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Biomedical subjects

M Jeevanandam

Publications and source records attributed to M Jeevanandam.

103 records · Page 6Linked to original sources
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Nutritional influence on the plasma and urine-free alkaline ribonuclease levels in severe trauma victims.

The significance of free alkaline ribonuclease (RNase) activity as a criterion of protein metabolism and nutrition in traumatized man is evaluated in this report. Plasma and urinary levels of RNase were measured in severely injured, hypermetabolic patients and in normal controls. Significant increases in the plasma and urinary RNase levels were seen in these polytrauma victims and they were positively correlated. Plasma RNase levels were also significantly related to blood urea nitrogen and daily urinary nitrogen excretion. Urinary clearance of RNase was increased by 220% in trauma victims, although the creatinine clearance was not affected by trauma. In a subgroup of eight patients who were fed intravenously (1.4 times basal energy expenditure calories and 250-300 mg of N per kilogram per day) for 6 days, the daily excretions of urinary RNase, nitrogen, 3-methylhistidine, creatinine, and catecholamines were measured. There was a significant negative correlation between daily urine RNase and nitrogen balance. A general increase in all the metabolic parameters on the first day of feeding was seen, suggesting a nutritional stress superimposed on the trauma-induced metabolic stress. Excretion of RNase, 3-methylhistidine, and creatinine peaked on the first day of feeding and then decreased. The normal levels could not be reached even after 6 days of adequate nutrition. The results suggest that RNase levels could be used as a biomarker of protein metabolism.

Adult↗
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Insulin sensitivity in septic cancer-bearing patients.

Resistance to insulin's effect on glucose metabolism is a well-documented phenomenon. The magnitude of resistance to insulin's antilipolytic action is usually less than the resistance to insulin's action on glucose metabolism. In sepsis, resistance to the antilipolytic effect of insulin may be more prominent than resistance to insulin's action on glucose metabolism. Therefore, free fatty acid (FFA) turnover, FFA concentration, glucose tissue uptake, and endogenous glucose production were measured in nine septic cancer-bearing patients and six healthy volunteers during a constant glucose load at two different insulin concentrations. During infusion of glucose alone, plasma insulin concentration in patients and control subjects were, respectively 33 +/- 7 mU/L and 23 +/- 4 mU/L. When plasma glucose was clamped at the low normal range these values were, respectively, 85 +/- 17 mU/L and 28 +/- 5 mU/L (p less than 0.05). Glucose tissue uptake and endogenous glucose production were not significantly different in patients and control subjects in both parts of the study. FFA turnover and FFA concentrations were significantly higher in the patients compared with the control subjects (p less than 0.001) in both parts of the study. It is concluded that in septic cancer-bearing patients, resistance to insulin's effect on FFA turnover is more pronounced than resistance to its inhibiting effect on endogenous glucose production and its stimulating effect on glucose tissue uptake.

Adolescent↗
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Substrate efficacy in early nutrition support of critically ill multiple trauma victims.

The metabolic consequences of excessive nutrition support in patients have been increasingly recognized in recent years. Time-dependent optimal nutrition support is desired for an early and uncomplicated recovery after severe injury or illness. Metabolic effects of adding balanced amino acids to glucose infusion during total parenteral nutrition were investigated in 18 patients after major trauma (injury severity score 32 +/- 2). Two studies were conducted on each subject, one in the early "flow" phase of injury (40-60 hours postinjury) in the basal state without any dietary intake and then after 4 to 6 days of intravenous nutrition provided solely as glucose (24 +/- 2 kcal/kg per day, 80% resting energy expenditure, n = 8) or isocaloric glucose (28 +/- 3 kcal/kg per day) with amino acids (275 +/- 28 mg of nitrogen per kilogram per day, n = 10). Whole-body fuel substrate kinetics were studied for energy metabolism (indirect calorimetry), protein kinetics (primed-constant infusion of 15N glycine), and lipid mobilization (two-stage infusion of 10% glycerol). Injury-induced hypoaminoacidemia was equally modulated whether the glucose-based nutrition had amino acids or not. The negative nitrogen balance is reduced similarly in both groups. Protein breakdown rate is significantly (p = .025) decreased in both groups and it is more so (30% vs 18%) in patients receiving total parenteral nutrition. Intravenous nutrition could not stimulate protein synthesis. Whole-body lipolysis rate as well as net fat oxidation rate are suppressed more when glucose alone is given, and this also results in less reesterification. Provision of intravenous glucose alone, not to exceed the resting energy expenditure, seems to be superior to isocaloric glucose with amino acids during this early catabolic flow phase of injury because the injured body could not assimilate this exogenous amino acid.

