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David N Herndon - One of the best experts on this subject based on the ideXlab platform.
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Oxandrolone protects against the development of multiorgan failure modulates the systemic inflammatory response and promotes wound healing during burn injury
Burns, 2019Co-Authors: Akbar Ahmad, David N Herndon, Csaba SzaboAbstract:Oxandrolone is a synthetic oral non-aromatizable testosterone derivative. This drug has been used successfully for several decades to safely treat growth delays in various diseases including Turner's syndrome. Currently the use of Oxandrolone is under clinical testing in children with burn injury; the available data indicate that the anabolic steroid increases net muscle protein balance, maintains lean body mass, and reduces intensive care unit stay. Although Oxandrolone is already in clinical trials in burn patients, preclinical burn-related studies with Oxandrolone - especially those that go beyond muscle-related parameters and focus on burn-associated organ dysfunction, inflammatory response and wound healing - remain to be conducted. In the current project, using a well-characterized murine model of third-degree burn, we have tested the effect of Oxandrolone on indices of organ injury, clinical chemistry parameters and plasma levels of inflammatory mediators. In Oxandrolone-treated mice (1mg/kg/day for up to 21 days) there was a significant amelioration of burn-induced accumulation of myeloperoxidase levels in heart and lung (but not the liver and kidney) and significantly lower degree of malon dialdehyde accumulation in the liver (but not the heart, lung and kidney). Oxandrolone-treated mice showed a significant attenuation of the burn-induced elevation in circulating alkaline aminotransferase and amylase levels, while blood urea nitrogen and creatinine levels remained unaffected, indicative of protective effects of the anabolic hormone against burn-induced hepatic and pancreatic (but not renal) functional impairment. Multiple burn-induced inflammatory mediators (TNF-α, IL-1α, IL-1β, IL-4, IL-6, IL-10, IL-12, IP-10, G-CSF, GM-CSF and interferon-γ) were significantly lower in the plasma of Oxandrolone-treated animals after burn injury than in the plasma of controls subjected to burns. Finally, Oxandrolone significantly accelerated burn wound healing. We conclude that Oxandrolone improves organ function, modulates the systemic inflammatory response and accelerates wound healing in a murine model of burn injury.
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Oxandrolone coadministration does not alter plasma propranolol concentrations in severely burned pediatric patients
Journal of Burn Care & Research, 2017Co-Authors: Ashley N Guillory, Oscar E Suman, David N Herndon, Clark R Andersen, Michael B Silva, Celeste C FinnertyAbstract:The systemic impact of severe burn injury results in a variety of disorders that require therapeutic intervention. Propranolol, a nonselective β1, β2-adrenergic receptor antagonist, reduces resting heart rate and cardiac work caused by elevated circulating catecholamines. Oxandrolone, a testosterone mimetic, promotes protein synthesis and anabolism to counter muscle wasting. Coadministration of these drugs is expected to synergistically improve patient outcomes. Testosterone administration is known to alter β-adrenergic receptor-mediated signaling. Here, we determined whether the coadministration of Oxandrolone alters plasma propranolol concentrations. Ninety-two pediatric patients with burns covering ≥30% of the TBSA were enrolled in this institutional review board-approved study and randomized to receive propranolol (n = 49) or Oxandrolone + propranolol (n = 43). Plasma propranolol concentrations were determined following two dosing strategies: Q6 (liquid formulation; n = 86) and Q24 (extended-release capsule; n = 22). Samples were drawn before drug administration and at regular intervals throughout the next two dosing periods. Heart rate and blood pressure were recorded throughout the study. Propranolol half-life was 3.3 hours for the Q6 drug dosing frequency (P < .0001) and 11.2 hours for the Q24 strategy (P < .0001). Percentage of predicted heart rate declined by 2.8% for each doubling of the propranolol concentration in the Q6 dosing schedule (P < .0001). Percentage of predicted heart rate declined by 2.5% for each doubling of propranolol concentration on the Q24 dosing schedule (P < .0001). Maximum and minimum propranolol plasma concentrations were similar with either dosing regimen. The addition of Oxandrolone did not affect any of the measured parameters. Oxandrolone coadministration does not alter propranolol's plasma concentration, half-life, or effect on heart rate. This study is registered at clincialtrials.gov: NCT00675714.
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long term administration of Oxandrolone improves lung function in pediatric burned patients
Journal of Burn Care & Research, 2016Co-Authors: Linda E Sousse, David N Herndon, Ronald P Mlcak, Clark R Andersen, Celeste C Finnerty, Jong O Lee, Andrew ZovathAbstract:Pulmonary dysfunction is a significant contributor to morbidity and mortality in the pediatric burned population. We have previously reported that the administration of a synthetic testosterone derivative, Oxandrolone, significantly reduced hypermetabolism, and significantly increased height percentile, bone mineral content, lean body mass, and strength in pediatric burned patients. We hypothesize that the administration of Oxandrolone will improve pulmonary function in burned pediatric subjects. A subset of severely burned pediatric subjects from a prospective clinical trial (n = 222) were included in our study (n = 54, 7-18 years, ≥30% TBSA burn). The subjects were previously randomized to either the control arm (n = 35) or the Oxandrolone arm (0.1 mg/kg twice/day for 12 months, n = 19). Maximum voluntary ventilation, the ratio between forced expiratory volume and forced vital capacity, and diffusion capacity were measured 6 months following burn injury, and results were compared between burned subjects with and without Oxandrolone administration. Maximum expired ventilation (VEmax) was also measured in a subset of burned subjects. Subjects treated with Oxandrolone had a significantly higher maximum voluntary ventilation (98 ± 53 L/min vs 115 ± 56 with treatment, P = .03). During maximal exercise, subjects treated with Oxandrolone had a significantly higher VEmax compared with untreated subjects (32.0 ± 8.7 L/min vs 43.7 ± 13.6 with treatment, P = .02). The administration of Oxandrolone was associated with improved lung function in pediatric burned patients.
