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Objective/hypothesis: Children who fail to develop adequate language skills and/or appropriate social skills by age 2 years often are referred to the department of otolaryngology for otolaryngologic examination and evaluation of possible hearing deficits. Discovering a gross disparity between hearing function and language ability often uncovers an underlying developmental disorder satisfying criteria for diagnosis on the spectrum of autism and pervasive developmental delay (PDD). The otolaryngologist has a unique opportunity to identify these autistic children and initiate their evaluation and management.Study Design: Retrospective review.Methods: Review of charts of children referred over the past 4 years to the Department of Otolaryngology for possible hearing loss identified 15 children who were later diagnosed with PDD.Results: Fifteen children initially referred for hearing evaluation were subsequently identified with a diagnosis of PDD. Males outnumbered females 4 to 1, with the average age of referral being 2 years. One third of the patients displayed middle ear disease that improved with PE tube placement. One third of the patients showed brainstem conduction dysfunction on auditory brainstem evoked response testing.Conclusions: Children with developmental delays, especially higher functioning ones, may present with a myriad of language and communication deficits that are often mistakenly attributed to hearing loss. Otolaryngologists and audiologists can assist in their early identification and appropriate referral for therapy. [ABSTRACT FROM AUTHOR]

Evidence has emerged that oxygen free radicals contribute to middle-ear mucosa damage in acute otitis media (AOM). Streptococcus pneumoniae is the most common pathogen in AOM and produces hydrogen peroxide, a free radical intermediate, as it grows. To better characterize the mechanism of free radical damage in AOM, an experiment was conducted to examine the production of hydrogen peroxide. Thirty-two guinea pigs were injected transtympanically with bacteria in the left (infected) middle ear and sterile saline into the right (control) middle ear. Middle-ear fluid was removed and analyzed for quantity of hydrogen peroxide. Results indicated significantly greater hydrogen peroxide levels in infected versus control middle-ear fluid at 6, 12, and 24 h. Likely sources of hydrogen peroxide include both the neutrophil response to infection and pneumococcal growth and death. [ABSTRACT FROM AUTHOR]

Introduction: Behavioral difficulties associated with sleep-disordered breathing (SDB) improve after tonsillectomy, but surgery may lead to the development of short-term postoperative maladaptive behavioral changes (PMBCs). These PMBCs have not been compared between total and partial tonsillectomy patients., Methods: SDB patients aged 1-6 years undergoing tonsillectomy were recruited. Parent phone surveys were conducted at 48-72 hours and 1-2 weeks postoperatively. Parents identified PMBCs using the Post-Hospital Behavior Questionnaire (PHBQ), scoring changes in behavior compared to baseline. PMBCs were defined by PHBQ scores >0 and compared by one-tailed t-test. Postoperative pain was categorized as mild, moderate, and severe pain using the Parents' Postoperative Pain Measure (PPPM). Differences in pain levels were analyzed by Chi-squared test. A p-value <0.05 was deemed statistically significant., Results: Seventy-eight children completed the study, with 29 total tonsillectomy and 49 partial tonsillectomy patients. At both time points after surgery, PHBQ scores were higher in total tonsillectomy patients than in partial tonsillectomy patients (3.41 ± 3.53 versus 1.94 ± 2.25 at 2-3 days, p = .013). PMBCs were also more frequent in total than partial tonsillectomy patients (76% versus 59% at 2-3 days; 28% versus 7% at 1-2 weeks). Meanwhile, distribution of pain levels was similar between both partial and total tonsillectomy patients., Conclusions: Our study indicates that total tonsillectomy patients more frequently experience PMBCs than do partial tonsillectomy patients despite similar distributions in pain levels postoperatively. This difference in PHBQ scores between total and partial tonsillectomy patients should be further explored., (Copyright © 2018. Published by Elsevier B.V.)

