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Biomedical subjects

M Jeevanandam

Publications and source records attributed to M Jeevanandam.

At least 91 records · Page 5Linked to original sources
PubMed1984

Measurement of glycerol turnover by infusion of nonisotopic glycerol in normal and injured subjects.

A new technique for measuring glycerol turnover in human subjects is presented using a staged infusion of unlabeled glycerol. A total of 105 measurements was made in normal subjects and postoperative or acutely ill patients. The relation between glycerol turnover rate (R tau) and concentration (C) (R tau = 31 + 2.07C) from 80 staged infusion measurements in 21 normal subjects did not differ significantly from observations of others made by isotope dilution. In 11 patients, glycerol turnover was also measured by dilution of isotopic glycerol. Mean values did not differ significantly between the two methods. The average difference, regardless of sign, for individual values was 17%. This agreement tends to validate the assumptions of both methods. Advantages of the staged infusion method are that it is quicker and easier to perform and does not entail a risk due to administration of radioactive materials. Evidence obtained in this study from a three-stage procedure indicates that satisfactory information may be obtained from a two-stage infusion at successive rates of 250 and 600 mumol/min for 70 min each, with a prime of 2 mmol given as a bolus at the start of each stage.

Adult↗
PubMed1984

Gluconeogenesis in tumor-influenced hepatocytes.

The growth of a tumor leads to alterations in host carbohydrate metabolism. In this study we examined gluconeogenic capacity and amino acid transport in tumor-influenced and control rat hepatocytes. Serum glucose level decreased with increasing tumor burden and a significant correlation (r = -0.80) was observed. Hepatic glycogen content was similar in both groups after an overnight fast. Endogenous glucose production was 27% higher in tumor-influenced hepatocytes. The presence of 10mM of alanine led to 72% stimulation of gluconeogenesis in tumor-influenced hepatocytes as compared to 48% stimulation in control hepatocytes. The same trends were present when lactate was used as a substrate. Alanine transport into the cells was increased in tumor-influenced hepatocytes by 55% +/- 5% at a physiologic level of substrate. In conclusion, gluconeogenesis from alanine and lactate is significantly increased in tumor-influenced hepatocytes despite decreased serum glucose levels. This is associated with increased gluconeogenic capacity and accelerated alanine transport.

Alanine↗
PubMed1983

Evaluation of whole body nitrogen kinetics in acute metabolic acidosis.

The data obtained after a pulse dose of L-[15N] alanine and [13C] urea in control and acidotic conscious dogs were analyzed to compute the whole body nitrogen turnover rates. Acute acidosis was induced and maintained by continuous HCl infusion. On the basis of a four pool model, the mean daily protein synthesis rate in the normal dog was calculated to be 10.8 g/kg compared to 7.6 g/kg in acidosis. Since all dogs were in negative nitrogen balance, the daily catabolic rate of protein was greater than the synthetic rate and the mean daily catabolic rate was 14.4 g protein/kg in normal dogs compared to 10.5 g protein/kg in acidotic dogs. The body urea pool size and excretion rates were decreased by 24 and 27%, respectively, due to acute acidosis, without any change in the fractional turnover rate. Thus the adaptive response to the induced acid challenge appears to be a reduction in the synthesis and breakdown rates of protein and also a decrease in the production and excretion rate of urea.

Acidosis↗
PubMed1981

Increasing glucose intake during total parenteral nutrition increases norepinephrine excretion in trauma and sepsis.

Total Parenteral Nutrition (TPN) was given to 15 traumatized or infected patients with all of the non-protein calories, either as intravenous glucose (Glucose System), or as 50% glucose + 50% intravenous fat (Lipid System). Before the administration of TPN, mean urinary excretion of unconjugated norepinephrine was 2.37 +/- 0.52 (SEM) microgram/kg/day, which is significantly higher than for normal subjects (0.62 +/- 0.04 microgram/kg/day; n = 56). TPN with the Glucose System for 4-6 days significantly increased the norepinephrine excretion from 1.95 +/- 0.47 to 6.77 +/- 0.95 microgram/kg/day (P less than 0.01). When TPN with the Lipid System was given the increase (from 3.05 +/- 0.89 to 4.26 +/- 0.70 microgram/kg/day) was not statistically significant. A modest increase in resting energy expenditure was seen with the Glucose System but not with the Lipid System. The administration of high glucose loads during TPN, in addition to providing nutritional support, may exert a metabolic stress as reflected by increased metabolic rate and increased catecholamine excretion. These metabolic changes are reduced when intravenous fat emulsions are substituted for a major part of glucose calories.