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reversal of growth arrest with the combined administration of Oxandrolone and propranolol in severely burned children
Annals of Surgery, 2016Co-Authors: David N Herndon, Gordon L Klein, Clark R Andersen, Ronald G Tompkins, Charles D Voigt, Karel D Capek, Paul Wurzer, Ashley N Guillory, Andrea Kline, Oscar E SumanAbstract:Background The hypercatabolic response in severely burned pediatric patients is associated with increased production of catecholamines and corticosteroids, decreased formation of testosterone, and reduced strength alongside growth arrest for up to 2 years after injury. We have previously shown that, in the pediatric burned population, the administration of the testosterone analog Oxandrolone improves lean body mass accretion and bone mineral content and that the administration of the β1-, β2-adrenoceptor antagonist propranolol decreases cardiac work and resting energy expenditure while increasing peripheral lean mass. Here, we determined whether the combined administration of Oxandrolone and propranolol has added benefit. Methods In this prospective, randomized study of 612 burned children [52% ± 1% of total body surface area burned, ages 0.5-14 years (boys); ages 0.5-12 years (girls)], we compared controls to the individual administration of these drugs, and the combined administration of Oxandrolone and propranolol at the same doses, for 1 year after burn. Data were recorded at discharge, 6 months, and 1 and 2 years after injury. Results Combined use of Oxandrolone and propranolol shortened the period of growth arrest by 84 days (P = 0.0125 vs control) and increased growth rate by 1.7 cm/yr (P = 0.0024 vs control). Conclusions Combined administration of Oxandrolone and propranolol attenuates burn-induced growth arrest in pediatric burn patients. The present study is registered at clinicaltrials.gov: NCT00675714 and NCT00239668.
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five year outcomes after long term Oxandrolone administration in severely burned children a randomized clinical trial
Shock, 2015Co-Authors: Patrick T Reeves, David N Herndon, Jessica Tanksley, Kristofer Jennings, Gordon L Klein, Ronald P Mlcak, Robert P Clayton, Nancy N Crites, Joshua P Hays, Clark R AndersenAbstract:Administration of Oxandrolone, a nonaromatizable testosterone analog, to children for 12 months following severe burn injury has been shown to improve height, increase bone mineral content (BMC), reduce cardiac work, and augment muscle strength. Surprisingly, the increase in BMC persists well beyond the period of Oxandrolone administration. This study was undertaken to determine if administration of Oxandrolone for 2 years yields greater effects on long-term BMC and bone mineral density (BMD). Patients between 0 and 18 years of age with ≥30% of total body surface area burned were consented to an IRB-approved protocol and randomized to receive either placebo (n = 84) or 0.1 mg/kg Oxandrolone orally twice daily for 24 months (n = 35). Patients were followed prospectively from the time of admission until 5 years postburn in a single-center, intent-to-treat setting. Height, weight, BMC, and BMD were recorded annually through 5 years postinjury. The long-term administration of Oxandrolone for 16 ± 1 months postburn (range, 12.1-25.2 months) significantly increased whole-body (WB) BMC (p < 0.02) and lumbar spine (LS) BMC (p < 0.05); these effects were significantly pronounced for a longer time in patients who were in growth spurt years (7-18 years). When adjusted for height, sex, and age, LS BMD was found to significantly increase with long-term Oxandrolone administration (p < 0.0009). Fewer patients receiving Oxandrolone exhibited LS BMD z scores below -2.0 as compared with controls, indicating a significantly reduced risk for future fracture with Oxandrolone administration. Long-term Oxandrolone patients had significantly greater height velocity than controls throughout the first 2-year postburn (p < 0.05). No adverse side effects were attributed to the long-term administration of Oxandrolone. A comparison of the current patients receiving long-term Oxandrolone to previously described patients receiving 12 months of Oxandrolone revealed that long-term Oxandrolone administration imparted significantly greater increases in WB-BMC, WB-BMD, and LS-BMD (p < 0.05). In conclusion, the administration of Oxandrolone for up to 24 months to severely burned pediatric patients significantly improves WB BMC, LS BMC, LS BMD, and height velocity. The administration of long-term Oxandrolone was more efficacious than administration for 12 months. Additionally, fewer patients in the Oxandrolone cohort met the diagnostic criteria for pediatric osteoporosis, pointing to a reduced risk for future bone fracture. This study demonstrates that administering Oxandrolone for up to 2 years following severe burn injury results in greater improvements in BMC, BMD, and height velocity.
David L Chinkes - One of the best experts on this subject based on the ideXlab platform.
