Showing papers by "Shriners Hospitals for Children - Galveston published in 2005"
TL;DR: Oxandrolone improved body composition and strength in severely burned children during the 12 months of treatment and its effect on height and weight continued after treatment was discontinued.
Abstract: 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.
96 citations
TL;DR: It is indicated that Flt3L can increase the resistance of mice to a P. aeruginosa burn wound infection through both stimulation of dendritic cell production and enhancement of dendedritic cell function.
Abstract: Fms-like tyrosine kinase-3 ligand (Flt3L) is a hemopoietic cytokine that stimulates the production of dendritic cells. This study evaluated the ability of Flt3L-enhanced dendritic cell production to increase the resistance of mice to a burn wound infection with Pseudomonas aeruginosa, a common source of infections in burn patients that have impaired immunity and are susceptible to opportunistic microorganisms. Treatment of mice with Flt3L for 5 days caused a significant increase in dendritic cell numbers in the spleen and significantly increased survival upon a subsequent burn wound infection. Improved survival in Flt3L-treated mice was associated with limited bacterial growth and spread within the burn wounds and a decrease in systemic dissemination of P. aeruginosa. Resistance to burn wound infection could also be conferred to recipient mice by the adoptive transfer of dendritic cells that had been isolated from spleens of Flt3L-treated mice. Adoptive transfer of the same number of splenic dendritic cells from nontreated mice did not confer resistance to burn wound infection. These data indicate that Flt3L can increase the resistance of mice to a P. aeruginosa burn wound infection through both stimulation of dendritic cell production and enhancement of dendritic cell function.
86 citations
TL;DR: Exogenous, continuous low-dose insulin infusion, beta-blockade with propranolol, and the use of the synthetic testosterone analogue oxandrolone are the most cost-effective and least toxic therapies to date and are effective in burned patients with and without sepsis.
62 citations
TL;DR: In this article, the authors focused on weekly dressing changes as a cost-containment issue and concluded that weekly dressing change with AgNO3 is feasible and medically congruous.
Abstract: The organic salt AgNO3 has been available as a topical armamentarium to the medical arena for centuries and for burns for the past 60 years. Thirty-five (1968) years later, Charles Fox introduced and popularized a new topical agent known as silver sulfadiazine. More recently, several new slow-release silver dressings came to the forefront. Acticoat (Smith & Nephew, Largo, FL) Silverlon (Argentum, Lakemont, GA) & Silvasorb (Medline Industries, Inc, Mundelein, IL). Because the standard of care is to change dressings daily, our study focused in on weekly dressing changes as a cost-containment issue. Sprague-Dawley rats received a standard contact burn (20% TBSA). On day 3, the wound was excised and infected with Pseudomonas aeruginosa and Staphylococcus aureus at 5.0 x 10 cfu/ml. The animals were divided into four groups (n = 5 each group): untreated control, Acticoat group, Silvasorb group, and Silverlon group. The dressings remained on the wounds for 10 days when the wounds were quantitatively assessed. Mean wound counts of the control ranged from 1.2 x 10(5) to 6.5 x 10(5) for P. aeruginosa and S. aureus, respectively. Acticoat dressing counts for both organisms were 0 and 1.8 x 10(3) (median alpha); Silvasorb was 0 and 6.3 x 10(3) and Silverlon was 1.5 x 10(4) x 7.4 x 10(4) (median), Acticoat and Silvasorb were both significantly lower (P < .05) than the control for P. aeruginosa, and Acticoat was significantly lower (P < .05) than the control for S. aureus. Although counts for Silvasorb (M) appear significantly lower than the controls for S. aureus, the numbers were not sufficient to be significant. However, Silverlon did achieve a slight significance. These preliminary data suggest that weekly dressing changes with these new silver dressings are feasible and economically and medically congruous.
62 citations
TL;DR: Induction of LPS tolerance enhanced systemic clearance of Pseudomonas aeruginosa and that this effect was augmented by neutralization of IL-10, which reversed the endotoxin-tolerant state.