Background: The majority of cleft lip with or without cleft palate cases appear as an isolated, nonsyndromic entity (NSCLP). With the advent of next generation sequencing, whole exome sequencing (WES) has been used to identify single nucleotide variants and insertion/deletions which cause or increase the risk of NSCLP. However, to our knowledge, there are no published studies using WES in NSCLP to investigate copy number changes (CNCs), which are a major component of human genetic variation. Our study aimed to identify CNCs associated with NSCLP in a Honduran population using WES., Methods: WES was performed on two to four members of 27 multiplex Honduran families. CNCs were identified using two algorithms, CoNIFER and XHMM. Priority was given to CNCs that were identified in more than one patient and had variant frequencies of less than 5% in reference data sets., Results: WES completion was defined as >90% of the WES target at >8 × coverage and >80% of the WES target at >20 × coverage. Twenty-four CNCs that met our inclusion criteria were identified by both CoNIFER and XHMM. These CNCs were confirmed using quantitative PCR. Pedigree analysis produced three CNCs corresponding to ADH7, AHR, and CRYZ segregating with NSCLP. Two of the three CNCs implicate genes, AHR and ADH7, whose known biological functions could plausibly play a role in NSCLP., Conclusion: WES can be used to detect candidate CNCs that may be involved in the pathophysiology of NSCLP. Birth Defects Research 109:1257-1267, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Objectives/hypothesis: A candidate variant (p.Val496Ala) of the ACSS2 gene (T > C missense, rs59088485 variant at chr20: bp37 33509608) was previously found to consistently segregate with nonsyndromic cleft lip and/or palate (NSCLP) in three Honduran families. Objectives of this study were 1) to investigate the frequency of this ACSS2 variant in Honduran unrelated NSCLP patients and unrelated unaffected controls and 2) to investigate the frequency of this variant in Colombian unrelated affected NSCLP patients and unrelated unaffected controls., Study Design: Case-control studies., Methods: Sanger sequencing of 99 unrelated Honduran NSCLP patients and 215 unrelated unaffected controls for the p.Val496Ala ACSS2 variant was used to determine the carrier frequency in NSCLP patients and controls. Sanger sequencing of 230 unrelated Colombian NSCLP patients and 146 unrelated unaffected controls for the p.Val496Ala ACSS2 variant was used to determine the carrier frequency in NSCLP patients and controls., Results: In the Honduran population, the odds ratio of having NSCLP among carriers of the p.Val496Ala ACSS2 variant was 4.0 (P = .03), with a carrier frequency of seven of 99 (7.1%) in unrelated affected and four of 215 (1.9%) in unrelated unaffected individuals. In the Colombian population, the odds ratio of having NSCLP among carriers of the p.Val496Ala ACSS2 variant was 2.6 (P = .04), with a carrier frequency of 23 of 230 (10.0%) in unrelated affected and six of 146 (4.1%) in unrelated unaffected individuals., Conclusions: These findings support the role of ACSS2 in NSCLP in two independent Hispanic populations from Honduras and Colombia., Level of Evidence: NA Laryngoscope, 127:E336-E339, 2017., (© 2017 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Nasal septal abscess (NSA) is a rare condition most commonly seen as a complication of nasal trauma. The diagnosis of NSA requires emergent treatment, because delayed management can result in significant morbidity. Typically, NSA presents as a purulent collection that can be managed with drainage, either surgically or at bedside., Case Report: We report an unusual presentation of a spontaneous NSA in a 7-year-old boy as a solid nasal mass eroding the nasal septum. The solid, tumor-like nature of the mass necessitated intervention beyond drainage and was ultimately excised. Imaging initiated in the emergency department revealed a partially cystic mass and erosion of the septum, which was key to the diagnosis. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Given the ease with which a diagnosis of NSA may be missed and the need for urgent management upon diagnosis of a NSA, we aim to highlight the clinical, radiologic, and histopathologic aspects that aid in diagnosis of NSA. Imaging, obtaining culture results, and initiation of antibiotics are paramount in management. In addition, NSAs may also necessitate bedside drainage given their emergent nature., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Studies suggest that nonsyndromic cleft lip and palate (NSCLP) is polygenic with variable penetrance, presenting a challenge in identifying all causal genetic variants. Despite relatively high prevalence of NSCLP among Amerindian populations, no large whole exome sequencing (WES) studies have been completed in this population. Our goal was to identify candidate genes with rare genetic variants for NSCLP in a Honduran population using WES. WES was performed on two to four members of 27 multiplex Honduran families. Genetic variants with a minor allele frequency > 1% in reference databases were removed. Heterozygous variants consistent with dominant disease with incomplete penetrance were ascertained, and variants with predicted functional consequence were prioritized for analysis. Pedigree-specific P-values were calculated as the probability of all affected members in the pedigree being carriers, given that at least one is a carrier. Preliminary results identified 3,727 heterozygous rare variants; 1,282 were predicted to be functionally consequential. Twenty-three genes had variants of interest in ≥3 families, where some genes had different variants in each family, giving a total of 50 variants. Variant validation via Sanger sequencing of the families and unrelated unaffected controls excluded variants that were sequencing errors or common variants not in databases, leaving four genes with candidate variants in ≥3 families. Of these, candidate variants in two genes consistently segregate with NSCLP as a dominant variant with incomplete penetrance: ACSS2 and PHYH. Rare variants found at the same gene in all affected individuals in several families are likely to be directly related to NSCLP., (© 2016 WILEY PERIODICALS, INC.)

Objectives/hypothesis: To examine differences between total tonsillectomy and partial intracapsular tonsillectomy techniques that may lead to differences in overall cost and resource utilization between these procedures. Preoperative, perioperative, and postoperative management and outcome factors were examined., Study Design: Retrospective review at two university-based tertiary care hospitals from January 2007 to June 2010., Methods: Pediatric patients with obstructive symptoms were divided into those undergoing total tonsillectomy and those undergoing partial intracapsular tonsillectomy. The records of 289 patients who underwent total tonsillectomy and 289 patients who underwent partial intracapsular tonsillectomy were reviewed., Results: The average age of patients undergoing total and partial tonsillectomies was 5.0 years for both groups. Significant differences for patients undergoing total versus partial tonsillectomies were as follows: operative time (32.4 vs. 26.4 minutes, P < .0001), postanesthesia care unit (PACU) time (174 vs. 91.6 minutes, P < .0001), percent admitted postoperatively (21.5% vs. 1.7%, P < .0001), number requiring pediatric intensive care unit stay (3.5% vs. 0.3%, P < .05), number of readmissions after discharge (3.5% vs. 0.3%, P < .05), and number of postoperative emergency room visits separate from those requiring readmission (4.8% vs. 0%, P < .05). Factors that were not found to be significantly different included number of patients with postoperative hemorrhage and number requiring second operations for tonsillar regrowth., Conclusions: Previous studies have shown equivalent effectiveness between these two procedures; our study suggests decreased cost and resource utilization with partial tonsillectomy through reduced operative and PACU times and number of postoperative admissions and emergency department visits. As in all retrospective reviews, the findings are potentially confounded by unmeasured variables, including patient and demographic factors., (Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: Orofacial clefts are the most common craniofacial birth defects in humans, with the majority of orofacial clefts occurring as nonsyndromic cleft lip with or without cleft palate (NSCLP). We previously demonstrated associations between single-nucleotide polymorphisms (SNPs) in the IRF6 gene and NSCLP in the Honduran population. Here we investigated other candidate genes and chromosomal regions associated with NSCLP identified from genome-wide association studies (GWAS), including MAFB, ABCA4, 8q24, 9q22, 10q25, and 17q22 in two independent Hispanic populations., Study Design: Case-control and family-based association testing., Methods: Honduran families with two or more members with NSCLP (multiplex) were identified. DNA was collected from affected and unaffected family members (488) and 99 gender-matched controls. NSCLP Colombian families were identified; DNA was collected from 26 proband-parent trios. All participants were genotyped for 17 SNPs in six chromosomal regions. Case-control association and family-based association testing (FBAT) analyses were conducted., Results: Seven SNPs demonstrated association in at least one model in the Honduran population. In the Colombian families, five SNPs demonstrated significance in FBAT when patients with isolated cleft palate (CP) were included; four overlapped with SNPs demonstrating significance in the Honduran population, two with the same allele. One SNP retained significance with CP excluded., Conclusions: This study supports the previous GWAS findings and is the first to suggest a role for FOXE1, ABCA4, and MAFB in orofacial clefting in two separate Hispanic populations., (Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.)

