From chemical analysis of the body ... to metabolic insights provided by the new methodology.
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Biomedical subjects
Publications and source records attributed to S A Jebb.
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Obesity is not a single disorder but a heterogeneous group of conditions with multiple causes each of which are ultimately expressed as an obese phenotype. Fatness does run in families, but the genetic component does not follow simple Mendelian principles and the influence of the genotype on the aetiology of obesity may be attenuated or exacerbated by non-genetic factors. Body weight is ultimately determined by the interaction of genetic, environmental and psychosocial factors acting through the physiological mediators of energy intake and expenditure.
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1. Our objectives were to measure total energy expenditure, the daily variation in total energy expenditure and the physical activity level in a group of HIV-positive subjects using the bicarbonate-urea method. The study also aimed to asses the practicalities of using the bicarbonate-urea technique in free-living conditions. 2. Total energy expenditure was measured with the bicarbonate-urea method over 2 consecutive days (1 day in one subject) in 10 male patients with HIV infection (median CD4 count = 30). Resting energy expenditure was measured by indirect calorimetry. Physical activity level (total energy expenditure/resting energy expenditure) was calculated from these measurements and from activity diaries. 3. Resting energy expenditure was found to be 7.46 +/- 0.87 MJ/day, 5% higher than predicted values. Total energy expenditure was 10.69 +/- 1.95 MJ/day with an intra-individual day-to-day variation of 6 +/- 6%. The measured physical activity level was 1.42 +/- 0.14, higher than the diary estimate of 1.34 +/- 0.16 (P = 0.029), and there were large intermethod differences in individual values. The subcutaneous infusion of bicarbonate was well tolerated and did not seem to restrict normal activities. 4. Total energy expenditure was not elevated in the group of HIV-positive subjects when compared with reference values for normal subjects. The physical activity level of the patients in this study was lower than that measured using other techniques in healthy young men, but was compatible with that expected for people leading a sedentary lifestyle. Reductions in physical activity in patients with HIV are likely to contribute to the wasting process and physical activity level may thus be a clinically useful measure. This study has also provided the first tracer estimate of the day-to-day variation in total energy expenditure. The bicarbonate-urea method represents an important new investigative tool for measuring total energy expenditure which has previously only been possible within the confines of a whole-body calorimeter or using the expensive doubly labelled water method.
Dual-energy X-ray absorptiometry (DXA) is a novel, non-invasive technique for the measurement of gross body composition in small animals. In the present study the absolute accuracy of the Hologic QDR-1000W scanner was assessed by comparison with direct analysis in twelve rats with a range of body fat and bone mineral content (BMC) values. Fat masses measured by DXA and petroleum-ether extraction were significantly different (P < 0.0023). The DXA technique consistently overestimated fat mass by approximately one third of the measured fat content. BMC derived from the measurement of Ca in ash gave a mean of 8.26 (range 1.57-15.71)g. BMC measured by DXA was not significantly different for the group as a whole. However, there was a trend for DXA to overestimate BMC in animals with low BMC and underestimate in those with higher BMC, compared with direct analysis, such that the 95% limits of agreement for the two techniques were +2.73 to -2.58 g. These results suggest that the present small-animal software developed for use with currently available Hologic machines does not give an accurate measure of gross body composition compared with the results from classical direct analysis.
Alterations in energy balance must be accommodated by adjustments in the net storage of the major energy-yielding macronutrients: carbohydrate, protein, and fat. This study used continuous whole-body calorimetry to measure changes in energy expenditure and substrate oxidation during a 12-d imposed energy imbalance in six lean men on mixed diets (overfeeding: 16.5 MJ/d, +33%, n = 3; underfeeding: 3.5 MJ/d, -67%, n = 3). Changes in total energy expenditure (TEE) and its components were modest; TEE changed by +6.2% (overfeeding) and -10.5% (underfeeding). In consequence, body weight changed by +2.90 and -3.18 kg. Marked changes in metabolic fuel selection occurred over the course of the study. Carbohydrate intake (540 and 83 g/d for overfeeding and underfeeding, respectively) exerted direct autoregulatory feedback on carbohydrate oxidation (551 and 106 g/d at day 12 for overfeeding and underfeeding, respectively). Subjects were close to balance by day 5. Changes in protein oxidation were small and not sufficient to prevent the oxidation of body protein mass, or its accretion, in response to energy deficit or surplus. Fat oxidation (59 and 177 g/d for overfeeding and underfeeding, respectively) was not sensitive to dietary fat intake (150 and 20 g/d, for overfeeding and underfeeding, respectively), rather, its oxidation was inversely related to the oxidation of other substrates. Changes in fat balance accounted for 74.1% and 84.0% of the energy imbalance during overfeeding and underfeeding, respectively. This study shows a clear oxidative hierarchy for the macronutrients. Metabolic fuel selection is dominated by the need to maintain carbohydrate balance. This induces inappropriate counterregulatory alterations in fat oxidation during energy surplus.