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long term Oxandrolone treatment increases muscle protein net deposition via improving amino acid utilization in pediatric patients 6 months after burn injury
Surgery, 2011Co-Authors: Demidmaa Tuvdendorj, David L Chinkes, Xiaojun Zhang, Oscar E Suman, Asle AarslandAbstract:Background We recently showed that mechanisms of protein turnover in skeletal muscle are unresponsive to amino acid (AA) infusion in severely burned pediatric patients at 6 months postinjury. In the current study, we evaluated whether Oxandrolone treatment affects mechanisms of protein turnover in skeletal muscle and whole-body protein breakdown in pediatric burn patients 6 months postinjury. Methods At the time of admission, patients were randomized to control or Oxandrolone treatments. The treatment regimens were continued until 6 months postinjury, at which time patients (n = 26) underwent study with a stable isotope tracer infusion to measure muscle and whole-body protein turnover. Results Protein kinetics in leg muscle were expressed in nmol/min per 100 mL leg volume (mean ± SE). During AA infusion, rates of protein synthesis in leg muscle were increased (P Conclusion Long-term Oxandrolone treatment increased net deposition of leg muscle protein during AA infusion by attenuating protein breakdown, but did not affect whole-body protein breakdown.
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metabolic and hormonal changes of severely burned children receiving long term Oxandrolone treatment
Annals of Surgery, 2005Co-Authors: Rene Przkora, David L Chinkes, Oscar E Suman, Marc G Jeschke, Celeste C Finnerty, Jong O Lee, Walter J Meyer, Robert E Barrow, Arthur P Sanford, Ronald P MlcakAbstract:Severe burns represent a major physical and psychologic event in a child's life. Progress in the treatment of burns, such as fluid resuscitation, early burn wound excision, new antibiotics, and nutritional support has reduced burn mortality.1 A major determination of morbidity in burn patients is the extent and duration of the hypermetabolic and catabolic response to injury. These responses are characterized by tachycardia, increased resting energy expenditure, peripheral insulin resistance, fat and protein catabolism, and muscle and bone wasting, which last for 1 to 2 years after burn and lead to growth retardation.1,2 These posttraumatic responses delay recovery, rehabilitation, and social and psychologic integration back into society.3–6 Various therapeutic approaches have been introduced to ameliorate these adverse effects.7,8 We and others have hypothesized that the use of anabolic agents may attenuate the posttraumatic response and improve long-term outcomes.1,8 Oxandrolone, a synthetic analog of testosterone with minimal virilizing activity and liver toxicity, attenuates muscle wasting after severe trauma, malnutrition, or acquired immunodeficiency virus.9,10 In severely burned children treated during acute hospitalization, Oxandrolone significantly improved net protein synthesis, lean body mass, bone mineral content, synthesis of the hepatic constitutive proteins such as albumin and prealbumin, and attenuated the acute phase reactive protein levels.11–13 The aim of this study was to determine whether Oxandrolone, administered for 1 year after injury to severely burned children, would attenuate catabolism and growth arrest and whether these positive attributes would persist after the drug is discontinued.
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effects of long term Oxandrolone administration in severely burned children
Surgery, 2004Co-Authors: Kevin D Murphy, David L Chinkes, Gordon L Klein, Ronald P Mlcak, Suchmor Thomas, David N HerndonAbstract:Abstract Background Severe burns cause exaggerated catabolism of muscle protein and inhibit bone deposition. Weakness and bony growth arrest interfere with rehabilitation. The purpose of this study was to determine whether Oxandrolone administration for 1 year after the burn reverses muscle and bone catabolism in hypermetabolic pediatric burn patients. Methods Children with burns greater than 40% total body surface area were enrolled into a randomized controlled trial to receive Oxandrolone as a long-term anabolic agent. All patients received similar clinical care. Subjects were studied at discharge (95% healed) and at 6, 9, and 12 months after the burn, after treatment with 0.1 mg/kg po bid or placebo. Serum hepatic transaminases were measured. Lean body mass (LBM), bone mineral content (BMC,) and bone mineral density (BMD) were measured by dual energy x-ray absorptiometry. Patients completed a safety questionnaire and were reviewed clinically at intervals. Results The groups were similar in age, weight, and total body surface area burned. LBM was significantly greater with Oxandrolone at 6, 9, and 12 months after the burn (P Conclusions Long-term administration of Oxandrolone safely improves LBM, BMC, and BMD in severely burned children.
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the long term effect of Oxandrolone on hepatic acute phase proteins in severely burned children
Journal of Trauma-injury Infection and Critical Care, 2004Co-Authors: Suchmor Thomas, David L Chinkes, David N Herndon, Steven E Wolf, Kevin D Murphy, Basil A Pruitt, Nabil AtwehAbstract:Background Acute phase protein production is a hallmark of severe burns. We wondered whether anabolic treatment with Oxandrolone would affect these proteins.Methods Thirty-five children with ≥40% total body surface area burns were randomized to receive either placebo or Oxandrolone (0.1 mg/kg by mou
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improved net protein balance lean mass and gene expression changes with Oxandrolone treatment in the severely burned
Annals of Surgery, 2003Co-Authors: Steven E Wolf, David L Chinkes, Arny A Ferrando, Robert R Wolfe, Steven J Thomas, Mohan R Dasu, David N HerndonAbstract:Objective To determine the effects of the anabolic agent Oxandrolone on muscle protein and gene expression in severely burned children. Background Data The authors previously showed that Oxandrolone increased net muscle protein synthesis in emaciated burned patients receiving delayed treatment for severe burns. They hypothesized that similar effects would be seen in those treated early after burn. Methods Thirty-two severely burned children were enrolled in a prospective randomized trial. Subjects underwent studies to assess leg protein net balance 5 days after the first excision and grafting procedure. Immediately after these studies, treatment with placebo (n = 18) or 0.1 mg/kg Oxandrolone (n = 14) twice a day was started. One week after this, another net balance study was performed in each subject. Body weights and total body potassium counting were used to determine body compositional changes. Muscle biopsies were taken 1 week after treatment in Oxandrolone subjects to examine gene expression changes with gene array (12,600 genes). Results Protein net balance did not change in the placebo group, while Oxandrolone-treated subjects had a significant improvement. Body weights and fat free mass significantly decreased in the placebo group, while no changes were found in the Oxandrolone-treated subjects. Expression changes were seen in 14 genes in the Oxandrolone group compared to placebo. Some of these included myosin light chain (+2.7-fold change), tubulin (+2.3), calmodulin (-2.3), and protein phosphatase I inhibitor (-2.8). Conclusions Oxandrolone improves protein net balance and lean mass in the severely burned. These changes are associated with increased gene expression for functional muscle proteins.
