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  • 1. Akagi, Nana
    et al.
    Takumida, Masaya
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Anniko, Matti
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Effect of acute endolymphatic hydrops overload on the endolymphatic sac2008In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 128, no 3, 239-44 p.Article in journal (Refereed)
    Abstract [en]

    CONCLUSIONS: Homeostasis of endolymph volume is a complex mechanism, in which the endolymphatic sac (ES) may play an important role. OBJECTIVES: To elucidate the effect of acute endolymphatic hydrops (EH) on the ES and to gain further information about the volume and pressure regulative function of the ES. MATERIALS AND METHODS: Distilled water was injected into the middle ear cavity of adult CBA/J mice. The ESs were studied morphologically by light and transmission electron microscopy. RESULTS: Mild EH was found, particularly in the upper turn of the cochlea. Acute EH led to an increase in the size of the ES lumen, accompanied by collapse of the lateral intercellular spaces and dense perisaccular tissue, changes which had reversed 2 h after the injection.

  • 2. Akagi, Nana
    et al.
    Takumida, Masaya
    Anniko, Matti
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Effect of inner ear blood flow changes on the endolymphatic sac2008In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 128, no 11, 1187-95 p.Article in journal (Refereed)
    Abstract [en]

    CONCLUSIONS: That the endolymphatic sac (ES) reacts to changes in inner ear blood flow may be important for homeostasis of the inner ear fluid volume and pressure. OBJECTIVES: To elucidate the effect of changes in inner ear blood flow on the ES and to learn more about the volume and pressure regulatory function of the ES. MATERIALS AND METHODS: Epinephrine or sodium nitroprusside (SNP) was injected into the middle ear cavity of adult CBA/J mice. The ES were analyzed morphologically by light microscopy. RESULTS: Epinephrine reduced the luminal size of the ES leading to an accumulation of intraluminal homogeneous substance. Injection of SNP increased the size of the ES lumen, accompanied by a collapse of the lateral intercellular space (LIS) and dense perisaccular tissue. These changes were almost reversed 4 h after injection.

  • 3.
    Anantharaman, Devasena
    et al.
    Int Agcy Res Canc, Genet Epidemiol Grp, Lyon, France..
    Muller, David C.
    Int Agcy Res Canc, Genet Epidemiol Grp, Lyon, France..
    Lagiou, Pagona
    Univ Athens, Sch Med, Dept Hyg Epidemiol & Med Stat, Athens, Greece..
    Ahrens, Wolfgang
    BIPS, Leibniz Inst Prevent Res & Epidemiol, Bremen, Germany.;Univ Bremen, Fac Math & Comp Sci, Bremen, Germany..
    Holcatova, Ivana
    Charles Univ Prague, Fac Med 1, Inst Hyg & Epidemiol, Prague, Czech Republic..
    Merletti, Franco
    Univ Turin, Dept Med Sci, Canc Epidemiol Unit, Turin, Italy..
    Kjaerheim, Kristina
    Canc Registry Norway, Oslo, Norway..
    Polesel, Jerry
    CRO Aviano Natl Canc Inst, Unit Epidemiol & Biostat, Aviano, Italy..
    Simonato, Lorenzo
    Univ Padua, Dept Mol Med, Lab Publ Hlth & Populat Studies, Padua, Italy..
    Canova, Cristina
    Univ Padua, Dept Mol Med, Lab Publ Hlth & Populat Studies, Padua, Italy..
    Castellsague, Xavier
    CIBERESP, IDIBELL, ICO, Unit Infect & Canc, Barcelona, Spain..
    Macfarlane, Tatiana V.
    Univ Aberdeen, Sch Med & Dent, Aberdeen, Scotland..
    Znaor, Ariana
    Croatian Natl Inst Publ Hlth, Croatian Natl Canc Registry, Zagreb, Croatia.;Int Agcy Res Canc, Sect Canc Surveillance, Lyon, France..
    Thomson, Peter
    Newcastle Univ, Ctr Oral Hlth Res, Newcastle Upon Tyne, Tyne & Wear, England..
    Robinson, Max
    Newcastle Univ, Ctr Oral Hlth Res, Newcastle Upon Tyne, Tyne & Wear, England..
    Conway, David I.
    Univ Glasgow, Sch Dent, Coll Med Vet & Life Sci, Glasgow, Lanark, Scotland..
    Healy, Claire M.
    Trinity Coll Dublin, Sch Dent Sci, Dublin, Ireland..
    Tjönneland, Anne
    Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark..
    Westin, Ulla
    Lund Univ, Dept Otorhinolaryngol Malmo & Lund, Lund, Sweden..
    Ekström, Johanna
    Lund Univ, Dept Clin Sci, Lund, Sweden..
    Chang-Claude, Jenny
    German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany..
    Kaaks, Rudolf
    German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany..
    Overvad, Kim
    Inst Publ Hlth, Aarhus, Denmark..
    Drogan, Dagmar
    German Inst Human Nutr Potsdam Rehbruecke DIfE, Nuthetal, Germany..
    Hallmans, Göran
    Umea Univ, Dept Biobank Res, Umea, Sweden..
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Bueno-de-Mesquita, H. B.
    Natl Inst Publ Hlth & Environm RIVM, Dept Determinants Chron Dis DCD, Bilthoven, Netherlands.;Univ Med Ctr, Dept Gastroenterol & Hepatol, Utrecht, Netherlands.;Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;Univ Malaya, Fac Med, Dept Social & Prevent Med, Kuala Lumpur, Malaysia..
    Peeters, Petra H.
    Univ Med Ctr, Julius Ctr Hlth Sci & Primary Care, Dept Epidemiol, Utrecht, Netherlands.;Imperial Coll London, Sch Publ Hlth, MRC PHE, London, England..
    Agudo, Antonio
    ICO, Unit Nutr & Canc, Barcelona, Spain..
    Larranaga, Nerea
    BIODonostia Res Inst, Basque Hlth Dept, Publ Hlth Div Gipuzkoa, San Sebastian, Spain.;CIBER Epidemiol & Publ Hlth CIBERESP, Madrid, Spain..
    Travis, Ruth C.
    Univ Oxford, Nuffield Dept Populat Hlth, Canc Epidemiol Unit, Oxford, England..
    Palli, Domenico
    Canc Res & Prevent Inst ISPO, Mol & Nutr Epidemiol Unit, Florence, Italy..
    Barricarte, Aurelio
    CIBER Epidemiol & Publ Hlth CIBERESP, Madrid, Spain.;Navarre Publ Hlth Inst, Pamplona, Spain..
    Trichopoulou, Antonia
    Hellen Hlth Fdn, Athens, Greece.;Acad Athens, Bur Epidemiol Res, Athens, Greece..
    George, Saitakis
    Univ Athens, Sch Med, Dept Hyg Epidemiol & Med Stat, Athens, Greece.;Hellen Hlth Fdn, Athens, Greece..
    Trichopoulos, Dimitrios
    Hellen Hlth Fdn, Athens, Greece.;Acad Athens, Bur Epidemiol Res, Athens, Greece.;Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA..
    Ramon Quiros, J.
    Publ Hlth Directorate Asturias, Oviedo, Spain..
    Grioni, Sara
    Fdn IRCCS, Ist Nazl Tumori, Epidemiol & Prevent Unit, Milan, Italy..
    Sacerdote, Carlotta
    Univ Turin, Citta Salute & Sci Hosp, Canc Epidemiol Unit, Turin, Italy.;Ctr Canc Prevent CPO, Turin, Italy..
    Navarro, Carmen
    CIBER Epidemiol & Publ Hlth CIBERESP, Madrid, Spain.;IMIB Arrixaca, Murcia Reg Hlth Council, Dept Epidemiol, Murcia, Spain.;Univ Murcia, Dept Hlth & Social Sci, Murcia, Spain..
    Sanchez, Maria-Jose
    CIBER Epidemiol & Publ Hlth CIBERESP, Madrid, Spain.;Univ Granada, Inst Invest Biosanitaria, Granada, Spain..
    Tumino, Rosario
    Civ MP Arezzo Hosp, Canc Registry, Asp Ragusa, Ragusa, Italy.;Civ MP Arezzo Hosp, Histopathol Unit, Asp Ragusa, Ragusa, Italy..
    Severi, Gianluca
    Human Genet Fdn HuGeF, Turin, Italy.;Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia.;Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic 3010, Australia..
    Boutron-Ruault, Marie-Christine
    INSERM, Ctr Res Epidemiol & Populat Hlth CESP, Villejuif, France.;Univ Paris 11, Villejuif, France.;Inst Gustave Roussy, Villejuif, France..
    Clavel-Chapelon, Francoise
    INSERM, Ctr Res Epidemiol & Populat Hlth CESP, Villejuif, France.;Univ Paris 11, Villejuif, France.;Inst Gustave Roussy, Villejuif, France..
    Panico, Salvatore
    Univ Naples Federico II, Dipartimento Med Clin & Chirurgia, Naples, Italy..
    Weiderpass, Elisabete
    Arctic Univ Norway, Univ Tromso, Fac Hlth Sci, Dept Community Med, Tromso, Norway.;Canc Registry Norway, Oslo, Norway.;Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.;Folkhalsan Res Ctr, Dept Genet Epidemiol, Helsinki, Finland..
    Lund, Eiliv
    Arctic Univ Norway, Univ Tromso, Fac Hlth Sci, Dept Community Med, Tromso, Norway..
    Gram, Inger T.
    Arctic Univ Norway, Univ Tromso, Fac Hlth Sci, Dept Community Med, Tromso, Norway..
    Riboli, Elio
    Imperial Coll London, Sch Publ Hlth, London, England..
    Pawlita, Michael
    German Canc Res Ctr, Heidelberg, Germany..
    Waterboer, Tim
    German Canc Res Ctr, Heidelberg, Germany..
    Kreimer, Aimee R.
    NCI, NIH, Bethesda, MD 20892 USA..
    Johansson, Mattias
    Int Agcy Res Canc, Genet Epidemiol Grp, Lyon, France..
    Brennan, Paul
    Int Agcy Res Canc, Genet Epidemiol Grp, Lyon, France..
    Combined effects of smoking and HPV16 in oropharyngeal cancer2016In: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685, Vol. 45, no 3, 752-761 p.Article in journal (Refereed)
    Abstract [en]

    Background: Although smoking and HPV infection are recognized as important risk factors for oropharyngeal cancer, how their joint exposure impacts on oropharyngeal cancer risk is unclear. Specifically, whether smoking confers any additional risk to HPV-positive oropharyngeal cancer is not understood.

