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The metabolic effects of thermal injury

  • World Progress In Surgery
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Abstract

Major thermal injury is associated with extreme hypermetabolism and catabolism as the principal metabolic manifestations encountered following successful resuscitation from the shock phase of the burn injury. Substrate and hormonal measurements, indirect calorimetry, and nitrogen balance are biochemical metabolic parameters which are useful and more readily available biochemical parameters worthy of serial assessment for the metabolic management of burn patients. However, the application of stable isotopes with gas chromatography/mass spectroscopy and more recently, new immunoassays for growth factors and cytokines has increased our understanding of the metabolic manifestations of severe trauma.

The metabolic response to injury in burn patients is biphasic wherein the initialebb phase is followed by a hypermetabolic and catabolicflow phase of injury. The increased oxygen consumption/metabolic rate is in part fuelled by evaporative heat loss from wounds of trauma victims, but likely also by a direct central effect of inflammation upon the hypothalamus. Although carbohydrates in the form of glucose appear to be an important fuel source following injury, a maximum of 5–6 mg/kg/min only is beneficial. Burn patients have accelerated gluconeogenesis, glucose oxidation, and plasma clearance of glucose. Additionally, considerable futile cycling of carbohydrate intermediates occurs which includes anaerobic lactate metabolism and Cori cycle activity arising from wound metabolism of glucose and other substrates. Similarly, accelerated lipolysis and futile fatty acid cycling occurs following burn injury. However, recent evidence suggests that lipids in the diet of burned and other injured patients serve not only as an energy source, but also as an important immunomodulator of prostaglandin metabolism and other immune responses.

Amino acid metabolism in burn patients is characterized by increased oxidation, urea synthesis, and protein breakdown which is prolonged and difficult to reduce with current nutritional therapy. However, the current goal of nutritional support is to optimize protein synthesis. Specific unique requirements may exist for supplemental glutamine and arginine following burn injury but further research is needed before enhanced branched chain amino acids supplements can be recommended for burn patients. Recent research investigations have revealed the importance of enteral feeding to enhance mucosal defense against gut bacteria and endotoxin. Similarly, research has demonstrated that many of the metabolic perturbations of burns and sepsis may be due, at least in part, to inflammatory cytokines. Investigation of their pathogenesis and mechanism of action both at a tissue and a cellular level offer important prospects for improved understanding and therapeutic control of the metabolic disorders of burn patients.

Résumé

Après récupération de la première phase de choc survient un hypercatabolisme majeur. Des paramètres de surveillance de l'évolution et d'évaluation de l'efficacité du traitement sont facilement disponibles: dosages hormonaux et de différents subtats, calorimétrie indirecte et bilan azoté devraient être dosés de façon régulière chez les brûlés. Notre compréhension des perturbations métaboliques chez le blessé et chez la grand brûlé s'est améliorée ces dernières années en raison de l'application de techniques isotopiques avec des dosages par la chromatographie gazeuse et la spectrophotométrie de masse et plus récemment encore les dosages immunologiques des facteurs de croissance et des cytokines. La réponse métabolique à l'agression chez le brûlé est biphasique. La phase initiale est descendante, suivie d'une phase ascendante d'hypercatabolisme. L'augmentation de la consommation en oxygène et du métabolisme est en partie provoquée par la perte en chaleur au niveau des plaies, mais aussi, par un effet direct central, liée à l'inflammation qui agit sur l'hypothalamus. Bien que des hydrates de carbone, sous forme de glucose, semblent être une source importante d'énergie après un traumatisme, l'apport de seulement 5–6 mg/kg/min est suffisant. La néoglucogénèse, l'oxydation du glucose et la clairance plasmatique du glucose du brûlé sont accélérées. Les cycles métaboliques des hydrates de carbone, y compris le métabolisme anaérobie des lactates et le cycle de Cori sont inefficaces. De même, la lipolyse est accélérée et le cycle des acides gras est inefficace. Cependant, il est évident que les lipides chez le brûlé et d'autres patients victimes du traumatisme ne sont pas seulement une source d'énergie mais aussi un immunomodulateur du métabolisme des prostaglandines et d'autres voies de réponse immune. Le métabolisme des acides aminés chez le brûlé est caractérisé par une oxydation, une synthèse d'urée et un catabolisme protéique accrus, phénomènes prolongés et difficiles à réduire avec les moyens actuels de nutrition artificielle. Le but du soutien nutritionnel est cependant d'optimiser la synthèse protéique. Des besoins spécifiques peuvent nécessiter une supplémentation en glutamine et arginine après brûlures mais d'autres recherches sont nécessaires avant de pouvoir dire qu'une supplémentation en acides aminés branchés peut être utile. La recherche moderne a démontré l'importance de l'alimentation entérale qui empêche la traversée de la barrière muqueuse par les germes et les endotoxines. De même, il a été démontré que beaucoup des perturbations métaboliques dans les suites de brûlures et dans les états septiques sont dues, du moins en partie, aux cytokines inflammatoires. L'analyse de leur pathogénèse et leur mécanisme d'action à la fois au niveau tissulaire et cellulaire offrent d'importantes perspectives pour améliorer la compréhension et le contrôle thérapeutique des désordres métaboliques du brûlé.

Resumen

La lesión térmica mayor está relacionada con grados extremos de hipermetabolismo y catabolismo como las manifestaciones metabólicas principales que ocurren una vez cumplida exitosamente la resucitación de la fase de shock. Las determinaciones de sustratos y niveles hormonales, la calorimetría indirecta y el balance de nitrógeno son parámetros metabólicos de carácter bioquímico que son útiles y fácilmente disponibles, los cuales merecen estudios seriados para el manejo metabólico de los pacientes quemados. Sin embargo, la aplicación de isótopos estables con cromatografía de gas/espectrometría de masa y, más recientemente, nuevas inmunodeterminaciones para factores de crecimiento y citocinas, ha incrementado nuestro conocimiento y comprensión de las manifestaciones metabólicas del trauma severo.

