Abstract: The concerted action "The process for the assessment of the scientific support for claims on foods", PASSCLAIM, proposed criteria that could provide an international yardstick for the harmonised transparent assessment of evidence submitted to support a claim for a food or food component. The evidence would be systematically appraised against specific criteria: namely, (1) a characterisation of the food or food component to which the claimed effect is attributed; (2) human data, primarily from intervention studies that represent the target populations for the claim; (3) a dose response relationship; (4) evidence allowing for confounders such as lifestyle, consumption patterns, background diet and food matrix etc.; (5) an appropriate duration for the study; (6) a measure of compliance; (7) adequate statistical power to test the hypothesis. Validated and quality assured markers of intermediate or final outcomes could be used when ideal endpoints are not easily accessible for measurement as long as their relationship to the development of the principal outcome relevant to the claim is well characterised and substantiated. The overall coherence and totality of published and unpublished evidence should be considered in the process. Assessments for substantiation claims need expert judgement, weighting of the strength of the claim, and intelligent use of the criteria applied on an individual basis with respect both to gaps in the knowledge and to any need for new knowledge and data.
Abstract: Upper levels are estimates of the quantity of a nutrient that can be ingested daily over a lifetime without appreciable risk to health. The approach to establishing upper levels for nutrients, nutrient risk assessment, has derived from the risk assessment of foreign chemicals that are deliberately added to foods, or are in food as contaminants. This process of risk assessment is rigorous and transparent, particularly in dealing with the uncertainty arising from the data available and their assessment and extrapolation to human populations. Hazard identification and characterization, i.e., a dose-response pattern, as applied to xenobiotics, are discussed first, and then the difficulties of applying this approach to nutrients are reviewed. Nutrients, in contrast to foreign chemicals, have specific and selective metabolic pathways and homeostasis, as well as specific functions. This is the source of differences in the nutrient risk assessments produced by various national and international advisory bodies. Although the same data are used in such exercises, different judgments are made about identifying adverse effects, the nature of uncertainties in the assessment, and in matching the upper levels with exposure assessments and dietary reference values. The establishment of different upper levels for different national and international communities is a source of confusion in public health policy and practice and a barrier to trade. It is proposed that a basis for harmonizing the existing approaches used in nutrient risk assessment would be the collaborative development of the model for establishing upper levels of intake for nutrients and related substances that has been recently described by a Joint Task Force of the World Health Organization and the Food and Agriculture Organization.
Abstract: BACKGROUND: The prevalence of percutaneous endoscopic gastrostomy (PEG) feeding of children in the UK has increased. This study explored how gastrostomy feeding affects the daily lives of children and their families, from the parents' perspectives and developed a conceptual framework for assessing the impact of feeding on family life. METHODS: A semi-structured interview approach was used to obtain the parents' views regarding the impact of feeding on daily lives; both of the children and their family. The study was a cross-sectional qualitative design employing purposive sampling. Twenty-four interviews were conducted and data were analysed descriptively and thematically. RESULTS: Difficulties arising from PEG feeding included vomiting (71%), diarrhoea (33%), infection of the PEG site (46%) and leakage (54%). The key issues that emerged included delayed and disturbed sleep, restricted ability to go out, difficulties finding a place to feed, child care problems, negative attitudes of others towards feeding and family divisions. Parents primarily raised key issues regarding the impact of PEG feeding on themselves or the family rather than on the child. CONCLUSIONS: An assessment framework has been developed, based on the parents perceptions, for use in assessing the impact of feeding upon family life and identifying the support required for parents of children receiving PEG feeding. Provision of adequate support is likely to require a network of healthcare professionals, social care and support groups, all working together to meet identified needs.
Abstract: AIM: This paper is a report of a study to compare the perceptions of adult patients, family carers, nurses and dietitians regarding home percutaneous endoscopic gastrostomy feeding. BACKGROUND: Healthcare professionals have a major role in patient selection for gastrostomy placement and the provision of aftercare but it is not clear if patients, their carers and healthcare professionals have similar perceptions of the initiation and delivery of feeding and of the care in general. METHOD: A cross-sectional mixed-method study using purposive sampling, semi-structured interviews and questionnaires was performed. Interviews were undertaken during 2005 with adult patients and carers of adults receiving home feeding. A questionnaire containing comparable questions was distributed to the lead district nurse and dietitian providing the individual patient's care. Binomial regression was used to analyse any differences in perceptions across the groups of respondents. RESULTS: Nurses and dietitians had similar perceptions of gastrostomy feeding in adults. Family carers' perceptions matched those of professionals more closely than did those of patients. The greatest difference in perceptions was between patients and their family carers. Respondents' views about success of feeding and the appropriateness of the feeding regimen were similar, but greater differences existed regarding quality of life, withdrawal of feeding and choice in decision-making about tube placement. CONCLUSION: There is a need for increased patient and carer involvement in decision-making and for sufficient, appropriate information to facilitate informed decision-making. Practitioners who involve carers in decision-making, where patients lack capacity, need to be aware that carers may not represent the views of patients.
Abstract: Claims are used to support public health advocacy and marketing. Their evidence base is variable. Claims are made on (i) nutrient content, (ii) comparative merits, (iii) health benefits, and (iv) medical benefits. Experience with therapeutic agents has aided the development of recommendations for the substantiation of health claims for foods and food components, with which dietary supplements would be included. An EU Concerted Activity, Functional Food Science in Europe, suggested that such claims should be based on the general outcomes of 'enhanced function' and 'reduced risk of disease'. A further EU Concerted Activity, The Process for the Assessment of Scientific Support for Claims on Foods, proposed that the evidence base should provide: a characterization of the food or food component to which the claimed effect is attributed; human data, primarily from intervention studies that represent the target populations for the claim; a dose-response relationship: evidence of allowing for confounders including lifestyle, consumption patterns, background diet and food matrix; an appropriate duration for the study; a measure of compliance; and have adequate statistical power to test the hypothesis. When ideal endpoints are not easily accessible for measurement, validated and quality assured markers of the intermediate or final outcomes could be used, as long as their relationship is well characterized. Overall, the totality and coherence of published and unpublished evidence should be considered. Assessments for substantiation need expert judgement, weighting of the strength of the claim, and intelligent use of the criteria applied on an individual basis with respect both to gaps in knowledge and to any need for new knowledge and data.
