bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of p16, nm23‐H1, E‐cadherin, and CD44 Gene Products and Their Significance in Nasopharyngeal Carcinoma
Authors: Huang Guang‐Wu , Mo Wu‐Ning , Kuang Guo‐Qian , Nong Hui‐Tu , Wei Ming‐Yi , Sunagawa Masanori , Kosugi Tadayoshi
Published: November 2003

Objective The present study was aimed to determine whether p16/MTS1, nm23‐H1, E‐cadherin, and CD44 proteins were expressed in nasopharyngeal carcinoma (NPC) and whether those expressions were pathologically significant in the progress of NPC.

Method We examined non‐cancerous nasopharyngeal mucosa (20 cases) and NPC (80 cases) using immunohistochemistry with six different types of monoclonal antibodies against p16, nm23‐H1, E‐cadherin, CD44H, CD44v3, and CD44v6 proteins.

Results The results showed that 1) the rates of positive p16 protein expression and of preserved E‐cadherin protein expression in NPC were significantly lower than those in non‐cancerous tissue (P <.01); 2) no significant difference in the rate of positive expression of nm23‐H1, CD44H, CD44v3, and CD44v6 proteins were observed between non‐cancerous nasopharyngeal mucosa and NPC; 3) no significant difference in the expression of those proteins were found by respective correlation analyses of sex, stage, and size of primary tumor in NPC; and 4) no significant difference in the rates of positive expression of CD44H, CD44v3, and CD44v6 proteins were observed in NPC between with and without lymph node metastasis, indicating that those gene products did not correlate with lymph node metastasis in NPC. However, there were inverse correlations between the expression of p16, nm23‐H1, or E‐cadherin protein and lymph node metastasis (P <.05), indicating that the expression of p16, nm23‐H1, and E‐cadherin gene were related to the carcinogenesis and tumor progression of NPC.

Conclusion Detecting the expressions of those gene products may provide clinically valuable information for therapeutic strategy and for predicting the prognosis of patients with NPC.
The Effect of Vagal Nerve Stimulation on Voice
Authors: Charous Steven J. , Kempster Gail , Manders Ernest , Ristanovic Ruzica
Published: November 2003

Objective Vagal nerve stimulation therapy through implanted vagal nerve stimulators is an accepted therapy for refractory seizure disorders. One significant side effect of vagal nerve stimulation is voice change. This study evaluates the impact that these voice changes have on patients' lives, and the physiological effects that vagal nerve stimulation has on the larynx.

Methods Patients were selected from the pool of patients at Rush‐Presbyterian‐St. Luke's Medical Center who underwent implantation of vagal nerve stimulator devices. Three methods were used to evaluate the impact the devices had on patients and on their vocal cords. First, a questionnaire was sent to the patients to ascertain the degree of vocal and social impairment that occurs as a result of the implant. Second, videostroboscopy was used to analyze the effect that vagal nerve stimulation had on the larynx. Third, computerized voice analysis objectively analyzed the patients' voices both during and in between vagal nerve stimulations.

Results Although patients noted significant voice changes during stimulation of the implant, the impairment is well tolerated and less debilitating than the underlying seizure disorder. Hyperstimulation of the affected vocal cord was observed during vagal stimulation with paramedian positioning, vocal fold tensing, and loss of mucosal wave. Increase in jitter and shimmer was consistent.

Conclusion Vagal nerve implantation devices create significant but well‐tolerated vocal side effects. Investigation of these devices increases our understanding of laryngeal physiology and may give insight into future laryngeal pacing. Preimplantation laryngeal examination should be performed routinely to rule out laryngeal pathology that could lead to significant complications.
A Computer‐Assisted Anatomical Study of the Nasofrontal Region
Authors: Landsberg Roee , Friedman Michael
Published: November 2003

Objectives/Hypothesis Objectives were as follows: 1) to define the variations of the uncinate process' superior attachment, 2) to study the diameter of the frontal sinus ostium, 3) to study the prevalence of the agger nasi cells, and 4) to evaluate the side‐to‐side variability of these structures.

Study Design A retrospective clinical study at a tertiary care center.

Methods One hundred forty‐four consecutive computed tomography scans were studied with image‐guided surgery software (InstaTrak, Visualization Technology, Inc., Wilmington, MA) that provides continuous coronal, sagittal, and axial sections. We reported the superior attachment sites of the uncinate process, the diameter of the frontal sinus ostium, and prevalence of the agger nasi cells.

Results The uncinate process' main superior attachment into the surrounding structures was found to have the following distribution: 52% to the lamina papyracea, 18.5% to the posteromedial wall of the agger nasi cell, 17.5% to the lamina papyracea and the junction of the middle turbinate with the cribriform plate, 7% to the junction of the middle turbinate with the cribriform plate, 3.6% to the ethmoid roof, and 1.4% to the middle turbinate. The frontal ostium anterior–posterior diameter (mean ± SD) was 7.22 ± 2.78 mm and its transverse diameter (mean ± SD) was 8.92 ± 2.95 mm. Agger nasi cells were found in 78% of the scans.

