uu.seUppsala universitets publikasjoner
Endre søk
Begrens søket
1234567 151 - 200 of 463
RefereraExporteraLink til resultatlisten
Permanent link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Treff pr side
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sortering
  • Standard (Relevans)
  • Forfatter A-Ø
  • Forfatter Ø-A
  • Tittel A-Ø
  • Tittel Ø-A
  • Type publikasjon A-Ø
  • Type publikasjon Ø-A
  • Eldste først
  • Nyeste først
  • Skapad (Eldste først)
  • Skapad (Nyeste først)
  • Senast uppdaterad (Eldste først)
  • Senast uppdaterad (Nyeste først)
  • Disputationsdatum (tidligste først)
  • Disputationsdatum (siste først)
  • Standard (Relevans)
  • Forfatter A-Ø
  • Forfatter Ø-A
  • Tittel A-Ø
  • Tittel Ø-A
  • Type publikasjon A-Ø
  • Type publikasjon Ø-A
  • Eldste først
  • Nyeste først
  • Skapad (Eldste først)
  • Skapad (Nyeste først)
  • Senast uppdaterad (Eldste først)
  • Senast uppdaterad (Nyeste først)
  • Disputationsdatum (tidligste først)
  • Disputationsdatum (siste først)
Merk
Maxantalet träffar du kan exportera från sökgränssnittet är 250. Vid större uttag använd dig av utsökningar.
  • 151. Guo, Rui
    et al.
    Zhang, HongLei
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Chen, Wei
    Zhu, XiaoQuan
    Liu, Wei
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Rask-Andersen, Helge
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    The inferior cochlear vein: surgical aspects in cochlear implantation2016Inngår i: European Archives of Oto-Rhino-Laryngology, ISSN 0937-4477, E-ISSN 1434-4726, Vol. 273, nr 2, s. 355-361Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The patency of the inferior cochlear vein (ICV) may be challenged in cochlear implantation (CI) due to its location near the round window (RW). This may be essential to consider during selection of different trajectories for electrode insertion aiming at preserving residual hearing. Venous blood from the human cochlea is drained through the ICV. The vein also drains blood from the modiolus containing the spiral ganglion neurons. Surgical interference with this vein could cause neural damage influencing CI outcome. We analyzed the topographical relationship between the RW and ICV bony channel and cochlear aqueduct (CA) from a surgical standpoint. Archival human temporal bones were further microdissected to visualize the CA and its accessory canals (AC1 and AC2). This was combined with examinations of plastic and silicone molds of the human labyrinth. Metric analyses were made using photo stereomicroscopy documenting the proximal portion of the AC1, the internal aperture of the CA and the RW. The mean distance between the AC1 and the anterior rim of the RW was 0.81 mm in bone specimens and 0.67 mm assessed in corrosion casts. The AC1 runs from the floor of the scala tympani through the otic capsule passing parallel to the CA to the posterior cranial fossa. The mean distance between the CA and AC1 canal was 0.31 and 0.25 mm, respectively.

  • 152.
    Hallberg, Pär
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Nagy, Julia
    Karawajczyk, Malgorzata
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Nordang, Leif
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Islander, Gunilla
    Norling, Pia
    Johansson, Hans-Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Kämpe, Mary
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Lung- allergi- och sömnforskning.
    Hugosson, Svante
    Yue, Qun-Ying
    Wadelius, Mia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Comparison of Clinical Factors Between Patients With Angiotensin-Converting Enzyme Inhibitor-Induced Angioedema and Cough2017Inngår i: The Annals of Pharmacotherapy, ISSN 1060-0280, E-ISSN 1542-6270, Vol. 51, nr 4, s. 293-300Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Angioedema is a rare and serious adverse drug reaction (ADR) to angiotensin-converting enzyme (ACE) inhibitor treatment. Dry cough is a common side effect of ACE inhibitors and has been identified as a possible risk factor for angioedema.

    OBJECTIVE: We compared characteristics between patients with ACE inhibitor-induced angioedema and cough with the aim of identifying risk factors that differ between these adverse events.

    METHODS: Data on patients with angioedema or cough induced by ACE inhibitors were collected from the Swedish database of spontaneously reported ADRs or from collaborating clinicians. Wilcoxon rank sum test, Fisher's exact test, and odds ratios (ORs) with 95% CIs were used to test for between-group differences. The significance threshold was set to P <0.00128 to correct for multiple comparisons.

    RESULTS: Clinical characteristics were compared between 168 patients with angioedema and 121 with cough only. Smoking and concomitant selective calcium channel blocker treatment were more frequent among patients with angioedema than cough: OR = 4.3, 95% CI = 2.1-8.9, P = 2.2 × 10(-5), and OR = 3.7, 95% CI = 2.0-7.0, P = 1.7 × 10(-5). Angioedema cases were seen more often in male patients (OR = 2.2, 95% CI = 1.4-3.6, P = 1.3 × 10(-4)) and had longer time to onset and higher doses than those with cough ( P = 3.2 × 10(-10) and P = 2.6 × 10(-4)). A multiple model containing the variables smoking, concurrent calcium channel blocker treatment, male sex, and time to onset accounted for 26% of the variance between the groups.

    CONCLUSION: Smoking, comedication with selective calcium channel blockers, male sex, and longer treatment time were associated with ACE inhibitor-induced angioedema rather than cough.

  • 153.
    Halvorsen, Thomas
    et al.
    Haukeland Hosp, Dept Pediat, N-5021 Bergen, Norway.;Univ Bergen, Dept Clin Sci, Bergen, Norway..
    Walsted, Emil Schwarz
    Royal Brompton Hosp, Dept Resp Med, London, England.;Bispebjerg Hosp, Resp Res Unit, Copenhagen, Denmark..
    Bucca, Caterina
    Univ Turin, Dept Med Sci, Turin, Italy.;Citta Salute & Sci, Resp Unit, Turin, Italy..
    Bush, Andrew
    Imperial Coll, Paediat Resp Med, London, England.;Royal Brompton Hosp, London, England..
    Cantarella, Giovanna
    Fdn IRCCS Ca Granda Osped Maggiore Policlin, Dept Otolaryngol, Milan, Italy..
    Friedrich, Gerhard
    Med Univ Graz, ENT Hosp Graz, Dept Phoniatr Speech & Swallowing, Graz, Austria..
    Herth, Felix J. F.
    Heidelberg Univ, Dept Pneumol & Crit Care Med, Translat Lung Res Ctr Heidelberg, Thoraxklin, Heidelberg, Germany..
    Hull, James H.
    Royal Brompton Hosp, Dept Resp Med, London, England..
    Jung, Harald
    Hochgebirgsklin Davos, Davos, Switzerland..
    Maat, Robert
    Ropcke Zweers Hosp, Dept Otorhinolaryngol, Hardenberg, Netherlands..
    Nordang, Leif
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Remacle, Marc
    Louvain Univ Hosp Mt Godinne, Dept ORL Head & Neck Surg, Yvoir, Belgium..
    Rasmussen, Niels
    Rigshosp, Dept Otolaryngol Head & Neck Surg, Copenhagen, Denmark.;Univ Copenhagen, Copenhagen, Denmark..
    Wilson, Janet A.
    Newcastle Univ, Dept Otolaryngol Head & Neck Surg, Newcastle Upon Tyne, Tyne & Wear, England.;Freeman Rd Hosp, Newcastle Upon Tyne, Tyne & Wear, England..
    Heimdal, John-Helge
    Univ Bergen, Dept Clin Sci, Bergen, Norway.;Haukeland Hosp, Dept Surg, Bergen, Norway..
    Inducible laryngeal obstruction: an official joint European Respiratory Society and European Laryngological Society statement2017Inngår i: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 50, nr 3, artikkel-id 1602221Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Inducible laryngeal obstruction (ILO) describes an inappropriate, transient, reversible narrowing of the larynx in response to external triggers. ILO is an important cause of a variety of respiratory symptoms and can mimic asthma. Current understanding of ILO has been hampered by imprecise nomenclature and variable approaches to assessment and management. A task force of the European Respiratory Society (ERS) and European Laryngological Society (ELS) was thus set up to address this, and to identify research priorities. A literature search identified relevant articles published until June 2016, using all identifiable terms for ILO, although including only articles using laryngoscopy. In total, 172 out of 252 articles met the inclusion criteria, summarised in sections on diagnostic approach, aetiology, comorbidities, epidemiology and treatment. The consensus taxonomy published by ERS, ELS and the American College of Chest Physicians (ACCP) in 2015 is used throughout this statement. We highlight the high prevalence of ILO and the clinical impact for those affected. Despite recent advances, most aspects of this condition unfortunately remain incompletely understood, precluding firm guidance. Specifically, validated diagnostic and treatment algorithms are yet to be established, and no randomised control studies were identified in this search; hence we also make recommendations for future research.

  • 154. Hanner, Per
    et al.
    Rask-Andersen, Helge
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Lange, Stefan
    Jennische, Eva
    Antisecretory factor-inducing therapy improves the clinical outcome in patients with Meniere's disease2010Inngår i: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 130, nr 2, s. 223-227Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Conclusion: Intake of antisecretory factor (AF)-inducing SPC-flakes (R) significantly reduced vertigo in patients suffering from Meniere's disease (MD). The positive effect may be due to a modulation of the transport of water and ions in the endolymphatic space. Objective: To evaluate the effects of a 3-month treatment period with SPC-flakes (R) in patients suffering from MD. Patients and methods: A prospective, double-blind, placebo-controlled study was performed. A total of 51 adult patients with MD were included in the study: 27 subjects treated with SPC-flakes (R) and 24 subjects with control cereals. The patients received SPC-flakes (R) or control cereals (I g per kg body weight per 24 h in two servings) for 3 months. Otoneurological examinations were carried out before and after this period. Results: The severity of MD was classified according to the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) grading system. Fourteen of the 27 patients randomized to intake of the AF-inducing SPC-flakes (R) reported decreased vertigo, compared with 2 of 24 in the control group (p < 0.001). No consistent change in the otoneurological examinations could be demonstrated in any of the groups of patients.

