Fima Lifshitz

Breast and soy-formula feedings in early infancy and the prevalence of autoimmune thyroid disease in children.

It has been suggested that feeding practices in infancy may affect the development of various autoimmune diseases later in life. Since thyroid alterations are among the most frequently encountered autoimmune conditions in children, we studied whether breast and soy-containing formula feedings in early life were associated with the subsequent development of autoimmune thyroid disease. A detailed history of feeding practices was obtained in 59 children with autoimmune thyroid disease, their 76 healthy siblings, and 54 healthy nonrelated control children. There was no difference in the frequency and duration of breast feeding in early life among the three groups of children. However, the frequency of feedings with soy-based milk formulas in early life was significantly higher in children with autoimmune thyroid disease (prevalence 31%) as compared with their siblings (prevalence 12%; chi 2 = 7.22 with continuity factor; p less than 0.01), and healthy nonrelated control children (prevalence 13%, chi 2 = 5.03 with continuity factor; p less than 0.02). Therefore, this retrospective analysis documents the association of soy formula feedings in infancy and autoimmune thyroid disease.

Breast feeding and insulin-dependent diabetes mellitus in children.

We have evaluated the hypothesis of a protective effect of human milk on the development of insulin dependent diabetes mellitus (IDDM). We studied the feeding histories of 95 diabetic children and compared them with controls consisting of their non-diabetic siblings and a pair matched group of nondiabetic peers of the same age, sex, geographical location, and social background. The incidence of breast feeding in diabetic children was 18%. This was similar to the control group. The duration of breast feedings was also similar among all three groups. There was no difference in the age of introduction of solid food between diabetic and nondiabetic children. Twice as many diabetic children, however, received soy containing formula in infancy as compared to control children. The mean age of onset of IDDM was not related to the type of feeding during infancy. The incidence of positive thyroid antibodies was two and one half times higher in formula-fed diabetic children than in breast-fed ones. In our studies we were unable to document any relationship between the history of breast feeding and subsequent development of IDDM in children.

Alanine-based oral rehydration therapy for infants with acute diarrhea

Twenty male infants less than 1 year of age with acute diarrhea and dehydration were randomly assigned to a study group and studied in blind fashion in a metabolic unit to assess the efficacy of the addition of 30 mmol/L alanine to the standard World Health Organization (WHO) oral rehydration solution (ORS). Patients were exclusively rehydrated with one of two types of ORS during the first 24 hours of treatment. On the second day, oral feedings were started with a lactose-free formula, and ORS was given to replace stool losses. Body weight, ORS, food intake, vomitus, stool, and urine output were recorded at 6-hour intervals. Blood was drawn at the time of admission, after rehydration, and at 24 and 48 hours of hospitalization to monitor blood gases and electrolytes. Rehydration was satisfactory in both groups of patients. ORS that contained alanine did not reduce the purging rates of the infants compared with those who received standard ORS. Clinically no adverse effect of the alanine-based ORS was observed during hospitalization. None of the patients had significant hypernatremia or hyponatremia, and serum amino acid levels were not altered. These data show that the addition of 30 mmol/L alanine to the standard WHO-ORS produces no further improvement in the outcome of the infants with acute diarrhea compared with those fed the standard WHO-ORS.

Alterations in Jejunal Transport and (Na+-K+)-ATPase in an Experimental Model of Hypoxia in Rats

