Safety and efficacy of topical mitomycin C in myringotomy patency.

OBJECTIVE: To develop an alternative method for prolonged middle ear ventilation using topical mitomycin C. STUDY DESIGN AND SETTING: Twenty guinea pigs with normal ears had bilateral myringotomies performed using the argon laser. After myringotomy, either mitomycin C (0.4 mg/mL) or saline pledgets were applied topically. Monitoring consisted of otomicroscopy and distortion-product otoacoustic emissions. RESULTS: Before myringotomy, all tympanic membranes were intact, and distortion-product otoacoustic emissions were measurable. After myringotomy, none (0%) of the saline-treated myringotomies were patent at day 7 as compared with 100% of the mitomycin C-treated myringotomies. At day 42, 10 (52.6%) of 19 mitomycin-treated myringotomies remained patent and 4 (28.6%) of 14 were patent at 131 days. Five (13.1%) ears developed purulent otorrhea; 3 were mitomycin C-treated and 2 were treated with saline solution.- Distortion-product otoacoustic emissions testing did not document any evidence of ototoxicity. CONCLUSION: Topical mitomycin C appears to be safe and effective at prolonging the duration of myringotomy patency in the guinea pig. SIGNIFICANCE: Mitomycin C may be useful as an adjunct for preventing myringotomy closure.

Endoscopic cerebrospinal fluid rhinorrhea repair: is a lumbar drain necessary?

OBJECTIVES: To determine the necessity for lumbar drains during endoscopic cerebrospinal fluid (CSF) rhinorrhea repair. METHODS: Thirty-three patients underwent endoscopic repair of CSF rhinorrhea without a lumbar drain during a 7-year period. The size of the dural defect ranged from a microleak (less than 1 mm dural defect) to a 3-cm dural defect of the anterior skull base. RESULTS: All of the procedures in patients with smaller defects (<5 mm) were performed on an outpatient basis. Thirty-two patients (97%) had complete resolution of their CSF leak after 1 procedure without any recurrence (average follow-up 29 months). CONCLUSION: A lumbar drain is not routinely necessary for successful closure of CSF rhinorrhea of any size. Smaller dural defects may be safely performed on an outpatient basis without complications.

Suppression and enhancement of distortion-product otoacoustic emissions by interference tones above f(2). I. Basic findings in rabbits.

The present study measured interference-response areas (IRAs) for distortion-product otoacoustic emissions (DPOAEs) at 2f(1)-f(2), 3f(1)-2f(2), and 2f(2)-f(1). The IRAs were obtained in either awake or anesthetized rabbits, or in anesthetized guinea pigs and mice, by sweeping the frequencies and levels of an interference tone (IT) around a set of f(1) and f(2) primary tones, at several fixed frequencies and levels, while plotting the effects of the IT on DPOAE level. An unexpected outcome was the occurrence of regions of suppression and/or enhancement of DPOAE level when the IT was at a frequency slightly less than to more than an octave above f(2). The IRA of the 2f(1)-f(2) DPOAE typically displayed a high-frequency (HF) lobe of suppression, while the 2f(2)-f(1) emission often exhibited considerable amounts of enhancement. Moreover, for the 2f(2)-f(1) DPOAE, when enhancement was absent, its IRA usually tuned to a region above f(2). Whether or not suppression/enhancement was observed depended upon primary-tone level and frequency separation, as well as on the relative levels of the two primaries. Various physiological manipulations involving anesthesia, eighth-nerve section, diuretic administration, or pure-tone overstimulation showed that these phenomena were of cochlear origin, and were not dependent upon the acoustic reflex or cochlear-efferent activity. The aftereffects of applying diuretics or over-exposures revealed that suppression/enhancement required the presence of sensitive, low-level DPOAE-generator sources. Additionally, suppression/enhancement were general effects in that, in addition to rabbits, they were also observed in mice and guinea pigs. Further, corresponding plots of DPOAE phase often revealed areas of differing phase change in the vicinity of the primary tones as compared to regions above f(2). These findings, along with the effects of tonal exposures designed to fatigue regions above f(2), and instances in which DPOAE level was dependent upon the amount of suppression/enhancement, suggested that the interactions of two DPOAE-generator sources contributed, in some manner, to these phenomena.

Comparison of topical anti-ischemic agents in the salvage of failing random-pattern skin flaps in rats.

OBJECTIVE: To determine the efficacy of topical anti-ischemic drug therapy in the salvage of failing, random-pattern skin flaps. DESIGN: Prospective, randomized, placebo-controlled, therapeutic trial. SETTING: Academic medical center. SUBJECTS: Sixty-one adult male Sprague-Dawley rats. INTERVENTION: Each experimental rat underwent a caudally based random-pattern skin flap using the modified McFarlane technique. Rats were randomized to 1 of 6 treatment groups: topical nifedipine, topical trolamine salicylate, topical nitroglycerin, topical trolamine salicylate-nitroglycerin combination, topical nifedipine-trolamine salicylate-nitroglycerin combination, or inert carrier ointment (control). Treatment was initiated immediately following flap closure and continued every 6 hours for 7 days. At the end of the treatment period, animals were euthanized and flap survival was determined for each one. RESULTS: Topical anti-ischemic drug therapy resulted in a statistically significant reduction in ischemic flap necrosis for each drug (or combination) tested relative to the 44.2% mean necrosis observed in control animals. Treatment with the combination of topical nitroglycerin and topical trolamine salicylate resulted in the best salvage response (25.2% mean necrosis) with a statistically significant improvement in flap survival relative to both controls and nitroglycerin alone. CONCLUSIONS: Topical anti-ischemic agents are effective in reducing ischemic necrosis of failing, random-pattern skin flaps in the rat model. Although nitroglycerin, trolamine salicylate, and nifedipine possess unique pharmacologic mechanisms of action, each drug produced a statistically significant improvement in flap survival. The results of this study suggest that topical drug therapy may play an important role in clinical salvage of the failing skin flap. Further studies are needed to explore the potential of combination drug therapy.

