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  • 1.
    Aabel, Peder
    et al.
    Oslo Univ Hosp, Dept Med Biochem, Oslo, Norway;Akershus Univ Hosp, Ear Nose & Throat Dept, Div Surg, Lorenskog, Norway;Univ Oslo, Inst Clin Med, Div Surg, Oslo, Norway.
    Utheim, Tor Paaske
    Oslo Univ Hosp, Dept Med Biochem, Oslo, Norway;Univ Oslo, Inst Oral Biol, Fac Dent, Oslo, Norway.
    Olstad, Ole Kristoffer
    Oslo Univ Hosp, Dept Med Biochem, Oslo, Norway.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Dilley, Rodney James
    Ear Sci Inst Australia, Perth, WA, Australia;Univ Western Australia, Ear Sci Ctr, Nedlands, WA, Australia;Univ Western Australia, Ctr Cell Therapy & Regenerat Med, Nedlands, WA, Australia.
    von Unge, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Akershus Univ Hosp, Ear Nose & Throat Dept, Div Surg, Lorenskog, Norway;Univ Oslo, Inst Clin Med, Div Surg, Oslo, Norway.
    Transcription and microRNA Profiling of Cultured Human Tympanic Membrane Epidermal Keratinocytes2018In: Journal of the Association for Research in Otolaryngology, ISSN 1525-3961, E-ISSN 1438-7573, Vol. 19, no 3, p. 243-260Article in journal (Refereed)
    Abstract [en]

    The human tympanic membrane (TM) has a thin outer epidermal layer which plays an important role in TM homeostasis and ear health. The specialised cells of the TM epidermis have a different physiology compared to normal skin epidermal keratinocytes, displaying a dynamic and constitutive migration that maintains a clear TM surface and assists in regeneration. Here, we characterise and compare molecular phenotypes in keratinocyte cultures from TM and normal skin. TM keratinocytes were isolated by enzymatic digestion and cultured in vitro. We compared global mRNA and microRNA expression of the cultured cells with that of human epidermal keratinocyte cultures. Genes with either relatively higher or lower expression were analysed further using the biostatistical tools g:Profiler and Ingenuity Pathway Analysis. Approximately 500 genes were found differentially expressed. Gene ontology enrichment and Ingenuity analyses identified cellular migration and closely related biological processes to be the most significant functions of the genes highly expressed in the TM keratinocytes. The genes of low expression showed a marked difference in homeobox (HOX) genes of clusters A and C, giving the TM keratinocytes a strikingly low HOX gene expression profile. An in vitro scratch wound assay showed a more individualised cell movement in cells from the tympanic membrane than normal epidermal keratinocytes. We identified 10 microRNAs with differential expression, several of which can also be linked to regulation of cell migration and expression of HOX genes. Our data provides clues to understanding the specific physiological properties of TM keratinocytes, including candidate genes for constitutive migration, and may thus help focus further research.

  • 2.
    Agrawal, Sumit
    et al.
    Western Univ, Dept Otolaryngol Head & Neck Surg, London, ON, Canada.
    Schart-Moren, Nadine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Liu, Wei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Ladak, Hanif M.
    Western Univ, Dept Otolaryngol Head & Neck Surg, London, ON, Canada;Western Univ, Dept Med Biophys, London, ON, Canada;Western Univ, Dept Elect & Comp Engn, London, ON, Canada.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Li, Hao
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    The secondary spiral lamina and its relevance in cochlear implant surgery2018In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 123, no 1, p. 9-18Article in journal (Refereed)
    Abstract [en]

    Objective: We used synchrotron radiation phase contrast imaging (SR-PCI) to study the 3D microanatomy of the basilar membrane (BM) and its attachment to the spiral ligament (SL) (with a conceivable secondary spiral lamina [SSL] or secondary spiral plate) at the round window membrane (RWM) in the human cochlea. The conception of this complex anatomy may be essential for accomplishing structural preservation at cochlear implant surgery.

    Material and methods: Sixteen freshly fixed human temporal bones were used to reproduce the BM, SL, primary and secondary osseous spiral laminae (OSL), and RWM using volume-rendering software. Confocal microscopy immunohistochemistry (IHC) was performed to analyze the molecular constituents.

    Results: SR-PCI reproduced the soft tissues including the RWM, Reissner's membrane (RM), and the BM attachment to the lateral wall (LW) in three dimensions. A variable SR-PCI contrast enhancement was recognized in the caudal part of the SL facing the scala tympani (ST). It seemed to represent a SSL allied to the basilar crest (BC). The SSL extended along the postero-superior margin of the round window (RW) and immunohistochemically expressed type II collagen.

    Conclusions: Unlike in several mammalian species, the human SSL is restricted to the most basal portion of the cochlea around the RW. It anchors the BM and may influence its hydro-mechanical properties. It could also help to shield the BM from the RW. The microanatomy should be considered at cochlear implant surgery.

  • 3.
    Anderson, Malin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Boström, Marja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Pfaller, Kristian
    Glueckert, Rudolf
    Schrott-Fischer, Annelies
    Gerdin, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Structure and locomotion of adult in vitro regenerated spiral ganglion growth cones: a study using video microscopy and SEM2006In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 215, no 1-2, p. 97-107Article in journal (Refereed)
    Abstract [en]

    Neuronal development and neurite regeneration depends on the locomotion and navigation of nerve growth cones (GCs). There are few detailed descriptions of the GC function and structure in the adult auditory system. In this study, GCs of adult dissociated and cultured spiral ganglion (SG) neurons were analyzed in vitro utilizing combined high resolution scanning electron microscopy (SEM) and time lapse video microscopy (TLVM). Axon kinesis was assessed on planar substratum with growth factors BDNF, NT-3 and GDNF. At the nano-scale level, lamellipodial abdomen of the expanding GC was found to be decorated with short surface specializations, which at TLVM were considered to be related to their crawling capacity. Filopodia were devoid of these surface structures, supporting its generally described sensory role. Microspikes appearing on lamellipodia and axons, showed circular adhesions, which at TLVM were found to provide anchorage of the navigating and turning axon. Neurons and GCs expressed the DCC-receptor for the guidance molecule netrin-1. Asymmetric ligand-based stimulation initiated turning responses suggest that this attractant cue influences steering of GC in adult regenerating auditory neurites. Hopefully, these findings may be used for ensuing tentative navigation of spiral ganglion neurons to induce regenerative processes in the human ear.

  • 4. Anderson, Malin
    et al.
    Johnston, T.A.
    Newman, P.D.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Internalization of nanoparticles into spiral ganglion cells2009In: Journal of nanoneuroscience, ISSN 1939-0637, Vol. 1, no 1, p. 75-84Article in journal (Refereed)
    Abstract [en]

    The delivery of drugs or genes to the inner ear in a controlled and biocompatible manner could lead to new treatments for conditions such as Ménière's disease, tinnitus, schwannomas of the ear, and for improving hearing. The concept of multifunctional nanoparticles, which are targetable, biodegradable, and traceable, has led to new approaches to controlled drug release and localized delivery to specific cell populations. Tissue-specific delivery can be achieved by functionally "addressed" nanostructures loaded with a therapeutic molecule. In the present study, we investigated the incorporation, distribution, and toxicology of amphiphilic block copolymer nanoparticles (NPs) in spiral ganglion (SG) cell cultures. Adult human and guinea pig SG neurons and glia/Schwann dissociated cell cultures were expanded, grown for several weeks, and then studied live using time-lapse video microscopy and high-resolution light microscopy. The cells were further characterized using immunocytochemistry for the neural marker TuJ1 and the glia cell markers S-100 and GFAP, and their morphology was studied in more detail using scanning electron microscopy (SEM). These cell cultures were exposed to fluorescently (Dil)-loaded NPs for different time periods and at different concentrations, and the uptake was studied using fluorescence microscopy. The study demonstrates that Dil-loaded NPs can be internalized into guinea pig SG neurons as well as into human and guinea pig SG glia/Schwann cells without indication of toxicity or reduced viability. After 4 hours, almost 100% of both the neurons and the glia cells had incorporated the NPs into the cytoplasm. No uptake could be detected in the nucleus and no evidence of internalization could be seen in axons or in the growth cone area of the neuron. Especially in the glia cells, the NPs were detected in small vesicles surrounding the nucleus and occasionally in the periphery of the cytoplasm. This information could lead to the development of more specialized NPs, targeting only SG neurons or Schwann cells.

  • 5.
    Andersson, Gerhard
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Ekvall, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Kinnefors, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Nyberg, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Evaluation of quality of life and symptoms after translabyrinthine acoustic neuroma surgery1997In: The American journal of otology, ISSN 0192-9763, Vol. 18, no 4, p. 421-426Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    This study aimed to describe the consequences of acoustic neuroma surgery in terms of symptoms and quality of life.

    STUDY DESIGN:

    This study was a retrospective case review.

    SETTING:

    The surgery was conducted in Uppsala, Sweden.

    PATIENTS:

    A consecutive sample of acoustic neuroma patients operated on between 1988 and 1994.

    INTERVENTION:

    All patients had been operated on with the translabyrinthine technique.

