Two cases of rare subglottic MALT lymphoma of the larynx.

BACKGROUND: Primary MALT lymphoma of the larynx is a rare condition first described in 1990. There have been only 43 reported cases as of 2015. The disease appears to be indolent in nature and responds well to radiation therapy. Symptoms are non-specific and may be limited to a combination of hoarseness, sore throat, shortness of breath, or cough. METHODS: We describe two cases of subglottic laryngeal MALT lymphoma identified from one academic medical center within five years of each other. Though identical in pathology, the presentation of the two cases were distinct in both patient demographic and tumor appearance. One patient required dilation of a subglottic stenosis caused by tumor, and the other required surgical debulking of a ball-valve-like mass. Neither patient presented with B-symptoms (fever, night sweats, weight loss) that often characterize other lymphomas. RESULTS: In both cases, histopathological exam revealed extensive infiltration of mucosa with atypical monomorphous lymphocytes, consistent with MALT lymphoma. CONCLUSION: MALT lymphoma of the larynx may present with non-specific symptoms such as cough and/or hoarseness. Thorough evaluation including flexible laryngoscopy should be performed should these symptoms persist without a known cause. Surgical biopsy and histopathological exam are crucial to determine the etiology of unknown subglottic masses.

Stroke risk in African Americans with subclinical auditory dysfuntion evidenced by Distortion Product Otoacoustic Emissions: the Jackson heart study.

Objective: Distortion product otoacoustic emissions (DPOAEs) are sensitive to early indices of cochlear pathology. Pathology to the cochlea is in part mediated by ischaemic related mechanisms. We propose that DPOAEs may provide an objective measure of cardiovascular risk.Design: Cross-sectional.Study sample: The relationships between stroke risk and DPOAEs of 1,107 individuals from the Jackson Heart Study (JHS), an all-African-American cohort, were assessed. Linear regression models were used for analysis among all participants and delimited to normal hearing, defined as either a pure-tone threshold average of 500, 1000, 2000, and 4000 Hz (PTA4) ≤ 25 dBHL or pure-tone thresholds for all individual tested frequencies for each ear (500, 1000, 2000, 4000, and 8000 Hz) ≤ 25 dBHL.Results: We observed a significant inverse relationship between DPOAE amplitudes and stroke risk scores in the pooled cohort and in the subgroups with normal hearing defined by pure tone thresholds. Participants in the high-risk group had significantly lower DPOAE amplitudes than those in the low stroke risk group.Conclusions: Our results indicate that auditory dysfunction as measured by DPOAEs are related to stroke risk. Further prospective studies are needed to determine if DPOAEs could be used as a predictive tool for cardiovascular disease.

Jackson Heart Study: Aggregate cardiovascular disease risk and auditory profiles.

Objectives: Evaluate the relationship between cardiovascular disease (CVD) risk factors and cochlear function in African Americans. Methods: Relationships between hearing loss, cochlear function, and CVD risk factors were assessed in a cross-sectional analysis of 1106 Jackson Heart Study participants. Hearing loss was defined as puretone average (PTA0.5,1,2,4) > 15 dB HL. Distortion product otoacoustic emissions (DPOAEs) were collected for f 2 = 1.0-8.0 kHz. Two amplitude averages were computed: DPOAElow (f 2 ≤ 4 kHz) and DPOAEhigh (f 2 ≥ 6 kHz). Based on major CVD risk factors (diabetes, current smoking, total cholesterol ≥240 mg/dL or treatment, and systolic blood pressure [BP]/diastolic BP ≥ 140/≥90 mmHg or treatment), four risk groups were created: 0, 1, 2, and ≥3 risk factors. Logistic regression estimated the odds of hearing loss and absent/reduced DPOAElow and DPOAEhigh by CVD risk status adjusting for age, sex, education, BMI, vertigo, and noise exposure. Results: With multivariable adjustment, diabetes was associated with hearing loss (OR = 1.48 [95% CI: 1.04-2.10]). However, there was not a statistically significant relationship between CVD risk factors (individually or for overall risk) and DPOAEs. Conclusion: Diabetes was associated with hearing loss. Neither individual CVD risk factors nor overall risk showed a relationship to cochlear dysfunction. Level of Evidence: 2b.