OBJECTIVE: To assess the application of a Cole-Cole analysis of multiple frequency bioelectrical impedance analysis (MFBIA) measurements to predict total body water (TBW) and extracellular water (ECW) in humans. This technique has previously been shown to produce accurate and reliable estimates in both normal and abnormal animals. DESIGN: The whole body impedance of 60 healthy humans was measured at 496 frequencies (ranging from 4 kHz to 1 MHz) and the impedance at zero frequency, Ro, and at the characteristic frequency, Zc, were determined from the impedance spectrum, (Cole-Cole plot). TBW and ECW were independently determined using deuterium and bromide tracer dilution techniques. SETTING: At the Dunn Clinical Nutrition Centre and The Department of Biochemistry, University of Queensland. SUBJECTS: 60 healthy adult volunteers (27 men and 33 women, aged 18-45 years). RESULTS: The results presented suggest that the swept frequency bioimpedance technique estimates total body water, (SEE = 5.2%), and extracellular water, (SEE = 10%), only slightly better in normal, healthy subjects than a method based on single frequency bioimpedance or anthropometric estimates based on weight, height and gender. CONCLUSIONS: This study has undertaken the most extensive analysis to date of relationships between TBW (and ECW) and individual impedances obtained at different frequencies ( > 400 frequencies), and has shown marginal advantages of using one frequency over another, even if values predicted from theoretical bioimpedance models are used in the estimations. However in situations where there are disturbances of fluid distribution, values predicted from the Cole-Cole analysis of swept frequency bioimpedance measurements could prove to be more useful.
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The prevalence of clinical obesity in Britain has doubled in the past decade. The Health of the Nation initiative has set ambitious targets for reversing the trend in recognition of the serious health burden which will accrue, but efforts to develop prevention and treatment strategies are handicapped by uncertainty as to the aetiology of the problem. It is generally assumed that ready access to highly palatable foods induces excess consumption and that obesity is caused by simple gluttony. There is evidence that a high fat diet does override normal satiety mechanisms. However, average recorded energy intake in Britain has declined substantially as obesity rates have escalated. The implication is that levels of physical activity, and hence energy needs, have declined even faster. Evidence suggests that modern inactive lifestyles are at least as important as diet in the aetiology of obesity and possibly represent the dominant factor.
BACKGROUND: Increased expenditure of energy at rest has been considered a contributing factor to the negative energy balance and weight loss that occur in patients with human immunodeficiency virus (HIV) infection. However, the true determinant of energy balance is not resting but total energy expenditure. We sought to determine the contribution of total energy expenditure to weight changes in patients with HIV-associated wasting. METHODS: We performed 51 assessments of energy metabolism in 27 men with HIV infection at different stages of disease, including periods of both rapid and slow weight loss. Resting energy expenditure was measured by indirect calorimetry, total energy expenditure by the doubly-labeled-water technique, and energy intake by recording the weight of food consumed. The results were compared with the rate of weight loss or gain. RESULTS: The mean (+/- SD) total energy expended by the HIV-infected men was 2750 +/- 670 kcal per day, no more than that expended by normal men. There was a significant positive relation between total energy expenditure and the rate of weight change (r = 0.61, P < 0.001); thus, during rapid weight loss, total energy expenditure was reduced to 2180 +/- 580 kcal per day (P = 0.009), primarily because of reduced physical activity. During rapid weight loss, the negative energy balance (-850 +/- 580 kcal per day) was primarily the result of the reduction in energy intake, to 1330 +/- 610 kcal per day; intake correlated strongly with the rate of weight change (r = 0.84, P < 0.001). CONCLUSIONS: In patients with HIV infection, total energy expenditure is reduced during episodes of weight loss. Reduced energy intake, not elevated energy expenditure, is the prime determinant of weight loss in HIV-associated wasting.
Data from animal studies suggests that glutamine supplementation may reduce the incidence or severity of cytotoxic-induced mucositis. This study examined the effect of glutamine supplements on mucositis in patients receiving bone marrow transplants. 24 patients were randomly assigned to receive an oral supplement of either glutamine or placebo (16 g/day) from the time of transplantation until discharge from hospital. There was no significant difference in the incidence of oral mucositis, assessed either by the patient (mucositis score: glutamine 17 vs. placebo 26.6) or an independent observer (glutamine 31.1 vs. placebo 32.3), or the number of days of diarrhoea (glutamine 3.1 vs. placebo 3.3 days). Similarly there were no significant differences in haematological indices (haemoglobin, WBC, platelets), the requirement for parenteral nutrition or hospital stay. Possible reasons for this negative result, which contrasts with those obtained in recent studies of patients receiving intravenous glutamine after bone marrow transplants, are discussed.
1. There are few data regarding the accuracy of Hologic QDR-1000W dual-energy X-ray absorptiometry for the measurement of body composition. In two studies, one in an in vitro experimental system using oil and water mixtures and the other in samples of pork meat, the effect of depth and tissue thickness on the measured composition was assessed. In the latter study the measured fat mass was compared with that measured by direct analysis. 2. All data indicated a trend in the measured fat mass with depth, such that more fat was measured at extremes of depth (< 10 cm and > 25 cm) than at intermediate depths. 3. In samples of meat weighing approximately 55 kg, dual X-ray absorptiometry significantly under-estimated the absolute fat mass compared with direct analysis (mean 20.4 +/- 1.65%) by 5-8% or 1-4 kg of fat. 4. These findings are of direct relevance to both clinical and research work using this technique to measure body composition, in particular in circumstances in which changes in body composition and/or tissue thickness are anticipated.
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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.
29 patients with either haematological or solid tumours, and receiving allogeneic or autologous bone marrow transplants (BMT) were included in a double-blind, randomised study of glutamine-free versus glutamine-supplemented TPN. Patients were given isocaloric, isonitrogenous TPN after BMT until they consumed 50% of their required diet orally. Length of hospital stay was significantly (5.8 days) less in patients receiving TPN/GLN. Incidence of positive bacterial cultures, clinical infections and mortality did not differ significantly between the two groups.