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Biomedical subjects

J L Mullen

Publications and source records attributed to J L Mullen.

At least 73 records · Page 4Linked to original sources

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↗

Alteration of tumor cell kinetics by pulse total parenteral nutrition. Potential therapeutic implications.

Previous work has demonstrated that substrate-induced alterations of tumor metabolism can be exploited to potentiate tumor response to cycle-specific chemotherapy (methotrexate, Adriamycin [doxorubicin] ). This study was performed to investigate the biologic mechanism responsible for this phenomenon by determining the effect of short-term total parenteral nutrition (TPN) on tumor cytokinetics. Forty-two female Lewis/Wistar rats with subcutaneous mammary tumor implants (AC-33) underwent superior vena caval cannulation, and were randomized to receive either TPN or normal saline intravenously. Animals receiving TPN were killed at 2, 6, 12, 24, and 48 hours after initiating TPN; control animals given normal saline were killed at 0, 24, and 48 hours after randomization. At the time animals were killed tumor cytokinetic analysis was performed by flow cytophotometry. The percentage of tumor cells in S-phase was significantly increased in animals after only 2 hours of TPN (55.5 +/- 9.1%) compared with the control group (43.7 +/- 7.7%) (P less than 0.01). The ratio of sensitive/resistant tumor cells to S-phase-specific chemotherapy was effectively increased in animals receiving adjuvant TPN (1.31 +/- 0.43) compared with control animals (0.80 +/- 0.25) (P less than 0.015). This alteration in tumor cytokinetics provides one explanation for the enhanced tumor response to cycle-specific chemotherapy previously observed with pulse TPN administration.

Adenocarcinoma↗

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↗

Alteration in pyruvate metabolism in the liver of tumor-bearing rats.

Weight loss associated with tumor burden has been postulated to be due to an energy imbalance resulting from increased hepatic gluconeogenesis secondary to Cori cycle activity. The mechanisms which control pyruvate metabolism are inherent to the control of gluconeogenesis in the liver. Therefore, the metabolism of pyruvate was evaluated in a transplanted tumor model in rodents which has previously shown an increased rate of hepatic gluconeogenesis. Female Lewis-Wistar rats received a s.c. injection of a suspension of mammary tumor cells in the left flank. Tumor-bearing rats were allowed ad libitum food consumption, and non-tumor-bearing controls were pair-fed to the consumption of their tumor-bearing cohorts. At Days 12, 13, and 14 following inoculation, tumor-bearing and non-tumor-bearing controls were used for in vivo body composition analysis or subjected to isolated liver perfusion. Animals were not fasted prior to sacrifice. Pyruvate use by the livers of tumor-bearing and pair-fed non-tumor-bearing rats was evaluated in the presence of 8 mM glucose and 5 mM lactate. Pyruvate clearance was increased by 270%, and pyruvate intake was increased by 212% compared to pair-fed non-tumor-bearing rats. Oxidation of pyruvate to CO2 was increased 130%, and pyruvate conversion to lactate was increased by 197% above that seen in pair-fed non-tumor-bearing rats. Gluconeogenesis from pyruvate was increased by 184% in tumor-bearing rats. The increased gluconeogenesis in tumor-bearing rats above that of control animals at a 5 mM lactate concentration suggests that some factor, other than substrate supply, may stimulate gluconeogenesis in tumor-bearing rats. Although the use of pyruvate was greater in tumor-bearing rats, the disposal of pyruvate carbon into CO2, lactate, and glucose was proportionally the same in both groups. Therefore, these data suggest that the increased metabolism of pyruvate in tumor-bearing rats is controlled by a mechanism affecting cellular pyruvate transport.

Animals↗

Nutritional assessment in the seriously ill patient.

