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Objectives: Recurrent respiratory papillomatosis (RRP) is often described as a benign disease. However, the natural progression of dysplasia and transformation to squamous cell carcinoma has not been elucidated for RRP. This study delineates our extensive experience with dysplasia in RRP., Study Design/setting: Case series with chart review., Subjects and Methods: Demographic data and surgical pathology were analyzed for patients diagnosed with RRP at greater than 18 years of age who underwent operative intervention without cidofovir treatment for RRP between 2004 and 2009., Results: Fifty-four patients were identified. Dysplasia was identified in 27 of 54 patients (50%). Of the 54 patients, 50% had no dysplasia, 26% had mild dysplasia (grade 1), 11% had moderate dysplasia (grade 2), 4% had severe dysplasia (grade 3), 7% had carcinoma in situ, and 2% had squamous cell carcinoma as the highest documented degree of dysplasia. Thirty of 54 patients (55.6%) had 2 or more operative interventions. Nine of the 30 patients (30%) developed a higher dysplastic grade during the course of treatment. Time to progression averaged 16.2 ± 8.7 months for patients with initially benign disease. Of those patients with dysplasia progression, only 1 of 9 (11.1%) developed squamous cell carcinoma. Patients presenting with benign or mild dysplasia typically did not progress beyond mild dysplasia (22 of 24, 91.7%)., Conclusions: Dysplasia is common in RRP. Progression of dysplasia, especially with an initial dysplastic grading of benign or mild disease, is rare.

Objectives: To determine patient compliance with voice rest and the impact of voice rest on quality of life (QOL)., Study Design: Prospective., Setting: University hospital., Subjects and Methods: Demographics, self-reported compliance, QOL impact on a 100-mm visual analog scale (VAS), and communication methods were collected from 84 participants from 2 academic voice centers., Results: Of 84 participants, 36.9% were men, 63.1% were women, and 64.3% were singers. The mean age of participants was 47.2 years. The mean duration of voice rest was 8.8 days (range, 3-28), and the median was 7 days. Overall compliance was 34.5%. Postoperative voice rest patients were more compliant than non-postoperative patients (42.4% vs 16.0%, P = .04, χ(2)). Voice rest had an impact on QOL (mean ± SD, 68.5 ± 27.7). Voice rest also had a greater impact on singers than nonsingers (mean VAS 77.2 vs 63.6, P = .03, t test) and on those age <60 years than those age ≥ 60 years (mean VAS 74.4 vs 46.7, P < .001, t test). More talkative patients and those with longer periods of voice rest had worse QOL scores (Spearman correlation = 0.35, P = .001 and Spearman correlation = 0.24, P = .03, respectively). Restrictions in personal and social life were noted in 36.9% of patients, 46.4% were unable to work, 44.0% felt frustrated, and 38.1% reported feeling handicapped while on voice rest., Conclusions: Given poor patient compliance and the significant impact of voice rest on QOL, further studies are warranted to examine the efficacy of voice rest and factors that may contribute to patient noncompliance with treatment.

Background: Dilation of intercellular spaces is reported to be an early morphological marker in gastro-oesophageal reflux. It remains unknown if this marker is useful in diagnosing reflux-related chronic laryngitis., Aim: To determine histopathology and electron microscopic changes in oesophageal and laryngeal epithelium in chronic laryngitis., Methods: In this prospective blinded study, we enrolled 53 participants: 15 controls, 20 patients with GERD and 18 patients with chronic laryngitis. The latter two groups were subsequently treated with lansoprazole 30 mg bid for 12-weeks. Baseline and postacid suppressive therapy biopsies were obtained from distal oesophagus and laryngeal postcricoid areas. Biopsy specimens were evaluated for histopathology and dilated intercellular space changes., Results: There was no significant increase in oesophageal or laryngeal epithelium intercellular spaces among GERD or laryngitis patients compared with controls at baseline or postacid suppressive therapy. Only patients with GERD had significantly (P = 0.03) higher proportion of moderate-to-severe oesophageal spongiosis and basal cell hyperplasia, which normalized postacid suppressive therapy., Conclusions: There was no increase in the width of intercellular spaces in the oesophagus or larynx in GERD or chronic laryngitis at baseline or postacid suppressive therapy. Our findings question the uniform presence of dilated intercellular space in patients with GERD., (2010 Blackwell Publishing Ltd.)

Objective: To investigate the hypothesis that a transient episode of raised-intensity phonation causes a significant increase in vocal fold inflammatory messenger RNA (mRNA) expression in vivo., Study Design: Prospective animal study., Setting: Laboratory., Subjects and Methods: Ten New Zealand White breeder rabbits received 30 minutes of experimentally induced modal or raised-intensity phonation, followed by a 30-minute recovery period. A separate group of five rabbits served as sham controls. Real-time polymerase chain reaction was performed to investigate the mRNA expression of interleukin 1beta (IL-1beta), transforming growth factor beta-1 (TGFbeta1), and cyclooxygenase-2 (COX-2). Separate one-way analysis of variance (ANOVA) tests were used to investigate differences in gene expression across groups, with an appropriate alpha correction of 0.016 to control for type I error. Significant main effects were further examined using Fisher's least significant difference., Results: ANOVA revealed that there were differences for IL-1beta, TGFbeta1, and COX-2 between sham control, modal phonation, and raised-intensity phonation (P 0.0001). Pairwise comparisons revealed that the expression of IL-1beta, COX-2, and TGFbeta1 increased significantly during raised-intensity phonation, compared to modal phonation and sham control (P 0.0001)., Conclusion: Results provided support for the hypothesis that a transient episode of raised-intensity phonation causes a significant increase in vocal fold inflammatory mRNA expression. Future studies will investigate the signal transduction pathways and mechanisms regulating the vocal fold inflammatory response. The long-term goal of these studies is to advance understanding of the molecular and cellular events underlying phonation-related tissue alterations.

