Differentially expressed genes in the rat cochlear nucleus.

The cochlear nucleus is the first central pathway involved in the processing of peripheral auditory activity. The anterior ventral cochlear nucleus (AVCN), posterior ventral cochlear nucleus (PVCN) and dorsal cochlear nucleus (DCN) each contain predominant populations of neurons that have been well characterized regarding their morphological and electrophysiological properties. Little is known, however, of the underlying genetic factors that contribute to these properties and the initial steps in auditory processing. Serial analysis of gene expression (SAGE), supported by microarray experiments, was performed on each subdivision of the rat cochlear nucleus to identify genes that may sub-serve specialized roles in the central auditory system. Pair-wise comparisons between SAGE libraries from the AVCN, PVCN and DCN were correlated with microarray experiments to identify individual transcripts with significant differential expression. Twelve highly correlated genes were identified representing cytoskeletal, vesicular, metabolic and g-protein regulating proteins. Among these were Rgs4 which showed higher expression in the DCN, Sst and Cyp11b1 with very high expression in the AVCN and Calb2 with preferential expression in the PVCN. The differential expression of these genes was validated with real-time reverse transcriptase-polymerase chain reaction. These experiments provide a basis for understanding normal auditory processing on a molecular level and a template for investigating changes that may occur in the cochlear nucleus with hearing loss, the generation and percept of tinnitus, and central auditory processing disorders.

Bacterial colonization of endotracheal tubes in intubated neonates.

OBJECTIVE: To obtain in vivo bacterial colonization profiles on endotracheal tubes at different sites in the neonatal airway in an attempt to better characterize one potential element of chondritis. DESIGN: A case series in which cultures were obtained from calculated segments of 33 endotracheal tubes immediately following extubation. This allowed for sampling at specific levels of the airway corresponding to the trachea, the subglottis, and the oropharynx. Data collected included gender, race, duration of intubation, use of antibiotic therapy, comorbidities, gestational age at birth and extubation, crown-rump length, weight, radiographic distance from tube tip to carina, and culture results. SETTING: Newborn intensive care unit at a tertiary care medical center. PATIENTS: Twenty-nine neonates intubated for longer than 24 hours (range, 24 hours to 15 days). MAIN OUTCOME MEASURES: Bacterial and fungal cultures obtained from 3 endotracheal tube segments for each extubation. RESULTS: A statistically significant difference (P < .05) was found in colonization rates between patients intubated for less than 4 days and those intubated for longer periods. No significant difference was noted in bacterial profile between the 3 sites. CONCLUSIONS: Data demonstrate that bacterial colonization of an indwelling object in the neonatal airway increases with the duration of intubation. Furthermore, 4 days seems to represent a critical period in the formation of such colonization (possibly in the form of a biofilm). These bacteria may contribute to the chondritis known to precede the development of subglottic stenosis. Further studies are indicated to suggest ways to interrupt this process and reduce the incidence of airway injury.

Rapid resolution of fetal goiter associated with maternal Grave's disease: a case report.

The incidence of abnormal fetal thyroid function with maternal Grave's disease is about 2-12%. The development of larger fetal goiters can complicate labor and precipitate life-threatening airway obstruction at delivery. A case is presented of a large stable goiter confirmed by sonography, which unexpectedly resolved by the time of parturition. A 3 x 6 cm fetal goiter was detected at 34 weeks gestation in a mother treated with propylthiouracil for Grave's disease. A repeat sonogram at 36 weeks showed no change in goiter size. Umbilical blood sampling showed the fetus to be markedly hyperthyroid. Planned Cesarean section took place 11 days after the final sonogram. A multi-disciplinary operative team was present including the Otolaryngology service with equipment for emergency intubation, bronchoscopy and tracheotomy. Upon delivery, the infant had no evidence of goiter and no airway compromise. Fetal goiter is a rare entity, and recent advances in the field of maternal-fetal medicine have enabled intra-uterine diagnosis and treatment of such conditions. A review of published case reports demonstrates two trends in treated fetuses: preterm progressive resolution of the goiter, or delivery with gross evidence of goiter. This reported case is unique, as a persistent goiter resolved completely in less than 2 weeks. Otolaryngologic response to and management of potential congenital airway compromise is discussed.

Cochlear implantation for auditory rehabilitation in Camurati-Engelmann disease.

