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  • 1.
    Alkaissi, Aidah
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Anestesiologi med intensivvård. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Anestesi- och operationscentrum, Intensivvårdskliniken US.
    Ledin, Torbjörn
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Rekonstruktionscentrum, Öronkliniken US.
    Ödkvist, Lars
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Rekonstruktionscentrum, Öronkliniken US.
    Kalman, Sigga
    Linköpings universitet, Institutionen för medicin och hälsa, Anestesiologi med intensivvård. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Anestesi- och operationscentrum, Anestesi- och intensivvårdskliniken VIN.
    P6 acupressure increases tolerance to nausogenic motion stimulation in women with high risk for PONV2005Ingår i: Canadian Journal of Anesthesia, ISSN 1496-8975, Vol. 52, s. 703-709Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: In a previous study we noticed that P6 acupressure decreased postoperative nausea and vomiting (PONV) more markedly after discharge. As motion sickness susceptibility is increased by, for example, opioids we hypothesized that P6 acu-pressure decreased PONV by decreasing motion sickness susceptibility. We studied time to nausea by a laboratory motion challenge in a group of volunteers, during P6 and placebo acupressure.

    Methods: 60 women with high and low susceptibilities for motion sickness participated in a randomized and double-blind study with an active P6 acupressure, placebo acupressure, and a control group (n = 20 in each group). The risk score for PONV was over 50%. The motion challenge was by eccentric rotation in a chair, blindfolded and with chin to chest movements of the head. The challenge was stopped when women reported moderate nausea. Symptoms were recorded.

    Results: Mean time to moderate nausea was longer in the P6 acu-pressure group compared to the control group. P6 acupressure = 352 (259–445), mean (95% confidence interval) in seconds, control = 151 (121–181) and placebo acupressure = 280 (161–340); (P = 0.006). No difference was found between P6 and placebo acupressure or placebo acupressure and control groups. Previous severity of motion sickness did not influence time to nausea (P = 0.107). The cumulative number of symptoms differed between the three groups (P < 0.05). Fewer symptoms were reported in the P6 acupressure compared to the control group P < 0.009. Overall, P6 acupressure was only marginally more effective than placebo acupressure on the forearms.

    Conclusion: In females with a history of motion sickness P6 acu-pressure increased tolerance to experimental nauseogenic stimuli, and reduced the total number of symptoms reported.

  • 2.
    Almqvist, Bengt
    et al.
    Lunds universitet.
    Arlinger, Stig
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet.
    Handbok i hörselmätning1990Bok (Övrigt vetenskapligt)
    Abstract [sv]

    Denna bok ger en grundläggande kunskap om hörseln samt förmedlar förutsättningar för olika hörselmätmetoder. Viktiga inslag är felkällor vid hörselmätning, tolkning av mätresultat och lämplig teststrategi i olika tillämpningar. Inläst ur LIC, 1990

  • 3.
    Almqvist, Bengt
    et al.
    Lunds universitet.
    Arlinger, Stig
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet.
    Metodbok i praktisk hörselmätning1983Bok (Övrigt vetenskapligt)
    Abstract [sv]

    Denna bok är avsedd att användas vid utbildning av audionomer. Den kan dessutom vara en viktig referenskälla för alla övriga yrkesgrupper inom hörselvården. De metodbeskrivningar som presenteras i boken har goda förutsättningar att bidra till förbättrad hörselmätning

  • 4.
    Ansell, Anna
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet.
    Farnebo, Lovisa
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Rekonstruktionscentrum, Öronkliniken US.
    Grénman, Reidar
    Department of Otorhinolaryngology, Head & Neck Surgery, and Medical Biochemistry, University of Turku, Finland.
    Roberg, Karin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Rekonstruktionscentrum, Öronkliniken US.
    Thunell, Lena
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Polymorphism of FGFR4 in cancer development and sensitivity to cisplatin and radiation in head and neck cancer2009Ingår i: Oral Oncology, ISSN 1368-8375, E-ISSN 1879-0593, Vol. 45, nr 1, s. 23-29Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The aim of this study was to investigate the predisposition of the FGFR4 Gly/Arg polymorphism for development of head and neck squamous cell carcinoma (HNSCC) and, furthermore, to examine if the FGFR4 Arg(388) allele can be associated with resistance to chemo-and radiotherapy.

    When analysing 110 tumour biopsies a significant 1.7-fold increased risk to develop HNSCC in individuals carrying the Gly(388) allele (p = 0.026) was found. Moreover a 2-fold increased risk for mates harbouring the Gly(388) allele (p = 0.031) to develop HNSCC was detected. In 39 HNSCC cell lines the role of the Arg(388) allele for radiation and cisplatin sensitivity was investigated. Our results show no rote of the Arg(388) allele for the radiosensitivity (p = 0.996) but indicate a tendency to increased cisplatin sensitivity (p = 0.141). When screening the transmembrane and kinase domains in the FGFR4 gene a novel mutation, probably generating a truncated protein lacking exons 14-18, was found in six of eight selected cell lines.

    Taken together, we have here identified a marker that predicts the risk to develop HNSCC and possibly the sensitivity to cisplatin as well as a novel. mutation in the FGFR4 gene.

  • 5.
    Ansell, Anna
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet.
    Jerhammar, Fredrik
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet.
    Ceder, R
    Karolinska Institute, Institute Environm Med, Div Biochem Toxicol and Expt Canc Research, S-10401 Stockholm, Sweden .
    Grenman, R
    Turku University, Department Otorhinolaryngol Head and Neck Surg, Cent Hospital, Turku, Finland .
    Roberg, Karin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Rekonstruktionscentrum, Öronkliniken US.
    Matrix metalloproteinase-7 and-13 predict response to cisplatin in head and neck cancer in ORAL ONCOLOGY, vol , issue , pp 94-942009Ingår i: ORAL ONCOLOGY, 2009, s. 94-94Konferensbidrag (Refereegranskat)
    Abstract [en]

    n/a

  • 6.
    Ansell, Anna
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet.
    Jerhammar, Fredrik
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet.
    Ceder, Rebecca
    Karolinska Institute, Stockholm, Sweden.
    Grafström, Roland
    VTT Technical Research Centre of Finland.
    Grénman, Reidar
    VTT Technical Research Centre of Finland.
    Roberg, Karin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Rekonstruktionscentrum, Öronkliniken US.
    Matrix metalloproteinase-7 and -13 expression associate to cisplatin resistance in head and neck cancer cell lines.2009Ingår i: Oral Oncology, ISSN 1368-8375, E-ISSN 1879-0593, Vol. 45, nr 10, s. 866-871Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Concomitant chemoradiotherapy is a common treatment for advanced head and neck squamous cell carcinomas (HNSCC). Cisplatin is the backbone of chemotherapy regimens used to treat HNSCC. Therefore, the aim of this study was to identify predictive markers for cisplatin treatment outcome in HNSCC. The intrinsic cisplatin sensitivity (ICS) was determined in a panel of tumour cell lines. From this panel, one sensitive and two resistant cell lines were selected for comparative transcript profiling using microarray analysis. The enrichment of Gene Ontology (GO) categories in sensitive versus resistant cell lines were assessed using the Gene Ontology Tree Machine bioinformatics tool. In total, 781 transcripts were found to be differentially expressed and 11 GO categories were enriched. Transcripts contributing to this enrichment were further analyzed using Ingenuity Pathway Analysis (IPA) for identification of key regulator genes. IPA recognized 20 key regulator genes of which five were differentially expressed in sensitive versus resistant cell lines. The mRNA level of these five genes was further assessed in a panel of 25 HNSCC cell lines using quantitative real-time PCR. Among these key regulators, MMP-7 and MMP-13 are implicated as potential biomarkers of ICS. Taken together, genome-wide transcriptional analysis identified single genes, GO categories as well as molecular networks that are differentially expressed in HNSCC cell lines with different ICS. Furthermore, two novel predictive biomarkers for cisplatin resistance, MMP-7 and MMP-13, were identified.

  • 7.
    Ansell, Anna
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet.
    Jerhammar, Fredrik
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet.
    Ceder, Rebecca
    Institute of Environmental Medicine, Division of Biochemical Toxicology and Experimental Cancer Research, Karolinska Institution, Stockholm, Sweden.
    Grénman, Reidar
    Department of Otorhinolaryngology, Head & Neck Surgery, Turku University Central Hospital, Finland.
    Roberg, Karin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Rekonstruktionscentrum, Öronkliniken US.
    Matrix metalloproteinase-7 and -13 predict response to cisplatin in head and neck cancerManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Purpose: To identify gene ontology categories and key regulators with impact on the intrinsic cisplatin sensitivity (ICS) in head and neck squamous cell carcinoma (HNSCC).

    Experimental design: The ICS was determined in 35 HNSCC cell lines. Three of these cell lines, one sensitive and two resistant, were selected for microarray analysis. Gene Ontology (GO) categories were assessed using the gene ontology tree machine (GOTM) tool, and transcripts included in these categories were further analyzed using Ingenuity Pathway Analysis (IPA) for detection of key regulator genes. A group of key regulators were verified at protein level by Western blot analysis and on mRNA level using quantitative real-time PCR (qPCR).

    Results: 781 transcripts were detected as significantly differently expressed for the resistant cell lines compared to the sensitive cell line. A total of ten different categories were enriched in GOTM by these transcripts and a transcriptional profile was made from the 20 key regulators identified in the IPA analysis. Five key regulator genes, apolipoprotein E (APOE), catenin beta1 (CTNNB1), matrix metalloproteinase-7 (MMP-7), matrix metalloproteinase-13 (MMP-13), and thrombospondin 1 (THBS1), were verified in 25 HNSCC cell lines on mRNA level using qPCR. The results confirmed MMP-7 (p=0.0013) and implied MMP-13 (p=0.058) as potential biomarkers of ICS.

    Conclusions: We conclude that genome-wide transcriptional analysis and appropriate bioinformatics enable the identification of genes with impact on treatment response. Furthermore, we propose MMP-7 and MMP-13 as predictive markers of cisplatin resistance in HNSCC.

  • 8.
    Arlinger, Stig
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi.
    Audiologic diagnosis of infants2000Ingår i: Seminars in Hearing, ISSN 0734-0451, E-ISSN 1098-8955, Vol. 21, nr 4, s. 379-388Konferensbidrag (Övrigt vetenskapligt)
    Abstract [en]

    Audiologic diagnosis for infants requires an extensive test battery in order to provide all the information needed and wanted. Behavioral test methods continue to be an important tool, in particular visual reinforcement audiometry (VRA), with the limitation that children younger than 5 to 6 months of age cannot be expected to respond in a reliable way. Impedance audiometry provides an important means of assessing middle ear status, and the middle ear reflex also adds information about inner ear and cochlear nerve function. However, a higher probe tone frequency than the ordinary 226 Hz seems to provide more reliable test results in small children. Otoacoustic emissions are basic as a screening tool but in most cases provide little additional information on children with significant hearing loss, although there certainly are exceptions. The electrophysiologic methods form a very important part of the test battery. The recording of ABR is an obvious test when a hearing impairment is suspected. Electrocochleography provides more frequency-specific data and has the power of sometimes providing responses where no ABR can be recorded, especially when the transtympanic needle electrode is used. Steady-state evoked potentials (SSEP) constitute a relatively new test method with which rather few clinics so far have practical experience, but it certainly holds promise as an addition to the test battery allowing good frequency specificity and efficiency.

  • 9.
    Arlinger, Stig
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet.
    Elektronik för medicinare1971Bok (Övrigt vetenskapligt)
  • 10.
    Arlinger, Stig
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet.
    Höga ljudnivåer från musik och dess effekter på vuxna och barn: Rapport till Socialstyrelsen2011Rapport (Övrigt vetenskapligt)
    Abstract [sv]

    Syftet med denna översyn är att presentera ett förslag avseende om SOSFS 2005:7 behöver revideras eller ej, baserat på existerande vetenskapligt underlag om effekter på vuxna och barn från exponering för höga ljudnivåer från musik. De nuvarande riktvärdena har vid olika tillfällen ifrågasatts. Från arrangörer av musikfestivaler har hävdats att gränsvärdena är för låga och att det saknas vetenskapligt stöd för dem. Från organisationer med  hörselhälsa i fokus har man tvärtom menat att de borde sänkas eftersom för många enskilda fall har rapporterats, där hörselskada i form av hörselnedsättning och/eller tinnitus kunnat kopplas till en specifik exponering i samband med konsert eller diskoteksbesök.

    Syftet med denna översyn är att presentera ett förslag avseende om SOSFS 2005:7 behöver revideras eller ej, baserat på existerande vetenskapligt underlag om effekter på vuxna och barn från exponering för höga ljudnivåer från musik. De nuvarande riktvärdena har vid olika tillfällen ifrågasatts. Från arrangörer av musikfestivaler har hävdats att gränsvärdena är för låga och att det saknas vetenskapligt stöd för dem. Från organisationer med  hörselhälsa i fokus har man tvärtom menat att de borde sänkas eftersom för många enskilda fall har rapporterats, där hörselskada i form av hörselnedsättning och/eller tinnitus kunnat kopplas till en specifik exponering i samband med konsert eller diskoteksbesök.

    Arbetet som redovisas i denna rapport har baserats på sökning i den vetenskapliga litteraturen via framför allt databasen PubMed, granskning av referenslistor i relevanta rapporter, andra sökningar på Internet samt kontakter med internationella kollegor med insikter i aktuella regelverk. Söktermer har varit music, rock, jazz, discotheque, night-club, concert, hearing, hearing impairment,hearing loss, tinnitus, children i olika kombinationer. Rapporter som fokuserat helt på yrkesmusiker har som regel exkluderats, eftersom exponeringsförhållandena för musiker typiskt skiljer sig från publikens vid konserter, musikfestivaler etc.

    Randomiserade kontrollerade studier saknas med några få undantag för den aktuella frågeställningen, utan merparten är observationsstudier med eller utan kontrollgrupp. Värdet av kontrollgrupp i studier av temporär hörselnedsättning, TTS, efter musikexponering som pågått upp till några timmar är sannolikt begränsat, eftersom sannolikheten att hörtrösklarna för en oexponerad kontrollgrupp skulle förändras under denna begränsade tidsrymd är försumbar. Grundprinciperna för bedömning av kvaliteten i redovisade studier är i huvudsak hämtade från de principer som tillämpas av Statens beredning för medicinsk utvärdering, SBU. Enskilda studiers bevisvärde graderas som högt (1), måttligt (2) eller lågt (3). Följande principer har använts:

    Högt bevisvärde (1): Studier med fall-kontroll-grupper med n>50, med lämplig studieuppläggning och relevant statistisk analys.

    Måttligt bevisvärde (2): Som ovan men med mindre studiestorlek (n=10-50) eller observationsstudier utan kontrollgrupp med n=10-50 med lämplig studieuppläggning och relevant statistisk analys.

    Lågt bevisvärde (3): Studier som inte uppfyller kriterierna ovan. Studier med mera osäker relevans, t.ex. djurstudier.

    Rapporten har granskats av professor Ulf Rosenhall, Karolinska institutet, professor Claes Möller, Örebro universitet, docent Björn Hagerman, Karolinska institutet, och med.dr. och leg. audionom Kim Kähäri, Göteborgs universitet. Synpunkter och förslag framförda av dem har inlemmats i skrivningen.

  • 11.
    Arlinger, Stig
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet.
    Hörsel och hörselskador i arbetslivet: Kunskapssammanställning2013Rapport (Refereegranskat)
    Abstract [sv]

    Rapporten baserar sig på sammanställning av publicerade artiklar i vetenskapliga tidskrifter med tyngdpunkt på perioden från år 2000. Vissa äldre publikationer har också inkluderats när de har haft innehåll av betydelse för rapporten. Sökning har främst skett i databaserna PubMed och Google Scholar samt i referenslistor från identifierade relevanta arbeten. Söktermer har varit noise, hearing, noise-induced hearing loss, TTS, PTS, tinnitus, impulse noise, solvent, vibration i olika kombinationer.

    Fokus avseende hörselskador har traditionellt varit inriktat på hörselnedsättning, den försämrade känslighet som ofta men inte alltid är den uppenbara konsekvensen av en skada på hörselorganet. Men senare års forskning har visat att skador kan uppstå utan påtaglig påverkan på hörtrösklarna men i form av tinnitus, överkänslighet för starka ljud, förvrängd ljudupplevelse av olika slag, försämrad förmåga att uppfatta tal i svåra lyssningsmiljöer etc. Det har därför varit angeläget att lyfta fram dessa vidare aspekter på hörselskada.

    Många arbetsmiljöer domineras av en relativt kontinuerlig ljudnivå, men ibland förekommer också impulsbuller, d.v.s. ljudtoppar med kortvariga mycket höga ljudnivåer. Nya metoder som föreslagits för att mäta och säkrare värdera hörselskaderiskerna vid exponering för impulsbuller beskrivs också i rapporten.

    Följderna av bullerexponering på en individs hörsel beror inte alltid enbart på bullerexponeringen utan kan påverkas av andra faktorer. Dessa kan vara relaterade till arbetsmiljön men också till egenskaper hos den exponerade individen och kan därför behöva beaktas i skaderiskbedömningar.

    Djurförsök ha påvisat möjligheten att med farmakologiska medel minimera bullerskada efter en exponering och också att åtminstone delvis återskapa hörselfunktionen efter en bullerskada. Strävan är naturligtvis att kunna överföra denna kunskap och metodik till människa, men ännu återstår mycket arbete innan sådan behandling är tillgänglig.

  • 12.
    Arlinger, Stig
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Teknisk audiologi. Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi.
    Hörselutredning vid läs- och skrivsvårigheter2010Ingår i: Utredning av läs- och skrivsvårigheter / [ed] Britta Ericson, Stockholm: Studentlitteratur , 2010, s. 207-220Kapitel i bok, del av antologi (Övrigt vetenskapligt)
    Abstract [sv]

    För att hjälpa ett barn som har svårt att läsa och skriva behöver man ta reda på vad som hindrar framstegen i läsning och skrivning. Många gånger kan en pedagogisk utredning i kombination med en synundersökning ge svaret. I andra fall kan det vara nödvändigt att komplettera med utredning hos logoped, läkare, psykolog och sjukgymnast för att få en helhetsbild av barnets svårigheter och de psykosociala konsekvenserna. Ledande företrädare för olika yrkesområden beskriver i föreliggande bok hur läs- och skrivsvårigheter kan utredas. Denna reviderade fjärde upplaga har kompletterats med två nya kapitel. Det ena beskriver hur hörselundersökning kan komplettera en läs- och skrivutredning. Det andra kapitlet behandlar området läs- och skrivsvårigheter med fokus på elever med annat modersmål än svenska. Bokens målgrupp är blivande och verksamma lärare, specialpedagoger, logopeder, läkare, psykologer, sjukgymnaster, ortoptister och andra yrkesgrupper som behöver kunskap om orsaker till och utredning av läs- och skrivsvårigheter.