Central Auditory Processing and the Relationship to Perceived Hearing Difficulty: The Jackson Heart Study.

OBJECTIVE: There are limited population-based studies of central auditory processing (CAP). We aimed to determine the relationship between CAP measures and perceived hearing difficulty (PHD) despite normal pure-tone audiometry in an African-American population. STUDY DESIGN: Cross-sectional. SETTING: Jackson Heart Study (JHS), Jackson, MS. SUBJECTS: Participants of an African-American cohort (26% men; age 54.2, standard deviations [SD] 9.2) who self-reported hearing difficulty despite normal hearing sensitivity defined as audiometric pure-tone average (PTA-4: average of 500, 1000, 2000, and 4000 Hz) less than or equal to 25 dBHL (n = 911) or across all tested frequencies (PT-AF: 250-8000 Hz) less than or equal to 25 dBHL (n = 516). METHODS: The Quick Speech-in-Noise (QuickSIN) and Dichotic Digits, Double Pairs (DDT2) tests were used to assess CAP. Logistic regression was used to examine the association between measures of CAP and PHD; adjusted for age, sex, education, and pure tone audiogram. RESULTS: PHD was present in 251 (28%) and 137 (27%) of participants using the PTA-4 and PT-AF models, respectively. Fully adjusted regression models revealed that each one-point increase in QuickSIN increased the odds of reporting PHD by 13.7% (odds ratio [OR] 1.14, p < 0.01, 95% CI: 1.08, 1.19) using the PTA-4 model and 15.0% (OR 1.15, p < 0.01, 95% CI: 1.08, 1.23) using the PT-AF model. For DDT2 testing, each 1% reduction in score, increased the odds of reporting PHD by 7.7% (OR 0.92, p < 0.01, 95% CI: 0.88, 0.97) in a fully adjusted PTA-4 model and 6.6% (OR 0.93, p = 0.04, 95% CI: 0.87, 0.99) in the PT-AF model. CONCLUSION: CAP deficits were associated with increased odds of PHD in normal hearing participants within the JHS cohort.

Association Between Cardiometabolic Factors and Dizziness in African Americans: The Jackson Heart Study.

BACKGROUND: Balance dysfunction is a complex, disabling health condition that can present with multiple phenotypes and etiologies. Data regarding prevalence, characterization of dizziness, or associated factors is limited, especially in an African American population. PURPOSE: The aim of the study is to characterize balance dysfunction presentation and prevalence in an African American cohort, and balance dysfunction relationship to cardiometabolic factors. RESEARCH DESIGN: The study design is descriptive, cross sectional analysis. STUDY SAMPLE: The study sample consist of N = 1,314, participants in the Jackson Heart Study (JHS). DATA COLLECTION AND ANALYSIS: JHS participants were presented an initial Hearing health screening questionnaire (N = 1,314). Of these, 317 participants reported dizziness and completed a follow-up Dizziness History Questionnaire. Descriptive analysis was used to compare differences in the cohorts' social-demographic characteristics and cardiometabolic variables to the 997 participants who did not report dizziness on the initial screening questionnaire. Based on questionnaire responses, participants were grouped into dizziness profiles (orthostatic, migraine, and vestibular) to further examine differences in cardiometabolic markers as related to different profiles of dizziness. Logistical regression models were adjusted for age, sex, education, reported noise exposure, and hearing sensitivity. RESULTS: Participants that reported any dizziness were slightly older and predominantly women. Other significant complaints in the dizzy versus nondizzy cohort included hearing loss, tinnitus, and a history of noise exposure (p < 0.001). Participants that reported any dizziness had significantly higher prevalence of hypertension, blood pressure medication use, and higher body mass index (BMI). Individuals with symptoms alluding to an orthostatic or migraine etiology had significant differences in prevalence of hypertension, blood pressure medication use, and BMI (p < 0.001). Alternatively, cardiometabolic variables were not significantly related to the report of dizziness symptoms consistent with vestibular profiles. CONCLUSION: Dizziness among African Americans is comparable to the general population with regards to age and sex distribution, accordingly to previously published estimates. Participants with dizziness symptoms appear to have significant differences in BMI and blood pressure regulation, especially with associated orthostatic or migraine type profiles; this relationship does not appear to be conserved in participants who present with vestibular etiology symptoms.

