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Biomedical subjects

S A Bingham

Publications and source records attributed to S A Bingham.

At least 73 records · Page 4Linked to original sources

The use of 24-h urine samples and energy expenditure to validate dietary assessments.

The doubly labeled-water technique can be used as a noninvasive measure of energy expenditure, and, with no gains or losses in weight, expenditure should equal intake. Provided sufficiently complete urine collections are obtained, urine nitrogen is an accurate measure of protein intake in individuals in nitrogen balance. Validations of dietary surveys by using estimates of energy expenditure and the 24-h urine nitrogen technique show that inaccurate reports of food intake occur in a proportion of individuals within a group, leading to bias in overall average intakes for some nutrients, if only one method of dietary assessment is used. Errors between methods however are not usually correlated, so that improved estimates can be obtained from a combination of two or more methods of dietary assessment. All future dietary surveys should require independent evidence of their validity.

Adolescent↗

Measurements of total energy expenditure provide insights into the validity of dietary measurements of energy intake.

The quantification of errors inherent in methods of measuring dietary intake has been handicapped by the absence of independent markers for testing their validity. The doubly labeled water technique permits a precise measure of energy expenditure in free-living persons. Because energy expenditure must equal energy intake in populations in energy balance, this technique may be used to validate the assessment of energy intake. A series of studies demonstrated good agreement between mean energy intake and mean energy expenditure when food intake was recorded by observers or when it was self-reported by normal-weight, self-selected, highly motivated volunteer subjects using weighed records. However, in randomly recruited men and women, energy intake by weighed records was 82% and 81%, of energy expenditure, respectively, indicating underestimation of habitual intake. Men and women in the lowest third of reported intake recorded energy expenditure of only 69% and 61%, respectively. Reported intake of obese and previously obese women was only 73% and 64% of expenditure, whether measured by weighed record or by diet history, confirming suspicions that these subjects misrepresented their intake. Acceptable weighed records were obtained from 7- and 9-year-olds whereas 15- and 18-year-olds underestimated intake. Diet histories taken from the same children tended to overestimate intake. These studies suggest that, ideally, all dietary studies should include independent measures of validity.

Adolescent↗

Magnetic microcapsules as novel biomonitors of cross-linking agents and diet-dependent reactive oxygen species in the human gastrointestinal tract.

Six healthy, scientifically informed human volunteers were given 14C-labeled polyethyleneimine (PEI) microcapsules by mouth. Fecal 14C recovery was inversely related to mean gut transit time (r = -0.66), and the extent of cross-linking between the membrane and core PEI was inversely related to total fecal output (r = -0.81). Cross-linking of PEI microcapsules may be a biomonitor of endogenous cross-linking agents within the human gastrointestinal tract. Extensive loss of [14C]CH3 label occurred from the microcapsules during human transit and in in vitro fermentations with human fecal flora. A mechanism whereby reactive oxygen species could arise in the iron-rich core of these microcapsules, leading to loss of [14C]CH3 label, is proposed.

Adult↗

Fecal weight, colon cancer risk, and dietary intake of nonstarch polysaccharides (dietary fiber)

Low fecal weight and slow bowel transit time are thought to be associated with bowel cancer risk, but few published data defining bowel habits in different communities exist. Therefore, data on stool weight were collected from 20 populations in 12 countries to define this risk more accurately, and the relationship between stool weight and dietary intake of nonstarch polysaccharides (NSP) (dietary fiber) was quantified. In 220 healthy U.K. adults undertaking careful fecal collections, median daily stool weight was 106 g/day (men, 104 g/day; women, 99 g/day; P = 0.02) and whole-gut transit time was 60 hours (men, 55 hours; women, 72 hours; P = 0.05); 17% of women, but only 1% of men, passed < 50 g stool/day. Data from other populations of the world show average stool weight to vary from 72 to 470 g/day and to be inversely related to colon cancer risk (r = -0.78). Meta-analysis of 11 studies in which daily fecal weight was measured accurately in 26 groups of people (n = 206) on controlled diets of known NSP content shows a significant correlation between fiber intake and mean daily stool weight (r = 0.84). Stool weight in many Westernized populations is low (80-120 g/day), and this is associated with increased colon cancer risk. Fecal output is increased by dietary NSP. Diets characterized by high NSP intake (approximately 18 g/day) are associated with stool weights of 150 g/day and should reduce the risk of bowel cancer.

Adolescent↗

Novel detection by magnetic microcapsules in the human gastrointestinal tract of cross-linking agents and diet-dependent reactive oxygen species.

