A: Utility of B-type natriuretic peptide (BNP) as a screen for left ventricular dysfunction in patients with diabetes.

We assessed the effect of zinc supplementation on growth velocity in 79 children and adolescents (48 males, 38 females) with idiopathic short stature. Their height-for-age was < 5th percentile (NCHS standards) and their weight-for-age was normal. Patients were assigned randomly to a supplemented group (S) to receive Zn 10 mg/day or to a placebo (P) group, according to gender and age, and were followed-up for 12 months using a double-blind design. Weight, height, armspan, length of lower segment and plasma and hair concentrations of Zn were measured at 0, 3, 6 and 12 months. On admission and at 6 months, energy, protein, dietary fiber and zinc intakes were similar for groups S and P; mean zinc intake was < 6.5 mg/day. No differences were found in plasma zinc, hair zinc, weight, armspan or lower segment increments. Pre-adolescent males in group S had a significantly greater increase in stature compared with group P (6.2 +/- 2.1 versus 4.5 +/- 1.2 cm/year p < 0.025); z score improved from -2.42 to -2.24 in group S and from -2.63 to -2.61 in group P. For adolescent males, the difference was also significant (8.3 +/- 1.5 versus 6.2 +/- 2.1 cm/year; p < 0.025). No differences were noted in females. In Chilean male schoolchildren and adolescents with idiopathic short stature, zinc supplementation increases growth velocity over a 12-month period.

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To determine whether delay of puberty alters adult height, we retrospectively evaluated the adult height of 41 patients who met rigorous criteria for the diagnosis of isolated hypogonadotropic hypogonadism. The adult height of these patients was compared with the mean height of normal American men at age 18 in the 1979 National Center for Health Statistics survey and with the mean adult height of 50 male normal volunteers who had been studied on the same wards as the patients with hypogonadotropic hypogonadism. The mean adult height of the men with isolated hypogonadotropic hypogonadism was 179.7 cm, which exceeded the height of the 50 control subjects and the normal American men (both 176.8 cm) by 2.9 cm (P less than 0.05 and P less than 0.006, respectively). The mean age at treatment to induce puberty was 20.0 yr, which corresponded to a mean delay in the onset of puberty of more than 8 yr relative to normal males. The final height of the men with hypogonadotropic hypogonadism correlated significantly with the duration of pubertal delay (r = 0.32, P = 0.04). Most of the enhanced mean adult height of the patients with isolated hypogonadotropic hypogonadism was attributable to those patients in whom treatment to induce puberty had been delayed to age 18 or greater. The mean adult height of these patients was 182.4 cm, or 5.6 cm greater than the mean height of the 50 controls or of normal American men (P less than 0.001). The mean adult height of patients whose treatment began between 10 and 17 yr of age was 175.0 cm, which did not differ significantly from that of normal men. We conclude that prolonged delay of puberty (6 or more yr) in men with isolated hypogonadotropic hypogonadism is associated with a modest increase (approximately 5 cm) of adult height.

Acute myelogenous leukemia (AML) remains a challenging disease. Although responsible for only 15-20% of childhood leukemias, it amounts to up to a 30% of all leukemia-related deaths. 1 Over the last three decades, there has been significant progress in the treatment of this disease, mostly due to the introduction of multiple drug regimens, treatment intensification, and improvements in postremission therapy. Early mortality has been addressed by a number of authors, since it is responsible for a significant proportion of all AML deaths. 1-7 In general, it is said that approximately half of early deaths are due to treatment toxicity. 1 In developing countries, such as Chile, treatment toxicity may be even higher, mostly from infectious complications. Children under 15 years comprise approximately 40% of the population of Chile, or 5 600 000 million people. Most of these patients (over 75%) receive their care through the National Health Services. Since 1987, children with the most common pediatric malignancies receive uniform standardized treatment in all of Chile. To that effect, the National Program for Antineoplastic Drugs for Children (PINDA) was founded, and is responsible for creating and supervising treatment programs for pediatric cancers and leukemia. Currently, there are 11 accredited treatment centers throughout the country, mostly in the capital, Santiago. PINDA has developed three treatment protocols for AML, on 1987, 1992, and 1998, based on Berlin-Francfort-Muenster (BFM) protocols. The objective of this publication is to analyze the results of the first two protocols, PINDA 87 and 92, both based on BFM-83, with emphasis on treatment toxicity and early mortality. All patients under 15 years of age with newly diagnosed AML in Chile, between March 1st, 1987, and July 31st, 1999, are included, with the exception of patients with Down's syndrome, secondary myeloblastic leukemia, and myelosarcoma. These patients were treated in 11 Chilean hospitals, according to the protocols described below. The diagnosis was made by morphology, and cytochemichal stains at each treating center, without a central review of pathology. Immunophenotype was studied at Hospital Salvador one center in Santiago. Cytogenetic studies were performed for a group of patients. All cases were classified according to the French-American-British classification (FAB). All patients were treated alike, with no differences for risk groups. The two treatment protocols were quite similar, both based on AML-BFM 83. 10 The first protocol, PINDA 87 was used

