Biomedical subjects

M Jeevanandam

Publications and source records attributed to M Jeevanandam.

At least 55 records · Page 3Linked to original sources

PubMed1990

Effects of glucose on fuel utilization and glycerol turnover in normal and injured man.

Rates of fat mobilization (glycerol turnover), and fuel utilization and energy expenditure (indirect calorimetry) were measured in normal subjects and injured or septic patients maintained on high or low iv intakes of glucose as their sole nutrient source during 3-day periods. Regimens were given consecutively to each subject in random order. Concentrations of glucose, glycerol, fatty acids, 3-hydroxybutyrate, urea, insulin, and glucagon were determined in plasma, and of epinephrine and norepinephrine in urine. In normal subjects, there was no increase in energy expenditure with increasing glucose, although estimated costs of glucose storage as glycogen or fat could account for an increase of 4%. Thus, storage costs of glucose do not necessarily constitute an obligatory increase in energy expenditure. Rates of glycerol turnover and fat oxidation, and plasma glycerol concentrations were lower with the high than the low rate of glucose infusion, and lower than values reported by others during fasting or glucose infusion. Rates of fat oxidation were higher and glucose oxidation lower in patients than in controls, even though insulin concentrations were more than twice as high in patients. This confirms previous studies comparing injured and septic patients to depleted patients or historical controls. Triglyceride cycle activity was higher in the injured and septic patients than in normal subjects, and could account for from 6% to 15% of the increase in energy expenditure, in agreement with reports for burn patients.

Adolescent↗

PubMed1990

Influence of parenteral nutrition on rates of net substrate oxidation in severe trauma patients.

Optimal nutritional support should use a patient's energy expenditure as a guide for administering sufficient but not excessive caloric intake. Eight patients requiring parenteral nutrition were evaluated, using indirect calorimetry measurements, to determine the nutritional influence on the rates of substrate utilization in the critical period of catabolic illness due to accidental trauma. Five days of total parenteral nutrition, providing calories to match the measured basal resting energy expenditure and N to replace the initial urinary losses a) shifted the RQ from 0.74 +/- 0.03 to 0.81 +/- 0.03, b) improved but could not reverse negative N balance, c) decreased net fat oxidation, d) increased carbohydrate and protein oxidation, e) elevated daily norepinephrine and epinephrine excretion rates, and f) attained positive energy balance. The results suggest that positive energy balance could be achieved in trauma patients by providing total energy intake matching their basal measured energy expenditure plus 7% to 10% for activity energy expenditure. To prevent further loss of lean body mass, an N intake of 350 mg/kg.day was needed in these catabolic ICU patients.

Adolescent↗

PubMed1990

Nutritional impact on the energy cost of fat fuel mobilization in polytrauma victims.

In the "flow" phase of severe injury, mobilization of body fat and protein sources are accelerated to meet increased demands. Fat mobilization usually exceeds the need for oxidative substrates and the leftover fatty acids are re-esterified, resulting in a "futile" TG/FFA cycle. This contributes to increased energy expenditure and provision of nutrients may alter the activity of this cycle. We measured in nine adult (age 40 +/- 7 years, weight, 80 +/- 4 kg) severely traumatized (ISS 32 +/- 4) patients, the resting energy expenditure (REE) and net fat oxidation rate (NFO) by indirect calorimetry and whole body lipolysis rate (WBLR) by a two-stage, primed-constant infusion of glycerol. Fasting postinjury kinetic studies were performed within 48-96 hours after admission when the patients were receiving saline without calories or nitrogen. Glucose-based nutritional therapy was then started and continued for 5 to 7 days. The kinetic measurements were repeated after the nutritive solutions were replaced by normal saline for 12 to 15 hours to achieve a postabsorptive state. Trauma elicits an accelerated rate of fat mobilization with increased TG/FFA cycle activity. Adequate nutritional support for 5 to 7 days tends to reduce but cannot normalize the lipid metabolism. In acute trauma 47 +/- 7% of the mobilized fat was recycled to triglyceride and this is increased to 54 +/- 9% after providing nutrition. The energy cost of this cycling was 38 kcal/day, which is five times that seen in normals and corresponds to 1.34% REE.

Adolescent↗

PubMed1990

Glucose turnover, oxidation, and indices of recycling in severely traumatized patients.

