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John H Greinwald

Publications and source records attributed to John H Greinwald.

14 recordsLinked to original sources
PubMed2004

Genomic organization and expression analysis of the murine Fam3c gene.

Previously, we identified FAM3C as a candidate gene for autosomal recessive nonsyndromic hearing loss locus 17 (DFNB17). This gene has since been found to be a member of a cytokine-like gene family, but its function has not been determined. The purpose of this study was thus to elucidate the gene structure and pattern of expression, providing information that might allow a hypothesis to be developed about FAM3C function of in the inner ear. To do this we analyzed its mouse ortholog, Fam3c. Fam3c was found to be ubiquitously expressed in all analyzed tissues, and had two major transcript variants presumed to result from an alternative use of two distinct polyadenylation signals. In situ hybridization experiments revealed a predominant Fam3c pattern of expression in the nonsensory epithelium of the growing semicircular canals at embryonic day (E) 15.5. This expression pattern resembles the known pattern of the Nkx5 homeobox genes. Analysis of the Fam3c promoter region demonstrated a putative Nkx5.1 binding site. Based on our findings, we hypothesize that Fam3c may be a downstream target gene for the Nkx5.1 transcription factor, and may thus be involved in cell differentiation and proliferation during inner ear embryogenesis. Additionally, analyses of putative amino acid sequences of FAM3C orthologous proteins showed that their primary and secondary structures and overall topology were highly conserved. Further study is underway to determine the role of FAM3C in inner ear development.

Amino Acid Sequence↗
PubMed2004

A diagnostic paradigm for childhood idiopathic sensorineural hearing loss.

OBJECTIVE: Our objective was to determine the diagnostic yield of laboratory testing, radiological imaging, and GJB2 mutation screening in a large cohort of patients with differing severities of idiopathic sensorineural hearing loss (SNHL). DESIGN AND SETTING: We undertook a retrospective study of patients presenting with SNHL at our institution from 1993 to 2002. RESULTS: Laboratory testing had an extremely low yield. Patients with unilateral SNHL had a significantly higher imaging yield than those with bilateral. The diagnostic yield of GJB2 screening was significantly higher in patients with severe to profound SNHL than in those with less severe SNHL. However, a relatively large number of patients with mild to moderate SNHL had positive GJB2 screens. CONCLUSIONS: Based on diagnostic yields, we propose a cost-effective stepwise diagnostic paradigm to replace the more commonly used and costly simultaneous testing approach. EBM RATING: C.

Adolescent↗
PubMed2004

Bacterial tracheitis reexamined: is there a less severe manifestation?

OBJECTIVE: Bacterial tracheitis (BT) is a condition that can cause fatal airway obstruction. We evaluated our experience with BT over a 10-year period. STUDY DESIGN: Retrospective review of patients treated for BT between 1991 and 2001. RESULTS: Ninety-four cases were evaluated. The mean patient age was 7.9 years. At presentation, 60% were afebrile, and the mean WBC count was 10.8 x 10(3)/mm3 . Only 53% of patients required intubation. Younger children were more likely to require this intervention. S. aureus was the most commonly cultured bacteria, while isolation of M. catarrhalis was associated with a higher intubation rate. A pathologic virus was isolated in 64% of the 34 cultures performed. Only 9 patients were described as "toxic," and 6 presented in respiratory extremis. There were no deaths. CONCLUSION AND SIGNIFICANCE: A subset of patients with tracheal membranes has a less severe clinical appearance. Nonetheless, these patients require debridement and aggressive medical treatment. We propose that the term "exudative tracheitis" (ET) better describes this entity. Older patients who are less systemically ill and rapidly respond to local and systemic therapy are characteristic of ET. EBM RATING: C.

Adolescent↗
PubMed2004

Refining the DFNB17 interval in consanguineous Indian families.

We previously mapped the DFNB17 locus to a 3-4 cM interval on human chromosome 7q31 in a large consanguineous Indian family with congenital profound sensorineural hearing loss. To further refine this interval, 30 new highly polymorphic markers and 8 SNPs were analyzed against the pedigree. Re-analysis in the original DFNB 17 family and additional data from a second unrelated consanguineous family with congenital deafness found to map to the interval, limited the area of shared homozygosity-by-descent (HBD) to approximately 4 megabase (Mb) between markers D7S2453 and D7S525. Nineteen known genes and over 20 other cDNAs have been identified in the refined DFNB 17 interval, including the SLC26A4 gene. We have analyzed 4 other cochlear-expressed genes that map to the DFNB17 interval as candidate genes. Analysis of coding and splice site regions of these cochlear expressed genes did not reveal any disease causing mutations. Further study of other candidate genes is currently underway.

