Ralph B. Dell

Reduction of Plasma Cholesterol Levels in Normal Men on an American Heart Association Step 1 Diet or a Step 1 Diet with Added Monounsaturated Fat

The design of diets to achieve optimal changes in plasma lipid levels is controversial. In a randomized, double-blind trial involving 36 healthy young men, we evaluated the effects on plasma lipid levels of both an American Heart Association Step 1 diet (in which 30 percent of the total calories were consumed as fat: 10 percent saturated, 10 percent monounsaturated, and 10 percent polyunsaturated fats, with 250 mg of cholesterol per day) and a monounsaturated fat-enriched Step 1 diet (with 38 percent of the calories consumed as fat: 10 percent saturated, 18 percent monounsaturated, and 10 percent polyunsaturated fats, with 250 mg of cholesterol per day). The effects of these diets were then compared with those of an average American diet, in which 38 percent of the total calories were consumed as fat: 18 percent saturated, 10 percent monounsaturated, and 10 percent polyunsaturated fats, with 500 mg of cholesterol per day. The men consumed the average American diet for 10 weeks before random assignment to one of the two Step 1 diets or to continuation of the average diet for an additional 10 weeks. Caloric intake was adjusted to maintain a constant body weight. As compared with the mean (+/- SD) change in the plasma total cholesterol level in the group that followed the average American diet throughout the study (-0.05 +/- 0.36 mmol per liter), there were statistically significant reductions (P less than 0.025) in the plasma total cholesterol level in the group on the Step 1 diet (-0.37 +/- 0.27 mmol per liter) and in the group on the monounsaturated fat-enriched Step 1 diet (-0.46 +/- 0.36 mmol per liter). There were parallel reductions in the plasma low-density lipoprotein cholesterol levels in these two groups. Neither the plasma triglyceride levels nor the high-density lipoprotein cholesterol concentrations changed significantly with any diet. We conclude that enrichment of the Step 1 diet with monounsaturated fat does not alter the beneficial effects of the Step 1 diet on plasma lipid concentrations.

Metabolic Acidosis Resulting from Intravenous Alimentation Mixtures Containing Synthetic Amino Acids

Abstract Hyperchloremic metabolic acidosis was observed in 11 infants receiving total parenteral nutrition containing mixtures of synthetic L-amino acids. The observed acidosis was not due to excessive gastrointestinal or renal losses of base as judged by the stool undetermined anion content and the urinary net acid excretion, nor was it due to infusion of preformed hydrogen ion as judged by the titratable acidity of the synthetic amino acid mixtures. Instead, the synthetic amino acid mixtures contain an excess of cationic amino acids in relation to anionic amino acids or other organic anions. Metabolism of these cationic amino acids results in a net excess of hydrogen ion, explaining the observed acidosis.

Quantitative Displacement of Acid-Base Equilibrium in Metabolic Acidosis

Excerpt Metabolic acidosis is commonly encountered in a variety of disorders, all of which are characterized either by the gain of strong acid or by loss of bicarbonate from the extracellular fluid...

Growth, nutrient retention, and metabolic response in low birth weight infants fed varying intakes of protein and energy+

Growth, nutrient retention, and metabolic response were determined in low birth weight (LBW) infants fed daily protein and energy intakes, respectively, of 2.8 gm/kg and 119 kcal/kg (group 1), 3.8 gm/kg and 120 kcal/kg (group 2), and 3.9 gm/kg and 142 kcal/kg (group 3). The mean rates of both weight gain and nitrogen retention in group 1 were somewhat greater than intrauterine rates; plasma concentrations of transthyretin and albumin also were acceptable. Thus the lower protein intake appeared to be adequate. On the other hand, the rates of weight gain and nitrogen retention in groups 2 and 3 were greater than those in group 1, supporting the efficacy of the higher protein intake with respect to growth. However, blood urea nitrogen and plasma amino acid concentrations also were higher in groups 2 and 3; both were higher in group 2 than in group 3, reflecting the positive effect of the higher energy intake on protein utilization. This observation, combined with data from an earlier study, indicates that protein intakes in excess of 3 gm/100 kcal will not be utilized completely. Energy expenditure in group 3 was greater than in group 1 but not group 2, raising the possibility that protein intakes not utilized completely contribute to diet-induced thermogenesis. The higher energy intake in group 3 vs group 2 did not affect rate of weight gain significantly, but energy storage in group 3, and hence fat accretion, was greater than that of other groups. In all groups the ratio of protein accretion to fat accretion reflected dietary proportions of protein and energy.