La respuesta metabólica en los pacientes quemados es bifásica, en tanto que lafase ebb inicial es seguida de unafase flow hipermetabólica y catabólica. El aumento en el consumo de oxígeno/tasa metabólica se debe en parte a la pérdida evaporativa de calor a partir de las heridas de las víctimas de trauma, pero posiblemente también a un efecto central de la inflamación sobre el hipotálamo. Aunque los carbohidratos en forma de glucosa parecen ser una fuente energética importante, sólo hasta un máximo de 5–6 mg/kg/min son de beneficio. Los pacientes quemados exhiben aceleradas ratas de gluconeogénesis, oxidación de glucosa y depuración plasmática de glucosa. Además, se presenta considerable ciclaje futil de intermediarios de carbohidratos, lo cual incluye metabolismo anaeróbico de lactato y actividad del ciclo de Cori originados en el metabolismo de la glucosa y de otros sustratos a nivel de la herida. También se presenta lipolisis acelerada y ciclaje futil de ácidos grasos. Sin embargo, evidencias recientes sugieren que los lípidos en la dieta de los pacientes con quemaduras y otras formas de trauma sirven no sólo como fuentes energéticas, sino también como un factor importante de modulación del metabolismo de las prostaglandinas y de otras respuestas inmunitarias.

El metabolismo de aminoácidos en el paciente quemado se caracteriza por una oxidación incrementada, síntesis de urea y degradación proteica prolongada y difícil de controlar mediante la terapia nutricional actual. Sin embargo, el propósito actual del soporte nutricional es optimizar la síntesis proteica. Pueden existir requerimientos específicos de glutamina arginina suplementarias en las quemaduras, pero se requieren investigaciones adicionales antes de poder recomendar suplementos enriquecidos con aminoácidos racémicos en los pacientes quemados. Recientes investigaciones han revelado la importancia de la alimentación enteral para estimular las defensas de la mucosa intestinal contra bacterias y endotoxinas. También hay investigaciones que han demostrado que muchas de las alteraciones metabólicas de las quemaduras y las sepsis pueden ser debidas, por lo menos en parte, a las citocinas inflamatorias. La investigación de su patogénesis y mecanismo de acción, tanto al nivel tisular como celular, ofrece perspectivas importantes de una mejor comprensión y de superior control terapéutico de las alteraciones metabólicas de los pacientes quemados.

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References

  1. Tredget, T.E., Shankowsky, H.A., Taerum, T., Moysa, G.L., Alton, J.D.M.: The role of inhalation injury in burn trauma: A Canadian experience. Ann. Surg. (in press)

  2. Department of Health, Education, and Welfare: Reports of the Epidemiology and Surveillance of Injuries, Atlanta, Centers for Disease Control, 1982 (DHEW publication No. (HSM) 73–10001)

  3. Feller, I., Tholen, D., Cornell, R.G.: Improvements in burn care 1965 to 1979. J.A.M.A.244:2074, 1980

    PubMed  Google Scholar 

  4. Deitch, E.D.: The management of burns. N. Engl. J. Med.313:1389, 1985

    PubMed  Google Scholar 

  5. Gump, G.E., Kinney, J.M.: Energy balance and weight loss in burned patients. Arch. Surg.103:442, 1971

    PubMed  Google Scholar 

  6. Long, C.L., Spencer, J.L., Kinney, J.M.: Carbohydrate metabolism in man: Effect of elective operations and major trauma. J. Appl. Physiol.31:110, 1971

    PubMed  Google Scholar 

  7. Soroff, H.S., Pearson, E., Artz, C.P.: An estimation of the nitrogen requirements for equilibrium in burned patients. Surg. Gynecol. Obstet.112:159, 1961

    Google Scholar 

  8. Saffle, J.R., Medina, E., Raymond, J., Westenskow, D., Kravitz, M., Warden, G.D.: Use of indirect calorimetry in the nutritional management of burned patients. J. Trauma25:32, 1985

    PubMed  Google Scholar 

  9. Eccles, R.C., Swinamer, D.L., Jones, R.L., King, E.E.: Validation of a compact system for measuring gas exchange. Crit. Care Med.14:807, 1986

    PubMed  Google Scholar 

  10. Phang, P.T., Rich, T., Ronco, J.: A validation and comparison study of two metabolic monitors. J.P.E.N. J. Parenter. Enteral. Nutr.14:259, 1990

    Google Scholar 

  11. Matthews, D.E., Bier, D.M.: Stable isotope methods for nutritional investigation. Annu. Rev. Nutr.3:309, 1983

    PubMed  Google Scholar 

  12. Allsop, J.R., Wolfe, R.R., Burke, J.F.: Tracer priming the bicarbonate pool. J. Appl. Physiol.45:137, 1978

    PubMed  Google Scholar 

  13. Young, V.R.: Stable isotopes in nutrition research. Fed. Proc.41:2677, 1982

    Google Scholar 

  14. Fong, Y., Moldawer, L.L., Shires, G.T., Lowry, S.F.: The biologic characteristics of cytokines and their implication in surgical injury. Surg. Gynecol. Obstet.170:363, 1990

    PubMed  Google Scholar 

  15. Cuthbertson, D.P.: The disturbance of metabolism produced by bony and non-bony injury, with notes on certain abnormal conditions of bone. Biochem. J.24:1244, 1930

    Google Scholar 

  16. Cunningham, J.J., Hegarty, M.T., Meara, P.A., Burke, J.F.: Measured and predicted calorie requirements of adults during recovery from severe burn trauma. Am. J. Clin. Nutr.49:404, 1989

    PubMed  Google Scholar 

  17. Ireton, C.S., Turner, W.W., Hunt, J.L., Baxter, C.: Evaluation of energy expenditures in burn patients. J. Am. Diet. Assoc.86:331, 1986

    PubMed  Google Scholar 

  18. Burke, J.F., Quinby, W.C., Bondoc, C.C., Sheehy, E.M., Moreno, H.C.: The contribution of a bacterially isolated environment to the prevention of infection in seriously burned patients. Ann. Surg.186:377, 1987

    Google Scholar 

  19. Zawacki, B.E., Spitzer, K.W., Mason, A.D. Jr., Johns, L.A.: Does increased evaporative water loss cause hypermetabolism in burned patients? J. Appl. Physiol.38:593, 1975

    PubMed  Google Scholar 

  20. Kupper, T.S., Deitch, E.A., Baker, C.C., Wong, W.: The human burn wound as a primary source of interleukin-1 activity. Surgery100:409, 1986

    PubMed  Google Scholar 

  21. Ford, H.R., Hoffman, R.A., Wing, E.J.: Characterization of wound cytokine in the sponge matrix model. Arch. Surg.124:1422, 1989

    PubMed  Google Scholar 

  22. Walter, J.S., Meyers, P., Krueger, J.M.: Microinjection of interleukin-1 into brain: Separation of sleep and fever responses. Physiol. Behav.44:555, 1988

