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  • 151.
    Melin, Molly
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Jämställd tillgång till vård för patienter med munhålecancer och orofarynxcancer?2015Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 152.
    Midendal, Jennie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Komplikationer och re-operationer efter myringoplastik. Analys av nationellt kvalitetsregister.2015Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 153.
    Msghina, Sewit
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Patient satisfaction with Bone anchored hearing aid operations in Norrbotten: Soft tissue preserving method2016Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 154. Musk, G. C.
    et al.
    Kershaw, H.
    Tano, Krister
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Niklasson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    von Unge, M.
    Dilley, R. J.
    Reactions to Gudair® vaccination identified in sheep used for biomedical research2019In: Australian Veterinary Journal, ISSN 0005-0423, E-ISSN 1751-0813, Vol. 97, no 3, p. 56-60Article in journal (Refereed)
    Abstract [en]

    Case report: We report Gudair (R) vaccination (against ovine Johne's disease, Mycobacterium avium subsp. paratuberculosis) site reactions in sheep used as a surgical model in biomedical research and discuss the actual and potential impact these lesions may have on surgical procedures, particularly in otology. Nine female Merino-cross sheep (Ovis aries) were enrolled in a project designed to investigate the healing capabilities of the malleus bone in the middle ear. The sheep were 12-18 months of age. Eight sheep had lesions near the base of the right ear that were discovered when surgery was performed. The size of the lesions varied and all lesions had a thick capsule containing various amount of caseous material. Two lesions had a draining tract where purulent material was apparent at the lowest point. The prescapular lymph nodes were not palpable in any of the sheep. Aerobic growth of various organisms was reported from four sheep lesions when the purulent material was transferred to a broth media. Histopathological examination revealed intralesional Mycobacteria and focal caseous necrosis or granulomatous dermatitis and cellulitis in seven of the eight lesions. Mild necrotising to granulomatous dermatitis and cellulitis was described in the lesion where organisms were not found. Conclusions: The lesions were confirmed at the end of the study to be associated with the vaccination and did not cause any known adverse effects on the research. However, it is important to acknowledge the risk of contamination these lesions could have on a sterile surgical site.

  • 155. Myburgh, Hermanus C.
    et al.
    Jose, Stacy
    Swanepoel, De Wet
    Laurent, Claude
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology. Department of Audiology and Speech-Language Pathology, University of Pretoria, Pretoria, South Africa.
    Towards low cost automated smartphone- and cloud-based otitis media diagnosis2018In: Biomedical Signal Processing and Control, ISSN 1746-8094, E-ISSN 1746-8108, Vol. 39, p. 34-52Article in journal (Refereed)
    Abstract [en]

    Odds media is one of the most common childhood illnesses. Access to ear specialists and specialist equipment is rudimentary in many third world countries, and general practitioners do not always have enough experience in diagnosing the different otitis medias. In this paper a system recently proposed by three of the authors for automated diagnosis of middle ear pathology, or otitis media, is extended to enable the use of the system on a smartphone with an Internet connection. In addition, a neural network is also proposed in the current system as a classifier, and compared to a decision tree similar to what was proposed before. The system is able to diagnose with high accuracy (1) a normal tympanic membrane, (2) obstructing wax or foreign bodies in the external ear canal (W/O), (3) acute otitis media (AOM), (4) otitis media with effusion (OME) and (5) chronic suppurative otitis media (CSOM). The average classification accuracy of the proposed system is 81.58% (decision tree) and 86.84% (neural network) for images captured with commercial video-otoscopes, using 80% of the 389 images for training, and 20% for testing and validation. 

  • 156. Myburgh, Hermanus C.
    et al.
    van Zijl, Willemien H.
    Swanepoel, DeWet
    Hellstrom, Sten
    Laurent, Claude
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology. Department of Speech-Language Pathology and Audiology, University of Pretoria, Pretoria, South Africa.
    Otitis Media Diagnosis for Developing Countries Using Tympanic Membrane Image-Analysis2016In: EBioMedicine, ISSN 0360-0637, E-ISSN 2352-3964, Vol. 5, p. 156-160Article in journal (Refereed)
    Abstract [en]

    Background: Otitis media is one of the most common childhood diseases worldwide, but because of lack of doctors and health personnel in developing countries it is often misdiagnosed or not diagnosed at all. This may lead to serious, and life-threatening complications. There is, thus a need for an automated computer based image-analyzing system that could assist in making accurate otitis media diagnoses anywhere. Methods: A method for automated diagnosis of otitis media is proposed. The method uses image-processing techniques to classify otitis media. The system is trained using high quality pre-assessed images of tympanic membranes, captured by digital video-otoscopes, and classifies undiagnosed images into five otitis media categories based on predefined signs. Several verification tests analyzed the classification capability of the method. Findings: An accuracy of 80.6% was achieved for images taken with commercial video-otoscopes, while an accuracy of 78.7% was achieved for images captured on-site with a low cost custom-made video-otoscope. Interpretation: The high accuracy of the proposed otitis media classification system compares well with the classification accuracy of general practitioners and pediatricians (similar to 64% to 80%) using traditional otoscopes, and therefore holds promise for the future in making automated diagnosis of otitis media in medically underserved populations. (C) 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

  • 157.
    Månsson, Sofia
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Evaluation of the one-stop neck lump clinic at Sunderby hospital2018Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 158.
    Möller, Christian
    et al.
    Umeå University, Faculty of Medicine, Clinical Sciences, Otorhinolaryngology. Umeå University, Faculty of Medicine, Clinical Sciences, Paediatrics.
    Broström, Göran
    Umeå University, Faculty of Social Sciences, Department of Statistics.
    A new method to relate symptom scores with pollen counts, A dynamic model for comparison of treatments of allergy1989In: Grana, ISSN 0017-3134, E-ISSN 1651-2049, Vol. 14, p. 113-123Article in journal (Refereed)
  • 159.
    Niklasson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Malleus fracture: experimental and clinical aspects2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Patients with malleus fractures are described as rare in the literature. The cause of these fractures are most commonly trauma and digital manipulation of the ear canal, while in some cases the causes are unknown. At our clinic we record one new case every year, which leads to an incidence of approximately 40-50 new cases every year in Sweden. Different treatments have been proposed for this condition. However, since the condition is rare, no consensus has been reached regarding the best treatment. Additionally, it remains unclear whether malleus fractures can heal.

    Aim: To get a deeper understanding of how malleus fractures occur, how they should be treated surgically, and if the malleus shows any sign of bone healing.

    Materials and methods: Paper I. We carried out both a retrospective study of the medical records of nine Swedish patients with isolated malleus fractures, and a literature review of this condition. Symptoms, clinical findings and patients’ history were collected.Paper II. Ossiculoplasty on human temporal bones was performed in the presence of a malleus fracture. We developed a surgical model from freshly frozen human temporal bones, and we performed Laser Doppler vibrometry (LDV) measurements on this model both before and after ossiculoplasty.Paper III. We performed ossiculoplasties with different types of partial ossicular replacement prostheses (PORP) on human temporal bones and we measured the results with LDV.Paper IV. We performed an in vivo animal study on Merino sheep, in which we produced isolated malleus fractures. We then compared the bone healing of these fractures with that of the nasal bone and the mandible. Bone healing was detected with micro-CT.

    Results: Paper I. The most common cause of isolated malleus fractures was found to be a so-called “digital” trauma, which occurred when the patients had removed a finger from the wet ear canal after bath. The hearing loss was occasionally accompanied by tinnitus and transient pain. Pneumatic otoscopy and tympanometry showed a hypermobile tympanic membrane, while audiometry showed a conductive hearing loss that increased towards higher frequencies.Paper II. Our LDV measurements indicated that fixation of an isolated malleus with bone cement may give the best results after surgery.Paper III. The best LDV measurements were obtained when ossiculoplasty was done using a PORP in lateral contact with both the tympanic membrane and the malleus handle.Paper IV. In our animal study we found no signs of bone healing at micro-CT four weeks after producing the malleus fractures. In contrast, both the nasal bone and the mandible showed bone healing. This indicates that the bone healing properties of the ossicles probably differ from those of other bones in the body.