Conclusions The frontal sinus opens into the middle meatus medial to the uncinate process in 88% of the patients and lateral to the uncinate process in 12% of the patients. The naturally wide dimensions of the frontal ostium help to explain why postoperative patency can be achieved merely by exposing the ostium without the need to enlarge it. The frontal ostium dimensions in one side may differ considerably from the contralateral side. An agger nasi cell or a terminal recess, or both, are found in most cases. Image‐guided surgery software is a helpful new tool for anatomical studies and for preoperative evaluation.
Tumor Deposition of Laminin‐5 and the Relationship With Perineural Invasion
Authors: Anderson Timothy D. , Feldman Michael , Weber Randal S. , Ziober Amy F. , Ziober Barry L.
Published: November 2003

Objectives/Hypothesis Perineural invasion (PNI) is increasingly being recognized as an important indicator of aggressiveness in head and neck squamous cell carcinoma. The mechanisms of PNI are poorly understood. Laminin‐5, an important basement membrane constituent, has been shown to be essential in head and neck squamous cell carcinoma invasion and motility. We hypothesized that tumors exhibiting increased expression of laminin‐5 are more likely to be neurotropic.

Study Design Analysis of archived surgical specimens with and without PNI for presence and intensity of laminin‐5 tumor staining.

Methods Immunohistochemistry of archived head and neck squamous cell carcinoma specimens with known PNI was performed with anti–laminin‐5 antibodies and appropriate positive and negative control specimens. The staining patterns were characterized as follows: A, few to no tumor cells positive; B, some peripheral cells positive; C, all peripheral cells positive; and D, almost all tumor cells positive. Statistical analysis was by χ2 analysis.

Results Forty‐six PNI‐positive and 18 PNI‐negative specimens were analyzed. The staining distribution for the PNI‐positive specimens was as follows: 2% for A, 41% for B, 46% for C, and 11% for D. For tumors without PNI, the distribution was 28% for A, 50% for B, 22% for C, and 0% for D (P = .005). In PNI‐positive tumors, no significant difference in staining was seen between areas with and without PNI.

Conclusions We found a significant correlation between laminin‐5 staining and the presence of PNI in head and neck squamous cell carcinoma. Expression of laminin‐5 by tumors is, possibly, an important step in the process of PNI. These preliminary findings support the concept that deposition of basement membrane constituents are required in the multistep process of nerve invasion.
Investigation of Helicobacter pylori Colonization in Adenotonsillectomy Specimens By Means of the CLO Test
Authors: Unver Seref , Kubilay Utku , Sezen Ozan Seymen , Coskuner Temel
Published: November 2003

Objectives Investigation of Helicobacter pylori (HP) colonization in adenoid and tonsil tissues by using the CLO (Campylobacter‐like organism) test.

Study Design Prospective clinical study. Included in the study were 19 patients aged 4 to 38 who had undergone an adenoidectomy, tonsillectomy, or adenotonsillectomy procedure under local or general anesthesia.

Methods Tissue pieces with diameters of 2 mm, which had been obtained from each adenoid and tonsil specimens in the early postoperative stage, were placed in kits specially prepared for HP (CLO test). Color changes were noted after 20 minutes and after periods of 1, 3, and 24 hours.

Results Eleven (57.89%) of the 19 patients included in the study were shown to be HP positive, and 8 (42.11%) were negative, regardless of the type of specimen.

Conclusion It was shown that there was a high rate of HP colonization in tonsil and adenoid tissues.
Cyclooxygenase‐2 Expression in Human Thyroid Carcinoma and Hashimoto's Thyroiditis
Authors: Cornetta Anthony J. , Russell John P. , Cunnane Mary , Keane William M. , Rothstein Jay L.
Published: November 2003

Objectives Cyclooxygenases (COX) are enzymes that catalyze the conversion of arachidonic acid to prostaglandins. COX‐2, unlike the constitutively expressed COX‐1, is an inducible enzyme upregulated during cell proliferation and inflammation. More recently, COX‐2 has been implicated in the development of numerous types of epithelial cancers. In addition, COX‐2 is highly expressed in several inflammatory diseases. Because of its dual role in inflammation and cancer, we were interested in determining if COX‐2 plays a role in the development of human thyroid carcinoma and Hashimoto's thyroiditis, an autoimmune condition frequently associated with thyroid malignancy.

Materials and Methods Twenty paraffin‐embedded human tissue specimens, including normal, inflammatory, and neoplastic thyroid sections, were analyzed by immunohistochemical staining for expression of human COX‐2. In addition, COX‐2 protein expression was verified by Western blot in two specimens.

Results Immunohistochemical staining confirmed the presence of COX‐2 in thyroid epithelial neoplasms, including papillary and follicular carcinomas. Moreover, COX‐2 expression was observed in patients with Hashimoto's thyroiditis. COX‐2 expression, however, was not observed in normal thyroid tissue, multinodular goiter, or anaplastic carcinoma.

Conclusions We have shown that cyclooxygenase‐2 is expressed in thyroid carcinoma and thyroid epithelium from patients with Hashimoto's thyroiditis but not in normal thyroid. The expression of COX‐2 in both of these thyroid pathologies may provide a basis for the relationship between carcinogenesis and autoimmunity.
Three‐Layer Reconstruction for Large Defects of the Anterior Skull Base
Authors: Sinha Uttam K. , Johnson Terence E. , Crockett Dennis , Vadapalli Satish , Gruen Peter
Published: November 2003

Objectives To evaluate and discuss a three‐layer rigid reconstruction technique for large anterior skull base defects.

Study Design Prospective, non‐randomized, non‐blinded.