Abstract Hypoxia was induced by exposing rats to an atmosphere of 93% N2, 7% O2 for 4-48 hr. The animals became hypoxic as indicated by a decreased blood P aO2 (mean ± SEM: 48 ± 10 mm Hg). Hypoxia was accompanied by metabolic acidosis (pH 7.22 ± 0.02) and decreased serum bicarbonate levels (9.0 ± 4.0 meq/liter). Hypoxic rats also showed evidence of tissue hypoxia; liver tryptophan oxygenase levels were increased to 21 ±2 nmole/min/mg protein. In the hypoxic animals there was decreased jejunal mucosal (Na+-K+)-ATPase activity and an inhibition of active intestinal transport of sodium, glucose, 3-O-methylglucose, galactose, tyrosine, phenylalanine, and glycine as determined by in vivo perfusion studies. Jejunal fructose transport, which has a large passive component, was unaffected by hypoxia. The electrolyte, carbohydrate, and amino acid transport alterations produced by hypoxia were seen in the absence of an effect on jejunal cell number, DNA synthesis, or cell turnover. There was also no evidence of histological or ultrastructural damage. Furthermore, studies with a luminal macromolecular tracer, horseradish peroxidase, indicated that the jejunal lumen-to-blood barrier to macromolecules was also unaltered in these hypoxic animals. In vitro local oxygenation of the jejunum, by bubbling of 95% O2:5% CO2, markedly improved sodium and glucose (but not 3-O-methylglucose) absorption in hypoxic rats and control rats. The (Na+-K+)-ATPase activity of the jejunal mucosa of hypoxic rats was significantly enhanced by the local bubbling of 95% O2:5% CO2. Overall, our data indicate that during relatively mild conditions of hypoxia there is an inhibition of jejunal (Na+-K+)-ATPase activity and related transport processes that is prevented by in situ oxygenation.

The response to dietary treatment of patients with chronic post-infectious diarrhea and lactose intolerance.

The response to dietary treatment of patients with chronic post-infectious diarrhea and lactose intolerance was prospectively studied in 29 infants less than 1 year of age. All had gastroenteritis with diarrhea which persisted for more than 3 weeks. In the hospital, diarrhea continued and lactose intolerance was documented while being fed half-strength cows milk formula. They were given dietary treatment with one of three formulas used for treatment of diarrhea in infancy. Improvement of diarrhea was more frequently achieved with Pregestimil when given as the initial therapy than with the other two formulas. With Pregestimil nine of 10 patients improved whereas only four of nine infants fed Portagen and one of 10 patients initially treated with soy formula improved. Pregestimil was also effective in three of five patients who initially failed to improve with Portagen and in four of eight patients tried with soy formula with or without carbohydrate. Additionally, in the patients who improved, recovery was more rapidly achieved with Pregestimil than with the other two formulas. Formula failures were due to intolerance to glucose polymers in three patients, possibly to protein in seven infants, and an intolerance to all nutrients in five patients. The improvement of the diarrhea was slower in patients who had evidence of colitis in rectal biopsies regardless of the dietary treatment given, but was not correlated with other variables, i.e., etiology of diarrhea, jejunal histology, or duration of diarrhea prior to treatment. However, as a group, the patients who failed to respond to Pregestimil were younger (less than 3 months of age), had more formula changes and associated infections, and were given more antibiotics; they also had more prolonged diarrhea before treatment and more severe jejunal mucosal lesions and jejunal bacterial overgrowth. The data suggests that Pregestimil seems to be the most effective formula for the treatment of infants with chronic post-infectious diarrhea and lactose intolerance.

Growth Hormone Release in Response to Growth Hormone-Releasing Hormone in Term and Preterm Neonates

The growth hormone response to a single intravenous dose of human growth hormone-releasing hormone (GHRH) was examined in 23 healthy neonates (12 term and 11 preterm) aged 2-4 days. There were no significant increases in growth hormone concentrations at any point in time studied following GHRH administration in either group of newborns. The mean basal growth hormone levels of term neonates were significantly higher than those of the premature newborns (39.6 +/- 5.3 vs. 23.2 +/- 3.3 ng/ml; p less than 0.01) and this difference in growth hormone remained significant 15 and 30 min after GHRH injection. Gestational age correlated positively with both basal and peak growth hormone concentrations in our patients. In conclusion, first, neonates studied in their first days of life have high basal levels of growth hormone and fail to further secrete any significant amount of growth hormone following a single dose of GHRH, and, second, premature newborns secrete significantly less growth hormone than do term neonates.

