Hypermetabolism and advanced cancer.
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Cytokines↗
Biomedical subjects
J L Mullen
Publications and source records attributed to J L Mullen.
Early-onset repeated dieting reduces food intake and body weight but not adiposity in dietary-obese female rats.
As dieting behavior and attempts at weight loss are becoming increasingly common in adolescent girls, we wished to determine whether early-onset repeated dieting influenced the development of obesity and its metabolic correlates. Female rats were fed a high-fat diet and subjected to six cycles of dieting and regain, beginning in the peripubertal period. Although dieted rats weighted less than nondieted high-fat fed controls at the completion of the sixth cycle, body composition analysis revealed that the two groups were equally obese. Cumulative caloric intake was less in dieted rats, suggesting that the pattern of consumption promoted by dieting helped to establish the obesity. Resting metabolic rate did not differ between the two groups. These data suggest that although early-onset repeated dieting may result in reduced body weight, the eventual level of adiposity may be unknowingly elevated, potentially leading to long-term health risks.
Adipose Tissue↗
Surgical jejunostomy in aspiration risk patients.
One hundred patients underwent laparotomy for independent jejunal feeding tube placement. Neurologic disease was present in 50%, and obtundation (28) and oropharyngeal dysmotility (25) were the most common indications for enteral feeding. The post-pyloric route was chosen because of aspiration risk in almost all (94%) patients. Postoperative (30-day) mortality rate was 21%, because of cardiopulmonary failure in most (18). One death resulted directly from aspiration of tube feeds. Two surgical complications required reoperation: one wound dehiscence and one small bowel obstruction. Four wound infections occurred. Two patients underwent reoperation after tube removal, and four tubes required fluoroscopically guided reinsertion for peritubular drainage (2), removal (1), and occlusion (1). Aspiration pneumonia was present in 18 patients preoperatively and in eight postoperatively. None of the patients with feeding-related preoperative aspiration pneumonia (13) had a recurrence while fed by jejunostomy. Three patients developed postoperative aspiration pneumonia before initiation of jejunostomy feedings. Jejunostomy may be performed with low morbidity rate and substantial reduction of feeding-related aspiration pneumonia, and is the feeding route of choice in aspiration risk patients.
Adult↗
Contribution of skeletal muscle atrophy to exercise intolerance and altered muscle metabolism in heart failure.
BACKGROUND: The purpose of this study was to investigate the prevalence of skeletal muscle atrophy and its relation to exercise intolerance and abnormal muscle metabolism in patients with heart failure (HF). METHODS AND RESULTS: Peak VO2, percent ideal body weight (% IBW), 24-hour urine creatinine (Cr), and anthropometrics were measured in 62 ambulatory patients with HF. 31P magnetic resonance spectroscopy (MRS) and imaging (MRI) of the calf were performed in 15 patients with HF and 10 control subjects. Inorganic phosphorus (Pi), phosphocreatine (PCr), and intracellular pH were measured at rest and during exercise. Calf muscle volume was determined from the sum of the integrated area of muscle in 1-cm-thick contiguous axial images from the patella to the calcaneus. A reduced skeletal muscle mass was noted in 68% of patients, as evidenced by a decrease in Cr-to-height ratio of less than 7.4 mg/cm and/or upper arm circumference of less than 5% of normal. Calf muscle volume (MRI) was also reduced in the patients with HF (controls, 675 +/- 84 cm3/m2; HF, 567 +/- 112 cm3/m2; p less than 0.05). Fat stores were largely preserved with triceps skinfold of less than 5% of normal and/or IBW of less than 80% in only 8% of patients. Modest linear correlations were observed between peak VO2 and both calf muscle volume per meter squared (r = 0.48) and midarm muscle area (r = 0.36) (both p less than 0.05). 31P metabolic abnormalities during exercise were observed in the patients with HF, which is consistent with intrinsic oxidative abnormalities. The metabolic changes were weakly correlated with muscle volume (r = -0.42, p less than 0.05). CONCLUSIONS: These findings indicate that patients with chronic HF frequently develop significant skeletal muscle atrophy and metabolic abnormalities. Atrophy contributes modestly to both the reduced exercise capacity and altered muscle metabolism.
