Lon O. Crosby

Energy expenditure in malnourished cancer patients.

It is widely believed that the presence of a malignancy causes increased energy expenditure in the cancer patient. To test this hypothesis, resting energy expenditure (REE) was measured by bedside indirect calorimetry in 200 heterogeneous hospitalized cancer patients. Measured resting energy expenditure (REE-M) was compared with expected energy expenditure (REE-P) as defined by the Harris-Benedict formula. The study population consisted of 77 males and 123 females with a variety of tumor types: 44% with gastrointestinal malignancy, 29% with gynecologic malignancy, and 19% with a malignancy of genitourinary origin. Patients were classified as hypometabolic (REE < 90% of predicted), normometabolic (90–110% of predicted) or hypermetabolic(>110% of predicted). Fifty-nine per cent of patients exhibited aberrant energy expenditure outside the normal range. Thirty-three per cent were hypometabolic (79.2% REE-P), 41% were normometabolic (99.5% REE-P), and 26% were hypermetabolic (121.9% REE-P) (p < 0.001). Aberrations in REE were not due to age, height, weight, sex, nutritional status (% weight loss, visceral protein status), tumor burden (no gross tumor, local, or disseminated disease), or presence of liver metastasis. Hypermetabolic patients had significantly longer duration of disease (p < 0.04) than normometabolic patients (32.8 vs. 12.8 months), indicating that the duration of a malignancy may have a major impact upon energy metabolism. Cancer patients exhibit major aberrations in energy metabolism, but are not uniformly hypermetabolic. Energy expenditure cannot be accurately predicted in cancer patients using standard predictive formulae.

Effects of Intraoperative Glucose on Protein Catabolism and Plasma Glucose Levels in Patients with Supratentorial Tumors

Animal studies suggest that hyperglycemia (glucose concentrations > 225 mg/dl) occurring prior to periods of brain ischemia exacerbates neurologic damage. Neurosurgical patients, a group at risk for intraoperative brain ischemia, often receive glucose. Therefore, the effects of intraoperative glucose administration (IGA) on these patients were studied. Sixteen patients undergoing supratentorial craniotomy were randomly assigned to receive either 5% glucose in 0.9% sodium chloride solution (G) or 0.9% sodium chloride solution (S) infusion (both at a rate of 3–4 ml · kg−1 · h−1) during the first 4 h of surgery. All patients received glucose infusions postoperatively. Plasma glucose, insulin, free fatty acids, alanine, ketones, base excess, pH, triglycerides, and lactate were measured during the infusion period and 24 h postoperatively. Urinary nitrogen was measured, commencing with the infusion and continuing for 24 h. Neurologic testing included preoperative and postoperative neurologic and psychomotor exams, time to extubation (min), and degree of alertness at the completion of anesthesia. The G group had significantly greater intraoperative plasma glucose concentrations at all time periods studied during the infusion (P < 0.05). Glucose levels ranged from 200–242 mg/dl compared with 12–160 mg/dl in G and S groups, respectively. G group hyperglycemia was within the range associated with exacerbation of ischemic brain damage in animal studies. Free fatty acids and ketones were significantly greater (P < 0.05) intraoperatively in the S group. Lactate and insulin were significantly greater in the G group at 4 h. Total urinary nitrogen was comparable in both groups but was significantly greater intraoperatively (P < 0.05) in the G group (13 ± 2 vs. 7 ± 1 mg · kg−1 · h−1). No differences in the other metabolic indices were found. Likewise, no difference between groups was found in the neurologic variables; however, the number of patients studied was small. In summary, IGA produced plasma levels that have been associated with potentiation of ischemic neurologic damage, while patients receiving saline had much lower glucose levels. Because there does not appear to be any metabolic compromise in those not receiving glucose, the results suggest that glucose should be avoided during intracranial surgery.

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.