Setting Tertiary teaching medical center.

Methods Twenty consecutive patients underwent craniofacial resection for a variety of pathology. All patients had large anterior cranial base defects involving the cribriform plate, fovea ethmoidalis, and medial portion of the roof of the orbit at least on one side. A few patients had more extensive defects involving both roof of the orbits, planum sphenoidale, and bones of the upper third of the face. The defects were reconstructed with a three‐layer technique. A watertight seal was obtained with a pericranial flap separating the neurocranium from the viscerocranium. Rigid support was provided by bone grafts fixed to a titanium mesh, anchored laterally to the orbital roofs. All patients had a computed tomography scan of the skull on the first or second postoperative day. Patients were observed for immediate and long‐term postoperative complications after such reconstruction.

Results Postoperative computed tomography scans showed small pneumocephalus in all patients. It resolved spontaneously and did not produce neurologic deficits in any patient. There was no cerebrospinal fluid leak, hematoma, or infection. On long‐term follow‐up, exposures of bone graft or mesh, brain herniation, or transmission of brain pulsation to the eyes were not observed in any patient.

Conclusions Three‐layer reconstruction using bone grafts, titanium mesh, and pericranial flap provides an alternative technique for repair of large anterior cranial base defects. It is safe and effective, and provides rigid protection to the brain.
Microvascular Transfer of Long Tracheal Autograft Segments in the Canine Model
Authors: Genden Eric M. , Gannon Patrick J. , Smith Shane , Keck Nancy , Deftereos Maria , Urken Mark L.
Published: November 2003

Objective The reconstruction of long segment tracheal defects represents an unsolved clinical dilemma. Prior attempts to directly revascularize tracheal segments have been unsuccessful. The objective of this study was to evaluate orthotopic autotransplantation of revascularized long tracheal segments in the canine model.

Methods Ten randomly selected mongrel dogs underwent excision, orthotopic reimplantation, and microvascular revascularization of a long segment (8.0 cm) of cervical trachea. The cranial thyroid artery and the internal jugular vein served as the vascular supply for the tracheal segment. The animals were maintained for a period of 30 days during which time graft viability was measured by routine endoscopic assessment and tracheal biopsies. Ex vivo, tracheal autografts were examined grossly for graft healing and microscopically for histologic architecture.

Results Seven of 10 dogs survived the predetermined 30‐day postoperative study period without complications. Postmortem examination demonstrated that 7 dogs had healed tracheal autograft segments with normal histologic architecture, 2 dogs sustained a postoperative wound infection and tracheal dehiscence, and 1 dog sustained a fatal postoperative hematoma.

Conclusions For the first time, we have demonstrated direct revascularization of long segment tracheal autografts in the dog model using the cranial thyroid artery and internal jugular vein as the vascular supply.
Vestibular Rehabilitation Using Visual Displays: Preliminary Study
Authors: Viirre Erik , Sitarz Robert
Published: November 2003

Objectives/Hypothesis Interactive computer displays can alter vestibular function. We hypothesized that by placing a vestibulopathic subject with chronic vertigo in a computer scene, slowing the visual scene motion to a rate slightly higher than their vestibulo‐ocular reflex (VOR) gain, and gradually speeding up the scene, we could cause VOR improvement and symptom reduction.

Study Design Randomized, nonblinded treatment/control study.

Methods Subjects were selected for VOR gain less than 0.5 at 0.16, 0.32, or 0.64 Hz. They wore a computer display that interacted with the movement of their head. The scene magnification controlling image motion was initially set approximately 5% higher than the VOR gain. Subjects had interaction tasks for 10 sessions of 30 minutes twice daily for 5 days. The scene magnification was gradually increased over the sessions. Control subjects had a similar procedure but were shown a normal, ×1.0 magnification for each interaction session.

Results Nine subjects and six control subjects were tested. Test subjects showed an average increase in VOR gain of 0.05 at 0.16 Hz, 0.048 at 0.32 Hz, and 0.098 at 0.64 Hz. In contrast, control subjects showed a decrease of 0.008 at 0.16 Hz, an increase of 0.016 at 0.32 Hz, and a decrease of 0.058 at 0.64 Hz. Improvement remained after 1 week but at a lower level than immediately after testing. Subject Dizziness Handicap Inventory scores decreased by 2.8 from 38.5 in the first week. Control subjects reported no symptom improvement.

Conclusion Immersive computer environments can improve VOR function and reduce vertigo.
Management of Chronic Otitis Media in the Only Hearing Ear
Authors: Battaglia Alex S. , Sabri Alain N. , Jackson C. Gary
Published: November 2003

Objective Chronic ear surgery is difficult. The management of such a disease either with or without cholesteatoma and in an only hearing ear is particularly challenging. Consequences of disease or unintended outcomes of therapy can both result in patient lifestyle alterations of major proportion. This report offers a diagnostic and treatment plan for chronic otitis media with and without cholesteatoma in the only hearing ear.

Methods More than 10,000 charts of patients with chronic otitis media were retrospectively reviewed. Twenty‐seven charts of patients with chronic otitis media in an only hearing ear who underwent surgical treatment were identified. The patients were followed for an average time of 43 months.

Results Overall, the chronic otitis media was well controlled, and there was no change in the average discrimination or hearing thresholds when comparing preoperative and postoperative results.

