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Biomedical subjects

John S Oghalai

Publications and source records attributed to John S Oghalai.

At least 19 recordsLinked to original sources
PubMed2006

DNA sequence analysis of GJB2, encoding connexin 26: observations from a population of hearing impaired cases and variable carrier rates, complex genotypes, and ethnic stratification of alleles among controls.

Mutations in GJB2 are associated with hereditary hearing loss. DNA sequencing of GJB2 in a cohort of hearing impaired patients and a multi-ethnic control group is reported. Among 610 hearing impaired cases, 43 DNA sequence variations were identified in the coding region of GJB2 including 24 mutations, 8 polymorphisms, 3 unclassified variants (G4D, R127C, M163V), 1 controversial variant (V37I), and 7 novel variants (G12C, N14D, V63A, T86M, L132V, D159, 592_600delinsCAGTGTTCATGACATTC). Sixteen non-coding sequence variations were also identified among cases including the IVS1+1A>G mutation, 2 polymorphisms, and 13 novel variants. A diagnosis of GJB2-associated hearing loss was confirmed for 63 cases (10.3%). Heterozygous mutations were found in 39 cases (6.4%). Eleven cases carrying novel or unclassified variants (1.8 %) and 18 cases carrying the controversial V37I variant were identified (3%). In addition, 294 control subjects from 4 ethnic groups were sequenced for GJB2. Thirteen sequence variations in the coding region of GJB2 were identified among controls including 2 mutations, 6 polymorphisms, 2 unclassified variants (G4D, T123N), 1 controversial variant (V37I), and 2 novel variants (R127L, V207L). Nine sequence variations were identified among controls in the non-coding regions in and around GJB2 exon 2. Of particular interest among controls were the variability in carrier rates and ethnic stratification of alleles, and the complex genotypes among Asians, 47% of whom carried two to four sequence variations in the coding region of GJB2. These data provide new information about carrier rates for GJB2-based hearing loss in various ethnic groups and contribute to evaluation of the pathogenicity of the controversial V37I variant.

Alleles↗
PubMed2006

Photometric recording of transmembrane potential in outer hair cells.

Cochlear outer hair cells (OHCs) are polarized epithelial cells that have mechanoelectrical transduction channels within their apical stereocilia and produce electromotile force along their lateral wall. Phase shifts, or time delays, in the transmembrane voltage occurring at different axial locations along the cell may contribute to our understanding of how these cells operate at auditory frequencies. We developed a method to optically measure the phase of the OHC transmembrane potential using the voltage-sensitive dye (VSD) di-8-ANEPPS. The exit aperture of a fibre-optic light source was driven in two dimensions so that a 24 microm spot of excitation light could be positioned along the length of the OHC. We used the whole-cell patch-clamp technique in the current-clamp mode to stimulate the OHC at the base. The photometric response and the voltage response were monitored with a photodetector and patch-clamp amplifier, respectively. The photometric response was used to measure the regional changes in the membrane potential in response to maintained (dc) and sinusoidal (ac) current stimuli applied at the base of the cell. We used a neutral density filter to lower the excitation light intensity and reduce phototoxicity. A sensitive detector and lock-in amplifier were used to measure the small ac VSD signal. This permitted measurements of the ac photometric response below the noise floor of the static fluorescence. The amplitude and phase components of the photometric response were recorded for stimuli up to 800 Hz. VSD data at 400-800 Hz show the presence of a small phase delay between the stimulus voltage at the base of the cell and the local membrane potential measured along the lateral wall. Results are consistent with the hypothesis that OHCs exhibit inhomogeneous membrane potentials that vary with position in analogy with the voltage in nerve axons.

Animals↗
PubMed2006

Adult spontaneous CSF otorrhea: correlation with radiographic empty sella.