A consensus definition of malnutrition does not exist. We define "clinically relevant malnutrition" as the state of altered nutritional status that adversely affects clinical outcome. Over four years we have attempted to delineate a clinically applicable and validated nutritional assessment approach. This was accomplished through multiple clinical studies on a large number of surgical patients many of whom were seriously ill. Although an initial prospective study in 64 patients confirmed the relationship between certain nutritional markers and outcome, we found that 97% of patients had at least one abnormality, while 35% had three or more abnormalities, clearly documenting the imprecision in unselected battery testing. In a subsequent retrospective analysis of 161 patients, serum albumin (Alb), serum transferrin (TFN), triceps skinfold (TSF), and skin test reactivity (DH) proved to be the best markers of clinically relevant malnutrition and their relative quantitative importance is embodied in our Prognostic Nutritional Index (PNI), where PNI (% risk) = 158 - 16.6 (Alb) - 0.78 (TSF) - 0.20 (TFN) - 5.8 (DH). In numerous prospective studies of different patient groups, a large percentage of which were critically ill, the PNI has been shown to be a reliable nutritional assessment tool for diagnosing clinically relevant malnutrition. Furthermore, we have shown that seriously malnourished patients classified by the PNI will clinically benefit from preoperative nutritional support. The relevance of baseline and serial nutritional assessment to the nutritional care of the critically ill patient is discussed.

Critical Care↗

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 less than 90% of predicted), normometabolic (90-110% of predicted) or hypermetabolic (greater than 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 less than 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 less than 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.

Aged↗

Adjuvant, pulse total parenteral nutrition and tumor response to cycle-specific and cycle-nonspecific chemotherapy.

Previous work has demonstrated that substrate-induced alterations of tumor metabolism can be exploited to enhance tumor response to a cycle-specific chemotherapeutic agent (methotrexate). This study was designed to further investigate the biologic mechanism of this phenomenon by determination of tumor response to additional cycle-specific (Adriamycin) and cycle-nonspecific (Cytoxan) chemotherapeutic agents. Significant potentiation of tumor response during adjuvant total parenteral nutrition (TPN) was observed with methotrexate and Adriamycin but not with Cytoxan. This may imply that tumor sensitization by adjuvant TPN occurs by acceleration of the growth rate of proliferating tumor cells and not by recruitment of dormant tumor cells into the cell cycle.

Adenocarcinoma↗

Resting energy expenditure in morbid obesity.

Resting energy expenditure (REE) was measured in 112 morbidly obese adults prior to elective gastric bypass surgery. The patients studied ranged from 157 to 327% of ideal body weight. Standard nutritional assessment indices (serum total protein, albumin, total iron binding capacity, hematocrit, and white blood cell count) were within normal limits. REE was estimated by the Harris-Benedict formula using both current weight and ideal weight. Measured REE was significantly less than expected (p less than 0.01) using current weight and significantly greater than expected (p less than 0.01) when ideal weight was used as the standard. Linear regression analysis between standard indices that reflect resting metabolic rate in normal adults and measured REE in study patients did not demonstrate sufficient correlation to be clinically useful in this patient population. Standard surgical therapy may result in highly variable weight loss in this population if the wide range of resting energy expenditure and the consequential variability in individual caloric deficits is not considered. Standard predictors do not identify those patients likely to be unsuccessful with a given weight loss regimen.

Adult↗

A prospective study of prolonged central venous access in leukemia.

A three-year prospective study was conducted to evaluate right atrial silicone elastomer catheters for long-term venous access in adults with acute leukemia. Objectives included establishing the safety of catheter insertion in thrombocytopenic patients and the feasibility of maintaining the catheter during septicemia. Seventy-one catheters were placed in 57 consecutive patients entering intensive leukemia therapy. Excessive bleeding occurred at three catheter insertion sites. Eight catheter-related infections occurred. In 34 of 36 noncatheter-related and two catheter-related bacteremias, catheters were left in place with intensive monitoring. In 20, bacteremia cleared. Fourteen patients died; in eight autopsies, no evidence of catheter-related mortality was found. Catheters were in use 6,799 days, including 3,932 home use and 2,570 granulocytopenic days. The data indicate that thrombocytopenia does not preclude catheter insertion and that catheters can be safely maintained in septicemic granulocytopenic patients.

