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Biomedical subjects

L T Weaver

Publications and source records attributed to L T Weaver.

At least 91 records · Page 5Linked to original sources

Development of bowel habit in preterm infants.

The bowel habits in 844 preterm infants were observed during the first 56 days after birth. Delay in the passage of meconium beyond the second day occurred in 32%, and there was an inverse relation between gestational age and the day of first bowel action. Thereafter the increase in frequency of stools passed each day was related directly to the volume of milk ingested. Unfed infants had a modal defecation rate of one stool each day. For each 50 ml/kg increase in the volume of milk ingested the infants showed a further increase of one stool passed each day. Infants fed with human milk passed a greater number and softer stools than those who received cows' milk formula. In the absence of milk feeds an intrinsic pattern of large bowel motor activity, present as early as 25 weeks' gestation, ensures a defecation rate of one stool each day. The effect of enteral nutrition on this inherent motility is governed by the volume and composition of milk feeds, independently of gestational age.

Age Factors↗

Cystic fibrosis identified by neonatal screening: incidence, genotype, and early natural history.

The incidence of cystic fibrosis over the last 10 years in East Anglia (a region of the United Kingdom with a population of 2.1 million) has halved. This has happened during the establishment of a neonatal screening programme, which has enabled early diagnosis, genetic counselling, and lately the option of prenatal diagnosis in subsequent pregnancies. One hundred and seven children were born with cystic fibrosis between 1981 and 1990, eight of whom were siblings. The Guthrie blood spots of 82 infants detected by neonatal immunoreactive trypsin screening between 1981 and 1990 were examined for the presence of the most common cystic fibrosis gene mutation (delta F508). It was present in 135 (82%) of the 164 cystic fibrosis genes analysed with 54 (66%) cases being homozygous and 27 (33%) heterozygous. Sixty nine per cent of infants were symptomatic at the time of diagnosis regardless of genotype. No association was found between the early clinical or biochemical features of the disease and homozygosity or heterozygosity for this mutation. Screening for cystic fibrosis using the blood immunoreactive trypsin assay alone remains an effective method of identifying infants with the disease soon after birth, thereby allowing early therapeutic intervention. Genetic counselling and prenatal diagnosis have contributed to a reduction in the number of children born with cystic fibrosis, but may not entirely explain the decreasing incidence of the disease.

Cystic Fibrosis↗

Dual marker one day pancreolauryl test.

There is a pressing need for a simple non-invasive test of exocrine pancreatic function for use in children. The pancreolauryl test has been modified by the addition of a second marker (mannitol) to achieve a single day test without the need for two timed urine collections. Six healthy subjects and nine patients with cystic fibrosis were studied. Fluorescein, fluorescein dilaurate, and mannitol were taken by mouth, alone or in combinations, followed by 10 hour urine collections in two hourly aliquots to study the comparative pharmacokinetics of these markers. Urinary fluorescein was determined spectrophotometrically and urinary mannitol enzymatically. When fluorescein dilaurate and mannitol were taken together and the results expressed as ratios of percentage fluorescein to percentage mannitol recovery (F:M ratio) (mean (SD)) there was clear discrimination between healthy subjects and those with cystic fibrosis regardless of enzyme replacement treatment (57.3 (18.2) v 3.4 (1.4) v 3.2 (1.6) respectively). The differences in F:M ratios reached statistical significance in urinary aliquots collected between two and eight hours after marker ingestion. This single day tubeless test will greatly simplify the investigation of the child with suspected exocrine pancreatic dysfunction.

Administration, Oral↗

Measurement of fat digestion in early life using a stable isotope breath test.