OBJECTIVE: To determine the prevalence of radiographic empty sella in patients with spontaneous cerebrospinal fluid (CSF) otorrhea. STUDY DESIGN AND SETTING: Retrospective case series of adult patients with CSF otorhinorrhea at an academic tertiary medical center. Patients with history of skull base surgery, trauma, tumor, or chronic ear disease were excluded. Available imaging studies were reviewed with attention to the sella turcica. RESULTS: Eight patients were diagnosed with spontaneous CSF otorrhea. Five of seven patients with adequate imaging studies (71%) had a radiographic empty sella. Seven of eight patients were clinically obese, with a body mass index BMI>30 kg/m2. CONCLUSIONS: Empty sella is a common radiologic finding in patients with spontaneous CSF otorrhea. This supports the theory that increased intracranial pressure contributes to development of spontaneous CSF otorrhea. SIGNIFICANCE: Radiographic empty sella predicts elevated intracranial pressure, which may require further evaluation and treatment in patients with spontaneous CSF otorrhea. EBM RATING: C-4.

Adult↗
PubMed2006

Dyslipidemia and auditory function.

The relationship between dyslipidemia and hearing is unclear. This study was conducted to investigate whether elevated serum lipid levels impact auditory function in humans and in guinea pigs. In the human study, a cross-sectional study of 40 volunteers with dyslipidemia was conducted. Pure tone thresholds, distortion product otoacoustic emissions, and lipid profiles were analyzed. When controlled for patient age and sex, we found that elevated triglycerides were associated with reduced hearing. In the guinea pig study, a prospective study of animals fed a high-fat diet for 14 weeks was conducted. Although the high-fat diet led to a dramatic elevation in the average weight and total cholesterol in all animals (from 61 to 589 mg/dl), there were no meaningful changes in distortion product otoacoustic emission magnitudes. These results suggest that whereas chronic dyslipidemia associated with elevated triglycerides may reduce auditory function, short-term dietary changes may not.

Adult↗
PubMed2006

Circumferential petrosectomy for petrous apicitis and cranial base osteomyelitis.

OBJECTIVE: Petrous apicitis and cranial base osteomyelitis are life-threatening conditions. A surgical management may be necessary in cases that progress, in conditions that fail to improve with medical treatment, or in cases with impending complications. In this study, we describe a technique to remove the maximum amount of infected temporal bone while preserving the integrity of the peripheral auditory pathway and facial nerve. STUDY DESIGN: Retrospective study. SETTING: Tertiary referral hospital. PATIENTS: Five patients with impending complications, whose disease progressed or whose conditions failed to improve while on culture-directed antibiotics underwent circumferential petrosectomy. INTERVENTIONS: The circumferential petrosectomy removes most of the temporal bone around the external, middle, and inner ear. A combined retrolabyrinthine-apical petrosectomy is performed in conjunction with the fallopian bridge technique using a transmastoid and middle cranial fossa approach. A split temporalis muscle flap is used to bring vascularized tissue to the mastoid, jugular foramen, and petrous apex. MAIN OUTCOME MEASURES: Disease resolution, change in hearing or facial nerve function, complications. RESULTS: Each of the five patients had modifications to the procedure tailored to their disease extent: three had disease primarily involving the petrous apex and two had disease adjacent to the jugular foramen. Additional cultures of the infected bone were obtained during surgery. A culture-directed antibiotic therapy (duration, 6-10 weeks) was administered after surgery, which resulted in the complete resolution of the disease and the associated symptoms in all five patients. No patient experienced hearing loss or facial nerve dysfunction as a result of the surgery within at least 1 year of follow-up in four of the five patients in this series. CONCLUSION: The circumferential petrosectomy is a potential treatment option when medical treatment fails in patients with petrositis or cranial base osteomyelitis. It permits maximal temporal bone debridement while preserving hearing and facial nerve integrity in these life-threatening disease processes.

Adolescent↗
PubMed2006

Invasive cerebrospinal fluid cysts and cephaloceles of the petrous apex.

