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Biomedical subjects

P B Hammond

Publications and source records attributed to P B Hammond.

At least 19 recordsLinked to original sources
PubMed1995

Effects of supplemental nutrition on lead-induced depression of growth and food consumption in weanling rats.

The objective of this study was to determine whether growth-depressant effects of lead (Pb) could be prevented by preventing the accompanying depression of caloric intake from ad libitum food consumption by caloric supplementation. The animal used was the female weanling rat. Three experiments were performed in which progressively increasing levels of caloric supplementation were provided in order to attain a level of nutrition which would totally prevent growth depression from Pb exposure. Nutritional supplementation of Pb-exposed animals almost completely eliminated the Pb-induced depression of weight gains. We conclude that the deficit in growth due to Pb can be adequately explained on the basis of a primary effect on appetite, rather than being secondary to depression of proliferative responses of cells to growth factors, e.g., insulin-like growth factor I.

Animal Nutritional Physiological Phenomena↗
PubMed1994

Age-dependent effects of CCK and devazepide in male and female rats.

Peripheral administration of the brain/gut peptide cholecystokinin (CCK) has been demonstrated to inhibit food intake in a variety of species, and administration of the specific type A CCK receptor antagonist devazepide increases food intake in a variety of experimental paradigms. The potency of CCK to inhibit intake depends upon a variety of factors, but CCK is generally less potent under conditions of elevated food intake. At different developmental stages, rats' intake requirements differ as growth rates change. To determine whether CCK plays a variable role in the control of intake in rats of different ages, we examined the feeding-inhibitory effect of various doses of CCK and the feeding-enhancing potential of various doses of devazepide on glucose consumption (0.5 kcal/ml) in male and female rats at 45-70 and 110-130 days of age. CCK was more potent in older male and female rats than in younger rats, and inhibited intake in a dose-related fashion. In younger rats, the efficacy of CCK was attenuated and the inhibition was not dose related. Administration of devazepide had no effect on intake in younger rats of either sex, but significantly increased glucose consumption in the older rats. These data suggest that during a period of rapid growth and high levels of food intake relative to body weight, adolescent rats are relatively insensitive to exogenous CCK and endogenous CCK does not appear to play a significant role in controlling their intake.

Age Factors↗
PubMed1991

Lead exposure and growth in the early preschool child: a follow-up report from the Cincinnati Lead Study.

This report is a follow-up of an earlier study of the effects of low to moderate prenatal and postnatal lead exposure on children's growth in stature. Two hundred thirty-five subjects were assessed every 3 months for lead exposure (blood lead level) and stature (recumbent length) up to 33 months of age. Fetal lead exposure was indexed by maternal blood lead level during pregnancy. The adverse effects of lead on growth during the first year of life were reported previously. This analysis covers essentially the second and third years of life. The results indicate that mean blood lead level during this period was negatively associated with attained height at 33 months of age (P = .002). This association was, however, evidenced only among those children who had mean blood lead levels greater than the cohort median (greater than or equal to 10.77 micrograms/dL) during the 3- to 15-month interval. The results also suggest that the effect of lead exposure (both in utero as well as during the first year of life) are transient provided that subsequent exposure to lead is not excessive. It appears that maintaining an average blood lead level of 25 micrograms/dL or more during the second and third year of life was detrimental to the child's attained stature at 33 months of age. Approximately 15% of this cohort experienced these levels of lead exposure. Continued follow-up of this cohort will reveal whether these lead-related deficits persist and whether they continue to be dependent on the level of exposure in an earlier period.

Body Height↗
PubMed1990

Lead exposure in early life: health consequences.

Until very recently it has been considered that of the many manifestations of lead toxicity, those involving the elaboration and function of hemoproteins occur at lower levels of lead exposure than any others. The critical target seems to be the enzyme heme synthetase, which is essential for the insertion of iron into the precursor, protoporphyrin IX. The major consequences of this effect, which have been evaluated in both adults and children, are reduction of circulating levels of hemoglobin and cytochrome P-450-dependent Phase I drug metabolism. Lead clearly inhibits normal hemoprotein function in both respects. The threshold level of lead exposure for these effects seems to be at a circulating lead concentration (PbB) of approximately 30 to 40 micrograms/dL. A growing body of evidence suggests, however, that the functional integrity of the central nervous system is compromised at substantially lower levels of lead exposure, particularly in the human fetus and young child. Early postnatal neurobehavioral development is compromised at maternal or cord PbB of somewhat less than approximately 10 micrograms/dL, a level of lead exposure not uncommon in the general population. Results of more recent cross-sectional and prospective studies indicate that postnatal lead exposure resulting in PbBs as low as 25 micrograms/dL, and probably lower, also are associated with deficits in intellectual attainment, achievement, and behavior. The long-term consequences of these effects remain to be fully evaluated. Little is known concerning basic mechanisms that are responsible for these effects. They may be manifestations of a more basic common effect of lead on cell proliferation and differentiation.

