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Biomedical subjects

N J Fuller

Publications and source records attributed to N J Fuller.

At least 37 records · Page 2Linked to original sources

Components of total energy expenditure in free-living elderly men (over 75 years of age): measurement, predictability and relationship to quality-of-life indices.

Current recommendations for energy requirements in the elderly are based on assumed levels of physical activity relative to BMR (1.5 x BMR). The main aim of the present study was to establish whether these recommendations might be applicable to a randomly-selected group of free-living elderly men (all over 75 years of age). BMR was measured by indirect calorimetry and total energy expenditure (TEE) by the doubly-labelled-water technique. Further aims included evaluating the applicability of a variety of BMR prediction equations and whether assessed quality of life reflected any measured indices of energy expenditure. The mean value for daily energy requirement was found to be 1.5 x BMR (89 J/kg per min) but with substantial inter-individual variation (sd 0.2 x BMR; 14 J/kg per min). The bias between measured TEE and TEE estimated (1.5 x BMR) from the various BMR predictions varied according to which equation was used (-10- + 8% of the mean) with substantial 95% limits of agreement (28-30% of the mean). TEE and physical activity plus thermogenesis (TEE-BMR) were positively related to activities of daily living, but no relationships were apparent between these and perceived quality of life. It is concluded that, despite considerable inter-individual variability, national recommendations for energy requirements of elderly people are applicable to this randomly-selected group of free-living men over 75 years of age but that substantial variation exists when attempts are made to estimate TEE from measurements or predictions of BMR.

Activities of Daily Living↗

Estimating energy expenditure from specific activity of urine urea during lengthy subcutaneous NaH14CO3 infusion.

Five healthy male subjects were continuously infused subcutaneously with [14C]bicarbonate (12.3 microCi/day) using a mini pump for 5 days while in a whole body calorimeter. Energy expenditure was varied over a range of 1.35-1.75 times basal metabolic rate. Urine collections were obtained throughout the study and used to measure the specific activity of urea, from which CO2 production was estimated. It was assumed that the recovery of label in gaseous CO2 was 95% of that infused and that the specific activity of urea was 85% that of expired CO2. Continuous daily collections of calorimeter air revealed that 95.6 +/- 1.3% (SD) of infused label was recovered as gaseous CO2, with little daily variation. Another 1.5 +/- 0.4% was recovered as urinary urea. The estimated CO2 production, calculated from the specific activity of urea in 24-h urine samples corrected for the small effects due to changes in the size and specific activity of the urea pool, was found to be 100 +/- 5% of the calorimeter estimate for 1-day periods (20.80 +/- 1.44 mol CO2/day) and 100 +/- 2% for 4-day periods. This study suggests that, in healthy subjects, the labeled [14C]bicarbonate-urea method can provide reasonable estimates of net CO2 production over the range examined.

Adult↗

Comparative evaluation of body composition methods and predictions, and calculation of density and hydration fraction of fat-free mass, in obese women.

The objective of this study was to apply a three-component model of body composition to a group of obese women in order to (a) establish the relative value of a number of readily available prediction equations by comparison of the extent of agreement between these predictions and body composition estimated by the model and other reference methods and (b) evaluate density and hydration of fat-free mass. Estimation of body composition was carried out by reference methods and prediction equations and the usefulness of these prediction equations for application specifically to obese women was evaluated. The subjects were 15 obese, otherwise healthy, Caucasian women (body mass index > 30kg/m2 and body fat > 40% of body weight, as originally determined using densitometry). Body composition was estimated using three established reference methods (deuterium dilution which primarily measures total body water, densitometry for body fat and fat-free mass and total body potassium) and the three component model constructed from deuterium dilution and densitometry. Density and hydration fraction of the fat-free mass were calculated from appropriate values obtained as integral parts of the three-component model. In addition, body composition was predicted from various prediction equations incorporating weight and height (some of which include a factor for age), from a number of prediction equations utilizing different terms involving the same whole-body bio-electrical impedance measurement and from measurements of skinfold thickness and near infrared interactance. The extent of agreement between methods was assessed using bias and 95% limits of agreement. Mean density of fat-free mass was found to be 1.104 kg/l (s.d. 0.006kg/l) with a range of 1.093 to 1.117 kg/l, and mean hydration fraction was 0.712 (s.d. 0.016) with a range of hydration from 68.2% to 75.1% (all values were calculated from the three-component model). In general, the reference methods (densitometry, deuterium dilution, the three-component model and total body potassium) demonstrated better agreement with each other than with the prediction methods or equations. In these obese women, skinfold thickness measurements are apparently less reliable (large bias and 95% limits of agreement) than in the lean subjects of a variety of other studies. A majority of interpretations of weight and height measurements and predictions incorporating impedance/resistance measurements are apparently not applicable to this group of obese women, due to large values for both bias and 95% limits of agreement.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Comparison of abilities of various interpretations of bio-electrical impedance to predict reference method body composition assessment.

