ABSTRACT
BACKGROUND: Hearing-impaired persons with asymmetric hearing loss and a unilateral indication for a cochlear implant (CI) generally benefit from a bimodal hearing solution. The influence of bimodal fitting on speech comprehension (SC) over time has not yet been sufficiently investigated. The present study examines the influence of bimodal fitting on SC in bimodally fitted CI users with postlingual deafness at least 36 months after implantation and analyzes possible influencing factors. METHODS: Included in this retrospective longitudinal study were 54 bimodally fitted speech-competent CI users with at least 36 months of CI experience. Audiometric data of these CI users at predefined timepoints were compared. RESULTS: The change in the results of the Freiburg monosyllabic test (FT) over 36 months was significant (pâ¯< 5%) for the deafness group at <10 years for both the 65â¯dB sound pressure level (SPL) and at 80â¯dB SPL and also significant for the deafness group ≥10 years for 65â¯dB SPL. In the Oldenburg sentence test (OlSa) there was a highly significant change (pâ¯< 0.1%) for S0, S0N0, and S0NCI configurations and a very significant change (pâ¯< 1%) for S0NHA (HA: hearing aid). Age at implantation as a possible influencing factor could not be confirmed in the FT. In contrast, the duration of deafness was a negative influencing factor for SC with CI in the FT, whereas a longer duration of deafness was associated with worse results in the FT. The degree of hearing loss in the ear fitted with an HA did not influence SC. The median bimodal benefit (here: difference in SC with bimodal fitting compared to unilateral HA fitting for FT at 65â¯dB SPL) was 10% over the total study period. For a median of 79% of the test subjects, the bimodal benefit was found over the entire period of 36 months. CONCLUSION: Over time, SC improves significantly with a CI for the bimodal test subjects. The investigated influencing factors (age, duration of deafness, and degree of hearing loss in the contralateral ear) support the indication for bimodal provision in accordance with the guideline in Germany for cochlear implantation-regardless of age, duration of deafness, and hearing ability of the contralateral ear.
ABSTRACT
BACKGROUND: From spring 2020, SARS-CoV2 began to spread worldwide, with what is now known as the first wave of the pandemic, starting in March 2020. This resulted in restructuring and shift of resources at many hospitals. The aim of our work was to detect the effects of the pandemic on the german Oto-Rhino-Laryngology (ORL) university hospitals in terms of research, student teaching and further specialist training. MATERIAL AND METHODS: The chairmen of the 39 ORL university hospitals in Germany were asked about the effects of the pandemic on research, student teaching and ORL specialist training (residency) in the period from March to April 2020 using a structured online survey. RESULTS: All 39 chairmen took part in the survey. Of these, 74.4% (29/39) stated that their research activities had deteriorated as a result of the pandemic. In 61.5% (24/39) pandemic-related research issues were addressed. All hospitals reported a restriction for in-house teaching and 97.5% (38/39) introduced new digital teaching methods. During the observation period, 74.4% of the chairmen did not see ORL specialist training (residency)at risk. CONCLUSION: Our results provide an insight into the heterogeneous effects of the pandemic. The fast processing of pandemic-related research topics and the introduction of innovative digital concepts for student teaching impressively demonstrates the great innovative potential and the ability of the ORL university hospitals to react quickly in order to maintain their tasks in research, student teaching and ORL specialist training in the best possible way even during the pandemic.