  • 155.
    Hayashi, Hisamitsu
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar. Gifu Univ, Grad Sch Med, Dept Otolaryngol, 1-1 Yanagido, Gifu 5011194, Japan.
    Edin, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Li, Hao
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Liu, Wei
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Rask-Andersen, Helge
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    The effect of pulsed electric fields on the electrotactic migration of human neural progenitor cells through the involvement of intracellular calcium signaling2016Inngår i: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1652, s. 195-203Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Endogenous electric fields (EFs) are required for the physiological control of the central nervous system development. Application of the direct current EFs to neural stem cells has been studied for the possibility of stem cell transplantation as one of the therapies for brain injury. EFs generated within the nervous system are often associated with action potentials and synaptic activity, apparently resulting in a pulsed current in nature. The aim of this study is to investigate the effect of pulsed EF, which can reduce the cytotoxicity, on the migration of human neural progenitor cells (hNPCs). We applied the mono-directional pulsed EF with a strength of 250mV/mm to hNPCs for 6h. The migration distance of the hNPCs exposed to pulsed EF was significantly greater compared with the control not exposed to the EF. Pulsed EFs, however, had less of an effect on the migration of the differentiated hNPCs. There was no significant change in the survival of hNPCs after exposure to the pulsed EF. To investigate the role of Ca(2+) signaling in electrotactic migration of hNPCs, pharmacological inhibition of Ca(2+) channels in the EF-exposed cells revealed that the electrotactic migration of hNPCs exposed to Ca(2+) channel blockers was significantly lower compared to the control group. The findings suggest that the pulsed EF induced migration of hNPCs is partly influenced by intracellular Ca(2+) signaling.

  • 156.
    Hayashi, Hisamitsu
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar. Gifu Univ, Grad Sch Med, Dept Otolaryngol, Gifu, Gifu 5011194, Japan.
    Schrott-Fischer, Annelies
    Med Univ Innsbruck, Dept Otolaryngol, A-6020 Innsbruck, Austria.
    Glueckert, Rudolf
    Med Univ Innsbruck, Dept Otolaryngol, A-6020 Innsbruck, Austria.
    Liu, Wei
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Salvenmoser, Willi
    Univ Innsbruck, Inst Zool, A-6020 Innsbruck, Austria.
    Santi, Peter
    Univ Minnesota, Dept Otolaryngol, Minneapolis, MN 55455 USA.
    Rask-Andersen, Helge
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Molecular organization and fine structure of the human tectorial membrane: is it replenished?2015Inngår i: Cell and Tissue Research, ISSN 0302-766X, E-ISSN 1432-0878, Vol. 362, nr 3, s. 513-527Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Auditory sensitivity and frequency resolution depend on the physical properties of the basilar membrane in combination with outer hair cell-based amplification in the cochlea. The physiological role of the tectorial membrane (TM) in hair cell transduction has been controversial for decades. New insights into the TM structure and function have been gained from studies of targeted gene disruption. Several missense mutations in genes regulating the human TM structure have been described with phenotypic expressions. Here, we portray the remarkable gradient structure and molecular organization of the human TM. Ultrastructural analysis and confocal immunohistochemistry were performed in freshly fixed human cochleae obtained during surgery. Based on these findings and recent literature, we discuss the role of human TMs in hair cell activation. Moreover, the outcome proposes that the α-tectorin-positive amorphous layer of the human TM is replenished and partly undergoes regeneration during life.

  • 157.
    Haylock, Anna-Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Targeting molecules for diagnostics of Head and Neck squamous cell carcinoma2017Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    To personalize treatment for cancer, correct staging of the primary tumor, nodal disease and metastatic disease is of essence. By targeting tumor specific receptors with radiolabeled antibodies, specificity and accuracy of imaging may be improved. Radio-immunodiagnostics can potentially detect small volume disease, occult metastasis and recurrent cancer in treated tissue. This thesis focuses on evaluation of radio-immunoconjugates directed towards CD44v6, which is a surface receptor overexpressed in many head and neck squamous cell carcinomas. At the outset, the monoclonal chimeric antibody cMab U36 and its cleavage products Fab’ and F(ab’)2 were labeled with 125I and assessed in vitro and in vivo (paper I). The best distribution pattern and tumor to organ ratio was achieved with F(ab’)2. Due to the immunological responses humans can develop towards chimeric antibodies, they are not optimal for clinical use, and subsequently fully human antibody fragments were developed. AbD15179, which is a monovalent fragment, was labeled with 111In and 125I and evaluated in vitro and in mice bearing CD44v6-expressing tumors. Tumor to organ ratios were improved compared to cMab U36 derived fragments, and 111In-AbD15179 displayed a more favorable distribution compared to 125I-AbD15179 (Paper II). A bivalent Fab-dHXL, AbD19384 derived from AbD15179, was then constructed and labeled with 125I and evaluated in cell- and biodistribution studies. Furthermore, an imaging study in a small animal PET was performed with 124I-AbD19384 (Paper III). Uptake in kidneys was reduced and liver uptake increased compared to AbD15179 reflecting the larger molecule. The high CD44v6 expressing tumor was clearly visualized with maximum uptake at 48 hours post injection.In paper IV human single chain fragments towards CD44v6v were selected, and the top candidates A11 and H12 were further evaluated in vitro and in vivo. Single chain fragments are small molecules exhibiting fast clearance and high affinity to the target. The study proved this by demonstrating superior tumor to blood ratios of radiolabeled A11 and H12 compared to previously studied molecules. 

    Delarbeid
    1. A novel CD44v6 targeting antibody fragment with improved tumor-to-blood ratio
    Åpne denne publikasjonen i ny fane eller vindu >>A novel CD44v6 targeting antibody fragment with improved tumor-to-blood ratio
    Vise andre…
    2012 (engelsk)Inngår i: International Journal of Oncology, ISSN 1019-6439, Vol. 40, nr 5, s. 1525-1532Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The chimeric monoclonal antibody U36 (cMAb U36) recognizes the CD44v6 antigen. Its potential as a radioimmunotargeting agent, as well as its safety, has been shown in previous studies in head and neck cancer patients. However, intact MAbs have long circulation time in the blood and tumor targeting may also be hampered due to the slow and incomplete diffusion into solid tumors. In comparison, smaller monovalent Fab' and divalent F(ab')2 fragments are expected to exhibit shorter circulating half-lives, better tumor penetration and are thus more likely to yield better imaging results. In this study, novel F(ab')2 and Fab' fragments from cMAb U36 were radiolabeled with 125I and the characteristics of the conjugates in vitro were examined. The biodistribution of the conjugates were then evaluated in nude mice bearing CD44v6-expressing xenograft tumors. Furthermore, the penetration depth and distribution in tumor tissue was assessed by autoradiography in selected tumor samples. The in vitro experiments showed that the conjugates were stable and had intact affinity to CD44v6. The biodistribution study demonstrated superior tumor-to-blood ratio for the novel cMAb U36 fragment 125I-F(ab')2 compared with both the intact MAb and the monovalent fragment form. Autoradiography also revealed better tumor penetration for 125I-F(ab')2. This study demonstrates that the use of antibody fragments may improve radioimmunotargeting and possibly improve the management of head and neck malignancies.

    HSV kategori
    Forskningsprogram
    Oto-rhino-laryngologi
    Identifikatorer
    urn:nbn:se:uu:diva-170945 (URN)10.3892/ijo.2012.1352 (DOI)000302273400023 ()22307465 (PubMedID)
    Tilgjengelig fra: 2012-03-14 Laget: 2012-03-14 Sist oppdatert: 2017-12-07bibliografisk kontrollert
    2. In vivo characterization of the novel CD44v6-targeting Fab fragment AbD15179 for molecular imaging of squamous cell carcinoma: a dual-isotope study
    Åpne denne publikasjonen i ny fane eller vindu >>In vivo characterization of the novel CD44v6-targeting Fab fragment AbD15179 for molecular imaging of squamous cell carcinoma: a dual-isotope study
    Vise andre…
    2014 (engelsk)Inngår i: EJNMMI Research, ISSN 2191-219X, E-ISSN 2191-219X, Vol. 4, artikkel-id 11Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    BACKGROUND: Patients with squamous cell carcinoma in the head and neck region (HNSCC) offer a diagnostic challenge due to difficulties to detect small tumours and metastases. Imaging methods available are not sufficient, and radio-immunodiagnostics could increase specificity and sensitivity of diagnostics. The objective of this study was to evaluate, for the first time, the in vivo properties of the radiolabelled CD44v6-targeting fragment AbD15179 and to assess its utility as a targeting agent for radio-immunodiagnostics of CD44v6-expressing tumours.

    METHODS: The fully human CD44v6-targeting Fab fragment AbD15179 was labelled with 111In or 125I, as models for radionuclides suitable for imaging with SPECT or PET. Species specificity, antigen specificity and internalization properties were first assessed in vitro. In vivo specificity and biodistribution were then evaluated in tumour-bearing mice using a dual-tumour and dual-isotope setup.

    RESULTS: Both species-specific and antigen-specific binding of the conjugates were demonstrated in vitro, with no detectable internalization. The in vivo studies demonstrated specific tumour binding and favourable tumour targeting properties for both conjugates, albeit with higher tumour uptake, slower tumour dissociation, higher tumour-to-blood ratio and higher CD44v6 sensitivity for the 111In-labelled fragment. In contrast, the 125I-Fab demonstrated more favourable tumour-to-organ ratios for liver, spleen and kidneys.

    CONCLUSIONS: We conclude that AbD15179 efficiently targets CD44v6-expressing squamous cell carcinoma xenografts, and particularly, the 111In-Fab displayed high and specific tumour uptake. CD44v6 emerges as a suitable target for radio-immunodiagnostics, and a fully human antibody fragment such as AbD15179 can enable further clinical imaging studies.

    Emneord
    Radio-immunodiagnostics, Antibody fragment, CD44v6, Molecular imaging, Fab, I-125, In-111
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-221094 (URN)10.1186/2191-219X-4-11 (DOI)000357859200001 ()24598405 (PubMedID)
    Tilgjengelig fra: 2014-03-25 Laget: 2014-03-25 Sist oppdatert: 2017-12-05bibliografisk kontrollert
    3. Evaluation of a novel type of imaging probe based on a recombinant bivalent mini-antibody construct for detection of CD44v6-expressing squamous cell carcinoma
    Åpne denne publikasjonen i ny fane eller vindu >>Evaluation of a novel type of imaging probe based on a recombinant bivalent mini-antibody construct for detection of CD44v6-expressing squamous cell carcinoma
    Vise andre…
    2015 (engelsk)Inngår i: International journal of oncology, ISSN 1791-2423, Vol. 48, nr 2, s. 461-470Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    We have developed the CD44v6-targeting human bivalent antibody fragment AbD19384, an engineered recombinant human bivalent Fab antibody formed via dimerization of dHLX (synthetic double helix loop helix motif) domains, for potential use in antibody-based molecular imaging of squamous cell carcinoma in the head and neck region. This is a unique construct that has, to the best of our knowledge, never been assessed for molecular imaging in vivo before. The objective of the present study was to evaluate for the first time the in vitro and in vivo binding properties of radio-iodinated AbD19384, and to assess its utility as a targeting agent for molecular imaging of CD44v6-expressing tumors. Antigen specificity and binding properties were assessed in vitro. In vivo specificity and biodistribution of 125I-AbD19384 were next evaluated in tumor-bearing mice using a dual-tumor setup. Finally, AbD19384 was labeled with 124I, and its imaging properties were assessed by small animal PET/CT in tumor bearing mice, and compared with 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG). In vitro studies demonstrated CD44v6-specific binding with slow off-rate for AbD19384. A favorable biodistribution profile was seen in vivo, with tumor-specific uptake. Small animal PET/CT images of 124I-AbD19384 supported the results through clearly visible high CD44v6-expressing tumors and faintly visible low expressing tumors, with superior imaging properties compared to 18F-FDG. Tumor-to-blood ratios increased with time for the conjugate (assessed up to 72 h p.i.), although 48 h p.i. proved best for imaging. Biodistribution and small-animal PET studies demonstrated that the recombinant Fab-dHLX construct AbD19384 is a promising tracer for imaging of CD44v6 antigen expression in vivo, with the future aim to be used for individualized diagnosis and early detection of squamous cell carcinomas in the head and neck region. Furthermore, this proof-of-concept research established the feasibility of using recombinant Fab-dHLX constructs for in vivo imaging of tumor biomarkers.