    PubMed  Google Scholar 

  23. Dinarello, C.A., Cannon, J.G., Wolff, S.M.: New concepts on the pathogenesis of fever. Rev. Infect. Dis.10:168, 1988

    PubMed  Google Scholar 

  24. Allard, J.P., Jeejheebhoy, K.N., Whitwell, J., Pashutiniski, L., Peters, W.J.: Factors influencing energy expenditure in patients with burns. J. Trauma28:199, 1988

    PubMed  Google Scholar 

  25. Goodwin, C.W.: Metabolism and nutrition in the thermally injured patient. Crit. Care Clin.1:97, 1985

    PubMed  Google Scholar 

  26. Aulick, L.H., Wilmore, D.W.: Increased peripheral amino acid release following thermal injury. Ann. Surg.188:778, 1978

    PubMed  Google Scholar 

  27. Perlmutter, D., Goldberger, G., Dinarello, C.A., Mizel, S.B., Colten, H.R.: Cachetin/tumor necrosis factor regulates hepatic acute phase gene expression. J. Clin. Invest.78:1349, 1986

    PubMed  Google Scholar 

  28. Newsholme, E.A., Leech, A.R.: Regulation of glucose and fatty acid oxidation in relation to energy demand in muscle. In Biochemistry for the Medical Sciences, E.A. Newsholme, A.R. Leech, editors, Chicester-New York-Brisbane-Toronto-Singapore, John Wiley and Sons, 1983, pp. 300–335

    Google Scholar 

  29. Leninger, A.L.: Electron transport, oxidative phosphorylation, and regulation of ATP production. In Principles of Biochemistry, 3rd edition, S. Anderson, J. Fox, editors, New York, Worth Publishers, 1982, pp. 467–510

    Google Scholar 

  30. Wilmore, D.W., Aulick, L.H. Mason A. Jr., Pruitt, B.A. Jr.: Influence of the burn wound on local and systemic responses to injury. Ann. Surg.186:444, 1977

    PubMed  Google Scholar 

  31. Wolfe, R.R., Herndon, D.N., Jahoor, F., Miyoshi, H., Wolfe, M.H.: Effect of severe burn injury of substrate cycling by glucose and fatty acids. N. Engl. J. Med.317:403, 1987

    PubMed  Google Scholar 

  32. Shulman, G.I., Ladenson, P.W., Wolfe, M.H., Ridgway, E.C., Wolfe, R.R.: Substrate cycling between gluconeogenesis and glycolysis in euthyroid, hypothyroid, and hyperthyroid man. J. Clin. Invest.76:757, 1985

    PubMed  Google Scholar 

  33. Burke, J.F., Wolfe, R.R., Mullany, D.J., Matthews, D.E., Bier, D.M.: Glucose requirements following burn injury. Ann. Surg.190:274, 1979

    PubMed  Google Scholar 

  34. Wolfe, R.R., Durkot, M.J., Allsopo, J.R., Burke, J.F.: Glucose metabolism in severely burned patients. Metabolism28:1031, 1979

    PubMed  Google Scholar 

  35. Tredget, E.E., Burke, J.F.: Calorie and substrate requirements in trauma and sepsis. In Trauma, Sepsis, and Shock, the Physiologic Basis of Therapy, G.H.A. Clowes, Jr., editor, New York-Basel, Marcel Dekker, Inc., 1988, pp. 269–305

    Google Scholar 

  36. Aulick, L.H., Wilmore, D.W., Mason, A.D. Jr., Pruitt, B.A. Jr.: Peripheral blood flow in thermally injured patients. Fed. Proc.36:417, 1977

    Google Scholar 

  37. Wolfe, R.R., Burke, J.F.: Effect of burn trauma on glucose turnover, oxidation, and recycling in guinea pigs. Am. J. Physiol.233:E80, 1976

  38. Cori, C.F.: Mammalian carbohydrate metabolism. Physiol. Rev.11:143, 1931

    Google Scholar 

  39. Kreisbereg, R.A.: Pathogenesis and management of lactic acidosis. Ann. Rev. Med.35:181, 1984

    PubMed  Google Scholar 

  40. Laugness, U., Udenfriend, S.: Collagen proline hydroxylase activity and anaerobic metabolism. In Biology of the Fibroblast, E. Kulonen, J. Pikkarainen, editors, New York, Academic Press, 1973, pp. 373

    Google Scholar 

  41. Hunt, T.K., Conolly, W.B., Aronson, S.B.: Anaerobic metabolism and wound healing: An hypothesis for the initiation and cessation of collagen synthesis in wounds. Am. J. Surg.135:328, 1978

    PubMed  Google Scholar 

  42. Black, P.R., Brooks, D.C., Bessey, P.Q., Wolfe, R.R., Wilmore, D.W.: Mechanisms of insulin resistance following injury. Ann. Surg.196:420, 1982

    PubMed  Google Scholar 

  43. Jahoor, F., Wolfe, R.R.: Role of insulin and glucagon in the response of glucose and alanine kinetics in burn injured patients. J. Clin. Invest.78:807, 1986

    PubMed  Google Scholar 

  44. Czech, M.P.: New perspectives on the mechanism of insulin action. Recent Prog. Horm. Res.40:346, 1985

    Google Scholar 

  45. Brooks, D.C., Bessey, P.Q., Black, P.R., Wolfe, R.R., Wilmore, D.W.: Post-traumatic insulin resistance in uninjured forearm tissue. J. Surg. Res.37:100, 1984

    PubMed  Google Scholar 

  46. Shangraw, R.E., Jahoor, F., Miyoshi, H., Neff, W.A., Stuart, C.A., Herndon, D.N., Wolfe, R.R.: Differentiation between septic and postburn insulin resistance. Metabolism38:983, 1989

    PubMed  Google Scholar 

  47. Jahoor, F., Shangraw, R.E., Miyoshi, H., Wallfish, H., Herndon, D.N., Wolfe, R.R.: Role of insulin and glucose oxidation in mediating the protein catabolism of burns and sepsis. Am. J. Physiol.257:E323, 1989

  48. Gottschlich, M.M., Alexander, J.W.: Fat kinetics and recommended dietary intake in burns. J.P.E.N. J. Parenter. Enteral. Nutr.11:80, 1987

    Google Scholar 

  49. Galster, A.D., Bier, D.M., Cryer, P.E., Monafo, W.W.: Plasma palmitate turnover in subjects with thermal injury. J. Trauma24:938, 1984