    MAIN OUTCOME MEASURES:

    A questionnaire was constructed including questions about the surgery and symptoms. The House and Brackmann scale was used for grading facial function and the Brackmann and Bars scale was used for self-assessment of facial function.

    RESULTS:

    Follow-up data were collected by a postal questionnaire sent out and returned by 141 patients, which yielded a 90% response rate. Normal to moderately impaired facial function (House I-III) was evident in 85.2% of patients, although residual facial problems were reported. Most considered hearing to be worse after surgery (80%), and tinnitus was found in 60% of the sample. Balance problems (45%), dizziness (19%), and headache/pain (22%) were also reported. Work ability was affected in 23%, and 37% reported a continued need for medical consultations, mainly because of facial problems and pain. Most (89%) were pleased with the preoperative information.

    CONCLUSIONS:

    This study showed that few patients with acoustic neuroma had experienced negative social consequences after surgery. Although not linked to the operation, residual symptoms were reported that may necessitate further rehabilitation.

  • 6.
    Andersson, Gerhard
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Kinnefors, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Ekvall, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Tinnitus and translabyrinthine acoustic neuroma surgery1997In: Audiology & neuro-otology, ISSN 1420-3030, E-ISSN 1421-9700, Vol. 2, no 6, p. 403-409Article in journal (Refereed)
    Abstract [en]

    The purpose of this investigation was to study the effects of translabyrinthine acoustic neuroma surgery on tinnitus in a consecutive sample of patients operated on between 1988 and 1994 in Uppsala (Sweden). A postal questionnaire was returned by 141 patients, yielding a 90% response rate without reminder. The results showed that tinnitus was experienced by 70% of the patients before surgery and 60% after surgery. In general, low degrees of tinnitus distress were found, which was confirmed by the questionnaire results. Ratings of tinnitus distress after surgery, using the Klockhoff and Lindblom grading system, showed that 48% had tinnitus of grade I, 46% of grade II, and 6% of grade III. Pre- and postsurgery grading of distress did not change significantly. There was a 35% risk for developing tinnitus when no preoperative tinnitus was present and a 15% chance that tinnitus disappears when present preoperatively.

  • 7.
    Atturo, Francesca
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Barbara, Maurizio
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Is the Human Round Window Really Round?: An Anatomic Study With Surgical Implications2014In: Otology and Neurotology, ISSN 1531-7129, E-ISSN 1537-4505, Vol. 35, no 8, p. 1354-1360Article in journal (Refereed)
    Abstract [en]

    Hypothesis: Human round window (RW) presents anatomic variations that may influence surgical approach. Background: The true shape of the human RW has been divisive since its first description in 1772 by Antonio Scarpa. Introduction of novel surgical strategies in recent years have raised its significance. Here, the human RW size and shape variations were documented in microdissected human temporal bones. Methods: An archival collection of human microdissected temporal bones was analyzed. RW rim could be delineated and photographed from the labyrinthine aspect and its topography assessed. Results: Human RW is seldom round but ovoid or orthogonal, skewed, and nonplanar (saddlelike). Membrane is fan shaped or conical with an anteroinferior and a posterosuperior part. The mean longest diameter was 1.90 mm, and the smallest one is 1.54 mm. The mean diameter from the crista fenestra was 1.31 mm. The mean area of the RW was 2.08 mm(2), which varied between 0.99 and 3.20 mm(2). The crista fenestrae of the anterior component form a "doorstep" that may limit the entry to the scala tympani from the RW niche. Conclusion: The alternate anatomic features of the human RW may influence its surgical access and designs of implants aimed at targeting this region.

  • 8.
    Atturo, Francesca
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Barbara, Maurizio
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    On the Anatomy of the 'Hook' Region of the Human Cochlea and How It Relates to Cochlear Implantation2014In: Audiology & neuro-otology, ISSN 1420-3030, E-ISSN 1421-9700, Vol. 19, no 6, p. 378-385Article in journal (Refereed)
    Abstract [en]

    Background: The optimal insertion route for an electrode array in hearing preservation cochlear implantation (CI) surgery is still tentative. Both cochleostomy (CO) and round window (RW) techniques are used today. In the present study we analyzed size variations and topographic anatomy of the 'hook' region of the human cochlea to better comprehend the Testo effects of various electric array insertion modes. Material and Methods: Size variations of the cochlear 'hook' region were assessed in 23 human, microdissected temporal bones by measuring the distances between the oval and round windows, also outlining the spiral ligament/spiral lamina. Influence of size variations on spiral ligament position and fundamentals for different surgical approaches were evaluated in a subset of 'small' and 'large' cochleae performing different types of CO. In addition, the relationship between the microdissected accessory canal housing the inferior cochlear vein and the RW was analyzed. Results: The lateral vestibular wall and the cochlear 'hook' displayed large anatomic variations that greatly influenced the size of the potential surgical area. Results showed that only very inferiorly located CO entered the scala tympani without causing trauma to the spiral ligament and spiral lamina. An inferior approach may challenge the inferior cochlear vein. Conclusion: Preoperative assessment of the distance between the round and oval windows may direct the surgeon before CI hearing- preservation surgery. CO techniques, especially in 'small' ears, may lead to frequent damage to the inner ear structures. In those cases with substantial residual hearing, CI surgery may be better performed through a RW approach.  

  • 9.
    Atturo, Francesca
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Schart-Moren, Nadine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery. Uppsala Univ Hosp, Otolaryngol Sect, Dept Surg Sci Head & Neck Surg, Uppsala, Sweden.
    Li, Hao
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    The Human Cochlear Aqueduct and Accessory Canals: a Micro-CT Analysis Using a 3D Reconstruction Paradigm2018In: Otology and Neurotology, ISSN 1531-7129, E-ISSN 1537-4505, Vol. 39, no 6, p. e429-e435Article in journal (Refereed)
    Abstract [en]

    Objective: We sought to study the anatomic variations of the cochlear aqueduct and its accessory canals in human temporal bones using micro-CT and a 3D reconstruction paradigm. More knowledge about the anatomic variations of these structures, particularly at the basal turn of the cochlea and round window niche, may be important to better preserve residual hearing as well as the neural supply during cochlear implant surgery.

    Methods: An archival collection of 30 human temporal bones underwent micro-CT and 3D reconstruction. A surface enhancement paradigm was applied. The application displays reconstructed slices as a 3D object with realistic 3D visualization of scanned objects. Virtual sectioning or cropping of the petrous bone presented subsequent areas. Thereby, the bony canals could be followed from inside the basal turn of cochlea and middle ear to the jugular foramen.

    Results: The cochlear aqueduct was always paralleled by an accessory canal containing the inferior cochlear vein. It ran from the basal turn of the cochlea and exited laterally in the jugular foramen. In 70% of the cases, a secondary accessory canal was observed and it derived mostly from a depression or infundibulum located in the floor of the round window niche. This canal also exited in the jugular foramen. The secondary accessory canal occasionally anastomosed with the primary accessory canal suggesting that it contains a vein that drains middle ear blood to the cranial sinus.

    Conclusion: Micro-CT with 3D surface reconstruction paradigm offers new possibilities to study the topographic anatomy of minor details in the human inner ear. The technique creates simulated transparent castings of the labyrinth with a coinciding surface view through enhancement of contrast between boundaries. Accessory canals that drain blood from the cochlea, spiral ganglion, and middle ear could be characterized three-dimensionally.

  • 10. Bagger-Sjöbäck, Dan
    et al.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Pathology of the vestibular organ2008In: Scott-Brown textbook of otolaryngology / [ed] Michael Gleeson, London: Hodder Arnold , 2008, 7, p. 3147-3157Chapter in book (Other (popular science, discussion, etc.))
  • 11.
    Boström, Marja
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Anderson, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Lindholm, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Park, Kyoung-Ho
    Schrott-Fischer, Annelies
    Pfaller, Kristian
    Glueckert, Rudolf
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Neural network and "Ganglion" formations in vitro: a video microscopy and scanning electron microscopy study on adult cultured spiral ganglion cells.2007In: Otology and Neurotology, ISSN 1531-7129, E-ISSN 1537-4505, Vol. 28, no 8, p. 1109-1119Article in journal (Refereed)
    Abstract [en]

    Hypothesis: To analyze if adult-dissociated spiral ganglion cells may be propagated in vitro for later use in transplantation models to form integrated neural networks. Background: Hearing loss is often associated with primary or secondary spiral ganglion cell degeneration. New strategies for cell repair and tissue engineering warrants further elucidation of the regenerative capacity of the auditory nerve. Methods: We used in vitro/in video microscopy in combination with immunocytochemistry and field emission scanning electron microscopy to analyze neural development and network formation from dissociated adult guinea pig spiral ganglion cells. Cells were cultured in serum-free medium and in the presence of brain-derived neurotrophic factor, neurotrophin 3, and glia cell line-derived neurotrophic factor for up to 8 weeks. Results: Time-lapse video microscopy and scanning electron microscopy exposed the propagation of auditory neurons and the role of neural growth cones in axon locomotion, fasciculation, and nuclear migration, often ensuing in cell congregation (ganglion-like formations) during network formation. Axons were sometimes ensheathed by adjoining S-100/glia fibrillary acidic protein-expressing cells. A few expanding neurons were nestin positive and sometimes incorporated the markers of proliferating cells Ki67 and 5'-bromo-2-deoxyuridine. Neurons expressed the markers and transcription factors for neural development neurogenin 1, neurogenic differentiation factor 1, Brn3a, and GATA binding protein 3, as well as the neural markers beta-III tubulin, NeuN, and neurofilament 160 during this process. Conclusion: This method of culturing and expanding spiral ganglion neurons in vitro may be useful in further studies of cell transplantation models aiming to restore the injured inner ear.

