Keratinocyte growth factor (KGF) is a member of the fibroblast growth factor (FGF) family (hence the alternative designation FGF-7). It is produced by stromal cells, but acts as a mitogen for epithelial cells. We examined the effects of topically applied KGF on healing of wounds in a porcine model. In partial-thickness wounds, KGF stimulated the rate of reepithelialization (p < 0.0002), associated with a thickening of the epidermis (p < 0.0001). Epidermis from KGF-treated full-thickness wound sites was significantly thicker (0.31 +/- 0.22 mm) compared with mirror image control sites (0.18 +/- 0.12 mm) (p < 0.0001). Moreover, the majority (77%) of KGF-treated wounds exhibited epidermis with a deep rete ridge pattern as compared with control sites. These effects were observed as early as 14 d and persisted for at least 4 wk. KGF treatment also increased the number of serrated basal cells associated with increased deposition of collagen fibers in the superficial dermis adjacent to the acanthotic epidermis. Electron microscopy revealed better developed hemidesmosomes associated with thicker bundles of tonofilaments in the serrated cells. The pattern of epidermal thickening observed in KGF-treated wounds resembled psoriasis. Psoriasis is a disease associated with epidermal thickening, parakeratosis as well as hyperproliferation that extends beyond the basal layer. In striking contrast to psoriasis, KGF-treated wounds exhibited normal orthokeratotic maturation, and proliferation was localized to the basal cells. Our present findings have significant implications concerning the role of KGF as a paracrine modulator of epidermal proliferation and differentiation.
Fifteen consecutive patients with toxic epidermal necrolysis or the Stevens-Johnson syndrome managed without corticosteroids after transfer to the burn center (group 2) are compared to a previous consecutive group of 15 who received high doses of these drugs (group 1). Group 2 had a 66% survival, which was a significant improvement compared to the 33% survival in group 1 (p = 0.057). In group 1, mortality was associated with loss of more than 50% of the body surface area skin. In group 2, mortality was related to advanced age and associated diseases. Age, extent of skin loss, progression of skin loss after burn center admission, incidence of abnormal liver function tests, and the incidence of septic complications were not significantly different in the two groups (p greater than 0.10). The incidence of detected esophageal slough was similar in both groups. Nonsteroid (group 2) management was associated with a decreased incidence of ulceration of gastrointestinal columnar epithelium, Candida sepsis, and an increased survival after septic complications. The combined experience of these 30 patients suggests that corticosteroids are contraindicated in the burn center management of toxic epidermal necrolysis and the Stevens-Johnson syndrome.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.