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  • 301. Motohashi, Ray
    et al.
    Takumida, Masaya
    Shimizu, Akira
    Konomi, Ujimoto
    Fujita, Koji
    Hirakawa, Katsuhiro
    Suzuki, Mamoru
    Anniko, Matti
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Effects of age and sex on the expression of estrogen receptor alpha and beta in the mouse inner ear2010Inngår i: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 130, nr 2, s. 204-214Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Conclusion: Estrogen receptor (ER) alpha and beta were expressed in the inner ear, and expression decreased with increasing age. ER alpha may alter cochlear and vestibular sensory transduction, and ER beta may have a neuroprotective function in the inner ear. Objective: Expression of ER alpha and ER beta in the mouse inner ear and its alterations with sex and aging were analyzed. Materials and methods: Male and female CBA/J mice aged 8 weeks and 24 months were used. The localization and the intensity of ER alpha and ER beta immunoreactivity in the inner ear of young and old mice of both sexes were investigated by immunohistochemistry. Results: ER alpha and ER beta were co-expressed in the inner ear, i.e. in the nuclei of stria vascularis, outer and inner hair cells, spiral ganglion cells and vestibular ganglion cells, vestibular dark cells and endolymphatic sac. Strial marginal cells, outer hair cells and type II ganglion cells showed less expression of ER alpha. No gender-or age-related difference was noted in the expression pattern of ER alpha or ER beta but fluorescence intensity of ER alpha was stronger in young female mice than in voting male mice. In contrast, ER beta revealed no significant difference. In the old mice, fluorescence intensities of both ER alpha and ER beta were significantly decreased in both sexes.

  • 302. N, Browaldh
    et al.
    A, Markström
    Friberg, Danielle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Elective tracheostomy is an alternative treatment in patients with severe obstructive sleep apnoea syndrome and CPAP failure.2009Inngår i: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, s. 1121-1126Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Conclusions.Elective tracheostomy with custom-made tubes was tolerated in a majority of patients with severe obstructivesleep apnoea syndrome (OSAS), as it reduced daytime symptoms and served as a link to other treatments.Objectives.Toevaluate the tolerability of elective tracheostomy and changes in excessive daytime sleepiness and nocturnal oxygendesaturations (ODI) in patients with severe OSAS and obesity.Patients and methods.The medical records of 10 patients,median age 53.5 years (range 3177), BMI 36 kg/m2(3150), ODI 81 (55126) during a 5-year period were reviewed.Inclusion criteria were failure of continuous positive airway pressure (CPAP), acceptance of tracheostomy, excessivedaytime sleepiness and ODI50. All patients received a custom-made tube. Sleep apnoea recordings and questionnaireswith Epworth sleepiness scale (ESS) were performed before and after tracheostomy.Results.Eight of 10 patients toleratedthe tube for more than 6 months. The ESS score was reduced from median 18 (range 823) to 5 (07) and the ODI valuesfrom 81 (55126) to 13 (187). Two patients insisted on decannulation because they had nocturnal breathing problems,two underwent palatal surgery and were decannulated, and five still have their tubes. Severe cough, sputum infections andstoma granuloma were seen in all patients.

  • 303. N, Browaldh
    et al.
    Friberg, Danielle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    E, Svanborg
    P, Nerfeldt
    15-year efficacy of uvulopalatopharyngoplasty based on objective and subjective data2011Inngår i: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251Artikkel i tidsskrift (Fagfellevurdert)
  • 304. N, Browaldh
    et al.
    J, Bring
    Friberg, Danielle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    SKUP3: 6 and 24 months follow-up of changes in respiration and sleepiness after modified UPPP.2018Inngår i: The LaryngoscopeArtikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective

    Our previous randomized controlled trial of patients with obstructive sleep apnea syndrome (OSAS) showed that modified uvulopalatopharyngoplasty (UPPP), including tonsillectomy, significantly improved nocturnal respiration, daytime sleepiness, and quality of life in the intervention group compared to controls who had delayed surgery after 6 months. This is the continuous report with the 6‐ and 24‐month postoperative results.

    Study Design

    Single‐center prospective cohort study.

    Methods

    Sixty‐five patients with apnea–hypopnea index (AHI) ≥ 15, body mass index (BMI) < 36, Epworth Sleepiness Scale (ESS) ≥ 8, and Friedman stage I or II underwent UPPP after failing nonsurgical treatment. The results from polysomnography and ESS at 6 and 24 months were compared to baseline.

    Results

    Eight percent and 20% dropped out from the 6‐ and 24‐month follow‐ups, respectively. The AHI value decreased significantly from mean (standard deviation) 52.9 (20.5) at baseline to 23.6 (20.2) after 6 months, and to 24.1 (20.9) after 24 months (P < 0.001). Patients with tonsil size 2, and 3 to 4, had significant reductions in the AHI after both follow‐ups. The median ESS score decreased significantly from 13 (range 8–21) to 6.5 (1–18) after 6 months, and to 5 (2–17) after 24 months (P < 0.001). The BMI remained unchanged. There were significant modest correlations for the reductions in AHI and ESS after 24 months.

    Conclusion

    Modified UPPP was effective in improving nocturnal respiration and daytime sleepiness in OSAS patients at both 6‐ and 24‐month follow‐up. Patients with tonsil size 2, and 3 to 4, benefitted similarly from surgery with improved respiration.

  • 305. N, Browaldh
    et al.
    P, Nerfeldt
    M, Lysdahl
    J, Bring
    Friberg, Danielle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    SKUP3 randomised controlled trial: polysomnographic results after uvulopalatopharyngoplasty in selected patients with obstructive sleep apnoea.2013Inngår i: ThoraxArtikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective To assess the 6-month efficacy of uvulopalatopharyngoplasty (UPPP) compared with expectancy in selected patients with obstructive sleep apnoea syndrome (OSAS).

    Design A prospective single-centre randomised controlled trial with two parallel arms stratified by Friedman stage and body mass index (BMI).

    Participants 65 consecutive patients with moderate to severe OSAS (apnoea-hypopnoea index (AHI) ≥15 events/h sleep), BMI <36 kg/m2, Epworth sleepiness scale ≥8, Friedman stage I or II.

    Intervention Surgical treatment with UPPP. The control group underwent UPPP after a delay of 6 months.

    Outcomes Changes in AHI and other polysomnography parameters at baseline compared with the 6-month follow-up.

    Results All patients (32 in the intervention group and 33 in the control group) completed the trial. The mean (SD) AHI in the intervention group decreased significantly (p<0.001) by 60% from 53.3 (19.7) events/h to 21.1 (16.7) events/h . In the control group the mean AHI decreased by 11% from 52.6 (21.7) events/h to 46.8 (22.8) events/h, with a significant difference between the groups (p<0.001). The mean time in the supine position and the BMI were unchanged in both groups. Subgroup analyses for Friedman stage, BMI group and tonsil size all showed significant reductions in AHI in the intervention group compared with controls. There were no severe complications after surgery.

    Conclusions This trial demonstrates the efficacy of UPPP in treating selected patients with OSAS with a mean reduction in AHI of 60% compared with 11% in controls, a highly significant and clinically relevant difference between the groups.

    Trial registration number NCT01659671.

  • 306.
    Naessen, Tord
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Lindmark, Birgitta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Sjukgymnastik.
    Lagerström, Christel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Sjukgymnastik.
    Larsen, Hans-Christian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Persson, Ingemar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Early postmenopausal hormone therapy improves postural balance2007Inngår i: Menopause: The Journal of the North American Menopause, ISSN 1072-3714, E-ISSN 1530-0374, Vol. 14, nr 1, s. 14-19Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: Postmenopausal hormone therapy (HT) results in more substantial reductions in the risk of hip fracture when initiated sooner rather than later after menopause. We studied the effects of postmenopausal HT on the postural balance of postmenopausal women, with further assessment according to the time since they achieved menopause.

    Design: One hundred women with a mean age of 52.5 years (91 evaluable) were randomly and blindly assigned to either a sequential estradiol-norethisterone acetate regimen or placebo for 3 months, after which all participants received open HT for a further 3 months. Postural balance was assessed as sway velocity using a force platform.

    Results: After 3 months of HT, sway velocity had improved (decreased) from baseline by 7.0% (P = 0.007 vs baseline and P = 0.038 vs placebo). Continued HT for 6 months further improved sway velocity by 12% from baseline (P < 0.0001) to reach values similar to those historically found in younger women or in postmenopausal women after long-term HT. Closer proximity to menopause and more pronounced increases in serum estradiol values were associated with stronger improvements in sway velocity (P = 0.018 for interaction). HT also improved dizziness (P = 0.016 vs baseline and 0.022 vs placebo). (Nonparametric statistics are used throughout, except for analyses of interaction and dizziness.)

    Conclusions: Initiation of HT soon after menopause rapidly improved postural balance to levels normally seen in young women. We suggest that improved postural balance can contribute to the protection against fractures associated with HT and explain the more substantial reduction in hip fracture risk after HT initiated sooner, compared with later, after menopause. Further study is required to confirm these results.

  • 307. Nakagawa, H
    et al.
    Larsen, Hans Christian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Watanabe, Y
    Anniko, Matti
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Visual orientation in patients with Meniere's disease1995Inngår i: Meniere's Disease: Proceedings of the16th Danavox symposium, Kolding, Denmark / [ed] Vesterhauge, S., Katholm, M. and Mikines, P., Kolding, Denmark: Scanticon Publ , 1995, s. 135-138Konferansepaper (Annet vitenskapelig)
  • 308. Nakashimo, Yousuke
    et al.
    Takumida, Masaya
    Fukuiri, Takashi
    Anniko, Matti
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Hirakawa, Katsuhiro
    Expression of transient receptor potential channel vanilloid (TRPV) 1-4, melastin (TRPM) 5 and 8, and ankyrin (TRPA1) in the normal and methimazole-treated mouse olfactory epithelium2010Inngår i: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 130, nr 11, s. 1278-1286Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Conclusion: It is suggested that TRPV1, 2, 3, and 4, TRPM5 and 8, and TRPA1 may play several roles in the olfactory epithelium (OE), contributing to olfactory chemosensation, olfactory adaptation, olfactory-trigeminal interaction, and OE fluid homeostasis. In patients with olfactory disturbance, TRPV1 and TRPM8 may be closely related to a high rate of recognition of curry and menthol odors, while TRPV2 may also play a crucial role in the regeneration of olfactory receptor neurons. Objective: Expression of TRPV1-4, TRPM5 and 8, and TRPA1 in the normal and methimazole-treated mouse OE was analyzed. Methods: The localization of TRPV1-4, TRPM5 and 8, and TRPA1 in the OE of normal and methimazole-treated CBA/J mice was investigated by immunohistochemistry. Results: Normal OE showed a positive immunofluorescent reaction to TRPV1-4, TRPM5 and 8, and TRPA1. In lamina propria, the nerve fibers displayed TRPV 1, 2, and 3, TRPM8 and TRPA1. In the pathological condition, the expression of TRPV3, TRPV4, TRPM5, and TRPA1 was markedly reduced and took a long time to recover. In contrast, expression of TRPM8 was scarcely affected, even in the pathological condition, while TRPV1 and TRPV2 showed early recovery following methimazole treatment.