Owing to their vasodilatory effects, the phosphodiesterase-5 inhibitors have become widely used for the treatment of erectile dysfunction. Among the reported adverse events of these agents are epistaxis, variceal bleeding, intracranial hemorrhage, and hemorrhoidal bleeding. We report a case of vocal fold hemorrhage that occurred after vardenafil use in a 31-year-old man who was a professional singer.

Objectives/hypothesis: Age, vocal fold atrophy, glottic closure pattern, and the burden of medical problems are associated with voice therapy outcomes for presbyphonia., Study Design: Retrospective., Methods: Records of patients seen over a 3-year period at a voice center were screened. Inclusion criteria consisted of age over 55 years, primary complaint of hoarseness, presence of vocal fold atrophy on examination, and absence of laryngeal or neurological pathology. Videostroboscopic examinations on initial presentation were reviewed. Voice therapy outcomes were assessed with the American Speech-Language-Hearing Association National Outcomes Measurement System scale. Statistical analysis was performed with Spearman rank correlation and chi(2) tests., Results: Sixty-seven patients were included in the study. Of the patients, 85% demonstrated improvement with voice therapy. The most common type of glottic closure consisted of a slit gap. Gender or age had no effect on voice therapy outcomes. Larger glottic gaps on initial stroboscopy examination and more pronounced vocal fold atrophy were weakly correlated with less improvement from voice therapy. A weak correlation was also found between the number of chronic medical conditions and poorer outcomes from voice therapy., Conclusions: The degree of clinician-determined improvement in vocal function from voice therapy is independent of patient age but is influenced by the degree of vocal fold atrophy, glottic closure pattern, and the patient's burden of medical problems.

Objectives/hypothesis: Review of clinical experience and results using botulinum toxin type A (BTX) for the management of adult patients with respiratory compromise due to new onset bilateral vocal fold motion impairment (BVFMI)., Study Design: Retrospective case series., Methods: The records of 11 patients from two institutions with respiratory compromise due to bilateral vocal fold motion impairment were reviewed. Age, sex, etiology of motion impairment, subjective response to BTX injections, changes in pulmonary function studies pre- and postinjection when available, the dosage of botulinum toxin required to achieve response, the number of injections per patient, and complications were reported., Results: All patients were over 18 years old. There were three male and eight female subjects. The etiology of BVFMI was due to previous anterior cervical surgery in nine patients and prolonged intubation in two. Ten patients reported symptomatic improvement and returned for an average of nine injections over the 10-year period of study. The most common interval between injections was 3 months. In all patients the dose required to achieve symptomatic improvement was at least 2.5 mouse units injected into each vocal fold. One patient without relief of symptoms had bilateral cricoarytenoid joint fixation. Complications were limited to moderate dysphagia in one patient and breathy dysphonia in all patients., Conclusions: BTX injection into the vocal folds provides temporary relief of symptoms in airway obstruction in adult patients with BVFMI. Patients require an average of 2.5 units of botulinum injection into each vocal fold and have an average length of response of 3 months. BTX injection may be used as a form of temporary relief of airway obstruction in patients wishing to avoid ablative surgery or tracheotomy.

Objectives/hypothesis: Laryngopharyngeal reflux (LPR) represents a challenging field. Therapeutic studies of proton pump inhibitors in LPR have shown mixed results. The Restech pH catheter (Respiratory Technology Corp., San Diego, CA) is a minimally invasive device for detection of oropharyngeal acid reflux. The aim of this study was to provide normative data using this device in both distal esophagus and oropharynx., Study Design: Prospective observational study., Methods: Normal volunteers were recruited to undergo pH monitoring. A custom made longer catheter was used to assess distal esophageal pH. Oropharyngeal pH catheter was placed at the level of uvula. The distribution of % time was summarized using the 5th, 25th, 50th (median), 75th, and 95th quantiles for pH < 6, pH < 5, and pH < 4 for both upright and supine positions., Results: A total of 20 normal, healthy volunteers underwent pH monitoring for 14 to 24 hours (median 20.5 hours). The 95th percentile for % total time pH < 4, pH < 5, pH < 6 for the distal esophageal pH catheter were 4.52%, 10.91%, and 42.99%, respectively. For the oropharynx pH probe, the 95th percentile for % total time pH < 4, pH < 5, and pH < 6 were 0.02%, 2.33%, and 21.41% respectively. The 95th percentile for number of reflux events for total pH < 4, pH < 5, and pH < 6 were 1.3, 8.1, and 128.0, respectively., Conclusions: Oropharyngeal acid reflux is an infrequent occurrence in healthy volunteers without LPR. The normative data for Restech pH catheter may now be compared to those with suspected LPR.