    Methods: Using HPV serology as a marker of HPV-related cancer, we examined the interaction between smoking and HPV16 in 459 oropharyngeal (and 1445 oral cavity and laryngeal) cancer patients and 3024 control participants from two large European multicentre studies. Odds ratios and credible intervals [CrI], adjusted for potential confounders, were estimated using Bayesian logistic regression.

    Results: Both smoking [odds ratio (OR [CrI]: 6.82 [4.52, 10.29]) and HPV seropositivity (OR [CrI]: 235.69 [99.95, 555.74]) were independently associated with oropharyngeal cancer. The joint association of smoking and HPV seropositivity was consistent with that expected on the additive scale (synergy index [CrI]: 1.32 [0.51, 3.45]), suggesting they act as independent risk factors for oropharyngeal cancer.

    Conclusions: Smoking was consistently associated with increase in oropharyngeal cancer risk in models stratified by HPV16 seropositivity. In addition, we report that the prevalence of oropharyngeal cancer increases with smoking for both HPV16-positive and HPV16-negative persons. The impact of smoking on HPV16-positive oropharyngeal cancer highlights the continued need for smoking cessation programmes for primary prevention of head and neck cancer.

  • 4. Anderson, Malin
    et al.
    Johnston, T.A.
    Newman, P.D.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Internalization of nanoparticles into spiral ganglion cells2009In: Journal of nanoneuroscience, ISSN 1939-0637, Vol. 1, no 1, 75-84 p.Article in journal (Refereed)
    Abstract [en]

    The delivery of drugs or genes to the inner ear in a controlled and biocompatible manner could lead to new treatments for conditions such as Ménière's disease, tinnitus, schwannomas of the ear, and for improving hearing. The concept of multifunctional nanoparticles, which are targetable, biodegradable, and traceable, has led to new approaches to controlled drug release and localized delivery to specific cell populations. Tissue-specific delivery can be achieved by functionally "addressed" nanostructures loaded with a therapeutic molecule. In the present study, we investigated the incorporation, distribution, and toxicology of amphiphilic block copolymer nanoparticles (NPs) in spiral ganglion (SG) cell cultures. Adult human and guinea pig SG neurons and glia/Schwann dissociated cell cultures were expanded, grown for several weeks, and then studied live using time-lapse video microscopy and high-resolution light microscopy. The cells were further characterized using immunocytochemistry for the neural marker TuJ1 and the glia cell markers S-100 and GFAP, and their morphology was studied in more detail using scanning electron microscopy (SEM). These cell cultures were exposed to fluorescently (Dil)-loaded NPs for different time periods and at different concentrations, and the uptake was studied using fluorescence microscopy. The study demonstrates that Dil-loaded NPs can be internalized into guinea pig SG neurons as well as into human and guinea pig SG glia/Schwann cells without indication of toxicity or reduced viability. After 4 hours, almost 100% of both the neurons and the glia cells had incorporated the NPs into the cytoplasm. No uptake could be detected in the nucleus and no evidence of internalization could be seen in axons or in the growth cone area of the neuron. Especially in the glia cells, the NPs were detected in small vesicles surrounding the nucleus and occasionally in the periphery of the cytoplasm. This information could lead to the development of more specialized NPs, targeting only SG neurons or Schwann cells.

  • 5.
    Andersson, Camilla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Röing, Marta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Health Services Research.
    Ehrsson, Ylva Tiblom
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Johansson, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Lifestyle and rehabilitation in long term illness. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Psychology in Healthcare.
    It's a question of endurance: patients with head and neck cancer experiences of 18F-FDG PET/CT in a fixation mask2017In: European Journal of Oncology Nursing, ISSN 1462-3889, E-ISSN 1532-2122, Vol. 29, 85-90 p., S1462-3889(17)30082-0Article in journal (Refereed)
    Abstract [en]

    PURPOSE: This study aimed to explore how patients with head and neck cancer experienced undergoing an (18)F-fluoro-deoxy-glucose positrons emissions tomography/computed tomography ((18)F-FDG PET/CT) examination in a fixation mask.

    METHOD: Interviews were conducted with nine patients with known or suspected head and neck cancer who were scheduled for the examination for the first time. The phenomenological method according to van Manen and his four lifeworld existentials; lived space, lived body, lived time, and lived relation was used to analyse the interviews.

    RESULTS: The thoughts and feelings of the patients during the PET/CT examination varied, some found it very difficult, while others did not. However, for all the patients, it was an experience that required some form of coping to maintain composure for example distraction.

    CONCLUSIONS: PET/CT examnation in a fixation mask may be strenuous for some patients. Patients need more detailed information, including suggestions for coping behaviours, prior to the examination, as well as higher level of support during and after the examination. The results of this study may be used to improve patient care and optimize the procedure of PET/CT examination in a fixation mask.

  • 6.
    Andersson, Gerhard
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Ekvall, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Kinnefors, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Nyberg, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Evaluation of quality of life and symptoms after translabyrinthine acoustic neuroma surgery1997In: The American journal of otology, ISSN 0192-9763, Vol. 18, no 4, 421-426 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    This study aimed to describe the consequences of acoustic neuroma surgery in terms of symptoms and quality of life.

    STUDY DESIGN:

    This study was a retrospective case review.

    SETTING:

    The surgery was conducted in Uppsala, Sweden.

    PATIENTS:

    A consecutive sample of acoustic neuroma patients operated on between 1988 and 1994.

    INTERVENTION:

    All patients had been operated on with the translabyrinthine technique.

    MAIN OUTCOME MEASURES:

    A questionnaire was constructed including questions about the surgery and symptoms. The House and Brackmann scale was used for grading facial function and the Brackmann and Bars scale was used for self-assessment of facial function.

    RESULTS:

    Follow-up data were collected by a postal questionnaire sent out and returned by 141 patients, which yielded a 90% response rate. Normal to moderately impaired facial function (House I-III) was evident in 85.2% of patients, although residual facial problems were reported. Most considered hearing to be worse after surgery (80%), and tinnitus was found in 60% of the sample. Balance problems (45%), dizziness (19%), and headache/pain (22%) were also reported. Work ability was affected in 23%, and 37% reported a continued need for medical consultations, mainly because of facial problems and pain. Most (89%) were pleased with the preoperative information.

    CONCLUSIONS:

    This study showed that few patients with acoustic neuroma had experienced negative social consequences after surgery. Although not linked to the operation, residual symptoms were reported that may necessitate further rehabilitation.

  • 7.
    Andersson, Gerhard
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Kinnefors, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Ekvall, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Tinnitus and translabyrinthine acoustic neuroma surgery1997In: Audiology & neuro-otology, ISSN 1420-3030, E-ISSN 1421-9700, Vol. 2, no 6, 403-409 p.Article in journal (Refereed)
    Abstract [en]

    The purpose of this investigation was to study the effects of translabyrinthine acoustic neuroma surgery on tinnitus in a consecutive sample of patients operated on between 1988 and 1994 in Uppsala (Sweden). A postal questionnaire was returned by 141 patients, yielding a 90% response rate without reminder. The results showed that tinnitus was experienced by 70% of the patients before surgery and 60% after surgery. In general, low degrees of tinnitus distress were found, which was confirmed by the questionnaire results. Ratings of tinnitus distress after surgery, using the Klockhoff and Lindblom grading system, showed that 48% had tinnitus of grade I, 46% of grade II, and 6% of grade III. Pre- and postsurgery grading of distress did not change significantly. There was a 35% risk for developing tinnitus when no preoperative tinnitus was present and a 15% chance that tinnitus disappears when present preoperatively.

  • 8.
    Anniko, Matti
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Arnold, W
    Stigbrand, T
    Protein patterns in human vestibular ganglion cells and hair cells, with functional interpretations1993In: Acta oto-laryngologica. Supplementum, ISSN 0365-5237, Vol. 503, 136-142 p.Article in journal (Refereed)
    Abstract [en]

    Cytoskeletal organization was analysed in the vestibular ganglion cells and in the sensory epithelia of all five vestibular organs of the adult human temporal bone. A pancellular rigidity of the upper surfaces of the vestibular organs, evidenced by large quantities of intermediate filaments and actin, seems of importance for the mechanoelectrical transduction by opposing the motion of the cupulae and statoconial layers. Immunostaining for the calcium-binding protein synaptophysin in the sensory hair bundles and in the area close to the cuticular plates--the first of its kind to be demonstrated in human vestibular organs--indicates the presence of calcium-dependent ionic channels. The hypothesis is presented that the calyx might be involved in a short-loop feed back control of type I hair cells, i.e. of the mechanoelectrical transduction itself. Subpopulations of vestibular ganglion cells were identified by the staining pattern of cytoskeletal proteins, but not by ordinary ultrastructural analysis.

