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Biomedical subjects

M Jeevanandam

Publications and source records attributed to M Jeevanandam.

At least 37 records · Page 2Linked to original sources

Nutritional influence on the recovery of 14CO2 in critically ill trauma patients.

Several factors, including age, nutritional and metabolic status, and underlying pathological conditions, should be considered in estimating the correction factor for labeled CO2 retention. We have evaluated the nutritional influence of this correction factor in a group of severely injured (injury severity score = 33 +/- 5), hypermetabolic, and highly catabolic adult trauma patients. Primed-constant infusion of NaH14CO3 was used, and the breath 14CO2 radioactivity was measured. The experiment was conducted once in the fasting condition during the early catabolic "flow" phase of injury and again during and after a week of intravenous feeding. The mean value of the 14CO2 recovery (85.2 +/- 2.7%) in the basal fasting condition was higher than the value of 81% commonly used in normal subjects. During intravenous nutritional support the recovery was 100.8 +/- 1.7%. Recovery of tracer increased linearly with O2 uptake and CO2 production. The linear expression obtained between recovery and CO2 production could estimate the recovery within 3% in trauma patients, and that obtained by multiple regression with CO2 production and O2 uptake would predict the recovery within 1.5%.

Adult↗

Altered lipid kinetics in adjuvant recombinant human growth hormone-treated multiple-trauma patients.

Adjuvant recombinant human growth hormone therapy during the postinjury period may improve the efficiency of utilization of body energy stores. In a group of 20 severely injured highly catabolic hypermetabolic adult multiple-trauma victims, we have investigated the basic lipid kinetics of trauma (study I) and its modification after 7 days of intravenous feeding (total parenteral nutrition) with (group H, n = 10) or without (group C, n = 10) daily rhGH (0.15 mg somatotropin.kg-1.day-1) intramuscular injections (study II). Whole body lipolysis rate (2-stage primed constant infusion of 10% glycerol), substrate net oxidation rates (indirect calorimetry), and plasma levels of hormones were determined. Compared with the control group (group C) the treatment group (group H) showed significantly (P = 0.006) enhanced rates of lipolysis and free fatty acid reesterification (10 +/- 2 to 18 +/- 2 kcal.kg-1.day-1, P = 0.05). As a function of resting energy expenditure (REE), a trend of increased net glucose oxidation [32 +/- 10 vs. 56 +/- 7% REE, not significant (NS)] and decreased fat (40 +/- 8 vs. 25 +/- 5% REE, NS) and protein oxidation rates (28 +/- 2 vs. 19 +/- 2% REE, P = 0.007) were also indicated. The simultaneous operation of increased lipolytic and reesterification processes may allow the adipocyte to respond rapidly to changes in peripheral metabolic fuel requirements in injury.

Chemotherapy, Adjuvant↗

Protein and glucose fuel kinetics and hormonal changes in elderly trauma patients.

We investigated the responsiveness of whole-body protein and glucose kinetics to severe trauma and the role of regulatory hormones in the early catabolic "flow phase" of injury in a group of patients ranging in age from 19 to 85. Energy metabolism (indirect calorimetry), protein kinetics (primed-constant infusion of [15N]glycine), glucose metabolism (primed-constant infusion of [U-14C]glucose and [6-3H]glucose), and circulating hormone levels were measured during basal conditions within 48 to 60 hours after injury when the patients were receiving maintenance fluids without N or calories. Experimental data were analyzed as two groups (young, age 18 to 59, and elderly, age 60 to 85) and also as linear function of advancing age. The geriatric trauma (GT) group lost less N (11.9 +/- 1.3 v 17.7 +/- 1.7 g N/d, P = .025) than the younger group, mainly due to a significantly decreased whole-body protein breakdown (WBPB) rate. Despite a similar production and oxidation rate of glucose, hyperglycemia was more exaggerated in the elderly group. Advancing age resulted in significant positive correlations with plasma glucose levels and negative correlations with circulating growth hormone levels, urinary nitrogen loss, and protein turnover. These results suggest an age- and body composition-related reduced energy and protein metabolic response to severe trauma in elderly individuals.

Adolescent↗

Relative nutritional efficacy of arginine and ornithine salts of alpha-ketoisocaproic acid in traumatized rats.

