Search PubMed⌕ Search

Biomedical subjects

M Harding

Publications and source records attributed to M Harding.

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↗
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↗
PubMed2002

Identification and reconstitution of the yeast mitochondrial transporter for thiamine pyrophosphate.

The genome of Saccharomyces cerevisiae contains 35 members of a family of transport proteins that, with a single exception, are found in the inner membranes of mitochondria. The transport functions of the 15 biochemically identified mitochondrial carriers are concerned with shuttling substrates, biosynthetic intermediates and cofactors across the inner membrane. Here the identification of the mitochondrial carrier for the essential cofactor thiamine pyrophosphate (ThPP) is described. The protein has been overexpressed in bacteria, reconstituted into phospholipid vesicles and identified by its transport properties. In confirmation of its identity, cells lacking the gene for this carrier had reduced levels of ThPP in their mitochondria, and decreased activity of acetolactate synthase, a ThPP-requiring enzyme found in the organellar matrix. They also required thiamine for growth on fermentative carbon sources.

Carbon↗
PubMed2001

Extrapancreatic pseudoaneurysm after pancreas transplantation.

Pseudoaneurysms after pancreatic transplantation are an infrequent event. Repair usually involves removal of the transplant. We describe a patient with a pseudoaneurysm associated with pancreatic transplantation. The pseudoaneurysm originated from the external iliac artery distal to the donor Y-graft anastomosis. Diagnosis was made by duplex ultrasound. Surgical repair was effected through a retroperitoneal incision enabling vascular control. The patient has done well postoperatively, and with 1-year follow-up, continues to have normal renal and pancreatic allograft function.

Aneurysm, False↗
PubMed2001

De novo lipogenesis during controlled overfeeding with sucrose or glucose in lean and obese women.

BACKGROUND: The results of previous studies suggest that de novo lipogenesis may play an important role in the etiology of obesity, particularly during overconsumption of different carbohydrates. OBJECTIVE: We hypothesized that de novo lipogenesis would increase during overfeeding, would vary depending on the type of carbohydrate consumed, and would be greater in obese than in lean women. DESIGN: De novo lipogenesis was measured during 96 h of overfeeding by 50% with either sucrose or glucose and during an energy balance treatment (control) in 8 lean and 5 obese women. De novo lipogenesis was determined by measuring the amount of deuterium incorporation into plasma triacylglycerols. Fat and carbohydrate balance were measured simultaneously by continuous whole-body calorimetry. RESULTS: De novo lipogenesis did not differ significantly between lean and obese subjects, except with the control treatment, for which de novo lipogenesis was greater in the obese subjects. De novo lipogenesis was 2- to 3-fold higher after overfeeding by 50% than after the control treatment in all subjects. The type of carbohydrate overfeeding (sucrose or glucose) had no significant effect on de novo lipogenesis in either subject group. Estimated amounts of absolute VLDL production ranged from a minimum of 2 g/d (control) to a maximum of 10 g/d after overfeeding. This compares with a mean fat balance of approximately 275 g after 96 h of overfeeding. Individual subjects showed characteristic amounts of de novo lipogenesis, suggesting constitutive (possibly genetic) differences. CONCLUSION: De novo lipogenesis increases after overfeeding with glucose and sucrose to the same extent in lean and obese women but does not contribute greatly to total fat balance.

Body Composition↗
PubMed2000

Comparison of recoveries in breath carbon dioxide of H13CO-3 and H14CO-3 administered simultaneously by single 6 h constant unprimed intravenous infusion.

The aim of this study was to assess the bioequivalence of H13CO-3 and H14CO-3, by administering both labels simultaneously by single infusion and comparing their recovery in breath CO2 and urinary urea. Six healthy male subjects (age range 24-41 years; weight 76.7 (sd, 18.6) kg; height 1.79 (sd 0.05) m) were infused with unprimed solutions of HCO3- (110.0 mmol/kg) labelled with 13C (0.76 mmol 13C/h) and 14C (48 Bq/h) at a constant rate for 6 h, in a whole-body calorimeter (1400 litres) for measurement of CO2 production. Samples of breath were collected hourly in a Douglas bag and all urine was collected into two batches (0-4 h and 4-6 h) for estimating recovery of infused label by measurement of enrichment or specific activity. Recovery in breath CO2 of both labels increased from about 25 % for the first hour to 88 % and above for hours 3-4 onwards. Mean recovery of 13C in breath CO2 was slightly higher than that of 14C for all periods (mean difference always less than 1 % of infused label) but was significant only for the first 3 h (P < 0.05). Recovery of 14C in urea was significantly higher (P < 0.01) than 13C, but was confounded by substantial variability and uncertainties concerning 13CO2 background enrichments. These results suggest that there is no compelling need to alter factors currently used for recovery of 14C in breath when using 13C instead, and vice versa.