    PubMed  Google Scholar 

  50. Wolfe, R.R., Herndon, D.N., Peters, E.J., Jahoor, F., Desai, M.H., Holland, O.B.: Regulation of lipolysis in severely burned children. Ann. Surg.206:214, 1987

    PubMed  Google Scholar 

  51. Wilmore, D.W., Moylan, J.A., Jelmkamp, G.M., Pruitt, B.A. Jr.: Clinical evaluation of a 10% intravenous fat emulsion for parenteral nutrition in thermally injured patients. Ann. Surg.178:503, 1973

    PubMed  Google Scholar 

  52. Kudsk, K.A., Stone, J.M., Sheldon, G.F.: Nutrition in trauma and burns. Surg. Clin. North Am.62:183, 1982

    PubMed  Google Scholar 

  53. Wan, J.M.F., Teo, T.C., Babayan, V.K., Blackburn, G.L.: Lipids and the development of immune dysfunction and infection. J.P.E.N. J. Parenter. Enteral. Nutr.12:43S, 1988

  54. Wolfe, B.M., Ney, D.M.: Lipid metabolism in parenteral nutrition. In Parenteral Nutrition, J.L. Rombeau, M.D. Caldwell, editors, Philadelphia, W.B. Saunders, 1986, pp. 72–99

    Google Scholar 

  55. Kinsella, J.E., Lokesh, B., Broughton, S.: Dietary polyunsaturated fatty acids and eicosanoids: Potential effects on the modulation of inflammatory and immune cells: An Overview. Nutrition5:24, 1990

    Google Scholar 

  56. Hageman, J.R., McCulloch, K., Gora, P., Olsen, E.K., Pachman, L., Hunt, C.E.: Intralipid alterations in pulmonary prostaglandin metabolism and gas exchange. Crit. Care Med.11:794, 1983

    PubMed  Google Scholar 

  57. Abel, R.M., Fisch, D., Grossman, M.L.: Hemodynamic effects of intravenous 20% soy oil emulsion following coronary bypass surgery. J.P.E.N. J. Parenter. Enteral. Nutr.7:534, 1983

    Google Scholar 

  58. Hamaway, K.J., Moldawer, L.L., Georgieff, M., Valicenti, A.J., Babyan, V.K., Bistrian, B.R., Blackburn, G.L.: The effect of lipid emulsions on reticuloendothelial system function in the injured animal. J.P.E.N. J. Parenter. Enteral. Nutr.9:559, 1985

    Google Scholar 

  59. Freeman, J., Goldmann, D.A., Smith, N.E., Sidebottom, D.G., Epstein, M.F., Platt, R.: Association of intravenous lipid emulsion and coagulase-negative staphylococcal bacteremia in neonatal intensive care units. N. Engl. J. Med.323:301, 1990

    PubMed  Google Scholar 

  60. Griffin, E., Breckenridge, W.C., Kuksis, A., Bryan, M.H., Angel, A.: Appearance and characterization of lipoprotein X during continuous intralipid infusions in the neonate. J. Clin. Invest.64:1703, 1979

    PubMed  Google Scholar 

  61. Untraucht, S.: Alterations of serum lipoproteins resulting from total parenteral nutrition with intralipid. Biochim. Biophys. Acta711:176, 1982

    PubMed  Google Scholar 

  62. Alexander, J.W., Saito, H., Ogle, C.K., Trocki, O.: The importance of lipid type in the diet after burn injury. Ann. Surg.204:1, 1986

    PubMed  Google Scholar 

  63. Endres, S., Ghobani, R., Kelley, V.E., Cannon, J., Dinarello, C.A.: The effect of dietary supplementation with N-3 polyunsaturated fatty acids on the synthesis of interleukin-1 and tumor necrosis factor by mononuclear cells. N. Engl. J. Med.320:252, 1989

    PubMed  Google Scholar 

  64. Babayan, V.K.: Medium chain triglycerides and structured lipids. Lipids22:417, 1987

    PubMed  Google Scholar 

  65. Kinsella, J.E.: Lipids, membrane receptors, and enzymes: Effects of dietary fatty acids. J.P.E.N. J. Parenter. Enteral. Nutr.14:200S, 1990

  66. Jensen, G.L., Mascioli, E.A., Seidner, D.L., Istafan, N.W., Donmitch, A.M., Selleck, K., Babayan, V.K., Blackburn, G.L., Bistrian, B.R.: Parenteral infusion of long- and medium-chain triglycerides and reticuloendothelial system function in man. J.P.E.N. J. Parenter. Enteral. Nutr.14:467, 1990

    Google Scholar 

  67. DeMichele, S.J., Karlstad, M.D., Bistrian, B.R., Istafan, N., Babayan, V.K., Blackburn, G.L.: Enteral nutrition with structured lipid: Effect on protein metabolism in thermal injury. Am. J. Clin. Nutr.50:1295, 1989

    PubMed  Google Scholar 

  68. Mullen, J.L.: Consequences of malnutrition in the surgical patients. Surg. Clin. North Am.61:465, 1981

    PubMed  Google Scholar 

  69. Moore, F.D., Brennan, M.F.: Surgical injury. In Manual of Surgical Nutrition, F.D. Bellinger, editor, Philadelphia, Saunders, 1975, pp. 169–222

    Google Scholar 

  70. Kinney, J.M., Elwyn, D.H.: Protein metabolism and injury. Ann. Rev. Nutr.3:433, 1983

    Google Scholar 

  71. Jahoor, F., Desai, M., Herdon, D.N., Wolfe, R.R.: Dynamics of the protein metabolic response to burn injury. Metabolism4:330, 1988

    Google Scholar 

  72. Hedden, M.P., Mazuski, J.E., Chute, E.: General stimulation of muscle protein synthesis by branched-chain amino acidsin vitro. Proc. Soc. Exp. Bio. Med.160:410, 1979

    Google Scholar 

  73. Hagenfeldt, L., Eriksson, S., Wahren, J.: Influence of leucine on arterial concentrations and regional exchange of amino acids in healthy subjects. Clin. Sci.59:173, 1980

    PubMed  Google Scholar 

  74. Elia, M., Farrell, R., Ilie, V., Smith, R., Williamson, D.H.: The removal of infused leucine after injury, starvation and other conditions in man. Clin. Sci.59:275, 1980

