bluuebunny/crossref_metadata_2025 huggingface dataset:
Direct Electrical Stimulation of Heschl's Gyrus for Tinnitus Treatment
Authors: Seidman Michael D. , Ridder Dirk De , Elisevich Kost , Bowyer Susan M. , Darrat Ilaaf , Dria Jason , Stach Brad , Jiang Quan , Tepley Norman , Ewing James , Seidman Marlee , Zhang Jinsheng
Published: February 2009

Objectives/Hypothesis: The purpose of the study was to determine the effect of electrical stimulation of the auditory cortex in patients with tinnitus.

Study Design: Nonrandomized clinical trial.

Methods: Two patients with debilitating tinnitus refractory to conventional therapies were treated. Patients were evaluated with validated questionnaires and psychoacoustic measures to determine the frequency and pitch of their tinnitus. Tones at these frequencies were then presented to the first patient (RP) under magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) to determine the tonotopic map for these frequencies in Heschl's gyrus. These tonotopic sites were targeted for implant with a quadripolar electrode. In the second patient (MV), only the fMRI tonotopic map was performed. These fMRI results detected an area of increased activity, which was selected as the site for the implanted bipolar electrode.

Results: Patient RP (bilateral tinnitus for 2 years) has experienced a sustained reduction to near elimination of tinnitus with intracerebral implanted electrodes, whereas patient MV (unilateral tinnitus for 7 years) had an unsustained reduction in her tinnitus.

Conclusion: These findings suggest that the perception and annoyance of tinnitus may be modulated or reduced through electrical stimulation of the auditory cortex. These unsustained effects for patient MV may have been influenced by the longstanding nature of her tinnitus or by another reason as yet undetermined.
Anti‐Transforming Growth Factor Beta as a Treatment for Laryngotracheal Stenosis in a Canine Model
Authors: Simpson C Blake , White Stephen , McGuff H Stan
Published: February 2009

Objectives/Hypothesis:Laryngotracheal stenosis (LTS) represents a significant treatment dilemma faced by otolaryngologists. Recent topical use of Mitomycin C as an adjunctive treatment has proved helpful but does not completely prevent stenosis. Current literature suggests that transforming growth factor beta (TGFB) plays a significant role in the development of subglottic stenosis. We modified an existing canine model to test antitransforming growth factor beta (anti‐TGFB) as a possible treatment for laryngotracheal stenosis.

Study Design:Pilot study in a modified canine model.

Methods:Eight mixed‐breed dogs underwent cautery injury to the subglottic region creating subsequent laryngotracheal stenosis. Four dogs were treated with saline injection into the injury site and four dogs were treated with a combination of intravenous (5 mg/kg on day 0 and 5 of the experiment) and local injection of anti‐TGFB (50 micrograms).

Results:In the canine model of induced subglottic airway injury, a combination of intralesional and intravenous anti‐TGFB results in a reduction in tracheal stenosis (P< .05) and an increase in survival time (P< .03) when compared to the saline control subjects.

Conclusions:Anti‐TGFB appears to be a useful adjunct in the treatment of LTS. Further study regarding the optimal dosing, route of administration, and timing of delivery is needed to understand the role of anti‐TGFB in the treatment for laryngotracheal stenosis.
Longitudinal Follow‐Up of Adductor Spasmodic Dysphonia Patients After Botulinum Toxin Injection: Quality of Life Results
Authors: Paniello Randal C. , Barlow Jamie , Serna Jannie S.
Published: February 2009

Objective: Botulinum toxin injections are used routinely to treat patients with adductor spasmodic dysphonia. After an initial “breathy phase,” most patients experience improvement for a few weeks to months and then a gradual decline until their next injection. In this study, voice‐related quality of life (VRQOL) data were collected at 4 week intervals through one to three injection cycles in an attempt to quantify the proportion of each cycle during which patients experience meaningful benefit.

Study Design: Prospective, nonrandomized case series.

Methods: Patients receiving stable‐dose botulinum injections for adductor spasmodic dysphonia were invited to participate. Voice recordings and clinical outcomes data were collected by telephone every 4 weeks throughout each injection cycle. Quality of life data were normalized for cycle length and interpolated to generate composite curves.

Results: Twenty‐two patients completed data collection for at least one full injection cycle. The average cycle was 25.9 weeks; the mean age was 59.8 years. On a 100‐point scale, the total VRQOL scores peaked at 77.4, at 30% of the cycle, then gradually declined. The social‐emotional (SE) subscale scores were significantly better than the physical subscale scores (P < .05). The total VRQOL score exceeded 75 during only 14% of the cycle (52.6% for SE subscores, 0% for physical subscores). If the threshold is lowered to 70, the total VRQOL exceeded this level during 54.6% of the cycle (69.6% for SE subscores, 44.1% for physical subscores). For the 11 patients completing three full injection cycles, there were no significant differences between the three cycles, and the mean VRQOL scores were similar to the values given above. At the beginning and end of each cycle, the total VRQOL scores averaged 52.8 (56.0 for SE subscale, 50.7 for physical subscale).