OBJECTIVE: To describe the presentation, diagnostic evaluation, and surgical management of petrous apex cerebrospinal fluid (CSF) cysts and cephaloceles. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS: Six patients with symptomatic CSF cysts or cephaloceles. INTERVENTION(S): All patients underwent operative intervention. MAIN OUTCOME MEASURE(S): Presentation, imaging characteristics, operative findings, surgical approach, resolution of symptoms, and complications. RESULTS: Six patients presented with various neurotologic symptoms including vertigo, otalgia, diplopia, meningitis, hearing loss, and retroorbital headaches. Four lesions were centered within the anterior petrous apex and were classified as a cephalocele originating from Meckel's cave. The remaining two lesions were arachnoid cysts that involved the posterior petrous apex. Cysts and cephaloceles both demonstrated bone erosion on computed tomography and were hyperintense on T2-weighted magnetic resonance imaging and isointense or hypointense on T1-weighted magnetic resonance imaging. A variety of surgical approaches was used to treat these lesions. Preoperative symptoms were improved in five of six cases. One patient developed a postoperative CSF leak that resolved with conservative measures. CONCLUSION: Petrous apex CSF cysts and cephaloceles may present with a variety of neurotologic symptoms. Imaging often helps narrow the differential diagnosis, but these lesions can still be confused with other erosive skull base lesions such as cholesterol granulomas, epidermoids, or tumors. Optimal treatment of symptomatic posterior petrous apex CSF cysts is marsupialization via a posterior fossa approach (i.e., retrosigmoid or retrolabyrinthine). A middle fossa approach with obliteration of the anterior petrous apex may be used to treat symptomatic CSF cephaloceles arising from Meckel's cave.

Adult↗
PubMed2005

High frequency of the IVS2-2A>G DNA sequence variation in SLC26A5, encoding the cochlear motor protein prestin, precludes its involvement in hereditary hearing loss.

BACKGROUND: Cochlear outer hair cells change their length in response to variations in membrane potential. This capability, called electromotility, is believed to enable the sensitivity and frequency selectivity of the mammalian cochlea. Prestin is a transmembrane protein required for electromotility. Homozygous prestin knockout mice are profoundly hearing impaired. In humans, a single nucleotide change in SLC26A5, encoding prestin, has been reported in association with hearing loss. This DNA sequence variation, IVS2-2A>G, occurs in the exon 3 splice acceptor site and is expected to abolish splicing of exon 3. METHODS: To further explore the relationship between hearing loss and the IVS2-2A>G transition, and assess allele frequency, genomic DNA from hearing impaired and control subjects was analyzed by DNA sequencing. SLC26A5 genomic DNA sequences from human, chimp, rat, mouse, zebrafish and fruit fly were aligned and compared for evolutionary conservation of the exon 3 splice acceptor site. Alternative splice acceptor sites within intron 2 of human SLC26A5 were sought using a splice site prediction program from the Berkeley Drosophila Genome Project. RESULTS: The IVS2-2A>G variant was found in a heterozygous state in 4 of 74 hearing impaired subjects of Hispanic, Caucasian or uncertain ethnicity and 4 of 150 Hispanic or Caucasian controls (p = 0.45). The IVS2-2A>G variant was not found in 106 subjects of Asian or African American descent. No homozygous subjects were identified (n = 330). Sequence alignment of SLC26A5 orthologs demonstrated that the A nucleotide at position IVS2-2 is invariant among several eukaryotic species. Sequence analysis also revealed five potential alternative splice acceptor sites in intron 2 of human SLC26A5. CONCLUSION: These data suggest that the IVS2-2A>G variant may not occur more frequently in hearing impaired subjects than in controls. The identification of five potential alternative splice acceptor sites in intron 2 of human SLC26A5 suggests a potential mechanism by which expression of prestin might be maintained in cells carrying the SLC26A5 IVS2-2A>G DNA sequence variation. Additional studies are needed to evaluate the effect of the IVS2-2A>G transition on splicing of SLC26A5 transcripts and characterize the hearing status of individuals homozygous for the IVS2-2A>G variant.

Adenine↗
PubMed2005

Management of superior canal dehiscence syndrome with extensive skull-base deficiency.

Superior canal dehiscence syndrome is a recently described condition resulting in noise- or pressure-induced vertigo. We review the case of a 50-year-old woman who presented with debilitating pressure and noise-induced vertigo as well as a low-frequency conductive hearing loss. Imaging was consistent with superior semicircular canal dehiscence syndrome. An extradural middle fossa approach was used to approach the dehiscent superior canal. Intraoperatively, our patient was found to have extensive idiopathic skull base dehiscence of the temporal floor. Middle ear and mastoid mucosa was exposed with focal areas of dura prolapsed into the mastoid cavity. Because of these findings, temporalis fascia and bone pate were used to cover the dehiscent canal as well as a large area of the temporal floor. Additionally, a temporalis muscle flap was rotated between the dura and the dehiscent temporal floor to reconstruct the middle fossa skull base and prevent encephalocele.