    PubMed  Google Scholar 

  75. Desai, S.P., Bistrain, B.R., Moldawere, L.L., Miller, M.M., Blackburn, G.L.: Plasma amino acid concentrations during branched-chain amino acid infusion in stressed patients. J. Trauma22:747, 1982

    PubMed  Google Scholar 

  76. Wolfe, R.R., Goodenough, R.D., Burke, J.F., Wolfe, M.H.: Response of protein and urea kinetics in burn patients to different levels of protein intake. Ann. Surg.197:163, 1983

    PubMed  Google Scholar 

  77. Yu, Y.M., Wagner, D.A., Waleswski, J.C., Burke, J.F., Young, V.R.: A kinetic study of leucine metabolism in severely burned patients. Ann. Surg.207:421, 1988

    PubMed  Google Scholar 

  78. Milliken, W.J., Jr., Henderson, J.M., Galloweay, J.R.:In vivo measurement of leucine metabolism with stable isotopes in normal subjects and in those with cirrhosis fed conventional and branched-chain amino acid enriched diets. Surgery98:405, 1986

    Google Scholar 

  79. Wolfson, A.M.I.: Amino acids-their role as an energy source. Proc. Nutr. Soc.42:489, 1983

    PubMed  Google Scholar 

  80. Brennan, M.F., Cerra, F., Daly, J.M., Fischer, J.E., Moldawer, L.L., Smith, R.J., Vinnars, E., Wannemacher, R., Young, V.R.: Report of a research workshop: Branched-chain amino acids in stress and injury. J.P.E.N. J. Parenter. Enteral. Nutr.10:446, 1986

    Google Scholar 

  81. Garlick, P.J., Grant, I.: Amino acid infusion increases the sensitivity of muscle protein synthesisin vivo to insulin. Biochem. J.254:579, 1988

    PubMed  Google Scholar 

  82. Newsholme, E.A., Newsholme, D.P., Phil, D., Curi, R., Challoner, E., Ardawi, M.S.M.: A role for muscle in the immune system and its importance in surgery, trauma, sepsis and burns. Nutrition International4:261, 1988

    Google Scholar 

  83. Bergstrom, L., Furst, P., Noree, L.O., Vinnars, E.: Intracellular free amino acid concentration in human muscle tissue. J. Appl. Physiol.36:693, 1974

    PubMed  Google Scholar 

  84. Smith, R.J.: Regulation of protein degradation in differentiated skeletal muscle cells in monolayer culture, in intracellular protein catabolism. Prog. Clin. Biol. Res.180:633, 1984

    Google Scholar 

  85. Rennie, M.J., Hundal, H.S., Babil, P., MacLennan, P.A., Taylor, P.M., Watt, P.W.: Characteristics of a glutamine carrier in skeletal muscle have important consequence for nitrogen loss in injury, infection and chronic disease. Lancet2:1008, 1986

    PubMed  Google Scholar 

  86. Jepson, M.M., Bates, P.C., Broadbent, P., Pell, J.M., Millward, D.J.: Relationship between glutamine concentration and protein synthesis in rat skeletal muscle. Am. J. Physiol.255:E166, 1988

  87. Maclennan, P.A., Brown, R.A., Rennie, M.J.: A positive relationship between protein synthetic rate and intracellular glutamine concentration in perfused rat skeletal muscle. FEBS Lett.215:187, 1987

    PubMed  Google Scholar 

  88. Vinnars, E., Bergstrom, J., Furst, P.: Influence of postoperative state on the intracellular free amino acids in human muscle tissue. Ann. Surg.192:78, 1980

    PubMed  Google Scholar 

  89. Askanazi, J., Carpentier, J.A., Michelsen, C.B., Elwyn, U.H., Furst, P., Kantrowitz, L.R., Gump, F.E., Kinney, J.M.: Muscle and plasma amino acids following injury: Influence of intercurrent infection. Ann. Surg.192:78, 1980

    PubMed  Google Scholar 

  90. Hundal, H.S., Rennie, M.J., Watt, P.W.: Characteristics of glutamine transport in perfused rat skeletal muscle. J. Physiol. (Lond)393:283, 1987

    Google Scholar 

  91. Ahmed, A., Talor, P.M., Rennie, M.J.: Characteristics of glutamine transport in sarcolemmal vesicles from rat skeletal muscle. Am. J. Physiol.259:E284, 1990

  92. Newsholme, E.A., Leech, E.A.: Biochemistry for the Medical Sciences, Chichester, John Wiley & Sons, 1983, pp. 233–234

    Google Scholar 

  93. Newsholme, E.A., Crabtree, B., Ardawi, M.S.M.: The role of high rates of glycolysis and glutamine utilization in rapidly dividing cells. Biosci. Rep.4:393, 1985

    Google Scholar 

  94. Newsholme, E.A., Crabtree, B., Ardawi, M.S.M.: Glutamine metabolism in lymphocytes, its biochemical, physiological and clinical importance. Q. J. Exp. Physiol.70:473, 1985

    PubMed  Google Scholar 

  95. Newsholme, E.A., Newsholme, P., Curi, R.: The role of citric acid cycle in cells of the immune system and its importance in sepsis, trauma and burns. Biochem. Soc. Symp.54:145, 1987

    PubMed  Google Scholar 

  96. Newsholme, E.A., Parry-Billings, M., Phil, D.: Properties of glutamine release from muscle and its importance for the immune system. J.P.E.N. J. Parenter. Enteral. Nutr.14:63s, 1990

  97. Dimarchi, R.D., Tam, J.P., Kent, S.B., Merrifield, R.B.: Weak acid-catalyzed pyrrolidine carboxylic acid formation from glutamine during solid phase peptide synthesis. Int. J. Pept. Protein Res.19:88, 1982

    PubMed  Google Scholar 

  98. Stehle, P., Ratz, I., Furst, P.:In vivo utilization of intravenously supplied L-alanine-L-glutamine in various tissues of the rat. Nutrition5:411, 1989

    PubMed  Google Scholar 

  99. Adibi, S.A.: Experimental basis for use of peptides as substrate for parenteral nutrition: A review. Metabolism36:1001, 1987

    PubMed  Google Scholar 

  100. Furst, P., Albers, S., Stehle, P.: Glutamine-containing dipeptides in parenteral nutrition. J.P.E.N. J. Parenter. Enteral. Nutr.14:118s, 1990

  101. Stehle, P., Ratz, I., Furst, P.:In vivo utilization of intravenously supplied L-alanine-L-glutamine in various tissues of the rat. Nutrition5:411, 1989