    Conclusion: Digital trauma is the major cause of isolated malleus fractures. Pneumatic otoscopy and tympanometry showed a hypermobile tympanic membrane, while audiometry showed a conductive hearing loss increasing towards the higher frequencies. We developed a method to employ freshly frozen human temporal bones and we used LDV for detecting optimal results. This method allows to evaluate and develop otosurgery, aimed to restore hearing after an interrupted ossicular chain. The animal study indicates that malleus fractures will not heal spontaneously.

  • 160.
    Niklasson, Anders
    et al.
    Umeå University, Faculty of Medicine, Clinical Sciences, Otorhinolaryngology.
    Dahlqvist, Ake
    Umeå University, Faculty of Medicine, Clinical Sciences, Otorhinolaryngology.
    Antigen challenge induces a supraglottic but not a subglottic edema in the rat larynx.2005In: Otolaryngology and head and neck surgery, ISSN 0194-5998, E-ISSN 1097-6817, Vol. 132, no 5, p. 694-700Article in journal (Refereed)
  • 161.
    Niklasson, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Gladiné, Kilian
    Rönnblom, Anton
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    von Unge, Magnus
    Dirckx, Joris
    Tano, Krister
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    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.

  • 162.
    Niklasson, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Rönnblom, Anton
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Muyshondt, Pieter
    Dirckx, Joris
    von Unge, Magnus
    Tano, Krister
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Ossiculoplasty on Isolated Malleus Fractures: A Human Temporal Bone Study Using Laser Doppler Vibrometry2016In: Otology and Neurotology, ISSN 1531-7129, E-ISSN 1537-4505, Vol. 37, no 7, p. 895-901Article in journal (Refereed)
    Abstract [en]

    Hypothesis: In the literature several surgical methods have been reported that aim to improve hearing in patients with isolated malleus fractures; however, it is still not clear which method gives the best results.

    Background: In this study, laser Doppler vibrometry (LDV) was used to compare the outcome of different surgical methods on malleus fractures in fresh frozen human temporal bones.

    Methods: Fractured malleus shafts of defrosted human temporal bones were repaired with bone cement, with a malleus prosthesis from cortical bone, or with a partial ossicular replacement prosthesis (PORP) from cortical bone, and LDV measurements were obtained for analysis.

    Results: The best result was achieved with the bone cement only, applied directly at the site of the fracture. The malleus prosthesis and the PORP gave similar results.

    Conclusion: All three surgical methods gave good results, but when the distal end of the fractured malleus can be attached close to the proximal end, the technique using only cement tends to be the best option. If the parts are too far apart, a malleus prosthesis or a PORP would be good options.

  • 163.
    Niklasson, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Tano, Krister
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Dilley, R.
    Pavlos, N.
    Musk, G.
    Atlas, M.
    von Unge, M.
    Malleus fracture healing studied in a new sheep modelManuscript (preprint) (Other academic)
  • 164.
    Nilsson Borg, Erik
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Från misstanke till behandling – har ”Snabbspåret” kortat ledtider för patienter med ÖNH-cancer i Västernorrland?2014Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 165. Norling, Rikke
    et al.
    Grau, Cai
    Nielsen, Michael B
    Homøe, Preben
    Sørensen, Jens A
    Lambertsen, Karin
    Bundgaard, Troels
    Mäkitie, Antti
    Grénman, Reidar
    Larenne, Jussi
    Koivunen, Petri
    Virtaniemi, Jukka
    Gudjonsson, Arnar
    Jetlund, Olav
    Abendstein, Helmut
    Rikardsen, Oddveig
    Lybak, Stein
    Wennerberg, Johan
    Högmo, Anders
    Laurell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Westerborn, Anders
    Hammerlid, Eva
    Tytor, Wieslaw
    Cederblad, Lena
    von Buchwald, Christian
    Radiological imaging of the neck for initial decision-making in oral squamous cell carcinomas-A questionnaire survey in the Nordic countries2012In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 51, no 3, p. 355-361Article in journal (Refereed)
    Abstract [en]

    Background. Fast and accurate work-up is crucial to ensure the best possible treatment and prognosis for patients with head and neck cancer. The presence or absence of neck lymph node metastases is important for the prognosis and the choice of treatment. Clinical lymph node (N)-staging is done by palpation and diagnostic imaging of the neck. We investigated the current practice of the initial radiological work-up of patients with oral squamous cell carcinomas (OSCC) in the Nordic countries. Methods. A questionnaire regarding the availability and use of guidelines and imaging modalities for radiological N-staging in OSCC was distributed to 21 Head and Neck centres in Denmark (n = 4), Finland (n = 5), Iceland (n = 1), Norway (n = 4) and Sweden (n = 7). We also asked for a description of the radiological criteria for determining the lymph nodes as clinical positive (cN+) or negative (cN0). Results. All 21 Head and Neck centres responded to the questionnaire. Denmark and Finland have national guidelines, while Norway and Sweden have local or regional guidelines. Seventeen of the 19 centres with available guidelines recommended computed tomography (CT) of the cN0 neck. The waiting time may influence the imaging modalities used. Lymph node size was the most commonly used criteria for radiological cN+, but the cut-off measures vary from 0.8 to 2.0 cm. Conclusion. Overall, CT is the most commonly recommended and used imaging modality for OSCC. Despite availability of national guidelines the type and number of radiological examinations vary between centres within a country, but the implementation of a fast-track programme may facilitate fast access to imaging. The absence of uniform criteria for determining the lymph nodes of the neck as cN+ complicates the comparison of the accuracy of the imaging modalities. Well-defined radiological strategies and criteria are needed to optimise the radiological work-up in OSCC.

  • 166.
    Nyqvist, Johanna
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology. Department of Otolaryngology and Head and Neck Surgery, Skåne University Hospital, Lund.
    Fransson, Per
    Umeå University, Faculty of Medicine, Department of Nursing.
    Laurell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology. Department of Otolaryngology and Head and Neck Surgery, Uppsala University Hospital.
    Hammerlid, Eva
    Kjellén, Elisabeth
    Franzén, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Söderström, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Wickart-Johansson, Gun
    Friesland, Signe
    Sjödin, Helena
    Brun, Eva
    Ask, Anders
    Nilsson, Per
    Ekberg, Lars
    Björk-Eriksson, Thomas
    Nyman, Jan
    Lödén, Britta
    Lewin, Freddi
    Reizenstein, Johan
    Lundin, Erik
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Differences in health related quality of life in the randomised ARTSCAN study; accelerated vs. conventional radiotherapy for head and neck cancer: A five year follow up2016In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 118, no 2, p. 335-341Article in journal (Refereed)
    Abstract [en]

    Background and purpose: Health related quality of life (HRQoL) was assessed in the randomised, prospective ARTSCAN study comparing conventional radiotherapy (CF) with accelerated radiotherapy (AF) for head and neck cancer.

    Material and methods: 750 patients with squamous cell carcinoma (of any grade and stage) in the oral cavity, oro-, or hypopharynx or larynx (except T1-2, NO glottic carcinoma) without distant metastases were randomised to either conventional fractionation (2 Gy/day, 5 days/week in 49 days, total dose 68 Gy) or accelerated fractionation (1.1 + 2.0 Gy/day, 5 days/week in 35 days, total dose 68 Gy). HRQoL was assessed with EORTC QLQ-C30, QLQ-H&N35 and HADS at baseline, at end of radiotherapy (eRT) and at 3 and 6 months and 1, 2 and 5 years after start of treatment.

    Results: The AF group reported HRQoL was significantly lower at eRT and at 3 months for most symptoms, scales and functions. Few significant differences were noted between the groups at 6 months and 5 years. Scores related to functional oral intake never reached baseline.