Abstract: BACKGROUND: The perceptions of parents and professionals are important in deciding to feed children by gastrostomy, yet there are few published studies in this field. This study explored and compared the perceptions of parents to those of paediatric outreach nurses and paediatric dietitians. METHODS: A cross-sectional mixed-method study with purposive sampling was undertaken using structured interviews and questionnaires to explore perceptions of percutaneous endoscopic gastrostomy (PEG) placement and feeding. Binomial regression was used to investigate differences in perceptions across the groups of participants. RESULTS: Parents, paediatric outreach nurses and dietitians shared similar perceptions regarding success of feeding, support for gastrostomy reinsertion and the acceptability of the child's quality of life. Much greater differences in perceptions were evident regarding the parents' involvement in the decision-making process for PEG placement and the adequacy of the support received from healthcare professionals. CONCLUSIONS: A high level of support for feeding was demonstrated together with strong perceptions across all groups that feeding was successful. It is important for healthcare professionals to consider the perceptions of the parents throughout decision making and provision of care following PEG placement because it is highly likely there will be differences in the perceptions between parents and healthcare professionals.
Abstract: Survival of small premature infants has markedly improved during the last few decades. These infants are discharged from hospital care with body weight below the usual birth weight of healthy term infants. Early nutrition support of preterm infants influences long-term health outcomes. Therefore, the ESPGHAN Committee on Nutrition has reviewed available evidence on feeding preterm infants after hospital discharge. Close monitoring of growth during hospital stay and after discharge is recommended to enable the provision of adequate nutrition support. Measurements of length and head circumference, in addition to weight, must be used to identify those preterm infants with poor growth that may need additional nutrition support. Infants with an appropriate weight for postconceptional age at discharge should be breast-fed when possible. When formula-fed, such infants should be fed regular infant formula with provision of long-chain polyunsaturated fatty acids. Infants discharged with a subnormal weight for postconceptional age are at increased risk of long-term growth failure, and the human milk they consume should be supplemented, for example, with a human milk fortifier to provide an adequate nutrient supply. If formula-fed, such infants should receive special postdischarge formula with high contents of protein, minerals and trace elements as well as an long-chain polyunsaturated fatty acid supply, at least until a postconceptional age of 40 weeks, but possibly until about 52 weeks postconceptional age. Continued growth monitoring is required to adapt feeding choices to the needs of individual infants and to avoid underfeeding or overfeeding.
Abstract: The knowledge base underpinning the setting of nutrient requirements for children and adolescents is not very secure. The advent of the concepts of optimal nutrition and functional foods has encouraged the possible use of functional effects as criteria for adequate nutrition in this age group. Target functions have been identified for growth development and differentiation and for behavioural and cognitive development. However, ideal markers or effects for these are not generally available. Additionally, nutrition in young people should avoid predisposing them to diet-related disease in later life. It is suggested that functional effects should include markers of reduction of risks of disease (nutritional safety) as well of benefits for health and well-being. Such markers of functional effects should be expected to arise from fundamental studies of nutrient-gene interactions and post-genomic metabolism.
Abstract: The consumption of nondigestible carbohydrates is perceived as beneficial by health professionals and the general public, but the translation of this information into dietary practice, public health recommendations, and regulatory policy has proved difficult. Nondigestible carbohydrates are a heterogeneous entity, and their definition is problematic. Without a means to characterize the dietary components associated with particular health benefits, specific attributions of these cannot be made. Food labeling for "fiber" constituents can be given only in a general context, and the development of health policy, dietary advice, and education, and informed public understanding of nondigestible carbohydrates are limited. There have, however, been several important developments in our thinking about nondigestible carbohydrates during the past few years. The concept of fiber has expanded to include a range of nondigestible carbohydrates. Their fermentation, fate, and effects in the colon have become a defining characteristic; human milk, hitherto regarded as devoid of nondigestible carbohydrates, is now recognized as a source for infants, and the inclusion of nondigestible carbohydrates in the diet has been promoted for their "prebiotic" effects. Therefore, a review of the importance of nondigestible carbohydrates in the diets of infants and young children is timely. The aims of this commentary are to clarify the current definitions of nondigestible carbohydrates, to review published evidence for their biochemical, physiologic, nutritional, and clinical effects, and to discuss issues involved in defining dietary guidelines for infants and young children.
Abstract: The aim of this study was to quantify the effects of maternal cigarette smoking on placental morphology, paying particular attention to variables known to be influential in facilitating oxygen diffusion. Structural quantities were estimated by stereological analyses of placental samples drawn from non-smoking and smoking women whose smoking habits were assessed both subjectively (from volunteered cigarette consumption) and objectively (by determining levels of plasma cotinine, a major metabolite of nicotine). Concentrations of placental cadmium were also measured. In the smoking group, maternal and fetal haematocrits were elevated and mean birthweight was reduced. Within placentae, the most significant alterations were increases in cadmium levels, the relative volumes of maternal intervillous space, the relative surface areas of fetal capillaries and decreases in the relative and absolute volumes of fetal capillaries. Findings indicate that changes in capillary volume are the result of a decrease in mean capillary diameter rather than total length. The mean thickness of the trophoblast component of the villous membrane was also increased in the smoking group. Although increased haematocrits suggest that fetuses of smoking mothers suffer hypoxic stress, these morphological changes are likely to compromise, rather than assist, transplacental oxygen transfer. This is in marked contrast to the adaptive changes seen in pregnancies associated with preplacental hypoxia and suggests that other factors might be compromising the fetoplacental unit. Finally, although the morphological changes associated with maternal smoking seem to be the result of an all-or-none, rather than dose-dependent, effect, the available evidence is not conclusive.
Abstract: The current limited understanding of the ontogeny and mechanisms of the metabolism of iron, zinc, copper, selenium, iodine, and manganese in the micropremie are reviewed. The effects of early delivery on these processes are considered, as are the suggested amounts of these trace elements required for micropremies.
Abstract: The aim of this study was to test whether or not adaptations in partial, total and specific oxygen diffusive conductances occur in the placentae of women who smoke cigarettes during pregnancy and help to compensate for intrauterine fetal hypoxic stress. Tissue sections were randomly sampled from human term placentae divided into two groups (non-smokers and smokers) according to maternal smoking status. In smokers, status was expressed as either declared smoking rate or level of plasma cotinine (the major metabolite of nicotine). Sections were analysed stereologically to estimate key structural quantities (vascular volumes, exchange surface areas, tissue diffusion distances). These were combined with previously-published physicochemical quantities (oxygen-haemoglobin reaction rates and tissue oxygen diffusion coefficients) in order to estimate the partial conductances of six tissue compartments of the oxygen pathway: maternal erythrocytes and plasma, villous trophoblast, villous stroma (including fetal capillary wall), fetal plasma and erythrocytes. From partial conductances and birthweights, total and specific conductances were calculated for each placenta. Results were assessed statistically by analyses of variance and t -tests. Despite apparent improvements in the partial conductances of the maternal erythrocytes and plasma, total and specific conductances did not alter significantly in smoking groups. However, the relative biases affecting these estimates may be different in smokers and non-smokers. We conclude that total conductance does not increase in placentae associated with maternal smoking. However, given that the fetus suffers chronic hypoxic stress as a consequence of smoking (evidenced here by elevated haematocrits), even a constant diffusive conductance implies a reduced transplacental partial pressure gradient. This could be a contributory factor to the reduced birthweight.
