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[diablo69]

August 2011

GROWTH HORMONE AND INSULIN COMBINE TO IMPROVE WHOLE-BODY AND SKELETAL MUSCLE PROTEIN KINETICS

Ronald F Wolf, MD, Martin J Heslin MD, Elliott Newman, MD, David B Pearlstone, MD, Amnon Gonenne, Ph.D, and Murray F. Brennan, MD.

Background: A cooperative effect of exogenous insulin and recombinant human growth hormone (r-hGH) with respect to whole-body and skeletal muscle protein metabolism has not been demonstrated prevously. This study examined the effect of r-hGH and insulin administration during euglycemic clamping and concurrent amino acid supplementation.

Methods: Twenty-three normal volunteers in the postabsorptive state were either treated with r-hGH for 3 consecutive days before a metabolic study (GH group: n=10) or not treated (CTRL group; n=13). The r-hGH dose was 0.2mg/kg/day (n=5) or 0.1 mg/kg/day (n=5). All subjects then received an infusion of 14C-labeled leucine and tritiated phenylalanine, followed by m3easurement of baseline protein kinetics (GH and CTRL). Subsequently a euglycemic insulin infusion (1 mU/kg/min) with concurrent amino acid infusion was administered, and protein kinetic measurements were repeated at steady state.

Results: GH and insulin separately produced an increase in whole-body and skeletal muscle protein net balance. GH plus insulin was associated with a higher net balance of protein than was insulin alone.

Conclusion: r-hGH and insulin in the presence of amino acids and glucose combine to improve whole-body and skeletal muscle protein kinetics. (Surgery 1992:112; 284-292.)


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ANABOLIC THERAPY WITH GROWTH HORMONE ACCELERATES PROTEIN GAIN IN SURGICAL PATIENTS REQUIRING NUTRITIONAL REHABILITATION

Theresa A. Byrne, MS, RD, Thomas B. Morrissey, MD, Christopher Gatzen, FRCS (E), Kathleen Benfell, R.Ph, Thomas V Nattakom, MD, Marc R. Scheltinga, MD, Ph.D., Meryl S. Leboff, MD, Thomas R. Ziegler, MD, and Douglas W. Wilmore, MD.

From the Departments of Surgery, Medicine, and Pharmacy and the Laboratories for Surgical Metabolism and Nutrition, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts

Objective:The authors investigated the effects of exogenous growth hormone (GH) on protein accretion and the compsition of weight gain in a group of stable, nutritionally compromised postoperative patients receiving standard hypercaloric nutritional therapy.

Summary Background Data: A significant loss of body protein impairs normal physiologic functions and is associated with increased postoperative complications and prolonged hospitalization. Previous studies have demonstrated that standard methods of nutritional support enhance the deposition of fat and extracellular water but are ineffective in repleting body protein.

Methods:Fourteen patients requiring long-term nutritional support for severe gastrointestinal dysfunction received standard nutritional therapy (STD) providing approximately 50 kcal/kg/day and 2 g of protein/kg/day during an initial 7-day equilibrium period. The patients then continued on STD (n=4) or, in addition, received GH 0.14 mg/kg/day (n=10). On day 7 of the equilibrium period and again after 3 weeks of treatment, the components of body weight were determined; these included body fat, mineral content, lean (nonfat and non mineral-containing tissue) mass, total body water, extracellular water (ECW), and body protein. Daily and cumulative nutrient balance and substrate oxidation studies determined the distribution, efficiency, and utilization of calories for protein, fat, and carbohydrate deposition.

Results:The GH-treated patients gained minimal body fat but had significantly more lean mass (4.311± 0.6 kg vs 1.988± 0.2 kg, p< 0.03) and more protein (l.417± 0.3 kg vs. 0.086± 0.1 kg, p< 0.03) than did the STD-treated patients. The increase in lean mass was not associated with an inappropriate expansion of ECW. In contrast, patients receiving STD therapy tended to deposit a greater proportion of body weight as ECW and significantly more fat than did GH-treated patients (1.004± 0.3 kg vs 0.129± 0.2 kg, p< 0.05). GH administration altered substrate oxidation (respiratory quotient = 0.94± 0.02 GH vs. 1.18± 0.05 STD, p < 0.0002) and the use of available energy, resulting in a 66% increase in the efficiency of protein deposition (13.37± 0.8 g/1000 kcal vs. 8.04g± 3.06 g/1000 kcal, p< 0.04).

