Biomedical subjects
Publications and source records attributed to J M Miles.
Explore the source record for details and available documents.
A rapid and reproducible method for the assay of 14C radioactivity in ketone bodies is described, based on the heat lability of acetoacetate and the ability of beta-hydroxybutyrate to quantitatively bind to and elute from an ion exchange resin. Potential interference from 14C activity in the ketone body metabolites (CO2, bicarbonate and acetone) during infusion of 14C-labeled ketone bodies is eliminated. The method was validated both by in vitro recovery studies and by the determination of rates of appearance of ketone bodies during infusion of exogenous unlabeled beta-hydroxybutyrate in dogs. The technique avoids many of the potential sources of imprecision in previous methods and makes in vivo study of ketone body turnover more practical.
Adrenal imaging in the past has been limited in its clinical application by the long interval between administration of dose and visualization of adrenal glands. We review our experience with the use of a newer labeling agent, NP-59, in 29 patients with various adrenal disorders and in 4 normal subjects. With this agent, identification of adrenal lesions is possible with a high degree of accuracy, and diagnostic information is usually available within 48 hours. NP-59 is particularly useful in evaluating primary aldosteronism and selected cases of Cushing's syndrome.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
UNLABELLED: Triacetin, the water-soluble triglyceride of acetate, was infused in mongrel dogs at isocaloric (N = 6) or hypercaloric (approximately 1.5 REE, N = 7) rates in mongrel dogs for 3 hr. Ketone body and glucose production rates were quantified with [13C2] acetoacetate and [3H]glucose, respectively. Four additional animals were infused with glycerol to serve as controls for the hypercaloric triacetin infusion. Energy expenditure was determined in the isocaloric experiments. RESULTS: no evidence of acute toxicity was observed during triacetin infusion at either rate. Plasma acetate concentrations increased from basal levels to approximately 1 and approximately 13 mmol/liter in the isocaloric and hypercaloric experiments, respectively. Plasma lactate and pyruvate concentrations decreased dramatically after 30 min of both isocaloric and hypercaloric triacetin infusions. Glucose production rates did not increase in either group, but glucose clearance decreased significantly in both groups (p less than 0.05) over the last hour of triacetin infusion. Plasma ketone body concentrations increased from 1.4 to 3.5 and 1.8 to 13.5 mumol/kg.min, respectively, during isocaloric and hypercaloric triacetin infusion. Resting energy expenditure increased from 3.0 +/- 0.3 to 4.0 +/- 0.5 kcal/kg.hr during isocaloric triacetin infusion (p less than 0.05). These studies indicate that triacetin can be administered to dogs at high rates without overt toxicity. The decrease in glucose clearance may represent competition between carbohydrate (glucose) and lipid (acetate). Triacetin infusion resulted in significant increases in ketone body production and concentration. These preliminary data indicate that triacetin may have a future role as a parenteral nutrient, and that further studies of its use are warranted.
These studies were undertaken to investigate the relationship between medium-chain fatty acid availability, medium-chain fatty acid oxidation, and central nervous system toxicity during infusion of medium-chain triglycerides in dogs. Six dogs received a sequential, stepwise infusion of trioctanoin at three different rates for 80 min each, providing calories below and equal to resting energy expenditure in the species. Ketone body production rates (using a 14C beta-hydroxybutyrate tracer) and plasma concentrations of lactate and octanoate were monitored. Three animals were infused with saline to serve as controls. Blood-brain barrier integrity was assessed with Evans blue dye, and brain samples were taken at the end of the study to quantify brain water. Three animals were studied under anesthesia to obtain good quality EEG and intracranial pressure measurements. Results were (1) plasma octanoate increased to 0.37 +/- 0.13, 0.78 +/- 0.2, and 1.44 +/- 0.41 mmol/liter during the three infusion intervals; (2) emesis, somnolence, and coma were observed at the two highest trioctanoin rates; (3) ketone body concentrations and production increased from 102 +/- 15 to 859 +/- 54 mumol/liter and 3.6 +/- 0.43 to 18.5 +/- 1.7 mumol/kg/min, respectively, at the highest trioctanoin infusion rate; and (4) plasma lactate also increased from 1.3 +/- 0.1 to 4.3 +/- 0.9 mmol/liter at the highest infusion rate. EEG changes were also observed, consisting of high amplitude slowing and reduction in amplitude of faster components. There was no extravasation of Evans blue dye, nor change in brain water or intracranial pressure. The conclusion--medium-chain triglycerides have significant dose-related central nervous system toxicity in dogs. Therefore, caution should be exercised in clinical studies with MCTs, including careful measurement of medium-chain fatty acid concentrations.
Plasma-free fatty acids (FFA) are an important source of energy for a variety of tissues. Recently, there has been an increased interest in the measurement of FFA kinetics in vivo, using radiolabeled or stable isotopic tracers. Standard techniques for measurement of FFA-specific activity are relatively imprecise and have limited sensitivity. We have developed a method for determination of the concentration and specific activity of individual plasma FFA that is precise (coefficient of variation less than 2%) and sensitive (detection limit in the high femptomolar to low picomolar range). Using this method, one can measure the kinetics of three or more long-chain fatty acids simultaneously. Its sensitivity is a particular advantage if one wishes to measure low rates of FFA turnover such as are encountered during hyperinsulinemia. It has been suggested that, for optimal accuracy in the determination of substrate kinetics, the tracer should be administered in the left ventricle and mixed venous blood samples should be obtained from the right heart. We have conducted experiments in dogs which demonstrate that peripheral tracer infusion and more conventional arterial (or arterialized venous) sampling actually provide more accurate estimates of FFA turnover; this is fortunate, since intracardiac infusion and sampling are not practical for human studies.
Diets containing either triacetin (the water-soluble triglyceride of acetate) or long-chain triglycerides (LCTs) were fed to rats to determine the effects on intestinal mucosa cells and plasma substrates. Male Sprague-Dawley rats were fed one of three diets, a control diet containing 5% of energy as LCTs or one of two experimental diets that contained 30% of energy as lipid. The lipid component of the two experimental diets was either 100% LCTs or 95% triacetin/5% LCTs. Plasma lactate, glucose, and total ketone body concentrations were not significantly different among dietary treatment groups. Compared with animals fed LCTs and control diet, plasma pyruvate and free fatty acid concentrations were decreased in animals fed triacetin. In contrast, plasma triglyceride concentrations were elevated in animals fed triacetin compared with other groups. Intestinal biochemical measures included total DNA, RNA, protein, and the protein:DNA ratio. Histologic indices measured were villus height in the jejunum and crypt depth in the colon. No significant difference in mucosal protein concentration was observed in the jejunum and colon. Jejunal RNA was significantly decreased in animals fed triacetin compared with other diets. Triacetin feeding significantly increased the DNA content in the jejunum and colon (thereby lowering the protein:DNA ratio), indicating smaller, more numerous cells. Jejunal villus height and colonic crypt depth were not significantly different among dietary treatment groups. Provision of a balanced diet containing 28.5% of the total calories as triacetin had no adverse effects on metabolic substrates and resulted in smaller and more numerous mucosal cells in the jejunum and colon.(ABSTRACT TRUNCATED AT 250 WORDS)
Explore the source record for details and available documents.