  • 13.
    Arlinger, Stig
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi.
    Letter from the editor-in-chief2002Ingår i: International Journal of Audiology, ISSN 1499-2027, E-ISSN 1708-8186, Vol. 41, nr 1Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    [abstract not available]

  • 14.
    Arlinger, Stig
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet.
    Manual of practical audiometry. Vol. 11989Bok (Övrigt vetenskapligt)
  • 15.
    Arlinger, Stig
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet.
    Manual of practical audiometry, Vol. 21991Bok (Övrigt vetenskapligt)
  • 16.
    Arlinger, Stig
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet.
    Nordisk lärobok i audiologi2007Samlingsverk (redaktörskap) (Övrigt vetenskapligt)
    Abstract [sv]

    Innehåll:

    • Akustik
    • Psykoakustik
    • Språklig kommunikation
    • Hörselsystemets utveckling och genetik
    • Anatomi och fysiologi
    • Hörselmätning
    • Hörselskador
    • Medicinsk behandling
    • Tinnitus
    • Rehabilitering
    • Habilitering
    • Buller
    • Internationella standarder
  • 17.
    Arlinger, Stig
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet.
    Psychoacoustic audiometry2008Ingår i: Scott-Brown's otorhinolaryngology, head and neck surgery / [ed] Gleeson M., London: Hodder Arnold , 2008, 7, s. 3260-3275Kapitel i bok, del av antologi (Övrigt vetenskapligt)
    Abstract [en]

    Scott-Brown's Otolaryngology is used the world over as the definitive reference for trainee ENT surgeons, audiologists and trainee head and neck surgeons, as well as specialists who need detailed, reliable and authoritative information on all aspects of ear, nose and throat disease and treatment. This new edition has been fully updated by an international team of editors and contributors and is highly illustrated in colour throughout. The majority of the chapters are evidence-based and each contains useful features including key points, best clinical practice guidelines, details of the search strategies used to prepare the material, and suggestions for future research. These features provide quick access to relevant information about clinical conditions, and a starting point for further research. The stand-alone CD-ROM contains the same content as the print edition, is searchable, and has references linked to PubMed. It provides trainee surgeons (ENT and Head and Neck), audiologists and ENT physicians with a more portable version of this extensive reference work, and access to downloadable figures, bookmarking and annotation tools.System requirements: The following are minimum requirements for running the CD-ROM. However, we recommend that you run the CD-ROM on a machine with a 1Gz processor with 500 MB RAM, 1024 by 768 screen resolution, using Firefox as your web browser. The recommended specifications will ensure the CD-ROM runs at optimal speed and performance. PC: Intel(R) Pentium(R) III, 266 MHz processor (or 1 GHz for Vista), Windows(R) 2000, XP, Vista*, Browser: Firefox 2.0; Internet Explorer 6.2 SP1, or 7.0; Netscape 9**, 28 MB RAM (or 1 GB for Vista), 80 MB free hard-disk space, 24x CD-ROM or DVD drive, 800 x 600 screen resolution displaying 32-bit colour, Windows(TM) compatible mouse, Printer (optional), Internet connection (optional)***. Please note that it is not compatible with Windows 7. Mac(R): G3 or newer, 266 MHz processor, Mac(R) OS X 10.4 (OS X 10.5 is not supported)*, Browser: Firefox 2.0; Netscape 9; Safari 3.0**, 256 MB RAM, 80 MB free hard-disk space, 800 x 600 screen resolution displaying 32-bit colour, CD-ROM or DVD drive, Mouse, Printer (optional), Internet connection (optional)***. * Your keyboard should be set to English characters when you use the CD-ROM.** Your browser should be set to allow cookies and pop-ups and you will need to have JavaScript enabled. *** Although you do not need to have an internet connection to use the application, you must make sure that your browser is not set to work offline. You can deselect this option from the File menu in Internet Explorer, Netscape, and Firefox (this option is not available in Safari).

  • 18.
    Arlinger, Stig
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi.
    Danermark, Berth
    Espmark, Ann-Kristin
    Mäki-Torkko, Elina
    Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Rekonstruktionscentrum, Öronkliniken US.
    Möller, Claes
    Steorn, Monika
    Tengstrand, Tomas
    Uhlin, Pia
    Hörselrehabilitering till vuxna. Rapport från expertgruppen för hörselvård2008Rapport (Övrigt vetenskapligt)
    Abstract [sv]

      

  • 19.
    Arlinger, Stig
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet.
    Hagerman, Björn
    Karolinska Institutet.
    Ytterlind, Åke
    Institutionen för Folkhälsovetenskap, Karolinska Institutet.
    Ljuv musik och öronproppar: om hörsel, musik och hörselskador2001Bok (Övrig (populärvetenskap, debatt, mm))
  • 20.
    Arlinger, Stig
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet.
    Lunner, Thomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Teknisk audiologi. Linköpings universitet, Hälsouniversitetet.
    Lyxell, Björn
    Linköpings universitet, Institutionen för beteendevetenskap och lärande. Linköpings universitet, Filosofiska fakulteten. Östergötlands Läns Landsting, Rekonstruktionscentrum, Öronkliniken US.
    Pichora-Fuller, M Kathleen
    University of Toronto.
    The emergence of cognitive hearing science.2009Ingår i: Scandinavian journal of psychology, ISSN 1467-9450, Vol. 50, nr 5, s. 371-384Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Cognitive Hearing Science or Auditory Cognitive Science is an emerging field of interdisciplinary research concerning the interactions between hearing and cognition. It follows a trend over the last half century for interdisciplinary fields to develop, beginning with Neuroscience, then Cognitive Science, then Cognitive Neuroscience, and then Cognitive Vision Science. A common theme is that an interdisciplinary approach is necessary to understand complex human behaviors, to develop technologies incorporating knowledge of these behaviors, and to find solutions for individuals with impairments that undermine typical behaviors. Accordingly, researchers in traditional academic disciplines, such as Psychology, Physiology, Linguistics, Philosophy, Anthropology, and Sociology benefit from collaborations with each other, and with researchers in Computer Science and Engineering working on the design of technologies, and with health professionals working with individuals who have impairments. The factors that triggered the emergence of Cognitive Hearing Science include the maturation of the component disciplines of Hearing Science and Cognitive Science, new opportunities to use complex digital signal-processing to design technologies suited to performance in challenging everyday environments, and increasing social imperatives to help people whose communication problems span hearing and cognition. Cognitive Hearing Science is illustrated in research on three general topics: (1) language processing in challenging listening conditions; (2) use of auditory communication technologies or the visual modality to boost performance; (3) changes in performance with development, aging, and rehabilitative training. Future directions for modeling and the translation of research into practice are suggested.

  • 21.
    Ask, Per
    et al.
    Linköpings universitet, Institutionen för medicinsk teknik, Fysiologisk mätteknik. Linköpings universitet, Tekniska högskolan.
    Tibbling, Lita
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet.
    Öberg, Åke
    Linköpings universitet, Institutionen för medicinsk teknik, Fysiologisk mätteknik. Linköpings universitet, Tekniska högskolan.
    Compliance and bandwidth of oesophagus manometry systems1976Konferensbidrag (Övrigt vetenskapligt)
  • 22.
    Ask, Per
    et al.
    Linköpings universitet, Institutionen för medicinsk teknik, Fysiologisk mätteknik. Linköpings universitet, Tekniska högskolan.
    Tibbling, Lita
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet.
    Öberg, Åke
    Linköpings universitet, Institutionen för medicinsk teknik, Fysiologisk mätteknik. Linköpings universitet, Tekniska högskolan.
    Metodutveckling för oesophagus-diagnostik1976Konferensbidrag (Övrigt vetenskapligt)
  • 23.
    Ask, Per
    et al.
    Linköpings universitet, Institutionen för medicinsk teknik, Fysiologisk mätteknik. Linköpings universitet, Tekniska högskolan.
    Tibbling, Lita
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet.
    Öberg, Åke
    Linköpings universitet, Institutionen för medicinsk teknik, Fysiologisk mätteknik. Linköpings universitet, Tekniska högskolan.
    Metodutveckling för oesophagus-diagnostik1977Ingår i: Svensk ÖNH-Tidskrift, ISSN 1400-0121, Vol. 1, nr 1, s. 1-1Artikel i tidskrift (Refereegranskat)
  • 24.
    Asp, Filip
    et al.
    Karolinska Institutet.
    Mäki-Torkko, Elina
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Teknisk audiologi.
    Hergils, Leif
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi.
    Harder, Henrik
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Teknisk audiologi.
    Karltorp, Eva
    Karolinska Institutet.
    Stenfelt, Stefan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Teknisk audiologi. Linköpings universitet, Hälsouniversitetet.
    Bilateral cochlear implants in children: Longitudinal results and parental experiences2010Ingår i: 11th International Conference on Cochlear Implants and Other Auditory Implantable Technologies, 2010Konferensbidrag (Refereegranskat)
  • 25.
    Asp, Filip
    et al.
    Karolinska University Hospital, Sweden Karolinska Institute, Sweden .
    Mäki-Torkko, Elina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Teknisk audiologi. Linköpings universitet, Hälsouniversitetet.
    Karltorp, Eva
    Karolinska University Hospital, Sweden Karolinska Institute, Sweden .
    Harder, Henrik
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Öron- näsa- och halskliniken US.
    Hergils, Leif
    Linköpings universitet, Institutionen för medicin och hälsa, Medicinsk teknologiutvärdering. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Öron- näsa- och halskliniken US.
    Eskilsson, Gunnar
    Karolinska University Hospital, Sweden .
    Stenfelt, Stefan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Teknisk audiologi. Linköpings universitet, Hälsouniversitetet.
    Bilateral versus unilateral cochlear implants in children: Speech recognition, sound localization, and parental reports2012Ingår i: International Journal of Audiology, ISSN 1499-2027, E-ISSN 1708-8186, Vol. 51, nr 11, s. 817-832Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To compare bilateral and unilateral speech recognition in quiet and in multi-source noise, and horizontal sound localization of low and high frequency sounds in children with bilateral cochlear implants. Design: Bilateral performance was compared to performance of the implanted side with the best monaural speech recognition in quiet result. Parental reports were collected in a questionnaire. Results from the CI children were compared to binaural and monaural performance of normal-hearing peers. Study sample: Sixty-four children aged 5.1-11.9 years who were daily users of bilateral cochlear implants. Thirty normal-hearing children aged 4.8-9.0 years were recruited as controls. Results and Conclusions : Group data showed a statistically significant bilateral speech recognition and sound localization benefit, both behaviorally and in parental reports. The bilateral speech recognition benefit was smaller in quiet than in noise. The majority of subjects localized high and low frequency sounds significantly better than chance using bilateral implants, while localization accuracy was close to chance using unilateral implants. Binaural normal-hearing performance was better than bilateral performance in implanted children across tests, while bilaterally implanted children showed better localization than normal-hearing children under acute monaural conditions.