Effects of loop diuretics on the suppression tuning of distortion-product otoacoustic emissions in rabbits.

The suppression tuning of distortion-product otoacoustic emissions (DPOAEs) is commonly assumed to measure frequency selectivity, because the dominant features of suppression-tuning curves (STCs) are similar to the principal properties of the neural-tuning curves (NTCs) of single auditory-nerve fibers. In the present study, several common loop diuretics were used to affect the DPOAE-generation process to determine if reversible ototoxicity could adversely modify the characteristics of STCs, in a manner similar to that shown previously for NTCs. Contour plots of DPOAE level in the presence of a series of variable-level suppressor tones were obtained before and after administering diuretic drugs that reversibly reduced or eliminated DPOAEs. Primary-tone pairs were centered at 2.8 or 4 kHz, with L1 = L2, or L2 < L1. From the resulting plots, STC parameters including tip frequency, threshold at the tip frequency, and Q10 dB measures of tuning were extracted for four suppression criteria of 3, 6, 9, and 12 dB. In the pre-drug nonototoxic state, suppression tuning depended on both primary-tone level (L1, L2), and the relative levels of the primaries (L1-L2), with tuning being sharper for lower- than for higher-level equilevel primaries, and sharpest for offset-level primary tones. Following drug injection, the expected decrease in sharpness of tuning evidenced by changes in Q10 dB as well as the dramatically elevated tip thresholds normally seen for NTCs under similar conditions, were not observed. Overall, Q10 dB increased or decreased more or less randomly, with a slight tendency for STCs to become sharper than prior to drug dosing, for the two highest suppression criteria. The STC-tip frequencies demonstrated significant decreases following diuretic administration that were weakly correlated with the associated decreases in DPOAE amplitude. The most consistent changes in response to the drug-induced reduction in DPOAE level were increases in the STC-tip thresholds. However, these changes were relatively small and rarely exceeded 10 dB. In the absence of notable changes in overall STC shape, a major finding was a change in the effectiveness of suppression following ototoxic insult. However, when the amount of suppression was expressed as a percentage of the DPOAE remaining, the effects of diuretic dosing were often almost completely obscured. Overall, the results demonstrated that when the generation of DPOAEs was interfered with by the introduction of a suppressor tone to produce STCs that resemble NTCs, STCs behaved quite differently following reversible cochlear insult than their previously documented neural counterparts. These findings imply that STCs do not assess the frequency-selective aspects of the cochlear amplification process in a manner similar to NTCs.

Locus of generation for the 2f1-f2 vs 2f2-f1 distortion-product otoacoustic emissions in normal-hearing humans revealed by suppression tuning, onset latencies, and amplitude correlations.

The present study used distortion-product otoacoustic emission (DPOAE) suppression tuning curves (STCs), DPOAE onset latencies (OLs), and DPOAE amplitude correlations to investigate the locus of generation of the 2f1-f2 DPOAE versus the 2f2-f1 DPOAE in humans. The results of the tuning study revealed that, for the 2f1-f2 DPOAE, the tips of the STCs tuned consistently below the geometric-mean (GM) frequency of the primary tones. In contrast, for the 2f2-f1 DPOAE, STCs tuned above the GM of the primaries, with 50% of the tip frequencies at, or above, the 2f2-f1 frequency place. When the average ratio of the 2f2-f1 to the 2f1-f2 tip frequencies was computed, a factor of 1.44 provided an estimate of the frequency shift needed to align the two DPOAE generation sites. Other results showed that OLs for the 2f2-f1 DPOAE were uniformly shorter than those for the 2f1-f2, with differences at the low frequencies amounting to as much as 6-7 ms. Further, for both DPOAEs, curves describing latency decreases as a function of increasing GM frequencies were best fit by power functions. Shifting the GM frequency producing the 2f2-f1 DPOAE by a factor of 1.6 caused the latency distributions for both DPOAEs to overlap thus resulting in a single function that described cochlear delay as a function of GM frequency. Finally, for each GM frequency in the DP-gram, sliding correlations from 108 normal ears were performed on both DPOAEs by holding the primaries producing the 2f1-f2 DPOAE constant, while all 2f2-f1 DPOAE amplitudes were successively correlated with the 2f1-f2 amplitudes. This procedure demonstrated that, for a given GM frequency producing the 2f1-f2, the correlations between the two DPOAEs peaked when the primaries of the 2f2-f1 were at a GM frequency that positioned the 2f2-f1 frequency place near the GM of the primaries that produced the 2f1-f2 DPOAE. As a whole, the above findings strongly suggest that the 2f2-f1 DPOAE in humans is generated basal to the primary-tone place on the basilar membrane.