Conclusion: Although botulinum toxin injections provide significant improvement for these patients, the initial breathy phase and the late declining phase add up to a significant proportion of each cycle spent with a reduced quality of life. At best, the total VRQOL averaged below 80%. This longitudinal study provides a unique look at the effect of this condition and its treatment on these patients' lives. A suitable long‐term treatment for this condition is needed to eliminate the cyclical voice results experienced with the botulinum toxin injection approach.
Molecular Classification of Thyroid Nodules by Cytology
Authors: Pagedar Nitin A. , Chen Daniel H. , Wasman Jay K. , Savvides Panayiotis , Schluchter Mark D. , Wilhelm Scott M. , Lavertu Pierre
Published: February 2009

Objectives: Fine needle aspiration (FNA) biopsy of thyroid nodules provides cytologic specimens whose interpretation can direct patients toward either thyroidectomy or observation. Approximately 20% of FNA specimens yield an indeterminate result. Recent studies have characterized differences in gene expression between benign and malignant conditions, most often using whole tissue. Our goal was to determine the feasibility of quantitative polymerase chain reaction (qPCR)‐based gene expression analysis in cytologic samples. For five genes shown to be over‐expressed in thyroid carcinomas (fibronectin, galectin‐3, Met/HGFR, MUC1, and GA733‐precursor), we compared expression among pathologic states.

Study Design: Prospective laboratory analysis of 20 thyroidectomy specimens.

Methods: Routine microscopy was performed. Cytologic samples were obtained from the dominant nodules, and RNA was extracted. Preliminary analysis using fluorometry and reverse‐transcriptase (RT)‐PCR was performed. Expression levels of the test genes in nodules and from control samples were measured by real‐time qPCR. Fold changes in gene expression were compared.

Results: Only one specimen did not yield sufficient intact RNA for gene expression analysis. RT‐PCR revealed satisfactory RNA recovery in all other specimens. qPCR showed significant over‐expression of fibronectin in the papillary carcinomas compared with the goiters (P = .0013), follicular adenomas (P = .0014), and follicular carcinomas (P = .0001). Differences in both fibronectin and MUC1 expression between the follicular carcinomas and the follicular adenomas were also significant (P = .025 and .045, respectively).

Conclusions: Cytologic specimens were a satisfactory source of tissue for qPCR‐based gene expression analysis. Both fibronectin and MUC1 were differentially expressed in follicular adenomas and follicular carcinomas, and fibronectin expression differed in papillary carcinomas compared with the other lesions. These results may form the basis of a clinical predictor for lesions with indeterminate or suspicious cytology.
Topical Application of Calcium Channel Blockers to Reduce the Progression of Experimentally Induced Myringosclerosis and Tympanosclerosis
Authors: Selcuk Adin , Akdogan Ozgur , Ozcan Ibrahim , Giray Seren Gulsen , Dere Huseyin , Ozogul Candan
Published: February 2009

Objectives: This study aimed to evaluate the ability of topically applied calcium channel blockers (diltiazem) to reduce the progression of experimentally induced myringosclerosis and tympanosclerosis.

Study Design: Animal model. Experimental prospective study.

Methods: The study included 25 adult albino guinea pigs that were bilaterally myringotomized and inoculated with a suspension of Streptococcus pneumonia type 3. The right ears were treated with topical application of diltiazem, and the untreated left ears served as the control group. Otomicroscopy and remyringotomy were conducted every week. One animal was sacrificed after 1 week and the remaining at the end of 6 weeks. Temporal bones were dissected, and tympanic bullae were analyzed with light microscopy.

Results: The untreated control ears showed evidence of extensive myringosclerosis on otomicroscopy, and the ears treated with calcium channel blockers did as well although to a lesser degree. Under light microscopy, the lamina propria of both tympanic membranes and middle ear mucosae of the control group exhibited thicker (P < .1 and P < .05, respectively) and larger (P < .01 and P < .01, respectively) sclerotic tissue in comparison with the treatment group.

Conclusion: The results suggest that calcium channel blockers had an influence in the prevention of tympanosclerosis.
Diagnostic Accuracy of Peak Nasal Inspiratory Flow and Rhinomanometry in Functional Rhinosurgery
Authors: Bermüller Christian , Kirsche Hanspeter , Rettinger Gerhard , Riechelmann Herbert
Published: February 2009

Objectives: Sensitivity and specificity of active anterior rhinomanometry (RMM) and peak nasal inspiratory flow (PNIF) in the diagnosis of functionally relevant structural nasal deformities should be assessed. The reference standard was clinical judgment based on all clinical data available.

Study Design: Prospective study of diagnostic accuracy at a tertiary rhinologic referral center.

Methods: RMM and PNIF were performed on 53 patients with symptomatic nasal stenosis and 40 healthy volunteers. Cut‐offs for RMM and PNIF were defined by receiver operating characteristic analysis.

Results: A cut‐off between normal and pathological of 700 mL/second for RMM at a transnasal pressure difference of 150 Pa, and of 2,000 mL/second (120 l per minute) for PNIF was calculated. No significant differences in terms of sensitivity of RMM and PNIF (0.77 vs. 0.66), specificity (0.8 vs. 0.8) and diagnostic accuracy (0,79 vs. 0.72) were found.

Conclusion: RMM and PNIF provide valuable information to support clinical decision making. However, with both methods, approximately 25% of symptomatic patients with functionally relevant nasal structural deformity were not detected. A negative test outcome of RMM or PNIF does not exclude a functionally relevant nasal stenosis.
Effect of Proton Pump Inhibitor Pantoprazole on Growth and Morphology of Oral Lactobacillus Strains
Authors: Altman Kenneth W. , Chhaya Vina , Hammer Neal D. , Pavlova Sylvia , Vesper Benjamin J. , Tao Lin , Radosevich James A.
Published: February 2009

Objectives: Proton pump inhibitors (PPI) used to suppress acid secretion in the stomach are among the most widely prescribed medications. There is emerging evidence of proton secretion elsewhere in the aerodigestive tract, and acidic microenvironments are integral to oral flora such as Lactobacillus. The hypothesis of this study is that the growth rate and morphology of oral Lactobacillus strains are effected by PPIs.

