Luc Paunier

Role of aluminum hydroxide in raising serum aluminum levels in children undergoing continuous ambulatory peritoneal dialysis

Serum aluminum concentrations were measured in 16 children undergoing continuous ambulatory peritoneal dialysis after 7.9 +/- 2.1 (mean +/- SE) and 16.6 +/- 2.3 months of therapy, when the estimated simultaneous oral Al intake from Al hydroxide gels was 98 +/- 20 and 104 +/- 32 mg/kg/day, respectively. Serum Al concentrations were 55.2 +/- 11.4 and 59.8 +/- 10.4 micrograms/L, respectively, compared to 8.2 +/- 1.1 micrograms/L in normal children (P less than 0.001). Serum Al levels correlated with oral Al intake (r = 0.86, P less than 0.001) and inversely with body weight (r = -0.68, P less than 0.01) and age (r = -0.67, P less than 0.01). The youngest patient with the highest serum Al concentrations (208 and 174 micrograms/L) and greatest Al intake (310 and 192 mg/kg/day) had bone biopsy features characteristic of aluminum-related bone disease. Thus, higher aluminum intake per kilogram body weight given to young children is likely to raise the serum Al levels and increase the risk of osteomalacia. Aluminum-containing antacids should be used with caution in infants and young children with renal failure.

The secretion of adrenal androgens and growth patterns of patients with hypogonadotropic hypogonadism and idiopathic delayed puberty

Plasma concentrations of adrenal androgens (DHEA and DHEA-S) and the growth patterns of four male patients with hypogonadotropic hypogonadism have been compared and contrasted with those of eight male patients wit idiopathic delayed puberty. As a group the patients with HH presented at an older age with delayed puberty and normal heights; the growth rate and pattern have been normal except for an absence of the pubertal growth spurt. Adrenal androgens were usually normal for chronologic age and high for bone age. The patients with IDP presented at a younger age, usually with short stature, low adrenal androgens relative to the chronologic age, but normal relative to the bone age. Patients with IDP appear to exhibit a delay in maturation of both the adrenal cortex and the hypothalamo-pituitary gonadal axis usually with short stature and retardation of the bone age. The importance in measurements of adrenal androgens in the diagnosis of HH and of IDP is emphasized.

Hormonal Changes during Puberty

Longitudinal studies of plasma dehydroepiandrosterone sulfate (DHEA-S) and dehydroepiandrosterone (DHEA) were made in 13 girls aged 7 years and 14 aged 10 years, during 3 years, at 6-month intervals.

Effect of adrenergic stimulation and blockade on melatonin secretion in the human.

Publisher Summary The mechanisms that control release of melatonin from the human pineal gland are unknown. This chapter mentions experimental data in animals which are relevant to the present study in humans. It has been established in animals, that the pineal gland is innervated by post-ganghonic fibers from the superior cervical ganglia, which secrete the neurotransmitter noreprinephrine. The presence of β -adrenergic receptors on pineal cell membranes has been demonstrated by the ability of β -adrenergic receptor antagonists to competitively inhibit norepinephrine-induced actions in pinealocyte metabolism. Among the more important of these actions are the activation of adenyl cyclase and the induction of N-acetyl transferase activity, resulting eventually in increased melatonin synthesis. The ability of pharmacologic p-agonists such as isoproterenol to produce an increase of N-acetyl transferase activity, and of &blockers such as propanolol to inhibit it, confirms that, in the rat, melatonin synthesis and presumably release, are mediated by a β -adrenergic system. Further, the sensitivity of these receptors to stimulation appears to vary inversely with the extent of previous stimulation. In addition to a β -adrenergic system, there is some evidence of a dopaminergic influence on melatonin synthesis, as dopamine increases melatonin production in organ culture. In addition, L-dopa increases rat pineal melatonin concentration and N-acetyl transferase activity.

Serum and intracellular magnesium during normal pregnancy and in patients with pre‐eclampsia

Objective To determine the serum and lymphocyte magnesium concentrations during normal pregnancy and to compare the magnesium status in the third trimester of pregnancy between women with normal pregnancy and those with gestational hypertension (GH) or pre‐eclampsia (PE).

