Faculty Bibliography

Expressive language skills were assessed in two groups of prelingually-deafened children using the Reynell Developmental Language Scales (RDLS). Results from a group of 89 unimplanted subjects provided cross-sectional data which suggested that profoundly deaf children without implants, on average, could only be expected to make 5 months of expressive language growth in one year. Twenty-three children who received cochlear implants made up the second group of subjects and were administered the RDLS at three intervals: preimplant, 6-, and 12-months postimplant. The scores obtained at the post-implant intervals were then compared to scores that would be predicted on the basis of maturation alone, without the implant (these predictions were formulated based on the data obtained from the unimplanted subjects). At the 12-month postimplant interval, the observed mean language score was significantly higher than the predicted score. Although the mean group data were extremely encouraging, wide inter- subject variability was observed. Although the implant subjects, as a group, were substantially delayed compared with their normal hearing peers, their rate of language growth was found to match that of hearing peers, following implantation. Thus, the gap between chronological age and language age, which normally widens over time in deaf children, remained constant. Preliminary analyses over the first 2.5 years post-implant are consistent with this trend. These results suggest that early implantation (before age 3) might be beneficial to profoundly deaf children because the language delays at the time of implantation would be much smaller

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

BACKGROUND AND OBJECTIVES: Esophagogastric anastomotic leaks are a major source of morbidity after esophagectomy. Occult ischemia of the mobilized gastric fundus is an important etiological factor for this failure of healing. To test the hypothesis that ischemic conditioning (delay phenomenon) could improve esophagogastric anastomotic healing, anastomotic healing was studied in a rodent model of partial gastric devascularization. METHODS: Thirty-four Sprague-Dawley rats (two groups of 17 rats) underwent partial gastric devascularization and creation of esophagogastric anastomoses. In the acute ischemia group, devascularization and anastomosis were done at the same laparotomy. In the ischemic conditioned group, devascularization was done 3 weeks before anastomosis. Gastric tissue perfusion was assessed by laser-Doppler flowmetry before and after devascularization in both groups, and 3 weeks after devascularization in the ischemic conditioned group. All rats were killed 4 days after anastomosis, and the wounds assessed for dehiscence, breaking strength, and hydroxyproline concentration. RESULTS: Gastric tissue perfusion, measured in tissue perfusion units (TPU) decreased immediately after devascularization (before: 73.6 +/- 12.1 TPU; after: 25.0 +/- 6.5 TPU; P < 0.001). After 3 weeks, gastric tissue perfusion returned to baseline values in the ischemic conditioned rats (before: 72.3 +/- 11.0 TPU; 3 weeks, 71.1 +/- 15.1 TPU; P < 0.80). Ischemic conditioned rats had fewer anastomotic leaks (2 vs. 9, P < 0.023) and higher anastomotic wound breaking strengths (2.35 +/- 1.05 N vs. 1.56 +/- .76 N, P < 0.02) than the acute ischemic rats. Anastomotic would hydroxy-proline concentration was not significantly different in the two groups (acute ischemic--0.111 +/- .033 mumol/mg, ischemic conditions--0.097 +/- .026 mumol/mg, P < 0.20). CONCLUSIONS: In this rodent model of partial gastric devascularization, ischemic conditioning (delay phenomenon) ameliorated the harmful effect of ischemic on esophagogastric anastomotic wound healing

Microvascular free-tissue transfers have assumed particular importance as reconstructive techniques of choice in centers where ablative surgery for primary and recurrent malignant disease is a focus. In the context of malignant disease, issues of surveillance for recurrence are paramount. As clinical experience with the diagnostic imaging characteristics of flap reconstructions has been acquired, magnetic resonance imaging (MRI) has assumed a prominent role in the evaluation for recurrent malignant disease. This has provided an important supportive role for contemporary concepts of immediate reconstruction. The Precise-TM Microvascular Anastomotic Device (MACD) is based on the friction-fit union of implant rings composed of high-density polyethylene and surgical stainless steel. Many characteristics of the device have been described in histologic and laboratory studies. As yet uncharacterized is the effect of clinical MRI electromagnetic fields on the device, which is composed, in part, of type 316 stainless steel. The MACD is in wide use in centers where microsurgeons are experienced with the system and it is designed to facilitate the performance and reliability of microvascular anastomoses. The implications for MRI as a safe imaging modality for the acute perioperative evaluation of patients reconstructed with microvascular free flaps anastomosed with the MACD are obvious. MACD implants of varying sizes were evaluated for displacement in each of three orthogonal planes within a 1.5 Tesla magnetic field. No change in displacement was observed for any of the devices. Magnetic resonance imaging may thus be considered a safe imaging modality for the acute perioperative diagnostic imaging of free-tissue transfers that have been anastomosed with the MACD

