The Yugoslavia Prospective Lead Study: contributions of prenatal and postnatal lead exposure to early intelligence.

To investigate associations between the timing of lead (Pb) exposure on early intelligence, we examined the results of psychometric evaluations at ages 3, 4, 5, and 7 years, from 442 children whose mothers were recruited during pregnancy from a smelter town and a non-lead-exposed town in Yugoslavia. We compared the relative contribution of prenatal blood lead (BPb) with that of relative increases in BPb in either the early (0-2 years) or the later (from 2 years on) postnatal period to child intelligence measured longitudinally at ages 3 and 4 (McCarthy GCI), 5 (Wechsler Preschool and Primary Scale of Intelligence-Revised, WPPSI-R IQ), and 7 (Wechsler Intelligence Scale for Children-version III, WISC-III IQ), controlling for: Home Observation for Measurement of the Environment (HOME) quality; maternal age, intelligence, education, and ethnicity; and birthweight and gender. Elevations in both prenatal and postnatal BPb were associated with small decrements in young children's intelligence.

Hyperproduction of erythropoietin in nonanemic lead-exposed children.

Lead (Pb) poisoning has numerous effects on the erythropoietic system, but the precise mechanism whereby high dose exposure causes anemia is not entirely clear. We previously reported that Pb exposure is associated with depressed serum erythropoietin (EPO) in pregnant women residing in a Pb mining town and in a nonexposed town in Kosovo, Yugoslavia. In a prospective study, we tested the hypothesis that blood Pb concentration (BPb) may be associated with depressed EPO in children. BPb, hemoglobin (Hgb), and serum EPO were measured at ages 4.5, 6.5, and 9.5 years in 211, 178, and 234 children, respectively. At 4.5 years of age, mean BPbs were 38.9 and 9.0 microg/dl in the exposed and nonexposed towns, respectively; BPbs gradually declined to 28.2 and 6.5 microg/dl, respectively, by age 9.5 years. No differences were found in Hgb at any age. At age 4. 5 years, a positive association between BPb and EPO (beta = 0.21; p = 0.0001), controlled for Hgb, was found. The magnitude of this association declined to 0.11 at age 6.5 years (p = 0.0103) and 0.03 at age 9.5 years (p = 0.39). These results were confirmed using repeated measures analyses. We concluded that in Pb-exposed children, the maintenance of normal Hgb requires hyperproduction of EPO. With advancing age (and continuing exposure), this compensatory mechanism appears to be failing, suggesting a gradual loss of renal endocrine function due to Pb exposure.

Altered systemic iron metabolism in Parkinson's disease.

Iron deposition in the substantia nigra in Parkinson's disease has been associated with an increase in lactoferrin receptors and a reduction in ferritin concentration. This accumulation of iron in the brain may accelerate free radical formation, lipid peroxidation, and neuronal death. Remarkably, there are few data available concerning systemic iron metabolism in Parkinson's disease. We measured total iron binding capacity and circulating iron, ferritin, transferrin, and transferrin receptors; calculated transferrin saturation; and estimated dietary iron intake in patients with idiopathic Parkinson's disease and in controls. Concentrations of circulating iron, ferritin, and transferrin as well as total iron binding capacity and transferrin saturation were significantly lower in patients than controls. There were no differences in transferrin receptors or dietary intake of iron. The decrease in levels of systemic ferritin and transferrin and the total iron binding capacity parallels observations in a Parkinson's disease brain, but the reductions in serum iron concentrations and transferrin saturation do not, and were unexpected. These results suggest the existence of a defect in the systems that regulate the synthesis of the major proteins of iron metabolism in the liver as well as the brain in Parkinson's disease that may, over time, expedite entry of iron into the brain and decrease iron in the extracellular compartment.

Telling young children with leukemia their diagnosis: the flower garden as analogy.

A new approach to communicating the diagnosis of leukemia to the young child was carried out in the Pediatric Hematology Department in Monza over a 2-year period (1989 to 1991). Fifty patients ages 6 to 15 years were entered into the program. A physician communicated the diagnosis of leukemia directly to the child without the presence of the parents. A set of 25 slides was prepared. A garden with flowers and weeds was used as an analogy for leukemia. All 50 of the children expressed gratitude for understanding their disease and the families for being able to talk with their children about the disease without panic and stress.

Placental cadmium and birthweight in women living near a lead smelter.

It has been suggested that the accumulation of tobacco-derived cadmium (Cd) in the placenta is responsible for the adverse effect of cigarette smoking on infant birthweight. We chose to test this hypothesis; therefore, we studied a population of nonsmoking pregnant women who were exposed to low levels of smelter-derived Cd and a group of nonexposed women. A higher mean placental Cd concentration (p less than .0007) was found in the exposed women (n = 106), compared with those who were not exposed (n = 55); the observed Cd concentrations were comparable to concentrations reported previously for smoking and nonsmoking women, respectively. Least squares multiple regression (controlling for potentially confounding variables) revealed no association between placental Cd and birthweight. It was, therefore, concluded that the effect of smoking on birthweight was not mediated through Cd.

