Acquired copper deficiency following prolonged jejunostomy feeds.

A 19-year-old man who developed extensive oesophageal lye (Alkali) stricture and received long-term enteral nutrition (eight months) with a jejunostomy tube developed macrocytic anaemia (Hb: 41 g/L) with leucopenia (white blood cell [WBC]: 3.0 x 10(9)/L). The patient's serum vitamin B12, folate, iron and liver function tests were normal. Bone marrow examination revealed gross erythroid hyperplasia and cytoplasmic vacuolization of erythroid and myeloid elements. Further investigations revealed low serum copper (0.3 micromol/L) and ceruloplasmin concentrations (<30 mg/L) with marginally low normal serum concentration of red cell peroxidase (13 U/gHb), establishing the diagnosis of copper deficiency anaemia. The anaemia and leucopenia responded intermittently to intravenous copper therapy, but the serum copper concentration dropped when intravenous copper therapy was withdrawn. Enteral jejunostomy copper supplementation failed to maintain adequate serum copper concentrations. After stabilizing the general condition of the patient, a pharyngo-gastric anastamosis was performed and normal oral diet commenced, which restored normal serum copper concentration. This case report suggests that copper supplements in the form of copper sulphate are not adequately absorbed when administered through a jejunostomy tube.

Faecal calprotectin in the assessment of Crohn's disease activity.

BACKGROUND: Clinical and laboratory assessment of activity in Crohn's disease (CD) correlate poorly with endoscopic findings. Calprotectin is a calcium-binding protein abundant in neutrophil cytosol, and extremely stable in faeces. Faecal calprotectin (FC) is an excellent surrogate marker of neutrophil influx into the bowel lumen. AIM: To assess whether FC concentration from a spot stool sample reliably detects active inflammation in patients with CD. DESIGN: Cross-sectional comparative study. METHODS: Subjects had a previously confirmed diagnosis of CD and were suspected on clinical grounds to be in the midst of a relapse. Thirty-five entered the study; they underwent radiolabelled white cell scanning (WCS) and had a stool sample collected for calprotectin measurement on the same day. A Crohn's disease activity index (CDAI) was also calculated for each. The WCS scans were scored at six standard sites to give a mean total, 'extent', 'severity' and 'combined extent and severity' scores. RESULTS: FC was significantly and positively correlated with mean total (r = 0.73, p < 0.001), 'extent' (r = 0.71, p < 0.001), 'severity' (r = 0.64, p < 0.001) and combined 'extent and severity' WCS scores (r = 0.71, p < 0.001). A cut-off of faecal calprotectin > 100 microg/g gave a sensitivity of 80%, specificity of 67%, positive predictive value of 87% and a negative predictive value of 64% in identifying those with and without any inflammation on WCS. There was, however, no significant correlation between CDAI and mean total WCS score (r = 0.21, p = 0.24), nor between CDAI and FC (r = 0.33, p = 0.06). DISCUSSION: While the CDAI does not accurately reflect inflammatory activity in CD, a one-off FC reliably detects the presence or absence of intestinal inflammation in adult patients with CD, compared to WCS.

Reducing maltreated children's reluctance to answer hypothetical oath-taking competency questions.

Before allowing child witnesses to testify, courts routinely require children to describe what would happen to them if they lied. However, young children often refuse to reason hypothetically if they view the premises as implausible or undesirable, and might be more willing to discuss the consequences of lying if they are asked about another child rather than themselves. On the other hand, children might view themselves as invulnerable to punishment, and therefore believe that whereas other children will be punished for lying, they will not be. In this study, 64 maltreated 5- and 6-year-old children were asked to describe the consequences of lying to three professionals (a judge, a social worker, and a doctor). Participants in the "self" condition were asked what would happen to them if they lied, whereas participants in the "other" condition were asked to describe what would happen to a story child if he or she lied. Asking children about "other" children increased responsiveness, and did not reveal perceptions of invulnerability. The results suggest that young children's understanding that they will be punished for lying may make them reluctant to discuss the consequences of lying, leading to underestimation of their oath-taking competency.

DXA body composition studies are not affected by extracellular water measurements using stable sodium bromide dilution.

Body composition studies using dual energy x-ray absorptiometry (DXA) are being increasingly reported in the literature. When DXA body composition measurements are combined with body water studies, stable bromide is often administered to measure extracellular water. Bromine attenuates x-rays significantly more than soft tissue and so could affect DXA body composition analysis. DXA scans were performed on 26 adults (12 F, 14 M) before and after the intravenous injection of 3 g sodium bromide (NaBr). No significant differences were noted pre- and post-NaBr infusion for whole-body fat mass, fat-free soft tissue mass and bone mineral content. These findings were supported by a simple mathematical analysis of the likely effect of the sodium bromide infusion. This showed that when 3 g NaBr was introduced into the body, the effect on fat mass estimates was expected to be marginally less than the precision of the DXA technique.