Methods: Nineteen different strains of Lactobacilli were inoculated in microtiter plates at pH of 4.5 to 6.5 and exposed to twofold dilutions of pantoprazole at a range of 2.5 mg/mL to 2.5 μg/mL. Bacterial growth was monitored, and the minimum inhibitory concentration (MIC) of the drug was determined for the strains most sensitive to pantoprazole.

Results: In the unexposed (control) group, nine Lactobacilli strains were affected by pH changes from 6.5 to 4.5. In the group exposed to pantoprazole, 9 of the 19 Lactobacilli strains were found to have an MIC below 625 μg/mL, with L. plantarum 14917 being the most sensitive (MIC = 20 μg/mL). In some strains, such as L. s. salivarius 11741, Gram‐staining revealed conformational changes in the bacteria when grown in the presence of pantoprazole.

Conclusion: Growth rates and morphology of oral Lactobacillus are affected by the pH of the environment. Pantoprazole at supraphysiologic doses further affects growth rates and conformation in some strains.

Significance: The balance of oral flora and upper digestive tract homeostasis may be affected by unexpected targets of PPI pharmacotherapy, with possible unanticipated consequences.
Isolated Bilateral Facial Paralysis Revealing AIDS: A Unique Presentation
Authors: Abboud Olivier , Saliba Issam
Published: February 2009

HIV is a recognized etiologic agent in the development of peripheral facial paralysis (PFP). In most cases, the paralysis appears in the acute phase of the HIV infection, and its prognosis is similar to Bell's palsy. Other etiologic agents are generally involved in the development of the paralysis in the later stages of the disease. Bilateral facial palsy is a rare clinical entity in HIV infection. Only 19 cases have been reported. A case of facial diplegia revealing AIDS is described in this review. To the best of our knowledge, this is the first report of such an advanced state of the disease in a previously asymptomatic patient.
Treatment Outcomes for Radiotherapy Alone are Comparable With Neoadjuvant Chemotherapy Followed by Radiotherapy in Early‐Stage Nasopharyngeal Carcinoma
Authors: Song Chang Hoon , Wu Hong‐Gyun , Heo Dae Seog , Kim Kwang Hyun , Sung Myung‐Whun , Park Charn Il
Published: February 2009

Objectives:To analyze the impact of neoadjuvant chemotherapy (CT) on the treatment of early‐stage nasopharyngeal carcinoma (NPC) as compared with radiotherapy (RT) alone.

Methods:We analyzed retrospectively the outcome of 60 previously untreated and histologically confirmed early‐stage NPC patients treated with either RT alone or with neoadjuvant CT followed by RT (CT/RT) at the Seoul National University Hospital between 1986 and 2004. Neoadjuvant CT consisted of three cycles with 5‐fluourouracil and cisplatin. RT was given to the nasopharynx and neck nodes. The median dose to the primary site, involved nodes, and elective nodes was 70.2 Gy, 63 Gy, and 45 Gy, respectively. According to the 1997 American Joint Committee on Cancer staging system, 9 patients had stage I or IIA disease, and 22 patients had stage IIB disease in the RT group. For the CT/RT group, 8 patients had stage I or IIA disease, and 21 patients had stage IIB disease. The median follow‐up for all patients was 124.5 (range, 5–239) months.

Results:The 5‐year locoregional failure‐free (LRFF), distant metastasis‐free (DMF), disease‐free survival (DFS), and overall survival (OS) rate was 84%, 93%, 81%, and 84% for the RT group and 77%, 86%, 71%, and 79% for the CT/RT group, respectively. There were no significant differences in LRFF (P= .728), DMF (P= .433), DFS (P= .562), and OS (P= .625) rates between the RT and CT/RT groups. Multivariate analysis revealed that delaying RT for more than 81 days was significantly associated with an increased risk of locoregional failure in the subgroup of patients with stage IIB disease (P= .044).

Conclusions:In our retrospective analysis, the use of neoadjuvant CT showed no additional benefit to treatment with RT alone. Neoadjuvant CT may cause deleterious effect on stage IIB disease by delaying RT.
The Prognostic Impact of Extent of Bone Invasion and Extent of Bone Resection in Oral Carcinoma
Authors: Patel Rajan S. , Dirven Richard , Clark Jonathan R. , Swinson Brian D. , Gao Kan , O'Brien Christopher J.
Published: February 2009

Objective: The prognostic impact of mandibular invasion by oral squamous cell carcinoma (SCC) is controversial. The objective of this study was to assess the effect that extent of bone invasion has on recurrence and survival in patients treated with marginal and segmental mandible resection.

Study Design: A retrospective cohort study of patients whose clinicopathologic information had been collected prospectively into a dedicated head and neck database.

Methods: Local control and disease‐specific survival were retrospectively reviewed in 111 patients (median follow‐up, 44 months) with oral SCC undergoing marginal or segmental mandibulectomy.

Results: Bone invasion was present in 46% of marginal and 94% of segmental resections. Five‐year local control was similar following marginal (83%) and segmental mandibulectomy (86%). There was no correlation with presence or extent of bone invasion. Survival at 5 years was 71% and this correlated with bone invasion and involved margins (P < .05), but not with extent of mandible invasion or resection.

