Christine Slater

Total energy expenditure and physical activity in young Scottish children: mixed longitudinal study

Childhood obesity has been attributed to a decline in total energy expenditure (TEE). We measured TEE, physical activity, and sedentary behaviour in a representative sample of young children from Glasgow, UK, at age 3 years (n=78), and we did a follow-up study at age 5 years (n=72). Mean physical activity level (TEE/resting energy expenditure) was 1.56 (SD 0.39) at age 3 years and 1.61 (0.22) at age 5 years. Median time in sedentary behaviour was 79% of monitored hours at age 3 years (IQR 74-84) and 76% (71-80) at age 5 years. Median time spent in moderate to vigorous physical activity represented only 2% of monitored hours at age 3 years (IQR 1-4) and 4% at age 5 years (2-6). Modern British children establish a sedentary lifestyle at an early age.

Reduced total energy expenditure and physical activity in cachectic patients with pancreatic cancer can be modulated by an energy and protein dense oral supplement enriched with n-3 fatty acids

The aim of the study was to assess the total energy expenditure (TEE), resting energy expenditure (REE) and physical activity level (PAL) in home-living cachectic patients with advanced pancreatic cancer. The influence of an energy and protein dense oral supplement either enriched with or without the n-3 fatty acid eicosapentaenoic acid (EPA) and administered over an 8-week period was also determined. In total, 24 patients were studied at baseline. The total energy expenditure was measured using doubly labelled water and REE determined by indirect calorimetry. Patients were studied at baseline and then randomised to either oral nutritional supplement. Measurements were repeated at 8 weeks. At baseline, REE was increased compared with predicted values for healthy individuals (1387(42) vs 1268(32) kcal day−1, P=0.001), but TEE (1732(82) vs 1903(48) kcal day−1, P=0.023) and PAL (1.24(0.04) vs 1.50) were reduced. After 8 weeks, the REE, TEE and PAL of patients who received the control supplement did not change significantly. In contrast, although REE did not change, TEE and PAL increased significantly in those who received the n-3 (EPA) enriched supplement. In summary, patients with advanced pancreatic cancer were hypermetabolic. However, TEE was reduced and this was secondary to a reduction in physical activity. The control energy and protein dense oral supplement did not influence the physical activity component of TEE. In contrast, administration of the supplement enriched with EPA was associated with an increase in physical activity, which may reflect improved quality of life.

Albumin synthesis rates are not decreased in hypoalbuminemic cachectic cancer patients with an ongoing acute-phase protein response.

OBJECTIVE To determine whether suppression of albumin synthesis contributes to the hypoalbuminemia observed in weight-losing cancer patients with evidence of an ongoing acute-phase protein response (APPR). BACKGROUND DATA Proinflammatory cytokines such as tumor necrosis factor (TNF) and interleukin 6 (IL-6) are known to downregulate albumin synthesis and increase acute-phase protein production in isolated hepatocytes. However, whether albumin synthesis is suppressed in hypoalbuminemic cancer patients with evidence of an ongoing acute-phase response is unknown. METHODS Albumin synthesis rates were determined in six healthy controls and in six weight-losing pancreatic cancer patients with an ongoing APPR using a flooding dose technique with [2H5]-phenylalanine. The presence of an APPR was defined as a serum C-reactive protein concentration >10 mg/L. Serum cytokines (TNF, IL-6) and soluble TNF receptors (sTNF-R 55 and 75), along with serum cortisol and insulin, were also measured in both groups. RESULTS Cancer patients had reduced serum albumin (median 32 [range, 23-36] vs. 42 g/L [40-45]; p < 0.01) and increased serum C-reactive protein concentrations (72 [23-126] vs. <5 mg/L; p < 0.01) when compared with controls. TNF was not detected in either group. sTNF-R 55 levels were significantly elevated in the cancer patients (3.8 [1.9-8.1] vs. 1.2 pg/mL [0.9-2.2]; p < 0.01). Circulating IL-6, insulin, and cortisol concentrations were not significantly different between the groups. The intravascular albumin mass was lower (88 [56-93] vs. 133 g [105-177]; p < 0.01), but the intravascular albumin fractional synthetic rate was higher (13.9 [13.5-18.5] vs. 10.3%/d [71-11.3]; p < 0.01) in the cancer patients compared with the controls. The total intravascular albumin synthetic rate was, however, similar between the two groups (12.7 [7.7-15.7] vs. 11.7 g/d [8.5-18.7]; p NS). CONCLUSIONS In weight-losing pancreatic cancer patients with evidence of an ongoing APPR, hypoalbuminemia is not caused by a decreased rate of albumin synthesis.

Validation of energy intake by 24-hour multiple pass recall: comparison with total energy expenditure in children aged 5-7 years.