  • 26.
    Bruder, CEG
    et al.
    Univ Uppsala Hosp, Rudbeck Lab, Dept Genet & Pathol, SE-75185 Uppsala, Sweden Karolinska Hosp, Dept Mol Med, SE-17176 Stockholm, Sweden Univ Uppsala Hosp, Dept Otorhinolaryngol & Head & Neck Surg, SE-75185 Uppsala, Sweden Univ Calif San Francisco, Dept Lab Med, Ctr Canc, San Francisco, CA 94143 USA St Marys Hosp, Dept Med Genet, Manchester M13 0JH, Lancs, England INSERM, U434, Lab Genet Tumeurs, F-75010 Paris, France Univ Zurich, Inst Med Genet, CH-8001 Zurich, Switzerland Univ Zurich, Childrens Hosp, Div Pediat Neurol, CH-8032 Zurich, Switzerland Univ Florence, Dept Physiopathol, Med Genet Unit, I-500139 Florence, Italy Montreal Gen Hosp, Ctr Res Neurosci, Montreal, PQ H3G 1A4, Canada Univ Hosp Queen Giovanna, Dept Neurosurg, BG-1527 Sofia, Bulgaria Lab Mol Pathol, BG-1431 Sofia, Bulgaria Klinikum Nord Ochsenzoll, Dept Neurol, D-22419 Hamburg, Germany Univ Helsinki, Haartman Inst, Dept Pathol, FIN-00014 Helsinki, Finland House Ear Inst, Los Angeles, CA 90057 USA Karolinska Hosp, Dept Neurosurg, SE-17176 Stockholm, Sweden Sahlgrens Univ Hosp, Dept Audiol, SE-41335 Gothenburg, Sweden Cedars Sinai Med Ctr, Div Neurol, Los Angeles, CA 90048 USA Linkoping Univ Hosp, Dept Otorhinolaryngol, SE-58185 Linkoping, Sweden Univ Oslo, Rikshosp, Dept Med Genet, N-0027 Oslo, Norway Jikei Univ, Sch Med, Dept Dermatol, Minato Ku, Tokyo 1058461, Japan Univ Calif San Francisco, Ctr Canc, Inst Canc Res, San Francisco, CA 94143 USA.
    Hirvela, C
    Univ Uppsala Hosp, Rudbeck Lab, Dept Genet & Pathol, SE-75185 Uppsala, Sweden Karolinska Hosp, Dept Mol Med, SE-17176 Stockholm, Sweden Univ Uppsala Hosp, Dept Otorhinolaryngol & Head & Neck Surg, SE-75185 Uppsala, Sweden Univ Calif San Francisco, Dept Lab Med, Ctr Canc, San Francisco, CA 94143 USA St Marys Hosp, Dept Med Genet, Manchester M13 0JH, Lancs, England INSERM, U434, Lab Genet Tumeurs, F-75010 Paris, France Univ Zurich, Inst Med Genet, CH-8001 Zurich, Switzerland Univ Zurich, Childrens Hosp, Div Pediat Neurol, CH-8032 Zurich, Switzerland Univ Florence, Dept Physiopathol, Med Genet Unit, I-500139 Florence, Italy Montreal Gen Hosp, Ctr Res Neurosci, Montreal, PQ H3G 1A4, Canada Univ Hosp Queen Giovanna, Dept Neurosurg, BG-1527 Sofia, Bulgaria Lab Mol Pathol, BG-1431 Sofia, Bulgaria Klinikum Nord Ochsenzoll, Dept Neurol, D-22419 Hamburg, Germany Univ Helsinki, Haartman Inst, Dept Pathol, FIN-00014 Helsinki, Finland House Ear Inst, Los Angeles, CA 90057 USA Karolinska Hosp, Dept Neurosurg, SE-17176 Stockholm, Sweden Sahlgrens Univ Hosp, Dept Audiol, SE-41335 Gothenburg, Sweden Cedars Sinai Med Ctr, Div Neurol, Los Angeles, CA 90048 USA Linkoping Univ Hosp, Dept Otorhinolaryngol, SE-58185 Linkoping, Sweden Univ Oslo, Rikshosp, Dept Med Genet, N-0027 Oslo, Norway Jikei Univ, Sch Med, Dept Dermatol, Minato Ku, Tokyo 1058461, Japan Univ Calif San Francisco, Ctr Canc, Inst Canc Res, San Francisco, CA 94143 USA.
    Tapia-Paez, I
    Univ Uppsala Hosp, Rudbeck Lab, Dept Genet & Pathol, SE-75185 Uppsala, Sweden Karolinska Hosp, Dept Mol Med, SE-17176 Stockholm, Sweden Univ Uppsala Hosp, Dept Otorhinolaryngol & Head & Neck Surg, SE-75185 Uppsala, Sweden Univ Calif San Francisco, Dept Lab Med, Ctr Canc, San Francisco, CA 94143 USA St Marys Hosp, Dept Med Genet, Manchester M13 0JH, Lancs, England INSERM, U434, Lab Genet Tumeurs, F-75010 Paris, France Univ Zurich, Inst Med Genet, CH-8001 Zurich, Switzerland Univ Zurich, Childrens Hosp, Div Pediat Neurol, CH-8032 Zurich, Switzerland Univ Florence, Dept Physiopathol, Med Genet Unit, I-500139 Florence, Italy Montreal Gen Hosp, Ctr Res Neurosci, Montreal, PQ H3G 1A4, Canada Univ Hosp Queen Giovanna, Dept Neurosurg, BG-1527 Sofia, Bulgaria Lab Mol Pathol, BG-1431 Sofia, Bulgaria Klinikum Nord Ochsenzoll, Dept Neurol, D-22419 Hamburg, Germany Univ Helsinki, Haartman Inst, Dept Pathol, FIN-00014 Helsinki, Finland House Ear Inst, Los Angeles, CA 90057 USA Karolinska Hosp, Dept Neurosurg, SE-17176 Stockholm, Sweden Sahlgrens Univ Hosp, Dept Audiol, SE-41335 Gothenburg, Sweden Cedars Sinai Med Ctr, Div Neurol, Los Angeles, CA 90048 USA Linkoping Univ Hosp, Dept Otorhinolaryngol, SE-58185 Linkoping, Sweden Univ Oslo, Rikshosp, Dept Med Genet, N-0027 Oslo, Norway Jikei Univ, Sch Med, Dept Dermatol, Minato Ku, Tokyo 1058461, Japan Univ Calif San Francisco, Ctr Canc, Inst Canc Res, San Francisco, CA 94143 USA.
    Fransson, I
    Segraves, R
    Univ Uppsala Hosp, Rudbeck Lab, Dept Genet & Pathol, SE-75185 Uppsala, Sweden Karolinska Hosp, Dept Mol Med, SE-17176 Stockholm, Sweden Univ Uppsala Hosp, Dept Otorhinolaryngol & Head & Neck Surg, SE-75185 Uppsala, Sweden Univ Calif San Francisco, Dept Lab Med, Ctr Canc, San Francisco, CA 94143 USA St Marys Hosp, Dept Med Genet, Manchester M13 0JH, Lancs, England INSERM, U434, Lab Genet Tumeurs, F-75010 Paris, France Univ Zurich, Inst Med Genet, CH-8001 Zurich, Switzerland Univ Zurich, Childrens Hosp, Div Pediat Neurol, CH-8032 Zurich, Switzerland Univ Florence, Dept Physiopathol, Med Genet Unit, I-500139 Florence, Italy Montreal Gen Hosp, Ctr Res Neurosci, Montreal, PQ H3G 1A4, Canada Univ Hosp Queen Giovanna, Dept Neurosurg, BG-1527 Sofia, Bulgaria Lab Mol Pathol, BG-1431 Sofia, Bulgaria Klinikum Nord Ochsenzoll, Dept Neurol, D-22419 Hamburg, Germany Univ Helsinki, Haartman Inst, Dept Pathol, FIN-00014 Helsinki, Finland House Ear Inst, Los Angeles, CA 90057 USA Karolinska Hosp, Dept Neurosurg, SE-17176 Stockholm, Sweden Sahlgrens Univ Hosp, Dept Audiol, SE-41335 Gothenburg, Sweden Cedars Sinai Med Ctr, Div Neurol, Los Angeles, CA 90048 USA Linkoping Univ Hosp, Dept Otorhinolaryngol, SE-58185 Linkoping, Sweden Univ Oslo, Rikshosp, Dept Med Genet, N-0027 Oslo, Norway Jikei Univ, Sch Med, Dept Dermatol, Minato Ku, Tokyo 1058461, Japan Univ Calif San Francisco, Ctr Canc, Inst Canc Res, San Francisco, CA 94143 USA.
    Hamilton, G
    Univ Uppsala Hosp, Rudbeck Lab, Dept Genet & Pathol, SE-75185 Uppsala, Sweden Karolinska Hosp, Dept Mol Med, SE-17176 Stockholm, Sweden Univ Uppsala Hosp, Dept Otorhinolaryngol & Head & Neck Surg, SE-75185 Uppsala, Sweden Univ Calif San Francisco, Dept Lab Med, Ctr Canc, San Francisco, CA 94143 USA St Marys Hosp, Dept Med Genet, Manchester M13 0JH, Lancs, England INSERM, U434, Lab Genet Tumeurs, F-75010 Paris, France Univ Zurich, Inst Med Genet, CH-8001 Zurich, Switzerland Univ Zurich, Childrens Hosp, Div Pediat Neurol, CH-8032 Zurich, Switzerland Univ Florence, Dept Physiopathol, Med Genet Unit, I-500139 Florence, Italy Montreal Gen Hosp, Ctr Res Neurosci, Montreal, PQ H3G 1A4, Canada Univ Hosp Queen Giovanna, Dept Neurosurg, BG-1527 Sofia, Bulgaria Lab Mol Pathol, BG-1431 Sofia, Bulgaria Klinikum Nord Ochsenzoll, Dept Neurol, D-22419 Hamburg, Germany Univ Helsinki, Haartman Inst, Dept Pathol, FIN-00014 Helsinki, Finland House Ear Inst, Los Angeles, CA 90057 USA Karolinska Hosp, Dept Neurosurg, SE-17176 Stockholm, Sweden Sahlgrens Univ Hosp, Dept Audiol, SE-41335 Gothenburg, Sweden Cedars Sinai Med Ctr, Div Neurol, Los Angeles, CA 90048 USA Linkoping Univ Hosp, Dept Otorhinolaryngol, SE-58185 Linkoping, Sweden Univ Oslo, Rikshosp, Dept Med Genet, N-0027 Oslo, Norway Jikei Univ, Sch Med, Dept Dermatol, Minato Ku, Tokyo 1058461, Japan Univ Calif San Francisco, Ctr Canc, Inst Canc Res, San Francisco, CA 94143 USA.
    Zhang, XX
    Univ Uppsala Hosp, Rudbeck Lab, Dept Genet & Pathol, SE-75185 Uppsala, Sweden Karolinska Hosp, Dept Mol Med, SE-17176 Stockholm, Sweden Univ Uppsala Hosp, Dept Otorhinolaryngol & Head & Neck Surg, SE-75185 Uppsala, Sweden Univ Calif San Francisco, Dept Lab Med, Ctr Canc, San Francisco, CA 94143 USA St Marys Hosp, Dept Med Genet, Manchester M13 0JH, Lancs, England INSERM, U434, Lab Genet Tumeurs, F-75010 Paris, France Univ Zurich, Inst Med Genet, CH-8001 Zurich, Switzerland Univ Zurich, Childrens Hosp, Div Pediat Neurol, CH-8032 Zurich, Switzerland Univ Florence, Dept Physiopathol, Med Genet Unit, I-500139 Florence, Italy Montreal Gen Hosp, Ctr Res Neurosci, Montreal, PQ H3G 1A4, Canada Univ Hosp Queen Giovanna, Dept Neurosurg, BG-1527 Sofia, Bulgaria Lab Mol Pathol, BG-1431 Sofia, Bulgaria Klinikum Nord Ochsenzoll, Dept Neurol, D-22419 Hamburg, Germany Univ Helsinki, Haartman Inst, Dept Pathol, FIN-00014 Helsinki, Finland House Ear Inst, Los Angeles, CA 90057 USA Karolinska Hosp, Dept Neurosurg, SE-17176 Stockholm, Sweden Sahlgrens Univ Hosp, Dept Audiol, SE-41335 Gothenburg, Sweden Cedars Sinai Med Ctr, Div Neurol, Los Angeles, CA 90048 USA Linkoping Univ Hosp, Dept Otorhinolaryngol, SE-58185 Linkoping, Sweden Univ Oslo, Rikshosp, Dept Med Genet, N-0027 Oslo, Norway Jikei Univ, Sch Med, Dept Dermatol, Minato Ku, Tokyo 1058461, Japan Univ Calif San Francisco, Ctr Canc, Inst Canc Res, San Francisco, CA 94143 USA.
    Evans, DG
    Univ Uppsala Hosp, Rudbeck Lab, Dept Genet & Pathol, SE-75185 Uppsala, Sweden Karolinska Hosp, Dept Mol Med, SE-17176 Stockholm, Sweden Univ Uppsala Hosp, Dept Otorhinolaryngol & Head & Neck Surg, SE-75185 Uppsala, Sweden Univ Calif San Francisco, Dept Lab Med, Ctr Canc, San Francisco, CA 94143 USA St Marys Hosp, Dept Med Genet, Manchester M13 0JH, Lancs, England INSERM, U434, Lab Genet Tumeurs, F-75010 Paris, France Univ Zurich, Inst Med Genet, CH-8001 Zurich, Switzerland Univ Zurich, Childrens Hosp, Div Pediat Neurol, CH-8032 Zurich, Switzerland Univ Florence, Dept Physiopathol, Med Genet Unit, I-500139 Florence, Italy Montreal Gen Hosp, Ctr Res Neurosci, Montreal, PQ H3G 1A4, Canada Univ Hosp Queen Giovanna, Dept Neurosurg, BG-1527 Sofia, Bulgaria Lab Mol Pathol, BG-1431 Sofia, Bulgaria Klinikum Nord Ochsenzoll, Dept Neurol, D-22419 Hamburg, Germany Univ Helsinki, Haartman Inst, Dept Pathol, FIN-00014 Helsinki, Finland House Ear Inst, Los Angeles, CA 90057 USA Karolinska Hosp, Dept Neurosurg, SE-17176 Stockholm, Sweden Sahlgrens Univ Hosp, Dept Audiol, SE-41335 Gothenburg, Sweden Cedars Sinai Med Ctr, Div Neurol, Los Angeles, CA 90048 USA Linkoping Univ Hosp, Dept Otorhinolaryngol, SE-58185 Linkoping, Sweden Univ Oslo, Rikshosp, Dept Med Genet, N-0027 Oslo, Norway Jikei Univ, Sch Med, Dept Dermatol, Minato Ku, Tokyo 1058461, Japan Univ Calif San Francisco, Ctr Canc, Inst Canc Res, San Francisco, CA 94143 USA.
    Wallace, AJ
    Univ Uppsala Hosp, Rudbeck Lab, Dept Genet & Pathol, SE-75185 Uppsala, Sweden Karolinska Hosp, Dept Mol Med, SE-17176 Stockholm, Sweden Univ Uppsala Hosp, Dept Otorhinolaryngol & Head & Neck Surg, SE-75185 Uppsala, Sweden Univ Calif San Francisco, Dept Lab Med, Ctr Canc, San Francisco, CA 94143 USA St Marys Hosp, Dept Med Genet, Manchester M13 0JH, Lancs, England INSERM, U434, Lab Genet Tumeurs, F-75010 Paris, France Univ Zurich, Inst Med Genet, CH-8001 Zurich, Switzerland Univ Zurich, Childrens Hosp, Div Pediat Neurol, CH-8032 Zurich, Switzerland Univ Florence, Dept Physiopathol, Med Genet Unit, I-500139 Florence, Italy Montreal Gen Hosp, Ctr Res Neurosci, Montreal, PQ H3G 1A4, Canada Univ Hosp Queen Giovanna, Dept Neurosurg, BG-1527 Sofia, Bulgaria Lab Mol Pathol, BG-1431 Sofia, Bulgaria Klinikum Nord Ochsenzoll, Dept Neurol, D-22419 Hamburg, Germany Univ Helsinki, Haartman Inst, Dept Pathol, FIN-00014 Helsinki, Finland House Ear Inst, Los Angeles, CA 90057 USA Karolinska Hosp, Dept Neurosurg, SE-17176 Stockholm, Sweden Sahlgrens Univ Hosp, Dept Audiol, SE-41335 Gothenburg, Sweden Cedars Sinai Med Ctr, Div Neurol, Los Angeles, CA 90048 USA Linkoping Univ Hosp, Dept Otorhinolaryngol, SE-58185 Linkoping, Sweden Univ Oslo, Rikshosp, Dept Med Genet, N-0027 Oslo, Norway Jikei Univ, Sch Med, Dept Dermatol, Minato Ku, Tokyo 1058461, Japan Univ Calif San Francisco, Ctr Canc, Inst Canc Res, San Francisco, CA 94143 USA.
    Baser, ME
    Univ Uppsala Hosp, Rudbeck Lab, Dept Genet & Pathol, SE-75185 Uppsala, Sweden Karolinska Hosp, Dept Mol Med, SE-17176 Stockholm, Sweden Univ Uppsala Hosp, Dept Otorhinolaryngol & Head & Neck Surg, SE-75185 Uppsala, Sweden Univ Calif San Francisco, Dept Lab Med, Ctr Canc, San Francisco, CA 94143 USA St Marys Hosp, Dept Med Genet, Manchester M13 0JH, Lancs, England INSERM, U434, Lab Genet Tumeurs, F-75010 Paris, France Univ Zurich, Inst Med Genet, CH-8001 Zurich, Switzerland Univ Zurich, Childrens Hosp, Div Pediat Neurol, CH-8032 Zurich, Switzerland Univ Florence, Dept Physiopathol, Med Genet Unit, I-500139 Florence, Italy Montreal Gen Hosp, Ctr Res Neurosci, Montreal, PQ H3G 1A4, Canada Univ Hosp Queen Giovanna, Dept Neurosurg, BG-1527 Sofia, Bulgaria Lab Mol Pathol, BG-1431 Sofia, Bulgaria Klinikum Nord Ochsenzoll, Dept Neurol, D-22419 Hamburg, Germany Univ Helsinki, Haartman Inst, Dept Pathol, FIN-00014 Helsinki, Finland House Ear Inst, Los Angeles, CA 90057 USA Karolinska Hosp, Dept Neurosurg, SE-17176 Stockholm, Sweden Sahlgrens Univ Hosp, Dept Audiol, SE-41335 Gothenburg, Sweden Cedars Sinai Med Ctr, Div Neurol, Los Angeles, CA 90048 USA Linkoping Univ Hosp, Dept Otorhinolaryngol, SE-58185 Linkoping, Sweden Univ Oslo, Rikshosp, Dept Med Genet, N-0027 Oslo, Norway Jikei Univ, Sch Med, Dept Dermatol, Minato Ku, Tokyo 1058461, Japan Univ Calif San Francisco, Ctr Canc, Inst Canc Res, San Francisco, CA 94143 USA.
    Zucman-Rossi, J
    Univ Uppsala Hosp, Rudbeck Lab, Dept Genet & Pathol, SE-75185 Uppsala, Sweden Karolinska Hosp, Dept Mol Med, SE-17176 Stockholm, Sweden Univ Uppsala Hosp, Dept Otorhinolaryngol & Head & Neck Surg, SE-75185 Uppsala, Sweden Univ Calif San Francisco, Dept Lab Med, Ctr Canc, San Francisco, CA 94143 USA St Marys Hosp, Dept Med Genet, Manchester M13 0JH, Lancs, England INSERM, U434, Lab Genet Tumeurs, F-75010 Paris, France Univ Zurich, Inst Med Genet, CH-8001 Zurich, Switzerland Univ Zurich, Childrens Hosp, Div Pediat Neurol, CH-8032 Zurich, Switzerland Univ Florence, Dept Physiopathol, Med Genet Unit, I-500139 Florence, Italy Montreal Gen Hosp, Ctr Res Neurosci, Montreal, PQ H3G 1A4, Canada Univ Hosp Queen Giovanna, Dept Neurosurg, BG-1527 Sofia, Bulgaria Lab Mol Pathol, BG-1431 Sofia, Bulgaria Klinikum Nord Ochsenzoll, Dept Neurol, D-22419 Hamburg, Germany Univ Helsinki, Haartman Inst, Dept Pathol, FIN-00014 Helsinki, Finland House Ear Inst, Los Angeles, CA 90057 USA Karolinska Hosp, Dept Neurosurg, SE-17176 Stockholm, Sweden Sahlgrens Univ Hosp, Dept Audiol, SE-41335 Gothenburg, Sweden Cedars Sinai Med Ctr, Div Neurol, Los Angeles, CA 90048 USA Linkoping Univ Hosp, Dept Otorhinolaryngol, SE-58185 Linkoping, Sweden Univ Oslo, Rikshosp, Dept Med Genet, N-0027 Oslo, Norway Jikei Univ, Sch Med, Dept Dermatol, Minato Ku, Tokyo 1058461, Japan Univ Calif San Francisco, Ctr Canc, Inst Canc Res, San Francisco, CA 94143 USA.
    Hergersberg, M
    Univ Uppsala Hosp, Rudbeck Lab, Dept Genet & Pathol, SE-75185 Uppsala, Sweden Karolinska Hosp, Dept Mol Med, SE-17176 Stockholm, Sweden Univ Uppsala Hosp, Dept Otorhinolaryngol & Head & Neck Surg, SE-75185 Uppsala, Sweden Univ Calif San Francisco, Dept Lab Med, Ctr Canc, San Francisco, CA 94143 USA St Marys Hosp, Dept Med Genet, Manchester M13 0JH, Lancs, England INSERM, U434, Lab Genet Tumeurs, F-75010 Paris, France Univ Zurich, Inst Med Genet, CH-8001 Zurich, Switzerland Univ Zurich, Childrens Hosp, Div Pediat Neurol, CH-8032 Zurich, Switzerland Univ Florence, Dept Physiopathol, Med Genet Unit, I-500139 Florence, Italy Montreal Gen Hosp, Ctr Res Neurosci, Montreal, PQ H3G 1A4, Canada Univ Hosp Queen Giovanna, Dept Neurosurg, BG-1527 Sofia, Bulgaria Lab Mol Pathol, BG-1431 Sofia, Bulgaria Klinikum Nord Ochsenzoll, Dept Neurol, D-22419 Hamburg, Germany Univ Helsinki, Haartman Inst, Dept Pathol, FIN-00014 Helsinki, Finland House Ear Inst, Los Angeles, CA 90057 USA Karolinska Hosp, Dept Neurosurg, SE-17176 Stockholm, Sweden Sahlgrens Univ Hosp, Dept Audiol, SE-41335 Gothenburg, Sweden Cedars Sinai Med Ctr, Div Neurol, Los Angeles, CA 90048 USA Linkoping Univ Hosp, Dept Otorhinolaryngol, SE-58185 Linkoping, Sweden Univ Oslo, Rikshosp, Dept Med Genet, N-0027 Oslo, Norway Jikei Univ, Sch Med, Dept Dermatol, Minato Ku, Tokyo 1058461, Japan Univ Calif San Francisco, Ctr Canc, Inst Canc Res, San Francisco, CA 94143 USA.
    Boltshauser, E
    Univ Uppsala Hosp, Rudbeck Lab, Dept Genet & Pathol, SE-75185 Uppsala, Sweden Karolinska Hosp, Dept Mol Med, SE-17176 Stockholm, Sweden Univ Uppsala Hosp, Dept Otorhinolaryngol & Head & Neck Surg, SE-75185 Uppsala, Sweden Univ Calif San Francisco, Dept Lab Med, Ctr Canc, San Francisco, CA 94143 USA St Marys Hosp, Dept Med Genet, Manchester M13 0JH, Lancs, England INSERM, U434, Lab Genet Tumeurs, F-75010 Paris, France Univ Zurich, Inst Med Genet, CH-8001 Zurich, Switzerland Univ Zurich, Childrens Hosp, Div Pediat Neurol, CH-8032 Zurich, Switzerland Univ Florence, Dept Physiopathol, Med Genet Unit, I-500139 Florence, Italy Montreal Gen Hosp, Ctr Res Neurosci, Montreal, PQ H3G 1A4, Canada Univ Hosp Queen Giovanna, Dept Neurosurg, BG-1527 Sofia, Bulgaria Lab Mol Pathol, BG-1431 Sofia, Bulgaria Klinikum Nord Ochsenzoll, Dept Neurol, D-22419 Hamburg, Germany Univ Helsinki, Haartman Inst, Dept Pathol, FIN-00014 Helsinki, Finland House Ear Inst, Los Angeles, CA 90057 USA Karolinska Hosp, Dept Neurosurg, SE-17176 Stockholm, Sweden Sahlgrens Univ Hosp, Dept Audiol, SE-41335 Gothenburg, Sweden Cedars Sinai Med Ctr, Div Neurol, Los Angeles, CA 90048 USA Linkoping Univ Hosp, Dept Otorhinolaryngol, SE-58185 Linkoping, Sweden Univ Oslo, Rikshosp, Dept Med Genet, N-0027 Oslo, Norway Jikei Univ, Sch Med, Dept Dermatol, Minato Ku, Tokyo 1058461, Japan Univ Calif San Francisco, Ctr Canc, Inst Canc Res, San Francisco, CA 94143 USA.
    Papi, L
    Univ Uppsala Hosp, Rudbeck Lab, Dept Genet & Pathol, SE-75185 Uppsala, Sweden Karolinska Hosp, Dept Mol Med, SE-17176 Stockholm, Sweden Univ Uppsala Hosp, Dept Otorhinolaryngol & Head & Neck Surg, SE-75185 Uppsala, Sweden Univ Calif San Francisco, Dept Lab Med, Ctr Canc, San Francisco, CA 94143 USA St Marys Hosp, Dept Med Genet, Manchester M13 0JH, Lancs, England INSERM, U434, Lab Genet Tumeurs, F-75010 Paris, France Univ Zurich, Inst Med Genet, CH-8001 Zurich, Switzerland Univ Zurich, Childrens Hosp, Div Pediat Neurol, CH-8032 Zurich, Switzerland Univ Florence, Dept Physiopathol, Med Genet Unit, I-500139 Florence, Italy Montreal Gen Hosp, Ctr Res Neurosci, Montreal, PQ H3G 1A4, Canada Univ Hosp Queen Giovanna, Dept Neurosurg, BG-1527 Sofia, Bulgaria Lab Mol Pathol, BG-1431 Sofia, Bulgaria Klinikum Nord Ochsenzoll, Dept Neurol, D-22419 Hamburg, Germany Univ Helsinki, Haartman Inst, Dept Pathol, FIN-00014 Helsinki, Finland House Ear Inst, Los Angeles, CA 90057 USA Karolinska Hosp, Dept Neurosurg, SE-17176 Stockholm, Sweden Sahlgrens Univ Hosp, Dept Audiol, SE-41335 Gothenburg, Sweden Cedars Sinai Med Ctr, Div Neurol, Los Angeles, CA 90048 USA Linkoping Univ Hosp, Dept Otorhinolaryngol, SE-58185 Linkoping, Sweden Univ Oslo, Rikshosp, Dept Med Genet, N-0027 Oslo, Norway Jikei Univ, Sch Med, Dept Dermatol, Minato Ku, Tokyo 1058461, Japan Univ Calif San Francisco, Ctr Canc, Inst Canc Res, San Francisco, CA 94143 USA.
    Rouleau, GA
    Univ Uppsala Hosp, Rudbeck Lab, Dept Genet & Pathol, SE-75185 Uppsala, Sweden Karolinska Hosp, Dept Mol Med, SE-17176 Stockholm, Sweden Univ Uppsala Hosp, Dept Otorhinolaryngol & Head & Neck Surg, SE-75185 Uppsala, Sweden Univ Calif San Francisco, Dept Lab Med, Ctr Canc, San Francisco, CA 94143 USA St Marys Hosp, Dept Med Genet, Manchester M13 0JH, Lancs, England INSERM, U434, Lab Genet Tumeurs, F-75010 Paris, France Univ Zurich, Inst Med Genet, CH-8001 Zurich, Switzerland Univ Zurich, Childrens Hosp, Div Pediat Neurol, CH-8032 Zurich, Switzerland Univ Florence, Dept Physiopathol, Med Genet Unit, I-500139 Florence, Italy Montreal Gen Hosp, Ctr Res Neurosci, Montreal, PQ H3G 1A4, Canada Univ Hosp Queen Giovanna, Dept Neurosurg, BG-1527 Sofia, Bulgaria Lab Mol Pathol, BG-1431 Sofia, Bulgaria Klinikum Nord Ochsenzoll, Dept Neurol, D-22419 Hamburg, Germany Univ Helsinki, Haartman Inst, Dept Pathol, FIN-00014 Helsinki, Finland House Ear Inst, Los Angeles, CA 90057 USA Karolinska Hosp, Dept Neurosurg, SE-17176 Stockholm, Sweden Sahlgrens Univ Hosp, Dept Audiol, SE-41335 Gothenburg, Sweden Cedars Sinai Med Ctr, Div Neurol, Los Angeles, CA 90048 USA Linkoping Univ Hosp, Dept Otorhinolaryngol, SE-58185 Linkoping, Sweden Univ Oslo, Rikshosp, Dept Med Genet, N-0027 Oslo, Norway Jikei Univ, Sch Med, Dept Dermatol, Minato Ku, Tokyo 1058461, Japan Univ Calif San Francisco, Ctr Canc, Inst Canc Res, San Francisco, CA 94143 USA.
    Poptodorov, G
    Univ Uppsala Hosp, Rudbeck Lab, Dept Genet & Pathol, SE-75185 Uppsala, Sweden Karolinska Hosp, Dept Mol Med, SE-17176 Stockholm, Sweden Univ Uppsala Hosp, Dept Otorhinolaryngol & Head & Neck Surg, SE-75185 Uppsala, Sweden Univ Calif San Francisco, Dept Lab Med, Ctr Canc, San Francisco, CA 94143 USA St Marys Hosp, Dept Med Genet, Manchester M13 0JH, Lancs, England INSERM, U434, Lab Genet Tumeurs, F-75010 Paris, France Univ Zurich, Inst Med Genet, CH-8001 Zurich, Switzerland Univ Zurich, Childrens Hosp, Div Pediat Neurol, CH-8032 Zurich, Switzerland Univ Florence, Dept Physiopathol, Med Genet Unit, I-500139 Florence, Italy Montreal Gen Hosp, Ctr Res Neurosci, Montreal, PQ H3G 1A4, Canada Univ Hosp Queen Giovanna, Dept Neurosurg, BG-1527 Sofia, Bulgaria Lab Mol Pathol, BG-1431 Sofia, Bulgaria Klinikum Nord Ochsenzoll, Dept Neurol, D-22419 Hamburg, Germany Univ Helsinki, Haartman Inst, Dept Pathol, FIN-00014 Helsinki, Finland House Ear Inst, Los Angeles, CA 90057 USA Karolinska Hosp, Dept Neurosurg, SE-17176 Stockholm, Sweden Sahlgrens Univ Hosp, Dept Audiol, SE-41335 Gothenburg, Sweden Cedars Sinai Med Ctr, Div Neurol, Los Angeles, CA 90048 USA Linkoping Univ Hosp, Dept Otorhinolaryngol, SE-58185 Linkoping, Sweden Univ Oslo, Rikshosp, Dept Med Genet, N-0027 Oslo, Norway Jikei Univ, Sch Med, Dept Dermatol, Minato Ku, Tokyo 1058461, Japan Univ Calif San Francisco, Ctr Canc, Inst Canc Res, San Francisco, CA 94143 USA.
    Jordanova, A
    Univ Uppsala Hosp, Rudbeck Lab, Dept Genet & Pathol, SE-75185 Uppsala, Sweden Karolinska Hosp, Dept Mol Med, SE-17176 Stockholm, Sweden Univ Uppsala Hosp, Dept Otorhinolaryngol & Head & Neck Surg, SE-75185 Uppsala, Sweden Univ Calif San Francisco, Dept Lab Med, Ctr Canc, San Francisco, CA 94143 USA St Marys Hosp, Dept Med Genet, Manchester M13 0JH, Lancs, England INSERM, U434, Lab Genet Tumeurs, F-75010 Paris, France Univ Zurich, Inst Med Genet, CH-8001 Zurich, Switzerland Univ Zurich, Childrens Hosp, Div Pediat Neurol, CH-8032 Zurich, Switzerland Univ Florence, Dept Physiopathol, Med Genet Unit, I-500139 Florence, Italy Montreal Gen Hosp, Ctr Res Neurosci, Montreal, PQ H3G 1A4, Canada Univ Hosp Queen Giovanna, Dept Neurosurg, BG-1527 Sofia, Bulgaria Lab Mol Pathol, BG-1431 Sofia, Bulgaria Klinikum Nord Ochsenzoll, Dept Neurol, D-22419 Hamburg, Germany Univ Helsinki, Haartman Inst, Dept Pathol, FIN-00014 Helsinki, Finland House Ear Inst, Los Angeles, CA 90057 USA Karolinska Hosp, Dept Neurosurg, SE-17176 Stockholm, Sweden Sahlgrens Univ Hosp, Dept Audiol, SE-41335 Gothenburg, Sweden Cedars Sinai Med Ctr, Div Neurol, Los Angeles, CA 90048 USA Linkoping Univ Hosp, Dept Otorhinolaryngol, SE-58185 Linkoping, Sweden Univ Oslo, Rikshosp, Dept Med Genet, N-0027 Oslo, Norway Jikei Univ, Sch Med, Dept Dermatol, Minato Ku, Tokyo 1058461, Japan Univ Calif San Francisco, Ctr Canc, Inst Canc Res, San Francisco, CA 94143 USA.
    Rask-Andersen, H
    Univ Uppsala Hosp, Rudbeck Lab, Dept Genet & Pathol, SE-75185 Uppsala, Sweden Karolinska Hosp, Dept Mol Med, SE-17176 Stockholm, Sweden Univ Uppsala Hosp, Dept Otorhinolaryngol & Head & Neck Surg, SE-75185 Uppsala, Sweden Univ Calif San Francisco, Dept Lab Med, Ctr Canc, San Francisco, CA 94143 USA St Marys Hosp, Dept Med Genet, Manchester M13 0JH, Lancs, England INSERM, U434, Lab Genet Tumeurs, F-75010 Paris, France Univ Zurich, Inst Med Genet, CH-8001 Zurich, Switzerland Univ Zurich, Childrens Hosp, Div Pediat Neurol, CH-8032 Zurich, Switzerland Univ Florence, Dept Physiopathol, Med Genet Unit, I-500139 Florence, Italy Montreal Gen Hosp, Ctr Res Neurosci, Montreal, PQ H3G 1A4, Canada Univ Hosp Queen Giovanna, Dept Neurosurg, BG-1527 Sofia, Bulgaria Lab Mol Pathol, BG-1431 Sofia, Bulgaria Klinikum Nord Ochsenzoll, Dept Neurol, D-22419 Hamburg, Germany Univ Helsinki, Haartman Inst, Dept Pathol, FIN-00014 Helsinki, Finland House Ear Inst, Los Angeles, CA 90057 USA Karolinska Hosp, Dept Neurosurg, SE-17176 Stockholm, Sweden Sahlgrens Univ Hosp, Dept Audiol, SE-41335 Gothenburg, Sweden Cedars Sinai Med Ctr, Div Neurol, Los Angeles, CA 90048 USA Linkoping Univ Hosp, Dept Otorhinolaryngol, SE-58185 Linkoping, Sweden Univ Oslo, Rikshosp, Dept Med Genet, N-0027 Oslo, Norway Jikei Univ, Sch Med, Dept Dermatol, Minato Ku, Tokyo 1058461, Japan Univ Calif San Francisco, Ctr Canc, Inst Canc Res, San Francisco, CA 94143 USA.
    Kluwe, L
    Univ Uppsala Hosp, Rudbeck Lab, Dept Genet & Pathol, SE-75185 Uppsala, Sweden Karolinska Hosp, Dept Mol Med, SE-17176 Stockholm, Sweden Univ Uppsala Hosp, Dept Otorhinolaryngol & Head & Neck Surg, SE-75185 Uppsala, Sweden Univ Calif San Francisco, Dept Lab Med, Ctr Canc, San Francisco, CA 94143 USA St Marys Hosp, Dept Med Genet, Manchester M13 0JH, Lancs, England INSERM, U434, Lab Genet Tumeurs, F-75010 Paris, France Univ Zurich, Inst Med Genet, CH-8001 Zurich, Switzerland Univ Zurich, Childrens Hosp, Div Pediat Neurol, CH-8032 Zurich, Switzerland Univ Florence, Dept Physiopathol, Med Genet Unit, I-500139 Florence, Italy Montreal Gen Hosp, Ctr Res Neurosci, Montreal, PQ H3G 1A4, Canada Univ Hosp Queen Giovanna, Dept Neurosurg, BG-1527 Sofia, Bulgaria Lab Mol Pathol, BG-1431 Sofia, Bulgaria Klinikum Nord Ochsenzoll, Dept Neurol, D-22419 Hamburg, Germany Univ Helsinki, Haartman Inst, Dept Pathol, FIN-00014 Helsinki, Finland House Ear Inst, Los Angeles, CA 90057 USA Karolinska Hosp, Dept Neurosurg, SE-17176 Stockholm, Sweden Sahlgrens Univ Hosp, Dept Audiol, SE-41335 Gothenburg, Sweden Cedars Sinai Med Ctr, Div Neurol, Los Angeles, CA 90048 USA Linkoping Univ Hosp, Dept Otorhinolaryngol, SE-58185 Linkoping, Sweden Univ Oslo, Rikshosp, Dept Med Genet, N-0027 Oslo, Norway Jikei Univ, Sch Med, Dept Dermatol, Minato Ku, Tokyo 1058461, Japan Univ Calif San Francisco, Ctr Canc, Inst Canc Res, San Francisco, CA 94143 USA.
    Mautner, V
    Univ Uppsala Hosp, Rudbeck Lab, Dept Genet & Pathol, SE-75185 Uppsala, Sweden Karolinska Hosp, Dept Mol Med, SE-17176 Stockholm, Sweden Univ Uppsala Hosp, Dept Otorhinolaryngol & Head & Neck Surg, SE-75185 Uppsala, Sweden Univ Calif San Francisco, Dept Lab Med, Ctr Canc, San Francisco, CA 94143 USA St Marys Hosp, Dept Med Genet, Manchester M13 0JH, Lancs, England INSERM, U434, Lab Genet Tumeurs, F-75010 Paris, France Univ Zurich, Inst Med Genet, CH-8001 Zurich, Switzerland Univ Zurich, Childrens Hosp, Div Pediat Neurol, CH-8032 Zurich, Switzerland Univ Florence, Dept Physiopathol, Med Genet Unit, I-500139 Florence, Italy Montreal Gen Hosp, Ctr Res Neurosci, Montreal, PQ H3G 1A4, Canada Univ Hosp Queen Giovanna, Dept Neurosurg, BG-1527 Sofia, Bulgaria Lab Mol Pathol, BG-1431 Sofia, Bulgaria Klinikum Nord Ochsenzoll, Dept Neurol, D-22419 Hamburg, Germany Univ Helsinki, Haartman Inst, Dept Pathol, FIN-00014 Helsinki, Finland House Ear Inst, Los Angeles, CA 90057 USA Karolinska Hosp, Dept Neurosurg, SE-17176 Stockholm, Sweden Sahlgrens Univ Hosp, Dept Audiol, SE-41335 Gothenburg, Sweden Cedars Sinai Med Ctr, Div Neurol, Los Angeles, CA 90048 USA Linkoping Univ Hosp, Dept Otorhinolaryngol, SE-58185 Linkoping, Sweden Univ Oslo, Rikshosp, Dept Med Genet, N-0027 Oslo, Norway Jikei Univ, Sch Med, Dept Dermatol, Minato Ku, Tokyo 1058461, Japan Univ Calif San Francisco, Ctr Canc, Inst Canc Res, San Francisco, CA 94143 USA.
    Sainio, M
    Univ Uppsala Hosp, Rudbeck Lab, Dept Genet & Pathol, SE-75185 Uppsala, Sweden Karolinska Hosp, Dept Mol Med, SE-17176 Stockholm, Sweden Univ Uppsala Hosp, Dept Otorhinolaryngol & Head & Neck Surg, SE-75185 Uppsala, Sweden Univ Calif San Francisco, Dept Lab Med, Ctr Canc, San Francisco, CA 94143 USA St Marys Hosp, Dept Med Genet, Manchester M13 0JH, Lancs, England INSERM, U434, Lab Genet Tumeurs, F-75010 Paris, France Univ Zurich, Inst Med Genet, CH-8001 Zurich, Switzerland Univ Zurich, Childrens Hosp, Div Pediat Neurol, CH-8032 Zurich, Switzerland Univ Florence, Dept Physiopathol, Med Genet Unit, I-500139 Florence, Italy Montreal Gen Hosp, Ctr Res Neurosci, Montreal, PQ H3G 1A4, Canada Univ Hosp Queen Giovanna, Dept Neurosurg, BG-1527 Sofia, Bulgaria Lab Mol Pathol, BG-1431 Sofia, Bulgaria Klinikum Nord Ochsenzoll, Dept Neurol, D-22419 Hamburg, Germany Univ Helsinki, Haartman Inst, Dept Pathol, FIN-00014 Helsinki, Finland House Ear Inst, Los Angeles, CA 90057 USA Karolinska Hosp, Dept Neurosurg, SE-17176 Stockholm, Sweden Sahlgrens Univ Hosp, Dept Audiol, SE-41335 Gothenburg, Sweden Cedars Sinai Med Ctr, Div Neurol, Los Angeles, CA 90048 USA Linkoping Univ Hosp, Dept Otorhinolaryngol, SE-58185 Linkoping, Sweden Univ Oslo, Rikshosp, Dept Med Genet, N-0027 Oslo, Norway Jikei Univ, Sch Med, Dept Dermatol, Minato Ku, Tokyo 1058461, Japan Univ Calif San Francisco, Ctr Canc, Inst Canc Res, San Francisco, CA 94143 USA.
    Hung, G
    Univ Uppsala Hosp, Rudbeck Lab, Dept Genet & Pathol, SE-75185 Uppsala, Sweden Karolinska Hosp, Dept Mol Med, SE-17176 Stockholm, Sweden Univ Uppsala Hosp, Dept Otorhinolaryngol & Head & Neck Surg, SE-75185 Uppsala, Sweden Univ Calif San Francisco, Dept Lab Med, Ctr Canc, San Francisco, CA 94143 USA St Marys Hosp, Dept Med Genet, Manchester M13 0JH, Lancs, England INSERM, U434, Lab Genet Tumeurs, F-75010 Paris, France Univ Zurich, Inst Med Genet, CH-8001 Zurich, Switzerland Univ Zurich, Childrens Hosp, Div Pediat Neurol, CH-8032 Zurich, Switzerland Univ Florence, Dept Physiopathol, Med Genet Unit, I-500139 Florence, Italy Montreal Gen Hosp, Ctr Res Neurosci, Montreal, PQ H3G 1A4, Canada Univ Hosp Queen Giovanna, Dept Neurosurg, BG-1527 Sofia, Bulgaria Lab Mol Pathol, BG-1431 Sofia, Bulgaria Klinikum Nord Ochsenzoll, Dept Neurol, D-22419 Hamburg, Germany Univ Helsinki, Haartman Inst, Dept Pathol, FIN-00014 Helsinki, Finland House Ear Inst, Los Angeles, CA 90057 USA Karolinska Hosp, Dept Neurosurg, SE-17176 Stockholm, Sweden Sahlgrens Univ Hosp, Dept Audiol, SE-41335 Gothenburg, Sweden Cedars Sinai Med Ctr, Div Neurol, Los Angeles, CA 90048 USA Linkoping Univ Hosp, Dept Otorhinolaryngol, SE-58185 Linkoping, Sweden Univ Oslo, Rikshosp, Dept Med Genet, N-0027 Oslo, Norway Jikei Univ, Sch Med, Dept Dermatol, Minato Ku, Tokyo 1058461, Japan Univ Calif San Francisco, Ctr Canc, Inst Canc Res, San Francisco, CA 94143 USA.
    Mathiesen, T
    Univ Uppsala Hosp, Rudbeck Lab, Dept Genet & Pathol, SE-75185 Uppsala, Sweden Karolinska Hosp, Dept Mol Med, SE-17176 Stockholm, Sweden Univ Uppsala Hosp, Dept Otorhinolaryngol & Head & Neck Surg, SE-75185 Uppsala, Sweden Univ Calif San Francisco, Dept Lab Med, Ctr Canc, San Francisco, CA 94143 USA St Marys Hosp, Dept Med Genet, Manchester M13 0JH, Lancs, England INSERM, U434, Lab Genet Tumeurs, F-75010 Paris, France Univ Zurich, Inst Med Genet, CH-8001 Zurich, Switzerland Univ Zurich, Childrens Hosp, Div Pediat Neurol, CH-8032 Zurich, Switzerland Univ Florence, Dept Physiopathol, Med Genet Unit, I-500139 Florence, Italy Montreal Gen Hosp, Ctr Res Neurosci, Montreal, PQ H3G 1A4, Canada Univ Hosp Queen Giovanna, Dept Neurosurg, BG-1527 Sofia, Bulgaria Lab Mol Pathol, BG-1431 Sofia, Bulgaria Klinikum Nord Ochsenzoll, Dept Neurol, D-22419 Hamburg, Germany Univ Helsinki, Haartman Inst, Dept Pathol, FIN-00014 Helsinki, Finland House Ear Inst, Los Angeles, CA 90057 USA Karolinska Hosp, Dept Neurosurg, SE-17176 Stockholm, Sweden Sahlgrens Univ Hosp, Dept Audiol, SE-41335 Gothenburg, Sweden Cedars Sinai Med Ctr, Div Neurol, Los Angeles, CA 90048 USA Linkoping Univ Hosp, Dept Otorhinolaryngol, SE-58185 Linkoping, Sweden Univ Oslo, Rikshosp, Dept Med Genet, N-0027 Oslo, Norway Jikei Univ, Sch Med, Dept Dermatol, Minato Ku, Tokyo 1058461, Japan Univ Calif San Francisco, Ctr Canc, Inst Canc Res, San Francisco, CA 94143 USA.
    Moller, C
    Pulst, SM
    Univ Uppsala Hosp, Rudbeck Lab, Dept Genet & Pathol, SE-75185 Uppsala, Sweden Karolinska Hosp, Dept Mol Med, SE-17176 Stockholm, Sweden Univ Uppsala Hosp, Dept Otorhinolaryngol & Head & Neck Surg, SE-75185 Uppsala, Sweden Univ Calif San Francisco, Dept Lab Med, Ctr Canc, San Francisco, CA 94143 USA St Marys Hosp, Dept Med Genet, Manchester M13 0JH, Lancs, England INSERM, U434, Lab Genet Tumeurs, F-75010 Paris, France Univ Zurich, Inst Med Genet, CH-8001 Zurich, Switzerland Univ Zurich, Childrens Hosp, Div Pediat Neurol, CH-8032 Zurich, Switzerland Univ Florence, Dept Physiopathol, Med Genet Unit, I-500139 Florence, Italy Montreal Gen Hosp, Ctr Res Neurosci, Montreal, PQ H3G 1A4, Canada Univ Hosp Queen Giovanna, Dept Neurosurg, BG-1527 Sofia, Bulgaria Lab Mol Pathol, BG-1431 Sofia, Bulgaria Klinikum Nord Ochsenzoll, Dept Neurol, D-22419 Hamburg, Germany Univ Helsinki, Haartman Inst, Dept Pathol, FIN-00014 Helsinki, Finland House Ear Inst, Los Angeles, CA 90057 USA Karolinska Hosp, Dept Neurosurg, SE-17176 Stockholm, Sweden Sahlgrens Univ Hosp, Dept Audiol, SE-41335 Gothenburg, Sweden Cedars Sinai Med Ctr, Div Neurol, Los Angeles, CA 90048 USA Linkoping Univ Hosp, Dept Otorhinolaryngol, SE-58185 Linkoping, Sweden Univ Oslo, Rikshosp, Dept Med Genet, N-0027 Oslo, Norway Jikei Univ, Sch Med, Dept Dermatol, Minato Ku, Tokyo 1058461, Japan Univ Calif San Francisco, Ctr Canc, Inst Canc Res, San Francisco, CA 94143 USA.
    Harder, Henrik
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Östergötlands Läns Landsting, Rekonstruktionscentrum, Öronkliniken US.
    Heiberg, A
    Univ Uppsala Hosp, Rudbeck Lab, Dept Genet & Pathol, SE-75185 Uppsala, Sweden Karolinska Hosp, Dept Mol Med, SE-17176 Stockholm, Sweden Univ Uppsala Hosp, Dept Otorhinolaryngol & Head & Neck Surg, SE-75185 Uppsala, Sweden Univ Calif San Francisco, Dept Lab Med, Ctr Canc, San Francisco, CA 94143 USA St Marys Hosp, Dept Med Genet, Manchester M13 0JH, Lancs, England INSERM, U434, Lab Genet Tumeurs, F-75010 Paris, France Univ Zurich, Inst Med Genet, CH-8001 Zurich, Switzerland Univ Zurich, Childrens Hosp, Div Pediat Neurol, CH-8032 Zurich, Switzerland Univ Florence, Dept Physiopathol, Med Genet Unit, I-500139 Florence, Italy Montreal Gen Hosp, Ctr Res Neurosci, Montreal, PQ H3G 1A4, Canada Univ Hosp Queen Giovanna, Dept Neurosurg, BG-1527 Sofia, Bulgaria Lab Mol Pathol, BG-1431 Sofia, Bulgaria Klinikum Nord Ochsenzoll, Dept Neurol, D-22419 Hamburg, Germany Univ Helsinki, Haartman Inst, Dept Pathol, FIN-00014 Helsinki, Finland House Ear Inst, Los Angeles, CA 90057 USA Karolinska Hosp, Dept Neurosurg, SE-17176 Stockholm, Sweden Sahlgrens Univ Hosp, Dept Audiol, SE-41335 Gothenburg, Sweden Cedars Sinai Med Ctr, Div Neurol, Los Angeles, CA 90048 USA Linkoping Univ Hosp, Dept Otorhinolaryngol, SE-58185 Linkoping, Sweden Univ Oslo, Rikshosp, Dept Med Genet, N-0027 Oslo, Norway Jikei Univ, Sch Med, Dept Dermatol, Minato Ku, Tokyo 1058461, Japan Univ Calif San Francisco, Ctr Canc, Inst Canc Res, San Francisco, CA 94143 USA.
    Honda, M
    Univ Uppsala Hosp, Rudbeck Lab, Dept Genet & Pathol, SE-75185 Uppsala, Sweden Karolinska Hosp, Dept Mol Med, SE-17176 Stockholm, Sweden Univ Uppsala Hosp, Dept Otorhinolaryngol & Head & Neck Surg, SE-75185 Uppsala, Sweden Univ Calif San Francisco, Dept Lab Med, Ctr Canc, San Francisco, CA 94143 USA St Marys Hosp, Dept Med Genet, Manchester M13 0JH, Lancs, England INSERM, U434, Lab Genet Tumeurs, F-75010 Paris, France Univ Zurich, Inst Med Genet, CH-8001 Zurich, Switzerland Univ Zurich, Childrens Hosp, Div Pediat Neurol, CH-8032 Zurich, Switzerland Univ Florence, Dept Physiopathol, Med Genet Unit, I-500139 Florence, Italy Montreal Gen Hosp, Ctr Res Neurosci, Montreal, PQ H3G 1A4, Canada Univ Hosp Queen Giovanna, Dept Neurosurg, BG-1527 Sofia, Bulgaria Lab Mol Pathol, BG-1431 Sofia, Bulgaria Klinikum Nord Ochsenzoll, Dept Neurol, D-22419 Hamburg, Germany Univ Helsinki, Haartman Inst, Dept Pathol, FIN-00014 Helsinki, Finland House Ear Inst, Los Angeles, CA 90057 USA Karolinska Hosp, Dept Neurosurg, SE-17176 Stockholm, Sweden Sahlgrens Univ Hosp, Dept Audiol, SE-41335 Gothenburg, Sweden Cedars Sinai Med Ctr, Div Neurol, Los Angeles, CA 90048 USA Linkoping Univ Hosp, Dept Otorhinolaryngol, SE-58185 Linkoping, Sweden Univ Oslo, Rikshosp, Dept Med Genet, N-0027 Oslo, Norway Jikei Univ, Sch Med, Dept Dermatol, Minato Ku, Tokyo 1058461, Japan Univ Calif San Francisco, Ctr Canc, Inst Canc Res, San Francisco, CA 94143 USA.
    Miimura, M
    Univ Uppsala Hosp, Rudbeck Lab, Dept Genet & Pathol, SE-75185 Uppsala, Sweden Karolinska Hosp, Dept Mol Med, SE-17176 Stockholm, Sweden Univ Uppsala Hosp, Dept Otorhinolaryngol & Head & Neck Surg, SE-75185 Uppsala, Sweden Univ Calif San Francisco, Dept Lab Med, Ctr Canc, San Francisco, CA 94143 USA St Marys Hosp, Dept Med Genet, Manchester M13 0JH, Lancs, England INSERM, U434, Lab Genet Tumeurs, F-75010 Paris, France Univ Zurich, Inst Med Genet, CH-8001 Zurich, Switzerland Univ Zurich, Childrens Hosp, Div Pediat Neurol, CH-8032 Zurich, Switzerland Univ Florence, Dept Physiopathol, Med Genet Unit, I-500139 Florence, Italy Montreal Gen Hosp, Ctr Res Neurosci, Montreal, PQ H3G 1A4, Canada Univ Hosp Queen Giovanna, Dept Neurosurg, BG-1527 Sofia, Bulgaria Lab Mol Pathol, BG-1431 Sofia, Bulgaria Klinikum Nord Ochsenzoll, Dept Neurol, D-22419 Hamburg, Germany Univ Helsinki, Haartman Inst, Dept Pathol, FIN-00014 Helsinki, Finland House Ear Inst, Los Angeles, CA 90057 USA Karolinska Hosp, Dept Neurosurg, SE-17176 Stockholm, Sweden Sahlgrens Univ Hosp, Dept Audiol, SE-41335 Gothenburg, Sweden Cedars Sinai Med Ctr, Div Neurol, Los Angeles, CA 90048 USA Linkoping Univ Hosp, Dept Otorhinolaryngol, SE-58185 Linkoping, Sweden Univ Oslo, Rikshosp, Dept Med Genet, N-0027 Oslo, Norway Jikei Univ, Sch Med, Dept Dermatol, Minato Ku, Tokyo 1058461, Japan Univ Calif San Francisco, Ctr Canc, Inst Canc Res, San Francisco, CA 94143 USA.
    Sahlen, S
    Univ Uppsala Hosp, Rudbeck Lab, Dept Genet & Pathol, SE-75185 Uppsala, Sweden Karolinska Hosp, Dept Mol Med, SE-17176 Stockholm, Sweden Univ Uppsala Hosp, Dept Otorhinolaryngol & Head & Neck Surg, SE-75185 Uppsala, Sweden Univ Calif San Francisco, Dept Lab Med, Ctr Canc, San Francisco, CA 94143 USA St Marys Hosp, Dept Med Genet, Manchester M13 0JH, Lancs, England INSERM, U434, Lab Genet Tumeurs, F-75010 Paris, France Univ Zurich, Inst Med Genet, CH-8001 Zurich, Switzerland Univ Zurich, Childrens Hosp, Div Pediat Neurol, CH-8032 Zurich, Switzerland Univ Florence, Dept Physiopathol, Med Genet Unit, I-500139 Florence, Italy Montreal Gen Hosp, Ctr Res Neurosci, Montreal, PQ H3G 1A4, Canada Univ Hosp Queen Giovanna, Dept Neurosurg, BG-1527 Sofia, Bulgaria Lab Mol Pathol, BG-1431 Sofia, Bulgaria Klinikum Nord Ochsenzoll, Dept Neurol, D-22419 Hamburg, Germany Univ Helsinki, Haartman Inst, Dept Pathol, FIN-00014 Helsinki, Finland House Ear Inst, Los Angeles, CA 90057 USA Karolinska Hosp, Dept Neurosurg, SE-17176 Stockholm, Sweden Sahlgrens Univ Hosp, Dept Audiol, SE-41335 Gothenburg, Sweden Cedars Sinai Med Ctr, Div Neurol, Los Angeles, CA 90048 USA Linkoping Univ Hosp, Dept Otorhinolaryngol, SE-58185 Linkoping, Sweden Univ Oslo, Rikshosp, Dept Med Genet, N-0027 Oslo, Norway Jikei Univ, Sch Med, Dept Dermatol, Minato Ku, Tokyo 1058461, Japan Univ Calif San Francisco, Ctr Canc, Inst Canc Res, San Francisco, CA 94143 USA.
    Blennow, E
    Univ Uppsala Hosp, Rudbeck Lab, Dept Genet & Pathol, SE-75185 Uppsala, Sweden Karolinska Hosp, Dept Mol Med, SE-17176 Stockholm, Sweden Univ Uppsala Hosp, Dept Otorhinolaryngol & Head & Neck Surg, SE-75185 Uppsala, Sweden Univ Calif San Francisco, Dept Lab Med, Ctr Canc, San Francisco, CA 94143 USA St Marys Hosp, Dept Med Genet, Manchester M13 0JH, Lancs, England INSERM, U434, Lab Genet Tumeurs, F-75010 Paris, France Univ Zurich, Inst Med Genet, CH-8001 Zurich, Switzerland Univ Zurich, Childrens Hosp, Div Pediat Neurol, CH-8032 Zurich, Switzerland Univ Florence, Dept Physiopathol, Med Genet Unit, I-500139 Florence, Italy Montreal Gen Hosp, Ctr Res Neurosci, Montreal, PQ H3G 1A4, Canada Univ Hosp Queen Giovanna, Dept Neurosurg, BG-1527 Sofia, Bulgaria Lab Mol Pathol, BG-1431 Sofia, Bulgaria Klinikum Nord Ochsenzoll, Dept Neurol, D-22419 Hamburg, Germany Univ Helsinki, Haartman Inst, Dept Pathol, FIN-00014 Helsinki, Finland House Ear Inst, Los Angeles, CA 90057 USA Karolinska Hosp, Dept Neurosurg, SE-17176 Stockholm, Sweden Sahlgrens Univ Hosp, Dept Audiol, SE-41335 Gothenburg, Sweden Cedars Sinai Med Ctr, Div Neurol, Los Angeles, CA 90048 USA Linkoping Univ Hosp, Dept Otorhinolaryngol, SE-58185 Linkoping, Sweden Univ Oslo, Rikshosp, Dept Med Genet, N-0027 Oslo, Norway Jikei Univ, Sch Med, Dept Dermatol, Minato Ku, Tokyo 1058461, Japan Univ Calif San Francisco, Ctr Canc, Inst Canc Res, San Francisco, CA 94143 USA.
    Albertson, DG
    Univ Uppsala Hosp, Rudbeck Lab, Dept Genet & Pathol, SE-75185 Uppsala, Sweden Karolinska Hosp, Dept Mol Med, SE-17176 Stockholm, Sweden Univ Uppsala Hosp, Dept Otorhinolaryngol & Head & Neck Surg, SE-75185 Uppsala, Sweden Univ Calif San Francisco, Dept Lab Med, Ctr Canc, San Francisco, CA 94143 USA St Marys Hosp, Dept Med Genet, Manchester M13 0JH, Lancs, England INSERM, U434, Lab Genet Tumeurs, F-75010 Paris, France Univ Zurich, Inst Med Genet, CH-8001 Zurich, Switzerland Univ Zurich, Childrens Hosp, Div Pediat Neurol, CH-8032 Zurich, Switzerland Univ Florence, Dept Physiopathol, Med Genet Unit, I-500139 Florence, Italy Montreal Gen Hosp, Ctr Res Neurosci, Montreal, PQ H3G 1A4, Canada Univ Hosp Queen Giovanna, Dept Neurosurg, BG-1527 Sofia, Bulgaria Lab Mol Pathol, BG-1431 Sofia, Bulgaria Klinikum Nord Ochsenzoll, Dept Neurol, D-22419 Hamburg, Germany Univ Helsinki, Haartman Inst, Dept Pathol, FIN-00014 Helsinki, Finland House Ear Inst, Los Angeles, CA 90057 USA Karolinska Hosp, Dept Neurosurg, SE-17176 Stockholm, Sweden Sahlgrens Univ Hosp, Dept Audiol, SE-41335 Gothenburg, Sweden Cedars Sinai Med Ctr, Div Neurol, Los Angeles, CA 90048 USA Linkoping Univ Hosp, Dept Otorhinolaryngol, SE-58185 Linkoping, Sweden Univ Oslo, Rikshosp, Dept Med Genet, N-0027 Oslo, Norway Jikei Univ, Sch Med, Dept Dermatol, Minato Ku, Tokyo 1058461, Japan Univ Calif San Francisco, Ctr Canc, Inst Canc Res, San Francisco, CA 94143 USA.
    Pinkel, D
    Univ Uppsala Hosp, Rudbeck Lab, Dept Genet & Pathol, SE-75185 Uppsala, Sweden Karolinska Hosp, Dept Mol Med, SE-17176 Stockholm, Sweden Univ Uppsala Hosp, Dept Otorhinolaryngol & Head & Neck Surg, SE-75185 Uppsala, Sweden Univ Calif San Francisco, Dept Lab Med, Ctr Canc, San Francisco, CA 94143 USA St Marys Hosp, Dept Med Genet, Manchester M13 0JH, Lancs, England INSERM, U434, Lab Genet Tumeurs, F-75010 Paris, France Univ Zurich, Inst Med Genet, CH-8001 Zurich, Switzerland Univ Zurich, Childrens Hosp, Div Pediat Neurol, CH-8032 Zurich, Switzerland Univ Florence, Dept Physiopathol, Med Genet Unit, I-500139 Florence, Italy Montreal Gen Hosp, Ctr Res Neurosci, Montreal, PQ H3G 1A4, Canada Univ Hosp Queen Giovanna, Dept Neurosurg, BG-1527 Sofia, Bulgaria Lab Mol Pathol, BG-1431 Sofia, Bulgaria Klinikum Nord Ochsenzoll, Dept Neurol, D-22419 Hamburg, Germany Univ Helsinki, Haartman Inst, Dept Pathol, FIN-00014 Helsinki, Finland House Ear Inst, Los Angeles, CA 90057 USA Karolinska Hosp, Dept Neurosurg, SE-17176 Stockholm, Sweden Sahlgrens Univ Hosp, Dept Audiol, SE-41335 Gothenburg, Sweden Cedars Sinai Med Ctr, Div Neurol, Los Angeles, CA 90048 USA Linkoping Univ Hosp, Dept Otorhinolaryngol, SE-58185 Linkoping, Sweden Univ Oslo, Rikshosp, Dept Med Genet, N-0027 Oslo, Norway Jikei Univ, Sch Med, Dept Dermatol, Minato Ku, Tokyo 1058461, Japan Univ Calif San Francisco, Ctr Canc, Inst Canc Res, San Francisco, CA 94143 USA.
    Dumanski, JP
    Univ Uppsala Hosp, Rudbeck Lab, Dept Genet & Pathol, SE-75185 Uppsala, Sweden Karolinska Hosp, Dept Mol Med, SE-17176 Stockholm, Sweden Univ Uppsala Hosp, Dept Otorhinolaryngol & Head & Neck Surg, SE-75185 Uppsala, Sweden Univ Calif San Francisco, Dept Lab Med, Ctr Canc, San Francisco, CA 94143 USA St Marys Hosp, Dept Med Genet, Manchester M13 0JH, Lancs, England INSERM, U434, Lab Genet Tumeurs, F-75010 Paris, France Univ Zurich, Inst Med Genet, CH-8001 Zurich, Switzerland Univ Zurich, Childrens Hosp, Div Pediat Neurol, CH-8032 Zurich, Switzerland Univ Florence, Dept Physiopathol, Med Genet Unit, I-500139 Florence, Italy Montreal Gen Hosp, Ctr Res Neurosci, Montreal, PQ H3G 1A4, Canada Univ Hosp Queen Giovanna, Dept Neurosurg, BG-1527 Sofia, Bulgaria Lab Mol Pathol, BG-1431 Sofia, Bulgaria Klinikum Nord Ochsenzoll, Dept Neurol, D-22419 Hamburg, Germany Univ Helsinki, Haartman Inst, Dept Pathol, FIN-00014 Helsinki, Finland House Ear Inst, Los Angeles, CA 90057 USA Karolinska Hosp, Dept Neurosurg, SE-17176 Stockholm, Sweden Sahlgrens Univ Hosp, Dept Audiol, SE-41335 Gothenburg, Sweden Cedars Sinai Med Ctr, Div Neurol, Los Angeles, CA 90048 USA Linkoping Univ Hosp, Dept Otorhinolaryngol, SE-58185 Linkoping, Sweden Univ Oslo, Rikshosp, Dept Med Genet, N-0027 Oslo, Norway Jikei Univ, Sch Med, Dept Dermatol, Minato Ku, Tokyo 1058461, Japan Univ Calif San Francisco, Ctr Canc, Inst Canc Res, San Francisco, CA 94143 USA.
    High resolution deletion analysis of constitutional DNA from neurofibromatosis type 2 (NF2) patients using microarray-CGH2001Ingår i: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 10, nr 3, s. 271-282Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder whose hallmark is bilateral vestibular schwannoma. It displays a pronounced clinical heterogeneity with mild to severe forms. The NF2 tumor suppressor (merlin/schwannomin) has been cloned and extensively analyzed for mutations in patients with different clinical variants of the disease. Correlation between the type of the NF2 gene mutation and the patient phenotype has been suggested to exist. However, several independent studies have shown that a fraction of NF2 patients with various phenotypes have constitutional deletions that partly or entirely remove one copy of the NF2 gene. The purpose of this study was to examine a 7 Mb interval in the vicinity of the NF2 gene in a large series of NF2 patients in order to determine the frequency and extent of deletions. A total of 116 NF2 patients were analyzed using high-resolution array-comparative genomic hybridization (CGH) on an array covering at least 90% of this region of 22q around the NF2 locus. Deletions, which remove one copy of the entire gene or are predicted to truncate the schwannomin protein, were detected in 8 severe, 10 moderate and 6 mild patients. This result does not support the correlation between the type of mutation affecting the NF2 gene and the disease phenotype. This work also demonstrates the general usefulness of the array-CON methodology for rapid and comprehensive detection of small (down to 40 kb) heterozygous and/or homozygous deletions occurring in constitutional or tumor-derived DNA.

