bluuebunny/crossref_metadata_2025_split huggingface dataset:
S300 – Comparison of Endoscopy Diagrams for Obstructive Sleep Apnea
Authors: Nakajima Masami , Woodson B Tucker 
Published: August 2008

ObjectivesMost methods of waking and sedated sleep endoscopy evaluating the upper airway in obstructive sleep apnea inconsistently predict surgical results. Goals of exam have been to identify levels of obstruction or levels of tissue vibration. Examinations provide little information on airway structure. A novel method of describing airway collapse using airway structures has been developed. The objectives of this study are to compare sleep and wake examination: 1) during inspiration, and 2) expiration.MethodsA retrospective review evaluated waking and sedated clinical endoscopic endoscopy. Clinical endoscopic examination was performed supine at end expiration. Sedated endoscopy used propofol anesthesia evaluated the airway during both inspiration, expiration, and with elimination of airway mechanoreceptors. Defined structural butressess included salpingo/palatopharyngeus, levator, and uvular muscle groups for the epi‐pharynx and the epiglottis, lateral hypopharynx, vallecular and proximal tongue base for the hypopharynx. Structures were scored on 3 and 4 point scales with agreement indicating exact matching.ResultsSeverity of obstruction scored higher on sedated exam than clinical exam. Structural agreement in epipharynx was 52%, 29%, and 24%, and in hypopharynx, 48%,24%, and 38%. False negative and positive assessment occurred in epipharynx (levator 30% and uvula 40%) but not in hypopharynx.ConclusionsConsistent with a greater loss of muscle tone during sleep, exact agreement between wake and sleep exams was low, however, supine end expiratory exam predicted patterns of airway collapse in hypopharynx. Pattern of collapse in epipharynx is confounded by ventilation during wake.
S301 – ZPPP Combined with RF Surgery for Moderate/Severe OSAHS
Authors: Lin Hsin‐Ching , Friedman Michael 
Published: August 2008

ObjectivesTo retrospectively investigate the outcomes of Z‐palatopharyngoplasty (ZPPP) combined with radiofrequency (RF) surgery for the treatment of moderate/severe obstructive sleep apnea/hypopnea syndrome (OSAHS).Methods43 patients with moderate/severe OSAHS who failed CPAP therapy and then underwent ZPPP combined with RF tongue base reduction were enrolled in this study. The subjective symptoms and objective PSG parameters were collected preoperatively and 6 months postoperatively. Statistical analysis was determined by paired t‐test.Results2 females and 41 males (mean, 39 years) had a minimum follow‐up of 6 months and complete data available for analysis. None of the patients had perioperative or postoperative complications. No long‐term velopharyngeal insufficiency was encountered. The classical success rate was 60.5% (26/43). 6 months after the treatment, the Epworth sleepiness scale changed from 12.8 ± 5.1 to 10.0 ± 4.3 (P = 0.002). The apnea/hypopnea index (/hr.), lowest oxygen saturation (%), and bedpartner's snoring visual analog scale (0–10) changed from 51.5 ± 25.4 to 23.4 ± 24.7, 75.5 ± 10.4 to 82.1 ± 10.9, 8.4 ± 1.6 to 2.9 ± 1.6, respectively (all p<0.0001).ConclusionsThis study shows the significant benefits of ZPPP combined with RF surgery in moderate/severe OSAHS patients.
Skeletal Muscle Regeneration: MSC versus Satellite Cells
Authors: Stern‐Straeter Jens , Stephanie Juritz , Bran Gregor , Riedel Frank , Sadick Haneen , Hörmann Karl , Goessler Ulrich R. 
Published: August 2008

ProblemDifferentiating stem cells into the myogenic linage in order to create functional muscle tissue is a challenging endeavour. In this work, adipose‐derived mesenchymal stem cells (MSC) and satellite cells derived from muscle biopsies were compared regarding proliferation and myogenic differentiation potential under standardized cell culture conditions. This data was obtained in order to discover the most promising type of stem cell for regeneration of muscle tissue and to determine the optimal culture conditions for later clinical use.MethodsHuman MSC were isolated from adipose tissue, and primary human skeletal myoblasts were extracted from muscle biopsies by enzymatic digestion. Proliferation was analysed using the AlamarBlue® assay. Gene expression of marker genes – such as Myogenin, Myo D, Myf 5 and MHC – were analysed by RT‐PCR. Immunostainings against desmin and sarcomeric‐actin were performed as differentiation markers.ResultsMSC cell cultures showed a greater proliferation rate compared with satellite cell cultures. In both stem cell cultures, myogenic differentiation/heritage could be verified by immunostainings against the muscle‐specific marker desmin. Gene expression and protein analysis revealed a more stable differentiation of human satellite cell cultures.ConclusionCharacterization of both human MSC cultures and satellite cell cultures – and thereby an understanding of myogenesis – might lead to their clinical usage in skeletal muscle tissue engineering. The results in this study appear to indicate that human satellite cell cultures have a more stable differentiation under in vitro conditions and that they might offer a greater potential for skeletal muscle tissue engineering purposes.SignificanceOur study contributes to the understanding of myogenic differentiation of MSC and satellite cells and helps to improve culture systems for later clinical utilization.
Tissue Engineered Human Septal Cartilage in a Murine Model
Authors: Chang Angela , August Sage , Schumacher Barbara L , Gregory Williams , Sah Robert L , Watson Deborah 
Published: August 2008