Chromosome Mapping↗
PubMed2004

Co-expression of pendrin, vacuolar H+-ATPase alpha4-subunit and carbonic anhydrase II in epithelial cells of the murine endolymphatic sac.

The endolymph in the endolymphatic sac (ES) is acidic (pH 6.6-7). Maintaining this acidic lumen is believed to be important for the normal function of the ES. The acid-base regulation mechanisms of the ES are unknown. Here we investigated the expression patterns of acid-base regulators, including vacuolar (v)H+-ATPase (proton pump), carbonic anhydrase (CA) II, and pendrin in the murine ES epithelium by immunohistochemistry (IHC) and compared their expression patterns by double immunostaining. We found that pendrin and vH+-ATPase were co-localized in the apical membrane of a specific type of ES epithelial cell. Pendrin- and vH+-ATPase-positive cells also expressed cytoplasmic CA II. Co-expression of pendrin, vH+-ATPase, and CA II in the same subgroup of ES cells suggests that this specific type of ES cell is responsible for the acid-base balance processes in the ES and pendrin, vH+-ATPase, and CA II are involved in these processes.

Animals↗
PubMed2004

The cochlear cleft.

BACKGROUND AND PURPOSE: Recent advances in the display of medical images permit the routine study of temporal bone CT images at high magnification. We noted an unfamiliar structure, which we now call the "cochlear cleft," in the otic capsule. To our knowledge, this report represents the first description of this structure in the medical imaging literature. METHODS: Temporal bone CT performed in 100 pediatric patients without sensorineural hearing loss were examined for the presence of cochlear clefts. Incidence of cochlear clefts as well as the relationship between age and incidence was examined. RESULTS: Cochlear clefts were present in 41% of the subjects. Incidence decreased with age. CONCLUSION: We describe a cleft in the otic capsule that is frequently seen on magnified images of temporal bone CT studies in children. The cleft may be the fissula ante fenestram.

Adolescent↗
PubMed2003

Genotypic and phenotypic correlations of DFNB1-related hearing impairment in the Midwestern United States.

OBJECTIVE: To determine the genotypic and phenotypic correlations of hearing impairment (HI) in a midwestern US population related to autosomal recessive nonsyndromic hearing loss locus 1 (DFNB1). DESIGN: A retrospective review. SETTING: Tertiary care children's hospital. PATIENTS: A total of 160 consecutive children diagnosed with idiopathic sensorineural hearing loss. MAIN OUTCOME MEASURES: GJB2 genotype and audiometric phenotype. RESULTS: The prevalence of subjects with HI having biallelic GJB2-related mutations was 15.3% (24/157). Of these 24 patients, 9 (38%) were homozygous 35delG, 6 (25%) had other biallelic nonsense mutations, and 9 (38%) had a missense mutation of at least 1 allele. The allelic prevalence of 35delG was 8.6% (27/314) in the study population and 48% (23/48) in the DFNB1 group. The M34T allele mutation was next most prevalent at 2.2% (7/314) in the study population and 10% (5/48) in the DFNB1 group. Severe to profound HI occurred in 59% of DFNB1 subjects. Genotypes with biallelic nonsense mutations had a high risk of severe to profound HI (88%). DFNB1-related HI was usually bilateral, symmetric, nonprogressive, and had flat audiograms. However, asymmetric HI (22%), sloping audiograms (26%), and even borderline-normal hearing in 1 ear was observed, and these were associated with the presence of at least 1 missense mutation. Two novel mutations, K15T and L90V, were identified. A subject presenting to our clinic with severe to profound HI had a 40% risk of biallelic GJB2 mutation. CONCLUSIONS: Our population represents a consecutively enrolled clinic population with sensorineural hearing loss. In our DFNB1-related HI cohort, the 35delG mutation and severe to profound HI rates were lower than previously reported. Our missense mutation and M34T allelic prevalence rates were higher than expected and were associated with a less severe hearing loss. The presence of biallelic nonsense mutations was associated with severe to profound hearing loss in nearly 90% of cases. Mild asymmetric HI and sloping audiograms were more often associated with missense mutations.

