Searched for: Department/Unit:Otolaryngology
Cannabinoids attenuate cancer pain and proliferation in a mouse model
Saghafi, Negin; Lam, David K; Schmidt, Brian L
We investigated the effects of cannabinoid receptor agonists on (1) oral cancer cell viability in vitro and (2) oral cancer pain and tumor growth in a mouse cancer model. We utilized immunohistochemistry and Western blot to show that human oral cancer cells express CBr1 and CBr2. When treated with WIN55,212-2 (non-selective), ACEA (CBr1-selective) or AM1241 (CBr2-selective) agonists in vitro, oral cancer cell proliferation was significantly attenuated in a dose-dependent manner. In vivo, systemic administration (0.013M) of WIN55,212-2, ACEA, or AM1241 significantly attenuated cancer-induced mechanical allodynia. Tumor growth was also significantly attenuated with systemic AM1241 administration. Our findings suggest a direct role for cannabinoid mechanisms in oral cancer pain and proliferation. The systemic administration of cannabinoid receptor agonists may have important therapeutic implications wherein cannabinoid receptor agonists may reduce morbidity and mortality of oral cancer
PMCID:3099480
PMID: 21094209
ISSN: 1872-7972
CID: 132003
Identifying risk factors for postoperative cardiovascular and respiratory complications after major oral cancer surgery
Dillon, Jasjit K; Liu, Stanley Y; Patel, Chirag M; Schmidt, Brian L
BACKGROUND: Surgical resection of oral cancer can be associated with significant postoperative cardiovascular and respiratory complications that require more sensitive predictors. METHODS: All patients with oral squamous cell carcinoma treated from July 2005 to April 2008 were retrospectively reviewed. The Goldman Revised Cardiac Risk Index (GRCRI) was used to predict cardiovascular complications. Other evidence-based a priori predictors were applied in an h-fold cross-validation model. RESULTS: Operating room (OR) time was an independent predictor of cardiovascular complications (odds ratio = 1.54, p = .002, 95% confidence interval [CI] = 1.18-2.02) and respiratory complications (odds ratio = 1.3, p = .06, 95% CI = 0.99-1.64) after multivariate adjustment. OR time and estimated blood loss predicted cardiovascular complications with 73% sensitivity. The GRCRI achieved 37% sensitivity. OR time and tracheostomy predicted respiratory complications with 75% sensitivity. CONCLUSIONS: The GRCRI was not prognostic for cardiovascular complications in patients with oral cancer. The most sensitive predictors for cardiovascular complications were OR time and estimated blood loss; for respiratory complications they were OR time and tracheostomy
PMID: 20578073
ISSN: 1097-0347
CID: 132004
Cultured vestibular ganglion neurons demonstrate latent HSV1 reactivation
Roehm, Pamela C; Camarena, Vladimir; Nayak, Shruti; Gardner, James B; Wilson, Angus; Mohr, Ian; Chao, Moses V
OBJECTIVES/HYPOTHESIS: Vestibular neuritis is a common cause of both acute and chronic vestibular dysfunction. Multiple pathologies have been hypothesized to be the causative agent of vestibular neuritis; however, whether herpes simplex type I (HSV1) reactivation occurs within the vestibular ganglion has not been demonstrated previously by experimental evidence. We developed an in vitro system to study HSV1 infection of vestibular ganglion neurons (VGNs) using a cell culture model system. STUDY DESIGN: basic science study. RESULTS: Lytic infection of cultured rat VGNs was observed following low viral multiplicity of infection (MOI). Inclusion of acyclovir suppressed lytic replication and allowed latency to be established. Upon removal of acyclovir, latent infection was confirmed with reverse-transcription polymerase chain reaction and by RNA fluorescent in situ hybridization for the latency-associated transcript (LAT). A total of 29% cells in latently infected cultures were LAT positive. The lytic ICP27 transcript was not detected by reverse-transcription polymerase chain reaction (RT-PCR). Reactivation of HSV1 occurred at a high frequency in latently infected cultures following treatment with trichostatin A (TSA), a histone deactylase inhibitor. CONCLUSIONS: VGNs can be both lytically and latently infected with HSV1. Furthermore, latently infected VGNs can be induced to reactivate using TSA. This demonstrates that reactivation of latent HSV1 infection in the vestibular ganglion can occur in a cell culture model, and suggests that reactivation of HSV1 infection a plausible etiologic mechanism of vestibular neuritis