Hyperglycemia is often seen in trauma patients and its etiology is not clearly understood. We have determined parameters of glucose metabolism by using simultaneous primed-constant intravenous infusion of both [6-3H] glucose and [U-14C] glucose in ten severely traumatized hypermetabolic subjects during the early "flow phase" of injury and in six post-absorptive normal volunteers. The mean rate of glucose production (determined by means of [6-3H] glucose) was 3.96 +/- 0.40 mg/kg/min in trauma patients, which was significantly (p = 0.025) higher than the value of 2.75 +/- 0.13 observed in normal volunteers. Glucose turnover rates determined with [U-14C] glucose as tracer were lower in all subjects. The difference between the turnover rates determined by the two tracers represents an index of recycling of glucose through three-carbon fragments. This recycling index was similar in both groups of subjects in amount (0.24 +/- 0.07 vs. 0.26 +/- 0.08 mg glucose/kg/min) but different when expressed as percentage of total glucose turnover (5.6 +/- 1.4% vs. 9.8 +/- 1.7%; p = 0.05). The absolute rates of glucose clearance, oxidation, and recycling were similar in stressed trauma patients and unstressed controls although the rate of production was increased by 44% due to injury. Post-trauma hyperglycemia was mainly due to an increased hepatic output of glucose and not due to a decreased ability of the tissue to extract glucose from the plasma. Hyperglycemia may be the driving force in the metabolic effects of injury.

Adult↗

PubMed1989

Measured energy expenditure in pediatric intensive care patients.

Few data are available on energy requirements of mechanically ventilated, critically ill children. We measured the resting energy expenditure in 18 mechanically ventilated patients between ages 2 and 18 years, using indirect calorimetry. All patients had fractional inspired oxygen concentration less than 0.6, no spontaneous respirations, hemodynamic stability, and no fever or active infection, and were receiving 5% dextrose. All subjects were hypermetabolic, since the measured resting energy expenditure divided by the predicted basal energy expenditure from the Harris-Benedict equations was 1.48 +/- 0.09 (mean +/- SEM). The energy requirements calculated using "injury factors" and "activity factors" adapted for adults is 1.62 times basal energy expenditure. The injury factor for the pediatric multiple trauma patients should be 1.25 compared with 1.35 in adults. In these pediatric intensive care patients 33% +/- 8% of the energy is derived from carbohydrates, 53% +/- 8% from fat, and 14% +/- 2% from protein oxidation. In individual critically ill pediatric patients, energy requirements should be estimated by measuring their resting energy expenditure whenever possible and adding 5% for their activity. In the absence of the actual measurement of resting energy expenditure, the recommended energy requirement is 1.5 times basal energy expenditure. In this acute phase of injury, the daily nitrogen requirement is 250 mg per kilogram of body weight.

Adolescent↗

PubMed1989

Endogenous protein-synthesis efficiency in trauma victims.

Hyperglycemia despite increased glucose oxidation and hypoaminoacidemia despite increased rate of protein breakdown are frequently seen in hypermetabolic and highly catabolic patients with major trauma. The extent of reutilization of endogeneously produced amino acids in the synthesis of new proteins (protein recycling) by the traumatized human is poorly understood. The protein synthesis efficiency was measured in ten multiple trauma patients during the early "flow" phase of injury, and these data were compared with normal and depleted patients. In acute trauma the synthetic efficiency of protein is significantly (P = .01) low (61% +/- 4%) compared with other pathologic states (78% +/- 1%). This suggests that the priority is preferentially set to meet the increased demands of glucose production, and a major portion of the amino acids are utilized for purposes other than synthesis of body proteins. This observation should be taken into account in the early management of acute trauma patients before the body adapts to accept the exogenous supply of amino acids.

Acute-Phase Proteins↗

PubMed1989

Polyamine levels as biomarkers of injury response in polytrauma victims.

Enhanced protein mobilization and synthesis are common responses to severe trauma. The hypothesis that extracellular polyamine levels could be valid biomarkers for these responses has been investigated. The three polyamines, spermidine, spermine and their precursor putrescine are directly involved in cell growth/death kinetics through regulation of protein metabolism. The lack of tissue uptake of extracellular polyamines and their rapid conjugation and excretion make them excellent biomarkers of variations in cellular kinetics. The polyamine levels in plasma and urine of severely traumatized patients were measured during the early "flow" phase of injury and compared with unstressed normals. Significantly elevated urinary levels of free and total putrescine and spermidine indicate the increase in the protein synthesis and breakdown rates, respectively, in polytrauma patients. Urinary spermidine level correlates well with other known parameters of protein catabolism, such as isotopically measured whole body protein breakdown rate in the basal state and 3-methylhistidine excretion and nitrogen loss in the basal condition and during nutritional therapy. Whole-body protein synthesis rate positively correlates with putrescine levels in urine. Based on these observations, urinary levels of the polyamines spermidine and putrescine may be applied as valid biomarkers of protein breakdown and synthesis rates, respectively, both for the existing pathology of severe trauma and for the response to nutritional therapy.