A two-compartment model for zinc in humans.

The oral absorption of zinc, from a test meal of minced beef, mashed potatoes and peas, have been measured in 19 healthy adults using the radiotracer 65Zn. The oral absorption, expressed as a percentage of the administered dose, was 20 +/- 5% (mean +/- 1 SD) in good agreement with previous results. In a subset of 9 subjects, tracer retention in whole body and whole blood was followed out to one year. The data were fitted to a simple two compartment model yielding total body zinc (TBZn), the zinc content in each of the 2 compartments and zinc turnover. The TBZn values ranged from 15.5 to 35.9 mmol while zinc turnover ranged from 0.043 to 0.073 mmol/d in keeping with results reported for significantly more complicated compartmental models applied to more comprehensive 65Zn tracer data sets. Additionally, TBZn correlated well with total body potassium, a measure of lean body mass, measured by whole body counting of the naturally-occurring potassium radioisotope, 40K. The zinc content of the more rapidly turning over compartment ranged from 3.2 to 5.6 mmol in reasonable agreement with exchangeable zinc pool estimations reported for short term studies using stable zinc isotopes. Therefore, the simple dataset and model employed in the present study yielded information on the short- and long-term behaviour of zinc compatible with both more complex radiotracer studies and analytically more demanding stable isotope studies.

Cadmium concentrations in human kidney in the UK: 1978-1993.

Almost 2700 samples of human renal cortex have been collected from throughout the UK over a 16 year period from 1978 to 1993. The mean Cd concentration was 19 micrograms g-1 and the median 16 micrograms g-1. Smokers were, on average, about 5 micrograms g-1 higher than non-smokers. Cd increased from low concentration in the young to a maximum of 23 micrograms g-1 in middle age followed by a decrease in old age. Subjects who had died of renal disease had lower Cd concentrations. Geographical variations in the UK are small and the concentrations appear to be static over the 16 year period. Some 3.9% of the population had Cd concentrations > 50 micrograms g-1, the critical level at which beta 2-microglobulin appears in urine.

Determination of low concentrations of potentially toxic elements in human liver from newborns and infants.

One hundred and fifty-seven liver samples from newborns and infants who had died from sudden infant death syndrome (SIDS) or other known causes have been analysed by ICP-MS for Ag, Cd, Co, Pb and Sb. The median concentrations found were: 15.4 (Ag), 2.9 (Cd), 15.9 (Co), 65.2 (Pb) and 1.8 (Sb) ng g-1 wet mass. There was no measurable difference in the concentrations of any of these elements between the SIDS and non-SIDS groups. The validity of the results was assessed by analysis of appropriate reference materials, interlaboratory comparison and isotope dilution analysis. The instrumental limits of detection were 0.25 (Ag), 0.14 (Cd), 0.21 (Co), 3.8 (Pb) and 0.38 (Sb) ng g-1 wet mass. The limits of detection of the method depend on the reagent blank and the extent of background contamination.

Reasoning about moral aspects of illness and treatment by preschoolers who are healthy or who have a chronic illness.

Our study evaluates the moral reasoning skills of healthy and chronically ill 3 and 4 year olds with respect to illness and treatment, by use of an interview technique that reduces verbal demands on the child. We presented children with pairs of scenarios comparing ill characters with characters acting immorally and characters being punished, as well as with pairs of scenarios comparing treated characters with characters acting immorally and characters being punished. We asked children to point to the character who did something "naughty." With the exception of the chronically ill 3 year olds, the children performed consistently above chance and did not confuse illness and immorality. Older and healthy children performed better than younger and chronically ill ones (differences were the result of differing receptive vocabulary skill levels). This research has implications for evaluating young children's reasoning abilities and suggests that medical professionals should use tools that reduce demands on children's verbal proficiency.

Nickel metabolism in humans investigated with an oral stable isotope.

We report the results of the first complete study of nickel metabolism in human subjects using a stable nickel isotope (62Ni) as tracer. Four healthy adult subjects (two women and two men) fasted overnight before ingesting 10 microg 62Ni/kg body wt. Blood samples were drawn after fixed intervals of time and the total daily output of urine and feces was collected for the first 5 d after dose ingestion. 62Ni in plasma, urine, and feces was determined by isotope-dilution inductively coupled plasma-mass spectrometry with 61Ni. The direct measurement of the fecal excretion of the tracer allowed a reliable assessment of nickel absorption from the gastrointestinal tract and we found no evidence of the excretion of absorbed nickel via the gut. The percentage absorption calculated from the amount of 62Ni excreted in the feces ranged from 29% to 40%. Urinary excretion over 5 d ranged from 51% to 82% of the absorbed dose. Plasma 62Ni peaked between 1.5 and 2.5 h after ingestion and decreased by a factor of > 10 over the next few days. We observed low between-subject variability of nickel absorption and excretion. Confounding factors such as contamination and dietary intake of nickel, which hampered earlier measurements in subjects dosed with naturally abundant nickel, were eliminated by using the tracer isotope 62Ni.

