摘要:

The responsibilities of the National Institute of Child Health and Human Development (NICHD) in nutrition research comprise a variety of biomedical and behavioral areas. These include the nutrient requirements of the pregnant and nursing woman, the fetus, infant, child, and adolescent; nutritional antecedents of disease; assessment of nutritional status at all developmental stages; and the role of nutrition in the treatment of inborn errors of metabolism. To meet these responsibilities better, the NICHD staff tries to keep the Institute's programs current with contemporary science by periodically sponsoring an assessment of research progress in the appropriate areas and analyzing the needs and opportunities for nutrition research.The last such NICHD-sponsored assessment of nutrition research, called the Nutrition Research Plan, was published 10 years ago. Since then, the nutrition field has entered a new world of opportunities, and there has been a need for an update in our plans. Accordingly, the staff of the Endocrinology, Nutrition and Growth (ENG) branch of the NICHD recently invited a multidisciplinary panel of noted investigators from the ranks of active scientists outside the Institute to describe the state of nutrition science in the relevant areas and to identify promising research questions. These consultants divided their topics into 13 chapters, drafted the chapters, and submitted them to the group for review and discussion. The final product represents a consensus of the group on the chapter contents, statements, and recommendations. Research directions and opportunities described in the chapters, which exceed current budgetary capacity for implementation, were reviewed by staff of the NICHD for feasibility and relevance to the specific mandate of the Institute. At the end of each chapter is a staff response, representing the staff's best judgment on desirable actions for the future, taking into account the Institute's mission and the likely availability of resources.Members of the National Advisory Child Health and Human Development Council participated in the development of this plan. The document was reviewed by the Planning and Agenda Committee of the Council and endorsed by the entire Council before publication.The names of the consultants who formulated the plan and a summary of their recommendations and the staff responses are printed below.Requests for reprints of this summary or for copies of the complete plan may be made to: Office of Research Reporting, National Institute of Child Health and Human Development, Building 31, Room 2A32, Bethesda, MD 20892; phone: 301–496-4757. Other inquiries should be addressed to: Ephraim Y. Levin, M.D., Medical Officer, Endocrinology, Nutrition and Growth Branch, National Institute of Child Health and Human Development, Executive Plaza North Building, Room 637, Bethesda, MD 20892.

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

We assessed pediatric cardiology research by reviewing pediatric cardiology abstracts submitted in 1990 to the Society of Pediatric Research, American Academy of Pediatrics, and American Heart Association national meetings. Included were accepted and rejected studies. Abstracts were reviewed for disease being studied, methodology used to answer the research question, study design, and acceptance/rejection. Abstracts were analyzed from 123 institutions, 81 American and 42 foreign. Out of 423 abstracts, 307 (72.6%) were clinical and the remainder were basic science investigations. Slightly more than half of the clinical submissions were related to congenital heart disease. Coronary artery disease and inflammatory diseases accounted for 12% of clinical submissions. Echocardiography, clinical outcome measures, and electrophysiology were the most common research methodologies. Almost 80% of basic science research was performed in normal tissues; animal physiology, fetal physiology, and cellular/biochemical studies were the most common methodologies. With regard to study design, half of the clinical studies were retrospective and only 6% were either prospective epidemiologic or prospective controlled intervention trials. For basic sciences, 38% of abstracts were descriptions of phenomena and 62% were hypothesis testing, with developmental hypotheses being most common. Acceptance rates favored higher quality study design. However, areas of greatest interest to cardiologists, congenital heart disease, cardiomyopathy, and electrophysiology, had poorer quality study design than did other areas. We have shown broad interest in pediatric cardiology research. However, clinical studies frequently were retrospective or had uncontrolled study designs. Basic science research was performed at a small number of institutions and emphasized either description of phenomena or developmental biology of normal tissues.

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Respiratory parameters of skeletal muscle were determined in permeabilized muscle fibers by adapting a technique described by Veksler et al. for cardiac fibers (Biochim Biophys Acta, 892:191–196, 1987). This method consists of the permeabilization of muscle fibers by saponin by allowing respiratory substrates and inhibitors to reach the mitochondria. In this way, the mitochondria may be studied inside the fibers as if they were isolated. We have verified, using various techniques, that the mitochondria remain intact during this procedure. This method has been applied to the study of six newborn infants for whom a diagnosis of a mitochondrial defect was suspected. In all cases, the defect was to be found on the permeabilized fibers, and this was confirmed by an enzymatic study. The advantage of this new method, associated with the measurement of the enzymatic activities on a crude homogenate, is to enable a simple and rapid diagnosis on a small amount of sample without damaging the mitochondria during the isolation procedure.

