James J. Klemens

Prevention of noise- and drug-induced hearing loss with d-methionine ☆

A number of otoprotective agents are currently being investigated. Various types of agents have been found in animal studies to protect against hearing loss induced by cisplatin, carboplatin, aminoglycosides, or noise exposure. For over a decade we have been investigating D-methionine (D-met) as an otoprotective agent. Studies in our laboratory and others around the world have documented D-mets otoprotective action, in a variety of species, against a variety of ototoxic insults including cisplatin-, carboplatin-, aminoglycoside- and noise-induced auditory threshold elevations and cochlear hair cell loss. For cisplatin-induced ototoxicity, protection of the stria vascularis has also been documented. Further D-met has an excellent safety profile. D-met may act as both a direct and indirect antioxidant. In this report, we provide the results of three experiments, expanding findings in D-met protection in three of our translational research areas: protection from platinum based chemotherapy-, aminoglycoside- and noise-induced hearing loss. These experiments demonstrate oral D-met protection against cisplatin-induced ototoxicity, D-met protection against amikacin-induced ototoxicity, and D-met rescue from permanent noise-induced hearing loss when D-met is initiated 1h after noise exposure. These studies demonstrate some of the animal experiments needed as steps to translate a protective agent from bench to bedside.

Persistent Inflammation and Hyperresponsiveness Following Viral Rhinosinusitis

Objectives: To develop a murine model of viral rhinosinusitis.

Effect of montelukast on bacterial sinusitis in allergic mice

BACKGROUND In mice, allergic rhinitis augments the infectious and inflammatory response to Streptococcus pneumoniae-induced sinusitis. OBJECTIVE To investigate the effects of cysteinyl leukotriene antagonism on the severity of bacterial infection. METHODS We performed 3 parallel, placebo-controlled experiments. In the first, mice were ovalbumin sensitized and ovalbumin challenged to show the effects of montelukast on the allergic inflammation; in the second, we evaluated the effect of montelukast on S. pneumoniae infection; in the third, we used mice that were both allergic and infected. Montelukast was given starting 2 days after sensitization until the day before euthanasia. One day after drug treatment began, the mice were inoculated intranasally with S. pneumoniae in the infected groups. Nasal hypersensitivity was measured with histamine challenges before the first sensitization and on the day before euthanasia. On the fifth day after infection, mice were euthanized, nasal lavage was performed, bacteria were cultured, and inflammatory cells in the sinuses were quantified. RESULTS Mice that were infected only tended toward having increased bacterial counts from nasal lavage in the montelukast-treated group. The mice that were allergic and infected experienced significantly higher bacterial counts (P < .05). All 3 montelukast treatment groups had significantly decreased eosinophil counts as well as T-lymphocyte counts. CONCLUSIONS Montelukast reduces the manifestations of allergic rhinitis in mice. Surprisingly, montelukast led to an increase in bacterial growth in infected mice. This suggests an effect of the cysteinyl leukotrienes on the innate response to bacterial infection.

Is simultaneous bilateral mastoidectomy ever advisable

INTRODUCTION We report our experience with bilateral, simultaneous tympanomastoidectomies and the results of an opinion survey of otologists. METHODS A chart review of 116 tympanomastoidectomies revealed 12 patients who underwent bilateral, simultaneous tympanomastoidectomies. An opinion survey generated 121 responses. RESULTS Of the 12 patients, none suffered any outcome which would have been avoided by staging the procedures. Twenty-three of 24 operated ears had the same or better hearing post-operatively. Of the survey respondents, 74 felt that performing bilateral, simultaneous tympanomastoidectomies was unsafe, largely because of the risk of bilateral sensorineural hearing loss. DISCUSSION Although bilateral, simultaneous tympanomastoidectomies carry double the risk of unilateral sensorineural hearing loss, compared with the unilateral procedure, the risk of bilateral sensorineural hearing loss is only 0.006-0.2 per cent, as derived mathematically from historical data. Respondents to the survey were mostly opposed to bilateral, simultaneous tympanomastoidectomies, but even those opposed gave indications for simultaneous procedures. This finding probably reflects an ambivalence about the theoretical risks of the operation versus the potential patient benefits. A decision tree for proceeding to the second case is presented.

Simultaneous bilateral mastoidectomies: A safe alternative to a two-stage procedure

Introduction: We report our experience with simultaneous bilateral mastoidectomies on 18 patients who underwent bilateral simultaneous mastoidectomies. Materials and Methods: Chart review of patients who underwent tympanomastoidectomies since 2002 revealed 18 patients who underwent bilateral simultaneous mastoidectomies. Results: Of the 18 patients, none had any complications from the surgeries that would have been avoided by staging the procedures. Of the 36 operated ears, 34 of them had the same or better hearing postoperatively. Discussion: This article re-emphasizes the safety of performing bilateral simultaneous tympanomastoidectomies. Although this procedure carries a theoretical risk of unilateral sensorineural hearing loss, compared with the unilateral procedure, the risk of bilateral sensorineural hearing loss is only 0.006- 0.2%, as derived mathematically from historical data. Conclusion: In carefully selected cases of parental request and noncompliance, simultaneous bilateral mastoidecomies are a safe and effective alternative to the traditional two-stage procedure.

Primary treatment of thin subglottic stenosis with laser excision and topical mitomycin c

Abstract Objectives: Subglottic stenosis (SGS) is the most common complication of endotracheal intubation in the pediatric age group, with an incidence of approximately 2%. These patients require numerous procedures, and the poor success rates are reflected by the multitude of treatment strategies that are available. Mitomycin C, a chemotherapeutic agent has been used topically to prevent scar formation but never as a primary treatment. Methods: A retrospective review of 3 patients tracheotomized for thin (1 cm long stenotic segment) subglottic stenosis who were treated primarily with serial laser excision and application of mitomycin C was performed. The charts were reviewed for initial Cotton grade, Cotton grade after each procedure, number of procedures required for decannulation, time from first operation until decannulation, operation performed, and concentration of mitomycin C used. Results: Two patients with an initial Cotton grade III were decannulated, one 9 months after tracheotomy and the other 1 year after tracheotomy, with grade I stenoses. These patients required 5 and 6 procedures, respectively. The third patient had an initial Cotton grade II and was decannulated 9 months after tracheotomy with a grade I stenosis after 3 procedures. None of the patients had any complications. Conclusion: Although laser excision and dilation of subglottic stenosis has historically failed due to restenosis, use of mitomycin C may improve the outcome in selected patients. Patients who require tracheotomy for thin segment (less than 1 cm) stenosis may benefit from this minimally invasive treatment.