Management of recurrent laryngeal sensory neuropathic symptoms.

OBJECTIVES: We identify management strategies for the treatment of upper respiratory tract symptoms stemming from dysfunction of the recurrent laryngeal nerve. METHODS: We present a retrospective case series of patients who had symptoms of sensory neuropathy, including persistent dysphonia, laryngospasm, and chronic cough. The patients were followed for symptomatic improvement after initiation of treatment with a neuromodulator. Treatment outcome was defined by improvement or resolution of symptoms on a self-reported outcome scale. RESULTS: Of 12 patients identified, 75% exhibited evidence of motor neuropathy on laryngoscopy and 83% had symptoms related to chronic cough treated with neuromodulator therapy over a mean follow-up of 20.4 months. The median dose of amitriptyline hydrochloride was 25 mg daily, and that of gabapentin was 300 mg 3 times daily. The mean time from the initiation of therapy to a complete response was 2 months. CONCLUSIONS: Patients with suspected neuropathy of the recurrent laryngeal nerve frequently respond to neuromodulator therapy. The addition of reflux precautions and acid suppression therapy is helpful in cases of chronic and recurrent laryngospasm. Patients with evidence of motor neuropathy appear to have better outcomes with neuromodulator therapy.

Relationship of Overall Cardiovascular Health and Hearing Loss in The Jackson Heart Study Population.

OBJECTIVES: To evaluate the relationships among the overall cardiovascular health scoring tool, Life's Simple 7 (LS7), and hearing in an African-American cardiovascular study cohort. METHODS: Using the Jackson Heart Study's cohort of African Americans, the relationships between the LS7 scoring metric and hearing of 1314 individuals were assessed. Standard audiometric data was collected and hearing loss was defined as a four-frequency average of 500, 1000, 2000, and 4000 Hz greater than 25 dBHL (PTA4). Measures of reported tinnitus and dizziness were also collected. The LS7 scoring tool, which consists of seven individual categories (abstinence from smoking, body mass index, physical activity, healthy diet, total cholesterol <200 mg/dL, normotension, and absence of diabetes mellitus), was used as measure of overall cardiovascular health. Each category of the LS7 was broken down into poor, intermediate, and ideal subgroups as in accordance with the American Heart Association Strategic Planning Task Force and Statistics Committee. Unadjusted and adjusted gamma regression and logistic regression models were constructed for determining relationships between LS7 and hearing loss. RESULTS: Higher total LS7 scores (per 1-unit increase) were associated with lower PTA4 in gamma regression analyses (RR = 0.942, 95% CI, 0.926-0.958, P < .001). This held true even after adjustments for age, sex, education, and history of noise exposure. Using logistic regression analyses to compare LS7 scores to presence of hearing loss, tinnitus, and vertigo; only hearing loss showed a statically significant relationship after adjustments for age, sex, education, and history of noise exposure. CONCLUSIONS: This study shows a significant, graded association between higher life's simple seven scores and lower incidence of hearing loss. LEVEL OF EVIDENCE: 2b. Laryngoscope, 2019.

Cell density of the lamina propria of neonatal vocal folds.

OBJECTIVES: We undertook (1) to measure the cell density within the lamina propria of the neonatal vocal folds and (2) to examine changes in cell density in the lamina propria with increasing gestational age of the neonatal vocal folds. METHODS: Intact neonatal larynges were obtained from fresh cadaveric specimens. Hematoxylin and eosin-stained slides were used to visualize the laryngeal structures, and photomicrographs of the vocal folds were taken at 100x magnification. The cell density of the lamina propria was calculated by counting the cells within each of five 100-microm2 regions within the study area, and the totals were then averaged for each area. RESULTS: A total of 62 sections from 14 larynges with gestational ages of 19 to 36 weeks were examined. Histologic analysis revealed a uniform appearance of the vocal fold without apparent layers. The cell density of the lamina propria was 30 or more cells per 100 microm2 for 51.2% of larynges with less than 27 weeks of gestation. However, only 14.3% of the larynges with 27 or more weeks of gestation had an average cell density of 30 or more cells per region (p < 0.005). CONCLUSIONS: As described by previous studies, the lamina propria of the neonatal vocal folds is a hypercellular monolayer. The process of vocal fold maturation appears to occur earlier than previously thought, with decreasing cell density in the lamina propria by 27 weeks' gestation.

