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Biomedical subjects

A A Jackson

Publications and source records attributed to A A Jackson.

At least 127 records · Page 7Linked to original sources

Urea production and recycling in neonates.

Urea represents 15% of the nitrogen in breast milk, but its functional significance is unclear. We have proposed that the urea may be utilised as a valuable source of nitrogen in neonates. We report the first measurements of urea kinetics in newborn, full-term infants. Six neonates received a continuous nasogastric infusion of 15N15N-urea over 24 hours. Urine was collected every 2 hours and the isotopic enrichment in urea was measured by mass spectrometry. Urea kinetics were calculated by the method of Jackson. The urea production rate was 17.3 mmol/kg/d (range, 15.6 to 19.2), but the urinary urea excretion rate, 3.5 mmol/kg/d (range, 1.2 to 4.9), was only 20% of production. Hence, 80% of urea produced was hydrolysed in the colon and the nitrogen made available for further metabolism. These data show that urinary urea excretion is a poor indication of urea production in the newborn and that there is substantial salvaging of urea nitrogen by the colon.

Body Weight↗

Enhanced retention of urea-nitrogen in patients on total parenteral nutrition for intestinal failure.

Urea, the main end product of human nitrogen metabolism, is either excreted in the urine or salvaged for further metabolic interaction, through the activity of the colonic microflora. In patients on TPN (total parenteral nutrition) the bowel is 'defunctioned' insofar as the microflora are deprived of exogenous substrate, and it might be expected that urea salvaging is reduced to low levels. The recovery of labelled urea-nitrogen was measured in 7 patients on TPN and compared with 4 normals. Following a single intravenous dose of 15N15N-urea, urine was collected for 48h and analysed for 15N. In normals the median retention of 15N was 17% (range 13-17) of the dose compared with 38% (24-52) in 5 TPN patients not on antibiotics (p < 0.05). TPN patients on antibiotics retained 11 and 15%. Despite the absence of exogenous substrate, the 'defunctioned' bowel of patients on TPN appears more active in hydrolysing urea than in normals, and the hydrolysis is sensitive to the effect of antibiotics.

Journal Article↗

Basal metabolic rate, body composition and whole-body protein turnover in Indian men with differing nutritional status.

1. Three groups of adult men were studied in Bangalore, India: two groups were controls who had been receiving an adequate diet. Of these, one group, designated 'normal weight controls', had a mean body mass index of 22; the other group, 'underweight controls', had a mean body mass index of 16.7. The third group consisted of poor labourers, whose daily food intake had been less than 10 MJ and whose mean body mass index was 16.6. Previous studies had shown that such men had a lower basal metabolic rate than well-nourished Indian control subjects. 2. The object of the present study was to find out whether a reduced rate of protein turnover, measured after a single dose of [15N]glycine, contributed to a lower basal metabolic rate. It was found, however, that after adjusting for body weight and fat-free mass by analysis of co-variance there was no significant difference in basal metabolic rate between the three groups. Adjusted rates of protein synthesis were higher in the underweight controls and the undernourished labourers than in the normal weight controls, but not significantly so. 3. Estimates based on creatinine excretion showed that within the fat-free mass the underweight groups had a higher proportion of non-muscle to muscle mass. This may explain the somewhat higher rates of protein turnover in these groups. 4. Nitrogen flux (Q) was determined from 15N abundance in two end products, urea (QU) and ammonia (QA). In the underweight and undernourished groups the ratio QU/QA was increased compared with the normal weight group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effect of vitamin A deficiency on the immune response to epizootic diarrhoea of infant mice (EDIM) rotavirus infection in mice.

The effect of vitamin A deficiency on the immune response to epizootic diarrhoea of infant mice (EDIM) rotavirus was studied in mice. The virus was given by oral dosing or by intraperitoneal injection. For oral challenge, weanling mice were fed on either a control or vitamin A-deficient diet ad lib. or pair-fed the control diet to the intake of the vitamin A-deficient group. A fourth group was fed on the vitamin A-deficient diet ad lib. for 10 weeks and then refed the control diet for 2 weeks. On day 77, mice were each given 30 microliters EDIM rotavirus orally and the animals were killed and examined 1 week later. The delayed-type hypersensitivity (DTH) response to picryl chloride was measured as an index of cell-mediated immunity. For intraperitoneal challenge, weanling mice were fed on either the control diet or the vitamin A-deficient diet ad lib. or pair-fed the control diet to the intake of the vitamin A-deficient group. On day 77, mice were each injected intraperitoneally with 30 microliters EDIM rotavirus and 1 week later antibody production was measured. In both experiments the body-weight, liver and serum vitamin A levels of the vitamin A-deficient group were significantly lower than the control or pair-fed groups. Following oral dosing the serum antibody levels specific to rotavirus were statistically significantly lower in vitamin A-deficient animals than the control or pair-fed groups. Vitamin A-deficient mice also showed an impaired DTH response compared with the control and pair-fed animals. Animals refed vitamin A for a short period showed a partial restoration of the antibody response. Following intraperitoneal challenge no statistically significant changes were observed in the serum antibody levels between any of the dietary groups. It is concluded that vitamin A deficiency impaired antibody production when rotavirus was given orally. Vitamin A deficiency also impaired cell-mediated immunity.