Adult↗
PubMed1990

Lead exposure lowers the set point for food consumption and growth in weanling rats.

Lead (Pb) depresses growth in infants and young children. Our earlier studies using a weanling rat model of Pb exposure suggest that this Pb effect is due to depression of appetite. In the present study we examined whether this depression of appetite is consistent with a down-regulation of the appetite "set point" as described using dietary manipulations following either lesions of certain hypothalamic regions or 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure. Two types of dietary manipulations were employed: (a) consumatory response to hyperalimentation (force-feeding), and (b) consumatory and growth response during the catch-up period following food restriction. In the hyperalimentation experiments, food intake was determined (a) with and without force-feeding, and (b) without Pb and with Pb administered either orally or systemically. Pb exposure reduced food consumption compared to controls. Force-feeding of a liquid diet further reduced food consumption, but only to the level that maintained total caloric intake at, or close to, the level of Pb animals not force-fed. In the food-restriction experiments, weanling rats had their food intake restricted for 4 days and then were provided free access to food, at which time one subgroup of these animals was exposed to Pb. Catch-up of previously food-restricted animals, in terms of food consumption and growth, was the same in the first 2 days, regardless of whether Pb was administered. During the next 10 days, the food intake and growth of the non-Pb-exposed, food-restricted animals gradually converged on the previously free-fed, non-Pb-exposed animals, whereas the food-restricted. Pb-exposed animals converged on the growth-depressed, previously free-fed Pb-exposed animals. All these responses to dietary manipulations are consistent with a reduced set point for appetite rather than with a nonspecific effect of Pb, e.g., aversion to food or general malaise.

Animals↗
PubMed1990

Lead exposure and neurobehavioral development in later infancy.

A prospective methodology was used to assess the neurobehavioral effects of fetal and postnatal lead exposure during the first 2 years of life. Lead was measured in whole blood prenatally in mothers and at quarterly intervals in the infant. Prenatal blood lead levels were low (mean = 8.0 micrograms/dL). However, approximately 25% of the study infants had at least one serial blood lead level of 25 micrograms/dL or higher during the second year of life. Multiple regression and structural equation analyses revealed statistically significant relationships between prenatal and neonatal blood lead level and 3- and 6-month Bayley Mental and/or Psychomotor Development Index. However, by 2 years of age, no statistically significant effects of prenatal or postnatal lead exposure on neurobehavioral development could be detected. Data consistent with the hypothesis that a postnatal neurobehavioral growth catch-up occurred in infants exposed fetally to higher levels of lead are presented.

Child Behavior↗
PubMed1989

Mechanisms by which lead depresses linear and ponderal growth in weanling rats.

Lead is known to reduce linear and ponderal growth in children, even at levels of exposure common in the general population. The mechanism involved is not known. The present study was conducted in order to establish the role of food consumption and insulin-like growth factor (IGFI), also commonly known as somatomedin C (SmC), in lead-induced reduction in growth in weanling rats. A further purpose was to test the hypothesis that depressed growth could be prevented by administration of growth hormone and thyroxine, a procedure which prevents arrested growth due to hypophysectomy. Treatment with growth hormone in combination with thyroxine had no effect on depressed growth or food consumption. The reduction in linear and ponderal growth due to lead (approximately 17%) could be largely though not completely accounted for on the basis of reduced food consumption, apparently by a mechanism not involving growth hormone or thyroxine (see above). Plasma SmC was reduced in proportion to reduced food intake, regardless of whether due to Pb or to restriction of food intake in a pair-feeding experiment thereby ruling out an effect of lead on SmC synthesis or activity other than through reduced food consumption. The experiments leading to these conclusions all involved administration of lead in the drinking water, suggesting the possibility that reduced food consumption was peripherally mediated as a result of contact of lead with appetite-depressant receptors in the gastrointestinal tract, e.g., taste receptors. An additional experiment therefore was conducted comparing food consumption and growth resulting from oral lead administration to subcutaneous administration. Similar depressant effects on food consumption and growth resulted at similar concentrations of lead and zinc protoporphyrin in blood. These effects were significantly greater following oral administration, however, suggesting that lead depresses appetite by both a systemic mechanism and one operating at the level of the gastrointestinal tract.

Animals↗
PubMed1989

Fetal and infant lead exposure: effects on growth in stature.

