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Biomedical subjects

M E Burt

Publications and source records attributed to M E Burt.

At least 91 records · Page 5Linked to original sources
PubMed1985

Fasting plasma amino acid levels in cancer patients.

The concentration in plasma of 15 fasting amino acids were measured in 14 control volunteers and 55 cancer patients. In addition, 16 patients (7 with, 9 without total parenteral nutrition [TPN] ) with metastatic sarcoma had sequential amino acid profiles measured during 6 weeks of ablative chemotherapy. In four cancer patient groups (lymphoma, sarcoma, osteosarcoma and metastatic sarcoma) with no or minimal weight loss, most plasma amino acid levels were similar to controls. Proline levels were significantly reduced in the lymphoma and sarcoma patients. Esophageal cancer patients with 20% body weight loss had a marked reduction in total and individual amino acid levels (except branched chain amino acids) compared to controls and all others. The metastatic sarcoma patients who received parenteral nutrition had higher levels of plasma lysine and tyrosine during chemotherapy than controls; however, TPN failed to change the majority of amino acid levels. It appears that plasma amino acid levels except proline were well maintained in cancer patients without weight loss. Esophageal cancer patients with weight loss demonstrated marked reduction in all circulating amino acids except branched chain. Parenteral nutrition did not significantly alter the amino acid profile of cancer patients undergoing chemotherapy.

Adolescent↗
PubMed1984

Whole-body protein metabolism in cancer-bearing patients. Effect of total parenteral nutrition and associated serum insulin response.

Aggressive nutritional support of the cancer patient undergoing treatment has become widespread standard practice. In order to evaluate the effect of total parenteral nutrition (TPN) on protein metabolism, 11 patients with localized squamous cell carcinoma of the distal esophagus were studied in the postabsorptive state and again after 2 weeks of TPN. After two weeks of TPN, these cancer patients demonstrated a significant increase in body weight associated with positive nitrogen balance and an insignificant increase in total body potassium (determined by whole body 40K scanning), a measure of lean body mass. Serum transferrin, ceruloplasmin, and total protein did not change significantly, whereas serum albumin decreased significantly (3.5 +/- 0.1 to 3.1 +/- 0.1 g dl-1). Evaluation of whole-body protein kinetics by constant infusion of 15N-glycine demonstrated a significant increase in protein flux (2.79 +/- 0.20 to 4.02 +/- 0.33 g protein kg-1 day-1). In the group as a whole, protein synthesis increased and catabolism decreased, but not significantly. Skeletal muscle protein catabolism, as measured by the rate of excretion of urinary 3-methylhistidine (mumol kg-1 day-1) decreased significantly after 2 weeks of TPN (2.5 +/- 0.1 to 1.9 +/- 0.2). A change from basal to stimulated (TPN) serum insulin level of 40 to 120 microU/ml was found to be associated with optimal changes in protein synthesis and skeletal muscle catabolism. Five patients fell within this optimal range of serum insulin, and demonstrated a significant increase in the rate of wholebody protein synthesis (2.13 +/- 0.35 to 3.56 +/- 0.45 g protein kg-1 day-1) with an insignificant increase in whole-body protein catabolism (2.74 +/- 0.42 to 3.16 +/- 0.43), and a significant decrease in urinary 3-methylhistidine excretion (2.50 +/- 0.35 to 1.53 +/- 0.24) after 2 weeks of TPN. It is concluded that optimum nutritional support with TPN is beneficial to the cancer patients' protein economy by stimulating whole body protein synthesis while decreasing skeletal muscle protein catabolism. It is also concluded that there exists a range of serum insulin in which whole-body protein synthesis and catabolism are optimized.

Body Weight↗
PubMed1983

A controlled, randomized trial evaluating the effects of enteral and parenteral nutrition on protein metabolism in cancer-bearing man.