Conclusions Chronic otitis media with and without cholesteatoma in an only hearing ear can be treated successfully with hearing preservation. Canal wall down tympanomastoidectomy is performed in most cases. Manipulation of the ossicular chain is avoided, and cholesteatoma that lies over a potential fistula is exteriorized.
Increased Botulinum Toxin Type A Dosage Is More Effective in Patients With Frey's Syndrome
Authors: Guntinas‐Lichius Orlando
Published: November 2003

Objective To compare the duration of effect of two dosage regimes of botulinum toxin A to treat patients with Frey's syndrome.

Study Design Prospective study of two unselected cohorts of 20 patients each.

Methods The dimension of the affected skin area was determined with Minor's iodine–starch test. The skin was infiltrated with botulinum toxin type A (Dysport, Ipsen Pharma, Ettlingen, Germany) using an interinjection distance of 1 cm. In the first group, a concentration of 10 mount units (MU)/0.1 mL and in the second group a concentration of 20 MU/0.1 mL was used. At each injection site, 0.1 mL of the respective solution was injected. The outcome measures were the time of reappearance of gustatory sweating, and the results of an iodine–starch test 10 and 20 months after treatment.

Results Using the lower concentration, the mean duration of effectiveness was 8.3 ± 2 months (mean ± standard deviation). Using the higher concentration, the effect was much longer at 16.5 ± 6 months. Eighty‐five percent of the first group but only 5% of the second had a positive Minor's iodine–starch test 10 months after treatment. After 20 months four patients in the second group still had a negative iodine–starch test. In both groups, the amount of required botulinum toxin for the second treatment after recurrence of Frey's syndrome was the same as for the first treatment.

Conclusions Using a higher concentration of botulinum toxin type A (20 MU Dysport/0.1 mL) is more effective than a lower concentration (10 MU Dysport/0.1 mL) in the treatment of Frey's syndrome.
Tumor Angiogenesis as a Predictive Marker for Organ Preservation in Patients With Advanced Laryngeal Carcinoma
Authors: Teknos Theodoros N. , Cox Claudell , Barrios Martin A. , Chepeha Douglas B. , Bradford Carol R. , Fisher Susan G. , Wolf Gregory T.
Published: November 2003

Background The purpose of this study was to retrospectively investigate tumor angiogenesis as a predictive marker for response to neoadjuvant chemotherapy, organ preservation, and survival in patients with advanced laryngeal carcinoma.

Methods A total of 332 patients with stage III (188 patients) or stage IV (144 patients) squamous cell carcinoma of the larynx were entered in the prospective trial conducted by the Department of Veteran Affairs Laryngeal Cancer Study Group. Of this patient population, 20 pretreatment biopsy specimens were available from the chemotherapy arm for immunohistochemical analysis of Factor VIII expression. Two blinded investigators determined microvessel density in each patient by manual inspection of 10 high‐power (400×) fields (HPF).

Results The patients who had a partial response (>50% decrease in tumor volume) or complete response to chemotherapy had a mean value of 20.90 (± 8.09 standard deviation [SD]) blood vessels per HPF. Those who did not respond to chemotherapy and thus required a total laryngectomy had a mean value of 32.99 (± 10.10 SD) vessels per HPF. The difference of the means was statistically significant using a two‐tailed t test (P <.0085). Kaplan‐Meier survival curve analysis also revealed that patients with vessel counts above the mean tended to have poorer survival than those below the mean regardless of treatment selection. The most‐vascular tumors, those greater than 1 SD above the mean, had a statistically significant difference in survival and laryngeal preservation (P = .0345).

Conclusions These results indicate that tumor angiogenesis, as measured by number of vessels per HPF, was associated with decreased responsiveness to chemotherapy and radiation for larynx preservation. The most‐vascular tumors also were associated with poorer survival than those with lesser degrees of angiogenesis.
Acanthamoeba: A Rare Primary Cause of Rhinosinusitis
Authors: Rivera Miguel A. , Padhya Tapan A.
Published: November 2003

Parasitic infections, especially Acanthamoeba, are rarely implicated as a specific cause of rhinosinusitis. It is a fatal disease found in the immunocompromised population, in particular in patients infected with the human immunodeficiency virus (HIV). Less than 10 cases of Acanthamebic rhinosinusitis have been reported in the literature, and only 1 has survived. This case report presents an Acanthamebic infection misdiagnosed as a squamous cell carcinoma of the nasal septum on a presumptive healthy, immunocompetent 35‐year‐old woman. She was later diagnosed with AIDS (AIDS) along with disseminated Acanthamoebiasis and became the second reported case surviving this deadly illness. This case report also discusses the difficulty in diagnosing this rare parasite, the pathogenesis, and the multidisciplinary treatment required to control and manage this uniformly fatal disease.
Long‐Term Follow‐up of Fat Injection Laryngoplasty for Unilateral Vocal Cord Paralysis
Authors: McCulloch Timothy M. , Andrews Brian T. , Hoffman Henry T. , Graham Scott M. , Karnell Michael P. , Minnick Corey
Published: November 2003

Objective The objective of the study was to evaluate the results of autologous fat injection laryngoplasty in the long‐term management of unilateral vocal cord paralysis.

Study Design A retrospective chart review and clinical voice re‐evaluation of patients treated for unilateral vocal cord paralysis with autologous fat injection at the University of Iowa Hospitals and Clinics (Iowa City, IA) between May 1992 and September 1999.

