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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.
    Berling Holm, Katarina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Bornefalk Hermansson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Knutsson, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery. Örebro Univ Hosp, Dept Otolaryngol, Örebro, Sweden.
    von Unge, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery. Akershus Univ Hosp, Dept Otorhinolaryngol, Oslo, Norway; Univ Oslo, Oslo, Norway.
    Surgery for Chronic Otitis Media Causes Greater Taste Disturbance Than Surgery for Otosclerosis.2019In: Otology and Neurotology, ISSN 1531-7129, E-ISSN 1537-4505, Vol. 40, no 1, p. e32-e39Article in journal (Refereed)
    Abstract [en]

    Objectives: Patients with otosclerosis more often complain about postoperative taste disturbance than patients with chronic otitis media, which seems paradoxical. We aim to investigate if and potentially why this seems to be the case, since the chorda tympani nerve (CTN) is thought to be severely traumatized less frequently during surgery in the former than in the latter.

    Study Design: Prospective cohort study.

    Setting: Department of Otorhinolaryngology at Hospital of Vastmanland, Vasteras, Sweden.

    Patients: Sixty-five adults undergoing primary middle ear surgery were included. Thirty-seven were operated on for chronic suppurative otitis media with or without cholesteatoma (CSOM) and 28 for otosclerosis.

    Interventions: Middle ear surgery due to otosclerosis or CSOM. Subjective and objective taste measurements and quality of life (QoL) questionnaire.

    Main Outcome Measures: Taste was assessed using electrogustometry (EGM) and the filter paper disc (FPD) method before and up to 1 year after surgery. Questionnaires on taste disturbance, including a visual analogue scale (VAS), and QoL were completed before and up to 1 year after surgery.

    Results: Subjective taste disturbance anytime during the 1-year follow-up were reported by 62 and 46%, respectively. The difference in EGM 1 week after surgery compared with preoperative EGM was significantly greater among CSOM patients than otosclerosis. One year postoperatively, the difference is non-significant.

    Conclusion: Surgery for CSOM causes greater initial and more long-lasting taste disturbances as compared with surgery for otosclerosis. One-year postoperative taste normalizes for both CSOM and otosclerosis patients according to VAS and EGM measurements. No real change in QoL was seen 1-year postoperatively.

    Level of evidence: Level 2 evidence is prospective observational research with an experimental design.

  • 3.
    Berling Holm, Katarina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Knutsson, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    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.
    Papatziamos, Georgios
    Karolinska Univ Hosp, ENT Dept, Stockholm, Sweden.
    Rosenblad, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    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, Dept Otorhinolaryngol, Lorenskog, Norway; Univ Oslo, N-0316 Oslo, Norway.
    Taste disturbance after stapes surgery: an evaluation of frequency, severity, duration, and quality-of-life2017In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 37, no 1, p. 39-43Article in journal (Refereed)
    Abstract [en]

     Conclusion: The incidence of taste disturbance after stapes surgery is high (61.9 %), whereas the majority (94.8 %) recovers within 1 year. More severe surgical nerve trauma caused more disturbance, implying that the nerve should be handled carefully during surgery.

     

    Objectives: Patients operated on for otosclerosis seem more often to complain about post-operative taste disturbance than those operated on for chronic otitis media, although the chorda tympani nerve more seldom becomes maltreated in stapedotomy. These observations seem paradoxical. It is unclear to what extent a post-operative taste disturbance affects the quality-of-life. This study aims to shed light on the occurrence of post-operative taste disturbances, on possible prognostic factors, and to what extent post-operative taste disturbance impairs the quality-of-life.

     

    Methods: One hundred and thirty-four adults undergoing primary stapedotomy were included. Questionnaires on taste disturbance and quality-of-life (SF-36) were answered before and after surgery, until 1 year post-operatively.

     

    Results: Eighty-three (61.9%) study persons reported post-operative taste disturbance. Seven (5.2%) reported persisting disturbance at 1 year. Surgically more traumatized chorda tympani nerves correlated with more severe taste disturbance post-operatively than less traumatized.  Taste disturbance at 1 year post-operatively correlate with a decrease of the physical function domain in the SF-36.