To characterize the effects of enteral versus parenteral nutritional support on protein metabolism in the cancer patient, patients with localized, squamous cell carcinoma of the distal esophagus were randomized to receive nutritional support as follows: (1) if there was a loss of less than 20% of the preillness body weight, patients were randomized to continue eating ad libitum (group I) versus receiving total parenteral nutrition (TPN) (group II); (2) if there was a loss greater than 20% of the preillness body weight and/or the patient was unable to swallow, patients were randomized to jejunostomy feedings (group III) versus TPN (group IV). Patients were initially studied in the postabsorptive state and again 2 weeks after beginning, and while receiving, enteral or parenteral feedings. Stable isotopic tracer methods utilizing constant infusion of [15N]glycine were used to determine whole-body protein turnover (flux), synthesis, and catabolism. Skeletal muscle catabolism was determined by measuring the urinary excretion of 3-methylhistidine and lean tissue mass was evaluated by determining total-body potassium by 40K whole-body scanning. Positive nitrogen balance was obtained in groups II and IV associated with significant weight gain in both; the changes in weight were not significant in groups I and III. Whole-body protein flux increased in all groups, but significantly only in group II. Synthesis increased in groups II and IV and decreased in I and III, but not significantly. Catabolism tended to decrease in all groups but group I. Urinary 3-methylhistidine excretion decreased in groups II and IV signifying decreased skeletal muscle catabolism, but increased in groups I and III. Total body potassium tended to increase in groups II and IV. In this group of patients with localized squamous cell carcinoma of the esophagus, both TPN and jejunal feedings tended to stabilize nutritional status and whole-body protein economics. TPN appeared to be slightly more efficacious, although the differences between enteral and parenteral nutritional support in this study were slight.

Aged↗
PubMed1983

Peripheral tissue metabolism in cancer-bearing man.

Whole-body tracer studies have documented abnormal glucose and amino acid kinetics in cancer-bearing man. Whether these abnormalities are related to systemic or local tumor effects is questioned. Forearm metabolism was examined in six patients with localized squamous cell carcinoma of the distal esophagus and six healthy normal male volunteers. Substrate arterio-venous differences and blood flow across forearm tissues were determined and substrate flux calculated. The mean forearm blood flow (ml min-1 100 ml forearm-1) was not significantly different between cancer patients (3.67 +/- 0.12) and normal subjects (2.80 +/- 0.40). The uptake of glucose (mumol min-1 100 ml forearm-1) was significantly higher in cancer patients (1.99 +/- 0.45) compared to control subjects without weight loss (0.47 +/- 0.18). Lactic acid release (mumol min-1 100 ml forearm-1) was significantly higher in cancer patients (-1.15 +/- 0.35) compared to control subjects (-0.26 +/- 0.14). There was no significant difference in the flux of individual amino acids between the groups, although the mean total nitrogen released from forearms of cancer-bearing patients was greater than that from normal controls. The arterial serum insulin level was significantly lower and the arterial plasma glucagon level significantly higher in cancer patients compared to control subjects. These data cannot be explained by weight loss alone and suggest a peripheral defect in metabolism in this group of cancer-bearing patients.

Adult↗
PubMed1982

A controlled, prospective, randomized trial evaluating the metabolic effects of enteral and parenteral nutrition in the cancer patient.

In order to evaluate the metabolic effects of enteral versus parenteral nutritional support in the cancer patient, patients with localized, squamous cell carcinoma of the distal esophagus were randomized to one of three nutritional regimens: oral feeding, jejunal feeding, or total parenteral nutrition (TPN). Patients were initially studied in the postabsorptive state and again two weeks after beginning, and while receiving, enteral or parenteral feedings. Radioisotopic tracer methods were utilized to evaluate parameters of glucose and alanine kinetics, and arterial substrate and hormone levels were measured. Arterial plasma glucose and blood lactate levels increased and plasma free fatty acid, serum triglyceride, and serum cholesterol levels decreased to comparable levels in patients receiving jejunal feedings or TPN. Changes in serum insulin, plasma glucagon, serum cortisol, serum growth hormone, and serum thyroxine were similar in patients receiving enteral and parenteral nutrition. Enteral and parenteral nutrition also had comparable effects on both alanine and glucose kinetics. In particular, both jejunal feedings and TPN were equally efficacious in markedly suppressing gluconeogenesis in the cancer patient. Our data would support the conclusion that there are few, if any, differences in the measured metabolic effects of enteral venous parenteral nutritional support in the group of cancer patients studied.

Aged↗
PubMed1982

The impact of total parenteral nutrition on liver function tests in patients with cancer.

In 143 patients undergoing 199 cycles of total parenteral nutrition (TPN), alkaline phosphatase (AP), serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic-pyruvic transaminase (SGPT), direct bilirubin (DB), total bilirubin (TB), and lactic dehydrogenase (LDH) were measured and recorded before initiating TPN and weekly for seven weeks or until TPN was discontinued. Patterns of change were elevations and then plateaued. Direct bilirubin, TB and LDH showed no significant change. The patterns were independent of patient age, amount of fat emulsion administered, tumor burden, and nonprotein calorie to basal energy expenditure ratio.

Adolescent↗
PubMed1982

Multi-enzyme-targeted chemotherapy by acivicin and actinomycin.

