Effect of amino acid infusion on glucose production in trauma patients.

The relationship between precursor supply and hepatic glucose output (HGO) was examined in 8 control subjects and 12 trauma patients after a fasting period of approximately 60 hours. Glucose kinetics were measured with a primed-constant infusion of [U-14C]glucose and [6-3H]glucose. The basal rate of HGO was 5.45 +/- 0.22 micromol x kg-1 x min-1 in the controls and 13.16 +/- 0.76 micromol x kg-1 x min-1 following trauma (p < 0.001). Four hours after amino acid infusion of 1.3 g x kg-1 x 24 h-1, HGO in the controls was unchanged at 5.35 +/- 0.22 micromol x kg-1 x min-1 but it had decreased to 11.71 +/- 0.67 micromol x kg-1 after trauma (p < 0.001). We conclude that increasing the supply of gluconeogenic precursors does not stimulate HGO in normal subjects after fasting or after severe trauma and that factors other than to availability of amino acids are responsible for the enhanced rate of HGO in trauma patients.

Impact of enteral feeding of a glutamine-supplemented formula on the hypoaminoacidemic response in trauma patients.

Plasma amino acid concentrations were measured during fasting and after 3 days of enteral feeding in 16 trauma patients on a glutamine-supplemented diet and 14 patients on an isonitrogenous control diet. During fasting, total amino acids, including glutamine, were depressed by 50% and this was attributed to a reduction in both essential and nonessential amino acids. The essential amino acid concentrations increased in both groups after feeding. The nonessential amino acid concentrations also increased in the control group but not in the glutamine group during feeding. Repletion of the glutamine extracellular pool was not evident after an average intake of 27.1 g per day of glutamine for 3 days. Nitrogen balance was similar for the two groups during feeding. We conclude that in this study, enteral glutamine did not increase the glutamine plasma concentration. In addition, both formulas improved the hypoaminoacidemia of essential amino acids but only the control diet improved the nonessential amino acids plasma concentration.

Relationship between low estrogen receptor values and other prognostic factors in primary breast tumors.

BACKGROUND: The current study compared the immunocytochemical expression of estrogen (ER) and progesterone (PgR) receptors by malignant breast cells to the hormone receptor concentrations reported from radioligand assays. These values were examined in relation to DNA ploidy and the fraction of cells in S phase. METHODS: ER and PgR concentrations, DNA ploidy, and S-phase fractions were measured by standard techniques with 124 samples of invasive ductal carcinoma. Suspensions of tumor cells were examined by immunocytochemical assay (ICA) for the percentages of ER and PgR positive cells. RESULTS: Twenty-six of the 38 tumors from patients 50 years of age or younger were classified as high S-phase fraction, and 28 tumors had aneuploid levels of DNA. The 20 ER positive tumors each contained less than 100 fmol/mg. Thirty-nine of the 86 tumors from patients older than 50 years were classified as high S phase, and 41 were aneuploid. Sixty-five samples were considered ER positive by radioligand assay. ICA showed that tumors in either age group with less than 40 fmol/mg did not contain ER positive cells. The proportion of samples with PgR levels between 10 and 100 fmol/mg was small, and fewer PgR positive tumors were categorized as negative when examined by ICA for receptor containing cells. The reclassification of the hormone receptor status of a tumor based on ICA appeared to be independent of S-phase and ploidy values. CONCLUSIONS: Tumors that are classified as ER or PgR positive based on accepted cutoff values for radioligand assays may actually be receptor negative because the tumors do not appear to contain receptor positive cells.

Protein and energy balance following femoral neck fracture in geriatric patients.