Objectives/hypothesis: Cleft lip with or without cleft palate (CL/P) is a common birth defect throughout the world. Linkage studies have shown interferon regulatory factor 6 (IRF6) to be associated with CL/P in multiple populations, including one in Honduras. It is unknown, however, whether rare sporadic mutations or common variants are the cause of this association, and reports exist supporting both hypotheses. Thus, it is important to determine the cause for this association in a Honduran population., Study Design: Case-control and family-based association studies., Methods: Families with two or more members affected by CL/P were identified. We collected DNA from affected and unaffected family members (608 total), and from 100 gender-matched controls from Honduras. We sequenced the exons of IRF6 for mutations in probands and controls. All patients were genotyped for single nucleotide polymorphisms (SNPs) rs642961 and rs2235371, which are proposed to have potential biological significance to IRF6 expression and function., Results: We found no mutations in IRF6 in our CL/P probands. We found a risk association with the G allele of rs2235371 in both case-control (P = .01) and family-based association (P = .01) studies. We found no association with either allele of rs642961., Conclusions: This study suggests that common variants, rather than rare mutations, are the cause for association between IRF6 and nonsyndromic CL/P. rs2235371, but not rs642961, shows association with CL/P, suggesting a functional role for this polymorphism in our Honduran population. rs642961 has been previously reported to have an effect in other populations, suggesting that different populations may be affected by different polymorphisms., (Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.)

Van der Woude syndrome (VWS) is an autosomal dominant inherited disease characterized by lower lip pits, cleft lip and/or cleft palate. Missense, nonsense and frameshift mutations in IRF6 have been revealed to be responsible for VWS in European, Asian, North American and Brazilian populations. However, the mutations responsible for VWS have not been studied in Central American populations. Here, we investigated the role of IRF6 in patients with VWS in a previously unstudied Honduran population. IRF6 mutations were identified in four out of five VWS families examined, which strongly suggests that mutations in IRF6 are responsible for VWS in this population. We reported three novel mutations and one previously described mutation. In the first family, a mother and daughter both exhibited a p.N88I mutation in the DNA-binding region of IRF6 that was not present in unaffected family members. In the second, we found a unique p.K101QfsX15 mutation in the affected patient, leading to a frameshift and early stop codon. In the third, we identified a p.Q208X mutation occurring in exon 6. In the fourth, we found a nonsense mutation in exon 9 (p.R412X), previously described in Brazilian and Northern European populations. In the fifth, we did not identify any unique exonic missense, nonsense or frameshift mutations. This study reports the first cases of IRF6 mutations in VWS patients in a Central American population, further confirming that the causal link between IRF6 and VWS is consistent across multiple populations.

Objectives/hypothesis: Interferon regulatory factor 6 (IRF6), the gene that causes van der Woude syndrome (VWS), is a candidate gene for nonsyndromic cleft lip with or without cleft palate (NSCLP) because a number of studies have supported an association between NSCLP and single nucleotide polymorphisms (SNPs) in IRF6 in several populations. This project investigated the contribution of IRF6 to NSCLP in the Honduran population, a previously unstudied group with a high prevalence of NSCLP., Study Design: Family-based joint linkage and association study., Methods: A set of five SNPs in and around IRF6 previously reported to be associated with NSCLP were tested for association with NSCLP in 276 affected and unaffected Honduran individuals from 59 families with at least two members affected by clefting and at least one member with confirmed NSCLP., Results: We observed support of linkage for three SNPs-rs1856161, rs2235371, and rs2235377-under a dominant model (log of odds [LODs] = 1.97, 1.56, 1.73, respectively). Subsequent single-point, haplotype, and joint linkage and association analyses continued to support the association with NSCLP (P < or = .05) at these three SNPs. When analysis was restricted to NSCLP cases, excluding cleft palate only cases, support for association strengthened., Conclusions: This is the first study to demonstrate that three candidate SNPs within IRF6 are significantly associated with NSCLP in the Honduran population, providing the first genetic clue to NSCLP observed in the Honduran population and confirming findings from populations in other parts of the world. Further studies are needed to identify the putative variant(s).

The full set of microRNAs (miRNAs) in the human genome is not known. Because presently known miRNAs have been identified by virtue of their abundant expression in a few cell types, many tissue-specific miRNAs remain unrevealed. To understand the role of miRNAs in B cell function and lymphomagenesis, we generated short-RNA libraries from normal human B cells at different stages of development (naive, germinal center, memory) and from a Burkitt lymphoma cell line. A combination of cloning and computational analysis identified 178 miRNAs (miRNome) expressed in normal and/or transformed B cell libraries. Most notably, the B cell miRNome included 75 miRNAs which to our knowledge have not been previously reported and of which 66 have been validated by RNA blot and/or RT-PCR analyses. Numerous miRNAs were expressed in a stage- or transformation-specific fashion in B cells, suggesting specific functional or pathologic roles. These results provide a resource for studying the role of miRNAs in B cell development, immune function, and lymphomagenesis.