Conclusions: Marginal mandibulectomy does not adversely alter outcome in selected patients with bone invasion provided margins are not compromised.
Free‐Flap Head and Neck Reconstruction and Quality of Life: A 2‐Year Prospective Study
Authors: Bozec Alexandre , Poissonnet Gilles , Chamorey Emmanuel , Casanova Cédric , Vallicioni Jacques , Demard François , Mahdyoun Pouya , Peyrade Frédéric , Follana Philippe , Bensadoun René‐Jean , Benezery Karen , Thariat Juliette , Marcy Pierre‐Yves , Sudaka Anne , Dassonville Olivier
Published: February 2009

Objectives: This prospective study was designed to evaluate quality of life (QOL) after free‐flap head and neck reconstruction.

Study Design: Prospective study.

Methods: Between January 2004 and December 2005, a total of 95 patients underwent microvascular reconstruction of the head and neck at our Institution (Centre Antoine‐Lacassagne, Nice, France) and were initially included in this study. The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire and the EORTC Head and Neck Cancer Quality of Life Questionnaire were completed before surgery, and at 6 and 12 months thereafter. Sixty‐five patients completed the questionnaires on at least two of the assessment dates. Predictive factors of Quality of Life (QOL) scores at 6 months were researched among the following: age, sex, comorbidity, radiotherapy, tumor recurrence, tumor stage, and type of surgery.

Results: Global QOL remained stable over time. Physical, social, and role functioning deteriorated significantly after treatment. Pain decreased markedly. Social eating, senses, and speech difficulties increased significantly at 6 months, but stabilized between 6 and 12 months. Problems concerning mouth opening and social contact augmented progressively until the 12th postoperative month. Sex, type of surgery, and radiotherapy were the main factors influencing QOL 6 months after treatment.

Conclusions: Despite some functional impairments, global QOL was preserved after major head and neck ablative surgery and microvascular free‐flap reconstruction.
Recurrent Respiratory Papillomatosis: A Review
Authors: Derkay Craig S. , Wiatrak Brian
Published: February 2009

Recurrent respiratory papillomatosis (RRP), which is caused by human papillomavirus types 6 and 11, is the most common benign neoplasm of the larynx among children and the second most frequent cause of childhood hoarseness. After changes in voice, stridor is the second most common symptom, first inspiratory and then biphasic. Less common presenting symptoms include chronic cough, recurrent pneumonia, failure to thrive, dyspnea, dysphagia, or acute respiratory distress, especially in infants with an upper respiratory tract infection. Differential diagnoses include asthma, croup, allergies, vocal nodules, or bronchitis. Reports estimate the incidence of RRP in the United States at 4.3 per 100,000 children and 1.8 per 100,000 adults. Infection in children has been associated with vertical transmission during vaginal delivery from an infected mother. Younger age at diagnosis is associated with more aggressive disease and the need for more frequent surgical procedures to decrease the airway burden. When surgical therapy is needed more frequently than four times in 12 months or there is evidence of RRP outside the larynx, adjuvant medical therapy should be considered. Adjuvant therapies that have been investigated include dietary supplements, control of extra‐esophageal reflux disease, potent antiviral and chemotherapeutic agents, and photodynamic therapies; although several have shown promise, none to date has “cured” RRP, and some may have serious side effects. Because RRP, although histologicallybenign, is so difficult to control and can cause severe morbidity and death, better therapies are needed. The potential for a quadrivalent human papilloma vaccine is being explored to reduce the incidence of this disease.
Immunodefense of the Round Window
Authors: Engmér Cecilia , Laurell Göran , Bagger‐Sjöbäck Dan , Rask‐Andersen Helge
Published: February 2009

A systematic analysis using serial sectioning of the round window membrane (RWM) in the cynomolgus monkey was performed. Light and transmission electron microscopy (LM and TEM) revealed that the RWM rim may be endowed with gland‐like structures with glyco‐protein material secernated into the window niche. This was detected in one third of the specimens. The secreted material displayed waste material and scavenger cells. There was also a rich network of capillaries, lymph channels, and sinusoidal veins containing leukocytes. Their abluminal surfaces displayed mature plasma cells and monocytes. These findings suggest that in certain primates the middle ear may have developed specific immunoprotective means for disposal of foreign and noxious substances before they reach the inner ear.
Flexible Endoscopic Clip‐Assisted Zenker's Diverticulotomy: The First Case Series (With Videos)
Authors: Tang Shou‐jiang , Jazrawi Saad F. , Chen Edward , Tang Linda , Myers Larry L.
Published: February 2009

Background: In treating Zenker's diverticulum (ZD), there are potential risks associated with performing flexible endoscopic diverticulotomy without suturing or stapling. We recently introduced flexible endoscopic clip‐assisted diverticulotomy (ECD) in treating ZD by securing the septum prior to dissection.

Objective: To evaluate the feasibility and safety of ECD for complete septum dissection.

Study Design: Case series at an academic center. Seven consecutive patients (mean age 71 y; range 48–91 y) with symptomatic ZD of various craniocaudal sizes based on radiographic measurements (mean 2.6 cm; range 0.8 cm–4.5 cm) were included. The mean depth of the septum was 1.73 cm (range 0.3 cm–3.1 cm). The mean duration of symptoms was 4.8 years (range 0.5–10 y).

Methods: After endoclips were placed on either side of the cricopharyngeal bar, the septum was dissected between these two clips down to the inferior end of the diverticulum with a needle‐knife. Procedures including “one‐step ECD” (n = 1), “stepwise ECD” (n = 3), and “bottom ECD” (n = 2) were performed based on the septum depth of the ZD during endoscopy. ECD was not performed on one patient due to severe mucosal fragility of the esophageal inlet. Iatrogenic blunt dissection of the septum by the endoscopic hood occurred secondary to patient retching during the procedure. Main outcome measurements were symptom resolution and complications.