Abstract: Studies from animal models and in human volunteers have permitted to construct a provisional continuum of acceptable intakes of copper that would avoid copper deficiency and/or toxicity: acceptable intakes may vary between 10 and 50 mg/kg body weight.
Abstract: Different approaches are used to determine ideal ranges of intakes and threshold levels of safe intakes for nutrients. A consequence of this is that, for inorganic nutrients particularly, a safe level set by traditional toxicologic procedures might be compromised because it is inconsistent with physiologic observations and customary intakes and because the levels set may allow an inordinately narrow range of safe intakes above the upper limit of recommended intakes. This article used data from studies in animal models and in human volunteers to construct a provisional continuum of adaptive processes and pathophysiologic phenomena associated with a range of copper intakes extending from toxic to deficient to suggest an approach to establishing an acceptable range of intakes for copper that would address simultaneously the advisory and regulatory needs of nutritionists and toxicologists.
Abstract: Few other aspects of food supply and metabolism are of greater biological importance than the feeding of mothers during pregnancy and lactation, and of their infants and young children. Nutritional factors during early development not only have short-term effects on growth, body composition and body functions but also exert long-term effects on health, disease and mortality risks in adulthood, as well as development of neural functions and behaviour, a phenomenon called 'metabolic programming'. The interaction of nutrients and gene expression may form the basis of many of these programming effects and needs to be investigated in more detail. The relation between availability of food ingredients and cell and tissue differentiation and its possible uses for promoting health and development requires further exploration. The course of pregnancy, childbirth and lactation as well as human milk composition and the short- and long-term outcome of the child are influenced by the intake of foods and particularly micronutrients, e.g. polyunsaturated fatty acids, Fe, Zn and I. Folic acid supplementation from before conception through the first weeks of pregnancy can markedly reduce the occurrence of severe embryonic malformations; other potential benefits of modulating nutrient supply on maternal and child health should be further evaluated. The evaluation of dietary effects on child growth requires epidemiological and field studies as well as evaluation of specific cell and tissue growth. Novel substrates, growth factors and conditionally essential nutrients (e.g. growth factors, amino acids, polyunsaturated fatty acids) may be potentially useful as ingredients in functional foods and need to be assessed carefully. Intestinal growth, maturation, and adaptation as well as long-term function may be influenced by food ingredients such as oligosaccharides, gangliosides, high-molecular-mass glycoproteins, bile salt-activated lipase, pre- and probiotics. There are indications for some beneficial effects of functional foods on the developing immune response, for example induced by antioxidant vitamins, trace elements, fatty acids, arginine, nucleotides, and altered antigen contents in infant foods. Peak bone mass at the end of adolescence can be increased by dietary means, which is expected to be of long-term importance for the prevention of osteoporosis at older ages. Future studies should be directed to the combined effects of Ca and other constituents of growing bone, such as P, Mg and Zn, as well as vitamins D and K, and the trace elements F and B. Pregnancy and the first postnatal months are critical time periods for the growth and development of the human nervous system, processes for which adequate substrate supplies are essential. Early diet seems to have long-term effects on sensory and cognitive abilities as well as behaviour. The potential beneficial effects of a balanced supply of nutrients such as I, Fe, Zn and polyunsaturated fatty acids should be further evaluated. Possible long-term effects of early exposure to tastes and flavours on later food choice preferences may have a major impact on public health and need to be further elucidated. The use of biotechnology and recombinant techniques may offer the opportunity to include various bioactive substances in special dietary products, such as human milk proteins, peptides, growth factors, which may have beneficial physiological effects, particularly in infancy and early childhood.
Abstract: This overview demonstrates the increasing use of low natural abundance stable isotopes in the investigation of mineral metabolism. There are many practical problems associated with their use and analysis and their expense has limited their application in some areas such as studies in adults. Undoubtedly we will have to assess our ideas and protocols as the practical problems and their metabolic implications become better appreciated but none the less, the use of such isotopes will certainly refine our understanding of the way the body uses elements such as zinc, copper, iron and selenium and other essential elements and will enable us to determine our dietary requirements for these nutrients and to find ways of detecting more efficiently early deficiency and toxicity states.
Abstract: We evaluated the effect of increased dietary fiber (DF) content in weaning cereals based on wheat/soy (8.0 and 1.8% DF) and wheat/milk (5.3 and 2.0% DF) in healthy, formula-fed infants 7-17 weeks old. The study had a cross-over design, each infant acting as his or her own control. Stool characteristics and anthropometry were monitored over 4-week periods in groups of 34 (wheat/soy) and 23 (wheat/milk) infants. Absorption of zinc (Zn) and calcium (Ca) was studied by measuring the fecal excretion of stable isotopes during 72 h (70Zn and 42Ca) in a subgroup of the infants consuming wheat/soy cereals. Iron (Fe) bioavailability was evaluated by analysis of the incorporation of 58Fe into erythrocytes 14 days after administration. Fractional absorption (X +/- SD: 8.0 versus 1.8% DF) was 45.3 +/- 27.5 versus 41.2 +/- 19.4% of 70Zn and 63.4 +/- 15.8 versus 64.4 +/- 10.6% of 42Ca. Bioavailability of 58Fe varied between 1.0% and 5.4% (8.0% DF) and from <0.9% to 9.1% (1.8% DF). No significant difference in energy (95.3 +/- 2.0% versus 95.7 +/- 1.2%) or nitrogen (92.6 +/- 2.3% versus 93.0 +/- 1.6%) apparent absorption from the total diet was found during consumption of cereal with 8.0 and 1.8% DF. The intake of cereal decreased with higher DF content in the wheat/soy product: 34 +/- 23 g/d (8.0% DF) versus 42 +/- 23 g/d (1.8% DF), p < 0.01. While consuming the 8.0% DF product, 11 infants were reported to have "gritty stools"; no other differences were observed between different groups in stool characteristics or anthropometry. These results demonstrate no negative effect on the absorption of energy and nutrients with higher dietary fiber intake in primarily formula-fed infants. The impact of increased dietary fiber levels remains unknown in less well-nourished infants.
