T4, total T3 and the response to TRH were determined in 6 patients with anorexia nervosa in an effort to evaluate discriminately thyroid hormone activity at the physiologic levels of the hypothalamus, pituitary gland, thyroid gland and peripheral tissue. The results, expressed as the mean value ± SEM, are summarized in the following table: The most striking finding was the markedly depressed T3 levels. Animal studies suggest that in acute starvation, peripheral deiodination of thyroxine is increased. Our data suggest that during chronic starvation, peripheral deiodination of T4 to T3 is diminished. Sullivan et al have suggested that severely ill but euthyroid patients have decreased deiodination and decreased intracellular T3. Teleologically, decreased deiodination may be a protective mechanism during chronic stress.

Yellow hyaline membrane (YHM) have been correlated with hyperbilirubinemia (HBILI) and with bronchopulmonary dysplasia. Also data have suggested a protective effect of HBILI on O2 damage to lungs and a role of phototherapy (P) in the development of lung damage. To test the relationship of P, HBILI and high FIO2, and to develop a model for study 7 to 13 day old GUNN rats (jj and Jj phenotypes) were exposed to four experimental conditions for 24 to 72 hours: I) FIO2 > .75+P, II) FIO2 > .75 without P, III) FIO2 .21+ P and IV) FIO2 .21 without P. Hct. Indirect Bili were measured. The lungs were examined in a masked fashion. Lung Path = Pulmonary hemmorrhage ± hyaline membranes. The Data indicate no effect of O2 and P in acute phase lung damage but suggest a protective effect of HBILI. Additional study with longer exposure and larger numbers are needed.

There are conflicting data about the effect of PROM on the development of HMD. We performed a retrospective analysis of 95 neonates with PROM. 41% received antenatal glucocorticoids and 59% were managed expectantly. Labor was induced for signs of chorioamnionitis. The charts were analyzed for presence of HMD, birth weight (BW), Apgar score, length of PROM, sex, gestational age (GA) and route of delivery. The data were analyzed by step wise multiple regression and chi square with all factors weighed against HMD for each group (I: PROM with steroid; II: PROM alone). BW was the only factor correlating with HMD. BW and GA were the only correlating variables. There was no difference in the incidence of HMD in the presence or absence of steroids in this PROM population.