    Conclusion: In comparison to CF, AF has a stronger adverse effect on HRQoL in the acute phase.

  • 167.
    Nörbrant, Gabriella
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Resorberbar intrakutan sutur jämfört med icke-resorberbar sutur i ansiktet: Analys av data 14 dagar postoperativt.2015Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 168.
    Olofsson, Katarina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Immune cells in human pharyngeal and palatine tonsils and in the uvula: tissue distribution, cellular composition and functional properties1999Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The adenoid (pharyngeal tonsil), the palatine tonsils and the uvula are strategically located at the entrance of the upper airodigestive tract. By virtue of their location they are incessantly exposed to inhaled and ingested antigens. Severe nasal obstruction, otitis media with effusion, recurrent tinsillitis and obstructive airways during sleep are conditions often due to diseases in these organs.

    To advance our knowledge about the etiology and pathogenesis of these diseases, we have compared immune cell composition, cytokine expression and microbial colonisation in adenoids from children with hypertrophic obstructive adenoid (HOA) and chronically infected adenoid (CIA). Similarly, we compared immune cell composition in palatine tonsils from children with idiopathic tonsillar hypertrophy and recurrent tonsillitis. Finally, we wanted to characterise the human uvula from an immunological point of view, which had previously not been done. Its composition and distribution of immune cells, its cytokine profile, connective tissue elements and ultrastructure was studied.

    When comparing adenoids from children with HOA and CIA, the most striking finding was their similarity. A cytokine profile that was independent of diagnosis but seemed characteristic for the adenoid emerged. T cell expression of IL-5 and TGF-β1 but not IL-4 suggested an ongoing humoral response driven by a "mucosal TH2" cell. αβ T cells also expressed TNF-α, IFN-γ and IL-2, indicating a concomitant cell mediated response. Cell mediated immune responses often reflect viral infection. In line with this, adenovirus DNA was found in 80% of the adenoid samples. Furthermore, IL-6, IL-8 and TNF-α expressed in the non-T cell fraction suggested that the tissue macrophages were activated. TNF-α, IFN-γ and TGF-β1 were expressed by γδ T cells. The following differences between HOA and CIA were however, noted: i) most intraepithelial lymphocytes were CD8+ γδ T cells in HOA, while CD8+ αβ T cells dominated intraepithelially in CIA; ii) the number of follicles was twice as high in CIA as in HOA; iii) there were signifacantly more granulocytes in the interfollicular area in CIA than in HOA; iv)IL-6 mRNA expressing γδ T cells were only found in HOA and v) there was a tendency of higher TNF-α mRNA levels in non-T cells of CIA compared to HOA. The following scenarios emerge: in CIA there appears to be an inadequate first line of defence, with a low frequency of intraepithelial γδ T cells and a high frequency of cytotoxic CD8+ αβ T cells eliminating infected epithelial cells. Togehter, these two conditions cause a "leaky" epithelium, allowing infiltration of microbes into the underlying tissue and subsequent recruitment of granulocytes and follicle formation initiated by activated macrophages. In HOA, activated intraepithelial γδ T cells appear to be involved in antimicrobial defence reactions and surveillance of the epithelium.

    The difference in leukocyte profiles between tonsils from patients subjected to surgery due to idiopathic tonsillar hypertrophy or recurrent tonsillitis was limited to the surface epithelium. CD8+ γδ T cells utilising the unusual combination Vδ1/Vγ9 in their T cell receptor constituted the majority of intraepithelial lymphocytes in both groups. However, the frequency of these cells was significantly higher in recurrent tonsillitis. These results suggest that CD8+ Vδ1/Vγ9+ γδ T cells are characteristic of palatine tonsils and selectively expanded in recurrent tonsillitis. These γδ T cells may be involved in clearing infectious bacteria at the surface of the tonsil.

    Tissue macrophages, αβ T cells, γδ T cells, mast cells and B cells constituted, in declining order, the immune cell populations in the uvula. No fillicle-like structures were present. Most T cells had a CD8+ CD28-TCR-αβ+ phenotype, suggesting a down-regulatory function. Production of the down-regulatory cytokine TGF-β was also noted. This is consistent with the hypothesis that the uvula contributes to the development of mucosal tolerance. Furthermore, the uvula seems to be protected from pathogens penetrating the internal milieu by a subepithelial barrier of γδ T cells and macrophages. TNF-α secreting immune cells were found at this location. TNF-α and TGF-β may cause tissue fibrosis, TNF-α indirectly by stimulating mast cells to release histamine. Tissue fibrosis in conjunction with water binding to hyaluronan present in the connective tissue is the most likely explanation for the observed enlargement of the uvula in patients with sleeping disorders.

  • 169. Olofsson, Katarina
    et al.
    Hellström, S
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Hammarström, Marie-Louise
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Abundance of intraepithelial gamma delta T cells in hypertrophic obstructive but not in chronically infected adenoids1996In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 106, no 2, p. 396-403Article in journal (Refereed)
    Abstract [en]

    Using quantitative morphometric analysis of immunohistochemically stained tissue sections we compared hypertrophic obstructive adenoids (HOA, n = 10) from children without middle ear disease with chronically infected adenoids (CIA, n = 10) from children with middle ear disease. gamma delta T cell receptor (TCR)+ cells constituted the dominating T cell population in the surface epithelium of HOA, while alpha beta TCR+ cells were the dominating intraepithelial T cell population in CIA. Intraepithelially CD8+ cells dominated over CD4+ cells in both diseases. Intraepithelially B cells were not detected. The cellular composition of follicles, with B cells dominating followed by activated CD4+ alpha beta TCR+ cells, was the same in both groups. However, the number of follicles in CIA was twice as many as in HOA. In the deeper interfollicular areas granulocytes were more abundant in CIA than in HOA. The latter two findings suggest a more pronounced inflammatory response in the adenoids of patients with middle ear disease. There was no significant difference with regard to pathogenic bacterial strains colonizing the adenoid surface when comparing the two patient groups. These results suggest that in patients with HOA gamma delta TCR+ T cells help to maintain the integrity of the surface epithelium, thereby preserving its protective function. On the basis of our results we speculate that CIA have a malfunctioning defence, thereby facilitating long-standing infections deep in the adenoid. This may be the main reason for development of middle ear disease and an indication for adenoidectomy in patients with CIA.

  • 170.
    Olofsson, Katarina
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Hellström, S
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Hammarström, Marie-Louise
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Human uvula: characterization of resident leukocytes and local cytokine production2000In: Annals of Otology, Rhinology and Laryngology, ISSN 0003-4894, E-ISSN 1943-572X, Vol. 109, no 5, p. 488-496Article in journal (Refereed)
    Abstract [en]

    Upper airway infections often lead to macroscopic changes in the architecture of the uvula. Using immunomorphometric analysis, we investigated the frequency and distribution of immune cells and of cytokine-producing cells in uvular samples. Tissue macrophages, alphabeta T cells, gammadelta T cells, and B cells were, in declining order, the main cell populations. Gammadelta T cells and B cells exhibited reciprocal localization, with almost all gammadelta T cells residing in the vicinity of the epithelium, and all B cells in the glandular area. The presence of cells expressing the suppressor phenotype CD8+CD28- alphabeta T cells is suggested. Fifteen to twenty-five percent of the immune cells expressed the down-regulatory cytokine tumor growth factor beta. Most macrophages were located subepithelially, in the vicinity of the basal lamina. The composition and cytokine profile of leukocytes in the tissue suggest that the uvula may be a site, additional to the jejunal mucosa, for induction of mucosal tolerance to inhaled and ingested antigens. Concomitantly, the uvula appears to be protected from invasion of microbial pathogens by a subepithelial barrier of macrophages and gammadelta T cells.

