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Biomedical subjects

Fred H Linthicum

Publications and source records attributed to Fred H Linthicum.

At least 37 records · Page 2Linked to original sources

Morphometry of the human cochlear wall and implications for cochlear surgery.

OBJECTIVE: To study the lateral wall of the cochlea in human temporal bones (TBs), in order to evaluate the feasibility of performing micro-dissection of the spiral ligament and an endosteal electrode implantation. MATERIAL AND METHODS: We reviewed the database of the TB bank of The House Ear Institute in search of bones that did not distort the otic capsule or spiral ligament, and selected 36 horizontally sectioned TBs. All bones had been removed using the en bloc technique, fixed in formalin, decalcified in EDTA, embedded in celloidin and cut into 20-pm serial sections. We evaluated sections stained with hematoxylin-eosin under a microscope, and made several measurements of the lateral wall of the cochlea using optical appliances. A total of 20 measurements were made at 3 levels: midmodiolar sections; sections at the round window niche; and sections containing the anterior border of the stapes footplate. RESULTS: The selected sections provide useful data when applied during surgery. All the numerical data were analyzed statistically and, although individual variability occurred, most of the measurements seemed to be quite homogeneous. CONCLUSIONS: A greater understanding of the microscopic anatomy and dimensions of the human TB will help to understand the surgical relationships at the lateral wall of the cochlea. Our study provides some numerical references for the dimensions of the cochlea that may help in cochlear surgery. These dimensions would be of particular interest in cochlear implantation, especially in the design of endosteal electrodes.

Adult↗

Hurler disease.

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Child↗

Expression of neuregulin and activation of erbB receptors in vestibular schwannomas: possible autocrine loop stimulation.

HYPOTHESIS: We sought to determine whether vestibular schwannomas are capable of producing and responding to the glial growth factor neuregulin. BACKGROUND: Neuregulin is a neuronally derived trophic factor that interacts with erbB2 and erbB3 receptors on Schwann cells and is required for normal Schwann cell proliferation, survival, and development. Vestibular schwannomas grow several millimeters or even centimeters away from adjacent axons, suggesting that vestibular schwannomas do not depend critically on axons for their proliferation or survival. This raises the possibility that vestibular schwannomas themselves produce and respond to trophic factors in an autocrine fashion. METHODS: Pathologic specimens from eight patients undergoing microsurgical removal of vestibular schwannomas and one patient undergoing vestibular nerve section were immunostained with anti-neuregulin, anti-erbB2, anti-erbB3, and anti-phosphorylated-erbB2 antibodies. Three patients had received previous gamma knife radiation therapy and two patients had neurofibromatosis Type 2. RESULTS: The Scarpa ganglion neurons express neuregulin, and normal vestibular Schwann cells express erbB2 and erbB3. Vestibular schwannomas from all eight patients demonstrated neuregulin, erbB2, and erbB3 immunoreactivity. In addition, all vestibular schwannomas demonstrated immunoreactivity to anti-phosphorylated-erbB2 antibody that only recognizes erbB2 when it is phosphorylated, or activated. CONCLUSION: These results demonstrate that vestibular schwannomas express neuregulin and its receptors, erbB2 and erbB3. Because erbB2 exists in an activated state, as evidenced by phosphorylated-erbB2 immunoreactivity, it likely responds to the locally produced neuregulin. This suggests the possibility that vestibular schwannomas produce and respond to neuregulin in an autocrine fashion.

Adolescent↗

Spiral ligament and stria vascularis changes in cochlear otosclerosis: effect on hearing level.

OBJECTIVE: To investigate the effect of changes within the spiral ligament and stria vascularis on hearing in cochlear otosclerosis, we examined spiral ligament hyalinization, stria vascularis atrophy, and sensory hearing loss in cochlear otosclerosis and described changes in ion transport molecule expression. STUDY DESIGN: Retrospective. SETTING: Tertiary referral center. PATIENTS: Thirty-two cochleae from 24 temporal bone donors with histologic evidence of cochlear otosclerosis, including spiral ligament hyalinization. INTERVENTION: Audiography. MAIN OUTCOME MEASURES: Measurements of spiral ligament width, stria vascularis, and bone-conduction thresholds were compared by the amount of hyalinization. Expression of the ion transport molecules Na,K-ATPase, connexin 26, and carbonic anhydrase II were assessed by immunohistochemical techniques. RESULTS: Hyalinization most often involved the posterior basal turn (88%) and the posterior middle turn (27%). Spiral ligament hyalinization correlated significantly with stria vascularis atrophy in the posterior middle turn of the cochlea (rho = -0.63, p < 0.01). There was a trend toward a significant association in the posterior basal turn (rho = -0.31, p < 0.08). Bone-conduction thresholds at 2,000 and 4,000 Hz were significantly associated with the amount of stria vascularis atrophy (rho = -0.44, -0.40, p < 0.05). In addition, we observed decreased immunostaining for both carbonic anhydrase II with Type I fibrocytes and Na,K-ATPase with stria vascularis and Type II and Type IV fibrocytes of the spiral ligament in cochlear otosclerosis sections compared with normal cochlea. Na,K-ATPase staining within the stria vascularis was further decreased in the presence of spiral ligament hyalinization. No significant differences were seen with connexin 26 immunostaining. However, immunostaining results were somewhat inconsistent. CONCLUSION: These data suggest that spiral ligament structure and function are essential for stria vascularis survival. In addition, dampened expression of ion transport molecules within the spiral ligament and stria vascularis may disrupt potassium ion recycling, resulting in loss of endocochlear potential and sensory hearing loss.

