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Biomedical subjects

L T Weaver

Publications and source records attributed to L T Weaver.

At least 19 recordsLinked to original sources

Gastrointestinal handling of glycosyl [13C]ureides.

OBJECTIVES: Lactose [(13)C]ureide has been proposed as a noninvasive marker for oro-caecal transit time in adults and children. The present study investigates the handling of lactose [(13)C]ureide ((13)C LU) and glucose [(13)C]ureide ((13)C GU) by the gastrointestinal tract and describes the metabolic fates of these substrates and describes the extent of tracer excretion by different routes. STUDY DESIGN AND SUBJECTS: Four subjects underwent five studies in which they ingested a test meal plus (1) no substrate, (2) (13)C LU, (3) (13)C GU, (4) (13)C LU after predosing with unlabelled lactose ureide and (5) (13)C LU after predosing with glucose ureide. Subjects were studied at home with at least 1 week between tests and they all completed the study. Breath was analysed for (13)CO(2) recovery and urine was analysed for total (13)C recovery, (13)C urea recovery and (13)C GU recovery. RESULTS: The profiles and extent of tracer recovery in breath and urine were similar when either (13)C GU or (13)C LU was used, suggesting similar handling of these substrates by the gut. (13)C GU was the major (13)C-enriched species recovered in the urine even when (13)C LU was consumed. Predosing with either lactose ureide or glucose ureide increased the rate of appearance of tracer, but did not alter transit times. CONCLUSIONS: (13)C LU is hydrolysed to (13)C GU in the small intestine with the fraction of (13)C GU appearing in the urine probably limited by small intestinal permeability. Either (13)C LU or (13)C GU can be used to measure oro-caecal transit time.

Adult↗

Maternal docosahexaenoic acid supplementation during pregnancy and visual evoked potential development in term infants: a double blind, prospective, randomised trial.

AIM: To test the hypothesis that maternal docosahexaenoic acid (DHA) supplementation during pregnancy enhances maturation of the visual evoked potential (VEP) in healthy term infants. METHODS: One hundred women were supplemented with either fish oil capsules rich in DHA (n = 50) or placebo capsules (n = 50) from week 15 of pregnancy until delivery. Total fatty acids in red blood cells and plasma were measured at weeks 15, 28, and 40 of pregnancy and at delivery in umbilical cord blood. Infant visual pathway development was assessed using VEPs recorded to flash stimuli shortly after birth and to both flash and pattern-reversal stimuli at 50 and 66 weeks post-conceptional age (PCA). RESULTS: Maternal supplementation did not significantly elevate the level of DHA in umbilical cord blood. Moreover, there were no significant differences in any of the VEP measures observed between supplementation groups. However, maturity of the pattern-reversal VEP at 50 and 66 weeks PCA was associated with DHA status of the infants at birth. Infants with higher DHA status, both as a concentration and as a percentage of total fatty acids, showed shorter P100 peak latencies of the pattern-reversal VEP than those with lower DHA status. CONCLUSIONS: Maternal DHA supplementation during pregnancy did not enhance VEP maturation in healthy term infants. However, these results show an association between the DHA status of infants at term and early postnatal development of the pattern-reversal VEP, suggesting that DHA status itself may influence maturation of the central visual pathways.

Body Height↗

Detection of Helicobacter pylori DNA in drinking water biofilms: implications for transmission in early life.

AIMS: To provide evidence of water quality as a risk factor for acquisition of Helicobacter pylori in early life, and to identify evidence for its presence within pots used to store drinking water. METHODS AND RESULTS: A prospective cohort study of 65 infants was conducted in the rural village of Keneba, The Gambia. Age of H. pylori colonization was determined and water pot biofilms were tested for H. pylori by sequencing of amplified DNA. Use of supplemental water was a strong risk factor for H. pylori colonization in infants (OR 4.71, 95% CI 1.17-22.5). DNA with 95% homology to the 16S rRNA gene of H. pylori was isolated from biofilms of water pots. CONCLUSIONS: Drinking water may be a reservoir for H. pylori in areas of the developing world where water quality is poor. Early introduction of water, particularly if stored in, or collected from contaminated sources, may be associated with an increased rate of H. pylori colonization.

Base Sequence↗

Analysis of 13C-mixed triacylglycerol in stool by bulk (EA-IRMS) and compound specific (GC/MS) methods.

