Showing papers by "Shriners Hospitals for Children - Galveston published in 2007"

Burn size determines the inflammatory and hypermetabolic response

Abstract: Increased burn size leads to increased mortality of burned patients. Whether mortality is due to inflammation, hypermetabolism or other pathophysiologic contributing factors is not entirely determined. The purpose of the present study was to determine in a large prospective clinical trial whether different burn sizes are associated with differences in inflammation, body composition, protein synthesis, or organ function. Pediatric burned patients were divided into four burn size groups: 80% TBSA burn. Demographic and clinical data, hypermetabolism, the inflammatory response, body composition, the muscle protein net balance, serum and urine hormones and proteins, and cardiac function and changes in liver size were determined. One hundred and eighty-nine pediatric patients of similar age and gender distribution were included in the study ( 80% TBSA burn, n = 21). Patients with larger burns had more operations, a greater incidence of infections and sepsis, and higher mortality rates compared with the other groups (P 80% TBSA group, followed by the 60–79% TBSA burn group (P 80% burns lost the most body weight, lean body mass, muscle protein and bone mineral content (P < 0.05). The urine cortisol concentration was highest in the 80–99% and 60–79% TBSA burn groups, associated with significant myocardial depression and increased change in liver size (P < 0.05). The cytokine profile showed distinct differences in expression of IL-8, TNF, IL-6, IL-12p70, monocyte chemoattractant protein-1 and granulocyte–macrophage colony-stimulating factor (P < 0.05). Morbidity and mortality in burned patients is burn size dependent, starts at a 60% TBSA burn and is due to an increased hypermetabolic and inflammatory reaction, along with impaired cardiac function.

Longitudinal assessment of Integra in primary burn management: A randomized pediatric clinical trial*

Abstract: Background:Early excision with autograft-allograft closure is standard in severe burn management. Cadaver skin is associated with risks such as antigenicity, infection, and limited availability and shelf life. Previous studies have shown that Integra is safe to use in burns of <20% total body surfac

Serum cytokine differences in severely burned children with and without sepsis.

Abstract: The aim was to determine whether serum cytokine profiling early after burn can be used to identify patients at high risk of developing and subsequently dying of sepsis. A case series study was designed to determine whether serum cytokine profiling allows identification of patients at highest risk of developing and dying of sepsis at the time of hospital admission. All patients were treated according to the standard of burn care at our facility. Forty-four children (1-19 years old) with more than 40% of total body surface area and admitted within 7 days postburn were studied. None had infections or sepsis at the time of admission. Serum was collected before the first operation, and concentrations of 17 cytokines were measured. Diagnosis of sepsis was made at autopsy with identification of the pathogen. Fifteen patients developed sepsis and died, whereas 29 patients did not develop sepsis and survived. Significant elevations in serum interleukin (IL) 6, IL-8, IL-10, granulocyte-monocyte colony-stimulating factor, interferon gamma (IFN-gamma), tumor necrosis factor (TNF), and IL-12 p70 were found at the time of admission of patients who subsequently developed and died of sepsis when compared with burned patients who did not develop sepsis (P < 0.05). Multiple logistic regression analysis revealed that patients with a combination of elevated IL-6 and IL-12 p70 and lower TNF had an elevated risk of dying of sepsis. Serum IL-6, IL-8, IL-10, granulocyte-monocyte colony-stimulating factor, IFN-gamma, TNF, and IL-12 p70 are expressed differently in patients who die of sepsis versus those who never become septic. In addition, serum IL-6, IL-12 p70, and TNF can be used to identify burned patients who are at high risk of death from sepsis.

Gene therapy in wound healing: present status and future directions

Abstract: Gene therapy was traditionally considered a treatment modality for patients with congenital defects of key metabolic functions or late-stage malignancies. The realization that gene therapy applications were much vaster has opened up endless opportunities for therapeutic genetic manipulations, especially in the skin and external wounds. Cutaneous wound healing is a complicated, multistep process with numerous mediators that act in a network of activation and inhibition processes. Gene delivery in this environment poses a particular challenge. Numerous models of gene delivery have been developed, including naked DNA application, viral transfection, high-pressure injection, liposomal delivery, and more. Of the various methods for gene transfer, cationic cholesterol-containing liposomal constructs are emerging as a method with great potential for non-viral gene transfer in the wound. This article aims to review the research on gene therapy in wound healing and possible future directions in this exciting field.