To elucidate the effect of total peripheral parenteral nutrition (TPPN) on protein kinetics following injury, we compared the whole-body leucine kinetic response using a primed-constant infusion of L-[1-14C]leucine in 33 elderly patients (aged 82 +/- 1.0 years) following hip fracture and 33 healthy elderly control subjects (aged 75 +/- 0.7 years). Following a 36-hour fast, leucine release from protein breakdown was 1.2 +/- 0.10 mumol.kg-1.min-1 and leucine incorporation into protein was 0.94 +/- 0.095 mumol.kg-1.min-1 in control subjects, and in injured subjects leucine release from protein breakdown was 1.3 +/- 0.14 mumol.kg-1.min-1 and leucine incorporation into protein was 0.97 +/- 0.092 mumol.kg-1.min-1. Control and injured subjects were then administered TPPN (protein, 1.5 g amino acids.kg-1; carbohydrate, 10.0 kcal.kg-1; lipid, 15.0 kcal.kg-1) for 24 hours, and leucine kinetics were redetermined. Compared with protein kinetics in the fasting state, leucine release from protein decreased to 1.0 +/- 0.14 mumol.kg-1.min-1 and leucine incorporation into protein increased to 1.16 +/- 0.097 mumol.kg-1.min-1 in control subjects. Injured patients also responded to TPPN with a decrease in leucine release from protein breakdown (1.12 +/- 0.156 mumol.kg-1.min-1) and an increase in leucine incorporation into protein (1.29 +/- 0.164 mumol.kg-1.min-1). These results indicate that in a geriatric population, whole-body leucine kinetics following hip fracture and the anabolic response to TPPN are not significantly altered from those of uninjured subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Management of coexistent carotid and coronary artery disease.

Simultaneous coronary artery bypass grafting (CABG) and carotid endarterectomy (CE) were done on 133 patients over an 8-year period. Twenty-seven patients (20%) had previous transient ischemic attacks (TIAs), 12 (9%) had previous strokes, and the remainder (71%) were asymptomatic. All asymptomatic patients had greater than 85% stenosis of the internal carotid artery demonstrated by noninvasive ultrasonography and four-vessel angiography. CE was performed prior to the sternotomy for coronary artery bypass, under the same anesthesia. Nineteen patients had bilateral carotid artery disease. Postoperatively, three patients (2.3%) suffered strokes, an additional three patients (2.3%) suffered transient upper extremity weakness, and one patient from each of these groups died. There were no postoperative strokes or TIAs in patients with bilateral carotid artery disease. Average length of hospital stay was 10 days. Our experience leads us to conclude that the morbidity and mortality of the simultaneous procedure are not affected by bilateral carotid artery disease. In patients with symptomatic coronary artery disease and symptomatic carotid artery disease or asymptomatic carotid artery disease with a high-grade stenosis, we think that simultaneous repair of both lesions should be done.

Protein turnover in advanced lung cancer patients.

Understanding the extent to which changes in whole-body protein kinetics contribute to the commonly observed weight loss and decrease in lean body mass (LBM) in patients with cancer is currently obscured by conflicting reports in the literature. While several studies have reported significant increases in whole-body protein turnover (WBPT), synthesis (WBPS), and catabolism (WBPC) in patients with cancer, others have failed to confirm these observations. We have measured whole-body protein kinetics using a primed constant infusion of 15N-glycine in a homogenous group of 32 newly diagnosed advanced lung cancer patients with comparable staging and before any antineoplastic treatment, and in 19 normal healthy volunteer controls. Urinary urea and ammonia 15N enrichment was determined in individually collected urine samples obtained during the 24-hour study period and averaged for the determination of protein kinetics. During the last 6 hours of urine collection, samples were obtained hourly for determination of 15N plateau enrichment. Twenty-four-hour urinary nitrogen and creatinine excretion was determined from 24-hour pooled urine samples. Resting metabolic expenditure (RME) was determined by indirect calorimetry and LBM was estimated from deuterium oxide dilution. Age body weight, LBM, RME, and 24-hour urinary nitrogen excretion did not differ between cancer and control subjects. WBPT, WBPC, and WBPS (g/kg/d) were significantly increased in lung cancer patients. However, when the same results were expressed either per kilogram LBM or per gram 24-hour urinary creatinine excretion, WBPT, WBPC, and WBPS rates were not statistically different from those of the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Glucose metabolism in advanced lung cancer patients.