Adult↗
PubMedDate not supplied

Adjuvant recombinant human growth hormone normalizes plasma amino acids in parenterally fed trauma patients.

BACKGROUND: The addition of an anabolic stimulant during intensive nutrition therapy in trauma patients seems to be a reasonable adjuvant for minimizing muscle-mass erosion. The plasma free amino acid pattern is the mirror of the net amino acid metabolism, and we have measured the progressive changes resulting from recombinant human growth hormone therapy in trauma victims during nutritional repletion in the early catabolic flow phase of injury. METHODS: In 20 severely injured (injury severity scale = 31 +/- 2), highly catabolic, and hypermetabolic adult multiple-trauma patients, we have measured the fasting (day 0) plasma amino acid levels (48 to 60 hours after injury before starting the nutrition therapy) and their progressive changes during 7 days of IV nutrition support (total parenteral nutrition, 1.1 x resting energy expenditure calories, 250 mg of nitrogen per kilogram per day) with or without adjuvant recombinant human growth hormone. Group H (n = 10) randomly received daily recombinant human growth hormone (0.15 mg of Somatropin per kilogram per day) and Group C (n = 10) received the vehicle of infusion. RESULTS: Hypoaminoacidemia of trauma is normalized by infusion of recombinant human growth hormone, which indicates its anabolic nature, and this is confirmed in the cumulative nitrogen balance (-281 +/- 139 mg of nitrogen per kilogram per 7 days compared with -809 +/- 151 mg of nitrogen per kilogram per 7 days without recombinant human growth hormone; p < or = .005). This improved nitrogen retention is also reflected in the significantly low blood urea nitrogen levels in the recombinant human growth hormone group, which represents the efficient utilization of the infused amino acids for synthesis of proteins. Elevated plasma insulin-like growth factor-1 levels in Group H compared with those in Group C may also account for this altered amino acid metabolism. CONCLUSIONS: Recombinant human growth hormone treatment in combination with conventional total parenteral nutrition in the immediate posttraumatic period improved nitrogen metabolism and normalized the plasma free amino acid levels.

Adult↗
PubMedDate not supplied

Plasma leptin levels in trauma patients: effect of adjuvant recombinant human growth hormone in intravenously fed multiple trauma patients.

BACKGROUND: Leptin, the newly discovered ob gene product, is synthesized primarily in adipose tissue and circulates to all parts of the body. Injury elicits significant metabolic changes, and it is not known how these changes affect the circulating leptin levels. METHODS: Plasma leptin levels were measured in postabsorptive normal subjects (n = 14, 5 men and 9 women) and severely injured (injury severity score [ISS], 34+/-2), hypermetabolic (resting energy expenditure [REE]/basal energy expenditure [BEE], 1.31+/-0.04), adult (39+/-4 years; n = 28, 18 men and 10 women) trauma patients within 48 to 60 hours after injury when they were receiving no nitrogen or calories. The nutritional influence on plasma leptin in these patients was monitored during the subsequent 7 days of total parenteral nutrition (TPN). During TPN the patients were randomized to receive or not to receive recombinant human growth hormone (rhGH) supplementation (0.15 mg/kg/d). RESULTS: Trauma significantly lowered plasma leptin levels, both in women (56%) and in men (68%). Gender dimorphism in plasma leptin levels was seen in normal subjects and in both fasted and fed trauma patients, and in all cases female patients had significantly higher levels. Body mass index showed significantly positive correlations with plasma leptin both in normal and injured subjects. One day of TPN restored normal levels of leptin, both in men and women. Adjuvant rhGH treatment did not show any significant changes over that seen with TPN alone. CONCLUSIONS: Decreased plasma leptin levels seen due to trauma may be partly related to the fasting conditions, because 1 day of refeeding restored normalcy. Leptin metabolism in trauma patients seemed to be not altered during rhGH supplementation, suggesting a relatively minor metabolic role of leptin.