Aged↗

Basilar membrane displacement related to endolymphatic sac volume.

OBJECTIVE: To demonstrate that the amount of basilar membrane displacement toward the scala tympani and its attachment to the bony wall of the scala tympani (i.e., interscalar septum) in hydropic temporal bones is related to the intraosseous endolymphatic sac volume. STUDY DESIGN: A retrospective analysis of temporal bones from individuals with the histopathologic diagnosis of "endolymphatic hydrops." METHODS: Fifty-two temporal bones, from 38 patients, with the histopathologic findings of "endolymphatic hydrops" were analyzed microscopically. Data were obtained regarding the displacement of the basilar membrane, endolymphatic sac volume, hair cell loss, strial atrophy, ganglion cell loss, and last measured auditory thresholds. The relationships between these variables were examined statistically. RESULTS: Nineteen of the 52 temporal bones (36.5%) with endolymphatic hydrops showed displacement of the basilar membrane toward the scala tympani in the apical and middle segments of the cochlea. A reduced volume of the endolymphatic sac was significantly related to increased severity of basilar membrane deformation (Rho = -.646; P < or = .001). Multiple regression analysis showed that severity of basilar membrane deformation was the single best predictor of low frequency thresholds while loss of hair cells was the best predictor of pure-tone average threshold. CONCLUSIONS: The displacement of the basilar membrane in the apical and middle segments that may occur with endolymphatic hydrops, to the extent that it impinges on the interscalar septum, is related to a reduction in the intraosseous endolymphatic sac volume.

Aged↗

Activation of a Src-dependent Raf-MEK1/2-ERK signaling pathway is required for IL-1alpha-induced upregulation of beta-defensin 2 in human middle ear epithelial cells.

beta-defensin 2 is produced by a variety of epithelial cell types in the body and exhibits potent antimicrobial activity against a variety of pathogens, including the bacteria that are most commonly associated with otitis media (OM). The human beta-defensin 2 (hBD-2) gene is an NF-kappa B regulated gene and a variety of proinflammatory stimuli can induce its expression. Although the presence of molecules of innate immunity such as lysozyme and lactoferrin has been demonstrated in the middle ear, to date there have been no reports on the expression of beta-defensin 2. In the present study, we demonstrate that beta-defensin 2 is expressed in the middle ear mucosa of humans and rats. We also show that it is expressed in a human middle ear epithelial cell line and that its expression is induced by proinflammatory stimuli such as interleukin 1 alpha (IL-1 alpha), tumor necrosis factor alpha (TNF-alpha), and lipopolysaccharide (LPS). Moreover, we demonstrate that the transcriptional activation of hBD-2 gene by IL-1 alpha is mediated through an Src-dependent Raf-MEK1/2-ERK signaling pathway.

Animals↗

Histopathologic changes in the vestibule after cochlear implantation.

OBJECTIVE: The study goal was to determine the histopathologic changes of the vestibular end organs after cochlear implantation and to relate them to clinical performance. STUDY DESIGN: To differentiate the effect of implantation from the disease process that originally destroyed the hearing, 11 pairs of temporal bones from unilateral implantees were studied with light microscopy to compare the vestibular damage in the implanted ears with that in the nonimplanted ears. RESULTS: Significant histopathologic damage of the vestibular end organs was noted in 6 patients (54.5%). The major histopathologic findings were fibrosis in the vestibule, saccule membrane distortion, new bone formation, and reactive neuromas. The scala vestibuli involvement, as a result of damage to the osseous spiral lamina or basilar membrane in cochlear basal turn, was highly correlated with vestibular damage (75%). CONCLUSIONS: Although the clinical incidence of balance disturbance after cochlear implantation is low, damage of the vestibular end organs may occur and be asymptomatic. Keeping the electrode array in the scala tympani will minimize vestibular damage.

Adult↗

The fate of mastoid obliteration tissue: a histopathological study.

OBJECTIVES: To demonstrate the histopathological fate of tissues used for mastoid obliteration over a period of 30 years. STUDY DESIGN: Retrospective histopathological analysis of archival temporal bone microscopic sections. METHODS: From the database of the laboratory, the 17 temporal bones from subjects who had undergone mastoid obliteration procedures were identified. The microscopic appearance of the obliteration tissue was described, and microphotographs made of significant findings. RESULTS: Fat and bone chips, or paté, retained their bulk in the obliterated space, whereas subcutaneous tissue and muscle lost bulk but seemed to promote healing. Some substances, such as bone wax, used for hemostasis and buried under obliteration tissue, were found to produce a subclinical inflammatory reaction, but other materials, such as Surgicel and Gelfoam, did not. CONCLUSIONS: Fat and bone chips, or paté, used as mastoid obliteration tissue, retained their bulk and identity, whereas subcutaneous tissue and muscle did not.

Adipose Tissue↗