Subject(s)
COVID-19 , Otolaryngology , Germany/epidemiology , Hospitals, University , Humans , Pandemics , SARS-CoV-2 , Students , TeachingABSTRACT
INTRODUCTION: Since December 2019, the SARS-CoV-2 virus has been rapidly spreading worldwide. In Germany, an exponential increase in the number of infections was registered at the beginning of March 2020 and led to a call of the Ministry of Health to create more capacity for intensive medical treatment in hospitals. The aim of the present study was to determine the effects of the SARS-CoV-2 pandemic on Oto-Rhino-Laryngology (ORL) university hospitals regarding patient care. MATERIALS AND METHODS: An online survey was sent out to all chairmen of the 39 ORL university hospitals in Germany. The answers to the questions referred to the defined period from March 15th to April 15th 2020 and were carried out using the online survey tool "SurveyMonkey". 87 questions focused on general information, health care, and structural effects in the respective institution. RESULTS: All chairmen of the 39 university hospitals in Germany participated in the survey. The collected data prove the considerable impact on organizational, structural and medical aspects of patient care. For example, the surveyed clinics reported a decrease in outpatient cases by 73.8â% to 26.2â±â14.2â% and in surgical treatments by 65.9â% to 34.1â±â13.9â%. In contrast, emergency treatment remained unchanged or even increased in 80â% of the facilities and surgical treatment of emergency patients remained unchanged or even increased in more than 90â%. Emergency outpatient and surgical treatment of patients was provided throughout the pandemic in all facilities. In total, about 35â000 outpatients and about 12â000 surgical cases were postponed. As a result of the acute structural changes, the potential danger of falling below current treatment standards was seen in individual areas of patient care. DISCUSSION: The assessment of the impact of the SARS-CoV-2 pandemic is heterogeneous. The majority of the chairmen are critically aware of the risk of falling below current medical treatment standards or guidelines. In the phase of an exponential increase in the number of infections, significant changes in treatment processes had to be accepted for understandable reasons. However, with the currently significantly reduced number of infections, falling below treatment standards and guidelines should not be allowed to remain constant and tolerated. SUMMARY: This study shows a differentiated picture with regard to the effects of the SARS-CoV-2 pandemic on outpatient, inpatient and operative patient care at the ORL university hospitals in Germany and illustrates the importance of these institutions for ensuring patient care during this critical phase.
Subject(s)
Coronavirus Infections , Otolaryngology , Pandemics , Pneumonia, Viral , Severe Acute Respiratory Syndrome/epidemiology , Severe Acute Respiratory Syndrome/therapy , Betacoronavirus , COVID-19 , Germany , Hospitals, University , Humans , SARS-CoV-2ABSTRACT
BACKGROUND: Since emergence of the new coronavirus in China in December 2019, many countries have been struggling to control skyrocketing numbers of infections, including among healthcare personnel. It has now been clearly demonstrated that SARS-CoV2 resides in the upper airways and transmits easily via aerosols and droplets, which significantly increases the risk of infection when performing upper airway procedures. Ventilated COVID-19 patients in a critical condition in the intensive care unit may require tracheotomy for long-term ventilation and to improve weaning. However, the risk of secondary infection of medical personnel performing subsequent tracheostomy care remains unclear. OBJECTIVE: This study aimed to evaluate the risk of droplet dispersion during tracheostomy tube change and overview tracheostomy tube change in COVID-19 patients. MATERIALS AND METHODS: The current literature was reviewed, quantitative and qualitative analyses of droplet formation during tracheostomy tube change in nâ¯= 8 patients were performed, and an overview of and checklist for tracheostomy tube change were compiled. RESULTS: This study demonstrates that tracheostomy tube change, in particular insertion of the new tube, may cause significant droplet formation. The aerosolization of particles smaller than 5⯵m was not analyzed. CONCLUSION: Our data, together with the current literature, clearly emphasize that tracheostomy care is associated with a high infection risk and should only be performed by a small group of well-trained, maximally protected healthcare personnel.
Subject(s)
Coronavirus Infections/therapy , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Intubation, Intratracheal/adverse effects , Pneumonia, Viral/therapy , Tracheostomy , Aerosols , Betacoronavirus , COVID-19 , Humans , Pandemics , SARS-CoV-2ABSTRACT
BACKGROUND: Cochlea sparing can reduce late ototoxicity in head and neck cancer patients treated with cisplatin-based radiochemotherapy. In this situation, a mean cochlear dose (MCD) constraint of 10â¯Gy has been suggested by others based on the dose-effect relationship of clinical data. We aimed to investigate whether this is feasible for primary and postoperative radiochemotherapy in locoregionally advanced tumors without compromising target coverage. PATIENTS AND METHODS: Ten patients treated with definitive and ten patients treated with adjuvant intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy were investigated. The cochleae and a planning risk volume (PRV) with a 3â¯mm margin were newly delineated, whereas target volumes and other organs at risk were not changed. The initial plan was recalculated with a constraint of 10â¯Gy (MCD) on the low-risk side. The quality of the resulting plan was evaluated using the difference in the equivalent uniform dose (EUD). RESULTS: A unilateral MCD of below 10â¯Gy could be achieved in every patient. The mean MCD was 6.8â¯Gy in the adjuvant cohort and 7.6â¯Gy in the definitive cohort, while the non-spared side showed a mean MCD of 18.7 and 30.3â¯Gy, respectively. The mean PRV doses were 7.8 and 8.4â¯Gy for the spared side and 18.5 and 29.8â¯Gy for the non-spared side, respectively. The mean EUD values of the initial and recalculated plans were identical. Target volume was not compromised. CONCLUSION: Unilateral cochlea sparing with an MCD of less than 10â¯Gy is feasible without compromising the target volume or dose coverage in locoregionally advanced head and neck cancer patients treated with IMRT. A prospective evaluation of the clinical benefit of this approach as well as further investigation of the dose-response relationship for future treatment modification appears promising.
