Faculty Bibliography

BACKGROUND: Resistance to thyroid hormone (RTH) is a syndrome characterized by refractoriness of the pituitary and/or peripheral tissues to the action of thyroid hormone. Mutations in the thyroid hormone receptor beta (TR beta) gene result in TR beta 1 mutants that mediate the clinical phenotype by interfering with transcription of thyroid hormone-regulated genes via a dominant negative effect. In this study, we developed transgenic mice harboring PV, a potent dominant negative human mutant TR beta 1 devoid of thyroid hormone binding and transcriptional activation, as an animal model to understand the molecular basis of this human disease. MATERIALS AND METHODS: Standard molecular biology approaches were used to obtain a cDNA fragment containing mutant PV which was injected into the pronucleus of fertilized egg. Founders were identified by Southern analysis and the expression of PV in tissues was determined by RNA and immunohistochemistry. Thyroid function was determined by radioimmunoassays of the hormones and the behavior of mice was observed using standard methods. RESULTS: The expression of mutant PV was directed by the beta-actin promoter. Mutant PV mRNA was detected in all tissues of transgenic mice, but the levels varied with tissues and with different lines of founders. Thyroid function tests in transgenic mice with high expression of mutant PV showed a significantly (approximately 1.5-fold) higher mean serum total of L-thyroxine levels (p < 0.01) than those of nontransgenic mice. Moreover, thyroid-stimulating hormone levels were not significantly different from those of nontransgenic mice. In addition, these mice displayed decreased weights and a behavioral phenotype characterized by hyperactivity. CONCLUSIONS: These mice have phenotypic features consistent with the commonly observed clinical features of RTH and could be used as a model system to better understand the action of mutant TR beta 1 in a physiological context, which could lead to better treatment for this disease

OBJECTIVE: The aim of this study was to identify distinguishing characteristics of uncommon lesions of the cerebellopontine angle (CPA) and internal auditory canal (IAC) in order to attain the correct diagnosis and thus formulate an appropriate therapeutic protocol. STUDY DESIGN: A retrospective chart analysis was performed on all patients with surgically managed lesions of the IAC and CPA referred to neuropathology from January 1985 to April 1996. SETTING: All patients were treated by New York University faculty at a tertiary referral center. PATIENTS: Among 426 surgical cases identified, 384 patients (90.1%) with acoustic neuromas and 18 patients (4.2%) with meningiomas were excluded. The remaining 24 cases, involving 17 women and seven men with a median age of 34 years, were analyzed. INTERVENTION: Most patients underwent audiovestibular evaluations, as well as magnetic resonance imaging (MRI) and computed tomographic (CT) scanning, and all patients underwent neurotologic surgery as part of their management protocol. MAIN OUTCOME MEASURES: Correlating patient presentation, preoperative imaging, and surgical findings often identified distinguishing characteristics of unusual CPA and IAC lesions. RESULTS: Unusual lesions identified at the CPA and IAC included: four epidermoids, four lipomas, two facial neuromas, two arachnoid cysts, two choroid plexus papillomas, two metastatic adenocarcinomas, one metastatic neuroblastoma, one ependymoma, one lymphoma, one cholesterol cyst, one angioleiomyoma, one venous hemangioma, one cavernous angioma, and one pontine glioma. CONCLUSIONS: Preoperative tumor differentiation based on the patient history, physical examination, audiovestibular testing, CT, and MRI help the surgeon to formulate an appropriate treatment protocol

OBJECTIVE: To assess and document the development of open-set speech recognition in congenitally deaf children implanted with the Nucleus multichannel cochlear prosthesis at < 5 years of age. STUDY DESIGN: The study group consisted of 38 consecutively chosen children in whom the decision to proceed with implantation had already been made. PATIENTS AND SETTING: Congenitally profoundly deaf children were implanted with the Nucleus multichannel cochlear implant at < 5 years of age and followed at NYU Medical Center for a period of 1-5 years. MAIN OUTCOME MEASURES: Open-set speech perception was evaluated preoperatively and postoperatively using the following: the Glendonald Auditory Screening Procedure (GASP) word subset, the GASP sentence subtest, Phonetically Balanced Kindergarten monosyllabic word lists, Common Phrases test, Multisyllabic Lexical Neighborhood test, and Lexical Neighborhood test. RESULTS: Correlation coefficients were calculated between scores at each interval and age at implantation; one-way analyses of variance were performed independently. Results showed that all subjects had significant open-set speech recognition at the time of the last postoperative evaluation. Thirty-seven of the children use oral language as their sole means of communication. CONCLUSIONS: Multichannel cochlear implants provide significant and usable open-set speech perception in congenitally deaf children given implants at < 5 years of age

Profound changes in our society occurring over the past few decades have resulted in a major shift in societal emphasis from labor to communication. The widespread use of personal computers has enhanced the importance of information-communication in daily life. People with communication disorders are at substantial risk of underemployment and lowered quality of life. Advances in medical science and hearing health care have placed us on the thresholds of being able to correct, rather than remediate, certain types of hearing loss. The finding that auditory hair cells of submammalian species regenerate has stimulated greatly the field of auditory research. A new lexicon is required to describe this emerging field. Methods exist to protect against hearing loss, repair affected structures prior to their degeneration, promote dedifferentiation-redifferentiation of undamaged structures into sensory cells, and, finally, promote regeneration of new sensory cells from precursor cells. Each of these processes has unique requirements, and all may be required to promote the restoration of hearing following damage or disease.