The Relationship of Cardiometabolic Risk and Auditory Processing among African Americans: The Jackson Heart Study.

OBJECTIVES: There is limited research in population-based studies on auditory processing. The purpose of this work is to determine the prevalence of auditory processing impairment in the Jackson Heart Study cohort and to identify potential relationships with cardiometabolic risk factors. STUDY DESIGN: Cross-sectional study. SETTING: Jackson Heart Study in Jackson, Mississippi. SUBJECTS: Participants of an all-African American cardiovascular study cohort (n = 1314). METHODS: The Quick Speech-in-Noise and Dichotic Digits, Double Pairs tests were used to assess auditory processing. Logistic regression and multinomial logistic regression models were used to examine how participants' cardiometabolic risk factors and audiologic characteristics were associated with speech perception in noise and binaural integration. RESULTS: Quick Speech-in-Noise and Dichotic Digits, Double Pairs testing showed a prevalence of auditory processing impairment in 69% and 71% of the cohort, respectively, which was significantly related to age, hearing thresholds, sex, and education level. With covariate adjustment in statistical models for age, sex, pure tone average, and education level, waist circumference, systolic blood pressure, and hypertension were statistically predictive of auditory processing impairment ( P < .05). CONCLUSION: The results suggest a high prevalence of auditory processing deficits in the Jackson Heart Study cohort. In addition, cardiometabolic and audiologic factors show a statistically significant independent relationship with auditory impairment measures.

Audiologic profile of the jackson heart study cohort and comparison to other cohorts.

OBJECTIVES/HYPOTHESIS: The objective of this study was to determine the audiological profile of an African American cohort, identify related factors, and compare them to other datasets. STUDY DESIGN: Cross-sectional, longitudinal cohort study. METHODS: The Jackson Heart Study (JHS) is a longitudinal cohort study of 5,306 African Americans living in the metropolitan Jackson, Mississippi area, with a focus on cardiometabolic health. The JHS Hearing Study (n = 1,314) was implemented to measure the prevalence of hearing, tinnitus, and balance outcomes and relationship to predictor variables. Here we present prevalence and covariate relationships in comparison to the Epidemiology of Hearing Loss Study and the National Health and Nutrition Examination Survey. RESULTS: The prevalence of self-reported hearing difficulty was 38.1% (n = 500). The prevalence of hearing loss based on audiometric pure tone threshold average (0.5, 1.0, 2.0, 4.0 kHz) of the better ear was 19.8% (n = 260) and for the worse ear 29.8% (n = 392). The prevalence of tinnitus was 29.5% (n = 388) and balance dysfunction 24.1% (n = 317). Relationships of hearing loss to demographic, cardiometabolic, and audiologic variables are presented. CONCLUSIONS: These results demonstrate that hearing loss, tinnitus, and balance dysfunction are common issues affecting adult African Americans, and that hearing loss is related to numerous modifiable and nonmodifiable risk factors. Furthermore, our findings are consistent with lower prevalence of hearing loss in African Americans compared to the non-African American populations. However, despite the lower audiometric evidence of hearing loss, nearly 40% of participants reported hearing difficulty. LEVEL OF EVIDENCE: 2b Laryngoscope, 129:2391-2397, 2019.

Genome-wide association meta-analysis identifies five novel loci for age-related hearing impairment.

Previous research has shown that genes play a substantial role in determining a person's susceptibility to age-related hearing impairment. The existing studies on this subject have different results, which may be caused by difficulties in determining the phenotype or the limited number of participants involved. Here, we have gathered the largest sample to date (discovery n = 9,675; replication n = 10,963; validation n = 356,141), and examined phenotypes that represented low/mid and high frequency hearing loss on the pure tone audiogram. We identified 7 loci that were either replicated and/or validated, of which 5 loci are novel in hearing. Especially the ILDR1 gene is a high profile candidate, as it contains our top SNP, is a known hearing loss gene, has been linked to age-related hearing impairment before, and in addition is preferentially expressed within hair cells of the inner ear. By verifying all previously published SNPs, we can present a paper that combines all new and existing findings to date, giving a complete overview of the genetic architecture of age-related hearing impairment. This is of importance as age-related hearing impairment is highly prevalent in our ageing society and represents a large socio-economic burden.