Adolescent↗
PubMedDate not supplied

Urinary excretion of polyamines in the adult respiratory distress syndrome.

Polyamines are low molecular weight polycations that are critically important in cellular proliferation and differentiation. To investigate their potential role in acute lung injury, the polyamines spermidine, spermine, and putrescine were measured in 24-h urine collections from intubated patients with ARDS (n = 12) or congestive heart failure with cardiogenic pulmonary edema (CHF, n = 10) and in normal subjects (n = 10). Mean concentrations of putrescine were similar between groups, but spermidine concentrations in patients with ARDS (52.7 +/- 19.7 nmol/mg creatinine) were significantly higher than in normal subjects (4.9 +/- 0.7 nmol/mg), p < .05. Mean concentrations of spermine in ARDS (270.6 +/- 78.1 nmol/mg) were higher than in CHF (1.0 +/- 0.5 nmol/mg), p < .05, and normal subjects (0.3 +/- 0.1 nmol/mg), p < .05. Concentrations of putrescine increased significantly during the first 7 days of ARDS (241.5 +/- 127.1% above baseline, n = 6), p < .05. Urinary polyamine excretion did not correlate with severity of gas exchange or death. These results are the first to suggest a potential role for polyamines in the pathophysiology of ARDS.

Adult↗
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Proinflammatory cytokine production by mitogen-stimulated peripheral blood mononuclear cells (PBMCs) in trauma patients fed immune-enhancing enteral diets.

Widespread metabolic changes associated with injury facilitate the delivery of nutrients to the immune system. The effect of specific nutrients administered by the enteral route on the immune response in trauma victims is not well understood. The purpose of this study was to examine whether the synthesis of proinflammatory cytokines (tumor necrosis factor-alpha [TNF-alpha], interleukin-1 beta [IL-1 beta], and interleukin-6 [IL-6]) by peripheral blood mononuclear cells (PBMCs) are influenced by the nature of the dietary fat in critically injured trauma victims. We measured plasma TNF-alpha, IL-1 beta, and IL-6 and their release stimulated by phytohemagglutinin (PHA) and endotoxin (lipopolysaccharide, LPS) from PBMCs of 13 severely injured (injury severity score = 30 +/- 2) patients once within 48-60 h after injury and then after 7 d of enteral feeding (1.5 g protein[P].kg-1.d-1). Group I (n = 6) received diet A (Crucial) and group II (n = 7) received diet B (Impact). The plasma levels of TNF-alpha and IL-1 beta in trauma patients are not significantly different from those in healthy volunteers, but plasma IL-6 levels are significantly increased (five times) in severely injured patients. Stimulation of TNF-alpha and IL-1 beta secretion by LPS and PHA were significantly higher in patients than in control subjects; in contrast, there was no stimulation of IL-6 because of trauma or nutritional support by either of the diets. Stimulation of IL-1 beta by LPS was normalized by Crucial but was further enhanced by Impact. The higher fat content in Crucial may contribute in part to the apparent immunomodulation. Crucial seems to be a better choice in correcting the nutritional deficiency.

Adult↗
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Effect of nutritional therapy on polyamine metabolism in severely traumatized patients.

