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Biomedical subjects

L O Crosby

Publications and source records attributed to L O Crosby.

At least 19 recordsLinked to original sources

Controlled trial of the metabolic effects of a very-low-calorie diet: short- and long-term effects.

Resting energy expenditure (REE), weight, and body composition were measured up to seven times in 13 obese women during a 24-wk study. Patients were randomly assigned to a very-low-calorie diet (VLCD, 500 kcal/d) or a balanced-deficit diet (BDD, 1200 kcal/d). After 8 wk of supplemented fasting, REE of the VLCD patients decreased by 17% whereas that of the BDD patients was virtually unchanged. REE of the VLCD patients increased during 12 subsequent weeks of realimentation such that differences in REE between the two groups were not statistically significant at week 24 (VLCD = -11%, BDD = -2%). Reductions in weight and fat-free mass (FFM) were 12.1% and 3.6% for the VLCD patients and 10.6% and 4.1% for the BDD patients, respectively. There were no significant differences between the groups in pre- to posttreatment changes in REE normalized to FFM. Results suggest that REE recovers partially after consumption of a VLCD. They also provide evidence of a possible metabolic advantage of weight loss by a more moderate restriction.

Body Composition↗

A randomized clinical trial of total parenteral nutrition in malnourished surgical patients: the rationale and impact of previous clinical trials and pilot study on protocol design.

The rationale for a large-scale clinical trial of preoperative total parenteral nutrition (TPN) is described in the context of previous clinical trials that have attempted to demonstrate reduction of operative morbidity with preoperative TPN. Defects in study design or execution potentially compromising the validity of these studies are analyzed. Results of a single-institution pilot study performed during the planning phase of the multiinstitutional preoperative TPN trial are presented. This literature review and pilot study provided the data necessary to permit appropriate design of many critical elements in the protocol for the clinical trial including sample size, eligibility criteria, duration and intensity of treatment regimens, and end-point criteria. The rationale underlying critical decisions in protocol design are presented in detail to allow more meaningful interpretation of the results of the clinical trial.

Clinical Trials as Topic↗

Study protocol: a randomized clinical trial of total parenteral nutrition in malnourished surgical patients.

CSP #221 is a randomized multiinstitutional clinical trial to assess the efficacy of 10 d of perioperative total parenteral nutrition (TPN) in reducing morbidity and mortality in malnourished patients undergoing intraperitoneal and/or intrathoracic operations. In this paper a detailed protocol for the clinical efficacy trial is presented primarily as a reference document for use in interpretation of the results of the clinical trial. It is also anticipated, however, that review of this protocol may be useful to other investigators planning future clinical nutrition intervention trials.

Clinical Trials as Topic↗

Calorie-nitrogen interactions in the parenterally fed primate.

To test the hypothesis that nonprotein calorie intake and nitrogen intake are equally important in establishing positive nitrogen balance, weight gain, and serum protein response in the depleted primate treated with total parenteral nutrition (TPN), 10 adult male chair-adapted primates (Macaque fascicularis) were studied. After 10 days of nutritional depletion (nothing by mouth; 5% dextrose with electrolytes administered intravenously) animals were randomized to receive one of four TPN diets for 10 days. The depletion/repletion cycle was repeated, after 1 month of caged free feeding, until all animals had received the four TPN diets. Two levels of nonprotein caloric intake (155% and 100% of primate resting energy expenditure) and two levels of nitrogen intake (200% and 100% of primate nitrogen requirement) were used to make the four different diets. Nitrogen balance (p = 0.01) and serum total iron-binding capacity response (p = 0.02) were significantly influenced by the level of nitrogen intake but not by nonprotein calorie intake, which significantly influenced only weight gain (p = 0.03). Fluid balance was not significantly different for any diet. Fat and protein stores may be selectively repleted in this model by adjusting the nonprotein calorie and nitrogen content of TPN.

