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  • 51.
    Emgård, Per
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences.
    Hellström, Sten
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Ohlander, Bengt
    Wennmo, Carsten
    Effects of betamethasone dipropionate plus an antihistamine in patients with external otitis1999In: Current Therapeutic Research: Clinical and Experimental, ISSN 0011-393X, E-ISSN 1879-0313, Vol. 60, no 7, p. 364-370Article in journal (Refereed)
    Abstract [en]

    In a prospective multicenter, randomized, double-masked trial, 30 patients with external otitis received betamethasone dipropionate in a 0.05% solution for 11 days. Fifty percent of the patients were assigned randomly to receive concomitant treatment with loratadine to help control itching, and 50% received placebo. The status of the external auditory canal (EAC) was assessed on days 0, 3, 7, 11, and 21 according to a new scoring system that graded color, the extension of redness outside the EAC, swelling, and effusion. Eighteen patients underwent sampling for a bacteriologic culture at the start of treatment; 14 cultures showed positive findings. The EAC status improved rapidly, and by day 11 it was almost normal in all patients. Pain and sleep disturbances disappeared by day 7; at which point itching was either nonexistent or mild. All patients were able to resume work after 3 days of treatment. At the end of the study, 29 (97%) of the 30 patients were cured. The addition of loratadine to the treatment did not improve results significantly. External otitis is generally treated with a combination of a steroid and an antibiotic. Results of this study suggest that external otitis, whether culture-positive or not, can be cured using a group III steroid alone.

  • 52. Engmér, Cecilia
    et al.
    Laurell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Bagger-Sjöbäck, Dan
    Rask-Andersen, Helge
    Immunodefense of the round window2008In: The Laryngoscope, ISSN 0023-852X, E-ISSN 1531-4995, Vol. 118, no 6, p. 1057-1062Article in journal (Refereed)
    Abstract [en]

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

  • 53. Engstrand, I
    et al.
    Bohlin, Lennart
    Umeå University, Faculty of Medicine, Clinical Sciences, Otorhinolaryngology.
    Carlborg, B
    Hellström, Sten
    Umeå University, Faculty of Medicine, Clinical Sciences, Otorhinolaryngology.
    Kjellén, G
    Kumlien, J
    Månsson, I
    Weitz, P
    Kvaliteten i öron-, näs- och halssjukvården: patienten får bedöma2004In: Läkartidningen, no 50, p. 4119-4120Article in journal (Other (popular science, discussion, etc.))
  • 54.
    Eriksson, Jennie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Hörselnedsättning i Västernorrland 1998-20182018Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 55.
    Eriksson, Per Olof
    Umeå University, Faculty of Medicine, Clinical Sciences, Otorhinolaryngology.
    Developing otitis media: experimental studies in particular regarding inflammatory changes in the tympanic membrane2004Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Otitis media (OM), one of the commonest of childhood diseases, causes much suffering. OM exists in a variety of forms, two of which are acute otitis media (AOM) and otitis media with effusion (OME). The clinical courses of these conditions differ, AOM usually presenting with earache, fever and/or aural discharge, and the OME usually with hearing impairment. The tympanic membrane (TM) mirrors the events in the middle ear cavity, and pars flaccida (PF) is the initial site of inflammatory changes in the TM. PF is rich in mast cells (MCs), which by releasing various mediators, may trigger TM inflammation.

    The aims of the present studies were to investigate early inflammatory changes in the TM in rat models of OM; after mast cell degranulation, in response to AOM, and OME, after myringotomy in AOM and in normal ears. Furthermore, we developed a new rat AOM model, that excludes surgical trauma and resembles the natural route of infection in man.

    AOM and OME elicited the first inflammatory response in PF of the TM. The response to OME was discrete, but a slight increase in macrophages was found. During the first 48 hours of AOM, the inflammatory response was intense, following a bimodal pattern. This reaction is similar to that found after MC degranulation. In AOM, macrophages were the predominant cell in PF, while in pars tensa (PT), polymorphonuclear cells (mainly neutrophils) predominated.

    When myringotomy was performed in AOM ears, the healing time was shorter than that of myringotomy in normal ears. The highly inflamed lamina propria seemed to promote healing.

    During early AOM, as well as following myringotomy, fibrin extravasates into PF and PT. This fibrin deposition may be involved in regulating the inflammatory response.

    Repeated nasal challenge with the otitis media pathogen Streptococcus pneumoniae provoked AOM and concomitant TM stimulation reduced the number of AOM cases. This new rat AOM model has the advantage of avoiding trauma in the middle ear cavity, while eliciting an intense inflammatory response in the middle ear cavity (MEC).

  • 56.
    Eriksson, Per Olof
    et al.
    Umeå University, Faculty of Medicine, Clinical Sciences, Otorhinolaryngology.
    Hellström, Sten
    Umeå University, Faculty of Medicine, Clinical Sciences, Otorhinolaryngology.
    Acute otitis media develops in the rat after intranasal challenge of Streptococcus pneumoniae.2003In: The Laryngoscope, ISSN 0023-852X, E-ISSN 1531-4995, Vol. 113, no 11, p. 2047-2051Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES/HYPOTHESIS: The rat is a frequently used animal model for middle ear research. To date, acute otitis media (AOM) has been evoked after instillation of bacteria directly into the middle ear cavity or after traumatizing the tympanic membrane. The purpose of the study was to examine whether, with an intact tympanic membrane and middle ear cavity, intranasally deposited bacteria cause AOM and how tympanic membrane stimulation influences this procedure. STUDY DESIGN: In vivo, murine model. METHODS: In a rat model, Streptococcus pneumoniae, type 3, was intranasally inoculated for 5 consecutive days. The tympanic membrane was treated with saline or with compound 48/80 or was left untreated. The development of AOM was evaluated by otomicroscopy, light microscopy, and middle ear culture. RESULTS: Ninety percent of the ears developed AOM. However, when the tympanic membranes were treated with saline or compound 48/80, only 40% and 57%, respectively, developed AOM. In all, 23 of 40 ears developed AOM and 20 ears showed growth of bacteria. CONCLUSION: Repeated intranasal deposition of S. pneumoniae, type 3, causes AOM in the rat. The development of AOM can be influenced by tympanic membrane stimulation.

  • 57.
    Eriksson, Per Olof
    et al.
    Umeå University, Faculty of Medicine, Clinical Sciences, Otorhinolaryngology.
    Hellström, Sten
    Umeå University, Faculty of Medicine, Clinical Sciences, Otorhinolaryngology.
    Degranulation of mast cells provokes a massive inflammatory reaction in the tympanic membrane.2001In: The Laryngoscope, ISSN 0023-852X, E-ISSN 1531-4995, Vol. 111, no 7, p. 1264-1270Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The pars flaccida is extremely rich in mast cells. On stimulation the mast cells release preformed and de novo synthesized inflammatory substances. The purpose of this study was to examine how these mast cell substances provoke inflammatory changes in the tympanic membrane. STUDY DESIGN: In vivo, murine model. METHODS: In a rat model, the mast cell secretagogue compound 48/80 was applied locally to the tympanic membrane on 4 consecutive days and the ensuing inflammatory changes were evaluated by otological, light, and electron microscopy 3, 6, 9, 12, 18, 24, 36, and 48 hours and 4, 6, and 8 days later. RESULTS: Degranulation of the mast cells occurred within 3 hours of applying compound 48/80. Release of the mast cell substances coincided with an inflammatory event characterized by a two-stage reaction: an edema stage, peaking 6 hours after application, followed by a massive invasion of inflammatory cells, peaking at 24 and 48 hours. Pars flaccida and pars tensa were both involved, pars flaccida showing the earliest changes. Pars tensa exhibited the same biphasic reaction as pars flaccida, but approximately 6 hours later. CONCLUSIONS: The mast cells of the pars flaccida have the capacity to elicit an intense inflammation of the tympanic membrane. The biphasic reaction pattern resembles that observed in experimental otitis media, suggesting involvement of the mast cells in this inflammatory condition of the middle ear.