Abstract: Endotoxin (lipopolysaccharide [LPS]) tolerance is an altered state of immunity caused by prior exposure to LPS, in which production of many cytokines, including gamma interferon (IFN-γ) and interleukin-12 (IL-12), are reduced but secretion of the anti-inflammatory cytokine IL-10 is increased in response to a subsequent LPS challenge. This pattern of cytokine production is also characteristic of postinflammatory immunosuppression. Therefore, we hypothesized that LPS-primed mice would exhibit an impaired ability to respond to systemic infection with the opportunistic pathogen Pseudomonas aeruginosa. We further hypothesized that depletion of IL-10 would reverse the endotoxin-tolerant state. To test this hypothesis, systemic clearance of Pseudomonas aeruginosa was measured for LPS-primed wild-type and IL-10-deficient mice. LPS-primed wild-type mice exhibited significant suppression of LPS-induced IFN-γ and IL-12 but increased IL-10 production in blood and spleen compared to levels exhibited by saline-primed wild-type mice. The suppressed production of IFN-γ and IL-12 caused by LPS priming was ablated in the spleens, but not blood, of IL-10 knockout mice. LPS-primed wild-type mice cleared Pseudomonas aeruginosa from lungs and blood more effectively than saline-primed mice. LPS-primed IL-10-deficient mice were particularly efficient in clearing Pseudomonas aeruginosa after systemic challenge. These studies show that induction of LPS tolerance enhanced systemic clearance of Pseudomonas aeruginosa and that this effect was augmented by neutralization of IL-10.
46 citations
TL;DR: The results suggest that MRSA infection in thermally injured patients is controlled immunologically through the induction of anti‐MRSA effector cells and elimination of burn‐associated alternatively activated Mφ, which are cells that inhibit the generation of classically activated M φ.
Abstract: Staphylococcus aureus, especially methicillin-resistant S aureus (MRSA), is a major cause of sepsis in patients who are immunosuppressed by their burns In this study, an immunological regulation of MRSA infection was attempted in a mouse model of thermal injury SCIDbg mice were resistant to MRSA infection, while SCIDbgMN mice (SCIDbg mice depleted of neutrophils and macrophages (Mphi)) were susceptible to the same infection Also, thermally injured SCIDbg mice were shown to be susceptible to MRSA infection On the other hand, the resistance of SCIDbgMN mice to the infection was completely recovered after an inoculation with Mphi from normal mice However, anti-MRSA resistance was not shown in SCIDbgMN mice inoculated with Mphi from thermally injured mice Mphi from MRSA-infected thermally injured mice were identified as alternatively activated Mphi, and Mphi from MRSA-infected unburned mice were characterized as classically activated Mphi Mphi from thermally injured SCIDbg mice previously treated with 2-carboxyethylgermanium sesquioxide (Ge-132) protected SCIDbgMN mice against MRSA infection Ge-132 has been described as an inhibitor of alternatively activated Mphi generation These results suggest that MRSA infection in thermally injured patients is controlled immunologically through the induction of anti-MRSA effector cells and elimination of burn-associated alternatively activated Mphi, which are cells that inhibit the generation of classically activated Mphi
41 citations
TL;DR: It is demonstrated that early institution of enteral feeding can attenuate the stress response, abate hypermetabolism, and improve patient outcome in the burn patient.
Abstract: Significant weight loss is a common complication of a major burn injury. Before the modern era of early enteral nutrition support, such a complication contributed significantly to impaired wound healing, raised risk of infectious morbidity, and ultimately increased mortality. Nutrition management of the burn patient is designed to promote wound healing while minimizing loss of lean body mass. The burn patient characteristically demonstrates an increase in energy expenditure after the initial injury and period of resuscitation. Studies have demonstrated that early institution of enteral feeding can attenuate the stress response, abate hypermetabolism, and improve patient outcome.
41 citations
TL;DR: It is unlikely that a nutritional intervention alone would be effective in maintaining lean body mass during severe stress, and it may be necessary to concomitantly reduce the catabolic influence of cortisol or provide another anabolic stimulus.
