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David R Friedland

Publications and source records attributed to David R Friedland.

9 recordsLinked to original sources
PubMed2006

Structure and function in the auditory system: From cochlea to cortex.

This special issue of the Anatomical Record examines the relationship between structure and function in the auditory system. Early anatomical studies defined this relationship on a macroscopic level and described the roles of structures such as the tympanic membrane, ossicular chain, Eustachian tube, and cochlea. As new tools emerged, the microscopic structure of the organ of Corti was described and later the brain stem regions involved in auditory processing were identified. Further technical advances allowed the description of cells within these central auditory regions in both morphological and physiological terms. More recently, studies of the auditory system have employed molecular biological techniques and novel imaging protocols. All these techniques continue to provide important insights into the structure and function of the auditory system on gross, cellular, and molecular levels. This issue expounds on this theme by demonstrating the importance of anatomy, whether the shape of the otic capsule or the sequence of a gene, in determining the function of the system and even the phenotype of the organism. The articles in this issue represent the cutting edge of today's auditory science and look back at the evolution of hearing and balance, as well as forward toward improving cochlear implant outcomes and gene therapies for treating sensorineural hearing loss.

Animals↗
PubMed2006

Differential expression of cytoskeletal genes in the cochlear nucleus.

The relationship between structure and function is clearly illustrated by emerging evidence demonstrating the role of the neuronal cytoskeleton in physiological processes. For example, alterations in axonal caliber, a feature of the cytoskeleton, have been shown to affect reflex arc latencies and are prominent features of several neuropathological disorders. Even in the nonpathologic situation, however, axonal diameter may be a crucial element for the normal function of specialized auditory neurons. To investigate this relationship, we used serial analysis of gene expression and microarray analyses to characterize the expression of cytoskeletal genes in the central auditory system. These data, confirmed by real-time RT-PCR, identified differential expression of intermediate neurofilament transcripts (i.e., Nefh, Nef3, and Nfl) among the subdivisions of the cochlear nucleus. In situ hybridization was used to identify specific classes of neurons within the cochlear nucleus expressing these neurofilament genes. Robust neurofilament expression was seen in bushy cells and cochlear nerve root neurons, suggesting an association between cytoskeletal structure and rapid conduction velocities. Gene expression data were also identified for other classes of cytoskeletal and structural genes important in neuronal function. These results may help to explain some causes of hearing loss in hereditary neuropathies and provide an anatomic basis for understanding normal neuronal function in the central auditory system.

Animals↗
PubMed2006

Cranial thickness in superior canal dehiscence syndrome: implications for canal resurfacing surgery.

OBJECTIVE: To use morphometric analyses of cranial thickness to investigate 2 cases of unanticipated calvarial bone resorption in superior canal dehiscence (SCD) resurfacing surgery. DESIGN: Retrospective morphometric analysis of high-resolution computed tomography (CT) temporal bone scans in normal and control subjects with accompanying case reports. SETTING: Tertiary care referral center. PATIENTS: Two patients with SCD and failed resurfacing because of bone resorption. Temporal bone CT scans from 30 sex-matched controls. INTERVENTION: Resurfacing of SCD via a middle fossa approach using a split thickness calvarial graft from the craniotomy site. MAIN OUTCOME MEASURE: Mean cross-sectional area of the middle fossa craniotomy bone flap and mean cranial thickness at 30 and 45 degrees above the middle fossa floor. RESULTS: Two patients had delayed failure of SCD resurfacing surgery as manifested by return of symptoms. High-resolution CT scans in both, and intraoperative confirmation in one, confirmed resorption of the bone graft. Measurements of cross-sectional area of the middle fossa craniotomy on high-resolution CT scans demonstrated significantly reduced values in the two SCD patients as compared with normal controls (Mann-Whitney U test, p<0.05). Cranial thickness outside the squamous temporal bone was reduced but did not reach statistical significance. CONCLUSION: Morphometric measurements of the calvarium have demonstrated that the squamous temporal bone is thinner in patients with SCD as compared with controls. Thus, the process leading to defects in the tegmen extends beyond the petrous pyramid. This suggests that there may be extratemporal factors leading to the development of a dehiscence. These findings also have implications for the surgical treatment of this disorder. Resurfacing methods may have a higher failure rate as the bone graft has reduced mass and maybe prone to resorption. Canal plugging methods may provide a more definitive means of addressing the dehiscent labyrinth than resurfacing.