Body composition was assessed in 28 normal men and women using three established reference methods (deuterium dilution for total body water, and densitometry and dual-energy X-ray absorptiometry for body fat and fat-free mass), the four- and three-component models based on these methods, and eight different predictions of the same whole-body bio-electrical impedance measurement. The comparative value of each prediction was assessed using bias and 95% limits of agreement against all reference methods. The magnitude of bias between each interpretation of whole body impedance and each reference method estimate was found to vary considerably, but in general this was consistent over the range studied. However, with few exceptions, magnitudes of the limits of agreement were considerable. For example, a majority of values of 95% limits of agreement in predicting total body water reached bias+/-3 kg or above, and all values in predicting fat (% body weight) for all subjects reached bias+/-6%, and for most purposes these could well be unacceptable. Although in absolute terms bias and limits of agreement for fat-free mass were the same as for body fat, estimates of fat-free mass were relatively more acceptable because fat-free mass was (as is the usual case) the larger of these two body components.

Journal Article↗

Plasma folate levels in preterm infants, with and without a 1 mg daily folate supplement.

One hundred and four preterm infants were studied during the first few months of life in the Special Care Baby Unit of Addenbrooke's Hospital, Cambridge, United Kingdom. Previously, it had been the daily practice within the Unit to give a 1 mg oral supplement of folate (in the form of pteroylglutamic acid), once the infants had commenced full enteral feeding. At least one blood sample was obtained from 70 infants before oral folate supplementation was started. In these, the plasma folate levels fell progressively from a median value of 45 micrograms/l to a median of 12 micrograms/l, by the 2nd-3rd week of life. Once started on the oral supplement, 83 of the infants provided at least one blood sample. The plasma folate level of these infants rose immediately to a median value of 300 micrograms/l and a maximum of 1000 micrograms/l. Within individuals, these plasma folate levels decreased progressively following the introduction of the supplement, despite continuing daily supplementation. In a typical baby this decrease appeared to be explained by an increase in body-size, i.e. dilution of the folate into a larger pool. The implications of this level of supplementation are discussed, and in the light of our observations we suggest that daily supplementation in the range, 0.05-0.2 mg folate may be preferable for well preterm infants.

Dose-Response Relationship, Drug↗

High folate intakes related to zinc status in preterm infants.

The former practice of giving 1 mg (2.27 mumoles) oral folic acid daily to premature infants receiving enteral feeds was assessed with respect to zinc status in Cambridge, United Kingdom. A group of 60 preterm infants, 80% of whom were receiving 1 mg oral folic acid daily, were studied for up to the first 16 weeks of life. Plasma folate and plasma zinc were measured for each subject. A significant inverse relationship was found between the maximum attained serum folate level and the minimum attained serum zinc level, (t = 5.0, 58 df, P less than 0.0001). This remained significant after corrections had been made for gestational age at birth, fetal growth retardation, birth weight, sex, diet, assisted ventilation and length of time to full enteral feeding. The hypothesis that very high folate intakes may adversely affect serum zinc levels and, by inference, zinc status in preterm infants could not be rejected. Caution is therefore advised when prescribing such very high folate doses daily for small preterm infants.

Dose-Response Relationship, Drug↗

Four-component model for the assessment of body composition in humans: comparison with alternative methods, and evaluation of the density and hydration of fat-free mass.