Acute Disease↗

Parenteral nutrition and human gastrointestinal tumor protein metabolism.

UNLABELLED: We determined the tissue free amino acid distribution in human gastrointestinal tumors and the adjacent normal tissue in two groups of patients. The patients were maintained on dietary control for 7--10 days prior to the surgical removal of the tumor. Patients in Group I ate the house diet ad lib. Their nutritional intake was about half their normal requirement. The second group received parenteral nutrition. Both groups were equally malnourished at the beginning of the period of nutritional control. Group I were 88.2 +/- 7.8% of ideal body weight and Group II, 90.6 +/- 13.8% of ideal body weight. The net calorie and nitrogen intake was about double that of Group I. Tissue-free amino acid analyses were done by gas chromatography. RESULTS: There was a statistically significant increase in the essential amino acids in the tumor tissue relative to the normal tissue in Group II, in contrast to the orally fed Group I where no discernible differences were found.

Amino Acids↗

Peritoneovenous shunt for hydrothorax associated with ascites.

Two patients with massive hydrothorax associated with ascites resistant to intensive long-term medical management were treated by insertion of a peritoneovenous (LeVeen) shunt. In each case the effusion was resolved within one month after insertion. With one revision each, the two shunts have remained clear for nine and 18 months. The peritoneovenous shunt is an alternative to medical therapy for large effusions. Its effectiveness in resolving them supports the idea that diaphragmatic defects help cause their formation.

Adult↗

Preoperative total parenteral nutrition and surgical outcome in patients with inflammatory bowel disease.

Further trials are needed to identify the preoperative patient who will have a significantly improved postoperative outcome with the use of total parenteral nutrition. Better nutritional markers are needed to evaluate the response to total parenteral nutrition and to help identify the irreducible minimum that should be given. In our series, patients who received preoperative total parenteral nutrition for at least 5 days had significantly fewer postoperative complications (p less than 0.05) than those who did not. All patients with postoperative complications had either a preoperative serum albumin level less than 3.5 g/dl or a serum transferrin level less than 150 mg/dl. Preoperative total parenteral nutrition for at least 5 days is strongly recommended in patients with inflammatory bowel disease who have severe protein depletion.

Adult↗

Immunocompetency in anorexia nervosa.

Twenty-two consecutively admitted patients diagnosed for anorexia nervosa were evaluated for cellular immune functioning by means of an anergy panel to test delayed hypersensitivity. The panel included candida, streptokinase-streptodornase, and mumps antigen administered by a standard protocol. A standard nutritional profile including current weight, usual weight, total protein, albumin, total iron-binding capacity, white blood cell count, total lymphocyte count, triceps skinfold, and arm muscle circumference was concurrently compiled on these subjects. Six of 22 patients studied were anergic. Visceral protein measures were generally within normal limits even in the most depleted patients. Malnutrition as measured by severity of weight loss and triceps skinfolds was significantly related to anergy, whereas visceral protein indicators (serum albumin, total iron binding capacity, transferrin) were not correlated with anergy. Anergy appeared to be related more strongly to anthropometric indices of malnutrition than to visceral protein values. Cellular immunity was generally preserved until weight loss was far advanced.

Adult↗

Caloric requirements in patients with inflammatory bowel disease.

Measured resting energy expenditure (REE) was compared to predicted basal energy expenditure (BEE) in 35 consecutive patients with nonseptic inflammatory bowel disease (IBD) and 20 healthy volunteers. Patients with IBD were groups greater or less than 90% ideal body weight (IBW). The BEE in kcal/day was found to be equivalent to the measured REE in both patient groups. It is suggested that the BEE be used to determine caloric requirements in nonseptic patients with inflammatory bowel disease. Patients less than 90% IBW had significantly higher measured energy expenditure (26.4 +/- 1.0) per kg body weight than either controls (21.2 +/- 0.7) or patients greater than or equal to 90% IBW (21.2 +/- 0.8), p less than 0.001. It is suggested that this increased expenditure is due to a combined effect of weight loss and intrinsic disease.

Adult↗