Results: All patients (n = 6) who underwent ECD had complete resolution of esophageal symptoms at a minimum 6‐month follow‐up. There were no procedural complications. The patient who did not undergo ECD developed an esophageal perforation. She was managed conservatively without surgical intervention. On follow‐up, her dysphagia was completely resolved.

Conclusions: ECD is feasible, safe, and effective for complete septum dissection. ECD and endoscopic stapler‐assisted diverticulotomy are complimentary rather than competing strategies in approaching ZD. Study limitations include the case series design and limited follow‐up period.
Human Nasal Cartilage Ultrastructure: Characteristics and Comparison Using Scanning Electron Microscopy
Authors: Holden Paul K. , Liaw Li‐Huei , Wong Brian J.‐F.
Published: February 2009

Objectives/Hypothesis: Human nasal cartilage is hyaline cartilage, although the function and loads placed on it are different depending on the location. We hypothesized that important differences exist between the nasal septal cartilage and lower lateral cartilage (LLC) ultrastructures. Such differences would be important in the field of cartilage engineering.

Methods: Ten specimens (6 septum and 4 LLC) of cartilage from patients undergoing nasal surgery (rhinoplasty or septoplasty) were obtained and examined using scanning electron microscopy. Micrographs were then analyzed and measured using photograph analysis software.

Results: The collagen fibers of septal cartilage were found to be arranged in a mesh framework, with larger lacunae and thicker fibers measuring 3.18 μm (standard deviation = 0.75 μm), with a 99.9% confidence interval of 2.74 to 3.54 μm. LLC fibers, on the other hand, were arranged in less‐organized sheets, with fibrous extensions, and had fewer, narrower lacunae. The fibers from the LLC averaged 2.29 μm, with a 99.9% confidence interval of 1.17 to 3.42 μm.

Conclusions: Significant ultrastructural differences exist between the cartilage of the nasal septum and LLC. These are almost certainly the result of their embryologic origins and different forces placed on the structures they support. A less‐organized pattern with smaller collagen fibers is present in the LLC versus the more‐organized, layered, thicker collagen fibers of the septum. These differences may prove to be critical in the future of cartilage engineering.
Fistula Analysis After Radial Forearm Free Flap Reconstruction of Hypopharyngeal Defects
Authors: Andrades Patricio , Pehler Stephen F. , Baranano Christopher F. , Magnuson Jeffery S. , Carroll William R. , Rosenthal Eben L.
Published: February 2009

Objective/Hypothesis: To evaluate risk factors and management options for fistula formation after hypopharyngeal reconstruction using the radial forearm free flap reconstruction.

Study Design: Retrospective cohort study.

Methods: Patients undergoing radial forearm free flap for hypopharyngeal reconstruction were retrospectively reviewed. A total of 104 patients underwent this procedure between 2001 and 2007. Fistulas were classified as mild or severe depending on the response to conservative management. Demographics, operative details, pathology, and postoperative course were recorded as the prognostic variables. Univariate analysis and a logistic regression model were used to identify associated factors.

Results: Pharyngocutaneous fistula developed in 30 (28.8%) patients. Recurrence, cancer stage, cancer location, type of ablative surgery, and the addition of other oncologic procedures were identified as significant predictors of fistula formation. Fistula significantly increases hospital stay and recipient site complications such as flap survival, infection, and bleeding. Functional results such as diet, deformity, and socialization were also negatively affected by fistula development. One third of the cases responded to conservative management, and 20 cases required a surgical procedure to definitively close the fistulous track.

Conclusions: Fistula formation remains a significant cause of morbidity associated with hypopharyngealreconstruction. Postoperative course and successful preventive strategies are discussed.
Maintenance Repetitive Transcranial Magnetic Stimulation Can Inhibit the Return of Tinnitus
Authors: Mennemeier Mark , Chelette Kenneth C. , Myhill Jeffery , Taylor‐Cooke Patricia , Bartel Twyla , Triggs William , Kimbrell Timothy , Dornhoffer John
Published: February 2009

Objectives/Hypothesis: A single patient was tested to examine the safety and feasibility of using maintenance sessions of low‐frequency repetitive transcranial magnetic stimulation (1 Hz rTMS) to reduce tinnitus loudness and prevent its return over time.

Study Design: Interrupted time series with multiple replications.

Methods: Tinnitus loudness was assessed using a visual analogue rating (VAR) with 0 = no tinnitus, and 100 = loudest tinnitus experienced; 1,800 TMS pulses delivered at 1 Hz and 110% of motor threshold were administered over the posterior, superior lateral temporal gyrus of the subject's right hemisphere until subjective tinnitus fell to a VAR of 25. TMS was reapplied as tinnitus returned to a VAR of 25 or higher. Cerebral metabolism was measured using positron emission tomography before and after treatment.

Results: In this patient, tinnitus could be reduced to a VAR of 6 or lower each time it reoccurred using one to three maintenance sessions of rTMS. Tinnitus loudness remained at or below a VAR of 25 and was reported to be unobtrusive in daily life when last assessed 4 months after the third and final round of maintenance treatment. Asymmetric increased cerebral metabolism in the right hemisphere reduced following treatment and as tinnitus improved. Maintenance treatment was well tolerated with no side effects.