  • 58.
    Eriksson, Per-Olof
    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.
    Ny, Tor
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Hellström, Sten
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Spontaneous development of otitis media in plasminogen-deficient mice2006In: International Journal of Medical Microbiology, ISSN 1438-4221, E-ISSN 1618-0607, Vol. 296, no 7, p. 501-509Article in journal (Refereed)
    Abstract [en]

    Inflammatory conditions of the ear, otitis media, are one of the most common disease entities in children. In this study, the role of the plasminogen (plg)/plasmin system for the spontaneous development of chronic otitis media was investigated by the analysis of plg-deficient mice. Whereas essentially all of the wild-type control mice kept a healthy status of the middle ear, all the plg-deficient mice gradually developed chronic otitis media with various degrees of inflammatory changes during an 18-week observation period. Five bacterial strains were identified in materials obtained from the middle ear cavities of six plg-deficient mice. Morphological studies revealed the formation of an amorphous mass tissue and inflammatory changes in the middle ears of plg-deficient mice. Immunohistochemical studies further indicate a mass infiltration of neutrophils and macrophages as well as the presence of T and B cells in the middle ear mucosa of these mice. Extensive fibrin deposition and an abnormal keratin formation were also observed in the tympanic membrane, the middle ear cavity and external ear canal in these mice. These results suggest that plg plays an essential role in protecting against the spontaneous development of chronic otitis media. Our findings also suggest the possibility of using plg for clinical therapy of certain types of otitis media.

  • 59.
    Eriksson Salander, Annina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Ensidig hörselnedsättning hos barn i landstinget Västernorrland2016Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 60.
    Fejle, Linda
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Epidemiologi och karakteristika hos patienter som sökt akut för yrsel och erhållit en oto-vestibulär diagnos: En kartläggning av patienter som under åren 2012-2013 sökt akutmottagningen på Norrlands universitetssjukhus p.g.a. akut yrsel2016Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 61. Forslund, Ola
    et al.
    Schwartz, Stefan
    Olofsson, Katarina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Rydell, Roland
    Viral load and mRNA expression of HPV type 6 among cases with recurrent respiratory papillomatosis2016In: The Laryngoscope, ISSN 0023-852X, E-ISSN 1531-4995, Vol. 126, no 1, p. 122-127Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES/HYPOTHESIS: To determine viral load of human papillomavirus type 6 (HPV6), physical state of HPV6-DNA, and transcription level of HPV6 E7-mRNA in laryngeal papilloma and in adjacent healthy mucosa.

    STUDY DESIGN: Case series.

    METHODS: A papilloma biopsy was collected from each of 25 adult patients with respiratory recurrent papillomatosis. From 14 of the 25 patients, we first collected a biopsy from healthy mucosa of the false vocal fold and another from the papilloma. Quantity of HPV6 and E7-mRNA was measured by polymerase chain reaction.

    RESULTS: For the papilloma, the median load of HPV6 was 41 copies/cell, and the lowest amount was 5.4 copies/cell. Human papillomavirus type 6 was detected in 50% (7/14) of the healthy mucosa, with a median of 1.1 copies/cell, and the highest amount was 6.6 copies/cell. Overall, viral load was higher in papilloma than in healthy mucosa (P < 0.05). The average HPV6 E2/E7-DNA ratio was 1.3, indicating an episomal state. Human papillomavirus type 6-mRNA was detected in all HPV6-DNA-positive samples. The transcription median ratio of HPV6-mRNA/HPV6-DNA was 1.5 in papilloma and 3.8 in healthy mucosa.

    CONCLUSION: The amount of HPV6-DNA was consistently higher in the papilloma than in healthy mucosa. The transcription level of HPV6 E7 mRNA was similar in the papilloma and in normal mucosa. We suggest that interfering with replication of HPV6 and suppression of HPV6 to fewer than five copies/cell may be curative.

    LEVEL OF EVIDENCE: N/A. Laryngoscope, 126:122-127, 2016.

  • 62.
    Franzén, Lars
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Sundström, Staffan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Histology and Cell Biology.
    Karlsson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Gustafsson, Hans
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Littbrand, Bo
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Fractionated irradiation and early changes in noradrenaline induced potassium efflux(86Rb+) in rat parotid gland1992In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 31, no 3, p. 359-364Article in journal (Refereed)
    Abstract [en]

    The effects of fractionated irradiation on the electrolyte fluid secretion from rat parotid gland were studied. Secretion was measured as noradrenaline stimulated potassium efflux in vitro with Rb-86+ as tracer for potassium. The irradiation was delivered either as a five-day schedule (total dose 20, 25, 30, 35, 40, 45 Gy) or a two-day schedule (total dose 24, 32 Gy). The noradrenaline stimulated efflux was decreased in comparison with contralateral controls 10 days after the last irradiation. The effect was dose-dependent. Based on the data available, alpha/beta ratio of the used system was calculated to about 20 Gy, which corresponds to other results regarding early radiation effects.

  • 63.
    Gammelgård, Sofia
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Kan identifiering och behandling av patienter med akut Benign Paroxysmal Positionell Vertigo optimeras?   En kartläggning av patienter som våren 2016 vårdats inneliggande på Norrlands Universitetssjukhus pga. akut yrsel.: En kartläggning av patienter som våren 2016 vårdats inneliggande på Norrlands Universitetssjukhus pga. akut yrsel.2016Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 64.
    Gu, Xiaolian
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Boldrup, Linda
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Coates, Philip J
    Fåhraeus, Robin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. RECAMO, Masaryk Memorial Cancer Institute, Brno, Czech Republic; Institut de Génétique Moléculaire, Université Paris 7, Hôpital St. Louis, Paris, France.
    Nylander, Elisabet
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Loizou, Christos
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Olofsson, Katarina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Norberg-Spaak, Lena
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Gärskog, Ola
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Nylander, Karin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Epigenetic regulation of OAS2 shows disease-specific DNA methylation profiles at individual CpG sites2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 32579Article in journal (Refereed)
    Abstract [en]

    Epigenetic modifications are essential regulators of biological processes. Decreased DNA methylation of OAS2 (2'-5'-Oligoadenylate Synthetase 2), encoding an antiviral protein, has been seen in psoriasis. To provide further insight into the epigenetic regulation of OAS2, we performed pyrosequencing to detect OAS2 DNA methylation status at 11 promoter and first exon located CpG sites in psoriasis (n = 12) and two common subtypes of squamous cell carcinoma (SCC) of the head and neck: tongue (n = 12) and tonsillar (n = 11). Compared to corresponding controls, a general hypomethylation was seen in psoriasis. In tongue and tonsillar SCC, hypomethylation was found at only two CpG sites, the same two sites that were least demethylated in psoriasis. Despite differences in the specific residues targeted for methylation/demethylation, OAS2 expression was upregulated in all conditions and correlations between methylation and expression were seen in psoriasis and tongue SCC. Distinctive methylation status at four successively located CpG sites within a genomic area of 63 bp reveals a delicately integrated epigenetic program and indicates that detailed analysis of individual CpGs provides additional information into the mechanisms of epigenetic regulation in specific disease states. Methylation analyses as clinical biomarkers need to be tailored according to disease-specific sites.

  • 65.
    Gu, Xiaolian
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Coates, Philip J.
    Boldrup, Linda
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Wang, Lixiao
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Krejci, Adam
    Hupp, Ted
    Fåhraeus, Robin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences. RECAMO, Masaryk Memorial Cancer Institute, Brno, Czech Republic; Institute of Molecular Genetics, University Paris 7, St. Louis Hospital, Paris, France.
    Norberg-Spaak, Lena
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Sgaramella, Nicola
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Wilms, Torben
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Nylander, Karin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Copy number variation: A prognostic marker for young patients with squamous cell carcinoma of the oral tongue2019In: Journal of Oral Pathology & Medicine, ISSN 0904-2512, E-ISSN 1600-0714, Vol. 48, no 1, p. 24-30Article in journal (Refereed)
    Abstract [en]

    Background The incidence of squamous cell carcinoma of the oral tongue (SCCOT) is increasing in people under age 40. There is an urgent need to identify prognostic markers that help identify young SCCOT patients with poor prognosis in order to select these for individualized treatment. Materials and methods To identify genetic markers that can serve as prognostic markers for young SCCOT patients, we first investigated four young (<= 40 years) and five elderly patients (>= 50 years) using global RNA sequencing and whole-exome sequencing. Next, we combined our data with data on SCCOT from the cancer genome atlas (TCGA), giving a total of 16 young and 104 elderly, to explore the correlations between genomic variations and clinical outcomes. Results In agreement with previous studies, we found that SCCOT from young and elderly patients was transcriptomically and also genomically similar with no significant differences regarding cancer driver genes, germline predisposition genes, or the burden of somatic single nucleotide variations (SNVs). However, a disparate copy number variation (CNV) was found in young patients with distinct clinical outcome. Combined with data from TCGA, we found that the overall survival was significantly better in young patients with low-CNV (n = 5) compared to high-CNV (n = 11) burden (P = 0.044). Conclusions Copy number variation burden is a useful single prognostic marker for SCCOT from young, but not elderly, patients. CNV burden thus holds promise to form an important contribution when selecting suitable treatment protocols for young patients with SCCOT.

