Faculty Bibliography

Sudden sensorineural hearing loss (SSNHL) is commonly encountered in audiologic and otolaryngologic practice. SSNHL is most commonly defined as sensorineural hearing loss of 30 dB or greater over at least three contiguous audiometric frequencies occurring within a 72-hr period. Although the differential for SSNHL is vast, for the majority of patients an etiologic factor is not identified. Treatment for SSNHL of known etiology is directed toward that agent, with poor hearing outcomes characteristic for discoverable etiologies that cause inner ear hair cell loss. Steroid therapy is the current mainstay of treatment of idiopathic SSNHL in the United States. The prognosis for hearing recovery for idiopathic SSNHL is dependent on a number of factors including the severity of hearing loss, age, presence of vertigo, and shape of the audiogram.

OBJECTIVES/HYPOTHESIS: Given the recent emergence of encouraging efficacy data regarding the utility of intralesional glucocorticoid (GC) injection for a variety of vocal fold pathologies, we sought to describe the location and expression pattern of the GC receptors within the vocal folds and quantify the effects of GCs on vocal fold fibroblasts. STUDY DESIGN: In vitro, in vivo. METHODS: Immunolocalization of the GC receptor was performed on normal rat vocal fold tissue. Receptor expression was also assayed in our human vocal fold fibroblast cell line. These cells were then treated with exogenous dexamethasone (DM) to quantify the effects of GCs on receptor expression, proliferation, transforming growth factor (TGF)-beta-induced collagen secretion, and matrix protease synthesis. RESULTS: Positive immunostaining for the GC receptor was found throughout the vocal fold with particularly strong staining in the epithelium and capillaries. Human vocal fold fibroblasts constitutively express the GC receptor, but this expression decreased in response to exogenous DM. DM also decreased fibroblast proliferation and TGF-beta-induced collagen synthesis. DM also abrogated TGF-beta-mediated effects on enzymes related extracellular matrix turnover. CONCLUSIONS: Our data are the first to provide mechanistic insight regarding the recently published favorable data regarding the utility of GCs in patients with vocal fold scar. Although further investigation is warranted, both the accessibility of this class of agents and the amenability to office-based procedures are likely to direct patient care models

Laryngomalacia is a common source of stridor and can lead to significant upper airway obstruction and feeding disturbances in infants. We describe a unique case of supraglottic dysgenesis presenting as laryngomalacia featuring a prominent "s-shaped" epiglottis with both posterior edges fused to the right aryepiglottic fold/arytenoid complex. Although this anomaly is not accounted for in any of the current laryngomalacia classification schemes, modified laser supraglottoplasty was a satisfactory approach leading to successful decannulation. Laryngeal embryology and possible timing of the pathogenesis of this rare occurrence are reviewed as well.

The nervous system must dynamically represent sensory information in order for animals to perceive and operate within a complex, changing environment. Receptive field plasticity in the auditory cortex allows cortical networks to organize around salient features of the sensory environment during postnatal development, and then subsequently refine these representations depending on behavioral context later in life. Here we review the major features of auditory cortical receptive field plasticity in young and adult animals, focusing on modifications to frequency tuning of synaptic inputs. Alteration in the patterns of acoustic input, including sensory deprivation and tonal exposure, leads to rapid adjustments of excitatory and inhibitory strengths that collectively determine the suprathreshold tuning curves of cortical neurons. Long-term cortical plasticity also requires co-activation of subcortical neuromodulatory control nuclei such as the cholinergic nucleus basalis, particularly in adults. Regardless of developmental stage, regulation of inhibition seems to be a general mechanism by which changes in sensory experience and neuromodulatory state can remodel cortical receptive fields. We discuss recent findings suggesting that the microdynamics of synaptic receptive field plasticity unfold as a multi-phase set of distinct phenomena, initiated by disrupting the balance between excitation and inhibition, and eventually leading to wide-scale changes to many synapses throughout the cortex. These changes are coordinated to enhance the representations of newly-significant stimuli, possibly for improved signal processing and language learning in humans