Methods The data analyzed included patient demographics, early and long‐term vocal outcomes, additional surgical treatments, and patient survival.

Results Fifty patients were treated with fat injection laryngoplasty, which included 44 treated for unilateral vocal cord paralysis. Thirty‐one of the patients had fat injection as their primary procedure for permanent voice restoration. Eight patients treated had preoperative and postoperative voice data available. Using the GRBAS subjective voice assessment scale (0, normal; 3, severely abnormal), mean grade improved from 2.1 to 1.3 and breathiness improved from 1.4 to 0.5, at a mean period of 52 days. Thirteen of the 31 patients (41%) required additional procedures to achieve acceptable vocal outcomes. The median time to failure for these patients was 163 days. The initial treatment failure rate at 2 years was 30%, and the rate reached 45% by 4 years.

Conclusion Although fat injection laryngoplasty reliably improves the voice over the short term, the long‐term voice outcome is unpredictable. Additional surgeries to deal with subsequent vocal deterioration are common. The role of autologous fat injection laryngoplasty in the modern era is limited.
Voice Quality After Radiofrequency Volumetric Tissue Reduction of the Soft Palate in Habitual Snorers
Authors: Haraldsson P. ‐O. , Karling J. , Lysdahl M. , Svanborg E.
Published: November 2003

Objective To evaluate whether radiofrequency volumetric tissue reduction of the soft palate is causing voice changes as a result of velopharyngeal insufficiency in patients with heavy snoring.

Study Design A prospective study of 16 habitual snorers (oxygen desaturation index, <6 in all cases) were investigated concerning nasopharyngeal competence before and, at minimum, 2 months after the procedure (mean period, 165 d). Speech evaluation was made objectively with a nasal‐oral ratio meter and also was made subjectively by a trained speech‐language pathologist. The patients received a mean of three Somnoplasty radiofrequency volumetric tissue reduction treatments of 1200 J each (600 J in the midline and 300 J on each side of the soft palate).

Result Comparison between preoperative and postoperative nasal‐oral ratio meter analysis of hypernasality revealed no significant change. Neither did listener judgment of hypernasality, nasal escape, or pharyngeal snort reveal any influence on velopharyngeal function by the surgical procedures. Snoring was somewhat successfully treated, as evaluated by spouses; snoring score was reduced from 8.2 ± 2.9 to 4.1 ± 2.5 (P <.01) on a 10‐grade rating scale. Maximum nocturnal decibel levels were also reduced in 79% of the cases.

Conclusion Radiofrequency volumetric tissue reduction in the soft palate as a treatment for snoring did not show any significant adverse effect on nasopharyngeal function.
Familial Head and Neck Cancer: Molecular Analysis of a New Clinical Entity
Authors: Yu Kathy K. , Zanation Adam M. , Moss Jonathan R. , Yarbrough Wendell G.
Published: November 2003

Objective The tumor suppressor gene p16 encodes a cyclin‐dependent kinase inhibitor that normally inhibits cell proliferation by causing a G1 cell cycle arrest. The p16 gene is frequently mutated in a variety of somatic tumors, as well as in familial melanoma and familial pancreatic carcinoma. We identified a family with a high incidence of head and neck squamous cell carcinoma (HNSCC) and melanoma. Molecular analyses of the p16 gene locus in blood and tumor DNA from this family was performed to determine whether an association between germline p16 gene mutation and HNSCC exists.

Study Design Molecular pedigree analyses.

Methods Exon 2 of p16 was polymerase chain reaction amplified from blood, tumor, or nontumor DNA isolated from affected and unaffected members, then directly sequenced and compared with consensus p16 sequence. Cell cycle position of cells expressing wild‐type or mutant p16 was determined by flow cytometry.

Results Molecular analyses revealed a nonfunctional germline point mutation within exon 2 of the p16 gene that encodes a mutant p16 protein substituting proline at amino acid position 87 for the wild‐type arginine (p16R87P). Relative to wild‐type p16, p16R87P lost ability to cause a growth arrest following ectopic expression. The mutant (p16R87P) allele segregated with cancer predisposition in tested family members, and analyses of HNSCC tumor tissues demonstrated universal loss of wild‐type allele.

Conclusions Significance of the mutant p16 (p16R87P) in HNSCC tumorigenesis is strongly suggested by its loss of cell cycle arrest activity and its retention in tumor tissue with simultaneous loss of the wild‐type allele. Further, the germline p16 mutation segregated with cancer predisposition within the family. In aggregate, these data suggest that there is a direct causal relationship between the germline p16 mutation in this family and HNSCC tumorigenesis. Based on our observations, the spectrum of familial cancers associated with p16 mutations should include a new clinical entity, familial HNSCC.
Effects of Gap Junction Uncoupling in the Gerbil Cochlea
Authors: Spiess Adam C. , Lang Hainan , Schulte Bradley A. , Spicer S. S. , Schmiedt Richard A.
Published: November 2003

Objective To gain insight into molecular and cellular mechanisms regulating cochlear potassium (K+) recycling, including the possible effects of mutations in the GJB2 gene, which encodes the gap junction protein connexin 26. Intercellular K+ flux was manipulated in vivo by infusion of the gap junction uncoupler proadifen (SKF‐525A) into perilymph. Functional and structural alterations induced by gap junction blockade were assessed by electrophysiological and morphologic analysis.