In current theories of sinusitis, obstruction at the ostiomeatal complex leads to localized inflammation and infection. Haller cells, an extension of ethmoid pneumatization along the maxillary antrum roof, have also been suggested as a causative factor in sinusitis because of their ability to cause narrowing of the infundibulum. Coronal CT scans were reviewed in 154 patients to evaluate the role of Haller cells in sinusitis. Haller cells were present in 34% of patients. The cells were graded as small, medium, or large, and correlated with radiologic evidence of sinusitis (e.g., mucosal thickening or opacification). A statistically significant increase in maxillary sinus mucosal disease was noted in patients with medium or large Haller cells (45.8%) versus those with small cells (28.9%, p < 0.05). Thus obstructive medium and large Haller cells may be an etiologic factor in sinusitis

Pathological differentiation of oligodendroglioma and mixed oligoastrocytoma from astrocytoma is difficult, relying on morphological characteristics due to the lack of reliable immunohistochemical stains. Oligodendrocytes, the presumed cell of origin of oligodendrogliomas, highly express the genes encoding myelin basic protein (MBP) and proteolipid protein (PLP). We analyzed the expression of these genes to determine whether they might be useful molecular markers of oligodendrocytic tumors. MBP and PLP were highly expressed in all oligodendrogliomas and minimally expressed in glioblastomas multiforme. MBP was highly expressed in mixed oligoastrocytomas, whereas PLP expression was minimal. The association between tumor classification and expression of the MBP and PLP genes was statistically significant. Expression of these genes may serve as a useful molecular marker for some subtypes of human gliomas

The purpose of this longitudinal study is to document improvements in speech intelligibility in children who have received multichannel cochlear implants, to compare their performance to that of a matched group of children with different levels of hearing loss who use conventional hearing aids. Speech intelligibility was measured by panels of listeners who analyzed recorded speech samples preimplant and at 6-month intervals following implantation. The results of this study demonstrate that prelingually deafened children with the Nucleus multichannel cochlear implant achieved significant improvements in speech intelligibility. By the 4.5- to 7.5-year intervals, the speech intelligibility exceeded 40%. $$:

Previous investigations of exfoliated oropharyngeal cells from individuals suffering from infectious mononucleosis (IM) suggested that the oropharyngeal epithelia are the primary target and also the site of life-long persistence of the Epstein-Barr virus (EBV). This concept was widely accepted. However, the investigation of histological sections with more sensitive EBV detection techniques has drawn this concept into doubt since EBV proved to be constantly absent in normal epithelial cells. To elucidate the discrepancy, throat washings and peripheral mononuclear blood cells from 16 patients suffering from IM were investigated for EBV-DNA and EBV gene products employing highly sensitive in situ hybridization, immunocytochemistry, and polymerase chain reaction. Although all patients exhibited latently infected B lymphocytes in peripheral blood, samples of exfoliated oropharyngeal cells were constantly EBV-negative with the exception of three cases. In these cases, the patients additionally suffered from purulent ulcerating tonsillitis, EBV-infected B cells, but no EBV-infected epithelial cells were detectable. These findings support the view that recirculating lymphocytes of B-cell origin, but not epithelial cells are the initial target of EBV during primary infection and that B cells also represent the site of life-long viral persistence

Cerebrovascular disease is a major cause of death in patients with end-stage renal disease, particularly in those with diabetes mellitus. Cardiac disease frequently presents itself atypically in diabetic patients. This awareness has led to earlier detection and treatment of cardiac disease in diabetic patients. Whether cerebrovascular disease may also present itself in a highly atypical fashion in the diabetic patient with end-stage renal disease has never been addressed. We report the case of a diabetic hemodialysis patient who had an extremely unusual manifestation of stroke. A 67-year-old diabetic hemodialysis patient had marked distress secondary to the sudden onset of a foreign body sensation in the oropharynx. Results of a laryngoscopy were negative; x-rays of the neck and computerized tomography of the head and neck showed no abnormalities. Neurologic evaluation revealed an inability to detect oropharyngeal stimuli and an absent gag reflex but no other deficits. Magnetic resonance imaging of the brain revealed an infarction in the left corona radiata that extended to the thalamocapsular region and external capsule, and a lacunar infarct in the right pons. Cerebrovascular disease in the diabetic patient with end-stage renal disease may present itself atypically, and we suggest that cerebrovascular disease in these patients merits the same level of suspicion as cardiac disease