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Biomedical subjects

D Choo

Publications and source records attributed to D Choo.

14 recordsLinked to original sources
PubMed2005

GJB2 mutations and additional disabilities in a pediatric cochlear implant population.

BACKGROUND: Children with severe to profound sensorineural hearing loss due to GJB2 mutations have often been deemed good cochlear implant candidates. Studies on children with GJB2 mutations and cochlear implants have typically excluded children with additional disabilities. OBJECTIVE: To investigate the presence of additional disabilities among children with and without GJB2 mutations in a cochlear implant population. METHODS: A retrospective chart review was performed of children with non-syndromic sensorineural hearing loss (SNHL) who received a cochlear implant between 1993 and 2004. RESULTS: Among 108 children within the cochlear implant database; 46 patients met the inclusion criteria of idiopathic non-syndromic hearing loss. Sixteen children had GJB2 mutations, 12 were GJB2 negative, and 17 did not receive GJB2 testing but had no other identifiable etiology or risk factor contributing to hearing loss. The proportion of children with additional disabilities that would affect either pre-operative assessments or post-operative results in the GJB2 positive group was 44% compared to 33% of children in the GJB2 negative. Additional disabilities were present in 41% of the children who did not receive GJB2 testing. The disabilities in the GJB2 positive group included specific learning disability, apraxia, epileptiform aphasia, attention deficit disorder, global developmental delay, and gross motor delay. The GJB2 negative and those children not receiving GJB2 testing had motor delays, language delay, autism, specific learning disability, and attention deficit disorder. The proportion of children with at least 6 months CI use who relied on oral communication was 62% in the GJB2 positive group, 66% in the GJB2 negative group, and 38% in the untested group. A majority of the genetic alleles were 35delG (81%) and 10 of 16 (63%) patients with GJB2 mutations were homozygous 35delG. The rate of developmental diagnoses was similar in patients with homozygous GJB2 compared to compound heterozygous genotypes. CONCLUSIONS: The presence of biallelic GJB2 mutations does not rule out non-hearing related disorders that can have an effect on speech, language and learning. Forty-four percent of children with GJB2 mutations had other conditions that could directly affect pre-implant evaluation and post-implant performance. This rate is similar to the reported prevalence among the overall population of children with hearing loss. All children should have a comprehensive evaluation of development and behavior regardless of the etiology of hearing loss.

Adolescent↗
PubMed2000

Developmental expression of aquaporin 2 in the mouse inner ear.

OBJECTIVES: The maintenance of endolymph homeostasis is critical for the inner ear to perform its functions of hearing and maintaining balance. The identification and cloning of aquaporins (a family of water channel proteins) has allowed the study of a novel cellular mechanism potentially involved in endolymph homeostasis. The objective of the present study was to define the developmental temporal and spatial expression pattern of aquaporin 2 (Aqp2) in the developing mouse inner ear. STUDY DESIGN: A systematic immunohistochemical study of Aqp2 protein expression was performed on embryonic mouse inner ears ranging from embryonic day 10 (otocyst stage) to embryonic day 18 (just before birth). METHODS: Serial cryosections of embryonic mouse inner ears were used for immunohistochemical experiments. A rabbit polyclonal antisera raised against a synthetic Aqp2 peptide was used with a standard nickel intensified 3,3-diaminobenzidine reaction protocol for immunolocalization of Aqp2 in tissue sections. RESULTS: Aquaporin 2 is expressed diffusely in the early otocyst, then becomes progressively restricted as the inner ear matures. During early cochlear duct formation (embryonic days 12 and 13), expression of Aqp2 is homogeneous; later, it becomes restricted to specific regions of the endolymphatic compartment (embryonic days 15 and 18). Similar restriction of expression patterns could be noted for the vestibular structures. Endolymphatic duct and sac and stria vascularis expression of Aqp2 was noted to occur fairly late during development but demonstrated a distinct pattern of immunolabeling. CONCLUSIONS: Aquaporin 2 shows an early and specific pattern of expression in the developing mouse inner ear, suggesting a significant role for this water channel protein in the development of endolymph homeostasis and meriting further functional studies of Aqp2 in the inner ear.

Animals↗
PubMed1999

Otx1 and Otx2 activities are required for the normal development of the mouse inner ear.