Abstract: Muscular inactivity is inherent in many circumstances, including convalescence from serious illness or injury, spaceflight, and the progression of aging. Inactivity in a healthy individual leads to a decrease in whole-body protein turnover composed primarily of a decrease in muscle protein synthesis. The decrease in muscle protein synthesis leads to a substantial loss of lean body mass. We have demonstrated that this loss of lean mass is greater when inactivity is accompanied by stress, specifically hypercortisolemia. During convalescence from trauma or injury, the anabolic stimulus provided by nutrient ingestion represents a primary means of ameliorating the loss of muscle protein. We have previously demonstrated that ingestion of essential amino acids (EAAs), formulated to mimic the proportion of EAAs in muscle, provides a potent anabolic stimulus for muscle protein. Recently, we demonstrated that EAA supplementation throughout 28 d of bed rest stimulated net muscle protein synthesis. The repeated stimulation translated to maintenance of lean body mass and an amelioration of functional decrement compared to a placebo treatment. We have also demonstrated that this EAA supplement stimulates net protein synthesis during acute hypercortisolemia and are currently testing the effects during prolonged inactivity. Although EAAs promote muscle anabolism during hypercortisolemia, it is unlikely that a nutritional intervention alone would be effective in maintaining lean body mass during severe stress. It may be necessary to concomitantly reduce the catabolic influence of cortisol or provide another anabolic stimulus.
37 citations
TL;DR: The new rat model affords insight into the complex molecular pathophysiology of smoke inhalation in the brain, and microarray analysis revealed increased brain expression of nitric oxide synthase (NOS) and NOS ligand after inhalation of smoke.
34 citations
TL;DR: The new precursor-product methods have enabled assessment in clinical trials of protein breakdown for proteins other than myofibrillar proteins and in circumstances in which arteriovenous sampling is not feasible.
Abstract: Purpose of reviewTo describe the latest innovations in measuring protein breakdown in vivo, particularly in muscle.Recent findingsThe traditional method of using 3-methylhistidine excretion to measure muscle protein breakdown has been updated to include arteriovenous or microdialysis measurements, w
30 citations
TL;DR: Administration of a dual ET-1 receptor antagonist prevented an increase in PVRI after injury and reduced the degree of bronchiolar obstruction in sheep with S+B; however, treated sheep showed higher levels of NOx and increased lung lymph flow.
Abstract: Studies have suggested that ET-1 (endothelin-1) is associated with lung injury, airway inflammation and increased vascular permeability. In the present study we have tested the hypothesis that treatment with a dual ET-1 receptor antagonist will decrease airway obstruction and improve pulmonary function in sheep with combined S+B (smoke inhalation and burn) injury. Twelve sheep received S+B injury using the following protocol: six sheep were treated with tezosentan, an ETA and ETB receptor antagonist, and six sheep received an equivalent volume of vehicle. Physiological and morphological variables were assessed during the 48 h study period and at the end of the study. There was no statistically significant difference in the PaO2/FiO2 (partial pressure of O2 in arterial blood/fraction of O2 in the inspired gas) ratio of the tezosentan-treated animals compared with controls; however, lung lymph flow was significantly higher (P<0.05) in the treated animals. PVRI (pulmonary vascular resistance index) was significantly reduced (P<0.05) in the tezosentan-treated animals. Assessment of NOx (nitric oxide metabolite) levels in plasma and lymph showed significantly elevated (P<0.05) levels in the tezosentan-treated animals compared with levels in untreated sheep. The degree of bronchial obstruction was similar in both treated and control sheep; however, bronchiolar obstruction was reduced in sheep treated with tezosentan. Histopathologically, no difference in the degree of parenchymal injury was detected. In conclusion, administration of a dual ET-1 receptor antagonist prevented an increase in PVRI after injury and reduced the degree of bronchiolar obstruction in sheep with S+B; however, treated sheep showed higher levels of NOx and increased lung lymph flow. Tezosentan treatment was ineffective in protecting against acute lung injury in this model.
TL;DR: Results indicated that by inhibiting CCL3 production the sympathetic nervous system contributes to the increased susceptibility of TI-mice to sepsis.
TL;DR: The results indicate that severely burned children treated with long-term GH show a significant improvement in left ventricular ejection fraction.
TL;DR: It is proposed that nitric oxide inhalation has potential for beneficial effect in the treatment of patients suffering from smoke inhalation and is associated with marked increase in pulmonary microvascular resistance, pulmonary artery pressure, and decrease in reflection coefficient.
Journal Article•
TL;DR: The purpose of this article is to explore principles related to the use of medical interpreters, examine different models of interpreter services, and identify available resources to assist providers in accessing interpreter services (e.g., books, online resources, articles, and videos).
