Mechanisms of nutritional repletion during total parenteral nutrition.
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Biomedical subjects
Publications and source records attributed to M Elia.
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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.
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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.
The effect of ingesting a meal containing 3,275 kJ (47.3% carbohydrate, two-thirds of which was in the form of simple sugars, 39.4% fat, and 13.2% protein) on the oxidation of carbohydrate fat and protein (or amino acids) was assessed by indirect calorimetry and measurement of the rate of excretion of nitrogenous end products in urine and changes in the plasma urea concentration. Simultaneously, an assessment was made of substrate metabolism in forearm muscle by measuring forearm blood flow and concentration of metabolites in arterialized and deep venous blood. The mean resting energy expenditure during the first four hours after food ingestion was 15% higher than in the preprandial period (P less than .01). The extra energy dissipated during this time is equivalent to 5.3% of the energy provided in the meal. Carbohydrate oxidation increased by 111% (P less than .01), protein oxidation increased by 40% (P less than .05), and fat oxidation decreased by 21% (P less than .05). The concentration of glucose and amino acids and their uptake by muscle increased after food ingestion, while the reverse occurred with nonesterified fatty acids (NEFA). In the early postprandial period there was a marked suppression in the uptake of NEFA by muscle and a tendency toward decreased rather than increased release of glycolytic products (lactate + pyruvate + alanine), despite an up to sevenfold increase in the uptake of glucose. Fructose, which accounted for about 30% of the carbohydrate in the diet, was not taken up by muscle to any significant extent. It is estimated that during the first four hours after the meal muscle accounted for the uptake of 20% to 25% of the carbohydrate provided in the meal. This was associated with a small and nonsignificant change in the oxygen uptake by muscle. The data suggest that: (1) the increased uptake of glucose by muscle in the postprandial period does not necessarily increase the release of glycolytic products or increase the activity of the glucose-alanine and Cori cycles between muscle and liver; (2) triglyceride may become a more important energy source for muscle than circulating NEFA, especially in the early postprandial period; (3) muscle is not a major site of dietary-induced thermogenesis (zero to four hours); and (4) it is likely that nonmuscular tissues took up more carbohydrate (including fructose) than skeletal muscle during the first four hours after ingestion of this meal (even if it is assumed that as little as 50% of the dietary carbohydrate had been absorbed by four hours).
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A critical examination is made of the validity of indirect calorimetry when the nonprotein respiratory quotient is greater than 1. The different published stoichiometries for lipogenesis from glucose are excluded as a source of uncertainty in the interpretation of gaseous exchange measurements. The validity of indirect calorimetry is proved independently by an algebraic approach which, in contrast to previous attempts, makes minimal assumptions about stoichiometries. Although equations relating the respiratory quotient to the heat equivalent of oxygen are found valid, there is uncertainty in using these equations to predict accurately carbohydrate utilization and fat oxidized or synthesized. Reference tables interrelating respiratory data, the heat equivalent of oxygen, and net fuel utilization or synthesis for specified fuels are provided. A suggested framework for calculating energy expenditure in terms of ATP gain is given as an appendix.
Sources of error in the interpretation of respiratory data are evaluated and reviewed with special reference to the detailed composition of foods. Estimates of fuel utilization or synthesis are 12-fold more sensitive to errors in the nonprotein respiratory quotient than is the heat equivalent of oxygen. Estimates of protein oxidation from nitrogen excretion can be in error from +14 to -39% of the true value. Heat equivalents of oxygen, respiratory quotients, and urinary nitrogen-to-oxygen conversion ratios are considered for 60 artificial and 101 conventional food proteins, 36 artificial and 125 conventional food fats, and the different carbohydrates contained in these foods. It is concluded that there is considerable uncertainty when the mix of fuels utilized is assessed accurately. Accuracy is best within 5% of the true values. This analysis is completed with descriptions of some physiological sources of error in an appendix.
The effects of E. coli endotoxin 0127 B8 on oxygen consumption, temperature, and on the activity of the proton conductance pathway in brown adipose tissue (BAT) were investigated in rats and mice. In rats an increase was observed in rectal and skin temperature, whole body oxygen consumption and GDP binding in BAT. In mice only the rise in rectal and skin temperature were significantly changed by endotoxin administration. These findings suggest that in some species BAT is involved in the production of endotoxin induced fever and increased energy expenditure.