Background & Aims: Intraluminal impedance monitoring has given new dimensions to the diagnosis of reflux disease. However, there is no defined algorithm for evaluating refractory reflux symptoms. We studied whether combined impedance/pH monitoring in patients on therapy can predict acid reflux in patients off therapy and whether testing should be carried out when patients are on or off therapy., Methods: Thirty-nine adults (mean age, 50 years; 24 female) with refractory reflux symptoms were evaluated by impedance/pH monitoring while on therapy, followed by wireless pH monitoring while off therapy. Non-acid reflux events in patients on therapy were correlated with acid reflux parameters studied off therapy. In addition, the likelihood of test abnormalities on and off therapy was determined., Results: In 25 of 39 patients (64%) on therapy, impedance testing was normal, with a median of 69 events (interquartile, 63.0-78.0). The percentage of time at pH <4 was within the normal range for all patients who were on therapy. The pH test results were abnormal in 28 of 39 patients (72%) when studied off therapy. Ninety-three of patients with abnormal impedance on therapy also had abnormal acid reflux off therapy. When both groups were off therapy, the patients with abnormal impedance parameters on therapy had significantly higher median (interquartile) 2-day baseline levels of esophageal acid exposure (8.7%, 6.9%-12.5%), compared with those of patients with normal impedance parameters while on therapy (6.0%, 2.8%-9.4%; P = .026)., Conclusions: Abnormal impedance in patients on therapy predicts acid reflux in patients off therapy. In patients with refractory reflux, combined impedance/pH monitoring might provide the single best strategy for evaluation of reflux symptoms.

Introduction: Otolaryngologists implement transnasal esophagoscopy (TNE) to assess esophageal pathology. Previous studies using TNE are largely retrospective and deal with select patient populations. The prevalence of esophageal pathology in patients presenting with throat symptoms to an otolaryngology voice center is presently unknown., Objective: To assess the prevalence of esophageal pathology in this population and determine the interobserver variability of the findings reviewed by an otolaryngologist and a gastroenterologist., Study Design: A prospective study., Setting: This study was conducted in a laryngology/voice subspecialty clinic., Subjects and Methods: Fifty patients with throat symptoms presenting to the voice center were asked prospectively to undergo TNE. The findings were videotaped and reviewed by an otolaryngologist and a gastroenterologist blinded to the patients' presenting complaint., Results: Hoarseness was the most common presenting symptom (68%). According to the gastroenterologist, the prevalence of esophageal findings was: z-line irregularity suspicious for Barrett esophagus (12%), esophagitis (10%), hiatal hernia (32%), and esophageal stricture (10%). The percent agreement for a normal study was 72 percent. The percent agreement for various pathological findings were as follows: Barrett esophagus 86 percent, esophagitis 88 percent, hiatal hernia 76 percent, and esophageal stricture 96 percent. For an abnormal study, the percent agreement was 80 percent., Conclusion: Esophageal abnormalities are common in patients presenting to a voice subspecialty clinic.

The diagnosis of laryngopharyngeal reflux (LPR) is increasingly common in otolaryngology practice. Patients with nonspecific throat and voice symptoms, such as throat clearing, hoarseness, cough, sore throat, and globus, are frequently treated empirically with antireflux medication by otolaryngologists and primary care physicians. Physical findings such as laryngeal erythema, edema, and posterior laryngeal mucosal thickening are also frequently attributed to LPR. The literature has been inconsistent, with few prospective, randomized trials showing efficacy for this clinical practice. Because of the lack of specific signs and symptoms of LPR, clinicians should be aware of other potential causes for these clinical presentations. Recently published studies describe the association between allergy or asthma and many of the same symptoms attributed to reflux disease. Muscle tension dysphonia can also present with hoarseness and symptoms of throat irritation. Although LPR can cause the symptoms and signs described previously, it should not be the only diagnosis considered by the evaluating physician. Failure to consider other possible causes may result in unnecessary treatment and potential delay in diagnosis. This article discusses this topic, citing some of the pertinent literature published over the past 2 years.

Objective: This study will determine factors that influence the self-perceived handicap associated with singing voice problems., Study Design: A prospective cohort., Subject and Methods: Singers presenting to a voice clinic prospectively completed the Singing Voice Handicap Index (SVHI) before evaluation and treatment. Demographic data, singing style, professional status, duration of symptoms, medical problems, and diagnosis were collected. Univariate and multivariate analysis was performed., Results: One hundred seventy-one singers completed the SVHI. The duration of symptoms, being an amateur singer or singing teacher, benign vocal fold lesions, and neurologic voice disorders were associated with increased SVHI scores (P < 0.05, multiple linear regression). Age greater than 50 years and gospel singing were predictive of increased SVHI scores only on univariate analysis (P < 0.05, t test)., Conclusion: Singers experience significant handicap as a result of their singing problems with certain factors associated with greater impairment. Targeting interventions at patients more severely affected may improve outcomes.

Objective/hypothesis: This study will test the hypothesis that proton pump inhibitor (PPI) use is prevalent among patients referred for hoarseness and will assess the ultimate diagnosis and factors associated with patients' voice outcomes., Study Design: Retrospective review of patients in a tertiary care voice clinic., Methods: Patients with a primary diagnosis of hoarseness, who were taking or had taken PPIs in the previous 2 months and referred to a tertiary care voice clinic, were identified. The dosage and length of PPI administration, patient report of gastroesophageal reflux (GER), presence of findings suggesting muscle tension dysphonia (MTD), patient demographics, diagnosis, chronicity of symptoms, interventions, follow-up, and outcome were determined., Results: Of 299 patients, 264 met the inclusion criteria. The mean age was 47.2 years, with a range of 18 to 89 years, with 26.7% male and 73.3% female. Among patients referred for voice problems, 148 (56.1%) had previously tried PPIs or were currently on PPI treatment; 44 (29.7%) stopped taking their PPI because of continued hoarseness, and 104 (70.3%) had persistent hoarseness and associated throat complaints despite continued PPI treatment. Among patients who quit taking their PPI because of continued voice complaints, 79.5% did not have traditional GER symptoms of heartburn or regurgitation. The most common treatment after referral was voice therapy, with an overall voice therapy response rate of 62.7%., Conclusions: PPI use is prevalent among patients referred because of persistent hoarseness. Whether patients have GER or MTD may influence patients' voice outcomes in response to PPI treatment.