Bone Diseases↗
PubMed2005

Predicting the effect of post-implant cochlear fibrosis on residual hearing.

Intracochlear scarring is a well-described sequela of cochlear implantation. We developed a mathematical model of passive cochlear mechanics to predict the impact that this might have upon residual acoustical hearing after implantation. The cochlea was modeled using lumped impedance terms for scala vestibuli (SV), scala tympani (ST), and the cochlear partition (CP). The damping of ST and CP was increased in the basal one half of the cochlea to simulate the effect of scar tissue. We found that increasing the damping of the ST predominantly reduced basilar membrane vibrations in the apex of the cochlea while increasing the damping of the CP predominantly reduced basilar membrane vibrations in the base of the cochlea. As long as intracochlear scarring continues to occur with cochlear implantation, there will be limitations on hearing preservation. Newer surgical techniques and electrode technologies that do not result in as much scar tissue formation will permit improved hearing preservation.

Animals↗
PubMed2005

Repair of iatrogenic temporal lobe encephalocele after canal wall down mastoidectomy in the presence of active cholesteatoma.

OBJECTIVE: Although mastoid and middle ear obliteration provides the ultimate repair of an encephalocele, retained squamous epithelium may result in the occult recurrence of cholesteatoma. For most patients, a preferable technique is to perform a canal-wall-up mastoidectomy with middle fossa craniotomy. However, temporal lobe encephaloceles are occasionally found in patients with canal-wall-down cavities along with active cholesteatoma. We sought to describe our management strategy for this dilemma. STUDY DESIGN: Retrospective review. SETTING: Tertiary referral center. PATIENTS: We reviewed all patients with encephaloceles treated by the primary surgeon. Patients without active cholesteatoma and a canal-wall-down cavity were excluded. INTERVENTION: Surgical management of the encephalocele and cholesteatoma. MAIN OUTCOME MEASURE: Successful repair and a noninfected ear. RESULTS: Three patients met the inclusion criteria. All had previous canal-wall-down surgery for cholesteatoma by outside surgeons and presented with chronic otorrhea, large tegmen defects, and brain herniation into the mastoid cavity. All had incomplete removal of their posterior canal wall. Our management strategy involved completing the canal-wall-down mastoidectomy and repairing the temporal floor defect using a three-layer closure via a middle fossa craniotomy. This included suture repair of the dural defect with or without a graft, a temporalis muscle rotation flap, and a split-calvarial bone graft. All patients recovered from their surgery without evidence of further cerebrospinal fluid leak, encephalocele, or cholesteatoma with a minimum follow-up time of 6 months. CONCLUSIONS: A temporal lobe encephalocele can be safely repaired while maintaining a mastoid bowl. This may be the safest treatment option for patients with active cholesteatoma.

Adult↗
PubMed2005

Skull base chondrosarcoma originating from the petroclival junction.

OBJECTIVE: To define the presentation of patients with skull base chondrosarcoma, to elucidate surgical strategies, and to identify the role of postoperative radiotherapy. STUDY DESIGN: Retrospective review. SETTING: Tertiary referral center. PATIENTS: All patients (n = 33) with skull base chondrosarcoma managed at our institution. The average follow-up time was 7.7 years (range, 0-20 years). MAIN OUTCOME MEASURES: Tumor location, presenting symptoms, presence of residual or recurrent tumor, and mortality. RESULTS: The most common tumor location was the petroclival junction (n = 29). Common presenting symptoms were diplopia (48%) and headache (45%). Surgical approaches included retrosigmoid, transtemporal, transfacial, and frontotemporal craniotomies. Biopsy only was performed in four patients, subtotal resection in 19 patients, and total resection in nine patients. Most patients received postoperative radiotherapy (82%). Follow-up revealed residual, stable disease in 28% of patients and recurrent disease in 24% of patients. The mean time to recurrence was 3.0 +/- 2.8 years. The lack of postoperative radiation was significantly correlated with an increased risk of recurrence (odds ratio, 28; p = 0.007) but incomplete tumor resection was not (p = 0.6). Life-table analysis revealed that the 5-year survival rate was 85% and the 10-year survival rate was 77%. Five patients died; four of the deaths attributable to recurrent disease. CONCLUSION: The characteristic growth pattern of skull base chondrosarcoma is tumor eroding the petroclival junction. Current therapeutic strategy is resection through an extradural subtemporal craniotomy with removal of the petrous apex and clivus. Radical resection of uninvolved structures is often not necessary. Nonetheless, gross total removal is often achievable. Postoperative radiotherapy reduces the chance of tumor recurrence.