  • 9.
    Anniko, Matti
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Nordang, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Middle Ear exotin and endolymphatic sac response-an immune reaction?2001In: Oto-Rhino-Laryngologia Nova, ISSN 1423-0283, Vol. 10, 276-296 p.Article in journal (Refereed)
  • 10.
    Anniko, Matti
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Takumida, Masaya
    Lidian, Adnan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Linder, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Nordang, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Stenkvist-Asplund, Monika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Exotoxin in the middle ear: risk factor for hearing impairment2005In: Yearbook of Spanish Society of ORL and H&N Surgery, 2005Chapter in book (Other (popular science, discussion, etc.))
  • 11.
    Anniko, Matti
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Takumida, Masaya
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Lidian, Adnan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Linder, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Nordang, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Stenqvist, Monika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Exotoxin in the middle ear: risk factor for hearing impairment2005Book (Other academic)
  • 12.
    Asplund, Monika Stenkvist
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Holmström, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Chemotherapy in severe nasal polyposis - a possible beneficial effect?: A report of three cases2010In: Rhinology, ISSN 0300-0729, E-ISSN 1996-8604, Vol. 48, no 3, 374-376 p.Article in journal (Refereed)
    Abstract [en]

    Background: Nasal polyposis is an inflammatory process of the nasal mucosa. Treatment has changed from surgery to an anti-inflammatory approach, but neither of these treatments addresses the underlying cause. Topical steroids and occasional use of systemic steroids in patients with nasal polyposis can frequently control the polypoid disease. In a few cases, when the disease is more aggressive, the repeated application of systemic steroids together with sinus surgery is required. Material and Methods: We present our experience with one case of rheumatoid arthritis and two cases with malignant diseases, all of which were treated with chemotherapy and were also accompanied by severe nasal polyposis. All of our patients had eosinophilic polypoid disease. Various chemotherapeutic treatment schemes were utilized. Results: During chemotherapy all three patients were markedly improved symptomatically including olfaction along with a significant reduction in their nasal polyposis. Duration of remission lasted for a few months in two cases and for three years, in a third case. Conclusion: This is the first report describing the successful treatment of severe nasal polyposis with chemotherapy. Based on this experience, we suggest a phase II trial with chemotherapy, preferably "low dose" methotrexate, in patients with severe nasal polyposis.

  • 13.
    Assadian, Farzaneh
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN USA..
    Kamel, Wael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Svensson, Catharina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Punga, Tanel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Akusjärvi, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Expression profile of Epstein-Barr virus and human adenovirus small RNAs in tonsillar B and T lymphocytes2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 5, e0177275Article in journal (Refereed)
    Abstract [en]

    We have used high-throughput small RNA sequencing to characterize viral small RNA expression in purified tonsillar B and T lymphocytes isolated from patients tested positive for Epstein-Barr virus (EBV) or human adenovirus (HAdV) infections, respectively. In the small set of patients analyzed, the expression profile of EBV and HAdV miRNAs could not distinguish between patients diagnosed with tonsillar hypertrophy or chronic/recurrent tonsillitis. The EBV miR-BART expression profile among the patients diagnosed with tonsillar diseases resembles most closely the pattern seen in EBV+ tumors (Latency II/I). The miRBARTs that appear to be absent in normal EBV infected cells are essentially all detectable in the diseased tonsillar B lymphocytes. In the EBV+ B cells we detected 44 EBV miRBARTs derived from the proposed BART precursor hairpins whereof five are not annotated in miRBase v21. One previously undetected miRNA, BART16b-5p, originates from the miR-BART16 precursor hairpin as an alternative 5 A miR-BART16 located precisely upstream of the annotated miR-BART16-5p. Further, our analysis revealed an extensive sequence variation among the EBV miRNAs with isomiRs having a constant 5 A end but alternative 3 A ends. A range of small RNAs was also detected from the terminal stem of the EBER RNAs and the 3 A part of v-snoRNA1. During a lytic HAdV infection in established cell lines the terminal stem of the viral non-coding VA RNAs are processed to highly abundant viral miRNAs (mivaRNAs). In contrast, mivaRNA expression in HAdV positive tonsillar T lymphocytes was very low. The small RNA profile further showed that the 5 A mivaRNA from VA RNAI and the 3 A mivaRNA from VA RNAII were as predicted, whereas the 3 A mivaRNA from VA RNAI showed an aberrant processing upstream of the expected Dicer cleavage site.

  • 14.
    Assadian, Farzaneh
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Sandström, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Bondeson, Kåre
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Lidian, Adnan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Svensson, Catharina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Akusjärvi, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Bergqvist, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Punga, Tanel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Distribution and Molecular Characterization of Human Adenovirus and Epstein-Barr Virus Infections in Tonsillar Lymphocytes Isolated from Patients Diagnosed with Tonsillar Diseases2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 5, e0154814Article in journal (Refereed)
    Abstract [en]

    Surgically removed palatine tonsils provide a conveniently accessible source of T and B lymphocytes to study the interplay between foreign pathogens and the host immune system. In this study we have characterised the distribution of human adenovirus (HAdV), Epstein-Barr virus (EBV) and human cytomegalovirus (HCMV) in purified tonsillar T and B cell-enriched fractions isolated from three patient age groups diagnosed with tonsillar hypertrophy and chronic/recurrent tonsillitis. HAdV DNA was detected in 93 out of 111 patients (84%), while EBV DNA was detected in 58 patients (52%). The most abundant adenovirus type was HAdV-5 (68%). None of the patients were positive for HCMV. Furthermore, 43 patients (39%) showed a co-infection of HAdV and EBV. The majority of young patients diagnosed with tonsillar hypertrophy were positive for HAdV, whereas all adult patients diagnosed with chronic/recurrent tonsillitis were positive for either HAdV or EBV. Most of the tonsils from patients diagnosed with either tonsillar hypertrophy or chronic/recurrent tonsillitis showed a higher HAdV DNA copy number in T compared to B cell-enriched fraction. Interestingly, in the majority of the tonsils from patients with chronic/recurrent tonsillitis HAdV DNA was detected in T cells only, whereas hypertrophic tonsils demonstrated HAdV DNA in both T and B cell-enriched fractions. In contrast, the majority of EBV positive tonsils revealed a preference for EBV DNA accumulation in the B cell-enriched fraction compared to T cell fraction irrespective of the patients' age.

  • 15.
    Assadian, Farzaneh
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Sandström, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Svensson, Catharina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Akusjärvi, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Punga, Tanel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Efficient Isolation Protocol for B and T Lymphocytes from Human Palatine Tonsils2015In: Journal of Visualized Experiments, ISSN 1940-087X, E-ISSN 1940-087X, Vol. 105, e53374Article in journal (Refereed)
    Abstract [en]

    Palatine tonsils are a rich source of B and T lymphocytes. Here we provide an easy, efficient and rapid protocol to isolate B and T lymphocytes from human palatine tonsils. The method described has been specifically adapted for studies of the viral etiology of tonsil inflammation known as tonsillitis.

  • 16.
    Atturo, Francesca
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Barbara, Maurizio
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Is the Human Round Window Really Round?: An Anatomic Study With Surgical Implications2014In: Otology and Neurotology, ISSN 1531-7129, E-ISSN 1537-4505, Vol. 35, no 8, 1354-1360 p.Article in journal (Refereed)
    Abstract [en]

    Hypothesis: Human round window (RW) presents anatomic variations that may influence surgical approach. Background: The true shape of the human RW has been divisive since its first description in 1772 by Antonio Scarpa. Introduction of novel surgical strategies in recent years have raised its significance. Here, the human RW size and shape variations were documented in microdissected human temporal bones. Methods: An archival collection of human microdissected temporal bones was analyzed. RW rim could be delineated and photographed from the labyrinthine aspect and its topography assessed. Results: Human RW is seldom round but ovoid or orthogonal, skewed, and nonplanar (saddlelike). Membrane is fan shaped or conical with an anteroinferior and a posterosuperior part. The mean longest diameter was 1.90 mm, and the smallest one is 1.54 mm. The mean diameter from the crista fenestra was 1.31 mm. The mean area of the RW was 2.08 mm(2), which varied between 0.99 and 3.20 mm(2). The crista fenestrae of the anterior component form a "doorstep" that may limit the entry to the scala tympani from the RW niche. Conclusion: The alternate anatomic features of the human RW may influence its surgical access and designs of implants aimed at targeting this region.

  • 17.
    Atturo, Francesca
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Barbara, Maurizio
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    On the Anatomy of the 'Hook' Region of the Human Cochlea and How It Relates to Cochlear Implantation2014In: Audiology & neuro-otology, ISSN 1420-3030, E-ISSN 1421-9700, Vol. 19, no 6, 378-385 p.Article in journal (Refereed)
    Abstract [en]

    Background: The optimal insertion route for an electrode array in hearing preservation cochlear implantation (CI) surgery is still tentative. Both cochleostomy (CO) and round window (RW) techniques are used today. In the present study we analyzed size variations and topographic anatomy of the 'hook' region of the human cochlea to better comprehend the Testo effects of various electric array insertion modes. Material and Methods: Size variations of the cochlear 'hook' region were assessed in 23 human, microdissected temporal bones by measuring the distances between the oval and round windows, also outlining the spiral ligament/spiral lamina. Influence of size variations on spiral ligament position and fundamentals for different surgical approaches were evaluated in a subset of 'small' and 'large' cochleae performing different types of CO. In addition, the relationship between the microdissected accessory canal housing the inferior cochlear vein and the RW was analyzed. Results: The lateral vestibular wall and the cochlear 'hook' displayed large anatomic variations that greatly influenced the size of the potential surgical area. Results showed that only very inferiorly located CO entered the scala tympani without causing trauma to the spiral ligament and spiral lamina. An inferior approach may challenge the inferior cochlear vein. Conclusion: Preoperative assessment of the distance between the round and oval windows may direct the surgeon before CI hearing- preservation surgery. CO techniques, especially in 'small' ears, may lead to frequent damage to the inner ear structures. In those cases with substantial residual hearing, CI surgery may be better performed through a RW approach.  

