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Biomedical subjects

J L Mullen

Publications and source records attributed to J L Mullen.

At least 37 records · Page 2Linked to original sources

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↗

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↗

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↗

Energy metabolism during transplantation rejection.

The effect of transplantation rejection on energy metabolism is unknown. In order to investigate energy expenditure changes in this setting, we used an eight-cage rat indirect calorimeter to measure resting energy expenditure (REE) in the well-defined model of rat cardiac transplantation. Preoperative baseline measurements of REE were performed on Lewis recipients of allogeneic (Wistar Furth) or syngeneic (Lewis) heterotopic abdominal cardiac grafts (80.3 +/- 3.3 kcal0.75/day). Postoperatively, REE was measured on days 1 through 10, 15, and 20. An abnormal REE was defined as a greater than 10% change from the preoperative value. All cardiac allografts were rejected on postoperative day 7, whereas syngeneic hearts contracted for more than 100 days. Both groups of animals had a hypermetabolic response to surgery on postoperative day 1 compared with preoperative values (93.0 +/- 7.6 kcal/kg0.75/day, p less than 0.01). On postoperative day 2, REE normalized to preoperative baseline values in the syngeneic group and remained unchanged for the duration of the study (80.4 +/- 1.0, p = 0.49). In the allogeneic group, on postoperative days 3 through 6 an abnormal REE was recorded in 22 of 28 measurements compared with only 3 of 16 in the syngeneic group (p less than 0.001). After transplant rejection, REE normalized to preoperative values in the allogeneic group. Characteristic changes in energy expenditure occur during transplantation rejection. These changes in REE preceded rejection in this animal model.

Animals↗

Reduction of methotrexate toxicity with improved nutritional status in tumor-bearing animals.

The administration of chemotherapy in clinical situations is limited frequently because of the associated toxicity to normal bone marrow cells, gastrointestinal epithelium, and other host tissues. Although nutritional support has been advocated to reduce chemotherapy-related toxicity in cancer patients, few studies substantiate this clinical impression. The current study was performed to determine the role of nutritional status and enteral nutrient intake as determinants of methotrexate (MTX) toxicity in a well-controlled, tumor-bearing animal model. After subcutaneous mammary tumor (AC-33) inoculation, 56 female Lewis/Wistar rats were assigned randomly to one of the following two nutritional regimens for 14 days: (1) protein-depleted chow (PC) (0.03% protein; 4.27 kcal/g) or (2) standard chow (RC) (22.0% protein; 3.50 kcal/g). After 7 days of dietary control, all animals received one of three weight-adjusted doses of MTX (5, 10, or 20 mg/kg intramuscularly [IM] ) or placebo. All animals received leucovorin rescue (0.6 mg IM) at 6 and 24 hours after MTX injection. Improved nutritional status was associated with a significant reduction in objective measures of MTX-related morbidity and mortality. At low doses of MTX (5 and 10 mg/kg), the mean duration of clinical signs of toxicity (i.e., hair loss, lethargy, and diarrhea) and severity of leukopenia were greater in protein-depleted (PD) animals. With high-dose MTX (20 mg/kg), mortality was increased significantly in PD animals (100%) compared with well-nourished animals (0%). Equivalent tumor response was observed in PD and well-nourished animals. Thus, improved nutritional status by enteral nutrition reduced the morbidity and mortality associated with MTX significantly in this tumor-bearing animal model.

Adenocarcinoma↗

Resting energy expenditure, body composition, and excess weight in the obese.

This study investigated differences between measured and predicted resting energy expenditure (REE) in 80 women who averaged 104.6 kg in weight and were 49 kg and 88% overweight. Body composition analysis showed that 68% of the excess weight was fat and 32% was fat-free mass (FFM). Normalized for height, total body potassium (TBK) was 113 +/- 15% and total body water (TBW) was 133 +/- 21% of values in nonobese controls. The health of the FFM, defined as the potassium content per kg of FFM, was 84 +/- 13% of normal. Measured and predicted REE were only modestly related (r = +.59), and only 59% of measured REEs were within 10% of predicted values. A stepwise multiple regression indicated that weight was the single best predictor of measured REE and that the size of the FFM made a significantly greater contribution to REE than did the size of the fat mass. Commonly used equations for the prediction of REE are not appropriate for moderately or severely obese patients. Caloric prescription for weight reduction must be tailored to individuals rather than recommending the same caloric intake to persons with varying metabolic rates.

Adipose Tissue↗

The link between nutritional status and clinical outcome: can nutritional intervention modify it?

Most clinicians subjectively feel that malnutrition in surgical patients is associated with poor clinical outcome. This overview provides a chronologic review of studies relating poor nutritional status to increased surgical morbidity. Techniques for identifying surgical patients with clinically important nutritional deficits are discussed. Retrospective and/or non-randomized clinical studies evaluating the efficacy of perioperative forced feeding are reviewed. These data suggest a possible role for preoperative nutritional support of selected malnourished surgical candidates and provide the rationale for a large-scale nutrition-intervention clinical trial.

Clinical Trials as Topic↗

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↗