Adult↗
PubMed1999

13C and H2 breath tests to study extent and site of starch digestion in children with cystic fibrosis.

BACKGROUND: Starch is an important source of energy for children with cystic fibrosis, but little is known about their capacity to digest it. METHODS: A 13C breath test was used to measure starch digestion and oxidation in 16 children with cystic fibrosis (median [range] age, 7.9 [4-15] years; 7 girls, 9 boys) and 5 normal healthy control subjects (median age, 8.3 [7-13] years; 3 girls, 2 boys). A test meal of 13C flour and lactulose was consumed and breath samples were obtained half-hourly thereafter for 6 hours to measure 13C enrichment by isotope ratio mass spectrometry and H2 by electrochemistry. The test was repeated on 10 children with cystic fibrosis when they were taking pancreatic supplements. RESULTS: The median (range) cumulative percentage 13C dose recovery (cPDR), was 35% (18-52%) in control subjects, 18% (9-33%) in children with cystic fibrosis without enzymes, and 29% (22-51%) in those with pancreatic supplements. cPDR differed significantly between healthy control subjects and children with cystic fibrosis without enzymes (p = 0.01) and between children with cystic fibrosis with and without enzymes (p < 0.0001), but there was no difference between control subjects and children with cystic fibrosis taking enzymes (p = 0.5). Eight children with cystic fibrosis had a cPDR within control range, and in six there was a second peak in 13CO2 enrichment coincident with an increase in H2. CONCLUSIONS: Starch digestion and oxidation are diminished in children with cystic fibrosis, but pancreatic enzymes restored them to near normal levels. A second peak in 13CO2 enrichment, suggestive of colonic starch fermentation was absent in healthy children, but present in some children with cystic fibrosis and abolished by pancreatic enzymes.

Adolescent↗
PubMed1999

Development of fat digestion in infancy.

AIM: To measure the development of fat digestion in early life, using a stable isotope breath test. METHODS: A combined longitudinal and cross sectional study was performed on 30 term and preterm infants using 13C-labelled mixed triglyceride (MTG). Seventy six tests were performed in all. Results were expressed as cumulative percentage dose recovered over 6 hours (cPDR). RESULTS: Eighteen of 34 tests performed on infants under 30 days of age showed cPDRs below the normal range for adults and older children. The remainder of tests, performed on infants over 57 days of age, all showed cPDRs within the normal range. Peak PDR correlated significantly (r = 0. 928, p<0.01) with cPDR. CONCLUSION: The capacity to digest fat is incomplete at birth, but quickly develops to normal levels during the first months of life. The MTG breath test is a useful non-invasive method to measure the development of fat digestion in early life.

Breath Tests↗
PubMed1999

Helicobacter pylori colonization in early life.

Helicobacter pylori infection is a major cause of upper gastrointestinal disease throughout the world. Colonization begins in childhood, although little is known about its age of onset, rate, or mode of colonization. Our aim was to identify the age of acquisition of H. pylori colonization in Gambian children. A cohort of 248 Gambian children aged 3 to 45 months was studied at intervals of 3 months for 2 years, using the 13C-urea breath test, specific IgM and specific IgG serology. The prevalence of positive breath tests rose from 19% at 3 months of age to 84% by age 30 months. Elevated specific IgG and IgM antibody levels were associated with positive breath tests, although there was discrepancy between breath test results and serology, particularly IgG serology, during the 1st year of life. Neither IgG nor IgM serology could be validated as reliable diagnostic tools for infant H. pylori colonization compared with the 13C-urea breath test. Reversion to negative breath test, in association with declining specific antibody levels, occurred in 48/248 (20%) of children. On the assumption that the 13C-urea breath test is a reliable index of H. pylori colonization, we conclude that the infection is extremely common from an early age in Gambian children. Transient colonization may occur. Previous studies relying on serodiagnosis may have significantly underestimated the true early prevalence of colonization in the developing world, where the target age for intervention studies is probably early infancy.

Antibodies, Bacterial↗
PubMed1999

Interpreting the 13C-urea breath test among a large population of young children from a developing country.