Adult↗

PubMed1989

Measurement of fatty acid oxidation: validation of isotopic equilibrium extrapolation.

Measurement of whole body substrate oxidation requires prolonged isotope infusion to attain plateau specific activity (SA) of expired CO2. We have investigated in 13 hospitalized patients a technique whereby plateau 14CO2 SA is extrapolated using computer curve fitting based upon the early exponential rise. A primed-constant infusion of albumin-bound 1-14C-palmitate was continued for 260 minutes with isotope priming of the secondary bicarbonate pool at 70 minutes. Plasma free fatty acid (FFA) SA reached steady state by 40 minutes and was 91% +/- 4% (SE) of values obtained at 190 to 260 minutes. At 70 minutes 14CO2 SA reached only 44% +/- 1% of the 190 to 260 minute values, which were consistently at plateau. The predicted steady state 14CO2 SA from the 40 to 70 minute curves and the FFA oxidation rates calculated from those values were 94% +/- 2% and 102% +/- 4%, respectively, of values measured at steady state (190 to 260 minutes). The relationship between predicted and measured values approximated the line of identity for 14CO2 SA (y = 0.90x + 0.14, r = .98, P less than .001) and FFA oxidation (y = 1.02x, r = .98, P less than .001). The results suggest that FFA oxidation can be accurately calculated using a short infusion of labeled FFA without bicarbonate pool priming, thus avoiding overpriming or underpriming and possibly allowing multiple studies and diminished radioisotope exposure.

Adult↗

PubMed1989

Exercise-mediated peripheral tissue and whole-body amino acid metabolism during intravenous feeding in normal man.

1. The effect of a daily submaximal exercise regimen on whole-body and peripheral tissue amino acid metabolism during weight-stable intravenous feeding (IVF) was evaluated in 11 normal volunteers. Five of the subjects performed 1 h of daily bicycle exercise at 75 W during IVF, while the remaining six subjects received IVF without daily exercise. Body nitrogen balance, leg and forearm plasma amino acid flux and whole-body kinetics were measured before and on day 10 of IVF using a [1-13C]leucine and [15N]glycine tracer. 2. At the end of the IVF period, exercised subjects demonstrated leg uptake of total amino acids (237 +/- 103 nmol min-1 100 ml-1 of tissue, mean +/- SEM) which was significantly (P less than 0.05) different than in non-exercised subjects (-1101 +/- 253 nmol min-1 100 ml-1 of tissue). 3. In the non-exercised forearm, a significant (P less than 0.05) decrease in total amino acid flux was observed in exercised subjects (-162 +/- 88 nmol min-1 100 ml-1 of tissue) compared with non-exercised subjects (-460 +/- 105 nmol min-1 100 ml-1 of tissue) on day 10 of IVF. 4. Efflux of 3-methylhistidine significantly (P less than 0.05) decreased from the leg in those subjects who performed daily exercise (-0.29 +/- 0.12 nmol min-1 100 ml-1 of tissue) compared with those subjects receiving IVF without daily exercise (-1.46 +/- 0.35 nmol min-1 100 ml-1 of tissue).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1989

Aminoaciduria of severe trauma.

Plasma and urine levels of free amino acids were measured in 15 severely traumatized adult patients while they were receiving fluids free of calories and nitrogen. Endogenous plasma clearance and the relative rates of reabsorption of free amino acids from renal tubules were calculated. These data were compared with similar studies of eight control subjects. Multiple injury provoked distinct patterns of free amino acids in plasma and urine. Hypoaminoacidemia and hyperaminoaciduria were seen in severe trauma. There was a marked depletion of nonessential amino acids in plasma of trauma victims. In contrast, the urinary loss of all amino acids was increased 5-10 times. This enhanced loss in patients, however, represented only 2.1% of total N excreted compared with 0.7% in control subjects. Considerable variations were seen in the selectivity with which various amino acids were reabsorbed by renal tubules. This may partly be due to the abnormal pattern of amino acids presented to renal tubules.

Absorption↗

PubMed1989

A rapid, automated micromethod for measuring free fatty acids in plasma/serum.

The investigation of mobilization and utilization of fat as fuel in human subjects requires the quantification of free fatty acids (FFA) in the circulating plasma. Methods in current use involve tedious extraction and titration, or enzymatic reaction with colorimetric or fluorometric detections. A rapid and reliable micro-technique is needed. We have adapted the manual enzymatic method of the Wako NEFAC kit to an automated rapid assay performed with a micro-centrifugal analyzer. This method depends upon the specific acylation of CoA by FFA, followed by oxidation and condensation to form a purple adduct measurable at 550 nm. The acylation step requires incubation at 37 degrees C for 10 min, a critical step for serum/plasma analysis. Only 4 microL of plasma is needed, and 20 tests can be performed in 20 min. The precision (CV) of sample analysis is within 2%. The results for the samples analyzed by this technique are within 4% (SEM 1%) of results by the manual method. Thus accurate results are achieved at reduced cost, time, and sample size.