The Otx1 and Otx2 genes are two murine orthologues of the Orthodenticle (Otd) gene in Drosophila. In the developing mouse embryo, both Otx genes are expressed in the rostral head region and in certain sense organs such as the inner ear. Previous studies have shown that mice lacking Otx1 display abnormal patterning of the brain, whereas embryos lacking Otx2 develop without heads. In this study, we examined, at different developmental stages, the inner ears of mice lacking both Otx1 and Otx2 genes. In wild-type inner ears, Otx1, but not Otx2, was expressed in the lateral canal and ampulla, as well as part of the utricle. Ventral to the mid-level of the presumptive utricle, Otx1 and Otx2 were co-expressed, in regions such as the saccule and cochlea. Paint-filled membranous labyrinths of Otx1-/- mutants showed an absence of the lateral semicircular canal, lateral ampulla, utriculosaccular duct and cochleosaccular duct, and a poorly defined hook (the proximal part) of the cochlea. Defects in the shape of the saccule and cochlea were variable in Otx1-/- mice and were much more severe in an Otx1-/-;Otx2(+/)- background. Histological and in situ hybridization experiments of both Otx1-/- and Otx1-/-;Otx2(+/)- mutants revealed that the lateral crista was absent. In addition, the maculae of the utricle and saccule were partially fused. In mutant mice in which both copies of the Otx1 gene were replaced with a human Otx2 cDNA (hOtx2(1)/ hOtx2(1)), most of the defects associated with Otx1-/- mutants were rescued. However, within the inner ear, hOtx2 expression failed to rescue the lateral canal and ampulla phenotypes, and only variable rescues were observed in regions where both Otx1 and Otx2 are normally expressed. These results suggest that both Otx genes play important and differing roles in the morphogenesis of the mouse inner ear and the development of its sensory organs.

Animals↗
PubMed1999

Differential transcriptional control as the major molecular event in generating Otx1-/- and Otx2-/- divergent phenotypes.

Otx1 and Otx2, two murine homologs of the Drosophila orthodenticle (otd) gene, show a limited amino acid sequence divergence. Their embryonic expression patterns overlap in spatial and temporal profiles with two major exceptions: until 8 days post coitum (d.p.c. ) only Otx2 is expressed in gastrulating embryos, and from 11 d.p.c. onwards only Otx1 is transcribed within the dorsal telencephalon. Otx1 null mice exhibit spontaneous epileptic seizures and multiple abnormalities affecting primarily the dorsal telencephalic cortex and components of the acoustic and visual sense organs. Otx2 null mice show heavy gastrulation abnormalities and lack the rostral neuroectoderm corresponding to the forebrain, midbrain and rostral hindbrain. In order to define whether these contrasting phenotypes reflect differences in expression pattern or coding sequence of Otx1 and Otx2 genes, we replaced Otx1 with a human Otx2 (hOtx2) full-coding cDNA. Interestingly, homozygous mutant mice (hOtx2(1)/hOtx2(1)) fully rescued epilepsy and corticogenesis abnormalities and showed a significant improvement of mesencephalon, cerebellum, eye and lachrymal gland defects. In contrast, the lateral semicircular canal of the inner ear was never recovered, strongly supporting an Otx1-specific requirement for the specification of this structure. These data indicate an extended functional homology between OTX1 and OTX2 proteins and provide evidence that, with the exception of the inner ear, in Otx1 and Otx2 null mice contrasting phenotypes stem from differences in expression patterns rather than in amino acid sequences.

Animals↗
PubMed1999

Aspergillus mastoiditis in acquired immunodeficiency syndrome.

OBJECTIVE: This study aimed to analyze the clinical presentation, diagnosis, management, and results of treatment in a series of three patients with acquired immunodeficiency syndrome (AIDS) in whom Aspergillus mastoiditis developed. This study also aimed to compare these aspects of Aspergillus mastoiditis in patients with AIDS with three additional cases present in the current literature. A classification system for fungal infections of the ear and temporal bone is proposed. STUDY DESIGN: The study design was a retrospective case review. SETTING: The study was conducted at multiple tertiary referral centers. PATIENTS: Three individuals with diagnosed AIDS and mastoiditis resulting from culture-proven Aspergillus were studied. INTERVENTION: Patients were treated with both medical and surgical methods including local and systemic antimicrobial/antifungal agents and mastoidectomy. MAIN OUTCOME MEASURES: These measures included return of facial nerve function, control/resolution of disease, and survival. RESULTS: All three patients in this series initially presented with otalgia and otorrhea and intact facial nerve function. Facial nerve paresis developed in all patients between 5 and 12 weeks after initial symptoms. Paresis uniformly improved or resolved after mastoidectomy. Two patients treated with systemic antifungal therapy and prompt surgical debridement after development of facial palsy had full resolution of infection. One patient had full recovery of facial paresis and the other had partial recovery. The third patient was lost to follow-up after initial treatment with antimicrobials and surgery and died 3 months later without a clear etiology. CONCLUSIONS: Aspergillus mastoiditis is an unusual infection in patients with AIDS. Because of its rarity, fungal mastoiditis in immunocompromised individuals can result in a significant delay in diagnosis and treatment. The decision between conservative antimicrobial therapy and aggressive surgical treatment also can present a therapeutic challenge in the management of these life-threatening infections, especially in patients with existing immunodeficiency and illness. Early surgical debridement followed by antimicrobial therapy may be life preserving in this patient population.