    Emneord
    molecular imaging, CD44v6; Fab-dHLX; F(ab')(2), recombinant antibodies, immuno-PET, head and neck squamous cell carcinoma
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-270259 (URN)10.3892/ijo.2015.3290 (DOI)000366897500003 ()26676731 (PubMedID)
    Tilgjengelig fra: 2015-12-22 Laget: 2015-12-22 Sist oppdatert: 2020-01-07bibliografisk kontrollert
    4. Generation and evaluation of antibody agents for molecular imaging of CD44v6 expressing cancers
    Åpne denne publikasjonen i ny fane eller vindu >>Generation and evaluation of antibody agents for molecular imaging of CD44v6 expressing cancers
    Vise andre…
    (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    Emneord
    scFv, recombinant antibody formats, CD44v6, squamous cell carcinoma, molecular imaging
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-316722 (URN)
    Tilgjengelig fra: 2017-03-14 Laget: 2017-03-14 Sist oppdatert: 2018-01-13
  • 158.
    Haylock, Anna-Karin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar. Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden..
    Nilvebrant, Johan
    Royal Inst Technol, Sch Biotechnol, Div Prot Technol, Stockholm, Sweden..
    Mortensen, Anja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk strålningsvetenskap.
    Velikyan, Irina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för Molekylär Avbildning.
    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 immunologi, genetik och patologi, Medicinsk strålningsvetenskap.
    Falk, Ronny
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Generation and evaluation of antibody agents for molecular imaging of CD44v6-expressing cancers2017Inngår i: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 8, nr 39, s. 65152-65170Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aim: The aim of this study was to generate and characterize scFv antibodies directed to human CD44v6, as well as to radiolabel and evaluate top candidates in vitro and in vivo for their potential use in CD44v6-targeted molecular imaging in cancer patients.

    Materials and methods: Phage display selections were used to isolate CD44v6-specific scFvs. A chain shuffling strategy was employed for affinity maturation based on a set of CD44v6-specific first-generation clones. Two second-generation scFv clones were then chosen for labeling with 111In or 125I and assessed for CD44v6-specific binding on cultured tumor cells. In vivo uptake and distribution was evaluated in tumor-bearing mice using a dual tumor model. Finally, a proof-of-concept small animal PET-CT study was performed on one of the candidates labeled with 124I.

    Results: Two affinity-matured clones, CD44v6-scFv-A11 and CD44v6-scFv-H12, displayed promising binding kinetics. Seven out of eight radiolabeled conjugates demonstrated CD44v6-specific binding. In vivo studies on selected candidates demonstrated very advantageous tumor-to-organ ratios, in particular for iodinated conjugates, where 125I-labeled scFvs exhibited favorable kinetics and tumor-to-blood ratios above five already at 24 hours p. i.. The small animal PET-CT study using 124I-labeled CD44v6-scFv-H12 was in line with the biodistribution data, clearly visualizing the high CD44v6-expressing tumor.

    Conclusion: The single chain fragments, CD44v6-scFv-A11 and CD44v6-scFv-H12 specifically bind to CD44v6, and the radiolabeled counterparts provide high tumor-to-blood ratios and fast clearance from organs and blood. We conclude that radioiodinated CD44v6-scFv-A11 and CD44v6-scFv-H12 possess features highly suitable for stringent molecular imaging.

  • 159.
    Haylock, Anna-Karin
    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 immunologi, genetik och patologi.
    Spiegelberg, Diana
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk strålningsvetenskap.
    Mortensen, Anja C.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk strålningsvetenskap.
    Selvaraju, Ram K.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Nilvebrant, Johan
    Royal Inst Technol, Sch Biotechnol, Div Prot Technol, Stockholm, Sweden.
    Eriksson, Olof
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Tolmachev, Vladimir
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk strålningsvetenskap.
    Nestor, Marika V
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk strålningsvetenskap. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Evaluation of a novel type of imaging probe based on a recombinant bivalent mini-antibody construct for detection of CD44v6-expressing squamous cell carcinoma2015Inngår i: International journal of oncology, ISSN 1791-2423, Vol. 48, nr 2, s. 461-470Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We have developed the CD44v6-targeting human bivalent antibody fragment AbD19384, an engineered recombinant human bivalent Fab antibody formed via dimerization of dHLX (synthetic double helix loop helix motif) domains, for potential use in antibody-based molecular imaging of squamous cell carcinoma in the head and neck region. This is a unique construct that has, to the best of our knowledge, never been assessed for molecular imaging in vivo before. The objective of the present study was to evaluate for the first time the in vitro and in vivo binding properties of radio-iodinated AbD19384, and to assess its utility as a targeting agent for molecular imaging of CD44v6-expressing tumors. Antigen specificity and binding properties were assessed in vitro. In vivo specificity and biodistribution of 125I-AbD19384 were next evaluated in tumor-bearing mice using a dual-tumor setup. Finally, AbD19384 was labeled with 124I, and its imaging properties were assessed by small animal PET/CT in tumor bearing mice, and compared with 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG). In vitro studies demonstrated CD44v6-specific binding with slow off-rate for AbD19384. A favorable biodistribution profile was seen in vivo, with tumor-specific uptake. Small animal PET/CT images of 124I-AbD19384 supported the results through clearly visible high CD44v6-expressing tumors and faintly visible low expressing tumors, with superior imaging properties compared to 18F-FDG. Tumor-to-blood ratios increased with time for the conjugate (assessed up to 72 h p.i.), although 48 h p.i. proved best for imaging. Biodistribution and small-animal PET studies demonstrated that the recombinant Fab-dHLX construct AbD19384 is a promising tracer for imaging of CD44v6 antigen expression in vivo, with the future aim to be used for individualized diagnosis and early detection of squamous cell carcinomas in the head and neck region. Furthermore, this proof-of-concept research established the feasibility of using recombinant Fab-dHLX constructs for in vivo imaging of tumor biomarkers.

  • 160.
    Haylock, Anna-Karin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Spiegelberg, Diana
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk strålningsvetenskap.
    Mortensen, Anja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk strålningsvetenskap.
    Selvaraju, Ram Kumar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Nilvebrant, Johan
    Division of Protein Technology, School of Biotechnology, Royal Institute of Technology, Stockholm, Sweden.
    Eriksson, Olof
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Tolmachev, Vladimir
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk strålningsvetenskap.
    Nestor, Marika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk strålningsvetenskap.
    Molecular imaging of CD44v6-expressing squamous cell carcinoma using a novel engineered bivalent antibody fragmentArtikkel i tidsskrift (Fagfellevurdert)
  • 161.
    Haylock, Anna-Karin
    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.
    Spiegelberg, Diana
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för biomedicinsk strålningsvetenskap.
    Nilvebrant, Johan
    Royal Inst Technol, AlbaNova Univ Ctr, Sch Biotechnol, Div Prot Technol, SE-10691 Stockholm, Sweden.
    Sandström, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    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.
    In vivo characterization of the novel CD44v6-targeting Fab fragment AbD15179 for molecular imaging of squamous cell carcinoma: a dual-isotope study2014Inngår i: EJNMMI Research, ISSN 2191-219X, E-ISSN 2191-219X, Vol. 4, artikkel-id 11Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Patients with squamous cell carcinoma in the head and neck region (HNSCC) offer a diagnostic challenge due to difficulties to detect small tumours and metastases. Imaging methods available are not sufficient, and radio-immunodiagnostics could increase specificity and sensitivity of diagnostics. The objective of this study was to evaluate, for the first time, the in vivo properties of the radiolabelled CD44v6-targeting fragment AbD15179 and to assess its utility as a targeting agent for radio-immunodiagnostics of CD44v6-expressing tumours.

    METHODS: The fully human CD44v6-targeting Fab fragment AbD15179 was labelled with 111In or 125I, as models for radionuclides suitable for imaging with SPECT or PET. Species specificity, antigen specificity and internalization properties were first assessed in vitro. In vivo specificity and biodistribution were then evaluated in tumour-bearing mice using a dual-tumour and dual-isotope setup.

    RESULTS: Both species-specific and antigen-specific binding of the conjugates were demonstrated in vitro, with no detectable internalization. The in vivo studies demonstrated specific tumour binding and favourable tumour targeting properties for both conjugates, albeit with higher tumour uptake, slower tumour dissociation, higher tumour-to-blood ratio and higher CD44v6 sensitivity for the 111In-labelled fragment. In contrast, the 125I-Fab demonstrated more favourable tumour-to-organ ratios for liver, spleen and kidneys.

    CONCLUSIONS: We conclude that AbD15179 efficiently targets CD44v6-expressing squamous cell carcinoma xenografts, and particularly, the 111In-Fab displayed high and specific tumour uptake. CD44v6 emerges as a suitable target for radio-immunodiagnostics, and a fully human antibody fragment such as AbD15179 can enable further clinical imaging studies.

  • 162.
    Heimdal, John-Helge
    et al.
    Bergen Univ, Haukeland Univ Hosp, Dept Surg, Bergen, Norway;Bergen Univ, Haukeland Univ Hosp, Dept Otorhinolaryngol Head & Neck Surg, Bergen, Norway.
    Maat, Robert
    Ropcke Zweers Hosp, Dept Otolaryngol, Jan Weitkamplaan 4A, NL-7772 SE Hardenberg, Netherlands.
    Nordang, Leif
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar. Uppsala Univ, Dept Surg Sci Otorhinolaryngol & Head & Neck Surg, Akad Sjukhuset Ing 78-79, S-75185 Uppsala, Sweden.
    Surgical Intervention for Exercise-Induced Laryngeal Obstruction2018Inngår i: Immunology and allergy clinics of North America, ISSN 0889-8561, E-ISSN 1557-8607, Vol. 38, nr 2, s. 317-324Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Respiratory distress during exercise can be caused by exercise-induced laryngeal obstruction (EILO). The obstruction may appear at the level of the laryngeal inlet (supraglottic), similar to supraglottic collapse observed in infants with congenital laryngomalacia (CLM). This observation has encouraged surgeons to treat supraglottic EILO with procedures proven efficient for severe CLM. This article summarizes key features of the published experience related to surgical treatment of EILO. Supraglottoplasty is an irreversible procedure with potential complications. Surgery should be restricted to cases where the supraglottic laryngeal obstruction significantly affects the quality of life in patients for whom conservative treatment modalities have failed.

