Timothy T. K. Jung

Prostaglandins, leukotrienes, and other arachidonic acid metabolites in the pathogenesis of otitis media

Among the various inflammatory mediators of otitis media (OM), metabolites of arachidonic acid (AA) such as prostaglandins (PGs) and leukotrienes (LTs) appear to play an important role in the pathogenesis of otitis media. In an effort to investigate the role of AA metabolites on the pathogenesis of otitis media, concentrations of AA metabolites were measured in middle ear effusion (MEE) from human and paralleling animal models of otitis media and the effects of inhibitors of AA metabolism, antibiotics, and tympanostomy tube (TT) on the outcome of animal models of OM were studied.

The role of inflammatory mediators in the pathogenesis of otitis media and sequelae.

This review deals with the characteristics of various inflammatory mediators identified in the middle ear during otitis media and in cholesteatoma. The role of each inflammatory mediator in the pathogenesis of otitis media and cholesteatoma has been discussed. Further, the relation of each inflammatory mediator to the pathophysiology of the middle and inner ear along with its mechanisms of pathological change has been described. The mechanisms of hearing loss including sensorineural hearing loss (SNHL) as a sequela of otitis media are also discussed. The passage of inflammatory mediators through the round window membrane into the scala tympani is indicated. In an experimental animal model, an application of cytokines and lipopolysaccharide (LPS), a bacterial toxin, on the round window membrane induced sensorineural hearing loss as identified through auditory brainstem response threshold shifts. An increase in permeability of the blood-labyrinth barrier (BLB) was observed following application of these inflammatory mediators and LPS. The leakage of the blood components into the lateral wall of the cochlea through an increase in BLB permeability appears to be related to the sensorineural hearing loss by hindering K+ recycling through the lateral wall disrupting the ion homeostasis of the endolymph. Further studies on the roles of various inflammatory mediators and bacterial toxins in inducing the sensorineumral hearing loss in otitis media should be pursued.

Prostaglandins, leukotrienes, and other arachidonic acid metabolites in nasal polyps and nasal mucosa†

Prostaglandins (PGs) and leukotrienes (LTs) are known to play an important role in allergic inflammatory reactions. The triad of aspirin sensitivity, nasal polyposis, and asthma led us to suspect that PGs, LTs and other arachidonic acid metabolites may be involved in the pathogenesis of nasal polyps. The purpose of this study was to determine arachidonic acid metabolites and to measure concentrations of PGs and LTs in nasal polyps and nasal mucosa.

Experimental Otitis Media with Effusion Induced by Platelet Activating Factor

This study tested the hypothesis that platelet activating factor (PAF) in the middle ear can induce otitis media with effusion (OME) and that PAF antagonists can prevent PAF-induced OME. An initial trial of 16 μg of PAF was injected into chinchilla bullae, and all ears developed middle ear effusion (MEE) within 48 hours. Subsequent trials were performed to test dose dependency. Interestingly, 1 or 16 μg of PAF caused more MEE and inflammation than did 4 or 8 μg. A dose of 0.5 μg PAF did not cause MEE. Middle ear effusion from injected bullae contained the full spectrum of lipoxygenase and cyclooxygenase products; additionally, more PAF was detected than was injected. Finally, a PAF antagonist (WEB 2170) injected intraperitoneally prevented PAF-induced OME. This study demonstrates that PAF injected into the middle ear can induce OME and that PAF antagonists effectively prevent PAF-induced OME. These findings suggest that PAF plays an important role in the pathogenesis of OME.

Dysphagia in Laryngectomized Patients

Records of 226 laryngectomies performed at the University of Minnesota Hospitals and Minneapolis Veterans Administration Hospital from 1967 to 1976 were surveyed, yielding 36 patients with significant dysphagia. The majority of these patients were treated with combined therapy of preoperative radiation followed by surgical intervention. They were evaluated by esophagographic and endoscopic examinations. Among this group of patients, 16 had a benign pharyngeal stricture, 14 had recurrent tumor, two had lower esophageal stricture, and four had malignant esophageal carcinoma. Early detection of recurrent tumor is often difficult in a firm, woody radiated neck. Dysphagia may be the first sign of recurrence preceding obvious detectable recurrent tumors by several months. A barium swallow may show signs of early recurrence that may not be detectable by endoscopic examination. The radiographic evidence of recurrent tumor is described.