Animals↗

Theory of the etiology of human toxemia of pregnancy: fetal hyperinsulinemia as a compensatory response to decreased uterine blood flow.

Toxemia of pregnancy is a perplexing clinical problem that has defied accurate elucidation of its etiology because the disorder does not occur in undisturbed lower mammalian species that are currently used as animal models of reproductive physiology. We propose that toxemia of pregnancy occurs as the end stage human fetal-placental unit response to decreased maternal uterine blood flow, and that this fetal-placental unit response may be unique to the human species. The human fetus increases insulin secretion in response to progressive intrauterine asphyxia, which may result in decreased fetal-placental prostacyclin production (a vasodilator and inhibitor of platelet aggregation) and increased fetal-placental thromboxane A2 production (a vasoconstrictor). This could result in increased uteroplacental perfusion pressure, maternal hypertension, and increased maternal platelet aggregation. We also suggest that women who develop idiopathic toxemia of pregnancy are at increased risk for adult onset diabetes later on in life because they have a mild derangement in glucose-insulin homeostasis during their reproductive years that results in increased uterine vascular damage, that leads to decreased uterine blood flow, and ultimately the fetal hyperinsulinemia-prostaglandin pressor release mechanism. Therefore, prevention of toxemia may be possible by correction of mild derangements in glucose-insulin receptor homeostasis before conception occurs.

Female↗

Term human fetal umbilical vein oxygen content, placental weight, and maternal blood pressure.

The relationship of umbilical venous oxygen content to placental weight and mean maternal arterial blood pressure was investigated in 38 normal nonlaboring subjects undergoing elective cesarean section at 38.4 +/- 0.2 weeks (mean +/- SEM). In 14 subjects breathing room air, umbilical vein oxygen content was found to be a function of the lowest mean maternal arterial blood pressure (r = 0.48, P = 0.04), but not to placental weight. In 24 subjects breathing supplemental oxygen, umbilical vein oxygen content was not related to placental weight or lowest mean maternal arterial blood pressure. Fetuses attached to placentas less than 396 g had a higher hemoglobin concentration than fetuses attached to placentas greater than 396 g. This suggests the possibility of chronic in utero hypoxemia in human fetuses attached to small placentas.

Adult↗

The ultraendurance triathlete: a physiological profile.

To better characterize the athletes who participate in ultraendurance triathlons, 14 triathletes in training for the Hawaii IRONMAN triathlon were studied. A physical and physiological profile was developed from anthropometric measurements and oxygen uptake during maximal exercise on a treadmill, cycle ergometer, and arm ergometer. A comparison of the maximal values among exercise modes and between males and females was made. A comparison of height, weight, and percent body fat of these triathletes with elite athletes from the sports of swimming, cycling, and running showed the physique of triathletes to be most similar to that of cyclists. Oxygen uptake at maximal exercise was, for males and females, respectively: 68.8 ml X kg-1 X min-1, 65.9 ml X kg-1 X min-1 on the treadmill; 66.7 ml X kg-1 X min-1, 61.6 ml X kg-1 X min-1 on the cycle ergometer; and 49.1 ml X kg-1 X min-1, 39.7 ml X kg-1 X min-1 on the arm ergometer. When comparing the highest oxygen uptake attained at maximal exercise in any one of the three exercise modes, the male triathletes are comparable to swimmers, but have a lower aerobic capacity than cyclists or distance runners. The female triathletes studied were able to attain oxygen uptake values greater than those previously reported for female athletes.

Adult↗

Alterations in exogenous substrate metabolism in sepsis.

Metabolic rates and substrate utilization patterns were evaluated by using a rate cecal ligation and perforation model. Animals that survived for 48 hours after the induction of sepsis were hypermetabolic and responded appropriately to varying exogenous substrate infusions. In contrast, animals that did not survive to 48 hours were premorbidly hypometabolic and failed to adjust their oxidation patterns in response to the exogenous substrate supply. These findings suggest the benefit of individually tailoring the supply of exogenous nutrients in critically ill patients with sepsis and of frequent reassessment of metabolic parameters, including the resting energy expenditure and respiratory quotient.