Subject(s)
Chemoradiotherapy/adverse effects , Cisplatin/adverse effects , Cochlea/drug effects , Cochlea/radiation effects , Organ Sparing Treatments , Otorhinolaryngologic Neoplasms/therapy , Radiotherapy, Intensity-Modulated/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Chemoradiotherapy, Adjuvant/adverse effects , Cisplatin/therapeutic use , Combined Modality Therapy , Feasibility Studies , Female , Humans , Male , Neoplasm Grading , Neoplasm Staging , Otorhinolaryngologic Neoplasms/pathology , Radiation Dosage , Radiotherapy Planning, Computer-AssistedABSTRACT
BACKGROUND: High-intensity noise exposure from impulse and blast noise events often leads to acute hearing loss and may cause irreversible permanent hearing loss as a long-term consequence. Here, a treatment regime was developed to limit permanent damage based on a preclinical animal model of acute noise trauma. AIM: To develop clinical trials for the treatment of acute noise traumas using approved drugs. The otoprotective potential of glucocorticoids applied locally to the inner ear was examined. MATERIALS AND METHODS: A series of experiments with different impulse noise exposures were performed. Permanent hearing loss and hair cell density were assessed 14 days after exposure. Hearing and hair cell preservation were investigated as a function of the glucocorticoid dose. RESULTS: After impulse noise exposure, local application to the round window of the cochlea of high-dose prednisolone (25 mg/ml) or methylprednisolone (12.5 mg/ml) resulted in a statistically significant reduction in hearing loss compared with the control group. CONCLUSION: The local application of high doses of the drugs to the round window of the cochlea appears to be an effective treatment for acute noise trauma.
Subject(s)
Auditory Perception/drug effects , Ear, Inner/drug effects , Ear, Inner/physiopathology , Glucocorticoids/administration & dosage , Hearing Loss, Noise-Induced/drug therapy , Hearing Loss, Noise-Induced/physiopathology , Administration, Topical , Animals , Chronic Disease , Guinea Pigs , Hearing Loss, Noise-Induced/diagnostic imaging , Treatment OutcomeABSTRACT
BACKGROUND: High-intensity noise exposure from impulse and blast noise events often leads to acute hearing loss and may cause irreversible permanent hearing loss as a long-term consequence. Here, a treatment regime was developed to limit permanent damage based on a preclinical animal model of acute noise trauma. AIM: To develop clinical trials for the treatment of acute noise traumas using approved drugs. The otoprotective potential of glucocorticoids applied locally to the inner ear was examined. MATERIALS AND METHODS: A series of experiments with different impulse noise exposures was performed. Permanent hearing loss and hair cell density were assessed 14 days after exposure. Hearing and hair cell preservation were investigated as a function of glucocorticoid dose. RESULTS: After impulse noise exposure, local application of high-dose prednisolone (25 mg/ml) or methylprednisolone (12.5 mg/ml) to the round window of the cochlea resulted in a statistically significant reduction in hearing loss compared to the control group. CONCLUSION: Local application of high doses of the drugs to the round window of the cochlea appears to be an effective treatment for acute noise trauma.