Abstract: Fractional apparent absorption of Zn and Ca from a wheat-milk-based infant cereal was studied in six healthy infants (18-30 weeks old). Mineral absorption was measured by a stable-isotope technique based on faecal excretion of the isotopes. Each test meal (40 g cereal) was extrinsically labelled with 70Zn and 42Ca before intake. All faecal material passed during the 21 d following intake of the labelled test meal was collected on trace-element-free nappies. Individual stool samples were analysed for their content of 70Zn and 42Ca by thermal ionization mass spectrometry. Apparent absorption was calculated as intake minus total faecal excretion of the isotopes over 68-92 h after administration. The fractional apparent absorption values for Zn and Ca were 33.9 (SD 16.4) % (range 19.2-63.9%) and 53.5 (SD 12.6) % (range 36.7-71.7%) respectively. Re-excretion of absorbed 70Zn (> 68-92 h to 21 d after intake of the labelled meal) was 0.44 (SD 0.38) % of administered dose while only one infant re-excreted detectable amounts of 42Ca (1.74% of administered dose). The analysis of individual stool samples confirmed that 72 h is a sufficient time period for complete collections of non-absorbed isotopes in faecal material from infants during the weaning period and that re-excretion of initially absorbed 70Zn and 42Ca (> 68-92 h to 21 d after intake of the labelled meal) is negligible.
Abstract: Coronary heart disease is a major cause of morbidity and mortality in Europe, particularly northern, central, and eastern Europe. Several strategies have been recommended for children and adolescents to promote a healthy lifestyle and thereby reduce the risk of coronary heart disease in later life. The European Society of Pediatric Gastroenterology and Nutrition (ESPGAN) Committee on Nutrition reviewed some of these strategies, and our conclusions and recommendations are reported herein.
Abstract: This review summarises the methods available for the analysis of phytate and structurally related molecules, i.e., inositol polyphosphates. Phytate has been determined by colorimetry, low pressure ion exchange column chromatography, phosphorus-31 fourier transform nuclear magnetic resonance spectroscopy (31P FT NMR), near-infrared reflectance spectroscopy and high performance liquid chromatography (HPLC). Among these techniques anion exchange column chromatography and HPLC were shown to be best suited for separation of inositol phosphates. Since inositol phosphates do not have a characteristic absorption spectrum, their detection in HPLC analysis is limited to methods employing monitoring of refractive index, post column reaction products, conductivity or indirect detection although other detection methods may be feasible. As refractive index detection under isocratic eluent conditions is relatively easy to manipulate, anion-exchange HPLC methods using a low capacity column or ion-pair HPLC methods are recommended for the analysis of inositol phosphates in nutritional studies.
Abstract: An evaluation of indices of poor zinc status was undertaken in five male subjects in whom dietary zinc intake was reduced from 85 mumol d-1 in an initial phase of the study to 14 mumol d-1. One of the subjects developed features consistent with zinc deficiency after receiving the low zinc diet for 12 days. These features included retroauricular acneform macullo-papular lesions on the face, neck, and shoulders and reductions in plasma zinc, red blood cell zinc, neutrophil zinc and plasma alkaline phosphatase activity. Alcohol induced hepatitis, which was suspected in this subject, may have caused a predisposition to altered zinc metabolism and possible zinc deficiency which was exacerbated by subsequent zinc deprivation. The report supports the value of neutrophil zinc concentration as an indicator of poor zinc status.
Abstract: The uptake of Zinc (Zn) by microvillus border membrane vesicles formed from the trophoblast of term human placentae is markedly increased over brief periods of incubation with much slower increases persisting for up to 2 h of incubation. Zinc is both bound to membrane components and transported into intravesicular osmotically active space. Uptake is saturable, temperature dependent from 4 to 37 degrees C with a Q10 of 1.7, and is inhibited by the sulphydryl agent DTNB. About 20 per cent of the uptake is susceptible to inhibition by Cadmium (Cd) at concentrations from 5 to 50 microM, a significant part of the action of this metal being on the transmembrane component of Zn uptake.
Abstract: The mechanisms involved in the homeostatic regulation of zinc were studied in five male subjects by using stable 70Zn as a marker. When dietary zinc was reduced from 85 to 12 mumol/d, adaptation was achieved by a mean (+/- SEM) reduction in urine zinc of 48 +/- 7% and in fecal zinc of 46 +/- 12% over 25 d in four subjects. The latter was caused by an increase in the efficiency of zinc absorption from 38 +/- 3% to 93 +/- 1% after 15 d of zinic deprivation and by a reduction in intestinal endogenous losses of zinc. In a fifth subject, who had some evidence of a resolving alcohol-induced hepatitis, urine and fecal zinc were reduced by 64% and 41%, respectively, in 15 d and zinc absorption increased from 46% to 93%. More information on adaptive responses is needed to enable current dietary recommendations to be reconsidered.
Abstract: The absorption and intestinal losses of endogenous Cu in response to a low Zn diet were studied in five young male subjects using stable 65Cu as an oral tracer. The subjects received a semi-purified formula diet providing 85 mumol (5.6 mg) Zn/d during 15-day baseline and repletion phases and 12 mumol (0.8 mg) Zn/d during an intervening period of 25 days. Thirty-eight mumol (2.4 mg) Cu/d was provided throughout the study. In four of the subjects, the mean +/- SEM luminal disappearance of 65Cu was 37 +/- 4 per cent during the baseline phase and was unaffected by Zn deprivation (32 +/- 7 per cent) or repletion (30 +/- 7 per cent) as were intestinal losses of endogenous Cu [7 +/- 4, 8 +/- 3, 8 +/- 3 mumol/d (0.4 +/- 0.1, 0.5 +/- 0.1, 0.5 +/- 0.1 mg/d) during baseline, Zn deprivation and Zn repletion phases, respectively]. In a fifth subject, who had some evidence of a resolving alcohol-induced hepatitis, the luminal disappearance of 65Cu was 31, 44 and 42 per cent and the intestinal losses of endogenous Cu 11, 2 and 6 mumol/d (0.7, 0.1 and 0.4 mg/d) during the baseline, Zn deprivation and Zn repletion phases respectively. Plasma Cu concentrations, however, fell throughout the study in all the subjects, despite consistently positive Cu balances. There may be subtle effects of a low dietary intake of Zn on Cu metabolism which were not revealed by the methods used in this study.