  • 66.
    Gu, Xiaolian
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Coates, Philip
    MacCallum, Stephanie
    Boldrup, Linda
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Sjöström, Björn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Nylander, Karin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    TRAF4 is potently induced by TAp63 isoforms and localised according to differentiation in SCCHN2007In: Cancer Biology & Therapy, ISSN 1538-4047, E-ISSN 1555-8576, Vol. 6, no 12, p. 1979-1983Article in journal (Refereed)
    Abstract [en]

    p63, a member of the p53 family, is overexpressed in squamous cell carcinoma of the head and neck (SCCHN) and some other tumors of epithelial origin. As a transcription factor, p63 can bind to p53-type response elements and there is some overlap between p53 family transcriptional targets. Tumor necrosis factor receptor associated factor 4 (TRAF4) is a p53 regulated gene which is overexpressed in many human carcinomas. We investigated the involvement of p63 in regulation of TRAF4 and the expression of the TRAF4 protein in SCCHN. Disrupting endogenous p63 expression resulted in downregulation of TRAF4 mRNA and protein in an SCCHN cell line. Endogenous p63 bound to the TRAF4 promoter in vivo and reporter assays showed that p63, p73 and p53 can all transactivate TRAF4, with TAp63 isoforms being the most potent activators. The level of TRAF4 activation by TAp63 was two-fold higher than by p53, and TRAF4 was ten-fold more responsive to TAp63 than another p63-target, IGFBP3. Nuclear expression of TRAF4 was seen in normal oral epithelium and highly/moderately differentiated SCCHN, whereas cytoplasmic expression of TRAF4 was seen in poorly differentiated SCCHN. These results indicate that TRAF4 is a common target of p53 family members and that localization of TRAF4 is associated with differentiation of SCCHN cells.

  • 67.
    Gu, Xiaolian
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Wang, Lixiao
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Boldrup, Linda
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Coates, Philip J.
    Fåhraeus, Robin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. RECAMO, Masaryk Memorial Cancer Institute, 656 53 Brno, Czech Republic; Équipe Labellisée Ligue Contre le Cancer, INSERM UMRS1162, Institut de Génétique Moléculaire, Université Paris 7, IUH Hôpital St. Louis, 75010 Paris, France.
    Sgaramella, Nicola
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Wilms, Torben
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Nylander, Karin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    AP001056.1, A Prognosis-Related Enhancer RNA in Squamous Cell Carcinoma of the Head and Neck2019In: Cancers, ISSN 2072-6694, Vol. 11, no 3, article id 347Article in journal (Refereed)
    Abstract [en]

    A growing number of long non-coding RNAs (lncRNAs) have been linked to squamous cell carcinoma of the head and neck (SCCHN). A subclass of lncRNAs, termed enhancer RNAs (eRNAs), are derived from enhancer regions and could contribute to enhancer function. In this study, we developed an integrated data analysis approach to identify key eRNAs in SCCHN. Tissue-specific enhancer-derived RNAs and their regulated genes previously predicted using the computational pipeline PreSTIGE, were considered as putative eRNA-target pairs. The interactive web servers, TANRIC (the Atlas of Noncoding RNAs in Cancer) and cBioPortal, were used to explore the RNA levels and clinical data from the Cancer Genome Atlas (TCGA) project. Requiring that key eRNAs should show significant associations with overall survival (Kaplan-Meier log-rank test, p < 0.05) and the predicted target (correlation coefficient r > 0.4, p < 0.001), we identified five key eRNA candidates. The most significant survival-associated eRNA was AP001056.1 with ICOSLG encoding an immune checkpoint protein as its regulated target. Another 1640 genes also showed significant correlation with AP001056.1 (r > 0.4, p < 0.001), with the "immune system process" being the most significantly enriched biological process (adjusted p < 0.001). Our results suggest that AP001056.1 is a key immune-related eRNA in SCCHN with a positive impact on clinical outcome.

  • 68.
    Gustafsson, Hans
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Histology and Cell Biology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Salivary gland neoplasms: studies on the cytoskeleton, the secretory apparatus and the nuclear DNA content1986Doctoral thesis, monograph (Other academic)
    Abstract [en]

    The heterogeneity of salivary gland neoplasms have made classification and prognostication of these tumours sometimes difficult, and the in­troduction of techniques, such as enzyme and carbohydrate histochemis­try and electron microscopy have only to a certain extent increased our knowledge in these respects. In the present study immunohistochemical methods have been used to identify intermediate filament proteins (IFP) in normal fetal and adult parotid glands, as well as in salivary neo­plasms. The intermediate filaments (IF) make up the cytoskeleton in eucaryotic cells. Epithelial tissue contains IF composed of different cytokeratins (CK 1-19) whilst mesenchymal tissue generally contains IF composed of vimentin, and the IFP pattern is very stable even during cell transformation. It would thus be possible to further clarify the histogenesis of salivary neoplasms by identifying IFP, in addition the IFP pattern would probably be useful in tumour typing. Furthermore, ultrastructural cytochemical studies, microspectorphotometry on nuclear DNA as well as enzyme secretory studies of certain tumour types were carried out, in order to further characterize the biology of salivary neoplasms.

    The immunohistochemical investigations showed that in normal parotid tissue, the different cell types differed in IFP expression: acinar cells express mainly CK 18 and myoepithelial cells mainly CK 17 and 19, whilst duct cells contained a broad range of CK. Vimentin could in ad­dition to CK be detected in myoepithelial cells and basal cells of ex­cretory ducts. Fetal parotid cells showed a similar CK pattern as mature duct cells. In addition, vimentin could be found in some basal cells of the terminal tubules of the fetal glands. Salivary neoplasms could be divided into three types with regard to their IFP pattern:

    1.  Acinic cell carcinomas showed a CK-pattern similar to normal acinar cells but a co-expression of CK and vimentin was present in some cells.
    2.  Adenoid cystic carcinomas, mixed tumours and basal cell adenomas showed a CK-pattern of normal duct or myoepithelial cells. The peri­pheral cells were also vimentin positive. 3. Mucoepidermoid carcinomas and adenocarcinomas had a similar CK-pattern as duct cells, and no tu­mour cells contained vimentin. This indicates that typing of IFP may be useful for subgrouping of salivary neoplasms.

    By stereological measurements, the cells of acinic cell carcinomas were found to be very similar to normal parotid acinar cells. Furthermore, they contained amylase and after stimulation by norepiphrine a secre­tory response was induced, with a rise in intracellular cAMP as well as a release of amylase. By single cell measurements of nuclear DNA con­tent, no difference was found between acinic cell carcinomas with de­finite metastasis and those without recurrence, both in paraffin sec­tions and cytological smears.

  • 69.
    H, Diamant
    et al.
    Umeå University, Faculty of Medicine, Clinical Sciences, Otorhinolaryngology.
    Sten, Hellström
    Umeå University, Faculty of Medicine, Clinical Sciences, Otorhinolaryngology.
    Umeå öron-, näs- och halskliniks historia2004In: Svensk ÖNH-tidskrift, no 3, p. 1-4Article in journal (Other (popular science, discussion, etc.))
  • 70. Hallenstål, Niclas
    et al.
    Sunnergren, Ola
    Ericsson, Elisabeth
    Hemlin, Claes
    Sodermane, Anne-Charlotte Hessen
    Nerfeldt, Pia
    Odhagen, Erik
    Ryding, Marie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology. Department of Otorhinolaryngology, Östersund Hospital, Östersund, Sweden.
    Stalfors, Joacim
    Tonsil surgery in Sweden 2013-2015. Indications, surgical methods and patient-reported outcomes from the National Tonsil Surgery Register2017In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 137, no 10, p. 1096-1103Article in journal (Refereed)
    Abstract [en]

    Aim: To describes how tonsil surgery was performed in Sweden from 2013 to 2015 with data from the National Tonsil Surgery Registry in Sweden (NTSRS).

    Method: The registry collects data from both professionals and patients through questionnaires. A total of 33,870 tonsil surgeries were analysed, comprising approximately 80% of all tonsil surgeries in Sweden from 2013 to 2015.

