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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
PubMed2006

Human milk vacuolating cytotoxin A immunoglobulin A antibodies modify Helicobacter pylori infection in Gambian children.

We collected data, including the weights, urea breath test results, and presence of maternal milk cytotoxin-associated gene-specific and vacuolating cytotoxin A-specific immunoglobulin A monthly from 48 mothers and infants (to 44 weeks of age) in The Gambia. In all, 11 children (23%) had negative urea breath test results, and 37 (77%) had positive results. Weight loss associated with Helicobacter pylori colonization was restricted to children whose mothers did not produce anti-vacuolating cytotoxin A antibodies in their milk (P=.028, by t test).

Adult↗
PubMed2006

Improving the specificity of the [13C]mixed triacylglycerol breath test by estimating carbon dioxide production from heart rate.

BACKGROUND: The [13C]mixed triacylglycerol (MTG) breath test is a non-invasive measure of fat digestion and can be used to assess the need for enzyme replacement therapy in children with cystic fibrosis (CF). However, it lacks specificity. Quantitation of cumulative percent dose recovered (cPDR) requires knowledge of carbon dioxide production rate (VCO2). A resting value is assumed, but children are unlikely to remain at rest during the test. OBJECTIVE: To improve the specificity and therefore the positive predictive value (PPV) of the MTG breath test using calibrated heart rate monitors to estimate non-resting VCO2. DESIGN: Proof of concept study. SUBJECTS: Six children with CF, 10 healthy children and eight healthy adults performed [13C]MTG breath tests. METHODS: Heart rate monitors were worn throughout the test. Non-resting VCO2 was estimated continuously from heart rate. Percentage dose recovered was calculated using predicted resting VCO2, measured resting VCO2 and non-resting VCO2 estimated from heart rate. Physical activity level (PAL) was taken as cPDR calculated using non-resting VCO2 divided by cPDR calculated using measured resting VCO2. The cutoff point was determined using two graph-receiver operator characteristics. RESULTS: Use of calibrated heart rate monitors to estimate non-resting VCO2 improved the specificity of the test. The PPV increased from 0.67 to 0.99. PAL was 1.3 in adults and children who performed the test in hospital, and 1.7 in children who performed the test at home. CONCLUSION: Individually calibrated heart rate monitors are useful tools to estimate non-resting VCO2 during the [13C]MTG breath test.

Adolescent↗
PubMed2006

Analysis of the influence of OCTN1/2 variants within the IBD5 locus on disease susceptibility and growth indices in early onset inflammatory bowel disease.

BACKGROUND AND AIMS: The OCTN1 (SLC22A4 1672C-->T) and OCTN2 (SLC22A5 -207G-->C) variants within the IBD5 locus have been associated with susceptibility to adult onset Crohn's disease (CD), but their contribution in children has not been examined. METHODS: These OCTN1/2 variants and IBD5 marker single nucleotide polymorphisms (SNPs) (IGR2096a_1, IGR2198a_1, and IGR2230a_1) were examined in 299 Scottish children (200 with CD, 74 with ulcerative colitis (UC), and 25 with indeterminate colitis (IC)), together with 502 parents (for transmission disequilibrium testing) and 256 controls. RESULTS: All SNPs were in strong linkage disequilibrium (D' >0.94). TDT analysis showed association of the OCTN1 variant with inflammatory bowel disease (IBD) (p = 0.01) and CD (p = 0.04). Allele frequencies of the OCTN1/2 variants were significantly higher in IBD/CD cases (p<0.04). The homozygous mutant OCTN1/2 haplotype was increased in IBD (24.3% v 16.1%, p = 0.02) and UC (28.2% v 16.1%, p = 0.02) compared with controls. The OCTN1/2 variants were not independent of the background IBD5 risk haplotype in conferring disease susceptibility. Unifactorial analysis in CD patients showed that carriage of the TC haplotype was associated with lower weight, height, and BMI centile (<9(th) centile) at diagnosis (weight: 87.9% v 67.3% (p = 0.002), odds ratio (OR) = 3.52 (95% confidence interval, 1.51 to 8.22); height: 84.1% v 68.4% (p<0.05), OR = 2.44 (1.00 to 5.99); BMI: 79.6% v 61.1% (p = 0.02), OR = 2.49 (1.14 to 5.44)), and lower weight centile at follow up (87.5% v 64.6% (p = 0.03), OR = 3.83 (1.03 to 14.24)). Multifactorial binary logistic regression analysis confirmed association of the TC haplotype with lower weight centile at diagnosis (p = 0.02, OR = 3.41 (1.20 to 9.66)). CONCLUSIONS: These data implicate variants within the IBD5 haplotype, as determinants of disease susceptibility and growth indices in early onset IBD. The OCTN1/2 variants remain potential positional candidate genes, but require further analysis.