Conclusions: GH administration accelerated protein gain in stable adult patients receiving aggressive nutritional therapy without a significant increase in body fat or a disproportionate expansion of ECW. GH therapy accelerated nutritional repletion and, therefore, may shorten the convalescence of the malnourished patient requiring a major surgical procedure.


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INCREASED MORTALITY ASSOCIATED WITH GROWTH HORMONE TREATMENT IN CRITICALLY ILL ADULTS

Jukka Takala, MD, Ph.D., Esko Ruokonen, MD, PhD, Nigel R. Webster, MD, Michael S. Nielsen, MD, Durk F. Zandstra, MD, Guy Vundelinckx, MD, and Charles J. Hinds, MD.

Background: The administration of growth hormone can attenuate the catabolic response to injury, surgery, and sepsis. However, the effect of high doses of growth hormone on the length of stay in intensive care and in the hospital, the duration of mechanical ventilation, and the outcome in critically ill adults who are hospitalized for long periods is not known.

Methods: We carried out two prospective, multicenter, double-blind, randomized, placebo-controlled trials in parallel involving 247 Finnish patients and 285 patients in other European countries who had been in an intensive care unit for 5 to 7 days and who were expected to require intensive care for at least 10 days. The patients had had cardiac surgery, abdominal surgery, multiple trauma, or acute respiratory failure. The patients received either growth hormone (mean [± SD) daily dose, 0.10± 0.02 mg per kilogram of body weight) or placebo until discharge from intensive care or for a maximum of 21 days.

Results: The in-hospital mortality rate was higher in the patients who received growth hormone than in those who did not (P± < 0.001 for both studies). In the Finnish study, the mortality rate was 39 percent in the growth hormone group, as compared with 20 percent in the placebo group. The respective rates in the multinational study were 44 percent and 18 percent. The relative risk of death for patients receiving growth hormone was 1.9 (95 percent confidence interval, 1.3 to 2.9) in the Finnish study and 2.4 (95 percent confidence interval, 1.6 to 3.5) in the multinational study. Among the survivors, the length of stay in intensive care and in the hospital and the duration of mechanical ventilation were prolonged in the growth hormone group.

Conclusions: In patients with prolonged critical illness, high doses of growth hormone are associated with increased morbidity and mortality. (N Engl J Med 1999; 341:785-792)


Ronald F Wolf, MD, Martin J Heslin MD, Elliott Newman, MD, David B Pearlstone, MD, Amnon Gonenne, Ph.D, and Murray F. Brennan, MD.

Background: A cooperative effect of exogenous insulin and recombinant human growth hormone (r-hGH) with respect to whole-body and skeletal muscle protein metabolism has not been demonstrated prevously. This study examined the effect of r-hGH and insulin administration during euglycemic clamping and concurrent amino acid supplementation.

Methods: Twenty-three normal volunteers in the postabsorptive state were either treated with r-hGH for 3 consecutive days before a metabolic study (GH group: n=10) or not treated (CTRL group; n=13). The r-hGH dose was 0.2mg/kg/day (n=5) or 0.1 mg/kg/day (n=5). All subjects then received an infusion of 14C-labeled leucine and tritiated phenylalanine, followed by m3easurement of baseline protein kinetics (GH and CTRL). Subsequently a euglycemic insulin infusion (1 mU/kg/min) with concurrent amino acid infusion was administered, and protein kinetic measurements were repeated at steady state.

Results: GH and insulin separately produced an increase in whole-body and skeletal muscle protein net balance. GH plus insulin was associated with a higher net balance of protein than was insulin alone.

Conclusion: r-hGH and insulin in the presence of amino acids and glucose combine to improve whole-body and skeletal muscle protein kinetics. (Surgery 1992:112; 284-292.)


--------------------------------------------------------------------------------

ANABOLIC THERAPY WITH GROWTH HORMONE ACCELERATES PROTEIN GAIN IN SURGICAL PATIENTS REQUIRING NUTRITIONAL REHABILITATION

Theresa A. Byrne, MS, RD, Thomas B. Morrissey, MD, Christopher Gatzen, FRCS (E), Kathleen Benfell, R.Ph, Thomas V Nattakom, MD, Marc R. Scheltinga, MD, Ph.D., Meryl S. Leboff, MD, Thomas R. Ziegler, MD, and Douglas W. Wilmore, MD.