Although it is generally accepted that altered nutrient intake and metabolism are responsible for the progressive loss of body weight observed in most advanced cancer patients, there is still considerable controversy regarding the contributory role of changes in both resting energy expenditure (REE) and glucose metabolism. Several studies suggest increases in both REE and glucose appearance in advanced cancer patients compared with healthy control subjects, whereas others revealed no changes in either metabolic parameter. We measured REE with indirect calorimetry and glucose kinetics with a primed constant infusion of D-[U-14C]glucose and D-[6-3H]glucose over the last 4 h of a 24-h fast in 32 advanced lung cancer patients immediately after diagnosis and before any chemotherapy or radiotherapy and in 19 healthy volunteer subjects. REE for the lung cancer group was not significantly different from that in the control group (1535.8 +/- 78.0 vs. 1670.2 +/- 53.9 kcal/day, respectively, p = 0.151). When REE was expressed as a function of body weight, or lean body mass, no differences between the two groups were observed. The rate of glucose appearance was 9.88 +/- 0.36 mumol.kg-1.min-1 in the cancer patients and 10.15 +/- 0.53 mumol.kg-1.min-1 in control subjects (p = 0.667), of which 50.4 versus 58.2%, respectively, was oxidized. The amount of glucose recycled was 13.54 +/- 1.22% in cancer patients and 15.08 +/- 0.99% in control subjects (p = 0.394). The amount of VCO2 from direct oxidation of glucose was 23.39 +/- 0.74% in cancer patients and 27.45 +/- 1.36% in control subjects (p = 0.006).(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma amino acid concentrations in geriatric control and hip-fracture patients.

Changes in plasma amino acids, 24-h nitrogen balances, and resting metabolic expenditures (RMEs) were measured in 10 geriatric patients (aged 70-92 y) with hip fracture 1 d after surgical fixation during both a 24-h fasting state and while receiving total peripheral parenteral nutrition (TPPN) for 24 h at 1.5 g amino acids.kg-1.d-1 and 29-30 kcal.kg-1.d-1 and compared with 19 healthy volunteer subjects (aged 70-84 y). RME and 24-h urinary nitrogen losses were also elevated in the trauma patients during both fasting and TPPN. Positive nitrogen balances were evident in both groups during TPPN. Plasma total amino acid concentration was significantly lower in the trauma patients because of lower plasma concentrations of the nonessential amino acids. Phenylalanine and methionine concentrations were significantly higher and lysine lower in the trauma group. In addition, evaluation of the essential amino acid ratios after fasting and TPPN reveal that there are no limiting amino acids during TPPN.

Effect of deoxyribonucleic acid ploidy status on survival of patients with carcinoma of the endometrium.

This retrospective study was performed to determine the clinical usefulness of deoxyribonucleic acid (DNA) ploidy and the amount of DNA in the nucleus of the tumor cell on the prognosis of patients with carcinoma of the endometrium. Five year follow-up study was obtained for 121 patients. Flow cytometric analysis was used to determine tumor cell ploidy from paraffin-embedded specimens. Patients were grouped according to ploidy, clinical stage and grade and whether or not they received postoperative radiation. The data were subjected to a Cox proportional hazards regression analysis, and only ploidy status and clinical stage were significantly associated with survival time. Of the 121 patients observed, 44.6 per cent were aneuploid and 55.4 per cent, euploid. Preliminary chi-square analysis indicated a strong survival advantage to those patients with euploid endometrial carcinoma. The over-all five year survival rate for patients with aneuploid tumors was 53.7 per cent, as opposed to 80.6 per cent for patients with euploid tumors (p less than 0.01). Eighty-seven patients were Stage I, 39 aneuploid, 48 euploid. The five year survival rate for patients with Stage I aneuploid was 71.8 versus 85.4 per cent for those who were euploid. Twenty-one patients were Stage II; seven aneuploid and 14 euploid. The five year survival rate for aneuploid patients was 14.3 versus 85.7 per cent for euploid patients. The over-all five year survival rate for those with Stage I and II was 85.5 per cent euploid and 63.0 per cent aneuploid, p less than 0.05. Patients with Stage III or IV had poor outcome regardless of ploidy status. These data show that patients with euploid Stage I and II carcinoma of the endometrium have a significant survival advantage over patients with aneuploid tumors. We, therefore, believe that ploidy status may be used to facilitate the determination of prognosis in carcinoma of the endometrium.