  • 12.
    Boström, Marja
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Khalifa, Shaden
    Boström, Henrik
    Liu, Wei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Friberg, Ulla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Effects of Neurotrophic Factors on Growth and Glial Cell Alignment of Cultured Adult Spiral Ganglion Cells2009In: Audiology & neuro-otology, ISSN 1420-3030, E-ISSN 1421-9700, Vol. 15, no 3, p. 175-186Article in journal (Refereed)
    Abstract [en]

    Adult spiral ganglion cells were cultured in chorus to assess the influence of the neurotrophins brain-derived neurotrophic factor, neurotrophin 3 and glial cell line-derived neurotrophic factor (GDNF) on neurite growth and Schwann cell alignment. Over 1500 measurements were collected using each factor at 10 ng/ml and all three in combination. Evaluation was made with GDNF at concentrations of up to 100 ng/ml. Neurite dimensions were assessed at days 5, 7, 9 and 11 using a computer-based program (Axon Analyzer). GDNF had a strong effect on spiral ganglion cell growth almost attaining the level of all three factors in combination. GDNF increased glial cell alignment and nerve bundle formation. Results show the potential of GDNF to maintain and possibly restore auditory nerve integrity.

  • 13.
    Cai, Yixiao
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Edin, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Jin, Zhe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Alexsson, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Gudjonsson, Olafur
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Liu, Wei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Karlsson, Mikael
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Li, Hao
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Strategy towards independent electrical stimulation from cochlear implants: Guided auditory neuron growth on topographically modified nanocrystalline diamond2016In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 31, p. 211-220Article in journal (Refereed)
    Abstract [en]

    Cochlear implants (CI) have been used for several decades to treat patients with profound hearing loss. Nevertheless, results vary between individuals, and fine hearing is generally poor due to the lack of discrete neural stimulation from the individual receptor hair cells. A major problem is the deliverance of independent stimulation signals to individual auditory neurons. Fine hearing requires significantly more stimulation contacts with intimate neuron/electrode interphases from ordered axonal re-growth, something current CI technology cannot provide.

    Here, we demonstrate the potential application of micro-textured nanocrystalline diamond (NCD) surfaces on CI electrode arrays. Such textured NCD surfaces consist of micrometer-sized nail-head-shaped pillars (size 5 5 lm2) made with sequences of micro/nano-fabrication processes, including sputtering, photolithography and plasma etching.

    The results show that human and murine inner-ear ganglion neurites and, potentially, neural progenitor cells can attach to patterned NCD surfaces without an extracellular matrix coating. Microscopic methods revealed adhesion and neural growth, specifically along the nail-head-shaped NCD pillars in an ordered manner, rather than in non-textured areas. This pattern was established when the inter-NCD pillar distance varied between 4 and 9 lm.

    The findings demonstrate that regenerating auditory neurons show a strong affinity to the NCD pillars, and the technique could be used for neural guidance and the creation of new neural networks. Together with the NCD’s unique anti-bacterial and electrical properties, patterned NCD surfaces could provide designed neural/electrode interfaces to create independent electrical stimulation signals in CI electrode arrays for the neural population.

  • 14.
    Chacko, L. Johnson
    et al.
    Med Univ Innsbruck, Dept Otorhinolaryngol, Anichstr 35, A-6020 Innsbruck, Austria..
    Blumer, M. J. F.
    Med Univ Innsbruck, Dept Anat Histol & Embryol, Div Clin & Funct Anat, Muellerstr 59, A-6020 Innsbruck, Austria..
    Pechriggl, E.
    Med Univ Innsbruck, Dept Anat Histol & Embryol, Div Clin & Funct Anat, Muellerstr 59, A-6020 Innsbruck, Austria..
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Dietl, W.
    Med Univ Innsbruck, Dept Otorhinolaryngol, Anichstr 35, A-6020 Innsbruck, Austria..
    Haim, A.
    Med Univ Innsbruck, Dept Plast Reconstruct & Aesthet Surg, Innerkoflerstr 1, A-6020 Innsbruck, Austria..
    Fritsch, H.
    Med Univ Innsbruck, Dept Anat Histol & Embryol, Div Clin & Funct Anat, Muellerstr 59, A-6020 Innsbruck, Austria..
    Glueckert, R.
    Med Univ Innsbruck, Dept Otorhinolaryngol, Anichstr 35, A-6020 Innsbruck, Austria.;Tirol Kliniken, Univ Clin Innsbruck, Anichstr 35, A-6020 Innsbruck, Austria..
    Dudas, J.
    Med Univ Innsbruck, Dept Otorhinolaryngol, Anichstr 35, A-6020 Innsbruck, Austria..
    Schrott-Fischer, A.
    Med Univ Innsbruck, Dept Otorhinolaryngol, Anichstr 35, A-6020 Innsbruck, Austria..
    Role of BDNF and neurotrophic receptors in human inner ear development2017In: Cell and Tissue Research, ISSN 0302-766X, E-ISSN 1432-0878, Vol. 370, no 3, p. 347-363Article in journal (Refereed)
    Abstract [en]

    The expression patterns of the neurotrophin, brain-derived neurotrophic factor, BDNF, and the neurotrophic receptors-p75NTR and Trk receptors-in the developing human fetal inner ear between the gestational weeks (GW) 9 to 12 are examined via in situ hybridization and immunohistochemistry. BDNF mRNA expression was highest in the cochlea at GW 9 but declined in the course of development. In contrast to embryonic murine specimens, a decline in BDNF expression from the apical to the basal turn of the cochlea could not be observed. p75NTR immunostaining was most prominent in the nerve fibers that penetrate into the sensory epithelia of the cochlea, the urticule and the saccule as gestational age progresses. TrkB and TrkC expression intensified towards GW 12, at which point the BDNF mRNA localization was at its lowest. TrkA expression was limited to fiber subpopulations of the facial nerve at GW 10. In the adult human inner ear, we observed BDNF mRNA expression in the apical poles of the cochlear hair cells and supporting cells, while in the adult human utricle, the expression was localized in the vestibular hair cells. We demonstrate the highly specific staining patterns of BDNF mRNA and its putative receptors over a developmental period in which multiple hearing disorders are manifested. Our findings suggest that BDNF and neurotrophin receptors are important players during early human inner ear development. In particular, they seem to be important for the survival of the afferent sensory neurons.

  • 15. Couloigner, Vincent
    et al.
    Teixeira, Marie
    Sterkers, Olivier
    Rask-Andersen, Helge
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Ferrary, Evelyne
    [The endolymphatic sac: its roles in the inner ear]2004In: Med Sci (Paris), ISSN 0767-0974, Vol. 20, no 3, p. 304-10Article in journal (Other scientific)
  • 16.
    Danckwardt-Lillieström, Niklas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Friberg, Ulla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Kinnefors, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    "Endolymphatic sacitis" in a case of active Menière's disease: an ultrastructural histopathologic investigation1997In: Annals of Otology, Rhinology and Laryngology, ISSN 0003-4894, E-ISSN 1943-572X, Vol. 106, no 3, p. 190-198Article in journal (Refereed)
    Abstract [en]

    An ultrastructural analysis of an entire intraosseous endolymphatic sac (ES) from a patient with active, well-documented Menière's disease was performed for the first time. The results were compared with those obtained from ES biopsy material from patients with acoustic neuromas. The ES was small in size and showed signs of focal inflammation with intraepithelial invasion by mononuclear cells. At these places the normal fine structure, including the vascular anatomy, was altered. The possible relationship between these changes and Meniere's disease is discussed.

  • 17.
    Danckwardt-Lillieström, Niklas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Friberg, Ulla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Kinnefors, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Steriocilia-like structures in the endolymphatic sac in Ménière's disease and acoustic neuroma1998In: Journal for Oto-Rhino-Laryngology, ISSN 0301-1569, E-ISSN 1423-0275, Vol. 60, no 4, p. 190-197Article in journal (Refereed)
    Abstract [en]

    The vestibular aqueduct was surgically removed in 3 patients undergoing labyrinthectomy due to severe Ménière's disease (MD). Stereocilia-like structures were found in the luminal contents of the endolymphatic sac (ES) in all of these patients. The ES from 18 patients with acoustic neuroma were used as controls. In 1 of these, numerous stereocilia-like structures were found in the ES and in 3 additional patients, a few isolated cilia-like structures were disclosed. The findings may suggest an ongoing hair cell degeneration in the inner ear that is more advanced in patients with MD. The data also suggest that the endolymphatic duct is patent and that a longitudinal flow of endolymph also occurs in patients with MD.