    Results: The two most common procedures were tonsillectomy (41%) and tonsillotomy with adenoidectomy (38%). Tonsillectomy was most commonly performed to treat frequent tonsillitis, while the main indication for tonsil surgery with combined adenoidectomy and for tonsillotomy alone was upper airway obstruction. The most commonly used techniques were cold steel (70%) for tonsillectomy/adenotonsillectomy and radiofrequency (79%) for tonsillotomy/adenotonsillotomy. Ninety-five percent of patients reported symptom relief after 180 d. Day surgery was utilised in 70% of the surgeries. The rate of readmission due to post-tonsillectomy haemorrhage was 5.1%. Male patients more often underwent tonsil surgery at preschool ages due to upper airway obstruction; in comparison, female patients to a larger extent underwent surgery in their early teens because of previous infections.

    Conclusions: The NTSRS provides an opportunity to survey tonsil surgery in Sweden and to launch and follow up improvement programmes as desired.

  • 71.
    Hansson, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    The effects of plasminogen deficiency on the healing of tympanic membrane perforations2007Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The healing of tympanic membrane (TM) perforations is a complex wound healing process including inflammation, migration of keratinocytes and tissue remodelling. Most TM perforations in human heal spontaneously, however some perforations become chronic, and the reason to why is still largely unknown. In cutaneous wound healing plasminogen (plg) has been shown to play an important role. Plg is converted into the protease plasmin regulated by two plasminogen activators (PA), urokinase type PA (uPA) and tissue-type PA (tPA).

    The aim of the present thesis was to evaluate the role of plg in healing of TM perforations, both in vivo and in vitro. The main objectives were to determine the healing capacity of the TM, the involvement of keratinocytes, fibrin(ogen) and inflammatory cells in the healing process. The studies were performed in plg deficient and uPA deficient mice, with littermate wild type (wt) mice as controls

    It was shown that myringotomies of the TMs in plg deficient mice still remained open 143 days following a perforation. The wound area was characterized by an abundant recruitment and accumulation of inflammatory cells; mainly macrophages and neutrophils, an arrested keratinocyte migration and a fibrin deposition covering the surface of the TM. The TM perforations in the wt mice all healed within 11 days. Interestingly, the myringotomies of the plg deficient mice could be closed by reconstitution with systemic injections of plg, whereas injections of PBS had no affect on the healing.

    To characterize mechanisms involved in the development of persistent TM perforations in plg deficient mice after a myringotomy the early inflammatory response during the first 48 hours was studied. The recruitment and accumulation of inflammatory cells in the perforated TMs was found to be similar between the plg deficient and the wt mice.

    Myringotomized TMs in uPA deficient mice healed similar to perforations of wt controls. Neither did the keratinocyte migration nor the occurrence of inflammatory cells differ between these genotypes.

    In the in vitro experiments TMs from plg deficient and wt mice, were dissected out, perforated and cultured in absence or surplus of plg. A decrease in perforation size was seen in all groups regardless of genotype or amount of plg in the medium.

    In conclusion, the present studies show:

    • Plg is essential for the healing of TM perforations in mice.

    • The altered healing process after a myringotomy in plg deficient mice involves a disturbed keratinocyte migration, a massive deposition of fibrin and an abundant accumulation of inflammatory cells in the wound area.

    • Plasminogen deficiency does not alter the early inflammatory response, following a myringotomy.

    • Deficiency of uPA does not influence the healing of TM perforations.

    • During in vitro conditions healing of TM perforations is initiated irrespectively of genotype of the explant (plg deficient or wt) or supply of plg.

    The increased knowledge of the involvement of plg in the healing of TM perforations may open therapeutical possibilities in the treatment of chronic TM perforations in humans.

  • 72. Hardell, L
    et al.
    Hallquist, A
    Hansson Mild, K
    Carlberg, M
    Gertzén, H
    Schildt, E-B
    Dahlqvist, A
    Umeå University, Faculty of Medicine, Clinical Sciences, Otorhinolaryngology.
    No association between the use of cellular or cordless telephones and salivary gland tumours2004In: Occup Environ Med, ISSN 1470-7926, Vol. 61, no 8, p. 675-679Article in journal (Refereed)
  • 73. Hellberg, Victoria
    et al.
    Wallin, Inger
    Eriksson, Sofi
    Hernlund, Emma
    Jerremalm, Elin
    Berndtsson, Maria
    Eksborg, Staffan
    Arnér, Elias SJ
    Shoshan, Maria
    Ehrsson, Hans
    Laurell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Cisplatin and oxaliplatin toxicity: importance of cochlear kinetics as a determinant for ototoxicity2009In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 101, no 1, p. 37-47Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Cisplatin is a cornerstone anticancer drug with pronounced ototoxicity, whereas oxaliplatin, a platinum derivative with a different clinical profile, is rarely ototoxic. This difference has not been explained.

    METHODS: In HCT-116 cells, cisplatin (20 microM)-induced apoptosis was reduced by a calcium chelator from 9.9-fold induction (95% confidence interval [CI] = 8.1- to 11.7-fold), to 3.1-fold induction (95% CI = 2.0- to 4.2-fold) and by superoxide scavenging from 9.3-fold (95% CI = 8.8- to 9.8-fold), to 5.1-fold (95% CI = 4.4- to 5.8-fold). A guinea pig model (n = 23) was used to examine pharmacokinetics. Drug concentrations were determined by liquid chromatography with post-column derivatization. The total platinum concentration in cochlear tissue was determined by inductively coupled plasma mass spectrometry. Drug pharmacokinetics was assessed by determining the area under the concentration-time curve (AUC). Statistical tests were two-sided.

    RESULTS: In HCT-116 cells, cisplatin (20 microM)-induced apoptosis was reduced by a calcium chelator from 9.9-fold induction (95% confidence interval [CI] = 8.1- to 11.7-fold to 3.1-fold induction) (95% CI = 2.0- to 4.2-fold) and by superoxide scavenging (from 9.3-fold, 95% CI = 8.8- to 9.8-fold, to 5.1-fold, 95% CI = 4.4- to 5.8-fold). Oxaliplatin (20 microM)-induced apoptosis was unaffected by calcium chelation (from 7.1- to 6.2-fold induction) and by superoxide scavenging (from 5.9- to 5.6-fold induction). In guinea pig cochlea, total platinum concentration (0.12 vs 0.63 microg/kg, respectively, P = .008) and perilymphatic drug concentrations (238 vs 515 microM x minute, respectively, P < .001) were lower after intravenous oxaliplatin treatment (16.6 mg/kg) than after equimolar cisplatin treatment (12.5 mg/kg). However, after a non-ototoxic cisplatin dose (5 mg/kg) or the same oxaliplatin dose (16.6 mg/kg), the AUC for perilymphatic concentrations was similar, indicating that the two drugs have different cochlear pharmacokinetics.

    CONCLUSION: Cisplatin- but not oxaliplatin-induced apoptosis involved superoxide-related pathways. Lower cochlear uptake of oxaliplatin than cisplatin appears to be a major explanation for its lower ototoxicity.

  • 74.
    Hellström, Martin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Hyaluronan and the receptor CD 44 in the heart and vessels: a study in normal and pathological conditions2007Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Tissues are not solely composed of cells. The extracellular matrix is important for the cell well-being and cell-cell communication. The glycosaminoglycan hyaluronan (HYA) is a widely distributed extracellular matrix (ECM) component. The molecule has prominent physicochemical properties, foremost viscoelastic and osmotic, but participates in many biological processes such as cell migration, proliferation, tissue turnover, wound healing and angiogenesis. HYA is synthesised by either of three different hyaluronan-synthesising enzymes, HAS1-3, and its main ligand is the transmembrane receptor CD44. In the heart and vessels the matrix components are of great importance for endurance and elasticity which are prerequisites for a normal function. The aims of the study were to describe the distribution of HYA and its receptor CD44 in normal cardiovascular tissue and to investigate the ECM composition in myocardial hypertrophy.

    Normal conditions were studied in a rat model. These studies showed that the tunica adventitia in almost all vessels stained strongly for HYA. The expression in the tunica intima and media on the venous side, differed between the vessels and was almost absent on the arterial side. In the adult animals only minute amounts of CD44 were detected. The expression of both HYA and CD44 was increased in newborn rats.

