scholarly journals Initial Method for Characterization of Tympanic Membrane Drug Permeability in Human Temporal Bones In Situ

2021 ◽  
Vol 12 ◽  
Author(s):  
Samuel Early ◽  
Rong Yang ◽  
Xiyu Li ◽  
Zipei Zhang ◽  
Jens C. van der Valk ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Therapy ◽  
Tympanic Membrane ◽  
Middle Ear ◽  
Antibiotic Administration ◽  
Tissue Processing ◽  
Tissue Manipulation ◽  
Drug Flux ◽  
Temporal Bones

Background and Introduction: Acute otitis media is the most common reason for a visit to the pediatrician, often requiring systemic administration of oral antibiotics. Local drug therapy applied to the middle ear could avoid side effects associated with systemic antibiotic administration, however in the majority of patients this would require drugs to diffuse across an intact tympanic membrane. Experimental methods for testing trans-tympanic drug flux in human tissues in situ would be highly valuable to guide drug therapy development for local drug delivery to the middle ear.Materials and Methods: A total of 30 cadaveric human temporal bones were characterized by trans-tympanic impedance testing to determine how steps in tissue processing and storage might impact intactness of the tympanic membrane and thus suitability for use in studies of trans-tympanic drug flux. Ciprofloxacin drug solutions of varying concentrations were then applied to the lateral surface of the tympanic membrane in eight samples, and middle ear aspirate was collected over the following 48 h to evaluate trans-tympanic flux to the middle ear.Results: Tissue processing steps that involved extensive tissue manipulation were consistently associated with evidence of microperforations in the tympanic membrane tissue. Maintaining the tympanic membrane in situ within the temporal bone, while using an otologic drill to obtain transmastoid access to the middle ear, was demonstrated as a reliable, non-damaging technique for accessing both lateral and medial surfaces for trans-tympanic flux testing. Results in these bones demonstrated trans-tympanic flux of ciprofloxacin when administered at sufficiently high concentration.Discussion and Conclusion: The study describes key techniques and best practices, as well as pitfalls to avoid, in the development of a model for studying trans-tympanic drug flux in human temporal bones in situ. This model can be a valuable research tool in advancing progress toward eventual clinical studies for trans-tympanic drug delivery to the middle ear.

Middle ear endoscopy and trans-tympanic drug delivery using an interventional sialendoscope: a feasibility study in human cadaveric temporal bones

2010 ◽  
Vol 120 (S4) ◽  
pp. S216-S216 ◽  
Author(s):  
Geoffrey Peters ◽  
James Lin ◽  
Moises A. Arriaga ◽  
Dan W. Nuss ◽  
Barry Schaitkin ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Feasibility Study ◽  
Middle Ear ◽  
Temporal Bones

Computer simulation of human tympanic membrane

1992 ◽  
Vol 106 (10) ◽  
pp. 878-881 ◽  
Author(s):  
Avinash Bhide
Keyword(s):  
Mechanical Properties ◽  
Computer Simulation ◽  
Surface Structure ◽  
Tympanic Membrane ◽  
Middle Ear ◽  
Structural Data ◽  
Human Tympanic Membrane

AbstractBecause of the difficulties in studying the mechanical properties of the human tympanic membrane in situ, structural data from the cadaveric tympanic membrane samples is used for simulation of the surface structure of the tympanic membrane with the help of a computer. The hitherto poorly understood contour of the tympanic membrane is available for the development of a tympanic membrane and middle ear model.

Stapedectomy Postmortem Findings

1979 ◽  
Vol 88 (1_suppl) ◽  
pp. 1-43 ◽  
Author(s):  
Harold F. Schuknecht ◽  
Diane Deleo Jones
Keyword(s):  
Bone Resorption ◽  
Surgical Technique ◽  
Middle Ear ◽  
Functional Results ◽  
Oval Window ◽  
Histological Studies ◽  
Small Areas ◽  
Incomplete Closure ◽  
Temporal Bones

Histological studies were made of 16 temporal bones of 13 subjects who had stapedectomy operations. Photographs of the prostheses in situ are a special feature of the studies. It was found that prostheses which overlap the margins of the oval window cause incomplete closure of the air-bone gaps. Fibrous adhesions were a common consequence of trauma to the mucous membrane of the middle ear. Gelfoam® implantation promotes the formation of thin oval window membranes which tend to bulge out of the oval window. Most incudes show small areas of cortical bone resorption. In at least half the cases the surgical technique of stapedectomy, as judged from these studies, was less than ideal. Surgeons who perform stapedectomy should be cognizant of the relevant surgical pathology and adopt methods which will optimize functional results and minimize complications.