13C breath tests are a safe, non-invasive way of assessing nutrient digestion and absorption that can be used repeatedly in infancy and childhood. The aim of this study was to assess their value for measuring fat digestion in infants and young children with cystic fibrosis, and healthy controls whose pancreatic exocrine function is immature, and to monitor pancreatic enzyme supplementation. Six infants with cystic fibrosis (aged 10-18 months) and nine healthy controls (aged 6-19 months) were studied. After an overnight fast each child ingested 7.5 mg/kg 13C trioctanoin (99 atom % excess) followed by a known volume of milk. Breath samples were collected before and at 30 minute intervals thereafter for five hours. The 13C enrichment of expired carbon dioxide was measured by gas isotope ratio mass spectrometry. The mean (SD) percentage dose recovery of 13C was 13.5 (5.3) for the cystic fibrosis group and 24.2 (6.7) for the healthy controls. When those with cystic fibrosis were studied after supplementary pancreatic enzymes, the mean percentage dose recovery rose to 17.1 (6.9). Total intraluminal lipolysis was diminished by 44% in young children with cystic fibrosis. Pancreatic enzyme supplements improved digestion by 27%. The 13C trioctanoin breath test was effective in detecting fat maldigestion and can be used to measure the benefits of enzyme supplements in early life.

Breath Tests↗

New non-invasive test of gastric acid secretion for use in children.

Loss of the gastric acid barrier may lead to recurrent enteric infections, small intestinal bacterial overgrowth, persistent diarrhoea, and thus malnutrition. To investigate this possibility, a new, non-invasive test of gastric acid secretion was developed ideal for field use in the developing world, where chronic diarrhoea and undernutrition are common. The test relies on the capacity of the kidney to retain H+ during gastric acid secretion, leading to a post-prandial urine 'alkaline tide'. Gastric intubation studies of seven healthy adult volunteers showed a direct relation between changes in gastric acid secretion and changes in urine acid output (measured as the H+/creatinine molar ratio in spot urine samples). Subjects who secreted gastric acid in response to stimulation with a sham feed showed a fall in urine acid output > 0.5 mmol H+/mmol creatinine (range -7.4 to -1.52 mean -1.12). The most reproducible decrease in urine acid output in response to normal food was observed around the time breakfast was usually eaten and was abolished by 36 hours of treatment with ranitidine. Breakfast time reductions in postprandial urine acid output in 22 healthy English children were comparable with those in healthy adults, and significantly different from values in achlorhydric adults. They were much more variable, however, in 106 Gambian children in whom values spanned both normochlorhydric and achlorhydric ranges (-12.7 to +1.8). Measuring changes in urine acid output at breakfast time provides a reliable indirect measure of gastric acid secretion that can be used in field conditions, enabling the relation between gastric acid output and the development of diarrhoeal diseases to be investigated.

Adult↗

Isolation of Helicobacter pylori from human faeces.

Helicobacter pylori is arguably the commonest chronic infection in man. However, its route of transmission is unknown. We have isolated viable H pylori from the faeces of an infected individual from The Gambia. The organism was cultured on selective media after concentration of faecal bacteria by centrifugation in a buffer equilibrated with a microaerophilic gas mixture. Growth characteristics, microscopic appearances, and enzyme activities were the same as those of a typical gastric isolate of H pylori. Protein preparations derived from the new isolate and the typical strain were antigenically similar, and had very similar electrophoretic profiles (including two major protein bands of 62 and 26 kDa, corresponding to the urease enzyme subunits). With the same technique, organisms with the colony morphology, growth requirements, enzyme activities, and microscopic appearances of H pylori were isolated from the faeces of 9 of 23 randomly selected children aged 3-27 months from a Gambian village with a high prevalence of H pylori infection in early life. Faecal-oral transmission is probably important in the spread of infection in such communities.

Adult↗

Is cow's milk suitable for the dietary supplementation of rural Gambian children? 1. Prevalence of lactose maldigestion.

To define the age-related prevalence of lactose maldigestion (LM), 218 children aged 13-72 months from a rural Gambian village were studied using a lactose breath hydrogen test. There was a significant rise in LM from 21% to 76% between the 2nd and 3rd-5th years of life (p < 0.001). Only eight children had diarrhoea within 2 weeks before the test. Diarrhoea and abdominal discomfort followed in only seven children (3%). There was no difference in mean time of introduction of supplementary diet or cessation of breastfeeding between children aged 12-36 months with lactose digestion and LM. There was a greater proportion of children with normal lactose digestion than with LM in those still receiving breast milk (85% vs 15%), and a greater proportion of LM in the fully weaned group (63% vs 37%) (p < 0.001). There was no relation between weight-for-age or weight-for-height and the ability to digest lactose. The ability to digest lactose is lost in the majority of children during the 2nd year, coincident with the cessation of breastfeeding, but is not a major factor associated with growth failure thereafter.

