Faculty Bibliography

No widely accepted protocol or guideline exists for monitoring ototoxicity in patients who take powerful and potentially cochleotoxic and/or vestibulotoxic agents. Many physicians in other specialties who prescribe these drugs do not understand the important role of otolaryngologists and audiologists in pretreatment counseling and evaluation and the need for follow-up assessments of their patients' auditory function. Based on our combined experience of more than 50 years, we have developed a uniform yet flexible approach to monitoring cochlear and vestibular function in these patients. We discuss the mechanisms of ototoxic agents, risk factors for ototoxicity, the need for ongoing communication among the various disciplines, and the methods and timing of monitoring

We determined how the perceived naturalness of music and speech (male and female talkers) signals was affected by various forms of linear filtering, some of which were intended to mimic the spectral 'distortions' introduced by transducers such as microphones, loudspeakers, and earphones. The filters introduced spectral tilts and ripples of various types, variations in upper and lower cutoff frequency, and combinations of these. All of the differently filtered signals (168 conditions) were intermixed in random order within one block of trials. Levels were adjusted to give approximately equal loudness in all conditions. Listeners were required to judge the perceptual quality (naturalness) of the filtered signals on a scale from 1 to 10. For spectral ripples, perceived quality decreased with increasing ripple density up to 0.2 ripple/ERB(N) and with increasing ripple depth. Spectral tilts also degraded quality, and the effects were similar for positive and negative tilts. Ripples and/or tilts degraded quality more when they extended over a wide frequency range (87-6981 Hz) than when they extended over subranges. Low- and mid-frequency ranges were roughly equally important for music, but the mid-range was most important for speech. For music, the highest quality was obtained for the broadband signal (55-16,854 Hz). Increasing the lower cutoff frequency from 55 Hz resulted in a clear degradation of quality. There was also a distinct degradation as the upper cutoff frequency was decreased from 16,845 Hz. For speech, there was a marked degradation when the lower cutoff frequency was increased from 123 to 208 Hz and when the upper cutoff frequency was decreased from 10,869 Hz. Typical telephone bandwidth (313 to 3547 Hz) gave very poor quality

OBJECTIVE: Anomalies of the fourth branchial arch complex are exceedingly rare, with approximately forty cases reported in the literature since 1972. The authors report experience with six fourth arch anomalies. METHODS: Retrospective chart review of six consecutive patients presenting to the pediatric otolaryngology service at a tertiary care center with anomalies referable to the fourth branchial arch. RESULTS: All six patients presented within the first or second decade of life. All six had left-sided disease. Four patients presented with recurrent neck infection, one with asymptomatic cervical masses, and one with a neck mass and respiratory compromise. One patient had prior surgery presented with a recurrence. Diagnosis of fourth arch anomalies was suggested or confirmed by computed tomography and flexible laryngoscopy. Treatment was surgical in five patients; one patient is awaiting surgery. Surgical procedures included resection of the mass and endoscopic cauterization of the inner opening of the cyst. CONCLUSIONS: The presentation of a cervical mass, especially with recurrent infections and especially on the left side, in a child in the first or second decade of life heightens suspicion for an anomaly of the fourth branchial arch. Diagnosis can be difficult, but is aided by the use of flexible laryngoscopy, Computed tomography (CT) scanning and ultrasonography. Surgical resection of the cyst and cauterization of its pyriform sinus opening should be undertaken to minimize recurrence

BACKGROUND: Increasingly, deaf students are educated in mainstream school environments. This poses a question of how deaf children negotiate the demands of forming friendships with their hearing peers. The present study was designed to examine coping strategies of 35 deaf children attending full or partial mainstream school settings. METHOD: Using a qualitative analysis design, a range of coping strategies used by the children was described based on parents' reports. The relative success of these coping strategies in establishing relationships with hearing peers was assessed by examining strategies that increased the social success of deaf girls and boys. RESULTS: The results showed differences by gender in the effectiveness of coping strategies used by the participants. Deaf girls who were confident and frequently asked for clarifications or who were comfortable playing alone tended to achieve good relationships with hearing peers. In contrast, deaf boys' relationships with hearing peers benefited mostly from the boys' ability to perform well in sports. CONCLUSIONS: These findings are discussed in light of existing research on coping and current debates on the benefits of mainstreaming for deaf children

While intensive chemotherapy is recommended for the treatment of non-HIV related adult small non-cleaved lymphoma (SNCL), including Burkitt's and Burkitt-like lymphoma, optimal treatment for patients with HIV-associated SNCL is not known. We assessed remissions and survival in a cohort of 44 consecutive HIV positive patients diagnosed with SNCL at our hospital between June 2000 and November 2001 using chart and pathology data. Median follow-up, survival and survival at the median follow-up time were 4.5 months, 4 months and 49% respectively. Of this cohort 39% were complete responders (CR) and 36% were long-term lymphoma-free survivors. Two patients relapsed from CR. Short course intensive chemotherapy (McMaster) was administered to 23 patients; 17 received less intensive conventional combination chemotherapy; and four received single-agent chemotherapy or no treatment. In the McMaster group, 38% (9/23) achieved CR with no relapses. Seven patients (30%) died of toxicity compared with one (6%) in the less intensively treated group. Of the stage I patients, 75% (6/8) achieved long-term CR with half being treated conventionally. Conventional chemotherapy may be curative for early stage HIV-SNCL. In advanced disease, McMaster chemotherapy was found to be associated with substantial early mortality but was curative in a significant number of patients