Abstract: Erythrocyte superoxide dismutase (ESOD) activity reflects copper utilization and the risk of copper deficiency. To investigate the possible effects of inorganic iron on the metabolism of copper in low birth weight infants, we have measured ESOD activities in three groups of infants receiving different iron supplements. Fifty-five low birth weight infants were randomly assigned to receive daily from 28 d either 13.8 mg (HiFe), 7 mg (MidFe), or no elemental iron (NatFe) as iron edetate. At 27 d, 8, 12, and 20 wk postnatal age, infants were weighed and measured and hematologic indices, plasma ferritin, zinc, and copper concentrations, and ESOD activities were assayed. Anthropometrical and hematologic indices and plasma copper and zinc concentrations did not differ among treatment groups at any time, but at 20 wk, plasma ferritin concentrations [(micrograms/L) mean; SD] were lower in the NatFe group (17; 2.0) than in the HiFe group (32; 1.9: 95% confidence interval for mean difference 6.6 to 22.0, p less than 0.01). ESOD activities (U/g Hb) were similar in HiFe (1447; 263), MidFe (1552; 322), and NatFe (1538; 382) groups at 27 d, but by 20 wk activities in the HiFe group (1537; 211) were lower than in the MidFe (1789; 403: 95% confidence interval 38 to 466, p less than 0.05) and NatFe (1858; 304: 95% confidence interval 150 to 492, p less than 0.01) groups. The lower ESOD activities found in the HiFe group at 20 wk may reflect altered copper metabolism induced by the iron supplement, but the clinical importance of this observation is unknown.
Abstract: Hydrolysed yeast protein labelled with 15N was used to measure protein turnover, protein synthesis and protein breakdown in preterm infants. The yeast tracer was given as a bolus intragastric dose and protein turnover was determined from the 15N enrichment of urinary ammonia over known periods of about 12 h. Six boys (birthweight less than 1500 g) with gestation of 27-35 weeks were studied either two or three times at post-natal ages ranging from 13 to 54 d. There was no significant correlation between protein turnover with increasing post-conceptional or post-natal age. There was considerable interindividual variation and reproducibility varied between different infants. We suggest that this is a convenient non-invasive technique for monitoring serially nitrogen and protein metabolism in infants and that as such it merits further assessment.
Abstract: The effect of ascorbic acid (AA) [284 mumol (50 mg) twice daily] on the net intestinal absorption and maximum apparent retention of Fe, Cu, and Zn was investigated by metabolic balance studies in a randomised crossover study of six low-birth-weight (LBW) neonates fed a cows'-milk-based formula containing (mumol/L) Fe, 126; Cu, 11; Zn, 87; and AA, 400. Absorption +/- SD (Fe, -5.0 +/- 7.5; Cu, 0 +/- 0.4; Zn, -0.8 +/- 3.4) (mumol kg-1 day-1) was not altered by AA (Fe, -4.1 +/- 4.6; Cu, 0.3 +/- 0.6; Zn, -1.1 +/- 2.7) neither was retention (without AA: Fe, -6.0 +/- 8.4; Cu, -0.1 +/- 0.3; Zn, -2.4 +/- 4.2; with AA: Fe, -4.9 +/- 4.7; Cu, 0.1 +/- 0.6; and Zn, -2.7 +/- 3.1). Supplements of AA administered as in the circumstances of routine care of LBW neonates do not enhance the absorption and retention of Fe, nor do they impair these aspects of the metabolism of Cu and Zn.
Abstract: The course of a subcutaneous weight-related infection with Strongyloides ratti was followed in rats fed diets containing either 3 mg Zn/kg diet [zinc deficient (Zn-)] or 40 mg Zn/kg diet [zinc adequate (Zn+)]. At 19 d postinfection (dpi) the proportions of larvae persisting in the intestines as adult worms were 52 +/- 2% (means +/- SEM) for Zn-, 39.5 +/- 2.5% for pair-fed Zn- (Zn-PF), and 31.6 +/- 3.2% for Zn+ (p less than 0.001, analysis of variance); some Zn- rats were then transferred to the zinc-adequate diet [This was the zinc-repleted group (ZnR).] Both groups retained a group of pair-fed controls (Zn-PF and ZnRPF). Between 19 and 28 dpi ZnR animals gained weight faster than did Zn- animals and had heavier thymuses relative to body weight. Zinc deficiency enhances the establishment of S ratti larvae in the intestine of rats and alters the characteristics of intestinal expulsion of the nematodes; however, spontaneous cure was achieved by 38 dpi in both Zn- and control groups.
Abstract: The expulsion of a primary infection of Trichinella spiralis was studied in rats fed diets containing (per kg diet) either 3 mg Zn [zinc deficient (Zn-)] or 40 mg Zn [zinc adequate (Zn+)]. A dose of 2000 muscle larvae (ML) impaired weight gain (mg/g body wt) in all groups compared with uninfected controls [eg, 0-7 d postinfection (dpi): infected Zn-, -105 +/- 10 (means +/- SEM); uninfected Zn-, 54 +/- 19 (p less than 0.001)]. In a study with 20.5 ML/g body wt, some Zn- rats were transferred at the time of infection to the zinc-adequate diet. [This was the zinc-repleted group (ZnR).] Both groups retained a group of pair-fed controls (Zn-PF and ZnRPF). The percentage dose established at 7 dpi was similar in all groups (32.5-39.3%) but at 13 dpi recoveries were 19.4 +/- 2.2% for Zn-, 0.1 +/- 0.1% for Zn-PF, 1.6 +/- 0.9% for ZnR, 0.6 +/- 0.2% for ZnRPF, and 4.1 +/- 2.2% for Zn+ (p less than 0.001). Up to 13 dpi, all groups except ZnR lost weight. These results show that zinc deficiency impairs the expulsion of T spiralis in rats.
Abstract: The turnover of a radiolabeled (65Zn) pool of endogenous zinc was monitored by using a whole-body counter in eight patients with celiac disease (CD) and analyzed by using a two-compartment model. The biological half-life of the first compartment (1-3 wk postadministration) was similar in healthy volunteers (122 +/- 34 d, means +/- SD) and untreated patients (97 +/- 21 d). The second compartment in the patients (3-12 wk postadministration) was shorter (159 +/- 22.5 d. p less than 0.001) than were reference values (218 +/- 27 d) but increased (291 +/- 71 d) after the patients started gluten-free diets. The percentage absorption of 65Zn (9.25 kBq) from a test meal containing 31 mumol (2 mg) zinc was similar in untreated patients (30.0 +/- 13%) and healthy volunteers (32.5 +/- 12.4%). These data show that in mild untreated CD increased turnover and loss of endogenous zinc occurs whereas the absorption of zinc from a customary zinc intake may be normal. The pathophysiological basis of this loss was not investigated.