  • 309.
    Natan, Michal
    et al.
    Bar Ilan Univ, Mina & Everard Goodman Fac Life Sci, IL-52900 Ramat Gan, Israel.;Bar Ilan Univ, Ctr Adv Mat & Nanotechnol, IL-52900 Ramat Gan, Israel..
    Edin, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Perkas, Nina
    Bar Ilan Univ, Ctr Adv Mat & Nanotechnol, IL-52900 Ramat Gan, Israel.;Bar Ilan Univ, Dept Chem, IL-52900 Ramat Gan, Israel..
    Yacobi, Gila
    Bar Ilan Univ, Mina & Everard Goodman Fac Life Sci, IL-52900 Ramat Gan, Israel.;Bar Ilan Univ, Ctr Adv Mat & Nanotechnol, IL-52900 Ramat Gan, Israel..
    Perelshtein, Ilana
    Bar Ilan Univ, Ctr Adv Mat & Nanotechnol, IL-52900 Ramat Gan, Israel.;Bar Ilan Univ, Dept Chem, IL-52900 Ramat Gan, Israel..
    Segal, Elad
    Bar Ilan Univ, Ctr Adv Mat & Nanotechnol, IL-52900 Ramat Gan, Israel.;Bar Ilan Univ, Dept Chem, IL-52900 Ramat Gan, Israel..
    Homsy, Alexandra
    Univ Appl Sci Western Switzerland, Haute Ecole Arc Ingn, HES SO, Eplatures Grise 17, CH-2300 La Chaux De Fonds, Switzerland..
    Laux, Edith
    Univ Appl Sci Western Switzerland, Haute Ecole Arc Ingn, HES SO, Eplatures Grise 17, CH-2300 La Chaux De Fonds, Switzerland..
    Keppner, Herbert
    Univ Appl Sci Western Switzerland, Haute Ecole Arc Ingn, HES SO, Eplatures Grise 17, CH-2300 La Chaux De Fonds, Switzerland..
    Rask-Andersen, Helge
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Gedanken, Aharon
    Bar Ilan Univ, Ctr Adv Mat & Nanotechnol, IL-52900 Ramat Gan, Israel.;Bar Ilan Univ, Dept Chem, IL-52900 Ramat Gan, Israel..
    Banin, Ehud
    Bar Ilan Univ, Mina & Everard Goodman Fac Life Sci, IL-52900 Ramat Gan, Israel.;Bar Ilan Univ, Ctr Adv Mat & Nanotechnol, IL-52900 Ramat Gan, Israel..
    Two are Better than One: Combining ZnO and MgF2 Nanoparticles Reduces Streptococcus pneumoniae and Staphylococcus aureus Biofilm Formation on Cochlear Implants2016Inngår i: Advanced Functional Materials, ISSN 1616-301X, E-ISSN 1616-3028, Vol. 26, nr 15, s. 2473-2481Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Streptococcus pneumoniae (S. pneumoniae) and Staphylococcus aureus (S.aureus) are considered the most common colonizers of cochlear implants (CI), which have prompted the search for new ways to inhibit their growth and biofilm development. In the current study, CI-based platforms are prepared and sonochemically coated with ZnO or MgF2 nanoparticles (NPs), two agents previously shown to possess antibacterial properties. Additionally, a method is developed for coating both ZnO and MgF2 on the same platform to achieve synergistic activity against both pathogens. Each surface is characterized, and the optimal conditions for the NP homogenous distribution on the surface are determined. The ZnO-MgF2 surface significantly reduces the S. pneumoniae and S. aureus biofilm compared with the surfaces coated with either ZnO or MgF2, even though it contains smaller amounts of each NP type. Importantly, leaching assays show that the NPs remain anchored to the surface for at least 7 d. Finally, biocompatibility studies demonstrate that coating with low concentrations of ZnO-MgF2 results in no toxicity toward primary human fibroblasts from the auditory canal. Taken together, these findings underscore the potential of using NP combinations such as the one presented here to efficiently inhibit bacterial colonization and growth on medical devices such as CIs.

  • 310.
    Nestor, Marika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för biomedicinsk strålningsvetenskap.
    Conjugated Therapy: Cancer of the Head and Neck2010Inngår i: Targeted Radionuclide Therapy / [ed] Tod W. Speer, Philadelphia: Lippincott Williams & Wilkins , 2010Kapittel i bok, del av antologi (Annet vitenskapelig)
  • 311.
    Nestor, Marika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för biomedicinsk strålningsvetenskap.
    Effect of cetuximab treatment in squamous cell carcinomas2010Inngår i: Tumor Biology, ISSN 1010-4283, E-ISSN 1423-0380, Vol. 31, nr 2, s. 141-147Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The purpose of this study was to assess the effects of the monoclonal antibody cetuximab in a panel of cultured squamous cell carcinoma cell lines. This antibody, targeting the epidermal growth factor receptor (EGFR), is emerging as a promising agent for treatment of several cancers. As this antibody comes into clinical use, the identification of predictive markers of therapeutic benefit remains a pressing issue. Cells were first characterized according to EGFR expression, cell doubling time, and BRAF and K-ras mutations. The effects of cetuximab on cell-cycle distribution, proliferation, as well as cell growth rate were then evaluated. Cetuximab decreased cell proliferation in three out of four cell lines in a time-dependent manner, and all cell lines were found to exhibit wild type K-ras and BRAF genes. A possible correlation between EGFR expression and cetuximab effect on growth inhibition rate was observed, whereas reduction of cell doubling time seemed to be more dependent on initial growth rate. In addition, other factors may further influence the long-term treatment response of cetuximab. Moreover, the time-dependent manner of cetuximab response demonstrates the importance of long-term measurements for this substance.

  • 312.
    Nestor, Marika
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Andersson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för biomedicinsk strålningsvetenskap.
    Lundqvist, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för biomedicinsk strålningsvetenskap.
    Characterization of In-111 and Lu-177-labeled antibodies binding to CD44v6 using a novel automated radioimmunoassay2008Inngår i: Journal of Molecular Recognition, ISSN 0952-3499, E-ISSN 1099-1352, Vol. 21, nr 3, s. 179-183Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Targeted cancer therapies rely on bifunctional molecules, typically a protein that specifically recognizes tumor cells and a toxic component which is linked to the protein. Therefore, development of such therapies includes detailed characterizations of protein-cell interactions in order to find a good targeting agent. Knowledge of factors such as antibody-antigen specificity, as well as cellular uptake, retention and affinity of the antibody are necessary in order to be successful. In this paper, we have used a novel instrument, LigandTracer (R) Yellow, to characterize the interactions of In-111 and Lu-177-labeled monoclonal antibodies (MAbs) with CD44v6. Uptake studies with varying specific radioactivity of the chimeric MAb U36 and with an irrelevant antibody for the CD44v6 receptor verified the reliability of the method, as well as the specificity of the antibody-receptor binding. Uptake, retention, and affinity were very similar for the In-111 and Lu-177-labeled conjugate, and were in line with earlier studies using manual methods. The fact that no adverse effects from labeling were seen, together with the high retention, could make these conjugates promising candidates for imaging and therapy of certain cancer types in the future. The novel LigandTracer technology reduced the workload and reagent spending while providing data with superior time resolution. The obtained results were in agreement with previously reported findings. In addition the real-time detection and higher time resolution made more detailed studies of the interactions possible.

  • 313.
    Nestor, Marika
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Ekberg, Tomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Dring, John
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    van Dongen, Guus
    Wester, Kenneth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Tolmachev, Vladimir
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Anniko, Matti
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Quantification of CD44v6 and EGFR expression in head and neck squamous cell carcinomas using a single-dose radioimmunoassay2007Inngår i: Tumor Biology, ISSN 1010-4283, Vol. 28, nr 5, s. 253-263Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: In the growing field of tumor targeting, there is an urgent need to profile suitable molecular targets. In this study, CD44v6 and EGFR expression was quantified in samples of patients with head and neck squamous cell carcinoma (HNSCC) using a single-dose (SD) radioimmunoassay. Methods: The SD radioimmunoassay using 125I-chimeric monoclonal antibody (cMAb) U36 and 125I-cMAb cetuximab was first validated and then applied to quantify the expression of their target antigen molecules, CD44v6 and EGFR, in patient samples. Results were compared to immunohistochemical staining. Results: The SD assay provided sensitive quantitative values of the molecular targets studied, generally agreeing with the immunohistochemistry (IHC) results. The results indicated that expression of CD44v6 (0.2-20 nmol/μg membrane) was generally higher than that of EGFR (0.6-2.3 nmol/μg membrane) in the tumor samples analyzed, which corresponded to an average of 700,000 and 90,000 antigen molecules per cell, respectively. Conclusions: The SD radioimmunoassay is simple, reliable, and can be performed on a small amount (50 mg) of tissue. This assay could be a useful tool in the growing field of personalized cancer therapy, and can be used as a complement to IHC. In the tumors studied, CD44v6 was generally expressed at a higher level than EGFR, which might suggest that it could be more readily targeted by MAbs.

  • 314.
    Nestor, Marika
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för biomedicinsk strålningsvetenskap.
    Sundström, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Anniko, Matti
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Tolmachev, Vladimir
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för biomedicinsk strålningsvetenskap.
    Effect of cetuximab in combination with alpha-radioimmunotherapy in cultured squamous cell carcinomas2011Inngår i: Nuclear Medicine and Biology, ISSN 0969-8051, E-ISSN 1872-9614, Vol. 38, nr 1, s. 103-112Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aim

    The monoclonal antibody cetuximab, targeting the epidermal growth factor receptor (EGFR), is a promising molecular targeting agent to be used in combination with radiation for anticancer therapy. In this study, effects of cetuximab in combination with alpha-emitting radioimmunotherapy (RIT) in a panel of cultured human squamous cell carcinomas (SCCs) were assessed.

    Methods

    SCC cell lines were characterized and treated with cetuximab in combination with anti-CD44v6 RIT using the astatinated chimeric monoclonal antibody U36 (211At-cMAb U36). Effects on 211At-cMAb U36 uptake, internalization and cell proliferation were then assessed in SCC cells.

    Results

    Cetuximab in combination with 211At-cMAb U36 mediated increased growth inhibition compared to RIT or cetuximab alone in two cell lines. However, cetuximab also mediated radioprotective effects compared to RIT alone in two cell lines. The radioprotective effects occurred in the cell lines in which cetuximab clearly inhibited cell growth during radiation exposure. Cetuximab treatment also influenced 211At-cMAb-U36 uptake and internalization, suggesting interactions between CD44v6 and EGFR.

    Conclusions

    Results from this study demonstrate the vast importance of further clarifying the mechanisms of cetuximab and radiation response, and the relationship between EGFR and suitable RIT targets. This is important not only in order to avoid potential radioprotective effects, but also in order to find and utilize potential synergistic effects from these combinations.