Abstract: A critical part of every encounter between a pediatric nurse and a patient is obtaining accurate patient information. Unique obstacles are encountered when patients and their families have little or no understanding of the English language. Federal and state laws require health care systems that receive governmental funds to provide full language access to services. Both legal and ethical issues can arise when caring for non-English-speaking patients. Often, obtaining accurate patient information and a fully informed consent cannot be done without the use of an interpreter. The interpreter informs the family of all the risks and benefits of a specific avenue of care. When inappropriate interpreter services are used, such as when children in the family or other family members act as interpreters, concerns about accuracy, confidentiality, cultural congruency, and other issues may arise. The purpose of this article is to: (a) explore principles related to the use of medical interpreters, (b) examine different models of interpreter services, and (c) identify available resources to assist providers in accessing interpreter services (e.g., books, online resources, articles, and videos). The case study format will be used to illustrate key points.
TL;DR: FSCs showed that FSCs reduced the need for autografting of deep second degree burns, with little hypertrophy of new skin and no skin contraction.
Abstract: The management of patients with partial thickness (second degree) burns is problematic due to the different treatments needed for varying depths of injury A report recently published in The Lancet describes a novel treatment for deep second degree burns using a fetal skin construct (FSC) The authors included eight pediatric patients with small second degree burns They showed that FSCs reduced the need for autografting of deep second degree burns, with little hypertrophy of new skin and no skin contraction This technology is new and exciting, but in our opinion several issues must be addressed before FSCs can enter the clinical arena All of the patients were included in the treatment group, and therefore no comparison with conventional skin substitutes was possible There is no mention of the use of laser Doppler in any initial assessment of patients The debridement carried out before application of the FSC is not elaborated upon, and the surface areas involved in the study were very small in most cases, which limits the relevance to patients with larger burns The use of FSCs gives us an additional option in a range of possible treatments for this notoriously difficult-to-treat patient group
TL;DR: The studies demonstrated feasibility and usefulness of DNA microarrays for identifying pathways involved in the molecular pathophysiology of the aging process and lifespan control in complex organisms.
TL;DR: Gene changes can be identified for up to 18 months after burn but not at 24 months, which may provide information concerning what genes in skeletal muscle contribute to recovery from burn trauma.
Abstract: OBJECTIVE The purpose of this study was to identify gene-expression changes in leg muscle for up to 24 months after a severe thermal injury. SUMMARY BACKGROUND DATA Hypermetabolism associated with severe burns was thought to cease with wound healing and closure. It has been recently shown that hypermetabolism does not completely resolve after healing, and muscle catabolism continues after hospital discharge; however, just how long after discharge has not been established. METHODS : Six children, admitted to our hospital within 1 week after injury, were studied. Patients ranged in age from 3 to 18 years, with flame or scald burns covering more than 40% of their body surface area. At 1.5, 6, 12, 18, and 24 months postburn, a biopsy of the vastus lateralis muscle was taken and snap frozen at -80 degrees C. Total RNA was isolated and in vitro transcribed and hybridized to HG-U95 Av.2 Affymetrix arrays. The images were scanned and analyzed using Affymetrix GeneChip Analysis Suite 5.2 and dChip programs. Using 1 to 7 days after injury as baseline, comparisons were made of expression profiles at the various time intervals after injury. RESULTS When comparisons are made to nonburned children, 38 genes were significantly altered at 1.5 months, 10 genes remained altered at 6 months, 4 remained altered at 12 months, and 2 at 18 months. No differences could be shown at 24 months. Western blot analysis of beta-2 microglobulin and myosin light chain was used to corroborate the microarray data. CONCLUSIONS Gene changes can be identified for up to 18 months after burn but not at 24 months. These gene changes may provide information concerning what genes in skeletal muscle contribute to recovery from burn trauma.
TL;DR: Genes that are differentially expressed in skeletal muscle of burned children, but whose function in muscle is unknown, include those related to various transcription factors and those known to encode proteins involved in signaling pathways.
TL;DR: It is suggested that NKT cells lacking IL-4 producing abilities contribute to the CCL2-associated increase in the susceptibility of thermally injured patients to HSV-1 infection through the induction of Th2 cell generation.