Abstract: Nitrogen flux and protein synthesis and degradation were estimated using a single oral bolus of 15N glycine or 15N yeast protein hydrolysate and measuring the 15N enrichment of urinary ammonia in five low birth wt infants fed a low birth wt formula and in six who were receiving their own mother's breast milk. Results derived from using 15N-glycine and 15N-yeast hydrolysate tracers in a randomized crossover study in 10 studies on seven infants showed, with one exception, higher turnover rates and more interindividual variation with the 15N yeast. Both tracers showed good reproducibility in two infants who had repeated studies. Although wt gain was similar in both groups, nitrogen intake and retention were greater (p less than 0.01) in the formula-fed group. Mean nitrogen turnover was similar in both groups, but there was a greater variance in the human milk-fed group which also had a greater nitrogen turnover/U absorbed nitrogen (p less than 0.025) and a lower excretion of nitrogen/U flux.
Abstract: Knowledge of the metabolism of iron by young infants is incomplete but combining practical studies based on detecting the onset of iron depletion with isotopic studies of iron economy may improve our understanding of iron metabolism in infants and our strategies for ensuring their iron supply. The iron accumulated by the fetus is enough to delay the risk of iron deficiency until four, and two months of age in term and preterm infants respectively. Breast fed term infants may not need extra iron until they are six months or older; but whereas low iron formulas are adequate for other infants until about four months of age, thereafter infants need extra iron which can be provided effectively in iron fortified formulas. Breast fed low birth weight infants need iron supplements from two months of age but those fed specific low birth weight formulas which are iron fortified should not need extra iron.
Abstract: The effect of inorganic zinc on the absorption of inorganic iron (Fe+2) from a solution was assessed in two studies on healthy male volunteers. In the first study coadministration of 344 mumol of zinc had no effect (p less than 0.5) on the absorption of 842 mumol of radiolabeled Fe, assessed by the area under plasma Fe increment time curve during the 3 (AUC3) and 6 (AUC6) h postadministration (Fe alone AUC3 = 176.4 +/- 39.3; AUC6 = 387 +/- 101; Fe + Zn AUC3 = 180 +/- 33.1; AUC6 = 396 +/- 73.1 mumol.h-1.L-1), total plasma content of 59Fe, and whole-body retention of 59Fe. In the second study only the plasma appearance of Fe was monitored. After administration of 421 mumol of Fe alone, the AUC3 and AUC6 were 167 +/- 21.2 and 429.4 +/- 57 mumol.h-1.L-1, respectively; these were reduced to 56.4 +/- 17 and 119 +/- 34 (p less than 0.002) by 421 mumol Zn and further reduced by 1048 mumol Zn to 33 +/- 15 and 43.4 +/- 23.8 mumol.h-1.L-1 (p less than 0.001), respectively. It is concluded that Zn can impair the intestinal absorption of Fe.
Abstract: The role of zinc (Zn) in the immunological expulsion of the nematode Nippostrongylus brasiliensis (Nb) from the small intestine of the rat was investigated. Three groups of 28 rats each were fed a basal diet providing either 3 mg Zn/kg for the zinc-deficient group (-Zn) or 40 mg Zn/kg for ad libitum-fed and pair-fed controls. After 6 wk each group was divided into two equal subgroups and infected with either 1000 or 4000 infective Nb larvae/rat. The -Zn rats showed significant reductions (P less than 0.001) in food intake, weight gain and food conversion efficiency when compared to the rats fed ad libitum but not when compared to the pair-fed controls. Plasma zinc concentration in the -Zn rats (0.50 microgram/ml) was significantly lower than in both ad libitum-fed (1.33 micrograms/ml) and pair-fed (1.45 micrograms/ml) controls (P less than 0.001). The recovery of worms from the rats 3, 7 and 12 d postinfection was similar for the corresponding day and dose of infection in all groups. Expulsion was almost complete in all groups by 12 d post-infection. There were no significant differences in size and fecundity of worms recovered from the different groups of rats on 7 d postinfection. However, over the whole period of infection, the -Zn rats excreted significantly more parasite eggs than did controls (P less than 0.001). These results indicate that although zinc deficiency affected growth performance of the rats, it did not affect the establishment or expulsion of Nb. Impairment of the immune response of the zinc-deficient rat was manifested only by a significant increase in the number of parasite eggs excreted in feces.
Abstract: A survey of 57 neonatal units in the United Kingdom showed considerable disparity in iron supplementation policies for preterm low birthweight infants.
Abstract: The effect of picolinic acid (pyridine-2-carboxylic acid) on the efflux of divalent metal ions from multilamellar liposomes was examined to determine the possible specificity and mechanism for its reported beneficial effects on the intestinal absorption and systemic metabolism of zinc. Extraliposomal picolinic acid increased the efflux of Zn, Cu, Co, Mn, Ni, Cd, Pb, Fe(II) and Ca from the vesicles. However, when picolinic acid was trapped with Co, Cu and Zn within the liposomes, the loss of metals was reduced. In a partition study, picolinic acid increased the aqueous solubility of Zn, Cu, Co and Cd at alkaline pH, but did not transfer the metal to an organic bulk phase of chloroform. It is proposed that picolinic acid does not act as an ionophore and that any effect it may have on zinc metabolism is dependent upon its unselective chelating properties, which may also lead to altered dietary and systemic compartmentation of other divalent cations.
Abstract: Net zinc transfer between fetal and maternal circulation has been described in the in vitro perfused lobule of the human term placenta. The transfer results in a 3 microM differential between fetal and maternal perfusates which is comparable to estimated values in vivo. Tissue zinc concentration is more than 10 times perfusate concentration and is correlated with zinc flux across the fetal borders of the lobule. Open-circuit studies on net transport of zinc, and upon flow of 65Zn relative to tritiated water (3H2O), indicate these fluxes depend upon the non-protein-bound (free) zinc gradient across the fetal-facing membranes. On the other hand movement across the maternal surface is not related to diffusion gradients of free zinc and is either independent of, or inversely related to, the level of tissue zinc. It is concluded that the uptake of zinc from the maternal perfusate may be coupled to metabolism, whereas its transfer to fetal circulation is linked to the level of free zinc in the tissue.
Abstract: A variety of complex systemic, hepatic and neuropsychiatric syndromes result from inborn errors of trace metal metabolism. Some of these respond to treatment and prophylactic management while for some intractable conditions prenatal diagnosis is possible. All these abnormalities provide valuable insight into the normal metabolism of these vital elements.
Abstract: A longitudinal study of plasma zinc and copper concentration and plasma volume was carried out in 33 normal healthy primigravidae for comparison with 31 primigravidae selected as being at risk of delivering a growth retarded baby. Neither group received mineral or vitamin supplements. In Group A, plasma zinc concentration fell as plasma volume increased between 14 weeks and 35 weeks. Intravascular mass of zinc therefore increased and showed significant correlation with intravascular mass of albumin. Both of these were significantly lower in Group B, reflecting poorer plasma volume expansion. Plasma copper concentration mirrored the increase in plasma ceruloplasmin and was comparable in both groups. Plasma zinc and copper concentrations were unaffected by smoking or by method of feeding and there was no correlation found with percentile birth weight distribution. In both groups at 30 weeks daily dietary zinc intake was approximately half the Recommended Dietary Allowance.