  • 315.
    Nestor, Marika V.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för biomedicinsk strålningsvetenskap.
    Targeted radionuclide therapy in head and neck cancer2010Inngår i: Head and Neck, ISSN 1043-3074, E-ISSN 1097-0347, Vol. 32, nr 5, s. 666-678Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    There is great potential for targeted radionuclide therapy (TRT) in the treatment of head and neck cancer. In recent years, developments in fields such as antigen screening, protein engineering, and cancer biology have facilitated the rational design of targeted pharmaceuticals, with monoclonal antibodies forming the most rapidly expanding category. TRT may be a promising way to improve targeted treatment, especially in head and neck cancer, because of the intrinsic radiosensitivity of this tumor type. TRT may also provide a good foundation on which to build rational biologic combination therapies. In the next few years the use of TRT may offer new opportunities for further improvement of the therapeutic ratio that potentially may obviate or reduce the need for conventional cytotoxics.

  • 316. Nilsson, Olof
    et al.
    Norlander, Tomas
    Linder, Arne
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    ABC om främmande kropp i luftvägarna2012Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 109, nr 51-52, s. 2361-2365Artikkel i tidsskrift (Annet vitenskapelig)
  • 317. Nilvebrant, J.
    et al.
    Kuku, G.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap.
    Björkelund, Hanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för biomedicinsk strålningsvetenskap.
    Nestor, Marika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för biomedicinsk strålningsvetenskap. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Selection and characterisation of human CD44v6-binding antibody fragments for specific targeting of head and neck squamous cell carcinoma2012Inngår i: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 39, nr S2, s. S418-S418Artikkel i tidsskrift (Annet vitenskapelig)
  • 318. Nilvebrant, Johan
    et al.
    Kuku, Gamze
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för biomedicinsk strålningsvetenskap.
    Björkelund, Hanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för biomedicinsk strålningsvetenskap.
    Nestor, Marika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för biomedicinsk strålningsvetenskap. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Selection and in vitro characterization of human CD44v6-binding antibody fragments2012Inngår i: Biotechnology and applied biochemistry, ISSN 0885-4513, E-ISSN 1470-8744, Vol. 59, nr 5, s. 367-380Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The cluster of differentiation (CD) 44v6 antigen has been suggested to be involved in tumor formation, invasion, and metastasis formation, and has been observed in a majority of primary and metastatic squamous cell carcinomas of the head and neck. Probes specifically binding to this region may be utilized as tools for the challenging tasks of early detection and targeted treatments of small residual disease. In this project, an epitope-guided phage display selection of human fragment antigen-binding (Fab) fragments with affinity to the v6 sequence was performed. A selected set of Fab fragments was shown to specifically recognize increasingly complex forms of the target sequence, both in the form of a short synthetic or recombinant peptide and in the context of a purified extracellular domain of CD44. The binding was independent of known v6-sequence variation and posttranslational modifications that are common in the CD44 protein family. Furthermore, real-time interaction measurements on antibody fragments labeled with 125I showed specific and high-affinity binding to the antigen present on cultured head and neck squamous cell carcinoma cells. There was no cross-reactivity toward cells that lack the target protein. As hypothesized, characterization of the interaction between Fab fragments and the targets using the mathematical tool Interaction Map revealed more heterogeneous interactions on cells than with pure proteins analyzed by surface plasmon resonance. One main candidate Fab fragment with optimal affinity for all forms of the target sequence was identified. The flexible recombinant source of the Fab fragments might aid the development of tailored molecules adapted for therapeutic or diagnostic applications in the future.

  • 319.
    Nordang, L.
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Anniko, M.
    Rask-Andersen, H.
    Middle ear exotoxin and endolymphatic sac response: an immune reaction?2001Inngår i: Oto-Rhino-Laryngologia Nova, Vol. 10, s. 269-276Artikkel i tidsskrift (Fagfellevurdert)
  • 320.
    Nordang, Leif
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    The Round Window Membrane - Gateway to the Cochlea: A Morphological and Electrophysiological study2002Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Topical treatment of several inner ear diseases through the round window membrane (RWM) might be feasible in the near future. Bacteria toxins, ototoxic drugs and noise trauma seem to harm the inner ear by a common pathway which involves, excessive outflow of the afferent neurotransmitter glutamate and formation of nitric oxide (NO), which can severely damage cells/nerve endings and lead to cell death.

    In this study we used 98 Sprague-Dawley rats and seven human temporal bones. Various substances were instilled into the middle ear of the rat, such as Pseudomonas Aeruginosa Exotoxin (PaExoA), gentamicin, NO-inhibitor N-Omega-Nitro-L-Arginine Methyl Ester (L-NAME), and glucocorticoids. The effects of the substances were studied by morphological analysis of RWM and the endolymphatic sac (ES) by light and electron microscopic. Hearing level was measured in the rats by ABR technique. The human temporal bones were studied immunomorphologically to search for glutamate.

    In the human inner ear, glutamate receptors and glutamine synthetase, were identified. In the rat, we found, following PaExoA exposure, reversible and permanent hearing loss and morphological changes in the RWM. The ES showed increased numbers of macrophages and thickening of the epithelia. When L-NAME was used as an otoprotector from gentamicin ototoxicity a therapeutic effect in the high frequency area was found. Hydrocortisone (but not dexamethasone) exposure of the RWM resulted in membrane thickening, and adjacent to the membrane, inflammatory cells.

    The importance of the RWM as a portal for toxic substances and topical treatment of inner ear diseases was highlighted in this study. The difficulties of applying drugs in the round window niche were exposed. The results of this study add important knowledge concerning certain mechanisms of inner ear injury and help us to understand possibilities and problems of local treatment of inner ear diseases in patients.

    Delarbeid
    1. Hearing loss in relation to round window membrane morphology in experimental chronic otitis media
    Åpne denne publikasjonen i ny fane eller vindu >>Hearing loss in relation to round window membrane morphology in experimental chronic otitis media
    2001 (engelsk)Inngår i: Journal for Oto-Rhino-Laryngology, ISSN 0301-1569, E-ISSN 1423-0275, Vol. 63, nr 6, s. 333-340Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The present study was performed to test the effect of single and repeated Pseudomonas aeruginosa exotoxin A (PaExoA) instillations in the middle ear of the rat. The hearing level was examined by the ABR technique, round window membrane (RWM) thickness was measured and morphology was studied by light microscopy. The results showed both reversible and permanent hearing loss (HL). In animals that received a single dose of PaExoA, the RWM thickness doubled initially and remained thickened during the observation period. When PaExoA was instilled on several occasions, RWM thickness doubled, before decreasing to near-control levels. This study confirms the toxicity of PaExoA and the partially reversible HL occurring after a single application of the toxin. The diminished effect of repeated toxin instillations--despite the decreasing thickness of the RWM--is discussed.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-89796 (URN)10.1159/000055770 (DOI)11713421 (PubMedID)
    Tilgjengelig fra: 2002-04-10 Laget: 2002-04-10 Sist oppdatert: 2017-12-14bibliografisk kontrollert
    2. Middle ear exotoxin and endolymphatic sac response: an immune reaction?
    Åpne denne publikasjonen i ny fane eller vindu >>Middle ear exotoxin and endolymphatic sac response: an immune reaction?
    2001 Inngår i: Oto-Rhino-Laryngologia Nova, Vol. 10, s. 269-276Artikkel i tidsskrift (Fagfellevurdert) Published
    Identifikatorer
    urn:nbn:se:uu:diva-89797 (URN)
    Tilgjengelig fra: 2002-04-10 Laget: 2002-04-10bibliografisk kontrollert
    3. Glutamate is the afferent neurotransmitter in the human cochlea
    Åpne denne publikasjonen i ny fane eller vindu >>Glutamate is the afferent neurotransmitter in the human cochlea
    2000 (engelsk)Inngår i: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 120, nr 3, s. 359-362Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Glutamate, the most important afferent neurotransmitter in the auditory system, is thought to be the afferent transmitter between the cochlear inner hair cells and afferent neurons, hitherto visualized only in the cochlea of animal species. It has been identified for the first time in sections from the human inner ear. L-glutamate, NMDAR2B and the enzyme glutamine synthetase were identified by using monoclonal antibodies. The distribution pattern of the transmitter L-glutamate in the human cochlea is similar to that observed in other mammals. L-glutamate was identified adjacent to outer and inner hair cells and in the spiral ganglion. Similar distributions were found for glutamine synthetase and the ionotropic NMDA receptor subunit NMDAR2. The identification of neurotransmitters and their receptors in the human cochlea has implications for the pharmacotherapy of inner ear diseases.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-89798 (URN)10894409 (PubMedID)
    Tilgjengelig fra: 2002-04-10 Laget: 2002-04-10 Sist oppdatert: 2017-12-14bibliografisk kontrollert
    4. Nitro-L-arginine methyl ester: a potential protector against gentamicin ototoxicity
    Åpne denne publikasjonen i ny fane eller vindu >>Nitro-L-arginine methyl ester: a potential protector against gentamicin ototoxicity
    2005 (engelsk)Inngår i: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 125, nr 10, s. 1033-8Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The nitric oxide (NO) inhibitor nitro-L-arginine methyl ester (L-NAME) may act as an otoprotectant against high-frequency hearing loss caused by gentamicin, but further studies are needed to confirm this.Aminoglycoside antibiotics are still widely used by virtue of their efficacy and low cost. Their ototoxicity is a serious health problem and, as their ototoxic mechanism involves the production of NO, we need to assess the use of NO inhibitors for the prevention of aminoglycoside-induced sensorineural hearing loss. In this experimental study we used 30 Sprague-Dawley rats, 27 of which had gentamicin instilled into the middle ear. The otoprotectant L-NAME was administered topically to 12/27 animals. Its effect was determined in terms of attenuation of hearing loss, measured by shifts in the auditory brainstem response threshold. L-NAME reduced gentamicin-induced hearing loss in the high-frequency range, but gave no protection in the middle or low frequencies.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-89799 (URN)10.1080/00016480510038022 (DOI)16298782 (PubMedID)
    Tilgjengelig fra: 2002-04-10 Laget: 2002-04-10 Sist oppdatert: 2017-12-14bibliografisk kontrollert
    5. Morphological changes in round window membrane following topical hydrocortisone and dexamethasone treatment
    Åpne denne publikasjonen i ny fane eller vindu >>Morphological changes in round window membrane following topical hydrocortisone and dexamethasone treatment
    2003 (engelsk)Inngår i: Otology and Neurotology, ISSN 1531-7129, E-ISSN 1537-4505, Vol. 24, nr 2, s. 339-43Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    HYPOTHESIS: Are all glucocorticoids supposed to have the same effect on the round window membrane? BACKGROUND: Interest in glucocorticoids for topical treatment of inner ear diseases is increasing. The safety of such treatment should therefore be an important consideration before clinical use. METHODS: In this study the authors investigated the morphology of the round window membrane after topical instillation of dexamethasone or hydrocortisone into the middle ear. Twenty Sprague-Dawley rats were used. Five rats received 5 doses, and five rats 10 doses, of 1 microg (20 microl) dexamethasone in the right ear, and five others were given 5 doses, and five rats 10 doses, of 2% (20 microl) hydrocortisone solution, also in the right ear. Membrane morphology was studied in both light microscopy and transmission electron microscopy. The thickness of exposed membranes was measured and compared with that of control membranes. RESULTS: Thickening and microscopically signs of inflammation were observed in hydrocortisone-exposed membranes but not in dexamethasone-exposed membranes, which did not differ morphologically from those in control ears. CONCLUSION: Although hydrocortisone has anti-inflammatory properties, it seems to provoke inflammation in the round window membrane after topical instillation. Dexamethasone had no such effects, however.