  • 18.
    Danckwardt-Lillieström, Niklas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Friberg, Ulla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Kinnefors, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Ultrastructure of the endolymphatic sac in three patients with Meniere's disease. A preliminary report. 16th Danavox Symposium on Meniere's disease.Kolding, Denmark1995In: Ménière's disease: Proceedings of the 16th Danavox Symposium, September 19-22, 1995, Scanticon, Kolding, Denmark / [ed] Søren Vesterhauge, Morten Katholm & Pernille Mikines, 1995Conference paper (Other academic)
  • 19. Eckhard, A
    et al.
    Dos Santos, A
    Liu, Wei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Bassiouni, M
    Arnold, H
    Gleiser, C
    Hirt, B
    Harteneck, C
    Müller, M
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Löwenheim, H
    Regulation of the perilymphatic-endolymphatic water shunt in the cochlea by membrane translocation of aquaporin-52015In: Pflügers Archiv: European Journal of Physiology, ISSN 0031-6768, E-ISSN 1432-2013, Vol. 467, no 12, p. 2571-2588Article in journal (Refereed)
    Abstract [en]

    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.

  • 20. Eckhard, A
    et al.
    Müller, M
    Salt, A
    Smolders, J
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Löwenheim, H
    Water permeability of the mammalian cochlea: functional features of an aquaporin-facilitated water shunt at the perilymph-endolymph barrier2014In: Pflügers Archiv: European Journal of Physiology, ISSN 0031-6768, E-ISSN 1432-2013, Vol. 466, no 10, p. 1963-1985Article in journal (Refereed)
    Abstract [en]

    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 (P D) and osmotic (P f) 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 P D of the entire CDE (P D = 8.18 × 10(-5) cm s(-1)) and its individual partitions including Reissner's membrane (P D = 12.06 × 10(-5) cm s(-1)) and the organ of Corti (P D = 10.2 × 10(-5) cm s(-1)) were similar to other epithelia with AQP-facilitated water permeation. The P f of the CDE (P f = 6.15 × 10(-4) cm s(-1)) was also in the range of other epithelia while an exceptionally high P f was determined for an epithelial subdomain of outer sulcus cells in the cochlear apex co-expressing AQP4 and AQP5 (OSCs; P f = 156.90 × 10(-3) cm s(-1)). The P f/P D ratios of the CDE (P f/P D = 7.52) and OSCs (P f/P D = 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.

  • 21. Eckhard, Andreas
    et al.
    Gleiser, Corinna
    Arnold, Heinz
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Kumagami, Hidetaka
    Müller, Marcus
    Hirt, Bernhard
    Löwenheim, Hubert
    Water channel proteins in the inner ear and their link to hearing impairment and deafness2012In: Molecular Aspects of Medicine, ISSN 0098-2997, E-ISSN 1872-9452, Vol. 33, no 5-6, p. 612-637Article in journal (Refereed)
    Abstract [en]

    The inner ear is a fluid-filled sensory organ that transforms mechanical stimuli into the senses of hearing and balance. These neurosensory functions depend on the strict regulation of the volume of the two major extracellular fluid domains of the inner ear, the perilymph and the endolymph. Water channel proteins, or aquaporins (AQPs), are molecular candidates for the precise regulation of perilymph and endolymph volume. Eight AQP subtypes have been identified in the membranous labyrinth of the inner ear. Similar AQP subtypes are also expressed in the kidney, where they function in whole-body water regulation. In the inner ear, AQP subtypes are ubiquitously expressed in distinct cell types, suggesting that AQPs have an important physiological role in the volume regulation of perilymph and endolymph. Furthermore, disturbed AQP function may have pathophysiological relevance and may turn AQPs into therapeutic targets for the treatment of inner ear diseases. In this review, we present the currently available knowledge regarding the expression and function of AQPs in the inner ear. We give special consideration to AQP subtypes AQP2, AQP4 and AQP5, which have been studied most extensively. The potential functions of AQP2 and AQP5 in the resorption and secretion of endolymph and of AQP4 in the equilibration of cell volume are described. The pathophysiological implications of these AQP subtypes for inner ear diseases, that appear to involve impaired fluid regulation, such as Menière's disease and Sjögren's syndrome, are discussed.

  • 22. Eckhard, Andreas
    et al.
    Gleiser, Corinna
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Arnold, Heinz
    Liu, Wei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Mack, Andreas
    Müller, Marcus
    Löwenheim, Hubert
    Hirt, Bernhard
    Co-localisation of Kir4.1 and AQP4 in rat and human cochleae reveals a gap in water channel expression at the transduction sites of endocochlear K+ recycling routes2012In: Cell and Tissue Research, ISSN 0302-766X, E-ISSN 1432-0878, Vol. 350, no 1, p. 27-43Article in journal (Refereed)
    Abstract [en]

    Sensory transduction in the cochlea depends on perilymphatic-endolymphatic potassium (K+) recycling. It has been suggested that the epithelial supporting cells (SCs) of the cochlear duct may form the intracellular K+ recycling pathway. Thus, they must be endowed with molecular mechanisms that facilitate K+ uptake and release, along with concomitant osmotically driven water movements. As yet, no molecules have been described that would allow for volume-equilibrated transepithelial K+ fluxes across the SCs. This study describes the subcellular co-localisation of the Kir4.1 K+ channel (Kir4.1) and the aquaporin-4 water channel (AQP4) in SCs, on the basis of immunohistochemical double-labelling experiments in rat and human cochleae. The results of this study reveal the expression of Kir4.1 in the basal or basolateral membranes of the SCs in the sensory domain of the organ of Corti that are adjacent to hair cells and in the non-sensory domains of the inner and outer sulci that abut large extracellular fluid spaces. The SCs of the inner sulcus (interdental cells, inner sulcus cells) and the outer sulcus (Hensen’s cells, outer sulcus cells) display the co-localisation of Kir4.1 and AQP4 expression. However, the SCs in the sensory domain of the organ of Corti reveal a gap in the expression of AQP4. The outer pillar cell is devoid of both Kir4.1 and AQP4. The subcellular co-localisation of Kir4.1 and AQP4 in the SCs of the cochlea described in this study resembles that of the astroglia of the central nervous system and the glial Mueller cells in the retina.

  • 23.
    Edfeldt, Lennart
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Kinnefors, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Strömbäck, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Köbler, Susanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Surgical treatment of paediatric cholesteatoma: Long-term follow up in comparison with adults2012In: International Journal of Pediatric Otorhinolaryngology, ISSN 0165-5876, E-ISSN 1872-8464, Vol. 76, no 8, p. 1091-1097Article in journal (Refereed)
    Abstract [en]

    Objective: This study was designed to analyse long-term results after surgery of acquired (ACH) and congenital cholesteatoma (CCH) of the middle ear in children and compare these with adults.

    Methods: Computer-based analysis of consecutively operated paediatric patients for ACH and CCH in a tertiary referral centre was made in 57 cases under the age of 12 operated 1983-2004 by three surgeons using identical technique. A canal wall down and total reconstruction procedure (TRP) with obliteration of the mastoid cavity, canal wall reconstruction, ossiculoplasty with consistent use of autologous bone and an "aeration enhancement procedure" (AEP) with silicon sheet in selected cases were used. Pre- and post-operative PTA (0.5-3 kHz) and pure-tone average air-bone gap (PTA-ABG) together with surgical parameters were assessed 1, 3 and 6 years following surgery.

    Results: Results showed stable hearing over 6 years with low incidence of persistent and recurrent disease comparable with results from adult patients. In nearly half of the cases, silastic sheeting was used. In 21 cases, stapes was eroded. Bone conduction thresholds levels remained unaffected 6 years after surgery. No deaf ears, postoperative facial dysfunction or other lesions related to surgery were observed. Six years after surgery every evaluated ear was found to be water-resistant and infection-free.

    Conclusion: Our results suggest that one-stage eradication of ACH and CCH in children using total reconstruction procedure (TRP) provide long-term improvement or preservation of hearing, with a low incidence of persistent or recurrent disease. No difference in surgical outcome between children and adults was found.

  • 24.
    Edfeldt, Lennart
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Round window vibroplasty in chronic ear surgery: Comparison with conventional hearing rehabilitation2013In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 138, no 8, p. 814-825Article in journal (Refereed)
    Abstract [en]

    Conclusion:

    Functional hearing results with round window vibroplasty in chronically disabled middle ears were comparable and, at high frequencies, superior to the results achieved with previously used conventional hearing aids even after extended surgery. Soft tissue transfer appears to be more important than floating mass transducer (FMT) alignment with the round window membrane (RWM) for efficient coupling or sonoinversion.

    Objectives:

    To evaluate the functional hearing results of an active middle ear implant (AMEI) to the round window niche (RWN). The results were compared with previously used conventional hearing aids. The position of the FMT was determined by cone-beam computed tomography (CBCT).

    Study design:

    Prospective cohort study

    Setting:

    Tertiary referral center

    Material and Methods:

    Seven patients with severe middle ear disease were implanted with an AMEI with round window application. The postoperative hearing outcome was compared with preoperative hearing using unaided and conventionally aided conditions. The results were correlated with the physical/geometric relation of the FMT to the RWM as determined with CBCT.

    Results:

    Dislocation of the FMT was not observed. One patient was re-implanted due to accidental damage to the electrode. In all patients, the pertinent functional hearing results were achieved and were comparable to previous rehabilitation results.