Conclusions: Although a case study cannot establish treatment efficacy, this study demonstrates for the first time that it is feasible to use maintenance rTMS to manage chronic tinnitus. Maintenance rTMS might impede cortical expansion of the tinnitus frequency into adjacent cortical areas, but group studies are necessary to confirm this speculation.
Pneumolabyrinth Without Temporal Bone Fracture: Different Outcomes for Hearing Recovery
Authors: Woo Hyun‐Jae , Song Si‐Youn , Kim Yong‐Dae , Bai Chang Hoon
Published: February 2009

Pneumolabyrinth is a rare clinical manifestation seen in the practice of otology. It occurs usually after head trauma with temporal bone fracture. However, pneumolabyrinth without temporal bone fracture is a very rare occurrence. When it occurs, it is usually diagnosed by high‐resolution computed tomography of the temporal bone. Therapy for pneumolabyrinth is conservative treatment or an exploratory tympanotomy. Recently, we saw two cases of pneumolabyrinth after trauma without temporal bone fracture. The patients were treated with conservative management for the pneumolabyrinth. However, the degree of recovery from hearing loss was different for each patient.
Three‐Dimensional Fluid‐Attenuated Inversion Recovery Magnetic Resonance Imaging Findings and Prognosis in Sudden Sensorineural Hearing Loss
Authors: Yoshida Tadao , Sugiura Makoto , Naganawa Shinji , Teranishi Masaaki , Nakata Seiichi , Nakashima Tsutomu
Published: February 2009

Objectives/Hypothesis: Three‐dimensional fluid‐attenuated inversion recovery (3D‐FLAIR) magnetic resonance imaging (MRI) has recently been developed to detect high concentrations of protein or hemorrhage. We have previously reported that 50% of patients with sudden sensorineural hearing loss (SNHL) show high signals in the affected inner ear on 3D‐FLAIR MRI. However, the relationship between 3D‐FLAIR findings and hearing prognosis is unclear. Our objective was to evaluate the relationship between the results of 3D‐FLAIR MRI at 3 Tesla and prognosis in sudden SNHL.

Study Design and Methods: We used 3D‐FLAIR at 3 Tesla with and without gadolinium enhancement to evaluate the pathologic conditions in the inner ears of 48 patients with sudden SNHL.

Results: Thirty‐one of 48 patients with sudden SNHL showed high signals in the affected inner ear on precontrast 3D‐FLAIR. Hearing improvement in patients with high signals in the affected inner ear on precontrast 3D‐FLAIR (25 ± 19 dB) was significantly worse than that in patients with no signal (45 ± 27 dB; P < .05). Our analysis suggests that high signals in the affected inner ear on precontrast 3D‐FLAIR MRI is a new prognostic factor for sudden SNHL.

Conclusions: 3D‐FLAIR findings show that high signals in the cochlea on precontrast 3D‐FLAIR are related to a poor hearing prognosis. These signals may reflect minor hemorrhage or an increased concentration of protein in the inner ear, which has passed through blood vessels with increased permeability or has originated in disrupted cells in the inner ear.
Optical Coherence Tomography of the Cochlea in the Porcine Model
Authors: Sepehr Ali , Djalilian Hamid R. , Chang Janice E. , Chen Zhongping , Wong Brian J. F.
Published: February 2009

Objectives/Hypothesis: To demonstrate the feasibility of optical coherence tomography in microstructural imaging of the porcine cochlea.

Study Design: Ex vivo, porcine model.

Methods: Optical coherence tomographic images of the porcine cochlea were obtained by thinning the bone from the basal turn of the cochlea leaving the endosteum intact. The images were compared with the corresponding histological sections.

Results: In the areas of thinned bone, images were obtained of the stria vascularis, Reissner's membrane, basilar membrane, tectorial membrane, scala media, scala tympani, and scala vestibuli. The bone was too thick for adequate light penetration in the areas where it was not thinned. Good histological correlation was obtained.

Conclusions: Cochlear and vestibular microanatomic structures of the pig cochlea were clearly identified with histological confirmation, suggesting the potential application of this noninvasive imaging modality for in vivo imaging of the human cochlea.
Letters of Recommendation to an Otolaryngology/Head and Neck Surgery Residency Program: Their Function and the Role of Gender
Authors: Messner Anna H. , Shimahara Erika
Published: February 2009

Objectives/Hypothesis: To ascertain common features and gender differences in letters of recommendation (LORs) for applicants to an otolaryngology/head and neck surgery (OHNS) residency program.

Study Design: Retrospective review.

Methods: Seven hundred sixty‐three LORs submitted to one OHNS residency program in 2006 were reviewed.

Results: All 763 letters “recommended” the applicant for OHNS residency. Ninety‐one percent of letters were written by men, 68.4% by male otolaryngologists (OTOs), 4.2% by female OTOs, and 33% by OHNS department chairs or division chiefs (100% men). A comparison of female and male letter writers revealed five categories with significant differences: female letter writers were more likely to call an applicant a “team player” (P = .000), “compassionate,” (P = .001) and use strings of adjectives (P = .024). In contrast, they were less likely when compared with male letter writers, to mention an applicant's personal life (P = .003), or write “letters of minimal assurance” (P = .035). Evaluation of the letters by applicant gender revealed two findings: letter writers were more likely to use a gender term in letters for male applicants (P = .004), and male letter writers were more likely to make reference to a female candidate's physical appearance (P = .040).