  • 171.
    Olofsson, Katarina
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Hellström, S
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Hammarström, Marie-Louise
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    The surface epithelium of recurrent infected palatine tonsils is rich in gammadelta T cells1998In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 111, no 1, p. 36-47Article in journal (Refereed)
    Abstract [en]

    Using a large panel of MoAbs in quantitative morphometric analysis of immunohistochemically stained tissue sections, we compared the frequency and distribution of immune cells in palatine tonsils from patients with recurrent tonsillitis (RT) and patients with idiopathic tonsillar hypertrophy (ITH). We found that differences between the two patient groups in leucocyte populations were limited to the surface epithelium, whereas the cellular composition of interfollicular and follicular areas was similar. Most intraepithelial lymphocytes were CD8+ T cells in both groups. However, the number of intraepithelial T cells was significantly higher in RT compared with ITH. This was due to a selective increase in the number of intraepithelial CD8+ gammadelta T cells utilizing Vdelta1 and Vgamma9. In both patient groups the majority of the intraepithelial gammadelta T cells expressed Vdelta1 and Vgamma9. Subepithelially, gammadelta T cells utilizing Vgamma9 dominated over cells utilizing Vgamma8, while equal proportions expressed Vdelta1 and Vdelta2. These results suggest that cells utilizing the otherwise rare combination Vdelta1/Vgamma9 in their T cell receptors (TCR) may constitute a major gammadelta T cell population in palatine tonsils and are probably reactive to antigens specific to the tonsillar milieu. Furthermore, they indicate that preferentially this gammadelta T cell subpopulation is involved in immune reactions within the surface epithelium in RT. We speculate that gammadelta T cells are involved in clearing infectious bacteria at the tonsillar surface and in limiting inflammatory responses in the tonsils. Both local expansion and infiltration of blood cells probably contribute to the high numbers of gammadelta T cells in RT patients.

  • 172.
    Olofsson, Katarina
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Loizou, Christos
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Evander, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Mincheva-Nilsson, Lucia
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Laurell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Studie av larynxpapillom i norra Sverige: två fall av onkogena HPV bland 26 patienter2011In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 108, no 21, p. 1187-1189Article in journal (Refereed)
    Abstract [en]

    Laryngeal papilloma is associated with human papillomavirus (HPV) 6, 11, 16, 18 and 31. The variation in the frequency of surgical treatment between patients for the same subtypes of HPV is inconsistent and poorly understood. Comparisons of the female laryngeal papilloma group (n?=?8, median age 46 yrs) with the male (n= 18, median age 32 yrs) with respect to gender, age, time of disease, period of life for diagnosis, disease progression profile, frequency of surgery (CO2 laser) during time of disease, localisation of papilloma in the upper airway and HPV subtype did not reach significance. In contrast the comparison between the high frequency (Ž 1 treatment/yr, n?=?11, median age 31 yrs) and low frequency (<1 treatment/yr, n?=?15 median age 45 yrs) treatment groups with regard to the same parameters as the female-male comparison, showed a clear-cut higher median age in the low frequency group (P?=?0,01).

  • 173.
    Olofsson, Katarina
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Mattsson, C
    Hammarström, Marie-Louise
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Hellström, S
    Structure of the human uvula1999In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 119, no 6, p. 712-717Article in journal (Refereed)
    Abstract [en]

    Eleven uvular biopsies were investigated for their morphology, the presence of mast cells and the distribution of hyaluronan and its major ligand CD44. Three microanatomical sites--surface epithelium, subepithelial area and area of glands--were examined. The oral side of the uvula was covered by a 15-20 cell thick layer of keratinized/parakeratinized surface epithelium, firmly anchored to the underlying connective tissue by connective tissue papillae. The width of the intercellular spaces in the epithelium increased toward the basal lamina, a location that exhibited intense hyaluronan and anti-CD44 staining. Most mast cells were located in the vicinity of blood vessels, at which sites there was high staining intensity of hyaluronan. Tissue mast cells could also be observed in the connective tissue septa enclosing the acini. Glands and muscle fibres became more sparse from the proximal part of the uvula to the distal end, while the amount of connective tissue increased. The localization and architecture of connective tissue elements and mast cells are consistent with the ability of the uvula to resist mechanical stresses and to develop oedema and fibrosis, respectively.

  • 174.
    Olofsson, Katarina
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Sjöstedt, M
    Allard, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Hellström, S
    Hammarström, Marie-Louise
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    The cytokine profile of T cells in the pharyngeal tonsil of childrenManuscript (preprint) (Other academic)
  • 175.
    Olofsson, Katarina
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Van Doorn, Jan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Speech and Language Therapy.
    Kulneff, Linda
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Speech and Language Therapy.
    Linder, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Nordh, Erik
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neurophysiology.
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Djup hjärnstimulering vid dysfagi hos parkinsonpatienter: den självskattade sväljningsfunktionen förbättrades i pilotstudie2010In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 107, no 17, p. 1150-1154Article in journal (Other academic)
  • 176. Opheim, Leif Runar
    et al.
    Hellman, Urban
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Engström-Laurent, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Laurent, Claude
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology. Department of Speech/Language Pathology and Audiology, University of Pretoria, Pretoria, South Africa.
    Hyaluronan in Human Vocal Folds in Smokers and Nonsmokers: A Histochemical Study2016In: Journal of Voice, ISSN 0892-1997, E-ISSN 1873-4588, Vol. 30, no 3, p. 255-262Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES/HYPOTHESIS: To study the hyaluronan occurrence in human vocal folds, with special regards to gender and smoking and to discuss the implications of findings.

    STUDY DESIGN: This is a descriptive/morphologic study.

    METHODS: Sixteen cadaveric vocal folds from eight individuals between 58 and 90 years old (six women and two men) were removed and studied morphologically. Three of the individuals had been cigarette smokers. A direct method for hyaluronan histochemistry using a hyaluronan-binding protein probe (HABP) was used to visualize the polysaccharide. Five examiners performed an analysis of the intensities of hyaluronan staining, independently.

    RESULTS: We observed intense hyaluronan staining of the vocal folds of which those from women stained considerably stronger than those from men. Stratified squamous epithelium stained for hyaluronan in all sections, whereas respiratory epithelium only stained weakly or not at all. The highest accumulation of hyaluronan occurred subepithelially in the lamina propria, corresponding to Reinke's space. It was observed that vocal folds from smokers were more intensively stained than those from nonsmokers.

    CONCLUSIONS: Hyaluronan is found in all layers of the human vocal fold. Contradictory to earlier studies, hyaluronan was visualized in squamous epithelium, where it may function as an impact protector. The occurrence of hyaluronan in smokers may have implications in the development of vocal fold inflammation and tumor initiation as hyaluronan is an important molecule in these processes.

  • 177.
    Ottosson, Sandra
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Impact of disease and treatment on body weight and eating in patients with head and neck cancer: experiences from a multicenter study2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background Nutritional deterioration in patients with head and neck cancer (HNC) has a multifactorial etiology mainly associated with tumor and treatment related factors. The objective of the present thesis was to investigate the impact of the disease and treatment on body weight and eating in patients with HNC treated with radiation therapy (RT) as the single modality treatment or as preoperative RT by analyzing body weight and body mass index (BMI) over time, predictive factors for weight loss and BMI, weight loss and BMI as prognostic factors for survival, and by studying the patients’ own experience of food and eating.

    Methods ARTSCAN is a randomized prospective multicenter trial conducted between the years of 1998 - 2006. Data were collected during and after RT with a total follow-up time of five years. Nutritional data from the whole study cohort (n = 712), from patients with oropharyngeal cancer (n = 232) and from two of the participating treatment centers (n = 101) were retrospectively analyzed in the present thesis. In addition, interviews (n = 13) were conducted nine months after the termination of RT as part of a care development project.

    Results On a group level, the patients lost weight during and after RT with a nadir at five months after the termination of RT. Factors related to a higher weight loss were oropharyngeal cancer, a high BMI at the start of RT, post-treatment aspiration, no tube feeding at the start of RT, and larger treated volumes. Furthermore, a high BMI at the start of RT was shown to be significantly related to a better five-year overall survival in patients with oropharyngeal cancer, whereas weight loss was not. The patients’ own narratives showed that all aspects of food, eating and meals were affected by the remaining sequelae, and that the patients found ways to accept and cope with the changes that had to be done to facilitate eating.