Adult↗
PubMed2005

A modified Golgi staining protocol for use in the human brain stem and cerebellum.

The Golgi silver-impregnation method established itself as an important technique for distinguishing morphology at the individual neuron level. This technique has been especially useful for studying human neuroanatomy because it works on postmortem tissue but it is also unreliable and capricious. In this report, we describe a simple technique that was applied to human autopsy and tissue-bank material yielding useful results for the study of neuronal morphology in the brain stem and cerebellum. Human adult brain stems had been immersion-fixed in formalin for a period of time ranging from weeks to months. Brain stem tissue was cross-sectioned into 3-5mm thick slabs, centered about the cochlear nucleus. Slabs were processed under continuous vacuum (22-26 in. of Hg), a procedure that promoted penetration of reagents into the tissue. Tissue was sectioned using a Vibratome and mounted for light microscopy. The results demonstrated improved staining of neurons in the brain stem. Staining of the large synaptic endings of auditory nerve fibers called end bulbs of Held in the cochlear nucleus was especially evident. These results suggest that an age-graded series could be conducted to describe the development of these large auditory endings in humans.

Auditory Pathways↗
PubMed2004

Temporal bone fractures: traditional classification and clinical relevance.

OBJECTIVES/HYPOTHESIS: The objectives were to evaluate the clinical relevance of traditional temporal bone radiographic descriptors and to investigate the efficacy of an alternative fracture classification scheme. STUDY DESIGN: Retrospective consecutive case series. METHODS: Charts and computed tomography scans representing 155 temporal bone fractures at a level I trauma center were reviewed. Fracture types were correlated with clinical presentation and outcomes. RESULTS: The traditional classification system (i.e., longitudinal, transverse, or mixed) correlated poorly with clinical findings such as facial nerve weakness and cerebrospinal fluid leakage. It also had limited utility in predicting conductive hearing loss and sensorineural hearing. An alternative schema distinguishing petrous from nonpetrous involvement demonstrated better correlation with these measures. Cerebrospinal fluid leak was 1.1 times more common in transverse than in longitudinal fractures but was 9.8 times more common in petrous than in nonpetrous fractures. Similarly, facial nerve injury more strongly correlated with fractures through the petrous temporal bone than did the other fracture types. Sensorineural hearing loss did not correlate with the transverse fracture classification but was significantly more prevalent in petrous fractures. Likewise, conductive hearing loss did not correlate with longitudinal fractures but was four times more common in the "middle ear" subcategory of nonpetrous fractures. CONCLUSION: Traditional temporal bone fracture descriptions correlate poorly with clinical findings. However, simply distinguishing petrous from nonpetrous involvement demonstrates significant correlation with the occurrence of serious sequelae of temporal bone fractures. Subcategories of mastoid and middle ear involvement further refine this classification schema to correlate with minor complications. This simple, radiographically based scheme better focuses clinical resources and attention toward more likely sequelae.

Adolescent↗
PubMed2003

Ultrastructural examination of the somatic innervation of ventrotubercular cells in the rat.

Ventrotubercular cells are multipolar cells in the ventral cochlear nucleus (VCN) that project a collateral axon to the ipsilateral dorsal cochlear nucleus (DCN). These cells are thought to be involved in sensitizing DCN output neurons to spectral shapes that represent the location of a sound source in space. The present report focused on the neuronal composition of this pathway. Intracellular labeling studies in cats and mice have described two types of ventrotubercular cells (Smith and Rhode [1989] J Comp Neurol. 282:595-626; Oertel et al. [1990] J Comp Neurol. 295:136-154). In cats, one difference between the two classes is that type I multipolar neurons have fewer than 35% of their somata apposed by terminals, whereas type II cells have greater than 70% apposition values. Intracellular recordings from single cells, however, are difficult and thus limit the yield of data. We investigated whether a two-component description of the ventrotubercular pathway was representative of a larger population. This issue was addressed by retrogradely labeling ventrotubercular neurons with an extracellular injection of biotinylated dextran amine into the DCN of rats. These injections labeled many VCN neurons, thus providing a more complete view of the pathway than previous studies. Thirty-eight labeled cells were selected for electron microscopic analysis with respect to their location, cell body size, and ultrastructural morphology. We observed labeled type I and type II neurons, but unlike ventrotubercular cells in cats, many of these neurons in rats (17 of 38 cells) had appositions between 35% and 70%. On the basis of this analysis, a third class of ventrotubercular cell, called the adendritic neuron, was revealed. Adendritic neurons have small somata with many filopodial appendages, no observable dendrites, and high percentage of terminal appositions (>80%). The results demonstrated that the ventrotubercular pathway in the rat is diverse.