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Trichloroethylene (TCE) and dichloroethylene (DCE) are related halogenated aliphatic hydrocarbon industrial solvents that are frequently found as drinking water contaminants. TCE has been implicated as a cardiac teratogen in an epidemiologic study and in a chick model. The purpose of this study was to determine whether DCE was also a cardiac teratogen in the chick embryo. Fertilized White Leghorn chick eggs (n = 418) were inoculated just above the embryo with 30 μL of a test solution on d 3 of incubation. Two control groups were studied: normal saline (n = 96) and the diluent for the DCE, miners' oil (n = 108). DCE was studied at three doses: 5, 20, and 25 μM (n = 76, 62, and 76, respectively). Eggs were coded with a seven-digit number to mask identity. Chicks were terminated on d 18 of incubation, and, after external inspection, hearts and great vessels were dissected macroscopically according to a detailed protocol. Abnormal hearts were reviewed and the diagnosis was agreed upon by three investigators before decoding the seven-digit number and photographing the abnormality. Some embryo death and subsequent tissue autolysis occurred in all groups, but, compared to controls, it was not significantly greater in the treatment group. However, combining all controls and all experimentals, significantly more (p = 0.02) embryonic death occurred in the experimental group. Noncardiac anomalies occurred in 17 embryos and were highest in the saline (four), 5 μM (four), and 20 μM (seven) DCE groups. Cardiac and great vessel anomalies occurred in 4% of saline controls, 4% of mineral oil controls, 17% of the DCE 5 μ group (p < 0.05), 19% of the DCE 20 μM group (p < 0.05), and 2% of the DCE 25 μM group (p = 0.1). Cardiac anomalies included atrial and ventricular septal defects, malformations of all valves, and great vessel abnormalities. Results suggest that DCE is a more potent cardiac teratogen than a general teratogen in the chick. Results for DCE, including the marked decrease in cardiac teratogenicity between 20 and 25 μM treated groups, are almost identical to results found for TCE, which suggests that the cardiac teratogenic effect may be exerted through a common mechanism, possibly a common or similar metabolite.

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

A left to right shunt increases myocardial work and is often accompanied by increased catecholamine levels. Because both increased myocardial work and increased catecholamine levels may induce increased fatty acid utilization, which could increase resting myocardial oxygen consumption and therefore unfavorably affect coronary reserve, we studied myocardial uptake of glucose, pyruvate, lactate, β-OH-butyrate, acetoacetate, FFA, and triglycerides in 12 7-wk-old lambs with aortopulmonary left to right shunts (58 ± 2% of left ventricular output, mean ± SEM) and in 10 control lambs 2 wk after surgery. Despite the shunt, systemic blood flow in the shunt lambs was maintained at the same level as in the control lambs. This was accomplished by an increased heart rate and stroke volume. Furthermore, the shunt was accompanied by an increased myocardial oxygen consumption in the shunt lambs (834 ± 70 versus 528 ± 43 μmol O2min−1100 g−1; p < 0.05). There were no significant differences in arterial substrate concentrations between the two groups. The same was true for arteriovenous differences across the myocardium, with the exception of lactate, which was substantially higher in shunt than in control lambs (72 ± 25 versus 18 ± 23 μmol/L; p < 0.05). As a consequence, myocardial lactate uptake in the shunt lambs was increased 15-fold (18 ± 6 versus 1 ± 2 μmol.min−1.100 g−1; p < 0.02), whereas uptake of the other substrates merely paralleled the increased myocardial blood flow. Our data demonstrate that myocardial substrate uptake is not substantially different between shunt and control lambs, with the exception of lactate, of which the extraction is 10-fold higher than in control lambs. We speculate that the increased myocardial lactate utilization may reflect an increase of lactate and pyruvate dehydrogenase activities.