Oscar E Suman - One of the best experts on this subject based on the ideXlab platform.
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Oxandrolone coadministration does not alter plasma propranolol concentrations in severely burned pediatric patients
Journal of Burn Care & Research, 2017Co-Authors: Ashley N Guillory, Oscar E Suman, David N Herndon, Clark R Andersen, Michael B Silva, Celeste C FinnertyAbstract:The systemic impact of severe burn injury results in a variety of disorders that require therapeutic intervention. Propranolol, a nonselective β1, β2-adrenergic receptor antagonist, reduces resting heart rate and cardiac work caused by elevated circulating catecholamines. Oxandrolone, a testosterone mimetic, promotes protein synthesis and anabolism to counter muscle wasting. Coadministration of these drugs is expected to synergistically improve patient outcomes. Testosterone administration is known to alter β-adrenergic receptor-mediated signaling. Here, we determined whether the coadministration of Oxandrolone alters plasma propranolol concentrations. Ninety-two pediatric patients with burns covering ≥30% of the TBSA were enrolled in this institutional review board-approved study and randomized to receive propranolol (n = 49) or Oxandrolone + propranolol (n = 43). Plasma propranolol concentrations were determined following two dosing strategies: Q6 (liquid formulation; n = 86) and Q24 (extended-release capsule; n = 22). Samples were drawn before drug administration and at regular intervals throughout the next two dosing periods. Heart rate and blood pressure were recorded throughout the study. Propranolol half-life was 3.3 hours for the Q6 drug dosing frequency (P < .0001) and 11.2 hours for the Q24 strategy (P < .0001). Percentage of predicted heart rate declined by 2.8% for each doubling of the propranolol concentration in the Q6 dosing schedule (P < .0001). Percentage of predicted heart rate declined by 2.5% for each doubling of propranolol concentration on the Q24 dosing schedule (P < .0001). Maximum and minimum propranolol plasma concentrations were similar with either dosing regimen. The addition of Oxandrolone did not affect any of the measured parameters. Oxandrolone coadministration does not alter propranolol's plasma concentration, half-life, or effect on heart rate. This study is registered at clincialtrials.gov: NCT00675714.
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reversal of growth arrest with the combined administration of Oxandrolone and propranolol in severely burned children
Annals of Surgery, 2016Co-Authors: David N Herndon, Gordon L Klein, Clark R Andersen, Ronald G Tompkins, Charles D Voigt, Karel D Capek, Paul Wurzer, Ashley N Guillory, Andrea Kline, Oscar E SumanAbstract:Background The hypercatabolic response in severely burned pediatric patients is associated with increased production of catecholamines and corticosteroids, decreased formation of testosterone, and reduced strength alongside growth arrest for up to 2 years after injury. We have previously shown that, in the pediatric burned population, the administration of the testosterone analog Oxandrolone improves lean body mass accretion and bone mineral content and that the administration of the β1-, β2-adrenoceptor antagonist propranolol decreases cardiac work and resting energy expenditure while increasing peripheral lean mass. Here, we determined whether the combined administration of Oxandrolone and propranolol has added benefit. Methods In this prospective, randomized study of 612 burned children [52% ± 1% of total body surface area burned, ages 0.5-14 years (boys); ages 0.5-12 years (girls)], we compared controls to the individual administration of these drugs, and the combined administration of Oxandrolone and propranolol at the same doses, for 1 year after burn. Data were recorded at discharge, 6 months, and 1 and 2 years after injury. Results Combined use of Oxandrolone and propranolol shortened the period of growth arrest by 84 days (P = 0.0125 vs control) and increased growth rate by 1.7 cm/yr (P = 0.0024 vs control). Conclusions Combined administration of Oxandrolone and propranolol attenuates burn-induced growth arrest in pediatric burn patients. The present study is registered at clinicaltrials.gov: NCT00675714 and NCT00239668.
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long term Oxandrolone treatment increases muscle protein net deposition via improving amino acid utilization in pediatric patients 6 months after burn injury
Surgery, 2011Co-Authors: Demidmaa Tuvdendorj, David L Chinkes, Xiaojun Zhang, Oscar E Suman, Asle AarslandAbstract:Background We recently showed that mechanisms of protein turnover in skeletal muscle are unresponsive to amino acid (AA) infusion in severely burned pediatric patients at 6 months postinjury. In the current study, we evaluated whether Oxandrolone treatment affects mechanisms of protein turnover in skeletal muscle and whole-body protein breakdown in pediatric burn patients 6 months postinjury. Methods At the time of admission, patients were randomized to control or Oxandrolone treatments. The treatment regimens were continued until 6 months postinjury, at which time patients (n = 26) underwent study with a stable isotope tracer infusion to measure muscle and whole-body protein turnover. Results Protein kinetics in leg muscle were expressed in nmol/min per 100 mL leg volume (mean ± SE). During AA infusion, rates of protein synthesis in leg muscle were increased (P Conclusion Long-term Oxandrolone treatment increased net deposition of leg muscle protein during AA infusion by attenuating protein breakdown, but did not affect whole-body protein breakdown.