Study Design Laboratory study using an animal model.

Methods Physiological effects of acute and chronic uncoupling of gap junctions in the Mongolian gerbil inner ear were evaluated by measurement of compound action potential (CAP) thresholds and input‐output (I/O) functions, distortion product otoacoustic emissions (DPOAE), and the endocochlear potential (EP). Morphologic changes were assessed by electron microscopy.

Results Acute exposures to proadifen resulted in large decreases in EP values, DPOAE magnitudes, and CAP I/O maximum amplitudes and an increase in high‐frequency CAP thresholds. These physiological changes were accompanied by vacuolization of type II and type V fibrocytes in the lateral wall of the cochlea. Chronic treatments revealed some recovery in EP values and CAP thresholds, which showed a relatively flat 15‐ to 20‐dB elevation across frequencies.

Conclusions Gap junctions play a significant role in normal cochlear function. In particular they appear to be essential for maintaining the EP, an activity that could be related to their participation in K+ recycling. Thus, hearing losses associated with mutations in the GJB2 gene that alter the expression or function of connexin 26 may result from a diminished capacity to recycle K+ from perilymph back to the stria vascularis and a consequent decline in the EP.
Internal Carotid Artery Transposition as Risk Factor in Pharyngeal Surgery
Authors: Galletti Bruno , Bucolo Sebastiano , Abbate Giuseppe , Calabrese Giancarla , Romano Giuseppe , Quattrocchi Carmelo , Freni Francesco
Published: November 2003

Objective/Hypothesis Injuries to the internal carotid artery during simple pharyngeal surgical procedures can be catastrophic for the risk of massive bleeding. The aims of the study were 1) to report five cases of congenital and asymptomatic anomalies of the internal carotid artery with a review of the literature, 2) to assess the relationships between these anomalies and the possible risk in “routine” pharyngeal surgery, and 3) to determine the most accurate imaging techniques to evaluate these anomalies.

Study Design Retrospective study of five patients with congenital anomalies of the internal carotid artery bulging the pharyngeal wall.

Methods Clinical records, pathology reports, and original imaging features of these kind of vascular lesions (computed tomography scans, three‐dimensional time‐of‐flight magnetic resonance angiogram, and Doppler ultrasonography) were reviewed for each patient; vascular lesions were related to possible risk factors for pharyngeal surgery; and a review of the literature was made.

Results All the patients were admitted for other diseases. The five anomalies, except one, were bulging the posterior pharyngeal wall and were asymptomatic. The peculiar literature referred 14 previous descriptions of similar anomalies.

Conclusions Some of the anomalies of the internal carotid artery can determine a bulge of the posterior pharyngeal wall. Because of the submucous position of the carotid artery at this level, such anomalies can constitute a risk factor for serious hemorrhage in routine surgical procedures that have become outpatient procedures and are often performed by inexperienced surgeons. The three‐dimensional time‐of‐flight magnetic resonance angiogram together with Doppler ultrasonography were shown to be the most accurate imaging techniques to evaluate these anomalies.
Implication of 18F‐Fluoro‐2‐Deoxy‐D‐Glucose Positron Emission Tomography on Management of Carcinoma of Unknown Primary in the Head and Neck: A Danish Cohort Study
Authors: Johansen Jørgen , Eigtved Annika , Buchwald Christian , Theilgaard Sune A. , Hansen Hanne S.
Published: November 2003

Objectives To demonstrate the efficacy of whole‐body 18F‐fluoro‐2‐deoxy‐D‐glucose positron emission tomography (18F‐FDG PET) in the detection of a carcinoma of unknown primary after conventional diagnostic workup in patients with a metastatic neck lesion and to demonstrate how the treatment policy of wide‐field irradiation can be safely modified in relation to the findings from PET scanning.

Study Design Prospective cohort study of consecutive patients.

Methods Forty‐two consecutive patients with squamous cell or undifferentiated metastatic disease in the neck from a carcinoma of unknown primary were enrolled after standard clinical workups. These patients underwent extensive clinical investigations including endoscopy under anesthesia with multiple mucosal biopsies and diagnostic imaging as well. If no primary site was indicated at this stage, a whole‐body 18F‐FDG PET scan was performed.

Results Potential focal pathological uptake indicated a primary tumor in 20 of 42 cases (48%). After PET, this was confirmed by additional investigations in 10 patients (24%). Of these, seven primaries were found in the head and neck region (hypopharynx [three], base of tongue/vallecula [two], nasopharynx [1], floor of mouth [1]), and three primaries were found below the clavicles (lung [1], esophagus [1], and abdomen [1]. Positron emission tomography resulted in significant modifications of radiation treatment fields or fractionation prescriptions in all the patients who were diagnosed with a primary tumor after PET.

Conclusion With our present strategy of wide‐field irradiation in patients with neck node metastases from a carcinoma of unknown primary, whole‐body 18F‐FDG PET had treatment‐related implications in 24% (10 of 42) of the patients.
Acoustic Tensor Tympani Response and Vestibular‐Evoked Myogenic Potential
Authors: Ochi Kentaro , Ohashi Toru , Kinoshita Hirotsugu
Published: November 2003

Objective To investigate the acoustic response properties and the vestibular‐evoked myogenic potential (VEMP) in various lesions.

Study Design Retrospective study of the clinical records of patients.

