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.

Immunological control of methicillin-resistant Staphylococcus aureus (MRSA) infection in an immunodeficient murine model of thermal injuries

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

Stimulation of hematopoiesis by the Fms-like tyrosine kinase 3 ligand restores bacterial induction of Th1 cytokines in thermally injured mice.

Abstract: Patients with large burn injuries are susceptible to opportunistic infections due to impaired functions of multiple effector cells of innate immunity and acquired immunity, including macrophages, dendritic cells (DC), natural killer (NK) cells, and T cells. The ability of a host to produce Th1 cytokines, such as gamma interferon (IFN-γ) and interleukin-12 (IL-12), upon infectious challenge is also impaired after burn injury. Stimulation of hematopoiesis, to regenerate new immune cells, may be an effective strategy for improving resistance to infections after severe burn trauma. Fms-like tyrosine kinase 3 ligand (Flt3L) is a hematopoietic cytokine that stimulates the expansion and differentiation of NK cells and DC. Using a mouse model, we tested the hypothesis that Flt3L treatments after burn injury stimulate the production of functional effector cells of innate immunity and restore appropriate Th1 cytokine responses to Pseudomonas aeruginosa, a common source of pneumonia and wound infections in burn victims. Flt3L increased splenic cellularity in sham (uninjured) and burned mice and increased the numbers of NK cells (DX5+) and DC (CD11c+). In response to P. aeruginosa, significant increases in the serum IFN-γ levels and the numbers of splenic IFN-γ-producing DC, NK cells, and T cells were observed in Flt3L-treated burned mice compared to the values obtained for untreated burned mice. The splenic levels of IL-12 and IL-15 mRNAs and the IL-12 and IL-15 receptors were also increased. In addition, Flt3L treatment restored the ability of splenic cultures prepared from burned mice to produce IFN-γ and IL-12 after in vitro challenge with P. aeruginosa. Flt3L may have potential for restoring NK cell and DC functions and improving immunity after burn injury.

Transpulmonary thermodilution for hemodynamic measurements in severely burned children

Abstract: Introduction: Monitoring of hemodynamic and volumetric parameters after severe burns is of critical importance. Pulmonary artery catheters, however, have been associated with many risks. Our aim was to show the feasibility of continuous monitoring with minimally invasive transpulmonary thermodilution (TPTD) in severely burned pediatric patients. Methods: This prospective cohort study was conducted in patients with severe burns over 40% of the total body surface area (TBSA) who were admitted to the hospital within 96 hours after sustaining the injury. TPTD measurements were performed using the PiCCO system (Pulsion Medical Systems, Munich, Germany). Cardiac Index (CI), Intrathoracic Blood Volume Index (ITBVI) (Stewart-Hamilton equation), Extravascular Lung Water Index (EVLWI) and Systemic Vascular Resistance Index (SVRI) measurements were recorded twice daily. Statistical analysis was performed using one-way repeated measures analysis of variance with the post hoc Bonferroni test for intra- and intergroup comparisons. Results: Seventy-nine patients with a mean age (±SD) of 9 ± 5 years and a mean TBSA burn (±SD) of 64% ± 20% were studied. CI significantly increased compared to level at admission and was highest 3 weeks postburn. ITBVI increased significantly starting at 8 days postburn. SVRI continuously decreased early in the perioperative burn period. EVLWI increased significantly starting at 9 days postburn. Young children (0 to 5 years old) had a significantly increased EVLWI and decreased ITBVI compared to older children (12 to 18 years old). EVLWI was significantly higher in patients who did not survive burn injury. Conclusions: Continuous PiCCO measurements were performed for the first time in a large cohort of severely burned pediatric patients. The results suggest that hyperdynamic circulation begins within the first week after burn injury and continues throughout the entire intensive care unit stay.