We report a method, Expression-Microarray Copy Number Analysis (ECNA) for the detection of copy number changes using Affymetrix Human Genome U133 Plus 2.0 arrays, starting with as little as 5 ng input genomic DNA. An analytical approach was developed using DNA isolated from cell lines containing various X-chromosome numbers, and validated with DNA from cell lines with defined deletions and amplifications in other chromosomal locations. We applied this method to examine the copy number changes in DNA from 5 frozen gastrointestinal stromal tumors (GIST). We detected known copy number aberrations consistent with previously published results using conventional or BAC-array CGH, as well as novel changes in GIST tumors. These changes were concordant with results from Affymetrix 100K human SNP mapping arrays. Gene expression data for these GIST samples had previously been generated on U133A arrays, allowing us to explore correlations between chromosomal copy number and RNA expression levels. One of the novel aberrations identified in the GIST samples, a previously unreported gain on 1q21.1 containing the PEX11B gene, was confirmed in this study by FISH and was also shown to have significant differences in expression pattern when compared to a control sample. In summary, we have demonstrated the use of gene expression microarrays for the detection of genomic copy number aberrations in tumor samples. This method may be used to study copy number changes in other species for which RNA expression arrays are available, e.g. other mammals, plants, etc., and for which SNPs have not yet been mapped.

A complete and thorough vocal history and physical examination is the cornerstone of the evaluation of any patient who has a vocal complaint. Continued scientific progress in the understanding of vocal fold vibration and sound production combined with advances in technology have resulted in the availability of numerous supplemental diagnostic laboratory tools for an optimal voice evaluation. This article presents additional clinical tools accessible to the otolaryngologist that may aid in diagnosis and help elucidate difficult vocal tract pathology.

Objectives: We developed and validated a disorder-specific health status instrument (Singing Voice Handicap Index; SVHI) for use in patients with singing problems., Methods: Prospective instrument validation was performed. Of 81 original items, those with poor statistical validity were eliminated, resulting in 36 items. The ability to discriminate dysphonic from normal singers, test-retest reliability, internal consistency, and construct validity were assessed., Results: We included 112 dysphonic and 129 normal singers, professional and nonprofessional, of classical, country, rock, choral, and gospel repertoire. Dysphonic singers had worse SVHI scores than normal singers (p < or = .001, rank sum test). Test-retest reliability was high (Spearman correlation, 0.92; p < or = .001). Internal consistency demonstrated a Cronbach's alpha of .97, and the correlation between the SVHI and self-rated singing voice impairment was .63 (p < or = .001, Spearman correlation)., Conclusions: The SVHI is a reliable and valid tool for assessing self-perceived handicap associated with singing problems.

Objective: To evaluate the efficacy of voice therapy in the management of vocal fold polyps and cysts., Study Design and Setting: Retrospective review of vocal fold cysts and polyps undergoing voice therapy in a tertiary care center. Symptom resolution or persistence resulting in surgical intervention was the main outcome measure., Results: Fifty-seven patients were identified, of which 49.1% achieved symptom resolution with voice therapy alone. Patients with complete glottal closure and muscle tension dysphonia did not have a better response than those with incomplete glottal closure and without muscle tension dysphonia (P = 0.1, chi(2), respectively). Patients with translucent polyps more commonly responded to voice therapy than fibrotic, hyaline, or hemorrhagic polyps, 81.8% versus 15.4% and 25.0% response rate, respectively (P = 0.002, chi(2))., Conclusions: Voice therapy is an effective treatment modality for vocal fold polyps and cysts., Significance: A multidisciplinary approach including a trial of voice therapy is warranted.

Objectives: Several studies have explored posttreatment voice outcomes for early glottic cancer with varying results. To further clarify the voice-related quality of life (QOL) of T1 glottic cancer patients treated by external beam radiotherapy (EBRT) compared to endoscopic carbon dioxide laser excision (CLE), we performed a meta-analysis., Methods: We performed a meta-analysis review for the years 1966 to 2005 for the Voice Handicap Index (VHI), laryngeal cancer, voice outcome, voice quality, and quality of life. Studies in which the VHI was assessed at least 3 months after treatment for T1 glottic cancer were identified and analyzed by meta-analysis techniques., Results: Six studies with 208 patients (6 T1b and 202 T1a) treated with CLE and 91 patients (6 T1b and 85 T1a) treated with EBRT were identified. The posttreatment VHI scores were similar for the EBRT- and CLE-treated patients (p = .1, Wilcoxon rank sum test)., Conclusions: We conclude that CLE and EBRT provide comparable levels of voice handicap for patients with T1 glottic cancer.