Age at diagnosis, but not HPV type, is strongly associated with clinical course in recurrent respiratory papillomatosis.

BACKGROUND: Recurrent Respiratory Papillomatosis (RRP) is a rare disease characterized by the growth of papillomas in the airway and especially the larynx. The clinical course is highly variable among individuals and there is poor understanding of the factors that drive an aggressive vs an indolent course. METHODS: A convenience cohort of 339 affected subjects with papillomas positive for only HPV6 or HPV11 and clinical course data available for 1 year or more, from a large multicenter international study were included. Exploratory data analysis was conducted followed by inferential analyses with frequentist and Bayesian statistics. RESULTS: We examined 339 subjects: 82% were diagnosed prior to the age of 18 years, 65% were infected with HPV6, and 69% had an aggressive clinical course. When comparing age at diagnosis with clinical course, the probability of aggressiveness is high for children under five years of age then drops rapidly. For patients diagnosed after the age of 10 years, an indolent course is more common. After accounting for confounding between HPV11 and young age, HPV type was minimally associated with aggressiveness. Fast and Frugal Trees (FFTs) were utilized to determine which algorithms yield the highest accuracy to classify patients as having an indolent or aggressive clinical course and consistently created a branch for diagnostic age at ~5 years old. There was no reliable strong association between clinical course and socioeconomic or parental factors. CONCLUSION: In the largest cohort of its type, we have identified a critical age at diagnosis which demarcates a more aggressive from less aggressive clinical course.

Tinnitus and its risk factors in african americans: The Jackson Heart Study.

OBJECTIVES/HYPOTHESIS: To describe the prevalence of reported tinnitus and tinnitus handicap in the all-African American Jackson Heart Study (JHS) cohort, with assessment of the relationship to cardiometabolic risk and depression. STUDY DESIGN: Prospective cohort study. METHODS: Audiologic data were obtained from a sample of 1,314 participants of the JHS. Reported tinnitus was assessed dichotomously (yes/no) by interview and with the Tinnitus Handicap Inventory (THI). The statistical relationship of reported tinnitus and tinnitus handicap to various cardiometabolic risks (i.e., hypertension and waist circumference) and Center for Epidemiologic Studies Depression scale (CES-D) was assessed with logistic and gamma regression procedures. RESULTS: Tinnitus was found to be a highly prevalent condition (29.5%), with an additionally high rate of individuals who report at least slight tinnitus handicap (35%). Hypertension (ß = 1.344, 95% confidence interval [CI]: 1.015-1.780, P = .039) and waist circumference (ß = 1.009, 95% CI: 1.001-1.018, P = .021) were found to have a statistically significant relationship with THI score, depending on the level of covariate adjustment. Depression, as measured by the CES-D, was found to have a statistically significant relationship with both reported tinnitus (odds ratio [OR]: 1.051, 95% CI: 1.030-1.072, P < .001) and THI score (ß = 1.029, 95% CI: 1.013-1.047, P = .001), which persisted for all levels of covariate adjustment in statistical models. CONCLUSIONS: Tinnitus was found to be highly prevalent in the JHS, and certain measures of cardiometabolic risk are weakly related to both reported tinnitus and level of tinnitus handicap. A consistent relationship between depression and tinnitus/level of tinnitus handicap was observed. LEVEL OF EVIDENCE: 2b. Laryngoscope, 128:1668-1675, 2018.

Relationship of stroke risk and hearing loss in African Americans: The Jackson Heart Study.

OBJECTIVES/HYPOTHESIS: To evaluate the relationships among measures of stroke risk and hearing in an African American cardiovascular study cohort. STUDY DESIGN: Prospective cohort study. METHODS: The relationships between stroke risk profiles and hearing of 1,107 individuals from a cohort of African Americans were assessed. Several different hearing pure-tone averages (PTAs) were constructed representing different frequency regions of hearing, namely PTA low, PTA mid, and PTA high. Stroke risk profiles were calculated using validated 10-year cardiovascular disease risk scores. Gamma regression analyses were performed for each PTA given as a continuous variable with change in stroke risk score. Logistic regression analyses, presented as odds ratios, were performed with hearing loss defined as any PTA >25 dB hearing level. Stratification models were analyzed for age quarterlies and among sex. RESULTS: Single unit increases of stroke risk percentage were found to be predictive of increases in all PTA threshold levels in gamma regression analyses for the overall pooled sample. The relationship was influenced by age, where fewer significant relationships were observed at higher ages. When analyzed with respect to stroke risk categories, using low risk as the reference group, there was found to be a significant association between stroke risk and hearing loss in the medium- and high-risk groups, with a stronger relationship in the high-risk group for all PTA threshold levels. CONCLUSIONS: This study provides evidence that stroke risk has a positive predictive relationship with hearing pure-tone threshold. LEVEL OF EVIDENCE: 2b. Laryngoscope, 128:1438-1444, 2018.