  • 4.
    Gronseth, Torstein
    et al.
    Univ Oslo, Oslo, Norway.;Oslo Univ Hosp, Dept Otolaryngol Head & Neck Surg, Oslo, Norway..
    Vestby, Lene K.
    Norwegian Vet Inst, Oslo, Norway..
    Nesse, Live L.
    Norwegian Vet Inst, Oslo, Norway..
    Thoen, Even
    Norwegian Vet Inst, Oslo, Norway..
    Habimana, Olivier
    Univ Hong Kong, Sch Biol Sci, Pok Fu Lam Rd, Hong Kong, Hong Kong, Peoples R China..
    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, Dept Otolaryngol Head & Neck Surg, Lorenskog, Norway.;Univ Oslo, Campus Ahus, Oslo, Norway..
    Silvola, Juha T.
    Univ Oslo, Oslo, Norway.;Akershus Univ Hosp, Dept Otolaryngol Head & Neck Surg, Lorenskog, Norway.;Univ Oslo, Campus Ahus, Oslo, Norway..
    Lugol's solution eradicates Staphylococcus aureus biofilm in vitro2017In: International Journal of Pediatric Otorhinolaryngology, ISSN 0165-5876, E-ISSN 1872-8464, Vol. 103, p. 58-64Article in journal (Refereed)
    Abstract [en]

    Objectives: The aim of the study was to evaluate the antibacterial efficacy of Lugol's solution, acetic acid, and boric acid against Staphylococcus aureus biofilm. Methods: The efficacy of Lugol's solution 1%, 0.1%, and 0.05%, acetic acid 5% or boric acid 4.7% for treatment of Staphylococcus aureus biofilm in vitro was tested using 30 clinical strains. Susceptibility in the planktonic state was assessed by disk diffusion test. Antiseptic effect on bacteria in biofilm was evaluated by using a,Biofilm-oriented antiseptic test (BOAT) based on metabolic activity, a biofilm bactericidal test based on culturing of surviving bacteria and confocal laser scanning microscopy combined with LIVE/DEAD staining. Results: In the planktonic state, all tested S. aureus strains were susceptible to Lugol's solution and acetic acid, while 27 out of 30 tested strains were susceptible to boric acid. In biofilm the metabolic activity was significantly reduced following exposure to Lugol's solution and 5% acetic acid, while boric acid exposure led to no significant changes in metabolic activities. In biofilm, biocidal activity was observed for Lugol's solution 1% (30/30), 0.1% (30/30), and 0.05% (26/30). Acetic acid and boric acid showed no bactericidal activity in this test. Confocal laser scanning microscopy, assessed in 4/30 strains, revealed significantly fewer viable biofilm bacteria with Lugol's solution (1% p < 0.001, 0.1% p = 0.001 or 0.05% p = 0.001), acetic acid 5% for 10 min (p = 0.001) or 30 min (p = 0.015), but not for acetic acid for 1 min or boric acid. Conclusion: Lugol's solution 1.0% and 0.1% effectively eradicated S. aureus in biofilm and could be an alternative to conventional topical antibiotics where S. aureus biofilm is suspected such as external otitis, pharyngitis and wounds. (C) 2017 Elsevier B.V. All rights reserved.

  • 5.
    Knutsson, J
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    von Unge, M
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Five-year results for use of single-flanged tympanostomy tubes in children2008In: Journal of Laryngology and Otology, ISSN 0022-2151, E-ISSN 1748-5460, Vol. 122, p. 584-589Article in journal (Refereed)
    Abstract [en]

    Aims: To assess the five-year outcome of the use of single-flanged tympanostomy tubes in children,including the time to extrusion, rate of retained tubes and rate of persistent perforation.   Materials and methods: The medical records relating to 640 single-flanged tympanostomy tubesintended for short-term use in paediatric patients were retrospectively reviewed.   Results and analysis: We found that 36.4 per cent of the tubes had extruded within 12 months and 71.0per cent within 24 months. Results showed that 14.1 per cent of the tubes had been removed because ofprolonged retention, with a mean time to removal of 38.9 months. The time to extrusion was longerand the rate of retained tubes was higher than those reported for several other short-term tubes. Wefound that 4.5 per cent of tube insertions had resulted in a persistent perforation, a higher percentagethan previously reported for other tubes intended for short-term use. Within five years of tubeinsertion, 70.5 per cent of the tympanic membranes had normalised.

