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Anil K Lalwani

Publications and source records attributed to Anil K Lalwani.

At least 19 recordsLinked to original sources
PubMed2007

Implication of central asymmetry in speech processing on selecting the ear for cochlear implantation.

OBJECTIVE: Emerging evidence in auditory neuroscience suggests that central auditory pathways process speech asymmetrically. In concert with left cortical specialization for speech, a "right-ear advantage" in speech perception has been identified. The purpose of this study is to determine if this central asymmetry in speech processing has implications for selecting the ear for cochlear implantation. STUDY DESIGN: Retrospective cohort study. SETTING: Academic university medical center PATIENTS: One hundred one adults with bilateral severe-to-profound sensorineural hearing loss INTERVENTION: Cochlear implantation with the Nucleus 24 Contour device. MAIN OUTCOME MEASUREMENTS: Patients were divided into two groups according to the ear implanted. Results were compared between left-ear- and right-ear-implanted patients. Further subgroup analysis was undertaken, limited to right-handed patients. Postoperative improvement on audiograms and scores on speech perception tests (Hearing in Noise test, City University of New York in quiet and in noise test, Consonant-Vowel Nucleus- Consonant words, and phonemes) at 1 year was compared between groups. Analysis of covariance was used to control for any intergroup differences in preoperative characteristics. RESULTS: The groups were matched in age, duration of hearing loss, duration of hearing aid use, percentage implanted in the better hearing ear, and preoperative audiologic testing. Postoperatively, there were no differences between left-ear- and right-ear-implanted patients in improvement on speech recognition tests. CONCLUSION: Despite central asymmetry in speech processing, our data do not support a right-ear advantage in speech perception outcomes with cochlear implantation. Therefore, among the many factors in choosing the ear for cochlear implantation, central asymmetry in speech processing does not seem to be a contributor to postoperative speech recognition outcomes.

Adolescent↗
PubMed2006

Expression of Myh9 in the mammalian cochlea: localization within the stereocilia.

Mutations of non-muscle myosin Type IIA or MYH9 are linked to syndromic or nonsyndromic hearing loss. The biologic function of MYH9 in the auditory organ and the pathophysiology of its dysfunction remain to be determined. The mouse represents an excellent model for investigating the biologic role of MYH9 in the cells and tissues affected by its dysfunction. A primary step toward the understanding of the role of MYH9 in hearing and its dysfunction is the documentation of its cellular and sub-cellular localization within the cochlea, the auditory organ. We describe the localization of Myh9 within the mouse cochlea using a polyclonal anti-Myh9-antibody, generated against an 18 amino acid long peptide corresponding to the sequence at the C-terminus of mouse Myh9. The anti-Myh9 antibody identified a single, specific, immunoreactive band of 220 kDa in immunoblot analysis of homogenate from a variety of different mouse tissues. The Myh9 antibody cross-reacts with the rat but not the human orthologue. Myh9 is expressed predominantly within the spiral ligament as well as in the sensory hair cells of the organ of Corti. Confocal microscopy of cochlear surface preparations, identified Myh9 within the inner and outer hair cells and their stereocilia. Localization of Myh9 within the stereocilia raises the possibility that mutations of MYH9 may effect hearing loss though disruption of the stereocilia structure.

Animals↗
PubMed2006

Two temporal bone computed tomography measurements increase recognition of malformations and predict sensorineural hearing loss.

OBJECTIVES/HYPOTHESIS: The objectives of this prospective study were to assess the reproducibility of the measurements of the cochlea and lateral semicircular canal (LSCC) and to determine if abnormal measurements predict sensorineural hearing loss (SNHL). METHODS: Two readers independently measured the cochlear height on coronal section and the LSCC bony island width on axial section on 109 temporal bone computed tomography scans; audiologic data on these patients were collected independently from medical records. Inter- and intrareader variability was evaluated using intraclass correlation coefficients (ICCs) based on a random-effects model. The positive and negative predictive values of abnormal measurement for hearing loss were determined. RESULTS: There was excellent inter- and intraobserver agreement for both measurements (ICC >80%). The average cochlear height was 5.1 mm (normal range, 4.4-5.9 mm) and average LSCC bony island width was 3.7 mm (normal range, 2.6-4.8 mm). Review of the original radiology reports demonstrated that both cochlear hypoplasia and LSSC dysplasia were overlooked in >50% of patients with both abnormal measurements and SNHL. Cochlear hypoplasia (< 4.4 mm) had a positive predictive value of 100% for SNHL, whereas cochlear hyperplasia and bony island dysplasia were less predictive. CONCLUSION: The measurements of coronal cochlear height and axial LSCC bony width have excellent reproducibility and identify bony labyrinth abnormalities missed by visual inspection alone. In addition, cochlear hypoplasia is highly predictive of SNHL. To reliably identify inner ear malformations, measurement of the cochlear height and LSCC bony island width, in addition to the vestibular aqueduct, should be routinely performed on all temporal bone studies.