The 13C-urea breath test is a noninvasive tool for the diagnosis of gastric Helicobacter pylori infection. However, it has not been validated in young children from the developing world, where infection is very common. 13C urea breath tests were performed on 1532 occasions on 247 Gambian infants and children aged from 3 to 48 mo. The means and variances of the separate sub-populations of 13C enrichment results contained within the overall dataset were estimated by a Genstat procedure using the EM algorithm, thereby identifying a cut-off value to discriminate positive from negative results. To illustrate the appropriateness of this calculated cut-off value, 13C urea breath tests were performed upon a small group of 14 patients aged 6 to 28 mo undergoing diagnostic upper endoscopy. Fixed gastric antral biopsies were examined to identify H. pylori. Two subpopulations were identified within the large dataset. A cut-off value of 5.47 delta per thousand relative to Pee Dee Belemnite limestone above baseline at 30 min identified 95% of the normally distributed negative sub-population and 99.4% of the log normal distributed positive sub-population. Comparison with endoscopic data confirmed that this cut-off value was appropriate for this population, as 7/7 children without H. pylori on their gastric biopsies had negative urea breath tests, and 6/7 children with gastric H. pylori colonization had positive urea breath tests. These findings confirm the value of the urea breath test as a diagnostic tool in young children from developing countries. They also offer a way to calculate the most appropriate cut-off value for use in different populations and the likelihood that it will correctly assign any value into the appropriate sub-population, without the need for endoscopy.

Breath Tests↗
PubMed1998

Importance of measuring CO2-production rate when using 13C-breath tests to measure fat digestion.

Stable isotope breath tests offer a safe, repeatable non-invasive method of measuring fat digestion. They involve the ingestion of a substrate labelled with 13C followed by serial measurements of the 13C:12C ratio in expired CO2, from which the percentage of the 13C dose recovered (PDR) can be calculated. However PDR depends on the CO2-production rate. Our aim was to compare results obtained using directly measured CO2-production rates with those calculated from two predicted values. Twelve normal healthy children and twenty-four children with cystic fibrosis (CF) (without or with the normal dose of enzyme supplementation) were studied with 1,3-distearyl, 2[carboxyl-13C] octanoyl glycerol. The volume of CO2 produced (litres/min) was measured at rest for 30 min approximately 3 h after substrate ingestion, and the results were converted to mmol/min. For each subject the expected BMR was calculated from the equation of Schofield (1985), based on sex, age, weight and height, and from these values, CO2-production rate was derived. Surface area was calculated and an estimated value of 5 mmol/m2 per min (Shreeve et al. 1970) was used. Using these three CO2-production rates, three different PDR were calculated and compared. In healthy children there was a close concordance between measured and predicted CO2-production rates, but children with CF had a mean measured CO2-production rate 39% higher than normal children. This use of normal data for predicted CO2-production rates in children with CF underestimates cumulative PDR. If direct measurements of CO2-production rate are not available or impossible to perform the VCO2 obtained from the BMR calculated using the equations of Schofield (1985) or Shreeve et al. (1970) can be used in normal children. However, if accurate results for PDR are to be obtained, CO2-production rates should be measured when performing breath tests in conditions where energy expenditure and/or CO2-production rate are not expected to be normal.

Breath Tests↗
PubMed1998

Bile salt-stimulated lipase and digestion of non-breast milk fat.

BACKGROUND: 13 Carbon (13C)-lipid breath tests are an effective, noninvasive way of repeatedly measuring fat digestion. The purpose of this study was to assess the contribution of bile salt-stimulated lipase (BSSL) in human milk to the digestion of non-breast-milk fat in Gambian infants. METHODS: Twelve Gambian infants (aged 3-8 months) were studied on 4 days. 13C-Trioctanoin (7.5 mg/kg, digested by BSSL preduodenal and pancreatic lipases) and 13C-cholesteryl octanoate (25 mg/kg, digested by BSSL and pancreatic lipases) were used as substrates. The percentage dose recovery (PDR) of 13C in breath during 5 hours was compared after ingestion of each substrate with fresh, expressed breast milk (FBM) or heated, expressed breast milk (HBM). Gas isotope ratio-mass spectrometry was used to measure 13C enrichment, and breast milk samples were analysed for esterase activity. RESULTS: Heating breast milk significantly decreased esterase activity (mean +/- SD values: FBM = 12.2 +/- 2.9 IU/ml; HBM = 0.5 +/- 0.3 IU/ml), and there was no difference in the volumes of milk ingested on each test day (approximately 50 ml). The PDR of 13C was comparable to that previously described in healthy English infants and was not increased by BSSL. The mean +/- SD PDR of 13C from trioctanoin was 36.3 +/- 8.4% for FBM and 34.6 +/- 6.3% for HBM (NS). From cholesteryl octanoate, the mean +/- SD PDR of 13C was 24.3 +/- 8.7% for FBM and 27.1 +/- 7.5% for HBM (NS). CONCLUSIONS: Bile salt-stimulated lipase may enhance fat digestion in younger or malnourished infants who have a greater degree of pancreatic enzyme deficiency. However, this study suggests that it does not increase the digestion of non-breast-milk fat in healthy, well-nourished infants aged 3 to 8 months from an underprivileged background, who typically ingest frequent small quantities of breast milk.