Subject(s)
Glucocorticoids/administration & dosage , Hearing Loss, Noise-Induced/drug therapy , Hearing Loss, Noise-Induced/physiopathology , Round Window, Ear/drug effects , Administration, Topical , Animals , Dose-Response Relationship, Drug , Guinea Pigs , Hearing Loss, Noise-Induced/diagnosis , Treatment OutcomeABSTRACT
Volume homeostasis of the cochlear endolymph depends on radial and longitudinal endolymph movements (LEMs). LEMs measured in vivo have been exclusively recognized under physiologically challenging conditions, such as experimentally induced alterations of perilymph osmolarity or endolymph volume. The regulatory mechanisms that adjust LEMs to the physiological requirements of endolymph volume homeostasis remain unknown. Here, we describe the formation of an aquaporin (AQP)-based "water shunt" during the postnatal development of the mouse cochlea and its regulation by different triggers. The final complementary expression pattern of AQP5 (apical membrane) and AQP4 (basolateral membrane) in outer sulcus cells (OSCs) of the cochlear apex is acquired at the onset of hearing function (postnatal day (p)8-p12). In vitro, hyperosmolar perfusion of the perilymphatic fluid spaces or the administration of the muscarinic agonist pilocarpine in cochlear explants (p14) induced the translocation of AQP5 channel proteins into the apical membranes of OSCs. AQP5 membrane translocation was blocked by the muscarinic antagonist atropine. The muscarinic M3 acetylcholine (ACh) receptor (M3R) was identified in murine OSCs via mRNA expression, immunolabeling, and in vitro binding studies using an M3R-specific fluorescent ligand. Finally, the water shunt elements AQP4, AQP5, and M3R were also demonstrated in OSCs of the human cochlea. The regulation of the AQP4/AQP5 water shunt in OSCs of the cochlear apex provides a molecular basis for regulated endolymphatic volume homeostasis. Moreover, its dysregulation or disruption may have pathophysiologic implications for clinical conditions related to endolymphatic hydrops, such as Ménière's disease.
Subject(s)
Aquaporin 5/metabolism , Cell Membrane/metabolism , Cochlea/metabolism , Endolymph/metabolism , Animals , Aquaporin 4/genetics , Aquaporin 4/metabolism , Aquaporin 5/genetics , Cholinergic Agents/pharmacology , Cochlea/drug effects , Homeostasis , Humans , Mice , Receptor, Muscarinic M3/agonists , Receptor, Muscarinic M3/antagonists & inhibitors , Receptor, Muscarinic M3/metabolism , Water/metabolismABSTRACT
Human auditory nerve afferents consist of two separate systems; one is represented by the large type I cells innervating the inner hair cells and the other one by the small type II cells innervating the outer hair cells. Type I spiral ganglion neurons (SGNs) constitute 96% of the afferent nerve population and, in contrast to other mammals, their soma and pre- and post-somatic segments are unmyelinated. Type II nerve soma and fibers are unmyelinated. Histopathology and clinical experience imply that human SGNs can persist electrically excitable without dendrites, thus lacking connection to the organ of Corti. The biological background to this phenomenon remains elusive. We analyzed the pre- and post-somatic segments of the type I human SGNs using immunohistochemistry and transmission electron microscopy (TEM) in normal and pathological conditions. These segments were found surrounded by non-myelinated Schwann cells (NMSCs) showing strong intracellular expression of laminin-ß2/collagen IV. These cells also bordered the perikaryal entry zone and disclosed surface rugosities outlined by a folded basement membrane (BM) expressing laminin-ß2 and collagen IV. It is presumed that human large SGNs are demarcated by three cell categories: (a) myelinated Schwann cells, (b) NMSCs and (c) satellite glial cells (SGCs). Their BMs express laminin-ß2/collagen IV and reaches the BM of the sensory epithelium at the habenula perforata. We speculate that the NMSCs protect SGNs from further degeneration following dendrite loss. It may give further explanation why SGNs can persist as electrically excitable monopolar cells even after long-time deafness, a blessing for the deaf treated with cochlear implantation.