On the basis of our observation of the increased specific activities of glutamine-utilizing enzymes in purine and pyrimidine metabolism in hepatoma 3924A, and because the concentration of glutamine is ten times lower in the hepatomas than in the liver, the biochemical pharmacology of the anti-glutamine agent, acivicin, was examined. (1) Acivicin competitively inhibited the activities of amidophosphoribosyl-transferase, CTP synthetase and carbamoyl-phosphate synthetase II from extracts of liver and hepatoma 3924A. (2) In addition to the competitive inhibition exerted by acivicin, evidence was obtained that this drug also irreversibly inactivated in vitro the glutamine-utilizing enzymes. It is particularly relevant for the selectivity of acivicin that the activity of aspartate carbamoyltransferase, an enzyme present in the same complex as carbamoyl-phosphate synthetase II, was not affected by the anti-glutamine agent. (3) Acivicin in vivo brought down the activities of glutamine-utilizing enzymes in a period of 10 min to 1 hr after injection. CTP synthetase activity declined to less than 10% of that observed in the uninjected rats. The decreases were not reversible by various in vitro methods, but in vivo the activities returned to normal range in 72 hr. (4) The activity of aspartate carbamoyltransferase, which exists as a multi-enzyme complex with synthetase II, was not altered by acivicin injection. Similar results were observed in transplantable sarcoma in the rat. (5) The acivicin-induced decrease in enzymic activities could not be restored by purification of the enzymes. (6) In vitro studies indicated that addition of acivicin to liver or hepatoma extracts or purified enzymes rapidly decreased enzymic activities; the activities could not be restored. These results are consistent with an interpretation that acivicin acts either as a tight-binding inhibitor or as an inactivator through alkylation of the enzymes of glutamine utilization. (7) Acivicin in combination with actinomycin provided a synergistic kill of hepatoma cells in tissue culture and also inhibited the growth of transplantable solid hepatoma 3924A in the rat. (8) The synergistic biological results of combination chemotherapy with acivicin and actinomycin can be accounted for by the action of acivicin in inhibiting GMP and CTP synthetases, resulting in a decrease in GTP and CTP content, and by the actinomycin-caused inhibition of RNA polymerase in selectively blocking the utilization of GTP and CTP.

Animals↗
PubMed1982

Serum vitamin level maintenance in cancer patients on total parenteral nutrition.

The quantity of water and fat soluble vitamins required to maintain serum levels in cancer patients on total parenteral nutrition (TPN) has yet to be determined. A prospective evaluation of our current intravenous vitamin regimen during TPN was performed in order to define these requirements. Seventy-five patients receiving 97 TPN courses for seven to 60 days were studied. Serum levels of vitamins A (74 courses), B12 (85), folate (62), C (97), and 25-OH-cholecalciferol (25-OH-D) (9) were available for analysis. Daily vitamin intakes were recorded and serum levels were determined weekly. Restoration and maintenance of normal mean serum vitamin levels were achieved for all but 25-OH-D. However, analysis of individual courses in previously depleted patients revealed that serum levels were not restored in three patients (4%) for vitamin A and six patients (66%) for 25-OH-D. A TPN regimen designed to provide the following weekly vitamin quantities: A: 21,000 IU, D: 2100 IU, C: 3500 mg, B12: 126 micrograms, and folate: 7 mg will maintain mean serum vitamin levels for all but 25-OH-D. This regimen has the ability to uniformly restore and maintain vitamins B12, C, and folate in all patients but not in those patients previously deficient in vitamins A and D.

Adult↗
PubMed1982

Glucose metabolism and the percentage of glucose derived from alanine: response to exogenous glucose infusion in tumor-bearing and non-tumor-bearing rats.

Glucose and alanine metabolism were investigated in non-tumor-bearing (NTB) and tumor-bearing (TB) male F344 rats after a 24-hr fast and during the infusion of either 0.9% NaCl solution or glucose at 0.67 or 2.35 mg per 100 g total body weight per min. During 0.9% NaCl solution infusion, the plasma glucose level was higher (98.2 +/- 4.0 versus 85.8 +/- 8.1 mg per di; p less than 0.05), the whole-blood lactate level was lower (5.8 +/- 0.8 versus 8.3 +/- 1.6 mg per di; p less than 0.05), the glucose turnover rate was lower (0.72 +/- 0.04 versus 0.88 +/- 0.13 mg per 100 g total body weight per min; p less than 0.05), alanine turnover rate and the percentage of glucose derived from alanine was measured by [14C]alanine in the NTB and compared to the TB animals. In response to glucose infusions, the whole-blood lactate level rose in both groups but remained lower (7.1 +/- 0.9 versus 10.5 +/- 2.4 mg per dl at 0.67 mg per 100 g total body weight per min, p less than 0.05; 9.1 +/- 1.1 versus 19.3 +/- 5.5 mg per dl at 2.35 mg per 100 g total body weight per min, p less than 0.05; NTB versus TB) in the NTB than in the TB animals. The endogenous production rate of glucose as measured by [3H]glucose displayed a similar response to exogenous substrate in the NTB and TB animals but required a higher plasma glucose concentration to effect a similar degree of suppression in the TB group. The alanine turnover rate rose to a similar level, and the percentage of glucose derived from alanine was similarly depressed in the NTB and TB animals at each glucose infusion rate.