Abstract: 28 Gambian children and adolescents with acute tropical leg ulcers entered a double blind trial of oral zinc supplements as an adjunct to standard treatment. Analysis of the area healing of the ulcers resulted in a mathematical expression which showed that for each subject re-epithelialization reduced the ulcer radius at a constant healing rate (k). k was derived from the equation At = pi X (r - k X t)2, where At = residual ulcer area at time "t", r = initial ulcer radius and t = time from start of treatment. In the zinc treated group k was 0.55 +/- 0.39 mm/day, and 0.51 +/- 0.25 mm/day in the placebo group. The initial low plasma zinc of 6.5 +/- 1.9 mumol/L in the ulcerated subjects was not significantly lower than that of 7.5 +/- 3.6 mumol/L in the nonulcerated controls. Oral zinc supplements significantly elevated plasma zinc concentrations by 5.8 +/- 4.8 mumol/L compared to the placebo group's change of 0.4 +/- 2.0 mumol/L (p less than 0.001). Plasma alkaline phosphatase activities and fatty acid profiles did not change with zinc supplementation. Thus unequivocal clinical and biochemical evidence of zinc deficiency in these ulcerated subjects was not established, despite changes in plasma zinc. This study does not indicate any role for zinc supplementation in the management of acute tropical ulcers.
Abstract: Man depends on at least nine trace elements--iron, zinc, copper, manganese, iodine, chromium, selenium, molybdenum and cobalt--for optimum metabolic function. These elements serve a variety of functions including catalytic, structural and regulatory activities in which they interact with macromolecules such as enzymes, pro-hormones, pre-secretory granules and biological membranes. These micronutrients are involved, therefore, in all major metabolic pathways at levels which are so fundamental that the features of deficiency of many of them are protean and non-specific. In considering the metabolism of the elements themselves, they fall into two groups: those which exist normally as cations and those present as anions. The latter group are absorbed relatively easily and whole-body homeostasis is mediated mainly by renal excretion. The cations need specific pathways for absorption and their homeostasis is effected by gastrointestinal and biliary secretion. Some elements are absorbed more efficiently as organic complexes. The net achievement of the metabolic pathways for each element is to deliver it to its functional site(s) by exploiting its physicochemical characteristics to avoid interactions with other inorganic nutrients.
Abstract: Long-term selenium status in children from the North-East of Scotland was estimated using whole blood selenium content (BSe) and glutathione peroxidase activity (BGSH-Px). BSe was significantly lower than the reference range in children with cystic fibrosis, coeliac disease and in older patients with phenylketonuria. Whereas BGSH-Px of all the children with coeliac disease and those with cystic fibrosis aged over 6 years matched the reference range, it was reduced in younger patients with cystic fibrosis and in children with dietetically treated phenylketonuria. No child had clinical features of selenium deficiency. BSe in treated epileptics and asthmatics conformed to the reference range, but BGSH-Px in both groups was increased significantly; this was most evident in those receiving corticosteroid preparations.
Abstract: A brief review of the clinical and biochemical features of Acrodermatitis enteropathica is given. This condition in now known to be caused by a systemic zinc deficiency secondary to a defect in the intestinal absorption of zinc and it illustrates the metabolic importance of this element in man.
Abstract: A brief outline of the known biochemical roles of manganese and chromium is given before the problems of determining human trace metal status are discussed. The factors predisposing to trace metal deficiency are reviewed but particular emphasis is placed upon those which alter the bioavailability of essential trace metals from natural and synthetic diets. This is illustrated by practical examples which show the importance of investigating the bioavailability of the trace metal content of artificial diets used in paediatric care. The results of such studies highlight the need to assess similarly the adequacy of the trace element composition of the many meat substitutes and extenders available currently. Finally, some aspects of trace metal supplementation of intravenous feeding regimens are described.
Abstract: Two patients with acrodermatitis enteropathica had abnormal lysosomal inclusion bodies in the intestinal epithelial cells while in relapse but fewer smaller ones after zinc therapy. The third patient with acrodermatitis enteropathica in remission on zinc therapy had no inclusion bodies. The smaller inclusion bodies were similar to those found in coeliac disease.
Abstract: The increments in plasma zinc concentrations after an oral dose of elemental zinc (50 mg) as the sulphate were used to assess the intestinal absorption of the metal in 11 patients with dermatitis herpetiformis (DH) before starting a gluten-free diet, 12 patients with newly diagnosed celiac disease (CD), 10 patients known to have CD, and 15 healthy volunteers. The areas under the plasma zinc increment curve plotted against time were determined for 3 (AUC3) and 6 (AUC6) h. The AUC3 in healthy volunteers was 401 +/- 48 mumol 1(-1) 3 h (mean +/- SD); it was reduced in newly diagnosed CD 187 +/- 76 mumol 1(-1) 3 h (p less than 0.001), and in dermatitis herpetiformis 206 +/- 87 mumol 1(-1) 3 h (p less than 0.01); but it was normal in the known CD 396 +/- 204 mumol 1(-1) 3 h, the wide variation reflecting the variable compliance with a previously instituted gluten-free diet. The AUC6 was similarly affected, healthy volunteers 700 +/- 111 mumol 1(-1) 6 h, new CD 380 +/- 169 mumol 1(-1) 6 h (p less than 0.01); dermatitis herpetiformis 471 +/- 107 mumol 1(-1) 6 h (p less than 0.01); known CD 725 +/- 380 mumol 1(-1) 6 h. The AUC3 was more consistently abnormal than conventional tests of small intestinal function. In a prospective study the AUC3 and AUC6 improved and reflected compliance with a gluten-free diet.
Abstract: A trace element supplement used with a synthetic low lactose milk (Galactomins 17 and 18) has been evaluated by means of metabolic balance studies in 4 infants with dissacharide intolerances. The supplement was considered satisfactory for iron and manganese but increases in its zinc and copper content are probably necessary to ensure adequate retentions of these metals.
Abstract: Seventy patients with Crohn's disease, 50 with ulcerative colitis, and 58 control subjects were questioned about their sugar consumption, measurements were made of their taste acuity, and blood levels of various trace elements including zinc and selenium were estimated. Sugar consumption was significantly increased in Crohn's disease (p less than 0.01). There was only a minor reduction in taste acuity for acid taste in Crohn's disease. Plasma zinc and whole blood selenium were reduced in Crohn's disease. No relationship was found between sugar consumption, plasma zinc, and taste acuity in Crohn's disease.