    In the heart HYA was unevenly distributed in the interstitium. Strong HYA-staining was seen in the valves and in the adventitia of intramyocardial vessels. Almost no CD44-staining was observed. Notably, there was no obvious difference between newborn and adult animals.

    In an experimental rat model of pressure-induced cardiac hypertrophy the mRNA-levels of HAS1, HAS2, CD44, basic Fibroblast Growth Factor (FGF-2) and Fibroblast Growth Factor Receptor-1 (FGFR-1) were elevated on day 1 after aortic banding. HAS2, CD44 and FGFR-1 were at basal levels on day 42. The HYA-concentration was significally elevated on day 1. HYA was detected in the interstitium by histochemistry and CD44 was detected mainly in and around the intramyocardial vessels.

    The HYA-staining was increased in myectomi specimens from patients with HCM compared to controls. HYA was detected in the interstitium, in fibrous septas and in the adventitia of intramyocardial vessels. No CD44 was detected in HCM or in control specimens.

    Our results indicate that HYA and CD44 play an active role in the maturing vessel tree and that the ECM content of HYA is increased in experimental myocardial hypertrophy and human hypertrophic cardiomyopathy.

  • 75.
    Hellström, Martin
    et al.
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine. Umeå University, Faculty of Medicine, Clinical Sciences, Otorhinolaryngology.
    Engström Laurent, Anna
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine. Umeå University, Faculty of Medicine, Clinical Sciences, Otorhinolaryngology.
    Hellström, Sten
    Umeå University, Faculty of Medicine, Clinical Sciences, Otorhinolaryngology.
    Expression of the CD44 receptor in the blood vessel system: an experimental study in rat.2005In: Cells Tissues Organs, ISSN 1422-6405, E-ISSN 1422-6421, Vol. 179, no 3, p. 102-108Article in journal (Refereed)
  • 76.
    Hellström, Sten
    Umeå University, Faculty of Medicine, Clinical Sciences, Otorhinolaryngology.
    Dimeric Tympanic Membrane2004In: Advanced Therapy of Otitis Media, 2004, p. 392-393Chapter in book (Other academic)
  • 77.
    Hellström, Sten
    Umeå University, Faculty of Medicine, Clinical Sciences, Otorhinolaryngology.
    Salient Healing Features of the Tympanic Membrane2008In: Essential Tissue Healing of the Face and Neck, 2008Chapter in book (Other (popular science, discussion, etc.))
  • 78.
    Hellström, Sten
    Umeå University, Faculty of Medicine, Clinical Sciences, Otorhinolaryngology.
    Tympanic Membrane Perforation2004In: Advanced Therapy of Otitis Media, 2004, p. 382-386Chapter in book (Other (popular science, discussion, etc.))
  • 79.
    Hellström, Sten
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Pettersson, Agneta
    Tympanostomy tube treatment in otitis media. A systematic literature review. SBU summary and conclusions2008In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 105, no 30-31, p. 2104-2106Article in journal (Refereed)
    Abstract [en]

    The literature on tympanostomy tube treatment of children with recurrent and secretory otitis media was reviewed. The evidence for positive effects of tube treatment in secretory otitis media is verified. In contrast their efficiency in recurrent otitis media is less well studied. Some routines eg related to the surgical procedure and the prophylactic treatment of tube drainage lack evidence and should be avoided. The full report of the systematic literature review can be obtained at http://www.sbu.se. Based on this report the Swedish Society for Otorhinolaryngology, Head and Neck Surgery will now create national clinical guidelines for tube treatment in recurrent and secretory otitis media.

  • 80.
    Hellström, Sten
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Spratley, Jorge
    Department of Otorhinolaryngology, University of Porto Medical School Hospital, Porto, Portugal.
    Eriksson, Per-Olof
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Pais-Clemente, Manuel
    Department of Otorhinolaryngology, University of Porto Medical School Hospital, Porto, Portugal.
    Tympanic membrane vessel revisited: a study in an animal model2003In: Otology and Neurotology, ISSN 1531-7129, E-ISSN 1537-4505, Vol. 24, no 3, p. 494-499Article in journal (Refereed)
    Abstract [en]

    HYPOTHESIS: The present study aimed at elucidating whether there are blood vessels in the semitransparent portion of the tympanic membrane.

    BACKGROUND: The normal semitransparent portions of pars tensa show strikingly few, small-caliber vessels under the otomicroscope. The major portion of a pars tensa seems to be devoid of blood vessels. In inflammatory conditions of the middle ear, the vascular pattern of the tympanic membrane is dramatically altered, and blood vessels traversing the pars tensa can be discernable.

    METHODS: The study was performed in rats with healthy tympanic membranes and in tympanic membranes obtained from animals with purulent otitis media evoked by inoculation of Str. pneumoniae. The tympanic membrane vessels were dilated by injection of adenosin, and directly afterwards the animal was perfused with china ink. Vessels were also revealed by immunohistochemistry with antibodies for Thy-1 and the von Willebrand factor as well as by detection of carbon particles at an ultrastructural level.

    RESULTS: Adenosin caused a marked dilation of the mallear and annular vessels. However, no preexisting vasculature was revealed in the normally transparent portions of the pars tensa except single vessels in the posterior quadrant and in the lower quadrants. In Str. pneumoniae-induced acute otitis media, the tympanic membrane thickened, bulged, and discolored. Even then, at 12 hours after inoculation, no vessels could be distinguished in the normally transparent portions of the tympanic membrane. However, at 4 and 7 days of acute purulent otitis media, vessels developed in those areas, most probably through ingrowth of newly formed vessels.

    CONCLUSION: The results support the view that the semitransparent portions of the pars tensa lack vascularity. In inflammation, new vessels are formed in pars tensa to meet the demand for an increased blood supply.

  • 81. Henriksson, T-G
    et al.
    Naredi, S
    Olivecrona, M
    Sjöström, Björn
    Umeå University, Faculty of Medicine, Clinical Sciences, Otorhinolaryngology.
    Sammanfattning av symposium om naso-orbito-ethmoidala frakturer vid ÖNH-dagarna i Umeå2005In: Svensk ÖNH-tidskrift, no 1, p. 71-78Article in journal (Other (popular science, discussion, etc.))
  • 82. Hertegård, S
    et al.
    Cedervall, J
    Svensson, B
    Forsgren, Kristina
    Umeå University, Faculty of Medicine, Clinical Sciences, Otorhinolaryngology.
    Maurer, FH
    Vidovska, D
    Olivius, P
    Ahrlund-Richter, L
    Le Blanc, K
    Viscoelastic and histological properties in scarred rabbit vocal folds after mesenchymal stem cell injection2006In: The Laryngoscope, ISSN 0023-852X, E-ISSN 1531-4995, Vol. 116, no 7, p. 1248-54Article in journal (Refereed)
  • 83. Hertegård, S
    et al.
    Dahlqvist, A
    Umeå University, Faculty of Medicine, Clinical Sciences, Otorhinolaryngology.
    Goodyer, E
    Viscoelastic measurements after vocal fold scarring in rabbits: short-term results after hyaluronan injection2006In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 126, no 7, p. 758-763Article in journal (Refereed)
  • 84. Hertegård, Stellan
    et al.
    Hallén, Lars
    Umeå University, Faculty of Medicine, Clinical Sciences, Otorhinolaryngology.
    Laurent, Claude
    Umeå University, Faculty of Medicine, Clinical Sciences, Otorhinolaryngology.
    Lindström, Elisabeth
    Olofsson, Katarina
    Umeå University, Faculty of Medicine, Clinical Sciences, Otorhinolaryngology.
    Testad, Per
    Dahlqvist, Ake
    Umeå University, Faculty of Medicine, Clinical Sciences, Otorhinolaryngology.
    Cross-linked hyaluronan versus collagen for injection treatment of glottal insufficiency: 2-year follow-up.2004In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 124, no 10, p. 1208-1214Article in journal (Refereed)
  • 85.
    Hertegård, Stellan
    et al.
    Department of Logopedics and Phoniatrics, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
    Hallén, Lars
    Department of Otorhinolaryngology, Central Hospital, Falun, Sweden.
    Laurent, Claude
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Lindström, Elisabeth
    Department of Logopedics and Phoniatrics, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
    Olofsson, Katarina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Testad, Per
    Department of Speech Pathology, Central Hospital, Falun, Sweden.
    Dahlqvist, Åke
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Cross-linked hyaluronan used as augmentation substance for treatment of glottal insufficiency: safety aspects and vocal fold function2002In: The Laryngoscope, ISSN 0023-852X, E-ISSN 1531-4995, Vol. 112, no 12, p. 2211-2219Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To examine safety aspects and vocal fold function after vocal fold augmentation with a cross-linked hyaluronan derivative (hylan B gel) as compared with bovine collagen.