1. Body composition was assessed in 28 healthy subjects (body mass index 20-28 kg/m2) by dual-energy X-ray absorptiometry, deuterium dilution, densitometry, 40K counting and four prediction methods (skinfold thickness, bioelectrical impedance, near-i.r. interactance and body mass index). Three- and four-component models of body composition were constructed from combinations of the reference methods. The results of all methods were compared. Precision was evaluated by analysis of propagation of errors. The density and hydration fraction of the fat-free mass were determined. 2. From the precision of the basic measurements, the propagation of errors for the estimation of fat (+/- SD) by the four-component model was found to be +/- 0.54 kg, by the three-component model, +/- 0.49 kg, by deuterium dilution, +/- 0.62 kg, and by densitometry, +/- 0.78 kg. Precision for the measurement of the density and hydration fraction of fat-free mass was +/- 0.0020 kg/l and +/- 0.0066, respectively. 3. The agreement between reference methods was generally better than between reference and alternative methods. Dual-energy X-ray absorptiometry predicted three- and four-component model body composition slightly less well than densitometry or deuterium dilution (both of which greatly influence these multi-component models). 4. The hydration fraction of fat-free mass was calculated to be 0.7382 +/- 0.0213 (range 0.6941-0.7837) and the density of fat-free mass was 1.1015 +/- 0.0073 kg/l (range 1.0795-1.1110 kg/l), with no significant difference between men and women for either. 5. The results suggest that the three- and four-component models are not compromised by errors arising from individual techniques.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗

Assessment of the composition of major body regions by dual-energy X-ray absorptiometry (DEXA), with special reference to limb muscle mass.

Dual-energy X-ray absorptiometry (DEXA) has been used to assess and compare the composition of whole body and major body regions in 12 female (weight, 56.9 +/- 6.2 kg; BMI, 17-25 kg m-2) and 16 male (weight, 73.1 +/- 9.6 kg; BMI, 20-28 kg m-2) healthy subjects. Standard deviations (and % coefficients of variation) of the differences between repeated measurements of fat ranged from 0.11 kg (9.0%) for arms to 0.42 kg (3.0%) for whole body; for arm bone mineral, 0.01 kg (2.0%), and for fat-free soft tissue of the whole body, 0.42 kg (0.8%). Limb muscle mass was estimated using a new theoretical model of body composition, and the corresponding precision ranged from 0.15 kg (3.8%) to 0.27 kg (1.5%) for arms and total limb muscle mass, respectively. Proportions of each region consisting of fat were greater in females than in males (range, 20-31% vs. 16-18%), respectively, but the ratio of trunk to leg fat was lower (34:49% vs. 46:38%, respectively). Regional proportions of bone were similar between the sexes (all in the range 2.9-5.6%, for both females and males). Mean total limb muscle masses were 14.2 kg (arms, 2.8 kg; legs, 11.4 kg) for females and 22.2 kg (arms, 4.8 kg; legs, 17.4 kg) for males, which were 33.6% and 36.0% of fat-free mass, respectively. The correlation coefficients between limb muscle (DEXA) and other indices of muscle mass were: for DEXA vs. total body potassium, 0.90 (SEE 1.1 kg muscle mass) to 0.94 (1.6 kg); and for DEXA vs. anthropometry, 0.43 (1.2 kg) to 0.85 (1.3 kg). Those for limb volume (DEXA) vs. anthropometric volume, 0.91 (0.78 1) to 0.94 (1.91 1). It is concluded that DEXA enables the valid and reproducible estimation of fat, fat-free soft tissue, bone, and limb muscle mass.

Absorptiometry, Photon↗

Measurement of bicarbonate turnover in humans: applicability to estimation of energy expenditure.

Bicarbonate turnover and energy expenditure were assessed in six healthy male volunteers, by the use of a constant infusion of radiolabeled bicarbonate (NaH14CO3) administered over 36 h, while the volunteers were confined to a whole body indirect calorimeter. Recovery and dilution of isotope were assessed from measurements made on continuous collections of CO2, entering and leaving the calorimeter, urine, and intermittent spot breath and saliva samples. Mean recovery of infused label in gaseous CO2 was 95.6 +/- 1.1% (SD) between 12 and 36 h. Applying a 95% mean recovery of label to each subject individually enabled the use of integrated mean specific activity of CO2 in spot breath and urine samples to predict measured net CO2 production and energy expenditure to within about +/- 6%. Estimates based on urinary measurements were compromised slightly by the exchange of label through the bladder wall (this was dependent on pH and volume of urine). It is concluded that this constant-infusion labeled bicarbonate method offers a potentially useful means of assessing net CO2 production and total energy expenditure over the short term (e.g., 1-3 days).