The growth of a cohort of 260 infants was prospectively followed up from birth. Blood lead and stature measurements were obtained every 3 months until 15 months of age. Fetal lead exposure was indexed by measuring lead in maternal blood during pregnancy. A longitudinal analysis revealed that covariate adjusted growth rates in stature were negatively related to the infants' postnatal blood lead concentration, as indexed by increase in average blood lead values from 3 to 15 months. However, this relationship between growth rate and change in blood lead concentration was evidenced only among those infants whose mothers had prenatal blood lead levels greater than the maternal cohort median of 7.7 micrograms/dL is about 2 cm shorter at 15 months of age if, postnatally, the infant incurred a 10-micrograms/dL blood lead increase during the 3- to 15-month interval of life, compared with an infant who has no increase.

Cohort Studies↗
PubMed1988

Anodic stripping voltammetry procedure modified for improved accuracy of blood lead analysis.

In evaluating the accuracy and reliability of blood lead (PbB) measurements with the Environmental Science Associates Model 3010A Trace Metal Analyzer, intralaboratory comparison demonstrated that use of the operating conditions recommended by the manufacturer resulted in consistently underestimated PbB concentrations less than 400 micrograms/L and overestimated PbB values greater than 400 micrograms/L. At PbB concentrations less than 50 micrograms/L, measured concentrations were often registered as negative results. However, these negative values could be replicated to within +/- 10 micrograms/L, indicating good precision of the method, but obviously not good accuracy. In addition, lower-than-expected lead (Pb) values were measured in samples containing increased concentrations of copper (Cu), such as may occur in pregnant women. We modified the procedure to eliminate these inaccuracies by substituting manual peak-height measurements for reliance on the integrator and digital display of the instrument. We established the accuracy of the modified procedure by using calibration standards previously quantified by isotope dilution-mass spectroscopy. A quality-control program for monitoring PbB analysis is also described.

Copper↗
PubMed1987

Low-level fetal lead exposure effect on neurobehavioral development in early infancy.

A prospective method was used in this study to assess the effects of fetal lead exposure on neurodevelopmental status in 3- and 6-month old infants. At their first prenatal medical appointments, 305 lower socioeconomic status women residing in predesignated lead-hazardous areas of Cincinnati were recruited. Lead was measured in whole blood in both the mother and fetal-placental unit (prenatal and cord) and the neonate (ten days and 3 months). All blood lead levels were less than 30 micrograms/dL. Infant development was assessed with the Bayley scales at 3 and 6 months of age. Multiple regression analyses which treated perinatal health factors such as birth weight and gestation as confounders indicated an independent, inverse relationship between both prenatal and neonatal blood lead levels and performance on the Bayley Mental Developmental Index at both ages. Male infants and infants from the poorest families appeared to be especially sensitive to these psychoteratogenic influences. Further study using a structural equations approach indicated that neurobehavioral deficits were partly mediated by lead-related reductions in birth weight and gestation.

Age Factors↗
PubMed1986

Resistance of the rat to development of lead-induced renal functional deficits.

Lead nephropathy, characterized functionally by depression of effective renal plasma flow (ERPF), glomerular filtration rate (GFR), and maximum glucose reabsorption rate, is associated with prolonged occupational exposure to lead. Production of comparable lead-related renal functional deficits in rats has been difficult to achieve. We have examined in rats some of the factors that might be expected to influence the development of lead-induced renal functional damage, using GFR (as inulin clearance), ERPF (as para-aminohippurate clearance), and maximum glucose reabsorption rate as indices of renal functional competence. Although lead produces a significant weight loss, this can be accounted for by reduced food intake and is not associated with reduction in renal function. Even exposure to large amounts of lead in conjunction with other factors, such as controlled diet (NIH-07 and AIN-76) and early age of initial exposure, that might have been expected to increase the rats' susceptibility has not resulted in the development of renal functional deficits. It is unlikely that the rat can be successfully exploited as an animal model of human lead nephropathy with accompanying functional deficits.

Animals↗
PubMed1985

Condition and type of housing as an indicator of potential environmental lead exposure and pediatric blood lead levels.

Environmental evaluations in a prospective behavioral study of children with blood lead levels up to about 50 micrograms/dl were performed by an intensive environmental survey and by exterior visual evaluation of housing quality. Serial blood lead values for infants in the study were compared to exterior housing type and quality, which itself was also compared with results of the intensive environmental evaluation. Five housing condition and type categories were defined: public housing; private housing (satisfactory, deteriorated, and dilapidated); and rehabilitated private housing. In this interim report on the first subset of available data, the housing categories were found to differ in paint and environment dust lead levels, with public and rehabilitated housing having lowest values. Blood lead concentrations of children differed across housing categories as early as 6 months of age, with children residing in public housing having lowest levels, followed by those in rehabilitated housing. The spread in mean blood lead concentrations among the housing quality categories increased with increasing age of the children. Housing category accounted for over one-half of the blood lead variability in 18-month-old children.