    Conclusions and clinical implications The disease and treatment gave persistent effects on the HNC patients’ weight and BMI which calls for a prolonged nutritional follow-up. The predictive factors found for weight loss can be used during patient history to find patients at risk for nutritional deterioration. In oropharyngeal cancer, patients with a high BMI at the start of RT had the best survival. This finding indicates that patients with a low BMI should be encouraged to gain weight before RT start. All aspects of food, eating and meals were affected during and after RT, and therefore the nutritional treatment should be given with a holistic approach to meet the multifaceted need patients with HNC experience.

  • 178.
    Ottosson, Sandra
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology. Umeå University, Faculty of Social Sciences, Department of Food and Nutrition.
    Laurell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Olsson, Cecilia
    Umeå University, Faculty of Social Sciences, Department of Food and Nutrition.
    The experience of food, eating and meals following radiotherapy for head and neck cancer: a qualitative study2013In: Journal of Clinical Nursing, ISSN 0962-1067, E-ISSN 1365-2702, Vol. 22, no 7-8, p. 1034-1043Article in journal (Refereed)
    Abstract [en]

    Aims and objectives. To describe the experience of food, eating and meals following radiotherapy in patients with head and neck cancer.

    Background. Eating problems are common in patients with head and neck cancer and may remain for a long period of time after treatment.

    Design. A qualitative study design using in-depth semi-structured interviews.

    Methods. Interviews were conducted nine months after the termination of radiotherapy. A purposive sample of thirteen patients with head and neck cancer participated in the study. The interviews were tape-recorded, transcribed verbatim and analysed using content analysis.

    Results. The experience of food, eating and meals up to nine months after radiotherapy was captured in six categories: ‘Along journey – taking small steps to an uncertain future’, ‘A new way of eating’, ‘Eating without satisfaction’, ‘Challenging meals outside the family’, ‘Support and information – the key to a successful journey’ and ‘The creation and acceptance of a new normal’.

    Conclusion. This study provides new information on the long-term aspects of food, eating and meals in patients with head and neck cancer. Head and neck cancer signifies a long journey with problems affecting physical, psychological and social aspects of food. Information and support and the use of strategies are important for patients with head and neck cancer to adapt to new possibilities for living after cancer treatment. Relevance to clinical practice. All members of the multiprofessional team need to be aware of the struggles with food and eating experienced by patients with head and neck cancer during the convalescent period. It is therefore important that the follow-up focuses on all aspects of food, eating and meals as a part of a holistic approach.

  • 179.
    Ottosson, Sandra
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Lindblom, Ulrika
    Lunds universitet.
    Wahlberg, Peter
    Lunds universitet.
    Nilsson, Per
    Lunds universitet.
    Kjellén, Elisabeth
    Lunds universitet.
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Levring Jäghagen, Eva
    Umeå University, Faculty of Medicine, Department of Odontology.
    Laurell, Göran
    Uppsala universitet.
    Weight loss and Body Mass Index in relation to aspiration in patients treated for head and neck cancer: a long-term follow-up2014In: Supportive Care in Cancer, ISSN 0941-4355, E-ISSN 1433-7339, Vol. 22, no 9, p. 2361-2369Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Persistent severe swallowing dysfunction with aspiration is a common and sometimes overlooked sequelae after treatment for squamous cell carcinoma of the head and neck (SCCHN) and may impact food intake and nutritional status. More knowledge is needed to increase the understanding of severe swallowing dysfunction as a risk factor for persistent nutritional deteriorations in SCCHN survivors. The purpose of the study was to investigate weight loss and body mass index (BMI) in relation to pharyngeal swallowing function in a long-term perspective in patients after SCCHN treatment.

    METHODS: Data from 101 patients were available for the analyses. Swallowing function was assessed by videofluoroscopy at a mean of 71.6 months after the start of radiotherapy (RT). Percent weight change (calculated with weight at the start of RT as the reference) and BMI at follow-up were the primary nutritional measures.

    RESULTS: Aspiration was present in 48 of 101 patients (48 %). Patients with aspiration had a significantly higher mean weight loss and a lower BMI (-10.9 % and 23.1, respectively) at follow-up compared with patients without aspiration (-2.8 % and 26.0, respectively). Patients with aspiration were unable to gain weight after 23 months. Only ten of 101 patients (10 %) were underweight at follow-up.

    CONCLUSIONS: Swallowing dysfunction with aspiration was related to long-term weight loss and reduced BMI. Few patients were underweight despite the high prevalence of swallowing dysfunction.

  • 180.
    Ottosson, Sandra
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Söderström, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Kjellén, Elisabeth
    Lunds universitet.
    Nilsson, Per
    Lunds universitet.
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Laurell, Göran
    Uppsala universitet.
    Weight and body mass index in relation to irradiated volume and to overall survival in patients with oropharyngeal cancer: a retrospective cohort study2014In: Radiation Oncology, ISSN 1748-717X, E-ISSN 1748-717X, Vol. 9, p. 160-Article in journal (Refereed)
    Abstract [en]

    Background: Weight loss is a common problem in patients with Squamous Cell Carcinoma of the Head and Neck (SCCHN) treated with radiotherapy (RT). The aims of the present study were to determine if treated volume (TV), as a measure of the radiation dose burden, can predict weight loss in patients with oropharyngeal cancer and to analyze weight loss and body mass index (BMI) in the same patient group in relation to 5-year overall survival. Methods: The ARTSCAN trial is a prospective, randomized, multicenter trial in patients with SCCHN. Nutritional data from the ARTSCAN trial were analyzed retrospectively using univariate and multivariate statistical methods based on information on percentage weight loss from the start of RT up to five months after the termination of RT (study cohort 1, n = 232) and information on patients' BMI at the start of RT (study cohort 2, n = 203). TV was defined as the volume of the patient receiving at least 95% of the prescribed dose. TV64.6 (Gy) encompasses macroscopic tumor and TV43.7 (Gy) elective lymph nodes of the neck. Results: TV64.6 Gy and TV43.7 Gy were both significantly correlated with higher weight loss up to five months after the termination of RT in study cohort 1 (p < 0.001 for both). BMI at the start of RT was shown to be a prognostic factor for 5-year overall survival in study cohort 2 but weight loss was not. The hazard ratios and 95% confidence intervals were 3.78 (1.46-9.75) and 2.57 (1.43-4.62) in patients with underweight and normal weight, respectively. Conclusions: TV can predict weight loss during RT in patients with oropharyngeal cancer regardless of clinical stage. A high BMI (>25 kg/m(2)) at the start of RT is positively associated with survival in patients with oropharyngeal cancer.

  • 181.
    Ottosson, Sandra
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Kjellén, Elisabeth
    Lunds Universitet, Klinisk vetenskap.
    Nilsson, Per
    Lunds Universitet, Klinisk vetenskap.
    Laurell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Weight loss in patients with head and neck cancer during and after conventional and accelerated radiotherapy2013In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 52, no 4, p. 711-718Article in journal (Refereed)
    Abstract [en]

    Background. Weight loss is common among patients with squamous cell carcinoma of the head and neck (SCCHN) and is mainly due to tumor and treatment related factors. The aim of the present study was to evaluate weight loss in patients with SCCHN undergoing two different radiotherapy (RT) schedules.

    Material and methods. Nutritional data were analyzed from the ARTSCAN study, a controlled randomized prospective Swedish multicenter study conducted with the aim of comparing conventional fractionation (2.0 Gy per day, total 68 Gy during 7 weeks) and accelerated fractionation (1.1 + 2.0 Gy per day, total 68 Gy during 4.5 weeks). Seven hundred and fifty patients were randomized and 712 patients were followed from the start of RT in the present nutritional study.