The basal blood glycerol concentration was determined and the rate of glycerol turnover was assessed by a nonradioactive infusion technique in six healthy nonobese adults after an overnight fast and again after four days of total starvation. Simultaneously, estimates of total energy expenditure and net fat oxidation were made from measurements of oxygen consumption, carbon dioxide production, and urinary nitrogen excretion. The data were combined to provide quantitative estimates of the activity of the triglyceride/fatty acid cycle. The basal concentration of glycerol in venous blood rose from a mean value of 54 +/- 8 mumol/L (SEM) before starvation to 154 +/- 5 mumol/L on day 4 of starvation. Glycerol turnover rates correlated well with the basal blood glycerol concentration (r = .95) and increased from a mean value of 115 +/- 17 mumol/min before starvation (equivalent to mobilization of about 3.95 kJ triglyceride/min) to 304 +/- 20 mumol/min (equivalent to mobilization of about 18.41 kJ/min). The estimated rate of net fat oxidation was 3.00 +/- 0.47 kJ/min before starvation and 4.00 +/- 0.14 kJ/min on day +4 of starvation. The rate of triglyceride energy recycling or rate of deposition of triglyceride energy into fat stores was calculated from the difference in the rate of fat energy mobilization and the rate of energy released during net fat oxidation. The values were found to be 0.94 +/- 0.26 kJ/min before starvation and 6.29 +/- 0.54 kJ/min on day +4 of starvation.(ABSTRACT TRUNCATED AT 250 WORDS)
1. Factors affecting the intestinal uptake and urinary excretion of mannitol, lactulose and 51Cr-labelled ethylenediaminetetra-acetate (51Cr-EDTA), have been investigated in normal subjects and three patients with ileostomy. 2. The distribution volume of markers within the body, the rate of disappearance from plasma and renal clearance were assessed after an intravenous injection of a mixture of mannitol (2 g), [14C]mannitol (10 microCi), lactulose (0.1 g) and 51Cr-EDTA (5 microCi). 3. The urinary recovery of all the intravenously administered markers was close to 100%. Distribution volumes and patterns of excretion were virtually identical. Oxidation of intravenously administered mannitol accounted for only about 1% of the dose. 4. The passage of an orally administered mixture of markers was traced through the intestine and into urine. Transit time through the gastrointestinal tract was measured by the breath hydrogen method and by radionuclide scanning. 5. The passage of markers from mouth to the large bowel was essentially complete by 3.5 h. In some subjects the marker appeared in the large bowel as early as 30-40 min but in others it took three times as long. 6. After an oral dose the urinary excretion of mannitol fell progressively from 2 to 6 h, whereas the excretion of lactulose and 51Cr-EDTA increased slightly. As a consequence the lactulose/mannitol and 51Cr-EDTA/mannitol ratios in urine collected between 0 and 2 h were more than twofold higher than in urine collected between 4 and 6 h (P less than 0.001). After 6 h, the urinary excretion
1. The effect of total starvation for 4-5 days on the intestinal uptake and urinary excretion of markers from an orally administered mixture of mannitol (5g), [14C]mannitol (0.5 microCi), lactulose (10 g) and 51Cr-labelled ethylenediaminetetra-acetate (51Cr-EDTA) (30 microCi), was assessed in five lean (group 1) and four obese (group 2) subjects. The effect of a very low calorie diet for 1 week and of a subsequent 5 day period of total starvation on intestinal permeability was assessed in a similar way in another group of obese subjects (group 3). Transit time from mouth to caecum of the fastest component of the oral mixture was assessed by the appearance of hydrogen in breath (all subjects), and the configuration of the transit spectrum through various segments of the gastrointestinal tract, was assessed by a radionuclide scan method (group 2 subjects only). The effect of starvation on plasma/renal clearance of these markers in subjects of group 2 was assessed with the use of a bolus intravenous injection of a mixture of mannitol (2 g). [14C]mannitol (10 microCi), lactulose (0.1 g) and 51Cr-EDTA (5 microCi). 2. The uptake and urinary excretion of orally administered mannitol was decreased by total starvation. The mean decrease was 47% in the lean subjects (P less than 0.025), 33% in group 2 obese subjects (P less than 0.05) and 41% in group 3 obese subjects P greater than 0.05). In contrast, starvation produced no significant change in either the excretion of 51Cr-EDTA or lactulose.(ABSTRACT TRUNCATED AT 250 WORDS)
14C labelled-D-mannitol and aquo (ethylene-diaminetriacetoacetic acid) 51chromium (III) (51Cr EDTA) have been evaluated as markers of intestinal permeability in twenty-four healthy control subjects, sixteen patients with recently diagnosed coeliac disease and twenty subjects with coeliac disease in remission on a gluten-free diet. The percentage excretion of 14C mannitol in urine collected for 6 h was significantly less in patients with coeliac disease (mean 6.7%) than controls (mean 13.5%). Conversely the excretion of 51Cr EDTA was significantly greater in patients with coeliac disease (mean 1.23%) compared with controls (mean 0.28%). The mean ratio of the percentage excretion of 51Cr to the percentage excretion of 14C was 0.29 in patients with untreated coeliac disease compared with 0.023 for healthy control subjects (P less than 0.001). Patients with untreated coeliac disease were clearly separated from control subjects by use of the 51Cr EDTA: 14C mannitol ratio but not by the excretion of independent markers.
