Faculty Bibliography

In the inferior colliculus (IC), a brief period of acoustic conditioning can transiently enhance evoked discharge rate. The cellular basis of this phenomenon was assessed with whole cell current-clamp recordings in a gerbil IC brain slice preparation. The current needed to elicit a single action potential was first established for each neuron. A 5s synaptic stimulus train was delivered to the lateral lemniscus (LL), and followed immediately by the initial current pulse to assess a change in postsynaptic gain. The majority of IC neurons (66%) displayed an increase in current-evoked action potentials (Positive Gain). Despite the blockade of ionotropic glutamate receptors, this effect was correlated with membrane depolarization that occurred during the synaptic train. The postsynaptic mechanism for positive gain was examined by selective blockade of specific neurotransmitter receptors. Gain in action potentials was enhanced by antagonists of metabotropic glutamate, acetylcholine, GABA(A) and glycine receptors. In contrast, the gain was blocked or reduced by an antagonist to ionotropic serotonin receptors (5-HT(3)R). Blocking voltage-activated calcium channels with verapamil also reduced the effect. These results suggest that 5-HT(3)R activation, coupled with increased intracellular calcium, can transiently alter postsynaptic excitability in IC neurons

The standard treatment for locally advanced urothelial bladder carcinoma is radical cystectomy or chemoradiation. Sarcomatoid urothelial carcinoma, a rare tumour, is treated with radical cystectomy because the response to radiation therapy alone is poor in other sarcomas. We report a case of high-grade hyperinvasive urothelial bladder carcinoma with sarcomatoid differentiation. The patient refused cystectomy, and so a chemoradiation regimen was devised for her treatment. She completed the regimen and has since demonstrated a complete response to chemoradiation therapy clinically and pathologically by biopsy. The patient has therefore been able to attain a complete response while preserving a functional bladder

Ideal surgery for congenital microtia-atresia would offer excellent cosmetic and hearing rehabilitation, with minimal morbidity. Classic approaches require multiple procedures, including rib cartilage harvest and aural atresia repair. Our facial plastic and otologic team approach incorporates a high-density porous polyethylene (Medpor, Porex Surgical, Newnan, GA) auricular framework, followed by single-stage bone-anchored hearing aid (BAHA) implantation. We evaluated the efficacy, safety, and morbidity of this 2-stage dual system approach. A prospective database of microtia patients was used to identify patients undergoing combined Medpor/BAHA auricular reconstruction and hearing rehabilitation between 2003 and 2006. The first stage involves placement of a Medpor framework beneath a temporoparietal fascia flap, followed by a second-stage procedure for lobule transposition and BAHA implantation. Twenty-five patients (28 ears) were evaluated. Aesthetic quality of the implants was excellent, with a high degree of framework detail visible, and a postauricular crease created in all patients. All patients were satisfied with the cosmetic result. There were no major Medpor complications such as infection, extrusion, loss of implant, or flap necrosis, and a 10.7% incidence of minor complications requiring operative revision. BAHA significantly improved hearing in all patients, with a complication rate of 31.8%, mainly skin overgrowth and cellulitis. The Medpor/BAHA dual plastic-otologic approach to microtia-atresia has produced excellent cosmetic results and hearing outcomes, which compare favorably to traditional microtia-atresia repair. This is a 2-stage aesthetic and functional protocol with an acceptably low rate of complications, which safely and efficiently achieves both aesthetic and functional goals

PURPOSE: This study examined the ability of listeners using cochlear implants (CIs) and listeners with normal-hearing (NH) to identify silent gaps of different duration, and the relation of this ability to speech understanding in CI users. METHOD: Sixteen NH adults and eleven postlingually deafened adults with CIs identified synthetic vowel-like stimuli that were either continuous or contained an intervening silent gap ranging from 15 to 90 ms. Cumulative d', an index of discriminability, was calculated for each participant. Consonant and CNC word identification tasks were administered to the CI group. RESULTS: Overall, the ability to identify stimuli with gaps of different duration was better for the NH group than for the CI group. Seven CI users had cumulative d' scores that were no higher than those of any NH listener, and their CNC word scores ranged from 0 to 30%. The other four CI users had cumulative d' scores within the range of the NH group, and their CNC word scores ranged from 46% to 68%. For the CI group, cumulative d' scores were significantly correlated with their speech testing scores. CONCLUSIONS: The ability to identify silent gap duration may help explain individual differences in speech perception by CI users