    Results. The patients had a weight loss of 11.3% (± 8.6%) during the acute phase (start of RT up to five months after the termination of RT). No difference in weight loss was seen between the two RT fractionation schedules (p = 0.839). Three factors were significantly predictive for weight loss during the acute phase, i.e. tumor site, overweight/obesity or lack of tube feeding at the start of RT. Moreover, the nadir point of weight loss occurred at five months after the termination of RT.

    Conclusion. The results of the present study showed no difference in weight loss between the two RT fractionation schedules and also highlight that weight loss in SCCHN is a multifactorial problem. Moreover, the nadir of weight loss occurred at five months after the termination of treatment which calls for more intense nutritional interventions during the period after treatment.

  • 182.
    Prestwich, Annika Hansson
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Li, Jinan
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Eriksson, P O
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Ny, Tor
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Berggren, Diana
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Hellström, Sten
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Lack of plasminogen does not alter the early inflammatory response following a tympanic membrane perforation: a study in plasminogen-deficient mice.2008In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 128, no 12, p. 1294-1302Article in journal (Refereed)
    Abstract [en]

    CONCLUSIONS: The results of the present study show that the early inflammatory response in plasminogen (plg)-deficient mice is not altered compared to that in wild-type (wt) mice. Therefore the chronicity of the perforation in the long-term healing experiment cannot be explained by an impairment of the early inflammatory response, but rather by an impairment in activation of the inflammatory cells. These findings give further insight into the mechanisms resulting in a clinically seen chronic tympanic membrane (TM) perforation and thus possible therapeutic strategies to replace today's conventional surgical treatment of these perforations. OBJECTIVES: Plg has been shown to play an essential role in the healing of TM perforations. In plg-deficient mice a completely arrested healing reaction was seen, resulting in a chronic TM perforation. The mechanisms involved seem to be an abundant neutrophil recruitment, an accumulation of macrophages, an arrested keratinocyte migration, and a massive deposition of fibrin along the TM tissue. However, the exact functional role of plg in the early inflammatory response during healing of TM perforation remains unclear. This study aimed to evaluate the early inflammatory response, mainly the occurrence of macrophages and neutrophils, during the first 48 h following a perforation in the pars tensa (PT) of the TM, in mice lacking the plasminogen gene compared to the corresponding response in wt mice. MATERIALS AND METHODS: The TMs were perforated in 45 plg-deficient and 39 wt mice. Otomicroscopic evaluation was performed at 3, 6, 9, 12, 18, 24, and 48 h after the perforation was made. Mice were harvested at all time points and prepared for morphology including immunohistochemistry (IHC). IHC was performed with antibodies targeting macrophages, neutrophils, T and B cells, cytokeratin, and fibrin(ogen). Morphometry was performed regarding the volume percentage of TM tissue occupied by the different inflammatory cells. RESULTS: Perforation of the TM resulted in early otomicroscopic changes of the pars flaccida (PF) in both genotypes. Infiltration of inflammatory cells to PF and the presence of edema occurred as early as 6 h after the perforation was made, in both plg-deficient and wt mice. Morphometry did not reveal any significant differences between the genotypes concerning the occurrence of inflammatory cells. In contrast to the PF, the PT showed only sparse reactions during the experimental period. Furthermore, the migration pattern of keratinocytes did not differ between the genotypes throughout the experimental period.

  • 183. Qiu, Jian-xin
    et al.
    Fang, Xian-zhao
    Tong, Bu-shen
    Laurell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Duan, Mao-li
    [Study of sensitivity to impulse noise in guinea pig, rat and mouse]2004In: Zhonghua er bi yan hou ke za zhi, ISSN 0412-3948, Vol. 39, no 8, p. 472-475Article in journal (Refereed)
    Abstract [zh]

    OBJECTIVE: To study sensitivity to impulse noise in guinea pig, rat and mice. METHODS: Six groups were divided. Group I: Guinea pigs (n = 5) were exposed to 50 impulses of 160 dB SPL; Group II: Guinea pigs (n = 5) were exposed to 100 impulses of 160 dB SPL; Group III: Guinea pigs (n = 5) were exposed to 200 impulses of 160 dB SPL; Group IV: Guinea pigs (n = 6) were exposed 400 impulses of 160 dB SPL; Group V: Rats (n = 10) were exposed to 50 impulses of 160 dB SPL; Group VI: Mice (n = 10) were exposed to 50 impulses of 160 dB SPL. ABR thresholds were determined prior to, immediately, one day, one week, two weeks and four weeks after impulse noise exposure. RESULTS: The rat and mice were shown temporary threshold shift (TTS) and permanent threshold shift (PTS) after 50 times impulse noise (160), while no TTS and PTS in the guinea pigs but it was shown TTS and PTS after 400 times impulse noise (160). CONCLUSIONS: Sensitivity to impulse noise is different among guinea pig, rat and mouse. Guinea pig has less sensitivity to impulse noise while rat and mouse have higher sensitivity to impulse noise. In addition, rat has higher sensitivity to impulse noise than mouse.

  • 184.
    Rentoft, Matilda
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Coates, Philip John
    Laurell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Nylander, Karin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Transcriptional profiling of formalin fixed paraffin embedded tissue: pitfalls and recommendations for identifying biologically relevant changes2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 4, p. e35276-Article in journal (Refereed)
    Abstract [en]

    Expression profiling techniques have been used to study the biology of many types of cancer but have been limited to some extent by the requirement for collection of fresh tissue. In contrast, formalin fixed paraffin embedded (FFPE) samples are widely available and represent a vast resource of potential material. The techniques used to handle the degraded and modified RNA from these samples are relatively new and all the pitfalls and limitations of this material for whole genome expression profiling are not yet clarified. Here, we analyzed 70 FFPE tongue carcinoma samples and 17 controls using the whole genome DASL array covering nearly 21000 genes. We identified that sample age is related to quality of extracted RNA and that sample quality influences apparent expression levels in a non-random manner related to gene probe sequence, leading to spurious results. However, by removing sub-standard samples and analysing only those 28 cancers and 15 controls that had similar quality we were able to generate a list of 934 genes significantly altered in tongue cancer compared to control samples of tongue. This list contained previously identified changes and was enriched for genes involved in many cancer-related processes such as tissue remodelling, inflammation, differentiation and apoptosis. Four novel genes of potential importance in tongue cancer development and maintenance, SH3BGL2, SLC2A6, SLC16A3 and CXCL10, were independently confirmed, validating our data. Hence, gene expression profiling can be performed usefully on archival material if appropriate quality assurance steps are taken to ensure sample consistency and we present some recommendations for the use of FFPE material based on our findings.

  • 185.
    Rentoft, Matilda
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Coates, Philip John
    Univ Dundee, Ninewells Hosp & Med Sch, Tayside Tissue Bank, Med Res Inst, Dundee DD1 9SY, Scotland.
    Loljung, Lotta
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Wilms, Torben
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Laurell, Göran
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Univ Uppsala Hosp, Dept Surg Sci ENT, S-75185 Uppsala, Sweden.
    Nylander, Karin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Expression of CXCL10 is associated with response to radiotherapy and overall survival in squamous cell carcinoma of the tongue2014In: Tumor Biology, ISSN 1010-4283, E-ISSN 1423-0380, Vol. 35, no 5, p. 4191-4198Article in journal (Refereed)
    Abstract [en]

    Five-year survival for patients with oral cancer has been disappointingly stable during the last decades, creating a demand for new biomarkers and treatment targets. Lately, much focus has been set on immunomodulation as a possible treatment or an adjuvant increasing sensitivity to conventional treatments. The objective of this study was to evaluate the prognostic importance of response to radiotherapy in tongue carcinoma patients as well as the expression of the CXC-chemokines in correlation to radiation response in the same group of tumours. Thirty-eight patients with tongue carcinoma that had received radiotherapy followed by surgery were included. The prognostic impact of pathological response to radiotherapy, N-status, T-stage, age and gender was evaluated using Cox's regression models, Kaplan-Meier survival curves and chi-square test. The expression of 23 CXC-chemokine ligands and their receptors were evaluated in all patients using microarray and qPCR and correlated with response to treatment using logistic regression. Pathological response to radiotherapy was independently associated to overall survival with a 2-year survival probability of 81% for patients showing a complete pathological response, while patients with a non-complete response only had a probability of 42% to survive for 2 years (p = 0.016). The expression of one CXC-chemokine, CXCL10, was significantly associated with response to radiotherapy and the group of patients with the highest CXCL10 expression responded, especially poorly (p = 0.01). CXCL10 is a potential marker for response to radiotherapy and overall survival in patients with squamous cell carcinoma of the tongue.