Administration, Oral↗

Energy content of stools in normal healthy controls and patients with cystic fibrosis.

Stool energy losses and the sources of energy within the stool were determined in 20 healthy controls and 20 patients with cystic fibrosis while on their habitual pancreatic enzyme replacement treatment. Stool energy losses were equivalent to 3.5% of gross energy intake in healthy children (range 1.3-5.8%). Despite a comparable gross energy intake, stool energy losses were three times greater in patients with cystic fibrosis than controls averaging 10.6% of gross energy intake (range 4.9-19.7%). Stool lipid could account for only 29% and 41% of the energy within the stool in controls and patients with cystic fibrosis respectively and was poorly related to stool energy. Approximately 30% of the energy within the stool could be attributable to colonic bacteria in both the healthy children and patients with cystic fibrosis. These results suggest that stool energy losses in healthy children are relatively modest but that even when patients with cystic fibrosis are symptomatically well controlled on pancreatic enzyme replacement, raised stool energy losses may continue to contribute towards an energy deficit sufficient to limit growth in cystic fibrosis. As the energy content per gram wet weight remains relatively constant (8 kJ/g), stool energy losses may be estimated from simple measurements of stool wet weight.

Adolescent↗

Effect of severe food restriction on the gut following rotavirus infection in mice.

The effect of severe food restriction on the histopathology of the gut following infection with epizootic diarrhoea of infant mice (EDIM) rotavirus was studied in mice. Over a period of 12 weeks, weanling mice were fed either 70 or 50% of the diet eaten by a control group on the previous day. After 11 weeks of feeding, animals were given 30 microliters/mouse of EDIM rotavirus orally and the histopathology of the gut and lymphoid organs examined. The histology of the spleen and thymus of different dietary groups appeared normal and no changes were observed due to the rotavirus challenge. Both the control and 70% food group had normal villi in the small intestine. In contrast there was severe atrophy of the villi in the animals whose intake was reduced by 50%. No additional damage to the villi was seen in association with the rotavirus infection. It is concluded that a prolonged, balanced reduction in food intake can itself cause villous atrophy in the gut but following rotavirus infection, adult animals were able to resist further villous damage.

Animals↗

Effect of socio-demographic conditions on growth of urban school children of Bangladesh.

The relationship between socio-demographic variables and growth of 242 school children from five schools in Dhaka city, Bangladesh, was investigated. The socio-demographic data were collected by questionnaire and the anthropometric data were collected by visits to each school on a prefixed date. Children from the high-family-income group showed significantly higher body weight, height, MUAC, SFT, wt/age, and ht/age compared with children from the low-family-income group. When the effect of age, sex, father's occupation and family size were adjusted for by means of multiple analysis of variance, the family income still showed a significant contribution to the variation in the anthropometric indices of these children. These findings suggest that family income makes a significant contribution as a determinant of growth of urban school children in Bangladesh.

Analysis of Variance↗

Variation in measures of urea kinetics over four years in a single adult.

Urea kinetics was measured in a single woman on five occasions over four years by the prime/intermittent oral-dose method with [15N15N]-urea. On a nitrogen intake of 231 +/- 24 mg/kg/day, urea production was 198 +/- 22 mg/kg/day, with the urinary excretion of urea being 143 +/- 25 mg/kg/day. Urea hydrolysis and salvaging in the bowel was 55 +/- 6 mgN/kg/day. The coefficients of variation for production, 11 per cent, excretion, 18 per cent, and hydrolysis, 11 per cent, were similar to that for intake, 10 per cent, and substantially less than reported inter-individual variations from other studies. It is concluded that the method employed for measuring urea kinetics gives reproducible results and that the intra-individual variation in urea kinetics is much less than the inter-individual variation.

Administration, Oral↗

Treatment of short normal children with growth hormone--a cautionary tale?

41 short normal children were randomly allocated either to daily injections of growth hormone (rhGH) at 30 IU/m2 per week or to no treatment. 6 months of rhGH therapy produced up to 76% loss of fat mass and up to 25% increase in lean body mass (LBM). These changes were significantly different from those in the untreated group. LBM was the main determinant of resting energy expenditure (REE) expressed as kJ/24 h. REE expressed as kJ/kg LBM per 24 h correlated negatively with height, which was responsible for 66% of the variance in REE kJ/kg LBM per 24 h. Short children therefore expend more energy than tall children in fulfilling basic metabolic needs. After 6 months REE kJ/24 h increased significantly in treated children. However, treated children did not differ significantly from untreated children in REE kJ/kg LBM per 24 h. rhGH does not therefore seem to have a specific effect upon REE. The possibility that rhGH produces profound metabolic effects should limit its use in otherwise healthy children until the mechanism of action is more clearly elucidated.

Body Composition↗

Metabolism of 15N-labelled urea in the functioning and defunctioned human colon.