Objectives: This study explores whether videoendoscopic findings and patient history help make the diagnosis in bilateral vocal fold immobility (BVFI)., Methods: Medical records from 1995 to 2003 were searched to identify patients with posterior glottic stenosis (PGS) and bilateral vocal fold paralysis (BVFP) who also had videoendoscopic examinations. Videoendoscopic examination findings that could help differentiate PGS from BVFP were identified a priori. A weighted scoring index, based on the adjusted odds ratios of significant examination findings on multiple logistic regression, was derived. Associations between the weighted scoring index, patient history, and diagnosis were then evaluated., Results: Twenty-six patients with BVFP and 28 patients with PGS were identified. Posterior glottic scar (weight = 2), medial arytenoid erosion with a widened posterior glottis (weight = 1), and appropriate vocal fold motion (weight = 1) were significant variables (p < or = .05, multiple logistic regression) and constituted the weighted scoring index. A weighted scoring index of > or = 2 and a history of prolonged intubation predicted PGS in 95.2% of cases. A weighted scoring index of < or = 1 and a history of neck surgery predicted BVFP in 95.0% of cases., Conclusions: The weighted scoring index with the patient history provides an objective tool for diagnosing BVFI.

The intent of this chapter is to provide the reader with a review of GeneChip technology and the complete system it represents, including its versatility, components, and the exciting applications that are enabled by this platform. The following aspects of the technology are reviewed: array design and manufacturing, target preparation, instrumentation, data analysis, and both current and future applications. There are key differentiators between Affymetrix' GeneChip technology and other microarray-based methods. The most distinguishing feature of GeneChip microarrays is that their manufacture is directed by photochemical synthesis. Because of this manufacturing technology, more than a million different probes can be synthesized on an array roughly the size of a thumbnail. These numbers allow the inclusion of multiple probes to interrogate the same target sequence, providing statistical rigor to data interpretation. Over the years the GeneChip platform has proven to be a reliable and robust system, enabling many new discoveries and breakthroughs to be made by the scientific community.

This study evaluates how extraesophageal reflux affects membranous vocal fold healing in a canine model. We created membranous vocal fold injuries in the animals and randomly assigned them to topical application of acid and pepsin at pH 2 or pH 6 or of normal saline solution every other day for 12 days. The experimental vocal folds were compared to uninjured, control vocal folds from animals painlessly sacrificed for other reasons. Hematoxylin and eosin, fibronectin, and procollagen I staining were performed for histologic analysis. The injured specimens had three times greater cellular infiltrate (p < or = .001, analysis of variance) and twice as much fibronectin and procollagen I (p < or = .001, analysis of variance) as did the specimens from the control animals. No significant differences or trends were identified for cellular infiltrate, fibronectin, or procollagen I within the injured groups (p > .05, Bonferroni t-test). Acute wound healing did not appear to be influenced by the presence of acid and pepsin at pH 2 or 6 as compared to saline solution.

Preservation of the vocal fold cover during laryngeal surgery should optimize vocal outcomes for patients with benign glottal lesions. The aim of this study was to evaluate changes in the quality of life, perceptual voice evaluation, and acoustic and aerodynamic measures of patients before and after endoscopic laryngeal microsurgery for true vocal fold cysts, polyps, and scarring. Preoperative and postoperative Voice Handicap Index (VHI) scores, Short Form 36 scores, and perceptual, acoustic, and aerodynamic voice measures were obtained prospectively from 42 patients who underwent phonomicrosurgery from February 2000 through May 2003. The mean (+/-SD) preoperative VHI was 49.6 +/- 21. The mean postoperative VHI score at a minimum of 3 months after surgery decreased to 26.8 +/- 21 (p < .001). When divided by lesion type, VHI scores improved significantly after surgery for vocal fold polyps and cysts. Although patients with vocal fold scarring demonstrated improvement in VHI scores after surgery, statistical significance was not achieved. For the entire group, the Short Form 36 scores were not significantly different from US norms either before or after operation. The acoustic data showed statistically significant decreases in jitter (2.05% to 1.26%), shimmer (7.06% to 4.03%), and noise-to-harmonics ratio (0.18 to 0.13) after surgery (p < .05) in female patients. The upper pitch limit increased after surgery in women (495.3 Hz to 654.9 Hz, p < .001). These results indicate that the voice-related quality of life and some acoustic parameters improve significantly for patients who have undergone laryngeal microsurgery for vocal fold cysts and polyps. Vocal fold scarring remains a difficult clinical problem with less favorable outcomes following surgical treatment in this patient set.

Objectives/hypothesis: To compare open and CO2 laser-assisted endoscopic surgical management of Zenker's diverticulum., Study Design: A retrospective review of 49 consecutive surgically treated patients with Zenker's diverticulum was conducted., Methods: Patients' records were reviewed and analyzed for patient age and sex, size of diverticulum, incision time (time recorded from start of incision to surgical completion of case), length of hospital stay, complications, and follow-up management. A postoperative questionnaire inquiring about swallow function was conducted by mail or telephone. Swallow function was assessed on a four-point scale., Results: Various procedures performed included endoscopic CO2 laser-assisted diverticulotomy (n = 24) and open diverticulectomy with cricopharyngeal myotomy (n = 28). The average incision time of laser endoscopic cases (47 min) was significantly shorter (P <.001) than that of open diverticulectomy cases (170 min). Length of hospital stay did not significantly vary between the two groups. Five patients (21%) initially treated with laser endoscopic diverticulotomy demonstrated symptomatic persistent Zenker's diverticulum; three underwent repeat operation. No open cases required repeat operation. One endoscopic case was aborted secondary to esophageal injury from placement of the endoscope. Postoperative fever was seen in two (8%) endoscopic cases and four (14%) open approach cases. No major complications (recurrent laryngeal nerve paralysis, mediastinitis, or death) were encountered. More than 90% of respondents in each treatment group reported normal or near-normal swallow function., Conclusion: Laser endoscopic management is a reasonable and safe method for surgical treatment of Zenker's diverticulum in comparison with the open technique. Employment of the endoscopic approach reduces operative time and the complexity of postoperative care. Practitioners should be aware that the endoscopic approach may result in a higher failure rate.