  • 27.
    Ceder, Rebecca
    et al.
    Karolinska Institute.
    Haig, Ylva
    Karolinska Institute.
    Merne, Marina
    Karolinska Institute.
    Hansson, Annette
    Karolinska Institute.
    Zheng, Xi
    Karolinska Institute.
    Roberg, Karin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Öron- näsa- och halskliniken US.
    Nees, Matthias
    VTT Technical Research Centre Finland.
    Iljin, Kristiina
    VTT Technical Research Centre Finland.
    Bloor, Balvinder K
    Kings College London.
    Morgan, Peter R
    Kings College London.
    Fadeel, Bengt
    Karolinska Institute.
    Grafstrom, Roland C
    Karolinska Institute.
    Differentiation-Promoting Culture of Competent and Noncompetent Keratinocytes Identifies Biomarkers for Head and Neck Cancer2012Ingår i: American Journal of Pathology, ISSN 0002-9440, E-ISSN 1525-2191, Vol. 180, nr 2, s. 457-472Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aberrant contact-inhibited proliferation and differentiation induction couple with tumor severity, albeit with an imprecise association with prognosis. Assessment of contact inhibition and differentiation-promoting culture in this study of normal and immortalized oral keratinocytes (NOK and SVpgC2a, respectively) demonstrated elevated cloning ability and saturation density in the immortalized versus normal state, including consistent absence of differentiated morphological features. Transcriptomic analysis implicated 48 gene ontology categories, 8 molecular networks, and 10 key regulator genes in confluency-induced differentiation of NOK, all of which remained nonregulated in SVpgC2a. The SVpgC2a versus NOK transcriptome enriched 52 gene ontology categories altogether, 18 molecular networks, and 39 key regulator genes, several of which were associated with epithelial-mesenchymal transition. Assessment of the previously described gene sets relative to training data sets of head and neck squamous cell carcinoma samples, one including data on tumor differentiation and patient outcome and one present in the Human Gene Expression Map, identified four genes with association to poor survival (COX7A1, MFAP5, MPDU1, and POLD1). This gene set predicted poor outcome in an independent data set of 71 head and neck squamous cell carcinomas. The present study defines, for the first time to our knowledge, the broad gene spectrum that couples to induction, and loss, of oral keratinocyte differentiation. Bioinformatics assessments of the results relative to clinical data generated novel differentiation-related tumor biomarkers relevant to patient outcome.