Adult↗

Inter-observer variability in the measurement of body composition.

The inter-observer variation in simple bedside assessments of body composition has been evaluated in 12 healthy adult subjects (6 male and 6 female) by 6 observers. Systematic bias between observers was found to be evident in each of the basic measurements (except height) and in each of the estimates of body composition (except those derived from weight and height alone). The largest residual coefficients of variation (rCV) for the basic measurements were found for skinfold thickness (11-18 per cent for individual skinfold thicknesses, and 9 per cent for the sum of four skinfold thicknesses), and the lowest for weight (0.01 per cent for digital scales, and 0.05 per cent for beam balance) and height (0.4 per cent). The rCV for whole-body resistance (1.2 per cent), forearm resistance (5.4 per cent) and near infra-red interactance (optical density 1: 5.6 per cent and optical density 2: 6.2 per cent) measurements were found to have intermediate values. The variability in the estimate of body fat obtained by skinfold thickness (rCV = 4.6 per cent) and near infra-red interactance methods (rCV = 4.2 per cent) was found to be greater than that from the resistance method (rCV = 2.6 per cent) and by methods based on weight and height alone (rCV = 1.1 per cent). The variability in the estimate of fat-free mass showed the same trend as that for body fat, but the rCVs were less due to the greater mass of the fat-free body compared to body fat.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Does mitochondrial compartmentation of CO2 exist in man?

A comparison was made between the specific radioactivity of urea, and that of CO2 in breath, in urine and in arterialized blood, during a 36-h continuous infusion of 0.5 mCi and 100 mmol of sodium bicarbonate (NaH14CO3) into six normal male volunteers. After a period of equilibration, the mean specific radioactivity of urea was found to be only 16% below that of end expiratory CO2 and a similar amount below that of CO2 both in arterialized blood and in urine. This difference may be explained by isotopic dilution of 14CO2 by metabolic CO2 produced in the splanchnic tissues. It is concluded that, in these normal subjects, there is little or no compartmentation between cytosolic CO2 and the mitochondrial CO2 used for urea synthesis.

Adult↗

Potential use of bioelectrical impedance of the 'whole body' and of body segments for the assessment of body composition: comparison with densitometry and anthropometry.

The value of 'whole body' and segmental impedance measurements, and of simple anthropometric methods for predicting body composition was assessed in 24 normal (14m, 10f) subjects (BMI, 18.3-28.6), using densitometry as the reference method. The contribution of segmental impedance was assessed in a separate group of 24 normal (12m, 12f) subjects (BMI, 19.8-28.8) at two frequencies (1 kHz and 50 kHz). Estimates of specific resistivities of certain individual segments (upper arm, forearm, upper leg, and lower leg) were also made in this group, and compared to those obtained from a group of 7 obese female subjects (BMI, 32.6-56.1). The bias and 95 per cent limits of agreement between densitometrically determined body composition (fat and fat-free mass, and total body water) and the alternative methods were found to vary considerably, depending on the technique and/or equations employed. Estimates of whole body composition based on impedance or resistance measurements were found to be associated with only slightly smaller limits of agreement than those made by anthropometry. The upper limb was found to have the greatest influence on whole body impedance measurements. Indeed, the forearm, which accounts for 1.3 per cent of body weight contributes 25.0 per cent to 'whole body' impedance. The estimated specific resistivities of segments were found to be considerably greater in the obese individuals than in normal female subjects (for example, 75 per cent higher for the upper arm, P less than 0.001). The results suggest that: (a) there may be a systematic, population-related, error in predicting densitometric estimates of body composition with the use of standard equations, which incorporate variables such as weight, height, skinfold thicknesses, and impedance/resistance measurements; (b) in this population, impedance or resistance measurements confer only a small advantage over simple anthropometry for predicting body composition; (c) the impedance of the arm or leg may provide a simple alternative method for assessing the composition of the whole body; and (d) the estimated specific resistivity of individual body segments may be useful for assessing the composition of those segments.

Adult↗

Factors influencing the production of creatinine: implications for the determination and interpretation of urinary creatinine and creatine in man.