Erythrocyte magnesium in elderly patients: not a reliable guide to magnesium status.

To assess body magnesium status in various illness states in older people by measurement of serum magnesium (S Mg) and erythrocyte magnesium (E Mg) and to explore the limitations of E Mg measurement. S Mg and E Mg were measured in 150 consecutive out-patients, mean age 77 years, and in 100 consecutive in-patient admissions, mean age 80 years. Results were analysed for different diagnostic groups S Mg was normally distributed for both in-patients and out-patients, mean values 0.79 mmol/l and 0.77 mmol/l respectively. In-patient E Mg concentrations were often higher but the distribution was considerably skewed, median 2.28 mmol/l, mean 2.35 mmol/l. Out-patient E Mg concentration followed a near normal distribution, median 2.32 mmol/l, mean 2.30 mmol/l. There was a significant correlation between E Mg and S Mg for out-patients, R = 0.29 (p < 0.001). In-patients with infections and pressure sores had significantly raised E Mg concentrations but normal or low S Mg. High E Mg concentrations in illness are likely to be due to alterations in characteristics of the erythrocytes themselves rather than an indication of body magnesium excess. E Mg concentrations in illness should be interpreted with caution.

Determination of antimony in urine, blood and serum and in liver and lung tissues of infants by inductively coupled plasma mass spectrometry.

Methods are presented for the determination by ICP-MS of antimony in body fluids and tissues of infants. Urine, serum and whole blood specimens are prepared for analysis by simply diluting 200 microliters sample volumes (1 + 14) with water and adding indium as internal standard. Liver and lung tissues are digested using 16 M HNO3 either in open quartz vessels at 150 degrees C or in sealed vessels with microwave heating. The acid digests are diluted with water and indium is added as internal standard for ICP-MS measurements. All analyses were subjected to stringent internal quality control protocols. Accuracy was assessed by recoveries, repeated analyses and by analysis of NIST SRMs 1577a Bovine Liver and 1566a Oyster Tissue. Precisions of analyses were better than 5-10% in the ranges 0.1-0.3 microgram l-1 for urine, serum and blood; and at 7-25 ng g-1 in tissues. Detection limits were 0.7 ng g-1 in liver, 0.8 ng g-1 in lung, and 0.01 microgram l-1 in urine, serum and blood. The need to employ validated procedures for specimen collection and to give considerable attention to pre-analytical factors in order to avoid adventitious contamination with antimony is demonstrated.

Use of a stable copper isotope (65Cu) in the differential diagnosis of Wilson's disease.

1. 65Cu/63Cu stable-isotope ratios have been measured in blood serum after oral administration of the stable isotope 65Cu. The incorporation of the isotope into the plasma protein pool was followed at various times for up to 3 days. The resulting patterns of enrichment in healthy control subjects, in Wilson's disease patients and in heterozygotes for the Wilson's disease gene, were similar in appearance to those found by others using copper radioactive isotopes. After an initially high enrichment at 2 h after dosage, the Wilson's disease cases, in contrast to the control subjects, did not show a secondary rise in isotope enrichment of the plasma pool after 72 h, demonstrating a failure to incorporate copper into caeruloplasmin. The Wilson's disease heterozygotes had variable degrees of impairment of isotope incorporation, not always distinguished from those of control subjects. 2. The stability of the isotope also permits the copper tracer to be followed for a longer period. Ten healthy subjects were studied for over 40 days, allowing the biological half-time of an oral dose of copper to be determined (median 18.5 days, 95% confidence interval 14-26 days). Known heterozygotes for the Wilson's disease gene were found to have a significantly increased biological half-time for removal of copper from the plasma pool (median 43 days, 95% confidence interval 32-77 days). 3. The incorporation of 65 Cu in patients with diseases of the liver (other than Wilson's disease) was found to be similar to that in control subjects, aiding differential diagnosis.

Determination of aluminium in serum, dialysate fluid and water by inductively coupled plasma optical emission spectrometry.