    PubMed  Google Scholar 

  102. Adibi, S.A.: Experimental basis of for use of peptides as substrate for parenteral nutrition: A review. Metabolism36:1001, 1987

    PubMed  Google Scholar 

  103. Hammarqvist, F., Wernerman, J., Ali, R., Von Der Decken, A., Vinnars, E.: Addition of glutamine to total parenteral nutrition after elective abdominal surgery spares free glutamine in muscle, counteracts the fall in muscle protein synthesis, and improves nitrogen balance. Ann. Surg.209:455, 1989

    PubMed  Google Scholar 

  104. Stehle, P., Zander, J., Mertes, N., Albers, S., Puchstein, C., Lawin, P., Furst, P.: Effect of parenteral glutamine peptide supplements on muscle glutamine loss and nitrogen balance after major surgery. Lancet1:231, 1989

    PubMed  Google Scholar 

  105. Ziegler, T.R., Benfell, K., Smith, R.J., Young, L.S., Brown, E., Ferrari-Baliviera, E., Lowe, D.K., Wilmore, D.W.: Safety and metabolic effects of L-glutamine administration in humans. J.P.E.N. J. Parenter. Enteral Nutr.14:137s, 1990

  106. Grant, J.P., Snyder, P.J.: Use of L-glutamine in total parenteral nutrition. J. Surg. Res.44:506, 1988

    PubMed  Google Scholar 

  107. Souba, W.W., Klimberg, V.S., Hautamaki, R.D., Mendenhall, W.H., Bova, F.C., Howard, R.J., Bland, K.I., Copeland, E.M.: Oral glutamine reduces bacterial translocation following abdominal radiation. J. Surg. Res.48:1, 1990

    PubMed  Google Scholar 

  108. Souba, W.W., Klimberg, V.S., Plumley, D.A., Salloum, R.M., Flynn, T.C., Bland, K.I., Copeland, E.M.: The role of glutamine in maintaining gut structure and function and supporting the metabolic response to injury and infection. J. Surg. Res.48:383, 1990

    PubMed  Google Scholar 

  109. Seifter, E., Rettura, G., Barbul, A., Levenson, S.M.: Arginine: An essential amino acid for injured rats. Surgery84:224, 1978

    PubMed  Google Scholar 

  110. Barbul, A.: Arginine: Biochemistry, physiology and therapeutic implications. J.P.E.N. J. Parenter. Enteral. Nutr.10:227, 1986

    Google Scholar 

  111. Saito, H., Trocki, O., Wang, S.L., Gonce, S.J., Joffe, S.N., Alexander, J.W.: Metabolic and immune effects of dietary arginine supplementation after burn. Arch. Surg.122:784, 1987

    PubMed  Google Scholar 

  112. Alexander, J.W., Gottschlich, M.M.: Nutritional immunomodulation in burn patients. Crit. Care Med.18:S149, 1990

  113. Daly, J.M., Reynolds, J., Thom, A., Kinsley, L., Dietrick-Gallagher, M.: Metabolic effects of arginine in the surgical patients. Ann. Surg.208:512, 1988

    PubMed  Google Scholar 

  114. Barbul, A., Wasserkrug, H.L., Penberthy, L.T., Norman, N.Y., Tao, R.C., Efron, G.: Optimal levels of arginine in maintenance intravenous hyperalimentation. J.P.E.N. J. Parenter. Enteral. Nutr.8:281, 1984

    Google Scholar 

  115. Barbul, A.: Arginine: Biochemistry, physiology and therapeutic implications. J.P.E.N. J. Parenter. Enteral. Nutr.10:227, 1986

    Google Scholar 

  116. Barbul, A., Lazarou, S.A., Efron, D.T., Wasserkrug, H.L., Effron, G.: Arginine enhances wound healing and lymphocyte immune responses in humans. Surgery108:331, 1990

    PubMed  Google Scholar 

  117. Hibbs, J.B., Taintor, R.R., Vavrin, Z.: Macrophage cytotoxicity: Role for L-arginine deaminase and imino nitrogen oxidation to nitrite. Science235:473, 1987

    PubMed  Google Scholar 

  118. Granger, D.L., Hibbs, J.B., Jr., Perfect, J.R., Durack, D.T.: Specific amino acid (L-arginine) requirement for the microbiostatic activity of murine macrophages. J. Clin. Invest.81:1129, 1988

    PubMed  Google Scholar 

  119. Granger, D.L., Hibbs, J.B., Jr., Perfect, J.R., Durack, D.T.: Metabolic fats of L-arginine in relation to microstatic capability of murine macrophages. J. Clin. Invest.85:264, 1990

    PubMed  Google Scholar 

  120. Randomski, M.W., Palmer, R.M.J., Moncada, S.: An L-arginine/nitric oxide pathway present in human platelets regulates aggregation. Proc. Natl. Acad. Sci.87:5193, 1990

    PubMed  Google Scholar 

  121. Leaf, C.D., Wishnock, J.S., Tennenbaum, S.R.: L-arginine is a precursor for nitrate biosynthesis in humans. Biochem. Biophys. Res. Commun.163:1032, 1989

    PubMed  Google Scholar 

  122. Albina, J.E., Mills, C.D., Barbul, A., Thirkill, C.E., Henry, W.L., Jr., Mastrofrancesco, B., Caldwell, M.D.: Arginine metabolism in wounds. Am. J. Physiol.254:E459, 1988

  123. Albina, J.E., Mills, C.D., Henry, W.L., Jr., Caldwell, M.D.: Temporal expression of different pathways of L-arginine metabolism in healing wounds. J. Immunol.144:3877, 1990

    PubMed  Google Scholar 

  124. Barbul, A., Rettura, G., Prior, E., Levenson, S.M., Seifter, E.: Supplemental arginine, wound healing and thymus: Arginine-pituitary interactions. Surg. Forum29:93, 1978

    PubMed  Google Scholar 

  125. Barbul, A., Lazarou, S.A., Efron, D.T., Wasserkrug, H.L., Efron, G.: Arginine enhances wound healing and lymphocyte immune response in humans. Surgery108:331, 1990

    PubMed  Google Scholar 

  126. Manson, J.M., Wilmore, D.W.: Positive nitrogen balance with human growth hormone and hypocaloric intravenous feeding. Surgery100:188, 1986

    PubMed  Google Scholar 

  127. Windmueller, H.G., Spaeth, A.E.: Respiratory fuel and nitrogen metabolismin vivo in small intestine of fed rats. J. Biol. Chem.255:107, 1980

