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Biomedical subjects

N F Krebs

Publications and source records attributed to N F Krebs.

At least 19 recordsLinked to original sources
PubMed2001

Normal bone mineral density after treatment for childhood acute lymphoblastic leukemia diagnosed between 1991 and 1998.

OBJECTIVE: We investigated whether previous reports of reduced bone mineral density after management for childhood acute lymphoblastic leukemia (chALL) were confirmed in a more recently treated cohort. STUDY DESIGN: In a cross-sectional study 75 subjects who were given the diagnosis of chALL between January 1, 1991, and December 31, 1997 (69% standard, 31% high risk), at Denver Children's Hospital and who were 11 to 82 months post-diagnosis with no history of relapse, secondary malignancy, or transplant underwent whole body areal bone mineral densitometry (BMD(A) expressed as age- and sex-standardized z scores), a food frequency questionnaire, and a weight-bearing activity survey. RESULTS: Overall, the mean whole body BMD(A) z score was normal (+0.22 +/- 0.96). A significant positive association was found with whole body BMD(A) z score and years elapsed since the beginning of maintenance (linear regression coefficient = +0.2 Deltaz score/year; 95% CI = 0.09 to 0.3) after adjustment was done for risk status/age category, history of cranial radiation, and total days hospitalized. No association was found with high risk/older age at diagnosis, nutrient intake, chemotherapy dosage, or weight-bearing activity. CONCLUSION: Contrary to previous reports in which cranial radiation and longer hospitalizations were prominent components of therapy, our study suggests that more recently treated patients with chALL do not have persistent abnormalities of bone mineral density after completion of therapy.

Biomarkers↗
PubMed2001

Bioavailability of dietary supplements and impact of physiologic state: infants, children and adolescents.

Bioavailability can be broadly defined as the absorption and utilization of a nutrient, both of which may be affected by such host factors as gender, physiologic state and coexisting pathologic conditions. This report highlights factors of particular importance for the bioavailability of nutrients for infants, children and adolescents. Considerations for nutrient bioavailability for pediatric populations include maturation of the gastrointestinal tract, growth, character of the diet, and nutritional status. Critical periods of development include early infancy (0-6 mo), late infancy/early childhood (6-24 mo) and adolescence (12-18 yr). Iron, zinc and calcium are minerals of particular interest and importance to pediatric populations and are susceptible to alterations in bioavailability. In the young infant, iron and zinc are highly bioavailable from human milk. By approximately 6 mo of age, other dietary sources are needed to maintain continued normal status. In breastfed infants who were born prematurely or with low birth weight, earlier supplemental iron is often recommended. For the older infant and toddler, iron and zinc are also important for normal growth and development. The bioavailability of these trace minerals in complementary foods is discussed. During adolescence, adequate calcium intake is critical to normal bone mineralization. In girls, peak calcium absorption and calcium deposition in bones occur at or near menarche, which illustrates the importance of the physiologic state on mineral bioavailability. Investigations into nutrient bioavailability must carefully consider these factors, because the failure to have well-matched comparison groups with respect to age and/or nutritional status may inadvertently mask differences in nutrient utilization.

Adolescent↗
PubMed2001

Interrelationships of key variables of human zinc homeostasis: relevance to dietary zinc requirements.

Currently, estimates of human zinc requirements depend primarily on a factorial approach. The availability of tracer techniques employing zinc stable isotopes has facilitated the acquisition of data on major variables of zinc homeostasis in addition to those that can be measured with careful metabolic balance techniques. These data have promising potential to facilitate and improve the factorial approach. The thesis proposed in this paper is that realistic estimations of dietary zinc requirements by a factorial approach require attention to the dynamic interrelationships between major variables of zinc homeostasis. This applies especially to the positive relationship between endogenous fecal zinc and total absorbed zinc, which is the essential starting point in estimating physiologic and, from there, dietary requirements.

Diet↗
PubMed2000

Dietary phytate reduction improves zinc absorption in Malawian children recovering from tuberculosis but not in well children.