Age Factors↗

Is cow's milk suitable for the dietary supplementation of rural Gambian children? 2. Patterns of cow's milk intake.

Cow's milk has been advocated as a source of supplementary diet for children in many parts of the developing world. The frequency and forms of cow's milk intake and the factors regulating its availability and consumption by 507 children aged up to 6 years in three Gambian villages were measured. Nineteen per cent of mothers did not give cow's milk to their children. Of 413 children taking cow's milk, 41% consumed it only once a week, 32% two to four times a week, 19% once a day and 8% more than once a day. Eighty per cent of children took both fresh and sour milk. Forty-one per cent of infants up to 1 year old received cow's milk at some time. There was a decrease with age in the proportion of children taking fresh milk and a rise with age in the proportion taking sour milk alone (p < 0.001) and both forms of milk. Only 2% of children were reported to have an adverse reaction to fresh cow's milk. The main factors affecting intake were the availability of money and milk. The consumption of cow's milk in early life is common and free of adverse effects. When it is available, it should be used to supplement the diet of the weaned child.

Animals↗

Carnitine deficiency: a possible cause of gastrointestinal dysmotility.

An infant with delayed development and peripheral myopathy, nourished on a soy-based liquid diet deficient in carnitine, had gastrointestinal dysmotility manifested by postprandial vomiting, oral drooling, delayed gastric emptying and infrequent bowel movements. Oesophageal manometry showed a reduced lower oesophageal sphincter pressure for age with abnormal distal motility. Serum carnitine concentration was 9.9 mumol l-1. After dietary supplementation of carnitine the gastrointestinal symptoms resolved, oesophageal manometry returned to normal, and serum carnitine increased to 37.2 mumol l-1. Dietary carnitine deficiency in infancy may be a cause of smooth muscle dysmotility of the gastrointestinal tract.

Bottle Feeding↗

Starch digestion in young children with cystic fibrosis measured using a 13C breath test.

The study was designed to evaluate a non-invasive breath test using naturally 13C-rich corn (maize) as substrate to provide quantitative information about the digestion of starch by children in health and disease. The variability of background 13C:12C of young British children was investigated by collecting breath samples over 6 h from 17 healthy children, 6-35 mo old, and from seven children with cystic fibrosis, 25-48 mo old, in their homes. Background 13C enrichment was -26.6 and -25.4 delta per mil in the healthy and cystic fibrosis groups, respectively (p less than 0.01), and varied little during the day (SD = 0.4 delta per mil). Eight healthy children and five with cystic fibrosis were given a test breakfast of corn starch cooked in milk with sugar. The cystic fibrosis group repeated the test with the addition of an enzyme supplement containing alpha-amylase. Subjects accepted variable amounts of starch (range 0.2-2.8 g/kg body wt). The percentage of ingested 13C recovered during the 6 h after the meal increased with age in the healthy children (range 15-53%). Three children with cystic fibrosis had negligible 13C recoveries, and the other two had lower recoveries than expected for their age. The addition of enzymes did not consistently improve 13C recovery. We conclude that the 13C breath test based on corn has potential for investigating starch digestion in young children. Initial results suggest that starch digestion is impaired in some children with cystic fibrosis and that enzyme supplements do not improve digestion consistently or completely.

Breath Tests↗

Riboflavin deficiency in the rat: effects on iron utilization and loss.

Iron absorption and daily loss of Fe were measured in riboflavin-deficient (B2-) Norwegian hooded rats and controls (B2+). Animals were fed on a test meal extrinsically labelled with 59Fe and whole-body radioactivity measured for 15 d. Riboflavin deficiency led to a reduction in the percentage of the 59Fe dose absorbed and an increased rate of 59Fe loss. All post-absorption 59Fe loss could be accounted for by faecal 59Fe, confirming that the loss was gastrointestinal. Fe concentrations and 59Fe as a percentage of retained whole-body 59Fe were higher in the small intestine of riboflavin-deficient animals than their controls, 14 d after the test meal. A separate experiment demonstrated that riboflavin deficiency was associated with a significant proliferative response of the duodenal crypts of the small intestine. These observations may explain the enhanced Fe loss in riboflavin deficiency.