ProblemTissue engineering of human nasal septal cartilage represents an alternative technique for creating large quantities of autologous material for use in reconstructive surgery of the head and neck. Septal neocartilage constructs developed in vitro by the alginate method have demonstrated cartilaginous extracellular matrix production, but their biocompatibility and development in vivo remains largely unknown.MethodsA murine model was used to examine the behavior of neocartilage constructs in vivo. Chondrocytes collected from donors undergoing septoplasty were expanded in monolayer and suspended in alginate beads for three‐dimensional culture in media containing human serum and growth factors. After in vitro incubation for 5 weeks, the neocartilage constructs were implanted subcutaneously in the dorsum of athymic mice for 30 days (n=3). The mice were sacrificed and the constructs were explanted for assessment of cell viability, gross morphology, and histology.ResultsThe mice survived and tolerated the implant well. Infection and extrusion were not observed. Neocartilage constructs maintained their general shape and size, and demonstrated cell viability after implantation. Explanted constructs were firm and opaque, sharing closer semblance to native septal tissue relative to the gelatinous, translucent pre‐implant constructs. On hematoxylin and eosin staining, the explanted constructs exhibited distinct morphologies characteristic of native tissue, which were not observed in pre‐implant constructs.ConclusionNeocartilage constructs are viable in an in vivo murine model. The morphologic and histologic features of explanted constructs more closely resemble native septal tissue when compared to pre‐implant constructs.SignificanceSeptal neocartilage constructs are biocompatible and demonstrate potential for in vivo maturation with eventual clinical application.
Detecting Aberrantly Methylated Genes in HNSCC Saliva
Authors: Sethi Seema , Chen Kang‐Mei , Benninger Michael S , Worsham Maria J 
Published: August 2008

ProblemAberrant promoter hypermethylation of multiple tumor suppressor genes is an early event in carcinogenesis of HNSCC. Saliva is a non‐invasive sample which has immense potential for use in molecular screening and early diagnosis of head and neck cancers due to ease of collection, patient compliance allowing repeatabililty. We evaluated saliva DNA for simultaneous detection of promoter hypermethylation in multiple genes in HNSCC cases and compared them with normal controls.MethodsSaliva was collected in a prospective cohort of 37 study subjects: 27 HNSCC patients and 10 normal controls. Saliva DNA was interrogated for aberrant methylation status using a multicandidate gene probe panel. 35 unique genes related to HNSCC were simultaneously examined of which 22 were tumor suppressor genes. Methylation‐specific multiplex ligation‐dependent probe amplification (MS‐MLPA) assay was used.ResultsOf the 22 tumor suppressor genes examined simultaneously in the saliva DNA of the study subjects, four HNSCC cases showed aberrant promoter hypermethylation in one or more genes. Aberrantly methylated genes included TIMP3, APC, MLH1, RARB and CDKN1B, CDKN2B, GSTP1, CD44, and ESR. aberrant methylation of CDKN2B was observed in 3/4 cases and GSTP1 in 2/4 cases. Only one of the 10 controls had aberrant methylation of CDKN2B.ConclusionIn this exploratory study, MS‐MLPA identified multiple aberrantly methylated genes simultaneously in the same assay run. The most important advantage is its utility as a high throughput multi‐gene screening approach requiring very small amounts of DNA, unlike more laborious single gene methods such as MSP.SignificanceEpigenetic signatures from MS‐MLPA profiling, upon subsequent validation as diagnostic or prognostic biomarkers, can become reduced to a more definitive candidate gene panel of only a few key genes for early detection and screening of HNSCC.SupportHFHS A10236; NIH R01 DE15990.
Levels of Oxidative Damage in Thyroid Neoplasia
Authors: Young Orla G , O'Sullivan Jacintha N , O'Connell Rohana , Thomas Crotty , Curran Aongus J. 
Published: August 2008