Animals↗

The relationship of serum cholesterol and vitamin A in hospitalized patients with and without cancer.

Interrelationships among circulating levels of cholesterol, vitamin A, and selected transport proteins, as well as other nutritional variables were examined in a large population of hospitalized cancer (CA, n = 94) and noncancer (NONCA, n = 432) patients in order to help clarify a relationship between serum cholesterol and vitamin A. Serum cholesterol and vitamin A levels were positively correlated (r = 0.39; p less than 0.001) in both CA and NONCA groups. One hypothesis that might explain such a relationship was investigated. Results suggest that serum-transport protein levels and nutritional status are important factors that lead to a correlation between serum cholesterol and vitamin A by virtue of their mutual associations with both substances. Results suggest also that NONCA patients may have a more complex relationship of variates to serum-vitamin A levels than CA patients and that low levels of both cholesterol and vitamin A in CA patients may be related more to nutritional status than to the presence of cancer.

Aged↗

Estimation of human fetal-placental unit metabolic rate by application of the Bohr principle.

The Bohr Principle via continuous indirect calorimetry was used to estimate human fetal-placental unit metabolic rate in 12 normal women undergoing elective caesarean section under continuous lumbar epidural anaesthesia. Maternal oxygen consumption decreased after umbilical cord clamping and after placental removal. Fetal-placental unit oxygen consumption was 10.7 +/- 1.3 ml/min per kg (mean +/- SEM). Fetal oxygen consumption was 6.8 +/- 1.4 ml/min per kg. Placental oxygen consumption was 37 +/- 12 ml/min per kg. Fetal-placental unit carbon dioxide production was 9.2 +/- 1.2 ml/min per kg. These mean values agree favourably with measurements of uterine and fetal metabolism from other mammalian species. Maternal minute ventilation decreased with removal of the fetal-placental unit, and this decrease was found to be linearly related to the fetal-placental unit carbon dioxide production.

Adult↗

A quantitative evaluation of stress associated with indwelling superior vena cava cannulae in rats.

"Nonrestraining" superior vena cava (SVC) cannulae are commonly used in rat metabolic studies. The objective of this study was to evaluate the level of stress and metabolic alterations associated with surgical placement and subsequent maintenance and use of an indwelling intravenous cannula as measured by resting energy expenditure (REE), respiratory quotient (RQ), urinary nitrogen excretion, and substrate utilization pattern. Nine rats underwent SVC cannulation and six rats underwent sham operation. Postoperatively, animals were starved for 48 hr and then refed either parenterally or orally for 48 hr. Sham-operated animals adapted appropriately to starvation within 24 hr by decreasing REE 14% and increasing utilization of fat (RQ:0.89----0.78). Hypometabolic adaptation to starvation was delayed in cannulated animals until the second postoperative day, but appropriate alterations in energy substrate utilization were not affected by the presence of cannulae. Cannulae did not affect the metabolic response to oral refeeding with similar increases in REE and similar patterns of substrate utilization in sham-operated and cannulated animals. Animals refed parenterally demonstrated higher REE and apparent fat deposition (RQ greater than 1) consistent with continuous hypercaloric glucose administration. Urinary nitrogen excretion was not affected by the presence of cannulae. Cannula-associated metabolic alterations are minimal and transient and do not preclude detection and quantification of alterations associated with composition or utilization of exogenous substrates.

Animals↗

Interval nitrogen excretion and maintenance nitrogen requirements for parenteral nutrition in primates.