The rates of creatine/creatinine inter-conversions and their equilibrium were studied under controlled conditions of temperature and pH that simulate urine storage conditions. The concentrations and ratios of creatine to creatinine in urine obtained from subjects with various pathophysiological conditions were determined, both before and after storage. The observed changes occurring during storage were compared with predicted changes based on observations of standard solutions. The initial reaction rate was found to increase with temperature, occurring maximally at about pH 3.7 for the conversion of creatine to creatinine, and at about pH 5.0 for the conversion of creatinine to creatine. At low pHs the equilibrium position was displaced towards creatinine. Above about pH 6.0 the equilibrium was associated with approximately equimolar quantities of creatine and creatinine. The creatine content of urine ranged from virtually nil to about double that of creatinine and changed predictably during storage. These findings have implications for the use of creatinine as an index of muscle mass and nutritional status, and as a marker for the completeness of urine collections.

Adult↗

The effects of dietary folate and zinc on the outcome of pregnancy and early growth in rats.

1. The objective of the present study was to determine the effects of two levels of folic acid and two levels of zinc in the diets of rats during pregnancy and lactation. It addressed, among other things, the question of whether an inhibitory effect of folic (pteroylmonoglutamic) acid on Zn absorption might result in a secondary Zn deficiency in either the dams or the pups. 2. A purified diet was given to four groups of female DNL (Norwegian) Hooded rats, before and during pregnancy and during lactation. It contained the four possible combinations of: no added folic acid or 100 micrograms added pteroylmonoglutamic acid/g, and 6.6 or 20.2 micrograms Zn/g. Pups and dams were killed on day 20 of gestation or on day 20 postpartum. Measurements of body-weights, food intakes, blood folate and tissue Zn levels were performed. 3. The group with low Zn and low folate intake had a satisfactory reproductive outcome, and there were only minor effects of the supplements on body-weights. 4. Additional folate greatly increased blood (erythrocyte and plasma) folate levels, but did not compromise tissue Zn concentrations. Zn supplementation also enhanced blood folate levels, for reasons which are not yet clear. 5. There was a moderate enhancing effect of the Zn supplement on Zn levels in the livers and kidneys of pregnant dams, and the kidneys of lactating dams. 6. If the conclusions can be extrapolated to humans, then the results provide some reassurance that a high folate intake from prenatal supplementation need not necessarily cause Zn depletion, and hence functional Zn deficiency in pregnant women and their offspring.

Animals↗

The effects of antimalarials and folate supplements on haematological indices and red cell folate levels in Gambian children.

Haematological indices and red cell folate levels (RCF) were measured during two annual surveys in a group of Gambian children aged 3 months-5 years who were participating in a trial of malaria chemoprophylaxis with Maloprim or chlorproguanil given with or without folate supplements. Chlorproguanil was given in an adult dose of 20 mg, Maloprim as one quarter or one half of the adult dose of 25 mg pyrimethamine and 100 mg dapsone. Antimalarials and folate supplements were given fortnightly. About 20% of children had low RCF levels (less than 100 ng/ml). Among children who did not receive supplementation with folate there were no significant differences in mean RCF levels between children who received Maloprim, chlorproguanil or placebo. Among children who received folate supplements, the mean RCF was significantly lower among those receiving chlorproguanil than among the controls. Mean RCF values were similar in children who received Maloprim or placebo. If chlorproguanil is used for malaria chemoprophylaxis in young children an age-related dose should be used.

Antimalarials↗

Decreased brown adipose tissue thermogenic activity following a reduction in brain serotonin by intraventricular p-chlorophenylalanine.

The effects of reducing brain serotonin (5-HT) levels by means of intracerebral-ventricular injections of the tryptophan antagonist p-chlorophenylalanine (PCPA) were investigated in male rats. Six days after the operation, PCPA-treated rats, either fed ad libitum or pair-fed to the food intake of control rats, showed decreased thermogenic activity and capacity in their interscapular brown adipose tissue (BAT) and also increased fat storage in their white adipose tissue (WAT). These results indicate that serotonergic synapses might play a regulatory role in the sympathetic control of BAT thermogenesis and in the rate of WAT deposition (by an as yet unidentified mechanism), in addition to their well established role in controlling food intake.

Adipose Tissue↗