Objective: To explore interrater and intrarater reliability (R (inter) and R (intra), respectively) of a standardized scale applied to nasoendoscopic assessment of velopharyngeal (VP) function, across multiple centers., Design: Multicenter blinded R (inter) and R (intra) study., Setting: Eight academic tertiary care centers., Participants: Sixteen otolaryngologists from 8 centers., Main Outcome Measures: Raters estimated lateral pharyngeal and palatal movement on nasoendoscopic tapes from 50 different patients. Raters were asked to (1) estimate gap size during phonation and (2) note the presence of the Passavant ridge, a midline palatal notch on the nasal surface of the soft palate, and aberrant pulsations. Primary outcome measures were R (inter) and R (intra) coefficients for estimated gap size, lateral wall, and palatal movement; kappa coefficients for the Passavant ridge, a midline palatal notch on the nasal soft palate, and aberrant pulsations were also calculated., Results: The R (inter) coefficients were 0.63 for estimated gap size, 0.41 for lateral wall movement, and 0.43 for palate movement; corresponding R (intra) coefficients were 0.86, 0.79, and 0.83, respectively. Interrater kappa values for qualitative features were 0.10 for the Passavant ridge; 0.48 for a notch on the nasal surface of the soft palate, 0.56 for aberrant pulsations, and 0.39 for estimation of gap size., Conclusions: In these data, there was good R (intra) and fair R (inter) when using the Golding-Kushner scale for rating VP function based on nasoendoscopy. Estimates of VP gap size demonstrate higher reliability coefficients than total lateral wall, mean palate estimates, and categorical estimate of gap size. The reliability of rating qualitative characteristics (ie, the presence of the Passavant ridge, aberrant pulsations, and notch on the nasal surface of the soft palate) is variable.

Advising and mentoring programs for medical students vary in their official names, scope, and structures. Catalyzed by negative student feedback regarding career advising and a perceived disconnection between faculty and students, in academic year 2003-2004, Columbia University College of Physicians and Surgeons implemented its formal Advisory Dean (AD) Program and disbanded its former advising system that used faculty volunteers. The AD Program has become a key element for enhancing the students' professional development throughout their student training, focusing on topics including, but not limited to, career counseling, professionalism, humanism, and wellness resources. Advisory deans and the dean for student affairs, familiar with resources for academic development, student support, and extracurricular activities, operate at the nexus of the program, providing personalized mentoring and advising for each student. Fully supported by administration and faculty, the program has shown early success according to student feedback. Early feedback from the Class of 2006, who had been involved in our AD Program for three years, has been encouraging. Out of 152 students, 104 (68%) provided feedback, with 93 (89%) of the respondents reporting the AD Program as a valuable initiative. Expecting to further improve on this early positive response, the AD Program will continue to foster an environment conducive to a seamless transition from student to physician.

Memory B cells provide rapid protection to previously encountered antigens; however, how these cells develop from germinal center B cells is not well understood. A previously described in vitro culture system using human tonsillar germinal center B cells was used to study the transcriptional changes that occur during differentiation of human memory B cells. Kinetic studies monitoring the expression levels of several known late B cell transcription factors revealed that BCL-6 is not expressed in memory B cells generated in vitro, and gene expression profiling studies confirmed that BCL-6 is not expressed in these memory B cells. Furthermore, ectopic expression of BCL-6 in human B cell cultures resulted in formation of fewer memory B cells. In addition, the expression profile of in vitro memory B cells showed a unique pattern that includes expression of genes encoding multiple costimulatory molecules and cytokine receptors, antiapoptotic proteins, T cell chemokines, and transcription factors. These studies establish new molecular criteria for defining the memory B cell stage in human B cells.

Objectives/hypothesis: Nontuberculous mycobacterial adenitis of the parotid gland is often difficult to diagnose. The rarity of these infections in the parotid region and the lack of specific guidelines pose a treatment challenge to the clinician. Three cases of nontuberculous mycobacterial adenitis are presented, with clinical response to antibiotics before surgery., Study Design: Retrospective chart review was made of children up to 18 years of age presenting with a parotid mass diagnosed as nontuberculous mycobacterial infection., Methods: Three patients (age range, 15 to 30 mo) with nontuberculous mycobacteria-induced parotid lymphadenitis were treated with a combination antibiotic regimen of clarithromycin and rifabutin or with clarithromycin alone., Results: All three patients responded clinically to the antibiotic treatment as evidenced by a smaller mass size and resolution of the overlying discoloration. Subsequent parotidectomy or biopsy appeared to be easier to perform because of decreased inflammation and edema and a more readily dissectible facial nerve., Conclusion: Children with nontuberculous mycobacteria-induced parotid lymphadenitis should be started on a trial of antibiotic treatment before surgery. Although surgery remains the definitive treatment modality, a larger study of preoperative antibiotic use against nontuberculous mycobacterial adenitis of the parotid in children is necessary.

Background: With the increasing amount and complexity of medical information, medical schools are challenged with incorporating surgical subspecialty education, such as otolaryngology (OTO), into a time-limited curriculum., Objectives: To understand the state of OTO education in US medical schools and to generate a discussion of the role of surgical subspecialty education in the medical school curriculum., Design: Mail survey and follow-up letter and telephone survey conducted in 2000 to 2001., Participants: Academic faculty at each of the 125 US medical schools., Results: Responses were obtained from all 122 OTO programs associated with the 125 US medical schools with Liaison Committee on Medical Education-accredited programs. One third (33.6%) of the schools have a required rotation in OTO in the clinical years, with others offering elective rotations; only 5.2% offered no exposure in the third year of medical school. Most schools offer some OTO in the first 2 years; 71.1% and 87.2% taught OTO in the first and second years, respectively, mostly in anatomy and physical diagnosis. In the fourth year, almost 68.9% of schools reported student participation in an OTO elective., Conclusion: Most medical schools in the United States offer some teaching and clinical exposure to OTO, with considerable variability in the type of experience.