This paper discusses a regression technique for determining maintenance nitrogen requirements in well-nourished primates (M fascicularis) on total parenteral nutrition. Animals were administered a continuous glucose infusion, and parenteral nitrogen intake was varied at constant time intervals in a random order (from 0 to 1 g nitrogen/kg/day). Interval nitrogen balance (intake minus urinary nitrogen output) was plotted against interval nitrogen intake. The x-intercept was defined as the maintenance nitrogen requirement. First, 24-h intervals were used at a nonprotein caloric intake of 85 kcal/kg/day (approximately 175% of primate resting energy expenditure) and the nutritional adequacy of the estimated requirement evaluated prospectively. Next, 8-h balance intervals were used and the maintenance nitrogen requirements predicted by this abbreviated technique were compared to those obtained using the longer method. Finally, the short-interval technique was repeated at two other levels of continuous glucose infusion (60 kcal/kg/day and 8 kcal/kg/day) and the effect on predicted nitrogen requirement examined. Maintenance parenteral nitrogen requirements for primates may be determined in 48 h using the abbreviated techniques.

Animals↗

Energy expenditure in acute trauma to the head with and without barbiturate therapy.

The increased energy expenditure associated with severe trauma to the head appears genuine but exhibits wide variation in its magnitude. Patients with severe acute trauma to the head without barbiturate treatment are hypermetabolic with an average energy expenditure 26 per cent over predicted. Barbiturate therapy abolishes this hypermetabolism and decreases energy expenditure to 14 per cent below predicted. In the individual patient, there appears to be a close relationship between the degree of suppression of energy expenditure and the serum barbiturate level. However, this relationship would appear to be different in each patient, and therefore, for this group, a significant correlation between energy expenditure and serum barbiturate level does not exist. The wide variability of energy expenditure in individual patients makes the estimation of energy expenditure by population predictive formulas imprecise. This may lead to incorrect estimates of caloric requirements and inappropriate provision of exogenous energy substrates. Although for those patients receiving energy expenditure and serum barbiturate levels in the individual may further aid in estimating the caloric expenditure for each individual, in order to provide appropriate amounts of calories to the patient with trauma to the head, energy expenditure should be measured in each instance.

Adolescent↗

The effect of anorexia nervosa on bone morphometry in young women.

Changes in bone morphometry during chronic undernutrition were evaluated in 14 young women with anorexia nervosa (mean age +/- SEM = 25.5 +/- 4.4 yrs). Bone morphometry studies using the second metacarpal of the left hand showed significant depression for percent cortical area (p less than 0.05); cortical area (p less than 0.001) and combined cortical thickness (p less than 0.01) as compared to age, sex and race matched controls. A trend (p less than 0.10) was observed in study subjects for reductions in bone width and total area. Using percent cortical area (PCA) as the standard, subjects had mean cortical bone morphometry equivalent to 60-year-old women. Appendicular bone mass is significantly decreased in adults with anorexia nervosa. Anorexia nervosa should be considered in the differential diagnosis of osteopenia in young women, and serves as a model for studying the effects of chronic calorie and mineral malnutrition on bone remodeling at the time of attainment of peak bone mass.

Adult↗

Energy expenditure in malnourished gastrointestinal cancer patients.

Cancer cachexia, a common finding in patients with gastrointestinal (GI) malignancy, is frequently attributed to tumor-induced aberrations in host energy expenditure. To characterize the frequency and severity of aberrations in energy expenditure in GI cancer patients, and to identify the potential influence of tumor characteristics in this group, the authors measured resting energy expenditure (REE) by indirect calorimetry in 173 patients and compared REE to predicted-energy expenditure (PEE) from the Harris-Benedict formulae based on current body weight. Fifty-eight percent of patients had abnormal REE (normal REE = +/- 10% PEE); 36% (62 of 173) were hypometabolic (REE less than 90% PEE), and 22% (39 of 173) were hypermetabolic (REE greater than 110% PEE). Host and tumor factors were compared between metabolic groups to identify potential determinants of abnormal energy expenditure. Differences between groups cannot be explained by differences in patient age, sex, body size, nutritional status, tumor burden, or duration of disease. Resting energy expenditure does not correlate with percent of weight loss, serum albumin, or duration of disease. Analysis by tumor site reveals patients with pancreatic or hepatobiliary tumors to be predominantly hypometabolic; gastric cancer patients tend to be hypermetabolic, whereas patients with colorectal or esophageal neoplasms are more evenly distributed across metabolic groups, the largest portion being normometabolic (X2 = 20.7, P less than 0.02). The majority of GI cancer patients have abnormal REE which is unpredictable and not uniformly hypermetabolic. The determinants of these abnormalities do not appear to be age, sex, body size, nutritional status or tumor burden. Primary tumor site is a major determinant of energy expenditure in GI cancer patients.