Subject(s)
Neurons/cytology , Spiral Ganglion/cytology , Adult , Basement Membrane/cytology , Basement Membrane/metabolism , Basement Membrane/pathology , Cochlear Implantation , Collagen/metabolism , Female , Humans , Imaging, Three-Dimensional , Immunohistochemistry , Laminin/metabolism , Male , Microscopy, Confocal , Microscopy, Electron, Scanning , Microscopy, Electron, Transmission , Middle Aged , Neurons/metabolism , Neurons/pathology , Satellite Cells, Perineuronal/cytology , Satellite Cells, Perineuronal/metabolism , Satellite Cells, Perineuronal/pathology , Schwann Cells/cytology , Schwann Cells/metabolism , Schwann Cells/pathology , Spiral Ganglion/metabolism , Spiral Ganglion/pathologyABSTRACT
BACKGROUND: Sound transduction in the cochlea critically depends on the circulation of potassium ions (K(+)) along so-called "K(+) recycling routes" between the endolymph and perilymph. These K(+) currents generate high ionic and osmotic gradients, which potentially impair the excitability of sensory hair cells and threaten cell survival in the entire cochlear duct. Molecular water channels-aquaporins (AQP)-are expressed in all cochlear supporting cells along the K(+) recycling routes; however, their significance for osmotic equilibration in cochlear duct cells is unknown. METHODS: The diffusive and osmotic water permeabilies of Reissner's membrane, the organ of Corti and the entire cochlear duct epithelium were determined. Expression of the potassium channel Kir4.1 and the water channel AQP4 in the cochlear duct was investigated by immunohistochemistry. RESULTS: The calculated water permeability values indicate the extent of AQP-facilitated water flux across the cochlear duct epithelium. Immunohistochemically, Kir4.1 and AQP4 were found to colocalize in distinct membrane domains of supporting cells along the K(+)-recycling routes. CONCLUSION: These observations suggest the presence of a rapid AQP-mediated water exchange between the endolymph, the cells of the cochlear duct and the perilymph. The subcellular colocalization of Kir4.1 and AQP4 in epithelial supporting cells indicates functional coupling of potassium and water flow in the cochlea. Finally, this offers an explanation for the hearing impairment observed in individuals with mutations in the AQP4 gene.
Subject(s)
Aquaporins/metabolism , Body Water/metabolism , Cochlea/physiology , Hearing/physiology , Mechanotransduction, Cellular/physiology , Potassium/metabolism , Water-Electrolyte Balance/physiology , Animals , Guinea Pigs , Ion Channel Gating/physiologyABSTRACT
Hereditary retinal degeneration (RD) relates to a heterogeneous group of blinding human diseases in which the light sensitive neurons of the retina, the photoreceptors, die. RD is currently untreatable and the underlying cellular mechanisms remain poorly understood. However, the activity of the enzyme poly-ADP-ribose polymerase-1 (PARP1) and excessive generation of poly-ADP-ribose (PAR) polymers in photoreceptor nuclei have been shown to be causally involved in RD. The activity of PARP1 is to a large extent governed by its functional antagonist, poly-ADP-glycohydrolase (PARG), which thus also may have a role in RD. To investigate this, we analyzed PARG expression in the retina of wild-type (wt) mice and in the rd1 mouse model for human RD, and detected increased PARG protein in a subset of degenerating rd1 photoreceptors. Knockout (KO) animals lacking the 110 kDa nuclear PARG isoform were furthermore analyzed, and their retinal morphology and function were indistinguishable from wild-type animals. Organotypic wt retinal explants can be experimentally treated to induce rd1-like photoreceptor death, but PARG110 KO retinal explants were unexpectedly highly resistant to such treatment. The resistance was associated with decreased PAR accumulation and low PARP activity, indicating that PARG110 may positively regulate PARP1, an event that therefore is absent in PARG110 KO tissue. Our study demonstrates a causal involvement of PARG110 in the process of photoreceptor degeneration. Contrasting its anticipated role as a functional antagonist, absence of PARG110 correlated with low PARP activity, suggesting that PARG110 and PARP1 act in a positive feedback loop, which is especially active under pathologic conditions. This in turn highlights both PARG110 and PARP1 as potential targets for neuroprotective treatments for RD.