The relative dietary efficacy of arginine alpha-ketoisocaproate (AKIC) and ornithine alpha-ketoisocaproate (OKIC) is evaluated in a rat (Sprague-Dawley) trauma (bilateral femur fracture) model. Both control and traumatized rats were starved for 2 d and then pair-fed for 2 or 4 d one of three liquid diets: diet 1 was a basic casein diet; diets 2 and 3 were the basic diet in which 10% of nitrogen was replaced by AKIC or OKIC nitrogen, respectively. Irrespective of the diet, the protein-efficiency ratio, defined as the gain in body weight per grams nitrogen consumed, was 27% less in traumatized rats than in control rats. More improvement in apparent nitrogen balance, particularly in traumatized rats, was seen with the AKIC supplement. Plasma amino acid patterns demonstrated stimulation of net protein synthesis with AKIC and not with OKIC. Dietary supplementation with AKIC may be beneficial to promote nitrogen economy in trauma victims.

Amino Acids↗

Is the metabolic response to injury different with or without severe head injury? Significance of plasma glutamine levels.

Acute brain injury is the single largest cause of trauma center deaths. Injury that does not involve the brain directly can lead to a cascade of changes in neuroendocrine system function. In order to evaluate the effect of head injury in severely traumatized patients on the response of body fuel mobilization and utilization, 42 adult patients were studied in the early "flow" phase of injury in the fasting state. They were divided into two groups: (1) multiple trauma patients without head injury (MI group, n = 21); and (2) multiple trauma patients with severe head injury (HMI group, n = 21). This enabled evaluation of the influence of injured brain on the general response to body injury. Kinetic measurements of protein (primed-constant infusion of 15N glycine), glucose (14C and 3H isotopic glucoses), fat (two-stage glycerol infusion), and energy metabolism (indirect calorimetry) were made along with hormone and substrate determinations. The results of this integrated approach demonstrated similar hormonal and metabolic changes between these two groups of patients. However, hepatic glucose production and whole body lipolysis rates were significantly decreased in HMI patients. In addition, hyperglycemia and hypoglutaminemia were more pronounced in injured patients with associated head injury. Glutamine release, which forms a significant net release of brain amino acids in normal subjects may be impaired in HMI patients. Associated brain injury appears to moderate the systemic effect of trauma.

Adolescent↗

Altered tissue polyamine levels due to ornithine-alpha-ketoglutarate in traumatized growing rats.

All cells contain significant amounts of polyamines (PA), and their concentrations are highly regulated. Metabolic activity within a tissue may be reflected in the amount of intracellular PA. Since trauma involves accelerated death and regeneration of tissues, the related levels of PA in extracellular and intracellular fluids may reflect altered protein metabolism. Trauma induces an increased excretion of urinary PA, and the tissues responsible for this whole-body activity are not known. During posttraumatic nutritional management, supplementation with ornithine-alpha-ketoglutarate (OKG) seems to improve nitrogen economy. The present study evaluates the significance of muscle, liver, and intestine PA responses in traumatized (bilateral femur fractures) rats to the feeding of an isonitrogenous liquid diet supplemented with or without OKG. Uninjured control rats were pair-fed with respective traumatized rats. After 2 days of starvation and 4 days of feeding, the traumatized and control rats were killed and the tissues were excised and analyzed. Starvation decreases and refeeding increases urinary PA excretion. Trauma-induced PA response is predominantly seen in muscle tissues, and this may be responsible for parallel increases in PA excretion. Liver PA responses show a varying tendency confirming the increased protein synthetic activity due to trauma. Intestine has the highest intracellular PA levels, and there is a general smaller (statistically insignificant) increase in all the individual PA contents due to trauma. OKG supplementation augments tissue and urine PA responses in control rats; however, in trauma rats muscle PA levels show very little change, although nitrogen retention is significantly better (88% to 77%). Mechanistic studies are needed to evaluate the significances of the time-dependent, injury-induced, individual intracellular PA levels.

Acetylation↗

Acute IGF-1 deficiency in multiple trauma victims.