Adolescent↗
PubMed2005

Two families with nonsyndromic low-frequency hearing loss harbor novel mutations in Wolfram syndrome gene 1.

Although hereditary hearing loss is highly heterogeneous, only a few loci have been implicated with low-frequency hearing loss. Mutations in one single gene, Wolfram syndrome 1 (WFS1), have been reported to account for most familial cases with this type of hearing impairment. This study was conducted to determine the cause of nonsyndromic low-frequency hereditary hearing impairment in two large families. Two large families from Switzerland and United States with low-frequency hearing loss were identified. Genomewide linkage analysis was performed followed by mutation screening in the candidate gene WFS1 with direct DNA sequencing and restriction fragment analysis. Both families were linked to DFNA6/14/38 with lod scores>3. Two novel heterozygous missense mutations in WFS1 were identified: c.2311G>C leading to p.D771H in the Swiss family and c.2576G>C leading to p.R859P in the US family. The sequence alteration was absent in 100 control chromosomes. Nonsyndromic low-frequency hereditary hearing impairment seems to be predominantly a monogenic disorder due to WFS1. We confirm that most mutations in WFS1 associated with isolated low-frequency hearing loss are clustered in the C-terminal protein domain coded by exon 8.

Adult↗
PubMed2005

Sensorineural hearing loss, early greying, and essential tremor: a new hereditary syndrome?

OBJECTIVE: To present a syndrome composed of sensorineural hearing loss, early greying of scalp hair, and adult-onset essential tremor. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary care academic hospital. RESULTS: Three individuals were seen with this triad, each with family members with similar features. Our patients are a 65-year-old man and two women in their 40s. Two noted hearing loss in adulthood, one as a child. All had complete greying in their 20s. The women developed essential tremor in their 20s, and the man in his 50s. All individuals have blue eyes without heterochromia. Additional evaluation failed to further categorize these patients. Each has two or more immediate family members with a combination of these findings. Molecular genetic testing suggests this is not a variant of Waardenburg syndrome. CONCLUSION: We believe this represents a previously unreported hereditary syndrome. SIGNIFICANCE: This new syndrome should be considered in the context of other syndromes involving audition, pigmentation, and movement.

Adult↗
PubMed2005

Audiologic testing and molecular analysis of 12S rRNA in patients receiving aminoglycosides.

BACKGROUND: Pathogenic mutations in the mitochondrial genome are associated with a wide variety of maternally inherited human diseases including sensorineural hearing loss (HL). A specific mutation, m.1555A>G in the mitochondrial 12S rRNA gene, is associated with predisposition to aminoglycoside ototoxicity and HL. Mutation screening in this gene has been recommended before use of aminoglycosides as a preventative strategy to reduce the risk of ototoxicity. OBJECTIVE: To study the incidence of mutations in the 12S rRNA gene in patients being treated with aminoglycosides and its correlation with ototoxicity. METHODS: Patients undergoing treatment with aminoglycosides were prospectively enrolled in this study (n = 27). Total dosage administered and therapeutic levels of the antibiotic were noted. All patients underwent high-frequency pure-tone audiometry pre- and posttherapy and sequencing of the 12S rRNA gene. In addition, 12S rRNA gene was also sequenced in 50 controls to characterize population specific polymorphisms. RESULTS: Five of 27 patients suffered from HL involving the high frequencies: four mild and one moderate. Only one of the five patients with ototoxicity harbored two sequence alterations in 12S rRNA of uncertain pathogenicity. The m.1555A>G and m.961delTInsCn mutations were not detected. CONCLUSIONS: High-frequency pure-tone audiometry is critical for detection of aminoglycoside-induced HL. In the Swiss population, screening for mutations in the 12S rRNA gene, before the initiation of aminoglycoside therapy, is not supported by this limited study. A larger multicenter and multicultural study is warranted to more definitively address this critical clinical issue.

Adolescent↗
PubMed2004

DFNA54, a third locus for low-frequency hearing loss.