This paper was presented in poster form at the 17th International Congress of Nutrition, August 27-31, Vienna, Austria (Annals of Nutrition & Metabolism 2001; 45(Suppl.1):349). Some of the data were also presented in poster form at the British Society of Gastroenterology Meeting, March 18-21, Glasgow, UK (Gut 2001; 48(Suppl.1):A91). The 13C-mixed triacylglycerol (MTG) breath test is used to measure intraluminal fat digestion. In normal digestion, 20-40% of the ingested 13C label is recovered in breath CO2. We aimed to identify the proportions of ingested label excreted in stool, as well as breath following ingestion of 13C-MTG by children with impaired exocrine pancreatic function and healthy controls. 13C enrichment of breath samples was measured by continuous flow isotope ratio mass spectrometry (IRMS) and cumulative percent dose recovered (cPDR) in 10 h was calculated. Total 13C of a faecal fat extract from each stool was measured by elemental analyser-IRMS, and 13C enrichment and concentration of the TBDMS derivative of octanoic acid was measured by GC/MS after hydrolysis of the fat extract. Stool 5-day cPDR was calculated. Mean breath cPDR was 35%. Mean cPDR in stool by combustion-IRMS and GC/ MS, respectively, was 0.8% and 1.0%. Therefore, the remaining 64% of the 13C label must remain in the body and variability in breath cPDR is due to postabsorptive rather than predigestive factors.

Caprylates↗

Production of 13C labelled pea flour for use in human digestion and fermentation studies.

Stable isotope breath tests offer a new approach to the study of digestion and fermentation of carbohydrates in man. In this study, 13C labelled peas were grown by pulsing 250 ml 13CO2 into a sealed growth chamber. A second pulse was added to a portion of the peas to increase the 13C enrichment. This generated pea flour with an enrichment of 2.36 at.% excess (range 2.09-2.71 n = 3) and 8.64 atom % excess (range 7.37-9.78 n = 3) respectively. This represented incorporation of an absolute yield of 3.8% of the 13CO2 into peas in the 'once-labelled' treatment and 7.5% in the 'twice-labelled' treatment. Ingestion of a mixture of the labelled pea flour (300 mg) by two volunteers generated measurable 13CO2 excretion for breath test analysis. The profile of breath 13CO2 enrichment increased to a maximum within three hours after consuming the pea flour followed by a decrease almost back to baseline by 13 hours. Breath 13CO2 appeared to rise again after this apparent nadir at 13 hours until the end of the sampling period. Mathematical analysis of the data suggested that two peaks best described the profile of breath 13CO2 up to 13 hours. A third peak was necessary to describe the late rise in breath 13CO2 enrichment. This use of 13C enriched pea flour may provide a useful non invasive method for measurement of digestion and fermentation in vivo.

Adult↗

Disseminating weaning messages: an intervention trial.

This article reports a non-randomized intervention study conducted in two market towns to find out whether participant-centred health education discussions improve parents' knowledge and actions concerning infant feeding. Following an initial quiz, parents of 8-week-old infants attended a discussion on weaning (intervention) or home safety (control). They were then asked to complete a questionnaire about their knowledge and actions concerning weaning when their infants were 7-9 months old. A total of 61 parents took part in the intervention and 49 in the control. In the post-intervention questionnaire, the intervention group reported using more home-cooked foods and less commercially-prepared foods and knew the optimum time to register their infants with the dentist. These results suggest that participant-centred discussions are an effective way of disseminating public health messages concerning infant feeding.

Adult↗

Stable isotopes and the international system of units.

It is now over 60 years since Nier built the first isotope ratio mass spectrometer. The introduction of continuous-flow techniques heralded a huge expansion in the use of stable isotopes in biomedical and environmental sciences, yet there is no consensus on the appropriate units, especially in the biomedical field. Most isotope ratio mass spectrometry (IRMS) instruments calculate isotopic abundance in terms of delta notation (delta, per thousand, per mil), which is a convention determined by geochemistry, because most of the original IRMS instruments were developed in isotope geochemistry laboratories to measure natural abundance variations. Delta units are not SI units. This paper considers the appropriate units for studies using stable isotopes based on the International System of Units (SI). The SI base unit for concentration is the mol, from which atom fraction and mol fraction are derived. The units of stable isotope abundance, atom % and mol %, are the atom and mol fractions expressed as percentages. Atom % excess and mol % excess are the SI units of enrichment and are to be recommended for use in tracer studies.