    STUDY DESIGN; A prospective, randomized trial.

    METHODS: Eighty-three patients with glottal insufficiency were treated with injection augmentation with hylan B gel and bovine collagen and were examined at 1, 6, and 12 months after treatment. Seventy patients with unilateral vocal fold paresis (n = 35) or atrophy (n = 35) were randomly assigned to receive either hylan B gel (n = 47) or collagen (n = 23) injections into one vocal fold. Thirteen patients with glottal insufficiency caused by scar defects or paresis resulting from malignant disease were included in a nonrandomized group and were treated only with hylan B gel. Evaluations were made from patients' subjective ratings (visual analogue scales), digitized videostroboscopic measurements, phonetograms, maximum phonation time, and phonation quotients.

    RESULTS: Twelve months after injections, the patients' self-ratings were significantly improved for both the hylan B gel and the collagen groups. In addition, the videostroboscopic measurements showed significantly improved glottal closure for both groups. However, for the hylan B gel group, vibration amplitude and glottal area variations were preserved, and this group showed significantly less resorption at the injected vocal fold edge. Furthermore, maximum phonation time had increased significantly for the hylan B gel patients (collagen, nonsignificant). No serious adverse events were observed; three patients injected with hylan B gel had temporary inflammation at the injection site, which resolved without sequelae.

    CONCLUSIONS: The results showed that both hylan B gel and collagen can be safely used for injection treatment of glottal insufficiency. Both treatments resulted in significantly improved voice as rated by the patients. However, the patients treated with hylan B gel showed better vocal fold status and longer maximum phonation time at 12 months after treatment as compared with patients treated with collagen.

  • 86.
    Holm, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Allard, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Eriksson, Irene
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Laurell, Göran
    Department of Surgical Sciences, Division of Otorhinolaryngology, Uppsala University.
    Nylander, Karin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Olofsson, Katarina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Absence of high-risk human papilloma virus in p16 positive inverted sinonasal papillomaManuscript (preprint) (Other academic)
    Abstract [en]

    Objectives: Sinonasal inverted papilloma (SIP) is a relatively rare disease, and its etiology is not understood. It is characterized by locally aggressive growth and a strong tendency to recur despite its benign histology.

    Aims: The aim of this study was to identify the presence of human papilloma virus (HPV) and its surrogate marker p16 in SIP tissue samples from a regional cohort.

    Material and Methods: Subjects were identified from our regional center cohort of 88 SIP patients treated between 1984-2014. From these subjects, 54 were included in this study.  Of these, 53 biopsies were analyzed with PCR, and 54 samples were immunohistochemically stained for p16. DNA was extracted from histopathologically verified SIP.  Genotype screening for 13 high risk-, 5 oncogenic and 6 low risk HPV types was performed using the PapilloCheck® HPV-screening test.

    Results: HPV analysis was successful for 38 of 53 samples. Of the 38 successfully analyzed samples, only 2 samples were positive for HPV 11.  Notably, p16 was present in the epithelia in all samples, and in the papilloma lesions in 37 samples.

    Conclusion: Since only 2 out of 38 SIPs were positive for HPV (type 11), and at the same time p16 was positive in epithelia in all samples and in 37 of 38 papilloma lesions of the samples, it is concluded that p16 cannot be used as a surrogate marker for high-risk HPV-infection in SIP. We are currently planning a prospective, multicenter study in order to increase the study power and in order to be able to better evaluate the clinical implications of HPV-and p16 in SIP.

  • 87.
    Holm, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Forslund, Ola
    Rydell, Roland
    Olofsson, Katarina
    Kirurgi vid respiratoriska papillom kräver god ventilation: personalen måste skyddas mot HPV-smitta – högfrekvent jetventilationsteknik kan ge bättre operationsresultat2016In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 113, no 41, article id D3CPArticle in journal (Refereed)
    Abstract [en]

    We describe a non-smoking patient with juvenile onset recurrent respiratory papillomatosis (RRP), genotyped as human papilloma virus (HPV)11. The patient has undergone a total of 133 surgical CO2 laser sessions, whereof the last 28 using a high frequency jet ventilation technique (HFJV). Since completed vaccination (Gardasil) in February 2013, the patient underwent one surgery in September 2013 and was considered being in remission. In March 2015, the patient was diagnosed with a left-sided lung cancer, genotyped as HPV11, a HPV subtype associated with a more aggressive disease with higher morbidity and mortality. We advocate that RRP patients should be ventilated with HFJV technique in order to enhance surgical radicality. Furthermore, the operation should be performed in operating theaters with high air exchange/minute, optimized local exhaust ventilation, and specific masks to ensure safe conditions for patients and staff.

  • 88.
    Holm, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Hellman, Urban
    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 and Language Pathology and Audiology, University of Pretoria, South Africa.
    Laurell, Göran
    Nylander, Karin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Olofsson, Katarina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Hyaluronan in vocal folds and false vocal folds in patients with recurrent respiratory papillomatosis2018In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 138, no 11, p. 1020-1027Article in journal (Refereed)
    Abstract [en]

    Background: Hyaluronan (HA) is a glycosaminoglycan with viscoelastic properties necessary for vocal fold (VF) vibration and voice production. Changes in HAs molecular mass, possibly related to human papilloma virus, could affect formation/persistence of recurrent respiratory papillomatosis (RRP).

    Aims/Objective: Describing mass and localization of HA and localization of HA receptor CD44 in VF and false vocal folds (FVF) in RRP.

    Materials and Methods: Biopsies from VF and FVF from 24 RRP patients. Twelve were studied with histo-/immunohistochemistry for HA and CD44 in epithelium, stroma and RRP lesions. Twelve samples were analyzed for HA molecular mass distribution with gas-phase-electrophoretic-molecular-mobility-analyzer (GEMMA).

    Results: Three of 23 stains (VF and FVF combined) showed faint HA staining in the epithelium; there was more extensive staining in the stroma. CD44 was present throughout all areas in FVF and VF, it did not concur with HA. GEMMA analysis revealed very high mass HA (vHMHA) with more varying amounts in VF.

    Conclusions/Significance: HA was mainly distributed in the stroma. CD44 not binding to HA might explain the non-inflammatory response described in RRP. Possibly crosslinked vHMHA was seen in VF and FVF, with more variable amounts in VF samples. Counteracting HA crosslinking could become a treatment option in RRP.

  • 89.
    Holm, Anna M.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Human papillomavirus in sinonasal inverted papilloma, recurrent respiratory papilloma and non-malignant tonsils2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Human papillomavirus (HPV) is known to cause recurrent respiratory papilloma (RRP) and certain types of oropharyngeal cancer. HPV has also been associated with sinonasal inverted papilloma (SIP). HPV transmission routes are under investigation and the conviction is that the infection occurs sexually at an adult stage, however, vertical transmission at birth with a dormant viral condition until disease eruption/co-activation has been stated as a possibility.

    Purpose: The purpose of this work was to contribute to the understanding of HPV related chronic diseases in the airway. Specific aims were: 1. To increase understanding regarding changes in the immune system as well as of the glycosaminoglycan hyaluronan in patients with RRP. 2. To evaluate prevalence of HPV and its surrogate marker p16 in SIP as well as HPV, p16 and Epstein-Barr virus (EBV) in benign tonsillar disease. HPV and EBV in non-malignant tonsillar disease were studied due to the fact that incidence of HPV positive tonsillar cancer is increasing and the time of viral infection is unknown.

    Methods: A phenotypic characterization of peripheral blood from 16 RRP patients and 12 age-matched controls, using immunoflow cytometry, and monoclonal antibodies against differentiation and activation markers, was performed. The cytokine mRNA profile of monocytes, T helper-, T cytotoxic-, and NK cells was assessed using RT-qPCR. 54 SIP samples were studied of which 53 were available for analyzation with PCR. Genotype screening for 18 high risk and six low risk HPV types was performed using the PapilloCheck® HPV-screening test (a PCR method). 54 samples were immunohistochemically (IHC) stained for p16. Biopsies from vocal folds (VFs) and false vocal folds (FVFs) were collected from 24 patients with RRP, 12 were randomly selected to histochemistry for Hyaluronan (HA) and IHC staining for CD44 in the epithelium, stroma and RRP lesions. The remaining 12 patients were analyzed for HA molecular mass distribution with a gas-phase electrophoretic molecular mobility analyzer (GEMMA). Eight VF samples and four FVF samples were successfully analyzed. Biopsies from 40 non-malignant tonsils were analyzed using Papillocheck® for HPV, IHC for p16 and EBER analysis for EBV.