ProblemTo assess levels of oxidative damage: DNA adduct (8 oxo dG) and lipid peroxidation (4HNE) in follicular carcinomas (FTC), papillary carcinomas (PTC) and follicular adenomas (FTA) and their corresponding matched normal tissue.MethodsUsing tissue microarrays and immunohistochemistry, we examined expression levels of nuclear and cytoplasmic (mitochondrial) 8 oxo dG and 4HNE in matched tumor and normal tissues from 16 FTC's, 15 PTC's and 39 FTA's.ResultsThere were higher levels of mitochondrial 8 oxo dG expression in the FTA, FTC and PTC tissue compared to matched normal tissue (p values <0.001, <0.001, <0.03, respectively). This trend remained significant for the levels of mitochondrial 4HNE expression in these groups. (All p values < 0.01.) The levels of nuclear 4HNE expression were elevated in FTA and FTC compared to matched normal tissue (p values <0.001, <0.01, respectively). In contrast, the levels of nuclear 8 oxo dG expression was only statistically significant in the FTA group compared to matched normal tissue. Comparing all three groups to each other, there were higher levels of nuclear 8 oxo dG expression in FTA compared to FTC (p<0.01). This difference was not detected for 4HNE expression.ConclusionOxidative stress is a key feature of benign and malignant thyroid neoplasms. Interestingly, levels of oxidative damage are higher in adenoma compared to the carcinoma groups.SignificanceThe higher levels of oxidative damage in thyroid adenoma compared to carcinoma groups indicates the accumulation of this damage is an early event which could promote further genomic instability with subsequent risk of mutational events.
Short‐Term Culture and In‐Vivo Modeling of Primary HNSCC
Authors: Whigham Amy , Brandee Brown , Kochiashvili Avtandyl , Netterville James L , Burkey Brian B , Sinard Robert J , Yarbrough Wendell G 
Published: August 2008

ProblemHead and neck squamous cell carcinoma (HNSCC) accounts for 4% of annual U.S. cancer deaths. In‐vivo models exist using established HNSCC lines, but currently there is no such model that allows consistent growth of HNSCC from primary tumors.MethodsPrimary HNSCC tissue was obtained from 103 patients at biopsy/resection, disaggregated and seeded onto collagen‐coated plates in keratinocyte growth media with 10% FBS, additives and antibiotics. After short‐term growth in culture, cells were transferred to denuded rat tracheas and implanted subcutaneously in nude mice. Indirect immunofluorescent staining using antibodies specific to cytokeratin, vimentin and nuclear Ku was performed to determine cell lineage and origin.ResultsCultured cells exhibited morphology consistent with epithelial or stromal derivation. 80% of cultures had viable cells present at 10 days and 24% were maintained 30 days or longer. 5 cultures (5%) proliferated after multiple passages and thrived on uncoated plates in the absence of mesenchymal cells. The xenograft model was able to successfully establish tumors in vivo from 59% of primary tumors. Immunostaining for nuclear Ku and cytokeratin confirmed human origin and epithelial cell lineage, respectively.ConclusionThe high success rate indicates that selective growth and survival pressures for short‐term culture of primary HNSCC may be considerably less than for establishment of cell lines. Additionally, the techniques permit tumor‐derived epithelial and mesenchymal cells to be cultured simultaneously. Preliminary data for the in‐vivo trachea xenograft model is promising. A luciferase lentiviral system has been created to allow monitoring of tumor growth in vivo with serial live animal imaging.SignificanceThese short‐term culture techniques may more accurately characterize both the biological diversity of HNSCC and tumor‐stromal cell interactions. Once optimized, the trachea xenograft model can be used to determine the in‐vivo response of a heterogeneous group of HNSCC to standard and novel therapies.SupportFunds provided by an endowment for the Barry Baker Laboratory for Head and Neck Oncology, the Vanderbilt Ingram Cancer Center Endowed Professorship Fund, and the Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation.
Tonsillolith: Not Just a Stone But a Living Biofilm
Authors: Krespi Yosef P , Arora Anil , Longwell Mark , Nistico Laura , Hall‐Stoodley Luanne , de Beer Dirk , Stoodley Paul 
Published: August 2008