Alanine↗
PubMed1981

Metabolic alterations in a noncachectic animal tumor system.

The increased energy expended by the host to synthesize substrate, which is utilized by the tumor, is a potential cause of cancer cachexia. In vivo glucose and alanine kinetics were examined by tracer methodology in a sarcoma-bearing rat model. The effects of 3-mercaptopicolinic acid, a potent inhibitor of gluconeogenesis, was also examined on this model. Both tumor-bearing (TB) and nontumor bearing (NTB) animals were gaining weight prior to study and the tumors were relatively small. The TB animals had significantly lower plasma glucose and higher blood lactic acid levels compared with NTB animals. After inhibition of gluconeogenesis, the plasma glucose decreased and the blood lactate increased significantly more in TB than NTB animals. The glucose turnover rate was significantly greater in TB compared with NTB animals, as was the rate of glucose recycling and the rate of gluconeogenesis (alanine leads to glucose), both energy demanding processes. These results suggest that the tumor-bearing animal, even prior to significant cachexia, has an excess demand for energy, the provision of which may be a significant factor in malignant cachexia.

Alanine↗
PubMed1981

Germ-cell tumors in patients with apparently normal testes.

Germ-cell tumors occasionally occur in patients with clinically normal testes. Although data exist correlating serial serum hCG and AFP in gem-cell neoplasms of testicular origin, the literature is sparse concerning the patients presenting with clinically normal testes. Presented in this report are data to confirm the reliability and usefulness of serial serum hCG and AFP levels in those patients with extragonadal germ-cell tumors and apparently normal testes. Six patients with nonseminomatous extragonadal tumors are presented. Serial serum hCG and AFP levels correlated with the clinical course in each of the patients. The serum hCG and/or AFP decreased with response to therapy and increased with progression of disease. It is concluded that serial serum hCG and AFP determinations are very useful parameters to evaluate and follow the course of disease in this group of patients.

Adult↗
PubMed1981

Prospective evaluation of aspiration needle, cutting needle, transbronchial, and open lung biopsy in patients with pulmonary infiltrates.

Twenty consecutive patients with pulmonary infiltrates undiagnosed by routine, noninvasive methods were entered into a prospective study designed to evaluate the diagnostic yield of four methods of lung biopsy. Percutaneous aspiration needle, cutting needle, transbronchial, and open (anterior thoracotomy) biopsy were performed synchronously on all patients. Specimens were evaluated by microbiological, virological, and pathological methods. The diagnostic yields of the four methods were as follows: aspiration needle, 29%; cutting needle, 53%; transbronchial, 59%; and open lung biopsy, 94%. Open lung biopsy was significantly better in yielding a diagnosis than aspiration needle (p less than 0.001), cutting needle (p less than 0.001), and transbronchial biopsy (p less than 0.04).

Adolescent↗
PubMed1981

Glucose turnover and gluconeogenesis in a patient with somatostatinoma.

Previous evidence has documented the hyperglycemia and glucose intolerance that occur during prolonged infusions of somatostatin and in patients with somatostatinoma. We studied glucose utilization and production and gluconeogenesis (from alanine) in a patient with the somatostatinoma syndrome (peripheral somatostatin levels 20,000 pg/ml) during saline (basal state) and glucose infusion (1.78 mg/kg . min). Plasma glucose levels increased from 163 to 229 mg/100 ml during glucose infusion, whereas lactate, free fatty acid, and glucagon levels did not change. Endogenous glucose production decreased from 7.34 to 0.0 mumol/kg . min, and the percentage of glucose derived from alanine also decreased from 10.5 to 7.4. Glucose clearance decreased from 0.81 to 0.74 cc/kg . min and suggests that the hyperglycemia of the somatostatinoma syndrome is secondary to reduced peripheral glucose utilization secondary to relative insulin deficiency.

Adenoma, Islet Cell↗