The circulating levels of IGF-1 in the catabolic flow phase of injury were measured in multiple trauma victims once before nutritional support and again after 4 days of intravenous feeding. The hypermetabolic and highly catabolic state of injury is characterized by a diminished level of IGF-1 along with increased levels of stress hormones. Inverse relationships of adiposity and aging on IGF-1 levels are seen both in injured and uninjured subjects. Feeding could restore the IGF-1 levels in non-obese, young patients but it is delayed in obese or elderly subjects. This diminished responsiveness to feeding of IGF-1 hormone deficiency in obese and elderly subjects should be taken into consideration in their post-trauma treatment and may warrant adjuvant administration in these types of patients.

Journal Article↗

Decreased growth hormone levels in the catabolic phase of severe injury.

BACKGROUND: Human growth hormone (hGH) is a potent anabolic agent, which has profound effects on protein, carbohydrate, and lipid metabolism. The role of this primarily anabolic hormone in the severe catabolic state of trauma is not known. METHODS: In a group of young, obese, and elderly patients with multiple traumas, plasma hGH levels were measured in the catabolic "flow" phase of injury, once before and then after 4 to 6 days of nutritional support sufficient to match their initial loss of calories and nitrogen. RESULTS: A decreased hGH level was noted in the hyperglycemic and hypercatabolic injured state, particularly in victims of trauma who were young and not obese, compared to respective volunteers. A significant (p = 0.025) inverse relationship was observed between age and plasma hGH levels in this group of patients who had experienced trauma. Nutritional therapy improved the protein and fat metabolism but could not reverse to the normal state. In young patients who had experienced trauma and who were not obese, the hGH levels were significantly improved because of dietary intake, whereas in elderly patients or patients who were obese no change was noted. CONCLUSION: These results are consistent with less lipid mobilization and inefficient utilization of fatty acids in the elderly patients or patients who were obese who had abundant fat sources to spare. Elevation of hGH level by exogenous administration may improve the nitrogen economy and lipid mobilization, particularly so in the elderly patients or patients who were overweight. Our study supports the view that provision of adequate nutrition with daily administration of human hGH in the first week after trauma would enhance the metabolic status of the patient, resulting in reduced morbidity and earlier discharge from the hospital.

Adult↗

Altered plasma free amino acid levels in obese traumatized man.

Obesity is a major nutritional disorder that produces many abnormal metabolic responses. The effect of injury-induced stresses acting synergistically with the state of excessive body fat is not well known. Plasma levels of circulating free amino acids reflect the net status of protein breakdown and utilization. Hypoaminoacidemia is a common finding in severe injury and its significance in obese subjects was investigated. We measured in 10 obese (body mass index [BMI] greater than 30) and 10 non-obese (BMI less than 30) traumatized (Injury Severity Score [ISS] 17 to 50) patients, the plasma levels of free amino acids in the early "flow" phase of injury when subjects were receiving maintenance fluids without calories or nitrogen. Postabsorptive control samples were obtained from 10 obese and 10 non-obese volunteers. Obese controls showed an increase in valine, leucine, isoleucine, and glutamic acid levels, and a decrease in glycine, tryptophan, threonine, histidine, taurine, citrulline, and cystine levels compared with lean controls. Hypoaminoacidemia was equally seen in traumatized obese and non-obese patients, and it was mainly due to a 24% decrease in nonessential amino acids. Remarkably, essential amino acid levels were the same in all groups. Arginine and ornithine levels were significantly different in traumatized obese compared with non-obese patients. The hypoglycinemia seen in non-obese trauma patients was absent in obese patients. The changes in levels of sulphur-containing amino acids also suggest that monitoring of these levels should be included in the nutritional management of obese trauma patients.

Adult↗

Glucose infusion improves endogenous protein synthesis efficiency in multiple trauma victims.

