Cardiac abnormalities in children with burns: an autopsy analysis.

After observing several cases of endocarditis-related deaths, we determined the contribution of cardiac abnormalities to burn mortality. Autopsy reports of all burn-related deaths between 1964 and 1992 (n = 212) were reviewed for cardiac disease. Cardiac abnormalities were categorized into infectious, acquired, or congenital. Cardiac abnormalities of all forms were associated with longer hospitalizations before death and affected a larger proportion of females than expected in the male-dominated burn population. The highest incidence of endocarditis (17.3% of all deaths) occurred in the past 5 years. The frequency of other forms of cardiac abnormalities has not changed over time. Improved burn management has resulted not only in improved survival but has also prolonged the duration of hospitalization of those patients who ultimately die of their injuries. As patients are kept alive for longer periods, the incidence of endocarditis and the cardiac manifestations of multiple organ failure have increased.

PDGF and TGF-alpha act synergistically to improve wound healing in the genetically diabetic mouse.

Impaired wound healing results in significant morbidity for the surgical patient. The genetically diabetic (C57BL/KsJ-db/db) mouse is obese, hyperglycemic, insulin-resistant, and exhibits markedly impaired wound healing. Previous studies have demonstrated that the fibroblast mitogens, BB homodimer of platelet-derived growth factor (PDGF-BB) or basic fibroblast growth factor, plus insulin-like growth factor, act synergistically to enhance wound closure in the genetically diabetic mouse. The purpose of this study was to determine whether the keratinocyte mitogens, epidermal growth factor (EGF) or transforming growth factor-alpha (TGF-alpha), in combination with the fibroblast mitogen, PDGF-BB, would produce a similar synergistic enhancement in tissue repair. Full-thickness skin wounds created on the backs of diabetic mice received topical applications of vehicle (5% polyethylene glycol), PDGF-BB (10 micrograms), EGF (1 microgram), TGF-alpha (1 microgram), or the combination of PDGF (10 micrograms) and EGF (1 microgram) or TGF-alpha (1 microgram) for 5 consecutive days starting at wounding. Application of PDGF-BB or TGF-alpha alone to wounds in diabetic animals improved wound closure when compared to vehicle treatment. EGF did not affect healing and did not have any additive effects when combined with PDGF-BB. Significant improvements in wound closure were observed with the combination of PDGF-BB and TGF-alpha when compared to treatment with the individual growth factors. The PDGF-BB/TGF-alpha combination accelerated healing in the diabetic animals to a rate that was closer to that seen in nondiabetic mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Synergistic actions of platelet-derived growth factor and the insulin-like growth factors in vivo.

Topical application of growth factors has been shown to benefit both normal and impaired wound healing. In normal tissue repair, resident cells produce a "cocktail" of various types of growth factors that overlap in function. In vitro studies have proved that growth factor combinations can act synergistically to enhance cellular function beyond that achieved with individual growth factors. To determine whether similar combinations have a synergistic effect in vivo, we applied growth factor combinations topically to full-thickness skin wounds created in genetically diabetic mice. The C57BL/KsJ-db/db mouse is obese and has insulin-resistant diabetes, and it has been proved that this mouse has markedly impaired wound healing. Topical application of platelet-derived growth factor, insulin-like growth factor-I, or insulin-like growth factor-II enhances healing in this model. Marked synergism was found when platelet-derived growth factor and insulin-like growth factor-II were combined to produce augmentation in wound closure beyond that achieved by application of the individual growth factors. The synergistic effect allowed for improved tissue repair at doses of platelet-derived growth factor and insulin-like growth factor-II that were ineffective when applied individually. The addition of insulin-like growth factor-I or insulin to platelet-derived growth factor produced no significant synergism. Because multiple growth factors are released in the wound during the healing process, it is not surprising that their combination further enhances healing. Growth factor combinations should become an important addition to the armamentarium for the treatment of chronic, nonhealing wounds.