Adolescent↗
PubMed2006

Comparison of accuracy and precision of heart rate calibration methods to estimate total carbon dioxide production during 13C-breath tests.

BACKGROUND: 13C-breath tests are noninvasive tools to measure gastrointestinal function and nutritional interventions. Calculation of percentage dose recovered of 13C in exhaled breath requires knowledge of CO2 production rate (VC02). A resting value is usually assumed, but this can underestimate VC02 because subjects are unlikely to remain at rest during tests that last for many hours. There is a need for a method to estimate nonresting VC02 during 13C-breath tests. OBJECTIVE: To calibrate a heart rate monitor to continually estimate VC02 during 13C-breath tests. DESIGN: Proof of concept study. SUBJECTS: Eight healthy adults, 10 healthy children and six children with cystic fibrosis. METHODS: Heart rate and VC02 were measured simultaneously at resting and nonresting levels. A new calibration method (smoothing heart rate and fitting a sigmoid function) was compared with published methods. A [ 3C]acetate breath test was used to demonstrate the range of physical activity during breath tests. RESULTS: The new calibration method was more accurate than existing methods (mean bias -0.0002%, 95% confidence interval (CI) -0.0007, 0.0003% of the mean measured VC02). Smoothing heart rate gave a more precise estimate of VC02 and a more accurate estimate of resting energy expenditure (mean bias -0.09, 95% Cl -0.22, 0.05 mmol CO2 min-' m-2 body surface area) than using raw data (mean bias -0.21, 95% Cl -0.38, -0.04 mmol CO2 min' m-2 body surface area). Physical activity level ranged from 1.0 to 2.5 in children, and 1.0 to 1.5 in adults. CONCLUSION: Use of smoothed HR with a sigmoid function provides an accurate method of estimating nonresting VC02 during 13C-breath tests.

Adolescent↗
PubMed2006

The Black Death and AIDS: CCR5-Delta32 in genetics and history.

Black Death and AIDS are global pandemics that have captured the popular imagination, both attracting extravagant hypotheses to account for their origins and geographical distributions. Medical scientists have recently attempted to connect these two great pandemics. Some argue that the Black Death of 1346-52 was responsible for a genetic shift that conferred a degree of resistance to HIV 1 infection, that this shift was almost unique to European descendents, and that it mirrors the intensity of Black Death mortality within Europe. Such a hypothesis is not supported by the historical evidence: the Black Death did not strike Europe alone but spread from the east, devastating regions such as China, North Africa, and the Middle East as much or even more than Europe. Further, in Europe its levels of mortality do not correspond with the geographic distribution of the proportion of descendents with this CCR5 gene. If anything, the gradient of Black Death mortality sloped in the opposite direction from that of present-day genotypes: the heaviest casualties were in the Mediterranean, the very regions whose descendents account for the lowest incidences of the HIV-1 resistant allele. We argue that closer collaboration between historians and scientists is needed to understand the selective pressures on genetic mutation, and the possible triggers for changes in genetic spatial frequencies over the past millennia. This requires care and respect for each other's methods of evaluating data.

Disease Outbreaks↗
PubMed2006

Dietary and social characteristics of children with severe tooth decay.