Metabolic costs of excessive nutritional support in stressed patients have been increasingly recognized. The decreased endogenous protein synthesis efficiency (PSE) following major injury has been attributed to the predominant need of amino acid precursors for gluconeogenesis. The present study tested the hypothesis that provision of glucose alone, not to exceed the resting energy expenditure (REE), for the first 4 to 5 days after trauma would be enough to restore PSE and stimulate the injured body to accept full nutrition. Eight severely injured, adult, hypermetabolic, and highly catabolic patients admitted to the Trauma Intensive Care Unit (TICU) served as our subjects. Integrated measurements of whole body fuel-substrate kinetics were obtained for energy metabolism (indirect calorimetry), protein kinetics (primed constant infusion of 15N-glycine), and glucose kinetics (labeled glucose infusions). Two studies were conducted on each same subject, one in the early flow phase of injury (48 to 60 hours after trauma) and a second after 4 to 5 days of hypertonic glucose (4.1 +/- 0.5 mg/kg/min; 80% REE calories) infusion with electrolytes, trace elements, and minerals. Significant (P less than .05) increases in PSE (14%, 65% +/- 2% to 74% +/- 2%), plasma growth hormone and insulin levels, and respiratory quotient (RQ) (31%, 0.74 +/- 0.03 to 0.97 +/- 0.04), and decreases in endogenous glucose appearance rate (55%, 3.1 +/- 0.5 to 1.4 +/- 0.1 mg/kg/min), and negative N balance (48%, 219 +/- 26 to 114 +/- 15 mgN/kg/d) were observed. The results suggest that hypertonic glucose infusion alone may be sufficient for physiological adaptation in the immediate posttrauma days. This therapy restores normal PSE, which should protect the labile protein pool.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Efficacy of ornithine-alpha-ketoglutarate (OKGA) as a dietary supplement in growing rats.

New substrates of potential benefit to critically ill patients receiving traditional nutritional support have been suggested to meet organ or tissue specific needs. The addition of an anabolic stimulus during nutritional support therefore appears to be a reasonable adjunct to augment protein synthesis. The purpose of this investigation was to evaluate the efficacy of the neutral salt ornithine alphaketoglutarate (OKGA) as a dietary supplement to promote growth in young rats by enhancing protein metabolism. A group of 16 male Sprague-Dawley rats (150-170g) were housed in individual metabolic cages and after dark-light cycle adaptation were fed ad libitum an oral liquid diet for 7 days. Half of the animals were given the control diet and the other half was fed a test diet. This isonitrogenous test diet contained the control diet with 2.3% of nitrogen (N) replaced by N from OKGA. Daily weight, food intake and urinary excretions of N, creatinine, urea, orotic acid, polyamines and amino-acids were determined. At the end of 7 days of free-feeding, the rats were sacrificed and blood was collected for free amino-acids. Rats fed the OKGA supplemented diet consumed 16% more diet, retained 11% more nitrogen and gained 15% more weight. The accelerated protein metabolism is reflected in the changes in plasma and urinary free amino-acid levels. Enhanced protein anabolism is evident from the increased urinary excretion of polyamines in the OKGA fed rats. The increased ratio of urinary urea N to total N and the decreased orotic acid excretion in OKGA fed rats suggests thata NH(4)(+) was efficiently diverted through urea cycle. It is concluded that in growing rats, supplementing isonitrogenous diet with OKGA significantly stimulates food intake compared to controls. This results in better weight gain and improvement in protein metabolism.

Journal Article↗

Mild orotic aciduria and uricosuria in severe trauma victims.

Hypermetabolic responses with respect to pyrimidine and purine kinetics in trauma victims were investigated during the catabolic phase before and after nutritional support. Orotic acid and uric acid excretions were measured in 32 adult, severely traumatized, hypermetabolic, and highly catabolic patients while they were receiving fluids with no calories or nitrogen. Patients were then fed intravenously amino acids and glucose or glucose alone or fed enterally for 5-6 d. Daily excretions of orotic acid, uric acid, urea, nitrogen, and creatinine were monitored. Mild orotic aciduria and uricosuria with hypouricemia were the basal-trauma responses. The significant (P = 0.001, r = 0.70) positive correlation between orotic and uric acid excretion demonstrates the parallelism between pyrimidine and purine metabolism. Feeding for 5-6 d could decrease but not readily abolish the injury-induced metabolic changes in nitrogen, pyrimidine, and purine metabolism. Glucose infusion alone may be sufficient to counteract the metabolic effects of trauma in the early flow phase of injury.

Adult↗

Elevated urinary C-peptide excretion in multiple trauma patients.