Algorithms↗

Rapid quality control analysis of (13)C-enriched substrate synthesis by isotope ratio mass spectrometry.

There is a growing interest in the use of (13)C-enriched substrates to investigate metabolic processes in humans. The non-invasive nature of (13)C breath tests makes them attractive to clinicians, particularly because they can be safely used in children. The availability of suitable (13)C-enriched substrates can limit the application of this biotechnology. We have used isotope ratio mass spectrometry to assay the chemical purity and isotopic enrichment of substrates that were synthesised to study gut transit and colonic fermentation. Lactose ureide and lactose [(13)C]ureide were synthesised by acid-catalysed condensation of lactose and urea or (13)C urea, respectively. Glucose ureide and glucose [(13)C]ureide were synthesised by similar methods but required an additional purification step to remove urea of crystallisation. Substrates were analysed by standard analytical techniques and combustion isotope ratio mass spectrometry for carbon and nitrogen content and (13)C-enrichment. Monitoring the C/N ratio proved to be a sensitive assay of chemical purity. Analysis of the percentage composition of C and N (and hence O + H) suggested that lactose ureide crystallises as the dihydrate. It was synthesised with approximately 99% chemical purity and with the theoretical enrichment. Glucose ureide was synthesised with approximately 98% chemical purity but with lower than theoretical enrichment.

Breath Tests↗

Fatty acid status of women of reproductive age.

OBJECTIVE: Healthy foetal and infant development is dependent on an adequate maternal supply of essential and polyunsaturated fatty acids (PUFA). While there are published data on the fatty acid status of pregnant women, there are few on the status of non-pregnant women of reproductive age. The aims of this study were to test the hypotheses that the fatty acid status of non-pregnant women is affected by socio-economic status and anthropometric, behavioural and obstetric factors. DESIGN: Observational study METHODS: One-hundred and thirty-five women of child-bearing age (mean 29.8 y, s.d. 6.92) were invited to provide a blood sample and to answer a questionnaire, of whom 114 were included in the study. Plasma and red cell total fatty acids were measured as their methyl esters by gas chromatography mass spectrometry. RESULTS: On multivariate analyses, use of hormonal contraception was independently associated with lower plasma polyunsaturated fatty acids (difference between means -2.76, 95% confidence interval (-4.64, -0.88), P=0.0034), whereas cigarette smoking was associated with higher red cell oleic acid (0.74 (0.18, 1.29), P=0.0094). Fish intake was associated with higher red cell total n-3 fatty acids (0.62 (0.27, 0.85), P=0.0014). CONCLUSIONS: We have reported data on the range of the fatty acids of plasma and red blood cells (RBC) total lipids of 114 healthy women of reproductive age. These data provide further information on how socio-economic, anthropometric, behavioural and obstetric factors may be relevant to female and nutrition and health. SPONSORSHIP: University of Glasgow.

Adult↗

Liver disease does not affect lipolysis as measured with the 13C-mixed triacylglycerol breath test in children with cystic fibrosis.

BACKGROUND: Liver disease associated with cystic fibrosis may not only limit the solubilisation and absorption of the products of fat digestion, but also may depress the activity of pancreatic lipase. The purpose of this study was to measure the effect of liver disease on triacylglycerol lipolysis using the 13C-mixed triacylglycerol breath test. METHODS: Forty children with cystic fibrosis took 13C-mixed triacylglycerol with a standard breakfast and the child's normal pancreatic enzyme replacement therapy. Breath samples were collected before and every 30 minutes after ingestion for 6 hours. The cumulative percentage dose of 13C recovered at 6 hours was calculated from sequential measurements of 13C enrichment of breath CO2, measured by isotope ratio mass spectrometry. Liver abnormalities and portal hypertension were defined by ultrasound scan and clinical examination. RESULTS: Twenty-four children had liver abnormalities, including 5 with portal hypertension. No difference was found between cumulative percentage dose of 13C recovered at 6 hours in 16 children with no liver abnormality (mean, 21.4%+/-11.1%), 19 children with liver abnormalities (22.2%+/-10.0%) and 5 children with portal hypertension (20.9%+/-7.1%). CONCLUSION: Intestinal lipolysis is not reduced in cystic fibrosis liver disease when measured using the 13C mixed triacylglycerol breath test. These findings affirm the test's use as an indirect measure of fat digestion that is not affected by inadequate intraluminal bile salts or liver disease.