  • 163.
    Hellberg, Victoria
    et al.
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden..
    Gahm, Caroline
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden..
    Ehrsson, Hans
    Karolinska Univ Hosp, Karolinska Pharm, Stockholm, Sweden..
    Liu, Wei
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Rask-Andersen, Helge
    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.
    In Response to Immunohistochemical Localization of OCT2 in the Cochlea of Various Species2016Inngår i: The Laryngoscope, ISSN 0023-852X, E-ISSN 1531-4995, Vol. 126, nr 6, s. E232-E232Artikkel i tidsskrift (Fagfellevurdert)
  • 164.
    Hellberg, Victoria
    et al.
    Karolinska Univ Hosp, Dept Clin Sci Intervent & Technol, S-14186 Stockholm, Sweden..
    Gahm, Caroline
    Karolinska Univ Hosp, Dept Clin Sci Intervent & Technol, S-14186 Stockholm, Sweden..
    Liu, Wei
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Ehrsson, Hans
    Karolinska Univ Hosp, Karolinska Pharm, S-14186 Stockholm, Sweden..
    Rask-Andersen, Helge
    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.
    Immunohistochemical localization of OCT2 in the cochlea of various species2015Inngår i: The Laryngoscope, ISSN 0023-852X, E-ISSN 1531-4995, Vol. 125, nr 9, s. E320-E325Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    ObjectiveTo locate the organic cation transporter 2 (OCT2) in the cochlea of three different species and to modulate the ototoxicity of cisplatin in the guinea pig by pretreatment with phenformin, having a known affinity for OCT2. Study DesignImmunohistochemical and in vivo study. MethodsSections from the auditory end organs were subjected to immunohistochemical staining in order to identify OCT2 in cochlea from untreated rats, guinea pigs, and a pig. In the in vivo study, guinea pigs were given phenformin intravenously 30 minutes before cisplatin administration. Electrophysiological hearing thresholds were determined, and hair cells loss was assessed 96 hours later. The total amount of platinum in cochlear tissue was determined using mass spectrometry. ResultsOrganic cation transporter 2 was found in the supporting cells and in type I spiral ganglion cells in the cochlea of all species studied. Pretreatment with phenformin did not reduce the ototoxic side effect of cisplatin. Furthermore, the concentration of platinum in the cochlea was not affected by phenformin. ConclusionsThe localization of OCT2 in the supporting cells and type I spiral ganglion cells suggests that this transport protein is not primarily involved in cisplatin uptake from the systemic circulation. We hypothesize that OCT2 transport intensifies cisplatin ototoxicity via transport mechanisms in alternate compartments of the cochlea. Level of EvidenceN/A. Laryngoscope, 125:E320-E325, 2015

  • 165. Hellberg, Victoria
    et al.
    Wallin, Inger
    Ehrsson, Hans
    Laurell, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Cochlear Pharmacokinetics of Cisplatin: An In Vivo Study in the Guinea Pig2013Inngår i: The Laryngoscope, ISSN 0023-852X, E-ISSN 1531-4995, Vol. 123, nr 12, s. 3172-3177Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives/HypothesisCisplatin produces toxic lesions to outer hair cells (OHCs) in the cochlear base but not in the apex. The objective of this study was to compare the pharmacokinetic profile of cisplatin in scala tympani (ST) perilymph in the cochlear base and apex, respectively. Study DesignIn vivo animal study. MethodsForty-seven guinea pigs were given an intravenous bolus injection of an ototoxic dose of cisplatin. Ten to 240 minutes after cisplatin was given, blood, cerebrospinal fluid (CSF), and ST perilymph were aspirated within the same target time. ST perilymph was aspirated from the basal turn and from the apex of the cochlea by two different sampling techniques. Liquid chromatography with postcolumn derivatization was used for quantitative determination of the parent drug. ResultsTen minutes after administration, the concentration of cisplatin in ST perilymph was 4-fold higher in the basal turn of the cochlea than in the apex. At 30 minutes, the drug concentrations did not differ. At 60 minutes, the level of cisplatin in ST perilymph and blood UF was equivalent. The perilymph-blood ratio increased thereafter with time. ConclusionThe pharmacokinetic findings of an early high concentration of cisplatin in the base of the cochlea and delayed elimination of cisplatin from ST perilymph compared to blood might correlate to the cisplatin-induced loss of OHCs in the base of the cochlea. Level of EvidenceN/A. Laryngoscope, 123:3172-3177, 2013

  • 166. Henson, M.M.
    et al.
    Madden, V.J.
    Rask-Andersen, Helge
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Henson, O.W. jr
    Smooth muscle in the annulus fibrosus of the tympanic membrane in bats, rodents, insectivores and humans2005Inngår i: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 200, nr 1-2, s. 29-37Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The annulus fibrosus and its attachment to the bony tympanic ring were studied in a series of mammals. In the pallid bat, Antrozous pallidus, there is an extensive plexus of large interconnected blood sinuses in the part of the annulus that borders the tympanic bone. The spaces between the sinuses are packed with smooth muscle cells. Most of the cells have a predominately radial orientation; they extend from the bony tympanic sulcus to a dense collagenous matrix (apical zone) where radially oriented fibers of the pars tensa are confluent with the annulus. The muscles and vessels constitute a myovascular zone. A structurally similar myovascular zone is also present in the European hedgehog. In rodents, the annulus lacks the large interconnected blood sinuses but many small vessels are present. Smooth muscle is concentrated in the broad area of attachment of the annulus to the tympanic bone. In the gerbil, smooth muscle seems to be concentrated in the central part of the width of the annulus where it is attached to bone and radiates toward the tympanic membrane. In humans collections of radially oriented smooth muscle cells were found in several locations. The smooth muscle in all species studied appears to form a rim of contractile elements for the pars tensa. This arrangement suggests a role in controlling blood flow and/or creating and maintaining tension on the tympanic membrane.

  • 167. Hirt, B.
    et al.
    Penkova, Z. H.
    Eckhard, A.
    Liu, Wei
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Rask-Andersen, Helge
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Müller, M.
    Löwenheim, H.
    The subcellular distribution of aquaporin 5 in the cochlea reveals a water shunt at the perilymph-endolymph barrier2010Inngår i: Neuroscience, ISSN 0306-4522, E-ISSN 1873-7544, Vol. 168, nr 4, s. 957-970Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aquaporins are membrane water channel proteins that have also been identified in the cochlea. Auditory function critically depends on the homeostasis of the cochlear fluids perilymph and endolymph. In particular, the ion and water regulation of the endolymph is essential for sensory transduction. Within the cochlear duct the lateral wall epithelium has been proposed to secrete endolymph by an aquaporin-mediated flow of water across its epithelial tight junction barrier. This study identifies interspecies differences in the cellular distribution of aquaporin 5 (AQP5) in the cochlear lateral wall of mice, rats, gerbils and guinea pigs. In addition the cellular expression pattern of AQP5 is described in the human cochlea. Developmental changes in rats demonstrate longitudinal and radial gradients along the cochlear duct. During early postnatal development a pancochlear expression is detected. However a regression to the apical quadrant and limitation to outer sulcus cells (OSCs) is observed in the adult. This developmental loss of AQP5 expression in the basal cochlear segments coincides with a morphological loss of contact between OSCs and the endolymph. At the subcellular level, AQP5 exhibits polarized expression in the apical plasma membrane of the OSCs. Complementary, the basolateral membrane in the root processes of the OSCs exhibits AQP4 expression. This differential localization of AQP5 and AQP4 in the apical and basolateral membranes of the same epithelial cell type suggests a direct aquaporin-mediated transcellular water shunt between the perilymph and endolymph in the OSCs of the cochlear lateral wall. In the human cochlea these findings may have pathophysiological implications attributed to a dysfunctional water regulation by AQP5 such as endolymphatic hydrops (i.e. in Meniere's disease) or sensorineural hearing loss (i.e. in Sjögren's syndrome).

  • 168.
    Hjort, Klas
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Mikrosystemteknik.
    Rask-Andersen, Helge
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Li, Hao
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Softer, thinner and more compliant implants2018Konferansepaper (Fagfellevurdert)
    Abstract [en]

    Tissue irritation is caused by two main reasons – chemical and mechanical. In recent years, material chemical biocompatibility has been much improved but most implants used in soft tissue still have low compliance. This is especially severe in the brain, where the tissue often has a compliance of a soft hydrogel and ordinary silicone materials like PDMS have an elastic modulus up to 1,000 times higher, i.e. like a wooden stick irritating your skin. Starting from the remaining challenges of the highly successful Cochlear Implants and recent work on stretchable electronics this review conclude on the merits with soft stretchable printed circuitboards, with components of fluids, gels, and sprinkled with a smart dust of small chips.

  • 169. Holgersson, Georg
    et al.
    Ekman, Simon
    Reizenstein, Johan
    Bergqvist, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Pontén, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Uhlén, Mattias
    Magnusson, Kristina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Jonnalagadda, Pallavi
    Asplund, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Strömberg, Sara
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Linder, Arne
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Blomquist, Erik
    Liljeholm, Martin
    Lödén, Britta
    Hellström, Karin
    Bergström, Stefan
    Molecular profiling using tissue microarrays as a tool to identify predictive biomarkers in laryngeal cancer treated with radiotherapy2010Inngår i: Cancer Genomics & Proteomics, ISSN 1109-6535, E-ISSN 1790-6245, Vol. 7, nr 1, s. 1-7Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    AIM: To explore the usefulness of the expression of five potential cancer biomarkers in predicting outcome in patients with laryngeal cancer. MATERIALS AND METHODS: In the present study, the Swedish National Cancer Registry databases were used to identify patients with laryngeal cancer diagnosed during the years 1978-2004 in the Uppsala-Orebro region and treated with radiotherapy. The expression of Ki-67, MutS homolog 2, (MSH2), p53, B-cell CLL/lymphoma 2 (Bcl-2) and cyclin D1 in the cancer cells was assessed immunohistochemically using tissue microarrays (TMAs) and its predicitve value on survival and relapse was analyzed using Cox regression models. RESULTS: A total of 39 patients were included in the present study. Nuclear MSH2 staining was statistically significantly correlated to Ki-67 expression (p=0.022). However, univariate and multivariate Cox analyses showed no statistically significant association between the expression of the investigated biomarkers and overall survival or relapse. CONCLUSION: The present exploratory study does not show any significant predictive value of the biomarkers examined with respect to survival or relapse. However, with larger patient cohorts, we believe that protein profiling using TMAs and immunohistochemistry is a feasible strategy for prognostic and predictive biomarker screening in laryngeal cancer.