A prospective study was designed to characterize patients with typical and extraesophageal reflux (EER) symptoms and seek predictive patterns for each group. Fifteen subjects without symptoms, 16 patients with symptomatic gastroesophageal reflux disease (GERD), and 37 patients with symptomatic EER were evaluated with outcomes tools, videolaryngoscopy, and 24-hour triple-probe pH monitoring. Higher symptom scores, Voice Handicap Index scores, and Gastrointestinal Symptom Rating Scale scores, as well as similarly decreased quality of life as measured by the Short Form 36, were noted among the two symptomatic groups. Patients with clinically diagnosed EER were more likely to have multiple abnormalities on laryngoscopy. There was a trend toward more pharyngeal reflux episodes in EER patients (6.9 +/- 8.9) as compared to GERD patients (6.0 +/- 9) and asymptomatic subjects (1.1 +/- 1.9). On the basis of the pH monitoring of asymptomatic subjects, we define pathological pharyngeal reflux as more than 5 episodes in 24 hours. Pharyngeal acid exposure is more common in patients presumed to have EER, but some pharyngeal reflux does occur in asymptomatic subjects. Neither symptom scores nor videolaryngoscopic findings were predictive of pathological EER as indicated by pH monitoring.

Pseudomonas aeruginosa is a ubiquitous environmental bacterium capable of causing a variety of life-threatening human infections. The genetic basis for preferential infection of certain immunocompromised patients or individuals with cystic fibrosis by P. aeruginosa is not understood. To establish whether variation in the genomic repertoire of P. aeruginosa strains can be associated with a particular type of infection, we used a whole-genome DNA microarray to determine the genome content of 18 strains isolated from the most common human infections and environmental sources. A remarkable conservation of genes including those encoding nearly all known virulence factors was observed. Phylogenetic analysis of strain-specific genes revealed no correlation between genome content and infection type. Clusters of strain-specific genes in the P. aeruginosa genome, termed variable segments, appear to be preferential sites for the integration of novel genetic material. A specialized cloning vector was developed for capture and analysis of these genomic segments. With this capture system a site associated with the strain-specific ExoU cytotoxin-encoding gene was interrogated and an 80-kb genomic island carrying exoU was identified. These studies demonstrate that P. aeruginosa strains possess a highly conserved genome that encodes genes important for survival in numerous environments and allows it to cause a variety of human infections. The acquisition of novel genetic material, such as the exoU genomic island, through horizontal gene transfer may enhance colonization and survival in different host environments.

We investigated wound healing of vocal fold mucosal excisions using a canine model, comparing cold steel, the continuous wave (CW) carbon dioxide (CO2) laser, and a new, microsecond-pulsed CO2 laser. The thermal injury to the surrounding normal tissues produced by the laser increases the risk for scar formation and poor functional voice outcome. This injury may be reduced with a pulsed CO2 laser. Acute, 2-week, and 6-week studies of 15 dogs were made with blinded observers and nonparametric statistical analyses. Histologic comparison showed less thermal injury and scar formation in the vocal folds treated with the pulsed CO2 laser than with the CW CO2 laser. Functional outcomes as studied with laryngeal videostroboscopy revealed better vibratory characteristics with the pulsed CO2 laser as compared with the CW CO2 laser. No differences were seen on these measures between the pulsed laser and cold techniques. Pulsed CO2 lasers may offer the ease of laser laryngology and the superior wound healing of cold steel.

For evaluation of the effect of topical mitomycin-C on vocal fold healing and return of function after surgical excision of mucosa, 6 dogs underwent suspension microlaryngoscopy with bilateral microflap excision of vocal fold mucosa. Topical mitomycin-C, a chemotherapeutic agent and a fibroblast inhibitor, was applied randomly to one side, with the contralateral side serving as the control. Laryngeal videostroboscopy (LVS) was performed on each animal before the operation, at 2 weeks, and before sacrifice at 4 weeks. Both functional analysis with LVS and histologic analysis were performed in a blinded fashion to determine the effect of mitomycin-C on healing. Histologic analysis was augmented with computer morphometrics. The LVS revealed diminished mucosal wave vibration in the vocal folds treated with mitomycin-C, as well as a more atrophic appearance to the vibratory surface. The vocal folds treated with mitomycin-C showed fewer fibroblasts and less collagen within the superficial layer of the lamina propria than the control vocal folds (p < .05, Student's t-test, paired analysis). Inflammatory infiltrate was not significantly different between the two sides. Consistent with the known suppression of fibroblast proliferation by mitomycin-C, the treated vocal folds showed less connective tissue response to the surgical injury. In contrast to the reported positive effects of mitomycin-C on tracheal and glottic stenosis, the observed decrease in the healing response in the present study had negative consequences on the vocal fold vibratory pattern.

Optimal vocal outcome is the major goal of treatment of benign non-neoplastic vocal fold lesions. Current phonomicrosurgery techniques are based on a complete understanding of vocal fold anatomy and the physiology of vocal fold vibration. With the knowledge that these lesions typically involve the superficial layer of the lamina propria and not the overlying epithelium, dissection and excision should be limited to this layer. Vocal fold microflap techniques leave the overlying epithelium and the mucosal cover intact to minimize postoperative scarring and possible tethering to the underlying vocal ligament. Surgical excision is followed by a program of vocal rehabilitation.

