Shriners Hospitals for Children - Galveston

About: Shriners Hospitals for Children - Galveston is a healthcare organization based out in Galveston, Texas, United States. It is known for research contribution in the topics: Burn injury & Lean body mass. The organization has 249 authors who have published 420 publications receiving 15311 citations.

Thermal injury initiates pervasive fibrogenesis in skeletal muscle.

Abstract: Severe burn injury induces a myriad of deleterious effects to skeletal muscle, resulting in impaired function and delayed recovery. Following burn, catabolic signaling and myofiber atrophy are key fiber-intrinsic determinants of weakness; less well understood are alterations in the interstitial environment surrounding myofibers. Muscle quality, specifically alterations in the extracellular matrix (ECM), modulates force transmission and strength. We sought to determine the impact of severe thermal injury on adaptation to the muscle ECM and quantify muscle fibrotic burden. After a 30% total body surface area dorsal burn, spinotrapezius muscle was harvested from mice at 7 (7d, n = 5), 14 (14d, n = 4), and 21 days (21d, n = 4), and a sham control group was also examined (Sham, n = 4). Expression of transforming growth factor-β (TGFβ), myostatin, and downstream effectors and proteases involved in fibrosis and collagen remodeling were measured by immunoblotting, and immunohistochemical and biochemical analyses assessed fibrogenic cell abundance and collagen deposition. Myostatin signaling increased progressively through 21 days postburn alongside fibrogenic/adipogenic progenitor cell expansion, with abundance peaking at 14 days postburn. Postburn, elevated expression of tissue inhibitor of matrix metalloproteinase 1 supported collagen remodeling resulting in a net accumulation of muscle collagen content. Collagen accumulation peaked at 14 days postburn but remained elevated through 21 days postburn, demonstrating minimal resolution of burn-induced fibrosis. These findings highlight a progressive upregulation of fibrogenic processes following burn injury, eliciting a fibrotic muscle phenotype that hinders regenerative capacity and is not resolved with 21 days of recovery.

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].

Comparison of carbon monoxide (CO) single breath pulmonary diffusing capacity with non-rebreathing, open-circuit CO pulmonary diffusing capacity in healthy children.

Abstract: Introduction The standard technique for assessing pulmonary diffusing capacity of the lungs (DL) for carbon monoxide (CO) is the single breath (SB) technique. SB_DLco in children can be problematic because it requires a vital capacity >1.5 L. We have developed an open-circuit technique (OC), which uses the wash-in of CO over a series of 8–10 normal breaths that does not require rebreathing. In this study, we compared the SB_DLco against the OC_DLco. Methods Nineteen healthy children between 7 and 18 years performed SB_DLco and OC_DLco tests. The mean SB_DLco was significantly larger than the mean OC_DLco. The mean difference OC_DLco minus SB_ DLco was: −2.92 ± 4.21 ml/min/mm Hg, though the difference was negatively correlated with the mean of the two (r = 0.73). The lower mean OC_DLco was in part due to lower lung volume (as measured by alveolar volume (VA)) during the maneuver. In both groups there was a positive correlation between VA and DLco, and the mean VA was −2.17 ± 1.07 L lower using OC compared to SB. The difference was again negatively correlated with the mean (r = 0.82). The mean OC minus SB difference in DLco/VA was: 6.06 ± 1.98 ml/min/mm Hg/L, though this difference was positively correlated with the mean, r = 0.76. Conclusions We found a good correlation between both techniques for DLco, VA, and DLco/VA. The OC offers the advantage of minimal subject cooperation, and may be preferable to use in children. Pediatr Pulmonol. 2006, 41:1095–1102. © 2006 Wiley-Liss, Inc.

Metabolic changes following major burn injury: How to improve outcome

Abstract: The changes in patient metabolism following a major burn may be seen for more than 12 months after the initial injury. The ensuing period of hypermetabolism and catabolism post-burn leads to impaired immune function, decreased wound healing, erosion of lean body mass, and hinders rehabilitative efforts delaying reintegration into normal society. The typical changes in metabolism are the development of a hyperdynamic circulation [1], increased body temperature [2], increased protein catabolism with peripheral protein wasting [3], increased lipolysis leading to fatty infiltration of the liver [4], increased glycolysis and futile substrate cycling 5. These changes are responsible for much of the morbidity and mortality seen with such an injury and as such are important targets for available treatments including: early excision and grafting; aggressive 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 erosion of lean body mass; these include anabolic agents such as recombinant human growth hormone, insulin, oxandrolone and beta-blockade with propranolol. This chapter will discuss the metabolic changes seen following a major burn and how different treatment options affect outcome.

Is the limulus amebocyte lysate the sole predictor of septic episodes in major thermal injuries

Abstract: Septic episodes in thermal injuries are usually hallmarked by a series of physiologic parameters that include tachypnea, prolonged paralytic ileus, hyperthermia or hypothermia, altered mental status, thrombocytopenia, leukocytosis or unexplained leukopenia, acidosis, and hyperglycemia. Recent studies with polycystic kidney disease have clearly indicated that the limulus amebocyte lysate (LAL) assays were predictive of fungal infections in this patient population. Because both bacteria and fungi produce lipopolysaccharide that can be identified with the LAL assay, we randomly assayed sequential sera of 45 patients with major thermal injuries for positivity in the LAL assay, with use of the QCL-1000 kit (BioWhittaker, Walkersville, Md). The average burn size of this patient population was 63.43% total body surface area. The average age of the patient was 6.2 years. The sex distribution included 30 males and 15 females. The infectious agents included gram-positive cocci and gram-negative rods, and 14 patients had concomitant fungal infections. Eighty-five percent of the patients tested were positive for endotoxin, with levels ranging from 1.0 EU/mL. The predominant organism isolated before or on the date the serum was drawn was Pseudomonas aeruginosa (51%), followed by Klebsiella pneumoniae (15%). The remaining 34% were a variety of Enterobacteriaceae. Of the 14 patients who yielded a fungus, 3 had negative LAL assays. Two patients with an elevated LAL grew only Staphylococcus epidermidis in the bloodstream and the wounds. These data clearly indicate that the LAL assay cannot be relied on as the sole predictor of septic episodes; however, it can be an adjunctive test to confirm sepsis when the other parameters have been considered.