Methods Neurotological tests including acoustic response and VEMP were performed and analyzed in 62 patients with facial palsy, otosclerosis, ossicular chain interruption, sensorineural hearing loss, or acoustic tumor.

Results Inverted acoustic responses were observed in 25 of 38 (65.8%) patients with facial palsy, in 5 of 6 (83.3%) patients with acoustic tumor, and in all patients with otosclerosis, ossicular chain interruption, or sensorineural hearing loss. These inverted responses were obtained only when ipsilateral stimulation was used. The thresholds of the inverted responses were statistically significantly higher than those of the normal response.

Conclusions The vibration of the eardrum is thought to stimulate the ipsilateral trigeminal nerve, leading to contraction of the tensor tympani muscle. The stapedius response had an inhibitory effect on the inverted response. Vibration of the stapes footplate (which requires a normal middle ear conduction system) is necessary to induce the VEMP, whereas the functioning of the facial and cochlear nerves is independent of the VEMP response.
Quality of Life, Functional Outcome, and Costs of Early Glottic Cancer
Authors: Smith Jonathan C. , Johnson Jonas T. , Cognetti David M. , Landsittel Douglas P. , Gooding William E. , Cano Elmer R. , Myers Eugene N.
Published: November 2003

Objective To analyze quality of life, functional outcome, and hidden costs by primary treatment with surgery or radiation therapy in patients with early glottic cancer.

Study Design Retrospective study in a tertiary care facility.

Methods A group of 101 patients with carcinoma in situ and T1 invasive squamous cell carcinoma treated primarily with either surgery or radiation, between January 1990 and December 2000, were identified from searching our tumor registry. Patients completed two previously validated questionnaires and one local questionnaire. Statistical significance was assessed with the rank sum test, χ2 test, or Fisher's Exact test.

Results Questionnaires were completed in 59% (44 of 74) of the surgical cohort and 41% (11 of 27) of the radiation therapy cohort. The primary surgical treatments were endoscopic excision (86%), hemilaryngectomy (12%), and total laryngectomy (1%). Patient‐reported problems with swallowing, chewing, speech, taste, saliva, pain, activity, recreation, and appearance showed no difference between the endoscopic excision or radiation therapy cohorts. Comparing endoscopic excision versus radiation therapy, respectively, median number of treatments (2 vs. 35), total median travel distance (150 vs. 660 miles), total median travel time (180 vs. 1440 min), and total median number of hours of work missed (76 vs. 24) all differed significantly (P <.01).

Conclusions Almost all patients with early glottic cancer, whether treated with surgery or radiation therapy, reported excellent quality of life outcomes and functional results. In addition to actual costs, the hidden costs for radiation therapy versus endoscopic excision were all greater in terms of total number of hours of work missed, total travel time, and total travel distance.
Antigenic as Well as Nonantigenic Stimuli Induce Similar Middle Ear Responses in the Rat
Authors: Tonnaer Edith L. G. M. , Ingels Koen J. A. O. , Rijkers Ger T. , Curfs Jo H. A. J.
Published: November 2003

Objectives/Hypothesis The observation that during otitis media many different types of micro‐organisms have been cultured from effusions indicate that, once present in the middle ear cavity, most types of micro‐organisms are able to trigger an inflammatory reaction leading to otitis media. The present study was designed to determine the middle ear response after injection of different substances into the middle ear cavity.

Study Design To determine whether and to what extent an inflammatory response of the middle ear depends on the entering agent, the response in the tympanic cavity was studied by otomicroscopy and histological examination after inoculation of various substances.

Methods Lewis rats were inoculated in transtympanic fashion either with live or heat‐killed bacteria (pathogenic and nonpathogenic), Keyhole limpet hemocyanin, active charcoal, or saline. The mucosal response of the challenged middle ears was studied histologically.

Results Irrespective of the inoculated substance, no essential differences in the mucosal response were found. The intensity of the inflammatory response was greater when live bacteria were inoculated.

Conclusions The present study demonstrates that any substance reaching the middle ear cavity is likely to induce otitis media. These observations emphasize the role of the eustachian tube as “porte d'entrée” in the pathogenesis of this disorder. Determination of specific aspects of the eustachian tube involved in protection or in facilitating bacterial translocation will be important for the understanding of the pathogenesis of otitis media and the subsequent development of new therapeutic strategies. In addition, elucidation of bacterial factors involved in the process of colonization and translocation will be of equal importance.
Duplicate Publications in the Otolaryngology Literature
Authors: Rosenthal Eben L. , Masdon Jimmy Lee , Buckman Christy , Hawn Mary
Published: November 2003

Objective/Hypothesis A duplicate publication duplicates other published work by the same author(s). The purpose of the study was to define the extent of this problem within the otolaryngology literature.

Study Design Retrospective review of the literature.

Methods Original articles published in Archives of Otolaryngology—Head and Neck Surgery and Laryngoscope in 1999 were reviewed using the OVID search engine. Titles and abstracts from English articles written by the same first, second, or last author were analyzed, and suspected publications were evaluated. Duplicate publications were classified as dual (identical data set and conclusions) or suspected dual (nearly identical data set and conclusions) publications.

Results Of the 492 articles evaluated, 40 index articles were identified. These led to a total of 42 (8.5%) duplicate articles of which 27 were classified as dual and 15 as suspected dual publications. Approximately half of the duplicate publications were published by authors in the United States (55%). Duplicate articles usually appeared within 12 months of the each other (74%) and failed to cross‐reference the earlier publication (83%).