1. The luminal metabolism of urea was studied using double-labelled urea ([15N2]urea) which was placed in the lumen of the colon through a colostomy. The recovery of label was measured as [15N2]urea or [14N, 15N]urea in urine and as 15N in stool. 2. Five patients with a loop colostomy allowed a comparison of the right functioning colon with the left defunctioned colon in the same individual. Five subjects with a left end-colostomy enabled a comparison of the right with the left functioning colon. 3. A significantly greater proportion of labelled urea was recovered as [15N2]urea in the urine when the dose was placed in the left defunctioned colon (29%) compared with either the left or the right functioning colon (9 and 4%, respectively). This is interpreted as being a result of a decrease in the bacterial activity and concomitant urea hydrolysis in the defunctioned colon. 4. On average more than half of the label was retained in the body, regardless of whether the urea was placed in the functioning or the defunctioned colon, on the left or on the right. 5. The data confirm that the colon is permeable to the intact urea molecule. Intraluminal urea is readily hydrolysed in the functioning colon. A large proportion of the nitrogen released by urea hydrolysis may be retained within the metabolic nitrogen pool of the host. There are significant differences in the handling of urea nitrogen in the defunctioned colon relative to the functioning colon.

Aged↗

The effect of the level of dietary protein, carbohydrate and fat on urea kinetics in young children during rapid catch-up weight gain.

The kinetics of urea metabolism were measured in children recovering from severe malnutrition. For a period of up to 10 d they received one of four diets which provided 711 kJ (170 kcal)/kg per d. Two groups received a diet with a high protein:energy (P:E) ratio of 10-6% (HP), enriched with either fat (HP/F) or maize starch and sucrose (HP/C). Two groups received a diet with a low P:E ratio of 8.8% (LP), enriched with either fat (LP/F) or maize starch and sucrose (LP/C). The rate of weight gain on the HP diets was significantly greater than on the LP diets. There was no difference in urea production between any of the four diets: HP/F 1.23 (SE 0.12), HP/C 1.37 (SE 0.14), LP/F 1.64 (SE 0.22), LP/C 1.15 (SE 0.15) mmol nitrogen/kg per h. On the HP diets urea excretion was 0.77 (SE 0.07) mmol N/kg per h, 61% of production. There was significantly less urea excreted in the urine on diet LP/C than on LP/F (0.36 (SE 0.05) and 0.64 (SE 0.04) mmol N/kg per h respectively). A significantly greater percentage of the urea production was hydrolysed on the LP diets (61%) compared with the HP diets (39%), with the consequence that 50% of urea-N produced was available for synthetic activity on the LP diets compared with 30% on the HP diets. The increase in the urea hydrolysed on the LP diets was equivalent in magnitude to the decreased intake of N, so that overall intake plus hydrolysis did not differ between the LP and the HP diets. Crude N balance was similar on diets HP/F, HP/C and LP/C, but was significantly reduced on diet LP/F. These results show that there is an accommodation in urea kinetics during rapid catch-up weight gain, which becomes evident when the P:E ratio of the diet falls to 8.8%. It is proposed that, for a P:E ratio of 8.8%, protein is limiting for catch-up growth. When the intake has a P:E ratio of 8.8% the pattern of urea kinetics can be modified by the relative proportions of fat and carbohydrate in the diet. The measurement of urea kinetics provides a useful approach to the definition of the adequacy of the protein in the diet.

Child, Preschool↗

Adaptation to a marginal intake of energy in young children.

Six male children, aged 8-28 months, were studied for three consecutive periods of 1 week each. They were given diets that provided 1.7 g protein/kg per d and supplements of minerals and vitamins, with a metabolizable energy intake during the 1st, 2nd and 3rd week of 419, 293 and 335 kJ (100, 70 and 80 kcal)/kg per d, diets 1, 2 and 3 respectively. All the food offered was consumed. Each child was weighed at the same time each day on an electronic balance. On the 6th and 7th day of each study period urine and stool were collected for 24 h to assess nitrogen balance. Using linear regression analysis it was shown that all children gained weight on diet 1, 2.3 (SD 1.3) g/kg per d, and five of six children gained weight on diet 3, the mean for the whole group being 2.7 (SD 2.3) g/kg per d, not significantly different. On diet 2 all children lost weight, -5.4 (SD 1.3) g/kg per d, highly significantly different from each of the other dietary periods. Using asymptotic regression analysis it could be shown that the rate of weight loss during the first part of the week on diet 2, -11 g/kg per d, was greater than at the end of the week, -2 g/kg per d, with a tendency towards a steady weight by day 7. Apparent N retention (mg/kg per d) was positive at the end of each of the three dietary periods: diet 1, 112 (SD 25); diet 2, 54 (SD 34); diet 3, 82 (SD 20). In five of the six children there was a marked reduction in stool frequency on diet 2 compared with diet 1, that was maintained to the period on diet 3. The findings suggest that during the period on diet 2 there was a saving of energy of the order of 105 kJ (25 kcal)/kg per d, which lasted through into the period on diet 3.

Adaptation, Physiological↗