Absorption↗

Small intestinal length: a factor essential for gut adaptation.

Changes in small intestinal structure, cytokinetics, and function are dynamic ways in which the gut adapts to diet, disease, and damage. Adequate length provides a static 'reserve' permitting an immediate response to pathophysiological changes. The length of the small intestine from conception to adulthood using data taken from eight published reports of necropsy measurement of 1010 guts is described. Mean length at 20 weeks' gestation was 125 cm, at 30 weeks' 200 cm, at term 275 cm, at 1 year 380 cm, at 5 years 450 cm, at 10 years 500 cm, and at 20 years 575 cm. Prenatal small intestinal growth exceeded that of body length according to the law: small intestinal length alpha body length to the power 4/3. After birth there was a noticeable deceleration: small intestinal length alpha body length to the power 1/2. The coefficient of variation of small intestinal length postnatally was 24%, sixfold greater than for body length. The rapid prenatal small intestinal growth rate ensures that the mature newborn has adequate small intestine to meet postnatal nutritional demands, but handicaps the preterm infant who undergoes intestinal resection. The wide variation in lengths suggests a 'surplus' surface area that is immediately available to respond, independent of dynamic mucosal changes, to fluctuations in food availability, local intestinal disease, damage, rapid transit, and resection.

Adaptation, Physiological↗

Neonatal gastrointestinal growth and function: are they regulated by composition of feeds?

The effects of natural suckling versus a cow's milk formula on gastrointestinal growth and mucosal function were measured in newborn guinea pigs during the first 8 days of postnatal life. Comparable growth was achieved between the two groups. Both feeds appeared to be a stimulus for the growth of the gastrointestinal tract and expression of disaccharidases, but not for mucosal growth. Formula feeding was associated with a diminished rate of lactase expression and an enhanced rate of maltase and sucrase expression suggesting that the effect of natural suckling is regulatory, acting to delay expression of an inherent ontogenic programme uncovered by formula feeding. These finding in the precocial guinea pig contrast with those in the altricial rat, and have implications for our understanding of the regulation of gastrointestinal development and effects of formula feeds, in other species, including man.

Animal Nutritional Physiological Phenomena↗

Uptake and transport of epidermal growth factor by the small intestinal epithelium of the fetal rat.

Epidermal growth factor may play an important part in postnatal gastrointestinal development. However, little is known of its role prenatally. The aim of this study was to detect epidermal growth factor in amniotic fluid and to study its uptake and transfer across the epithelium of fetal rat small intestine. Anesthetized 20-day gestation rats underwent caesarean section. Three fetuses were exteriorized, their abdomens were opened, and ligated loops of proximal and distal small intestine were infused with 100 micrograms epidermal growth factor. Infused segments were removed 30 min later and processed for electron microscopy, and tissue was embedded in LR gold resin. Sections were treated with rabbit anti-rat epidermal growth factor antibody, followed by 5 nm gold-labeled goat anti-rabbit immunoglobulin before staining. Epidermal growth factor was measured in amniotic fluid by radioimmunoassay. In the proximal and distal small intestine epidermal growth factor was found membrane-associated along the luminal surface of microvilli, within apical invaginations and endosomal compartments, free from the membrane in multivesicular bodies, within large clear vesicles, basal vesicles and in association with the basolateral membrane and beyond. Epidermal growth factor was found in amniotic fluid at a concentration of 0.38 +/- 0.07 (SD) ng/ml. This study shows that epidermal growth factor is present in amniotic fluid and is transported across the epithelium of fetal rats by an endocytotic process in both the upper and lower small intestine. It is likely that amniotic fluid epidermal growth factor plays a part in intestinal mucosal development, and may be active systemically after transepithelial passage in utero.

Amniotic Fluid↗