Acylation↗

PubMed1988

Relationship between glucose oxidation and FFA concentration in septic cancer-bearing patients.

Glucose oxidation is inhibited in severely ill patients. The present investigation was designed to study the relationship between glucose tissue uptake, glucose oxidation, and FFA concentration in septic cancer-bearing patients. The influence of glucose infusion alone (3.9 mg x kg-1 x min-1), followed by a euglycemic clamp with the same glucose load, on oxidation of glucose, plasma FFA concentration, and lipid oxidation were measured in eight septic cancer-bearing patients. During infusion of 3.9 mg glucose x kg-1 x min-1 glucose tissue uptake was 4.6 +/- 0.3 mg x kg-1 x min-1, glucose oxidation 0.5 +/- 0.2 mg x kg-1 x min-1, FFA concentration 377 +/- 52 mumol x L-1, and lipid oxidation 2.0 +/- 0.2 mumol x kg-1 x min-1. During the euglycemic clamp glucose tissue uptake was 4.4 +/- 0.3 mg x kg-1 x min-1, glucose oxidation rose to 1.8 mg x kg-1 x min-1 (.001 less than P less than .01), FFA concentration dropped to 202 +/- 23 mumol x L-1 (P less than .001), and lipid oxidation to 1.2 +/- 0.2 mumol x kg-1 x min-1 (.001 less than P less than .01). Nonprotein respiratory quotient rose from 0.73 +/- 0.02 to 0.85 +/- 0.02 (.001 less than P less than .01); 11% +/- 5% of the total amount of glucose taken up by the tissues was oxidized during infusion of glucose alone and increased to 42% +/- 6% during the euglycemic glucose clamp. It is concluded that in septic cancer-bearing patients glucose oxidation is inhibited during infusion of 3.9 mg glucose x kg-1 x min-1, even when expressed as percentage of glucose tissue uptake. With insulin, glucose tissue uptake was not influenced, but glucose oxidation expressed as percentage of glucose tissue uptake was normalized.

Adult↗

PubMed1988

Free fatty acid turnover and lipolysis in septic mechanically ventilated cancer-bearing humans.

Loss of body fat and lean body mass are features of critical illness, and anabolism is difficult to achieve despite parenteral nutrition. Resting energy expenditure (REE), free fatty acid turnover (FFT) and glycerol turnover (glyTO) were measured in septic, mechanically ventilated cancer-bearing patients, both fasting and immediately following or during a glucose infusion providing 87% of REE. No patient was in septic shock nor required pressor support. In the fasting state, REE was greatly elevated compared with basal energy expenditure calculated using the Harris-Benedict equations. Fasting FFT (14.2 +/- 0.9 mumol/kg/min) and glyTO (4.7 +/- 0.5 mumol/kg/min) were elevated compared with normal humans. Fasting respiratory quotient (RQ) was 0.68 +/- 0.02 and did not rise significantly with glucose. Fat appears to be the preferred calorie source in septic, cancer-bearing humans even in the presence of glucose. As similar, but less pronounced, changes have been seen in septic and injured humans without cancer, it is likely that these changes are not cancer-specific.

Adolescent↗

PubMed1988

Protein and substrate metabolism during starvation and parenteral refeeding.

1. Healthy male volunteers underwent 10 days of hospitalized protein-calorie starvation and a subsequent 10 day repletion phase with complete intravenous nutritional support (IVF). Non-protein calories were provided as either all D-glucose or as 50% D-glucose/50% lipid. 2. In comparison with starvation, whole-body protein breakdown, as assessed by [15N]glycine, [13C]leucine and urinary excretion of 3-methylhistidine (3-MH), was diminished during IVF. The administration of parenteral nutrition did not specifically suppress peripheral tissue protein breakdown, as measured by extremity 3-MH efflux. 3. Despite the differential insulin response to D-glucose/amino acid (50 +/- 6 m-units/ml) as compared with the D-glucose/lipid/amino acid regimen (25 +/- 4 m-units/ml), there was no difference in nitrogen retention between the regimens. Indirect calorimetric determinations revealed that oxidation of substrate during IVF was related to the proportion of D-glucose and lipid infusion.

Adult↗

PubMed1988

Effect of helicopter transport of trauma victims on survival in an urban trauma center.