  • 170.
    Holm, Anna
    et al.
    Umeå Univ, Dept Clin Sci, Div Otorhinolaryngol, Umeå, Sweden.
    Hellman, Urban
    Umeå Univ, Dept Publ Hlth & Clin Med, Umeå, Sweden.
    Laurent, Claude
    Umeå Univ, Dept Clin Sci, Div Otorhinolaryngol, Umeå, Sweden; Univ Pretoria, Dept Speech & Language Pathol & Audiol, Pretoria, South Africa.
    Laurell, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Nylander, Karin
    Umeå Univ, Dept Med Biosci, Div Pathol, Umeå, Sweden.
    Olofsson, Katarina
    Umeå Univ, Dept Clin Sci, Div Otorhinolaryngol, Umeå, Sweden.
    Hyaluronan in vocal folds and false vocal folds in patients with recurrent respiratory papillomatosis2018Inngår i: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 138, nr 11, s. 1020-1027Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

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

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

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

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

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

  • 171.
    Holm, Anna
    et al.
    Umea Univ, Div Otorhinolaryngol, Dept Clin Sci, SE-90185 Umea, Sweden..
    Nagaeva, Olga
    Umea Univ, Div Clin Immunol, Dept Clin Microbiol, Umea, Sweden..
    Nagaev, Ivan
    Umea Univ, Div Clin Immunol, Dept Clin Microbiol, Umea, Sweden..
    Loizou, Christos
    Umea Univ, Div Otorhinolaryngol, Dept Clin Sci, SE-90185 Umea, Sweden..
    Laurell, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Mincheva-Nilsson, Lucia
    Umea Univ, Div Clin Immunol, Dept Clin Microbiol, Umea, Sweden..
    Nylander, Karin
    Umea Univ, Div Pathol, Dept Med Biosci, Umea, Sweden..
    Olofsson, Katarina
    Umea Univ, Div Otorhinolaryngol, Dept Clin Sci, SE-90185 Umea, Sweden..
    Lymphocyte profile and cytokine mRNA expression in peripheral blood mononuclear cells of patients with recurrent respiratory papillomatosis suggest dysregulated cytokine mRNA response and impaired cytotoxic capacity2017Inngår i: Immunity, Inflammation and Disease, E-ISSN 2050-4527, Vol. 5, nr 4, s. 541-550Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

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

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

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

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

  • 172.
    Holm, Anna
    et al.
    Östersunds Hosp, Div Otorhinolaryngol, Dept Clin Sci, Ostersund, Sweden.
    Schindele, Alexandra
    Östersunds Hosp, Div Otorhinolaryngol, Dept Clin Sci, Östersund, Sweden;Jämtland Hadedalen Cty Council, Östersund, Sweden.
    Allard, Annika
    Ostersunds Hosp, Div Clin Virol, Dept Clin Microbiol, Ostersund, Sweden.
    Eriksson, Irene
    Ostersunds Hosp, Div Clin Virol, Dept Clin Microbiol, Ostersund, Sweden.
    Sandström, Karl
    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.
    Nylander, Karin
    Ostersunds Hosp, Div Pathol, Dept Ear Nose & Throat, Ostersund, Sweden.
    Olofsson, Katarina
    Ostersunds Hosp, Div Otorhinolaryngol, Dept Clin Sci, Ostersund, Sweden.
    Mapping of human papilloma virus, p16, and epstein-barr virus in non-malignant tonsillar disease2019Inngår i: LARYNGOSCOPE INVESTIGATIVE OTOLARYNGOLOGY, ISSN 2378-8038, Vol. 4, nr 3, s. 285-291Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives Due to their location in the entrance of the aero-digestive tract, tonsils are steadily exposed to viruses. Human papilloma virus (HPV) and Epstein-Barr virus (EBV) are two potentially oncogenic viruses that tonsils encounter. The incidence of HPV positive tonsillar cancer is on the rise and it is unknown when infection with HPV occurs. Aim To investigate if tonsils are infected with HPV and EBV, to study the co-expression of HPV and its surrogate marker p16, and to evaluate the number of EBV positive cells in benign tonsillar disease. Materials and Methods Tonsils from 40 patients in a university hospital were removed due to hypertrophy, chronic or recurrent infection. These were analyzed for presence of HPV, its surrogate marker p16, and EBV. HPV was studied using PapilloCheck (a PCR method), while p16 was identified in epithelial and lymphoid tissue with immunohistochemistry and EBV using EBER-ISH (Epstein-Barr encoding region-in situ hybridization). Results HPV was not detected, and p16 was present at low numbers in all epithelial samples as well as in 92.5% of the lymphoid tonsillar samples. At least one EBER-positive cell was seen in 65% of cases. Larger numbers of EBER-expressing cells were only seen in two cases. Conclusion These findings demonstrate that EBV and HPV infect tonsils independently, but further studies are warranted to confirm their infectious relationship.

  • 173.
    Holmström, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Internationella behandlingsriktlinjer för rinosinuit ger bra vägledning: Kan minska svenskt antibiotikatryck2008Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 105, nr 45, s. 3202-6Artikkel i tidsskrift (Fagfellevurdert)
  • 174.
    Holmström, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    The use of objective measures in selecting patients for septal surgery2010Inngår i: Rhinology, ISSN 0300-0729, E-ISSN 1996-8604, Vol. 48, nr 4, s. 387-393Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    To improve results in septal surgery, patient selection is the mainstay of a successful outcome. Patient history is the basis as well as clinical examination but both are subjective and must be considered towards a background with a high frequency of septal deviation in the population and a lack of good correlation between function and status. Rhinomanometry and acoustic rhinometry as well as nasal peak inspiratory flow are tests of different nasal parameters as resistance to breathing, nasal dimensions and flow. This article illuminates the use of these more objective tests in selection of patients for septoplasty. Objective tests have in several studies shown to predict postoperative satisfaction while normal values can be a marker for a poor surgical outcome. Pros and cons with objective tests are discussed and the conclusion is: operate when there is a good correlation between the patient's status, history and the results of rhinometry!

  • 175.
    Holmström, Mats
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Thelin, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Kolmodin-Hedman, Birgitta
    Van Hage, Marianne
    Nasal complaints and signs of disease in farmers: a methodological study2008Inngår i: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 128, nr 2, s. 193-200Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    CONCLUSION: The methods used in this study are suitable for field studies that involve examinations of groups of workers. For individual examinations, there is no gold standard method that can discriminate work-related discomfort from other causes of rhinitis. OBJECTIVES: Studies of the effects of occupation on farmers' health have mainly focused on lower airways; few studies have examined effects on upper airways. This study investigated nasal functions in three groups of farmers (swine, milk and grain producers) and a control group using different methods, suitable for field studies. SUBJECTS AND METHODS: Health-related complaints were examined and several functional tests, such as expirogram, olfactory threshold test, acoustic rhinometry, nasal lavage with biomarkers of inflammation (eosinophilic cationic proteins (ECP), myeloperoxidase (MPO), tryptase, albumin) and allergy tests were performed. The different tests were correlated to nasal complaints and to each other. RESULTS: Nasal blockage complaints were more common among farmers; overall, nasal polyps were more frequent in grain producers. Objective parameters showed more pronounced mucosal swelling in farmers and higher concentrations of ECP in nasal lavage compared with controls. Lung function, olfactory threshold, atopy frequency and allergen-specific IgE to the storage mite Lepidoglyphus destructor did not differ between farmers and controls. Mucosal swelling measured with acoustic rhinometry was more pronounced in subjects with nasal complaints, hypersensitivity, nasal polyps and symptoms from lower airways. There was a correlation between biomarkers in nasal lavage (MPO, albumin and ECP).

  • 176. Hultcrantz, Elisabeth
    et al.
    Linder, Arne
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Markström, Agneta
    Tonsillectomy or tonsillotomy?:  a randomized study comparing postoperative pain and long-term effects 1999Inngår i: International Journal of Pediatric Otorhinolaryngology, ISSN 0165-5876, E-ISSN 1872-8464, Vol. 51, nr 3, s. 171-6Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: tonsillectomy (TE) is currently the most common treatment for children with snoring and sleep apnea. Many of these children have not had any severe throat infections. To cure such children from their obstructive problems, without influencing the immunological function of the tonsils, tonsillotomy (TT) with CO2-laser was performed in a randomized study comparing it to regular tonsillectomy, with special attention to postoperative pain and symptom recurrence. Method: 41 children 3.5–8 years-old were included — 21 ‘TT’s’ and 20 ‘TE’s’. They were all operated under the same anesthesia and followed the same postoperative scheme for analgesia. A visual analogue scale for pain measurements with faces was used for the first 24 h. After that, each day until pain-free, the parents registered the child’s pain on a three graded scale, what the child was able to eat, and the amount of analgesic drugs used. Results: all the children were cured from their breathing obstruction. The mean time used for the surgery was the same and no postoperative bleeding was seen in either group. ‘TT children’ were pain-free after 5 days and ‘TE children’ after 8 days. Eight to ten days after surgery, the TT-children had gained weight and the TE children lost weight significantly. The TE group used twice as much analgesic drugs as the TT group during the first postoperative week. The TT group was healed with normal-looking, but small tonsils after 8–10 days; the TE group often still showed edema and crusts. At the one-year follow-up 2/21among the ‘TT-children’ snored, but did not require re-surgery. Conclusion: tonsillotomy is much less painful than TE and children recover more quickly. Results with respect to breathing obstruction are almost the same for both methods at 1-year follow-up.