    PubMed  Google Scholar 

  128. Windmueller, H.G., Spaeth, A.E.: Intestinal metabolism of glutamine and glutamate from the lumen as compared to glutamine from blood. Arch. Biophys. Biochem.171:662, 1975

    Google Scholar 

  129. Wilmore, D.W., Smith, R.J., O'Dwyer, S.T., Jacobs, D.O., Ziegler, T.R., Wang, X.D.: The gut: A central organ after surgical stress. Surgery104:917, 1988

    PubMed  Google Scholar 

  130. Muhlbacher, F., Kapadia, C.R., Colpoys, M.F., Smith, R.J., Wilmore, D.W.: Effects of glucocorticoids on glutamine metabolism in skeletal muscle. Am. J. Physiol.247:E75, 1984

  131. Brooks, D., Bessey, P.Q., Black, P.R., Aoki, T.T., Wilmore, D.W.: Insulin stimulated branched-chain amino acid uptake diminishes nitrogen efflux from skeletal muscle of injured patients. J. Surg. Res.40:395, 1986

    PubMed  Google Scholar 

  132. Souba, W.W., Herskowitz, K., Salloum, R.M., Chen, M.K., Austgen, T.R.: Gut glutamine metabolism. J.P.E.N. J. Parenter. Enteral. Nutr.14:45s, 1990

  133. Barry, G.: Structure, biochemistry, and assembly of epithelial tight junctions. Am. J. Physiol.253:c749, 1987

  134. Madara, J.L.: Loosening tight junctions: Lessons from the intestine. J. Clin. Invest.83:1089, 1989

    PubMed  Google Scholar 

  135. Dobbins, W.O., 3rd.: Gut immunophysiology: A gastroenterologist's view with emphasis on pathophysiology. Am. J. Physiol.242:G1, 1982

  136. Wells, C.L., Maddaus, M.A., Simons, R.L.: Proposed mechanisms for the translocation of intestinal bacteria. Rev. Infect. Dis.10:958, 1988

    PubMed  Google Scholar 

  137. Deitch, E.A.: The management of burns. N. Engl. J. Med.323:1249, 1990

    PubMed  Google Scholar 

  138. Levine, G.M., Deren, J.J., Steiger, E.: Role of oral intake in maintenance of gut mass and disaccharidase activity. Gastroenterology67:975, 1974

    PubMed  Google Scholar 

  139. Dworkin, L.D., Levine, G.M., Farber, N.J.: Small intestinal mass of the rat is partially determined by indirect effects of intraluminal nutrition. Gastroenterology71:626, 1976

    PubMed  Google Scholar 

  140. Johnson, L.R., Copeland, E.M., Dudrick, J.J.: Structural and hormonal alterations in the gastrointestinal tract of parenterally fed rats. Gastroenterology68:117, 1975

    Google Scholar 

  141. Alverdy, J.A., Chi, H.S., Sheldon, G.S.: The effect of parenteral nutrition on gastrointestinal immunity: The importance of intestinal stimulation. Ann. Surg.202:681, 1985

    PubMed  Google Scholar 

  142. Moore, F.A., Moore, E.E., Jones, T.N., McCroskey, B.L., Peterson, V.M.: TEN vs TPN following major abdominal trauma: Reduced septic morbidity. J. Trauma29:916, 1989

    PubMed  Google Scholar 

  143. Border, J.R., Massett, J., LaDuca, J., Seibel, R., Steinberg, S., Mills, B., Losi, P., Border, D.: The gut origin septic states in blunt multiple trauma (ISS-40) in the ICU. Ann. Surg.206:427, 1987

    PubMed  Google Scholar 

  144. Wilmore, D.W.: Nutrition and metabolism following thermal injury. Clin. Plast. Surg.1:603, 1979

    Google Scholar 

  145. Bessey, P.Q., Watters, J.M., Aoki, T.T., Wilmore, D.W.: Combined hormonal infusion stimulates the metabolic response to injury. Ann. Surg.200:264, 1984

    PubMed  Google Scholar 

  146. Shamoon, H.M., Hendler, R., Sherwin, R.S.: Synergistic interactions among anti-insulin hormones in the pathogenesis of stress hyperglycemia in humans. J. Clin. Endocrinol. Metab.52:1235, 1985

    Google Scholar 

  147. Watters, J.M., Bessey, P.Q., Dinarello, C.A., Wolff, S.M., Wilmore, D.W.: Both inflammatory and endocrine mediators stimulate host responses to sepsis. Arch. Surg.121:179, 1986

    PubMed  Google Scholar 

  148. Kupper, T.S., Deitch, E. A., Baker, C.C., Wong, W.: The human burn wound as a primary source of interleuekin-1 activity. Surgery100:409, 1986

    PubMed  Google Scholar 

  149. Sauder, D.N., Monick, M.M., Hunninghake, G.W.: Epidermal cell derived thymocyte activating factor (ETAF) is a potent T cell chemoattractant. J. Invest. Dermatol.85:431, 1985

    PubMed  Google Scholar 

  150. Heideman, M.: Complement activation by thermal injury and its possible consequences for immune defense. In The Immune Consequences of Thermal Injury, J.L. Ninneman, editor, Baltimore, Williams and Wilkins, 1981, pp. 127–131

    Google Scholar 

  151. Okusawa, S., Dinarello, C.A., Yancey, K.B., Endres, S., Lawley, J.J., Frank, M.M., Burke, J.F., Gelfand, J.A.: C5a induction of human interleukin-1. J. Immunol.139:2635, 1985

    Google Scholar 

  152. Marano, M.A., Fong, Y., Moldawer, L.L., Tracey, K.J., Lowry, S.F., Beutler, B., Shires, T.S.: Serum cachectin/TNF in critically ill burn patients correlates with infection and mortality. Surg. Gynecol. Obstet.170:32, 1990

    PubMed  Google Scholar 

  153. Guo, J., Dickerson, C., Chrest, F.J., Adler, W.H., Munster, A.M., Winchurch, R.A.: Increased levels of circulating interleukin-6 in burn patients. Clin. Immunol. Immunopathol.54:361, 1990

    PubMed  Google Scholar 

  154. Tredget, E.E., Yu, Y.M., Zhong, S., Burini, R., Okusawa, S., Gelfand, J.A., Dinarello, C.A., Young, V.R., Burke, J.F.: Role of interleukin 1 and tumor necrosis factor on energy metabolism in rabbits. Am. J. Physiol.255:E760, 1988