Semi-permeable magnetic microcapsules previously shown able to trap gastrointestinal carcinogens and containing polyethyleneimine (PEI) were covalently labelled with [14CH3], and administered for the first time to humans (six healthy volunteers, 1.3 microCi/dose) in gelatin capsules together with radio-opaque gut transit markers (ROM), in order both to seek human endogenous cross-linking or bifunctional alkylating agents and assess gut transit features. No ill-effects were reported. Faecal ROM and 14C excretions were well correlated (r = 0.96), and net 14C recovery in faeces was 83-96%. Microcapsules were separated magnetically from faeces and 29-81% of specific labelling of microcapsules (nCi/10(6)) was found to have been removed during GI transit. Label cleavage out of these microcapsules was also found following in vitro anaerobic incubation with faecal slurries from two volunteers. On treatment with H2O2, label was removed selectively from the Fe-containing core in a dose-dependent manner. Therefore, label cleavage in vivo (not observed in rats consuming chow but found notably on consumption of low-fibre and/or high-beef human diets) is likely to arise from low mol. wt substances that give Fenton reaction producing hydroxyl radicals and oxidative demethylation. After GI transit, extensive core to membrane cross-linking in the microcapsules was found and was inversely related to faecal output. Cross-linking also was obtained to a greater extent during in vitro anaerobic incubation with faecal slurries. The GI mucosa would also be exposed to both types of agents, and several features of this microcapsule monitoring are in accord with putative risk-modulating effects. This first use of microcapsules for biomonitoring of the human GI tract thus seemed to be without hazard, and revealed extensive levels of agents likely to cause DNA damage.

Animals↗

para-amino benzoic acid in the assessment of completeness of 24-hour urine collections from hospital outpatients and the effect of impaired renal function.

Eighteen (29%) of 24-h urine collections made by 63 hospital outpatients attending a gastroenterology clinic were incomplete, as judged by 24 h urine recovery of an oral marker, para-amino benzoic acid (PABA), despite more than the usual efforts to obtain complete collections. Incomplete collections contained significantly less sodium, urea and total nitrogen than full collections. Average outputs were 134 mmol and 103 mmol per day for sodium (P less than 0.02); 301 mmol and 223 mmol for urea (P less than 0.001); and 10.1 g and 8.3 g nitrogen (P less than 0.01) in the complete and incomplete collections respectively. In renal outpatients with a plasma creatinine in excess of 125 mumol per litre, urine recoveries of PABA were reduced, but within the expected range in renal patients whose plasma creatinine was normal.

4-Aminobenzoic Acid↗

Limitations of the various methods for collecting dietary intake data.

The dietary intake of population groups may be assessed using food consumption level estimates on a national basis and household food surveys. These may be useful for monitoring secular trends and geographical differences with stable and well-documented populations, but analytical studies of diet and health require data on individuals. Assessment techniques designed to assess the diet of individuals ranging from records with weights of food to questionnaires and biological markers have been critically reviewed in order to assess the accuracy of each. Quantitative estimates of the errors involved will be given. For example, the co-efficients of variation of differences incurred from asking subjects to estimate the weight of food portions, rather than weighing them, may regularly be in the 50% range for foods and 20% for nutrients. A variety of studies suggests that the co-efficients of differences in nutrient intake estimated over 1 day from the 24-hour recall method when compared with observed intakes ranged from 4 to 400%. These errors are believed to be random, and precision can be improved by increasing the numbers of observations on each individual or by increasing the numbers of individuals within each group. However, a substantial loss of power is incurred with errors of this magnitude. A more serious potential source of error is systematic bias due either to differences between different methods of dietary assessment or from deliberate over- or underreporting by the subjects themselves. Studies with the doubly labelled water technique have suggested that substantial underrecording of food intake can occur both in free-living individuals and in athletes. 24-hour urine nitrogen can be used to validate dietary assessments in individuals in nitrogen balance, and on-going studies in Cambridge show that within a group, underreporting occurs in specific individuals rather than in the group as a whole. Independent methods of validating dietary assessments, such as the doubly labelled water technique or the 24-hour urine nitrogen output, must be included in any study of free-living individuals.

Diet Surveys↗

Mechanisms and experimental and epidemiological evidence relating dietary fibre (non-starch polysaccharides) and starch to protection against large bowel cancer.