ProblemTo study the morphology and activity of tonsilloliths ex vivo, using confocal microscopy and microelectrodes. Understanding the similarities of tonsilloliths to dental biofilm by demonstrating oxygen respiration, de‐nitrification, and acid production.MethodsTonsilloliths were harvested from several patients with cryptic pockets and sent to the laboratory under sterile conditions. The tonsilloliths were examined by confocal microscopy to determine the presence and distribution of bacteria. Microelectrodes (dissolved oxygen, nitrous oxide, and pH) were used to measure the rates of aerobic and anaerobic respiration, and acid production, when exposed to saliva (10%) and after sucrose and fluoride addition.ResultsMorphologically, the tonsilloliths were similar to dental‐plaque biofilms, containing ‘corn‐cob’ structures, filaments and cocci. The microorganisms respired both oxygen and nitrate in physiological concentrations. The oxygen concentration in the center of the tonsillolith (500 microns) was depleted to approximately 1/10th that of the overlying fluid. The addition of 10% sucrose resulted in the production of acid within the tonsillolith by dropping the pH from 7.3 to 5.8 at a depth of 200 microns. On addition of fluoride (1000 pm) the pH increased to 6.1, suggesting that fluoride suppressed the acid fermentation of sucrose. The profiles showed, aerobic respiration near the top, de‐nitrification slightly lower and acidification towards the center. The tonsillolith therefore, had stratified layers, similar to dental (and other) biofilms. The depletion of oxygen and acid production following addition of sucrose may encourage the proliferation of anaerobic/acidophilic bacteria within the tonsillolith.ConclusionTonsilloliths exhibit biofilm structure and the formation of chemical gradients through physiological activity.SignificanceWhile complete or intracapsular tonsillectomy is an option for treating chronic cryptic infections, understanding the morphology and biofilm characteristics of tonsilloliths may stimulate scientists in using limited or non‐surgical remedies in treating chronic cryptic infections in the future.SupportThis study was funded by Valam and Philips Oral Healthcare.
Connexins Within the Rat Larynx
Authors: Van Deusen Mark , Lyon Michael J 
Published: August 2008

ProblemTo determine the various types of connexins and their localization within the rat larynx.MethodsEight larynges from 3–4 month old Fisher‐344 rats were used. Four were immediately dissected to obtain the epiglottis, vocal folds, supraglottic and subglottic mucosa. RNA was extracted and used as a template for production of cDNA, which was used with primers for Cx26, Cx30, Cx32, Cx37, Cx40, and Cx43 and RT‐PCR performed. Four others were serially sectioned and the sections processed for immunohistochemistry.ResultsRT‐PCR revealed a high level of Cx43, Cx32, and Cx30 within epiglottis and Cx43 in the vocal folds. Immunohistochemical staining confirmed these results.ConclusionThe rat epiglottis is rich in Cx43, Cx32, and Cx30 while the vocal folds contain Cx43. Their localizations suggest involvement in secretion for protective purposes and they may play a key role in laryngeal pathologies.SignificanceCxs in the larynx may be disrupted by decreased pH, alcohol ingestion, and smoke inhalation. These three factors contribute significantly to the pathology that patients commonly present to the otolaryngologist. Potential pharmacologic treatments are on the horizon and further characterization of the laryngeal connexins needs to be carried out before such treatments can be utilized.
COX II Expression in Laryngeal Lesions
Authors: Brys Agata K. , Haben C Michael 
Published: August 2008

ProblemOver expression of Cyclooxygenase II (COX II) is noted in a variety of inflammatory and neoplastic conditions, including laryngeal cancer. Although smoking is a known risk factor for laryngeal carcinoma, non‐smokers are occasionally diagnosed. Possible etiologic factors include up regulation of COX II expression. This study compares COX II expression in benign, dysplastic and cancerous laryngeal tissue specimens in smokers and non‐smokers.MethodsPathology specimens from consecutive patients who underwent excision of a laryngeal lesion for unrelated reasons from 2003 to 2006 were collected. Patients with severe laryngopharyngeal reflux were excluded. Patients’ smoking history was collected. Immunocytochemical studies were used to detect COX II expression. A blinded pathologist graded the intensity of COX II expression based on a visual analog scale. Statistical analysis was used to determine differences.Results49 samples from 22 smokers and 18 non‐smokers were tested. COX II expression was significantly larger in cancerous lesions of smokers vs non‐smokers and in dysplastic vs benign lesions in non‐smokers. A non‐statistically significant trend of consistent and progressive increase in COX II expression with increasing dysplasia in smokers was noted.ConclusionThe increase in COX II expression between benign and dysplastic lesions in non‐smokers may be due to a loss of regulation of cell metabolism. This effect may be HPV mediated and further studies comparing HPV positivity with COX II expression are underway. The significantly higher COX II expression in cancerous lesions of smokers vs non‐smokers be due to the persistent and chronic mucosal irritation from smoking.SignificanceThis translational research may affect treatment and prevention of laryngeal carcinoma in non‐smokers. A correlation between increased COX II expression and pathologic diagnosis would support the role for the use of COX II inhibitors in the prevention of progression of laryngeal lesions.SupportResearch grant from the Department of Otolaryngology, University of Rochester, New York.
GM‐CSF‐Mediated Amplification of Airway Fibrosis
Authors: Sethna Anita , Mattox Douglas E , Guidot David M , Mitchell Patrick 
Published: August 2008