  • 18. Axelsson, S.
    et al.
    Berg, T.
    Jonsson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Engström, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Kanerva, M.
    Stjernquist-Desatnik, A.
    Bell's palsy: the effect of prednisolone and/or valaciclovir versus placebo in relation to baseline severity in a randomised controlled trial2012In: Clinical Otolaryngology, ISSN 1749-4478, E-ISSN 1365-2273, Vol. 37, no 4, 283-290 p.Article in journal (Refereed)
    Abstract [en]

    Objectives: To evaluate the treatment effect of prednisolone and/or valaciclovir in Bells palsy patients with different baseline severity of palsy.

    Design: Patient data were collected from the Scandinavian Bells Palsy Study, a prospective, randomised, double-blind, placebo-controlled, multi-centre trial.

    Setting: Sixteen otorhinolaryngological centres in Sweden and one in Finland.

    Participants: Altogether, 829 patients aged 1875 years were treated within 72 h of palsy onset. Patients were randomly assigned to treatment with prednisolone plus placebo (n = 210), valaciclovir plus placebo (n = 207), prednisolone plus valaciclovir (n = 206), placebo plus placebo (n = 206). Follow-up was 12 months.

    Main outcome measures: Facial function was assessed using the Sunnybrook grading scale at baseline and at 12 months. Complete recovery was defined as Sunnybrook score = 100.

    Results: All patients, regardless of baseline severity, showed significantly higher complete recovery rates if treated with prednisolone compared with no prednisolone. In patients with severe palsy, recovery at 12 months was 51% with prednisolone treatment versus 31% without prednisolone (P = 0.02). Corresponding results were 68%versus 51% (P = 0.004) for moderate, and 83%versus 73% (P = 0.02) for mild palsy. In patient groups with moderate and mild palsy at baseline, significantly fewer prednisolone-treated patients had synkinesis at 12 months (P = 0.04 and P < 0.0001, respectively). For patients with severe palsy at baseline, prednisolone versus no prednisolone made no significant difference regarding synkinesis at 12 months. Valaciclovir did not add any significant effect to prednisolone regarding recovery rate or synkinesis at 12 months.

    Conclusion: Prednisolone treatment resulted in higher complete recovery rates, regardless of severity at baseline. Prednisolone treatment should be considered in all patients irrespective of degree of palsy.

  • 19. Axelsson, Sara
    et al.
    Berg, Thomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Jonsson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Engström, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Kanerva, Mervi
    Pitkäranta, Anne
    Stjernquist-Desatnik, Anna
    Prednisolone in Bell's Palsy Related to Treatment Start and Age2011In: Otology and Neurotology, ISSN 1531-7129, E-ISSN 1537-4505, Vol. 32, no 1, 141-146 p.Article in journal (Refereed)
    Abstract [en]

    Objective: To evaluate if treatment start and age are related to the outcome in Bell's palsy patients treated with prednisolone. Study Design: Prospective, randomized, double-blind, placebo-controlled, multicenter trial. Setting: Sixteen otorhinolaryngologic centers in Sweden and 1 in Finland. Patients: Data were collected from the Scandinavian Bell's palsy study. A total of 829 patients were treated within 72 hours of onset of palsy. Follow-up was 12 months. Intervention: Patients were randomly assigned to treatment with placebo plus placebo (n = 206), prednisolone plus placebo (n = 210), valacyclovir plus placebo (n = 207), or prednisolone plus valacyclovir (n = 206). Main Outcome Measures: Facial function was assessed with the Sunnybrook grading system, and complete recovery was defined as Sunnybrook = 100. Time from onset of palsy to treatment start was registered. Results: Patients treated with prednisolone within 24 hours and 25 to 48 hours had significantly higher complete recovery rates, 66% (103/156) and 76% (128/168), than patients given no prednisolone, 51% (77/152) and 58% (102/177) (p = 0.008 and p = 0.0003, respectively). For patients treated within 49 to 72 hours of palsy onset, there were no significant differences. Patients aged 40 years or older had significantly higher complete recovery rates if treated with prednisolone, whereas patients aged younger than 40 years did not differ with respect to prednisolone treatment. However, synkinesis was significantly less in patients younger than 40 years given prednisolone (p = 0.002). Conclusion: Treatment with prednisolone within 48 hours of onset of palsy resulted in significantly higher complete recovery rates and less synkinesis compared with no prednisolone.

  • 20. Bagger-Sjoback, Dan
    et al.
    Strömbäck, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Hakizimana, Pierre
    Plue, Jan
    Larsson, Christina
    Hultcrantz, Malou
    Papatziamos, Georgios
    Smeds, Henrik
    Danckwardt-Lilliestrom, Niklas
    Department of Otolaryngology, Academic Hospital, Uppsala, Sweden.
    Hellstrom, Sten
    Johansson, Ann
    Tideholm, Bo
    Fridberger, Anders
    A Randomised, Double Blind Trial of N-Acetylcysteine for Hearing Protection during Stapes Surgery2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 3, e0115657Article in journal (Refereed)
    Abstract [en]

    Background Otosclerosis is a disorder that impairs middle ear function, leading to conductive hearing loss. Surgical treatment results in large improvement of hearing at low sound frequencies, but high-frequency hearing often suffers. A likely reason for this is that inner ear sensory cells are damaged by surgical trauma and loud sounds generated during the operation. Animal studies have shown that antioxidants such as N-Acetylcysteine can protect the inner ear from noise, surgical trauma, and some ototoxic substances, but it is not known if this works in humans. This trial was performed to determine whether antioxidants improve surgical results at high frequencies. Methods We performed a randomized, double-blind and placebo-controlled parallel group clinical trial at three Swedish university clinics. Using block-stratified randomization, 156 adult patients undergoing stapedotomy were assigned to intravenous N-Acetylcysteine (150 mg/kg body weight) or matching placebo (1:1 ratio), starting one hour before surgery. The primary outcome was the hearing threshold at 6 and 8 kHz; secondary outcomes included the severity of tinnitus and vertigo. Findings One year after surgery, high-frequency hearing had improved 2.7 +/- 3.8 dB in the placebo group (67 patients analysed) and 2.4 +/- 3.7 dB in the treated group (72 patients; means +/- 95% confidence interval, p = 0.54; linear mixed model). Surgery improved tinnitus, but there was no significant intergroup difference. Post-operative balance disturbance was common but improved during the first year, without significant difference between groups. Four patients receiving N-Acetylcysteine experienced mild side effects such as nausea and vomiting. Conclusions N-Acetylcysteine has no effect on hearing thresholds, tinnitus, or balance disturbance after stapedotomy.

  • 21. Bagger-Sjoback, Dan
    et al.
    Strömbäck, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Hultcrantz, Malou
    Papatziamos, Georgios
    Smeds, Henrik
    Danckwardt-Lillieström, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Tideholm, Bo
    Johansson, Ann
    Hellstrom, Sten
    Hakizimana, Pierre
    Fridberger, Anders
    High-frequency hearing, tinnitus, and patient satisfaction with stapedotomy: A randomized prospective study2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, 13341Article in journal (Refereed)
    Abstract [en]

    Otosclerosis is a common disorder that leads to conductive hearing loss. Most patients with otosclerosis also have tinnitus, and surgical treatment is known to improve hearing as well as tinnitus. Some patients however experience worsening of tinnitus after the operation, but there are no known factors that allow surgeons to predict who will be at risk. In this prospective observational study on 133 patients undergoing stapedotomy, we show that postoperative air conduction thresholds at very high stimulus frequencies predict improvement of tinnitus, as assessed with proportional odds logistic regression models. Young patients were significantly more likely to experience reduction of tinnitus and patients whose tinnitus became better were also more satisfied with the outcome of the operation. These findings have practical importance for patients and their surgeons. Young patients can be advised that surgery is likely to be beneficial for their tinnitus, but a less positive message should be conveyed to older patients.