A group of central auditory neurons residing in the lateral superior olivary nucleus (LSO) responds selectively to interaural level differences and may contribute to sound localization. In this simple circuit, ipsilateral sound increases firing of LSO neurons, whereas contralateral sound inhibits the firing rate via activation of the medial nucleus of the trapezoid body (MNTB). During development, individual MNTB fibers arborize within the LSO, but they undergo a restriction of their boutons that ultimately leads to mature topography. A critical issue is whether a distinct form of inhibitory synaptic plasticity contributes to MNTB synapse elimination within LSO. Whole-cell recording from LSO neurons in brain slices from developing gerbils show robust long-term depression (LTD) of the MNTB-evoked IPSP/Cs when the MNTB was activated at a low frequency (1 Hz). These inhibitory synapses also display mixed GABA/glycinergic transmission during development, as assessed physiologically and immunohistochemically (Kotak et al. 1998). While either glycine or GABA(A) receptors could independently display inhibitory LTD, focal delivery of GABA, but not glycine, at the postsynaptic-locus induces depression. Furthermore, the GABA(B) receptor antagonist, SCH-50911, prevents GABA or synaptically induced depression. Preliminary evidence also indicated strengthening of inhibitory transmission (LTP) by a distinct pattern of inhibitory activity. These data support the idea that GABA is crucial for the expression inhibitory LTD and that this plasticity may underlie the early refinement of inhibitory synaptic connections in the LSO

Glycinergic transmission shapes the coding properties of the lateral superior olivary nucleus (LSO). We investigated intracellular pH responses in the LSO to glycine using BCECF-AM in brain slices. With extracellular bicarbonate, glycine produced an alkalinization followed by an acidification while, in the nominal absence of bicarbonate, glycine produced acidifications. Separately, in whole-cell recordings from LSO neurons, glycine caused hyperpolarization followed by long-lasting depolarization. While the bicarbonate-dependent intracellular alkalinization could be related to chloride/bicarbonate exchange, bicarbonate-independent acidification may be triggered by depolarization

Inhibitory transmission is critically involved in the functional maturation of neural circuits within the brain. However, the mechanisms involved in its plasticity and development remain poorly understood. At an inhibitory synapse of the developing auditory brain stem, we used whole cell recordings to determine the site of induction and expression of long-term depression (LTD), a robust activity-dependent phenomenon that decreases inhibitory synaptic gain and is postulated to underlie synapse elimination. Recordings were obtained from lateral superior olivary (LSO) neurons, and hyperpolarizing inhibitory potentials were evoked by stimulation of the medial nucleus of the trapezoid body (MNTB). Both postsynaptic glycine and GABAA receptors could independently display LTD when isolated pharmacologically. Focal application of GABA, but not glycine, on the postsynaptic LSO neuron was sufficient to induce depression of the amino acid-evoked response, or MNTB-evoked inhibitory postsynaptic potentials. This GABA-mediated depression, in the absence of MNTB stimulation, was blocked by a GABAB receptor antagonist. To assess whether a change in neurotransmitter release is associated with the LTD, the polyvalent cation, ruthenium red, was used to increase the frequency of miniature inhibitory synaptic events. Consistent with a postsynaptic locus of expression, we found that the mean amplitude of miniature events decreased after LTD with no change in their frequency of occurrence. Furthermore, there was no change in the paired-pulse ratio or release kinetics of evoked inhibitory responses. Together, these results provide direct evidence that activity-dependent LTD of inhibition has a postsynaptic locus of induction and alteration, and that GABA but not glycine plays a pivotal role

The nasolabial flap is a straightforward and time-tested reconstructive option suitable for a variety of facial and oral defects. The superiorly and inferiorly based variants are well described in the literature and offer a rapid and reliable alternative to time-consuming microvascular free flaps and less esthetic skin grafts. Despite newer and more complex alternatives, the nasolabial flap maintains its prominent position in the reconstructive armamentarium of the oral and maxillofacial surgeon

We have previously shown that the integrin beta6 is neo-expressed in invasive oral squamous cell carcinoma (SCC) and is correlated with oral tumor progression. However, the mechanism by which the integrin beta6 promotes oral tumor progression is not well understood. The purpose of the present study was to determine whether integrin beta6 signaling activates Fyn and thus promotes oral squamous cell carcinoma progression. We analyzed the integrin beta6 signaling complex and investigated the function of these signaling molecules in oral SCC cells. We found that, upon ligation of the integrin beta6 with fibronectin, beta6 complexed with Fyn and activated it. The activation of Fyn recruited and activated focal adhesion kinase to this complex. This complex was necessary to activate Shc and to couple beta6 signaling to the Raf-ERK/MAPK pathway. This pathway transcriptionally activated the matrix metalloproteinase-3 gene and promoted oral SCC cell proliferation and experimental metastasis in vivo. These findings indicate that integrin beta6 signaling activates Fyn and thus promotes oral cancer progression