Plasma Growth Hormone, Insulin, and Glucagon Responses to Arginine Infusion in Children and Adolescents with Idiopathic Short Stature, Isolated Growth Hormone Deficiency, Panhypopituitarism, and Anorexia Nervosa

Extract: The effects of intravenous infusion of arginine (20 g/m2) after an overnight fast on plasma immunoreactive growth hormone (GH), insulin (IRI), and glucagon (IRG), and blood glucose were examined in five groups of children and adolescents: 10 normal individuals, 18 with idiopathic short stature, 6 with isolated growth hormone deficiency, 8 with panhypopituitarism, and 6 with anorexia nervosa. The mean fasting plasma GH concentration was significantly elevated in the group with anorexia nervosa (P < 0.05), and similar to the value for the normal group in all other groups. After arginine infusion, four- to sixfold increases of plasma GH were observed in the normal children, and similar increases were seen in those with idiopathic short stature as well as in those with anorexia nervosa; whereas, in the children with isolated growth hormone deficiency or panhypopituitarism, there was no significant increase in plasma GH. Fasting blood glucose concentrations were significantly lower than normal in subjects with isolated growth hormone deficiency (p < 0.05), panhypopituitarism (P < 0.001), and anorexia nervosa (P < 0.001), whereas fasting plasma IRI and IRG concentrations were similar to the values in the normal group. Plasma IRI increased eightfold at the end of the 30-min arginine infusion in the normal subjects; the increase was slightly but not significantly less in those with idiopathic short stature, and significantly less in those with isolated growth hormone deficiency (P < 0.05), panhypopituitarism (P < 0.001), and anorexia nervosa (P < 0.05). Arginine infusion resulted in two- to threefold increases of plasma IRG in the normal group, and similar increases were observed in all of the other groups tested. These results suggest that whereas pancreatic β cell responsiveness may be deficient in children and adolescents with isolated growth hormone deficiency, panhypopituitarism, or anorexia nervosa, pancreatic α cell responsiveness, to arginine at least, appears to be intact under these conditions.Speculation: Although plasma glucagon responses to arginine infusion were not less in subjects with hypopituitarism or anorexia nervosa than in normal subjects, relative hypoglucagonemia may have existed, since both basal and postarginine infusion plasma glucagon levels were not higher than normal in the presence of significantly lower blood glucose values. Thus, the present study does not exclude a deficient pancreatic α cell response to hypoglycemia. Alternatively, nonavailability of substrates for gluconeogenesis may have a more important influence than hormonal factors in the genesis of the hypoglycemia observed in these states.

Response to 2-deoxy-D-glucose and to glucagon in "ketotic hypoglycemia" of childhood: evidence for epinephrine deficiency and altered alanine availability.

Extract: The commonest clinical type of hypoglycemia in childhood presents as “ketotic hypoglycemia,” a syndrome which typically remits spontaneously before adolescence. In young children with the severe form of this syndrome, deficient catecholamine secretion and, recently, decreased mobilization of gluconeogenic substrate (alanine) have been shown. The present study concerns five children with ketotic hypoglycemia, aged 2.5 to 9.5 years, and six control children, of similar ages. Each received (7) an infusion of 2-deoxy-D-glucose (2-DG) to test the catecholamine response and (2) intravenous glucagon before and after a 26–28-hr fast, to define possible difference in the response of substrates and hormones, with particular reference to alanine. In the control group, the infusion of 2-DG, 50 mg/kg body wt over 30 min, induced anxiety, hunger or thirst and sweating, as well as a sustained rise in plasma glucose from 78 ± 5 (mean ± SEM) to 156 ± 13.5 mg/100 ml from 1—3 hr after beginning the infusion. There was a transient rise in renin activity in plasma (PRA) from 2.0 ± 0.5 to a peak of 5.8 ± 1.2 ng/ml/hr. By contrast, in the children with hypoglycemia, no clinical response was observed, and there was no change in either glucose in plasma, which remained at 77 ± 6 mg/100 ml, or in PRA (1.3 ± 0.3 to 1.0 ± 0.5 ng/ml/hr). After a period of unrestricted diet, and after an overnight fast, values of plasma glucose, insulin, glucagon, β-hydroxybutyrate, and alanine were the same in the two groups. In both groups intravenous glucagon, 30 μg/kg, was followed by a comparable rise in glucose in plasma and immunoreactive insulin and a comparable fall in alanine in plasma. During the subsequent fast, glucose and insulin in plasma declined similarly. Ketonuria appeared at the same time and β-hydroxybutyrate in plasma rose to equivalent values. The response to a second glucagon infusion was smaller after fasting both as to glucose in blood and plasma insulin, but once again similar for control and hypoglycemia groups. However, the fall in alanine in plasma was significantly greater in the hypoglycemic group during fasting (to 200 ± 13 μM for the control group compared with 151 ± 13 μM for the hypoglycemia group, P < 0.05) and at five time points (10, 30, 60, 90, and 120 min) after the second glucagon administration. Absence of hyperglycemic response to 2-DG in ketotic hypoglycemia suggests impaired catecholamine response. Further, after provocation by fasting and subsequent glucagon administration, the hypoalaninemia which resulted was more marked. Because epinephrine has been shown to raise alanine levels in plasma in man, it is hypothesized that a connection may exist between defective catechol secretion and alanine mobilization in ketotic hypoglycemia.Speculation: Decreased availability of alanine in so-called ketotic hypoglycemia probably represents a defective metabolic system by which neoglucogenic substrates are not readily mobilized, rather than an absolute absence of substrate. One of the possible defective metabolic systems might be through the epinephrine secretion. However, the mobilizable pool of one of these neoglucogenic factors such as alanine could be small in the infants, and become bigger as muscle, which is a storage compartment of alanine, develops with age and puberty. If such is the case, it could be an explanation of the decrease of the frequency of attacks with age, generally at puberty.