    Emneord
    Administration; Topical, Animals, Anti-Inflammatory Agents/*pharmacology/*therapeutic use, Basilar Membrane/*drug effects/*pathology/ultrastructure, Dexamethasone/administration & dosage/*pharmacology/*therapeutic use, Epithelium/drug effects/ultrastructure, Hydrocortisone/administration & dosage/*pharmacology, Male, Microscopy; Electron, Rats, Rats; Sprague-Dawley, Round Window/*drug effects/*pathology/ultrastructure
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-89800 (URN)12621354 (PubMedID)
    Tilgjengelig fra: 2002-04-10 Laget: 2002-04-10 Sist oppdatert: 2017-12-14bibliografisk kontrollert
  • 321.
    Nordang, Leif
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Anniko, Matti
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Hearing loss in relation to round window membrane morphology in experimental chronic otitis media2001Inngår i: Journal for Oto-Rhino-Laryngology, ISSN 0301-1569, E-ISSN 1423-0275, Vol. 63, nr 6, s. 333-340Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The present study was performed to test the effect of single and repeated Pseudomonas aeruginosa exotoxin A (PaExoA) instillations in the middle ear of the rat. The hearing level was examined by the ABR technique, round window membrane (RWM) thickness was measured and morphology was studied by light microscopy. The results showed both reversible and permanent hearing loss (HL). In animals that received a single dose of PaExoA, the RWM thickness doubled initially and remained thickened during the observation period. When PaExoA was instilled on several occasions, RWM thickness doubled, before decreasing to near-control levels. This study confirms the toxicity of PaExoA and the partially reversible HL occurring after a single application of the toxin. The diminished effect of repeated toxin instillations--despite the decreasing thickness of the RWM--is discussed.

  • 322.
    Nordang, Leif
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Anniko, Matti
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Nitro-L-arginine methyl ester: a potential protector against gentamicin ototoxicity2005Inngår i: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 125, nr 10, s. 1033-8Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The nitric oxide (NO) inhibitor nitro-L-arginine methyl ester (L-NAME) may act as an otoprotectant against high-frequency hearing loss caused by gentamicin, but further studies are needed to confirm this.Aminoglycoside antibiotics are still widely used by virtue of their efficacy and low cost. Their ototoxicity is a serious health problem and, as their ototoxic mechanism involves the production of NO, we need to assess the use of NO inhibitors for the prevention of aminoglycoside-induced sensorineural hearing loss. In this experimental study we used 30 Sprague-Dawley rats, 27 of which had gentamicin instilled into the middle ear. The otoprotectant L-NAME was administered topically to 12/27 animals. Its effect was determined in terms of attenuation of hearing loss, measured by shifts in the auditory brainstem response threshold. L-NAME reduced gentamicin-induced hearing loss in the high-frequency range, but gave no protection in the middle or low frequencies.

  • 323.
    Nordang, Leif
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Laurent, C
    Mollnes, T E
    Complement activation in sudden deafness.1998Inngår i: Archives of Otolaryngology - Head & Neck Surgery, ISSN 0886-4470, E-ISSN 1538-361X, Vol. 124, nr 6, s. 633-6Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: To test whether complement activation is associated with sudden deafness.

    DESIGN: Plasma samples obtained from patients in the acute phase of sudden deafness were analyzed for complement activation measured by C3bc levels and terminal complement complex. Comparisons were made with plasma samples from healthy controls.

    PATIENTS: Twenty-five adult patients with unilateral sudden deafness. The criteria for inclusion were symptoms of hearing loss for not longer than 14 days and a hearing loss of 35 dB or more measured at entry.

    RESULTS: Levels of C3bc were higher in patients compared with controls (P<.001). There were no differences in the formation of terminal complement complex in patients and controls.

    CONCLUSIONS: The elevated levels of C3bc in patients with sudden deafness indicate an activation of the first part of the complement cascade and therefore suspected inflammatory causes. Measurements of C3bc levels might identify patients with sudden deafness who would benefit from treatment with anti-inflammatory drugs.

  • 324.
    Nordang, Leif
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Linder, Birgitta
    Anniko, Matti
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Morphological changes in round window membrane following topical hydrocortisone and dexamethasone treatment2003Inngår i: Otology and Neurotology, ISSN 1531-7129, E-ISSN 1537-4505, Vol. 24, nr 2, s. 339-43Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    HYPOTHESIS: Are all glucocorticoids supposed to have the same effect on the round window membrane? BACKGROUND: Interest in glucocorticoids for topical treatment of inner ear diseases is increasing. The safety of such treatment should therefore be an important consideration before clinical use. METHODS: In this study the authors investigated the morphology of the round window membrane after topical instillation of dexamethasone or hydrocortisone into the middle ear. Twenty Sprague-Dawley rats were used. Five rats received 5 doses, and five rats 10 doses, of 1 microg (20 microl) dexamethasone in the right ear, and five others were given 5 doses, and five rats 10 doses, of 2% (20 microl) hydrocortisone solution, also in the right ear. Membrane morphology was studied in both light microscopy and transmission electron microscopy. The thickness of exposed membranes was measured and compared with that of control membranes. RESULTS: Thickening and microscopically signs of inflammation were observed in hydrocortisone-exposed membranes but not in dexamethasone-exposed membranes, which did not differ morphologically from those in control ears. CONCLUSION: Although hydrocortisone has anti-inflammatory properties, it seems to provoke inflammation in the round window membrane after topical instillation. Dexamethasone had no such effects, however.

  • 325.
    Nordang, Leif
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Lindholm, Carl-Eric
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Larsson, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Hälso- och sjukvårdsforskning.
    Linder, Arne
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Early laryngeal outcome of prolonged intubation using an anatomical tube: a double blind, randomised study2016Inngår i: European Archives of Oto-Rhino-Laryngology, ISSN 0937-4477, E-ISSN 1434-4726, Vol. 273, nr 3, s. 703-708Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The objective of this study was to study the short-term impact on larynx by a newly designed anatomical tube. A prospective randomised trial of a newly designed anatomical tube versus a standard endotracheal tube in patients operated under general anaesthesia for at least 12 h. Seventy adults were included and randomised to either type of tube. The patients were evaluated by means of fibre-optic laryngoscopy and VAS-rating of symptoms on two occasions in the first post-operative week. The evaluating investigators and the patients were blinded to the type of tube used. 27 cases and 23 controls had complete data for evaluation. Age, gender and intubation times were comparable. Symptoms such as hoarseness, coughing, and pain were rated above 30 % of maximum during at least one of the first post-operative days by 21 and 19 patients, respectively. At the first examination (within 24 h), 38 % of patients in the anatomical tube group stated no hoarseness; compared to 13 % of the controls (p = 0.057). Fibre-optic laryngoscopy showed some kind of pathology in all the patients examined within 24 h of extubation. After 3-6 days, seven patients with the anatomical tube and four patients in the control group showed complete resolution of the lesions, and the changes were limited to redness in the vocal process area in another seven and four, respectively. The differences between the groups did not attain statistical significance. The study shows considerable short-term laryngeal morbidity after prolonged intubation, and the anatomical tube only showed an advantage concerning hoarseness. Further improvement of the endotracheal tubes and intubation routines are still needed.

  • 326.
    Nordang, Leif
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Morén, Staffan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Johansson, Henrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Fysioterapi.
    Wenngren, Ewa
    Nordvall, Lennart
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Exercise-induced asthma could be laryngeal obstruction. Not uncommon among young sportsmen--avoiding the wrong treatment is important2009Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518Artikkel i tidsskrift (Fagfellevurdert)
    Abstract
  • 327.
    Nordang, Leif
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Norlander, Katarina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Walsted, Emil Schwarz
    Bispebjerg Hosp, Dept Resp Med, Resp Res Unit, Bispebjerg Bakke 23, DK-2400 Copenhagen, Denmark;Royal Brompton Hosp, Resp Dept, Dovehouse St, London SW3 6JY, England.
    Exercise-Induced Laryngeal Obstruction-An Overview2018Inngår i: Immunology and allergy clinics of North America, ISSN 0889-8561, E-ISSN 1557-8607, Vol. 38, nr 2, s. 271-280Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Exertional dyspnea is common in health and disease. Despite having known for centuries that breathlessness can arise from the larynx, exercise-induced laryngeal obstruction is a more prevalent condition than previously assumed. This article provides a brief overview of the history, epidemiology, and pathophysiology of exercise-induced laryngeal obstruction.

  • 328.
    Nordang, Leif
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Oestreicher, E.
    Arnold, Wolfgang
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Anniko, Matti
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Glutamate is the afferent neurotransmitter in the human cochlea2000Inngår i: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 120, nr 3, s. 359-362Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Glutamate, the most important afferent neurotransmitter in the auditory system, is thought to be the afferent transmitter between the cochlear inner hair cells and afferent neurons, hitherto visualized only in the cochlea of animal species. It has been identified for the first time in sections from the human inner ear. L-glutamate, NMDAR2B and the enzyme glutamine synthetase were identified by using monoclonal antibodies. The distribution pattern of the transmitter L-glutamate in the human cochlea is similar to that observed in other mammals. L-glutamate was identified adjacent to outer and inner hair cells and in the spiral ganglion. Similar distributions were found for glutamine synthetase and the ionotropic NMDA receptor subunit NMDAR2. The identification of neurotransmitters and their receptors in the human cochlea has implications for the pharmacotherapy of inner ear diseases.

  • 329.
    Nordling, Sofia
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Hong, Jaan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Fromell, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Edin, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Brännström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Larsson, Rolf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Nilsson, Bo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Magnusson, Peetra U.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Vascular repair utilising immobilised heparin conjugate for protection against early activation of inflammation and coagulation2015Inngår i: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 113, nr 6, s. 1312-1322Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Ischaemia-reperfusion injury (IRI) poses a major challenge in many thrombotic conditions and in whole organ transplantation. Activation of the endothelial cells and shedding of the protective vascular glycocalyx during IRI increase the risk of innate immune activation, cell infiltration and severe thrombus formation, promoting damage to the tissue. Here, we present a novel one-step strategy to protect the vas, culature by immobilisation of a unique multi-arm heparin conjugate to the endothelium. Applying a new in vitro blood endothelial cell chamber model, the heparin conjugate was found to bind not only to primary human endothelial cells but also directly to the collagen to which the cells adhered. Incubation of hypoxic endothelial cells with freshly drawn human blood in the blood chambers elicited coagulation activation reflected by thrombin anti-thrombin formation and binding of platelets and neutrophils. Immobilisation of the heparin conjugate to the hypoxic endothelial cells created a protective coating, leading to a Significant reduction of the recruitment of blood cells and coagulation activation compared to untreated hypoxic endothelial cells. This novel approach of immobilising multi-arm heparin conjugates on the endothelial cells and collagen of the basement membrane ensures to protect the endothelium against IRI in thrombotic disorders and in transplantation.

