Role of sensation in swallowing function.

OBJECTIVES: Sensation in the oral cavity and laryngopharynx has long been believed to be crucial for normal swallowing. One illustration of this belief has been intense interest in reconstruction after cancer resection using sensate tissue transfer as a means of improving swallowing function. A contrarian view is that mucosal sensation, by itself, is, in fact, relatively unimportant to swallowing function. STUDY DESIGN: A prospective study was designed to test the hypothesis that normal swallow function can occur with anesthesia of the upper aerodigestive tract mucosa. METHODS: Baseline (sensate) swallowing function of 13 healthy adults was assessed via video endoscopic swallow studies (VESS). Each subject was then topically anesthetized with lidocaine applied to the oral cavity, oropharynx, hypopharynx, and larynx. Swallowing was then reassessed via VESS and compared to the baseline examination to look for differences in function. RESULTS: There was little difference in swallowing ability between sensate and anesthetized states, even though all the subjects felt that their swallowing had been profoundly disrupted after lidocaine was applied. The main difference was a small increase in the time from food administration to swallowing. A few experienced trace aspiration, which was instantly eliminated on subsequent swallows with simple coaching. CONCLUSION: Normal swallowing can occur spontaneously or with simple coaching even with complete anesthesia of the upper aerodigestive tract mucosa. Current beliefs about the value of sensate free flaps and the importance of sensation in swallowing in general may need refinement.

Ototoxicity resulting from combined administration of metronidazole and gentamicin.

HYPOTHESIS: The hypothesis that metronidazole can augment the ototoxicity of gentamicin was tested. BACKGROUND: Metronidazole and gentamicin are antibiotics that are used in combination to provide broad-spectrum antimicrobial coverage. It has been observed clinically that an increased ototoxic effect occurs when these agents are used in combination. METHODS: Groups of guinea pigs were given various doses of gentamicin alone, various doses of gentamicin in combination with metronidazole, or metronidazole alone. Auditory damage was determined electrophysiologically by measurement of the compound action potential. Hair cell damage was quantified by immunofluorescent microscopy. RESULTS: Electrophysiologic data revealed an augmented ototoxic effect when metronidazole was given with both a moderate and a high dose of gentamicin. Thresholds (dB SPLp) for the compound action potential (N1) for animals receiving a medium dose of gentamicin alone (50 mg/kg) were approximately 20-dB SPLp. This threshold increased to approximately 50-dB SPLp when metronidazole (35 mg/kg) was administered along with the medium-dose gentamicin. Additionally, animals receiving high-dose gentamicin (75 mg/kg) alone demonstrated increased N1 thresholds from 85 to 95 when metronidazole (35 mg/kg) was added to the gentamicin regimen. This effect was evident histopathologically by increased cochlear hair cell damage. Outer hair cell loss for animals receiving medium-dose gentamicin alone did not differ from that of controls. When metronidazole (35 mg/kg) was combined, however, outer hair cell loss increased to approximately 50%. CONCLUSIONS: These data support the clinical observation of augmented ototoxicity in patients receiving combined gentamicin and metronidazole. Caution should be used when administering these two agents together. Clinicians should consider other antibiotic strategies whenever possible.

Ototoxicity resulting from combined administration of cisplatin and gentamicin.

The hypothesis that cisplatin can augment the ototoxicity of gentamicin was tested. Seven groups of 11 guinea pigs each were given a single dose of cisplatin either alone or 14 days before, at the beginning, midway through, or at the end of a course of gentamicin administered daily for 14 days. Blood and perilymph gentamicin and cisplatin concentrations were determined in three of the animals from each group. Auditory damage was determined in the remaining 8 animals electrophysiologically by measuring the compound action potential and alternating-current cochlear potential. Hair cell damage was determined using the surface preparation technique. An augmented ototoxic effect occurred when the cisplatin was given early in the 14-day course of gentamicin and did not occur when it was given at the end of treatment.

Quantitative study of vestibulotoxicity induced by gentamicin or cisplatin in the guinea pig.

Although aminoglycoside vestibulotoxicity is well established, the question of cisplatin vestibulotoxicity is controversial. The goals of this study were 1. to determine whether cisplatin induces vestibulotoxicity as measured histologically, and 2. to compare the vestibulotoxicity between gentamicin and cisplatin. Guinea pigs' vestibular end-organ hair bundles in control, gentamicin, and cisplatin groups were compared. In the lateral cristae of the cisplatin group, hair bundles decreased 21% on the central apex portion. In the gentamicin group, a slight decrease (17%) of hair bundles on the striola from the utricular maculae was observed, as was severe damage on the entire cristae, especially on the central apex (70%). These results indicate that gentamicin and cisplatin may not influence vestibular function of the otolithic membrane. However, gentamicin may severely damage and cisplatin may slightly damage the crista ampullaris hair bundles.

Temporal bone histopathology of cisplatin ototoxicity.

Cisplatin (cis-diamminedichloroplatinum II) is a potent chemotherapeutic agent that is useful in the treatment of a variety of malignancies. Ototoxicity is a well-known adverse side effect of this drug and has been widely described in reports on clinical and animal studies. Few human temporal bone studies, however, have been performed for cisplatin ototoxicity. This report presents four cases of cisplatin ototoxicity in patients from whom temporal bone specimens with minimal post-mortem autolysis were obtained at autopsy. All patients received between 1 and 6 cycles of cisplatin with doses ranging from 100 to 165 mg/M2 per cycle. None of the patients received significant amounts of aminoglycosides or loop diuretics. Histopathologic changes included loss of inner and outer hair cells in the basal turn of the cochlea, degeneration of the stria vascularis, and a significant decrease in spiral ganglion cells predominantly in the upper turns.

Influence of ophthalmic formulations on sodium cromoglycate disposition in the albino rabbit eye.

The effect of different ophthalmic vehicles on the disposition of sodium cromoglycate in tears and ocular tissues of the rabbit eye has been studied over 6 h. The vehicles contained sodium cromoglycate, 2% in an aqueous solution, 2 and 4% in an oleaginous formulation of polyethylene and mineral oil (Plastibase 5W), and 4% in an absorption ointment base of 10% hypoallergenic acetylated lanolin (Modulan) in paraffins. The last formulation was superior to all others studied over 6 h in prolonging the retention of sodium cromoglycate in the precorneal area and the conjunctiva. The concentration of sodium cromoglycate in the tears, conjunctiva and cornea 6 h after administration of the acetylated lanolin base equalled or exceeded the concentrations obtained with the aqueous solution 1 h post-instillation.