Effect of inspiratory nasal loading on pharyngeal resistance.

Nasal obstruction has been shown to increase the number of apneas during sleep in normal subjects and in some may actually cause the sleep apnea syndrome. We postulated that the pharynx may act as a Starling resistor, where increases in negative inspiratory pressure result in elevated resistance across a collapsible pharyngeal segment. To test this theory in normal subjects we studied 10 men and 10 women during wakefulness. Pharyngeal resistance (the resistance across the airway segment between the choanae and the epiglottis) was determined in the normal state and with three inspiratory loads added externally. Flow was measured using a pneumotachometer and a sealed face mask; epiglottic pressure by a latex balloon placed just above the epiglottis and choanal pressure by anterior rhinometry. Pharyngeal resistance (measured at 300 ml/s) could thus be determined. Base-line inspiratory pharnygeal resistance was 1.6 +/- 0.2 cmH2O . l-1 . s. This increased to 2.3 +/- 0.3, 2.8 +/- 0.4, and 2.9 +/- 0.4 cmH2O . l-1 . s, respectively, with the addition of 1.3, 2.7, and 6.7 cmH2O . l-1 . s inspiratory load. The resistance at each level of load was significantly different from the base-line resistance determination (P less than 0.05) but not different from each other. We conclude that added nasal resistive loads during inspiration cause an increase in pharyngeal resistance during wakefulness but that this resistance does not increase further with additional increments of load.

Dissociation of maximum concentration of kanamycin in plasma and perilymph from ototoxic effect.

Kanamycin was administered in total daily doses of 0 (vehicle), 100, 200 or 300 mg/kg to different groups of guinea pigs for two weeks. These total daily doses were administered according to three different dosing schedules, either as a single injection given once a day, divided into two equal doses and given twice a day, or divided into four equal doses and administered four times a day. It was found that the magnitude of the ototoxicity resulting from kanamycin administration was related to the total daily dose alone and not the dosing schedule. This lack of relationship between the dosing schedule and the magnitude of the ototoxicity due to kanamycin is the reverse of that reported for the nephrotoxicity resulting from gentamicin, tobramycin and netilmicin.

The ototoxic interaction of viomycin, capreomycin and polymyxin B with ethacrynic acid.

The ototoxic interaction between the aminoglycoside antibiotics (streptomycin, kanamycin, etc.) and the loop-inhibiting diuretics (ethacrynic acid, furosemide and bumetanide) has been well documented. This interaction causes extensive destruction of the hair cells of the cochlea. Brummett et al. (1974) demonstrated that this interaction did not occur with the non-loop-inhibiting diuretics and kanamycin. The present study was undertaken to determine if antibiotics other than the aminoglycosides could produce the ototoxic interaction when combined with a loop-inhibiting diuretic. Three antibiotics-viomycin, capreomycin, and polymyxin B- when given with ethacrynic acid were found to produce cochlear hair cell damage that was similar to that produced by aminoglycoside antibiotics administered with ethacrynic acid. Therefore, the interaction appears to be specific to the loop-inhibiting diuretics but not specific for the aminoglycoside antibiotics.

Combined effects of noise and kanamycin. Cochlear pathology and pharmacology.

Concurrent administration of aminoglycoside antibiotics and acoustic exposure is reported to result in a cochlear damage level exceeding that predicted from the effects of either agent given alone. To investigate this interaction, guinea pigs were given daily subcutaneous injections of kanamycin sulfate at 200, 300, or 400 mg/kg followed by a ten-hour noise exposure (115 or 45 dB) for seven consecutive days. Drug levels in plasma and perilymph were measured during the 24 hours after injection and during the seven-day period of drug and noise exposures. Electrophysiological and morphological evaluation of cochlear function confirmed a dramatic interaction at the 300-mg/kg dosage. Augmentation of damage was minimal at 200 mg/kg and masked by ceiling effects at 400 mg/kg. No alteration in accumulation or elimination of kanamycin occurred as a result of high-intensity acoustic exposure.