BACKGROUND AND AIMS: Dental decay remains a major public health problem in Scottish children. The aim of this study was to investigate the relationship between diet, bowel habit, social class, and body mass index (BMI) in children with severe tooth decay. CHILDREN AND METHODS: A cross sectional study of 165 children aged 3 -11 years attending Glasgow Dental Hospital for extraction of teeth under dental general anaesthesia (DGA), was undertaken. A structured questionnaire was used to obtain information from each child on diet, bowel habit, and social status of their parents. Fibre and sugar scores were calculated from the frequency of consumption of a range of relevant foods. RESULTS: The children (mean age 5.7 (SD1.8) years) had between 1 and 20 decayed, missing or filled primary teeth (dmft) with a mean dmft of 7.9 (SD 3.5). 37% ate a chocolate bar daily, and 29% regularly drank a sugary drink after brushing their teeth. An excess of children were from the most deprived parts of the city and they had the worst decay. Children with the worst decay were also significantly thinner. No relationship was found between tooth decay and bowel habit. CONCLUSIONS: In this selected group of children with poor dental health, those from deprived families were over-represented and had significantly more decay. Severe dental decay was also associated with underweight.

Body Mass Index↗
PubMed2005

Vitamin A and preterm infants: what we know, what we don't know, and what we need to know.

Vitamin A is essential for optimal growth and development. In the developing world, vitamin A supplementation of the newborn infant reduces mortality. In the developed world, extremely preterm infants are born with low body stores of vitamin A and are at high risk of vitamin A deficiency. Optimal vitamin A supplementation for this population is not clearly defined, however, and, despite evidence of benefit, early vitamin A supplementation of extremely preterm infants is not uniformly practised in the United Kingdom. There is an urgent need for studies in preterm infants that include quantification of hepatic stores and functional assessment of vitamin A status as well as long term outcome.

Dietary Supplements↗
PubMed2004

Bone mineral assessment by dual energy X-ray absorptiometry in children with inflammatory bowel disease: evaluation by age or bone area.

BACKGROUND: Abnormal linear growth and deficient bone mineral acquisition may coexist in children with inflammatory bowel disease (IBD). Traditionally, bone mineral assessment by dual energy x-ray absorptiometry (DXA) involves comparison to age- and gender-matched reference ranges, and these studies in children with IBD show a high prevalence of osteopenia. AIMS: To compare the prevalence of osteopenia using two methods of interpretation; one adjusted for age and gender and the other adjusted for bone size and gender. PATIENTS: Forty-seven patients with Crohn disease (CD) and 26 patients with ulcerative colitis (UC) with a median age of 13.5 years (range, 5.5-18.2 years) were evaluated. METHODS: Lumbar spine (LS) and total body (TB) bone mineral content (BMC) were measured by DXA and converted to bone mineral density (BMD, g/cm) corresponding to BMC divided by the bone area. Age and gender-matched BMD standard deviation scores (SDS) were based on reference data providing age- and gender-matched BMC and bone area. These data also allowed calculation of percentage of predicted bone area for age and gender (ppBone Area) and percentage of predicted BMC for Bone Area (ppBMC). RESULTS: Patients with CD were shorter than those with UC (median height, SDS, -0.9 v 0, P < 0.05). Median ppBone Area for LS and TB for the whole group was 85% (10th centile, 68; 90th centile 99) and 81% (10th centile 66; 90th centile, 97), respectively. The ppBone Area at both sites was directly related to height SDS and BMI SDS (r > 0.5; P < 0.005). Median BMD SDS for LS and TB was -1.6 (10th centile -3.6; 90th centile, -0.2) and -0.9 (10th centile, -2.4; 90th centile, 0.4), respectively. Median ppBMC for LS and TB was 98% (10th centile, 84%; 90th centile, 113%) and 101% (10th centile 94%; 90th centile, 107%), respectively. The ppBMC showed no relationship to ppBone Area (r = 0.1, NS). Failure to account for bone area led to a label of moderate or severe osteopenia in 65% of cases. After adjustment for bone area, the proportion of children with osteopenia fell to 22%. CONCLUSIONS: The data suggest that children with IBD often have small bones for age because they have growth retardation. When DXA data are interpreted with adjustment for bone size, most children were found to have adequate bone mass. Correct interpretation of DXA is important for identifying children who may be at a real risk of osteoporosis.