  • 22. Bagger-Sjöbäck, Dan
    et al.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Pathology of the vestibular organ2008In: Scott-Brown textbook of otolaryngology / [ed] Michael Gleeson, London: Hodder Arnold , 2008, 7, 3147-3157 p.Chapter in book (Other (popular science, discussion, etc.))
  • 23.
    Bengtsson, Caroline
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Jonsson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Holmstrom, M.
    Svensson, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Theorell-Haglöw, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Lindberg, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Impact of nasal obstruction on sleep quality - a community based study of women2014In: Journal of Sleep Research, ISSN 0962-1105, E-ISSN 1365-2869, Vol. 23, 149-149 p.Article in journal (Other academic)
  • 24.
    Bengtsson, Caroline
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Jonsson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Holmström, Mats
    Svensson, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Theorell-Haglöw, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Lindberg, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Impact of nasal obstruction on sleep quality: a community-based study of women2015In: European Archives of Oto-Rhino-Laryngology, ISSN 0937-4477, E-ISSN 1434-4726, Vol. 272, no 1, 97-103 p.Article in journal (Refereed)
    Abstract [en]

    The aim of the study was to analyse the impact of self-reported nasal obstruction on sleep quality in women. A community-based sample of 400 women underwent a full night of polysomnography. Airway diseases, allergies and sleep-related symptoms were assessed by questionnaires. Women with subjective nasal obstruction were subdivided into three groups: persistent nasal obstruction (PNO, n = 46), hay fever (n = 88) and nasal obstruction at night (NON, n = 30). Sleep problems and related daytime symptoms were most prevalent among women with NON. After adjusting for age, BMI, smoking and asthma, NON was an independent predictor of 'Difficulties inducing sleep due to nasal obstruction' [adjusted odds ratio (95 % CI): 89.5 (27.0-296.7)], 'Snoring' [4.2 (1.7-10.2)], 'Sweating at night' [2.6 (1.1-6.1)], 'Difficulties maintaining sleep' [2.7 (1.2-6.2)], and 'Waking up hastily gasping for breath' [32.2 (8.7-119.1)]. 'Dry mouth on awakening' [7.7 (3.2-18.4)], 'Waking up unrefreshed' [2.7 (1.2-6.0)], 'Excessive daytime sleepiness' [2.6 (1.1-6.0)], and 'Daytime nasal obstruction' [12.2 (4.8-31.2)] were also associated with NON. Persistent nasal obstruction and hay fever were both associated with some reported sleep problems due to an overlap with NON. When women with NON were excluded, only 'Daytime nasal obstruction' was still significantly associated with PNO, while hay fever was associated with 'Daytime nasal obstruction' and 'Waking up hastily gasping for breath'. There were no significant differences in objectively measured sleep variables between any of the three subgroups and the study cohort. Self-reported nasal obstruction at night in women has a significant effect on several subjective day- and nighttime symptoms, but it does not appear to affect objectively measured sleep quality.

  • 25.
    Bengtsson, Caroline
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Lindberg, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Jonsson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Holmström, Mats
    Karolinska Univ Hosp, Dept Clin Sci Intervent & Technol, Div Ear Nose & Throat Dis, Huddinge, Sweden.
    Sundbom, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Hedner, Jan
    Sahlgrens Univ Hosp, Dept Sleep Med Resp Med & Allergol, Gothenburg, Sweden.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Middelveld, Roelinde
    Karolinska Inst, Ctr Allergy Res, Stockholm, Sweden.; Karolinska Inst, Inst Environm Med, Stockholm, Sweden.
    Forsberg, Bertil
    Umea Univ, Dept Publ Hlth & Clin Med, Occupat & Environm Med, Umea, Sweden.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Chronic rhinosinusitis impairs sleep quality: Results of the GA(2)LEN study2017In: Sleep, ISSN 0161-8105, E-ISSN 1550-9109, Vol. 40, no 1, zsw021Article in journal (Refereed)
    Abstract [en]

    STUDY OBJECTIVES: To analyse the prevalence of sleep problems in subjects with CRS and to determine whether the disease severity of CRS affects sleep quality.

    METHODS: Questionnaires were sent to a random sample of 45 000 adults in four Swedish cities. Questions on CRS, asthma, allergic rhinitis, co-morbidities, tobacco use, educational level and physical activity were included. CRS was defined according to the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) epidemiological criteria. The disease severity of CRS was defined by the number of reported CRS symptoms. Sleep quality was assessed using the Basic Nordic Sleep Questionnaire.

    RESULTS: Of the 26 647 subjects, 2249 (8.4%) had CRS. Reported sleep problems were 50-90% more common among subjects with CRS compared with those without or the total population. The prevalence of reported sleep problems increased in conjunction with the severity of CRS. After adjusting for gender, BMI, age, tobacco use, asthma, somatic diseases, physical activity level and educational level, participants with four symptoms of CRS (compared with subjects without CRS symptoms) displayed a higher risk of snoring (adj. OR (95% CI): 3.13 (2.22-4.41)), difficulties inducing sleep (3.98 (2.94-5.40)), difficulties maintaining sleep (3.44 (2.55-4.64)), early morning awakening (4.71 (3.47-6.38)) and excessive daytime sleepiness (4.56 (3.36-6.18)). The addition of persistent allergic rhinitis to CRS further increased the risk of sleep problems.

    CONCLUSIONS: Sleep problems are highly prevalent among subjects with CRS. The disease severity of CRS negatively affects sleep quality.

  • 26.
    Berg, Thomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Medical Treatment and Grading of Bell's Palsy2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The main aim of this thesis was to evaluate the effect of prednisolone and valaciclovir in a large number of Bell's palsy patients. The incidence and intensity of pain around the ear, in the face or in the neck during the first two months of palsy, and its prognostic value, was also assessed. We also investigated how study design and choice of analysis method affect the rate of facial recovery. Furthermore, the agreement between the Sunnybrook, House-Brackmann and Yanagihara facial grading systems was evaluated.

    From May 2001 to September 2007, a prospective, randomised, double-blind, placebo-controlled, multicentre trial with 12-month follow-up was performed in patients with Bell's palsy. Of 839 randomised patients, 829 were included in the intention-to-treat analysis; 206 received placebo plus placebo, 210 prednisolone plus placebo, 207 valaciclovir plus placebo, and 206 prednisolone plus valaciclovir. Time to recovery was significantly shorter in the 416 patients who received prednisolone compared with the 413 who did not (p<0.0001). At 12 months, 300 of 416 patients (72%) in the prednisolone group had recovered compared with 237 of 413 patients (57%) in the no prednisolone group (p<0.0001). Valaciclovir was not found to affect time to facial recovery or outcome at 12 months. Prednisolone and/or valaciclovir did not affect the incidence or intensity of pain. Presence of pain at day 11 to 17 indicated a worse prognosis for facial recovery at 12 months. We also found that recovery rates in a Bell's palsy trial are substantially affected by the choice of analysis method and definition of facial recovery.

    We used weighted Kappa statistics in 100 examinations of patients with facial palsy to assess the agreement between the Sunnybrook, House-Brackmann and Yanagihara scales. The highest agreement was found between the regional Sunnybrook and Yanagihara scales. An evaluative difference between the Sunnybrook and House-Brackmann systems was observed.

  • 27.
    Berg, Thomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Axelsson, Sara
    Engström, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Stjernquist-Desatnik, Anna
    Pitkaranta, Anne
    Kanerva, Mervi
    Jonsson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    The Course of Pain in Bell's Palsy: Treatment With Prednisolone and Valacyclovir2009In: Otology and Neurotology, ISSN 1531-7129, E-ISSN 1537-4505, Vol. 30, no 6, 842-846 p.Article in journal (Refereed)
    Abstract [en]

    Objective: To evaluate the effect of prednisolone and valacyclovir on ipsilateral pain around the ear and in the face or neck in Bell's palsy. The incidence and intensity of pain during the first 2 months of palsy and its prognostic value were also assessed. Study Design: Prospective, randomized, double-blind, placebo-controlled, multicenter trial. Setting: Sixteen tertiary referral centers in Sweden and 1 in Finland. Patients: Data are part of the Scandinavian Bell's palsy study; 829 patients aged 18 to 75 years with onset of palsy within 72 hours were included. Follow-up time was 12 months. Intervention: Patients were assigned to 1 of 4 treatment arms in a factorial fashion: placebo plus placebo; prednisolone 60 mg daily for 5 days, then tapering for 5 days, plus placebo; valacyclovir 1,000 mg 3 times daily for 7 days plus placebo; or prednisolone plus valacyclovir. Main Outcome Measures: Pain was registered on a visual analog scale within 72 hours, at Days 11 to 17, 1 month, and 2 months. Facial function was assessed with the Sunnybrook and House-Brackmann systems. Results: Prednisolone and/or valacyclovir did not significantly affect the incidence or intensity of pain during the first 2 months. Pain was registered in 542 (65%) of 829 patients. At 2 months, 53 (8%) of 637 patients still reported pain. Subjects with pain at Days 11 to 17 had lower facial recovery rates at 12 months than those with no pain (p < 0.0001). Conclusion: Prednisolone and/or valacyclovir did not affect the incidence or intensity of ipsilateral pain in Bell's palsy. The incidence of pain was similar during the first 2 weeks and then decreased. Presence of pain at Days 11 to 17 indicated a worse prognosis for facial recovery.

  • 28. Berg, Thomas
    et al.
    Bylund, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Marsk, Elin
    Jonsson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Kanerva, Mervi
    Hultcrantz, Malou
    Engström, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    The Effect of Prednisolone on Sequelae in Bell's Palsy2012In: Archives of Otolaryngology - Head & Neck Surgery, ISSN 0886-4470, E-ISSN 1538-361X, Vol. 138, no 5, 443-447 p.Article in journal (Refereed)
    Abstract [en]

    Objective: To study whether prednisolone reduces sequelae in Bell's palsy. Design: Prospective, randomized, double-blind, placebo-controlled, multicenter trial with 12 months of follow-up. Setting: Seventeen referral centers. Patients: In all, 829 patients aged 18 to 75 years. Interventions: Randomization within 72 hours in a factorial fashion to placebo plus placebo (n=206); prednisolone, 60 mg/d for 5 days, with the dosage then tapered for 5 days, plus placebo (n=210); valacyclovir hydrochloride, 1000 mg 3 times daily for 7 days, plus placebo (n=207); or prednisolone plus valacyclovir (n=206). Main Outcome Measures: Facial function at 12 months assessed with the Sunnybrook and House-Brackmann grading systems. Results: In 184 of the 829 patients, the Sunnybrook score was less than 90 at 12 months; 71 had been treated with prednisolone and 113 had not (P<.001). In 98 patients, the Sunnybrook score was less than 70; 33 had received prednisolone and 65 had not (P<.001). The difference between patients who received prednisolone and who did not in House-Brackmann gradings higher than I and higher than II was also significant (P<.001 and P=.01, respectively). No significant difference was found between patients who received prednisolone and those who did not in Sunnybrook scores less than 50 (P=.10) or House-Brackmann grades higher than III (P=.80). Synkinesis was assessed with the Sunnybrook score in 743 patients. Ninety-six patients had a synkinesis score more than 2, of whom 33 had received prednisolone and 63 had not (P=.001). Sixty patients had a synkinesis score more than 4, of whom 22 had received prednisolone and 38 had not (P=.005). Conclusion: Prednisolone significantly reduces mild and moderate sequelae in Bell's palsy.