Camurati-Engelmann disease (progressive hereditary diaphyseal dysplasia) is a rare sclerotic bone disease involving the diaphyses of the long bones, skull base, and clavicles. Progressive sclerosis of cranial nerve foramina has been implicated in cranial nerve deficits. including facial nerve palsy, vestibular disturbances, and hearing loss. Two patients with Camurati-Engelmann disease and concomitant sensorineural hearing loss are presented. Both patients were evaluated for cochlear implantation. One patient was successfully implanted after preoperative imaging revealed no involvement of the internal auditory canals. The porous nature of the affected bone, however. necessitated the inactivation of 1 electrode to prevent facial nerve stimulation. A second patient was rejected as a potential implant recipient due, in part, to narrow internal auditory canals and rapidly progressive disease. The otologic manifestations of Camurati-Engelmann disease are reviewed, and issues related to cochlear implantation in this rare disease are discussed.

A critical appraisal of spontaneous perilymphatic fistulas of the inner ear.

OBJECTIVE: This article provides an overview of relevant data supporting and refuting the existence of spontaneous perilymph fistula, as well as critically reviewing the literature pertaining to their evaluation and management. DATA SOURCES: Sources used were relevant English language clinical and basic science publications. STUDY SELECTION: A Medline search dating back to 1966 for articles concerning perilymphatic fistula, including both human and animal data, was performed. Articles were included if they contained relevant data or were significant reviews of the subject. A traditional bibliography search was then completed to acquire articles missed by the computerized search, including works published before 1966. DATA EXTRACTION: The data from each publication were critically reviewed. Emphasis on understanding the clinical features of surgically created perilymph fistulas was used to more objectively assess the data regarding spontaneous perilymph fistulas. DATA SYNTHESIS: The data were not amenable to formal meta-analysis or valid data summarization; however, when possible trends and contrasting data were emphasized. CONCLUSIONS: Spontaneous perilymph fistulas are very rare occurrences and the majority are likely incited by a pressure-altering event. Current methodologies do not provide sufficient specificity and sensitivity to accurately diagnose perilymph fistulas. The results of endoscopic studies of the middle ear in the evaluation of perilymphatic fistula suggest a low incidence compared with the large number of fistulas reported in the literature. A high index of suspicion must be maintained, and appropriate preoperative counseling should reflect the current controversies. Questions must continue to be asked and further research pursued to help distinguish reality from myth.

Evaluation of surgical approaches to endoscopic auditory brainstem implantation.

OBJECTIVES: This study investigates the use of endoscopy for the placement of an auditory brainstem implant by translabyrinthine, retrosigmoid (suboccipital), and middle cranial fossa approaches. STUDY DESIGN: Cadaver dissection and endoscope-assisted placement of the auditory brainstem implant. METHODS: Translabyrinthine, retrosigmoid, and middle cranial fossa dissections were performed bilaterally in five cadaveric heads. An auditory brainstem implant was placed within the lateral recess of the fourth ventricle under endoscopic visualization. The implantation was performed with all approaches and documented by digital image capture followed by production of dye-sublimation photographic prints. RESULTS: The lateral recess was visualized with the endoscope in all three approaches to the brainstem. The 30 degrees endoscope provided the best visualization by translabyrinthine and retrosigmoid dissection and was essential for the middle cranial fossa approach. Refinement of implant position was readily achieved, as even the deepest portion of the recess could be seen with all three approaches. CONCLUSIONS: This study finds that endoscopy provides superior visualization of the lateral recess of the fourth ventricle than the operating microscope with all approaches. The retrosigmoid approach is recommended, as it provides the best view of the implantation site and the easiest angle for placement of the prosthesis. The use of the endoscope may allow for a smaller craniotomy than with conventional microscopic techniques, depending on tumor size. The translabyrinthine approach provides a good view of the lateral recess but had no advantage over other approaches. The middle cranial fossa approach is only possible with angled endoscopes; however, it is technically the most difficult and places the facial nerve at greatest risk.

A cost-effectiveness analysis of the high risk register and auditory brainstem response.

OBJECTIVE: To evaluate an infant hearing screening program utilizing the high risk register (HRR) and auditory brainstem response (ABR). DESIGN: A cost-effectiveness analysis of the screening program employing a retrospective cohort identified by chart review. The analysis was performed on a hypothetical cohort of 100,000 births and the results compared with a base model derived from literature review. SETTING: Mount Sinai Hospital, New York City, an urban, tertiary care institution. PATIENTS: All infants born between November 1990 and October 1993, approximately 16,500. Cost-effectiveness analysis focused on test results of 420 infants failing the HRR and 381 who subsequently received ABR. RESULTS: Analysis of the Mount Sinai Hospital (MSH) protocol showed it to be less cost-effective than other similar programs. The cost per hearing loss was far more at MSH than that found elsewhere. Further, the MSH program was ineffective in detecting infants with congenital hearing loss--identifying only one case between 1990 and 1993. Analysis of high risk criteria finds a low incidence of family history of hearing loss in the Mount Sinai cohort while other studies find a very high incidence. CONCLUSIONS: It appears that the poor performance of the MSH protocol is due to low specificity and sensitivity of the HRR. This generates a costly and ineffective program as follow-up exams focus on ruling-out false-positives rather than correctly identifying true hearing losses. Further evaluation is needed to determine whether changes in the application of the HRR or utilization of newer, low-cost tests such as otoacoustic emissions (OAE) may be effective in universal infant hearing screening.