  • 330.
    Norlander, Katarina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Exercise-induced laryngeal obstruction: Prevalence, laryngeal findings and evaluation of treatment2017Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Exercise-induced laryngeal obstruction (EILO) is one of many different causes for adolescents to experience dyspnoea during exercise. Objective exercise-testing with continuous video laryngoscopy is crucial for a correct diagnosis since it is difficult to differentiate EILO from other exercise related conditions in the airways only on the symptomatology. The main symptom in EILO is inspiratory stridor arising from an obstruction at the laryngeal level during ongoing exercise which quickly resolves after the exercise has stopped. EILO is often misdiagnosed as exercise-induced bronchoconstriction (EIB), which is obstruction in the peripheral airways that typically arises after cessation of exercise.

    From a previous survey investigating self-reported exercise-induced dyspnoea in all 12-13-year-old adolescents in Uppsala (n=3,838, response rate 60.2%) a subset of 150 randomly selected adolescents (103 with dyspnoea and 47 controls) performed standardized treadmill exercise-tests for EIB and EILO.

    During the exercise-test for EIB the subjects breathed dry air according to the current recommended guidelines. EIB was defined as a decrease in FEV1 ≥10% from baseline. EILO was diagnosed during a continuous laryngoscopy exercise (CLE) test by use of the CLE-score method and was defined as an obstruction of grade 2 at either glottic or/and supraglottic laryngeal level. The estimated prevalence of EIB in the general population was 19.2% and the estimated prevalence of EILO was 5.7%. No gender differences were detected.

    A diagnostic software program for EILO, EILOMEA, was compared with the CLE-score and the methods were found to be compatible. EILOMEA was used to map and compare laryngeal response patterns in adolescents with exercise-induced dyspnoea (EIB and/or EILO), in adolescents with dyspnoea but without a diagnosis of EIB or EILO, and in healthy controls, all of whom had performed the CLE-test. No differences were seen between the healthy controls and the adolescents with dyspnoea without a diagnosis. Only adolescents diagnosed with EILO showed a significant different laryngeal response pattern which strongly suggests that the diagnostic procedure is reliable.

    In a follow-up study of patients referred for investigation of exercise-induced dyspnoea, we investigated the outcome of surgical vs. conservative treatment of EILO-positive subjects and subjects tested negative for the diagnosis, regarding the level of exercise-induced dyspnoea and physical activity. Surgically treated patients had less breathing problems and were more physically active than both conservatively treated patients and patients who were tested negative.

    Delarbeid
    1. Comparison between two assessment methods for exercise-induced laryngeal obstructions
    Åpne denne publikasjonen i ny fane eller vindu >>Comparison between two assessment methods for exercise-induced laryngeal obstructions
    Vise andre…
    2016 (engelsk)Inngår i: European Archives of Oto-Rhino-Laryngology, ISSN 0937-4477, E-ISSN 1434-4726, Vol. 273, nr 2, s. 425-430Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Exercise-induced laryngeal obstructions (E-ILOs) are important differential diagnoses to exercise-induced asthma and are diagnosed by the continuous laryngoscopy exercise (CLE) test. There are two different methods for evaluating the severity of E-ILOs using recordings from the CLE test; the CLE score and EILOMEA. The aim of this study was to investigate the consistency between these methods. Using their respective method, the developers of each method evaluated 60 laryngoscopic recordings from patients with different subtypes and various levels of severity of E-ILOs. The CLE score evaluates glottic and supraglottic obstructions on a 4-grade scale. EILOMEA uses software to calculate the obstruction severity on continuous scales from a still frame of the larynx during maximal obstruction giving three parameters reflecting glottic and supraglottic obstruction. The means of the EILOMEA measures differed significantly for CLE score 1 vs. 2 and 2 vs. 3, but not for 0 vs. 1 for glottic as well as supraglottic obstructions. The EILOMEA method does not distinguish between CLE score 0 and 1, but otherwise the methods correlate. Since previous studies have suggested that only CLE scores of 2 and 3 reflect a severity of E-ILOs of clinical importance, this lack of the EILOMEA method is not crucial for a correct medical evaluation.

    Emneord
    E-ILO; Continuous laryngoscopy exercise test; CLE score; EILOMEA; Exercise-induced respiratory difficulties
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-266447 (URN)10.1007/s00405-015-3758-7 (DOI)000368990700022 ()26351037 (PubMedID)
    Eksternt samarbeid:
    Tilgjengelig fra: 2015-11-10 Laget: 2015-11-10 Sist oppdatert: 2017-12-01bibliografisk kontrollert
    2. Prevalence of exercise-induced bronchoconstriction and exercise-induced laryngeal obstruction in a general adolescent population
    Åpne denne publikasjonen i ny fane eller vindu >>Prevalence of exercise-induced bronchoconstriction and exercise-induced laryngeal obstruction in a general adolescent population
    Vise andre…
    2015 (engelsk)Inngår i: Thorax, ISSN 0040-6376, E-ISSN 1468-3296, Vol. 70, nr 1, s. 57-63Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Background Exercise-induced respiratory symptoms are common among adolescents. Exercise is a known stimulus for transient narrowing of the airways, such as exercise-induced bronchoconstriction (EIB) and exercise-induced laryngeal obstruction (EILO). Our aim was to investigate the prevalence of EIB and EILO in a general population of adolescents. Methods In this cross-sectional study, a questionnaire on exercise-induced dyspnoea was sent to all adolescents born in 1997 and 1998 in Uppsala, Sweden (n=3838). A random subsample of 146 adolescents (99 with self-reported exercise-induced dyspnoea and 47 without this condition) underwent standardised treadmill exercise tests for EIB and EILO. The exercise test for EIB was performed while breathing dry air; a positive test was defined as a decrease of >= 10% in FEV1 from baseline. EILO was investigated using continuous laryngoscopy during exercise. Results The estimated prevalence of EIB and EILO in the total population was 19.2% and 5.7%, respectively. No gender differences were found. In adolescents with exercise-induced dyspnoea, 39.8% had EIB, 6% had EILO and 4.8% had both conditions. In this group, significantly more boys than girls had neither EIB nor EILO (64.7% vs 38.8%; p=0.026). There were no significant differences in body mass index, lung function, diagnosed asthma or medication between the participants with exercise-induced dyspnoea who had or did not have a positive EIB or EILO test result. Conclusions Both EIB and EILO are common causes of exercise-induced dyspnoea in adolescents. EILO is equally common among girls and boys and can coexist with EIB.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-241953 (URN)10.1136/thoraxjnl-2014-205738 (DOI)000346338300012 ()
    Merknad

    Henrik Johansson and Katarina Norlander have shared first authorship on this paper.

    Tilgjengelig fra: 2015-01-20 Laget: 2015-01-19 Sist oppdatert: 2017-12-05bibliografisk kontrollert
    3. Laryngeal findings during exercise in healthy and dyspneic adolescents
    Åpne denne publikasjonen i ny fane eller vindu >>Laryngeal findings during exercise in healthy and dyspneic adolescents
    (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-315122 (URN)
    Tilgjengelig fra: 2017-02-09 Laget: 2017-02-09 Sist oppdatert: 2017-02-09
    4. Surgical treatment is effective in severe cases of exercise-induced laryngeal obstruction: A follow-up study
    Åpne denne publikasjonen i ny fane eller vindu >>Surgical treatment is effective in severe cases of exercise-induced laryngeal obstruction: A follow-up study
    Vise andre…
    2015 (engelsk)Inngår i: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 135, nr 11, s. 1152-1159Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Conclusions: Surgery is an effective treatment in severe cases of supraglottic exercise-induced laryngeal obstruction (E-ILO). Conservatively treated subjects and subjects tested negative for E-ILO, who still experience breathing problems 1–3 years after diagnosis, tend to adjust their physical activity to a greater extent than surgically treated subjects. Objective: To investigate how symptoms and level of physical activity change over time in patients with E-ILO who have undergone surgery, patients with E-ILO treated conservatively and patients who tested negative for laryngeal obstruction at continuous laryngoscopy exercise-test (CLE-test). Methods: Patients referred for exercise-induced breathing difficulties answered questionnaires at diagnostic CLE-test and at follow-up. Questions regarded exercise-induced breathing problems, current physical activity level, and medical history of asthma and perennial allergy. Results: Out of 84 invited subjects, 59 (70%) answered both questionnaires. Surgically treated subjects had less breathing problems at follow-up compared with conservatively treated subjects and subjects who tested negative (p < 0.001). None of the surgically treated subjects were less physically active or had changed sport due to exercise-induced dyspnoea, whereas 41.7% of the conservatively treated subjects had made such adjustments (p < 0.001).

    Emneord
    Laryngoplasty; exercice-induced dyspnoea; vocal cord dysfunction; physical activity; E-ILO
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-264379 (URN)10.3109/00016489.2015.1062548 (DOI)000369936800010 ()26200564 (PubMedID)
    Tilgjengelig fra: 2015-10-10 Laget: 2015-10-10 Sist oppdatert: 2017-12-01bibliografisk kontrollert
  • 331.
    Norlander, Katarina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Christensen, Pernille M
    Maat, Robert C
    Halvorsen, Thomas
    Heimdal, John Helge
    Morén, Staffan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Rasmussen, Niels
    Nordang, Leif
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Comparison between two assessment methods for exercise-induced laryngeal obstructions2016Inngår i: European Archives of Oto-Rhino-Laryngology, ISSN 0937-4477, E-ISSN 1434-4726, Vol. 273, nr 2, s. 425-430Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Exercise-induced laryngeal obstructions (E-ILOs) are important differential diagnoses to exercise-induced asthma and are diagnosed by the continuous laryngoscopy exercise (CLE) test. There are two different methods for evaluating the severity of E-ILOs using recordings from the CLE test; the CLE score and EILOMEA. The aim of this study was to investigate the consistency between these methods. Using their respective method, the developers of each method evaluated 60 laryngoscopic recordings from patients with different subtypes and various levels of severity of E-ILOs. The CLE score evaluates glottic and supraglottic obstructions on a 4-grade scale. EILOMEA uses software to calculate the obstruction severity on continuous scales from a still frame of the larynx during maximal obstruction giving three parameters reflecting glottic and supraglottic obstruction. The means of the EILOMEA measures differed significantly for CLE score 1 vs. 2 and 2 vs. 3, but not for 0 vs. 1 for glottic as well as supraglottic obstructions. The EILOMEA method does not distinguish between CLE score 0 and 1, but otherwise the methods correlate. Since previous studies have suggested that only CLE scores of 2 and 3 reflect a severity of E-ILOs of clinical importance, this lack of the EILOMEA method is not crucial for a correct medical evaluation.