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the effect of Oxandrolone on the endocrinologic inflammatory and hypermetabolic responses during the acute phase postburn
Annals of Surgery, 2007Co-Authors: Marc G Jeschke, Oscar E Suman, Ronald P Mlcak, Celeste C Finnerty, Gabriela A Kulp, David N HerndonAbstract:Objective and Summary Background Data: Postbum long-term Oxandrolone treatment improves hypermetabolism and body composition. The effects of Oxandrolone on clinical outcome, body composition, endocrine system, and inflammation during the acute phase postburn in a large prospective randomized single-center trial have not been studied. Methods: Burned children (n = 235) with >40% total body surface area burn were randomized (block randomization 4:1) to receive standard burn care (control, n = 190) or standard burn care plus Oxandrolone for at least 7 days (Oxandrolone 0.1 mg/kg body weight q.12 hours p.o, n = 45). Clinical parameters, body composition, serum hormones, and cytokine expression profiles were measured throughout acute hospitalization. Statistical analysis was performed by Student t test, or ANOVA followed by Bonferroni correction with significance accepted at P < 0.05. Results: Demographics and clinical data were similar in both groups. Length of intensive care unit stay was significantly decreased in Oxandrolone-treated patients (0.48 ± 0.02 days/% burn) compared with controls (0.56 ± 0.02 days/% burn), (P < 0.05). Control patients lost 8 ± 1% of their lean body mass (LBM), whereas Oxandrolone-treated patients had preserved LBM (+9 ± 4%), P < 0.05. Oxandrolone significantly increased serum prealbumin, total protein, testosterone, and AST/ALT, whereas it significantly decreased α2-macroglobulin and complement C3, P < 0.05. Oxandrolone did not adversely affect the endocrine and inflammatory response as we found no significant differences in the hormone panels and cytokine expression profiles. Conclusions: In this large prospective, double-blinded, randomized single-center study, Oxandrolone shortened length of acute hospital stay, maintained LBM, improved body composition and hepatic protein synthesis while having no adverse effects on the endocrine axis postburn, but was associated with an increase in AST and ALT.
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the effects of Oxandrolone and exercise on muscle mass and function in children with severe burns
Pediatrics, 2007Co-Authors: Rene Przkora, David N Herndon, Oscar E SumanAbstract:OBJECTIVES Severe burns are associated with a significant loss of muscle and strength. Studies have reported that Oxandrolone improves lean body mass in muscle-wasting conditions. Also shown previously in burned children is that an exercise program increases lean body mass and muscle strength. We hypothesized that Oxandrolone, in combination with exercise, would increase lean body mass and muscle strength in severely burned children more than Oxandrolone alone or exercise alone.
Ronald P Mlcak - One of the best experts on this subject based on the ideXlab platform.
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long term administration of Oxandrolone improves lung function in pediatric burned patients
Journal of Burn Care & Research, 2016Co-Authors: Linda E Sousse, David N Herndon, Ronald P Mlcak, Clark R Andersen, Celeste C Finnerty, Jong O Lee, Andrew ZovathAbstract:Pulmonary dysfunction is a significant contributor to morbidity and mortality in the pediatric burned population. We have previously reported that the administration of a synthetic testosterone derivative, Oxandrolone, significantly reduced hypermetabolism, and significantly increased height percentile, bone mineral content, lean body mass, and strength in pediatric burned patients. We hypothesize that the administration of Oxandrolone will improve pulmonary function in burned pediatric subjects. A subset of severely burned pediatric subjects from a prospective clinical trial (n = 222) were included in our study (n = 54, 7-18 years, ≥30% TBSA burn). The subjects were previously randomized to either the control arm (n = 35) or the Oxandrolone arm (0.1 mg/kg twice/day for 12 months, n = 19). Maximum voluntary ventilation, the ratio between forced expiratory volume and forced vital capacity, and diffusion capacity were measured 6 months following burn injury, and results were compared between burned subjects with and without Oxandrolone administration. Maximum expired ventilation (VEmax) was also measured in a subset of burned subjects. Subjects treated with Oxandrolone had a significantly higher maximum voluntary ventilation (98 ± 53 L/min vs 115 ± 56 with treatment, P = .03). During maximal exercise, subjects treated with Oxandrolone had a significantly higher VEmax compared with untreated subjects (32.0 ± 8.7 L/min vs 43.7 ± 13.6 with treatment, P = .02). The administration of Oxandrolone was associated with improved lung function in pediatric burned patients.