  • 177.
    Hultgård Ekwall, Anna-Karin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Couloigner, Vincent
    Rubin, Kristofer
    Rask-Andersen, Helge
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Network organization of interstitial connective tissue cells in the human endolymphatic duct2003Inngår i: Journal of Histochemistry and Cytochemistry, ISSN 0022-1554, Vol. 51, nr 11, s. 1491-1500Artikkel i tidsskrift (Fagfellevurdert)
  • 178. Hultgård-Ekwall, Anna-Karin H
    et al.
    Couloigner, Vincent
    Rubin, Kristofer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Rask-Andersen, Helge
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Network organization of interstitial connective tissue cells in the human endolymphatic duct2003Inngår i: Journal of Histochemistry and Cytochemistry, ISSN 0022-1554, E-ISSN 1551-5044, Vol. 51, nr 11, s. 1491-500Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The human endolymphatic duct (ED) and sac of the inner ear have been suggested to control endolymph volume and pressure. However, the physiological mechanisms for these processes remain obscure. We investigated the organization of the periductal interstitial connective tissue cells and extracellular matrix (ECM) in four freshly fixed human EDs by transmission electron microscopy and by immunohistochemistry. The unique surgical material allowed a greatly improved structural and epitopic preservation of tissue. Periductal connective tissue cells formed frequent intercellular contacts and focally occurring electron-dense contacts to ECM structures, creating a complex tissue network. The connective tissue cells also formed contacts with the basal lamina of the ED epithelium and the bone matrix, connecting the ED with the surrounding bone of the vestibular aqueduct. The interstitial connective tissue cells were non-endothelial and non-smooth muscle fibroblastoid cells. We suggest that the ED tissue network forms a functional mechanical entity that takes part in the control of inner ear fluid pressure and endolymph resorption.

  • 179.
    Huttunen, Kerttu
    et al.
    Univ Oulu, Fac Humanities, Logoped, Oulu, Finland;Univ Oulu, Child Language Res Ctr, Oulu, Finland;Univ Oulu, PEDEGO Res Unit, Oulu, Finland;MRC Oulu, Oulu, Finland;Oulu Univ Hosp, Dept Otorhinolaryngol Head & Neck Surg, Oulu, Finland.
    Erixon, Elsa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Lofkvist, Ulrika
    Univ Oslo, Dept Special Needs Educ, Oslo, Norway;Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.
    Maki-Torkko, Elina
    Orebro Univ, Sch Med Sci, Orebro, Sweden;Orebro Univ Hosp, Audiol Res Ctr, Orebro, Sweden.
    The impact of permanent early-onset unilateral hearing impairment in children - A systematic review2019Inngår i: International Journal of Pediatric Otorhinolaryngology, ISSN 0165-5876, E-ISSN 1872-8464, Vol. 120, s. 173-183Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Background: Decision-making on treatment and (re)habilitation needs to be based on clinical expertise and scientific evidence. Research evidence for the impact of permanent unilateral hearing impairment (UHI) on children's development has been mixed and, in some of the reports, based on fairly small, heterogeneous samples. Additionally, treatment provided has been highly variable, ranging from no action taken or watchful waiting up to single-sided cochlear implantation. Published information about the effects of treatment has also been heterogeneous. Moreover, earlier reviews and meta-analyses published on the impact of UHI on children's development have generally focused on select areas of development. Objectives: This systematic review aimed to summarize the impact of children's congenital or early onset unilateral hearing impairment on listening and auditory skills, communication, speech and language development, cognitive development, educational achievements, psycho-social development, and quality of life. Methods: Literature searches were performed to identify reports published from inception to February 16th, 2018 with the main electronic bibliographic databases in medicine, psychology, education, and speech and hearing sciences as the data sources. PubMed, CINALH, ERIC, LLBA, PsychINFO, and ISI Web of Science were searched for unilateral hearing impairment with its synonyms and consequences of congenital or early onset unilateral hearing impairment. Eligible were articles written in English, German, or Swedish on permanent unilateral hearing impairments that are congenital or with onset before three years of age. Hearing impairment had to be of at least a moderate degree with PTA >= 40 dB averaged over frequencies 0.5 to 2 or 0.5-4 kHz, hearing in the contralateral ear had to have PTA(0.5-2 kHz) or PTA(0.5-4 kHz) <= 20 dB, and consequences of unilateral hearing impairment needed to be reported in an unanimously defined population in at least one of the areas the review focused on. Four researchers independently screened 1618 abstracts and 566 full-text articles for evaluation of study eligibility. Eligible full-text articles were then reviewed to summarize the results and assess the quality of evidence. Additionally, data from 13 eligible case and multi-case studies, each having less than 10 participants, were extracted to summarize their results. Quality assessment of evidence was made adapting the Grades of Recommendations, Assessment, Development, and Evaluation (GRADE) process, and reporting of the results adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. Results: Three articles with the quality of evidence graded as very-low to low, fulfilled the eligibility criteria set. Due to the heterogeneity of the articles, only a descriptive summary could be generated from the results. Unilateral hearing impairment was reported to have a negative impact on preverbal vocalization of infants and on sound localization and speech perception both in quiet and in noise. Conclusions: No high-quality studies of consequences of early-onset UHI in children were found. Inconsistency in assessing and reporting outcomes, the relatively small number of participants, low directness of evidence, and the potential risk of confounding factors in the reviewed studies prevented any definite conclusions. Further well-designed prospective research using larger samples is warranted on this topic.

  • 180.
    Hägg, Mary
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Correlation between lip force and swallowing capacity in stroke patients and in healthy controlsInngår i: Eur Arc OtorhinolaryngologyArtikkel i tidsskrift (Fagfellevurdert)
  • 181.
    Hägg, Mary
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Sensorimotor Brain Plasticity in Stroke Patients with Dysphagia: A Methodological Study on Investigation and Treatment2007Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Aims

    The aims of the thesis were to validate investigation instruments for stroke patients with dysphagia, and to improve oropharyngeal dysphagia therapies.

    Methods/Results

    A Lip Force Meter, LF 100, affirmed excellent intra- and inter-reliability, sensitivity and specificity. Controls had significantly stronger lip force (LF) and swallowing capacity (SC) than stroke patients. A normal lower limit of LF was set to 15 Newton. Dysphagia symptoms improved in 7 stroke patients after a 5-week sensorimotor stimulation therapy comprising manual body and facial regulation in combination with palatal plate application. Impaired LF and impaired SC were parallel phenomena in 22 acute stroke patients and did not differ regardless of presence or absence of facial palsy. LF and SC improved and were parallel phenomena in 30 stroke patients and did not differ regardless of presence or absence of facial palsy, time lag between stroke attack and start of treatment, or age. SC was normalized in 19 of 30 dysphagia patients after a 5-8-week daily lip muscle self-training with an oral screen.

    Conclusions

    LF100 is an appropriate and reliable instrument for measuring lip force. Dysphagia improvement, by body and facial sensorimotor stimulation in combination with palatal plate application, or by training with an oral screen is excellent examples of brain plasticity and cortical reorganisation. . Swallowing capacity and lip force in stroke patients are parallel phenomena. A sub clinical facial paresis seems to be present in most stroke patients. Training with an oral screen can improve LF and SC in stroke patients with oropharyngeal dysphagia.

    Delarbeid
    1. Effects of motor and sensory stimulation in stroke patients with long-lasting dysphagia
    Åpne denne publikasjonen i ny fane eller vindu >>Effects of motor and sensory stimulation in stroke patients with long-lasting dysphagia
    2004 (engelsk)Inngår i: Dysphagia (New York. Print), ISSN 0179-051X, E-ISSN 1432-0460, Vol. 19, nr 4, s. 219-230Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Dysphagia is a common poststroke symptom with negative effects on recovery and rehabilitation. However, the orofacial regulation therapy, developed by Castillo Morales, comprising body regulation and orofacial regulation in combination with a palatal plate application has shown promising results in stroke patients. This therapy is based not only on muscle exercises but also on an improvement of the entire sensory-motor reflex arc involved in normal deglutition, and on the knowledge that the function of face and oropharynx at deglutition is closely interrelated with the entire body posture as well as with appropriate breathing. The treatment concept is relatively unknown to caregivers, partly due to lack of scientific evaluation of treatment results. The present investigation aimed to assess the effect of motor and sensory stimulation in stroke patients with dysphagia persisting for more than six months. Seven patients were evaluated with respect to orofacial and pharyngeal motility and sensory function before and two weeks after a five-week treatment period. The evaluation comprised a swallowing capacity test, a meal observation test, clinical examination of oral motor and sensory function, a velopharyngeal closure test, and videofluoroscopy. In addition, the symptoms were scored by the patients. An overall single-blind estimation showed objective and self-assessed swallowing improvement in all seven patients. Kappa coefficients are calculated on all reliability data, both inter- and intrarater reliabilities. Sensory and motor stimulation seems to be a promising therapy in stroke patients with long-lasting and persistent oropharyngeal dysphagia.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-96516 (URN)10.1007/s00455-004-0016-3 (DOI)15667056 (PubMedID)
    Tilgjengelig fra: 2007-11-23 Laget: 2007-11-23 Sist oppdatert: 2017-12-14bibliografisk kontrollert
    2. Reliable Lip force measurement in healthy controls and in patients with stroke: methodological study
    Åpne denne publikasjonen i ny fane eller vindu >>Reliable Lip force measurement in healthy controls and in patients with stroke: methodological study
    2008 (engelsk)Inngår i: Dysphagia (New York. Print), ISSN 0179-051X, E-ISSN 1432-0460, Vol. 23, nr 3, s. 291-296Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    A prefabricated oral screen has shown promising results as a muscle self-training device to improve the lip function of stroke patients affected by oropharyngeal dysphagia. However, a technique for the measurement of lip muscle force, whether in healthy individuals or in stroke patients, is lacking. The present study was designed to (1) test the intra- and interreliability of lip force measurements by means of a newly devised Lip Force Meter, LF100, (2) determine a normal lower limit for lip force in newtons (N), and (3) ascertain the instrument's sensitivity and specificity. LF100 is a modified strain gauge for recording the ability of lips to withstand pressure from a predentally placed oral screen. Forty-two healthy controls and 22 stroke patients agreed to participate in the trial. The controls and patients were examined three times with the LF100, with 2-min rest intervals, twice by investigator MH and once by investigator MO. Intrainvestigator reliability with the LF100 proved excellent in both controls and patients: ICC was 0.83 and 0.90, respectively. Interinvestigator reliability was good or excellent in both groups: ICC was 0.71 and 0.91. There was a significant difference in lip force between controls and stroke patients (mean = 24.7 +/- 6.3 N and 9.5 +/- 5.5 N, p < ; 0.001). The sensitivity of LF100 was 91% and the specificity 95%. The cutoff level for normal lip force was 15 N. The LF100 showed itself to be a suitable and reliable instrument for measuring lip force.