Protein C activity, stage of disease, and vascular thrombosis in colon carcinoma.

To determine the etiology of the increased incidence of postoperative deep venous thrombosis (DVT) in patients with carcinoma of the colon, serum levels of protein C were measured preoperatively in 65 patients with colorectal adenocarcinoma. Noninvasive lower-extremity Doppler studies were performed on all patients prior to discharge to assess patency of the deep veins. Six patients (9%) were found to have DVT. The protein C level was considered elevated if it was greater than 125% of control values and reduced if less than 75% of control values. The development of DVT was found to be independent of the serum carcinoembryonic antigen, albumin, total protein, hemoglobin, hematocrit, platelet count, prothrombin time, partial thromboplastin time, and the patient's age and percentage of ideal body weight. There was an inverse relationship between the protein C level (p less than 0.001), Dukes stage of the tumor (p less than 0.001), and the development of DVT. Linear regression analysis revealed that only the tumor stage and the protein C level could be used to predict the development of DVT. The data show that for these patients with colorectal malignancy, the development of DVT may be related to decreased levels of protein C.

Regulation of glucose kinetics in trauma patients by insulin and glucagon.

The current study was undertaken to evaluate the contribution of insulin and glucagon to regulation of glucose metabolism in man following severe, traumatic injury by manipulating concentrations of insulin and glucagon with infusions of somatostatin. Glucose kinetics were assessed with [U-14C, 6-(3)H]glucose in severely injured patients and compared with data obtained from patients recovering from minor, elective operative procedures. Glucose production was significantly increased in subjects with traumatic injury compared with control subjects (13.0 +/- 0.63 mumol/kg/min v 8.6 +/- 0.27 mumol/kg/min). There was no impairment in glucose oxidation by the injured patients. Modulation of insulin and glucagon with somatostatin indicated that non-insulin-mediated glucose uptake (NIMGU) was significantly elevated in injured patients (12.2 +/- 0.94 mumol/kg/min v 7.4 +/- 0.61 mumol/kg/min). Hepatic glucose output (HGO) in the absence of glucagon was also significantly elevated in injured patients (12.2 +/- 1.20 mumol/kg/min v 5.8 +/- 1.08 mumol/kg/min). Indirect calorimetry showed a 27% increase in resting energy expenditure (REE). Increased protein oxidation accounted for 56% of the increase in REE. Changes in carbohydrate and lipid oxidation accounted for 28% and 15% of the increase in REE. There was no correlation between the injury severity score of the injured patient and the degree of metabolic abnormality. It is concluded from these studies that (1) injured patients have a high rate of glucose turnover in the absence of glucagon and insulin; (2) the reliance on glucose as a source of energy is not diminished in injured subjects; and (3) increases in protein oxidation account for the majority of the increased REE found in injured patients.

Prognostic applications of DNA analysis in solid malignant lesions in humans.

Analysis of the DNA of tumors using flow cytometry is a technologic method that can be used to investigate the biologic nature of tumors. While not conclusive, results suggest that this biologic information may be useful in identifying patients with malignant disease who have a worse prognosis. The differentiation of patients with aneuploid tumors into those with hypoploid tumors and those whose tumors are hyperploid may be a further refinement of the technique. Also, a combination of this biologic criteria may allow a more accurate selection of patients than either method alone. Further investigative work needs to be done to fully evaluate the clinical usefulness of flow cytometric DNA analysis and answer these and other questions.