Metabolism modulators in sepsis: Propranolol

Abstract: Sepsis is accompanied by an enormous increase in catecholamine expression, leading to metabolism of lipids and glucose, changes in cardiovascular output, immunomodulatory effects, and changes in protein metabolism, all of which push the body into a catabolic state. Deleterious beta-adrenoceptor controlled responses to stress and sepsis are well documented; therefore, it would seem appropriate to use propranolol under such circumstances. There are arguments both for and against the use of beta-adrenoceptor blockade during episodes of stress and infection. The definition of sepsis itself is a clinical one in most cases. There are guidelines concerning the diagnosis of sepsis (systemic inflammatory response syndrome [SIRS] in the presence of significant infection). However, when the cause of SIRS is not infection, for example, in burn patients, is it not possible, and indeed preferable, to tackle the stress response in a more aggressive fashion? The effects of SIRS on the body are myriad and have been defined and illustrated in many fine reviews. The effects of sepsis on the body, as well, have been discussed in the world literature and are beyond the scope of this article. In this article we attempt to demonstrate the effects of sepsis (SIRS plus infection) on whole body metabolism, outline the mediators of these changes, and then show the ability of propranolol to attenuate the changes seen.

PPAR-α agonism improves whole body and muscle mitochondrial fat oxidation, but does not alter intracellular fat concentrations in burn trauma children in a randomized controlled trial

Abstract: Insulin resistance is often associated with increased levels of intracellular triglycerides, diacylglycerol and decreased fat β-oxidation. It was unknown if this relationship was present in patients with acute insulin resistance induced by trauma. A double blind placebo controlled trial was conducted in 18 children with severe burn injury. Metabolic studies to assess whole body palmitate oxidation and insulin sensitivity, muscle biopsies for mitochondrial palmitate oxidation, diacylglycerol, fatty acyl Co-A and fatty acyl carnitine concentrations, and magnetic resonance spectroscopy for muscle and liver triglycerides were compared before and after two weeks of placebo or PPAR-α agonist treatment. Insulin sensitivity and basal whole body palmitate oxidation as measured with an isotope tracer increased significantly (P = 0.003 and P = 0.004, respectively) after PPAR-α agonist treatment compared to placebo. Mitochondrial palmitate oxidation rates in muscle samples increased significantly after PPAR-α treatment (P = 0.002). However, the concentrations of muscle triglyceride, diacylglycerol, fatty acyl CoA, fatty acyl carnitine, and liver triglycerides did not change with either treatment. PKC-θ activation during hyper-insulinemia decreased significantly following PPAR-α treatment. PPAR-α agonist treatment increases palmitate oxidation and decreases PKC activity along with reduced insulin sensitivity in acute trauma, However, a direct link between these responses cannot be attributed to alterations in intracellular lipid concentrations.

The Hepatic Response to Severe Injury

Abstract: After severe injury, such as thermal injury, a variable degree of liver injury is present and it is usually related to the severity of the thermal injury. Fatty changes, a very common finding, are per se reversible and their significance depends on the cause and severity of accumulation [1]. However, autopsies of burned children who died have shown that fatty liver infiltration was associated with increased bacterial translocation, liver failure, and endotoxemia, thus delineating the crucial role of the liver during the post-burn response [2, 3, 4]. In a recent study in 102 children, 41 females and 61 males with a total body burn size of 58 ± 2% and third degree burns in 45 ± 2%, we found that liver size and weight significantly increased during the first week post-burn (+85 ± 5%), peaked at 2 weeks post-burn (+126 ± 19%), and was increased by +89 ± 10% at discharge. At 6, 9, and 12 months the liver weight was increased by 40–50% compared to predicted liver weight. In addition, liver protein synthesis was impaired for a 6-month period with a shift from constitutive hepatic proteins to acute phase proteins [5]. Liver enzymes were significantly elevated over the first 3 weeks post-burn, normalizing over time. These findings indicate that the hepatic acute phase response perseveres for a longer time period than previously thought [5, 6].