Subject(s)
Cyclic AMP/metabolism , Glycoside Hydrolases/deficiency , Nerve Degeneration , Photoreceptor Cells, Vertebrate/enzymology , Retinal Degeneration/enzymology , Animals , Cell Death , Cyclic Nucleotide Phosphodiesterases, Type 6/antagonists & inhibitors , Cyclic Nucleotide Phosphodiesterases, Type 6/genetics , Disease Models, Animal , Enzyme Activation , Genetic Predisposition to Disease , Glycoside Hydrolases/genetics , Mice , Mice, Knockout , Mice, Mutant Strains , Mutation , Phenotype , Phosphodiesterase Inhibitors/pharmacology , Photoreceptor Cells, Vertebrate/drug effects , Photoreceptor Cells, Vertebrate/pathology , Poly (ADP-Ribose) Polymerase-1 , Poly Adenosine Diphosphate Ribose/metabolism , Poly(ADP-ribose) Polymerases/deficiency , Poly(ADP-ribose) Polymerases/genetics , Protein Isoforms , Retinal Degeneration/genetics , Retinal Degeneration/pathology , Time Factors , Tissue Culture TechniquesABSTRACT
The cochlear duct epithelium (CDE) constitutes a tight barrier that effectively separates the inner ear fluids, endolymph and perilymph, thereby maintaining distinct ionic and osmotic gradients that are essential for auditory function. However, in vivo experiments have demonstrated that the CDE allows for rapid water exchange between fluid compartments. The molecular mechanism governing water permeation across the CDE remains elusive. We computationally determined the diffusional (PD) and osmotic (Pf) water permeability coefficients for the mammalian CDE based on in silico simulations of cochlear water dynamics integrating previously derived in vivo experimental data on fluid flow with expression sites of molecular water channels (aquaporins, AQPs). The PD of the entire CDE (PD = 8.18 × 10(-5) cm s(-1)) and its individual partitions including Reissner's membrane (PD = 12.06 × 10(-5) cm s(-1)) and the organ of Corti (PD = 10.2 × 10(-5) cm s(-1)) were similar to other epithelia with AQP-facilitated water permeation. The Pf of the CDE (Pf = 6.15 × 10(-4) cm s(-1)) was also in the range of other epithelia while an exceptionally high Pf was determined for an epithelial subdomain of outer sulcus cells in the cochlear apex co-expressing AQP4 and AQP5 (OSCs; Pf = 156.90 × 10(-3) cm s(-1)). The Pf/PD ratios of the CDE (Pf/PD = 7.52) and OSCs (Pf/PD = 242.02) indicate an aqueous pore-facilitated water exchange and reveal a high-transfer region or "water shunt" in the cochlear apex. This "water shunt" explains experimentally determined phenomena of endolymphatic longitudinal flow towards the cochlear apex. The water permeability coefficients of the CDE emphasise the physiological and pathophysiological relevance of water dynamics in the cochlea in particular for endolymphatic hydrops and Ménière's disease.
Subject(s)
Aquaporin 4/metabolism , Aquaporin 5/metabolism , Capillary Permeability , Cochlear Duct/metabolism , Endolymph/metabolism , Perilymph/metabolism , Water/metabolism , Animals , Aquaporin 4/genetics , Aquaporin 5/genetics , Cell Membrane/metabolism , Epithelium/metabolism , Guinea Pigs , MaleABSTRACT
The water channel aquaporin-4 (AQP4) is expressed in the cochlea and is essential for normal hearing. Unlike other AQPs, multiple isoforms of AQP4 have been reported in diverse tissues, three of which, M1, M23, and Mz, function as water channels. In addition, these protein isoforms are found in higher order complexes. Morphologically these higher order complexes correspond to orthogonal arrays of particles (OAPs) that are found in cell membranes by freeze fracture analysis. Using RT-PCR, quantitative PCR and blue-native PAGE immunoblots we identified all functional AQP4 isoforms -M1, M23, and Mz- and the formation of higher-order complexes in the organ of Corti of the rat. Complementary freeze-fracture studies revealed OAPs distributed in the lateral and basal membrane domains of the cochlear duct supporting cells, specifically Hensen's cells and outer sulcus cells. The unique inter- and intracellular heterogeneity in size, density and shape of OAPs suggests exceptional physiological requirements for the maintenance of water homeostasis during auditory sensory transduction in the cochlea.