Absorptiometry, Photon↗
PubMed2004

Helicobacter pylori antigens in the faeces of asymptomatic children in the Buea and Limbe health districts of Cameroon: a pilot study.

OBJECTIVE: To determine the prevalence and identify intra-familial risk factors associated with Helicobacter pylori infection in a paediatric population. METHODS: Cross-sectional study in the Buea and Limbe health districts, South West Cameroon. Stool samples were collected from 176 randomly selected apparently healthy children from two communities with different socioeconomic status. They comprised 86 males and 90 females aged 0-10 years with a mean age of 4.29. Helicobacter pylori status was determined using an enzyme-linked immunosorbent assay, the H. pylori stool antigen (HpSA) test. The test uses polyclonal anti-H. pylori capture antibody to detect H. pylori antigens in human stool. Epidemiological data were analysed using the Fisher test and odds ratio (OR) at 95% confidence intervals (CI). RESULTS: The overall prevalence of H. pylori was 52.27% (92 of 176). Univariate analysis showed that H. pylori prevalence was significantly higher in children of the low socioeconomic class, 62.50% (55 of 88) than in those of the high socioeconomic class, 42.05% (37 of 88) (P < 0.05; OR = 2.41, 95% CI: 1.26-4.64). Helicobacter pylori prevalence increased with age from 37.50% (12 of 32) for children aged <3 years, 50.00% (53 of 106) aged 3-6 years and 71.05% (27 of 38) aged 7-10 years (P > 0.05; OR = 0.81, 95% CI: 0.34-1.91). The frequency of infection was significantly higher in males, 64.00% (55 of 86) than in females, 41.11% (37 of 90), (P < 0.05; OR = 2.67, 95% CI: 1.39-5.17). CONCLUSIONS: This study highlights the continuing importance of age, sex and socioeconomic status in the acquisition of H. pylori infection.

Antigens, Bacterial↗
PubMed2004

Early Helicobacter pylori colonisation: the association with growth faltering in The Gambia.

BACKGROUND: Helicobacter pylori is one of the commonest causes of chronic infection of mankind, yet the natural history of acute infection is poorly understood. Some studies suggest that gastric colonisation with H pylori is associated with suboptimal nutrition and growth in childhood. AIMS: To describe the clinical features of early H pylori colonisation and assess its role in the development of infant malnutrition and growth faltering. METHODS: Two consecutive prospective longitudinal cohort studies were conducted at the Medical Research Council Laboratories in a rural community in The Gambia, West Africa. The first birth cohort of 125 infants was followed by a second of 65 children from the same community. H pylori colonisation was detected by sequential 13C urea breath tests, and infant growth was monitored by serial measurements. RESULTS: Children with early H pylori colonisation became significantly lighter, shorter, and thinner than their peers in late infancy. The association was found in both cohorts. No socioeconomic or demographic confounding variables were identified to explain this, and the weight deficit was no longer detectable when the children were aged 5-8 years. CONCLUSIONS: Results suggest that H pylori colonisation in early infancy predisposes to the development of malnutrition and growth faltering, although the effect did not persist into later childhood.

Breath Tests↗
PubMed2004

Helicobacter pylori in children is strongly associated with poverty.

BACKGROUND AND AIMS: To examine the association between prevalence of H. pylori colonisation and social deprivation in a sample of children investigated in hospital. METHODS: A retrospective review of the hospital records of all children (n = 626) who underwent 13C-urea breath testing for suspected H. pylori infection at the Royal Hospital for Sick Children, Glasgow, Scotland between August 1995 to December 2002 was performed. Prevalence of H. pylori colonisation was measured by the 13C-urea breath test and socioeconomic status was measured by the Carstairs and Morris index of deprivation. RESULTS: The overall prevalence of H. pylori was 26%. There was a highly significant positive association between H. pylori colonisation and poor socioeconomic status (p < 0.000). The prevalence of colonisation was significantly higher in children from the most deprived areas (DepCat 6 and 7; 34%) compared to children from intermediate (DepCat 3 to 5; 22%) and the most affluent areas (DepCat 1 and 2; 16%) (p < 0.0001). CONCLUSIONS: Socioeconomic deprivation in childhood is associated with a high prevalence of H. pylori colonisation. While the incidence of H. pylori may be declining, it remains common in poor families. If the prevalence of H. pylori (26%) in this selected group reflects that of the population at large, then over 9000 (5%) of Glasgow's children are at risk of this preventable disease. In a city where the majority of adults are colonised with H. pylori, colonisation in early life adds to the burden of health risks to which deprived children are exposed.