    Emneord
    controls, lip force, reliability, sensitivity, specificity, stroke; deglutition, deglutition disorders
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-96517 (URN)10.1007/s00455-007-9143-y (DOI)000258673300011 ()18253790 (PubMedID)
    Tilgjengelig fra: 2007-11-23 Laget: 2007-11-23 Sist oppdatert: 2017-12-14bibliografisk kontrollert
    3. Correlation between lip force and swallowing capacity in stroke patients and in healthy controls
    Åpne denne publikasjonen i ny fane eller vindu >>Correlation between lip force and swallowing capacity in stroke patients and in healthy controls
    Inngår i: Eur Arc OtorhinolaryngologyArtikkel i tidsskrift (Fagfellevurdert) Submitted
    Identifikatorer
    urn:nbn:se:uu:diva-96518 (URN)
    Tilgjengelig fra: 2007-11-23 Laget: 2007-11-23bibliografisk kontrollert
    4. Lip muscle training in stroke patients with dysphagia
    Åpne denne publikasjonen i ny fane eller vindu >>Lip muscle training in stroke patients with dysphagia
    2008 (engelsk)Inngår i: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 128, nr 9, s. 1027-1033Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Conclusion. Training with an oral screen can improve lip force (LF) and swallowing capacity (SC) in stroke patients with oropharyngeal dysphagia, irrespective of the duration of pretreatment of dysphagia, and irrespective of the presence or absence of central facial paresis. It is more plausible that treatment results are attributable to sensory motor stimulation and the plasticity of the central nervous system than to the training of the lip muscles per se. Objectives. A close relationship has been demonstrated between LF and SC in stroke patients whether or not they are affected by facial paresis. It is not known how training of lip function can improve swallowing capacity. The present study was therefore designed to ascertain: (i) if training with an oral screen can improve the LF and SC of stroke patients with oropharyngeal dysphagia, to establish (ii) if improvement in LF and SC is connected with the presence or absence of central facial palsy, (iii) on the interval between stroke onset and initiation of treatment, (iv) on age, or (v) on sex. Subjects and methods. This was a retrospective study of 30 stroke patients, 49-88 years old, who were investigated with a Lip Force Meter, LF100 (LF100) and a swallowing capacity test (SCT) before and after a period of self-training lasting at least 5-8 weeks, using an oral screen. Initial central facial paresis was present in 24 patients. Results. The median LF was 7 Newtons (N) (range 0-27) before treatment and 18.5 N (range 7-44) after treatment (p < , 0.001). The median SC was 0 ml/s (range 0-9.1) before treatment and 12.1 ml/s (range 0-36.7) at follow-up (p < , 0.001). There was no significant difference in swallowing improvement between patients with versus those without facial paresis. The interval between stroke attack and start of treatment, ranging from a few days up to 10 years, had no significant influence on the treatment results, nor did age or sex. The facial paresis was improved or at least ameliorated in all patients after the lip training period.

    Emneord
    brain plasticity, facial palsy, lip force, dysphagia, muscle training; swallowing capacity, stroke
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-96519 (URN)10.1080/00016480701813814 (DOI)000258371500012 ()19086198 (PubMedID)
    Tilgjengelig fra: 2007-11-23 Laget: 2007-11-23 Sist oppdatert: 2017-12-14bibliografisk kontrollert
  • 182.
    Hägg, Mary
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg.
    Anniko, Matti
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Influence of lip force on swallowing capacity in stroke patients and in healthy subjects2010Inngår i: Acta oto-laryngologica, ISSN 1651-2251, Vol. 130, nr 11, s. 1204-1208Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Conclusion: In spite of no clinical signs of facial paresis, a pathological lip force (LF) will strongly influence swallowing capacity (SC). Stroke patients with impaired SC suffer a subclinical facial paresis. The results support earlier findings that LF training can be used to treat dysphagia. Objectives: Lip muscle training with an oral screen can improve both LF and SC in stroke patients, irrespective of the presence or absence of facial palsy. The aim was therefore to study the influence of LF on SC. Methods: This prospective study included 22 stroke patients, aged 38-90 years, with dysphagia, 12 with initial unilateral facial paresis and 45 healthy subjects, aged 25-87 years. All were investigated with a Lip Force Meter (LF100), and with an SC test. Results: A significant correlation was found between LF/SC (p = 0.012) in stroke patients but not in healthy subjects. LF/SC was not age-related in stroke patients. LF was not age-dependent in healthy subjects, but SC decreased with increasing age (p < 0.0001). However, SC did not reach a pathological value and a regression analysis showed that 73% of the variation in SC is attributable to LF and age.

  • 183.
    Hägg, Mary
    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.
    Lip muscle training in stroke patients with dysphagia2008Inngår i: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 128, nr 9, s. 1027-1033Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Conclusion. Training with an oral screen can improve lip force (LF) and swallowing capacity (SC) in stroke patients with oropharyngeal dysphagia, irrespective of the duration of pretreatment of dysphagia, and irrespective of the presence or absence of central facial paresis. It is more plausible that treatment results are attributable to sensory motor stimulation and the plasticity of the central nervous system than to the training of the lip muscles per se. Objectives. A close relationship has been demonstrated between LF and SC in stroke patients whether or not they are affected by facial paresis. It is not known how training of lip function can improve swallowing capacity. The present study was therefore designed to ascertain: (i) if training with an oral screen can improve the LF and SC of stroke patients with oropharyngeal dysphagia, to establish (ii) if improvement in LF and SC is connected with the presence or absence of central facial palsy, (iii) on the interval between stroke onset and initiation of treatment, (iv) on age, or (v) on sex. Subjects and methods. This was a retrospective study of 30 stroke patients, 49-88 years old, who were investigated with a Lip Force Meter, LF100 (LF100) and a swallowing capacity test (SCT) before and after a period of self-training lasting at least 5-8 weeks, using an oral screen. Initial central facial paresis was present in 24 patients. Results. The median LF was 7 Newtons (N) (range 0-27) before treatment and 18.5 N (range 7-44) after treatment (p < , 0.001). The median SC was 0 ml/s (range 0-9.1) before treatment and 12.1 ml/s (range 0-36.7) at follow-up (p < , 0.001). There was no significant difference in swallowing improvement between patients with versus those without facial paresis. The interval between stroke attack and start of treatment, ranging from a few days up to 10 years, had no significant influence on the treatment results, nor did age or sex. The facial paresis was improved or at least ameliorated in all patients after the lip training period.

  • 184.
    Hägg, Mary
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg.
    Olgarsson, Margaretha
    Anniko, Matti
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Reliable Lip force measurement in healthy controls and in patients with stroke: methodological study2008Inngår i: Dysphagia (New York. Print), ISSN 0179-051X, E-ISSN 1432-0460, Vol. 23, nr 3, s. 291-296Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A prefabricated oral screen has shown promising results as a muscle self-training device to improve the lip function of stroke patients affected by oropharyngeal dysphagia. However, a technique for the measurement of lip muscle force, whether in healthy individuals or in stroke patients, is lacking. The present study was designed to (1) test the intra- and interreliability of lip force measurements by means of a newly devised Lip Force Meter, LF100, (2) determine a normal lower limit for lip force in newtons (N), and (3) ascertain the instrument's sensitivity and specificity. LF100 is a modified strain gauge for recording the ability of lips to withstand pressure from a predentally placed oral screen. Forty-two healthy controls and 22 stroke patients agreed to participate in the trial. The controls and patients were examined three times with the LF100, with 2-min rest intervals, twice by investigator MH and once by investigator MO. Intrainvestigator reliability with the LF100 proved excellent in both controls and patients: ICC was 0.83 and 0.90, respectively. Interinvestigator reliability was good or excellent in both groups: ICC was 0.71 and 0.91. There was a significant difference in lip force between controls and stroke patients (mean = 24.7 +/- 6.3 N and 9.5 +/- 5.5 N, p < ; 0.001). The sensitivity of LF100 was 91% and the specificity 95%. The cutoff level for normal lip force was 15 N. The LF100 showed itself to be a suitable and reliable instrument for measuring lip force.

  • 185.
    Häggblad Sahlberg, Sara
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för biomedicinsk strålningsvetenskap.
    Spiegelberg, Diana
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för biomedicinsk strålningsvetenskap.
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Stenerlöw, Bo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för biomedicinsk strålningsvetenskap.
    Nestor, Marika
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. 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.
    Evaluation of cancer stem cell markers CD133, CD44, CD24: association with AKT isoforms and radiation resistance in colon cancer cells.2014Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 4, s. e94621-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The cell surface proteins CD133, CD24 and CD44 are putative markers for cancer stem cell populations in colon cancer, associated with aggressive cancer types and poor prognosis. It is important to understand how these markers may predict treatment outcomes, determined by factors such as radioresistance. The scope of this study was to assess the connection between EGFR, CD133, CD24, and CD44 (including isoforms) expression levels and radiation sensitivity, and furthermore analyze the influence of AKT isoforms on the expression patterns of these markers, to better understand the underlying molecular mechanisms in the cell. Three colon cancer cell-lines were used, HT-29, DLD-1, and HCT116, together with DLD-1 isogenic AKT knock-out cell-lines. All three cell-lines (HT-29, HCT116 and DLD-1) expressed varying amounts of CD133, CD24 and CD44 and the top ten percent of CD133 and CD44 expressing cells (CD133(high)/CD44(high)) were more resistant to gamma radiation than the ten percent with lowest expression (CD133(low)/CD44(low)). The AKT expression was lower in the fraction of cells with low CD133/CD44. Depletion of AKT1 or AKT2 using knock out cells showed for the first time that CD133 expression was associated with AKT1 but not AKT2, whereas the CD44 expression was influenced by the presence of either AKT1 or AKT2. There were several genes in the cell adhesion pathway which had significantly higher expression in the AKT2 KO cell-line compared to the AKT1 KO cell-line; however important genes in the epithelial to mesenchymal transition pathway (CDH1, VIM, TWIST1, SNAI1, SNAI2, ZEB1, ZEB2, FN1, FOXC2 and CDH2) did not differ. Our results demonstrate that CD133(high)/CD44(high) expressing colon cancer cells are associated with AKT and increased radiation resistance, and that different AKT isoforms have varying effects on the expression of cancer stem cell markers, which is an important consideration when targeting AKT in a clinical setting.

  • 186. Idrizbegovic, Esma
    et al.
    Hederstierna, Christina
    Dahlquist, Martin
    Kämpfe Nordström, Charlotta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Jelic, Vesna
    Rosenhall, Ulf
    Central auditory function in early Alzheimer's disease and in mild cognitive impairment.2011Inngår i: Age and Ageing, ISSN 0002-0729, E-ISSN 1468-2834, Vol. 40, nr 2Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: to investigate auditory function in subjects with early Alzheimer's disease, mild cognitive impairment and with subjective memory complaints, in search of signs of central auditory processing dysfunction even in early stages of cognitive impairment.

    DESIGN AND SUBJECTS: a consecutive group of men and women, referred to the Memory Clinic at the Karolinska University Hospital, was approached for inclusion in this prospective study. One hundred and thirty-six subjects, mean age 64 years (range 50-78 years), diagnosed with Alzheimer's disease (n = 43), mild cognitive impairment (n = 59) or with subjective memory complaints (n = 34), were included.