Adolescent↗

Comparison of an enzyme immunoassay for the detection of Helicobacter pylori antigens in the faeces with the urea breath test.

BACKGROUND: Current diagnostic tests for Helicobacter pylori are invasive (endoscopy) or indirect (urea breath test, serology). AIMS: To evaluate a new enzyme immunoassay (EIA) which detects H pylori antigens in faeces, by comparing its sensitivity and specificity in children with the (13)C urea breath test (UBT). METHODS: A total of 119 children underwent a UBT and provided a faecal sample for antigen testing within seven days. After an overnight fast each child provided a pretest breath sample, and samples at 30 and 40 minutes after ingestion of 100 mg (13)C labelled urea. (13)C enrichment of breath was measured by isotope ratio mass spectrometry. Faeces were stored at -70 degrees C until antigen testing, using the EIA. Samples were read spectrophotometrically at 450 nm and results were interpreted using recommended cut offs of optical density <0.14 as negative, >/=0.16 as positive, with >/=0.14 and <0. 16 representing equivocal results. Sensitivity and specificity were calculated using the manufacturer's cut off compared with UBT. RESULTS: Sensitivity and specificity were 88% and 82%, respectively. Negative and positive predictive values were 97% and 58%. CONCLUSIONS: The EIA is an alternative, non-invasive, and easy to use method for the detection of H pylori in children. Its high negative predictive value suggests a role in screening out uninfected children.

Adolescent↗

Infant cerebellar gray and white matter fatty acids in relation to age and diet.

There is little evidence as to the fatty acid composition of the cerebellum in infancy and it remains uncertain whether milk diet can influence its composition. We therefore examined cerebellar gray and white matter of infants less than 6 month old who had died unexpectedly. The fatty acid content of 33 gray and 21 white matter specimens from infants born at term and 6 gray and 5 white matter specimens from preterm infants was assessed by gas chromatographic/mass spectrometric analysis. Infants were grouped according to whether they had received human or manufactured formula milk. Whereas cerebellar cortex docosahexaenoic acid (DHA, 22:6n-3) concentrations were significantly lower (P<0.01) in the formula-fed than breast-fed infants, no differences existed between the term (n = 10) and preterm (n = 5) Synthetic Milk Adapted [corrected] (SMA) formula-fed infants. Cerebellar white matter DHA concentrations were similarly lower (P<0.01) in the SMA formula-fed infants (n = 8) than in an age-matched breast-fed group. Low concentrations of cerebellar white matter lignoceric (24:0) and nervonic acid (24:1n-9) in two 7-wk-old preterm infants appeared to correlate with postgestational rather than chronological age. Dietary long-chain polyunsaturated fatty acids, particularly DHA, are probably essential for normal development of the infant cerebellum.

Aging↗

Energy balance during acute respiratory exacerbations in children with cystic fibrosis.

Acute respiratory exacerbations have been proposed to contribute to the negative energy balance which causes undernutrition in cystic fibrosis. However, no studies have measured their effect on all components of energy balance. The aim of this study was to measure the effect of an acute respiratory exacerbation on energy balance. Fourteen children (six females, eight males, mean+/-SD age 9.9+/-2.4 yrs) were studied when well and during the course of an acute respiratory exacerbation treated with intravenous antimicrobial therapy. The total energy expenditure was measured using the doubly-labelled water method, resting energy expenditure by ventilated hood indirect calorimetry, energy intake by household measures records, and fat malabsorption from measurements of dietary fat intake and faecal fat output. The exacerbation was associated with a significant reduction in energy intake (mean paired difference 47 kJ x kg of body weight(-1) x day(-1), p<0.01). Changes in fat malabsorption and resting energy expenditure were negligible. The absence of significant changes in body weight and composition, together with the trend towards lower total energy expenditure, suggested no marked negative energy balance during the exacerbation. In conclusion, treatment of acute respiratory exacerbation with intravenous antimicrobial therapy represents a relatively minor challenge to energy balance and nutritional status in children with cystic fibrosis.

Acute Disease↗