Abstract: In this study amphotericin B released the divalent trace metals Zn2+, Co2+, Cu2+, Ni2+, Mn2+, Fe2+, Cd2+ and Pb2+ from multilamellar liposomes containing cholesterol. This observation is consistent with amphotericin B channels being permeable to these metals, and it is proposed, therefore, that the antibiotic may be useful in investigating the metabolism of these elements.
Abstract: A nine year-old girl with acrodermatitis enteropathica developed typical clinical and biochemical features of zinc deficiency on two occasions while on an oral zinc supplement. On both occasions, these features responded immediately when she was treated with amphotericin B lozenges. Studies in vitro showed that amphotericin increases the permeability to zinc of pure lipid membranes containing cholesterol. We suggest that the antibiotic enhanced zinc absorption from the oral supplement thereby effecting resolution of the patient's zinc deficiency.
Abstract: The percutaneous absorption of chlorhexidine during its routine use in topical antiseptic preparations used in umbilical cord care was investigated by determining plasma chlorhexidine concentrations at ages 5 and 9 days. These showed that percutaneous absorption of chlorhexidine occurred in preterm neonates treated with a 1% solution of chlorhexidine in ethanol, but not in term infants similarly treated, or in preterm infants treated only with a dusting powder containing 1% chlorhexidine and 3% zinc oxide.
Abstract: A normal paediatric range of plasma alpha-amylase activity was determined using the Phadebas blue starch method. The range for children over one year was 98--405 IU/l. Plasma amylase activity increased throughout infancy. Mature levels of activity were observed in some children by age 2 months and in most of them by 9 months.
Abstract: 21 patients (10 male, 11 female) aged between 11 months and 29 years with Shwachman's syndrome are reviewed. All patients had exocrine pancreatic insufficiency. Haematological features included neutropenia in 19 (95%), anaemia in 10 (50%), and thrombocytopenia in 14 (70%); one patient developed erythroleukaemia. Severe infections occurred in 17 (85%) from which 3 (15%) died. Only one child exceeded the 3rd centile for height, and growth retardation was particularly evident in the older patients. All had skeletal abnormalities or delayed skeletal maturation, or both. Metaphyseal dyschondroplasia affected 13 of the older patients and was associated with skeletal deformities. Eight of 9 children under 2 1/2 years had rib abnormalities. Respiratory function tests in children under 2 years demonstrated reduced thoracic gas volume and chest wall compliance. Older patients had reduced forced expiratory volume and forced vital capacity. Neurological assessment showed developmental retardation or reduced IQ assessments, or both, in 85% of patients studied. Other neurological abnormalities included hypotonia, deafness, and retinitis pigmentosa. Neonatal problems had been present in 16 (80%) of the patients and 5 were of low birthweights. Hepatomegaly with biochemical evidence of liver involvement occurred in the younger patients and resolved with age. Other associated features included dental abnormalities, renal dysfunction, an icthyotic maculopapular rash in 13 (65%), delayed puberty, diabetes mellitus, and various dysmorphic features. These findings stress the diverse manifestations of the syndrome and extend knowledge on a number of aspects. Sibship segregation ratios support an autosomal mode of inheritance and an hypothesis for the pathophysiological basis of this syndrome is advanced.
Abstract: A 2-month-old preterm boy who developed symptomatic zinc deficiency while being exclusively breast fed is described. Oral zinc supplements induced a complete remission but mucosal 65Zn uptake studies and metabolic balances conducted before and after withdrawal of the supplements excluded the diagnosis of acrodermatitis enteropathica. By age 12 months the boy was well and no longer required zinc supplements. Other possible causes of this patient's symptomatic zinc deficiency are discussed and these should be considered in the immediate and long-term management of preterm infants.
Abstract: Selected immunologic functions were assessed in 14 patients with the Shwachman syndrome. Nine patients were neutropenic and four had low levels of IgA or of IgM. Neutrophil mobility was significantly defective in the group of patients as a whole (in 12 it was below the lower limit of normal) and in their parents. No other consistent abnormality in immunity was found. These results suggest that the defective neutrophil mobility is a feature of Shwachman syndrome which may contribute to the vulnerability of these patients to frequent infections. The defect appears to be a primary genetic one, inherited as an autosomal recessive characteristic consistent with the assumed inheritance of Shwachman syndrome.
Abstract: 1. In a system in vitro, 65Zn accumulation by jejunal mucosal biopsies from patients with acrodermatitis enteropathica was found to be markedly reduced compared with controls. 2. We suggest that defective uptake of zinc by enterocytes is the primary abnormality responsible for the zinc deficiency underlying this disorder.
Abstract: A 4 year old male with primary hypomagnesaemia was studied using balance and steady-state perfusion techniques. Magnesium balance was negative and could be accounted for by increased faecal losses, renal conservation being normal; calcium balance was normal. After oral magnesium therapy magnesium balance became positive. The perfusion studies demonstrated net loss of magnesium into the intestinal lumen when low concentrations (1 and 2 mmol/l) of magnesium were perfused in contrast with control subjects; whereas at high concentrations (10 mmol/l a net absorption of a magnitude similar to control values was observed. In the control subjects sequential perfusion of increasing concentrations of magnesium demonstrated a curvilinear relationship between rates of absorption and the lower concentrations (1, 2, and 4 mmol/l) with an apparent Km and Vmax of 4.5 mmol/l and 91 nmol/min/cm respectively. At the higher concentrations (6 and 10 mmol/l) the relationship was linear. These data suggest that two separate transport systems participate in the absorption of magnesium from the proximal small intestine; a carrier-mediated system which saturates at low intraluminal concentrations, and a simple diffusional process. The possibility of the second transport system being a carrier-mediated process with a very much higher Km cannot be excluded. In primary hypomagnaesaemia the results suggest that the primary abnormality is a defect in carrier-mediated transport of magnesium from low intraluminal concentrations of magnesium.
Abstract: Earlier studies (Alexander et al., 1974; Lawson et al., 1977) suggested a suitable composition for a mineral and trace metal supplement for use with synthetic diets containing some natural food. Such a mixture has been evaluated in patients receiving a diet based on comminuted chicken and has been shown to be adequate. This conclusion was based on balance experiments measuring Zn, Cu, Mn, Fe, Ca, Mg, N, and P.
Abstract: Pethidine or an epidural injection of bupivacaine are common forms of obstetric analgesia in Britain. Bupivacaine has been thought to have little effect on the fetus, but neurobehavioural studies have cast doubt on this. We therefore investigated the elimination of these drugs by babies in similar population groups. Bupivacaine was largely eliminated in just over one day, while pethidine required between 2 and 6 days. This could account for the persisting depression in babies whose mothers had received pethidine.
