Faculty Bibliography

Emergency departments have the potential to maximize recruitment efficiency and minimize recruiting costs

BACKGROUND:Recently, balloon catheter (BC) dilatation of paranasal sinus ostia has been introduced. In this procedure, a balloon-tipped catheter is placed across a sinus ostium over a flexible wire under fluoroscopic guidance, and inflation of the balloon enlarges the ostium. Some rhinologists have criticized this procedure for its failure to remove tissue and bone, especially in the setting of sinonasal polyposis. This project seeks to develop strategies for incorporating BC technology into standard functional endoscopic sinus surgery procedures. METHODS:Endoscopic sinus dissection of three human cadaveric heads was performed with conventional instruments supplemented by lacrimal duct BCs (LacriCATH; Quest Medical, Allen, TX). No fluoroscopy was used. Each dissection was videotaped for later review. RESULTS:For frontal recess dissection, these steps were performed under endoscopic visualization: (1) passage of the BC between frontal recess partitions, (2) BC inflation, and (3) removal of fractured frontal recess partitions with conventional instruments. This approach was used successfully in each frontal recess. Under endoscopic visualization, a BC was passed into the sphenoid ostium and inflated; this maneuver successfully dilated each sphenoid ostium. It was not feasible to reliably pass the BC through the natural maxillary ostium. Each BC was inflated to 8 atm for 30 seconds. No evidence of orbital or skull base injury was noted. No fluoroscopy was used. CONCLUSION/CONCLUSIONS:BCs may be used as adjunctive instrumentation for endoscopic sinus dissection without fluoroscopy. This strategy warrants additional technical and clinical development.

Inflammatory myofibroblastic tumor is a recently characterized lesion, composed of exuberant myofibroblastic proliferation and an inflammatory component. Its etiology remains controversial, as to whether this represents a benign tumor with limited potential to recur or progress. Exaggerated response to trauma or infection has also been implicated. Only a few cases of laryngeal inflammatory myofibroblastic tumor have been described in English after it has been assigned the new name. The prototype lesion, inflammatory pseudotumor, has been best described in association with the lung but has also been reported involving various organs. We report 2 additional cases with a considerable variation in the presentation and histology of the lesion, thus expanding the morphological spectrum of the entity. Both lesions appeared aggressive in clinical presentation. One case had relatively more pleomorphic appearance and increased mitotic rate. Both lesions were surgically resected, and complete voice preservation was achieved. No postoperative complications or recurrence were noticed. This uncommon neoplasm may appear clinically as a large infiltrating mass and may be mistaken as a malignant growth. Conservative resection of the tumor may provide a cure with adequate voice preservation.

The Hodgkin-Reed-Sternberg (HRS) malignant cells in Hodgkin's lymphoma (HL) originate from germinal center B lymphocytes that did not undergo apoptosis. Protein Kinase C (PKC), a family of serine/threonine kinases, plays a crucial role in signal transduction modulating cell growth, differentiation and apoptosis. Here, we report the expression of PKC isoforms in two HL-derived cell lines, L428 and KMH2 and their correlation with drug resistance to CPT and doxorubicin. Among the PKC isoforms examined, only PKCeta and PKCbetaII were preferentially expressed in the drug resistant L428 cells. We have shown correlation between the response to apoptosis of L428 and KMH2 cells and PKCeta expression in these cell lines. In order to directly demonstrate a role for PKCeta in apoptosis, its expression was knocked-down by siRNA in the resistant L428 cells. Downregulation of PKCeta rendered L428 cells more sensitive to doxorubicin and CPT. Furthermore, PKCeta knocked-down cells showed increased PARP-1 cleavage, cytochrome c release and caspase 7 activation. It appears that PKCeta functions as an anti-apoptotic protein in HL-derived cell lines, and as we show here that it is also expressed in HRS of HL biopsies, it may have therapeutic relevance in HL. Thus, PKCeta could provide a new target aimed to reduce resistance to anti-cancer treatments of HL and other cancer patients.

Botulinum toxin A is an effective and safe treatment for perioral rejuvenation. This article explores the application of this toxin for cosmetic use in the perioral region, facial asymmetry, and improved facial wound healing. This article also describes how the use of botulinum toxin A, which has traditionally been used on the upper one third of the face, has expanded to the lower two thirds with the advent of a new formulation that consists of botulinum toxin combined with an anesthetic agent and a vasoconstrictor. The new formula provides the injecting physician with immediate feedback on the eventual treatment effect and reduces local diffusion of the simultaneously injected agents, potentially limiting systemic absorption and diffusion to neighboring muscle groups and adding to an already remarkable safety profile.

Recent studies have demonstrated that delivery of genes to the inner ear can achieve a variety of effects ranging from support of auditory neuron survival to protection and restoration of hair cells, demonstrating the utility of vector based gene delivery. Translation of these findings to useful experimental systems or even clinical applications requires a detailed understanding of the pharmacokinetics of gene delivery in the inner ear. Ideal gene delivery systems will employ a well tolerated vector which efficiently transduces the appropriate target cells within a tissue, but spare non-target structures. Adenovectors based on serotype 5 (Ad 5) are commonly used vectors, are easy to construct and have a long track record of efficacious gene transfer in the inner ear. In this study we demonstrate that distribution of Ad5 vector occurs in a basal to apical gradient with rapid distribution of vector to the vestibule after delivery via a round window cochleostomy. Transduction of the vector and expression of the delivered transgene occurs by 10 min post vector delivery. At 24 h post delivery only 16% of vector that was initially detectable within the inner ear by quantitative PCR remained. Perilymph sampling was used to determine that vector concentrations in perilymph peaked at 30 min post delivery and then declined rapidly. Understanding these basic distribution patterns and parameters for delivery are important for the design of gene delivery vectors and vital for modeling dose responses to achieve safe efficacious delivery of a therapeutic agent.

HYPOTHESIS: Delivery of math1 using an adenovector (Admath1.11D) results in vestibular hair cell regeneration and recovery of balance function in ototoxin-treated adult mice. BACKGROUND: Loss of peripheral vestibular function is associated with disease processes such as vestibular neuronitis, aminoglycoside ototoxicity, and aging. Loss of vestibular hair cells is one of the mechanisms underlying balance dysfunction in all of these disorders. Currently, recovery from these diseases relies on central vestibular compensation rather than on local tissue recovery. Overexpression of the mammalian atonal homologue math1 has been demonstrated to induce generation of hair cells in neonatal organ of Corti cultures and in the guinea pig cochlea in vivo and could thus provide an approach to local tissue recovery. METHODS: Admath1.11D was applied to cultures of aminoglycoside-treated macular organs or in vivo in a mouse aminoglycoside ototoxicity model. Outcome measures included histologic examination, immunohistochemistry, swim testing, and evaluation of the horizontal vestibulo-ocular reflex. RESULTS: Delivery of math1 resulted in the generation of vestibular hair cells in vitro after aminoglycoside-mediated loss of hair cells. Math1-treated mice showed recovery of the vestibular neuroepithelium within 8 weeks after Admath1.11D treatment. Assessment of animals after vector infusion demonstrated a recovery of vestibular function compared with aminoglycoside-only-treated mice. CONCLUSION: Molecular replacement of math1 may provide a therapeutic means of restoring vestibular function related to vestibular hair cell loss.