Treatment Effects of Parenteral Vitamins in Total Parenteral Nutrition Patients

To determine the prevalence of abnormal vitamin levels in an adult hospitalized population requiring total parenteral nutrition (TPN) and to assess the effect of routine parenteral vitamin therapy on vitamin levels, we studied 35 general surgical patients. Assays for 12 vitamins were performed both before and after a standard 10-day course of TPN. Patients were given nothing by mouth. The first 25 patients received a daily parenteral vitamin mixture tailored to the recommendations of the Nutrition Advisory Group of The American Medical Association (maintenance dose). The final 10 patients were given a parenteral multivitamin dose providing substantially greater amounts of most vitamins (repletion dose). Only 58% (190/324) of pre-TPN vitamin levels were normal, 25% were low, and 17% were high. No patient had fewer than two abnormal baseline levels. Vitamin levels did not correlate with serum albumin, body weight, or nitrogen balance. After 10 days of treatment, only 39% of low pre-TPN vitamin levels improved; most (45/62) of the low posttreatment levels were low at baseline. The higher repletion dose resulted in a significantly (p less than 0.01) greater percent increase in vitamin A, C, and pyridoxine levels. The prevalence of abnormal vitamin levels in this population is high (42%). Standard parenteral vitamin therapy leads to marginal improvement in abnormally low pre-TPN vitamin levels.

Tumor Effects on Gluconeogenesis in the Isolated Perfused Rat Liver

Alterations in metabolism in the tumor-bearing host can be explained by: 1) alterations of metabolic processes in the tumor itself, and/or 2) tumor effects on host metabolism. Tumor effects on host liver metabolism were studied using an isolated perfused rat liver preparation. The livers of fasted female Lewis Wistar rats with and without transplanted subcutaneous mammary tumors were perfused for 1 hr with medium containing 5 mM glucose and physiological levels of amino acids. The rate of gluconeogenesis, as measured by conversion of 14C-lactate to 14C-glucose, showed a significant increase in the rate of glucose production from lactate in tumor-bearing rats (2.40 vs 2.00 mumol/min/100 gm). Hepatic glycogen and 14C-glycogen content were not significantly different between the two groups. In order to evaluate whether this tumor model exhibits characteristic changes in metabolism previously reported in other animal tumor models, serum lactate, triglyceride, glucose, and blood urea nitrogen were measured in non-perfused animals. The serum concentration of lactate and triglycerides were significantly higher in tumor-bearing rats (0.9 mM vs 2.7 mM lactate; 244 mg % vs 365.5 mg % triglycerides). Serum glucose and blood urea nitrogen were not significantly different in the two groups. An effect of tumor on host energy metabolism and serum metabolite levels is demonstrated. A method for the study of host-tumor metabolic interactions is described.

Prehepatic Total Parenteral Nutrition in the Chair-adapted Primate:

The relative efficacy of prehepatic and central venous infusion of total parenteral nutrition (TPN) was evaluated in a chair-adapted primate model. Four adult male monkeys (Macaca fascicularis) underwent surgical placement of a silastic catheter in both the portal vein (PV) and superior vena cava (SVC). Following recovery (10 days), each animal received two courses of TPN (100 kcal and 4 g of protein/kg/day) for 10 days each via the PV and SVC in an alternating crossover manner. The prehepatic (PV) infusion of TPN in the well nourished, chair-adapted primate results in maintenance of weight (PV: delta - 0.07 kg; SVC:delta - 0.07 kg), nitrogen equilibrium (PV:+ 0.8 g N/day; SVC: + 0.7 g N/day), and trends in serum albumin (PV:delta - 0.35 g %; SVC: delta - 0.38 g %), and total iron binding capacity (PV:delta + 44 mg %; SVC:delta + 8.67 mg %) comparable to the SVC route. No significant abnormalities in liver enzyme production were observed with either route of infusion. Whole body protein synthesis rates using 15N-glycine tracer were likewise comparable (PV = 2.05 g N/kg/day; SVC = 2.18 g N/kg/day). Prehepatic delivery and primary hepatic modulation of substrates does not substantially improve the efficacy of parenteral nutrient administration. Intestinal modification of substrates may be the most important contributing factor in the supposed superiority of enteral alimentation.