PMCID:3696486
PMID: 21898423
ISSN: 1531-4995
CID: 137886
Measurement of Mycotoxins in Patients with Chronic Rhinosinusitis
Lieberman SM; Jacobs JB; Lebowitz RA; Fitzgerald MB; Crawford J; Feigenbaum BA
Mycotoxins are toxic secondary metabolites produced by a variety of fungi including Aspergillus, Alternaria, and Penicillium species. The presence of mycotoxins in sinonasal tissue and secretions and any possible link to chronic rhinosinusitis (CRS) or other diseases of the head and neck have not been reported. The authors performed an exploratory study to determine the presence and levels of mycotoxins in the sinonasal tissue and secretions of 18 subjects undergoing endoscopic sinus surgery for CRS. Using commercial enzyme-linked immunosorbent assay kits, samples were analyzed for the following mycotoxins: aflatoxin, deoxynivalenol, zearalenone, ochratoxin, and fumonisin. All specimens were negative for aflatoxin, deoxynivalenol, zearalenone, and fumonisin. Four (22%) of 18 specimens were positive for ochratoxin. The clinical significance of this finding remains to be determined
PMID: 21493263
ISSN: 1097-6817
CID: 137919
Auditory rehabilitation of patients with neurofibromatosis Type 2 by using cochlear implants
Roehm, Pamela C; Mallen-St Clair, Jon; Jethanamest, Daniel; Golfinos, John G; Shapiro, William; Waltzman, Susan; Roland, J Thomas Jr
OBJECT: The aim of this study was to determine whether patients with neurofibromatosis Type 2 (NF2) who have intact ipsilateral cochlear nerves can have open-set speech discrimination following cochlear implantation. METHODS: Records of 7 patients with documented NF2 were reviewed to determine speech discrimination outcomes following cochlear implantation. Outcomes were measured using consonant-nucleus-consonant words and phonemes; Hearing in Noise Test sentences in quiet; and City University of New York sentences in quiet and in noise. RESULTS: Preoperatively, none of the patients had open-set speech discrimination. Five of the 7 patients had previously undergone excision of ipsilateral vestibular schwannoma (VS). One of the patients who received a cochlear implant had received radiation therapy for ipsilateral VS, and another was undergoing observation for a small ipsilateral VS. Following cochlear implantation, 4 of 7 patients with NF2 had open-set speech discrimination following cochlear implantation during extended follow-up (15-120 months). Two of the 3 patients without open-set speech understanding had a prolonged period between ipsilateral VS resection and cochlear implantation (120 and 132 months), and had cochlear ossification at the time of implantation. The other patient without open-set speech understanding had good contralateral hearing at the time of cochlear implantation. Despite these findings, 6 of the 7 patients were daily users of their cochlear implants, and the seventh is an occasional user, indicating that all of the patients subjectively gained some benefit from their implants. CONCLUSIONS: Cochlear implantation can provide long-term auditory rehabilitation, with open-set speech discrimination for patients with NF2 who have intact ipsilateral cochlear nerves. Factors that can affect implant performance include the following: 1) a prolonged time between VS resection and implantation; and 2) cochlear ossification
PMCID:3590004
PMID: 21761973
ISSN: 1933-0693
CID: 141067
Glucocorticoids regulate extracellular matrix metabolism in human vocal fold fibroblasts
Zhou, Hang; Sivasankar, Mahalakshmi; Kraus, Dennis H; Sandulache, Vlad C; Amin, Milan; Branski, Ryan C
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
PMCID:3205428
PMID: 22024844
ISSN: 1531-4995
CID: 140046
First bite syndrome as a presenting symptom of a parapharyngeal space malignancy
Lieberman, Seth M; Har-El, Gady
BACKGROUND: First bite syndrome is a known complication after parapharyngeal space surgery. This syndrome is usually encountered when the surgery is extensive but the parotid gland is preserved. A disruption in the balance between sympathetic and parasympathetic innervation to the parotid gland has been posited to play a role. METHODS: We report a 74-year-old woman with a parapharyngeal space malignancy who presented with first bite syndrome prior to any surgical intervention. The tumor and left parotid gland were resected via a transcervical approach. During the operation, the sympathetic chain was found to be directly involved with the tumor. RESULTS: The patient reported complete resolution of first bite syndrome immediately after the operation, and remained free of this symptom at 6 months' follow-up. CONCLUSION: To our knowledge, this is the first report of first bite syndrome presenting prior to any surgical intervention. Parotidectomy, if included in the surgical plan, may lead to the resolution of first bite syndrome