  • 332.
    Norlander, Katarina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Johansson, Henrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Fysioterapi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Janson, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Lungmedicin och allergologi.
    Nordvall, Lennart
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Pediatrik.
    Nordang, Leif
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Surgical treatment is effective in severe cases of exercise-induced laryngeal obstruction: A follow-up study2015Inngår i: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 135, nr 11, s. 1152-1159Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Conclusions: Surgery is an effective treatment in severe cases of supraglottic exercise-induced laryngeal obstruction (E-ILO). Conservatively treated subjects and subjects tested negative for E-ILO, who still experience breathing problems 1–3 years after diagnosis, tend to adjust their physical activity to a greater extent than surgically treated subjects. Objective: To investigate how symptoms and level of physical activity change over time in patients with E-ILO who have undergone surgery, patients with E-ILO treated conservatively and patients who tested negative for laryngeal obstruction at continuous laryngoscopy exercise-test (CLE-test). Methods: Patients referred for exercise-induced breathing difficulties answered questionnaires at diagnostic CLE-test and at follow-up. Questions regarded exercise-induced breathing problems, current physical activity level, and medical history of asthma and perennial allergy. Results: Out of 84 invited subjects, 59 (70%) answered both questionnaires. Surgically treated subjects had less breathing problems at follow-up compared with conservatively treated subjects and subjects who tested negative (p < 0.001). None of the surgically treated subjects were less physically active or had changed sport due to exercise-induced dyspnoea, whereas 41.7% of the conservatively treated subjects had made such adjustments (p < 0.001).

  • 333.
    Nyqvist, Johanna
    et al.
    Skane Univ Hosp, Dept Otolaryngol & Head & Neck Surg, Lund, Sweden.;Umea Univ, Dept Clin Sci Otolaryngol & Head & Neck Surg, S-90187 Umea, Sweden..
    Fransson, Per
    Umea Univ, Dept Nursing, S-90187 Umea, Sweden..
    Laurell, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar. Umea Univ, Dept Clin Sci Otolaryngol & Head & Neck Surg, S-90187 Umea, Sweden..
    Hammerlid, Eva
    Sahlgrens Univ Hosp, Dept Otolaryngol & Head & Neck Surg, Gothenburg, Sweden..
    Kjellen, Elisabeth
    Lund Univ, Skane Univ Hosp, Dept Oncol & Radiat Phys, S-22100 Lund, Sweden..
    Franzen, Lars
    Umea Univ, Dept Radiat Sci Oncol, S-90187 Umea, Sweden..
    Soderstrom, Karin
    Umea Univ, Dept Radiat Sci Oncol, S-90187 Umea, Sweden..
    Wickart-Johansson, Gun
    Karolinska Univ Hosp, Dept Oncol, Stockholm, Sweden..
    Friesland, Signe
    Karolinska Univ Hosp, Dept Oncol, Stockholm, Sweden..
    Sjodin, Helena
    Karolinska Univ Hosp, Dept Oncol, Stockholm, Sweden..
    Brun, Eva
    Lund Univ, Skane Univ Hosp, Dept Oncol & Radiat Phys, S-22100 Lund, Sweden..
    Ask, Anders
    Lund Univ, Skane Univ Hosp, Dept Oncol & Radiat Phys, S-22100 Lund, Sweden..
    Nilsson, Per
    Lund Univ, Skane Univ Hosp, Dept Oncol & Radiat Phys, S-22100 Lund, Sweden..
    Ekberg, Lars
    Lund Univ, Skane Univ Hosp, Dept Oncol & Radiat Phys, S-22100 Lund, Sweden..
    Bjork-Eriksson, Thomas
    Sahlgrens Univ Hosp, Dept Oncol, Gothenburg, Sweden..
    Nyman, Jan
    Sahlgrens Univ Hosp, Dept Oncol, Gothenburg, Sweden..
    Loden, Britta
    Karlstad Cent Hosp, Dept Clin Oncol, Karlskrona, Sweden..
    Lewin, Freddi
    Ryhov Cty Hosp, Dept Oncol, Jonkoping, Sweden..
    Reizenstein, Johan
    Orebro Univ Hosp, Dept Oncol, Orebro, Sweden..
    Lundin, Erik
    Ryhov Cty Hosp, Dept Oncol, Jonkoping, Sweden..
    Zackrisson, Bjorn
    Umea Univ, Dept Radiat Sci Oncol, S-90187 Umea, Sweden..
    Differences in health related quality of life in the randomised ARTSCAN study; accelerated vs. conventional radiotherapy for head and neck cancer. A five year follow up2016Inngår i: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 118, nr 2, s. 335-341Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background and purpose: Health related quality of life (HRQoL) was assessed in the randomised, prospective ARTSCAN study comparing conventional radiotherapy (CF) with accelerated radiotherapy (AF) for head and neck cancer. Material and methods: 750 patients with squamous cell carcinoma (of any grade and stage) in the oral cavity, oro-, or hypopharynx or larynx (except T1-2, NO glottic carcinoma) without distant metastases were randomised to either conventional fractionation (2 Gy/day, 5 days/week in 49 days, total dose 68 Gy) or accelerated fractionation (1.1 + 2.0 Gy/day, 5 days/week in 35 days, total dose 68 Gy). HRQoL was assessed with EORTC QLQ-C30, QLQ-H&N35 and HADS at baseline, at end of radiotherapy (eRT) and at 3 and 6 months and 1, 2 and 5 years after start of treatment. Results: The AF group reported HRQoL was significantly lower at eRT and at 3 months for most symptoms, scales and functions. Few significant differences were noted between the groups at 6 months and 5 years. Scores related to functional oral intake never reached baseline. Conclusion: In comparison to CF, AF has a stronger adverse effect on HRQoL in the acute phase.

  • 334. Oberg, Marie
    et al.
    Bohn, Therese
    Larsson, Ulrika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Short- and Long-Term Effects of the Modified Swedish Version of the Active Communication Education (ACE) Program for Adults with Hearing Loss2014Inngår i: JOURNAL OF THE AMERICAN ACADEMY OF AUDIOLOGY, ISSN 1050-0545, Vol. 25, nr 9, s. 848-858Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: In Sweden, there is a lack of evidence-based rehabilitation programs for hearing loss. The Active Communication Education program (ACE) has successfully been used in Australia and was translated and evaluated in a Swedish pilot study. The pilot study included 23 participants (age 87 yr). No statistically significant effects were found, but the qualitative assessments indicated that this population found the program to be beneficial. The participants requested more focus on the psychosocial consequences of hearing loss, and the modules in the original ACE program were modified. Purpose: The aim of this study was to explore the effects of a modified Swedish version of the ACE program in a population aged 39-82 yr old. Research Design: Design was a between-group and within-group intervention study. Study Sample: The participants were recruited from the hearing health clinic in Linkoping during 2010 and 2012. A total of 73 participante agreed to undergo the ACE, and 67 (92%) completed three or more sessions. Intervention: The ACE program consists of five weekly 2 hr group sessions with 6 to 10 participants per group. Data Collection and Analysis: The outcomes were measured before initiation of the program, 3 wk after program completion, and 6 mo after program completion and included communication strategy use, activity and participation, health-related quality of life, and anxiety and depression. In addition, outcomes were measured after program completion using the International Outcome Inventory Alternative Interventions, a modified version of the Client Oriented Scale of Improvement, and qualitative feedback was obtained about the response to the program and actions taken as a result of participation. The treatment effects were examined using repeated-measures analyses of variance. Results: Statistically significant effects were found for communication strategy use, activity and participation, and psychosocial well-being. Statistically significant effects were found for gender and degree of hearing loss, indicating that women and those with mild hearing loss significantly improved communication strategies. Conclusions: It is suggested that the program be implemented as part of regular audiological rehabilitation and offered in an early stage of rehabilitation.

  • 335. Ottosson, Sandra
    et al.
    Laurell, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Olsson, Cecilia
    The experience of food, eating and meals following radiotherapy for head and neck cancer: a qualitative study2013Inngår i: Journal of Clinical Nursing, ISSN 0962-1067, E-ISSN 1365-2702, Vol. 22, nr 7-8, s. 1034-1043Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aims and objectives To describe the experience of food, eating and meals following radiotherapy in patients with head and neck cancer. Background Eating problems are common in patients with head and neck cancer and may remain for a long period of time after treatment. Design A qualitative study design using in-depth semi-structured interviews. Methods Interviews were conducted nine months after the termination of radiotherapy. A purposive sample of thirteen patients with head and neck cancer participated in the study. The interviews were tape-recorded, transcribed verbatim and analysed using content analysis. Results The experience of food, eating and meals up to nine months after radiotherapy was captured in six categories: A long journey taking small steps to an uncertain future', A new way of eating', Eating without satisfaction', Challenging meals outside the family', Support and information the key to a successful journey' and The creation and acceptance of a new normal'. Conclusion This study provides new information on the long-term aspects of food, eating and meals in patients with head and neck cancer. Head and neck cancer signifies a long journey with problems affecting physical, psychological and social aspects of food. Information and support and the use of strategies are important for patients with head and neck cancer to adapt to new possibilities for living after cancer treatment. Relevance to clinical practice All members of the multiprofessional team need to be aware of the struggles with food and eating experienced by patients with head and neck cancer during the convalescent period. It is therefore important that the follow-up focuses on all aspects of food, eating and meals as a part of a holistic approach.

  • 336. Ottosson, Sandra
    et al.
    Lindblom, Ulrika
    Wahlberg, Peter
    Nilsson, Per
    Kjellen, Elisabeth
    Zackrisson, Bjorn
    Jaghagen, Eva Levring
    Laurell, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Weight loss and body mass index in relation to aspiration in patients treated for head and neck cancer: a long-term follow-up2014Inngår i: Supportive Care in Cancer, ISSN 0941-4355, E-ISSN 1433-7339, Vol. 22, nr 9, s. 2361-2369Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Persistent severe swallowing dysfunction with aspiration is a common and sometimes overlooked sequelae after treatment for squamous cell carcinoma of the head and neck (SCCHN) and may impact food intake and nutritional status. More knowledge is needed to increase the understanding of severe swallowing dysfunction as a risk factor for persistent nutritional deteriorations in SCCHN survivors. The purpose of the study was to investigate weight loss and body mass index (BMI) in relation to pharyngeal swallowing function in a long-term perspective in patients after SCCHN treatment. Data from 101 patients were available for the analyses. Swallowing function was assessed by videofluoroscopy at a mean of 71.6 months after the start of radiotherapy (RT). Percent weight change (calculated with weight at the start of RT as the reference) and BMI at follow-up were the primary nutritional measures. Aspiration was present in 48 of 101 patients (48 %). Patients with aspiration had a significantly higher mean weight loss and a lower BMI (-10.9 % and 23.1, respectively) at follow-up compared with patients without aspiration (-2.8 % and 26.0, respectively). Patients with aspiration were unable to gain weight after 23 months. Only ten of 101 patients (10 %) were underweight at follow-up. Swallowing dysfunction with aspiration was related to long-term weight loss and reduced BMI. Few patients were underweight despite the high prevalence of swallowing dysfunction.