Influence of 2,3-dimercaptosuccinic acid on gastrointestinal lead absorption and whole-body lead retention.

2,3-Dimercaptosuccinic acid (DMSA) is a new orally active heavy metal chelator for the treatment of childhood Pb intoxication on an outpatient basis. The influence of DMSA, as well as other chelating agents, on gastrointestinal 203Pb absorption and whole-body 203Pb retention was examined. Groups of Sprague-Dawley rats (230-260 g) were gavaged with a solution containing approximately 25 mg/kg Pb [as Pb(NO3)2] plus 15 microCi 203Pb. Some groups were then immediately given 0.11 mmol/kg of either DMSA, CaNa2EDTA, D-penicillamine, or BAL by oral gavage, while other groups received the same drugs by ip injection. Control groups received solutions of the drug vehicles po or ip. Whole-body Pb retention and gastrointestinal Pb absorption (whole body retention + urinary Pb excretion) were significantly decreased in rats that received DMSA po. This finding implies that the use of DMSA to treat childhood lead intoxication on an outpatient basis is not associated with a risk for increased Pb absorption.

Anthropometric data, urinary electrolytes excretion, and blood pressure in adolescents.

Relationships between arterial pressure, age, sex, anthropometric measurements, body fat, and urinary excretion of electrolytes were examined in a group of 120 adolescents from 11 to 14 years of age. Body weight and triceps skinfold thickness are two variables that have the highest correlation with arterial pressure levels, especially among girls. Only a slight correlation was found between urinary excretion of sodium and arterial hypertension. The apparent contradiction between positive correlation of fat percent and arterial pressure and the negative correlation between urinary excretion of sodium and arterial pressure can possibly be explained by the low sodium content of the diet of the subjects studied. Their typical Mediterranean diet was abundant in fresh food, mainly based on carbohydrates (macaroni, bread, vegetables), rather than conserved foods in which salt plays an important role in the conservation process (butter, bacon, salad, etc.), typical of the continental diet.

2,3-Dimercaptosuccinic acid as an antidote for lead intoxication.

2,3-Dimercaptosuccinic acid (DMSA) is an orally effective drug more specific and with a wider therapeutic index than currently available drugs for lead intoxication. Eighteen men with elevated blood lead (BPb) concentrations received either 30, 20, or 10 mg/kg DMSA for 5 days in three divided daily doses. The mean BPb level decreased 72.5%, 58.3%, and 35.5% of the pretreatment values, with a simultaneous elevation in urinary Pb excretion. Clinical symptoms and biochemical indices of lead toxicity also improved. Red blood cell d-aminolevulinic acid dehydratase activity increased, while urinary excretion of d-aminolevulinic acid and coproporphyrin fell. DMSA was well tolerated; the only observed adverse drug reaction was a mild, transient elevation of serum SGPT levels in two subjects. DMSA appears promising and may greatly simplify the treatment of lead intoxication.

Chelation therapy in beta-thalassemia major. III. The role of splenectomy in achieving iron balance.

Transfusion requirements for 1978 were compiled for 79 patients with thalassemia major (ages 1 to 29 years) who were maintained at hemoglobin concentrations of greater than 10 gm/dl. In 46 patients with intact spleens, the mean transfusion requirement was 258 ml/kg/year, and there was a clear increase with age. The transfusion history prior to 1978 had no influence on the increase of transfusion requirement with age. In contrast, in 33 splenectomized patients, the mean transfusion requirement was 203 ml/kg/year and it did not increase with age. Urinary iron excretion in response to deferoxamine increased with age, with no obvious difference between splenectomized and nonsplenectomized patients. The ability to achieve iron balance with a daily dose of 20 mg/kg of deferoxamine was a function of the transfusion requirement splenectomized patients with lower blood requirements generally achieved negative iron balance, whereas nonsplenectomized patients did not. We conclude that the spleen should be removed when the transfusion requirement exceeds 250 ml/kg/year, which usually occurs between 6 and 8 years of age. In young patients with intact spleens, a higher dose of deferoxamine may be use in order to prevent hemosiderosis.

["Beat to beat" variations in diabetic patients]. / Variazioni del "Beat to Beat" in pazienti diabetici.

Our aim is to find a way to test the autonomic nervous dysfunction in diabetes mellitus by performing maximal deep-breathings during ECg recording. The subjects underwent ECG recording continously for 2 minutes: during the first minute they breathed regularly, in the second minute they accomplished 6 maximal deep breathings. The R-R intervals in the 1st, as well as the shortest R-R intervals during inspiration and the longest ones during expiration in the second minute were measured and expiration-inspiration ratio (E:I ratio) was calculated. A decreased variation of the R-R intervals from deep-breathings reveals the autonomic nervouis dysfunction . Our data suggest that in diabetes mellitus, R-R intervals show a decreased variation, able to demonstrate earlier autonomic neuropathy.