The transnasal esophagoscopy documentation dilemma.

OBJECTIVE: To determine radiographically the anatomic length difference between the nasal and oral aerodigestive tracts and to clarify gaps in the literature regarding standardized landmark measurements and documentation techniques in transnasal esophagoscopy, as opposed to traditional transoral esophagoscopy. STUDY DESIGN: This is a prospective radiographic cohort study. METHODS: Digital computerized tomography measurement techniques were used to determine the difference in length between the nasal and oral aerodigestive tracts. Using sagittal plane images from consecutive patients, the mean nares-cricoid (NC) distance, upper incisor-cricoid (IC) distance, and their mean differences were determined. Male, female, and overall distances and differences were calculated. Standard deviations, 95% confidence intervals, and 90% prediction intervals were also calculated. Mean difference data were applied to reported standard oral esophagoscopy landmark measurements to convert to standard landmark measurements from the nares. RESULTS: Overall mean NC and IC distances were 175.4 mm and 147.5 mm, respectively. For males, these mean distances were 185.5 mm and 155.0 mm, respectively. For females, these mean distances were 165.3 mm and 140.0 mm, respectively. Overall mean NC to IC difference was 27.9 mm. The mean NC to IC difference for males and females was 30.5 mm and 25.2 mm, respectively. CONCLUSIONS: Historically, landmark and report measurements in esophagoscopy have been measured and standardized from the upper incisor. This study demonstrates and clarifies the inherent anatomic length difference of the nasal and oral aerodigestive tracts and the resultant documentation dilemma produced by transnasal esophagoscopy techniques. These data provide easy conversion of esophagoscopy measurements reported from the incisors or nares, providing better communication between endoscopists of different disciplines and techniques.

Interactive instruction in otolaryngology resident education.

Today's academic faculty was typically trained under an education system based entirely on didactic lectures. However, if the aim is to teach thinking or change attitudes beyond the simple transmission of factual knowledge, then lectures alone, without active involvement of the students, are not the most effective method of teaching. If the goals of teaching are to arouse and keep students' interest, give facts and details, to make students think critically about the subject, and to prepare for independent studies by demonstration of problem solving and professional reasoning, then only two of these purposes are suited to didactic lectures. The problem then is how to organize lecture material so that individual student's learning needs are better addressed. The education literature suggests that instruction include a variety of activities designed to stimulate individual thought. These activities include small group discussion, working problems during lecture time, questions included in the lecture, and quizzes at the end of lecture, among others. The current study was undertaken to examine the feasibility of using these types of interactive learning techniques in an otolaryngology residency program. Possibilities considered in the current study include standard interactive lecturing, facilitated discussion, brainstorming, small group activities, problem solving, competitive large group exercises, and the use of illustrative cliff hanger and incident cases. The feasibility of these methodologies being effectively incorporated into a residency curriculum is discussed.

Lifelong learning in otolaryngology: self-directed learning.

Although nothing in didactic form approaches the learning experience of the real world, the educational process up to graduation is based on a teacher-directed model of learning. Active engagement in self-planned learning activities tends to be more effective than passive learning. Lifelong learning involves finding and implementing solutions to everyday problems encountered in the clinic, emergency room, and operating room and on the wards. The process by which much of this education occurs is via self-directed learning, in which learners challenge themselves to pursue activities that arise from their own experiences using their own emerging styles. The acquisition of self-directed learning is a complex process that involves numerous skills and competencies relied upon to complete challenges.

High level expression of human epithelial beta-defensins (hBD-1, 2 and 3) in papillomavirus induced lesions.