From the Departments of Surgery, Medicine, and Pharmacy and the Laboratories for Surgical Metabolism and Nutrition, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts

Objective:The authors investigated the effects of exogenous growth hormone (GH) on protein accretion and the compsition of weight gain in a group of stable, nutritionally compromised postoperative patients receiving standard hypercaloric nutritional therapy.

Summary Background Data: A significant loss of body protein impairs normal physiologic functions and is associated with increased postoperative complications and prolonged hospitalization. Previous studies have demonstrated that standard methods of nutritional support enhance the deposition of fat and extracellular water but are ineffective in repleting body protein.

Methods:Fourteen patients requiring long-term nutritional support for severe gastrointestinal dysfunction received standard nutritional therapy (STD) providing approximately 50 kcal/kg/day and 2 g of protein/kg/day during an initial 7-day equilibrium period. The patients then continued on STD (n=4) or, in addition, received GH 0.14 mg/kg/day (n=10). On day 7 of the equilibrium period and again after 3 weeks of treatment, the components of body weight were determined; these included body fat, mineral content, lean (nonfat and non mineral-containing tissue) mass, total body water, extracellular water (ECW), and body protein. Daily and cumulative nutrient balance and substrate oxidation studies determined the distribution, efficiency, and utilization of calories for protein, fat, and carbohydrate deposition.

Results:The GH-treated patients gained minimal body fat but had significantly more lean mass (4.311± 0.6 kg vs 1.988± 0.2 kg, p< 0.03) and more protein (l.417± 0.3 kg vs. 0.086± 0.1 kg, p< 0.03) than did the STD-treated patients. The increase in lean mass was not associated with an inappropriate expansion of ECW. In contrast, patients receiving STD therapy tended to deposit a greater proportion of body weight as ECW and significantly more fat than did GH-treated patients (1.004± 0.3 kg vs 0.129± 0.2 kg, p< 0.05). GH administration altered substrate oxidation (respiratory quotient = 0.94± 0.02 GH vs. 1.18± 0.05 STD, p < 0.0002) and the use of available energy, resulting in a 66% increase in the efficiency of protein deposition (13.37± 0.8 g/1000 kcal vs. 8.04g± 3.06 g/1000 kcal, p< 0.04).

Conclusions: GH administration accelerated protein gain in stable adult patients receiving aggressive nutritional therapy without a significant increase in body fat or a disproportionate expansion of ECW. GH therapy accelerated nutritional repletion and, therefore, may shorten the convalescence of the malnourished patient requiring a major surgical procedure.


--------------------------------------------------------------------------------

INCREASED MORTALITY ASSOCIATED WITH GROWTH HORMONE TREATMENT IN CRITICALLY ILL ADULTS

Jukka Takala, MD, Ph.D., Esko Ruokonen, MD, PhD, Nigel R. Webster, MD, Michael S. Nielsen, MD, Durk F. Zandstra, MD, Guy Vundelinckx, MD, and Charles J. Hinds, MD.

Background: The administration of growth hormone can attenuate the catabolic response to injury, surgery, and sepsis. However, the effect of high doses of growth hormone on the length of stay in intensive care and in the hospital, the duration of mechanical ventilation, and the outcome in critically ill adults who are hospitalized for long periods is not known.

Methods: We carried out two prospective, multicenter, double-blind, randomized, placebo-controlled trials in parallel involving 247 Finnish patients and 285 patients in other European countries who had been in an intensive care unit for 5 to 7 days and who were expected to require intensive care for at least 10 days. The patients had had cardiac surgery, abdominal surgery, multiple trauma, or acute respiratory failure. The patients received either growth hormone (mean [± SD) daily dose, 0.10± 0.02 mg per kilogram of body weight) or placebo until discharge from intensive care or for a maximum of 21 days.

Results: The in-hospital mortality rate was higher in the patients who received growth hormone than in those who did not (P± < 0.001 for both studies). In the Finnish study, the mortality rate was 39 percent in the growth hormone group, as compared with 20 percent in the placebo group. The respective rates in the multinational study were 44 percent and 18 percent. The relative risk of death for patients receiving growth hormone was 1.9 (95 percent confidence interval, 1.3 to 2.9) in the Finnish study and 2.4 (95 percent confidence interval, 1.6 to 3.5) in the multinational study. Among the survivors, the length of stay in intensive care and in the hospital and the duration of mechanical ventilation were prolonged in the growth hormone group.

Conclusions: In patients with prolonged critical illness, high doses of growth hormone are associated with increased morbidity and mortality. (N Engl J Med 1999; 341:785-792)