The cause of human colo-rectal cancer is unknown, although international and racial comparisons suggest that diet may be important. Within populations, risk of cancer is also affected by genetic factors which remain to be elucidated. Dietary fibre and NSP consumption is not always high in populations at low risk of colo-rectal cancer, but rates are fast increasing with westernization (and meat and fat consumption) in Japan. The suggestion that dietary fibre is protective in colo-rectal cancer is based on the fact that cereal fibre from bran increases faecal weight, dilutes large intestinal contents, and speeds up transit time. In animal models, bran reduces the number of tumours induced by chemical carcinogens, and cellulose may have a similar effect. The faeces of some individuals contain mutagens, some of which have been identified as fecapentaenes and heterocyclic amines. Bran reduces faecal mutagenicity, although the mutagen concerned is unknown. Most dietary fibre is fermented in the large gut by anaerobic bacteria and little remains in faecal matter. Recent observations have shown that substantial amounts of starch survive digestion in the small bowel and are available also for fermentation in the large gut. The metabolic consequences of fermentation may be important in carcinogenesis via altered N metabolism, SCFA production, and pH reduction. Methane is also produced in some individuals, but, contrary to previous findings, is not a risk factor for large bowel cancer. Starch appears to be beneficial as a substrate for fermentation because yields of the SCFA butyrate are increased both in vitro and in vivo. Butyrate is an energy substrate for the colonic mucosa and an anti-proliferative and differentiating agent in cell culture lines. Possible mechanisms whereby starch and NSP may protect against colo-rectal cancer, therefore, exist. The majority of individual case-control epidemiological studies suggest that fibre-containing foods are protective in colo-rectal cancer, although this effect is largely due to vegetable, rather than cereal, consumption. Case-control studies of diet and large bowel cancer may, however, reflect the effect rather than the cause of the disease, so that confirmation of the possible protective effects of starch and NSP is needed from accurate prospective studies both of diet and associated risk factors.

Animals↗

Effect of exercise and physical fitness on large intestinal function.

The effect of exercise on large intestinal function has been determined in 14 healthy but normally sedentary men and women, aged 22-34 yr while on a constant diet. For an initial 3-5-wk period (control) no activity was allowed. Six subjects then undertook a 9-wk training schedule by the end of which they were capable of jogging for 1 h per day, 5 days a week. A further 6 subjects undertook a similar training schedule that lasted for only 7 wk, at the end of which they were jogging for 45 min per day. Finally, 2 subjects were studied continuously while taking light exercise for 6 wk and then jogging for a further 3 wk. Physical fitness was monitored and showed significant changes with maximum aerobic capacity increasing from 2.4 +/- 0.5 to 3.1 +/- 0.4 L/min, maximum heart rate after a step test falling from 152 +/- 8 to 129 +/- 5 beats per minute, and resting pulse rate also falling from 56 +/- 4 to 50 +/- 5 beats per minute. High-density lipoprotein cholesterol also increased significantly. Colonic function was assessed by measurement of stool weight and transit time, using the continuous radiopaque marker technique, fecal pH, nitrogen excretion, and ammonia concentration. No change was observed overall in mean daily fecal weight [124 +/- 39 (control) and 129 +/- 49 g/day (exercise)], transit time [55 +/- 20 (control), 54 +/- 23 h (exercise)], nor in fecal frequency, dry stool weight, pH, ammonia, or total nitrogen excretion. Significant changes did occur in 5 individuals with significant slowing of transit time in 2 and speeding up in 3. Overall transit time increased in 9 subjects and decreased in 5; hence, when diet is constant, exercise has marked effects on physical fitness but no consistent effect on large bowel function.

Adult↗

The effect of exercise and improved physical fitness on basal metabolic rate.

1. The suggestion that there is a sustained enhancement in metabolic rate after exercise was investigated during the course of a study in which six normal-weight volunteers (three men, three women) took part in a 9-week training programme. Baseline values were assessed in a 3-5 week control period of minimal activity before training. At the end of the study the subjects were capable of running for 1 h/d, 5 d/week. 2. Throughout the entire study the subjects were maintained on a constant diet. Measurement of energy expenditure by the doubly-labelled water (2H2(18)O) method showed that the subjects had an energy imbalance of +3% in the control and -20% at the end of the training period. The subjects were in positive (1.1 (SE 0.2) g) nitrogen balance in the second week of the control, and in negative (-0.6 (SE 0.3) g) N balance in the last week of the exercise period. 3. Over the course of the study maximum oxygen consumption (VO2max) and high-density-lipoprotein-cholesterol levels increased by 30%. Heart rate at rest and when performing a standard step test fell significantly. 4. Body composition was assessed weekly by 40K counting and skinfold thickness measurements, in addition to 2H2 dilution at the beginning and end of the study. Fat-free mass was apparently gained in the early phases of the study, but there was lack of agreement between the different methods of assessing body composition. Changes in body-weight were not significant. 5. Basal metabolic rate (BMR), overnight metabolic rate (OMR) and sleeping metabolic rate (SMR) were measured on three occasions: in the control period, and the beginning and end of the training periods. Average BMR in the control period was 5.91 (SE 0.39) MJ/24 h and was not changed with activity. There were no changes in OMR (5.71 (SE 0.27) MJ/24 h in the control) nor in SMR (5.18 (SE 0.27) MJ/24 h in the control), nor in BMR, OMR or SMR when expressed per kg body-weight, or per kg fat-free mass. 6. These results do not support the suggestions that there is a sustained increase in BMR following exercise that can usefully assist in weight-loss programmes.