Building the research teams of the future: Changing the paradigm

Abstract: Scientific knowledge about the treatment of burn injuries and the care of burn patients continues to advance, ever changing the nature of the research questions to be asked. At a meeting to review the state of the science, we look forward to meeting challenges of the next 5 years and preview the evolution that the burn research community will undergo in meeting those challenges. As the burn research paradigm changes, the basic model of a process that melds basic science with clinical research and clinical care must not change. Integrating scientific research with clinical care has been promoted throughout the recent history of burn care. In the late 1940s, the first U.S. burn center at the Medical College of Virginia and the U.S. Army Surgical Research Unit, later renamed the U.S. Army Institute of Surgical Research emphasized the importance of collaboration between clinical care and basic scientific disciplines. In 1947, the freighter SS Grandcamp exploded in Texas City, Texas, killing 653 and injuring thousands. Dr. Truman Blocker cared for many of those who were burned in that disaster and then led the way to establish one of the world’s first designated burn units at the University of Texas Medical Branch in Galveston, Texas. In 1966, under Dr. Blocker’s continued leadership, the first Shriners Burns Hospital (SBH) opened in Galveston, affiliated with the University of Texas Medical Branch. Dr. Blocker believed in interdisciplinary research and care and that belief formed the philosophy that has continued to thrive through the 40 years since the hospital opened. In 2006, we still have interdisciplinary research teams and collaborative projects to improve the care of burn injuries. Clinicians, basic scientists, allied health specialists, and students interact to pose research questions based on clinical problems, to look for answers in the laboratories, and then in the clinical setting in a perpetual positive feedback loop. The interest of the clinicians and the concerns of the patients spark excitement in the researchers. The researchers’ enthusiasm elicits interest among the clinicians. Advances in burn care attest to the value of a dedicated burn unit organized around the concept of a collegial group of basic scientists, clinical researchers, and clinical care givers, all asking questions of each other, sharing observations and information, and together seeking solutions to improve the welfare of their patients. Much past research has been directed to solving problems that would enhance the probability of survival. Now, a significant decrease in burn mortality has been widely recognized (Table 1). That decrease has been the result of advances in knowledge stemming from that interactive, interdisciplinary process that led to changes in resuscitation, control of infection, support of the hypermetabolic response to trauma, and early closure of the burn wound. Scientifically sound analyses of patient data have led to the development of formulae for fluid resuscitation and nutritional support. Clinical research has demonstrated the utility of topical antimicrobials in delaying onset of sepsis. Prospective randomized clinical trials have determined the efficacy of early surgical therapy in improving survival for many burned patients by decreasing blood loss and by diminishing the occurrence of sepsis. Basic science and clinical research have contributed to decreased mortality by describing pathophysiology related to inhalation injury and suggesting treatment methods which have decreased the incidence of pulmonary edema and pneumonia. Scientific investigations of the hypermetabolic response to major burn injury have led to improved management of this life–threatening phenomenon, resulting not only in diminished loss of life but also promising improved quality of life. The continued interaction of the basic and clinical scientists with each other and with other caretakers as well as patients kept the proFrom the University of Texas Medical Branch and Shriners Hospitals for Children, Galveston Burns Hospital, Galveston, Texas. Address correspondence to Patricia Blakeney, PhD, 693 County Road 251, Valley View, Texas 76272. Copyright © 2007 by the American Burn Association. 1559-047X/2007

Effects of neuronal nitric oxide synthase in ovine lung injury

Abstract: Excessive production of nitric oxide is a major factor contributing to acute lung injury and systemic inflammation after burn and smoke inhalation injury. We hypothesized that the use of 7-nitroindazole (7-NI), a selective nNOS inhibitor, blocks molecular mechanisms in this pathogenesis.

Early Manipulation of Metabolic Changes due to Severe Burns in Children

Abstract: Burns account for around 700,000 emergency department visits every year resulting in around 50,000 admissions to hospital in the United States [1]. Around 50% of these admissions have burns of less than 10% total body surface area (TBSA) and, as such, have near normal metabolic rates. For the remainder, the rise in metabolic rate is linked to burn size and for those with severe thermal injuries (>40% TBSA) the change in patient metabolism is, if left unchecked, set to last for more than 12 months. The change contributes, at least in part, to long term deleterious effects on the individual. It has been previously shown that the ensuing period of hypermetabolism and catabolism following a severe burn leads to impaired immune function, decreased wound healing, erosion of lean body mass, and hinders rehabilitative efforts delaying reintegration into normal society. However, the magnitude and longevity of these changes has yet to be fully elucidated. Strategies for attenuating these maladaptive responses may be divided into pharmacological and non-pharmacological. Non-pharmacological approaches include prompt, early excision and closure of wounds, pertinacious surveillance for and treatment of sepsis, early commencement of high protein high carbohydrate enteral feeding, elevation of the immediate environmental temperature to 31.5°C (± 0.7°C), and early institution of an aerobic resistive exercise program. Several pharmacotherapeutic options are also available to further reduce metabolic rate and as such attenuate the erosion of lean body mass; these include anabolic agents such as recombinant human growth hormone, insulin, and oxandrolone and also beta blockade using propranolol.