Effects of varying protein and energy intakes on growth and metabolic response in low birth weight infants

Growth (weight, length, head circumference, and skinfold thickness), retention of major nutrients (nitrogen, sodium, potassium, chloride, calcium, and phosphorus), and chemical indices of protein adequacy (plasma albumin and transthyretin concentrations) and excess (blood urea nitrogen concentration and acid-base status; plasma amino acid concentrations) were determined serially from the time desired intake was tolerated until discharge weight (2200 gm) was reached in low birth weight infants (birth weight 900 to 1750 gm) fed one of three formulas, which provided protein and energy intakes, respectively, of 2.24 gm/kg/day and 115 kcal/kg/day (group 1), 3.6 gm/kg/day and 115 kcal/kg/day (group 2), and 3.5 gm/kg/day and 149 kcal/kg/day (group 3). Weight gain and rate of increase in length and head circumference were less in group 1 than in groups 2 and 3. Retention of most major nutrients also was less in group 1, as was blood urea nitrogen concentration, plasma albumin and transthyretin concentrations, and plasma concentrations of several amino acids. The rate of weight gain was not significantly greater in group 3 than in group 2, but the rate of increase in skinfold thickness was greater in this group. Neither nutrient retention nor metabolic indices differed between groups 2 and 3. These results suggest that a protein intake of 2.24 gm/kg/day is inadequate for the type of LBW infants studied, that the higher protein intakes are well tolerated, and that an energy intake of 149 vs 115 kcal/kg/day does not enhance utilization of the higher protein intakes studied.

Measurement of Regional Myocardial Perfusion in Man with 133 Xenon and a Scintillation Camera

A method was devised to quantitate regional capillary perfusion in the human heart by measuring the clearance constants (k) of Xenon-133 washout from multiple areas of the myocardium with a multiple-crystal scintillation camera. In 17 subjects, (133)Xe was injected into the right or left coronary artery or both and counts per second (cps) were recorded simultaneously on magnetic tape from each of 294 scintillation crystals viewing the precordium through a multichannel collimator. Data were processed by a digital computer. Crystals detecting the myocardial washout of (133)Xe were distinguished from those monitoring pulmonary excretion by positioning radioactive markers at the cardiac margins, and by a computer printout of the peak cps recorded by each crystal and its time after isotope injection into the coronary artery. The slopes of the initial segment of the multiple (133)Xe curves obtained in each study were calculated by the method of least squares using a monoexponential model. Myocardial blood flow rates in the cardiac regions viewed by the individual crystals were calculated (assuming a blood to myocardium partition coefficient of 0.72) along with the SD of every flow measurement. The pattern of myocardial perfusion rates so obtained was superimposed over a tracing of the subjects coronary arteriogram. Scintiphotographs showing the arrival and washout of isotope from various regions of myocardium and the area of tissue perfused by each coronary artery were obtained by replaying the data tape on an oscilloscope. Significant regional variations in local myocardial perfusion rates were observed in hearts with normal coronary arteries. When capillary flow measurements from crystals overlying the various cardiac chambers were averaged in each subject, the mean myocardial blood flow rate of the left ventricle in 17 patients, 64.1 +/-13.9 (SD) ml/100 g.min, significantly exceeded that of the right ventricle, 47.8 +/-10.9 ml/100 g.min, and of the right atrial region, 33.6 +/-10.3 ml/100 g.min. The approach may facilitate more objective assessment of: myocardial capillary perfusion in patients with angina pactoris, the pharmacology of antianginal drugs, and the efficacy of surgical procedures to revascularize ischemic myocardium.

Regional Myocardial Perfusion Rates in Patients with Coronary Artery Disease

Regional myocardial perfusion rates were estimated from the myocardial washout of (133)Xenon in 24 patients with heart disease whose coronary arteriograms were abnormal and 17 similar subjects whose coronary arteriograms were judged to be normal. Disappearance rates of (133)Xe from multiple areas of the heart were monitored externally with a multiple-crystal scintillation camera after the isotope had been injected into a coronary artery and local myocardial perfusion rates were calculated by the Kety formula. The mean myocardial perfusion rates in the left ventricle exceeded those in the right ventricle or atrial regions in subjects without demonstrable coronary artery disease. In this group there was a significant lack of homogeneity of local perfusion rates in left ventricular myocardium; the mean coefficient of variation of left ventricular local perfusion rates was 15.8%. In the patients with radiographically demonstrable coronary artery disease, a variety of myocardial perfusion patterns were observed. Local capillary blood flow rates were depressed throughout the myocardium of patients with diffuse coronary disease but were subnormal only in discrete myocardial regions of others with localized occlusive disease. Local myocardial perfusion rates were similar to those found in the group with normal coronary arteriograms in patients with slight degrees of coronary disease and in those areas of myocardium distal to marked coronary constrictions or occlusions which were well supplied by collateral vessels. In subjects with right coronary disease, the mean right ventricular perfusion rates were significantly subnormal; in seven subjects of this group perfusion of the inferior left ventricle by a dominant right coronary artery was absent or depressed. The average mean left ventricular perfusion rate of 12 subjects with significant disease of two or more branches of the left coronary artery was significantly lower than that of the group with normal left coronary arteriograms. In the patients with abnormal left coronary arteriograms, the average coefficient of variation of local left ventricular perfusion rates was significantly increased (24.8%). The studies provide evidence that coronary artery disease is associated with increased heterogeneity of local myocardial perfusion rates. They indicate that radiographically significant vascular pathology of the right or left coronary artery may be associated with significant reductions of myocardial capillary perfusion in the region supplied by the diseased vessel.