Dust↗
PubMed1985

Evolution of efficient methods to sample lead sources, such as house dust and hand dust, in the homes of children.

Efficient sampling methods to recover lead-containing house dust and hand dust have been evolved so that sufficient lead is collected for analysis, and to ensure that correlational analyses linking these two parameters to blood lead are not dependent on the efficiency of sampling. Precise collection of loose house dust from a 1-unit area (484 cm2) with a Tygon or stainless steel sampling tube connected to a portable sampling pump (1.2 to 2.5 liters/min) required repetitive sampling (three times). The Tygon tube sampling technique for loose house dust less than 177 microns in diameter was around 72% efficient with respect to dust weight and lead collection. A representative house dust contained 81% of its total weight in this fraction. A single handwipe for applied loose hand dust was not acceptably efficient or precise, and at least three wipes were necessary to achieve recoveries of greater than 80% of the lead applied. House dusts of different particle sizes less than 246 microns adhered equally well to hands. Analysis of lead-containing material usually required at least three digestions/decantations using hot plate or microwave techniques to allow at least 90% of the lead to be recovered. It was recommended that other investigators validate their handwiping, house dust sampling, and digestion techniques to facilitate comparison of results across studies. The final methodology for the Cincinnati longitudinal study was three sampling passes for surface dust using a stainless steel sampling tube; three microwave digestions/decantations for analysis of dust and paint; and three wipes with handwipes with one digestion/decantation for the analysis of six handwipes together.

Adult↗
PubMed1985

The influence of social and environmental factors on dust lead, hand lead, and blood lead levels in young children.

The roles of environmental and behavioral factors in determining blood levels were studied in a cohort of young children living in an urban environment. The subjects were observed at 3-month intervals from birth to 24 months of age. Repeated measurements were made of the children's blood lead levels, environmental levels of lead in house dust, and in the dust found on the children's hands. A qualitative rating of the residence and of the socioeconomic status of the family was obtained. Interviews and direct observation of parent and child at home were used to evaluate various aspects of caretaker-child interactions. Data analysis consisted of a comparison of results obtained by simple correlational analysis, multiple regression analysis, and structural equations analysis. The results demonstrated that structural equation modeling offers a useful approach to unraveling the complex interactions present in the data set. In this preliminary analysis, the suspected relationship between the levels of lead in house dust and on hands and the blood lead level was clearly demonstrated. Furthermore, the analyses indicated an important interplay between environmental sources and social factors in the determination of hand lead and blood lead levels in very young children.

Child, Preschool↗
PubMed1985

Postnatal lead exposure and early sensorimotor development.

The relationship between postnatal lead (Pb) exposure and early sensorimotor development was prospectively investigated in a group of infants born to parents residing in lead-hazardous areas of Cincinnati, Ohio. Few significant relationships were found between current or cumulative infant blood Pb levels and indices of sensorimotor development during the first year of life. When important developmental covariates such as birth weight and home environment were included in the analyses, no significant relationship between Pb exposure and development remained. To date, there appears to be no evidence in these data that postnatal low-level Pb exposure increases an infant's risk for delays in early sensorimotor development.

Child Development↗
PubMed1985

Dose-effect and dose-response relationships of blood lead to erythrocytic protoporphyrin in young children.

Dose-effect and dose-response relationships were analyzed for blood lead concentration (PbB) vs blood protoporphyrin concentration using multiple data points from 165 children, ages 3-36 months. Protoporphyrin concentrations were measured using a front-face fluorometer designed to measure zinc protoporphyrin (ZPP) and an extraction method designed to measure total protoporphyrin as the free base (FEP). Estimations were made of the threshold for PbB effects on FEP and ZPP, as well as the slopes of the PbB-FEP and PbB-ZPP interactions. There was essentially no difference in thresholds estimated using ZPP vs FEP as the effect parameter. There was no apparent effect of age on threshold. However, the slope for PbB vs ZPP was less steep than the slope for PbB vs FEP. Moreover, the average ratio FEP:ZPP was markedly elevated at 3 months (1.84:1) and decreased slowly, attaining unity at 33 months. The possible reasons for this discrepancy are discussed, as well as the implications for interpretation of lead screening program data.

Aging↗
PubMed1985

Contribution of social and developmental factors to lead exposure during the first year of life.

The social and developmental correlates of early lead exposure were explored in an interim analysis of data from an ongoing longitudinal investigation in Cincinnati. Regardless of the apparent net availability of lead in the infant's physical environment, parental behavior was still significantly associated with infant blood lead levels. However, this was only the case after infants in the study reached 6 months of age and beyond when prewalking progression and early walking made parental management all the more critical. Future lead screening and abatement programs should include supports for the caretaker-child relationship.

Child Development↗