  • 28.
    Cederbrant, Karin
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Patologi. Linköpings universitet, Hälsouniversitetet.
    Hultman, Per
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Patologi. Linköpings universitet, Hälsouniversitetet.
    Marcusson, Jan A.
    Department of Dermatology, Huddinge Hospital, Huddinge.
    Tibbling, Lita
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet.
    In vitro Lymphocyte Proliferation as Compared to Patch Test Using Gold, Palladium and Nickel1997Ingår i: International Archives of Allergy and Immunology, ISSN 1018-2438, E-ISSN 1423-0097, Vol. 112, nr 3, s. 212-217Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: A conventional lymphocyte transformation test (LTT) was compared to the commercially available MELISA® (memory lymphocyte immuno-stimulation assay), a lymphoproliferative assay that has been suggested to be a valuable instrument for the diagnosis of metal allergy. Sensitivity and specificity of the two assays were calculated using a patch test as a reference method.

    Methods: 34 patients were patch-tested for gold sodium thiosulfate, palladium chloride and nickel sulfate, and the lymphocyte proliferation to these metals was tested in vitro using mononuclear cells from peripheral blood.

    Results: No significant differences regarding sensitivity and specificity were found between MELISA and conventional LTT. The sensitivity varied between 55 and 95% and the specificity between 17 and 79%.

    Conclusions: The low specificity of the two in vitro assays suggests that they are not useful for diagnosis of contact allergy to the metals gold, palladium and nickel, since a large number of false-positive results will be obtained.

  • 29.
    Dahlman, Joakim
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Rehabiliteringsmedicin. Linköpings universitet, Hälsouniversitetet.
    Sjörs, Anna
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Rehabiliteringsmedicin. Linköpings universitet, Hälsouniversitetet.
    Ledin, Torbjörn
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Rekonstruktionscentrum, Öronkliniken US.
    Falkmer, Torbjörn
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Rehabiliteringsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Habiliteringen: Barn- och ungdomshabiliteringen, LSS Råd och stöd.
    Could sound be used as a strategy for reducing symptoms of perceived motion sickness?2008Ingår i: Journal of NeuroEngineering and Rehabilitation, ISSN 1743-0003, E-ISSN 1743-0003, Vol. 5, nr 35Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Working while exposed to motions, physically and psychologically affects a person. Traditionally, motion sickness symptom reduction has implied use of medication, which can lead to detrimental effects on performance. Non-pharmaceutical strategies, in turn, often require cognitive and perceptual attention. Hence, for people working in high demand environments where it is impossible to reallocate focus of attention, other strategies are called upon. The aim of the study was to investigate possible impact of a mitigation strategy on perceived motion sickness and psychophysiological responses, based on an artificial sound horizon compared with a non-positioned sound source.