Adolescent↗
PubMed2003

Expression of aquaporin 1 and 5 in the developing mouse inner ear and audiovestibular assessment of an Aqp5 null mutant.

To examine the potential roles of aquaporins 1 and 5 (AQP1 and AQP5, respectively) in inner ear development and function, we defined their spatial and temporal expression patterns in the developing mouse inner ear and examined the morphologic and physiologic effects of loss of Aqp5 function. Standard in situ hybridization (ISH) and immunohistochemical (IHC) assays were used for expression studies with routine morphologic, behavioral, and physiologic assessments of hearing and balance in Aqp5 null mutant mice. AQP1 was first detected at embryonic day 10.5 (E10.5) in the otocyst but eventually localized to specific nonsensory portions of the inner ear and connective tissue cells surrounding the membranous labyrinth. AQP5 displayed specific cochlear expression, first detectable at E15.5 in the nonsensory epithelium and later restricted to the lateral wall of the cochlear duct near the spiral prominence. AQP5 expression continued through postnatal periods with a change of expression domain to the stria vascularis between postnatal day 7 (P7) and P14. By in situ hybridization and immunohistochemical techniques, subtle differences between transcript and protein expression patterns were noted for both AQP1 and 5. Although AQP5 is dynamically expressed in the developing mouse inner ear, adult Aqp5 knockout mice show normal hearing when tested and normal inner ear structural development. These results suggest redundant or alternative mechanisms that likely regulate water homeostasis in the developing and mature inner ear.

Aging↗
PubMed2003

Temporal bone abnormalities associated with hearing loss in Waardenburg syndrome.

OBJECTIVES/HYPOTHESIS: The objectives were to correlate audiometric thresholds with radiological findings and to determine the prevalence of inner ear radiological abnormalities in patients with hearing loss and Waardenburg syndrome. STUDY DESIGN: The study was a retrospective review of patients with Waardenburg syndrome identified in a pediatric hearing-impaired population and human genetics clinic. METHODS: Nine children with Waardenburg syndrome were identified. Eighty-nine children without sensorineural hearing loss served as control subjects. Clinical data, audiometric thresholds, and radiographic temporal bone measurements in these children were analyzed. RESULTS: Seven children were identified with hearing loss and Waardenburg syndrome. Four children had Waardenburg syndrome type 1, and three children had Waardenburg syndrome type 2. The overall prevalence of hearing loss in the total study population with Waardenburg syndrome was 78%. The mean pure-tone average was 99 dB. All of the children had sensorineural hearing loss. The hearing outcome was stable in 86% of the children. Twelve temporal bones were available for radiological analysis by computed tomography. Enlargement of the vestibular aqueduct was found in 50% of the CT scans. There was a significant difference in measurements of vestibular aqueduct width at the midpoint between the patients with Waardenburg syndrome and the control group (P <.05). There were also significant differences in the measurements of the vestibule (P =.0484), internal auditory canal (P =.0092), and modiolus (P =.0045) between the children with Waardenburg syndrome and the control group. CONCLUSION: A profound sensorineural hearing loss was characteristic of the study population with Waardenburg syndrome. Overall, 100% of patients with hearing loss and Waardenburg syndrome had temporal bone anomalies on at least one measurement of their inner ear, and 50% had an enlargement of the vestibular aqueduct at the midpoint. As shown by computed tomography, enlargement of the vestibular aqueduct and the upper vestibule, narrowing of the internal auditory canal porus, and hypoplasia of the modiolus are features of Waardenburg syndrome.

Audiometry, Pure-Tone↗
PubMed2002

Treatment of lymphangiomas with OK-432 (Picibanil) sclerotherapy: a prospective multi-institutional trial.