Estimation of Fecal Nitrogen in Patients with Liver Disease

The use of a fecal nitrogen (FN) predictive equation (Am J Clin Nutr 1978; 31:12-22, Cheng) based on dietary nitrogen intake (Nin) [FN (mg/kg/day) = 10.817 + 0.03 Nin(mg/kg/day)] was evaluated in patients with liver disease with and without concomitant lactulose therapy. Ten male cirrhotics were studied in 27 3-day nitrogen balance studies including measured daily total urinary nitrogen, total FN, and Nin calculated from weighted food records. The Cheng formula accurately predicted FN in cirrhotics not receiving lactulose who demonstrated normal digestion and absorption of dietary protein. However, the formula did not accurately reflect FN excretion in patients receiving lactulose who showed impaired protein digestibility and significantly increased fecal weight. The Cheng predictive equation is a useful index of FN excretion in patients with liver disease whose digestive and absorptive capacities are not compromised by exogenous factors.

Indirect Calorimetry in Chair-Adapted Primates

This paper describes the construction of an indirect calorimeter for measurement of respiratory gas exchange in the chaired primate. Preliminary determinations of energy expenditure and respiratory quotient in five animals under a variety of dietary conditions suggest that this system will prove useful in the laboratory study of primate nutrition, energy metabolism, and cardiorespiratory physiology. Other possible uses and limitations are discussed.

Relationships between Serum Total Iron-Binding Capacity and Transferrin

The relationship between serum transferrin ( TFN ) and serum total iron-binding capacity (TIBC) in a clinical setting was evaluated in two related studies. The initial study evaluated 101 blood samples representing a cross-section of hospitalized adults. The samples were double assayed for TIBC using clinical and research methodologies. TFN was assayed by a commercial radial immunodiffusion method. Clinical laboratory TIBC correlated well with research laboratory TIBC (r = 0.87, slope = 0.97, p less than 0.001, n = 50) and the relationship of TIBC to TFN yielded the following equation: TFN = 0.83 TIBC -5.6 (r = 0.82, p less than 0.001, n = 101) where TFN = mg/100 ml and TIBC = micrograms/100 ml. The second study evaluated a new TIBC assay and its effect on the TIBC/ TFN relationship. Additionally, the TFN -TIBC relationship was evaluated at low normal and abnormal TIBC levels. In this second study, TFN = 1.0 TIBC -18.8 (r = 0.88, p less than 0.01, n = 126). Subsample analysis for specimens with TIBC between 105 and 160 showed a TIBC- TFN regression line that was not significantly different than the entire sample. Inclusion of ancillary patient data such as hemoglobin and hematocrit did not improve the relationship between TFN and TIBC in either study. The relationship was unaffected by age, sex, race, disease, treatment, fever, surgery, degree of nutritional support, blood transfusion, or blood chemistry parameters in either study. Laboratories deriving TFN from measured TIBC as a nutritional status indicator must determine the relationship for the specific procedures being used in their laboratories.

Urea Nitrogen Excretion in Chair-Adapted Primates

To evaluate the temporal pattern of urea excretion in chair-adapted primates (Macaque fascicularis) on continuous total parenteral nutrition (TPN), two groups of five animals were studied. Group I received continuous TPN (75 glucose kcal; 0.56 g nitrogen; and 100 ml fluid per kg per day) while Group II received a single morning isonitrogenous oral meal along with a continuous isovolemic intravenous infusion of 0.45% saline. Urine was collected hourly in group I for 2 days and every 4 hr in group II for 5 days and analyzed for urea content. Time series analysis revealed no periodicity of urea excretion in either group. Six animals were then studied for a total of 46 TPN days to define the relationship between the urea content of a single 3-hr morning urine aliquot and its respective content in a 24-hr collection. A significant linear relationship was found (r = +0.76, p less than 0.01). However, using this relationship, a reasonable estimate (+20%) of measured 24-hr urea output was achieved only 50% of the time using a single 3-hr urea output. Chair-adapted primates maintained on continuous TPN or a single oral meal with continuous saline infusion do not exhibit a periodic pattern of urea excretion. The variability in 3-hr urinary urea output in the chaired primate on continuous TPN does not consistently permit accurate estimation of the coincident 24-hr urinary urea output.