    Method: Twenty-three healthy subjects were seated on a motion platform in an artificial sound horizon or in non-positioned sound, in random order with one week interval between the trials. Perceived motion sickness (Mal), maximum duration of exposure (ST), skin conductance, blood volume pulse, temperature, respiration rate, eye movements and heart rate were measured continuously throughout the trials.

    Results: Mal scores increased over time in both sound conditions, but the artificial sound horizon, applied as a mitigation strategy for perceived motion sickness, showed no significant effect on Mal scores or ST. The number of fixations increased with time in the non-positioned sound condition. Moreover, fixation time was longer in the nonpositioned sound condition compared with sound horizon, indicating that the subjects used more time to fixate and, hence, assumingly made fewer saccades.

    Conclusion: A subliminally presented artificial sound horizon did not significantly affect perceived motion sickness, psychophysiological variables or the time the subjects endured the motion sickness triggering stimuli. The number of fixations and fixation times increased over time in the non-positioned sound condition.

  • 30.
    Dahlman, Joakim
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Rehabiliteringsmedicin. Linköpings universitet, Hälsouniversitetet.
    Sjörs, Anna
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Rehabiliteringsmedicin. Linköpings universitet, Hälsouniversitetet.
    Lindström, Johan
    Östergötlands Läns Landsting, Rekonstruktionscentrum, Öronkliniken US.
    Ledin, Torbjörn
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Rekonstruktionscentrum, Öronkliniken US.
    Falkmer, Torbjörn
    Jönköping University, Jönköping Sweden.
    Performance and Autonomic Responses during Motion Sickness2009Ingår i: Human Factors, ISSN 0018-7208, E-ISSN 1547-8181, Vol. 51, nr 1, s. 56-66Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: The aim of the study was to investigate how motion sickness, triggered by an optokinetic drum, affects short term memory performance and to explore autonomic responses to perceived motion sickness.

    Background: Previous research has found motion sickness to decrease performance, but it is not known how short term memory in particular is affected.

    Method: Thirty-eight healthy participants performed a listening span test while seated in a rotating optokinetic drum. Measurements of motion sickness, performance, heart rate, skin conductance, blood volume pulse, and pupil size were performed simultaneously throughout the experiment.

    Results: A total of 16 participants terminated the trial due to severe nausea, while the other 22 endured the full 25 minutes. Perceived motion sickness increased over time in both groups, but less among those who endured the trial. Short term memory performance decreased towards the end for those who terminated, while it increased for the other group. Results from the measured autonomic responses were ambiguous.

    Conclusion: The present study concludes that performance, measured as short term memory, declines as perceived motion sickness progresses.

    Application: This research has potential implications for command and control personnel in risk of developing motion sickness.

  • 31.
    Dahlman, Joakim
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Rehabiliteringsmedicin. Linköpings universitet, Hälsouniversitetet.
    Sjörs, Anna
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Rehabiliteringsmedicin. Linköpings universitet, Hälsouniversitetet.
    Lundgren, Pontus
    Östergötlands Läns Landsting, Rekonstruktionscentrum, Rehabiliteringsmedicinska kliniken US.
    Ledin, Torbjörn
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Rekonstruktionscentrum, Öronkliniken US.
    Falkmer, Torbjörn
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Rehabiliteringsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Habiliteringen: Barn- och ungdomshabiliteringen, LSS Råd och stöd.
    Effects of Motion Sickness on Encoding and Retrieval2010Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: In this study, possible effects of motion sickness on encoding and retrieval of words were investigated.

    Background: The impact of motion sickness on human performance has been studied with regards to psychomotor functions and over learned skills, as well as to novel situations requiring encoding and retrieval skills through the use of short term memory. In this study, possible effects of motion sickness on encoding and retrieval of words were investigated.

    Method: Forty healthy participants, half of them males, performed a continuous recognition task (CRT) during exposure to a motion sickness triggering optokinetic drum. The CRT was employed as a measurement of performance and consisted of encoding and retrieval of words. The task consisted of three consecutive phases 1) encoding of familiar words; 2) encoding and retrieval of words under the influence of motion sickness; 3) retrieval of words after exposure.

    Results: Data analysis revealed no significant differences in the ability to encode or retrieve words during motion sickness compared with a control condition. In addition, there were no significant correlations between the level of motion sickness and performance of the CRT.

    Conclusion: The results indicate that encoding and retrieval of words are not affected by moderate levels of motion sickness. Application: This research has implications for operational settings where professionals experience moderate levels of motion sickness.

  • 32.
    Ericsson, Elisabeth
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Rekonstruktionscentrum, Öronkliniken US.
    Health and well-being of children and young adults in relation to surgery of the tonsils2007Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Tonsillectomy is one of the most frequently performed surgical procedures in children and youths. The aim of this thesis was to study children and youths in relation to tonsil surgery with the goal of improving the care, and to describe partial tonsillectomy/tonsillotomy (TT) using radiofrequency technique (RF) (Ellman International) in comparison with the more commonly used total tonsillectomy (TE).

    The thesis covers studies of wo age-groups with obstructive problems, with or without recurrent tonsillitis. Randomization to surgery was done from the existing waiting list; 92 children, 5-15 years old to 49/TT and 43/TE, (I-III) and 76 youths, 16-25 years old to 32/TT and 44/TE (IV-V).

    The first purpose (I, IV) was to compare the two surgical techniques with respect to pain and postoperative morbidity. Pain measures were for the children the Face Pain Scale and for the youths and parents and staff a verbal-pain-rating-scale. From the first day, the TT-groups scored significantly less pain than the TE-groups. The doses of pain-killing drugs (paracetamol and diclofenac) taken were significantly less for the children and youths receiving the TT-surgery, they could stop taking pain-killers sooner, and were back to normal activity three (5-15yrs) or four (16-25yrs) days earlier compared with TE-groups.

    Paper II focused on the child’s behavior (Child Behavior Checklist/CBCL), experience of pain, anxiety (State-Trait-Anxiety Inventory for Children /STAIC), previous experiences of surgery/tonsillitis, and the management of pain. The children scored higher on CBCL than a normative group before surgery, but no connection was observed between CBCL rating and experience of pain reported post surgically. There was no relation between preoperative anxiety and reported pain, but the postoperative anxiety level correlated with pain. The Egroup scored higher anxiety after surgery. Previous experience of surgery or tonsillitis did not influence the postoperative pain. The nurses scored pain lower than the parents/children and under-medicated.

    The second purpose was to compare the long-term effects of TT and TE-surgery after one and three years (5-15yrs) and one year (16-25yrs) (III, IV). The effect on snoring was the same for both TT and TE-groups and the rate of recurrence of throat infections was low after both surgical techniques.

    After one year, all children (TT/TE) showed improvements on CBCL to the same degree and there was no longer a difference between total behavior and normative values. They also scored improvements in health-related quality of life (HRQL) with Glasgow-Children-Benefit-Inventory.

    For both TT and TE, the older group reported lower HRQL preoperatively on all dimensions of Study-Short-Form (SF-36) compared with a normal population. After one year, a large improvement was found in HRQL in both groups and there were no differences compared with a normal population.

    Conclusion: Preoperative obstructive problems, in combination with recurrent tonsillitis have a negative impact on HRQL. Both after TE and TT there are large improvements in HRQL, infections, obstructive, and behavior problems one to three years after surgery, indicating that both surgical methods are equally effective. With fewer postoperative complications, less pain, shorter recovery time, and lower cost, TT with RF should be considered as method of choice.

    Delarbeten
    1. Pediatric Tonsillotomy with Radiofrequency Technique: Less Morbidity and Pain
    Öppna denna publikation i ny flik eller fönster >>Pediatric Tonsillotomy with Radiofrequency Technique: Less Morbidity and Pain
    2004 (Engelska)Ingår i: The Laryngoscope, ISSN 0023-852X, Vol. 114, nr 5, s. 871-877Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    OBJECTIVE: To compare two techniques for pediatric tonsil surgery with respect to pain and postoperative morbidity. The two methods were the partial tonsil resection using radiofrequency (RF) technique (tonsillotomy [TT]) versus traditional tonsillectomy (TE).

    STUDY DESIGN: Prospective clinical randomized study in one tertiary care ENT clinic and two secondary care clinics.

    METHOD: One hundred fifty children, between 5 and 15 years of age, were randomized to either TT with RF using the Surgitron Ellman, 1.7 MHz, or regular TE. Randomization was performed from the waiting list, including children with both a history of obstructive problems and recurrent tonsillitis. The TT was performed with a specially made sling electrode using a cut/coagulation mode.

    RESULTS: Forty-nine children were operated on with TT and 43 with TE. There was significantly less bleeding in the TT group, although two cases of primary postoperative bleeding occurred among the TT children and one in the TE group. The pain recordings showed significantly less pain for the TT children from the second hour postoperatively onward, and the TT children were pain free and in school 3 days earlier than the TE group. The TT group had less need of the prescribed drugs (diclofenac and paracetamol). After 9 days, 73% of the TT children were completely healed, but only 31% of the TE children. By that time, the TE children had lost a mean of 660 g, and the TT children had gained 127 g. The effect on snoring was the same for both groups.

    CONCLUSION: RF appears to be a safe and reliable method for tonsil surgery with much less postoperative morbidity than regular TE.

    Nyckelord
    Tonsils, tonsil surgery, RF surgery, snoring, sleep apnea
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-14510 (URN)10.1097/00005537-200405000-00016 (DOI)
    Tillgänglig från: 2007-05-21 Skapad: 2007-05-21 Senast uppdaterad: 2009-05-19
    2. Pre-surgical Child Behavior Ratings and Pain Management after Two Different Techniques of Tonsil Surger
    Öppna denna publikation i ny flik eller fönster >>Pre-surgical Child Behavior Ratings and Pain Management after Two Different Techniques of Tonsil Surger
    2006 (Engelska)Ingår i: International Journal of Pediatric Otorhinolaryngology, ISSN 0165-5876, E-ISSN 1872-8464, Vol. 70, nr 10, s. 1749-1758Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Objective

    The purpose of this investigation was to compare child behavior before surgery with experience of pain and anxiety in relation to two techniques of tonsil surgery, to relate previous experiences of surgery/tonsillitis with anxiety and pain, and to compare the children's, parent's and nurse's rating of pain.

    Method

    Ninety-two children (5–15 years) with sleep-disordered breathing (SDB) and with or without recurrent tonsillitis were randomized to partial tonsil resection/tonsillotomy (TT) or full tonsillectomy (TE). Measures: Parents: Child Behavior Checklist (CBCL). Children: State-Trait-Anxiety Inventory for Children (STAIC) and seven-point Faces Pain Scale (FPS). Parents/staff: seven-point Verbal Pain Rating Scale (VPRS). Pain relievers were opoids, paracetamol and diclophenac.

    Results

    These children with SDB scored significantly higher on CBCL than did normative groups, but no connection was observed between CBCL rating and experience of pain. There was no relation between pre-operative anxiety and pain. The post-operative anxiety level (STAIC) correlated with pain. The TE-group scored higher on STAIC after surgery. Previous experience of surgery or tonsillitis did not influence post-operative pain. The TE-group rated higher experience of pain despite more medication. The nurses scored pain lower than the parents/children and under-medicated.

    Conclusion

    SDB may influence children's behavior, but with no relation to post-operative pain. The surgical method predicts pain better than does the child's behavior rating. The nurses underestimated the pain experienced by the child.

    Nyckelord
    Children; Post-operative pain; Anxiety; Behavior; Tonsil surgery; Anesthesia
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-14511 (URN)10.1016/j.ijporl.2006.05.017 (DOI)
    Tillgänglig från: 2007-05-21 Skapad: 2007-05-21 Senast uppdaterad: 2017-12-13
    3. Pediatric Tonsillotomy with the Radiofrequency Technique – Long-term Follow-up
    Öppna denna publikation i ny flik eller fönster >>Pediatric Tonsillotomy with the Radiofrequency Technique – Long-term Follow-up
    2006 (Engelska)Ingår i: The Laryngoscope, ISSN 0023-852X, E-ISSN 1531-4995, Vol. 116, nr 10, s. 1851-1857Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Objectives: Compare the effects of partial tonsil resection using a radiofrequency technique, tonsillotomy (TT), with total tonsillectomy (TE, blunt dissection) after 1 and 3 years. Compare frequency of relapse in snoring or infections and possible long-term changes in behavior among TT children with those in TE children.

    Method: Ninety-two children (5-15 yr) randomized to TT (n = 49) or TE (n = 43) groups because of obstructive problems with or without recurrent tonsillitis. One year after surgery, general health, degree of obstruction, history of infections, and behavior were investigated using two questionnaires, the Qu1 and Child Behavior Checklist, as well as an ENT visit. After 3 years, two questionnaires, Qu2 and the Glasgow Children's Benefit Inventory, were answered by mail.

    Results: After 1 year, both groups were in good health. The effect on snoring and total behavior was the same for both groups, and the rate of recurrence of infections was not higher in the TT group. After 3 years, two children in the TT group were tonsillectomized (4%, 2/49), one because of peritonsillitis and another because of increased snoring. Otherwise, no differences existed between the groups in general health, snoring, or number of infections.

    Conclusion: Removing only the protruding parts of the tonsils has the same beneficial long-term effect on obstructive symptoms and recurrent throat infections as complete TE in the majority of cases. The need for re-operation is low; therefore, it appears inadvisable to follow the current common practice of routinely removing the whole tonsil given its higher morbidity and risk for serious complications.

    Nyckelord
    Tonsil surgery, tonsillotomy, snoring, behavior, reduced morbidity, immunology, long-term follow-up
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-14512 (URN)10.1097/01.mlg.0000234941.95636.e6 (DOI)
    Tillgänglig från: 2007-05-21 Skapad: 2007-05-21 Senast uppdaterad: 2017-12-13
    4. Tonsil Surgery in Youths – Good Results with Less Invasive Method
    Öppna denna publikation i ny flik eller fönster >>Tonsil Surgery in Youths – Good Results with Less Invasive Method
    2007 (Engelska)Ingår i: The Laryngoscope, ISSN 0023-852X, E-ISSN 1531-4995, Vol. 117, nr 4, s. 654-661Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Objective: Comparison of two types of tonsil surgery for 16- to 25-year-old patients, with respect to primary morbidity, snoring, and recurrent infections after 1 year. Teenagers and young adults are a significant proportion (26%) of the population that receive tonsil surgery each year and appear to suffer more pain than younger children. Recurrent tonsillitis, in combination with obstructive problems, is the main indication for surgery.

    Method: One hundred fourteen patients 16 to 25 years of age were randomized to tonsillotomy (TT) with radiosurgery (RF) (Ellman International) or to cold tonsillectomy (TE). Pain and analgesics were logged until patients were pain free.

    Results: Thirty-two patients were operated on with TT and 44 with TE. The TT group had less blood loss during surgery and no postoperative bleedings, compared with the TE group (2 primary and 4 late hemorrhages). The TT group recorded significantly less pain from the first day, had less need of analgesics (diclofenac and paracetamol), and were pain free and in school/at work 4 days earlier than the TE group. After 7 days, the TE patients had lost a mean of 1.8 kg compared with TT, with no significant weight loss. After 1 year, both groups were satisfied. The positive effect on snoring was the same for both groups. There were few throat infections in both groups.

    Conclusion: TT with RF is an effective method for tonsil surgery for many teenagers and young adults, with much less postoperative morbidity than regular TE. Long-term follow-up is necessary.

    Nyckelord
    Tonsillotomy, tonsillectomy, radiofrequency surgery, postoperative pain, snoring, recurrent tonsillitis
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-14513 (URN)10.1097/mlg.0b013e318030ca69 (DOI)
    Tillgänglig från: 2007-05-21 Skapad: 2007-05-21 Senast uppdaterad: 2017-12-13
    5. Long-Term Improvement of Quality of Life as a Result of Tonsillotomy (With Radiofrequency Technique) and Tonsillectomy in Youths
    Öppna denna publikation i ny flik eller fönster >>Long-Term Improvement of Quality of Life as a Result of Tonsillotomy (With Radiofrequency Technique) and Tonsillectomy in Youths
    2007 (Engelska)Ingår i: The Laryngoscope, ISSN 0023-852X, E-ISSN 1531-4995, Vol. 117, nr 7, s. 1272-1279Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Objective: This is a 1 year follow-up to compare the effects of partial tonsil resection using the radiofrequency technique (RF) tonsillotomy (TT) with total tonsillectomy (TE) (blunt dissection). Obstructive symptoms, tendency for infections, and health-related quality of life (HRQL) were studied and compared with the HRQL data from a normal population.

    Method: The study group consisted of 74 patients (16-25 yr old) randomized to TT (n = 31) or TE (n = 43) with obstructive throat problems with or without recurrent tonsillitis. The Short Form 36 (SF-36) and EuroQul Visual Analogue Scale were used to evaluate HRQL. A questionnaire investigated the degree of obstruction and history of infections.

    Results: Preoperatively, both groups reported significantly lower HRQL in all dimensions of the SF-36 compared with the normal population (P < .05-P < .001). After 1 year, a large improvement (P < .01-P < .001) in both groups in HRQL was found. No differences were found when these groups were compared with the normal population or between the study groups. The effect on snoring was the same for both groups, and the rate of recurrence of infections was low and not any higher in the TT group.

    Conclusion: Preoperative obstructive problems in combination with recurrent tonsillitis have a negative impact on HRQL. Both the TT and TE groups demonstrated large improvements on HRQL, infections, and obstructive problems 1 year after surgery, indicating that the surgical methods are equally effective. With its reduced postoperative complications, less pain, shorter recovery time, and cost reduction, TT with RF should be considered the method of choice.

    Nyckelord
    tonsillotomy, tonsillectomy, health-related quality of life, Short Form 36, snoring, recurrent tonsillitis
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-14514 (URN)10.1097/MLG.0b013e31805559e1 (DOI)
    Tillgänglig från: 2007-05-21 Skapad: 2007-05-21 Senast uppdaterad: 2017-12-13
  • 33.
    Ericsson, Elisabeth
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet.
    Graf, Jonas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet.
    Hultcrantz, Elisabeth
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet.
    Pediatric Tonsillotomy with the Radiofrequency Technique – Long-term Follow-up2006Ingår i: The Laryngoscope, ISSN 0023-852X, E-ISSN 1531-4995, Vol. 116, nr 10, s. 1851-1857Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: Compare the effects of partial tonsil resection using a radiofrequency technique, tonsillotomy (TT), with total tonsillectomy (TE, blunt dissection) after 1 and 3 years. Compare frequency of relapse in snoring or infections and possible long-term changes in behavior among TT children with those in TE children.

    Method: Ninety-two children (5-15 yr) randomized to TT (n = 49) or TE (n = 43) groups because of obstructive problems with or without recurrent tonsillitis. One year after surgery, general health, degree of obstruction, history of infections, and behavior were investigated using two questionnaires, the Qu1 and Child Behavior Checklist, as well as an ENT visit. After 3 years, two questionnaires, Qu2 and the Glasgow Children's Benefit Inventory, were answered by mail.

    Results: After 1 year, both groups were in good health. The effect on snoring and total behavior was the same for both groups, and the rate of recurrence of infections was not higher in the TT group. After 3 years, two children in the TT group were tonsillectomized (4%, 2/49), one because of peritonsillitis and another because of increased snoring. Otherwise, no differences existed between the groups in general health, snoring, or number of infections.

    Conclusion: Removing only the protruding parts of the tonsils has the same beneficial long-term effect on obstructive symptoms and recurrent throat infections as complete TE in the majority of cases. The need for re-operation is low; therefore, it appears inadvisable to follow the current common practice of routinely removing the whole tonsil given its higher morbidity and risk for serious complications.