Adult↗

Meat, starch, and nonstarch polysaccharides and large bowel cancer.

Starch and nonstarch polysaccharides enter the large gut where they are available for fermentation by the bacterial flora. The effect of fermentation on nitrogen metabolism, the supply of nutrients to the mucosa, and the carcinogen production is discussed in relation to epidemiological associations between dietary intake and large bowel cancer incidence.

Animals↗

Reference values for analytes of 24-h urine collections known to be complete.

One hundred and twenty two 24-h urine collections were obtained from a representative sample of men and women in the general population aged 25-44 years. The collections were verified for their completeness by urine recovery of oral doses of para-amino benzoic acid. Means (with 0.95 reference intervals) for both sexes for 24-h urinary output were determined for nitrogen, urea, creatinine, urate, ammonia, sodium, potassium, volume, and pH. Within person variation in nitrogen, urea, creatinine, ammonia, sodium and potassium was estimated for a consecutive 28-day series of 24-h urine collections for eight individuals. Within person variation was greatest for sodium and least for creatinine. These differences when compared with the between person variation in the analytes studied have implications for the precision with which a result from a single specimen can be used to place an individual within a distribution of values for epidemiological purposes. In clinical biochemistry, the population results reported here should be appropriate as a reference base for comparison with individual patient results.

4-Aminobenzoic Acid↗

Dietary fibre, fermentation and large bowel cancer.

Diet, especially the amount of starch and dietary fibre which escape digestion in the small intestine, are major determinants of colon function in man. These carbohydrates are the principal substrates for fermentation by the large bowel flora. Carbohydrate fermentation results in lowered caecal pH and the production of short chain fatty acids of which butyric acid may protect the colon epithelium from dysplastic change. Protein digestion and amino acid fermentation also occur in the large bowel but the nature of its endproducts varies in relation to the amount of carbohydrate available. During active carbohydrate breakdown amino acid fermentation endproducts such as ammonia are used by the bacteria for protein synthesis during microbial growth, but in carbon-limited fermentation amines, ammonia, phenols and indoles, etc, accumulate. Fermentation also results in changes in colon pH which alters the metabolism of bile acids, nitrate, sulphate and other substances. Fermentation is thus controlled to a great extent by substrate availability, especially of carbohydrates which are derived from the diet. The potential to induce mutagenic change in colon epithelial cells and promote tumour growth may readily be influenced by diet.

Ammonia↗

Sodium and potassium intakes in a representative population sample: estimation from 24 h urine collections known to be complete in a Cambridgeshire village.

1. A representative sample of eighty men aged 25-44 years from a Cambridgeshire village, each carried out one 24-h urine collection which was analysed for sodium, potassium, creatinine and urea content. The completeness of the collections was verified using oral doses of p-aminobenzoic acid (PABA; the PABA check test). 2. In the seventy-one collections shown to be complete, the average 24 h excretion of Na was 172 mmol and the average 24 h excretion of K was 74 mmol. 3. Fifty-one of these men's wives also made complete 24 h collections. The average content of these was 128 mmol Na and 61 mmol K. 4. Self reports and creatinine index would have identified as incomplete only 29 and 14% respectively of collections so judged by PABA. 5. Average excretion of 150 mmol Na/d was similar to estimated intakes of 140-167 mmol/d from the National Food Survey (Bull & Buss, 1980).

4-Aminobenzoic Acid↗

Dietary fibre consumption and its association with large bowel cancer in man.

The hypothesis that lack of fibre in the diet is responsible for a variety of large bowel problems, including cancer, has stimulated much discussion and research over the past 15 years. However, the epidemiological examination of this hypothesis has been hampered by the absence of data on the fibre content of most of the world's foods. In studies in Britain and Scandinavia where consumption of the chemical fraction of dietary fibre, the non-starch polysaccharides, has been determined using accurate methods, significant negative association between colon cancer occurrence and NSP consumption have been shown. Fibre may therefore be protective to populations otherwise assumed to be at risk from a westernised type of diet. At present, methodological problems preclude the use of case-control studies in confirming or refuting these associations.

Africa↗