  • 25.
    Edfeldt, Lennart
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Strömbäck, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Danckwardt-Lillieström, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Abdasaleh, Shahin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Non-echo planar diffusion-weighted MRI increases follow-up accuracy after one-step step canal wall-down obliteration surgery for cholesteatoma2013In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 133, no 6, p. 574-583Article in journal (Refereed)
    Abstract [en]

    Conclusion:

    Non-echo planar (non-EPI) diffusion-weighted (DW) magnetic resonance imaging (MRI) increases the number of detected cholesteatoma after one-step canal-wall down (CWD) obliteration surgery for cholesteatoma compared with clinical evaluation alone.

    Objective:

    To evaluate the use of DW-MRI for detection of cholesteatoma after surgical treatment using CWD obliteration technique.

    Methods:

    Thirty-eight adult patients (41 ears) treated with identical one-step canal-wall down obliteration surgical technique were included in a prospective and blinded study. All patients were investigated with non-EPI and EPI DW-MRI 1-9 months after the clinical examination. Follow-up time after primary surgery varied between 10 and 234 months. DW-MRI were assessed by two neuroradiologists and compared with clinical results. Inter-rater agreement was calculated. Positive non-EPI DW-MRI cases underwent revision surgery within 18-159 days after imaging.

    Results:

    Out of 41 cases seven were evaluated as positive for cholesteatoma on non-EPI DW-MRI. Since one patient refused surgery six of these seven cases underwent surgical revision and all were verified. There was agreement between clinical and non-EPI findings in five of eight cases. EPI findings correlated poorly with non-EPI and clinical findings. Inter-rater agreement (Cohen´s kappa) was 0.91 for non-EPIDW-MRI (p<0.001) and -0.062 for EPI DW-MRI (p=0.43)

     

  • 26.
    Edfeldt, Lennart
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Strömbäck, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Kinnefors, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Surgical treatment of adult cholesteatoma: long-term follow-up using total reconstruction procedure without staging2013In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 133, no 1, p. 28-34Article in journal (Refereed)
    Abstract [en]

    Conclusions:

    A total of 330 cases of adult cholesteatoma were operated with canal-wall down (CWD) and total reconstruction procedure (TRP) without staging. Independent of preoperative middle ear conditions, cholesteatoma extent and localization, long-term improvement of hearing with a low incidence of residual and recurrent disease were achieved.

    Objectives:

    To evaluate long-term surgical and hearing results using a well-defined surgical technique without staging in adult cholesteatoma.

    Methods:

    The same CWD surgical technique, including obliteration of the mastoid cavity, reconstruction of the canal wall, and ossiculoplasty with autologous bone, was used by three senior surgeons (1982-2004). Preoperative and postoperative pure tone average (PTA) for air conduction (AC), bone conduction (BC), and air-bone gap (ABG) were assessed and compared 1, 3, and 6 years after surgery. Various prognostic factors with potential influence on long-term hearing outcome were evaluated.

    Results:

    Recurrence of AC occurred in 10%, residual disease in 3%. Six years after surgery all patients except one had a dry ear and over 92% of all cases were water resistant. Three patients developed complete deafness. Long-lasting improvement and/or preservation of hearing, with maintenance of PTA-ABG closure in 68% of all cases within 20 dB, were obtained. Sixty-four (19%) ossicular revisions were performed.

  • 27.
    Edin, Fredrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Liu, Wei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Boström, Marja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Magnusson, Peetra U.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Differentiation of human neural progenitor cell-derived spiral ganglion-like neurons: a time-lapse video study2014In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 134, no 5, p. 441-447Article in journal (Refereed)
    Abstract [en]

    Conclusions: Human neural progenitor cells can differentiate into spiral ganglion-like cells when exposed to inner ear-associated growth factors. The phenotype bears resemblance to human sphere-derived neurons. Objective: To establish an in vitro model for the human auditory nerve to replace and complement in vivo animal experiments and ultimately human in vivo transplantation. Methods: Human neural progenitors were differentiated under conditions developed for in vitro survival of human primary spiral ganglion culture with media containing growth factors associated with inner ear development. Differentiation was documented using time-lapse video microscopy. Time-dependent marker expression was evaluated using immunocytochemistry with fluorescence and laser confocal microscopy. Results: Within 14 days of differentiation, neural progenitors adopted neural phenotype and expressed spiral ganglion-associated markers.

  • 28.
    Edin, Fredrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Liu, Wei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Li, Hao
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Atturo, Francesca
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Magnusson, Peetra U
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    3-D gel culture and time-lapse video microscopy of the human vestibular nerve2014In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 134, no 12, p. 1211-1218Article in journal (Refereed)
    Abstract [en]

    UNLABELLED: Abstract Conclusions: Human inner ear neurons have an innate regenerative capacity and can be cultured in vitro in a 3-D gel. The culture technique is valuable for experimental investigations of human inner ear neuron signaling and regeneration.

    OBJECTIVES: To establish a new in vitro model to study human inner ear nerve signaling and regeneration.

    METHODS: Human superior vestibular ganglion (SVG) was harvested during translabyrinthine surgery for removal of vestibular schwannoma. After dissection tissue explants were embedded and cultured in a laminin-based 3-D matrix (Matrigel™). 3-D growth cone (GC) expansion was analyzed using time-lapse video microscopy (TLVM). Neural marker expression was appraised using immunocytochemistry with fluorescence and laser confocal microscopy.

    RESULTS: Tissue explants from adult human SVG could be cultured in 3-D in a gel, indicating an innate potential for regeneration. Cultured GCs were found to expand dynamically in the gel. Growth cone expansion and axonal Schwann cell alignment were documented using TLVM. Neurons were identified morphologically and through immunohistochemical staining.

  • 29.
    Edvardsson Rasmussen, Jesper
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Eriksson, Per Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    The proteome of perilymph in patients with vestibular schwannoma: A possibility to identify biomarkers for tumor associated hearing loss?2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 6, article id e0198442Article in journal (Refereed)
    Abstract [en]

    Background Due to the surrounding bone, the human inner ear is relatively inaccessible and difficult to reach for cellular and molecular analyses. However, these types of investigations are needed to better understand the etiology, pathophysiology and progression of several inner ear disorders. Moreover, the fluid from the inner ear cannot be sampled for micro-chemical analyses from healthy individuals in vivo. Therefore, in the present paper, we studied patients with vestibular schwannoma (VS) undergoing trans-labyrinthine surgery (TLS). Our primary aim was to identify perilymph proteins in patients with VS on an individual level. Our second aim was to investigate the proteins identified at a functional level and our final aim was to search for biological markers for tumor-associated hearing loss and tumor diameter. Methods and findings Sixteen patients underwent TLS for sporadic VS. Perilymph was aspirated through the round window before opening the labyrinth. One sample was contaminated and excluded resulting in 15 usable samples. Perilymph samples were analyzed with an online tandem LTQ-Orbitrap mass spectrometer. Data were analyzed with MaxQuant software to identify the total number of proteins and to quantify proteins in individual samples. Protein function was analyzed using the PANTHER Overrepresentation tool. Associations between perilymph protein content, clinical parameters, tumor-associated hearing loss and tumor diameter were assessed using Random Forest and Boruta. In total, 314 proteins were identified; 60 in all 15 patients and 130 proteins only once in 15 patients. Ninety-one proteins were detected in at least 12 out of 15 patients. Random Forest followed by Boruta analysis confirmed that alpha-2-HS-glycoprotein (P02765) was an independent variable for tumor-associated hearing loss. In addition, functional analysis showed that numerous processes were significantly increased in the perilymph. The top three enriched biological processes were: 1) secondary metabolic processes; 2) complement activation and 3) cell recognition. Conclusions The proteome of perilymph in patients with vestibular schwannoma has an inter-individual stable section. However, even in a cohort with homogenous disease, the variation between individuals represented the majority of the detected proteins. Alpha-2-HS-glycoprotein, P02765, was shown to be an independent variable for tumor-associated hearing loss, a finding that needs to be verified in other studies. In pathway analysis perilymph had highly enriched functions, particularly in terms of increased immune and metabolic processes.

  • 30. Engmér, Cecilia
    et al.
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Bagger-Sjöbäck, Dan
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Immunodefense of the round window2008In: The Laryngoscope, ISSN 0023-852X, E-ISSN 1531-4995, Vol. 118, no 6, p. 1057-62Article in journal (Refereed)
    Abstract [en]

    A systematic analysis using serial sectioning of the round window membrane (RWM) in the cynomolgus monkey was performed. Light and transmission electron microscopy (LM and TEM) revealed that the RWM rim may be endowed with gland-like structures with glyco-protein material secernated into the window niche. This was detected in one third of the specimens. The secreted material displayed waste material and scavenger cells. There was also a rich network of capillaries, lymph channels, and sinusoidal veins containing leukocytes. Their abluminal surfaces displayed mature plasma cells and monocytes. These findings suggest that in certain primates the middle ear may have developed specific immunoprotective means for disposal of foreign and noxious substances before they reach the inner ear.