Adolescent↗
PubMed1981

Whole-body protein metabolism due to trauma in man as estimated by L-[15N]alanine.

Changes in whole-body protein metabolism due to several skeletal trauma were estimated in five male volunteers and four male trauma patients using a single pulse of [15N]alanine and [13C]urea. The isotopic decay data were computer curve-fitted to obtain the best estimates for eight parameters of a four-pool model. The trauma patients excreted almost 5 times as much urinary nitrogen and utilized 33% more energy than did the volunteers on the same hypocaloric, protein-free diet. Trauma was found to expand the "active metabolic nitrogen" pool and the transfer rates of nitrogen into and out of a "slow turnover protein" pool. Whole-body protein synthesis increased 37% above normal and protein breakdown increased 79% above normal due to trauma. These values were in agreement with those determined at the same time using a [14C]leucine continuous infusion method. The data show that trauma accelerates the nitrogen flow and both protein synthesis and breakdown. This mechanism for negative nitrogen balance is consistent with that found for other severe stresses but is different from milder stresses.

Alanine↗
PubMed1981

Metabolic and endocrine effects of fasting followed by infusion of five-percent glucose.

Isotonic glucose is often the sole nutrient provided to hospitalized patients with varying degrees of protein calorie malnutrition. To study the effects of such diets uncomplicated by illness, normal human subjects were fasted (6 to 14 days) before receiving an infusion of 5% dextrose (5 to 7 days). Norepinephrine excretion rose steadily-to six times control values-during the first 6 days of the fast and changed little thereafter. It remained high during the first 3 days of glucose infusion and subsequently returned toward normal. The rate of NTau-methylhistidine excretion changed little during the fast but decreased abruptly with glucose infusion. The magnitude of NTau-methylhistidine excretion indicated that undirectional muscle protein degradation was about equal to nitrogen excretion during the fast, and that the decrease in muscle protein degradation could account for the abrupt decrease in nitrogen excretion (from 91 to 30 mg N/kg . day) after glucose infusion. This suggests that the conservation of muscle protein caused by glucose infusion in this setting is affected by decreased degradation rather than by increased synthesis. Changes in NTau-methylhistidine excretion and total nitrogen excretion were more rapid than, and therefore not mediated by, changes in insulin concentration or norepinephrine excretion.

Adult↗
PubMed1981

Energy expenditure, nitrogen balance, and norepinephrine excretion after injury.

In this study we examine the effect of different hypocaloric nutritional regimens on nitrogen balance in patients following total hip replacement and compare it to that of normal subjects on strict bed rest. The interrelationship between nitrogen balance, energy expenditure, and urinary free norepinephrine excretion is analyzed with emphasis on the effects of nutrition on these relationships. Amino acid infusions following major elective orthopedic surgery had no nitrogen-sparing effect above that of 5% dextrose. Optimum nitrogen balance was obtained by administration of both 5% dextose and 3.5% amino acids. Patients receiving 5% dextrose showed no increase in resting energy expenditure in postoperative period compared to the preoperative control value. However, patients receiving amino acid infusions showed a 14% rise in energy expenditure postoperatively. Failure to administer 5% dextrose was associated with a high urinary norepinephrine excretion postoperatively. In normal subjects on bed rest either 5% dextrose or total starvation resulted in a marked fall in resting energy expenditure, whereas amino acid infusions isocaloric to the carbohydrate intake prevented any fall in resting energy expenditure. Nitrogen balance was improved with amino acid infusions in normal subjects. This study suggests the effect of amino acid infusions is highly dependent on the metabolic state of the patient.