Atrial natriuretic factor in patients with congenital heart disease: Correlation with hemodynamic variables

To investigate the alpha-atrial natriuretic factor in congenital cardiac malformations, three groups of children, aged 7 months to 16 years, with different hemodynamic situations were studied during routine cardiac catheterization. Twenty-one (group I) had tetralogy of Fallot, 24 (group II) had a left to right shunt with pulmonary hypertension and 12 (control group) had a minor cardiac lesion. Alpha-atrial natriuretic factor levels were determined by a radioimmunoassay on blood samples from the inferior vena cava, right atrium, pulmonary artery, left atrium and aorta. To evaluate the effect of an acute volume load, measurements of hormone and pressures were repeated after right ventriculography. Alpha-atrial natriuretic factor levels varied over a wide range in all groups and in all chambers investigated. Nevertheless, children with pulmonary hypertension had significantly higher levels of the hormone (p less than 0.01) and were well separated from the control group, but less well from those with tetralogy of Fallot. A 50% increase of alpha-atrial natriuretic factor from the inferior vena cava to the right atrium occurred in patients with shunt lesions with pulmonary hypertension and in patients with tetralogy of Fallot (p less than 0.001) and a further 30% increase from the right atrium to the pulmonary artery (p less than 0.05). After right ventriculography, a 100% to 200% increase of alpha-atrial natriuretic factor was observed in the total sample (p less than 0.001). A positive correlation was observed between right atrial mean pressure and right atrial alpha-atrial natriuretic factor (r = 0.63) and between pulmonary artery mean pressure and pulmonary artery alpha-atrial natriuretic factor (r = 0.61).(ABSTRACT TRUNCATED AT 250 WORDS)

Melatonin Secretion in Relation to Sleep in Epileptics

Publisher Summary The nocturnal rise of melatonin secretion has been well documented in humans. The relationship of this rise to sleep has not been well defined. Vaughan and others have found that reversal of the sleep-wake cycle in humans is not associated with a sleep-induced rise of melatonin during day time, and, in a later study, that no relationship exists between the mean melatonin level during the sleep cycle and the duration of any of the stages of sleep within that cycle. Analysis of plasma melatonin levels in 19 epileptics during sleep has shown a relationship of melatonin with REM sleep. However, in the preliminary study of six normal male volunteers, this relationship was found at a lesser statistical level. The limitations of the sampling inherent to the present study necessitate further confirmation in normal humans with more subjects and frequent blood samplings.

Renal osteodystrophy in children undergoing continuous ambulatory peritoneal dialysis.

Summary: This paper describes a retrospective evaluation of the course of renal bone disease in 14 children undergoing treatment with continuous ambulatory peritoneal dialysis (CAPD) for an average of 11.9 ± 1.5 months (mean ± SE). The patients were divided in two groups according to the changes in serum alkaline phosphatase activity during the period of observation: five patients had alkaline phosphatase activity that decreased or was relatively stable (group I), and nine patients exhibited a rising serum alkaline phosphatase activity (group II). Serial radiological examinations showed adequate control of renal osteodystrophy in the patients of group I, whereas the patients of group II had no improvement or worsening of their bone disease. Group I had higher serum calcium and lower parathyroid hormone levels than group II at the end of period of observation despite similar dosage of vitamin D metabolite. The progression of bone disease was not related to the duration of CAPD or type of previous treatment for end stage renal disease.The observation that the radiological manifestations of secondary hyperparathyroidism were prevented in patients whose serum calcium levels were frequently above 2.62 mmol/liter (group I) while serum calcium levels between 2.25 and 2.50 mmol/liter in group II patients failed to lead to regression of secondary hyperparathyroidism is consistent with the existence of altered “setpoint” regulation of the parathyroid gland in children undergoing CAPD.