Conclusions Journal editors have become aware of an increase in the number of duplicate publications in the medical literature. The incidence of duplicate publications in the otolaryngology literature appears to be similar to that in other specialties.
Delivery of an Adenoviral Vector to the Crushed Recurrent Laryngeal Nerve
Authors: Rubin Adam , Mobley Bret , Hogikyan Norman , Bell Kimberly , Sullivan Kelli , Boulis Nicholas , Feldman Eva
Published: November 2003

Objectives Objectives were to create a model of recurrent laryngeal nerve injury for testing the efficacy of potential therapeutic viral gene therapy vectors and to demonstrate that remote injection of a viral vector does not cause significant additional neuronal injury.

Study Design Animal model.

Methods Rats were randomly assigned to three groups of 10 animals each. In group I, the recurrent laryngeal nerve was crushed. In group II, the nerve was crushed and then injected with an adenoviral vector containing no transgene. In group III, the nerve was identified but was not crushed. Rats were killed at 1 week, and their larynges and brainstems were cryosectioned in 15‐μm sections. Laryngeal cryosections were processed for acetylcholine histochemical analysis (motor endplates) followed by neurofilament immunoperoxidase (nerve fibers). Percentage of nerve–endplate contact was determined and compared between groups. Fluorescent in situ hybridization was performed on brainstem sections from rats in group II to confirm the presence of virus.

Results No significant difference in percentage of nerve–endplate contact exists between the two crushed‐nerve groups (groups I and II) (P = .88). The difference between both crushed‐nerve groups and the group with noncrushed nerves (group III) was highly significant (P <.0001). The presence of virus was confirmed in group II rats.

Conclusions Crush provides a significant measurable injury to the recurrent laryngeal nerve and may be used as a model to explore therapeutic interventions for nerve injury. The remote injection of viral vector did not cause significant additional neuronal injury. Remote delivery of viral vectors to the central nervous system holds promise in the treatment of recurrent laryngeal nerve injury and central nervous system diseases.
Effects of Pituitary Adenylate Cyclase—Activating Polypeptide on Facial Nerve Recovery in the Guinea Pig
Authors: Kimura Hiromoto , Kawatani Masahito , Ito Eiko , Ishikawa Kazuo
Published: November 2003

Objectives/Hypothesis Pituitary adenylate cyclase–activating polypeptide (PACAP) has neurotrophic effects of neural regeneration and gives protection to the nervous system. We investigated whether PACAP had a neurotrophic effect on peripheral motoneurons and whether PACAP could facilitate glial cell line–derived neurotrophic factor (GDNF), a neurotrophin, in nerve regeneration. The presence and distribution of PACAP receptors following facial nerve transection were also investigated.

Study Design Animal experiment.

Methods Unilateral transection of the facial nerve was performed in male Hartley guinea pigs, and PACAP was injected at the site. Saline was substituted as a control. Compound muscle action potentials were recorded to measure the changes of latency. Glial cell line–derived neurotrophic factor (GDNF) content in facial target muscle was measured using enzyme‐linked immunosorbent assay. The regenerating site was taken for histological studies.

Results Pituitary adenylate cyclase–activating polypeptide hastened the appearance of compound muscle action potentials and shortened the latency. Pituitary adenylate cyclase–activating polypeptide increased and prolonged the nerve transection‐induced GDNF increase in the facial muscles. The number of myelinated fibers at 1 to 4 weeks after the transection was increased. PAC1 receptor or VPAC1 receptor or both were identified in the injury area at 2 to 4 weeks.

Conclusions Pituitary adenylate cyclase–activating polypeptide facilitated the recovery of latency of compound muscle action potentials or the number of myelinated axons, or both. Pituitary adenylate cyclase–activating polypeptide prolonged the GDNF levels in target organs. These data indicated that PACAP promoted regeneration of the facial nerve.
Pitch‐Raising Surgery in Fourteen Male‐to‐Female Transsexuals
Authors: Wagner Isabelle , Fugain Claude , Monneron‐Girard Lucile , Cordier Bernard , Chabolle Frédéric
Published: November 2003

Objective To evaluate the indications and results of pitch‐raising surgery in male‐to‐female transsexual patients.

Study Design Retrospective study of male‐to‐female transsexual patients who underwent pitch‐raising surgery between 1994 and 2001 at a single institution.

Methods The 14 patients had inadequate improvements after speech therapy alone. After anterior commissure advancement (n = 2), cricothyroid approximation (n = 9), or both (n = 3), results were evaluated subjectively by the patients and speech therapists and objectively by electroglottographic measurement of fundamental frequencies (usual, maximal, and minimal), postoperative gain in usual fundamental frequency, and the percentage of irregularities.

Results Cricothyropexy disruption occurred in two patients. Median follow‐up was 6.5 months. Subjective success rates were 78.5% and 71.5% according to the patients and speech therapists, respectively. Usual, maximal, and minimal frequencies increased significantly; median postoperative gain in usual fundamental frequency was 11 Hz. Three of the four patients with a poor objective result continued to smoke after surgery.

Conclusion Pitch‐raising surgery induces subjective and objective improvements but should be reserved for patients in whom speech therapy is not sufficiently effective.