Caprylates↗
PubMed1998

Helicobacter pylori infection, gastric acid secretion, and infant growth.

BACKGROUND: Helicobacter pylori infection is very common in Gambian infants and children, who are also at risk of chronic diarrhoea and undernutrition. Acute H. pylori infection is associated with depressed gastric acid secretion, and loss of the gastric acid barrier may predispose to enteric infections. METHODS: In a prospective study a noninvasive test of gastric acid output (measurement of change in urine acid output before and after a feed) was performed on a population of Gambian infants at high risk of H. pylori infection. The 13C urea breath tests was used to measure the prevalence of H. pylori infection and growth was measured by serial anthropometry. RESULTS: In 101 infants aged 3 to 12 months, there was a significant relation between H. pylori infection and depressed urine acid output in those aged 6 months, during weaning when growth failure and malnutrition begin. Those infants with sustained H. pylori infection grew less well than those without. CONCLUSIONS: We speculate that H. pylori, acquired in infancy, could be a "key that opens the door" to enteric infection in childhood, leading to recurrent diarrhoea, malnutrition, and growth failure.

Breath Tests↗
PubMed1998

Effectiveness and tolerability of tomoxetine in adults with attention deficit hyperactivity disorder.

OBJECTIVE: The authors assessed the experimental noradrenergic compound tomoxetine as an alternative treatment for adult attention deficit hyperactivity disorder (ADHD). METHOD: They conducted a double-blind, placebo-controlled, crossover study of tomoxetine in 22 adults with well-characterized ADHD. RESULTS: Treatment with tomoxetine at an average oral dose of 76 mg/day was well tolerated. Drug-specific improvement in ADHD symptom was highly significant overall and sufficiently robust to be detectable in a parallel-groups comparison restricted to the first 3 weeks of the protocol. Eleven of 21 patients showed improvement after receiving tomoxetine, compared with only two of 21 patients who improved after receiving placebo. Significant tomoxetine-associated improvement was noted on neuropsychological measures of inhibitory capacity from Stroop tests. CONCLUSIONS: This preliminary study showed that tomoxetine was effective in treating adult ADHD and was well tolerated. These promising results provide support for further studies of tomoxetine over an extended period of treatment.

Adult↗
PubMed1998

New purchasing measures for stellar performance.

According to this article, many manufacturing companies evaluate their purchasing departments using inappropriate measures. One reason is that the measures chosen are easy to use. Another is that the companies tend to favor predictability, and they thus prefer numbers that they can try to achieve. But predictability is not always a virtue. In fact, an obsession with predictability can prevent the kind of flexibility that is often necessary to respond to changes in the market. The article suggests that the best measures to use in evaluating purchasing departments are behavior measures, not price, delivery, or quality measures.

Commerce↗
PubMed1998

Disentangling the overlap between Tourette's disorder and ADHD.

OBJECTIVE: To identify similarities and differences in neuropsychiatric correlates in children with Tourette's syndrome (TS) and those with ADHD. METHOD: The sample consisted of children with Tourette's syndrome with ADHD (N = 79), children with Tourette's syndrome without ADHD (N = 18), children with ADHD (N = 563), psychiatrically referred children (N = 212), and healthy controls (N = 140). RESULTS: Disorders specifically associated with Tourette's syndrome were obsessive compulsive disorder (OCD) and simple phobias. Rates of other disorders, including other disruptive behavioral, mood, and anxiety disorders, neuropsychologic correlates, and social and school functioning were indistinguishable in children with Tourette's and ADHD. However, children with Tourette's syndrome plus ADHD had more additional comorbid disorders overall and lower psychosocial function than children with ADHD. CONCLUSIONS: These findings confirm previously noted associations between Tourette's syndrome and OCD but suggest that disruptive behavioral, mood, and anxiety disorders as well as cognitive dysfunctions may be accounted for by comorbidity with ADHD. However, Tourette's syndrome plus ADHD appears to be a more severe condition than ADHD alone.

Adolescent↗