Conclusions: LORs for OHNS residency universally advocate for the applicant. The letters are writtenpredominately by the highest‐ranking male OTOs in academic medicine. In the LORs, male and female applicants are described similarly. Male and female letter writers, however, often describe applicants in different ways regardless of applicant gender.
Disarrangement of Collagen Fibers in Reinke's Edema
Authors: Sakae Flavio Akira , Imamura Rui , Sennes Luiz U. , Mauad Thais , Saldiva Paulo H. , Tsuji Domingos H.
Published: February 2009

Objective/Hypothesis: To describe the arrangement of collagen fibers in the superficial layer of the lamina propria of the vocal folds with Reinke' edema.

Study Design: Cross sectional analysis of the lamina propria of the vocal folds with Reinke's edema (RE).

Method: The picrosirius polarization method was used to study the arrangement of collagen fiber. Findings of collagen disarrangement were categorized semiquantitatively and correlated with RE severity, age, cigarette smoking and duration of dysphonia.

Results: Analysis of 20 specimens of vocal folds with RE showed that the intertwined network of collagen fibers resembling a wicker‐basket normally observed in vocal folds was disarranged in RE. The collagen fibers were loosely arranged, fragmented and intermixed with varying amounts of myxoid stroma. Moderate and large areas of disarrangement (90% of cases) predominated. Collagen fiber arrangement in the region underneath the epithelium was better preserved when compared with fibers in the deeper region of the superficial layer of the lamina propria. There was a statistical difference in collagen disarrangement between grade II and grade III severity (P = .007) that appeared to be due to the large areas of disarrangement observed in 73% of patients with grade III severity and in 44% of grade II severity. Age was the only variable correlated with collagen fiber disarrangement (r = 0.47, P = .037).

Conclusion: Our findings suggest that the flexible framework which maintains the uniformity of the lamina propria was lost in RE caused by the disarrangement of the collagen fibers.
A Test for Measuring Gustatory Function
Authors: Smutzer Gregory , Lam Si , Hastings Lloyd , Desai Hetvi , Abarintos Ray A. , Sobel Marc , Sayed Nabil
Published: February 2009

Objectives/Hypothesis: The purpose of this study was to determine the usefulness of edible taste strips for measuring human gustatory function.

Study Design: The physical properties of edible taste strips were examined to determine their potential for delivering threshold and suprathreshold amounts of taste stimuli to the oral cavity. Taste strips were then assayed by fluorescence to analyze the uniformity and distribution of bitter tastant in the strips. Finally, taste recognition thresholds for sweet taste were examined to determine whether or not taste strips could detect recognition thresholds that were equal to or better than those obtained from aqueous tests.

Methods: Edible strips were prepared from pullulan‐hydroxypropyl methylcellulose solutions that were dried to a thin film. The maximal amount of a tastant that could be incorporated in a 2.54 cm2 taste strip was identified by including representative taste stimuli for each class of tastant (sweet, sour, salty, bitter, and umami) during strip formation. Distribution of the bitter tastant quinine hydrochloride in taste strips was assayed by fluorescence emission spectroscopy. The efficacy of taste strips for evaluating human gustatory function was examined by using a single series ascending method of limits protocol. Sucrose taste recognition threshold data from edible strips was then compared with results that were obtained from a standard “sip and spit” recognition threshold test.

Results: Edible films that formed from a pullulan‐hydroxypropyl methylcellulose polymer mixture can be used to prepare clear, thin strips that have essentially no background taste and leave no physical presence after release of tastant. Edible taste strips could uniformly incorporate up to 5% of their composition as tastant. Taste recognition thresholds for sweet taste were over one order of magnitude lower with edible taste strips when compared with an aqueous taste test.

Conclusion: Edible taste strips are a highly sensitive method for examining taste recognition thresholds in humans. This new means of presenting taste stimuli should have widespread applications for examining human taste function in the laboratory, in the clinic, or at remote locations.
Long‐Term Results of Radiotherapy for T1a and T1bN0M0 Glottic Carcinoma
Authors: Nomiya Takuma , Nemoto Kenji , Wada Hitoshi , Takai Yoshihiro , Yamada Shogo
Published: February 2009

Objective/Hypothesis: The purpose of this study is to determine the prognostic factors for local control and significance of total radiation dose in T1 glottic cancer.

Study Design: Retrospective study.

Methods: Data from 163 patients with T1 N0 M0 Stage I glottic squamous cell carcinoma (T1a: 115, T1b: 48) who were treated with radiotherapy alone during 1976 to 2002 were analyzed retrospectively. Age, source, total dose, field size, overall treatment time, and average fraction size were set as variables in multivariate analysis.

Results: The 5‐year local control rates (LCR) were 92.3% and 85.0% for patients with T1a and T1b glottic carcinoma, respectively. Only total radiation dose (P = .048) was a significant prognostic factor for local control in multivariate analysis of T1b glottic carcinoma. Local control in the higher total dose group was better than that in the lower total dose group (5 year LCRs were 100% and 76% for the group of >66 Gy and the group of ≤66 Gy, respectively. P = .024, logrank test). None of the treatment parameters were shown to be significant prognostic factors in multivariate analysis of T1a glottic carcinoma.

Conclusions: Radiotherapy with a total dose of 67 to 70 Gy seemed to be required for local control in T1b glottic carcinoma. No significant benefit of total radiation dose >64 Gy was shown in the analysis of T1a glottic carcinoma.
Computed Tomography Imaging of Patients With Obstructive Sleep Apnea
Authors: Barkdull Gregory C. , Kohl Chad A. , Patel Minal , Davidson Terence M.
Published: February 2009

Objectives/Hypothesis: This study used computed tomography (CT) to identify anatomic features of the awake upper respiratory tract (URT) that correlate with severity of obstructive sleep apnea (OSA).