High dietary phytate content that compromises zinc nutriture is thought to be a major problem among children of the developing world. Zinc stable isotope techniques permit the quantitative assessment of the effect of phytate reduction on zinc homeostasis. We tested the hypothesis that zinc absorption would be increased in Malawian children fed a reduced-phytate corn-plus-soy diet compared with a standard high phytate diet. Twenty-three children hospitalized in Blantyre, Malawi, were enrolled. Children were selected from those recovering from tuberculosis and from well children (those with minor injuries, those awaiting elective surgery or healthy siblings). Children received a diet of corn-plus-soy porridge (either low phytate or high phytate) for a period of 3-7 d and then participated in a zinc stable isotope study. The study included the administration of oral and intravenous zinc stable isotopes and 7-d collections of urine and stool. The diet was maintained throughout the duration of specimen collection. Zinc isotopic enrichments in urine and stool were measured, and zinc fractional absorption, total zinc absorption, endogenous fecal zinc, net zinc retention and size of the exchangeable zinc pool were calculated. Among the 14 children recovering from tuberculosis, dietary phytate reduction resulted in higher fractional absorption (0.41 +/- 0.14 versus 0.24 +/- 0.09, mean +/- SD, P: < 0.05) and total zinc absorption (169 +/- 55 versus 100 +/- 46 microg/(kg. d), P: < 0.05). No effect of phytate reduction was seen in the well children (n = 9). Phytate reduction did not decrease the absolute endogenous fecal zinc, but it did decrease it relative to total absorbed zinc. These preliminary results indicate that phytate reduction may be beneficial in improving zinc nutriture in groups with increased zinc requirements who consume a cereal-based diet.

Adolescent↗
PubMed2000

Dietary zinc and iron sources, physical growth and cognitive development of breastfed infants.

Iron and zinc are trace minerals that are of critical importance to the young infant for normal growth and development. Exclusive feeding of human milk provides adequate amounts of both of these nutrients for normal term infants for approximately the first 6 mo. of life. Current recommendations for introduction of complementary foods at this age do not emphasize the order of introduction of specific foods because the infant's gastrointestinal tract is considered mature at this time. Consideration of nutritional needs at 6 mo. has generally focused on the increasing risk of iron deficiency the longer the diet is without an additional source of iron. Recently, there has been more recognition of the risk of zinc deficiency in the second half of the first year of life in breastfed infants. Review of common feeding practices indicates that early complementary foods are typically iron fortified but low in zinc. Several studies have now investigated the effects of meat as an earlier complementary food on iron and zinc status. Results of these studies, although requiring further verification, suggest that increased meat intake by breastfed infants >6 mo. old would adequately support both iron and zinc requirements.

Breast Feeding↗
PubMed2000

Overview of zinc absorption and excretion in the human gastrointestinal tract.

Zinc homeostasis is primarily maintained via the gastrointestinal system by the processes of absorption of exogenous zinc and gastrointestinal secretion and excretion of endogenous zinc. Although these processes modulate net absorption and the size of the readily exchangeable zinc pools, there are limits to the effectiveness of the homeostatic mechanisms of these and other systems. As a result of the interplay of the subcellular regulation of these mechanisms and host, dietary and environmental factors, zinc deficiency is not uncommon, especially on a global basis. This overview briefly reviews current understanding about the subcellular mechanisms of zinc absorption and transport. Factors recognized to affect zinc absorption at the whole body level are reviewed and include the amount and form of zinc consumed; dietary promoters, such as animal protein and low-molecular-weight organic compounds; dietary inhibitors, such as phytate and possibly iron and calcium when consumed as supplements; and physiologic states, such as pregnancy, lactation and early infancy, all of which increase the demand for absorbed zinc. The control of endogenously secreted zinc is less well understood. Available data suggest that the quantity of secreted zinc with each meal may be considerable and that efficient reabsorption is critical to the maintenance of normal zinc balance. Factors that have been proposed to interfere with the normal reabsorption of endogenous zinc include phytate and unabsorbed fat. Understanding of the dietary, physiologic, pathologic and environmental factors that may adversely affect these processes, and therefore zinc homeostasis, will be critical to preventing and treating zinc deficiency in human populations.