PMID: 20848432
ISSN: 1097-0347
CID: 142787
A systematic review of medical interventions for oral submucous fibrosis and future research opportunities
Kerr, A R; Warnakulasuriya, S; Mighell, A J; Dietrich, T; Nasser, M; Rimal, J; Jalil, A; Bornstein, M M; Nagao, T; Fortune, F; Hazarey, V H; Reichart, P A; Silverman, S; Johnson, N W
Oral Diseases (2011) 17 (Suppl. 1), 42-57 Oral submucous fibrosis (OSF) is a chronic, insidious disease caused by areca nut use, and is associated with both significant morbidity (including pain and reduced oral opening) and an increased risk for malignancy. This systematic review explored and updated the current medical (i.e., non-surgical) interventions available for the management of OSF. Of the 27 published medical interventions, there were four randomized controlled trials. The overall quality of these randomized controlled studies was assessed using the GRADE approach and significant limitations that challenged the conclusions were found. However, this review was valuable in terms of identifying opportunities to provide recommendations for future research, in terms of the populations to research, the types of interventions needed, the types of outcomes to be measured, the study designs needed, and the infrastructure required to conduct studies. The next step is to initiate a pathway for a low-cost research plan leading to the development of a brief protocol for future clinical trials in this field, with an emphasis on conducting studies in regions of the world where OSF is prevalent
PMID: 21382138
ISSN: 1601-0825
CID: 155246
Local drug delivery for oral mucosal diseases: challenges and opportunities
Sankar, V; Hearnden, V; Hull, K; Juras, D Vidovic; Greenberg, M S; Kerr, A R; Lockhart, P B; Patton, L L; Porter, S; Thornhill, M
There are few topical formulations used for oral medicine applications most of which have been developed for the management of dermatological conditions. As such, numerous obstacles are faced when utilizing these preparations in the oral cavity, namely enzymatic degradation, taste, limited surface area, poor tissue penetration and accidental swallowing. In this review, we discuss common mucosal diseases such as oral cancer, mucositis, vesiculo-erosive conditions, infections, neuropathic pain and salivary dysfunction, which could benefit from topical delivery systems designed specifically for the oral mucosa, which are capable of sustained release. Each condition requires distinct penetration and drug retention profiles in order to optimize treatment and minimize side effects. Local drug delivery may provide a more targeted and efficient drug-delivery option than systemic delivery for diseases of the oral mucosa. We identify those mucosal diseases currently being treated, the challenges that must be overcome and the potential of novel therapies. Novel biological therapies such as macromolecular biological drugs, peptides and gene therapy may be of value in the treatment of many chronic oral conditions and thus in oral medicine if their delivery can be optimized
PMID: 21382140
ISSN: 1601-0825
CID: 155256
Severe and rapid erosion of dental enamel from swimming: A clinical report
Jahangiri, Leila; Pigliacelli, Steven; Kerr, A Ross
The diagnosis and treatment of a patient with excessive and rapid erosion of enamel is presented. Although the Center for Disease Control and the dental literature have reported on dental enamel erosion resulting from swimming pool chlorination, the awareness of such etiology among dental professionals may be limited. Common findings in these reports include cold sensitivity, a distinctive appearance resembling laminate veneer preparations of the facial surfaces of anterior teeth, occurrence of diastemas, and at times, a rough or gritty texture of the remaining tooth structure. Clinical presentations of erosive lesions can be diagnosed and the best course of treatment determined
PMID: 21962583
ISSN: 1097-6841
CID: 155399