  • 31.
    Erixon, Elsa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Köbler, Susanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Cochlear implantation and hearing preservation: results in 21 consecutively operated patients using the round window approach2012In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 132, no 9, p. 923-931Article in journal (Refereed)
    Abstract [en]

    Conclusion:

    Prevalent hearing conservation may be achieved after round window (RW) cochlear implantation using soft and flexible electrode arrays if variations of RW anatomy, topography, and facial nerve position are considered. The most favorable electrode insertion depth remains to be established.

    Objectives:

    We assessed the incidence of cochlear function after cochlear implant (CI) electrode insertion through the RW in our first 21 consecutively operated patients aimed at hearing conservation.

    Methods:

    Eleven patients had a preoperative low frequency hearing suitable for electro-acoustic stimulation. Hearing was preserved in an additional nine patients at their request with the intention to use full frequency CI stimulation. Anatomic variations of the RW were carefully considered using our temporal bone collection of micro-dissected ears. Electrode extension was assessed on X-ray by measuring the insertion angle of the first electrode and intra-cochlear length and correlated with audiometric data.

    Results:

    There was no incidence of total loss of residual hearing in any of the patients. A slight deterioration of low frequency thresholds occurred in some patients. Mean hearing loss at 125-500 Hz was 14.4 dB at 1 month following surgery and 15.6 dB after 1 year. Insertion angle (300-540°) and depth (17.5-28.5 mm) were not statistically correlated to hearing loss.

  • 32.
    Erixon, Elsa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Hearing and Patient Satisfaction Among 19 Patients Who Received Implants Intended for Hybrid Hearing: A Two-Year Follow-Up2015In: Ear and Hearing, ISSN 0196-0202, E-ISSN 1538-4667, Vol. 36, no 5, p. E271-E278Article in journal (Refereed)
    Abstract [en]

    Objectives: To measure patient satisfaction and correlate to hearing results in partially deaf patients, after hearing preservation cochlear implant surgery with hybrid hearing strategy, and to evaluate the stability of residual low-frequency hearing (LFH) over time. Design: A patient satisfaction survey and a retrospective, 2-year follow-up journal study. Nineteen partially deaf patients intended for hybrid hearing responded to a questionnaire when they had used their cochlear implants for at least a year. The questionnaire consisted of the International Outcome Inventory for Hearing Aids, EuroQol Group visual analogue scale and nine questions about hybrid hearing. Pure-tone audiometry, monosyllables, and hearing in noise test results from the patients' medical records were evaluated and compared with the results from the patient satisfaction survey. Results: All of the patients were satisfied with their CIs. The mean International Outcome Inventory for Hearing Aids score was 29. The CIs provided a major contribution to the speech comprehension of these partially deaf patients. Two years after surgery, the patients' mean binaural score on tests of monosyllables was 58%, and the mean signal to noise ratio was 4.6 dB. We observed ongoing deteriorations in the residual hearing of the operated ears that surpassed the deteriorations observed in the contralateral ears. One month after surgery, the LFH loss (125-500 Hz) was 17 dB, and after 2 years, this loss was 24 dB compared with 5 dB in the nonoperated ear. There were no significant correlations between preserved LFH and patient satisfaction or speech perception results. Conclusions: Electric stimulation provided a major contribution to speech comprehension of partially deaf patients. The gain reached in speech understanding widely exceeded the downside in losing some residual hearing. All the patients showed a high degree of satisfaction with their CIs regardless of varying hearing preservation.

  • 33.
    Erixon, Elsa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    How to predict cochlear length before cochlear implantation surgery2013In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 133, no 12, p. 1258-1265Article in journal (Refereed)
    Abstract [en]

    Conclusions: The basal turn diameter of the human cochlea predicts the outer wall length of the basal and two first turns relatively well but there was less correlation for the total cochlear length. The linear regression graph defines the length of the basal turn within an error of +/- 1 mm and could be used clinically to distinguish small and large cochleae. Objective: The human cochlea varies in size. The preoperative assessment of cochlear length can be crucial for non-traumatic electrode insertion and hearing preservation. In this study, we estimated the external cochlear wall length by assessing the basal turn diameter. Methods: A total of 51 non-selected, human inner ear moulds were analysed. A line was drawn from the midpoint of the round window through the cochlear mid-portion to the opposite side (A) and correlated to the cochlear turn lengths. Linear regression analyses were carried out. Results: Mean diameter A was 9.3 mm. The mean basal turn length was 22.8 mm, the two first turns were 35.1 mm and the total length was 41.2 mm. Linear regression analyses indicated a coefficient of determination (R-2) of 0.74 for diameter A and the basal turn length, R-2 = 0.70 for the two-turn length and R-2 = 0.39 for the total length.

  • 34. Felder, E
    et al.
    Kanonier, G
    Scholtz, A
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Schrott-Fischer, A
    Quantitative evaluation of cochlear neurons and computer-aided three-dimensional reconstruction of spiral ganglion cells in humans with a peripheral loss of nerve fibres1997In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 105, no 1-2, p. 183-190Article in journal (Refereed)
    Abstract [en]

    Quantitative data on human cochlear neuronal elements were collected from various regions in five patients with high-tone hearing loss due to presbycusis and in two patients with normal hearing. The number of nerve fibers was assessed in the spiral lamina and in the inner acoustic meatus together with counts of spiral ganglion cells. The results show that the number of neurons decreased peripherally, i.e., with increasing distance from the central nervous system in patients with high-tone hearing loss due to presbycusis. In two patients with normal hearing no significant difference in the number of neurons was found in the lamina spiralis as compared to the inner acoustic canal. Computer-aided 3-dimensional reconstruction of the human spiral ganglion displayed large bipolar neurons (type I cells), but also large ganglion cells with one missing axon. The results may indicate that a slow retrograde degeneration occurs from the periphery towards the spiral ganglion in presbycusis. Transmission electron microscopy analysis of freshly fixed human spiral ganglions displayed interneural connections. It is speculated whether a trophic supply from other neurons at the level of the spiral ganglion can prevent or delay further degeneration of the central axon.

  • 35.
    Friberg, Ulla
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Rask-Andersen, Helge
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Vascular occlusion in the endolymphatic sac in Ménière's disease2002In: Annals of Otology, Rhinology & Laryngology, Vol. 111, p. 237-Article in journal (Refereed)
  • 36.
    Frick, Claudia
    et al.
    Department of Otolaryngology, Head and Neck Surgery, Tübingen Hearing Research Centre, Eberhard Karls University Tübingen, DE-72076 Tübingen, Germany.
    Müller, Marcus
    Department of Otolaryngology, Head and Neck Surgery, Tübingen Hearing Research Centre, Eberhard Karls University Tübingen, DE-72076 Tübingen, Germany.
    Wank, Ute
    EMC Microcollect GmbH, DE-72070 Tubingen, Germany.
    Tropitzsch, Anke
    Department of Otolaryngology, Head and Neck Surgery, Tübingen Hearing Research Centre, Eberhard Karls University Tübingen, DE-72076 Tübingen, Germany.
    Kramer, Benedikt
    Department of Otolaryngology, Head and Neck Surgery, Tübingen Hearing Research Centre, Eberhard Karls University Tübingen, DE-72076 Tübingen, Germany.
    Senn, Pascal
    Univ Hosp Geneva, HUG, Serv Otorhinolaryngol Head & Neck Surg, Dept Clin Neurosci, CH-1211 Geneva 14, Switzerland.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Wiesmüller, Karl-Heinz
    Löwenheim, Hubert
    Department of Otolaryngology, Head and Neck Surgery, Tübingen Hearing Research Centre, Eberhard Karls University Tübingen, DE-72076 Tübingen, Germany.
    Biofunctionalized peptide-based hydrogels provide permissive scaffolds to attract neurite outgrowth from spiral ganglion neurons2017In: Colloids and Surfaces B: Biointerfaces, ISSN 0927-7765, E-ISSN 1873-4367, Vol. 149, p. 105-114Article in journal (Refereed)
    Abstract [en]

    Cochlear implants (CI) allow for hearing rehabilitation in patients with sensorineural hearing loss or deafness. Restricted CI performance results from the spatial gap between spiral ganglion neurons and the CI, causing current spread that limits spatially restricted stimulation and impairs frequency resolution. This may be substantially improved by guiding peripheral processes of spiral ganglion neurons towards and onto the CI electrode contacts. An injectable, peptide-based hydrogel was developed which may provide a permissive scaffold to facilitate neurite growth towards the CI. To test hydrogel capacity to attract spiral ganglion neurites, neurite outgrowth was quantified in an in vitro model using a custom-designed hydrogel scaffold and PuraMatrix(®). Neurite attachment to native hydrogels is poor, but significantly improved by incorporation of brain-derived neurotrophic factor (BDNF), covalent coupling of the bioactive laminin epitope IKVAV and the incorporation a full length laminin to hydrogel scaffolds. Incorporation of full length laminin protein into a novel custom-designed biofunctionalized hydrogel (IKVAV-GGG-SIINFEKL) allows for neurite outgrowth into the hydrogel scaffold. The study demonstrates that peptide-based hydrogels can be specifically biofunctionalized to provide a permissive scaffold to attract neurite outgrowth from spiral ganglion neurons. Such biomaterials appear suitable to bridge the spatial gap between neurons and the CI.