Animals↗
PubMed2000

Zinc homeostasis in healthy infants fed a casein hydrolysate formula.

BACKGROUND: The results of earlier, nonquantitative studies suggested that absorption of zinc from a semielemental (casein hydrolysate) formula was inferior to absorption from a cow's milk-based formula. The objective of this study was to compare fractional, total and net zinc absorption, and fecal excretion of endogenous zinc in the same healthy young infants when fed a casein hydrolysate versus cow's milk-based formula. METHODS: Fractional absorption of zinc and fecal excretion of endogenous zinc were determined from measurement of cumulative fecal excretion of unabsorbed tracer and by an isotope dilution technique, respectively, after oral administration of a 70Zn tracer with all formula feedings for 1 day. Six infants were assigned randomly to receive the test or control formula, and the other formula was administered 2 to 5 weeks later. RESULTS: Mean (+/-SD) fractional absorption of zinc from the casein hydrolysate formula (0.47 +/- 0.17) was double that from the cow's milk-based formula (0.22 +/- 0.04; P = 0.01) with a correspondingly greater total zinc absorption (3.23 +/- 1.67 mg Zn/day vs. 1.55 +/- 0.55 mg Zn/day; P = 0.05). Because the excretion of endogenous zinc in the feces did not differ between formulas (0.90 +/- 0.44 mg Zn/day vs. 0.91 +/- 0.29 mg Zn/day), net absorption of zinc was also higher with the casein hydrolysate formula (2.33 +/- 1.65 mg Zn/day vs. 0.81 +/- 0.67 mg Zn/day; P = 0.02). CONCLUSIONS: Retention of zinc appeared to be adequate to meet the needs for growth during feeding with cow's milk-based formula and was more than adequate during short-term feeding with the casein hydrolysate formula.

Absorption↗
PubMed2000

Development of a compartmental model of human zinc metabolism: identifiability and multiple studies analyses.

A compartmental model of zinc metabolism has been developed from stable isotope tracer studies of five healthy adults. Multiple isotope tracers were administered orally and intravenously, and the resulting enrichment was measured in plasma, erythrocytes, urine, and feces for as long as 3 wk. Data from total zinc measurements and model-independent calculations of various steady-state parameters were also modeled with the kinetic data. A structure comprised of 14 compartments and as many as 25 unknown kinetic parameters was developed to adequately model the data from each of the individual studies. The structural identifiability of the model was established using the GLOBI2 identifiability analysis software. Numerical identifiability of parameter estimates was evaluated using statistical data provided by SAAM. A majority of the model parameters was estimated with sufficient statistical certainty to be considered well determined. After the fitting of the model and data from the individual studies using SAAM/CONSAM, results were submitted to SAAM extended multiple studies analysis for aggregation into a single set of population parameters and statistics. The model was judged to be valid based on criteria described elsewhere.

Adult↗
PubMed2000

Abnormalities in zinc homeostasis in young infants with cystic fibrosis.