Effects of Inflammatory Mediators on Middle Ear Pathology and on Inner Ear Function

Inflammatory mediators released in the middle-ear cavity appear to play an important role in the pathogenesis of otitis media (OM) and can cause functional as well as morphological changes in the inner ear. Inflammatory mediators can be defined as biochemical components (peptide, glycoproteins, phospholipids, and others) produced by epithelial cells, infiltrating inflammatory cells, and endothelial cells, which mediate inflammatory reactions in a sequential manner. In the beginning, the only known target was microcirculation. In the late 1930s, Menkin’ showed that the accumulation of leukocytes could be explained in terms of mediators. As the number of known mediators has grown, the number of targets has also grown. At the present time, any cell is known to be a fair target of mediators, including epithelial cells, mast cells, fibroblasts, smooth muscles, endothelium, and white cells. As the number of known cell targets has increased, so has the number of possible cell responses, because every cell, when stimulated, will react according to its particular receptors and metabolism. All cells are known to exist in two forms, namely, resting and activated. Activated cells can produce many materials, including new mediators. According to Majno et a].: inflammatory mediators represent the basic language of cells. Cells must communicate through chemical messengers, whether they are resting or activated. The reason for so many mediators may be that

Protective Effect of Corticosteroid against the Cytotoxicity of Aminoglycoside Otic Drops on Isolated Cochlear Outer Hair Cells

Objectives Otic drops are commonly used not only for otitis externa but also for otorrhea in the presence of tympanic membrane perforation or tympanostomy tube. Many studies demonstrated the ototoxicity of aminoglycoside. In our previous study, we observed that gentamicin (GM), when activated with liver extract, demonstrated significant cytotoxicity. The purpose of this study was to assess the protective effect of corticosteroid against the cytotoxicity of GM and tobramycin drops using isolated cochlear outer hair cells (OHCs) in vitro with liver extract.

Determination of Ototoxicity of Common Otic Drops Using Isolated Cochlear Outer Hair Cells

Objectives Otic drops are commonly used not only for otitis externa, but also for otorrhea in the presence of tympanostomy tubes or tympanic membrane perforations. Many studies have demonstrated the ototoxicity of common otic preparations such as Cortisporin® otic drops (Monarch Pharmaceuticals, Bristol, TN). The purpose of this study was to assess the relative ototoxicity of common otic preparations by direct exposure to isolated cochlear outer hair cells (OHCs).

CLASSIFICATION OF OTITIS MEDIA AND SURGICAL PRINCIPLES

Otitis media is an important disease of children and adults and is caused by multiple interrelated factors, including infection, eustachian tube dysfunction, allergy, and barotrauma. This article includes a pertinent review of the literature regarding otitis media. The pathogenesis, classification, and treatment of otitis media in children and adults are also reviewed in this article. Additionally, therapy is discussed with emphasis on the surgical options appropriate at each stage.

Effects of Common Topical Otic Preparations on the Morphology of Isolated Cochlear Outer Hair Cells

Otic drops are commonly used not only for otitis externa but also for otorrhea in the presence of tympanostomy tube or tympanic membrane perforation. Many studies have demonstrated the ototoxicity of common otic preparations such as Cortisporin otic drops. Recent studies have suggested the use of fluoroquinolone antibiotic drops as an alternative owing to their excellent antimicrobial coverage and no ototoxic effect. The purpose of this study was to assess the relative ototoxicity of four common otic preparations by direct exposure to isolated cochlear outer hair cells (OHCs). OHCs from adult chinchilla cochlea were exposed to standard bathing solution (control), Cortisporin, Cipro HC, Ciloxan, and Floxin. The cells were observed using an inverted microscope, and the images recorded in digital still-frame and video, and analyzed on the Image Pro-Plus 3.0 program. As measured by time to cell death and change in morphology of OHCs, Cortisporin was most toxic to OHCs. Among the fluoroquinolone drops, Floxin was more toxic than Ciloxan or Cipro HC.Otic drops are commonly used not only for otitis externa but also for otorrhea in the presence of tympanostomy tube or tympanic membrane perforation. Many studies have demonstrated the ototoxicity of common otic preparations such as Cortisporin® otic drops. Recent studies have suggested the use of fluoroquinolone antibiotic drops as an alternative owing to their excellent antimicrobial coverage and no ototoxic effect. The purpose of this study was to assess the relative ototoxicity of four common otic preparations by direct exposure to isolated cochlear outer hair cells (OHCs). OHCs from adult chinchilla cochlea were exposed to standard bathing solution (control), Cortisporin, Cipro HC®, Ciloxan®, and Floxin®. The cells were observed using an inverted microscope, and the images recorded in digital still-frame and video, and analyzed on the Image Pro-Plus® 3.0 program. As measured by time to cell death and change in morphology of OHCs, Cortisporin was most toxic to OHCs. Among the fluoroquinolone drops, Floxin was more toxic than Ciloxan or Cipro HC.