Adult↗
PubMed1980

Influence of total parenteral nutrition on fuel utilization in injury and sepsis.

Total parenteral nutrition with hypertonic glucose/AA solutions given to eighteen nutritionally depleted patients resulted in a rise in the respiratory quotient (RQ) from 0.83 to 1.05 (p less than .001), while oxygen consumption (VO2) increased only 3%. Excess glucose in depleted patients was converted to fat as evidenced by an RQ greater than 1.0. Administration of a similar glucose load to fourteen hypermetabolic patients (injury/infection) resulted in a rise in RQ from 0.76 to 0.90 while VO2 increased 29% (p less than .001) In hypermetabolic patients, even with administration of glucose in quantities above energy expenditure, there was still ongoing utilization of fat for energy, resulting in a RQ significantly less than 1.0. Excess glucose under these circumstances is apparently converted to glycogen while fat stores are utilized to partially meet energy needs. Septic and injuried man seems to preferentially utilize endogenous fat as an energy source. Administration of a large glucose load to hypermetabolic patients does not totally suppress the net fat oxidation as it does in depleted patients. Rather there is an increase in VO2, continuing oxidation of fat and apparently an increase in the conversion of glucose to glycogen.

Adult↗
PubMed1979

Kinetics of intravenously administered 15N-L-alanine in the evaluation of protein turnover.

After a pulse injection of 15N-L-alanine to a healthy male subject, the distribution of 15N in the various components of blood and urine were determined as function of time. The rapid appearance of the isotope both in the urinary urea and ammonia and in the plasma amide and urea suggests that transamination (and not deamination) may be the key step in the interaction. After 30 to 60 min postinjection, the tracer dynamics represents the overall metabolic pool characteristics and does not reflect the metabolism of alanine only. The nitrogen of alanine is used effectively in the synthesis of body protein.

Adult↗
PubMed1979

Influence of increasing carbohydrate intake on glucose kinetics in injured patients.

The metabolic and hormonal effect of glucose loads, ranging from 125 to 504 g/70 kg/day, were studied in severely injured patients. There was little or no correlation of glucose intake with nitrogen balance, plasma glucose, fatty acid concentrations, or epinephrine excretion. Increased norepinephrine excretion correlated with and may have resulted from increased glucose intake. Serum glucagon concentrations averaged 320 pg/ml and were not depressed by glucose intake. Insulin concentrations rose with glucose intake but were low for the level of plasma glucose. Glucose oxidation and non-oxidative metabolism, including glycogen deposition, correlated well with glucose intake. Gluconeogenesis from alanine was much higher than normal but was completely suppressed at very high intakes. The data imply that cycling of glucose, with glycerol, glycogen, or both, increased with increasing glucose intake.

Adult↗
PubMed1979

Effects of hypercaloric glucose infusion on lipid metabolism in injury and sepsis.

UNLABELLED: Lipolysis was studied by measuring glycerol turnover (GTO) in injured and infected patients. GTO was elevated two to three times the normal values in five injured and four infected patients during D5W infusion. No correlation was found between GTO and plasma glycerol concentration in the two patient groups. GTO showed similar levels when measured during TPN in five injured and three infected patients. During TPN, plasma FFA levels remained unchanged in injured but decreased by 48% in septic patients. B-OH butyrate concentrations were high during D5W and dropped in both groups during TPN. Norepinephrine urinary output was high in both groups during D5W and TPN. CONCLUSIONS: 1) GTO was elevated two to three times the normal range in injury and infection; plasma glycerol concentration was not related to GTO. 2) In face of high catecholamine output, the insulin response to TPN did not inhibit TG breakdown but did decrease plasma ketone body concentrations.

Adult↗
PubMed1978

Metabolism and recycling of urea in man.