BACKGROUND: Epithelial defensins including human beta-defensins (hBDs) and alpha-defensins (HDs) are antimicrobial peptides that play important roles in the mucosal defense system. However, the role of defensins in papillomavirus induced epithelial lesions is unknown. RESULTS: Papilloma tissues were prospectively collected from 15 patients with recurrent respiratory papillomatosis (RRP) and analyzed for defensins and chemokine IL-8 expression by quantitative, reverse-transcriptase polymerase chain reaction (RT-PCR) assays. HBD-1, -2 and -3 mRNAs were detectable in papilloma samples from all RRP patients and the levels were higher than in normal oral mucosal tissues from healthy individuals. Immunohistochemical analysis showed that both hBD-1 and 2 were localized in the upper epithelial layers of papilloma tissues. Expression of hBD-2 and hBD-3 appeared to be correlated as indicated by scatter plot analysis (r = 0.837, p < 0.01) suggesting that they were co-inducible in papillomavirus induced lesions. Unlike hBDs, only low levels of HD5 and HD6 were detectable in papillomas and in oral mucosa. CONCLUSION: Human beta-defensins are upregulated in respiratory papillomas. This novel finding suggests that hBDs might contribute to innate and adaptive immune responses targeted against papillomavirus-induced epithelial lesions.

Demographics of pediatric head and neck infections in a tertiary care hospital.

EDUCATIONAL OBJECTIVE: Discuss potential patterns in the epidemiology of infectious disease of the head and neck. STUDY OBJECTIVES: To investigate patterns in the epidemiology of severe head and neck infections that may reflect the impact of host factors. STUDY DESIGN: Population-based, historic cohort study. METHODS: Information on 1,010, incident head and neck infections occurring over a 5-year period was reviewed for demographics, location, and time of year. A nonparametric Kruskal-Wallis test was used to identify significant differences in the age distributions among the diagnosis groups. A Bonferroni, pair-wise comparison procedure was used for comparison of the average age of first onset of severe head and neck infections. Chi-square test was used to identify any significant association between season of the year and disease. RESULTS: Significant differences were identified in the age distributions among the diagnosis groups (P < .001). The average age of first onset of cellulitis of the neck and retropharyngeal abscess is earlier than peritonsillar abscess, at 2 to 3 years and 13 years, respectively. Parapharyngeal and periapical abscesses and cellulitis of the face occur at approximately age 6. The incidence of parapharyngeal abscess and diseases of the pharynx is decreased during Spring, whereas peritonsillar abscesses and acute periodontitis occurs more often in Spring and Summer. Age does not appear to be related to season of first occurrence. CONCLUSIONS: Head and neck infections are not random occurrences based on exposure alone; host factors are clearly important. Given the lack of correlation with school age, the results cannot be explained on the basis of exposure alone. Developmental patterns of the host immune response may be related to the age differential identified in the current study and are cause for further investigation.

Organotypic (raft) culture of biopsy-derived upper respiratory epithelium.

OBJECTIVE: The objective of this study was to derive a reliable technique for culturing biopsy-derived upper respiratory epithelium in a system that supports epithelial differentiation and simulates the normal epithelial life cycle. STUDY DESIGN: The authors conducted a prospective study of modification and development of an in vitro tissue culture method. METHODS: Thirty biopsy specimens from 16 individuals with recurrent respiratory papillomatosis and chronic tonsillitis, pretreated to prevent bacterial and fungal overgrowth, were digested with trypsin to create a supernatant of individual cells. The cells were plated and incubated. At 14 to 16 days, the resulting colonies were placed on a wire cloth raft and fed through diffusion from the underlying culture medium in an air-liquid interface. RESULTS: Eight specimens were successfully cultured for an average of over 32 days. The longest duration of sustained growth was 60 days. Low-risk human papillomavirus specimen-based cultures reproduced infection in cultured squamous epithelium with corresponding histopathologic features indicating a high level of stratification and differentiation. CONCLUSIONS: Unlike commercially available cell lines, biopsy-derived material is predisposed to contamination, and successful in vitro culture and experimentation creates many unique challenges. An organotypic culture system, capable of reproducing the differentiation-dependent replication cycle of human papillomavirus, may be used for culturing biopsy-derived specimens for a variety of studies.