  • 186.
    Rentoft, Matilda
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Fahlén, Jessica
    Umeå University, Faculty of Social Sciences, Department of Statistics.
    Coates, PJ
    Laurell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Sjöström, Björn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Rydén, Patrik
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Nylander, Karin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    miRNA analysis of formalin-fixed squamous cell carcinomas of the tongue is affected by age of the samples2011In: International Journal of Oncology, ISSN 1019-6439, Vol. 38, no 1, p. 61-69Article in journal (Refereed)
    Abstract [en]

    Global miRNA expression arrays were used for analysis of 836 miRNAs in formalin-fixed paraffin-embedded samples from 21 tongue cancer patients and 8 controls. Samples had been stored for one to eleven years. Results separated tumour samples from controls, however, the largest variation was correlated to sample storage time, detectable already after one year. With the use of a linear regression model we could adjust for the storage-dependent effect, leading to the identification of 54 differentially expressed miRNAs in tongue cancer, compared to 16 when using standard normalization, including up-regulation of a novel miRNA, miR-424.

  • 187.
    Rentoft, Matilda
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hultin, Sara
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Coates, Philip J
    Laurell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Nylander, Karin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Tubulin-α-6-chain is a stably expressed reference gene in archival samples of normal oral tissue and squamous cell carcinoma of the head and neck2010In: Experimental and Therapeutic Medicine, ISSN 1792-0981, Vol. 1, no 3, p. 419-423Article in journal (Refereed)
    Abstract [en]

    One of the most critical factors in gene expression studies using quantitative real-time PCR is the choice of reference gene. Many of the commonly used reference genes have been shown to vary during a number of biological processes as well as between tissues. It is therefore important to always verify the stability of the gene of choice for all new tissues and experimental conditions. Here, we used two publicly available computer software packages (GeNorm and NormFinder) to investigate the stability of eight potential reference genes in formalin-fixed paraffin-embedded (FFPE) samples from normal oral tissue of different origin as well as from oral squamous cell carcinomas. Both programs found the tubulin α-6 chain (TUBA6) and ribosomal protein S13 (RPS13) to have the most stable expression between malignant and non-malignant tissue. NormFinder also found TUBA6 to be the most stable gene when samples were grouped according to tissue origin. FFPE samples constitute a large research resource, which considerably increases the number of samples available for analysis, leading to more reliable conclusions. Verification of a proper reference gene in oral FFPE tissue is therefore of great importance for future studies.

  • 188.
    Rentoft, Matilda
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Johnsson, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Laurell, Goran
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Coates, Philip J.
    Nylander, Karin
    RNA expression profiling of archival tongue carcinoma samples2011Conference paper (Refereed)
  • 189.
    Rentoft, Matilda
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Laurell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Coates, Philip J
    Sjöström, Björn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Nylander, Karin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Comments on "Transcriptional profiling of oral squamous cell carcinoma using formalin-fixed paraffin-embedded samples" by Saleh et al., Oral Oncol 46 (2010) 379-386.2010In: Oral Oncology, ISSN 1368-8375, E-ISSN 1879-0593, Vol. 46, no 12, p. 891-892Article in journal (Other academic)
  • 190.
    Rentoft, Matilda
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Laurell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Coates, Philip John
    Sjöström, Björn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Nylander, Karin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Gene expression profiling of archival tongue squamous cell carcinomas provides sub-classification based on DNA repair genes2009In: International Journal of Oncology, ISSN 1019-6439, Vol. 35, no 6, p. 1321-1330Article in journal (Refereed)
    Abstract [en]

    A subgroup of patients with squamous cell carcinoma of the head and neck (SCCHN) comprise young persons under the age of 40, who have not been heavily exposed to the classical risk factors, smoking and alcohol. The number of SCCHN in young adults, particularly tongue tumours, is increasing in several parts of the world. Here we employed a novel gene expression array methodology specifically developed for analysis of degraded RNA and investigated the expression of 502 cancer-related genes in archival paraffin-embedded SCCHN of the tongue from young (< or =40) and elderly patients (> or =50). Genes detected as de-regulated in tumours compared to non-malignant controls were in concordance with results from earlier studies of fresh frozen material. No genes were detected as significantly differentially expressed between young and old patients suggesting that the overall pathobiology of SCCHN is similar in young and old. Unsupervised clustering divided tumours into three groups, irrespective of age, where several differentially expressed DNA repair genes were a prominent separation factor. High levels of DNA repair genes associated with impaired therapeutic response to radiation, suggesting that DNA repair genes play a role in clinical outcome after radiotherapy.

  • 191. Risberg-Berlin, B
    et al.
    Ylitalo, R
    Umeå University, Faculty of Medicine, Clinical Sciences, Otorhinolaryngology.
    Finizia, C
    Screening and Rehabilitation of Olfaction after Total Laryngectomy in Swedish Patients: Results From an Intervention Study Using the Nasal Airflow–Inducing Maneuver2006In: Archives of Otolaryngology - Head & Neck Surgery, ISSN 0886-4470, E-ISSN 1538-361X, Vol. 132, no 3, p. 301-306Article in journal (Refereed)
  • 192. Rodrigues, HP
    et al.
    Berggren, Diana
    Umeå University, Faculty of Medicine, Clinical Sciences, Otorhinolaryngology.
    Biology and treatment of sleep apnea2005In: Otolaryngology: Basic science and clinical review, Thieme New Your, Stuttgart , 2005, p. 71-82Chapter in book (Other (popular science, discussion, etc.))
  • 193.
    Rydberg, Frida
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Quality of Life After Cochlear Implant Surgery The Impact on Health-Related Quality of Life, Activity, Participation, and Coping2017Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 194. Saber, Amanj
    et al.
    Laurell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Bramer, Tobias
    Edsman, Katarina
    Engmér, Cecilia
    Ulfendahl, Mats
    Middle ear application of a sodium hyaluronate gel loaded with neomycin in a Guinea pig model.2009In: Ear and Hearing, ISSN 0196-0202, E-ISSN 1538-4667, Vol. 30, no 1, p. 81-89Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Establishing methods for topical administration of drugs to the inner ear have great clinical relevance and potential even in a relatively short perspective. To evaluate the efficacy of sodium hyaluronate (HYA) as a vehicle for drugs that could be used for treatment of inner ear disorders. METHODS: The cochlear hair cell loss and round window membrane (RWM) morphology were investigated after topical application of neomycin and HYA into the middle ear. Sixty-five albino guinea pigs were used and divided into groups depending on the type of the treatment. Neomycin was chosen as tracer for drug release and pharmacodynamic effect. HYA loaded with 3 different concentrations of neomycin was injected to the middle ear cavity of guinea pigs. Phalloidin stained surface preparations of the organ of Corti were used to estimate hair cell loss induced by neomycin. The thickness of the midportion of the RWM was measured and compared with that of controls using light and electron microscopy. All animal procedures were pe rformed in accordance with the ethical standards of Karolinska Institutet. RESULT: Neomycin induced a considerable hair cell loss in guinea pigs receiving a middle ear injection of HYA loaded with the drug, demonstrating that neomycin was released from the gel and delivered to the inner ear. The resulting hair cell loss showed a clear dose-dependence. Only small differences in hair cell loss were noted between animals receiving neomycin solution and animals exposed to neomycin in HYA suggesting that the vehicle neither facilitated nor hindered drug transport between the middle ear cavity and the inner ear. One week after topical application, the thickness of the RWM had increased and was dependent upon the concentration of neomycin administered to the middle ear. At 4 weeks the thickness of the RWM had returned to normal. CONCLUSION: HYA is a safe vehicle for drugs aimed to pass into the inner ear through the RWM. Neomycin was released from HYA and transported into the inner ear as evidenced by hair cell loss.