  • 29.
    Berg, Thomas
    et al.
    Department of Plastic Surgery, Rigshospitalet, Oslo.
    Jonsson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Are patients with Bell's palsy receiving the right treatment?2015In: Tidsskrift for Den norske lægeforening, ISSN 0029-2001, E-ISSN 0807-7096, Vol. 135, no 11, 1026-1027 p.Article in journal (Refereed)
  • 30.
    Berg, Thomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Jonsson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    In Response to The Effect of Study Design and Analysis Methods on Recovery Rates in Bell's Palsy2010In: The Laryngoscope, ISSN 0023-852X, E-ISSN 1531-4995, Vol. 120, no 3, 653-653 p.Article in journal (Refereed)
  • 31. Berg, Thomas
    et al.
    Jonsson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Peripheral Neuropathies: Corticosteroids And Antivirals In Bell Palsy2013In: Nature Reviews Neurology, ISSN 1759-4758, E-ISSN 1759-4766, Vol. 9, no 3, 128-129 p.Article in journal (Other academic)
    Abstract [en]

    The treatment of Bell palsy remains a matter of debate. A recent update of the American Academy of Neurology practice parameter concluded that corticosteroids should be offered to increase the probability of facial nerve recovery. The benefits of antiviral treatment, however, have not been established.

  • 32.
    Berg, Thomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Jonsson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Engström, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Agreement between the Sunnybrook, House-Brackmann, and Yanagihara facial nerve grading systems in Bell´s Palsy2004In: Otology and Neurotology, ISSN 1531-7129, E-ISSN 1537-4505, Vol. 25, no 6, 1020-1026 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    To assess the agreement between the Sunnybrook facial nerve grading system and the House-Brackmann and Yanagihara systems.

    STUDY DESIGN:

    Prospective clinical facial nerve grading.

    SETTING:

    Tertiary referral center.

    PATIENTS:

    One-hundred assessments, 94 in patients with Bell's palsy and 6 with herpes zoster.

    INTERVENTION:

    Diagnostic.

    MAIN OUTCOME MEASURES:

    Evaluation according to the weighted regional Sunnybrook system, the gross House-Brackmann system, and the unweighted regional Yanagihara system. Weighted kappa statistics was used to measure agreement between the grading systems.

    RESULTS:

    The average weighted kappa value between the Sunny-brook, House-Brackmann, and Yanagihara grading systems was 0.65; kappa values increased temporally (but not statistically significantly) up to day 180. The highest agreement value, 0.72, was found between the Sunnybrook and Yanagihara grading systems. The weighted kappa value between the Sunnybrook and House-Brackmann systems was 0.59. In Sunnybrook gradings less than 63, there was an overlap between House-Brackmann scores of III to VI. Reliable conversion tables between the gross House-Brackmann system and the regional Sunnybrook and Yanagihara systems could not be established.

    CONCLUSION:

    The Sunnybrook system scores at the same agreement level as the House-Brackmann and Yanagihara grading systems. There is an evaluative difference between the weighted regional Sunnybrook and the gross House-Brackmann systems. Substantial agreement was found between the regional Sunnybrook and Yanagihara scales. Sunnybrook grading is easy and quick. By adding objective measurements and additional secondary defects, the Sunnybrook system can be an alternative to the other predominating grading systems.

  • 33. Berg, Thomas
    et al.
    Marsk, Elin
    Engström, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Hultcrantz, Malou
    Hadziosmanovic, Nermin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    Jonsson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    The Effect of Study Design and Analysis Methods on Recovery Rates in Bell's Palsy2009In: The Laryngoscope, ISSN 0023-852X, E-ISSN 1531-4995, Vol. 119, no 10, 2046-2050 p.Article in journal (Refereed)
    Abstract [en]

    Objectives/Hypothesis: We investigated how study design affects the rate of recovery in Bell's palsy. Study Design: Prospective, randomized, double-blind, placebo-controlled, multicenter trial. Methods: Data were extracted from the Scandinavian Bell's palsy study, which included 829 patients. The study design was factorial; 416 patients given prednisolone, 413 not given prednisolone, 413 patients given valacyclovir, 416 not given valacyclovir. Data were analyzed with intention-to-treat principle and complete-case analysis methods and recovery was defined as Sunnybrook score 100, House-Brackmann grade I or <= grade II at 12 months. Results: With the intention-to-treat principle and last-observation-carried-forward method (n = 829) and recovery defined as Sunnybrook 100, 300 of the 416 patients (72%) receiving prednisolone had recovered compared with 237 of the 413 (57%) who did not receive prednisolone (P < .0001). With recovery defined as House-Brackmann grade 1, the corresponding recovery rates were 324 of 416 (78%) and 266 of 413 (64%) (P < .0001). With complete-case analysis and recovery defined House-Brackmann grade I (n = 782), 335 of 389 patients (86%) given prednisolone recovered compared with 277 of 393 (70%) in the group not given prednisolone (P < .0001). With recovery defined as House-Brackmann <= grade II (n = 797), the corresponding recovery rates were 380 of 396 (96%) and 353 of 401 (88%) (P < .0001). The analysis method affected the recovery rates in the valacyclovir and no-valacyclovir groups in a similar way as in the prednisolone and no-prednisolone groups. Conclusions: Recovery rates in a Bell's palsy study are substantially affected by the choice of analysis method and definition of recovery.

  • 34.
    Berg, Thomas
    et al.
    Department of Plastic Surgery, Rigshospitalet, Oslo.
    Stjernquist-Desatnik, Anna
    Kanerva, Mervi
    Hultcrantz, Malou
    Engström, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Jonsson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Bells pares ger resttillstånd hos 30 procent av vuxna patienter: Tidig behandling med kortison ökar utläkningen2015In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 112, 1-5 p., C6RDArticle in journal (Refereed)
  • 35.
    Berglin, Cecilia Engmer
    et al.
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Otorhinolaryngol, Stockholm, Sweden..
    Pierre, Pernilla Videhult
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery. Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden..
    Ekborn, Andreas
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Otorhinolaryngol, Stockholm, Sweden..
    Bramer, Tobias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Edsman, Katarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Hultcrantz, Malou
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Otorhinolaryngol, Stockholm, Sweden..
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Local treatment of the inner ear: A study of three different polymers aimed for middle ear administration2015In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 135, no 10, 985-994 p.Article in journal (Refereed)
    Abstract [en]

    Conclusion: A formulation based on sodium hyaluronate (NaHYA) was the most promising candidate vehicle for intra-tympanic drug administration regarding conductive hearing loss, inflammatory reactions, and elimination. Objectives: Recent advances in inner ear research support the idea of using the middle ear cavity for drug administration to target the inner ear. This paper presents rheological and safety assessments of three candidate polymer formulations for intra-tympanic drug administration. Method: The formulations were based on sodium carboxymethyl cellulose (NaCMC), sodium hyaluronate (NaHYA), and poloxamer 407 (POL). Rheological studies were performed with a controlled rate instrument of the couette type. Safety studies were performed in guinea pigs subjected to an intra-tympanic injection of the formulations. Hearing function was explored with ABR before and 1, 2, and 3 weeks after the injection. Elimination of the formulations marked with coal was explored with an endoscopic digital camera 1, 2, and 3 weeks after injection. Middle and inner ear morphology was examined with light microscopy 6 days after injection. Results: The results speak in favor of NaHYA, since it did not cause prolonged hearing threshold elevations. The results of the elimination and morphological investigations support the conclusion of NaHYA being the most promising candidate for intra-tympanic administration.

  • 36. Berglin, Cecilia Engmér
    et al.
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Bramer, Tobias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Edsman, Katarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Counter, S Allen
    Klason, Tomas
    Ekborn, Andreas
    Magnetic Resonance Imaging of the Middle and Inner Ear After Intratympanic Injection of a Gadolinium-Containing Gel2014In: Otology and Neurotology, ISSN 1531-7129, E-ISSN 1537-4505, Vol. 35, no 3, 526-532 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    To investigate the distribution and elimination of a gadolinium containing high viscosity formulation of sodium hyaluronan (HYA gel) after injection to the middle ear.

    MATERIALS AND METHODS:

    The T1 contrast agent gadolinium-diethylenetriamine pentaacetic acid-bis methylamine (Gd-DTPA-BMA) was added to HYA gel and delivered to the middle ear of 13 albino guinea pigs by 3 different ways of injection. Magnetic resonance imaging was performed with a 4.7 T MRI system using a T1-weighted 3-dimentional rapid acquisition with relaxation enhancement sequence.

    RESULTS:

    An injection technique where the Gd-DTPA-BMA-containing HYA gel was delivered to the middle ear through a percutaneous injection through the auditory bulla after a small incision had been made in the tympanic membrane gave the best filling of the middle ear, covering the cochlea and the region of the round window niche for 24 hours in a majority of the ears studied. Ears injected without an incision in the tympanic membrane showed an immediate uptake of Gd-DTPA-BMA in the inner ear as a sign of rupture of the round window membrane.