The polyamines (PA) spermidine (SD) and spermine and their precursor putrescine (PU) play a leading role in the regulation of protein, RNA and DNA synthesis. We examined the role of PA along with other biomarkers of injury in eight victims of multiple trauma in the early post-traumatic period when they were hypermetabolic and highly catabolic. Intravenous nutritional therapy (TPN) was started 48 to 60h after trauma and continued for 6 days. The basal response to severe trauma was a significant (twofold to threefold) rise in urinary PU (p = 0.05) and SD (p = 0.025) levels compared to normal subjects. Six days of TPN further enhanced the basal excretion of PU (157%) and SD (137%) peaking on the third day. There was a 20% reduction in the excretion of 3-methylhistidine on the first day of TPN, but it was still 40% above normal on the sixth day. The negative nitrogen balance was improved but not reversed. Injury stimulated ribonuclease and catecholamine levels were also enhanced by nutritional therapy, peaking on the first and fourth day of TPN, respectively. This study demonstrated for the first time elevated levels of PA in trauma patients that correlated well with the other known measures of protein metabolic response to injury and changes during nutritional therapy. Extracellular PA levels could be used as markers of both catabolic pathology in trauma and of its response to nutritional therapy.

Dopamine↗
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Posttraumatic hormonal environment during total parenteral nutrition.

Hormonal responses to major trauma trigger a cascade of metabolic adjustments leading to catabolism and substrate mobilization. Energy deficit and energy surfeit have profound effects on hormone levels. To characterize the course of changes in regulatory hormone levels after multiple injury, we measured the plasma levels of eight hormones, once within 48-60 h after injury in the fasting state and then daily for 5 days during the administration of total parenteral nutrition in 10 hypermetabolic, highly catabolic, and severely injured adult patients. Acute deficiency in anabolic insulinlike growth factor 1 (IGF-1) and growth hormone levels and elevated levels of counterregulatory stress hormones and insulin were seen as a result of trauma. Provision of nutrition on the 1st day has no effect on IGF-1 and cortisol levels. However, growth hormone levels are raised to normal, and the nitrogen balance is improved. Over the next 4 days, there were no appreciable changes in these parameters. The persistent low levels of IGF-1 reflect the altered nutrition status of the patients, as characterized by the continued negative nitrogen balance and elevated cortisol levels in the early posttrauma period. Anabolic IGF-1 and insulin levels showed significant negative correlation with the catabolic indicators 3-methylhistidine and catecholamine excretion. The results suggest that IGF-1 is regulated by nutritional intake independently of growth hormone and may be a better nutrition indicator.

Adult↗
PubMedDate not supplied

Efficacy of a mixture of medium-chain triglyceride (75%) and long-chain triglyceride (25%) fat emulsions in the nutritional management of multiple-trauma patients.

Ten severely injured patients who were admitted to the intensive care unit and who needed total parenteral nutrition (TPN) were randomly enrolled in a prospective double-blind study comparing two 20%-fat intravenous emulsions: one (MCT-LCT) containing a physical mixture of 75% medium-chain triglyceride (MCT) and 25% long-chain triglyceride (LCT) and another containing 100% LCT. TPN (30 kcal.kg-1.day-1) was given continuously as amino acids (20% of energy) and glucose (50% of energy) over 7 days with the respective lipid emulsion (30% of energy) provided from 0800 to 1600 each day. Plasma substrate concentrations, nitrogen balance, resting energy expenditure, substrate net oxidation rates, whole-body lipolysis rates, and fatty acid reesterification rates were measured or calculated. Plasma concentrations of lipid metabolites (glycerol, triglycerides, and fatty acids) indicated rapid hydrolysis and efficient use of the MCT-LCT emulsion. Whole-body lipolysis rate decreased by 53% in the MCT-LCT group and by 34% in the LCT group. Net fat oxidation was greater and FFA reesterification less with MCT-LCT than with LCT, indicating more efficient and rapid fuel utilization in the post-traumatic period with the MCT-LCT emulsion. In critically ill patients dependent on intravenous nutrition, an MCT-LCT mixture may be useful as an obligate fuel and to limit net hepatic lipogenesis.

Adolescent↗