Low plasma zinc concentrations have been reported in approximately 30% of young infants with cystic fibrosis identified by newborn screening. The objective of this study was to examine zinc homeostasis in this population by application of stable isotope methodology. Fifteen infants with cystic fibrosis (9 male, 6 female; 7 breast-fed, 8 formula-fed) were studied at a mean (+/-SD) age of 1.8 +/- 0.7 mo. On d 1, 70Zn was administered intravenously, and 67Zn was quantitatively administered with all human milk/formula feeds during the day. Three days later, a 3-d metabolic period was initiated, during which time intake was measured and complete urine and fecal collections were obtained. Fractional zinc absorption, total absorbed zinc, endogenous fecal zinc, and net absorbed zinc were measured; fecal fat excretion was also determined. Fractional absorption was significantly higher for the breast-fed infants (0.40 +/- 0.21) compared with the formula-fed group (0.13 +/- 0.06) (p = 0.01), but with the significantly higher dietary zinc intake of the formula-fed group, total absorbed zinc was higher for those receiving formula (p = 0.01). In 1 infants with complete zinc metabolic data, excretion of endogenous zinc was twofold greater for the formula-fed infants (p < 0.05); net absorption (mg zinc/d) was negative for both feeding groups: -0.04 +/- 0.52 for breast-fed; -0.28 +/- 0.57 for formula-fed. Endogenous fecal zinc losses correlated with fecal fat excretion (r = 0.89, n = 9, p = 0.001), suggesting interference with normal conservation of endogenously secreted zinc. These findings indicate impaired zinc homeostasis in this population and suggest an explanation for the observations of suboptimal zinc status in many young infants with cystic fibrosis prior to diagnosis and treatment.

Administration, Oral↗
PubMed1999

Zinc transfer to the breastfed infant.

Zinc is a micronutrient which is critical to normal growth and development. Zinc concentrations in human milk decline sharply during the early months post partum, regardless of maternal zinc intake. Milk zinc concentrations do not increase in response to increased maternal zinc intake if maternal zinc status is adequate. The mechanism of zinc secretion into milk is not fully understood. A mutation in the gene for a zinc transporter protein may account for abnormally low milk zinc concentrations associated with severe zinc deficiency in breastfed infants. The zinc requirements of breastfed infants are generally met with exclusive breastfeeding through 5-6 months of age, due to the favorable bioavailability of the zinc in human milk. Because of declining milk zinc concentrations and intake, zinc status in exclusively breastfed infants is likely to become marginal beyond 6 months of age, and may become suboptimal for some infants if exclusive breastfeeding continues. The choice of complementary foods is important to maintain adequate zinc status in breastfed infants after 6 months.

Breast Feeding↗
PubMed1999

American Academy of Pediatrics. Committee on Nutrition. Calcium requirements of infants, children, and adolescents.

This statement is intended to provide pediatric caregivers with advice about the nutritional needs of calcium of infants, children, and adolescents. It will review the physiology of calcium metabolism and provide a review of the data about the relationship between calcium intake and bone growth and metabolism. In particular, it will focus on the large number of recent studies that have identified a relationship between childhood calcium intake and bone mineralization and the potential relationship of these data to fractures in adolescents and the development of osteoporosis in adulthood. The specific needs of children and adolescents with eating disorders are not considered.

Adolescent↗
PubMed1998

Microwave method for preparing erythrocytes for measurement of zinc concentration and zinc stable isotope enrichment.

A microwave digestion method to prepare human erythrocytes for measurement of Zn concentration by atomic absorption spectrophotometry and stable isotope enrichment by mass spectrometry is described. Also described is a process for purifying digested erythrocyte samples enriched with Zn stable isotope for analysis by fast atom bombardment mass spectrometry. Microwave digestion was investigated as a way to increase sample throughput by replacing a more time-consuming conventional oven ashing/hot plate wet digestion method. Pooled red blood cells and NIST bovine liver standard reference material were digested by the two different methods and zinc recoveries compared by atomic absorption spectrophotometry. Microwave and conventional methods yielded 11.7 +/- 0.1 and 11.7 +/- 0.2 micrograms/g (wet wt), respectively, for the pooled erythrocytes, and Zn recovery from NIST bovine liver standard (certified 123 +/- 8 micrograms/g) was 128.2 +/- 1.2 and 127.4 +/- 1.3 micrograms/g, p > or = 0.282, respectively. Microwave digestion improved the processing of erythrocytes for atomic absorption spectrophotometry and mass spectrometry by reducing digestion time from 1 week to 2 h. In addition, a procedure for purifying digested erythrocyte samples by either extraction and ion-exchange chromatography in preparation for mass spectrometry analysis of Zn stable isotope enrichment is outlined.