Exercise↗
Jejunostomy and aspiration pneumonia.
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Humans↗
Laparoscopic-guided jejunostomy.
The proximal jejunum is the preferred site for long-term enteral access in the patient at risk for aspiration. Herein we describe a laparoscopic technique for the creation of a feeding tube jejunostomy. This minimally invasive approach is an alternative for patients requiring chronic postpyloric enteral feeding.
Humans↗
Nutritional assessment and indications for nutritional support.
The goal of nutritional assessment is to identify prospectively all those patients who would develop a nutrition-related complication. In practical terms, there is no single test capable of achieving this goal. At present, the best method of nutritional assessment is an organized step-by-step multifactorial approach. This involves assessment of the primary illness, the patient history, and the prognosis. A nutritional status examination is done, and the current intake is compared with the nutritional goals. A decision is then made whether to force feed. If forced feeding is initiated, the effectiveness of the therapy must be monitored frequently until the patient recovers and is able to be sustained by volitional oral intake.
Enteral Nutrition↗
Nutritional support in renal failure.
Adequate protein intake is necessary in renal failure to reduce morbidity. The desire to avoid dialysis should not be a justification to starve patients, particularly because fed patients have better survival rates in acute renal failure. The treatment techniques for renal failure may be used secondarily as a delivery route for nutrients.
Acute Kidney Injury↗
Indirect calorimetry in critical care.
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Basal Metabolism↗
Resting energy expenditure in patients with pancreatitis.
OBJECTIVE: To assess the resting energy expenditure of hospitalized patients with pancreatitis. DESIGN: Prospective, case-referent study. SETTING: Nutrition support service in a university tertiary care hospital. PATIENTS: Patients referred to the Nutrition Support Service with the diagnosis of pancreatitis. Excluded from study entry included those with cancer, obesity (greater than 150% ideal body weight), those measured within 3 postoperative days, or patients requiring ventilator support with an FIO2 of greater than 0.5. Forty-eight patients with either acute pancreatitis (n = 13), chronic pancreatitis (n = 24), acute pancreatitis with sepsis (n = 7), or chronic pancreatitis with sepsis (n = 7) were studied. The two septic groups were combined into a single pancreatitis-with-sepsis group, since no significant differences among measured variables were observed between individual septic groups. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Resting energy expenditure was measured by indirect calorimetry and compared with the predicted energy expenditure, as determined by the Harris-Benedict equations. Resting energy expenditure (percent of predicted energy expenditure) was significantly (p less than .02) greater for patients with pancreatitis complicated by sepsis (120 +/- 11%) compared with the nonseptic chronic pancreatitis group (105 +/- 14%). Resting energy expenditure for the nonseptic acute pancreatitis patients (112 +/- 17%) was not significantly different from the other groups. The septic pancreatitis group had the largest percentage (82%) of hypermetabolic (resting energy expenditure greater than 110% of predicted energy expenditure) patients, whereas 61% and 33% of the acute and chronic pancreatitis groups were hypermetabolic, respectively (p less than .02). CONCLUSIONS: Resting energy expenditure is variable in patients with pancreatitis (77% to 139% of predicted energy expenditure). The Harris-Benedict equations are an unreliable estimate of caloric expenditure. Septic complications are associated with hypermetabolism and may be the most important factor influencing resting energy expenditure in pancreatitis patients.
Acute Disease↗
Long-term effects of dieting on resting metabolic rate in obese outpatients.