Nonsyndromic hereditary hearing impairment (NSHHI) is a highly heterogeneous disorder with more than 90 loci mapped, of which nearly one-half of the responsible genes are identified. In dominant NSSHI hearing loss is typically biased towards the high frequencies while low-frequency hearing loss is unusual. Only two NSHHI loci, DFNA1 and DFNA6/14/38, are associated with predominantly low-frequency loss. We mapped the loci harboring the gene responsible for autosomal dominant low-frequency hearing loss in a multigenerational family. The pedigree of a Swiss family with low-frequency hearing loss was established. Using genomic DNA, DFNA1 and DFNA6/14/38 were excluded by linkage analysis or by direct sequencing of the responsible gene. Genome-wide linkage analysis was performed using commercially available microsatellite markers. Two-point linkage analysis demonstrated linkage to chromosome 5q31, the locus for DFNA15, with a lod score of 6.32 at recombination fraction theta=0 for marker D5S436. Critical recombinations were seen at markers D5S1972 and D5S410. Sequencing of the corresponding gene POU4F3 yielded no pathogenic mutation segregating with the affected members. In addition to Wolfram syndrome gene 1 (DFNA6/14/38) and diaphanous (DFNA1) there is evidence for a third gene involved in low-frequency hearing loss located at DFNA15. Because of the differences in auditory phenotype and the absence of pathogenic mutation in the coding region of POU4F3 it is likely that there is a second gene in 5q31, designated DFNA54, associated with NSHHI.

Adolescent↗
PubMed2004

Cloning and developmental expression of nonmuscle myosin IIA (Myh9) in the mammalian inner ear.

MYH9 encoding a nonmuscle myosin heavy chain has been linked to nonsyndromic and syndromic forms of autosomal dominant hereditary hearing loss, suggesting a critical biological role of this motor protein in the auditory organ. While Myh9 expression has been described in the adult mouse, critical parameters pertaining to its developmental expression remain to be characterized. The current study describes cloning of the mouse Myh9 cDNA and the temporal onset and spatial distribution of Myh9 expression in the inner ear of the developing fetus, the neonate, and the adult. The cloned Myh9 cDNA contained two single-base-pair differences from the published genomic sequence: T990C (G330G) and T5198A (L1733Q). Immunoblotting of embryonic (E15.5) and adult tissues from several organs, including the cochlea, identified a single 250-kDa anti-Myh9-immunoreactive band, supporting an absence of Myh9 splice variants in the fetus and the adult. In situ expression analysis identified Myh9 distributed within the epithelial layer of the otic vesicle at E10.5. Myh9 expression was found to persist within the epithelia surrounding the cochlear duct at E13.5 and E16.5. The sensory cells of the developing cochlea were positive for Myh9 expression at E16.5. Within the neonate and the adult cochlea, Myh9 expression was observed within the sensory hair cells and the supporting hair cells of the organ of Corti, the spiral ligament, and the spiral limbus, but not in the stria vascularis. Identification of Myh9 in the developing and mature inner ear suggests a role for this protein in the development and maintenance of auditory function.

Animals↗
PubMed2004

Genomic structure, cochlear expression, and mutation screening of KCNK6, a candidate gene for DFNA4.

KCNK6 encodes a tandem pore domain potassium channel, TWIK-2, that maps to chromosome 19. Both STS and linkage maps established KCNK6 as a positional candidate gene for DFNA4, a form of autosomal dominant nonsyndromic hereditary hearing loss. Identification and characterization of Kcnk6 expression within the mammalian cochlea established the gene as a functional candidate for DFNA4. Identification of Twik-2 expression in the mouse cochlea was initially established via RT-PCR assay of cochlear RNA. Subsequent immunoblot analysis of cochlear homogenate yielded a distinct 35-kDa band corresponding to the calculated molecular weight of the mouse Twik-2. Immunohistochemical studies localized Twik-2 expression in the cochlea predominantly within the stria vascularis. This vascular tissue borders the cochlear duct and is a critical regulator of potassium concentration in the endolymph. Genomic structure of TWIK-2 was subsequently determined and shown to consist of three coding exons with splice acceptor and donor sites in accordance with the consensus GT-AG rule. Two separate DFNA4 families were screened for KCNK6 sequence alterations. No mutations were found, thus excluding TWIK-2 as the DFNA4 candidate disease gene. Nevertheless, expression of Twik-2 within the stria vascularis suggests a potential role for this protein as one of the terminal components of the potassium ion-recycling pathway that contributes toward its reabsorption into the endolymph.

Animals↗
PubMed2004

GJB2 gene mutations in cochlear implant recipients: prevalence and impact on outcome.