Problem1. To determine if GM‐CSF (granulocyte macrophage‐colony stimulating factor) protects against fibrosis using an experimental animal model of tracheal injury. 2. To determine if GM‐CSF prevents cytokine‐induced expression of fibrotic markers in human bronchial epithelial cells in vitro.MethodsTracheae from GM‐CSF (20ng) or vehicle (PBS) treated Sprague‐Dawley donor rats were heterotopically transplanted into Fischer 344 recipients. Recipients were treated daily with either GM‐CSF or vehicle for seven days. Allografts were harvested on days 14 or 21 post‐transplantation and analyzed for luminal collagen deposition and the presence of intact epithelium. In parallel, human bronchial epithelial cells (Beas2B) were treated with pro‐fibrotic cytokines (TGFbeta1, IL‐13) with or without GM‐CSF. Treated cells were harvested and processed for RT‐PCR or immunocytochemical analyses for expression of fibrotic markers (alpha smooth muscle actin, fibroblast‐specific protein 1).ResultsTracheal allografts treated with GM‐CSF demonstrated a significant increase in luminal collagen deposition compared to vehicle‐treated allografts. GM‐CSF‐ treatment was associated with destruction of airway epithelium, contributing to amplification of fibrosis. Beas2B cells treated with the same concentration of GM‐CSF demonstrated increased expression of markers of tissue remodeling and fibrosis as well as decreased epithelial markers.ConclusionWe hypothesized that GM‐CSF‐mediated protection of the tracheal epithelium may prevent fibrosis of the airway. We show here that GM‐CSF increases luminal fibrosis and decreases epithelial viability in vivo. In addition, treatment of Beas2B cells with GM‐CSF in vitro increases expression of pro‐fibrotic markers. These data emphasize the critical role of the epithelium in preventing luminal fibrosis after tracheal injury.SignificanceVarious mediators have been considered in the etiology of tracheal stenosis. Previous studies in our lab have demonstrated the presence of GM‐CSF receptors in tracheal epithelium. Our hypothesis was that protection of this epithelium could prevent airway fibrosis. The current study demonstrates that airway fibrosis correlates with a loss in epithelium induced by GM‐CSF.
Model for Examining Recovery of Phonation after Nerve Damage
Authors: Bhama Prabhat K. , Hillel Allen D , Merati Albert L , Perkel David 
Published: August 2008

ProblemRecurrent laryngeal nerve injury remains a dominant clinical issue in laryngology. To date, no animal model of laryngeal reinnervation has offered an outcome measure that can reflect the degree of recovery based on vocal function. We present an avian model system for studying recovery of learned vocalizations following nerve injury.MethodsDigital recordings of bird song were made from 11 adult male zebra finches; 9 underwent bilateral crushing of the nerve supplying the vocal organ, and two birds underwent sham surgery. Song from all birds was then recorded regularly and analyzed based on temporal and spectral characteristics using computer software. Indices were calculated to indicate the degree of similarity between pre‐operative and post‐operative song.ResultsNerve crush caused audible differences in song quality and significant drops (p<0.05) in measured spectral and, to a lesser degree, temporal indices. Spectral indices recovered significantly (mean=43.0%; SD=40.7; p<0.02), and there was an insignificant trend towards recovery of temporal index (mean=28.0%; SD=41.4; p=0.0771). In 5/9(56%) birds, there was a greater than 50% recovery of spectral indices within a four week period. Two birds exhibited substantially less recovery of spectral indices, and two had a persistent decline in spectral indices. Recovery of temporal index was highly variable as well, ranging from persistent further declines of 45.1% to recovery of 87.0%. Neither sham bird exhibited significant (p>0.05) differences in song following nerve crush.ConclusionThe songbird model system allows functional analysis of learned vocalization following surgical damage to vocal nerves.SignificanceThe zebra finch provides an animal model for the study of phonatory function following neurolaryngeal injury.SupportThis project was supported by NIH grant T32DC000018.