AIDS-Related Opportunistic Infections↗
PubMed1998

The differential sensitivities of inner ear structures to retinoic acid during development.

In order to examine the mechanisms that underlie development of the inner ear, the normal processes were perturbed using all-trans-retinoic acid (RA). By implanting a resin exchange bead saturated with RA into stage 16 (Hamburger and Hamilton, 1951, J. Morphol. 88, 49-92) embryonic day 2.5 chick ears, it was possible to analyze its in vivo effects on inner ear development. There is a temporal window during which the developing chick inner ear is particularly susceptible to the effects of RA (stages 16-19). This RA period of sensitivity precedes evidence of gross morphologic or histologic differentiation by at least 24 h, suggesting that mechanisms controlling formation of key inner ear structures are already in progress. There is a dose dependence on RA, with increasing doses of RA generating increasingly severe phenotypic abnormalities. Data indicate that these effects are due to differential sensitivities of the various inner ear structures to RA during their formation. In general, the vestibular structures were more susceptible to RA effects than the cochlear duct. Furthermore, nonsensory structures such as semicircular canals seemed to display a greater susceptibility to RA than their associated sensory structures (i.e., cristae). Among the three semicircular canals, the superior canal was the most susceptible to RA treatment, whereas the common crus was particularly resistant, suggesting that the molecular mechanisms for each structure's formation are different. The defect in semicircular canal formation is due to problems in the initial outgrowth of the canal plate which in turn is related to a down-regulation of early otocyst cell proliferation. This perturbation model provides valuable insight into the processes involved in producing the intricate patterning of the inner ear.

Animals↗
PubMed1998

Development of the mouse inner ear and origin of its sensory organs.

The molecular mechanisms dictating the morphogenesis and differentiation of the mammalian inner ear are largely unknown. To better elucidate the normal development of this organ, two approaches were taken. First, the membranous labyrinths of mouse inner ears ranging from 10.25 to 17 d postcoitum (dpc) were filled with paint to reveal their gross development. Particular attention was focused on the developing utricle, saccule, and cochlea. Second, we used bone morphogenetic protein 4 (BMP4) and lunatic fringe (Fng) as molecular markers to identify the origin of the sensory structures. Our data showed that BMP4 was an early marker for the superior, lateral, and posterior cristae, whereas Fng served as an early marker for the macula utriculi, macula sacculi, and the sensory portion of the cochlea. The posterior crista was the first organ to appear at 11.5 dpc and was followed by the superior crista, the lateral crista, and the macula utriculi at 12 dpc. The macula sacculi and the cochlea were present at 12 dpc but became distinguishable from each other by 13 dpc. Based on the gene expression patterns, the anterior and lateral cristae may share a common origin. Similarly, three sensory organs, the macula utriculi, macula sacculi, and cochlea, seem to arise from a single region of the otocyst.

Animals↗
PubMed1998

Axial specification for sensory organs versus non-sensory structures of the chicken inner ear.

A mature inner ear is a complex labyrinth containing multiple sensory organs and nonsensory structures in a fixed configuration. Any perturbation in the structure of the labyrinth will undoubtedly lead to functional deficits. Therefore, it is important to understand molecularly how and when the position of each inner ear component is determined during development. To address this issue, each axis of the otocyst (embryonic day 2.5, E2.5, stage 16-17) was changed systematically at an age when axial information of the inner ear is predicted to be fixed based on gene expression patterns. Transplanted inner ears were analyzed at E4.5 for gene expression of BMP4 (bone morphogenetic protein), SOHo-1 (sensory organ homeobox-1), Otx1 (cognate of Drosophila orthodenticle gene), p75NGFR (nerve growth factor receptor) and Msx1 (muscle segment homeobox), or at E9 for their gross anatomy and sensory organ formation. Our results showed that axial specification in the chick inner ear occurs later than expected and patterning of sensory organs in the inner ear was first specified along the anterior/posterior (A/P) axis, followed by the dorsal/ventral (D/V) axis. Whereas the A/P axis of the sensory organs was fixed at the time of transplantation, the A/P axis for most non-sensory structures was not and was able to be re-specified according to the new axial information from the host. The D/V axis for the inner ear was not fixed at the time of transplantation. The asynchronous specification of the A/P and D/V axes of the chick inner ear suggests that sensory organ formation is a multi-step phenomenon, rather than a single inductive event.