Methods for the determination of aluminium in serum, dialysate fluid and water by inductively coupled plasma optical emission spectrometry are described and validated. Aluminium was measured at 167 nm using an argon purged monochromator. Matrix effects in serum and dialysate fluid were overcome by using an yttrium internal standard. Serum was found to have a complicated background in the region of 167 nm: careful selection of the wavelength used for background correction is therefore a pre-requisite for accurate analysis. The method for serum was validated by comparison with electrothermal atomization atomic spectrometry and the limit of agreement determined to be +/- 0.3 mumol/L. Routine performance in a quality assessment scheme has been highly satisfactory for a period of 1 year. The method is ideal for fast and accurate monitoring of patients potentially at risk from aluminium toxicity.

Copper associated childhood cirrhosis.

Several papers have reported severe liver disease in association with massive hepatic copper accumulation, which do not seem to be either of the recognised copper associated liver diseases, namely Wilson's disease and Indian childhood cirrhosis. A further case is reported in which novel copper kinetic studies were carried out using the stable isotope 65Cu, showing that this patient did not suffer from Wilson's disease. It is suggested that these cases can be divided into two groups on the basis of age, clinical course, and history of excessive copper ingestion. The benefits of using 65Cu for in vivo studies of copper metabolism is discussed.

Young children's understanding of "remember" and "forget".

3 studies examined young children's understanding that if one "remembers" or "forgot," one must have known at a prior time. In Study 1, 4-year-olds but not 3-year-olds understood the prior knowledge component of "forgot"; both groups understood that a character with prior knowledge was "gonna remember." Study 2 controlled for the possibility that good performance on "remember" might be due to a simple association of remembering with knowledge. A significant number of 4-year-olds but not 3-year-olds understood that when 2 characters currently knew, the one with prior knowledge remembered, and that when neither character currently knew, the one with prior knowledge forgot. Study 3 made prior knowledge more salient by making the remembered or forgotten item visible to the subjects throughout. 4-year-olds performed near ceiling on both verbs, whereas 3-year-olds' performance did not differ from chance. The results are discussed in relation to children's developing understanding of the mind.

Young children's understanding of forgetting over time.

2 studies investigated young children's understanding that as the retention interval increases, so do the chances that one will forget. In Study 1 (24 3-year-olds and 24 4-year-olds), 4-year-olds but not 3-year-olds understood that of 2 characters who simultaneously saw an object, the character who waited longer before attempting to find it would not remember where it was. In study 2 (24 3-year-olds and 24 4-year-olds), 4-year-olds but not 3-year-olds understood that of 2 objects seen by a character, the object that was seen a "long long time ago" would be forgotten and the object seen "a little while ago" would be remembered. The findings are discussed in relation to research on young children's understanding of the acquisition, retention, and retrieval of knowledge over time.

Mononuclear blood cell magnesium in older subjects: evaluation of its use in clinical practice.

Serum and mononuclear blood cell (MBC) magnesium were measured in 24 healthy community subjects, average age 76 years (67-93), and in 21 ill hospitalized subjects, average age 79 years (65-90). MBC magnesium, expressed as mumol/mg protein, was significantly lower in the in-patient group (P < 0.001), but tended to be higher in the same group when expressed as fmol/cell (not significant). Further samples from community subjects on the same day, and again at 7 days, revealed coefficients of variation for intrasubject analysis of 12% and 22%, respectively (fmol/cell). The equivalent intrasubject values for serum were 2.8% on the same day and 4% at 1 week. MBC magnesium values for inpatients were probably distorted by changes in cell size and cell protein content caused by illness. Biological variability and the effects of illness on the composition and size of cells seem to limit the usefulness of MBC magnesium measurement as a clinical tool for assessment of body magnesium status.

Comparison of inorganic elements from autopsy tissue of young and elderly subjects.

Concentrations of nine inorganic elements in autopsy samples of kidney, liver, heart and skeletal muscle from 33 aged subjects, mean age 80 years, were compared with concentrations in similar samples from 12 young healthy accident victims, mean age 29 years. Tissue samples were removed within 48 hours of death and dry weight was used as a frame of reference. Potassium and magnesium were significantly lower in muscle (P less than 0.001) and heart tissue (P less than 0.001) of elderly subjects. There was evidence of accumulation of zinc in liver tissue of the elderly (P less than 0.01). Copper was significantly lower in the heart tissue of elderly subjects (P less than 0.001) whereas manganese was lower in both the heart (P less than 0.01) and the kidney tissue (P less than 0.001) of the elderly. Selenium concentrations were lower in the kidney (P less than 0.001) of the elderly. Elderly heart tissue appeared to accumulate chromium (P = 0.007) and aluminium (P less than 0.001). No significant differences were found for iron concentrations between these two populations. These major differences in tissue element concentrations between young and aged subjects merit further attention.