  • 337. Ottosson, Sandra
    et al.
    Soderstrom, Karin
    Kjellen, Elisabeth
    Nilsson, Per
    Zackrisson, Bjorn
    Laurell, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Weight and body mass index in relation to irradiated volume and to overall survival in patients with oropharyngeal cancer: a retrospective cohort study2014Inngår i: Radiation Oncology, ISSN 1748-717X, E-ISSN 1748-717X, Vol. 9, s. 160-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

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

  • 338. P, Nerfeldt
    et al.
    BY, Nilsson
    J, Uddén
    S, Rössner
    Friberg, Danielle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Weight reduction improves nocturnal respiration in obese sleep apnoea patients-: A randomized controlled pilot study2008Inngår i: Obesity Research and Clinical Practice, ISSN 1871-403X, E-ISSN 1878-0318Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives

    Randomized controlled pilot study of the effect of weight reduction on nocturnal respiratory parameters in obese patients with obstructive sleep apnoea syndrome (OSAS).

    Methods

    Twenty consecutive obese male patients fulfilling OSAS criteria at Karolinska University Hospital were randomized into two groups. Intervention with an 8-week weight reduction programme consisting of a low-calorie diet, together with group meetings, was evaluated compared to expectancy alone for the control group, followed by a crossover. Follow-up at 3 months included anthropometrics and ambulant sleep apnoea recordings.

    Results

    Eleven of twenty men completed the protocol. There were significant differences between the intervention group (n = 6) and the control group (n = 5) in changes of weight (p < 0.01) and oxygen desaturation index (ODI4) (p < 0.05). We also found a significant positive correlation in these 11 males after the crossover between their reduction in weight and their reduction in ODI4 (p < 0.05).

    Conclusions

    This pilot study indicates that weight reduction improves nocturnal respiration in obese OSAS patients after 3 months’ dietary treatment compared to expectancy.

  • 339. P, Nerfeldt
    et al.
    BY, Nilsson
    L, Mayor
    J, Uddén
    Friberg, Danielle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    A two-year weight reduction program in obese sleep apnea patients2010Inngår i: Journal of Clinical Sleep Medicine (JCSM), ISSN 1550-9389, E-ISSN 1550-9397, Vol. 6, nr 5, s. 479-486Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Study Objectives:

    To evaluate the effects of a 2-year weight reduction program on respiratory disturbances, arousal index, daytime sleepiness, metabolic status, and quality of life in obese patients with obstructive sleep apnea syndrome (OSAS).

    Methods:

    Prospective intervention study of 33 consecutive obese OSAS patients (24 men, 9 women); 19 subjects used continuous positive airway pressure and 4 used mandibular retaining device, except during nights with sleep recording. The program consisted of 8 weeks of low calorie diet followed by group meetings with behavioral change support.

    Results:

    Seventy percent of the patients completed the program; 67% completed the sleep recordings. The success rate for the apnea-hypopnea index (AHI) (< 20 and reduction ≥ 50%) was 15% in the intention to treat (ITT) analysis. The AHI showed a nonsignificant decrease in mean values, from 43 to 28. The oxygen desaturation index (ODI) decreased from 42 to 23 (p = 0.010), arousal index from 24 to 11 (p = 0.019), body mass index from 40 to 35 (p = 0.003) and the Epworth Sleepiness Scale (ESS) from 9 to 5 (p = 0.026), all ITT. Metabolic status, physical functioning, and vitality evaluations improved only in the per protocol analysis. Reduction in weight correlated significantly to reductions in ESS (p = 0.038) and insulin levels (p = 0.002), respectively. There were no differences based on gender or use/non-use of OSAS treatment device.

    Conclusions:

    Our weight reduction program showed a limited success in reducing AHI. However, there were significant improvements in weight, ODI, arousal index, and subjective symptoms. We recommend the program as an adjunct treatment for well-motivated obese OSAS patients.

    Citation:

    Nerfeldt P; Nilsson BY; Mayor L; Uddén J; Friberg D. A two-year weight reduction program in obese sleep apnea patients. J Clin Sleep Med 2010;6(5):479-486.

    Keywords: Sleep apnea, obesity, weight reduction, diet, quality of life, sleepiness, behavioral therapy

  • 340. P, Nerfeldt
    et al.
    BY, Nilsson
    L, Mayor
    J, Uddén
    S, Rössner
    Friberg, Danielle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Weight reduction improves sleep, sleepiness and metabolic status in obese sleep apnoea patients.2008Inngår i: Obesity Research and Clinical Practice, ISSN 1871-403X, E-ISSN 1878-0318, Vol. 2, nr 4, s. 251-262Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Method

    In this prospective intervention study, 33 obese patients with obstructive sleep apnoea syndrome (OSAS) (24 men, 9 women) were consecutively enrolled for a weight reduction program at the Obesity Unit, Karolinska University Hospital. 23 of 33 patients used OSAS-device, 19 with Continuous Positive Airway Pressure and 4 with Mandibular Retaining Device. The patients were investigated with questionnaires, blood tests and ambulant nocturnal polysomnography before and after a 6-month program. Patients with OSAS-device slept without it during the sleep studies. The intervention consisted of 8 weeks low calorie diet and group meetings, followed by a day-care program of behaviour change support.

    Results

    27 of 33 patients (82%, 21 men and 6 women) completed the study. After the intervention there were highly significant decreases (p < 0.001) in Body Mass Index from mean(S.D.) 40(5) to 34(3), apnoea–hypopnoea index from 43(24) to 26(20) and Epworth Sleepiness Scale (ESS)-score from 9(4) to 6(4). Sleep quality (arousal index, sleep efficiency, percentage deep sleep) and metabolic status (blood pressure, blood glucose levels, lipidemia) were also significantly improved. There was a significant correlation between increased percentage deep sleep and reduced ESS-score. There were no differences due to gender or use/no use of OSAS-device.

    Conclusion

    The results suggest that weight loss, induced by low calorie diet and behaviour change support, significantly improves nocturnal respiratory parameters, sleep quality, daytime sleepiness and metabolic status in obese OSAS patients after 6 months.

  • 341. P, Nerfeldt
    et al.
    F, Aoki
    Friberg, Danielle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Polygraphy vs. polysomnography: missing osas in symptomatic snorers–a reminder for clinicians2014Inngår i: Sleep and Breathing, ISSN 1520-9512, E-ISSN 1522-1709Artikkel i tidsskrift (Fagfellevurdert)
  • 342. P, Nerfeldt
    et al.
    Friberg, Danielle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Effectiveness of Oral Appliances in Obstructive Sleep Apnea with Respiratory Arousals2016Inngår i: Journal of Clinical Sleep Medicine (JCSM), ISSN 1550-9389, E-ISSN 1550-9397, Vol. 15, nr 2Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Study Objectives

    To compare adherence and treatment effects with an oral appliance (OA) in patients with different types of obstructive sleep apnea (OSA): those with mainly respiratory arousals (“arousers”), and those with oxygen desaturations (“desaturaters”) at polysomnography (PSG).

    Methods

    A prospective intervention study on 72 “tired snorers” with “normal” home sleep study (HSS), but later diagnosed as OSA with PSG, who accepted OA treatment. They were offered evaluation with a follow-up PSG and questionnaires, including the Epworth Sleepiness Scale (ESS), general health (GH), satisfaction, and side effects.

    Results

    Sixty-six patients, 33 arousers and 33 desaturaters, were adapted to OA. The 1-year adherence rate was significantly higher among arousers (85%) than desaturaters (55%) (p = 0.034). Thirty-six of 66 patients underwent follow-up PSG; the apnea-hypopnea index was significantly reduced in 22 arousers from a median of 14 to 3 (p < 0.001), and in 14 desaturaters from 18 to 7 (p = 0.002; no significant group difference). ESS and GH showed no significant improvements in either group, although sleepy “arousers” (ESS ≥ 10) significantly improved their ESS. In total, 77% reported side effects, while 63% were still satisfied with the OA treatment. Gender analysis showed a significant dominance of females classified as “arousers” (p = 0.025).

    Conclusions

    OSA patients with mainly arousals at PSG showed higher adherence to OA treatment, compared to patients with desaturations. Both groups responded similarly to treatment: improved nocturnal respiration, but only a small reduction of symptoms. We suggest that “tired snorers” with “normal HSS” should be offered PSG, and if OSA, also OA treatment.

  • 343. P, Nerfeldt
    et al.
    P, Graf
    S, Borg
    Friberg, Danielle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Prevalence of high alcohol and benzodiazepine consumption in sleep apnea patients studied with blood and urine tests.2004Inngår i: Acta oto-laryngologicaArtikkel i tidsskrift (Fagfellevurdert)
  • 344. Pechriggl, Elisabeth J
    et al.
    Bitsche, Mario
    Glueckert, Rudolf
    Rask-Andersen, Helge
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Blumer, Michael J F
    Schrott-Fischer, Annelies
    Fritsch, Helga
    Development of the innervation of the human inner ear2015Inngår i: Developmental Neurobiology, ISSN 1932-8451, E-ISSN 1932-846X, Vol. 75, nr 7, s. 683-702Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Studies on the formation of neuronal structures of the human cochlea are rare, presumptively, due to the difficult accessibility of specimens, so that most investigations are performed on mouse models. By means of immunohistochemical and transmission electron microscopic techniques, we investigated an uninterrupted series of unique specimens from gestational week 8 to week 12. We were able to demonstrate the presence of nerve fibers in the prosensory domain at gestational week 8, followed by afferent synaptogenesis at week 11. We identified PAX2 as an early marker for hair cell differentiation. Glutamine synthetase-positive peripheral glial cells occurred at the beginning of week 8. Transcription factor MAF B was used to demonstrate maturation of the spiral ganglion neurons. The early expression of tyrosine hydroxylase could be assessed. This study provides insights in the early assembly of the neural circuit and organization in humans.