Animals↗
PubMed2003

Gene discovery using a human vestibular schwannoma cDNA library constructed from a patient with neurofibromatosis type 2 (NF2).

BACKGROUND: Despite a strong association of schwannomin/merlin gene mutations with vestibular schwannoma formation, the regulatory mechanisms and biologic pathways involved are still largely unknown. The hypothesis of this study is that the genesis and growth characteristics of neurofibromatosis type 2 (NF2)-associated vestibular schwannomas are determined by genetic alterations that vary in gene transcript expression; this transcript expression includes oncogenic gene products that may be identified by construction and sequencing of a cDNA library from NF2-associated vestibular schwannoma. METHODS: Approximately 3 mL of fresh tumor was obtained during resection of a 4-cm vestibular schwannoma from a patient with NF2. Poly(A)(+) mRNA was isolated, synthesized into double-stranded cDNA, and unidirectionally inserted into Uni-Zap XR (Stratagene, La Jolla, CA) bacteriophage vectors. Bacteriophage vectors containing cDNA inserts were processed into phagemids according to Uni-Zap XR protocol, and inserted vectors were sequenced and analyzed using BLAST software (National Institutes of Health, Bethesda, MD) with GenBank, EMBL, DDBJ, and PBD databases. RESULTS: The cDNA library contained 2.4 million primary plaques. Inserts averaged 1.8 kilobases (kb) in length, with a range of 0.8 to 3.0 kb. BLAST multidatabase comparison of the sequence data obtained from 50 randomly selected clones yielded identification of 13 sequences representing known human genes and 17 sequences representing cloned sequences with unknown function. Three clones represented sequences not previously described in vestibular schwannomas but strongly implicated in oncogenesis within other tissues. CONCLUSIONS: These data have implications for understanding the molecular mechanisms of vestibular schwannoma tumor biology. Identified genes may provide future diagnostic/prognostic markers and therapeutic targets.

Adult↗
PubMed2003

Choice of ear for cochlear implantation: the effect of history and residual hearing on predicted postoperative performance.

OBJECTIVE: This study used mathematical formulas predicting cochlear implant outcomes to investigate the effects of implantation in the poorer ear on postoperative speech recognition. DESIGN: Retrospective cohort study with mathematical and statistical analyses. This study used the University of Iowa formula for predicting outcomes derived from implantation of the better ear on the basis of duration of deafness and preoperative speech understanding, applying this predictive model to a cohort of patients undergoing implantation in the poorer ear at The Johns Hopkins Medical Center. SETTING: Tertiary referral center with active cochlear implant program. PATIENTS: Postlingually deafened adults (n = 58) with preoperative Central Institute for the Deaf sentence scores less than or equal to 40%. INTERVENTION: Cochlear implantation with all three Food and Drug Administration-approved devices. MAIN OUTCOME MEASURE: Postoperative monosyllabic word recognition scores and correlations between actual and predicted results. RESULTS: There was good statistical correlation between the predicted postoperative performance using the University of Iowa formula and the actual performance of our cohort of patients undergoing implantation in the poorer ear (r = 0.50, p < 0.0001). In addition, as a population, our cohort had a mean postoperative consonant-nucleus-consonant word score of 41.8%, which was statistically the same as that predicted by the University of Iowa formula (43.6%). CONCLUSIONS: The postoperative performance of cochlear implant patients is most closely correlated with duration of deafness. However, our results indicate that this measure may not be ear specific and is more reflective of the total auditory receptivity of the patient. These observations help to form guidelines for choice of ear for implantation.

Adolescent↗