Adult↗
PubMed2004

Laser irradiation of the guinea pig basilar membrane.

BACKGROUND AND OBJECTIVES: The cochlea is the part of the inner ear that transduces sound waves into neural signals. The basilar membrane, a connective tissue sheet within the cochlea, is tonotopically tuned based on the spatial variation of its mass, stiffness, and damping. These biophysical properties are mainly defined by its constituent collagen fibers. We sought to assess the effect of laser irradiation on collagen within the basilar membrane using histological analysis. STUDY DESIGN/MATERIALS AND METHODS: Four excised guinea pig cochleae were stained with trypan blue. From these, two were irradiated with a 600 nm pulsed dye laser and two were used as controls. Collagen organization was visualized using polarization microscopy. RESULTS: Laser irradiation reduced the birefringence within the basilar membrane as well as within other stained collagen-containing structures. Larger reductions in birefringence were measured when more laser pulses were given. The effects were similar across all turns of each cochlea. CONCLUSIONS: Laser irradiation causes immediate alterations in collagen organization within the cochlea that can be visualized with polarization microscopy. These alterations may affect cochlear tuning. Ongoing research is aimed at analyzing the effect of laser irradiation on cochlear function. It is conceivable that this technique may have therapeutic benefits for patients with high-frequency sensorineural hearing loss.

Animals↗
PubMed2004

Chlorpromazine inhibits cochlear function in guinea pigs.

Outer hair cell (OHC) electromotility provides mechanical positive feedback that functions as the cochlear amplifier. In isolated OHCs, chlorpromazine shifts the electromotility voltage-displacement transfer function in a depolarizing direction without affecting its magnitude. This study sought to measure the effects of chlorpromazine on cochlear function in vivo. Salicylate, a drug that greatly reduces the magnitude of electromotility, was used for comparison. Perilymphatic perfusion of the guinea pig cochlea with chlorpromazine or salicylate increased the compound action potential (CAP) threshold across the frequency spectrum (1-20 kHz). Both drugs also increased distortion product otoacoustic emission (DPOAE) thresholds in the higher frequencies (10-20 kHz). Complete reversibility of these effects occurred after washout. Both drugs demonstrated concentration-dependent reductions in cochlear function that followed sigmoidal curves with similar fits to previously reported results in isolated OHCs. The endolymphatic potential was not affected by either of these drugs. Thus, chlorpromazine inhibits cochlear function in a manner consistent with what would be expected from data in isolated OHCs. This suggests that shifting the electromotility transfer function correspondingly reduces the gain of the cochlear amplifier.

Acoustic Stimulation↗
PubMed2004

The fate of the tumor remnant after less-than-complete acoustic neuroma resection.

OBJECTIVES: We sought to determine the recurrence rate after near-total and subtotal resection of acoustic neuroma. STUDY DESIGN, SETTING, AND PATIENTS: We conducted a retrospective chart review of a total of 79 patients: 50 with near-total resections (remnant < or =25 mm(2) and < or =2 mm thick) and 29 with subtotal resections (any larger remnant). Surgical approach included 5 middle fossa, 17 retrosigmoid, and 57 translabyrinthine. MAIN OUTCOME MEASURES: Recurrence was defined as documented tumor growth by serial imaging or the recommendation for further treatment after a single scan. No recurrence was defined as no visible tumor on imaging for a minimum follow-up time of 3 years or tumor remnants that remained unchanged on serial scans (mean, 5-year follow-up). RESULTS: Fifty-two patients were included in the study group. Recurrences were seen in 1 (3%) of 33 patients who had a near-total resection compared with 6 (32%) of 19 patients who had a subtotal resection. After adjustment for follow-up time and large tumor size, the odds ratio for recurrence was 12 times larger for subtotal than for near-total resections (P = 0.033). All recurrences were seen following the translabyrinthine approach in the mid-cerebellopontine angle. None were encountered in the internal auditory canal. The mean time interval from surgery to the detection of a recurrence was 3 years (range, 1 to 5 years). CONCLUSIONS: The recurrence rate when performing a near-total resection is low but is substantially higher with a subtotal resection. Recurrences can be detected within the first 5 postoperative years. We recommend near-total resection in any patient if needed to preserve neural integrity. Subtotal resection is best avoided whenever possible; however, adjunctive treatment with stereotactic radiotherapy may be considered.