  • 34.
    Ericsson, Elisabeth
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Omvårdnad. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Öron- näsa- och halskliniken US.
    Hemlin, Claes
    Aleris Sabbatsberg Hospital, Stockholm.
    Hessén Söderman, Anne- Charlotte
    Karolinska University Hospital.
    Hultcrantz, Elisabeth
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Öron- näsa- och halskliniken US.
    Roos, Kristian
    Lundby Hospital, Göteborg.
    Sunnergren, Ola
    County Hospital Ryhov, Jönköping.
    Stalfors, Joacim
    Sahlgrenska University Hospital, Göteborg.
    Webb-based information for tonsillar surgery2012Konferensbidrag (Övrigt vetenskapligt)
  • 35.
    Ericsson, Elisabeth
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Rekonstruktionscentrum, Öronkliniken US.
    Hultcrantz, Elisabeth
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Rekonstruktionscentrum, Öronkliniken US.
    Tonsil Surgery in Youths – Good Results with Less Invasive Method2007Ingår i: The Laryngoscope, ISSN 0023-852X, E-ISSN 1531-4995, Vol. 117, nr 4, s. 654-661Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Comparison of two types of tonsil surgery for 16- to 25-year-old patients, with respect to primary morbidity, snoring, and recurrent infections after 1 year. Teenagers and young adults are a significant proportion (26%) of the population that receive tonsil surgery each year and appear to suffer more pain than younger children. Recurrent tonsillitis, in combination with obstructive problems, is the main indication for surgery.

    Method: One hundred fourteen patients 16 to 25 years of age were randomized to tonsillotomy (TT) with radiosurgery (RF) (Ellman International) or to cold tonsillectomy (TE). Pain and analgesics were logged until patients were pain free.

    Results: Thirty-two patients were operated on with TT and 44 with TE. The TT group had less blood loss during surgery and no postoperative bleedings, compared with the TE group (2 primary and 4 late hemorrhages). The TT group recorded significantly less pain from the first day, had less need of analgesics (diclofenac and paracetamol), and were pain free and in school/at work 4 days earlier than the TE group. After 7 days, the TE patients had lost a mean of 1.8 kg compared with TT, with no significant weight loss. After 1 year, both groups were satisfied. The positive effect on snoring was the same for both groups. There were few throat infections in both groups.

    Conclusion: TT with RF is an effective method for tonsil surgery for many teenagers and young adults, with much less postoperative morbidity than regular TE. Long-term follow-up is necessary.

  • 36.
    Ericsson, Elisabeth
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Omvårdnad. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Anestesi- och operationkliniken US.
    Hultcrantz, Elisabeth
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Öron- näsa- och halskliniken US.
    Tonsil Surgery in Youths: Good Results With A Less Invasive Method2011Konferensbidrag (Refereegranskat)
  • 37.
    Ericsson, Elisabeth
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Rekonstruktionscentrum, Öronkliniken US.
    Ledin, Torbjörn
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Rekonstruktionscentrum, Öronkliniken US.
    Hultcrantz, Elisabeth
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Rekonstruktionscentrum, Öronkliniken US.
    Long-Term Improvement of Quality of Life as a Result of Tonsillotomy (With Radiofrequency Technique) and Tonsillectomy in Youths2007Ingår i: The Laryngoscope, ISSN 0023-852X, E-ISSN 1531-4995, Vol. 117, nr 7, s. 1272-1279Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: This is a 1 year follow-up to compare the effects of partial tonsil resection using the radiofrequency technique (RF) tonsillotomy (TT) with total tonsillectomy (TE) (blunt dissection). Obstructive symptoms, tendency for infections, and health-related quality of life (HRQL) were studied and compared with the HRQL data from a normal population.

    Method: The study group consisted of 74 patients (16-25 yr old) randomized to TT (n = 31) or TE (n = 43) with obstructive throat problems with or without recurrent tonsillitis. The Short Form 36 (SF-36) and EuroQul Visual Analogue Scale were used to evaluate HRQL. A questionnaire investigated the degree of obstruction and history of infections.

    Results: Preoperatively, both groups reported significantly lower HRQL in all dimensions of the SF-36 compared with the normal population (P < .05-P < .001). After 1 year, a large improvement (P < .01-P < .001) in both groups in HRQL was found. No differences were found when these groups were compared with the normal population or between the study groups. The effect on snoring was the same for both groups, and the rate of recurrence of infections was low and not any higher in the TT group.

    Conclusion: Preoperative obstructive problems in combination with recurrent tonsillitis have a negative impact on HRQL. Both the TT and TE groups demonstrated large improvements on HRQL, infections, and obstructive problems 1 year after surgery, indicating that the surgical methods are equally effective. With its reduced postoperative complications, less pain, shorter recovery time, and cost reduction, TT with RF should be considered the method of choice.

  • 38.
    Ericsson, Elisabeth
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Rekonstruktionscentrum, Öronkliniken US.
    Lundeborg, Inger
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Logopedi. Linköpings universitet, Hälsouniversitetet.
    Hultcrantz, Elisabeth
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Rekonstruktionscentrum, Öronkliniken US.
    Child behavior and quality of life before and after tonsillotomy versus tonsillectomy2009Ingår i: International Journal of Pediatric Otorhinolaryngology, ISSN 0165-5876, E-ISSN 1872-8464, Vol. 73, nr 9, s. 1254-1262Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: Compare two techniques for pediatric tonsil surgery with respect to postoperative pain and morbidity and changes in sleep behavior, health related quality of life (HRQL) and benefits due to surgery. Methods: 67 children (4.5-5.5 years) with tonsillar hypertrophy and obstructive sleep-disordered breathing with or without recurrent tonsillitis were randomized to either regular tonsillectomy (TE) (n = 32) or intracapsular tonsillectomy/tonsillotomy (TT) (n = 35) with Radiofrequency surgical technique (ellman Int.). Before TT/TE, the parents completed a validated Quality of Life survey of pediatric obstructive sleep apnea, the OSA-18 (Obstructive Sleep Apnea-18) and a standardized assessment of their childrens behavior with the Child Behavior Checklist (CBCL). Six months after surgery, the parents repeated these measurements, and assessed the health related benefits of the surgery using the Glasgow Childrens Benefit Inventory (GCBI). Results: In the TT group, the children recorded less pain from the first day after surgery onwards, used fewer doses of painkillers and were pain-free 3 days earlier than the children in the TE group. Six months after surgery, there were no significant difference between TT and TE with regard to snoring and ENT-infections. The differences in the total scores and in all the individual domains between the initial OSA-18 and post-surgery scores were all significant (P andlt; 0.0001). The improvement in the total problem score measured with CBCL was also significant (P andlt; 0.01) and there was no difference between the TT and TE children. The improvements in all subscores of the GCBI indicated a significant health benefit of both TT and TE. Conclusions: TT with RF-surgery causes less pain and postoperative morbidity than regular TE and has an equal effect on snoring and recurrent infections. Pre-school children with tonsillar hypertrophy and obstructive sleep-disordered breathing all show an impact on HRQL and behavior before surgery and improve dramatically just as much after TT as after TE. Therefore TT would be considered for treatment of small children.

  • 39.
    Ericsson, Elisabeth
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Östergötlands Läns Landsting, Rekonstruktionscentrum, Öronkliniken US.
    LundeborgHammarström, Inger
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Logopedi.
    Graf, Jonas
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi.
    McAllister, Anita
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Logopedi. Östergötlands Läns Landsting, Rekonstruktionscentrum, Öronkliniken US.
    Hultcrantz, Elisabeth
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Östergötlands Läns Landsting, Rekonstruktionscentrum, Öronkliniken US.
    Child behavior and quality of life before and after tonsillotomy versus tonsillectomy2008Ingår i: International conference in pediatric otorhinolaryngology,2008, 2008, s. 40-40Konferensbidrag (Övrigt vetenskapligt)
    Abstract [en]

    Introduction: The objective of the present investigation was to compare two techniques for pediatric tonsil surgery with respect to postoperative pain and morbidity and changes in sleep behavior, health related quality of life (HRQL) and benefit due to surgery. Methods: 67 children (4,5-5,5 years) with tonsillar hypertrophy and obstructive sleep related distress with or without recurrent tonsillitis were randomized to either regular tonsillectomy (TE)(n=32) or intracapsular tonsillectomy/tonsillotomy (TT) (n=35) with Radiofrequency surgical technique (Ellman Int) Before TT/TE, the parents completed a validated Quality of Life survey of pediatric obstructive sleep apnea, the OSA18 (Obstructive Sleep Apnea-18) and a standardized assessment of their children-s behavior with the Child Behavior Checklist (CBCL). Six months after surgery, the parents repeated these measurements, and assessed the health related benefits of the surgery using the Glasgow Children´s Benefit Inventory (GCBI). Results: In the TT group, the children recorded less pain from the first day after surgery onwards, used fewer doses of painkillers and were pain-free 3 days earlier than the children in the TE group. Six months after surgery, there was no significant difference between TT and TE with regard to snoring and ENT-infections. The differences were all significant in the total scores and in all the individual domains between the initial OSA-18 and post-surgery scores (p<0.0001). The improvement in the total problem score measured with CBCL was also significant (p<0.01) and there were no differences between the TT and TE children. The improvements in all sub scores of the GCBI indicated a significant health benefit of both TT and TE. Conclusions: TT with RF-surgery is a safe method, which causes less pain and postoperative morbidity than regular TE and has a similar effect on snoring and recurrent infections. Young children with tonsillar hypertrophy and different degrees of obstructive sleep related distress all show an impact on HRQL and behavior. All improve dramatically after a tonsillar operation-improving just as much after TT as after TE. Based on these results, TT should be the first choice for treatment of these small children. Support: Financial support from the Research Council of South East Sweden (FORSS).

  • 40.
    Ericsson, Elisabeth
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet.
    Wadsby, Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Barn- och ungdomspsykiatri. Linköpings universitet, Hälsouniversitetet.
    Hultcrantz, Elisabeth
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet.
    Pre-surgical Child Behavior Ratings and Pain Management after Two Different Techniques of Tonsil Surger2006Ingår i: International Journal of Pediatric Otorhinolaryngology, ISSN 0165-5876, E-ISSN 1872-8464, Vol. 70, nr 10, s. 1749-1758Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective

    The purpose of this investigation was to compare child behavior before surgery with experience of pain and anxiety in relation to two techniques of tonsil surgery, to relate previous experiences of surgery/tonsillitis with anxiety and pain, and to compare the children's, parent's and nurse's rating of pain.

    Method

    Ninety-two children (5–15 years) with sleep-disordered breathing (SDB) and with or without recurrent tonsillitis were randomized to partial tonsil resection/tonsillotomy (TT) or full tonsillectomy (TE). Measures: Parents: Child Behavior Checklist (CBCL). Children: State-Trait-Anxiety Inventory for Children (STAIC) and seven-point Faces Pain Scale (FPS). Parents/staff: seven-point Verbal Pain Rating Scale (VPRS). Pain relievers were opoids, paracetamol and diclophenac.

    Results

    These children with SDB scored significantly higher on CBCL than did normative groups, but no connection was observed between CBCL rating and experience of pain. There was no relation between pre-operative anxiety and pain. The post-operative anxiety level (STAIC) correlated with pain. The TE-group scored higher on STAIC after surgery. Previous experience of surgery or tonsillitis did not influence post-operative pain. The TE-group rated higher experience of pain despite more medication. The nurses scored pain lower than the parents/children and under-medicated.

    Conclusion

    SDB may influence children's behavior, but with no relation to post-operative pain. The surgical method predicts pain better than does the child's behavior rating. The nurses underestimated the pain experienced by the child.

  • 41.
    Eriksson, Ida
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Experimentell patologi. Linköpings universitet, Hälsouniversitetet.
    Joosten, M.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Experimentell patologi. Linköpings universitet, Hälsouniversitetet.
    Roberg, Karin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Öron- näsa- och halskliniken US.
    Öllinger, Karin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Experimentell patologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    The histone deacetylase inhibitor trichostatin A reduces lysosomal pH and enhances cisplatin-induced apoptosis2013Ingår i: Experimental Cell Research, ISSN 0014-4827, E-ISSN 1090-2422, Vol. 319, nr 1, s. 12-20Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    High activity of histone deacetylases (HDACs) has been documented in several types of cancer and may be associated with survival advantage. In a head and neck squamous cell carcinoma cell line, cisplatin-induced apoptosis was augmented by pretreatment with the HDAC inhibitor trichostatin Apoptosis was accompanied by lysosomal membrane permeabilization (LMP), as shown by immunoblotting of the lysosomal marker protease cathepsin B in extracted cytosol and by immunofluorescence. Moreover, LAMP-2 (lysosomal associated membrane protein-2) was translocated from lysosomal membranes and found in a digitonin extractable fraction together with cytosolic proteins and pretreatment with trichostatin A potentiated the release. Overall, protein level of LAMP-2 was decreased during cell death and, interestingly, inhibition of cysteine cathepsins, by the pan-cysteine cathepsin inhibitor zFA-FMK, prevented loss of LAMP-2. The importance of LAMP-2 for lysosomal membrane stability, was confirmed by showing that LAMP-2 knockout MEFs (mouse embryonic fibroblasts) were more sensitive to cisplatin as compared to the corresponding wildtype cells. Trichostatin A reduced lysosomal pH from 4.46 to 4.25 and cell death was prevented when lysosomal pH was increased by NH4Cl, or when inhibiting the activity of lysosomal proteases. We conclude that trichostatin A enhances cisplatin induced cell death by decreasing lysosomal pH, which augments cathepsin activity resulting in reduced LAMP-2 level, and might promote LMP.

  • 42.
    Farnebo, Lovisa
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Rekonstruktionscentrum, Öronkliniken US.
    Predictive markers: for treatment sensitivity in head and neck squamous cell carcinoma2010Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Head and neck cancer is the sixth most common cancer world wide. In Sweden approximately 850 new cases are diagnosed each year, and two thirds are men. The past decades of improved treatment strategies have unfortunately not significantly improved the five-year survival rates for this group of patients. Therefore, it is important to rapidly find combinations of new and strong predictive markers for treatment response. Different predictive markers have been investigated for decades, without succeeding in finding means to securely predict response to treatment. Models to combine markers are called for.

    The aim of this thesis was to test multiple predictive markers on both gene and protein level to evaluate their predictive value for radiotherapy and cisplatin response. Furthermore, to combine, and correlate them to treatment response in order to extract the panel of markers that strongest correlated to the investigated treatment. Cell lines derived from 42 patients with head and neck squamous cell carcinoma (HNSCC) were used for protein quantification with Western blot and ELISA of the proteins survivin, Epidermal Growth Factor Receptor, Bcl-2, Bcl-XL, Bax, Bad, Bak, PUMA, Heat shock protein 70, MDM2, p53, SMAD4, Cyclooxygenase-2, and Cyclin D1. The expression of the selected proteins was related to the mean expression of normal oral keratinocytes (NOK) from healthy individuals. Furthermore, mutations in the p53 gene, along with single nucleotide polymorphisms in the genes of p53, MDM2, FGFR4, XRCC1, XRCC3, XPD, and XPC were analysed. To allow a large number of predictive markers on both protein and gene level to be combined and correlated to treatment response, the number of negative points (NNP) model was introduced. Both correlations of sensitivity to radiotherapy and to cisplatin treatment was analysed among the cell lines. In the first paper, including nine cell lines, the panel of EGFR, survivin, and splice site/missense p53 mutations correlated strongest to radioresponse. In paper II, 42 cell lines were used and the combination of survivin, Bcl-2, Bcl-XL, Bax, COX-2, and the p53 Arg72Pro polymorphism was found to most strongly correlate with radioresponse. In paper IV, the panel correlating strongest with cisplatin sensitivity consisted of EGFR, Hsp70, Bax, and Bcl-2 in combination with SNPs in the DNA-repair genes XRCC3 and XPD.

    The predisposition of the FGFR4 Gly388Arg polymorphism for the development of HNSCC was investigated in paper III. DNA was isolated from 110 tumour biopsies, and restriction fragment length polymorphism analysis showed that 58% of the individuals in the control group carried the FGFR4 Arg388 allele, whereas the frequency in the tumour group was 45%. The Gly388 allele gave a significantly higher risk of developing HNSCC, suggesting Gly388 to be the risk allele for cancer development. Furthermore, a novel mutation was found in the FGFR4 gene. The influence of this new mutation is however unknown.

    In conclusion, predictive markers for treatment sensitivity need to be combined to receive an accurate prediction of treatment response.

    Delarbeten
    1. Number of negative points: a novel method for predicting radiosensitivity in head and neck tumor cell lines.
    Öppna denna publikation i ny flik eller fönster >>Number of negative points: a novel method for predicting radiosensitivity in head and neck tumor cell lines.
    Visa övriga...
    2008 (Engelska)Ingår i: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 20, nr 2, s. 453-461Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    The present study was aimed at establishing a method that combines multiple factors of protein and genetic changes that enables prediction of radiosensitivity in the head and neck squamous cell carcinoma (HNSCC) cell lines. In nine HNSCC cell lines, the quantity of protein expression and the type of genetic alterations were translated into a point system, called the Number of Negative Points. The expression of 14 proteins involved in growth control and/or apoptosis was quantified using a densitometric assessment of Western blots. The blots were adjusted to actin and standardised to normal oral keratinocytes classifying them into four groups depending on the amount of protein expressed (0-3 points). Mutations of the p53 gene were classified into three groups and each mutation was given one point. Since the cell lines each had a known intrinsic radiosensitivity, a multivariate statistical calculation could then be performed to select for the combination of factors having the strongest correlation to radiosensitivity. The strongest correlation of the investigated factors was the combination of epidermal growth factor receptor, survivin and splice site/missense p53 mutations (R=0.990 and P<0.0001). No single factor had a significant correlation to the intrinsic radiosensitivity. Since a significant correlation to the intrinsic radiosensitivity was achieved only when two or more factors were combined, we conclude that a method such as the Number of Negative Points is necessary for prediction of treatment response. We present a novel method to combine factors which enables the prediction of radiosensitivity of HNSCC cell lines.

    Nyckelord
    Predictive markers, p53, epidermal growth factor receptor, survivin, squamous cell carcinoma
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-19558 (URN)10.3892/or_00000028 (DOI)18636211 (PubMedID)
    Tillgänglig från: 2009-06-26 Skapad: 2009-06-26 Senast uppdaterad: 2018-09-11Bibliografiskt granskad
    2. Combining factors on protein and gene level to predict radioresponse in head and neck cancer cell lines
    Öppna denna publikation i ny flik eller fönster >>Combining factors on protein and gene level to predict radioresponse in head and neck cancer cell lines
    Visa övriga...
    2011 (Engelska)Ingår i: Journal of Oral Pathology & Medicine, ISSN 0904-2512, E-ISSN 1600-0714, Vol. 40, nr 10, s. 739-746Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    BACKGROUND: Radiotherapy is the main therapy for head and neck squamous cell carcinoma (HNSCC); however, treatment resistance and local recurrence are significant problems, highlighting the need for predictive markers. In this study, we evaluated selected proteins, mutations, and single nucleotide polymorphisms (SNPs) involved in apoptosis, cell proliferation, and DNA repair alone or combined as predictive markers for radioresponse in 42 HNSCC cell lines.

    METHODS: The expression of epidermal growth factor receptor, survivin, Bax, Bcl-2, Bcl-XL, cyclooxygenase-2, and heat shock protein 70 was analyzed by ELISA. Furthermore, mutations and SNPs in the p53 gene as well as SNPs in the MDM2, XRCC1, and XRCC3 genes were analyzed for their relation to radioresponse. To enable the evaluation of the predictive value of several factors combined, each cell line was allocated points based on the number of negative points (NNP) system, and the NNP sum was correlated with radioresponse.

    RESULTS: Survivin was the only factor that alone was significantly correlated with the intrinsic radiosensitivity (r=0.36, p=0.02). The combination of survivin, Bax, Bcl-2, Bcl-XL, cyclooxygenase-2, and the p53 Arg72Pro polymorphism was found to most strongly correlate with radioresponse (r=0.553, p<0.001).

    CONCLUSION: These data indicate that the intrinsic radiosensitivity of 42 HNSCC cell lines can be predicted by a panel of factors on both the protein and gene levels. Moreover, among the investigated factors, survivin was the most promising biomarker of radioresponse.