    CONCLUSION:

    A percutaneous injection of a HYA gel into the tympanic bulla is distributed in a predictable way and gives a good filling of the middle ear cavity. The HYA gel remains in close vicinity to the RWM for more than 24 hours. Injection should be performed after an incision of the tympanic membrane has been made to prevent rupture of the round window membrane.

  • 37.
    Bergqvist, David
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Engström, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Tumörer i glomus caroticum: en multidisciplinär angelägenhet2009In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 106, no 20, 1362-1363 p.Article in journal (Refereed)
    Abstract [en]

    Carotid Body Tumours (CBT) are rare. In Sweden 1997-2006 only 28 operations were registered in the National Inpatient Registry, 2.8/year. Especially large tumours constitute a surgical challenge. This paper reports on the Uppsala experience of treating these tumours. Principles for diagnosis and treatment are discussed. A centralization is suggested.

  • 38.
    Berling Holm, Katarina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Knutsson, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Strömbäck, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Danckwardt-Lillieström, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Papatziamos, Georgios
    Rosenblad, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    von Unge, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Taste disturbance after stapes surgery: an evaluation of frequency, severity, duration, and quality-of-life2017In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 37, no 1, 39-43 p.Article in journal (Refereed)
    Abstract [en]

     

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

     

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

     

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

     

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

  • 39.
    Berling, Katarina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Mannstrom, Paula
    Ulfendahl, Mats
    Lillieström, Niklas Danckwardt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Von Unge, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    The chorda tympani degenerates during chronic otitis media: an electron microscopy study2015In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 135, no 6, 542-548 p.Article in journal (Refereed)
    Abstract [en]

    Conclusion: Chorda tympani nerve specimens from ears with chronic inflammatory middle ear disease exhibit structural signs of degeneration. These correlate well with taste disturbance. Simultaneously, they exhibit signs of regeneration, which may explain the ability for taste recovery. Objectives: The chorda tympani, the major taste nerve, runs uncovered through the middle ear cavity. This situation exposes it to various forms of middle ear pathology. A difference has been noticed regarding taste symptoms pre- and postoperatively between inflammatory and non-inflammatory diseases. The present study aimed to investigate ultrastructural changes of chorda tympani in different forms of inflammatory middle ear disease, such as chronic suppurative otitis media and cholesteatoma, as compared with normal. Methods: Five chorda tympani specimens were collected from healthy middle ears of patients subjected to surgery for acoustic neuroma, to be used as normal controls, and five from middle ears with chronic otitis media or cholesteatoma, where the nerve could not be saved during the operation. Light and electron microscopy were performed. Results: For all five nerves from diseased ears, microscopy showed a higher percentage of axon and myelin sheath degeneration than in the normal controls. Furthermore, three of the five also exhibited sprouting.

  • 40.
    Björck, Martin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Bergqvist, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Engström, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Glomustumörer, en kärlkirurgisk utmaning som kräver ett multidisciplinärt samarbete2009In: Svensk Kirurgi, ISSN 0346-847X, Vol. 67, no 3 Suppl., 35- p.Article in journal (Refereed)
  • 41.
    Bohman, Anton
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Oscarsson, Martin
    Holmberg, Kenneth
    Johansson, Leif
    Millqvist, Eva
    Nasic, Salmir
    Torinsson-Naluai, Asa
    Bende, Mats
    Heredity of nasal polyps2015In: Rhinology, ISSN 0300-0729, E-ISSN 1996-8604, Vol. 53, no 1, 25-28 p.Article in journal (Refereed)
    Abstract [en]

    Background: Nasal polyps is a common disease but little is known about its' pathogenesis. Our hypothesis was that there are genetic factors involved in the development of this disease. The aim of this study was to examine close relatives of patients with nasal polyps and comparing them with a general population with regard to prevalence of polyps. Methodology: Patients with nasal polyps who attended the clinic were recruited to the study and were asked whether they had any close adult relatives (siblings, parents or children). We intended to recruit two relatives per patient, one of each gender, for nasal endoscopy. The prevalence of nasal polyps in these relatives was compared with the prevalence of nasal polyps in a general population. Results: During a 4-year period, 368 patients and 410 relatives were recruited to the study. Although we were unable to recruit two close relatives for every patient, we were able to calculate nasal polyp prevalence within families as being 19.2%. Compared with the prevalence of nasal polyps among individuals in a general Swedish population from the same geographical area, the relative risk for polyps among relatives was almost five times higher. Conclusion: This study strongly indicates that heredity is a factor of importance for development of nasal polyps.

  • 42. Boldrup, L.
    et al.
    Coates, P. J.
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Wilms, T.
    Fahraeus, R.
    Nylander, K.
    Downregulation of miRNA-424: a sign of field cancerisation in clinically normal tongue adjacent to squamous cell carcinoma2015In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 112, no 11, 1760-1765 p.Article in journal (Refereed)
    Abstract [en]

    Background: The overall survival for patients with squamous cell carcinoma of the tongue is low and the search for early diagnostic and prognostic markers is thus essential. MicroRNAs have been suggested as potential prognostic and diagnostic candidates in squamous cell carcinoma of head and neck in general. Methods: On the basis of the known differences between sub-sites within the oral cavity, we investigated the expression and role of microRNA-424 in squamous cell carcinoma arising in tongue. MicroRNA levels were measured by qRT-PCR in both tissue and plasma samples. Results: Levels of microRNA-424 were upregulated in tongue squamous cell carcinoma, but not in tumours originating from gingiva or floor of the mouth. Interestingly, microRNA-424 was downregulated in clinically normal tongue tissue next to tumour compared with completely healthy tongue, indicating that microRNA-424 could be a marker of field cancerisation in this tumour type. However, expression of microRNA-424 in a tongue-derived epithelial cell line revealed no significant changes in the expression profile of proteins and genes. Conclusions: Our patient data show that microRNA-424 alterations are a marker of field cancerisation specific for tongue tumourigenesis, which also could have a role in development of tongue squamous cell carcinoma.

  • 43.
    Boldrup, Linda
    et al.
    Umea Univ, Dept Med Biosci Pathol, SE-90185 Umea, Sweden..
    Gu, Xiaolian
    Umea Univ, Dept Med Biosci Pathol, SE-90185 Umea, Sweden..
    Coates, Philip J.
    Masaryk Mem Canc Inst, RECAMO, Brno 65653, Czech Republic..
    Norberg-Spaak, Lena
    Umea Univ, Dept Clin Sci ENT, SE-90185 Umea, Sweden..
    Fahraeus, Robin
    Umea Univ, Dept Med Biosci Pathol, SE-90185 Umea, Sweden.;Masaryk Mem Canc Inst, RECAMO, Brno 65653, Czech Republic.;Univ Paris 07, Hop St Louis, Inst Genet Mol, F-75010 Paris, France..
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery. Umea Univ, Dept Clin Sci ENT, SE-90185 Umea, Sweden.
    Wilms, Torben
    Umea Univ, Dept Clin Sci ENT, SE-90185 Umea, Sweden..
    Nylander, Karin
    Umea Univ, Dept Med Biosci Pathol, SE-90185 Umea, Sweden..
    Gene expression changes in tumor free tongue tissue adjacent to tongue squamous cell carcinoma2017In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 8, no 12, 19389-19402 p.Article in journal (Refereed)
    Abstract [en]

    Due to the high frequency of loco-regional recurrences, which could be explained by changes in the field surrounding the tumor, patients with squamous cell carcinoma of head and neck show poor survival. Here we identified a total of 554 genes as dysregulated in clinically tumor free tongue tissue in patients with tongue tumors when compared to healthy control tongue tissue. Among the top dysregulated genes when comparing control and tumor free tissue were those involved in apoptosis (CIDEC, MUC1, ZBTB16, PRNP, ECT2), immune response (IFI27) and differentiation (KRT36). Data suggest that these are important findings which can aid in earlier diagnosis of tumor development, a relapse or a novel squamous cell carcinoma of the tongue, in the absence of histological signs of a tumor.

  • 44.
    Bondza, Sina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
    Stenberg, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
    Nestor, Marika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Andersson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
    Björkeund, Hanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
    Conjugation Effects on Antibody-Drug Conjugates: Evaluation of Interaction Kinetics in Real Time on Living Cells2014In: Molecular Pharmaceutics, ISSN 1543-8384, E-ISSN 1543-8392, Vol. 11, no 11, 4154-4163 p.Article in journal (Refereed)
    Abstract [en]

    Antibody-drug conjugates (ADC) have shown promising effects in cancer therapy by combining the target specificity of an antibody with the toxicity of a chemotherapeutic drug. As the number of therapeutic antibodies is significantly larger than those used as ADCs, there is unused potential for more effective therapies. However, the conjugation of an additional molecule to an antibody may affect the interaction with its target, altering association rate, dissociation rate, or both. Any changes of the binding kinetics can have subsequent effects on the efficacy of the ADCs, thus the kinetics are important to monitor during ADC development and production. This paper describes a method for the analysis of conjugation effects on antibody binding to its antigen, using the instrument LigandTracer and a fluorescent monovalent anti-IgG binder denoted FIBA, which did not affect the interaction. All measurements were done in real time using living cells which naturally expressed the antigens. With this method the binding profiles of different conjugations of the therapeutic anti-EGFR antibody cetuximab and the anti-CD44v6 antibody fragment AbD15171 were evaluated and compared. Even comparatively small modifications of cetuximab altered the interaction with the epidermal growth factor receptor (EGFR). In contrast, no impact on the AbD15171-CD44v6 interaction was observed upon conjugation. This illustrates the importance to study the binding profile for each ADC combination, as it is difficult to draw any general conclusion about conjugation effects. The modification of interaction kinetics through conjugation opens up new possibilities when optimizing an antibody or an ADC, since the conjugations can be used to create a binding profile more apt for a specific clinical need.