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five year outcomes after long term Oxandrolone administration in severely burned children a randomized clinical trial
Shock, 2015Co-Authors: Patrick T Reeves, David N Herndon, Jessica Tanksley, Kristofer Jennings, Gordon L Klein, Ronald P Mlcak, Robert P Clayton, Nancy N Crites, Joshua P Hays, Clark R AndersenAbstract:Administration of Oxandrolone, a nonaromatizable testosterone analog, to children for 12 months following severe burn injury has been shown to improve height, increase bone mineral content (BMC), reduce cardiac work, and augment muscle strength. Surprisingly, the increase in BMC persists well beyond the period of Oxandrolone administration. This study was undertaken to determine if administration of Oxandrolone for 2 years yields greater effects on long-term BMC and bone mineral density (BMD). Patients between 0 and 18 years of age with ≥30% of total body surface area burned were consented to an IRB-approved protocol and randomized to receive either placebo (n = 84) or 0.1 mg/kg Oxandrolone orally twice daily for 24 months (n = 35). Patients were followed prospectively from the time of admission until 5 years postburn in a single-center, intent-to-treat setting. Height, weight, BMC, and BMD were recorded annually through 5 years postinjury. The long-term administration of Oxandrolone for 16 ± 1 months postburn (range, 12.1-25.2 months) significantly increased whole-body (WB) BMC (p < 0.02) and lumbar spine (LS) BMC (p < 0.05); these effects were significantly pronounced for a longer time in patients who were in growth spurt years (7-18 years). When adjusted for height, sex, and age, LS BMD was found to significantly increase with long-term Oxandrolone administration (p < 0.0009). Fewer patients receiving Oxandrolone exhibited LS BMD z scores below -2.0 as compared with controls, indicating a significantly reduced risk for future fracture with Oxandrolone administration. Long-term Oxandrolone patients had significantly greater height velocity than controls throughout the first 2-year postburn (p < 0.05). No adverse side effects were attributed to the long-term administration of Oxandrolone. A comparison of the current patients receiving long-term Oxandrolone to previously described patients receiving 12 months of Oxandrolone revealed that long-term Oxandrolone administration imparted significantly greater increases in WB-BMC, WB-BMD, and LS-BMD (p < 0.05). In conclusion, the administration of Oxandrolone for up to 24 months to severely burned pediatric patients significantly improves WB BMC, LS BMC, LS BMD, and height velocity. The administration of long-term Oxandrolone was more efficacious than administration for 12 months. Additionally, fewer patients in the Oxandrolone cohort met the diagnostic criteria for pediatric osteoporosis, pointing to a reduced risk for future bone fracture. This study demonstrates that administering Oxandrolone for up to 2 years following severe burn injury results in greater improvements in BMC, BMD, and height velocity.
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five year outcomes after Oxandrolone administration in severely burned children a randomized clinical trial of safety and efficacy
Journal of The American College of Surgeons, 2012Co-Authors: Laura J Porro, David N Herndon, Kristofer Jennings, Gordon L Klein, Ronald P Mlcak, Noe A Rodriguez, Walter J MeyerAbstract:Background Oxandrolone, an anabolic agent, has been administered for 1 year post burn with beneficial effects in pediatric patients. However, the long-lasting effects of this treatment have not been studied. This single-center prospective trial determined the long-term effects of 1 year of Oxandrolone administration in severely burned children; assessments were continued for up to 4 years post therapy. Study Design Patients 0 to 18 years old with burns covering >30% of the total body surface area were randomized to receive placebo (n = 152) or Oxandrolone, 0.1 mg/kg twice daily for 12 months (n = 70). At hospital discharge, patients were randomized to a 12-week exercise program or to standard of care. Resting energy expenditure, standing height, weight, lean body mass, muscle strength, bone mineral content (BMC), cardiac work, rate pressure product, sexual maturation, and concentrations of serum inflammatory cytokines, hormones, and liver enzymes were monitored. Results Oxandrolone substantially decreased resting energy expenditure and rate pressure product, increased insulin-like growth factor-1 secretion during the first year after burn injury, and, in combination with exercise, increased lean body mass and muscle strength considerably. Oxandrolone-treated children exhibited improved height percentile and BMC content compared with controls. The maximal effect of Oxandrolone was found in children aged 7 to 18 years. No deleterious side effects were attributed to long-term administration. Conclusions Administration of Oxandrolone improves long-term recovery of severely burned children in height, BMC, cardiac work, and muscle strength; the increase in BMC is likely to occur by means of insulin-like growth factor-1. These benefits persist for up to 5 years post burn.
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the effect of Oxandrolone on the endocrinologic inflammatory and hypermetabolic responses during the acute phase postburn
Annals of Surgery, 2007Co-Authors: Marc G Jeschke, Oscar E Suman, Ronald P Mlcak, Celeste C Finnerty, Gabriela A Kulp, David N HerndonAbstract:Objective and Summary Background Data: Postbum long-term Oxandrolone treatment improves hypermetabolism and body composition. The effects of Oxandrolone on clinical outcome, body composition, endocrine system, and inflammation during the acute phase postburn in a large prospective randomized single-center trial have not been studied. Methods: Burned children (n = 235) with >40% total body surface area burn were randomized (block randomization 4:1) to receive standard burn care (control, n = 190) or standard burn care plus Oxandrolone for at least 7 days (Oxandrolone 0.1 mg/kg body weight q.12 hours p.o, n = 45). Clinical parameters, body composition, serum hormones, and cytokine expression profiles were measured throughout acute hospitalization. Statistical analysis was performed by Student t test, or ANOVA followed by Bonferroni correction with significance accepted at P < 0.05. Results: Demographics and clinical data were similar in both groups. Length of intensive care unit stay was significantly decreased in Oxandrolone-treated patients (0.48 ± 0.02 days/% burn) compared with controls (0.56 ± 0.02 days/% burn), (P < 0.05). Control patients lost 8 ± 1% of their lean body mass (LBM), whereas Oxandrolone-treated patients had preserved LBM (+9 ± 4%), P < 0.05. Oxandrolone significantly increased serum prealbumin, total protein, testosterone, and AST/ALT, whereas it significantly decreased α2-macroglobulin and complement C3, P < 0.05. Oxandrolone did not adversely affect the endocrine and inflammatory response as we found no significant differences in the hormone panels and cytokine expression profiles. Conclusions: In this large prospective, double-blinded, randomized single-center study, Oxandrolone shortened length of acute hospital stay, maintained LBM, improved body composition and hepatic protein synthesis while having no adverse effects on the endocrine axis postburn, but was associated with an increase in AST and ALT.