Animals↗
PubMed1996

Laser-assisted tympanostomy.

Laser-assisted tympanostomy (LAT) was performed in 70 ears to ventilate the middle ear space without using a pressure-equalizing tube. Using a CO2 laser attached to an operating microscope with a Microslad (microscope laser adaptor device), tympanostomies of 1.0 to 3.0 mm (average, 1.6 mm) in diameter were created and remained patent for an average of 3.14 weeks. Patency time was directly related to the size of the opening. Nearly all (97.9%) of the tympanostomies healed with no noticeable scarring and no persistent perforations. Seventy-eight percent of patients at the Florida Ear & Sinus Center (FESC, Sarasota, Fla.) and 84% of patients at the Head & Neck Surgery Group (New York) showed no evidence of recurrent effusion after a minimum follow-up of 3 months. LAT appears to be a safe, cost-effective procedure which can easily be performed in an office setting when bloodless opening in the tympanic membrane is needed for either treatment or diagnosis using endoscopes.

Adolescent↗
PubMed1996

Intratympanic steroid treatment of inner ear disease and tinnitus (preliminary report).

Intratympanic instillation of Depo-Medrol (80 mg/cc), dexamethasone ophthalmic solution (1 mg/cc), or dexamethasone intravenous (4 mg/cc) solution produces improvement of cochlear function in certain patients with Meniere's disease, autoimmune inner ear disease and sudden sensorineural deafness. Tinnitus improved in 47%, most often in patients with Meniere's disease (9 of 15; 60%). The SRT improvement of greater than 10 dB or SD greater than 15% was documented in 41% (average improvement in SRT: 15 dB; SD: 24%). Patients with tinnitus and bilateral sensorineural hearing loss (i.e., presbycusis) did not benefit from the treatment. Prior to treatment with intratympanic medication, laser assisted tympanostomy with middle ear exploration, using otoendoscopy to determine the status of the round window niche and remove mucosal folds, helps in making the round window membrane accessible to local application of drops. Placing Gelfoam into the round window niche under direct vision, and using a Venturi Bobbin tube in the tympanic membrane, appears to be a satisfactory method for delivering medication to the inner ear fluids. The medication can be injected by the physician through the tube into the middle ear, or the patient can perform self-treatment at home, placing medication in the external auditory canal. A double-blind, cross-over study in patients with Meniere's disease is now in progress with Institutional Review Board (IRB) approval, which will be reported at a later date. This preliminary study has shown that intratympanic steroids may affect the symptoms of hearing loss and tinnitus in patients with various inner ear problems. Patients with Meniere's disease appear to respond in the highest percentage of cases. Hopefully, additional research will suggest the appropriate drugs which can be used to treat inner ear disease. Direct application of the drug to the round window membrane may increase the concentration in the inner ear fluids, thus avoiding the systemic effects.

Aged↗
PubMed1990

Age-related changes in Schwann cells of the internal branch of the rat superior laryngeal nerve.

While previous studies have examined the role of neurons in age-related changes of laryngeal sensory nerve function, investigators have not focused on the significant role of Schwann cells in the aging process. This investigation used an electron microscopic morphometric technique to systematically study Schwann cells of the internal branch of the superior laryngeal nerve of three Wistar rat age groups: young = 3 to 5 months; old = 25 months; very old = 29 to 31 months. In Schwann cells of myelinated axons, a substantial and significant reduction (p = 0.0127) in mitochondrial volume fraction was found between the young and old groups, and also between the young and very old groups (young = 0.0034, old = 0.00175, very old = 0.0019). The volume fraction of compact myelin also showed a trend (p = 0.0683) toward decreasing with age. The volume fractions of cytoplasm, nuclei, and lipofuscin granules showed no significant age-related changes (lipofuscin in myelinating Schwann cells: young = 0.0025, old = 0.0020, very old = 0.0051; lipofuscin in non-myelinating Schwann cells: young = 0.012, old = 0.0061, very old = 0.0051). Our observations on mitochondria lead to two possible conclusions regarding energy availability in aged Schwann cells. One possibility is that aged cells have a decreased energy requirement, which is reflected in the decreased mitochondrial densities in old and very old specimens. The other possibility is the reduced mitochondrial volume fractions are independent of cellular energy requirements and are indicative of some aging or pathologic process.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