Adult↗
PubMed2004

Transjugular craniotomy for the management of jugular foramen tumors with intracranial extension.

OBJECTIVES: To elucidate indications and outcomes with the transjugular craniotomy for resection of jugular foramen tumors with intracranial extension. The transjugular approach is a lateral craniotomy conducted through a partial petrosectomy traversing the jugular fossa combined with resection of the sigmoid sinus and jugular bulb, which often have been occluded by disease. STUDY DESIGN: Retrospective review. SETTING: University medical center. PATIENTS: Twenty-eight patients with intracranial jugular foramen tumors who underwent a total of 30 surgical procedures. MAIN OUTCOME MEASURES: Pathologic findings, surgical approach, extent of tumor resection, rate of facial nerve mobilization and ear canal closure, facial and lower cranial nerve outcomes, and hearing preservation. RESULTS: Tumors included schwannoma (37%), meningioma (33%), glomus jugulare (23%), and chordoma (7%). The surgical approaches were tailored to maximize functional preservation, and included the transjugular (53%), translabyrinthine (17%), retrosigmoid (10%), and far lateral (7%) craniotomies. Translabyrinthine (3%) or transcondylarfar lateral (3%) approaches were occasionally used in combination with the trans-jugular approach. Most procedures were managed in a single stage (90%), but three patients with massive tumor in the neck required two stages. Microsurgical gross total and near-total tumor removal (37% each) were commonly achieved, although subtotal resections (27%) were occasionally performed. In only a minority of cases was facial nerve mobilization (7%) or ear canal closure (21%) required. If present preoperatively, Grade I facial nerve function was usually maintained (22 of 24 [92%]) and Hearing Class A or B could always be maintained (9 of 9 [100%]). As expected, new lower cranial nerve dysfunction was common (8 of 30 [27%]), although over half of the patients had complete lower nerve palsy preoperatively (16 of 30 [53%]). CONCLUSION: Most patients with jugular foramen tumors with intracranial extension can be managed with a single-stage transjugular craniotomy. Facial nerve mobilization or ear canal closure is usually not required, permitting conservation of facial function and hearing, when present preoperatively.

Adult↗
PubMed2004

Chronic pachymeningitis presenting as asymmetric sensorineural hearing loss.

OBJECTIVE: The objective of this study was to characterize the auditory dysfunction associated with chronic pachymeningitis (inflammation of the dura mater). STUDY DESIGN AND SETTING: We conducted a university-based retrospective review. RESULTS: Three patients were identified who were diagnosed with chronic pachymeningitis after being referred for asymmetric sensorineural hearing loss. All patients were found to have other neurologic symptoms and signs during careful neurotologic evaluation. Two varieties of chronic pachymeningitis exist: a hypertrophic mass lesion and a linear dural thickening. Although the hypertrophic variety could be easily detectable by noncontrast magnetic resonance imaging (MRI), the linear form is only visible with the use of gadolinium enhancement. CONCLUSION: Chronic pachymeningitis is a rare form of sensorineural hearing loss that could portend an underlying disease of greater concern. Extensive evaluation is needed to exclude identifiable causes of chronic pachymeningitis, including infectious, neoplastic, and autoimmune diseases. SIGNIFICANCE: The clinician should be aware that the evaluation of a patient with asymmetric sensorineural hearing loss involves more than simply ruling out an acoustic neuroma. Fast-spin echo MRI techniques without the use of gadolinium contrast could miss a number of potentially treatable diseases such as chronic pachymeningitis. Patients with asymmetric sensorineural hearing loss should be carefully evaluated for other neurologic findings, and imaging with enhanced MRI is recommended.

Adult↗