Age Factors↗

Weight gain and nutritional efficacy in anorexia nervosa.

To evaluate the usefulness of interval weight change in assessing nutritional support efficacy, we studied four anorexia nervosa patients (52% ideal body weight) requiring long-term total parenteral nutrition (TPN) for 63 +/- 18 days. Fluid and electrolyte deficits were corrected before the initiation of nutritional support. Resting energy expenditure was measured before the initiation of TPN and weekly thereafter, using indirect calorimetry. Daily caloric expenditure was estimated at 1.1 X resting energy expenditure, based on previous studies of continuous heart rate monitoring in this patient population. Daily excess calories were calculated as caloric intake minus caloric expenditure. Each patient was weighed daily and linear regression analysis (excess calories versus weight change) was performed for individual patients and the group over intervals of varying length. There was no individual or group correlation between excess calories and weight gain on a daily or weekly interval basis. Cumulative weight changes over the long-term course of TPN correlated significantly with cumulative excess calories for each patient and the whole group (r = +0.82, p less than 0.01). The excess calories required to gain a kilogram body weight ranged from 5569 to 15619 kcal/kg with a mean of 9768. Cumulative long-term weight changes during nutritional repletion in anorexia nervosa are meaningful indicators of caloric balance, but short interval weight changes (daily, weekly) are not. The caloric cost of weight gain is variable in this population.

Adolescent↗

Total body water and total body potassium in anorexia nervosa.

In the ill hospitalized patient with clinically relevant malnutrition, there is a measurable decrease in the ratio of the total body potassium to total body water (TBK/TBW) and a detectable increase in the ratio of total exchangeable sodium to total exchangeable potassium (Nae/Ke). To evaluate body composition analyses in anorexia nervosa patients with chronic uncomplicated semistarvation, TBK and TBW were measured by whole body K40 counting and deuterium oxide dilution in 10 females with stable anorexia nervosa and 10 age-matched female controls. The ratio of TBK/TBW was significantly (p less than 0.05) higher in anorexia nervosa patients than controls. The close inverse correlation found in published studies between TBK/TBW and Nae/Ke together with our results suggest that in anorexia nervosa, Nae/Ke may be low or normal. A decreased TBK/TBW is not a good indicator of malnutrition in the anorexia nervosa patient. The use of a decreased TBK/TBW ratio or an elevated Nae/Ke ratio as a definition of malnutrition may result in inappropriate nutritional management in the patient with severe nonstressed chronic semistarvation.

Adult↗

Energy expenditure in primary malnutrition during standardized exercise.

When eight malnourished females without organic disease, were subjected to a controlled treadmill exercise test, they expended less total energy than females of normal body weight. The malnourished subjects consumed less oxygen than the control subjects, but oxygen consumption increased with increasing work load. The resting energy expenditure of the malnourished subjects was less than predicted values, but body composition as determined by muscle mass, total body water and thyroxine levels were within normal limits. Although decreased energy expenditure associated with malnutrition, has been attributed to decreased oxygen transport and altered hemoglobin, the malnourished subjects in this study did not have reduced hemoglobin levels. Metabolic adaptation may have occurred in order to improve the efficiency of aerobic metabolism. In order to confirm this theory, energy expenditure should be assessed under conditions of maximal oxygen intake.

Adult↗