Spasmodic dysphonia (SD), a disabling focal dystonia involving the laryngeal musculature, is most commonly treated by the intramuscular injection of botulinum toxin (BTX). Although the treatment is well tolerated and generally produces clinical voice improvement, it has never been statistically shown to alter the patient's perception of voice quality or general health. Declining resources for medical care mandate that treatment outcomes be documented. A prospective analysis of the effects of BTX on the patient's perception of voice and general health was undertaken. The Voice Handicap Index (VHI) and Short Form 36 (SF-36) surveys were administered to patients before treatment and 1 month after. Pretreatment and posttreatment scores were analyzed with a Student's t-test. On the VHI, improvements in the patients' perception of their functional, physical, and emotional voice handicap reached statistical significance (p < or = .0005). On the SF-36, patients had statistically significant improvements in mental health (p < or = .03) and social functioning (p < or = .04). Treatment of SD with BTX significantly lessened the patients' perception of dysphonia. In addition, it improved their social functioning and their perception of their mental health. These outcome measures justify the continued treatment of SD with BTX.

The objective of this randomized, prospective study was to study the efficacy of topical mitomycin-C in the inhibition of subglottic stenosis in a canine model. Subglottic stenosis was elicited with the carbon dioxide laser in 10 mongrel dogs. Radial incision and serial dilation of the subglottic airway were then carried out. The animals were randomized to receive a topical solution of 1% mitomycin-C to the dilated area for a 5-minute duration or no further treatment. Weekly direct microlaryngoscopy and photodocumentation were performed during the 6-week study. Airway distress developed in 4 of the 5 control dogs, requiring early sacrifice, while all treatment group animals survived the duration of the study (p < or = .006). Morphometric analysis of the subglottic photographs confirmed a greater than 100% increase in the percentage of relative airway at sacrifice in the treatment group (p < or = .049). A statistically significant (p < or = .015) decrease in collagen formation in the subglottic scar of dogs treated with topical mitomycin-C was documented. Mitomycin-C favorably altered the clinical progression of subglottic stenosis, improved quantified airway patency, and reduced the amount of subglottic collagen formation in the canine model.

The histologic and functional effects of unilateral, layered corticosteroids on lateral microflap healing in 15 dogs were analyzed. Histologic sections of steroid-treated vocal folds (VFs) were studied with computer morphometry to examine differences in the tissue healing response. Paired analysis revealed increases in the inflammatory infiltrate around the microflap in the steroid-treated VFs at 2, 4, and 6 weeks (6.3%, 30.6%, and 34.9%, all with p < .02). The neovascular response in the steroid-treated VFs was less at 2 weeks (-20.9%, p < .005) but greater at 4 and 6 weeks (16.3% and 4.3%, p < .005). To better characterize the effect of steroids on the healing process, a normal, time-dependent distribution was applied to the histologic data and demonstrated a delay in the steroid-treated VF tissue response of 12 days for the inflammatory infiltrate and 21 days for the neovascular response. Qualitative and quantitative analysis of in vivo laryngeal videostroboscopy (LVS) samples taken preoperatively and at sacrifice could not identify significant differences in appearance, amplitude, mucosal wave, or suppleness between the 2 VFs. Therefore, although corticosteroids cause a delay in wound healing, LVS does not discern differences in microflap characteristics between healing steroid-treated and control VFs at 2, 4, or 6 weeks. If steroids are used, the surgeon should account for a probable delay in wound healing, but should not expect an overall difference in functional outcome.

The voice is the primary means of communication for humans socially and in the workplace. Although rarely life-threatening, voice problems cause tremendous alteration in daily living and should not be underestimated as a medical disorder. Besides affecting useful communication, voice problems may also signify the presence of more serious medical illnesses, such as malignancy or airway compromise. This article describes normal vocal anatomy and physiology and outlines a practical approach in evaluating patients with voice disorders.

This study develops a canine model for the treatment of laryngeal Teflon granulomas and demonstrates endoscopic ablation using the free-electron laser (FEL) set at a wavelength of 8.5 microm. Laryngeal Teflon granulomas may cause dysphonia and airway obstruction, and they are difficult to remove. The infrared absorption spectrum of Teflon reveals a strong absorption peak centered at 8.5 microm. In this study, 12 dogs had the right vocal cord injected with Teflon paste. Two months later, Teflon granuloma formation was confirmed histologically. Laser incisions into the granulomas were performed at 3 different wavelengths: 7.4 microm (FEL), 8.5 microm (FEL), and 10.6 microm (carbon dioxide laser). Histopathologic analysis was performed at 1 week and 6 weeks after the laser incisions. The FEL at the 8.5-microm wavelength was found to optimally ablate the Teflon granulomas, but the granulomas persisted in the specimens treated with 7.4 microm (FEL) and 10.6 microm (carbon dioxide laser).

The goal of microlaryngeal surgery is to treat the pathology while preserving or improving vocal function. The medial microflap technique was thus developed. An incision is made over or abutting the lesion, which is then dissected from the vocal ligament and overlying mucosa. Seventeen patients underwent medial microflap excision of their lesions. Postoperative videostroboscopic examinations revealed the presence of mucosal wave and improved glottic closure in 15 of the 17 patients. Acoustic and perceptual analyses revealed improved voice quality. The medial technique is a modification of the previously described lateral microflap technique. Patients whose stroboscopic examination implies lack of involvement of the vocal ligament are candidates for this technique. By identifying normal histologic planes without extensive dissection, lesions can be excised with minimal interruption of vibratory mechanics.