Subject(s)
Aquaporin 4/metabolism , Cochlea/metabolism , Animals , Aquaporin 4/genetics , Cochlea/cytology , Cochlear Duct/cytology , Cochlear Duct/metabolism , Electrophoresis, Gel, Two-Dimensional , Freeze Fracturing , Organ of Corti/cytology , Organ of Corti/metabolism , Protein Isoforms/genetics , Protein Isoforms/metabolism , RNA Isoforms/metabolism , RNA, Messenger/metabolism , Rats , Rats, Wistar , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
INTRODUCTION: Tff3 peptide exerts important functions in cytoprotection and restitution of the gastrointestinal (GI) tract epithelia. Moreover, its presence in the rodent inner ear and involvement in the hearing process was demonstrated recently. However, its role in the auditory system still remains elusive. Our previous results showed a deterioration of hearing with age in Tff3-deficient animals. RESULTS: Present detailed analysis of auditory brain stem response (ABR) measurements and immunohistochemical study of selected functional proteins indicated a normal function and phenotype of the cochlea in Tff3 mutants. However, a microarray-based screening of tissue derived from the auditory central nervous system revealed an alteration of securin (Pttg1) and serpina3n expression between wild-type and Tff3 knock-out animals. This was confirmed by qRT-PCR, immunostaining and western blots. CONCLUSIONS: We found highly down-regulated Pttg1 and up-regulated serpina3n expression as a consequence of genetically deleting Tff3 in mice, indicating a potential role of these factors during the development of presbyacusis.
Subject(s)
Acute-Phase Proteins/metabolism , Carrier Proteins/metabolism , Mucins/genetics , Presbycusis/metabolism , Serpins/metabolism , Acute-Phase Proteins/genetics , Acute-Phase Proteins/physiology , Animals , Carrier Proteins/genetics , Carrier Proteins/physiology , Cochlea/metabolism , Down-Regulation , Ear, Inner/metabolism , Evoked Potentials, Auditory, Brain Stem/physiology , Immunohistochemistry , Mice , Mice, Knockout , Mucins/deficiency , Mucins/metabolism , Phenotype , Securin , Serpins/genetics , Serpins/physiology , Trefoil Factor-3 , Up-RegulationABSTRACT
Aquaporins are membrane water channel proteins that have also been identified in the cochlea. Auditory function critically depends on the homeostasis of the cochlear fluids perilymph and endolymph. In particular, the ion and water regulation of the endolymph is essential for sensory transduction. Within the cochlear duct the lateral wall epithelium has been proposed to secrete endolymph by an aquaporin-mediated flow of water across its epithelial tight junction barrier. This study identifies interspecies differences in the cellular distribution of aquaporin 5 (AQP5) in the cochlear lateral wall of mice, rats, gerbils and guinea pigs. In addition the cellular expression pattern of AQP5 is described in the human cochlea. Developmental changes in rats demonstrate longitudinal and radial gradients along the cochlear duct. During early postnatal development a pancochlear expression is detected. However a regression to the apical quadrant and limitation to outer sulcus cells (OSCs) is observed in the adult. This developmental loss of AQP5 expression in the basal cochlear segments coincides with a morphological loss of contact between OSCs and the endolymph. At the subcellular level, AQP5 exhibits polarized expression in the apical plasma membrane of the OSCs. Complementary, the basolateral membrane in the root processes of the OSCs exhibits AQP4 expression. This differential localization of AQP5 and AQP4 in the apical and basolateral membranes of the same epithelial cell type suggests a direct aquaporin-mediated transcellular water shunt between the perilymph and endolymph in the OSCs of the cochlear lateral wall. In the human cochlea these findings may have pathophysiological implications attributed to a dysfunctional water regulation by AQP5 such as endolymphatic hydrops (i.e. in Meniere's disease) or sensorineural hearing loss (i.e. in Sjögren's syndrome).
Subject(s)
Aquaporin 5/metabolism , Cochlea/metabolism , Endolymph/metabolism , Perilymph/metabolism , Animals , Animals, Newborn , Cell Membrane/metabolism , Cochlea/growth & development , Epithelium/growth & development , Epithelium/metabolism , Female , Gerbillinae , Guinea Pigs , Humans , Male , Mice , Middle Aged , Rats , Species Specificity , Subcellular Fractions/metabolismABSTRACT
Mutations in the large GPR98 gene underlie Usher syndrome type 2C (USH2C), and all patients described to date have been female. It was speculated that GPR98 mutations cause a more severe, and eventually lethal, phenotype in males. We describe for the first time two male patients with USH2 with novel GPR98 mutations. Clinical characterization of a male patient and his affected sister revealed a typical USH2 phenotype in both. GPR98 may have been excluded from systematic investigation in previous studies, and the proportion of patients with USH2C probably underestimated. GPR98 should be considered in patients with USH2 of both sexes.