The germinal center (GC) reaction in T cell dependent antibody responses is crucial for the generation of B cell memory and plays a critical role in B cell lymphomagenesis. To gain insight into the physiology of this reaction, we identified the transcriptional changes that occur in B cells during the GC-transit (naïve B cells --> CD77(+) centroblasts (CBs) --> CD77(-) centrocytes (CCs) --> memory B cells) by DNA microarray experiments and the subsequent data analysis employing unsupervised and supervised hierarchical clustering. The naïve B cell is characterized by a nonproliferative, anti-apoptotic phenotype and the expression of various chemokine and cytokine receptors. The transition from naïve B cells to CBs is associated with (1) the up-regulation of genes associated with cellular proliferation, DNA-repair, and chromatin remodeling; (2) the acquisition of a pro-apoptotic phenotype; (3) the down-regulation of cytokine, chemokine, and adhesion receptors expressed in the naïve cells; and (4) the expression of a distinct adhesion repertoire. The CB and the CC revealed surprisingly few gene expression differences, suggesting that the CC is heterogeneous in its cellular composition. The CB/CC to memory B cell transition shows a general reversion to the profile characteristic for the naïve B cells, with the exception of the up-regulation of several surface receptors, including CD27, CD80, and IL-2Rbeta, and the simultaneous expression of both anti- and pro-apoptotic genes. These gene expression profiles of the normal B cell subpopulations are being used to identify the signals occurring during GC development, the cellular derivation of various types of B cell malignancies, and the genes deregulated in GC-derived tumors.

The germinal center (GC) reaction is crucial for T cell-dependent immune responses and is targeted by B cell lymphomagenesis. Here we analyzed the transcriptional changes that occur in B cells during GC transit (naive B cells --> centroblasts --> centrocytes --> memory B cells) by gene expression profiling. Naive B cells, characterized by the expression of cell cycle-inhibitory and antiapoptotic genes, become centroblasts by inducing an atypical proliferation program lacking c-Myc expression, switching to a proapoptotic program, and down-regulating cytokine, chemokine, and adhesion receptors. The transition from GC to memory cells is characterized by a return to a phenotype similar to that of naive cells except for an apoptotic program primed for both death and survival and for changes in the expression of cell surface receptors including IL-2 receptor beta. These results provide insights into the dynamics of the GC reaction and represent the basis for the analysis of B cell malignancies.

Background: Primary bone sarcomas arising in osseous structures of the head and neck are rare. These tumors are often incompletely resected and treated with radiotherapy for local control., Methods: We report a case of a 9-year-old girl with a maxillary Ewing's sarcoma. This patient was successfully treated with neoadjuvant chemotherapy followed by surgical resection and prosthetic reconstruction of the primary site. The surgical approach that was used consisted of a subtotal maxillectomy by means of a facial degloving approach, sparing the orbital contents and the inferior orbital rim and orbital floor., Results: This approach produced excellent cosmetic, functional, and oncologic outcome. The patient remains without evidence of disease recurrence more than 4 years after surgery., Conclusions: This case illustrates a novel surgical approach to the resection of a maxillary Ewing's sarcoma and highlights the need for a multidisciplinary team approach to the management of head and neck sarcomas in children., (Copyright 2003 Wiley Periodicals, Inc.)

Objective: To determine whether there is an increased amount of free radical-mediated damage in diseased vs healthy tissue from patients with chronic rhinosinusitis., Design: Pathophysiologic study. Samples of heathly and diseased tissue were taken from each patient. Lipid peroxides (LPOs) are a by-product of free radical-mediated damage; LPO levels and LPO/protein ratios were determined for each patient., Subjects: Consecutive series of 13 human subjects undergoing functional endoscopic sinus surgery to treat chronic rhinosinusitis., Results: The mean LPO/protein ratio for healthy tissue was 3.52 x 10(-5), while that for the diseased tissue was 3.49 x 10(-5). There was no statistically significant difference in the LPO/protein ratio between healthy and diseased tissue (95% confidence interval, -3.00 x 10(-5) to 2.94 x 10(-5))., Conclusion: Free radical-induced damage, if present, was the same in infected and control tissues in this pilot investigation into the pathophysiologic characteristics of human chronic rhinosinusitis.

Neonatal tracheal injury/perforation is an uncommon complication of traumatic deliveries or endotracheal intubation. We present a case of neonatal tracheal injury following delivery at term that presented with subcutaneous emphysema and pneumomediastinum before any attempt at intubation. The clinical course, treatment, and outcome are described.

Objectives: To determine the impact of adenotonsillectomy on quality of life (QOL) in children with obstructive sleep disorders (OSDs) before and after surgery., Design: Prospective, observational, before-and-after trial., Setting: Seven tertiary pediatric otolaryngology practices., Patients: Convenience sample of 101 children (mean age, 6.2 years) with adenotonsillar hypertrophy and OSD scheduled for adenotonsillectomy., Intervention: Adenotonsillectomy was performed in children for OSDs. Quality of life was assessed using the Obstructive Sleep Disorders-6 survey, a validated instrument for detecting QOL change in children with OSDs. Surveys were completed at the initial office visit (visit 1), the day of surgery (visit 2), and at the postoperative office visit (visit 3). Physical characteristics were assessed using tonsillar and orocraniofacial scales (visit 1). Satisfaction with health care decisions was assessed using the Satisfaction With Decision and Satisfaction With Office Visit scales (visit 1)., Main Outcome Measures: Short-term changes in QOL before (visits 1 and 2) and after (visits 2 and 3) surgery., Results: Changes in QOL before surgery were trivial or small, and smaller than changes after surgery (mean change score, 0.18 vs 2.3; P<.001). Large, moderate, and small improvements in QOL were seen in 74.5%, 6.1%, and 7.1% of children, respectively. Sleep disturbance, caregiver concern, and physical suffering were the most improved domains, although significant changes also occurred for speech and swallowing problems, emotional disturbance, and activity limitations. Five percent of children had poorer QOL after surgery, but no predictive factors were identified., Conclusion: Adenotonsillectomy produces large improvements in at least short-term QOL in most children with OSDs.