Cancers often cause excruciating pain and rapid weight loss, severely reducing quality of life in cancer patients. Cancer-induced pain and cachexia are often studied and treated independently, although both symptoms are strongly linked with chronic inflammation and sustained production of proinflammatory cytokines. Because nerve growth factor (NGF) plays a cardinal role in inflammation and pain, and because it interacts with multiple proinflammatory cytokines, we hypothesized that NGF acts as a key endogenous molecule involved in the orchestration of cancer-related inflammation. NGF might be a molecule common to the mechanisms responsible for clinically distinctive cancer symptoms such as pain and cachexia as well as cancer progression. Here we reported that NGF was highly elevated in human oral squamous cell carcinoma tumors and cell cultures. Using two validated mouse cancer models, we further showed that NGF blockade decreased tumor proliferation, nociception, and weight loss by orchestrating proinflammatory cytokines and leptin production. NGF blockade also decreased expression levels of nociceptive receptors TRPV1, TRPA1, and PAR-2. Together, these results identified NGF as a common link among proliferation, pain, and cachexia in oral cancer. Anti-NGF could be an important mechanism-based therapy for oral cancer and its related symptoms

In cochlear implants (CIs), simultaneous or sequential stimulation of adjacent electrodes can produce intermediate pitch percepts between those of the component electrodes. However, it is unclear whether simultaneous and sequential virtual channels (VCs) can be discriminated. In this study, CI users were asked to discriminate simultaneous and sequential VCs; discrimination was measured for monopolar (MP) and bipolar + 1 stimulation (BP + 1), i.e., relatively broad and focused stimulation modes. For sequential VCs, the interpulse interval (IPI) varied between 0.0 and 1.8 ms. All stimuli were presented at comfortably loud, loudness-balanced levels at a 250 pulse per second per electrode (ppse) stimulation rate. On average, CI subjects were able to reliably discriminate between sequential and simultaneous VCs. While there was no significant effect of IPI or stimulation mode on VC discrimination, some subjects exhibited better VC discrimination with BP + 1 stimulation. Subjects' discrimination between sequential and simultaneous VCs was correlated with electrode discrimination, suggesting that spatial selectivity may influence perception of sequential VCs. To maintain equal loudness, sequential VC amplitudes were nearly double those of simultaneous VCs, presumably resulting in a broader spread of excitation. These results suggest that perceptual differences between simultaneous and sequential VCs might be explained by differences in the spread of excitation.

Functional inhibitory synapses form in auditory cortex well before the onset of normal hearing. However, their properties change dramatically during normal development, and many of these maturational events are delayed by hearing loss. Here, we review recent findings on the developmental plasticity of inhibitory synapse strength, kinetics, and GABAA receptor localization in auditory cortex. Although hearing loss generally leads to a reduction of inhibitory strength, this depends on the type of presynaptic interneuron. Furthermore, plasticity of inhibitory synapses also depends on the postsynaptic target. Hearing loss leads reduced GABAA receptor localization to the membrane of excitatory, but not inhibitory neurons. A reduction in normal activity in development can also affect the use-dependent plasticity of inhibitory synapses. Even moderate hearing loss can disrupt inhibitory short- and long-term synaptic plasticity. Thus, the cortex did not compensate for the loss of inhibition in the brainstem, but rather exacerbated the response to hearing loss by further reducing inhibitory drive. Together, these results demonstrate that inhibitory synapses are exceptionally dynamic during development, and deafness-induced perturbation of inhibitory properties may have a profound impact on auditory processing

OBJECTIVE: To describe the complications and adverse effects of postoperative radiotherapy in patients with Fanconi anemia (FA). DESIGN: Cohort study. SETTING: Patients with FA treated at community and tertiary care hospitals throughout the United States. PATIENTS: The study included patients with FA who were enrolled in the International FA Registry (IFAR) and who developed head and neck squamous cell carcinoma and received postoperative radiotherapy. MAIN OUTCOME MEASURES: Demographics of patients with FA and adverse effects and dosages of radiotherapy. RESULTS: Twelve patients with FA (7 men and 5 women) were identified. They developed cancers at a mean age of 35.5 years (age range, 20-48 years). The sites of primary cancer were the oral cavity (n = 8), larynx (n = 2), pharynx (n = 1), and unknown (n = 1). The median radiation dose was 5590 cGy (range, 2500-7020 cGy). The most common adverse effects were mucositis (n = 9), dysphagia (n = 8), and pancytopenia (n = 6). Other complications included esophageal stenosis, laryngeal edema, and wound breakdown. Radiotherapy could not be completed in 5 cases. Overall, 8 patients died, 4 during the course of radiotherapy. The postoperative disease-free survival time ranged from 0 to 55 months. CONCLUSIONS: Patients with FA have a high rate of complications from radiotherapy. Common adverse effects, particularly mucositis, are especially prevalent and difficult to manage in this population. Pancytopenia is common and may lead to further complications, particularly bleeding and infection. Overall survival is poor. Further study of the response to radiotherapy in patients with FA should be attempted to establish appropriate dosages to balance treating disease while limiting adverse effects.