The rate of breakdown and reutilization of urea in man has been measured in five normal and two septic patients using 15N and 13C labeled ureas. The labeled molecules of the 15N urea dose were distinguished from the labeled molecules of the recycled urea by analyzing in a mass spectrometer the isotopic nitrogens produced when the recrystalized urine urea was treated with a hypobromite solution. In a normal subject with regular nitrogen intake, it was found that only 4/5 of the produced urea was excreted in urine and the rest was endogenously degraded. Seventy percent of the nitrogen and 63% of the carbon of the degraded urea were returned to the urea pool. On a nitrogen-free diet or after neomycin treatment with regular diet in the normal, the extent of urea splitting is considerably reduced. In the septic patients, breakdown, as well as recycling of urea was almost eliminated. It appears that the reate of endogenous catabolism of urea depends mainly on the activity of the gut flora which may be affected by dietary intake and clinical status of the subject. The method developed here could be applied for the quantitation of urea dynamics under different physiological and pathological conditions.

Adult↗
PubMed1977

Whole body protein synthesis and catabolism in septic man.

The protein catabolic response to sepsis has been measured in three patients and in two normal subjects using a pulse injections of L-[15N]alanine. In addition, the urea kinetics were measured using a pulse administration of [15N]urea. Several nitrogen models which simulated the metabolic pathways of nitrogen-labeled compounds were tried. Best curve fits and acceptable confidence limits were obtained with a four-pool model containing two metabolic pools and two urea pools. Using this model, synthesis and catabolism rates were calculated for a fast and slow protein turnover pool. The mean daily total protein synthesis rate in the normal was 3.695 g/kg compared to 4.479 g/kg in sepsis. Because all subjects were in negative nitrogen balance, the mean total protein catabolic rate in the normal was 4.379 g/kg, compared to 5.298 g/kg in sepsis. These data suggest an increase in both protein synthesis and catabolism during sepsis.

Abscess↗
PubMedDate not supplied

Integrated nutritional, hormonal, and metabolic effects of recombinant human growth hormone (rhGH) supplementation in trauma patients.

An anabolic stimulus is needed in addition to conventional nutritional support in the catabolic "flow" phase of severe trauma. One promising therapy appears to be rhGH infusion which has direct as well as hormonal mediated substrate effects. We investigated on a whole-body level, the basic metabolic effects of trauma within 48-60 h after injury in 20 severely injured (injury severity score [ISS] = 31 +/- 2), highly catabolic (N loss = 19 +/- 2 g/d), hypermetabolic (resting energy expenditure [REE] = 141 +/- 5% basal energy expenditure [BEE]), adult (age 46 +/- 5 y) multiple-trauma victims, before starting nutrition therapy and its modification after 1 wk of rhGH supplementation with TPN (1.1 x REE calories, 250 mg N.kg-1.d-1). Group H (n = 10) randomly received at 8:00 a.m. on a daily basis rhGH (0.15 mg.kg-1.d-1) and Group C (n = 10) received the vehicle of infusion. Protein metabolism (turnover, synthesis and breakdown rates, and N balance); glucose kinetics (production, oxidation, and recycling); lipid metabolism, (lipolysis and fat oxidation rates), daily metabolic and fuel substrate oxidation rate (indirect calorimetry); and plasma levels of hormones, substrates, and amino acids were quantified. In group H compared to group C: N balance is less negative (-41 +/- 18 vs -121 +/- 19 mg N.kg-1.d-1, P = 0.001); whole body protein synthesis rate is 28 +/- 2% (P = 0.05) higher; protein synthesis efficiency is higher (62 +/- 2% vs 48 +/- 3%, P = 0.010); plasma glucose level is significantly elevated (256 +/- 25 vs 202 +/- 17 mg/dL, P = 0.05) without affecting hepatic glucose output (1.51 +/- 0.20 vs 1.56 +/- 0.6 mg N.kg-1.min-1), glucose oxidation and recycling rates; significantly enhanced rate of lipolysis (P = 0.006) and free fatty acid reesterification (P = 0.05); significantly elevated plasma levels of anabolic GH, IGF-1, IGFBP-3, and insulin; trauma induced counter-regulatory hormone (cortisol, glucagon, catecholamines) levels are not altered; trauma induced hypoaminoacidemia is normalized (P < 0.05) and 3-methylhistidine excretion is significantly low (P < 0.001). Improved plasma IGF-1 levels in Group H compared with Group C account for protein anabolic effects of adjuvant rhGH and may be helpful in promoting tissue repair and early recovery. Skeletal muscle protein is spared by rhGH resulting in the stimulation of visceral protein breakdown. The hyperglycemic, hyperinsulinemia observed during rhGH supplementation may be due to defective nonoxidative glucose disposal, as well as inhibition of glucose transport activity into tissue cells. The simultaneous operation of increased lipolytic and reesterification processes may allow the adipocyte to respond rapidly to changes in peripheral metabolic fuel requirements during injury. This integral approach helps us to better understand the mechanism of the metabolic effects of rhGH.