There is growing concern that dieting may adversely affect the metabolic rate and exacerbate efforts to control weight. In this study we measured the resting metabolic rate nine times over 48 weeks in 18 obese women (108.0 +/- 3.1 kg) who were randomly assigned to one of two dietary conditions. Nine patients consumed approximately 5021 kJ/d (1200 kcal/d) throughout the 48 weeks, while the other nine consumed a 1757-kJ/d (420-kcal/d) diet for 16 of the first 17 weeks and a conventional reducing diet for the remainder of treatment. All patients increased their physical activity, primarily by walking. During the first 5 weeks, the fall in metabolic rate was more than double the relative reduction in weight. By contrast, at week 48, the metabolic rate of patients in the two conditions was reduced by 9.4% +/- 4.0% and 8.3% +/- 2.2%, respectively, while weight was reduced by 16.6% +/- 2.7% and 19.5% +/- 2.7%, respectively. Thus, neither dietary regimen, combined with modest physical activity, was associated with long-term reductions in resting metabolic rate that exceeded decreases anticipated with the achievement of a lower body weight.
Adult↗
Ablation of abnormal energy expenditure by curative tumor resection.
Resting energy expenditure is abnormal in most patients with cancer and may contribute to cancer cachexia. These metabolic abnormalities may be a direct measure of tumor metabolism, or represent alterations in the size or activity of the body cell mass, or both. To unravel this pathogenesis, we prospectively studied 68 preoperative patients with cancer about to undergo curative resection by measuring resting energy expenditure before and after tumor resection. The preoperative measured resting energy expenditure was compared with expected resting energy expenditure based on Harris-Benedict resting energy expenditure predictions: 10 patients were hypometabolic (less than 90% Harris-Benedict); 35 were normometabolic (90% to 110% Harris-Benedict); and 23 were hypermetabolic (greater than 110% Harris-Benedict). Using each patient as his or her own control, resting energy expenditure normalized or remained normal following curative resection. In contrast, after palliative resection, resting energy expenditure remained hypermetabolic or significantly increased toward hypermetabolism. Tumor induces an abnormal metabolic rate, since tumor removal results in prompt normalization of resting energy expenditure. The abnormal energy expenditure of patients with cancer cannot be solely attributed to abnormal host body composition.
Analysis of Variance↗
Effect of propranolol on nitrogen and energy metabolism in sepsis.
Pharmacologic therapy designed to block adrenergic activity or alter hormonal milieu may modulate energy and protein metabolism in stress. The metabolic effects of propranolol (beta adrenergic receptor blocker) in sepsis was investigated in 22 well-nourished rats that underwent superior vena caval cannulation, cecal ligation, and puncture. Animals were randomly assigned to receive either a continuous infusion of 0.7 mg/day of propranolol combined with parenteral nutrition (n = 11) or parenteral nutrition alone (n = 11). Both groups received isocaloric, isonitrogenous, isovolemic, parenteral nutrition post-operatively for 24 hr. Nitrogen balance was better for the propranolol group than for the control group (+743 +/- 84 mg/kg/day versus +300 +/- 63 mg/kg/day, respectively, P less than 0.05). A significant difference between the pharmacologic therapy and control groups was noted for urinary 3-methylhistidine excretion versus control (0.99 +/- 0.08 micrograms/kg/day versus 7.5 +/- 0.37 micrograms/kg/day, respectively, P less than 0.01). Measured energy expenditure was similar for both pharmacologic therapy and control groups (149 +/- 20 kcal/kg/day versus 134 +/- 11 kcal/kg/day, respectively, P = N.S.). No statistically significant difference was demonstrated for 24-hr survival between propranolol and control groups (73 and 64%, respectively). Continuous, low-dose propranolol promotes nitrogen retention and decreases 3-methylhistidine excretion without altering energy expenditure in parenterally fed septic rats.
Animals↗
Components of energy expenditure in tumor-bearing animals.