Objective: To describe the spectrum of pediatric tongue lesions treated surgically at Columbia-Presbyterian Medical Center from January 1990 to December 1999., Study Design and Setting: Retrospective case-series at the pediatric hospital of a tertiary care, academic medical center., Results: Seventeen patients were identified. Their ages ranged from 1 to 132 months (median, 7 months). Eight lesions were located anteriorly: mucous cyst (1), polyp (1), chronic inflammatory mass (1), hamartoma (1), squamous papilloma (2), cavernous hemangioma (1), and vascular malformation (1). Four lesions were located posteriorly: teratoma (1), glial choristoma (1), osseous choristoma (1), and benign epithelial cyst (1). Finally, there were 5 diffuse lesions including macroglossia (4) and massively infiltrating congenital lymphatic malformation (1). Symptoms included respiratory distress (3) and dysarthria (3); all other children were asymptomatic., Conclusions: This series revealed an interesting spectrum of rare solid tumors; compared with other large series, fewer lymphatic and vascular malformations were seen. Presenting symptoms, differential diagnosis, and surgical approach were differentiated according to lesion location.

Objectives: Oxygen free radicals are implicated in the pathogenesis of otitis media Recent investigations with animal models have demonstrated that free radical-mediated damage of the middle ear mucosa, measured as lipid hydroperoxide, occurs when the middle ear cavity is inoculated with Streptococcus pneumoniae. The present study was conducted to examine the effect of antibiotics on free radical-mediated damage in pneumococcal acute otitis media., Study Design: Animal model of acute otitis media., Methods: Seventy-eight guinea pigs underwent bilateral middle ear inoculation with 100 microl of 1) sterile saline as a control, 2) 50 microg/mL amoxicillin, 3) 10(7) colony forming units (CFU)/mL Streptococcus pneumoniae killed with 50 microg/mL amoxicillin, or 4) 10(7) CFU/mL S. pneumoniae. Animals were killed on postoperative day 1 or 5, and the middle ear mucosa was examined for lipid peroxidation as evidence of free radical damage., Results: Mucosal lipid hydroperoxide was significantly elevated compared with control subjects on day 1 in both the antibiotic-killed S. pneumoniae group and the S. pneumoniae-infected group. On day 5, the S. pneumoniae-infected mucosa had significantly higher lipid hydroperoxide levels compared with the antibiotic-killed group and the control subjects. Histological studies confirmed mucosal edema and the presence of inflammatory cells in the infected groups., Conclusions: Antibiotic-killed bacteria seem to produce free radical-mediated damage to the middle ear mucosa in the early phase of acute otitis media. The clinical implication of this study is that free radical damage to the middle ear mucosa may occur in otitis media despite appropriate antibiotic therapy.

Context: Children with chronic otitis media are at risk for nonsusceptible Streptococcus pneumoniae (NSP) infection. If these children undergo ventilating tube placement, there is an opportunity to culture middle ear fluid and the nasopharynx to determine carriage of NSP., Objective: To determine the incidence of NSP carriage, NSP antibiotic susceptibility and risk factors for NSP carriage in children with chronic otitis media undergoing tube placement., Design and Setting: Prospective cohort study in an academic medical center with recruitment of patients from an otolaryngology private practice and clinic., Patients: Children < 18 years of age undergoing tube placement for chronic otitis media., Interventions: Myringotomy and tube placement, with culture of middle ear fluid and nasopharynx., Main Outcome Measures: The incidence of NSP cultured from the middle ears and nasopharynx of recruited subjects with the use of the minimum inhibitory concentration break points for penicillin susceptibility recommended by the National Committee for Clinical Laboratory Standards., Results: S. pneumoniae was identified in at least 1 site from 23 of 300 study subjects (7.6%); of these 23, 12 case subjects (52.2%) harbored NSP. Of the risk factors assessed by preoperative questionnaire, only younger age was associated with NSP colonization (P < 0.0001). Of the six oral cephalosporins studied, cefpodoxime and cefuroxime showed good in vitro activity against S. pneumoniae isolates with intermediate penicillin resistance., Conclusions: Children with chronic otitis media undergoing tube placement may carry NSP and provide a means of monitoring the incidence of NSP and antibiotic susceptibilities for children with ear infections in their communities. Younger age is a risk factor for NSP carriage in this population.

Objective: To determine the proportion of children with acute otitis media (AOM) presenting in our catchment area in New York City who were infected with nonsusceptible Streptococcus pneumoniae and to determine the susceptibility of these organisms to penicillins and other antibiotics commonly used to treat AOM., Setting: Ambulatory clinics and the emergency department of a tertiary care, inner-city medical center., Patients: During a 2-year period from 1993 to 1995, 115 children (aged 6 months to 12 years) with AOM underwent tympanocentesis. Patients did not receive antibiotics for at least 1 week before tympanocentesis., Results: Thirty-one children were infected with S pneumoniae, and 83.9% of isolates were susceptible to penicillin. Of the 16.1% strains that were nonsusceptible, most (4 of 5 strains) were intermediately resistant, and only 1 exhibited high-level resistance to penicillin. Of all the cephalosporins tested, only cefotaxime had consistent activity against the intermediately resistant strains. Notably, all nonsusceptible pneumococci were inhibited by macrolides., Conclusions: This study provides unique reference data for nonsusceptible Streptococcus pneumoniae in children with AOM and documents that newer cephalosporin agents are not active against all of these strains.

Oxygen free radical damage has been demonstrated in the middle ear mucosa of a guinea pig model of acute otitis media (AOM). Potential sources of free radicals include both neutrophils responding to infection and Streptococcus pneumoniae, a common AOM pathogen. This project was conducted to examine the middle ear fluid in a guinea pig model of AOM for evidence of elevated lipid peroxide (LPO) as a marker of free radical damage. Twenty-one guinea pigs were injected transtympanically with bacteria into the left (infected) middle ear cavity and sterile saline into the right (control) middle ear. Middle ear fluid was recovered on postoperative day 5. The fluid was weighed and analyzed for quantity of LPO. Results indicated an increased absolute level of LPO, as well as an increased level of LPO divided by the weight of the fluid recovered. Histologic examination confirmed leukocyte infiltration and mucosal edema that were consistent with mucosal damage. While free radical damage to the middle ear mucosa in a guinea pig model of AOM is well documented, this is the first study to demonstrate evidence of free radical damage in middle ear fluid. These results are relevant because they correlate mucosal damage with lipoperoxidation in fluid. Additionally, this serves as an important precursor to human studies, since middle ear fluid is readily available in patients with otitis media.