    Results: We found a dominance of cytotoxic T cells, activated NK cells, and high numbers of stressed MIC A/B (MHC class I chain-related molecule A/B) expressing lymphocytes. The HPV analysis was successful for 38 SIP samples and two (5%) were positive for HPV 11. Notably, p16 was present in the epithelia of all samples and in the papilloma portions in 37 of 38 samples. We found extensive HA staining in the stroma of both VFs and FVFs. CD44 was expressed throughout the epithelium, stroma, and RRP lesions in both FVFs and VFs, it did however, not concur with the expression of HA. Very high mass HA was found in both VFs and FVFs, though more variation regarding amounts of HA was seen in the VFs compared to FVFs. No HPV was found in non-malignant tonsils, the p16 levels were low and the counted EBER positive cells showed great variation in numbers.

    Conclusions: Our findings demonstrate an immune dysregulation with inverted CD4+/CD8+ ratio and aberrant cytokine mRNA production in RRP patients, compared to healthy controls. We concluded that p16 cannot be used as a surrogate marker for high-risk HPV-infection in SIP and that HPV incidence was low (5%). CD44 does not seem to bind to HA, which might explain the noninflammatory response previously described in RRP. Very high mass HA possibly crosslinked was seen in both VFs and FVFs. A possibility to counteract inflammatory crosslinking of HA may be found for medical treatment options in RRP.

  • 90.
    Holm, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Nagaeva, Olga
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Nagaev, Ivan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Loizou, Christos
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Laurell, Göran
    Mincheva-Nilsson, Lucia
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Nylander, Karin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Olofsson, Katarina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Lymphocyte profile and cytokine mRNA expression in peripheral blood mononuclear cells of patients with recurrent respiratory papillomatosis suggest dysregulated cytokine mRNA response and impaired cytotoxic capacity2017In: Immunity, Inflammation and Disease, E-ISSN 2050-4527, Vol. 5, no 4, p. 541-550Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Recurrent respiratory papillomatosis (RRP) is a relatively rare, chronic disease caused by Human Papilloma Virus (HPV) 6 and 11, and characterized by wart-like lesions in the airway affecting voice and respiratory function. The majority of HPV infections are asymptomatic and resolve spontaneously, however, some individuals are afflicted with persistent HPV infections. Failure to eliminate HPV 6 and 11 due to a defect immune responsiveness to these specific genotypes is proposed to play a major role in the development of RRP.

    METHODS: We performed a phenotypic characterization of peripheral blood mononuclear cells (PBMC) collected from 16 RRP patients and 12 age-matched healthy controls, using immunoflow cytometry, and monoclonal antibodies against differentiation and activation markers. The cytokine mRNA profile of monocytes, T helper-, T cytotoxic-, and NK cells was assessed using RT-qPCR cytokine analysis, differentiating between Th1-, Th2-, Th3/regulatory-, and inflammatory immune responses.

    RESULTS: We found a dominance of cytotoxic T cells, activated NK cells, and high numbers of stressed MIC A/B expressing lymphocytes. There was an overall suppression of cytokine mRNA production and an aberrant cytokine mRNA profile in the activated NK cells.

    CONCLUSION: These findings demonstrate an immune dysregulation with inverted CD4(+) /CD8(+) ratio and aberrant cytokine mRNA production in RRP patients, compared to healthy controls.

  • 91.
    Holm, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Schindele, Alexandra
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology. Östersunds hospital, Sweden.
    Allard, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Section of Virology.
    Eriksson, Irene
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Section of Virology.
    Sandström, Karl
    Laurell, Göran
    Nylander, Karin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Olofsson, Katarina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Mapping of Human Papilloma Virus, p16, and Epstein-Barr Virusin Non-Malignant Tonsillar Disease2019In: Laryngoscope Investigative Otolaryngology, E-ISSN 2378-8038, Vol. 4, no 3, p. 285-291Article in journal (Refereed)
    Abstract [en]

    Objectives: Due to their location in the entrance of the aero‐digestive tract, tonsils are steadily exposed to viruses. Human papilloma virus (HPV) and Epstein‐Barr virus (EBV) are two potentially oncogenic viruses that tonsils encounter. The incidence of HPV positive tonsillar cancer is on the rise and it is unknown when infection with HPV occurs.

    Aim: To investigate if tonsils are infected with HPV and EBV, to study the co‐expression of HPV and its surrogate marker p16, and to evaluate the number of EBV positive cells in benign tonsillar disease.

    Materials and Methods: Tonsils from 40 patients in a university hospital were removed due to hypertrophy, chronic or recurrent infection. These were analyzed for presence of HPV, its surrogate marker p16, and EBV. HPV was studied using PapilloCheck (a PCR method), while p16 was identified in epithelial and lymphoid tissue with immunohistochemistry and EBV using EBER‐ISH (Epstein‐Barr encoding region–in situ hybridization).

    Results: HPV was not detected, and p16 was present at low numbers in all epithelial samples as well as in 92.5% of the lymphoid tonsillar samples. At least one EBER‐positive cell was seen in 65% of cases. Larger numbers of EBER‐expressing cells were only seen in two cases.

    Conclusion: These findings demonstrate that EBV and HPV infect tonsils independently, but further studies are warranted to confirm their infectious relationship.

    Level of Evidence: Cross‐sectional study

  • 92.
    Holmlund, Thorbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Evaluation of surgical methods for sleep apnea and snoring2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Snoring and obstructive sleep apnea (OSA) are both common disorders with a number of negative health effects. The safety and efficacy of treating snoring and OSA surgically have been questioned and there has been a lack of studies in the field. Aims: 1) To investigate the frequency of serious complications, including death, after surgery for the treatment of snoring and sleep apnea; 2) to evaluate the effect on daytime sleepiness after radiofrequency surgery of the soft palate in snoring men with mild or no OSA; 3) to evaluate the effect of tonsillectomy on sleep apnea in adults with OSA and tonsillar hypertrophy; 4) to investigate the morphology and cytoarchitecture of muscle fibers in human soft palatal muscles with immunohistochemical and morphological techniques. Methods and results: In paper 1, a retrospective database study. All Swedish adults who were treated surgically because of snoring or OSA from January 1997 to December 2005 were identified in the National Patient Register. None of the surgically treated patients died in the peri- and postoperative period. Severe complications were recorded in 37.1 of 1,000 patients treated with uvulopalatopharyngoplasty (UPPP), in 5.6 of 1,000 patients after uvulopalatoplasty (UPP) and in 8.8 of 1,000 patients after nasal surgery. In paper 2, the study was designed as a randomized, controlled trial. 35 snoring men with mild or no OSA were randomized to either radiofrequency or sham surgery of the soft palate. Radiofrequency surgery was not found to be effective since there was no significant difference between the two groups in relation to the Epworth Sleepiness Scale (ESS) or apnea-hypopnea index (AHI) at follow-up. Paper 3 was a prospective study, including 28 patients with an AHI of >10 and with large tonsils. In these patients, tonsillectomy was an effective treatment for OSA; the mean AHI was reduced from 40 units/h to 7 units/h (p<0.001), and the mean ESS was reduced from 10.1 to 6.0 (p<0.001) at the six-month follow-up after surgery. Minor and moderate swallowing dysfunction was found in seven of eight patients investigated before surgery and the swallowing function improved in 5 of them after surgery, while no one deteriorated. In paper 4, we investigated the morphology and cytoarchitecture in normal soft palate muscles. Human limb muscles were used as reference. The findings showed that the soft palate muscle fibers have a cytoskeletal architecture and cellmembrane complex that differs from that of the limb muscles. Conclusions No case of death related to surgery was found among 4,876 patients treated with UPPP, UPP or nasal surgery for snoring or OSA in Sweden between 1997 and 2005. Radiofrequency surgery of the soft palate has no effect on daytime sleepiness, snoring or apnea frequency in snoring men with mild or no OSA. Tonsillectomy can be an effective treatment for OSA in adults with large tonsils. A subgroup of muscle fibers in the human soft palate appears to have special biomechanical properties and their unique cytoarchitecture must be taken into account while assessing function and pathology in oropharyngeal muscles.