Accurate measurement of energy intake (EI) is essential in studies of energy balance in all age groups. Reported values for EI can be validated against total energy expenditure (TEE) measured using doubly labelled water (DLW). Our previous work has indicated that the use of the standardized 24 h multiple pass recall (24 h MPR) method produces slight overestimates of EI in pre-school children which are inaccurate at individual level but acceptable at group level. To extend this work, the current study validated EI by 24 h MPR against TEE by DLW in sixty-three (thirty-two boys) school-aged children (median age 6 years). In both boys and girls, reported EI was higher than TEE, although this difference was only significant in the girls (median difference 420 kJ/d, P=0.05). On analysis of agreement between TEE and EI, the group bias was an overestimation of EI by 250 kJ/d with wide limits of agreement (-2880, 2380 kJ/d). EI was over-reported relative to TEE by 7 % and 0.9 % in girls and boys, respectively. The bias in the current study was lower than in our previous study of pre-school children, suggesting that estimates of EI become less inaccurate as children age. However, the current study suggests that the 24 h MPR is inaccurate at the individual level.

(13)C natural abundance in the British diet: implications for (13)C breath tests.

Surprisingly little information is available on the natural abundance of the minor isotope of carbon, (13)C, in common foodstuffs in the British diet. This study therefore aimed to examine the (13)C natural abundance of foodstuffs from a small cross-section of the British diet. The isotopic abundance, delta per mil, was calculated by measurement of the isotope ratio (13)C:(12)C by isotope ratio mass spectrometry. Results from this study were also compared with results from a North American study to highlight the difference in isotopic abundance between Northern European foodstuffs and North American foodstuffs. Such data should prove useful to those planning tracer studies using the stable isotope (13)C where enrichment is measured against a large and variable natural abundance in the body. Minimisation of this basal variation, for example in breath CO(2), can be achieved by controlling dietary intake of foods naturally abundant in (13)C.

Simultaneous measurement of albumin and fibrinogen synthetic rates in normal fasted subjects.

Albumin and fibrinogen synthesis appear to account for the majority of protein exported by the liver and therefore make a substantial contribution to that of whole-body protein synthesis. However, data on the protein synthetic rates of albumin and fibrinogen in normal subjects are limited. Albumin and fibrinogen synthetic rates were measured simultaneously over a 120-min period in normal subjects (n = 6) by using a flooding dose of 2H5-phenylalanine. Tracer incorporation into proteins was measured by gas chromatography/mass spectrometry. Body mass index, circulating concentrations of insulin, albumin, fibrinogen, C-reactive protein, and plasma volumes of the subjects were all within the normal reference range. There was a small and transient rise in circulating insulin concentrations following the flooding dose of phenylalanine. The median fractional synthetic rate and absolute synthetic rate for albumin was 10.3%/d and 208 mg.kg-1.d-1, respectively. The median fractional synthetic rate and absolute synthetic rate for fibrinogen was 19.5%/d and 28 mg.kg-1.d-1. In the context of the current interest in manipulating the inflammatory response of patients with various disease states, we introduce the concept of an acute phase protein quotient (APPQ). The APPQ is defined as the absolute rate of fibrinogen synthesis divided by that of albumin. In this group of normal subjects, the median APPQ was 0.14.

Is there an advantage in normalising the results of the Helicobacter Pylori [13C]Urea breath test for CO2 production rate in children?

The urea breath test (UBT) is a non-invasive diagnostic test to detect the presence of Helicobacter pylori in the stomach, and is the simplest way to confirm eradication after treatment. The test is based on the capacity of H. pylori to secrete the enzyme urease, which hydrolyses urea to ammonia and carbon dioxide. The aim of this study was to determine whether there is an advantage in expressing the results of UBTs in terms of urea hydrolysis rate (UHR), rather than breath 13C enrichment alone. Retrospective analysis of data collected between 1995 and 2002 from 260 patients undergoing UBTs was performed. The cut-offs for positive tests using breath 30-minute enrichment (E30), UHR calculated using VCO2 estimated from height and weight (H/WT) and VCO2 estimated from weight only were determined using two-graph receiver operator characteristic (TG-ROC) analysis. The cut-off points were 3.5‰ or 38.7 ppm 13C excess, 7.04 µmol/h and 7.08 µmol/h, respectively. There was no advantage in expressing the results as UHR (θ0, Theta-zero, where sensitivity = specificity = 0.97 (UHR H/WT), 0.98 (UHR WT) and 1.00 (E30)) rather than breath 13CO2 enrichment alone. Differences in the extent of H. pylori colonisation and urease activity are more important than variation in VCO2 in determining breath 13CO2 enrichment in the UBT.