To investigate the dose-response relationship between thyroid hormone and linear growth, we studied 10 castrated prepubertal cynomolgus monkeys. Hypothyroidism was induced by administration of methimazole (0.0125% in drinking water) and was confirmed by high serum TSH levels (greater than 40 mU/L) in all animals. Subsequently, each animal received 1, 2, 4, or 8 micrograms/kg.day T4, im, for 9 weeks. The sequence of T4 doses was random, and 6 weeks elapsed between successive T4 doses. Serum T4, T3, TSH, and insulin-like growth factor I (IGF-I) levels and lower leg length were measured every 3 weeks. Methimazole administration decreased thyroid hormone and IGF-I levels and lower leg growth rate. With increasing doses of exogenous T4, serum T4, T3, and IGF-I as well as lower leg growth rate increased significantly. Animals not given T4 had a 65% decrease in lower leg growth rate (P less than 0.01). Animals given 4 and 8 micrograms/kg.day T4 had 56% and 73% increases, respectively, in lower leg growth rate compared to baseline (P less than 0.05 and P less than 0.01, respectively). Lower leg growth rate correlated better with serum T3 (r = 0.50; P less than 0.001) than with serum T4 (r = 0.29; P less than 0.05). Lower leg growth rate also correlated with serum IGF-I levels (r = 0.53; P less than 0.001). Serum IGF-I correlated with serum T3 (r = 0.47; P less than 0.001), but not with serum T4. We conclude that increased serum T4 and T3 levels cause progressive increases in growth velocity and IGF-I levels over a range from moderate hypothyroidism to moderate hyperthyroidism. Growth velocity and IGF-I levels correlated more strongly with the serum T3 than with the serum T4 level.

The GH-releasing peptides (GHRPs) are a family of hexa- and heptapeptides that specifically stimulate GH secretion in normal adults and children. They would be an attractive potential form of therapy for GH deficiency (GHD) if they are also active in these patients. Their action, however, appears to result at least in part through hypothalamic responses, which may be impaired in GHD, and their ability to evoke a GH response in these patients must therefore be directly examined. We studied GH responses to the heptapeptide GHRP-1 in 22 prepubertal children with previously documented GHD and growth failure and compared them to responses to GHRH and the two peptides administered together. Patients received 1 microgram/kg GHRH-(1-44)NH2, 1 microgram/kg GHRP-1, or both, in random order. Tests were separated by at least 1 week. GHRP-1 evoked a significant GH response in 60% of the patients, comparable to the 68% who responded to GHRH. The magnitudes of the peak responses were similar (7.5 +/- 8.0 micrograms/L to GHRP-1 and 11.2 +/- 12.1 to GHRH), although the duration of the GH rise was briefer after GHRP-1. Both responses were lower than those previously observed in normal subjects. There was a marked synergy in responses when the two were given together; the GH peak (34.2 +/- 44.8 micrograms/L) significantly exceeded the sum of the individual responses, and the proportion of patients who responded (86%) was also higher. Thus, despite the absence of endogenous GHRH reflexes in most patients with GHD, these children can respond to GHRP-1 similarly to GHRH, and GHRP-1 can markedly enhance the response to GHRH. These results suggest that GHRPs or their analogs could form the basis for therapy of GHD.

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