The endogenous peptide endothelin-1 (ET-1), originally identified as a potent vasoconstrictor, plays a role in a number of painful conditions. In this review article we discuss the mechanisms that are essential for local sensitization by subcutaneously administered ET-1, and report evidence of ET-1's ability to sensitize distant regions of the body, through the central nervous system and, likely, coupling through the spinal cord. In addition, we will review the latest information on the role of ET-1 in cancerous and non-cancerous conditions. Cancer pain has indeed been shown to be attenuated by antagonists of endothelin receptors, and ET-1 is known to be secreted by cancer cells of many different histologic types. Furthermore, a growing body of evidence links increased expression and secretion of ET-1 to the occurrence of non-cancer related pain syndromes, such as inflammatory and neuropathic pain syndromes.

PURPOSE OF REVIEW: The goals of this article are: to briefly review oropharyngeal anatomy; to provide a review of the epidemiology of oropharyngeal cancer in the Western Hemisphere; to review the literature on the association of human papilloma virus with oropharyngeal cancer; to review the recent literature on evolving diagnostic techniques for oropharyngeal cancer; and to summarize accepted management strategies for oropharyngeal cancer by subsite. RECENT FINDINGS: The incidence of oropharyngeal cancer may be increasing among younger age groups in the Western Hemisphere, and this may be related to an increased association with human papillomavirus 16. The implications of this viral association with regard to outcomes and management strategies remain under investigation. Screening with toluidine blue, autofluorescence, or both may be useful adjuncts to physical examination and panendoscopy in assessing potentially invasive or dysplastic lesions of the oropharynx. These techniques remain under study. MRI and PET scan are proving to be useful techniques for assessing local extension, regional metastases, and recurrences of squamous cell carcinoma (SCC) of the oropharynx in selected cases. However, serial computed tomography scanning remains the imaging modality of choice in the United States. Early SCCs of the oropharynx (T1-2), in general, may be managed effectively with either surgery or primary irradiation, though, with either technique, clinicians must have a management plan for the neck. Advanced SCCs of the oropharynx (T3-4, nodally aggressive, or both) require multimodal approaches consisting of either surgery along with adjuvant irradiation or concurrent chemoradiation along with salvage surgery (as necessary). SUMMARY: Management of SCC of the oropharynx is in a period of transition because of evolving changes in our understanding of the oncogenic process; evolving diagnostic techniques; and evolving combinations of therapies, both surgical and nonsurgical. For the time being, we propose using local subsite and disease stage to guide therapeutic decision-making.

We have previously described a novel conjugal DNA transfer process that occurs in Mycobacterium smegmatis. To identify donor genes required for transfer, we have performed a transposon mutagenesis screen; we report here that LpqM, a putative lipoprotein-metalloproteinase, is essential for efficient DNA transfer. Bioinformatic analyses predict that LpqM contains a signal peptide necessary for the protein's targeting to the cell envelope and a metal ion binding motif, the likely catalytic site for protease activity. Using targeted mutagenesis, we demonstrate that each of these motifs is necessary for DNA transfer and that LpqM is located in the cell envelope. The requirement for transfer is specific to the donor strain; an lpqM knockout mutant in the recipient is still proficient in transfer assays. The activity of LpqM is conserved among mycobacteria; homologues from both Mycobacterium tuberculosis and Mycobacterium avium can complement lpqM donor mutants, suggesting that the homologues recognize and process similar proteins. Lipoproteins constitute a significant proportion of the mycobacterial cell wall, but despite their abundance, very few have been assigned an activity. We discuss the potential role of LpqM in DNA transfer and the implications of the conservation of LpqM activity in M. tuberculosis.