scholarly journals Human β-Defensin-1 mRNA Is Transcribed in Tympanic Membrane and Adjacent Auditory Canal Epithelium

1999 ◽  
Vol 67 (9) ◽  
pp. 4843-4846 ◽  
Author(s):  
Roald Bøe ◽  
Juha Silvola ◽  
Jinghui Yang ◽  
Ugo Moens ◽  
Paul B. McCray ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Tympanic Membrane ◽  
Middle Ear ◽  
Broad Spectrum ◽  
External Auditory Canal ◽  
Hair Follicles ◽  
Epidermal Layer ◽  
Sebaceous Glands ◽  
Pars Flaccida

ABSTRACT The external auditory canal is less susceptible to infections than the sensitive middle-ear cavity. Since recent research has provided insight to the production of potent antimicrobial peptides from various surface epithelia, we wanted to investigate whether protection of the external auditory canal in part could be explained by the production of human β-defensin-1 (HBD-1). This particular peptide is known to be constitutively expressed in various surface epithelia, such as airway, skin, and urogenital tissues. By reverse transcriptase PCR we demonstrate HBD-1 mRNA in the pars tensa and pars flaccida of the tympanic membrane and in the meatal skin. In situ hybridization studies localized the HBD-1 mRNA to the epidermal layer of these tissues. The HBD-1 transcripts were also evident in the sebaceous glands and in hair follicles of the meatal skin. In contrast, HBD-1 mRNA was not detected in the tympanal epithelium of the eardrum. The widespread presence of mRNA encoding for this broad-spectrum antimicrobial peptide in the meatal skin and tympanic membrane suggests that HBD-1 participates in the innate antimicrobial defense of the external auditory canal and middle-ear cavity.

scholarly journals Direct Analysis of Pathogenic Structures Affixed to the Tympanic Membrane during Chronic Otitis Media

2018 ◽  
Vol 159 (1) ◽  
pp. 117-126 ◽  
Author(s):  
Guillermo L. Monroy ◽  
Wenzhou Hong ◽  
Pawjai Khampang ◽  
Ryan G. Porter ◽  
Michael A. Novak ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Tympanic Membrane ◽  
Otitis Media ◽  
Middle Ear ◽  
Mucosal Surface ◽  
Microbial Infection ◽  
Oct Imaging

Objective To characterize otitis media–associated structures affixed to the mucosal surface of the tympanic membrane (TM) in vivo and in surgically recovered in vitro samples. Study Design Prospective case series without comparison. Setting Outpatient surgical care center. Subjects and Methods Forty pediatric subjects scheduled for tympanostomy tube placement surgery were imaged intraoperatively under general anesthesia. Postmyringotomy, a portable optical coherence tomography (OCT) imaging system assessed for the presence of any biofilm affixed to the mucosal surface of the TM. Samples of suspected microbial infection–related structures were collected through the myringotomy incision. The sampled site was subsequently reimaged with OCT to confirm collection from the original image site on the TM. In vitro analysis based on confocal laser scanning microscope (CLSM) images of fluorescence in situ hybridization–tagged samples and polymerase chain reaction (PCR) provided microbiological characterization and verification of biofilm activity. Results OCT imaging was achieved for 38 of 40 subjects (95%). Images from 38 of 38 (100%) of subjects observed with OCT showed the presence of additional microbial infection–related structures. Thirty-four samples were collected from these 38 subjects. CLSM images provided evidence of clustered bacteria in 32 of 33 (97%) of samples. PCR detected the presence of active bacterial DNA signatures in 20 of 31 (65%) of samples. Conclusion PCR and CLSM analysis of fluorescence in situ hybridization–stained samples validates the presence of active bacteria that have formed into a middle ear biofilm that extends across the mucosal layer of the TM. OCT can rapidly and noninvasively identify middle ear biofilms in subjects with severe and persistent cases of otitis media.