    Ort, förlag, år, upplaga, sidor
    John Wiley and sons, 2011
    Nyckelord
    head and neck tumors, radiotherapy, survivin, Bcl-2 family, p53 Arg72Pro
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-61585 (URN)10.1111/j.1600-0714.2011.01036.x (DOI)000296607200002 ()
    Anmärkning
    Funding agencies|Swedish Laryng Foundation||County Council of Ostergotland (OLL)||Swedish Cancer Foundation||Foundation of Olle Engkvist||Linkoping University Hospital||Tillgänglig från: 2010-11-16 Skapad: 2010-11-16 Senast uppdaterad: 2017-12-12Bibliografiskt granskad
    3. Polymorphism of FGFR4 in cancer development and sensitivity to cisplatin and radiation in head and neck cancer
    Öppna denna publikation i ny flik eller fönster >>Polymorphism of FGFR4 in cancer development and sensitivity to cisplatin and radiation in head and neck cancer
    Visa övriga...
    2009 (Engelska)Ingår i: Oral Oncology, ISSN 1368-8375, E-ISSN 1879-0593, Vol. 45, nr 1, s. 23-29Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    The aim of this study was to investigate the predisposition of the FGFR4 Gly/Arg polymorphism for development of head and neck squamous cell carcinoma (HNSCC) and, furthermore, to examine if the FGFR4 Arg(388) allele can be associated with resistance to chemo-and radiotherapy.

    When analysing 110 tumour biopsies a significant 1.7-fold increased risk to develop HNSCC in individuals carrying the Gly(388) allele (p = 0.026) was found. Moreover a 2-fold increased risk for mates harbouring the Gly(388) allele (p = 0.031) to develop HNSCC was detected. In 39 HNSCC cell lines the role of the Arg(388) allele for radiation and cisplatin sensitivity was investigated. Our results show no rote of the Arg(388) allele for the radiosensitivity (p = 0.996) but indicate a tendency to increased cisplatin sensitivity (p = 0.141). When screening the transmembrane and kinase domains in the FGFR4 gene a novel mutation, probably generating a truncated protein lacking exons 14-18, was found in six of eight selected cell lines.

    Taken together, we have here identified a marker that predicts the risk to develop HNSCC and possibly the sensitivity to cisplatin as well as a novel. mutation in the FGFR4 gene.

    Ort, förlag, år, upplaga, sidor
    Elsevier, 2009
    Nyckelord
    Oral tumours, Radiotherapy, Chemotherapy
    Nationell ämneskategori
    Cancer och onkologi
    Identifikatorer
    urn:nbn:se:liu:diva-16724 (URN)10.1016/j.oraloncology.2008.03.007 (DOI)000262607900005 ()18487077 (PubMedID)
    Tillgänglig från: 2009-02-14 Skapad: 2009-02-13 Senast uppdaterad: 2017-12-14Bibliografiskt granskad
    4. Proteins and single nucleotide polymorphisms involved in apoptosis, growth control, and DNA repair predict cisplatin sensitivity in head and neck cancer cell lines
    Öppna denna publikation i ny flik eller fönster >>Proteins and single nucleotide polymorphisms involved in apoptosis, growth control, and DNA repair predict cisplatin sensitivity in head and neck cancer cell lines
    Visa övriga...
    2009 (Engelska)Ingår i: International Journal of Molecular Medicine, ISSN 1107-3756, E-ISSN 1791-244X, Vol. 24, nr 4, s. 549-556Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    The present study was undertaken to evaluate the possibility of using a panel of proteins and single nucleotide polymorphisms (SNPs) involved in apoptosis, growth control, and DNA repair as predictive markers for cisplatin sensitivity. For this purpose the intrinsic cisplatin sensitivity (ICS) was determined in 39 cell lines derived from squamous cell carcinomas of the head and neck using a colony-forming assay. In these cell lines and in normal oral keratinocytes (NOK), the expression of epidermal growth factor receptor (EGFR), Hsp70, Bax, Bcl-2, Bcl-XL, survivin, and COX-2 was determined. Moreover, the p53, MDM2, FGFR4, XPC, XPD, XRCC1, and XRCC3 genes were analyzed for the presence of specific single nucleotide polymorphisms (SNPs). Pearsons correlation test showed that EGFR was the only protein that was significantly correlated to the ICS (r=0.388, p=0.015). The combination of EGFR, Hsp70, Bax, and Bcl-2 gave the strongest correlation (r=0.566, p andlt;= 0.001), whereas Bax alone had the second highest influence on the ICS. Furthermore, all four SNPs within genes involved in DNA repair, i.e. XPC, XPD, XRCC1, and XRCC3, tended to influence the ICS. In order to find the combination of factors, on both protein and gene levels, with the highest correlation to ICS, a multivariate statistical calculation was performed. Our results indicate that SNPs in DNA repair genes (XRCC3(241) and XPD751) influence the ICS and together with the expression of EGFR, Hsp70, Bax, and Bcl-2, they could predict the cisplatin sensitivity of head and neck cancer cell lines (r=0.614, p andlt;= 0.001).

    Nyckelord
    epidermal growth factor receptor, Bax, Bcl-2, heat shock protein 70, DNA repair genes
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-21513 (URN)10.3892/ijmm_00000264 (DOI)
    Tillgänglig från: 2009-10-02 Skapad: 2009-10-02 Senast uppdaterad: 2017-12-13
  • 43.
    Farnebo, Lovisa
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Rekonstruktionscentrum, Öronkliniken US.
    Jedlinski, Adam
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Ansell, Anna
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet.
    Vainikka, Linda
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Thunell, Lena
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Grenman, Reidar
    University of Turku.
    Johansson, Ann-Charlotte
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Experimentell patologi. Linköpings universitet, Hälsouniversitetet.
    Roberg, Karin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Rekonstruktionscentrum, Öronkliniken US.
    Proteins and single nucleotide polymorphisms involved in apoptosis, growth control, and DNA repair predict cisplatin sensitivity in head and neck cancer cell lines2009Ingår i: International Journal of Molecular Medicine, ISSN 1107-3756, E-ISSN 1791-244X, Vol. 24, nr 4, s. 549-556Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The present study was undertaken to evaluate the possibility of using a panel of proteins and single nucleotide polymorphisms (SNPs) involved in apoptosis, growth control, and DNA repair as predictive markers for cisplatin sensitivity. For this purpose the intrinsic cisplatin sensitivity (ICS) was determined in 39 cell lines derived from squamous cell carcinomas of the head and neck using a colony-forming assay. In these cell lines and in normal oral keratinocytes (NOK), the expression of epidermal growth factor receptor (EGFR), Hsp70, Bax, Bcl-2, Bcl-XL, survivin, and COX-2 was determined. Moreover, the p53, MDM2, FGFR4, XPC, XPD, XRCC1, and XRCC3 genes were analyzed for the presence of specific single nucleotide polymorphisms (SNPs). Pearsons correlation test showed that EGFR was the only protein that was significantly correlated to the ICS (r=0.388, p=0.015). The combination of EGFR, Hsp70, Bax, and Bcl-2 gave the strongest correlation (r=0.566, p andlt;= 0.001), whereas Bax alone had the second highest influence on the ICS. Furthermore, all four SNPs within genes involved in DNA repair, i.e. XPC, XPD, XRCC1, and XRCC3, tended to influence the ICS. In order to find the combination of factors, on both protein and gene levels, with the highest correlation to ICS, a multivariate statistical calculation was performed. Our results indicate that SNPs in DNA repair genes (XRCC3(241) and XPD751) influence the ICS and together with the expression of EGFR, Hsp70, Bax, and Bcl-2, they could predict the cisplatin sensitivity of head and neck cancer cell lines (r=0.614, p andlt;= 0.001).

  • 44.
    Farnebo, Lovisa
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Rekonstruktionscentrum, Öronkliniken US.
    Jerhammar, Fredrik
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet.
    Ceder, Rebecca
    Institute of Environmental Medicine, Division of Biochemical Toxicology and Experimental Cancer Research, Karolinska Institute, Stockholm, Sweden.
    Grafström, Roland C
    Institute of Environmental Medicine, Division of Biochemical Toxicology and Experimental Cancer Research, Karolinska Institute, Stockholm, Sweden.
    Vainikka, Linda
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet.
    Thunell, Lena
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Grénman, Reidar
    Medical Biochemistry, University of Turku, Finland.
    Johansson, Ann-Charlotte
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Experimentell patologi. Linköpings universitet, Hälsouniversitetet.
    Roberg, Karin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet.
    Combining factors on protein and gene level to predict radioresponse in head and neck cancer cell lines2011Ingår i: Journal of Oral Pathology & Medicine, ISSN 0904-2512, E-ISSN 1600-0714, Vol. 40, nr 10, s. 739-746Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Radiotherapy is the main therapy for head and neck squamous cell carcinoma (HNSCC); however, treatment resistance and local recurrence are significant problems, highlighting the need for predictive markers. In this study, we evaluated selected proteins, mutations, and single nucleotide polymorphisms (SNPs) involved in apoptosis, cell proliferation, and DNA repair alone or combined as predictive markers for radioresponse in 42 HNSCC cell lines.

    METHODS: The expression of epidermal growth factor receptor, survivin, Bax, Bcl-2, Bcl-XL, cyclooxygenase-2, and heat shock protein 70 was analyzed by ELISA. Furthermore, mutations and SNPs in the p53 gene as well as SNPs in the MDM2, XRCC1, and XRCC3 genes were analyzed for their relation to radioresponse. To enable the evaluation of the predictive value of several factors combined, each cell line was allocated points based on the number of negative points (NNP) system, and the NNP sum was correlated with radioresponse.

    RESULTS: Survivin was the only factor that alone was significantly correlated with the intrinsic radiosensitivity (r=0.36, p=0.02). The combination of survivin, Bax, Bcl-2, Bcl-XL, cyclooxygenase-2, and the p53 Arg72Pro polymorphism was found to most strongly correlate with radioresponse (r=0.553, p<0.001).

    CONCLUSION: These data indicate that the intrinsic radiosensitivity of 42 HNSCC cell lines can be predicted by a panel of factors on both the protein and gene levels. Moreover, among the investigated factors, survivin was the most promising biomarker of radioresponse.

  • 45.
    Farnebo, Lovisa
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Rekonstruktionscentrum, Öronkliniken US.
    Jerhammar, Fredrik
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet.
    Vainikka, Linda
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Grénman, Reidar
    Department of Otorhinolaryngology, Head and Neck Surgery, Central Hospital and University of Turku and Medical Biochemistry, University of Turku, Finland.
    Norberg-Spaak, Lena
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet.
    Roberg, Karin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet.
    Number of negative points: a novel method for predicting radiosensitivity in head and neck tumor cell lines.2008Ingår i: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 20, nr 2, s. 453-461Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The present study was aimed at establishing a method that combines multiple factors of protein and genetic changes that enables prediction of radiosensitivity in the head and neck squamous cell carcinoma (HNSCC) cell lines. In nine HNSCC cell lines, the quantity of protein expression and the type of genetic alterations were translated into a point system, called the Number of Negative Points. The expression of 14 proteins involved in growth control and/or apoptosis was quantified using a densitometric assessment of Western blots. The blots were adjusted to actin and standardised to normal oral keratinocytes classifying them into four groups depending on the amount of protein expressed (0-3 points). Mutations of the p53 gene were classified into three groups and each mutation was given one point. Since the cell lines each had a known intrinsic radiosensitivity, a multivariate statistical calculation could then be performed to select for the combination of factors having the strongest correlation to radiosensitivity. The strongest correlation of the investigated factors was the combination of epidermal growth factor receptor, survivin and splice site/missense p53 mutations (R=0.990 and P<0.0001). No single factor had a significant correlation to the intrinsic radiosensitivity. Since a significant correlation to the intrinsic radiosensitivity was achieved only when two or more factors were combined, we conclude that a method such as the Number of Negative Points is necessary for prediction of treatment response. We present a novel method to combine factors which enables the prediction of radiosensitivity of HNSCC cell lines.

  • 46.
    Farnebo, Lovisa
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Öron- näsa- och halskliniken US.
    Tiefenböck, Katharina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Ansell, Anna
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neurovetenskap. Linköpings universitet, Hälsouniversitetet.
    Thunell, Lena
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Garvin, Stina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Roberg, Karin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neurovetenskap. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Öron- näsa- och halskliniken US.
    Strong expression of survivin is associated with positive response to radiotherapy and improved overall survival in head and neck squamous cell carcinoma patients2013Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 133, nr 8, s. 1994-2003Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Head and neck squamous cell carcinoma (HNSCC) is a malignancy that is associated with severe mortality despite advances in therapy. Todays standard treatment most commonly includes radiotherapy, often combined with chemotherapy or surgery. There are so far no established biomarkers to predict response to radiation, and thus the aim of this study was to investigate a series of markers that could potentially identify HNSCC patients who would benefit from radiotherapy. The selected markers, both proteins (epidermal growth factor receptor, survivin and p53), and single nucleotide polymorphisms (SNPs) in the genes of XRCC3, XRCC1, XPC, XPD, MDM2, p53 and FGFR4 were correlated to the response to radiotherapy and overall survival. Investigations were performed on pretreatment tumor biopsies from patients classified as responders or nonresponders to radiotherapy. Protein expression was examined using immunohistochemistry and the genotyping of specific SNPs was analyzed using PCR-RFLP or pyrosequencing. We found that survivin expression was significantly stronger in the responder group (p = 0.003) and that patients with a strong survivin expression had a significantly better overall survival (p andlt; 0.001). Moreover, downregulation of survivin by siRNA in two HNSCC cell lines significantly decreased their sensitivity to radiation. Among the SNPs analyzed, patients with the XPD Lys751Gln SNP had a significantly shorter overall survival (p = 0.048), and patients with the FGFR4 Gly388Arg SNP had a significantly longer overall survival (p = 0.010). In conclusion, our results suggest that survivin plays an important role in the response to radiotherapy and may be a useful marker for predicting radiotherapy response in patients with HNSCC. less thanbrgreater than less thanbrgreater thanWhats new? Resistance to radiation therapy is a significant problem in the treatment of head and neck squamous cell carcinoma (HNSCC) and has created a need for the discovery of markers predictive of radiotherapy response. One promising marker is survivin, an inhibitor of apoptosis. Here, in pre-treatment biopsies from 40 patients with HNSCC, strong survivin expression was significantly associated with response to radiotherapy and increased overall survival. The data also indicate that single nucleotide polymorphisms in the genes XPD and FGFR4 are other possible predictors of overall survival after radiotherapy.

  • 47.
    Graf, Jonas
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi.
    Ericsson, Elisabeth
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Östergötlands Läns Landsting, Rekonstruktionscentrum, Öronkliniken US.
    LundeborgHammarström, Inger
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Logopedi.
    Hultcrantz, Elisabeth
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Östergötlands Läns Landsting, Rekonstruktionscentrum, Öronkliniken US.
    Tonsillotomi på förskolebarn-räcker det?2008Ingår i: The Annual General Meeting for the Swedish Society for Medicine,2008, 2008Konferensbidrag (Refereegranskat)
    Abstract [sv]

     Under förskoleålder sker en fysiologisk ökning av den sk Waldeyerska ringen med tillväxt av tonsiller och adenoid som del i utvecklingen av barnets immunförsvar Många barn kan under denna tid debutera med obstruktionsbesvär(snarkning och sömnapné). Traditionellt har tonsillerna och adenoiden genom tonsillektomi och abrasio helt avlägsnats för att komma till rätta med dessa symptom, kirurgi förenad med hög postoperativ smärtnivå. På senare tid har tonsillotomi, dvs partiellt borttagande av tonsillerna, återinförts som en något mer skonsam operationsmetod. Immunsystemetpåverkas möjligtvis inte heller i lika stor omfattning. Frågan är om detta ingrepp är tillfyllest på barn som är i den ålder då tonsillerna fortfarande växer? Syftet med föreliggande studie var att jämföra tonsillotomi med radiofrekvenskirurgi med fullständig tonsillektomi på förskolebarn vad beträffar postoperativ morbiditet och långtidseffekt på snarkning och infektionsnbenägenhet upp till två år efter operation med tonsillektomi. 67 förskolebarn(4-5 år)med symtomgivade tonsillhypertrofi randomiserades till reguljär tonsillektomi(TE) eller tonsillotomi(TT) med radiofrekvensteknik. I de flesta fall utfördes samtidigt abrasio. 6 månader efter operationen svarade alla på frågeformulär och 2 år efter operationen bedömdes de åter av ÖNH-läkare. Snarkningen före, direkt efter operationen och vid tiden för läkarbesöket utvärderades då med VAS TT barnen registrerade lägre smärta från första dagen efter operation och var helt smärtfria 3 dagar tidigare än TE-barnen. Sex månader efter operationen förelåg ingen skillnad på grupperna vad gäller snarkning och infektionsbenägehet. Efter två år hade två av de 34 TT-barnen och ett av de 33 TE-barnen blivit re-opererade pga recidiv av obstruktionsbesvär, TE-barnet med reabrasio. Övriga barn i båda grupperna var i stort sett besvärsfria vad gäller snarkning och ingen ökad infektionsbenägehet noterades hos något barn. VAS före/ två år efter operationen var 8,4/1,3 för TE och 8,5/1,6 för TT. Tre av TT barnen hade tonsillvävnad något utanför tonsillogen och hälften av TE barnen hade små tonsillrester i logerna. Cirka 6 % risk föreligger att ett yngre barn som opereras med tonsillotomi för obstruktionsbesvär behöver göra om operationen inom 2 år. Denna risk bör vägas mot den betydligt lägre postoperativa morbiditeten för tonsillotomi jämfört med tonsillektomi.

  • 48.
    Grafstrom, Roland C.
    et al.
    Karolinska Institute, Sweden .
    Ceder, Rebecca
    Karolinska Institute, Sweden .
    Fadeel, Bengt
    Karolinska Institute, Sweden .
    Roberg, Karin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Öron- näsa- och halskliniken US.
    Willighagen, Egon
    Karolinska Institute, Sweden .
    Bioinformatics-based cancer research have wide toxicological applicability in TOXICOLOGY LETTERS, vol 211, issue , pp S160-S1602012Ingår i: TOXICOLOGY LETTERS, Elsevier , 2012, Vol. 211, s. S160-S160Konferensbidrag (Refereegranskat)
    Abstract [en]

    n/a

  • 49.
    Grahn Kronhed, Ann-Charlotte
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Socialmedicin och folkhälsovetenskap. Linköpings universitet, Hälsouniversitetet.
    Hallberg, Inger
    Linköpings universitet, Institutionen för medicin och hälsa, Omvårdnad. Linköpings universitet, Hälsouniversitetet.
    Ödkvist, Lars
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Rekonstruktionscentrum, Öronkliniken US.
    Möller, Margareta
    Centre for Health Care Sciences, Örebro University Hospital.
    Effect of training on health-related quality of life, pain and falls in osteoporotic women2009Ingår i: Advances in Physiotherapy, ISSN 1403-8196, E-ISSN 1651-1948, Vol. 11, nr 3, s. 154-165Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Physical inactivity is a risk factor for osteoporosis and fractures. The aim of the study was to see if supervised training would improve health-related quality of life (HRQL), reduce pain and falls in osteoporotic women. Women with established osteoporosis (n=124) were invited to a 1-year, follow-up study. Seventy-three women aged 60-81 years met the inclusion criteria and were randomized to an exercise (E) or control (C) group. A 4-month, supervised group training programme was designed. Participants were studied using HRQL questionnaires, clinical tests and dynamic posturography. Thirty-one women in the E-group and 34 women in the C-group completed the study. The E-group improved in six SF-36 domains and mental component summary (MCsum) index and also in worst pain intensity (p<0.01) after the supervised exercise training. Differences were found between the groups when comparing changes in four SF-36 domains, MCsum and worst pain (p=0.001). Physical activity level decreased in the E-group after the supervised period. Mean time to first fall occurred earlier in the C-group than in the E-group for the first 4 months but the trend did not last for the 1-year follow-up. The study suggests that supervised group training is beneficial for women with established osteoporosis.

  • 50.
    Granath, Anna
    et al.
    Karolinska Institute.
    Cardell, Lars-Olaf
    Karolinska Institute.
    Uddman, Rolf
    Lund University.
    Harder, Henrik
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Öron- näsa- och halskliniken US.
    Letter: Altered Toll- and Nod-like receptor expression in human middle ear mucosa from patients with chronic middle ear disease2011Ingår i: Journal of Infection, ISSN 0163-4453, E-ISSN 1532-2742, Vol. 63, nr 2, s. 174-176Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    n/a

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