Energy expenditure, energy balance, and composition of weight gain in low birth weight infants fed diets of different protein and energy content

The effect of energy and protein intakes on energy expenditure, energy balance, and amount and relative rate of both protein and fat deposition in new tissue was investigated in 19 low birth weight infants whose mean protein and energy intakes, respectively, were 2.24 g/kg/d and 113 kcal/kg/d (formula A, n = 8), 3.6 g/kg/d and 115 kcal/kg/d (formula B, n = 5), and 3.5 g/kg/d and 149 kcal/kg/d (formula C, n = 6). The higher energy intake (formula C) but not the higher protein intake (formula B) resulted in greater energy expenditure. Both the higher protein (formula B vs formula A) and higher energy intakes (formula C vs formula B) resulted in greater weight gain secondary, in group B, to a greater absolute rate of protein deposition and, in group C, to a greater absolute rate of fat deposition. The relative composition of the new tissue deposited reflected the proportional intakes of protein and energy. The numerical value of the protein/fat ratio (g/g) of the new tissue deposited by infants fed formulas A and C, the protein contents of which were low relative to energy contents, were similar and significantly lower than the numerical value of the protein/fat ratio of the new tissue deposited by infants fed formula B, which had a higher protein content relative to energy content. These findings suggest that the composition of weight gain is related to both the absolute amounts and the proportions of dietary protein and energy; thus, both must be considered in formulation of nutritional regimens for LBW infants.

A Weighted Least-Squares Technique for the Analysis of Kinetic Data and Its Application to the Study of Renal 133Xenon Washout in Dogs and Man

A computer program was written in PL/1 to successively fit the sum of two, three, and four exponential terms to data by an iterative least-squares technique, using a combination of the steepest-descent and the Newton-Raphson methods for convergence. Each data point was weighted by the reciprocal of its variance, assuming that the errors followed a Poisson distribution. A compartment, i.e., an exponential term, was declared nonsignificant if it did not significantly reduce the least-squares error about the fitted line as judged by an F test. Validity of the data was assessed by a “runs” test and by the frequency with which data points fell outside the 95% confidence range. Results of the analysis showed that (1) 9 of 12 normal human kidney 133Xe washout curves were best described by a four-compartment model, (2) 18 of 38 studies in patients with essential hypertension yielded a four-compartment curve with significant reduction in compartment-1 flow, (3) nine patients with congestive heart failure all had three-compartment washout curves, (4) two patients with oliguric renal failure had washout curves described best by a two-exponential equation (one of these patients responded to an injection of furosemide with the appearance of a third, more rapid compartment). Obviously, this form of analysis can be easily applied to other sets of data which are described by nonlinear equations.

Evaluation of a mathematical model for predicting the relationship between protein and energy intakes of low-birth-weight infants and the rate and composition of weight gain.

ABSTRACT: A model for predicting the relationship between protein and energy intakes of low-birth-weight (LBW) infants and the rate and composition of weight gain is described. It is based on linear multiple regression equations summarizing the rates of weight gain, nitrogen retention, and energy retention of 101 previously studied LBW infants fed protein intakes ranging from 2.25 to 3.9 g kg-1 d-1 and concomitant energy intakes ranging from 115 to 147 kcal kg-1 d-1 plus current theory concerning nutrient retention and body composition. To test the validity of the model, three combinations of protein and energy intake predicted by the model to result in specific rates and compositions of weight gain were fed to 44 LBW infants, and the observed rates of weight gain, protein accretion, and fat accretion were compared with the rates predicted by the model. Differences in these and other outcome variables between two of the groups, the intakes of which differed only in energy, also were compared to provide additional insight into the effect of concomitant energy intake on protein utilization. Across groups, actual outcomes correlated closely with predicted outcomes, supporting the validity of the model for the total population. However, outcomes of individual infants deviated as much as 30% from predicted outcomes; the magnitude of the deviation was independent of birth weight, gestational age, or size for gestational age. In addition, the mean rate of protein accretion of the group fed the highest protein/energy ratio was significantly less than predicted. The higher mean urinary nitrogen excretion as well as blood urea nitrogen and plasma amino acid concentrations of this group versus the group that received a similar protein intake with a higher energy intake suggest that the higher energy intake improved nitrogen utilization. In toto, the data support the concept that the rate and composition of weight gain of LBW infants can be manipulated by intake; however, for individual infants, the extent of manipulation seems to be dependent on as-yet-unidentified inherent biologic variables.