  • 93.
    Holmlund, Thorbjörn
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Franklin, Karl A.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Levring Jäghagen, Eva
    Umeå University, Faculty of Medicine, Department of Odontology.
    Lindqvist, Marie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health. Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Larsson, Torbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Sahlin, C.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Berggren, Diana
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Tonsillectomy in adults with obstructive sleep apnea2016In: Journal of Sleep Research, ISSN 0962-1105, E-ISSN 1365-2869, Vol. 25, p. 161-161Article in journal (Other academic)
  • 94.
    Holmlund, Thorbjörn
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Franklin, Karl A.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Levring Jäghagen, Eva
    Umeå University, Faculty of Medicine, Department of Odontology.
    Lindqvist, Marie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Larsson, Torbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Sahlin-Ingridsson, Carin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Berggren, Diana
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Tonsillectomy in adults with obstructive sleep apnea2016In: The Laryngoscope, ISSN 0023-852X, E-ISSN 1531-4995, Vol. 126, no 12, p. 2859-2862Article in journal (Refereed)
    Abstract [en]

    Objectives/Hypothesis To study whether tonsillectomy is effective on obstructive sleep apnea (OSA) in adults with large tonsils. Study Design A multicenter prospective interventional study. Methods The study comprised 28 patients with OSA, an apnea-hypopnea index of > 10, large tonsils (Friedman tonsil size 3 and 4), and age 18 to 59 years. They were derived from 41 consecutive males and females with large tonsils referred for a suspicion of sleep apnea to the ear, nose, and throat departments in Umea, Skelleftea, and Sunderbyn in northern Sweden. The primary outcome was the apnea-hypopnea index, measured with polygraphic sleep apnea recordings 6 months after surgery. Secondary outcomes included daytime sleepiness, as measured with the Epworth Sleepiness Scale, and swallowing function, using video-fluoroscopy. Results The apnea-hypopnea index was reduced from a mean of 40 units per hour (95% confidence interval [CI] 28-51) to seven units per hour (95% CI 3-11), P < 0.001, at the 6-month follow-up after surgery. The apnea-hypopnea index was reduced in all patients and 18 (64%) were cured. The Epworth Sleepiness Scale was reduced from a mean of 11 (95% CI 8-13) to 6.0 (95% CI 4-7), P < 0.001. A swallowing dysfunction was found in seven of eight investigated patients before surgery. Of those, swallowing function improved in five patients after surgery, whereas no one deteriorated. Conclusion Tonsillectomy may be effective treatment for adult patients with OSA and large tonsils. Tonsillectomy may be suggested for adults with OSA and large tonsils. Level of Evidence 4.

  • 95.
    Holmlund, Thorbjörn
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Levring Jäghagen, Eva
    Umeå University, Faculty of Medicine, Department of Odontology.
    Franklin, Karl A.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Lindkvist, Marie
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Berggren, Diana
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Effects of Radiofrequency versus Sham Surgery of the Soft Palate on Daytime Sleepiness2014In: The Laryngoscope, ISSN 0023-852X, E-ISSN 1531-4995, Vol. 124, no 10, p. 2422-2426Article in journal (Refereed)
    Abstract [en]

    Objectives/Hypothesis: To evaluate the effect of radiofrequency surgery of the soft palate on daytime sleepiness in snoring men with mild or no sleep apnea Study design: Randomized controlled trial Methods: Thirty-five men were recruited from consecutive patients referred to the Ear, Nose and Throat Clinic due to snoring and complaints of daytime sleepiness. The inclusion criteria were an apnea-hypopnea index of ≤ 15, male gender and age 18-65 years. Patients were randomized to either radiofrequency or sham surgery of the soft palate. All but one chose and received the option of three treatments. All patients participated in a follow-up including an overnight sleep apnea recording and questionnaires 12 months after the last treatment. The primary outcome was daytime sleepiness measured with the Epworth Sleepiness Scale (ESS) and other questionnaires. Secondary outcomes were effects on the apnea-hypopnea index and subjective snoring. Results: Thirty-two of 35 patients, 19 of 20 in the radiofrequency surgery group and 13 of 15 in the sham surgery group, completed the study. No differences between the two groups in relation to the ESS or apnea-hypopnea index were found at follow-up. Conclusion: Radiofrequency surgery of the soft palate has no effect on daytime sleepiness, snoring or apnea frequency in snoring men with mild or no sleep apnea, one year after surgery.

  • 96.
    Hulterström, Anna Karin
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, Dental Technology/Dental Materials Science.
    Sellin, Mats
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Berggren, Diana
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    High prevalence of S. aureus around symptomatic perforations of the nasal septumManuscript (preprint) (Other academic)
  • 97.
    Hulterström, Anna Karin
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, Dental Technology/Dental Materials Science.
    Sellin, Mats
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Berggren, Diana
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    The effect of obturator treatment on the microbial flora surrounding symptomatic nasal septal perforationsManuscript (preprint) (Other academic)
  • 98.
    Hulterström, Anna Karin
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, Dental Technology/Dental Materials Science.
    Sellin, Mats
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Berggren, Diana
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    The microbial flora in the nasal septum area prone to perforation2012In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 120, no 3, p. 210-214Article in journal (Refereed)
    Abstract [en]

    To explore the colonizing bacterial flora of the nasal septum area, that is mostly afflicted by perforations, 101 healthy police students had swab samples taken from that location. The described culture strategy recovered positive cultures from 95% of the test subjects and from 60% with more than one organism. In total, 191 bacterial isolates were classified according to colony morphology, Gram-stain and a panel of standard laboratory techniques. A part of the bacteria was identified to species-level by biochemical methods and by sequencing of the 16S rRNA gene. The predominant finding was Gram-positive irregular rods - 65 presumptive Corynebacterium isolates, both lipophilic and non-lipophilic, and 37 anaerobic Propionibacterium isolates. The second largest bacterial group was Gram-positive catalase-positive cocci, of which 13 isolates were identified as Staphylococcus aureus and 53 as coagulase-negative staphylococci. The few potential airway pathogens included Streptococcus pneumonia (n = 1) and Moraxella catarrhalis (n = 3) isolates. The bacterial flora colonizing the nasal septum mainly consists of Gram-positive bacteria. Although of low virulence, the microbial flora may impact on occlusion treatment of nasal septum perforations with silicone obturators.

  • 99.
    Hulterström, Anna Karin
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, Dental Technology/Dental Materials Science.
    Sellin, Mats
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Monsen, Tor
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Widerström, Micael
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Gurram, Bharath Kumar
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Berggren, Diana
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Bacterial flora and the epidemiology of staphylococcus aureus in the nose among patients with symptomatic nasal septal perforations2016In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 136, no 6, p. 620-625Article in journal (Refereed)
    Abstract [en]

    Conclusions Patients with symptomatic perforations of the nasal septum had a high prevalence of S. aureus in the nasal mucosa. Pulsed field gel electrophoresis (PFGE) analysis revealed a high genetic heterogeneity of S. aureus among both patients and controls. This indicates that presence of different strains of S. aureus can maintain a chronic inflammation in symptomatic nasal septal perforations. Objective The purpose of this study was to investigate the microbial flora around nasal septal perforations in patients having severe symptoms regarding bleeding, obstruction, and crustation associated with their perforation. Methods Twenty-five patients with untreated symptomatic nasal septal perforations were included. For culture, swabs around the perforations were collected. Bacteria were identified with standard laboratory techniques including a MALDI-TOF mass spectrometer. Epidemiological analysis was done using PFGE protocols. Bacteriological data were compared with data from a healthy control group. Results Staphylococcus aureus was present in the mucosa surrounding the nasal perforation significantly more often (p < 0.0001) in the patients (88%) compared to a control group (13%). Corynebacterium spp. and Propionibacterium spp. were significantly more frequently identified in the control group. The PFGE analysis of S. aureus strains revealed a high genetic heterogeneity and no specific S. aureus genotypes were associated with septal perforation.

  • 100.
    Hultin, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Semb, Olof
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Professionell Development.
    Tano, Krister
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Molander, Emil
    Umeå University, Faculty of Arts, Department of language studies.
    Morén, Gabriella
    Umeå University, Faculty of Arts, Department of language studies.
    Wennberg, Patrik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Design of a program for complementary education of International Medical Graduates in Sweden – to include Swedish or not2019Conference paper (Refereed)
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