Long-term evolution of glycerol intolerance syndrome

The two diagnostic tools used, ultrasonography and serum thyroglobulin determinations, were found to give complementary information about the presence and the functional state of the thyroid gland. In our athyroid patients, the absence of thyroid tissue on ultrasound evaluation was confirmed by undetectable serum Tg levels; conversely, Tg was measurable in serum when thyroid glands were visualized by sonography. In the five infants with hypoplastic thyroids glands, serum Tg levels varied widely, showing the existence of functioning thyroid tissue, although not to such a degree as to give normal serum hormone values. In these patients during thyroxine therapy, there was normalization of T4 and TSH values, with a reduction in Tg levels. A physiologic decrease of serum Tg levels has been reported during the first year of life? Our data are in accordance with the results of two recent reports ~,2 comparing serum Tg levels with thyroid scintigraphic findings in hypothyroid infants; we were able to document a similar good correlation between serum Tg levels and thyroid ultrasound data. This observation may have practical diagnostic relevance: if our results are confirmed in a larger series, the combined serum Tg assay and thyroid ultrasound evaluation may gain wide acceptance for the differential diagnosis of congenitally hypothyroid infants detected through neonatal screening programs. Thyroid ultrasound is a simple, sensitive, and noninvasive diagnostic tool that would be ideal for evaluating thyroid anatomy in early life and before therapy, possibly substituting for radionuclide scans. The functional information provided by serum Tg levels should be complemented by morphologic data obtained with ultrasound or radionuclide scan. In hypothyroid infants with undetectable serum Tg levels but with normally placed thyroid tissue, l the discordance between Tg assay and morphologic thyroid examination suggest a biosynthetic defect of thyroid hormone production ~ or a lack of thyroid stimulation caused by hypothalamic or pituitary defects.

The relationship between beta-endorphin and the growth hormone (GH) response to GH releasing hormone in prepubertal children

Endogenous opioids are thought to participate in the regulation of growth hormone (GH) release through the mediation of growth hormone releasing hormone (GHRH). This study was intended to investigate whether the endogenous opioid beta-endorphin could modulate the GH response to GHRH and if this hypothesis could be demonstrated in children with familial short stature with or without constitutional growth delay. Seventeen children (6 female and 11 male) with stature below the fifth percentile were studied to rule out disorders in growth hormone dynamics. All had normal growth velocities, had appropriate predicted heights for their families and had normal GH levels on standard testing. Eight were prepubertal and 9 were Tanner II. All were given 0.1 mcgm/kg (1-44)hpGHRH-NH2 IV. Blood for growth hormone was obtained at 0, 15, 30, 45, 60, 90 and 120 minutes. Blood for beta-endorphin and cortisol was obtained at 0 and 60 minutes. The basal beta-endorphin level significantly correlated with the peak GH level (r = 0.868, p less than 0.05) in the prepubertal group only. In the same group of children, the degree of the negative feedback on the beta-endorphin level correlated significantly with the rise in GH level (r = 0.912, p less than 0.01). However, there was no correlation between the basal beta-endorphin and the peak GH level nor between the rise in GH level and the change in beta-endorphin in the pubertal children. These data are compatible with the hypothesis that beta-endorphin levels affect the GH response to GHRH in prepubertal children, but have no discernible effect on the GH response to GHRH in pubertal children.

Inhibition of Sodium Intestinal Transport and Mucosal (Na+-K+)-ATPase in Experimental Fanconi Syndrome

Summary The administration of 1.5 or 9.0 mmoles/kg ip of maleate to rats induced, in addition to renal alterations similar to those occurring in the Fanconi syndrome, a decline in the intestinal mucosa (Na+-K+)-ATPase with a simultaneous decrease in sodium intestinal transport and an increase in potassium absorption. Further differences in the behavior of the two electrolytes were observed when the concentration of sodium in the perfusates was altered. No changes occurred in amino acid or glucose transport in experimental animals.