  155. Feingold, K.R., Grunfeld, C.: Tumor necrosis factor-alpha stimulates hepatic lipogenesis in the ratin vivo. J. Clin. Invest.80:184, 1987

    PubMed  Google Scholar 

  156. Perlmutter, D.H., Dinarello, C.A., Punsal, P.K., Colten, H.R.: Cachectin tumor necrosis factor regulates hepatic acute phase gene expression. J. Clin. Invest.78:1349, 1986

    PubMed  Google Scholar 

  157. Warren, R.S., Starnes, H.F., Gabrilove, J.L.: The acute metabolic effects of tumor necrosis factor administration. Arch. Surg.122:1396, 1987

    PubMed  Google Scholar 

  158. Dinarello, C.A., Mier, J.W.: Current concepts: Lymphokines. N. Engl. J. Med.317:940, 1987

    PubMed  Google Scholar 

  159. Tracey, K.J., Lowry, S.F., Fahey, T.J., III, Albert, J.D., Fong, Y., Hesse, D., Beutler, B., Manogue, K.R., Calvano, S., Wei, H., Cerami, A., Shires, G.R.: Cachectin/tumor necrosis factor induces lethal shock and stress hormone responses in the dog. Surg. Gynecol. Obstet.164:415, 1987

    PubMed  Google Scholar 

  160. Uehara, A., Gottschall, P.E., Dahl, R.R., Arimura, A.: Interleukin-1 stimulates ACTH release by an indirect action which requires endogenous corticotropin releasing factor. Endocrinology121:1580, 1987

    PubMed  Google Scholar 

  161. Sandler, S., Bentzen, K., Borg, L.A.H.: Studies on the mechanisms causing inhibition of insulin secretion in rat pancreatic islets exposed to human interleukin-1 beta indicate a perturbation in the mitochondrial function. Endocrinology124:1492, 1989

    PubMed  Google Scholar 

  162. Woloski, M.M.R.N.J., Smith, E.M., Meyer, W.J., III, Fuller, G.M., Blalock, J.E.: Corticotropin-releasing activity of monokines. Science230:1035, 1985

    PubMed  Google Scholar 

  163. Bernton, E.W., Beach, J.E., Holady, J.W., Smallridge, R.C., Fein, H.G.: Release of multiple hormones by a direct action of interleukin-1 on pituitary cells. Science238:521, 1987

    Google Scholar 

  164. Baracos, V., Rodemann, P., Dinarello, C.A., Goldberg, A.L.: Stimulation of muscle protein degradation and prostaglandin E2 release by leukocytic pyrogen (interleukin-1). N. Engl. J. Med.303:553, 1983

    Google Scholar 

  165. Libby, P., Ordovas, J.M., Auger, K.R., Robbins, A.H., Birinyi, L.K., Dinarello, C.A.: Endotoxin and tumor necrosis factor induce interleukin-1 gene expression in adult human vascular endothelial cells. Am. J. Pathol.124:179, 1986

    PubMed  Google Scholar 

  166. Dayer, J.M., DeRochemonteix, B., Burrus, B.: Human recombinant interleukin-1 stimulates collagenase and prostaglandin E2 production by human synovial cells. J. Clin. Invest.77:645, 1986

    PubMed  Google Scholar 

  167. Lee, M.D., Zentella, A., Pekala, P.H., Cerami, A.: Effect of endotoxin-induced monokines on glucose metabolism in the muscle cell line L6. Biochemistry84:2590, 1987

    Google Scholar 

  168. Vary, T.C., Siegel, J.H., Nakatani, T., Sato, T., Aoyama, H.: Effect of sepsis on activity of pyruvate dehydrogenase complex in skeletal muscle and liver. Am. J. Physiol.250:E634, 1986

  169. Sayeed, M.M.: Ion transport in circulatory and/or septic shock. Am. J. Physiol.252:R809, 1987

  170. Spitzer, J.A., Deaciuc, I.V.: IP3-independent Ca2+ release in permeabilized hepatocytes of endotoxemic and septic rats. Am. J. Physiol.16:E130, 1987

  171. Dinarello, C.A., Savage, N.: Interleukin-1 and its receptor. Crit. Rev. Immun.9:1, 1989

    Google Scholar 

  172. Kunkel, S.L., Remick, D.G., Strieter, R.M., Larrick, J.W.: Mechanisms that regulate the production and effects of tumor necrosis factor-alpha. Crit. Rev. Immunol.9:93, 1989

    PubMed  Google Scholar 

  173. Granger, D.L., Lehninger, A.L.: Sites of inhibition of mitochondrial electron transport in macrophage-injured neoplastic cells. J. Cell. Biol.95:527, 1982

    PubMed  Google Scholar 

  174. Kilbourn, R.G., Klostergaard, J., Lopez-Berestein, G.: Activated macrophages secrete a soluble factor that inhibits mitochondrial respiration of tumor cells. J. Immunol.133:2577, 1984

    PubMed  Google Scholar 

  175. Rosenstreitch, D.L., Yost, S.L., Brown, K.M.: Human urine-derived inhibitors of interleukin-1. Rev. Infect. Dis.9(suppl 5):594, 1987

    Google Scholar 

  176. Jiang, J., He, G., Zhang, S., Wang, X., Yang, N., Zhu, Y., Wilmore, D.W.: Low-dose growth hormone and hypocaloric nutrition attenuate the protein-catabolic response after major operation. Ann. Surg.210:513, 1989

    PubMed  Google Scholar 

  177. Tracey, K.J., Yuman, F., Hesse, D.G.: Anti-cachetin/TNF monoclonal antibodies prevent septic shock during lethal bacteremia. Nature33:662, 1987

    Google Scholar 

  178. Strock, L.L., Singh, H., Abdullah, A., Miller, J.A., Herndon, D.N.: The effect of insulin-like growth factor I on postburn hypermetabolism. Surgery108:161, 1990

    PubMed  Google Scholar 

  179. Herndon, D.N., Barrow, R.E., Kunkel, K.R., Broemeling, L., Rutan, R.L.: Effects of recombinant human growth hormone on donor-site healing in severely burned children. Ann. Surg.212:424, 1990

    PubMed  Google Scholar 

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Tredget, E.E., Yu, Y.M. The metabolic effects of thermal injury. World J. Surg. 16, 68–79 (1992). https://doi.org/10.1007/BF02067117

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