Quantification of rebound edema after steroid treatment.

OBJECTIVE: Return of edema after abrupt discontinuation of steroid treatment has never been studied or quantified. The purpose of this study was to measure the effect of abrupt cessation and tapering doses of steroids on tissue water content (TWC) in a rat skin flap model. DESIGN: A randomized controlled animal trial was designed to study the effects of discontinuation of steroid on skin flap edema. The animals were assigned to a control group (C), a steroid group (S), an abrupt steroid cessation (SC) group, or a tapering steroid (ST) group. MAIN OUTCOME MEASURES: In each group the skin flaps were biopsied at 30 and 36 hours. TWC was determined by a biopsy-drying technique. RESULTS: A significant difference (P = 0.05) was found between the C and S groups and between the SC and S groups at both 30 and 36 hours, with the C group having the highest TWC. No significant difference was noted between the SC and C groups. The ST group had significantly less edema than the C group and similar TWC to that of the S group. CONCLUSION: Edema rebounded in the skin flaps after abrupt cessation of steroids (SC was not different from C), presumably because of destabilization of inflammatory mediators. The rebound effect was not observed in the ST group. The control of rebound edema by a tapering steroid protocol may be important in skin flap survival and may have implications for the management of airway edema.

Effects of platelet activating factor on vascular permeability of the middle ear mucosa.

Platelet activating factor (PAF), a potent inflammatory mediator, seems to play a significant role in the pathogenesis of otitis media with effusion (OME), along with other inflammatory mediators such as leukotrienes and prostaglandins. The purpose of this study was to investigate the effect of PAF on the vascular permeability of middle ear mucosa, in an experimental OME model using chinchillas. We injected PAF in doses of 1, 4, 8, and 16 micrograms and normal saline as a control into the bullae of chinchillas. Vascular permeability was measured by the Evans blue vital dye technique. All the PAF-injected animals showed a significant increase in middle ear vascular permeability compared to the control group. This study demonstrated that PAF in the middle ear cavity contributes significantly to the development of OME by increasing the vascular permeability of the middle ear mucosa.

Effect of leukotriene inhibitor on salicylate induced morphologic changes of isolated cochlear outer hair cells.

Our previous studies have shown that salicylate ototoxicity is associated with decreased levels of prostaglandins (PGs) and increased levels of leukotrienes (LTs) in the perilymph. Other studies have demonstrated that salicylate ototoxicity is associated with decreased cochlear blood flow, reversible changes in isolated cochlear outer hair cells (OHCs), and decreased otoacoustic emission. We have shown that pretreatment with an LT inhibitor prevents salicylate induced hearing loss, a decrease in cochlear blood flow and changes in otoacoustic emissions. The objectives of the current study were to determine the effect of exposure of salicylate and LTs on the morphology of isolated OHSc and to determine the effect of LT inhibitors on salicylate induced morphologic changes of isolated OHCs. Isolated OHCs from chinchilla cochlea were exposed to different test solutions. The groups included sodium salicylate (10 mM) with or without pretreatment with an LT inhibitor (L-663, 536, 30 microM), 0.1 or 1.0 microM solution of LTC4, LTD4, LTE4, and two control solutions, standard bathing solution (SBS) or leukotriene inhibitor alone. Osomolality of all solutions were kept at 305 +/- 5 mmolkg-1. The OHCs were observed under an inverted microscope. Images were stored onto a computer and analyzed later. OHCs exposed to the salicyalate developed a decrease in mean cell length. The exposure of OHCs to LTC4, LTD4, and LTE4 also demonstrated a similar decrease in mean cell length. Cells in the control SBS or LT inhibitor alone groups did not show any change. OHCs exposed to salicylate in the presence of the LT inhibitor did not exhibit morphologic changes. This study suggest that arachidonic acid metabolites, especially an increase in the concentration of LTs, seem to play an important role in the pathogenesis of salicylate ototoxicity.