OBJECTIVE: To determine the prevalence of GJB2 gene mutations in patients undergoing cochlear implantation (CI) and their impact on rehabilitative outcome following implantation. DESIGN: Prospective determination of GJB2 mutation by sequence analysis by denaturing high-performance liquid chromatography and its correlation with outcome following CI. SETTINGS: Two tertiary academic medical centers. PATIENTS: Subjects who have met the audiologic criteria and have undergone CI. RESULTS: Of 77 cochlear implant recipients screened, 13 (18%) harbored a detectable sequence alteration in the GJB2 gene. Only 3 of these 13 patients had hearing loss clearly attributable to a biallelic GJB2 mutation. There were 2 patients with homozygous mutations, including a 35delG and a 167delT mutation, and a third with a compound heterozygous mutation. Of the remaining 10 patients, 8 had 1 deafness allele, while 2 had a normal polymorphism that was not believed to be implicated in the hearing loss. Six patients had the common 35delG mutation: 5 patients had heterozygous mutations, which are probably not related to the underlying hearing loss (a second deafness allele cannot be ruled out in these cases because of the screening methodology used), while 1 patient had a homozygous mutation, which was clearly implicated in the patient's deafness. Rehabilitative outcome among those with detectable sequence alterations, as well as the 3 patients with biallelic mutations, varied but were similar on average when compared with outcomes seen in our entire CI population. CONCLUSIONS: A large percentage of implant candidates harbor mutations or sequence alterations in the GJB2 gene, although only a small number of these changes are biallelic and a clear cause of the hearing loss. These results demonstrate that patients with GJB2-related deafness clearly benefit from CI.

Adolescent↗
PubMed2004

Quantitative analysis of fungal DNA in chronic rhinosinusitis.

OBJECTIVES/HYPOTHESIS: Fungi have been recognized as important pathogens in sinusitis; however, they are equally present in patients with and without sinusitis. The authors postulated that the quantity of fungal DNA in the nose is determinant of disease, is greater in patients with chronic rhinosinusitis, and is directly correlated to their quality of life. STUDY DESIGN: Prospective recruitment of patients with chronic rhinosinusitis. METHODS: Objective quality of life data were collected using three validated questionnaires: the Sinonasal Outcomes Test (SNOT-20), Medical Outcomes Short-Form 36 Survey (SF-36), and Guy Marks Asthma Questionnaire (GMAQ). Endoscopically guided middle meatus mucosal samples were collected from patients with chronic rhinosinusitis and normal control subjects. Fungal-specific polymerase chain reaction was performed on each sample. Every fungal-positive sample underwent fungal-specific quantitative polymerase chain reaction analysis. Statistical analysis was used to correlate fungal DNA quantities with outcomes indices between groups. RESULTS: Patients with chronic rhinosinusitis had a mean SNOT-20 index of 32.0 as compared with a SNOT-20 index of 17.3 (P <.01) in the normal control subjects. There were no statistical differences between the groups' indices for the SF-36 or GMAQ outcomes questionnaires. Four of 19 (21.1%) patients with chronic rhinosinusitis and 7 of 19 (36.8%) normal control subjects had positive findings for fungal DNA using polymerase chain reaction. The median relative quantity of fungal DNA to human DNA for chronic rhinosinusitis and control samples was identical (0.13) using quantitative polymerase chain reaction. CONCLUSION: The quantity of fungal DNA in the middle meatus did not differ in patients with and without chronic rhinosinusitis and was not correlated with quality of life outcomes. Therefore, the quantity of fungi does not explain pathogenicity in patients with chronic rhinosinusitis. However, because of small sample size, the study must be replicated in a larger patient population.

Chronic Disease↗
PubMed2004

Role of cytomegalovirus, Epstein-Barr virus, and human herpes virus-8 in benign lymphoepithelial cysts of the parotid gland.

OBJECTIVE: To provide background and evaluate the role of herpesviruses in benign lymphoepithelial cysts (BLC) of the parotid gland. STUDY DESIGN: Case series derived from review of pathology specimens. METHODS: Radiolabeled polymerase chain reaction (PCR) analysis was used to detect for the presence of cytomegalovirus (CMV), Epstein-Barr virus (EBV), and human herpes virus 8 (HHV-8) DNA sequences in 14 paraffin embedded specimens and 1 freshly aspirated BLC specimen. Thirteen normal parotid tissue specimens obtained from paraffin embedded blocks were used as a control group. RESULTS: CMV was detected with nearly equal frequency between the two groups (23% of normal vs. 20% in BLC). HHV-8 was found in 13% of the BLC group and in none of the normal group (P =.4841). There was significant difference in EBV detection between the normal (0%) and the BLC (33%) groups (P =.0437). CONCLUSION: CMV and HHV-8 does not appear to be associated with BLCs. Although EBV is found more frequently in BLC than in normal parotid controls, further studies are needed to elucidate the role of this virus in BLC pathogenesis.