To assess the errors in measurements of CO2 concentration that arise from the widespread use of drying agents in clinical and physiological studies, continuous measurements of CO2 concentration were made with an infra-red analyser before and after standard gas mixtures were passed through a tube containing one of several drying agents: calcium chloride; calcium sulphate (Drierite); alumina; silica gel; and magnesium perchlorate. The response time of the infra-red analyser was independent of the concentration of CO2 used (0-1%), but it was related to flow rate, dead space and the amount and drying agent used. At a low rate of 1 litre/min, alumina (145 g anhydrous weight) trapped virtually all the CO2 (0.8% in air) passing over it; silica gel (145 g anhydrous weight, mesh 6-20) adsorbed approximately 2 mmol CO2 (38% of total) over a period of 15 min; calcium sulphate (Drierite) absorbed a variable amount, depending on the bath; and calcium chloride adsorbed virtually no CO2. Increasing hydration of the drying agents reduced their capacity to adsorb CO2. Nitrogen was found to elute CO2 from the drying agents at about the same rate as it had been adsorbed. It is concluded that awareness of these adsorption/elution phenomena by drying agents should prevent errors from being made in the calibration of CO2 analysers, in the analysis of CO2, and in the measurement of specific activity or isotopic enrichment of CO2.
The gross and metabolizable energy values of artificial enteral and parenteral feeds have been calculated from detailed composition data for amino acid, fatty acid, saccharide and other oxidizable substrates and compared with similar values calculated for conventional foods. The background to the derivation and application of calorie conversion factors is briefly reviewed. There is evidence of widespread inappropriate application of calorie conversion factors for carbohydrates and amino acid mixtures. Appropriate digestibility or availability factors for the oxidizable fractions of artificial feeds is discussed for normal adult man and the intrinsic difficulty of obtaining availability values for subjects with varying types of malabsorption or urinary and tissue losses is emphasized. The nitrogen:protein conversion ratio and the availability of energy at a biochemical level (i.e. net ATP yield per calorie) is also considered. Finally, a more uniform and appropriate approach to calculating energy values for artificial feeds for the purposes of labelling, product description and estimating energy intake of patients is called for.
The effect of glucose infusion alone (175 mg/kg bolus dose followed by 4 mg min-1 kg-1 for 70 min) and in combination with forearm exercise on the exchange of glucose, alanine, glutamine and other metabolites and amino acids across forearm muscle was studied in six healthy individuals after an overnight fast. Arterial and deep venous blood was sampled and a mercury strain gauge plethysmograph was used to measure forearm blood flow. Total body energy expenditure and net glucose and fat oxidation were assessed by indirect calorimetry. The infusion of glucose increased the mean arterial blood glucose concentration from 4.95 +/- 0.19 (SEM) to a plateau of 9.6-9.9 mmol/l (P less than 0.01). The arterial blood concentrations of alanine and glutamine were not significantly altered but that of lactate increased from 0.50 +/- 0.02 to 0.65 +/- 0.05 mmol/l (P less than 0.02) and that of pyruvate increased from 46 +/- 5 to 72 +/- 6 mumol/l (P less than 0.01). In the resting state glucose administration did not significantly affect the lactate/pyruvate ratio in arterial or venous blood. Arterial plasma insulin concentration increased four-fold and total ketone body concentration decreased two- to three-fold. After glucose administration, alanine release was suppressed (in all subjects) from a mean value of 153 +/- 22 to 57 +/- 16 nmol min-1 100 ml-1 of forearm (P less than 0.02) whereas that of glutamine was not significantly affected (160 +/- 30 to 143 +/- 29 nmol min-1 100 ml-1 of forearm). Lactate release, like that of alanine, decreased, whereas pyruvate was slowly released in the basal state and was taken up during glucose administration (P less than 0.01). These changes were associated with a decrease in the uptake of total ketone bodies to one-fifth to one-tenth of that in the basal state. The net amino acid balance across the forearm muscle bed was negative throughout the study but decreased from a mean value of -567 in the basal state to -300 nmol min-1 100 ml-1 of forearm after glucose administration for 60 min. This was predominantly due to decreased release of effluxing amino acids, particularly alanine.(ABSTRACT TRUNCATED AT 400 WORDS)