  • 345.
    Pierre, Pernilla Videhult
    et al.
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Div Audiol, Stockholm, Sweden.
    Fransson, Anette
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Kisiel, Marta Alina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Damberg, Peter
    Karolinska Univ Hosp, Karolinska Expt Res & Imaging Ctr, Stockholm, Sweden.
    Aski, Sahar Nikkhou
    Karolinska Univ Hosp, Karolinska Expt Res & Imaging Ctr, Stockholm, Sweden.
    Andersson, Mats
    RISE Res Inst Sweden, Div Biosci & Mat, Sodertalje, Sweden.
    Hallgren, Lotta
    RISE Res Inst Sweden, Div Biosci & Mat, Sodertalje, Sweden.
    Laurell, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Middle Ear Administration of a Particulate Chitosan Gel in an in vivo Model of Cisplatin Ototoxicity2019Inngår i: Frontiers in Cellular Neuroscience, ISSN 1662-5102, E-ISSN 1662-5102, Vol. 13, artikkel-id 268Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Middle ear (intratympanic, IT) administration is a promising therapeutic method as it offers the possibility of achieving high inner ear drug concentrations with low systemic levels, thus minimizing the risk of systemic side effects and drug-drug interactions. Premature elimination through the Eustachian tube may be reduced by stabilizing drug solutions with a hydrogel, but this raises the secondary issue of conductive hearing loss. Aim: This study aimed to investigate the properties of a chitosan-based particulate hydrogel formulation when used as a drug carrier for IT administration in an in vivo model of ototoxicity. Materials and Methods: Two particulate chitosan-based IT delivery systems, Thio-25 and Thio-40, were investigated in albino guinea pigs (n = 94). Both contained the hearing protecting drug candidate sodium thiosulfate with different concentrations of chitosan gel particles (25% vs. 40%). The safety of the two systems was explored in vivo. The most promising system was then tested in guinea pigs subjected to a single intravenous injection with the anticancer drug cisplatin (8 mg/kg b.w.), which has ototoxic side effects. Hearing status was evaluated with acoustically evoked frequency-specific auditory brainstem response (ABR) and hair cell counting. Finally, in vivo magnetic resonance imaging was used to study the distribution and elimination of the chitosan-based system from the middle ear cavity in comparison to a hyaluronan-based system. Results: Both chitosan-based IT delivery systems caused ABR threshold elevations (p < 0.05) that remained after 10 days (p < 0.05) without evidence of hair cell loss, although the elevation induced by Thio-25 was significantly lower than for Thio-40 (p < 0.05). Thio-25 significantly reduced cisplatin-induced ABR threshold elevations (p < 0.05) and outer hair cell loss (p < 0.05). IT injection of the chitosan- and hyaluronan-based systems filled up most of the middle ear space. There were no significant differences between the systems in terms of distribution and elimination. Conclusion: Particulate chitosan is a promising drug carrier for IT administration. Future studies should assess whether the physical properties of this technique allow for a smaller injection volume that would reduce conductive hearing loss.

  • 346.
    Pierre, Pernilla Videhult
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar. Karolinska Inst, Div Audiol, Dept Clin Sci Intervent & Technol, Alfred Nobels Alle 10 Plan 5, SE-14183 Huddinge, Sweden.
    Haglöf, Jakob
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för analytisk farmaceutisk kemi.
    Linder, Birgitta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Engskog, Mikael K R
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för analytisk farmaceutisk kemi.
    Arvidsson, Torbjörn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för analytisk farmaceutisk kemi.
    Pettersson, Curt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för analytisk farmaceutisk kemi.
    Fransson, Anette E
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Laurell, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Cisplatin-induced metabolome changes in serum: an experimental approach to identify markers for ototoxicity2017Inngår i: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 137, nr 10, s. 1024-1030Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Ototoxicity from treatment with the anticancer drug cisplatin remains a clinical problem. A wide range of intracellular targets of cisplatin has been found in vivo.

    AIM: To investigate cisplatin-induced change of the serum metabolite profile and its association with ototoxicity.

    MATERIAL AND METHODS: Guinea pigs (n = 14) were treated with cisplatin (8 mg/kg b.w., i.v.) 30 min after administration of the otoprotector candidate sodium thiosulfate (group STS; n = 7) or sodium chloride (group NaCl; n = 7). Ototoxicity was evaluated by ABR (3-30 kHz) before and 4 d after drug treatment, and by assessment of hair cell loss. A blood sample was drawn before and 4 d after drug treatment and the polar metabolome in serum was analyzed using LC-MS.

    RESULTS: Cisplatin-treatment caused significant threshold elevations and outer hair cell (OHC) loss in both groups. The ototoxicity was generally lower in group STS, but a significant difference was reached only at 30 kHz (p = .007). Cisplatin treatment altered the metabolite profile significantly and similarly in both groups. A significant inverse correlation was found between L-acetylcarnitine, N-acetylneuraminic acid, ceramide, and cysteinylserine and high frequency hearing loss in group NaCl. The implication of these correlations should be explored in targeted studies.

  • 347.
    Pierre, Pernilla Videhult
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Johnson, Ann-Christin
    Fridberger, Anders
    Subjective and Clinically Assessed Hearing Loss; A Cross-Sectional Register-Based Study on a Swedish Population Aged 18 through 50 Years2015Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 4Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives Questionnaire studies suggest that hearing is declining among young adults. However, few studies have examined the reliability of hearing questionnaires among young adult subjects. This study examined the associations between pure tone audiometrically assessed (PTA) hearing loss and questionnaire responses in young to middle aged adults. Materials and Methods A cross-sectional study using questionnaire and screening PTA (500 through 6000 Hz) data from 15322 Swedish subjects (62% women) aged 18 through 50 years. PTA hearing loss was defined as a hearing threshold above 20 dB in both ears at one or more frequencies. Data were analysed with chi-square tests, nonlinear regression, binary logistic regression, and the generalized estimating equation (GEE) approach. Results The prevalence of PTA hearing loss was 6.0% in men and 2.9% in women (p < 0.001). Slight hearing impairment was reported by 18.5% of the men and 14.8% of the women (p < 0.001), whereas 0.5% of men and women reported very impaired hearing. Using multivariate GEE modelling, the odds ratio of PTA hearing loss was 30.4 (95% CI, 12.7-72.9) in men and 36.5 (17.2-77.3) in women reporting very impaired hearing. The corresponding figures in those reporting slightly impaired hearing were 7.06 (5.25-9.49) in men and 8.99 (6.38-12.7) in women. These values depended on the sound stimulus frequency (p = 0.001). The area under the ROC curve was 0.904 (0.892-0.915) in men and 0.886 (0.872-0.900) in women. Conclusions Subjective hearing impairment predicted clinically assessed hearing loss, suggesting that there is cause for concern as regards the future development of hearing in young to middle-aged people.

  • 348.
    Pirttilä, Kristian
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Analytisk farmaceutisk kemi.
    Pierre, Pernilla Videhult
    Karolinska Inst, Div Audiol, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.
    Haglöf, Jakob
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Analytisk farmaceutisk kemi.
    Engskog, Mikael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Analytisk farmaceutisk kemi.
    Hedeland, Mikael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Analytisk farmaceutisk kemi.
    Laurell, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Arvidsson, Torbjörn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Analytisk farmaceutisk kemi.
    Pettersson, Curt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Analytisk farmaceutisk kemi.
    An LCMS-based untargeted metabolomics protocol for cochlear perilymph: highlighting metabolic effects of hydrogen gas on the inner ear of noise exposed Guinea pigs2019Inngår i: Metabolomics, ISSN 1573-3882, E-ISSN 1573-3890, Vol. 15, nr 10, artikkel-id 138Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Introduction

    Noise-induced hearing loss (NIHL) is an increasing problem in society and accounts for a third of all cases of acquired hearing loss. NIHL is caused by formation of reactive oxygen species (ROS) in the cochlea causing oxidative stress. Hydrogen gas (H-2) can alleviate the damage caused by oxidative stress and can be easily administered through inhalation.

    Objectives

    To present a protocol for untargeted metabolomics of guinea pig perilymph and investigate the effect of H-2 administration on the perilymph metabolome of noise exposed guinea pigs.

    Methods

    The left ear of guinea pigs were exposed to hazardous impulse noise only (Noise, n = 10), noise and H-2 (Noise + H2, n = 10), only H-2 (H2, n = 4), or untreated (Control, n = 2). Scala tympani perilymph was sampled from the cochlea of both ears. The polar component of the perilymph metabolome was analyzed using a HILIC-UHPLC-Q-TOF-MS-based untargeted metabolomics protocol. Multivariate data analysis (MVDA) was performed separately for the exposed- and unexposed ear.

    Results

    MVDA allowed separation of groups Noise and Noise + H2 in both the exposed and unexposed ear and yielded 15 metabolites with differentiating relative abundances. Seven were found in both exposed and unexposed ear data and included two osmoprotectants. Eight metabolites were unique to the unexposed ear and included a number of short-chain acylcarnitines.

    Conclusions

    A HILIC-UHPLC-Q-TOF-MS-based protocol for untargeted metabolomics of perilymph is presented and shown to be fit-for-purpose. We found a clear difference in the perilymph metabolome of noise exposed guinea pigs with and without H-2 treatment.

  • 349.
    Popa, Raul
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Nitric Oxide in the Inner Ear with Particular Regard to Neurotansmission and Pharmacotherapy2002Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Research into nitric oxide (NO) in the inner ear has expanded explosively during recent years. There is evidence that NO is present in the various cochlear structures and its action is involved in physiological mechanisms, such as neurotransmission, and in pathological processes, e.g. ototoxicity. In order to obtain more data, sections of human cochlea were studied with immunostaining, using monoclonal antibodies to nitric oxide synthase (NOS) isoforms. Both constitutive NOS isoforms (I and III) were detected, but the predominant isoform was the neural type NOS I. Greatest affinity for NOS I was located in spiral ganglion (SG) cells and adjacent nerve fibres. The results imply that NO in the human cochlea could act as neurotransmitter. In the human inner ear, it has also been identified nicotinic acetylcholine receptors (n-ACh-r) by studying localization and distribution of α and β subunits. Both subunits were identified on SG cells, adjacent nerve fibres and in vestibular hair cells. It would appear that the subunits form an active complex at the level of these structures. Differences in the staining of β subunits at the level of the outer hair cells (OHC) suggest that different rows of OHCs could participate to different degrees in the function of n-ACh-r of the cochlea.

    The animal experiments were been designed to obtain information about NO involvement in the pathological mechanism of hearing impairment and to study the protection afforded by various drugs against damage to the inner ear associated with NO. The results of our investigations have demonstrated that NO produced by cNOS may mediate neurotoxicity in the inner ear early in the pathological process, whereas NO from inducible NOS may contribute by its cytotoxicity to the late phase of tissue damage in the inner ear. Analyses of the pharmacological effects of different drugs have shown that inhibitors of NO production and glutamate overproduction, as well as reactive oxygen species scavengers, could effectively protect the inner ear from injury caused by various pathological agents.

  • 350. Pritz, Christian Oliver
    et al.
    Dudas, Jozsef
    Rask-Andersen, Helge
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Schrott-Fischer, Anneliese
    Glueckert, Rudolf
    Nanomedicine strategies for drug delivery to the ear2013Inngår i: Nanomedicine, ISSN 1743-5889, E-ISSN 1748-6963, Vol. 8, nr 7, s. 1155-1172Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    The highly compartmentalized anatomy of the ear aggravates drug delivery, which is used to combat hearing-related diseases. Novel nanosized drug vehicles are thought to overcome the limitations of classic approaches. In this article, we summarize the nanotechnology-based efforts involving nano-objects, such as liposomes, polymersomes, lipidic nanocapsules and poly( lactic-co-glycolic acid) nanoparticles, as well as nanocoatings of implants to provide an efficient means for drug transfer in the ear. Modern strategies do not only enhance drug delivery efficiency, in the inner ear these vector systems also aim for specific uptake into hair cells and spiral ganglion neurons. These novel peptide-mediated strategies for specific delivery are reviewed in this article. Finally, the biosafety of these vector systems is still an outstanding issue, since long-term application to the ear has not yet been assessed.

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