Animals↗
PubMed1998

Human zinc metabolism: advances in the modeling of stable isotope data.

Compartmental modeling is a useful tool for investigating metabolic systems and processes. We and others have applied it to the study of zinc metabolism in humans. Because existing models could not be accurately fitted to our data, we have developed a new model of human zinc metabolism based on stable isotope tracer data from studies of five healthy adults. Multiple isotope tracers were administered orally and intravenously and the resulting enrichment measurement in plasma, erythrocytes, urine, and feces. These tracer kinetic data, along with other measured and calculated tracee and steady-state data, were used to develop the model. A single model structure composed of fourteen compartments was found to be suitable for all subjects. Model development and fitting of data and model for each subject were accomplished using the SAAM/CONSAM computer programs. The model development and fiting processes are described and exemplified using data from one of the subjects. While identifiability could not be demonstrated a priori due to the model's complexity, parameter statistics for the fitted models did show most parameters to be adequately identified a posteriori.

Administration, Oral↗
PubMed1998

Low plasma zinc concentrations in young infants with cystic fibrosis.

OBJECTIVES: The purpose of this study was to examine the zinc status of young infants with cystic fibrosis before and after the initiation of pancreatic enzyme therapy. STUDY DESIGN: Cross-sectional data were obtained for infants with cystic fibrosis identified by newborn screening. Plasma zinc concentrations were measured and analyzed according to enzyme use at the time of the blood draw. On a subgroup of infants, zinc concentrations were determined again after several weeks with enzyme therapy. RESULTS: Mean (+/-SD) plasma zinc concentration for the infants studied before the initiation of enzyme therapy was 10.4 +/- 2.2 micromol/L (68.3 +/- 14.7 microgram/dL) (n = 48), which was significantly lower than the mean for those receiving enzymes for >/=2 weeks, 11.8 +/- 2. 3 micromol/L (77.1 +/- 14.9 microgram/dL) (n = 15) (P =.03). For the group not yet receiving enzymes, 29% of infants had zinc concentrations in the deficient range. Data were available before and after enzyme therapy for 30 infants and indicated a mean increase of 1.64 +/- 3.0 micromol/L (10.7 +/- 19.3 microgram/dL) (P =. 005). CONCLUSIONS: These data suggest that many of the infants were zinc deficient at the time of diagnosis. We conclude that zinc should be included among the specific micronutrients given consideration in the management of cystic fibrosis, particularly in infants.

Cross-Sectional Studies↗
PubMed1998

Evaluation of zinc metabolism with use of stable-isotope techniques: implications for the assessment of zinc status.

Zinc stable isotopes can be applied to the identification of populations at risk for zinc deficiency and to monitoring the effects of zinc intervention studies designed to improve zinc nutriture. Techniques using these isotopes can provide information on how effectively the intestine is absorbing exogenous dietary zinc and conserving endogenous zinc. They can also yield estimates of the quantity of readily exchangeable zinc in the body. Data derived from stable-isotope studies can provide extensive information on zinc status and the bioavailability of dietary zinc, allowing researchers to relate zinc intake to physiologic and pathologic conditions. Application of these techniques in longitudinal studies can provide quantitative data on the effectiveness of prevention programs such as simple community measures aimed at reducing dietary phytate and zinc fortification and supplementation programs. Further, judicious application of zinc stable-isotope techniques could make an important contribution to progress toward the eradication of zinc deficiency in infants and young children in the developing world.

Animals↗
PubMed1998

Zinc supplementation during lactation.

The requirements for zinc during lactation are greater than those during pregnancy, especially during the early weeks postpartum. Therefore, lactation poses a significant threat to maternal zinc homeostasis, particularly in populations with chronically low dietary zinc intakes. The current knowledge of maternal zinc status in lactation, particularly in developing countries, is reviewed herein with emphasis on the effects of zinc supplementation trials. The studies that have examined the zinc status of breast-fed infants are also reviewed.

Dietary Supplements↗