Recent work with a guinea pig model of otitis media has demonstrated evidence of oxygen free radical damage to the middle ear mucosa. However, the relevance of an animal model to human disease is uncertain. Accordingly, the following pilot study was conducted to examine human middle ear fluid for lipid hydroperoxides as evidence of free radical damage. Thirty-five specimens of middle ear fluid from children with chronic otitis media were collected and described as mucoid (n = 19), purulent (n = 10), or serous (n = 6); specimens were weighed and analyzed for lipid hydroperoxide content. The results demonstrated the presence of lipid hydroperoxide in all 3 types of middle ear fluid. Additionally, there was a statistically significant elevation of total lipid hydroperoxide content in mucoid effusions compared with serous effusions, as well as a significant elevation of lipid hydroperoxide divided by weight of purulent effusions compared with serous effusions. This is the first study to document free radical damage in human otitis media.

Background: The objective of this study was to assess the relationship between Epstein-Barr virus (EBV) infection and posttransplantation lymphoproliferative disease (PTLD) in pediatric heart transplant recipients. EBV is implicated in the development of PTLD. However, the relationship between primary EBV infection and PTLD is not well understood., Methods: Serial EBV titers were determined prospectively in 50 children before and after heart transplantation. Results were correlated with the development of PTLD. The clinical presentation, management, and outcome of PTLD were characterized., Results: Before transplantation, EBV titers were positive in 19 and negative in 31 patients. After transplantation, all EBV-positive patients remained positive; 1 developed PTLD. Among EBV-negative patients, 12 of 31 remained negative; none developed PTLD. Nineteen patients demonstrated serologic evidence of primary EBV infection after heart transplantation; 12 developed PTLD. Mean follow-up after heart transplantation was 3.3 years (range 0.4 to 8.4 years). Mean time from heart transplantation to histologic confirmation of PTLD was 29 months (range 3 to 72 months). Survival with PTLD was 92%., Conclusions: Twelve of 13 pediatric heart transplant recipients who developed PTLD had evidence of primary EBV infection. Serial monitoring of EBV titers may lead to earlier identification and improved treatment of PTLD.

A 6-year retrospective chart review was conducted of all pediatric patients with the diagnosis of retropharyngeal abscess (RPA) at the Columbia-Presbyterian Medical Center. The charts were examined for signs, symptoms, and serologic findings consistent with recent acute Epstein-Barr virus (EBV) infection. Of the 7 patients we studied, 4 had elevated immunoglobulin G antibodies that were consistent with recent acute EBV infection, and 3 patients were not tested. The 4 patients with positive titers also presented with signs typical for acute EBV infection, including fever (3/4), lymphadenopathy (4/4), and pharyngitis (4/4). Of note, the 2 patients who were older than expected for RPA (ages 18 and 11) had the most severe infections. We submit that there may be a role for EBV infection in the pathogenesis of RPA formation in children. Increasing age may correlate with a more severe infection in this setting.

Free radicals participate in the development of disease under inflammatory conditions. Lipid peroxides such as malondialdehyde are regarded as markers of cell membrane damage by oxidative stresses. Previous work from our laboratory has demonstrated that lipidperoxidation is increased in acute otitis media in guinea pigs, implicating a role for free radicals as contributors to inflammation. In this study we examined the effect of lazaroid U-74389G, a 21-aminosteroid, on acute otitis media in guinea pigs. Streptococcus pneumoniae organisms were inoculated into the right tympanic cavity; sterilized phosphate-buffered saline solution was injected into the left ear to serve as a control. The guinea pigs were given intraperitoneal injections of 40 mg/kg of a lazaroid compound or its vehicle every 12 hours. Middle ear mucosa was collected and used for assay. We quantified lipid peroxide by means of the methylene blue-hemoglobin method and by means of measurement of thiobarbituric acid reactive substance. Lazaroid significantly (p < 0.05) suppressed production of lipid hyproperoxide of the middle ear mucosa of the guinea pigs with acute otitis media for up to 24 hours. These results suggest that lazaroid may reduce lipoperoxidation in the middle ear at an early stage of acute otitis media.

Objective and Importance: To our knowledge, this is the first reported case of the use of stereotactic radiotherapy for an eosinophilic granuloma (EG) of the clivus. We report follow-up information on two previously reported cases and suggest a management plan for this rare lesion., Clinical Presentation: We report the case of a 4.5-year-old boy who presented with a complete abducens palsy on the right with an associated head turn. A computed tomographic scan of his head revealed a lytic lesion on that side, and magnetic resonance imaging showed the mass to be of low intensity on T1-weighted images and of high intensity on T2-weighted images with heterogeneous enhancement., Intervention: A transnasal stereotactic biopsy was performed, revealing an EG. The patient was treated with stereotactic radiotherapy, and he became symptom-free with radiographic resolution of his lesion. Reviewing the literature, we found 13 series with 87 cases of EG in the petrous portion of the temporal bone. EG in the cranial base occurring outside of the temporal bone or in the temporal bone and extending intracranially is, however, quite rare, with only nine other cases reported, two of them clival., Conclusion: These findings suggest a classification schema in which cranial base EG lesions be grouped with either the more common extracranial petrous temporal bone lesions or the very rare intracranial lesions. Although there are few cases in the literature, treatment results indicate that clival EG, and perhaps all intracranial cranial base EGs, be treated by a biopsy alone, followed by surgery or stereotactic radiotherapy if there is an incomplete resolution of the symptoms or if there is a recurrence.