  • 45.
    Borota, Ljubisa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Mahmoud, Ehab
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Nyberg, Christoffer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Ekberg, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Combined percutaneous and transarterial devascularisation of juvenile nasopharyngeal angiofibroma with protection of internal carotid artery: A modification of the technique2015In: Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences, ISSN 1591-0199, Vol. 21, no 3, 390-396 p.Article in journal (Refereed)
    Abstract [en]

    Juvenile nasal angiofibroma (JNA) is a hypervascularised, benign, but locally aggressive tumour that grows in the posterior, upper part of the nasal cavity and invades surrounding anatomical structures. The treatment of choice is surgical removal, but complete resection of the tumour can be hampered because of profuse perioperative bleeding. Preoperative embolisation of the tumour has been proposed as an effective method for prevention of perioperative bleeding, thereby shortening of the time of the operation. In this report of five cases, we describe successful preoperative devascularisation of the tumour by applying a modified method of direct intratumoural injection of the liquid embolic agent Onyx combined with protection of the internal carotid artery. The control of bleeding during the embolisation and occlusion of the maxillary or sphenopalatine artery was achieved by using a bi-luminal balloon catheter. Such use of the dual-lumen catheter in treatment of JNA has not been reported so far in the medical literature.

  • 46.
    Boström, Marja
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Khalifa, Shaden
    Boström, Henrik
    Liu, Wei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Friberg, Ulla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Effects of Neurotrophic Factors on Growth and Glial Cell Alignment of Cultured Adult Spiral Ganglion Cells2009In: Audiology & neuro-otology, ISSN 1420-3030, E-ISSN 1421-9700, Vol. 15, no 3, 175-186 p.Article in journal (Refereed)
    Abstract [en]

    Adult spiral ganglion cells were cultured in chorus to assess the influence of the neurotrophins brain-derived neurotrophic factor, neurotrophin 3 and glial cell line-derived neurotrophic factor (GDNF) on neurite growth and Schwann cell alignment. Over 1500 measurements were collected using each factor at 10 ng/ml and all three in combination. Evaluation was made with GDNF at concentrations of up to 100 ng/ml. Neurite dimensions were assessed at days 5, 7, 9 and 11 using a computer-based program (Axon Analyzer). GDNF had a strong effect on spiral ganglion cell growth almost attaining the level of all three factors in combination. GDNF increased glial cell alignment and nerve bundle formation. Results show the potential of GDNF to maintain and possibly restore auditory nerve integrity.

  • 47.
    Botling, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Edlund, Karolina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Segersten, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Tahmasebpoor, Simin
    Engström, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Sundström, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Malmström, Per-Uno
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Micke, Patrick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Impact of thawing on RNA integrity and gene expression analysis in fresh frozen tissue2009In: Diagnostic molecular pathology (Print), ISSN 1052-9551, E-ISSN 1533-4066, Vol. 18, no 1, 44-52 p.Article in journal (Refereed)
    Abstract [en]

    Biobanks of fresh, unfixed human tissue represent a valuable source for gene expression analysis in translational research and molecular pathology. The aim of this study was to evaluate the impact of thawing on RNA integrity and gene expression in fresh frozen tissue specimens. Portions of snap frozen tonsil tissue, unfixed or immersed in RNAlater, were thawed at room temperature for 0 minute, 5 minutes, 30 minutes, 45 minutes, 1 hour, 3 hours, 6 hours, and 16 hours before RNA extraction. Additionally, tonsil tissue underwent repetitive freezing and thawing cycles. RNA integrity was analyzed by microchip gel electrophoresis and gene expression by quantitative real-time polymerase chain reaction for selected genes (FOS, TGFB1, HIF1A, BCL2, and PCNA). Minimal RNA degradation was detected after 30 minutes of thawing in unfixed samples. This degradation was accompanied by relevant changes in gene expression for FOS and BCL2 at 45 minutes. Modified primer design or the use of different housekeeping genes could not rectify the changes for FOS. Repetitive thawing cycles had similar effects on RNA integrity. The incubation of the tissue in RNAlater efficiently prevented RNA degradation. In conclusion, degradation of RNA in frozen tissue occurs first after several minutes of thawing. Already minimal decrease in RNA quality may result in significant changes in gene expression patterns in clinical tissue samples.

  • 48. Briem, Birgir
    et al.
    Thorvardsson, Ornolfur
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Petersen, Hannes
    Acute epiglottitis in Iceland 1983-20052009In: Auris, nasus, larynx, ISSN 0385-8146, E-ISSN 1879-1476, Vol. 36, no 1, 46-52 p.Article in journal (Refereed)
    Abstract [en]

    Objective: To describe the changes in the epidemiology of epiglottitis in Iceland from 1983 to 2005. Methods: All patients with the discharge diagnosis of epiglottitis during the study years were identified and diagnosis confirmed by chart review. Main outcome measures were age, gender, month/year of diagnosis, microbiology, airway management, ICU admissions, choice of antibiotics, length of hospital stay and major complications/mortality. Results: Fifty-seven patients were identified (annual incidence 0.93/100.000). The mean age was 33.3 years (1-82). Childhood epiglottitis disappeared after introduction of Haemophilus influenzae type b (Hib) vaccination in 1989 but adult disease showed non-significant increase. In the pre-vaccination era Hib was the most common organism cultured but it has not been diagnosed in Iceland since 1991 and Streptococci are now the leading cause of epiglottitis. The mean hospital stay was 5.05 nights with 51% of patients admitted to ICU. All children under 10 years and a total 30% of patients received airway intervention. Ninety percent of adults were observed without airway intervention. Major complications were rare and mortality was 0% in our series. Conclusion: There have been major changes in the epidemiology of epiglottitis in Iceland during the study period. Previously a childhood disease, epiglottitis has disappeared in children and is now almost exclusively found in adults. This can be attributed to widespread Hib vaccination, eliminating the major causative agent in children. The treatment of this life-threatening disease remains a challenge. Our series suggest that it is safe to observe patients with mild/moderate symptoms without airway intervention.

  • 49. Brown, Toby D
    et al.
    Edin, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Detta, Nicola
    Skelton, Anthony D
    Hutmacher, Dietmar W
    Dalton, Paul D
    Melt electrospinning of poly(ε-caprolactone) scaffolds: phenomenological observations associated with collection and direct writing.2014In: Materials science & engineering. C, biomimetic materials, sensors and systems, ISSN 0928-4931, E-ISSN 1873-0191, Vol. 45Article in journal (Refereed)
    Abstract [en]

    Melt electrospinning and its additive manufacturing analogue, melt electrospinning writing (MEW), are two processes which can produce porous materials for applications where solvent toxicity and accumulation in solution electrospinning are problematic. This study explores the melt electrospinning of poly(ε-caprolactone) (PCL) scaffolds, specifically for applications in tissue engineering. The research described here aims to inform researchers interested in melt electrospinning about technical aspects of the process. This includes rapid fiber characterization using glass microscope slides, allowing influential processing parameters on fiber morphology to be assessed, as well as observed fiber collection phenomena on different collector substrates. The distribution and alignment of melt electrospun PCL fibers can be controlled to a certain degree using patterned collectors to create large numbers of scaffolds with shaped macroporous architectures. However, the buildup of residual charge in the collected fibers limits the achievable thickness of the porous template through such scaffolds. One challenge identified for MEW is the ability to control charge buildup so that fibers can be placed accurately in close proximity, and in many centimeter heights. The scale and size of scaffolds produced using MEW, however, indicate that this emerging process will fill a technological niche in biofabrication.

  • 50.
    Bylund, Nina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Jensson, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Enghag, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Berg, T
    Marsk, E
    Hultcrantz, M
    Hadziosmanovic, Nermin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Rodriguez-Lorenzo, Andres
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Jonsson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Synkinesis in Bell's palsy in a randomised controlled trial2017In: Clinical Otolaryngology, ISSN 1749-4478, E-ISSN 1365-2273, Vol. 42, no 3, 673-680 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To study the development of synkinesis in Bell's palsy. Frequency, severity, gender aspects and predictors were analysed.

    DESIGN: Data from the randomised controlled Scandinavian Bell's palsy trial including 829 patients.

    MAIN OUTCOME MEASURES: Frequency and severity of synkinesis at 12 months were the main outcome measures. Mean Sunnybrook synkinesis scores, voluntary movement scores and composite scores between 6 and 12 months were compared.

    RESULTS: In 743 patients with a 12-month follow-up, synkinesis frequency was 21.3%. There was no gender difference. Synkinesis was moderate to severe in 6.6% of patients. Those with synkinesis at 6 months had a synkinesis score of 4.1 (±2.8 sd), which increased to 4.7 (±3.2) (P = 0.047) at 12 months (n = 93). Sunnybrook composite score at 1 month was the best predictor for synkinesis development with receiver operating characteristics and area under the curve (AUC) 0.87. Risk for synkinesis increased with a lower Sunnybrook composite score. Furthermore, at 1 month, symmetry of voluntary movement had higher predictive value for synkinesis than resting symmetry with AUC 0.87 and 0.77, respectively. Gentle eye closure and open-mouth smile were the only independent significant predictive items (AUC 0.86).

    CONCLUSIONS: Moderate-to-severe synkinesis was present in 6.6% of patients. The mean synkinesis score increased between 6 and 12 months, and outcome should therefore be evaluated after at least 12 months. Sunnybrook composite score and symmetry of voluntary movement at 1 month were good predictors for synkinesis.

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