Adult↗
PubMedDate not supplied

Serum acetaminophen assay using activated charcoal adsorption and gas chromatography without derivatization.

A quantitative assay of acetaminophen in serum has been developed. The drug, together with an internal standard 2-acetamidophenol, is adsorbed on activated charcoal and then extracted into a mixture of ethyl acetate and isopropanol. This extract is then analyzed, without any derivatization, by gas chromatography. The isothermal analysis yielded a good, highly reproducible separation. The drug peak was symmetrical and without any tailing. The peak height response ratio was found to be linear with concentrations ranging from 25-500 ng/L. No interference was observed with the various drugs or metabolites which are commonly encountered in human serum.

Acetaminophen↗
PubMedDate not supplied

High-branched chain amino acid solutions: relationship of composition to efficacy.

A prospective clinical trial was undertaken to determine the nitrogen-sparing efficacy of three amino acid solutions with different concentrations of branched-chain amino acids (BCAA) in 25 postoperative patients. The patients were a homogenous male population with stage I bladder cancer who underwent radical cystectomy. Administration rates of the intravenous solutions were designed to provide 30 kcal/kg/day and 1.5 g protein per kg per day during the 7-day study period. A control group (n = 4) received 5% dextrose in water (150 g/day). Nitrogen balance was determined daily and the whole body protein turnover was measured using a primed-constant infusion of 15N glycine on postoperative days 3 and 4. The group receiving the 45% BCAA enriched (low leucine) amino acid solution exhibited a significant decrease in cumulative (7 day) nitrogen balance (7.6 +/- 2.6 g) compared to the groups receiving either the standard 25% BCAA (19.9 +/- 2.1 g) or the 45% BCAA enriched (high leucine) (21.6 +/- 7.0 g) amino acid solution. The group receiving the 45% BCAA enriched (low leucine) amino acid solution exhibited a higher rate of mean whole body protein catabolism compared to the other groups. For patients undergoing major elective operations, the amount of leucine necessary for optimal daily nitrogen balance was 0.13 g/kg/day. These results demonstrate that the ratio of individual BCAA and the amount of leucine were more critical to nitrogen-sparing efficacy than the percentage total BCAA infused.

Aged↗
PubMedDate not supplied

Effect of total parenteral nutrition on whole body protein kinetics in cachectic patients with benign or malignant disease.

The metabolic effects of total parenteral nutrition on malnourished cancer and noncancer patients were investigated by determining whole-body protein metabolism before and during intravenous nutritional support. The results were compared to similar studies reported in normal subjects. Primed-continuous infusion of 15N glycine was used and the isotopic enrichments in urinary urea and ammonia were measured. The end product average values were used in the calculation of whole body protein turnover. After 10 days of nutritional support in cancer and noncancer patients whole body protein breakdown decreased by 50% (p = 0.01), and 59% (p = 0.001), whereas protein synthesis decreased by 21% (p = 0.005) and 33% (p = 0.025), respectively. Protein turnover did not change in noncancer patients but increased by 15% (p = 0.005) in cancer patients. The efficiency of utilization of the endogenous supply of amino acids from the breakdown of body proteins for synthetic purposes was 77% in this group of subjects. The utilization efficiency of the intravenously infused amino acids for synthesis of body protein was 39% in cancer and noncancer patients but 51% (p less than 0.05) in normals. The data suggest that depleted patients synthesize proteins from intravenous amino acids less well than normals.

Aged↗