A simple, indirect method of estimating integrated insulin secretion is the measurement of C-peptide, a byproduct of insulin biosynthesis, in plasma and in 24-hr urine samples. We determined, in 29 severely injured hypermetabolic and highly catabolic multiple trauma patients, the plasma level and daily excretion rate of C-peptide, 48-72 hrs postinjury. Data from a set of eight patients who underwent glucose-based total parenteral feeding for 6 days were analyzed for the course of changes in the excretory pattern of C-peptide and catecholamines. The molar ratio of plasma C-peptide to insulin in the trauma patients was similar to that in unstressed controls, indicating that the rate of hepatic insulin extraction is not appreciably altered due to trauma. This is also evident from a significant correlation (p = 0.001) between the plasma C-peptide and insulin levels. The excretion of C-peptide was elevated to three times the normal both in absolute terms and when normalized to creatinine excretion. This was also accompanied by a twofold increase in the plasma levels, indicating an enhanced secretion rate of C-peptide and hence of insulin in response to trauma. Injury-induced insulin resistance does not seem to be due to a decreased insulin secretion. An increase in insulin output would appear to be a significant and desirable response for a continued anabolic stimulus coexistent with the net catabolic phase. Parenteral feeding augmented the excretion of C-peptide and catecholamines and this effect peaked on the fourth day of nutritional therapy.

Adolescent↗

Obesity and the metabolic response to severe multiple trauma in man.

In the obese state profound metabolic disturbances exist and it is not known how this disrupted metabolism in obese subjects (body mass index greater than 30) may change their ability to respond to the superimposed, injury-induced stress. Understanding the mechanisms that modify the metabolic parameters in traumatized obese patients is essential in their nutritional assessment and further treatment. We have investigated in 7 obese and 10 nonobese multiple trauma patients, on a whole-body level, the energy metabolism, protein kinetics, and lipolysis in the early catabolic "flow phase" of severe injury when they were receiving maintenance fluids without calories or nitrogen. Traumatized obese patients mobilized relatively more protein and less fat compared with nonobese subjects. A relative block both in lipolysis and fat oxidation is experienced by injured obese patients that results in a shift to preferential use of proteins and carbohydrates. Reduced endogenous protein synthetic efficiency observed in obese patients implies increased protein recycling. Thus obese patients could not effectively use their most abundant fat fuel sources and have to depend on other fuel sources. The nutritional management of obese trauma victims should therefore be tailored towards provision of enough glucose calories to spare protein.

Adolescent↗

Energy cost of fat-fuel mobilization in geriatric trauma.

Age-related changes in body composition may result in varied responses to acute accidental injury. Gaining fat as age advances is common and therefore the mobilization of fat fuel resources in traumatized geriatric patients needs closer examination. We have measured in six elderly (age, 60 to 74 years) and seven young (age, 18 to 46) traumatized, hypermetabolic, and highly catabolic patients, in the "flow phase" of the metabolic response to injury, the rates of whole-body lipolysis and net fat oxidation. This enabled us to calculate the rate of triglyceride/free fatty acid (TG/FFA) cycling in the whole body and to assess its contribution to energy expenditure. Energy metabolism in general and the fat metabolism in particular were found to be somewhat slowed in elderly trauma patients compared with equally injured young individuals, although the aged patients had more total body fat. The energy cost of TG/FFA cycling is significantly (P less than .025) lower in elderly trauma victims (0.28 +/- 0.06 kcal/kg/d) compared with young patients (0.63 +/- 0.1 kcal/kg/d). This can account for approximately 3% to 4% of the elevation in metabolic rate over that predicted in the uninjured state.

Adipose Tissue↗

Effect of major trauma on plasma free amino acid concentrations in geriatric patients.

Age-associated decrease in lean body mass may lead to varied responses to severe trauma. Hypoaminoacidemia is generally common among trauma victims. We measured the plasma free amino acids in the early "flow," ie, catabolic, phase of injury in 9 elderly (aged 61-81 y) and 13 young (aged 20-38 y) traumatized patients. Postabsorptive control samples were obtained from 8 elderly and 10 young volunteers. The results were analyzed for age-related responses to major trauma. Older healthy control subjects showed a decrease in total amino acids, essential amino acids, proline, histidine, taurine, and cystine. The hypoaminoacidemia was less pronounced in geriatric trauma, mainly because of a larger decrease in nonessential amino acids in young trauma victims. Significant decreases in arginine and methionine and increases in ornithine and citrulline concentrations were seen in geriatric trauma. These results suggest a sluggish protein metabolic response to trauma in elderly individuals, which should be considered in their nutritional management.

Adult↗