  • 195.
    Salander, Pär
    et al.
    Umeå University, Faculty of Social Sciences, Department of Social Work.
    Isaksson, Joakim
    Umeå University, Faculty of Social Sciences, Department of Social Work.
    Granström, Brith
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Laurell, Göran
    Institutionen för kirurgiska vetenskaper, Öron- näs- och halssjukdomar.
    How patients make use of a specialist nurse function in head and neck cancer: an empirical study2014In: Psycho-Oncology, ISSN 1057-9249, E-ISSN 1099-1611, Vol. 23, no Special issue S3, p. 159-Article in journal (Other academic)
  • 196.
    Salander, Pär
    et al.
    Umeå University, Faculty of Social Sciences, Department of Social Work.
    Isaksson, Joakim
    Umeå University, Faculty of Social Sciences, Department of Social Work.
    Granström, Brith
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Laurell, Göran
    Uppsala Universitet, Department of Surgical Sciences - Otolaryngology and Head & Neck Surgery.
    Motives that head and neck cancer patients have for contacting a specialist nurse: an empirical study2016In: Journal of Clinical Nursing, ISSN 0962-1067, E-ISSN 1365-2702, Vol. 25, no 21-22, p. 3160-3166Article in journal (Refereed)
    Abstract [en]

    Aims and objectives: The purpose of this study is to systematically explore the motives for patients with head and neck cancer to contact a speciaist nurse during two years postdiagnosis.

    Background: Research focusing on the role of specialist nurses in cancer care almost exclusively concern cancers other than head and neck cancer

    Design: Qualitative, descriptive study based on the contacts between patients with head and neck cancer and a specialist nurse.

    Methods: Patients were invited to contact a specialist nurse by telephone. The specialist nurse took systematic field notes, that is, she registered who contacted her, the nature of the call and the outcome. Sixty patients were included.

    Results: In descending order, the motives for contact were questions about practical and uncomplicated matters, consultations about medical troubles/worries, presenting a report of the patient's situation, requests for additional information about the treatment plan and requests for medical information. The pattern of the patients' motivations for calling was not related to medical or social factors, suggesting that the initiative to make a contact is very much a question of the complexity of individual life circumstances. Very few referrals were sent from the specialist nurse to other professionals.

    Conclusions: The specialist nurse turned out to be more than just a coordinator of health-care resources. The findings bring up questions about the potential of the nurse's function as a coordinator, but also as a potential attachment figure, and questions about the nurse's relationships to other professionals.

    Relevance to clinical practice: When implementing a specialist nurse function, it is important to decide whether the function should be inspired by a broader relational perspectice. In addition to the indispensible competence and experience in the clinical field of head and neck cancer, training in counselling and acquaintance with object-relational psychology will then be desirable.

  • 197.
    Sandberg, Jonatan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    AVNRT (atrioventricular nodal reentry tachycardia) ablation; is the risk for pacemaker increased in the long run?2017Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 198.
    Sandin, Robin
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Risk of reduced working capacity among people reporting hearing problems and stress2017Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 199.
    Sandström, Josefin
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Swanepoel, De Wet
    Carel Myburgh, Hermanus
    Laurent, Claude
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology. Department of Speech-Language Pathology and Audiology, University of Pretoria, Pretoria, South Africa.
    Smartphone threshold audiometry in underserved primary health-care contexts2016In: International Journal of Audiology, ISSN 1499-2027, E-ISSN 1708-8186, Vol. 55, no 4, p. 232-238Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To validate a calibrated smartphone-based hearing test in a sound booth environment and in primary health-care clinics.

    DESIGN: A repeated-measure within-subject study design was employed whereby air-conduction hearing thresholds determined by smartphone-based audiometry was compared to conventional audiometry in a sound booth and a primary health-care clinic environment.

    STUDY SAMPLE: A total of 94 subjects (mean age 41 years ± 17.6 SD and range 18-88; 64% female) were assessed of whom 64 were tested in the sound booth and 30 within primary health-care clinics without a booth.

    RESULTS: In the sound booth 63.4% of conventional and smartphone thresholds indicated normal hearing (≤15 dBHL). Conventional thresholds exceeding 15 dB HL corresponded to smartphone thresholds within ≤10 dB in 80.6% of cases with an average threshold difference of -1.6 dB ± 9.9 SD. In primary health-care clinics 13.7% of conventional and smartphone thresholds indicated normal hearing (≤15 dBHL). Conventional thresholds exceeding 15 dBHL corresponded to smartphone thresholds within ≤10 dB in 92.9% of cases with an average threshold difference of -1.0 dB ± 7.1 SD.

    CONCLUSIONS: Accurate air-conduction audiometry can be conducted in a sound booth and without a sound booth in an underserved community health-care clinic using a smartphone.

  • 200.
    Schmidt, Sten-Hermann
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Topical anesthesia of the tympanic membrane: an experimental animal study1987Doctoral thesis, monograph (Other academic)
    Abstract [en]

    Myringotomy plays an important role in otological therapy. The procedure requires an efficient anesthesia, which can be obtained without general anesthesia. However, the use of local anesthetics on the tympanic membrane (TM) has been abandoned in many places, as general anesthesia has been readily available. In the present study the effects of some commonly used topical anesthetics on the TM structure and inner ear were tested in an animal model (rat and guinea pig).Four different anesthetic compounds—Xylocaine®, Bonain's liquid, phenol and Emla®—were applied to the TMs of the animals, which were sacrificed 10 minutes to 5 months after application. Morphological effects regarding time after treatment and number of applications were elucidated. At sacrifice the tissue was fixed and the TMs analysed by light microscopy (LM) and transmission electron microscopy (TEM). In nine animals phenol, Xylocaine® Spray or Emla® was applied to the round window niche and ABR recordings were made at 24 h to 6 months after exposure. After the final ABR evaluation the animals were sacrificed and the cochleae prepared for LM and scanning electron microscopy (SEM).On the TM phenol and Bonain's liquid caused instant destruction of the keratinizing stratified squamous epithelium followed by long-lasting hyperplasia of this epithelium and the underlying connective tissue. A pronounced hyperplasia of these two layers was also noted for the Xylocaine® Spray group, but without immediate destruction of the keratinizing epithelium. The extent of structural changes differed in relation to the extent of spreading of the agent. Emla® showed little, if any, sign of epithelial reaction and had no effect on the connective tissue. Regarding the inner ear Emla®, Xylocaine® Spray and phenol induced significantly impaired ABR thresholds mainly affecting the higher frequencies. However, the impaired ABR thresholds were reversible and at the end of the experiment there was no significant impairment compared to the control data. All agents, except Xylocaine®, damaged the hair cells in the basal part of the cochlea as shown by cytocochleogram and SEM analysis.Instant destruction of the epidermis seems to be necessary for an instant anesthetic effect. All agents caused profound connective tissue reactions. The manner of application, depending on the physical properties of the agent, determined the extent of the structural changes. The changes of the connective tissue were concentrated to the submucosal layer, which seems to be the area for reconstruction of the damaged TM. All agents caused functional inner ear changes. With the exception of Xylocaine® they also caused morphological alterations of the cochlea. The functional changes were partly reversible. Topical anesthetics applied to the TM should be used with caution and when used in an appropriate manner they can be considered safe, especially in an inflamed middle ear, with a thickened round window membrane, which should prevent the agents from reaching the inner ear structures.

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