Whole-body protein kinetics in elective surgical patients receiving peptide or amino acid solutions.

We compared the efficacy of two enteral solutions that were isonitrogenous and of identical amino acid composition but differed in that one solution contained only free amino acids whereas the other contained a mixture of free amino acids and peptides. Protein kinetics and nitrogen balance were evaluated in a group of six elective surgical patients. Primed-constant infusion with 15N-glycine was started 24h after gynecologic surgery and sustained over 3 days. During the first postoperative day, patients received enteral 0.45% saline. During postoperative days two and three, the patients received either the free amino acid solution or the mixture of peptides and free amino acids in a crossover design. There were no differences in protein kinetics or nitrogen balance with the two treatments.

A physiologic basis for the provision of fuel mixtures in normal and stressed patients.

It has been suggested that lipid is a preferred fuel in stressed patients. We evaluated glucose oxidation in 20 patients (sepsis, cancer of the colon, multiple trauma, controls) while they received TPN (5.65 mg glucose/kg/min). Respiratory quotient (RQ) was measured by indirect calorimetry and the percent VCO2 arising from the oxidation of glucose was measured using [U-14C] glucose. Since RQs were 1.0 or greater in all patients, the nonprotein energy utilized by them was calculated to be derived completely from glucose. However, the kinetic data showed that glucose contributed only 55-60% of the VCO2. Protein oxidation contributed less than 20% of the VCO2, as calculated from urinary nitrogen. The difference must have been derived from fatty acid oxidation. The glucose turnover that was not oxidized was presumed to be converted to lipid at an RQ of 8.6. The net oxygen consumption and carbon dioxide production from this overall distribution resulted in an RQ of about 1.0 with only 60% coming from glucose oxidation. Since all patients responded in the same manner, it appears that the proper ratio of glucose and lipid was dictated on a physiologic basis and not on the type of disease.

Comparison of three methods for the estimation of total nitrogen losses in hospitalized patients.

Since the measurement of total nitrogen output (TNO) is not routinely determined in the clinical setting, its level is frequently estimated using formulas based on the urinary urea nitrogen excretion (UUN). We measured TNO in 124 surgical patients over 990 days (TNO, 19.22 +/- 8.72 g N/day; total urinary nitrogen (TUN) 18.17 +/- 8.70 g N/day; UUN, 15.17 +/- 7.70 g N/day; mean gastrointestinal nitrogen (MGIN) 0.68 +/- 0.49 g N/day; integumental nitrogen (ITGN), 0.34 +/- 0.08 g N/day) and compared the results with the daily estimations using three different formulas: formula A, UUN + 4; formula B, UUN x 1.20 + 1.05, where 1.20 is the reciprocal of the mean ratio UUN/TUN and 1.05 the mean extraurinary nitrogen losses; and formula C, UUN x 1.0986 + 2.55, derived from the regression analysis of UUN vs TNO. TNO estimated by these formulas were 19.17 +/- 7.70, 19.26 +/- 9.24, and 19.22 +/- 8.70 g N/day, respectively. The regression analyses of the estimated TNO from the three formulas versus the measured TNO indicated that formulas A, B and C were equally accurate in estimating TNO over the entire range of UUN. However, when only values of UUN greater than or equal to 30 g N were considered, a modified formula A (UUN + 6) was the best predictor of TNO. Daily audits of the differences between the estimated and measured TNO showed comparable results for the three formulas. In 28.4 to 31.1% of the observed days the differences were higher than +/- 2 g N/day, an error which is not acceptable when estimating the protein requirements in many clinical conditions.(ABSTRACT TRUNCATED AT 250 WORDS)