The effect of topical analgesics on ex vivo skin growth and human keratinocyte and fibroblast behavior.

The application of topical analgesics to the donor site of split thickness skin grafts has been proven to be an effective method of pain management but little is known about their effects on wound reepithelialization. This study compares the effect of four analgesics on human keratinocytes and fibroblasts and whole skin explants in vitro to determine whether epithelial cell behavior is affected by topical analgesics. The effect of diclofenac, bupivacaine, lidocaine, and ketorolac was studied at concentrations between 10 mM and 1 nM. The effect on epithelial growth was measured using an ex vivo skin explant model. In addition, cell proliferation, and cytotoxicity were measured in cultured primary human keratinocytes and fibroblasts. Epithelial growth from the explant model was most inhibited by diclofenac with a significant reduction at 100 microM (p=>0.001). Diclofenac also exhibited the strongest inhibitory effect on cell proliferation especially in keratinocytes. Ketorolac was the most cytotoxic. Bupivacaine showed cytotoxicity in a dose-dependent manner with only the very highest concentrations having a significant inhibitory effect. Lidocaine showed no evidence of cytotoxicity at the concentrations tested in either the in vitro cell studies or the ex vivo explant model. Topical analgesics alter keratinocyte and fibroblast behavior and such inhibition may affect wound healing.

Bone resorption in stroke and institutionalized subjects.

Stroke increases the risk of hip fracture on the affected side. Although bone is lost by 1 year, rapidity of onset and relationship with immobility are uncertain. Using the bone resorption marker urinary cross-linked N telopeptide of type I collagen (uNTx), we examined bone resorption in the first 4 weeks after stroke, relating uNTx with bone density and mobility in subjects over 60 years. Two separate control groups acted as comparators, healthy (HC) and institutionalized (IC) controls, the latter to control for the effects of institutionalization. uNTx, urinary calcium (both related to creatinine and log-transformed), heel bone mineral density (BMD), Tinetti scores, and Barthel scores for prestroke function were measured. Log uNTx/Cr was lower in males compared with females, but this difference was not evident in stroke or IC subjects. Log uNTx/Cr was inversely related with BMD in females from both control groups and in male stroke subjects. Tinetti scores were divided into tertiles and were lower in stroke than IC subjects (P < 0.01). Log uNTx/Cr was similar in stroke and IC subjects in the lowest Tinetti tertile. Log uNTx/Cr was higher in stroke subjects of both sexes in the lowest tertile compared with the higher two tertiles combined (P < 0.05) and higher in all tertiles compared with HC subjects (P < 0.05). Subjects with a prestroke Barthel index of < or = 17 had higher log uNTx/Cr compared with HCs. Log uCa/Cr was higher only in male stroke patients. Bone resorption in stroke starts early, and measures to reduce this are merited.