Middle-ear endoscopy and trans-tympanic drug delivery using an interventional sialendoscope: feasibility study in human cadaveric temporal bones

2010 ◽  
Vol 124 (12) ◽  
pp. 1263-1267 ◽  
Author(s):  
G Peters ◽  
J Lin ◽  
M A Arriaga ◽  
D W Nuss ◽  
B Schaitkin ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Eustachian Tube ◽  
Middle Ear ◽  
Guide Wire ◽  
Round Window ◽  
Human Cadavers ◽  
Incudostapedial Joint ◽  
Round Window Niche ◽  
Temporal Bones ◽  
Inferior Quadrant

AbstractObjective:This study aimed to assess the feasibility of using a 1.3 mm, semi-rigid, interventional salivary endoscope for middle-ear endoscopy, and as a trans-tympanic route for delivery of medication, in human cadaveric temporal bones.Study design:Human cadaveric study.Methods:Five temporal bones harvested from human cadavers were examined. A 1.3 mm, interventional sialendoscope was used to make endoscopy-assisted myringotomy incisions in the postero-inferior quadrant (n = 5) and the antero-inferior quadrant (n = 3).Results:Middle-ear examination was successful in all specimens (n = 5). Access to the round window niche and adequate visualisation of the round window were achieved in all five temporal bones (100 per cent). A guide wire could be navigated to the round window niche without difficulty. Other structures identified in all specimens included the incudostapedial joint, stapedius tendon, pyramidal eminence and facial nerve via an extended myringotomy incision. The anterior middle-ear space was also successfully examined through an endoscope-guided anterior myringotomy. The opening to the eustachian tube was visualised and cannulated with a guide wire in all preparations in which this was attempted (n = 3).Conclusions:The 1.3 mm, interventional sialendoscope allowed adequate visualisation of the eustachian tube, middle-ear space and round window niche, with interventional capabilities, in a cadaveric model. Our result validates the feasibility of its use for trans-tympanic drug delivery.

How does Prosthesis Head Size Affect Vibration Transmission in Ossiculoplasty?

2007 ◽  
Vol 137 (1) ◽  
pp. 70-73 ◽  
Author(s):  
Manohar Bance ◽  
Alfredo Campos ◽  
Lillian Wong ◽  
David P. Morris ◽  
Rene van Wijhe
Keyword(s):  
Tympanic Membrane ◽  
Temporal Bone ◽  
Middle Ear ◽  
Laser Doppler Vibrometer ◽  
Head Size ◽  
Systematic Effect ◽  
Acoustic Frequency ◽  
Vibration Transmission ◽  
Stapes Footplate ◽  
Temporal Bones

OBJECTIVES: The transmission of vibrations from the tympanic membrane to the stapes footplate by an ossicular reconstruction prosthesis is affected by the size of the prosthesis head. We sought to determine if augmenting or reducing the head size of prosthesis had a systematic effect on transmission of vibrations to the stapes. STUDY DESIGN: We conducted a fresh cadaveric temporal bone middle ear study. METHODS: The incus was replaced with a prosthesis using a tympanic membrane to stapes head (TASH)-type hydroxyapatite prosthesis in nine fresh cadaveric temporal bones. Three prosthesis head sizes were created: unaltered, reduced, and augmented. Stapes vibrations were measured with a laser Doppler vibrometer in response to acoustic frequency chirps at 90 dB SPL. RESULTS: All three head size prostheses resulted in smaller stapes vibrations than the intact ear. There was no difference in the vibration transmission between the three different head sizes. All prostheses showed a vibration loss of 10 to 15 dB compared to the intact ear. CONCLUSIONS AND SIGNIFICANCE: Within the range of sizes tested, prosthesis head size had little impact on vibration transmission to the stapes footplate.

scholarly journals The impact of tympanic membrane perforations on middle ear transfer function

2021 ◽  
Author(s):  
Nicholas Bevis ◽  
Benjamin Sackmann ◽  
Thomas Effertz ◽  
Michael Lauxmann ◽  
Dirk Beutner
Keyword(s):  
Tympanic Membrane ◽  
Middle Ear ◽  
Transfer Functions ◽  
Single Point ◽  
Oscillation Amplitude ◽  
Fe Model ◽  
Lower Quadrant ◽  
Transmission Properties ◽  
Temporal Bones ◽  
The Impact