Adolescent↗
PubMed2004

Childhood H. pylori: disappearing disease or chronic infection?

Helicobacter pylori is one of the commonest chronic bacterial infections worldwide. It is acquired during childhood and its persistence has implications for health in later life. In adults, it is the principle cause of duodenal ulcer disease and there is evidence of an association between H. pylori and gastric cancer. However, most colonized people are asymptomatic. The prevalence of H. pylori increases with age but there is a striking difference between the rates in developed and developing countries. As no significant non-human or environmental source for this infection has been identified, person to person spread is almost certainly the main mode of transmission. Community nurses should be aware of this micro-organism as a potential cause of illness in children, and that they can play a role in promoting hygiene practices and educating families so that the risk of acquisition may be reduced. This review discusses the clinical features, prevalence, risk factors for transmission, diagnosis and treatment of H. pylori.

Age Distribution↗
PubMed2003

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↗
PubMed2003

Starch fermentation by faecal bacteria of infants, toddlers and adults: importance for energy salvage.

OBJECTIVE: Little is known of the degree to which the colon salvages energy through starch fermentation in young children. Using a simulated colonic environment, we aimed to account for the fate of fermented raw and cooked starch in two groups of young children and in adults. DESIGN: A slurry was prepared from faecal samples from six infants (7-10 months), six toddlers (16-21 months) and seven adults (24-56 y). Each slurry was anaerobically incubated with raw or cooked maize starch in MacCartney bottles in a shaking water bath. Parallel incubations were stopped at 4 and 24 h. The headspace gas volume was analysed for CO(2) and methane. The culture supernatant was analysed for short-chain fatty acids (SCFA), lactate and residual starch. RESULTS: Different patterns of fermentation were seen at 4 and 24 h. For raw starch, the production of SCFA decreased with subject age at 4 h but not at 24 h. With both substrates at 4 h, toddler stools produced significantly more CO(2) than infants or adults, but there were no statistical differences at 24 h. Methane was detected in three adults only. Lactate was detected mainly at 4 h in children. CONCLUSIONS: The results suggest that fermentation, particularly of raw starch, is a more rapid process in young children than in adults. A highly efficient energy salvage process may occur in the colon of young children.

Adult↗
PubMed2003

Evaluation of protocol using gene capture and PCR for detection of Helicobacter pylori DNA in feces.

The route of transmission of Helicobacter pylori, which is usually acquired in childhood and is one of the most common bacterial infections in humans, remains undetermined. Mapping the distribution of H. pylori genotypes within families could help to determine the routes of transmission and risk factors. Here we describe a noninvasive method for obtaining H. pylori DNA isolates from the feces of children. Children presenting with gastrointestinal symptoms at the Royal Hospital for Sick Children were tested for gastric H. pylori colonization by using the 13C-urea breath test (UBT) and were asked to provide fecal samples, which were tested for H. pylori by using the HpSA fecal antigen test. DNA was purified from fecal samples by using a novel method of gene capture with subsequent H. pylori PCR analysis. Fifteen UBT-positive and 15 UBT-negative children participated in the study. The positive and negative predictive values for the assay were 80 and 100%, respectively. Fecal DNA purification followed by H. pylori PCR analysis is an effective tool for harvesting H. pylori DNA isolates from the feces of children. This technique may be developed to allow the diagnosis and noninvasive genotyping of H. pylori in children and their families.

Antigens, Bacterial↗
PubMed2003

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↗