Study Design: An IRB approved radiographic study of 80 patients with OSA and 56 patients from the general population.

Methods: Awake, noncontrast CT was performed from the skull base to the thoracic inlet in patients with OSA. Cross‐sectional measurements of the retropalatal and retrolingual airways were made along with the size of the cervicomandibular ring and the percentage neck fat. The mandibular plane to hyoid distance, neck length, and laryngeal descent were also recorded. The posterior tongue fat content was estimated using the Hounsfield unit for radiodensity. The radiographic data were then compared with clinical information, including apnea‐hypopnea index (AHI), body mass index, and neck circumference using linear regression.

Results: AHI increases with smaller retrolingual cross‐sectional airway (P = .0026) and increasing mandibular plane to hyoid distance (P = .0003) but not retropalatal airway or laryngeal descent. The posterior tongue is hypodense with higher fat content than other muscles of the head and neck.

Conclusions: This study describes anatomic findings of the retrolingual airway in patients that correlate with OSA and can be measured on an upper airway CT. Patients with severe OSA (AHI ≥40) tend to have retrolingual airways less than 4% of the cross‐sectional area of the cervicomandibular ring. The retrolingual airspace is the major site of obstruction in severe OSA and should be carefully evaluated before surgical treatment is considered.
Atypical relaxation of structural constraints in Hox gene clusters of the green anole lizard
Authors: Di-Poï Nicolas , Montoya-Burgos Juan I. , Duboule Denis
Published: February 2009

Hox genes control many aspects of embryonic development in metazoans. Previous analyses of this gene family revealed a surprising diversity in terms of gene number and organization between various animal species. In vertebrates, Hox genes are grouped into tightly organized clusters, claimed to be devoid of repetitive sequences. Here, we report the genomic organization of the four Hox loci present in the green anole lizard and show that they have massively accumulated retrotransposons, leading to gene clusters larger in size when compared to other vertebrates. In addition, similar repeats are present in many other development-related gene-containing regions, also thought to be refractory to such repetitive elements. Transposable elements are major sources of genetic variations, including alterations of gene expression, and hence this situation, so far unique among vertebrates, may have been associated with the evolution of the spectacular realm of morphological variations in the body plans of Squamata. Finally, sequence alignments highlight some divergent evolution in highly conserved DNA regions between vertebrate Hox clusters, which may coincide with the emergence of mammalian-specific features.
Enhanced generalization of auditory conditioned fear in juvenile mice
Authors: Ito Wataru , Pan Bing-Xing , Yang Chao , Thakur Siddarth , Morozov Alexei
Published: February 2009

Increased emotionality is a characteristic of human adolescence, but its animal models are limited. Here we report that generalization of auditory conditioned fear between a conditional stimulus (CS+) and a novel auditory stimulus is stronger in 4–5-wk-old mice (juveniles) than in their 9–10-wk-old counterparts (adults), whereas nonassociative sensitization induced by foot shock (US) and the ability to discriminate CS+ from an explicitly unpaired stimulus (CS−) are not dependent on age. These results suggest that aversive associations are less precise in juvenile mice and can more easily produce conditional responses to stimuli different from CS+. Yet, through the explicit unpairing of CS− from US during training, juveniles are able to overcome this greater fear generalization and learn that CS− is not associated with foot shock.
Three lanthanide complexes derived from itaconic acid and 2,2′-bipyridine
Authors: Muñoz Juan Carlos , Atria Ana María , Garland Maria Teresa , Baggio Ricardo
Published: February 2009

The structures of three new polymeric lanthanide complexes, poly[[bis(2,2′-bipyridine)-μ4-itaconato-di-μ3-itaconato-digadolinium(III)] tetrahydrate], {[Gd2(C5H4O4)3(C10H8N2)2]·4H2O}n, (I), poly[diaqua(2,2′-bipyridine)di-μ3-itaconato-μ2-itaconato-digadolinium(III)], [Gd2(C5H4O4)3(C10H8N2)(H2O)2]n, (II), and poly[[bis(2,2′-bipyridine)-μ4-itaconato-di-μ3-itaconato-diholmium(III)] dihydrate], {[Ho2(C5H4O4)3(C10H8N2)2]·2H2O}n, (III), have been solved from twinned specimens. Compound (I) presents a two-dimensional polymeric structure parallel to (011) built up around two independent nine-coordinated Gd centres displaying similar GdO7N2environments, with both N-donor atoms in each provided by a chelating 2,2′-bipyridine (bpy) unit. The coordinating O atoms are from three different itaconate (ita) anions (itaconic acid is 2-methylidenebutanedioic acid). Compound (II) also presents two independent Gd centres (one ten- and the other eight-coordinated), but the overall formula and individual coordinations are different from those of (I). The chemical unit is in this case completed by one bpy ligand, three ita anions (one of them displaying a new, hitherto unreported, μ3-O,O′:O′,O′′:O′′′ binding mode) and two aqua ligands. The whole structure is built up around a twofold rotation axis passing through both cations, as well as through the centre of the bpy ligand and one of the ita anions, thus making only half of the chemical unit independent. Finally, compound (III) presents a single independent Ho centre, a bpy unit and one and a half ita anions (one of them bisected by a twofold rotation axis) in the asymmetric unit, plus two (disordered) nonbonded solvent water molecules. In compounds (II) and (III), those ita anions bisected by a symmetry element incompatible with the internal symmetry of the ligand exhibit disorder in the C=CH2group.