  • 6.
    Knutsson, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Bagger-Sjöbäck, Dan
    von Unge, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Distribution of different collagen types in the rat's tympanic membrane and its suspending structures2007In: Otology and Neurotology, ISSN 1531-7129, E-ISSN 1537-4505, Vol. 28, no 4, p. 486-491Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:: The objective of the study was to investigate the histological distribution of collagens in the healthy rat's tympanic membrane. METHODS:: Immunohistochemical analysis of collagen type I, II, III, and IV in the tympanic membranes in healthy adult female Sprague-Dawley rats. The staining was semiquantified using light microscopy in a blinded fashion, not knowing what type of collagen the slide had been stained for. RESULTS:: The pars tensa of the tympanic membrane was mainly stained for collagen type II and IV. The fibrous annulus could on immunohistochemistry be subdivided into an inner and an outer portion. The inner portion of the fibrous annulus was mainly stained for collagen type II, whereas the outer portion was most strongly stained for collagen type III and collagen type IV. The test-retest reliability of the semiquantative method was 81%. CONCLUSION:: Collagen type II and IV are the major collagen constituents of the pars tensa of the tympanic membrane. The outer portion of the fibrous annulus has collagen type III and IV as its major constituents, whereas the inner portion is made up of collagen type II.

  • 7.
    Knutsson, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Vasteras Hosp, Dept Otorhinolaryngol, Vasteras, Sweden.
    Kahlin, Annika
    Vasteras Hosp, Dept Otorhinolaryngol, Vasteras, Sweden..
    von Unge, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Vasteras Hosp, Dept Otorhinolaryngol, Vasteras, Sweden.; Akershus Univ Hosp, Dept Otorhinolaryngol, Oslo, Norway.;Univ Oslo, Oslo, Norway..
    Clinical and audiological short-term and long-term outcomes of fat graft myringoplasty2017In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 137, no 9, p. 940-944Article in journal (Refereed)
    Abstract [en]

    Introduction: Results of fat graft myringoplasty are often reported with only short-term follow-up. Audiological results are less commonly reported, as well as long-term follow-up results. Materials and methods: One hundred consecutive patients scheduled for fat graft myringoplasty were included in a prospective cohort study. Clinical and audiological outcomes were assessed at six weeks and one year postoperatively. Results: Perforation sizes ranged from 0.5 to 4 mm. The six-week follow-up showed a total perforation closure rate of 72.9% with a statistically significant (p = .03) higher rate for the pediatric age group (83.0%). 64.4% of all patients were healed at one-year follow-up. Statistical analyses for background factors did not reveal any significant difference in healing rates with regard to patient sex or location or cause of the perforation. The mean preoperative air-conduction (AC) threshold was 25dB with an air-bone gap of 12 dB. At the one-year follow-up the mean air conduction threshold for healed ears was improved to 16.6 dB, still 54.2% of them had a type B tympanogram. Conclusions: Children had a higher perforation closure rate at six-week follow-up than adult patients. Recurrent tympanic membrane perforations were common after initially successful fat graft myringoplasties. Long-term hearing was improved after successful fat graft myringoplasty, resulting in a mean AC threshold of 16.6 dB.

  • 8.
    Knutsson, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Vastmanland Cty Hosp, Dept Otorhinolaryngol, Vasteras, Sweden.;Orebro Univ Hosp, Dept Otolaryngol, Orebro, Sweden..
    Priwin, Claudia
    Sophiahemmet Univ, Dept Otorhinolaryngol, Stockholm, Sweden..
    Hessen-Soderman, Anne-Charlotte
    Cityakuten, Dept Otorhinolaryngol, Stockholm, Sweden.;Karolinska Inst, Div Clin Sci Intervent & Technol, Stockholm, Sweden..
    Rosenblad, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    von Unge, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Vastmanland Cty Hosp, Dept Otorhinolaryngol, Vasteras, Sweden.;Akershus Univ Hosp, Dept Otorhinolaryngol, Campus Ahus, Oslo, Norway.;Univ Oslo, Campus Ahus, Oslo, Norway..
    A randomized study of four different types of tympanostomy ventilation tubes: Full-term follow-up2018In: International Journal of Pediatric Otorhinolaryngology, ISSN 0165-5876, E-ISSN 1872-8464, Vol. 107, p. 140-144Article in journal (Refereed)
    Abstract [en]

    Objective: To evaluate the impact of tympanostomy ventilation tube material (silicone vs fluoroplastic) and shape (short vs long) regarding time to extrusion, occurrence of otorrhea, occlusion, tube removal and occurrence of persistent perforation.

    Methods and material: Four different types of ventilation tubes were used; Long Armstrong tubes, Donaldson tubes, Shepard tubes and straight tubes, representing four specific combinations of VT material (silicone or fluoroplastic) and shape (short, double flanged or long, single flanged). Four hundred children scheduled for bilateral tube insertion were included in a randomized trial. The patients received one type of tube in the right ear and another type in the left ear. The incidence of tube extrusion and complications were monitored post-operatively every third month by an otolaryngologist.

    Results: Twenty-two children were excluded during surgery. Out of the studied 378 children the mean age was 35.3 months. 63.8% were boys. Short tubes extruded earlier than long tubes; hazard ratio (HR) 4.84 (95% CI 3.50-6.69, p < 0.001). Long Armstrong tubes were least prone to extrude. Silicone tubes resulted in significantly longer time to first infection in a VT ear, HR 1.68 (95% CI 1.03-2.76, p = 0.039). Donaldson tubes rendered the longest mean time to first infection (p = 0.025). Infections did not affect tube extrusion rates significantly (p = 0.879). No significant differences were found regarding tube occlusion, tube extraction or persistent perforation.

    Conclusions: Long tubes are less prone to extrude early. Long Armstrong tubes have the least propensity to extrude early. Silicone tubes render significantly longer time to first infection. Donaldson tubes result in least infections. Infection does not affect extrusion rates significantly.

  • 9.
    Liew, Lawrence J.
    et al.
    Univ Western Australia, Sch Med, Ear Sci Ctr, Perth, WA, Australia;Ear Sci Inst Australia, Perth, WA, Australia.
    Chen, Linda Q.
    Ear Sci Inst Australia, Perth, WA, Australia;Murdoch Univ, Sch Vet & Life Sci, Perth, WA, Australia.
    Wang, Allen Y.
    Univ Western Australia, Sch Med, Ear Sci Ctr, Perth, WA, Australia;Ear Sci Inst Australia, Perth, WA, Australia;Sir Charles Gairdner Hosp, Skull Base Surg, Dept Otolaryngol Head & Neck, Perth, 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, Oslo, Norway;Univ Oslo, Oslo, Norway.
    Atlas, Marcus D.
    Univ Western Australia, Sch Med, Ear Sci Ctr, Perth, WA, Australia;Ear Sci Inst Australia, Perth, WA, Australia.
    Dilley, Rodney J.
    Univ Western Australia, Sch Med, Ear Sci Ctr, Perth, WA, Australia;Ear Sci Inst Australia, Perth, WA, Australia;Univ Western Australia, Sch Med, Ctr Cell Therapy & Regenerat Med, Perth, WA, Australia.
    Tympanic Membrane Derived Stem Cell-Like Cultures for Tissue Regeneration2018In: Stem Cells and Development, ISSN 1547-3287, E-ISSN 1557-8534, Vol. 27, no 10, p. 649-657Article in journal (Refereed)
    Abstract [en]

    Epidermal cells with stem cell-like characteristics have been identified in the tympanic membrane (TM) and localized specifically to the umbo and annulus regions. While they have been proposed to play a role in the regeneration of both acute and chronic TM perforations, evidence for the mechanism and regulation of their contribution is not yet described. Indeed, the behavior of these putative stem cells is largely unknown, in part due to a lack of refined methods for efficient cell isolation. In this study, we compared different explant techniques using normal and perforated rat TM tissues and investigated their ex vivo characteristics. TM after perforation in vivo showed increased staining for epidermal stem cell markers integrin 1 and cytokeratin (CK) 19, and for proliferation Ki-67, indicating activation of the proliferative centers. A mixed population of fibroblasts and epithelial cells were isolated from explant cultures. Excised TM umbo implanted on a culture well insert was the most effective technique. Explants made from perforated TM produced cells before those from unperforated TM. More importantly, the implanted TM umbo organoid was capable of producing cells in a continuous manner, allowing subsequent harvest using trypsin. Primary rat TM epithelial cell cultures positive for pancytokeratin had colony forming activity and could be enriched for CK 19-positive cells that were capable of culture expansion by proliferation and cell migration when subject to a wound assay. Taken together, trauma to the TM activated the proliferative centers and prompted early cell production from TM umbo organoid cultures, which produced TM stem cell-like cultures that proved suitable for tissue engineering of the TM.

  • 10.
    Niklasson, Anders
    et al.
    Umea Univ, Dept Clin Sci, Otorhinolaryngol, Umea, Sweden.
    Gladine, Kilian
    Univ Antwerp, Dept Phys, Antwerp, Belgium.
    Ronnblom, Anton
    Umea Univ, Dept Clin Sci, Otorhinolaryngol, Umea, Sweden.
    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, Dept Otorhinolaryngol, Lorenskog, Norway;Univ Oslo, Oslo, Norway.
    Dirckx, Joris
    Univ Antwerp, Dept Phys, Antwerp, Belgium.
    Tano, Krister
    Umea Univ, Dept Clin Sci, Otorhinolaryngol, Umea, Sweden.
    An Optimal Partial Ossicular Prosthesis Should Connect Both to the Tympanic Membrane and Malleus: A Temporal Bone Study Using Laser Doppler Vibrometry2018In: Otology and Neurotology, ISSN 1531-7129, E-ISSN 1537-4505, Vol. 39, no 3, p. 333-339Article in journal (Refereed)
    Abstract [en]

    Objective:To compare stapes vibrations in different partial ossicular replacement prosthesis (PORP) applications.

    Methods: Stapedial vibrations were measured on fresh frozen human temporal bones with laser Doppler vibrometry. Eight different types of common ossiculoplasty methods were compared regarding recovery of stapes vibrations in relation with the normal ossicular chain. The PORPs were divided into three groups: 1) PORPs with the lateral contact only with the tympanic membrane, 2) PORPs with lateral contact only to the malleus handle, and 3) PORPs with lateral contact with both the malleus handle and the tympanic membrane.

    Results: The PORPs with lateral contact only to the malleus handle performed better than the PORPs with lateral contact to the tympanic membrane only at 2 kHZ, but the best recovery was found in the group with contact both to the malleus handle and the tympanic membrane.

    Conclusion: The best sound transmission might be achieved by placing a PORP in contact with both the tympanic membrane and the handle of the malleus.

  • 11.
    Ong, Huan Ting
    et al.
    Ear Sci Inst Australia, Nedlands, WA, Australia.;Murdoch Univ, Sch Vet & Life Sci, Murdoch, WA, Australia..
    Redmond, Sharon L.
    Ear Sci Inst Australia, Nedlands, WA, Australia.;Univ Western Australia, Ear Sci Ctr, Perth, WA, Australia..
    Marano, Robert J.
    Ear Sci Inst Australia, Nedlands, WA, Australia.;Univ Western Australia, Ear Sci Ctr, Perth, WA, Australia..
    Atlas, Marcus D.
    Ear Sci Inst Australia, Nedlands, WA, Australia.;Univ Western Australia, Ear Sci Ctr, Perth, 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, Div Surg, Oslo, Norway.;Univ Oslo, Oslo, Norway..
    Aabel, Peder
    Akershus Univ Hosp, Div Surg, Oslo, Norway.;Univ Oslo, Oslo, Norway..
    Dilley, Rodney J.
    Ear Sci Inst Australia, Nedlands, WA, Australia.;Univ Western Australia, Ear Sci Ctr, Perth, WA, Australia.;Univ Western Australia, Ctr Cell Therapy & Regenerat Med, Perth, WA, Australia..
    Paracrine Activity from Adipose-Derived Stem Cells on In Vitro Wound Healing in Human Tympanic Membrane Keratinocytes2017In: Stem Cells and Development, ISSN 1547-3287, E-ISSN 1557-8534, Vol. 26, no 6, p. 405-418Article in journal (Refereed)
    Abstract [en]

    Stem cell therapies for tympanic membrane repair have shown initial experimental success using mesenchymal stem cells in rat models to promote healing; however, the mechanisms providing this benefit are not known. We investigated in vitro the paracrine effects of human adipose-derived stem cells (ADSCs) on wound healing mechanisms for human tympanic membrane-derived keratinocytes (hTM) and immortalized human keratinocytes (HaCaT). ADSC conditioned media (CMADSC) were assessed for paracrine activity on keratinocyte proliferation and migration, with hypoxic conditions for ADSC culture used to generate contrasting effects on cytokine gene expression. Keratinocytes cultured in CMADSC showed a significant increase in cell number compared to serum-free cultures and further significant increases in hypoxic CMADSC. Assessment of ADSC gene expression on a cytokine array showed a range of wound healing cytokines expressed and under stringent hypoxic and serum-free conditions was upregulated (VEGF A, MMP9, Tissue Factor, PAI-1) or downregulated (CXCL5, CCL7, TNF-). Several of these may contribute to the activity of conditioned media on the keratinocytes with potential applications in TM perforation repair. VEGFA protein was confirmed by immunoassay to be increased in conditioned media. Together with gene regulation associated with hypoxia in ADSCs, this study has provided several strong leads for a stem cell-derived approach to TM wound healing.

  • 12. Rahman, Anisur
    et al.
    Hultcrantz, Malou
    Dirckx, Joris
    von Unge, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Structural and functional properties of the healed tympanic membrane: a long-term follow-up after laser myringotomy2007In: Otology and Neurotology, ISSN 1531-7129, E-ISSN 1537-4505, Vol. 28, no 5, p. 685-691Article in journal (Refereed)
    Abstract [en]

    Hypothesis: The short-term healing scar that forms after experimental laser myringotomy will revert to a normal lamina propria in the long run. The mechanical stiffness will stay normal.

    Background: Recent studies have shown severe structural changes in the fibrous layer in the early course after experimental laser myringotomy, whereas the scar quickly restored the strength of the tympanic membrane (TM). A reorganization of the fiber layer is expected to occur.

    Methods: Potassium titanyl phosphate laser myringotomy was made on one side of the TM in Sprague-Dawley rats. The ear of the other side was untouched and used for control. After half a year of observation, the stiffness and strength of the healed TMs were measured with moiré interferometry and examined with otomicroscopy and light and electron microscopy.

    Results: The interferometry readings showed a slightly reduced strength in the myringotomized and healed TMs. After half a year, still there were immense structural changes including increased thickness over a wide area of the pars tensa with increased amounts of fibers. An obvious reorganization of the fiber layer was lacking.

    Conclusion: Laser myringotomy causes profound, long-standing, or permanent structural changes in the lamina propria of the pars tensa, whereas the strength of the TM may become slightly reduced.

  • 13. Rahman, Anisur
    et al.
    von Unge, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Olivius, Petri
    Dirckx, Joris
    Hultcrantz, Malou
    Healing time, long-term result and effects of stem cell treatment in acute tympanic membrane perforation2007In: International Journal of Pediatric Otorhinolaryngology, ISSN 0165-5876, E-ISSN 1872-8464, Vol. 71, no 7, p. 1129-1137Article in journal (Refereed)
    Abstract [en]

    Objective

    The incidence of otitis media in children between the age of 2 and 6 years is well documented. Repeated attacks may cause acute and chronic perforations. The surgical treatment for repairing chronic perforation is quite uncomfortable for the patients of this age group because of the invasiveness of this treatment. The aim of this study was to determine the long-term influence of embryonic stem cells on acute perforations and the effect of gelatin as a vehicle for applied stem cells. The possibility of teratogenic effects of the stem cells was also observed.

    Methods

    Bilateral laser myringotomy was performed in 17 adult Sprague–Dawley rats, divided into two groups. Gelatin, a substance suitable as vehicle for bioactive material was used bilaterally around the perforation in group A, to serve as a scaffold for repairing tissue. The stem cells were used in the right tympanic membrane perforation leaving the left tympanic membrane as a control. The animals in group B received the same treatment except for the use of gelatin and in addition received an immuno-suppressive agent. After half a year of observation the mechanical stiffness of the tympanic membrane was measured by moiré interferometry for group B and the morphological study was performed by light microscopy for both groups A and B and electron microscopy for group A.

    Results

    Stem cell treated ears did not show any enhanced healing of the perforation although a marked thickening of the lamina propria was observed compared with control group. After half a year the strength and the stiffness of the tympanic membrane was almost the same for both treated and untreated ears. No evidence of teratoma was found after half a year.

    Conclusion

    This study suggests that the stem cells stimulate the proliferation of connective tissue and fibers in the lamina propria, possibly mediated by secreted substances, although the stiffness properties do not seem to be altered. The use of gelatin does not seem to enhance the healing process of the tympanic membrane perforation.

  • 14.
    Schart-Moren, Nadine
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery. Uppsala Univ, Uppsala Univ Hosp, Dept Head & Neck Surg, Uppsala, Sweden..
    Mannström, Paula
    Karolinska Inst, Dept Clin Neurosci, 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. Uppsala Univ, Uppsala Univ Hosp, Dept Head & Neck Surg, Uppsala, Sweden..
    von Unge, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Univ Oslo, Akershus Univ Hosp, Dept ENT, Oslo, Norway..
    Effects of mechanical trauma to the human tympanic membrane: an experimental study using transmission electron microscopy2017In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 137, no 9, p. 928-934Article in journal (Refereed)
    Abstract [en]

    Hypothesis: To examine the cellular events following induced superficial lesions of the human tympanic membrane (TM). Such information could lead to enhanced appreciation of repair mechanisms and novel strategies to restore TM perforations. Background: Persistent perforation of the TM in chronic otitis media is a major global health problem and frequently necessitates surgical intervention. Most TM perforations heal spontaneously and swiftly, but sometimes healing fails. The underlying mechanisms and the reason for incomplete repair are often elusive, although some mechanisms have been proposed. Methods: Here, five healthy adult human TMs were sampled during vestibular schwannoma surgery. Three days before harvesting, three TMs were superficially lesioned, including the epithelial and sub-epithelial layers, using a needle and two TMs served as controls. Light and transmission electron microscopy were performed. Results: Surrounding lesion showed distinct ultrastructural changes. This included a keratinocyte frontier with electron-dense cells with abundant ribosomes and nuclei metamorphosis. Beneath, were activated fibroblasts and invaded/transformed free cells and signs of increased transcellular activity of adjacent blood vessels. Conclusions: The study describes dynamic morphological events of a human lesioned TM. The human model may be used for further investigations and understanding of TM healing mechanisms.

  • 15.
    Wang, Allen Y.
    et al.
    Univ Western Australia, Sch Surg, Ear Sci Ctr, Perth, WA, Australia.;Ear Sci Inst Australia, Perth, WA, Australia.;Sir Charles Gairdner Hosp, Dept Otolaryngol Head & Neck, Skull Base Surg, Perth, WA, Australia..
    Liew, Lawrence J.
    Univ Western Australia, Sch Surg, Ear Sci Ctr, Perth, WA, Australia.;Ear Sci Inst Australia, Perth, WA, Australia..
    Shen, Yi
    Univ Western Australia, Sch Surg, Ear Sci Ctr, Perth, WA, Australia.;Ear Sci Inst Australia, Perth, WA, Australia.;Ningbo Lihuili Hosp, Ningbo Med Ctr, Dept Otolaryngol Head & Neck Surg, Ningbo, Zhejiang, Peoples R China..
    Wang, Jeffrey T.
    Univ Western Australia, Sch Surg, Ear Sci Ctr, Perth, 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, Lorenskog, Norway.;Univ Oslo, N-0316 Oslo, Norway..
    Atlas, Marcus D.
    Univ Western Australia, Sch Surg, Ear Sci Ctr, Perth, WA, Australia.;Ear Sci Inst Australia, Perth, WA, Australia.;Sir Charles Gairdner Hosp, Dept Otolaryngol Head & Neck, Skull Base Surg, Perth, WA, Australia..
    Dilley, Rodney J.
    Univ Western Australia, Sch Surg, Ear Sci Ctr, Perth, WA, Australia.;Ear Sci Inst Australia, Perth, WA, Australia..
    Rat model of chronic tympanic membrane perforation: A longitudinal histological evaluation of underlying mechanisms2017In: International Journal of Pediatric Otorhinolaryngology, ISSN 0165-5876, E-ISSN 1872-8464, Vol. 93, p. 88-96Article in journal (Refereed)
    Abstract [en]

    Objective: To evaluate histologically the progressive development and underlying mechanisms of chronic tympanic membrane perforation (TMP) in a rat model using a two-weeks ventilation tube (VT) treatment combined with topical application of mitomycin Cidexamethasone (VT-MID), compared with normal tympanic membrane and acute TMPs. Methods: Fifty male Sprague-Dawley rats were divided into three experimental groups: a normal control group (n = 5), an acute TMP group (n = 5) (i.e. 3 days post-myringotomy) and a VT-M/D group (n = 40). The TMs were regularly assessed by otoscopy. The normal control animals were sacrificed on day 0 and the acute TMP group was sacrificed 3 days post-myringotomy for histological and immunohistochemical evaluations. The VT-M/D group was sacrificed at various time points - 14 and 17 days, 3, 4, 6, 8 and 10 weeks. Results: On longitudinal histological examination, compared with normal TM and acute TMP, the perforation edges at the later time points illustrated thickened stratified squamous epithelium rimming around the edges, significant increase in keratin and collagen deposition, increased macrophage infiltration as well as reduced cellular proliferation. Three phases of TMP healing process were identified the acute healing phase (3-17 days), the transition phase (3-4 weeks) and the chronic phase (6-10 weeks). Conclusion: Based on the histological results of this study, the progressive development of chronic TMPs appeared to be associated with increased epidermal thickening, collagen and keratin deposition, macrophage infiltration and reduced cellular proliferation. After the 3-4 weeks of transition phase, the TMPs seemed to have transformed into a non-healing chronic TMP between 6 and 10 weeks. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

  • 16.
    Wang, Allen Y.
    et al.
    Univ Western Australia, Sch Surg, Ear Sci Ctr, Perth, WA, Australia.;Ear Sci Inst Australia, Perth, WA, Australia.;Sir Charles Gairdner Hosp, Dept Otolaryngol Head & Neck, Skull Base Surg, Perth, WA, Australia..
    Liew, Lawrence J.
    Univ Western Australia, Sch Surg, Ear Sci Ctr, Perth, WA, Australia.;Ear Sci Inst Australia, Perth, WA, Australia..
    Shen, Yi
    Univ Western Australia, Sch Surg, Ear Sci Ctr, Perth, WA, Australia.;Ear Sci Inst Australia, Perth, WA, Australia.;Ningbo Lihuili Hosp, Ningbo Med Ctr, Dept Otolaryngol Head & Neck Surg, Ningbo, Zhejiang, Peoples R China..
    Wang, Jeffrey T.
    Univ Western Australia, Sch Surg, Ear Sci Ctr, Perth, 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, Oslo, Norway.;Univ Oslo, Oslo, Norway.
    Dilley, Rodney J.
    Univ Western Australia, Sch Surg, Ear Sci Ctr, Perth, WA, Australia.;Ear Sci Inst Australia, Perth, WA, Australia..
    In response to the letter to the editor regarding: Rat model of chronic tympanic membrane perforation: Ventilation tube with mitomycin C and dexamethasone2017In: International Journal of Pediatric Otorhinolaryngology, ISSN 0165-5876, E-ISSN 1872-8464, Vol. 100, p. 256-257Article in journal (Other academic)
1 - 16 of 16
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