Adult↗
PubMed2004

Cochlear implant outcomes in the elderly.

OBJECTIVE: This study aimed to review cochlear implantation with respect to surgical and auditory outcomes in subjects aged 70 years and older. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary referral centers. PATIENTS: Sixty-five patients aged 70 years or older at the time of implantation were compared to a group of patients aged <70 years. INTERVENTION: Patients underwent multichannel cochlear implantation with either the Clarion or Nucleus device. MAIN OUTCOME MEASURE: Presence or absence of surgical complications and auditory performance with open-set word and sentence recognition testing. RESULTS: In patients implanted at age 70 or older, significant improvement in speech understanding was demonstrated in performance scores using Consonant Nucleus Consonant words, Central Institute for the Deaf sentences, and Hearing in Noise Test sentences at 3, 6, and 12 months when compared to preimplantation scores. However, their performance was slightly poorer when compared to a control group of patients <70 years of age in the same measures at 3, 6, and 12 months. CONCLUSIONS: The elderly population showed significant improvement in auditory performance tests following cochlear implantation compared to their preimplantation scores but performed less well than younger patients.

Adult↗
PubMed2004

Molecular pathogenesis of skull base tumors.

OBJECTIVE: To review contemporary molecular biological literature related to skull base tumor biology and tumorigenesis. DATA SOURCES: PUBMED and Ovid literature searches were performed using keyword search. Only English language articles published between 1965 and December 4, 2003 were chosen. STUDY SELECTION AND DATA EXTRACTION: All relevant articles from the past 8 years, as well as landmark articles in years before 1995, were retrieved and reviewed. CONCLUSION: Consistent progress is being made toward the molecular genetic and biological basis of the most common skull base tumors. An understanding of these mechanisms will aid the neurotologist in future diagnosis and management of the lesions.

Chordoma↗
PubMed2004

Biological therapy for the inner ear.

Biological therapy for the inner ear has the potential to revolutionise the treatment of sensorineural hearing loss, the most common form of deafness. Progress in the molecular understanding of hearing and hearing loss, combined with advances in the fields of both gene and cellular therapy for the inner ear, is providing a robust foundation from which clinical translation is plausible. Potential areas of interest in gene therapy and its preclinical application to deafness are reviewed, and experimental progress that has occurred in cellular therapy for the inner ear is examined.

Animals↗
PubMed2003

Effect of SOD1 overexpression on age- and noise-related hearing loss.

Reactive oxygen species (ROS) have been implicated in hearing loss associated with aging and noise exposure. Superoxide dismutases (SODs) form a first line of defense against damage mediated by the superoxide anion, the most common ROS. Absence of Cu/Zn SOD (SOD1) has been shown to potentiate hearing loss related to noise exposure and age. Conversely, overexpression of SOD1 may be hypothesized to afford a protection from age- and noise-related hearing loss. This hypothesis may be tested using a transgenic mouse model carrying the human SOD1 gene. Contrary to expectations, here, we report that no protection against age-related hearing loss was observed in mice up to 7 months of age or from noise-induced hearing loss when 8 week old mice were exposed to broadband noise (4-45 kHz, 110 dB for 1 h). Mitochondrial DNA deletion, an index of aging, was elevated in the acoustic nerve of transgenic mice compared to nontransgenic littermates. The results indicate the complexity of oxidative metabolism in the cochlea is greater than previously hypothesized.

Age Factors↗
PubMed2003

Establishment of normative cochlear and vestibular measurements to aid in the diagnosis of inner ear malformations.

OBJECTIVE: We sought to establish normative measurements of the inner ear using computed tomography (CT) of the temporal bone to aid in the diagnosis of inner ear malformations. STUDY DESIGN AND SETTING: Prospective measurements of the inner ear structures were made on axial and coronal temporal bone CT scans on 15 patients with normal hearing and 15 patients with sensorineural hearing loss. RESULTS: The vertical height of the cochlea on coronal scan and the size of the central bony island within the lateral semicircular canal on axial scan along with visual inspection identified 7 inner ear abnormalities in 6 patients: 5 cases of lateral semicircular canal dysplasia and 2 cases of cochlear hypoplasia. In contrast, visual inspection alone identified only 4 of the 7 abnormalities. CONCLUSIONS AND SIGNIFICANCE: Routine measurement of the cochlear height and bony island of the lateral semicircular canal, in conjunction with visual inspection of CT images, will increase recognition of common inner ear malformations.

Adult↗