This paper reports a retrospective analysis of patients with serious yet substantially survivable injuries represented by ISS scores from 20 to 39 and whether or not survival was influenced by the use of helicopters. A review of 606 of these patients with blunt trauma was performed for the period from 1983 through 1986. When the group was evaluated there were 451 patients in the ISS cohort of 20-29 and 155 in the 30-39 group. The mean age was 30.5 years and 76% were males. A total of 259 patients were transported by ambulance and 347 by helicopter. Characteristics of the two groups were similar. The mean TS was 12.7 for ambulance and 12.1 for helicopter patients. Mean GCS was 10.4 in the ambulance group and 9.6 for helicopter patients. Overall the mortality for ambulance transported patients was 13% compared to 18% for the helicopter group. We conclude that there is no survival advantage in the helicopter transported group in an urban area with a sophisticated prehospital care system. Patients of rural origin deserve further study.

Adult↗

PubMed1988

Tumor necrosis factor and the acute metabolic response to tissue injury in man.

Tumor necrosis factor (cachectin), a protein produced by monocytes and macrophages, has been implicated as an important mediator of the lethal effects of endotoxic shock and the cachexia of chronic infection. Recombinant human tumor necrosis factor alpha (rTNF) was given intravenously to patients as part of an antineoplastic trial. Fever, tachycardia, and at higher doses, hypotension occurred after a single injection of rTNF. Metabolic effects after rTNF administration were dose related and included enhanced energy expenditure with elevated CO2 production, increased whole body protein metabolism and peripheral amino acid efflux from the forearm, and decreased total arterial amino acid levels associated with a significant increase in plasma cortisol. Elevated serum triglycerides, as well as increased glycerol and free fatty acid turnover were seen, suggesting increased whole body lipolysis and fat utilization after rTNF. These findings indicate that administration of TNF in man reproduces many of the acute physiologic and metabolic responses to tissue injury, including energy substrate mobilization.

Acute-Phase Reaction↗

PubMed1987

Immediate postoperative jejunostomy feeding. Clinical and metabolic results in a prospective trial.

A prospective clinical trial was designed to evaluate the efficacy of postoperative jejunostomy feedings using high (44 percent) and low (15 percent) branched-chain amino acid elemental diet formulations compared with no jejunostomy feedings in a homogeneous surgical population. Twenty-eight patients undergoing radical cystectomy and ileal diversion were randomized to the high branched-chain amino acid formula (11 patients) or the low branched-chain amino acid formula (9 patients). Eight patients received a 5 percent dextrose in water solution intravenously and served as a control group. Mean caloric intake per day in each group was 1,543 calories, 1,697 calories, and 550 calories, respectively; whereas the mean nitrogen intake of each group was 6.5 +/- 2.1 g/day, 8.2 +/- 2.4 g/day, and 0 g/day, respectively. Mean weight changes were minus 0.7 percent, 0.7 percent, and minus 0.3 percent, respectively. The mean daily nitrogen balance was minus 1.6 +/- 3.5 g/day, minus 1.1 +/- 4.4 g/day, and minus 6.6 +/- 1 g/day (p less than 0.001). Five patients (25 percent) in the jejunostomy groups progressed to an oral diet more rapidly than the control group, but gastrointestinal complications occurred in 11 patients (55 percent). Immediate postoperative jejunostomy feedings resulted in improved nitrogen balance compared with the control group values, but no metabolic advantage was noted by infusing a high branched-chain amino acid formula. Improved return to normal gastrointestinal function was noted in 25 percent of jejunostomy patients, but the gastrointestinal complications noted limited the overall usefulness of this technique.

Abdomen↗

PubMed1987

Comparison of hepatic protein synthesis in vivo versus in vitro in the tumor-bearing rat.

We have used the model of the freshly isolated hepatocyte to study liver metabolism in a rat tumor model and have reported elevations in the rates of protein synthesis, gluconeogenesis, alanine transport, and oxygen utilization by the tumor-influenced hepatocyte. While the metabolic activity of the isolated hepatocyte has been taken to reflect metabolism in the in vivo state, this assumption has not been validated. In the present study, we measure hepatic protein synthesis in vivo using a flooding dose of tracer amino acid, and in vitro in hepatocytes freshly isolated from tumor-bearing (TB) and pair-fed control rats. Increased protein synthesis was observed for the TB rats using both methods of analysis. However, the degree of stimulation seen in the TB animals was much greater in the in vitro assay than in the in vivo approach, suggesting that absolute protein synthetic rates in vitro must be interpreted with caution when extrapolating to the in vivo state.

Amino Acids↗