  • 37.
    Giese, Dina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Carotid Artery Compression Caused by the Cochlea2015In: Otology and Neurotology, ISSN 1531-7129, E-ISSN 1537-4505, Vol. 36, no 7, p. 1275-1278Article in journal (Refereed)
    Abstract [en]

    Hypothesis We investigated the possible interference between the human internal carotid artery and the cochlea. Background The cochlea and the internal carotid artery (ICA) are anatomically closely related in the human temporal bone. The intimacy may even result in functional interferences. Methods Here, we analyzed 324 human plastic inner ear corrosion casts including the ICA canal and jugular bulb. Results Results showed that in 23% (14 cases), the cochlea caused physical impression in the carotid canal (CA) with luminal restriction. In one case, there was no separation between the CC and the basal turn of the cochlea. The distance between the CC and the cochlea varied between 0 and 1 mm among these 14 specimens. The lumen restriction of the CC in the pyramid-axial projection varied between 39% and 79%. Conclusion We speculate that the reduction in ICA canal lumen size caused by the cochlea may form a predilection site for intratemporal ICA plaque formation and therefore be clinically relevant.

  • 38.
    Glueckert, R.
    et al.
    Med Univ Innsbruck, Dept Otolaryngol, Innsbruck, Austria;Univ Clin Ear Nose & Throat Med Innsbruck, Univ Clin Innsbruck, Tirol Kliniken, Innsbruck, Austria.
    Chacko, L. Johnson
    Med Univ Innsbruck, Dept Otolaryngol, Innsbruck, Austria.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Liu, Wei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Handschuh, S.
    Univ Vet Med, VetImaging, VetCore Facil Res, Vienna, Austria.
    Schrott-Fischer, A.
    Med Univ Innsbruck, Dept Otolaryngol, Innsbruck, Austria.
    Anatomical basis of drug delivery to the inner ear2018In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 368, p. 10-27Article, review/survey (Refereed)
    Abstract [en]

    The isolated anatomical position and blood-labyrinth barrier hampers systemic drug delivery to the mammalian inner ear. Intratympanic placement of drugs and permeation via the round-and oval window are established methods for local pharmaceutical treatment. Mechanisms of drug uptake and pathways for distribution within the inner ear are hard to predict. The complex microanatomy with fluid filled spaces separated by tight-and leaky barriers compose various compartments that connect via active and passive transport mechanisms. Here we provide a review on the inner ear architecture at light-and electron microscopy level, relevant for drug delivery. Focus is laid on the human inner ear architecture. Some new data add information on the human inner ear fluid spaces generated with high resolution microcomputed tomography at 15 urn resolution. Perilymphatic spaces are connected with the central modiolus by active transport mechanisms of mesothelial cells that provide access to spiral ganglion neurons. Reports on leaky barriers between scala tympani and the so-called cortilymph compartment likely open the best path for hair cell targeting. The complex barrier system of tight junction proteins such as occludins, claudins and tricellulin isolates the endolymphatic space for most drugs. Comparison of relevant differences of barriers, target cells and cell types involved in drug spread between main animal models and humans shall provide some translational aspects for inner ear drug applications. (C) 2018 The Authors. Published by Elsevier B.V.

  • 39. Glueckert, Rudolf
    et al.
    Pfaller, Kristian
    Kinnefors, Anders
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Rask-Andersen, Helge
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Schrott-Fischer, Anneliese
    The human spiral ganglion: new insights into ultrastructure, survival rate and implications for cochlear implants.2005In: Audiol Neurootol, ISSN 1420-3030, Vol. 10, no 5, p. 258-73Article in journal (Refereed)
  • 40. Glueckert, Rudolf
    et al.
    Pfaller, Kristian
    Kinnefors, Anders
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Rask-Andersen, Helge
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Schrott-Fischer, Anneliese
    Ultrastructure of the normal human organ of corti. new anatomical findings in surgical specimens.2005In: Acta Otolaryngol, ISSN 0001-6489, Vol. 125, no 5, p. 534-9Article in journal (Refereed)
  • 41. Glueckert, Rudolf
    et al.
    Pfaller, Kristian
    Kinnefors, Anders
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Schrott-Fischer, Anneliese
    Rask-Andersen, Helge
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    High resolution scanning electron microscopy of the human organ of Corti. A study using freshly fixed surgical specimens.2005In: Hear Res, ISSN 0378-5955, Vol. 199, no 1-2, p. 40-56Article in journal (Refereed)
  • 42. Glueckert, Rudolf
    et al.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Sergi, Consolato
    Schmutzhard, Joachim
    Mueller, Bert
    Beckmann, Felix
    Rittinger, Olaf
    Hoefsloot, Lies H.
    Schrott-Fischer, Anneliese
    Janecke, Andreas R.
    Histology and synchrotron radiation-based microtomography of the inner ear in a molecularly confirmed case of CHARGE syndrome2010In: American journal of medical genetics. Part A, ISSN 1552-4825, Vol. 152A, no 3, p. 665-673Article in journal (Refereed)
    Abstract [en]

    CHARGE (Coloboma of the iris or retina, heart defects, atresia of the choanae, retardation of growth and/or development, genital anomalies, ear anomalies) syndrome (OMIM #214800) affects about 1 in 10,000 children and is most often caused by chromodomain helicase DNA-binding protein-7 (CHD7) mutations. Inner ear defects and vestibular abnormalities are particularly common. Specifically, semicircular canal (SCC) hypoplasia/aplasia and the presence of a Mondini malformation can be considered pathognomonic in the context of congenital malformations of the CHARGE syndrome. We obtained a temporal bone (TB) of a patient with CHARGE syndrome who died from bacteremia at 3 months of age. The clinical diagnosis was confirmed in the patient by direct DNA sequencing and the detection of a de novo, truncating CHD7 mutation, c.6169dup (p.R2057fs). We assessed changes of the TB and the degree of neural preservation, which may influence the potential benefit of cochlear implantation. The TB was analyzed using synchrotron radiation-based micro computed tomography, and by light microscopy. The vestibular partition consisted of a rudimentary vestibule with agenesis of the SCCs. The cochlea was hypoplastic with poor or deficient interscaling and shortened (Mondini dysplasia). The organ of Corti had near normal structure and innervation. Modiolus and Rosenthal's canal were hypoplastic with perikarya displaced along the axon bundles into the internal acoustic meatus, which may be explained by the arrest or limited migration and translocation of the cell nuclei into the cochlear tube during development.

  • 43.
    Gunther, Mattias
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Danckwardt-Lillieström, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Gudjonsson, Olafur
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Nyberg, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Kinnefors, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Ekvall, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Surgical Treatment of Patients With Facial Neuromas: A Report of 26 Consecutive Operations2010In: Otology and Neurotology, ISSN 1531-7129, E-ISSN 1537-4505, Vol. 31, no 9, p. 1493-1497Article in journal (Refereed)
    Abstract [en]

    Objective: To analyze surgical treatment and outcome in patients with facial neuromas at a tertiary referral hospital. Study Design: A chart review of 26 patients treated between 1971 and 2006, with questionnaire follow-up ranging from 2 to 19 years. All patients except one were operated with radical tumor removal approaches. Results: Approximately 54% of the patients presented with symptoms related to the VIIth cranial nerve (facial palsy and facial spasm), 58% with symptoms related to the VIIIth cranial nerve (hearing deficit, tinnitus, and vertigo), and 8% related to the Vth cranial nerve (facial pain and facial sensory deficit). Approximately 39% presented with no facial symptoms. Twenty-one patients received a facial nerve graft from the greater auricular nerve or the sural nerve; 1 patient had an accessory-facial anastomosis. One patient had a subtotal tumor removal preserving the facial nerve. Three patients were not grafted. Most tumors (88%) affect the geniculate ganglion. Approximately 82% of the grafted patients regained a House-Brackmann facial nerve function (HB) grade III; 14% regained HB grades IV to V. No serious morbidity or mortality was reported. No recurrences have been reported where a total tumor removal was performed. Conclusion: Surgical removal of facial neuroma is a safe procedure with a low complication rate and a low recurrence rate. First symptoms are diverse and are predominantly derived from the facial and vestibulocochlear nerve. Facial nerve grafting is reliable, giving the patient an acceptable facial nerve function (HB III).

  • 44. Guo, Rui
    et al.
    Zhang, HongLei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Chen, Wei
    Zhu, XiaoQuan
    Liu, Wei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    The inferior cochlear vein: surgical aspects in cochlear implantation2016In: European Archives of Oto-Rhino-Laryngology, ISSN 0937-4477, E-ISSN 1434-4726, Vol. 273, no 2, p. 355-361Article in journal (Refereed)
    Abstract [en]

    The patency of the inferior cochlear vein (ICV) may be challenged in cochlear implantation (CI) due to its location near the round window (RW). This may be essential to consider during selection of different trajectories for electrode insertion aiming at preserving residual hearing. Venous blood from the human cochlea is drained through the ICV. The vein also drains blood from the modiolus containing the spiral ganglion neurons. Surgical interference with this vein could cause neural damage influencing CI outcome. We analyzed the topographical relationship between the RW and ICV bony channel and cochlear aqueduct (CA) from a surgical standpoint. Archival human temporal bones were further microdissected to visualize the CA and its accessory canals (AC1 and AC2). This was combined with examinations of plastic and silicone molds of the human labyrinth. Metric analyses were made using photo stereomicroscopy documenting the proximal portion of the AC1, the internal aperture of the CA and the RW. The mean distance between the AC1 and the anterior rim of the RW was 0.81 mm in bone specimens and 0.67 mm assessed in corrosion casts. The AC1 runs from the floor of the scala tympani through the otic capsule passing parallel to the CA to the posterior cranial fossa. The mean distance between the CA and AC1 canal was 0.31 and 0.25 mm, respectively.