Use of the novel carbocyanine tracer fast-DiI for investigating upper respiratory tract cranial nerves in prenatal rats.

The use of traditional neuroanatomic tracing methods with tracers such as horseradish peroxidase requires living systems to take up and transport the label. These tracers have limited application in the study of prenatal systems. The advent of the carbocyanine dye DiI provided a tool by which neuronal pathways may be traced in postmortem fixed tissue. This dye allows careful dissection of prenatal organisms and specific application of the tracer to the neuroanatomic structure under investigation. Although DiI has become increasingly popular, it is limited by the difficulty in applying crystals to peripheral nerves and in the lengthy trace times, particularly in fixed tissue. A chemically modified version of DiI has been introduced that may overcome some of the limitations in using this tracer. The newer dye, fast-DiI, is easy to apply and can trace neural pathways in a shorter period. We describe our experience with the use of fast-DiI in the prenatal rat for the investigation of motoneurons that subserve upper respiratory tract structures. We have determined protocols for fixation, application of dye, processing of tissue, and visualization of traces. The entire protocol can be completed within 1 week, and the use of fast-DiI is easy to learn and apply. The resultant labeling of traced nerves is specific and clearly demonstrates respective motor nuclei and individual motoneurons.

Naturally occurring motoneuron cell death in rat upper respiratory tract motor nuclei: a histological, fast DiI and immunocytochemical study in the hypoglossal nucleus.

We have previously reported on our investigation of motoneuron cell death (MCD) in the rat nucleus ambiguus (NA). This article focuses on the other major upper respiratory tract motor nucleus: the hypoglossal. The hypoglossal nucleus (XII) contains motoneurons to the tongue and, as such, plays a critical role in defining patterns of respiration, deglutition, and vocalization. Motoneuron counts were made in XII in a developmental series of rats. In addition, the neural tracer fast DiI was used to ensure that all hypoglossal motoneurons had migrated into the nucleus at the time cell death was assessed. Furthermore, an antibody to gamma-aminobutyric acid (GABA) was used to determine the potential effect of inadvertently counting large interneurons on motoneuron counts. Cell death in XII was shown to occur entirely prenatally with a loss of 35% of cells between embryonic day 16 (E16) and birth. Fast DiI tracings of the prenatal hypoglossal nerve indicated that all motoneurons were present in a well-defined nucleus by E15. Immunocytochemical staining for GABA demonstrated considerably fewer interneurons than motoneurons in XII. These findings in XII, in comparison with those previously reported for NA, demonstrate differences in the timing and amount of cell death between upper respiratory tract motor nuclei. These differences establish periods during which one nucleus may be preferentially insulted by environmental or teratogenic factors. Preferential insults may underlie some of the upper respiratory tract incoordination pathologies seen in the newborn such as the sudden infant death syndrome (SIDS).

Naturally occurring motoneuron cell death in rat upper respiratory tract motor nuclei: a histological, fast DiI and immunocytochemical study of the nucleus ambiguus.

The mammalian upper respiratory tract (URT) serves as the common modality for aspects of respiration, deglutition, and vocalization. Although these actions are dependent on coordinated and specific neuromuscular control, little is known about the development of URT control centers. As such, this study investigated the occurrence of naturally occurring motoneuron cell death (MCD) in the nucleus ambiguus (NA) of a developmental series of rats. Standard histological techniques were used to count motoneurons in the ventrolateral brainstem where the mature NA is found. In addition, the neural tracer, fast DiI, was used to determine whether motoneurons were still migrating into the region of the NA during the period that cell counts were first taken. Furthermore, to elucidate the potential effect of inadvertently counting large interneurons on the assessment of motoneuron numbers, an antibody to gamma-aminobutyric acid (GABA) was used. The results of this study have, for the first time, demonstrated that MCD occurs in a URT-related motor nucleus. Approximately a 50% cell death was observed during the prenatal development of NA, with no further loss seen postnatally. The fast DiI studies showed that by embryonic day 17, NA was fully formed, suggesting that motoneuron migration from the basal plate was complete. In addition, use of the GABA antibody showed a lack of inhibitory interneurons within the NA. The finding of MCD in the NA helps define a critical period in the formation of URT neuromuscular control. As the course of MCD is modifiable by epigenetic signals, insult to the organism during this prenatal period may compromise future URT control.