Single snapshot measurements of resting energy expenditure (REE) suggest that hypermetabolism contributes to cancer cachexia, but tumor impact on total 24-hr energy expenditure (TEE) is unknown. Automated multicage indirect calorimetry was employed to measure daily energy expenditure in adult Buffalo rats (n = 16) randomized to tumor inoculation or controls. Measurements included baseline REE, activity EE (AEE), thermic response to food (TEF), and TEE. Rats (n = 16) were randomized. Metabolic measurements, tumor size, and body weight were recorded weekly. Animals were sacrificed at Week 5 for analysis of host and tumor composition. Significant depletion of total lean body mass occurred in TB rats (greater than 15% wt loss, ANOVA P less than 0.001) which inversely correlated with tumor growth (r = -0.81, P less than 0.001). REE, TEF, AEE, and TEE did not change in controls (ANOVA P = n.s.). In TB rats, a 19.5% increase in REE occurred (119.4 +/- 3.3 to 138.7 +/- 1.8 kcal/kg LBM/day, P less than 0.01). TEE remained unchanged (157.3 +/- 5.6 vs 152.9 +/- 3.6 kcal/kg LBM/day, P = n.s.) due to a 66% decrease in AEE (32.9 +/- 3.1 to 10.5 +/- 1.7 kcal/kg LBM/day, P = 0.01). TEF did not change (4.7 +/- 0.8 vs 5.0 +/- 0.3 kcal/kg LBM/day, P = n.s.). Both TB and controls demonstrated a decreased REE in response to a 24-hr fast (7.9% vs 4.8%, P = n.s.). Respiratory quotient decreased in both groups when comparing fed to fasted values: TB (0.86 to 0.76) and controls (0.86 to 0.71), but the decline was greater in controls (P = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Increased contribution of protein oxidation to energy expenditure in head-injured patients.
Six patients with acute head injury (initial GCS 4.8 +/- 1.7) were studied to determine the contribution of protein oxidation to resting energy expenditure (REE). Patients were studied on the second or third day post-injury and prior to implementation of nutritional support. Variables measured included REE by indirect calorimetry (normalized to percent predicted energy expenditure calculated from the Harris-Benedict equation). 24-hr urinary nitrogen excretion, calorie, and nitrogen intake. All patients received dexamethasone (39 +/- 2 mg/day) and three received pentobarbital. Mean REE was widely variable, ranging from 43 to 128% of predicted (mean, 90 +/- 31%). Mean 24-hr urinary nitrogen excretion was 16.5 +/- 5.8 g. The contribution of protein oxidation to REE was 30 +/- 4%. The contribution of protein oxidation to REE did not parallel REE (r = -0.237, p = NS) or REE expressed as percent predicted (r = -0.258, p = NS). The contribution of protein oxidation to energy expenditure is greater in acute heat trauma than previously described soft tissue injury and sepsis. The observed excessive nitrogen catabolism and increased contribution of protein oxidation to resting energy expenditure suggest accentuated protein requirements in respect to energy needs in head-injured patients.
Adolescent↗
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↗
Successful use of double-lumen, silicone rubber catheters for permanent hemodialysis access.
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Catheterization, Central Venous↗
Barbiturate therapy reduces nitrogen excretion in acute head injury.
The effect of pentobarbital on nitrogen and energy metabolism was evaluated in seven severely head-injured patients (Glasgow Coma Scale 4.7 +/- 1.7) within the first week postinjury. Measured energy expenditure (% of predicted) was significantly lower in the pentobarbital group (n = 4) versus control (n = 3) (76 +/- 23% versus 132 +/- 28%, respectively, p less than 0.01). Similarly, 24-hour urinary nitrogen excretion was lower for the barbiturate group compared to control (11.2 +/- 4.0 gm versus 19.5 +/- 3.3 gm, respectively, p less than 0.01). No statistical difference was noted for urinary 3-methylhistidine excretion between the barbiturate and control groups (43 +/- 12 mcg/day versus 47 +/- 14 mcg/day, respectively, p = N.S.). Barbiturate therapy decreases measured energy expenditure and reduces nitrogen excretion without significantly altering 3-methylhistidine excretion in head-injured patients. The metabolic effects of pentobarbital may enable the ability to achieve energy and nitrogen equilibrium during metabolic support of acutely head-injured patients.
Adolescent↗