OBJECTIVE: To describe and to determine the robustness of our study evaluating the efficacy of OK-432 (Picibanil) as a therapeutic modality for lymphangiomas. DESIGN AND SETTING: Prospective, randomized trial and parallel-case series at 13 US tertiary care referral centers. SUBJECTS: Thirty patients diagnosed as having lymphangioma. Ages in 25 ranged from 6 months to 18 years. Twenty-nine had lesions located in the head-and-neck area. INTERVENTION: Every patient received a 4-dose injection series of OK-432 scheduled 6 to 8 weeks apart unless a contraindication existed or a complete response was observed before completion of all injections. A control group was observed for 6 months. OUTCOME MEASURES: Successful outcome of therapy was defined as a complete or a substantial (>60%) reduction in lymphangioma size as determined by calculated lesion volumes on computed tomographic or magnetic resonance imaging scans. RESULTS: Overall, 19 (86%) of the 22 patients with predominantly macrocystic lymphangiomas had a successful outcome. CONCLUSIONS: OK-432 should be efficacious in the treatment of lymphangiomas. Our study design is well structured to clearly define the role of this treatment agent.

Adolescent↗
PubMed2002

Ectopic cervical thymus: an uncommon diagnosis in the evaluation of pediatric neck masses.

Ectopic cervical thymic tissue is an uncommon cause of neck masses in children, with fewer than 100 cases reported in children who presented with primary neck masses. To illustrate the unique characteristics of these tumors, we report the case of a 13-month-old boy with ectopic thymic tissue presenting with asymptomatic, bilateral, and solid cervical masses. This case report highlights several unique findings: (1) the rare nature of solid thymic tumors compared with cystic lesions, (2) the utility of magnetic resonance imaging scanning with and without fat suppression for diagnosis, and (3) the risks of surgical removal of thymic tissue in children. Despite its infrequent occurrence and often asymptomatic presentation, ectopic cervical thymus masses should be included as a rare cause of cervical masses in the pediatric population. Awareness of this diagnosis will allow for appropriate preoperative diagnostic studies, which may preclude the need for biopsy.

Choristoma↗
PubMed2002

Clinical and audiological features in auditory neuropathy.

OBJECTIVE: To medically and audiologically characterize a population of children diagnosed as having auditory neuropathy (AN). STUDY DESIGN: Retrospective medical chart review. SETTING/SUBJECTS: We identified 22 patients from a pediatric otology clinic in a tertiary care pediatric hospital setting. RESULTS: A genetic factor in AN is suggested by our identification of 3 families with 2 affected children and 2 other children with family histories that were positive for hearing loss. Clinical features common among our population included a history of hyperbilirubinemia (n = 11 [50%]), prematurity (n = 10 [45%]), ototoxic drug exposure (n = 9 [41%]), family history of hearing loss (n = 8 [36%]), neonatal ventilator dependence (n = 8 [36%]), and cerebral palsy (n = 2 [9%]). Full clinical and audiological data were available for 18 of the 22 children, including otoacoustic emissions, auditory brainstem responses with cochlear microphonics, and age-appropriate audiometric findings. Significantly, 9 of these 18 patients showed improvement in behavioral thresholds over time, indicating that a subset of children with AN may recover useful hearing levels. Also significant was the success of cochlear implantation in 4 children. CONCLUSIONS: Management of AN in children requires serial clinical and audiometric evaluations, with a prominent role for behavioral testing. Prematurity, genetics, and hyperbilirubinemia appear to be significant factors in the development of AN; hyperbilirubinemia can be associated with spontaneous improvement of hearing thresholds. For those children not benefiting from amplification or FM systems, cochlear implantation remains a potentially successful method of habilitation.

Audiometry↗
PubMedDate not supplied

Adult laryngomalacia: an uncommon clinical entity.

A 27-year-old female presented with a several-day history of acute onset inspiratory stridor and shortness of breath that worsened with phonation and minimal exertion. Flexible fiberoptic direct laryngoscopy revealed prolapse of the mucosa overlying the arytenoid cartilages bilaterally, consistent with type 1 laryngomalacia. These symptoms persisted with only minimal improvement despite administration of short-term corticosteroids, several weeks of antireflux medications, and other conservative measures. The patient underwent a supraglottoplasty and exhibited a marked improvement in her symptoms. The literature describes several cases of exercise-induced laryngomalacia in both pediatric and adult populations in which symptoms of inspiratory stridor and shortness of breath are induced by exercise but resolve upon its discontinuation. Adult laryngomalacia appears to be a clinical entity distinct from exercise-induced laryngomalacia because symptoms fail to resolve after several weeks of medical therapy and discontinuation of exertional activity. This case suggests that adult laryngomalacia, unlike pediatric and exercise-induced laryngomalacia, is less likely to resolve over time with conservative management and may require surgical intervention with supraglottoplasty necessary to alleviate symptoms.

Adult↗