Isotope dilution analysis of combined nitrogen in natural waters. III. Nitrate and nitrite

The measurement of nitrate uptake is of major importance to our investigations of primary production and nitrogen regeneration in the photic zone. Endogenous nitrate production (nitrification), by diluting the enrichment of added 15N-nitrate, can lead to underestimation of nitrate uptake. Although nitrification is assumed to be minimal in the photic zone, this needs to be confirmed by experiment. We have developed a specific isotope dilution method based on the analysis of a volatile derivative of the azo dye, 1-phenylazo-2-naphthol (Sudan-1). Sea water is spiked to approximately 10% of the nitrate pool with a known quantity of 15N-nitrate. An aliquot is filtered immediately. A second aliquot is incubated in situ for a fixed period and is then filtered. Nitrate concentration is estimated by isotope dilution analysis of the first filtrate. Nitrification rate is estimated from the change in 15N enrichment between the first and second filtrate. Nitrate from a 10 mL aliquot is first reduced to nitrite. Sudan-1 is formed by diazotization with aniline and coupling to 2-naphthol. It is extracted by solid phase extraction using C-18 cartridges, with ethyl acetate as eluant. 4-Phenylazophenol is added as internal standard and the samples are dried. They are analysed as tert-butyldimethylsilyl derivatives, using gas chromatography/mass spectrometry in selected ion recording mode. The intense M-57 fragment ion formed under electron impact ionization is used for 15N analysis. The procedure is precise, sensitive and, unlike most previous methods, it is free from interference by other forms of nitrogen. This method compliments our existing isotope dilution methods for the analysis of ammonium and dissolved free amino acids. Here, the new method has been used to confirm that our estimates of nitrate uptake in the photic zone of the Southern Ocean are not compromised by high nitrification rates.

Isotope Dilution Analysis of Combined Nitrogen in Natural Waters: II. Amino Acids

Dissolved free amino acids (DFAA) are an overlooked and potentially very important substrate for primary production. In the open ocean, an understanding of the flux of regenerated nitrogen is fundamental to our studies of carbon and nitrogen turnover. A major aim of these studies is to provide more accurate estimates of the drawdown of atmospheric carbon dioxide. We have estimated the concentration and regeneration rate of DFAA in seawater using a novel stable isotope dilution technique. Seawater is first spiked to an estimated 10% of the DFAA pool with a known quantity of 15N-labelled algal protein hydrolysate. One portion is filtered immediately and the DFAA concentration analysed by isotope dilution. A second portion is incubated in situ. After a set period this is filtered and DFAA regeneration is estimated by isotope dilution analysis of the filtrate. Combination with data from analysis of particulate nitrogen provides an assay of DFAA uptake by phytoplankton. DFAA are extracted from 50 mL seawater by ligand exchange chromatography. Amino acids are eluted, concentrated and derivatized prior to GC/MS anslysis. The new procedure is sensitive, precise, accurate and, as it is based on mass spectrometric detection, it has greater selectivity than methods based on high-performance liquid chromatography/optical detection. Furthermore, the method can provide concentration and flux data on all protein amino acids and is applicable in a number of fields.

Comparison of accuracy and precision of heart rate calibration methods to estimate total carbon dioxide production during 13C-breath tests.

Background:13C-breath tests are noninvasive tools to measure gastrointestinal function and nutritional interventions. Calculation of percentage dose recovered of 13C in exhaled breath requires knowledge of CO2 production rate (VCO2). A resting value is usually assumed, but this can underestimate VCO2 because subjects are unlikely to remain at rest during tests that last for many hours. There is a need for a method to estimate nonresting VCO2 during 13C-breath tests.Objective:To calibrate a heart rate monitor to continually estimate VCO2 during 13C-breath tests.Design:Proof of concept study.Subjects:Eight healthy adults, 10 healthy children and six children with cystic fibrosis.Methods:Heart rate and VCO2 were measured simultaneously at resting and nonresting levels. A new calibration method (smoothing heart rate and fitting a sigmoid function) was compared with published methods. A [13C]acetate breath test was used to demonstrate the range of physical activity during breath tests.Results:The new calibration method was more accurate than existing methods (mean bias −0.0002%, 95% confidence interval (CI) −0.0007, 0.0003% of the mean measured VCO2). Smoothing heart rate gave a more precise estimate of VCO2 and a more accurate estimate of resting energy expenditure (mean bias −0.09, 95% CI −0.22, 0.05 mmol CO2 min−1 m−2 body surface area) than using raw data (mean bias −0.21, 95% CI −0.38, −0.04 mmol CO2 min−1 m−2 body surface area). Physical activity level ranged from 1.0 to 2.5 in children, and 1.0 to 1.5 in adults.Conclusion:Use of smoothed HR with a sigmoid function provides an accurate method of estimating nonresting VCO2 during 13C-breath tests.Sponsorship:The work described in this paper was funded by the University of Glasgow and UK Medical Research Council Joint Research Equipment Initiative.