HYPOTHESIS: The hypothesis tested in this article is that if cholesteatomas are a low-grade squamous cell neoplasm, then evidence of genetic instability, in the form of abnormal or aneuploid amounts of DNA, should be evident. BACKGROUND: Cholesteatoma is a destructive lesion of the middle ear and/or mastoid process that produces complications by erosion of the temporal bone. The clinical hallmarks of cholesteatomas, namely invasion, migration, uncoordinated proliferation, altered differentiation, aggressiveness, and recidivism, are traits typically associated with the neoplastic cell. However, there is little evidence to support or refute the speculation that cholesteatomas are a low-grade squamous cell neoplasm. the existence of defects in the genetic complement of the major cellular constituents comprising a cholesteatoma, fibroblasts and keratinocytes, would support the speculation that cholesteatomas are a neoplasm, since cancers commonly manifest quantitative and qualitative alterations in the normal euploid complement of genetic information, resulting in a cell that has an abnormal or aneuploid amount of DNA. METHODS: DNA content (ploidy) within cholesteatoma tissues was measured by flow cytometry and image analysis. RESULTS: The DNA content of 11 human cholesteatomas and nine postauricular skin specimens was analyzed using flow cytometry, while the DNA content of 10 cholesteatoma specimens was analyzed using image analysis. Interpretable data was obtained from 10 cholesteatoma specimens and six postauricular skin specimens. One cholesteatoma specimen demonstrated an abnormal aneuploid DNA content, whereas the remaining nine cholesteatomas and the six postauricular skin specimens demonstrated a normal euploid DNA content. CONCLUSIONS: We conclude that, due to the lack of overt genetic instability, as evidenced by the presence of a normal euploid DNA content, cholesteatomas are not low-grade neoplasms

BACKGROUND: Alveolar ridge squamous carcinomas develop in patients outside the usual constellation of risk factors. OBJECTIVE: To determine whether the use of dentures was a risk factor specific to patients with alveolar ridge carcinoma. DESIGN: Case-control method with a unique control group-a concurrent cohort of patients with head and neck cancer with primaries in the oropharynx, hypopharynx, and larynx. SETTING: Tertiary care hospital-based clinic. PATIENTS: Forty-one patients with squamous carcinomas centered on the maxillary or mandibular alveolar ridges. The control group was 175 concurrently seen patients with squamous carcinomas of the laryngopharynx for whom dental status was known. MAIN OUTCOME MEASURES: Age at diagnosis, sex, tobacco use, alcohol use, and denture use. RESULTS: Patients with alveolar ridge were more likely to be female, older, nonsmokers, and nondrinkers. The crude odds ratio of denture use in patients with alveolar ridge cancer was 2.28 (P=.03). Eliminating other confounding factors with logistic regression, the adjusted odds ratio dropped to 1.30 (P=.59). Among patients with alveolar ridge, smoking status correlated with age and gender: current smokers were on average 64.4 years old and 9 of 16 were men. Nonsmokers' average age was 79.1 years and 1 of 11 was a man. CONCLUSIONS: In this study, denture use was not an independent risk factor for alveolar ridge carcinomas. Among patients with little to no tobacco or alcohol exposure, the alveolar ridge carcinomas tended to occur in the elderly and in women

The objective of this study was to determine whether insertion length and number of active channels remained the same after reimplantation of a cochlear implant. A retrospective case review of 170 consecutively implanted multichannedl cochlear implants was conducted. Seventeen of these devices had to be replaced. Data were analyzed for the Nucleus cochlear implant users who were reimplanted in the same ear. For most subjects, insertion length and number of channels remained unchanged, but a few subjects experienced substantial decreases. When the whole group was considered, a small but statistically significant drop was noted for both parameters. In conclusion, although reimplantation is technically possible, the first procedure provides the optimal surgical environment

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

Traditionally surgeons have avoided performing rhinoplasty in conjunction with sinus surgery for rhinosinusitis. With advances in rhinoplasty and endoscopic sinonasal surgery and its added benefits of precision, minimal trauma, and hemorrhage, the combined procedure is now feasible. The indications, management, and results are discussed in 40 patients who underwent the combined procedure. Patients were divided into three categories based on the location and severity of the sinus disease: mild, moderate, or severe. The majority of patients had mild or moderate sinus disease. The most common presenting symptoms were nasal obstruction and postnasal drip. All patients had a history of sinusitis recalcitrant to conservative medical management. Results demonstrate the combined treatment modality to be safe and effective in patients with mild to moderate sinus disease and in selected patients with severe sinus disease