Abstract Purpose Injury or inflammation of the middle ear often results in the persistent tympanic membrane (TM) perforations, leading to conductive hearing loss (HL). However, in some cases the magnitude of HL exceeds that attributable by the TM perforation alone. The aim of the study is to better understand the effects of location and size of TM perforations on the sound transmission properties of the middle ear. Methods The middle ear transfer functions (METF) of six human temporal bones (TB) were compared before and after perforating the TM at different locations (anterior or posterior lower quadrant) and to different degrees (1 mm, ¼ of the TM, ½ of the TM, and full ablation). The sound-induced velocity of the stapes footplate was measured using single-point laser-Doppler-vibrometry (LDV). The METF were correlated with a Finite Element (FE) model of the middle ear, in which similar alterations were simulated. Results The measured and calculated METF showed frequency and perforation size dependent losses at all perforation locations. Starting at low frequencies, the loss expanded to higher frequencies with increased perforation size. In direct comparison, posterior TM perforations affected the transmission properties to a larger degree than anterior perforations. The asymmetry of the TM causes the malleus-incus complex to rotate and results in larger deflections in the posterior TM quadrants than in the anterior TM quadrants. Simulations in the FE model with a sealed cavity show that small perforations lead to a decrease in TM rigidity and thus to an increase in oscillation amplitude of the TM mainly above 1 kHz. Conclusion Size and location of TM perforations have a characteristic influence on the METF. The correlation of the experimental LDV measurements with an FE model contributes to a better understanding of the pathologic mechanisms of middle-ear diseases. If small perforations with significant HL are observed in daily clinical practice, additional middle ear pathologies should be considered. Further investigations on the loss of TM pretension due to perforations may be informative.

A study on the effect of ligament and tendon detachment on human middle ear sound transfer using mathematic model

2019 ◽  
Vol 233 (8) ◽  
pp. 784-792 ◽  
Author(s):  
Pengpeng Xie ◽  
Yong Peng ◽  
Junjiao Hu ◽  
Shengen Yi
Keyword(s):  
Transfer Function ◽  
Tympanic Membrane ◽  
Middle Ear ◽  
Acoustic Stimulus ◽  
Mathematic Model ◽  
Low Frequencies ◽  
Computed Tomography Scanning ◽  
Stapes Footplate ◽  
Temporal Bones ◽  
Human Middle Ear

The objective of this study is to investigate the effects of ligament and tendon detachment on human middle ear sound transfer. For this purpose, a geometric human middle ear model was reconstructed based on the computed tomography scanning data of the temporal bones from healthy adult volunteers. For the ear model, pars tensa was assumed to be fit for a 5-parameter Maxwell model and inverse method was used to obtain the necessary coefficients. Furthermore, frequency response method was implemented to investigate the vibration behaviors of tympanic membrane umbo and stapes footplate under an acoustic stimulus of 90 dB within 0.2–8 kHz. Meanwhile, nine patterns of fractured ligaments and tendons, whose effects on the middle ear sound transfer function were simulated by setting free the nodes of the ligaments and tendons of interest. The results indicate that the displacement of tympanic membrane umbo and stapes footplate as well as the velocity transfer function lies within the bounds of the published experimental data. The detachments of ligaments or tendons except for lateral mallear ligament may incur both gains as much as 15 dB and losses of –8 dB in the velocity of stapes footplate at low frequencies ( f≤ 1 kHz), while no significant changes were observed at high frequencies ( f > 1 kHz). However, detachment of the ligaments or tendons induces tiny changes in the displacement of stapes footplate at the frequencies of 0.2–8 kHz.

scholarly journals Finite Element Modelling of a Hearing Contact Lens Coupled to the Middle Ear

2021 ◽  
Vol 7 (2) ◽  
pp. 379-382
Author(s):  
Dmitrii Burovikhin ◽  
Michael Lauxmann ◽  
Ernst Dalhoff
Keyword(s):  
Finite Element ◽  
Tympanic Membrane ◽  
Middle Ear ◽  
Contact Lens ◽  
Laser Doppler Vibrometer ◽  
Coupled Model ◽  
Material Parameters ◽  
New Type ◽  
Main Components ◽  
Temporal Bones

Abstract Hearing contact lens (HCL) is a new type of hearing aid devices. One of its main components is a piezoelectric actuator (PEA). In order to evaluate and maximize the HCL’s performance, a model of the HCL coupled to the middle ear was developed using finite element (FE) approach. To validate the model, vibrational measurements on the HCL and temporal bones were performed using a Laser-Doppler-Vibrometer (LDV). The model was validated step by step starting with HCL only. Then a silicone cap was fitted onto the HCL to provide an interface between the HCL and the tympanic membrane. The HCL was placed on the tympanic membrane and additional measurements were performed to validate the coupled model. The model was used to evaluate the sensitivity of geometrical and material parameters with respect to performance measures of the HCL. Moreover, deeper insight was gained into the feedback behavior, which causes whistling sounds, and the contact between the HCL and tympanic membrane.

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