Subject(s)
Mutation , Receptors, G-Protein-Coupled/genetics , Usher Syndromes/genetics , DNA Mutational Analysis , Family Health , Female , Humans , Male , Pedigree , Usher Syndromes/classification , Usher Syndromes/pathology , Young AdultABSTRACT
Rhinoorbitocerebral mucormycosis is a rare invasive fungal infection that is fatal when untreated. We describe an immunosuppressed patient with chronic lymphatic leukaemia who developed a severe rhinoorbitocerebral mucormycosis after allogeneic bone marrow transplantation. Due to the potentially fulminant course and fatal outcome, radical excision of the necrotic area in combination with antifungal therapy is necessary in the presence of suspicious clinical signs of mucormycosis despite a lack of histopathologic confirmation.
Subject(s)
Immunocompromised Host/immunology , Mucormycosis/diagnosis , Mucormycosis/therapy , Orbital Diseases/diagnosis , Orbital Diseases/therapy , Female , Humans , Middle Aged , Mucormycosis/immunology , Orbital Diseases/immunology , Treatment OutcomeSubject(s)
Head and Neck Neoplasms/surgery , Otolaryngology/trends , Otorhinolaryngologic Diseases/surgery , Otorhinolaryngologic Surgical Procedures/trends , Regenerative Medicine/trends , Head and Neck Neoplasms/history , History, 15th Century , History, 16th Century , History, 17th Century , History, 18th Century , History, 19th Century , History, 20th Century , History, 21st Century , History, Ancient , History, Medieval , Humans , Otolaryngology/history , Otorhinolaryngologic Surgical Procedures/history , Regenerative Medicine/historyABSTRACT
Regenerative medicine offers the prospect of causal treatment of sensorineural hearing loss. In humans, the loss of sensory hair cells is irreversible and results in chronic hearing loss. Other vertebrates, particularly birds, have the capability to spontaneously regenerate lost sensory hair cells and restore hearing. In the bird model, regeneration of hair cells is based on the proliferation of supporting cells. In mammals, supporting cells have lost their proliferative capacity and are terminally differentiated. To gain an understanding about regeneration of hair cells in mammals, cell division of supporting cells has to be controlled. Gene disruption of the cell cycle inhibitor p27(Kip1) allows supporting cell proliferation in the organ of Corti in vivo. Furthermore, in vitro studies indicate that newly generated cells may differentiate into hair cells after p27(Kip1) disruption. Other current methods to induce hair cell regeneration include the gene transfer of Math1 and transplantation of stem cells to the inner ear.
Subject(s)
Genetic Therapy/trends , Hearing Loss, Sensorineural/therapy , Otorhinolaryngologic Surgical Procedures/trends , Plastic Surgery Procedures/methods , Regenerative Medicine/trends , Stem Cell Transplantation/trends , Tissue Engineering/trends , Genetic Therapy/methods , HumansABSTRACT
OBJECTIVE: It is impossible to precisely anticipate the crooked course of the transverse and sigmoid sinuses and their individual relationship to superficial landmarks such as the asterion during retrosigmoid approaches. This study was designed to evaluate this anatomical relationship with the help of a surgical planning system and to analyze the impact of these in vivo findings on trepanation placement in retrosigmoid craniotomies. METHODS: In a consecutive series of 123 patients with pathologies located in the cerebellopontine angle, 72 patients underwent surgical planning for retrosigmoid craniotomies based on 3D volumetric renderings of computed tomography venography. By opacity modulation of surfaces in 3D images the position of the asterion was assessed in relationship to the transverse-sigmoid sinus transition (TST) and compared to its intraoperative localization. We evaluated the impact of this additional information on trepanation placement. RESULTS: The spatial relationship of the asterion and the underlying TST complex could be identified and recorded in 66 out of 72 cases. In the remaining 6 cases the sutures were ossified and not visible in the 3D CT reconstructions. The asterion was located on top of the TST in 51 cases, above the TST in 4 cases, and below the TST in 11 cases. The location of the trepanation was modified in 27 cases due to the preoperative imaging findings with major and minor modifications in 10 and 17 cases, respectively. CONCLUSION: Volume-rendered images provide reliable 3D visualization of complex and hidden anatomical structures in the posterior fossa and thereby increase the precision in retrosigmoid approaches.