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Cardiovascular responses to feeding have been observed in several species during various periods of development and have been implicated in the development of cardiovascular regulation. In the rat, these responses are characterized by short-lasting, large increases in blood pressure (BP) and moderate increases in heart rate. These responses appear to be sympathetically mediated because pretreatment with ganglionic blockers eliminates the increase in BP associated with milk ingestion. The present study was designed to determine if similar cardiovascular responses occur during feeding in the newborn piglet. Piglets were obtained on postnatal d 2 and fed a milk diet via automatic feeder 6 times a day. On postnatal d 6, the piglets were instrumented with an external carotid artery catheter and an internal jugular vein catheter. On postnatal d 8 and 9, direct arterial BP and heart rate were recorded during feeding. BP responses to milk ingestion were immediate, and they reached a maximum increase of 50% above baseline on both test days and followed a response profile similar to that previously described in the 15-d-old rat. An increase in heart rate was also observed, reaching a maximum of 42% above baseline. The results show that early in life piglets have large cardiovascular response to milk ingestion similar to those observed in young rats and human infants. These responses appear to model the cardiovascular responses to feeding observed in human infants and might be useful as a noninvasive method for assessing neonatal autonomic reactivity. These responses also have the potential to cause adverse effects in newborns already at risk for cardiovascular and cerebrovascular disease.

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

An oral load of 20 mg/kg galactose produces significant changes in the31P magnetic resonance spectrum of the liver of a galactosemic patient. The peak at 5.2 ppm (which includes inorganic phosphate and galactose-1 -phosphate) increased on two occasions to about twice its original size 60 min after galactose administration. An oral load of 10 mg/kg galactose given to a second patient produced no discernible changes at 30 min. We have also used an animal model of galactose intolerance, in which galactose metabolism in rats was blocked by the acute administration of ethanol. Studies in vivo and in vitro showed that the increase in the peak at 5.2 ppm was largely due to galactose-1-phosphate. We have shown in this preliminary study that small amounts of galactose can produce significant elevation of hepatic galactose-1-phosphate, which can be detected by31P magnetic resonance spectroscopy.

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The study was designed to evaluate a non-invasive breath test using naturally13C-rich corn (maize) as substrate to provide quantitative information about the digestion of starch by children in health and disease. The variability of background13C:12C of young British children was investigated by collecting breath samples over 6 h from 17 healthy children, 6–35 mo old, and from seven children with cystic fibrosis, 25–48 mo old, in their homes. Background13C enrichment was —26.6 and —25.4 d per mil in the healthy and cystic fibrosis groups, respectively (p <0.01), and varied little during the day (SD = 0.4 ± per mil). Eight healthy children and five with cystic fibrosis were given a test breakfast of corn starch cooked in milk with sugar. The cystic fibrosis group repeated the test with the addition of an enzyme supplement containing α-amylase. Subjects accepted variable amounts of starch (range 0.2–2.8 g/kg body wt). The percentage of ingested13C recovered during the 6 h after the meal increased with age in the healthy children (range 15–53%). Three children with cystic fibrosis had negligible13C recoveries, and the other two had lower recoveries than expected for their age. The addition of enzymes did not consistently improve13C recovery. We conclude that the13C breath test based on corn has potential for investigating starch digestion in young children. Initial results suggest that starch digestion is impaired in some children with cystic fibrosis and that enzyme supplements do not improve digestion consistently or completely.

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The role of oral corticosterone (C) in the maturation of the neonatal rat jejunal barrier to the absorption of nonspecific macromolecules was evaluated. This was done by adding C to the diet of rat pups weaned at an early age, 17 d, from maternal milk (MM) to either a protein hydrolysate (PH) or soy (S) artificial formula. Both PH and S are known to cause a delay in small intestinal closure to the absorption of a 40-kD glycoprotein tracer, horseradish peroxidase (HRP), on d 21 of age. C was added to PH and S formulas from d 17 to 21 at 0.26 μmol/L (10 μg/dL), a level found in the MM of lactating rat dams, or at 10.29 μmol/L (400 Mg/dL) (PH + 10C, PH + 400C) (S + 10C, S + 400C). Controls consisted of rat pups fed PH or S without C and animals remaining with the dam on MM. The delay in jejunal closure to HRP on d 21 in both PH- and S-fed pups was prevented by C supplementation at both the higher and lower concentrations. Geometric mean (95% confidence intervals) jejunal HRP absorption in PH + 10C pups was 74 (32,167) IU HRP/mL ± cm ± min, less than in pups fed PH without C [353 (200,615); p <0.05] and indistinguishable from HRP absorption in MM-fed animals [111 (79,154)]. HRP absorption in PH + 400C pups [52 (23, 115)] was also less than that in animals fed PH without C (p < 0.01) and indistinguishable from those fed MM. In S-fed pups, closure delay was accompanied by a lamina propria eosinophilia not seen with PH or MM feedings; this did not occur in S + 400C pups. Our results lend support to the view that C, a glucocorticoid known to be present in rat MM, may play a role in the normal ontogenetic closure of the small intestine to macromolecular absorption in the neonatal rat.

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID