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von Unge, Magnus
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Publications (10 of 16) Show all publications
Berling Holm, K., Bornefalk Hermansson, A., Knutsson, J. & von Unge, M. (2019). Surgery for Chronic Otitis Media Causes Greater Taste Disturbance Than Surgery for Otosclerosis.. Otology and Neurotology, 40(1), e32-e39
Open this publication in new window or tab >>Surgery for Chronic Otitis Media Causes Greater Taste Disturbance Than Surgery for Otosclerosis.
2019 (English)In: Otology and Neurotology, ISSN 1531-7129, E-ISSN 1537-4505, Vol. 40, no 1, p. e32-e39Article in journal (Refereed) Published
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.

National Category
Otorhinolaryngology
Identifiers
urn:nbn:se:uu:diva-377869 (URN)10.1097/MAO.0000000000002048 (DOI)000457643500011 ()30540698 (PubMedID)
Available from: 2019-02-27 Created: 2019-02-27 Last updated: 2019-03-08Bibliographically approved
Knutsson, J., Priwin, C., Hessen-Soderman, A.-C., Rosenblad, A. & von Unge, M. (2018). A randomized study of four different types of tympanostomy ventilation tubes: Full-term follow-up. International Journal of Pediatric Otorhinolaryngology, 107, 140-144
Open this publication in new window or tab >>A randomized study of four different types of tympanostomy ventilation tubes: Full-term follow-up
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2018 (English)In: International Journal of Pediatric Otorhinolaryngology, ISSN 0165-5876, E-ISSN 1872-8464, Vol. 107, p. 140-144Article in journal (Refereed) Published
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.

Keywords
Ventilation tubes, Tympanostomy tubes, Secretory otitis media, Extrusion, Otorrhea, Occlusion, Complications, Material, Tympanic membrane perforation
National Category
Otorhinolaryngology
Identifiers
urn:nbn:se:uu:diva-351643 (URN)10.1016/j.ijporl.2018.02.012 (DOI)000428492100027 ()29501296 (PubMedID)
Available from: 2018-05-31 Created: 2018-05-31 Last updated: 2018-05-31Bibliographically approved
Niklasson, A., Gladine, K., Ronnblom, A., von Unge, M., Dirckx, J. & Tano, K. (2018). An Optimal Partial Ossicular Prosthesis Should Connect Both to the Tympanic Membrane and Malleus: A Temporal Bone Study Using Laser Doppler Vibrometry. Otology and Neurotology, 39(3), 333-339
Open this publication in new window or tab >>An Optimal Partial Ossicular Prosthesis Should Connect Both to the Tympanic Membrane and Malleus: A Temporal Bone Study Using Laser Doppler Vibrometry
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2018 (English)In: Otology and Neurotology, ISSN 1531-7129, E-ISSN 1537-4505, Vol. 39, no 3, p. 333-339Article in journal (Refereed) Published
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.

Keywords
Laser Doppler vibrometry, Middle ear, Ossiculoplasty
National Category
Otorhinolaryngology
Identifiers
urn:nbn:se:uu:diva-377731 (URN)10.1097/MAO.0000000000001699 (DOI)000457772600021 ()29342039 (PubMedID)
Available from: 2019-02-25 Created: 2019-02-25 Last updated: 2019-02-25Bibliographically approved
Aabel, P., Utheim, T. P., Olstad, O. K., Rask-Andersen, H., Dilley, R. J. & von Unge, M. (2018). Transcription and microRNA Profiling of Cultured Human Tympanic Membrane Epidermal Keratinocytes. Journal of the Association for Research in Otolaryngology, 19(3), 243-260
Open this publication in new window or tab >>Transcription and microRNA Profiling of Cultured Human Tympanic Membrane Epidermal Keratinocytes
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2018 (English)In: 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) Published
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.

Place, publisher, year, edition, pages
SPRINGER, 2018
Keywords
tympanic membrane, gene expression, microRNA, migration, FOXC2, HOX genes
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-357388 (URN)10.1007/s10162-018-0660-1 (DOI)000432985100002 ()29623476 (PubMedID)
Available from: 2018-08-23 Created: 2018-08-23 Last updated: 2018-08-23Bibliographically approved
Liew, L. J., Chen, L. Q., Wang, A. Y., von Unge, M., Atlas, M. D. & Dilley, R. J. (2018). Tympanic Membrane Derived Stem Cell-Like Cultures for Tissue Regeneration. Stem Cells and Development, 27(10), 649-657
Open this publication in new window or tab >>Tympanic Membrane Derived Stem Cell-Like Cultures for Tissue Regeneration
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2018 (English)In: Stem Cells and Development, ISSN 1547-3287, E-ISSN 1557-8534, Vol. 27, no 10, p. 649-657Article in journal (Refereed) Published
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.

Keywords
tympanic membrane, epidermal stem cells, explant culture, integrin 1, cytokeratin 19, culture well inserts
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-354113 (URN)10.1089/scd.2018.0021 (DOI)000430634900001 ()29571277 (PubMedID)
Available from: 2018-06-19 Created: 2018-06-19 Last updated: 2018-06-19Bibliographically approved
Knutsson, J., Kahlin, A. & von Unge, M. (2017). Clinical and audiological short-term and long-term outcomes of fat graft myringoplasty. Acta Oto-Laryngologica, 137(9), 940-944
Open this publication in new window or tab >>Clinical and audiological short-term and long-term outcomes of fat graft myringoplasty
2017 (English)In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 137, no 9, p. 940-944Article in journal (Refereed) Published
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.

Keywords
Tympanic membrane perforation, fat graft myringoplasty, pediatric patients, audiometry, tympanometry, healing result
National Category
Otorhinolaryngology
Identifiers
urn:nbn:se:uu:diva-331903 (URN)10.1080/00016489.2017.1326063 (DOI)000405304900007 ()28537107 (PubMedID)
Available from: 2017-10-24 Created: 2017-10-24 Last updated: 2017-10-24Bibliographically approved
Schart-Moren, N., Mannström, P., Rask-Andersen, H. & von Unge, M. (2017). Effects of mechanical trauma to the human tympanic membrane: an experimental study using transmission electron microscopy. Acta Oto-Laryngologica, 137(9), 928-934
Open this publication in new window or tab >>Effects of mechanical trauma to the human tympanic membrane: an experimental study using transmission electron microscopy
2017 (English)In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 137, no 9, p. 928-934Article in journal (Refereed) Published
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.

Keywords
Human, tympanic membrane, ultrastructure, perforation, healing
National Category
Otorhinolaryngology
Identifiers
urn:nbn:se:uu:diva-331902 (URN)10.1080/00016489.2017.1321139 (DOI)000405304900005 ()000405304900005 (PubMedID)
Available from: 2017-10-24 Created: 2017-10-24 Last updated: 2017-10-24Bibliographically approved
Wang, A. Y., Liew, L. J., Shen, Y., Wang, J. T., von Unge, M. & Dilley, R. J. (2017). In response to the letter to the editor regarding: Rat model of chronic tympanic membrane perforation: Ventilation tube with mitomycin C and dexamethasone [Letter to the editor]. International Journal of Pediatric Otorhinolaryngology, 100, 256-257
Open this publication in new window or tab >>In response to the letter to the editor regarding: Rat model of chronic tympanic membrane perforation: Ventilation tube with mitomycin C and dexamethasone
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2017 (English)In: International Journal of Pediatric Otorhinolaryngology, ISSN 0165-5876, E-ISSN 1872-8464, Vol. 100, p. 256-257Article in journal, Letter (Other academic) Published
National Category
Otorhinolaryngology
Identifiers
urn:nbn:se:uu:diva-346510 (URN)10.1016/j.ijporl.2017.06.033 (DOI)000409153800048 ()28720306 (PubMedID)
Available from: 2018-03-19 Created: 2018-03-19 Last updated: 2018-03-19Bibliographically approved
Gronseth, T., Vestby, L. K., Nesse, L. L., Thoen, E., Habimana, O., von Unge, M. & Silvola, J. T. (2017). Lugol's solution eradicates Staphylococcus aureus biofilm in vitro. International Journal of Pediatric Otorhinolaryngology, 103, 58-64
Open this publication in new window or tab >>Lugol's solution eradicates Staphylococcus aureus biofilm in vitro
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2017 (English)In: International Journal of Pediatric Otorhinolaryngology, ISSN 0165-5876, E-ISSN 1872-8464, Vol. 103, p. 58-64Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Elsevier, 2017
Keywords
Boric acid, Lugol's solution, Acetic acid, Biofilm, Staphylococcus aureus, Confocal laser scanning microscopy
National Category
Otorhinolaryngology
Identifiers
urn:nbn:se:uu:diva-345211 (URN)10.1016/j.ijporl.2017.09.025 (DOI)000423640200013 ()29224767 (PubMedID)
Available from: 2018-03-14 Created: 2018-03-14 Last updated: 2018-03-14Bibliographically approved
Ong, H. T., Redmond, S. L., Marano, R. J., Atlas, M. D., von Unge, M., Aabel, P. & Dilley, R. J. (2017). Paracrine Activity from Adipose-Derived Stem Cells on In Vitro Wound Healing in Human Tympanic Membrane Keratinocytes. Stem Cells and Development, 26(6), 405-418
Open this publication in new window or tab >>Paracrine Activity from Adipose-Derived Stem Cells on In Vitro Wound Healing in Human Tympanic Membrane Keratinocytes
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2017 (English)In: Stem Cells and Development, ISSN 1547-3287, E-ISSN 1557-8534, Vol. 26, no 6, p. 405-418Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
MARY ANN LIEBERT, INC, 2017
Keywords
gene expression, growth factors, MSC, wound healing
National Category
Cell and Molecular Biology Hematology
Identifiers
urn:nbn:se:uu:diva-320928 (URN)10.1089/scd.2016.0204 (DOI)000395585600003 ()28052725 (PubMedID)
Available from: 2017-04-27 Created: 2017-04-27 Last updated: 2018-01-13Bibliographically approved
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