Diabetes mellitus is a disease that affects multiple organ systems. In our laboratory it has been shown that there is a significant loss of outer hair cells in genetically diabetic rats. Galactosemia can also produce diabetic-like changes. This study was performed to demonstrate whether these changes also occur in the cochlea. Three groups of Sprague-Dawley rats were used and fed either a control diet, a 50% galactose diet, or a 50% galactose diet with the addition of an aldose reductase inhibitor. After 6 months the animals were killed, and the cochleas were removed, fixed, and stained. Diabetes-induced damage was assessed by counting the hair cells and calculating the neuroganglion cell density. The histopathologic changes induced by galactose were manifested as outer hair cell loss and a decrease in neuroganglion cell density. Control animals had the least amount of hair cell loss and the greatest neuroganglion cell density of all three groups. Galactose-only animals demonstrated the most pronounced changes in both hair cell loss and neuroganglion cell degeneration; however, only changes of neuroganglion cell density in the basal turn were significant. The addition of an aldose reductase inhibitor provided inconclusive results in both hair cell determination and neuroganglion cell density; however, generally the inhibitor partially prevented the damage produced by galactose. These results suggest that a high-galactose diet can induce diabetic-like changes in the cochlea.

"Hoarseness" is the term used by most people to describe a change in normal voice quality. It is a very nonspecific term somewhat similar to a patient's complaint of dizziness when describing symptoms from light-headedness to true vertigo. Hoarseness may imply breathiness, roughness, voice breaks, or unnatural changes in pitch. Laryngologists use the general term "dysphonia" to describe abnormal voice quality with no specific etiology implied. A complaint of hoarseness may represent serious disease and, therefore, should not be ignored, especially if it persists for more than two weeks. Before we proceed with a discussion of abnormal voice, it is imperative to understand normal voice production and the relative anatomy.

Oral antibiotic therapy can alter the gastrointestinal microflora and result in troublesome gastrointestinal complaints. Patients who have experience with broad-spectrum antibiotics may be reluctant to start or to comply with antibiotic therapy due to the associated discomfort. In the field of otolaryngology, oral antibiotic therapy is commonplace, and patient intolerance of a particular antibiotic may result in compromise to a less effective choice. Yogurt, which contains Lactobacillus acidophilus, is often recommended by practitioners to help reduce the side effects of oral antibiotic therapy. We wanted to objectively evaluate the effect of orally administered L. acidophilus on the gastrointestinal side effects of oral broad-spectrum antibiotic therapy. Twenty-seven outpatients, 10 years of age or older, with ear, sinus, or throat infections, in whom amoxicillin/clavulanate was felt to be the antibiotic of choice, were randomly assigned to amoxicillin/clavulanate only, or amoxicillin/clavulanate and Lactobacillus treatment groups. Each patient was advised by the nursing staff to consume a well-balanced diet, and a detailed explanation of the medication schedule was given. A questionnaire was given to each patient at the conclusion of therapy. The data were analyzed using Spearman's rank-order correlations. Concomitant therapy of L. acidophilus with amoxicillin/clavulanate was associated with a significant decrease in patient complaints of gastrointestinal side effects and yeast superinfection. Almost all patients (89%) reported resolution of infection during the course of therapy. We believe that use of L. acidophilus is warranted in patients on broad-spectrum antibiotic therapy with gastrointestinal complaints.

Cochlear blood flow has been shown to be controlled, in part, by the sympathetic nervous system. We have used immunocytochemical staining for tyrosine hydroxylase (TH) to further demonstrate the extent of catecholaminergic innervation of the cochlea. Deeply anesthetized Mongolian gerbils were systemically perfused with phosphate-buffered saline, followed by 4% paraformaldehyde. The cochleae were dissected out and post-fixed for 3 hours in 4% paraformaldehyde. They were then incubated in anti-TH antibody and subsequently processed using the avidin-biotin immunoperoxidase method. Microscopic examination of whole-mounted tissue revealed many immunoreactive fibers on the spiral modiolar artery. TH-positive fibers have also been found on both radiating arterioles and radial collecting venules, which has not been previously reported. With innervation of these small vessels, blood flow in the cochlea may be segmentally controlled. We also further describe the organization of TH-positive fibers in the osseous spiral lamina.

A technique is described for directly observing in vivo cochlear microvasculature in the gerbil for physiologic and experimentally induced changes in vessel diameter and blood flow velocity. Measurements are made from computer processed video images of surgically exposed microvessels. These images are obtained using intravital fluorescence microscopy (IFM) with epi-illumination. The Mongolian gerbil is an ideal animal model for circulatory studies of the inner ear. It has a stable heart rate and blood pressure under urethane/alpha-chloralose anesthesia and its cochlea is surgically accessible. A window is created over the feeding artery (anterior inferior cerebellar artery) and over the stria vascularis of the second turn of the cochlea, atraumatically exposing radiating arterioles and strial capillaries. Our system of IFM provides images that are videorecorded, digitally analyzed with a computer image processor, and enhanced according to the type of measurement desired. Velocity measurements are obtained by tracking plasma gaps or single fluorescent labeled red blood cells through successive frames of the videorecorded images. This experimental technique allows us to analyze circulatory responsiveness to a variety of vasoactive drugs administered regionally to the cochlea in concentrations not affecting systemic circulation.