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metabolic and hormonal changes of severely burned children receiving long term Oxandrolone treatment
Annals of Surgery, 2005Co-Authors: Rene Przkora, David L Chinkes, Oscar E Suman, Marc G Jeschke, Celeste C Finnerty, Jong O Lee, Walter J Meyer, Robert E Barrow, Arthur P Sanford, Ronald P MlcakAbstract:Severe burns represent a major physical and psychologic event in a child's life. Progress in the treatment of burns, such as fluid resuscitation, early burn wound excision, new antibiotics, and nutritional support has reduced burn mortality.1 A major determination of morbidity in burn patients is the extent and duration of the hypermetabolic and catabolic response to injury. These responses are characterized by tachycardia, increased resting energy expenditure, peripheral insulin resistance, fat and protein catabolism, and muscle and bone wasting, which last for 1 to 2 years after burn and lead to growth retardation.1,2 These posttraumatic responses delay recovery, rehabilitation, and social and psychologic integration back into society.3–6 Various therapeutic approaches have been introduced to ameliorate these adverse effects.7,8 We and others have hypothesized that the use of anabolic agents may attenuate the posttraumatic response and improve long-term outcomes.1,8 Oxandrolone, a synthetic analog of testosterone with minimal virilizing activity and liver toxicity, attenuates muscle wasting after severe trauma, malnutrition, or acquired immunodeficiency virus.9,10 In severely burned children treated during acute hospitalization, Oxandrolone significantly improved net protein synthesis, lean body mass, bone mineral content, synthesis of the hepatic constitutive proteins such as albumin and prealbumin, and attenuated the acute phase reactive protein levels.11–13 The aim of this study was to determine whether Oxandrolone, administered for 1 year after injury to severely burned children, would attenuate catabolism and growth arrest and whether these positive attributes would persist after the drug is discontinued.
Robert H Demling - One of the best experts on this subject based on the ideXlab platform.
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Oxandrolone induced lean mass gain during recovery from severe burns is maintained after discontinuation of the anabolic steroid
Burns, 2003Co-Authors: Robert H Demling, Leslie DesantiAbstract:Weight loss and lean mass loss from burn induced catabolism can be more rapidly restored when the anabolic steroid Oxandrolone is added to optimum nutrition compared to nutrition alone. Our purpose in this study was to determine whether the regained lean body mass (LBM) is retained 6 months after stopping Oxandrolone. Forty-five severe burn patients, entering the recovery phase were randomized into a nutrition group alone or with the addition of Oxandrolone, 20 mg per day upon admission to the acute burn rehabilitation (RH) unit. Oxandrolone was discontinued after at least 80% of the involuntary weight loss occurring in the acute burn period, was restored. Body composition was measured using bioelectric impedence analysis (BIA). We found that patients receiving Oxandrolone, in the rehabilitation unit, regained weight and lean mass two to three times faster than with nutrition alone. The difference was statistically significant (P<0.05). All patients were discharged from RH on a nutrition and exercise program and monitored in the outpatient burn center. After 6 months, body weight and body composition were again measured. We found that the body weight and lean mass which was restored during RH, was maintained 6 months after discontinuation of Oxandrolone. Lost lean mass was not yet restored in the nutrition alone group. We can conclude that body weight and lean mass which is lost, due to burn induced catabolism, can be effectively restored in the post-burn recovery period with Oxandrolone. The body weight and lost lean mass which is regained, is maintained 6 months after stopping the drug.
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the rate of restoration of body weight after burn injury using the anabolic agent Oxandrolone is not age dependent
Burns, 2001Co-Authors: Robert H Demling, Leslie DesantiAbstract:We determined the effect of age on the restoration of lost body weight and lean mass after burn injury, using the anabolic steroid Oxandrolone. Patients with deep burns of 30-55% of body surface were studied when entering the recovery phase of injury, defined as resolution of the hypermetabolic, catabolic state. Patients were provided optimum nutrition and exercise alone or with the addition of Oxandrolone. The rate of body weight and lean mass gain and improvement in physical function were measured over a 4-week period. Four groups were studied. A younger group, mean age of 34 years and burn size of 47+/-7% versus an older group, mean age 60 years and burn size 36+/-5%. The mean loss of body weight in the younger and older groups was 10+/-2 and 11+/-2% of total. Both groups were randomly divided into a control and Oxandrolone study group. Weight restoration, 74+/-5% of which was lean mass, averaged 1.7+/-0.4 kg and 1.6+/-0.3 kg per week in the young and older Oxandrolone groups. This rate was compared with 0.7+/-0.2 kg and 0.5+/-0.2 kg in the young and older control groups, with only 55% of weight gain being lean mass. These differences were statistically significant. The increase in the rate of weight gain with Oxandrolone corresponded with a 30% decrease in length of stay in the burn rehabilitation unit. We concluded that the ability of an anabolic steroid to restore lean mass and physical function after burn surgery is not related to age.