  • 45. Hanner, Per
    et al.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Lange, Stefan
    Jennische, Eva
    Antisecretory factor-inducing therapy improves the clinical outcome in patients with Meniere's disease2010In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 130, no 2, p. 223-227Article in journal (Refereed)
    Abstract [en]

    Conclusion: Intake of antisecretory factor (AF)-inducing SPC-flakes (R) significantly reduced vertigo in patients suffering from Meniere's disease (MD). The positive effect may be due to a modulation of the transport of water and ions in the endolymphatic space. Objective: To evaluate the effects of a 3-month treatment period with SPC-flakes (R) in patients suffering from MD. Patients and methods: A prospective, double-blind, placebo-controlled study was performed. A total of 51 adult patients with MD were included in the study: 27 subjects treated with SPC-flakes (R) and 24 subjects with control cereals. The patients received SPC-flakes (R) or control cereals (I g per kg body weight per 24 h in two servings) for 3 months. Otoneurological examinations were carried out before and after this period. Results: The severity of MD was classified according to the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) grading system. Fourteen of the 27 patients randomized to intake of the AF-inducing SPC-flakes (R) reported decreased vertigo, compared with 2 of 24 in the control group (p < 0.001). No consistent change in the otoneurological examinations could be demonstrated in any of the groups of patients.

  • 46.
    Hayashi, Hisamitsu
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery. Gifu Univ, Grad Sch Med, Dept Otolaryngol, 1-1 Yanagido, Gifu 5011194, Japan.
    Edin, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Li, Hao
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Liu, Wei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    The effect of pulsed electric fields on the electrotactic migration of human neural progenitor cells through the involvement of intracellular calcium signaling2016In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1652, p. 195-203Article in journal (Refereed)
    Abstract [en]

    Endogenous electric fields (EFs) are required for the physiological control of the central nervous system development. Application of the direct current EFs to neural stem cells has been studied for the possibility of stem cell transplantation as one of the therapies for brain injury. EFs generated within the nervous system are often associated with action potentials and synaptic activity, apparently resulting in a pulsed current in nature. The aim of this study is to investigate the effect of pulsed EF, which can reduce the cytotoxicity, on the migration of human neural progenitor cells (hNPCs). We applied the mono-directional pulsed EF with a strength of 250mV/mm to hNPCs for 6h. The migration distance of the hNPCs exposed to pulsed EF was significantly greater compared with the control not exposed to the EF. Pulsed EFs, however, had less of an effect on the migration of the differentiated hNPCs. There was no significant change in the survival of hNPCs after exposure to the pulsed EF. To investigate the role of Ca(2+) signaling in electrotactic migration of hNPCs, pharmacological inhibition of Ca(2+) channels in the EF-exposed cells revealed that the electrotactic migration of hNPCs exposed to Ca(2+) channel blockers was significantly lower compared to the control group. The findings suggest that the pulsed EF induced migration of hNPCs is partly influenced by intracellular Ca(2+) signaling.

  • 47.
    Hayashi, Hisamitsu
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery. Gifu Univ, Grad Sch Med, Dept Otolaryngol, Gifu, Gifu 5011194, Japan.
    Schrott-Fischer, Annelies
    Med Univ Innsbruck, Dept Otolaryngol, A-6020 Innsbruck, Austria.
    Glueckert, Rudolf
    Med Univ Innsbruck, Dept Otolaryngol, A-6020 Innsbruck, Austria.
    Liu, Wei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Salvenmoser, Willi
    Univ Innsbruck, Inst Zool, A-6020 Innsbruck, Austria.
    Santi, Peter
    Univ Minnesota, Dept Otolaryngol, Minneapolis, MN 55455 USA.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Molecular organization and fine structure of the human tectorial membrane: is it replenished?2015In: Cell and Tissue Research, ISSN 0302-766X, E-ISSN 1432-0878, Vol. 362, no 3, p. 513-527Article in journal (Refereed)
    Abstract [en]

    Auditory sensitivity and frequency resolution depend on the physical properties of the basilar membrane in combination with outer hair cell-based amplification in the cochlea. The physiological role of the tectorial membrane (TM) in hair cell transduction has been controversial for decades. New insights into the TM structure and function have been gained from studies of targeted gene disruption. Several missense mutations in genes regulating the human TM structure have been described with phenotypic expressions. Here, we portray the remarkable gradient structure and molecular organization of the human TM. Ultrastructural analysis and confocal immunohistochemistry were performed in freshly fixed human cochleae obtained during surgery. Based on these findings and recent literature, we discuss the role of human TMs in hair cell activation. Moreover, the outcome proposes that the α-tectorin-positive amorphous layer of the human TM is replenished and partly undergoes regeneration during life.

  • 48.
    Hellberg, Victoria
    et al.
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden..
    Gahm, Caroline
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden..
    Ehrsson, Hans
    Karolinska Univ Hosp, Karolinska Pharm, Stockholm, Sweden..
    Liu, Wei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    In Response to Immunohistochemical Localization of OCT2 in the Cochlea of Various Species2016In: The Laryngoscope, ISSN 0023-852X, E-ISSN 1531-4995, Vol. 126, no 6, p. E232-E232Article in journal (Refereed)
  • 49.
    Hellberg, Victoria
    et al.
    Karolinska Univ Hosp, Dept Clin Sci Intervent & Technol, S-14186 Stockholm, Sweden..
    Gahm, Caroline
    Karolinska Univ Hosp, Dept Clin Sci Intervent & Technol, S-14186 Stockholm, Sweden..
    Liu, Wei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Ehrsson, Hans
    Karolinska Univ Hosp, Karolinska Pharm, S-14186 Stockholm, Sweden..
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Immunohistochemical localization of OCT2 in the cochlea of various species2015In: The Laryngoscope, ISSN 0023-852X, E-ISSN 1531-4995, Vol. 125, no 9, p. E320-E325Article in journal (Refereed)
    Abstract [en]

    ObjectiveTo locate the organic cation transporter 2 (OCT2) in the cochlea of three different species and to modulate the ototoxicity of cisplatin in the guinea pig by pretreatment with phenformin, having a known affinity for OCT2. Study DesignImmunohistochemical and in vivo study. MethodsSections from the auditory end organs were subjected to immunohistochemical staining in order to identify OCT2 in cochlea from untreated rats, guinea pigs, and a pig. In the in vivo study, guinea pigs were given phenformin intravenously 30 minutes before cisplatin administration. Electrophysiological hearing thresholds were determined, and hair cells loss was assessed 96 hours later. The total amount of platinum in cochlear tissue was determined using mass spectrometry. ResultsOrganic cation transporter 2 was found in the supporting cells and in type I spiral ganglion cells in the cochlea of all species studied. Pretreatment with phenformin did not reduce the ototoxic side effect of cisplatin. Furthermore, the concentration of platinum in the cochlea was not affected by phenformin. ConclusionsThe localization of OCT2 in the supporting cells and type I spiral ganglion cells suggests that this transport protein is not primarily involved in cisplatin uptake from the systemic circulation. We hypothesize that OCT2 transport intensifies cisplatin ototoxicity via transport mechanisms in alternate compartments of the cochlea. Level of EvidenceN/A. Laryngoscope, 125:E320-E325, 2015

  • 50. Henson, M.M.
    et al.
    Madden, V.J.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Henson, O.W. jr
    Smooth muscle in the annulus fibrosus of the tympanic membrane in bats, rodents, insectivores and humans2005In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 200, no 1-2, p. 29-37Article in journal (Refereed)
    Abstract [en]

    The annulus fibrosus and its attachment to the bony tympanic ring were studied in a series of mammals. In the pallid bat, Antrozous pallidus, there is an extensive plexus of large interconnected blood sinuses in the part of the annulus that borders the tympanic bone. The spaces between the sinuses are packed with smooth muscle cells. Most of the cells have a predominately radial orientation; they extend from the bony tympanic sulcus to a dense collagenous matrix (apical zone) where radially oriented fibers of the pars tensa are confluent with the annulus. The muscles and vessels constitute a myovascular zone. A structurally similar myovascular zone is also present in the European hedgehog. In rodents, the annulus lacks the large interconnected blood sinuses but many small vessels are present. Smooth muscle is concentrated in the broad area of attachment of the annulus to the tympanic bone. In the gerbil, smooth muscle seems to be concentrated in the central part of the width of the annulus where it is attached to bone and radiates toward the tympanic membrane. In humans collections of radially oriented smooth muscle cells were found in several locations. The smooth muscle in all species studied appears to form a rim of contractile elements for the pars tensa. This arrangement suggests a role in controlling blood flow and/or creating and maintaining tension on the tympanic membrane.

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