Increasing evidence implicates free radicals in the pathogenesis of inflammatory disease, including otitis media. The anti-oxidant enzymes catalase, glutathione peroxidase and superoxide dismutase protect tissues from the destructive effects of free radicals. Our previous work has shown depressed levels of superoxide dismutase in the infected middle ears of a guinea pig model of otitis media in comparison with normal control ears. We studied the distribution and relative abundance of catalase in the middle ear of this animal model in an effort to elucidate the role free radicals play in the pathogenesis of otitis media. Catalase distribution was mapped immunohistochemically in the middle ears of guinea pigs with induced streptococcus otitis media, and compared with normal control ears. In the control ears, catalase was localized to the epithelium of the middle ear mucosa, with scant distribution in the submucosa. The infected ears demonstrated inflammatory cell invasion with hyperemia and submucosal edema. Catalase was localized to the epithelium and had scant distribution in the submucosa. This distribution was similar to that found previously with superoxide dismutase. Enzyme-linked immunosorbent assay of catalase demonstrated a mean value of 1.00 +/- 0.06 microgram/mg protein in the control ears, and 1.06 +/- 0.12 microgram/mg in the infected ears, but these two values were not statistically different.

Heat shock proteins (hsps) are essential for the survival of cells under an environmental insult. To elucidate the relationship between these intracellular proteins and acute otitis media (AOM), the authors studied hsp production in guinea pigs with AOM induced by inoculation of Streptococcus pneumoniae into the middle ear. Animals were sacrificed 1, 3, or 5 days after inoculation. Immunocytochemical study showed localization of hsp70 within the epithelium of infected ears, while the normal control epithelium showed very light staining. Western blot tests of the mucosal extraction confirmed the presence of hsp70 in otitis media. Enzyme-linked immunosorbent assay (ELISA) showed that hsp levels were higher in the infected mucosa than in the normal control mucosa. In contrast, hsp60 was not stimulated in infected ears. This study showed that hsp70, and not hsp60, was produced in the AOM model.

A retrospective chart review was undertaken at Columbia Presbyterian Medical Center to assess the incidence, etiology and management of head and neck infections in pediatric cardiac transplant patients on immunosuppression. From June 1984 to February 1992, 59 cardiac transplants were performed on 57 pediatric patients. Standard immunosuppressive therapy was used. Thirteen of these patients died within three months of transplant and were not included. Of the 44 patient charts reviewed, 82 head and neck infections were documented in 27 patients (61%). There were 26 episodes of sinusitis, 27 episodes of otitis media and 20 episodes of tonsillitis/pharyngitis. Unusual middle-ear pathogens seen included Morganella morgagni and Pseudomonas aeruginosa. These preliminary data suggest that children on immunosuppression for cardiac transplant may be at risk for head and neck infections from unusual or unsuspected organisms, and tympanocentesis plays an important role in diagnosis and treatment. A prospective study is planned to gain further data.

Cu, Zn superoxide dismutase (SOD) is a metalloprotein that catalyzes the dismutation of the superoxide anion into O2- and H2O2, and therefore functions to maintain a low intracellular concentration of an otherwise toxic metabolite of oxygen. SOD protects living tissue from the destructive effects of free radicals. Increasing evidence implicates free radicals, including the superoxide radical (O2-), in the pathogenesis of disease, including otitis media. In an effort to elucidate the role free radicals play in the pathogenesis of otitis media, SOD was localized immunocytochemically to determine its cellular distribution in specimens of guinea pig middle ear. In normal ears, SOD was found concentrated in the epithelium of the middle ear mucosa. Low quantities were characteristic of connective tissue, bone, and cartilage. In streptococcus-infected ears, SOD localized similarly, concentrating in the epithelium. The infected ears had extensive submucosal edema which stained poorly and appeared to have less SOD than did normal ears. This was confirmed by an assay using laser densitometry of Western blots to quantify the amount of SOD in the mucosa of normal versus infected middle ears. This demonstrated a value of SOD in normal mucosa of 1.77 +/- 0.48 micrograms/mg of protein compared with 1.02 +/- 0.28 micrograms/mg in the infected mucosa. The two groups were significantly different at P < 0.05. These findings are discussed, and suggestions for future experimentation addressed.

Free radicals have been implicated in the pathogenesis of an increasing number of diseases and inflammatory states. They may cause tissue damage by their chemical modification of proteins, carbohydrates, nucleotides, and lipids. Lipid peroxidation occurs as a consequence of free radicals acting on the polyunsaturated fatty acids of cellular membranes. To determine if free radicals play a role in the pathogenesis of otitis media, lipid peroxides and their by-products were assayed in the mucosa of a guinea pig model of otitis media. Both lipid hydroperoxide (LPO) and malondialdehyde (MDA) were measured in the tissues of the middle ear mucosa. Comparisons were made between an infected and a control group. Both LPO and MDA were found to be significantly elevated (P < .01 and P < .05, respectively) in the infected mucosa. Correlation of the biochemical data was made with histologic studies. The significance of these findings as well as suggestions for future experimentation are addressed.

Nasal continuous positive airway pressure (CPAP) is being used more frequently in neonatal intensive care units to avoid endotracheal intubation and its attendant complications. Nasal deformities secondary to the nares-occluding prongs employed to deliver the CPAP in former preterm infants have been recognized, and prevention and surgical treatment of these deformities are discussed. An awareness of the potential for these deformities is important to all pediatric otolaryngologists as nasal CPAP is gaining increasing favor as a primary treatment for respiratory disease of the newborn.

Acute otitis media is extremely common in children under 6 years of age. This article reviews the pathogenesis and epidemiology of this problem. Treatments are outlined, including choice of antibiotics, decision-making for tympanocentesis, and approaches to recurrent otitis media. Complications such as mastoiditis, although rare, still occur and are discussed. Prevention of acute otitis media also is reviewed, including information on vaccines.