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Oxandrolone an anabolic steroid enhances the healing of a cutaneous wound in the rat
Wound Repair and Regeneration, 2000Co-Authors: Robert H DemlingAbstract:The effect of the anabolic steroid Oxandrolone on the healing rate of a standardized full thickness linear wound on the back of the rat was studied. Oxandrolone was given orally by gavage in peanut oil at a dose of 0.1 mg/kg/day. A placebo powder in peanut oil was given at the same dose to a control group. Parameters monitored were time to complete wound closure, wound hydroxyproline content and tensile strength, as well as histology. We found that wounds closed completely in 12 ± 3 days with Oxandrolone, compared to 18 ± 3 days for a placebo, a statistically significant difference. The rate of body weight gain was identical in both groups. Hydroxyproline content of the healed incision site was 23 ± 4 mg/g tissue vs. 17 ± 3 mg/g tissue, while the tensile strength increased to 185 ± 13 g/mm2 vs. 102 ± 18 g/mm2 in the Oxandrolone and placebo groups, respectively. Both parameters were significantly increased with the anabolic steroid. Histologic examination showed a wound that contained more mature and densely packed collagen and was also hypercellular with Oxandrolone treatment. We conclude that the anabolic steroid Oxandrolone significantly enhanced wound healing unrelated to any generalized increase in protein mass as would be reflected in body weight.
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the anticatabolic and wound healing effects of the testosterone analog Oxandrolone after severe burn injury
Journal of Critical Care, 2000Co-Authors: Robert H Demling, Dennis P OrgillAbstract:Purpose: Severe burn injury leads to marked catabolism and decreased lean mass, which can impair healing. Anabolic agents can attenuate net catabolism. Our purpose was to determine whether the testosterone analog, Oxandrolone, given during the acute post burn period decreased the degree of nitrogen loss and loss of body weight while also increasing the healing rate of a skin donor site. Materials and Methods: Patients with burns between 40% and 70% of body surface were studied. A randomized double-blinded placebo-controlled study design was used. Patients were given Oxandrolone 20 mg/day (n = 11) or a placebo 20 mg/day (n = 9) beginning between days 2 and 3 post burn. Net nitrogen balance and the healing time of a standardized donor site were measured. Patients were monitored until transferred to a burn rehabilitation facility, an average time period of 33 ± 9 days. Results: Mean burn size was 49 ± 8% for placebo and 53 ± 9% of total body surface for the Oxandrolone group. Smoke inhalation was present in approximately 50% of patients in both groups. All patients survived the burn injury. Net weight loss was 8 ± 3.1 kg in the placebo group compared with 3 ± 1.9 kg in the Oxandrolone group, a statistically significant decrease. Net daily nitrogen loss over a 3-week period (days 7 to 28) was 13 ± 4 g in placebo treated compared with 4 ± 1.9 g for the Oxandrolone group, a statistically significant decrease. The healing time of a standardized donor site, decreased from the placebo group value of 13 ± 3 days to 9 ± 2 days for Oxandrolone treated patients, a significant improvement. No major liver dysfunction, or other complication attributable to an anabolic steroid was seen in either group. Conclusion: We found the anabolic agent, Oxandrolone, significantly decreased weight loss and net nitrogen loss and increased donor site wound healing compared with placebo controls. We noted no complications with the use of Oxandrolone. Copyright © 2000 by W.B. Saunders Company
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comparison of the anabolic effects and complications of human growth hormone and the testosterone analog Oxandrolone after severe burn injury
Burns, 1999Co-Authors: Robert H DemlingAbstract:This study compared the anticatabolic and wound healing effects of the anabolic agents human growth hormone, HGH, and the testosterone analogue, Oxandrolone, after severe burn injury. A randomized prospective study design was used. Patients were given HGH at a dose of 0.1 mg/kg/day (n = 20) or Oxandrolone, 20 mg/day (n = 16), beginning between days 7-10 post-burn. Data was compared to burn patients not placed on either agent (n = 24). Patients were monitored until they were sufficiently healed to be transferred to a rehabilitation center. The results of our study were as follows. All patients survived. Net weight loss was 8 +/- 2.1 kg in the control group compared with 4 +/- 1.8 kg with HGH and 3 +/- 1.2 kg with Oxandrolone, a significant decrease. Net daily nitrogen loss was 12 +/- 3 g in non-treated compared to 3 g or less for each of the anabolic groups, a significant decrease. The metabolic rate in untreated burns was 155 + 25% of predicted normal, compared to 178 +/- 28% for HGH and 156 +/- 20% for Oxandrolone treated patients. The complete healing time of a standardized donor site, decreased from the control value of 14 +/- 2 days to 10 +/- 3 days for HGH and 10 +/- 2 days for Oxandrolone treated patients, a significant improvement. Hyperglycemia (glucose over 225 mg/dl 12.5 mM) was present in 100% of HGH patients compared to 55% for control and 50% for Oxandrolone treated. We found that both anabolic agents significantly decreased weight and nitrogen loss and increased healing with nearly identical benefits. However HGH resulted in the significant complications of hyperglycemia and accentuated hypermetabolism. We noted no side effects with Oxandrolone.