    METHODS: auditory function was assessed with pure tone audiometry, speech perception in quiet and in background noise and dichotic digits tests with two or three digits.

    RESULTS: pure tone audiometry and speech perception scores in quiet and in background noise were normal for age and without between-group differences. Dichotic digits tests showed strongly significant differences between the three groups, where the Alzheimer's disease group performed significantly poorer than the other two groups, with the mild cognitive impairment group in an intermediate position.

    CONCLUSIONS: our results demonstrate that central auditory processing dysfunction is highly evident in subjects with Alzheimer's disease, and to a considerable extent even in subjects with mild cognitive impairment.

  • 187. Isaksson, Joakim
    et al.
    Salander, Par
    Granstrom, Brith
    Laurell, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Critical Incidents Reveal How Patients with Head and Neck Cancer Construct Their "Secure Base" as a "Helping System"2014Inngår i: Journal of psychosocial oncology, ISSN 0734-7332, E-ISSN 1540-7586, Vol. 32, nr 3, s. 322-341Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Most studies of the psychosocial needs of patients with head and neck cancers (HNC) use predefined categories and explicitly ask for specified needs. These studies are important but should be complemented with inductive studies based on patients' own descriptions of experiences. This qualitative study is such a contribution. In repeated interviews positive and negative incidents were collected from 137 patients with HNC, and these experiences were categorized in dimensions expressing needs. A core category-"being included-neglected by a helping system"-emerged from the narrated incidents and was based on the dimensions engagement, competence, and information. The findings are easily related to attachment theory by stressing the significance of establishing trustful relationships with the health care staff, as attachment figures, who respond flexibly and sensitively to the patient's needs. In the constitution of health care as a helping system, all encounters between the patient and health care staff matters. Further research should preferably focus on the creation of guidelines for the constitution of health care as a helping system, that is, how the found factors of a helping system can be operationalized in clinical practice.

  • 188. Isaksson, Joakim
    et al.
    Salander, Par
    Granstrom, Brith
    Laurell, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Patients With Head and Neck Cancer Narrate the Importance of Being Included in a Helping System2013Inngår i: Psycho-Oncology, ISSN 1057-9249, E-ISSN 1099-1611, Vol. 22, nr SI3, s. 63-63Artikkel i tidsskrift (Annet vitenskapelig)
  • 189.
    Isaksson, Joakim
    et al.
    Umea Univ, Dept Social Work, S-90187 Umea, Sweden..
    Salander, Par
    Umea Univ, Dept Social Work, S-90187 Umea, Sweden..
    Lilliehorn, Sara
    Umea Univ, Dept Social Work, S-90187 Umea, Sweden.;Umea Univ, Dept Radiat Sci Oncol, S-90187 Umea, Sweden..
    Laurell, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Living an everyday life with head and neck cancer 2-2.5 years post-diagnosis - A qualitative prospective study of 56 patients2016Inngår i: Social Science and Medicine, ISSN 0277-9536, E-ISSN 1873-5347, Vol. 154, s. 54-61Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Rationale: There are many studies available describing how patients are affected by head and neck cancer (HNC) and its treatment. Usually these studies are quantitative and focus on assessing patients' quality of life or distress post-treatment. These studies are important, but they are of limited value if we are interested in understanding more about HNC in an everyday life context. Objective: The purpose was to determine how life was lived and valued during and after treatment for HNC and to detect different transitions in returning to everyday life. Methods: During 2009-2012, 56 patients with HNC were consecutively included, and interviewed at 6, 12, and 24 months post-treatment about how they lived their lives. All patients received primary treatment at a tertiary referral university hospital in Sweden. Results: Four different trajectories and transitions emerged. The first group (n = 15) evaluated their illness experience as a past parenthesis in their life suggesting that they had psychologically left the illness behind. In the second group (n = 9), the impact of the disease seemed to be diluted by other strains in their life, and although these patients to some extent were still hampered by side effects, they regarded them as `no big deal'. The cancer really made a difference in the third group (n = 12) in both positive and negative ways and seemed to reflect a balance between such effects. In the fourth group (n = 20), the physical and/or psychological problems predominated and the patients' lives had changed for the worse. Conclusion: The narratives showed that being afflicted by HNC has different impacts depending on how the patients live their lives it is a matter of individual transition in an everyday life context. This idiosyncrasy challenges the meaningfulness of screening efforts to identify vulnerable groups for psychosocial intervention.

  • 190. Isaksson, Joakim
    et al.
    Salander, Par
    Lilliehorn, Sara
    Laurell, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    The Impact of Head and Neck Cancer on Living an Everyday Life 2 Years Post-treatment - A Qualitative Prospective Study2015Inngår i: Psycho-Oncology, ISSN 1057-9249, E-ISSN 1099-1611, Vol. 24, nr S2, s. 256-257, artikkel-id P2-52Artikkel i tidsskrift (Annet vitenskapelig)
  • 191.
    Isaksson, Joakim
    et al.
    Umeå Univ, Dept Social Work, Umeå, Sweden..
    Salander, Pär
    Umeå Univ, Dept Social Work, Umeå, Sweden..
    Lilliehorn, Sara
    Umeå Univ, Dept Social Work, Umeå, Sweden..
    Laurell, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar. Uppsala Univ, Dept Surg Sci Othorinolaryngol & Head & Neck Surg, Uppsala, Sweden..
    Different transitions in returning to everyday life for patients with head and neck cancer - a qualitative prospective study2016Inngår i: Psycho-Oncology, ISSN 1057-9249, E-ISSN 1099-1611, Vol. 25, nr SP. S3, s. 95-95Artikkel i tidsskrift (Annet vitenskapelig)
  • 192.
    Isaksson, Joakim
    et al.
    Umea Univ, Dept Social Work, SE-90187 Umea, Sweden.
    Wilms, Torben
    Umea Univ, Dept Med Biosci, SE-90187 Umea, Sweden;Umea Univ, Dept Clin Sci Otorhinolaryngol, SE-90187 Umea, Sweden.
    Laurell, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Fransson, Per
    Department of Nursing, Umeå University, Umeå, Sweden.
    Ehrsson, Ylva Tiblom
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Meaning of work and the process of returning after head and neck cancer2015Inngår i: Supportive Care in Cancer, ISSN 0941-4355, E-ISSN 1433-7339, Vol. 24, nr 1, s. 205-213Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE: The purposes of this study were (1) to investigate employment status at diagnosis, sick leave, and returning to work patterns in correlation to quality of life, anxiety, and depression in patients treated for head and neck cancer (HNC) and (2) to explore patients' experiences of the process of returning to work.

    METHODS: Sixty-six patients with HNC (aged 34-66 years) were repeatedly interviewed over a period of 24 months. Interview responses that concerned the patients' experiences and ideas about work were categorised using the similarities-differences technique. Questionnaires on quality of life, anxiety, and depression were used to describe the patient characteristics and the differences between groups.

    RESULTS: In total, 53 % of the patients had returned to work at 24 months after treatment, and 17 % were deceased. Several quality of life parameters were significantly worse for patients not working at 24 months after treatment. Nine categories were found to describe the return-to-work process starting with symptoms causing sick leave, thoughts about the sick leave, and ending with the return to work and/or retirement.

    CONCLUSIONS: Returning to work is an important part of life because it structures everyday life and strengthens the individual's identity. The quality of life results showed significant differences between workers and non-workers at the 24-month follow-up. The patients need to be both physically and mentally prepared for the process of returning to work. It is important to take an individual rehabilitation approach to guide and support the patients in returning to work and regaining an important aspect of their everyday life. In such an approach, it is vital to understand the patients' overall life context and the patients' own perspective on the process and meaning associated with work.

  • 193. Ishibashi, Takuya
    et al.
    Takumida, Masaya
    Akagi, Nana
    Hirakawa, Katsuhiro
    Anniko, Matti
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Changes in transient receptor potential vanilloid (TRPV) 1, 2, 3 and 4 expression in mouse inner ear following gentamicin challenge2009Inngår i: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 129, nr 2, s. 116-26Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    CONCLUSION: It is suggested that transient receptor potential vanilloid (TRPV)-1 and -2 may be of pathological significance for sensory cells and ganglions, while TRPV-3 and -4 may play an important part in neuroprotection of the inner ear. OBJECTIVE: Changes in the expression of TRPV-1, -2, -3, and -4 in gentamicin (GM)-treated mouse inner ear were studied. MATERIALS AND METHODS: CBA/J mice were used in this study. The localization of TRPV-1, -2, -3, and -4 in the inner ear of both untreated and GM-treated CBA/J animals (intratympanic injection of 5 mg GM) was investigated by immunohistochemistry. RESULTS: TRPV-1, -2, and -3 were co-expressed in the inner ear sensory and ganglion cells, while TRPV-4 was also expressed in the stria vascularis and vestibular dark cells. Following GM treatment, the intensity of immunofluorescent reaction to TRPV-1 and TRPV-2 increased, while that to TRPV-3 and TRPV-4 decreased.

  • 194. Ishibashi, Takuya
    et al.
    Takumida, Masaya
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Akagi, Nana
    Hirakawa, Katsuhiro
    Anniko, Matti
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Expression of transient receptor potential vanilloid (TRPV) 1, 2, 3, and 4 in mouse inner ear2008Inngår i: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 128, nr 12, s. 1286-93Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    CONCLUSION: It is suggested that transient receptor potential vanilloids (TRPVs) may play a functional role in cell physiology and TRPV-4 and -2 may play an important part in fluid homeostasis in the inner ear. OBJECTIVE: Expression of TRPV-1, -2, -3, and -4 in the normal mouse inner ear was studied. MATERIALS AND METHODS: CBA/J mice were used in this study. The localization of TRPV-1, -2, -3, and -4 in the inner ear, i.e. cochlea, vestibular end organs, and endolymphatic sac, was investigated by immunohistochemistry. RESULTS: TRPV-1, -2, and -3 were co-expressed in hair cells and supporting cells of the organ of Corti, in spiral ganglion cells, sensory cells in vestibular end organs, vestibular ganglion cells, and sensory nerve fibers. TRPV-2 was also detected in the stria vascularis, dark cells, and endolymphatic sac. TRPV-4 was expressed in hair cells and supporting cells of the organ of Corti, in marginal cells of the stria vascularis, spiral ganglion cells, vestibular sensory cells, vestibular dark cells, vestibular ganglion cells, and epithelial cells of the endolymphatic sac.

  • 195. J, Sundman
    et al.
    J, Bring
    Friberg, Danielle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Poor interexaminer agreement on Friedman tongue position.2017Inngår i: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 137, nr 5, s. 554-556Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Conclusion: The Friedman tongue position demonstrated only a slight inter-examiner agreement among 15 medical doctors, indicating that the method is difficult to perform and could be an uncertain method to select patients for uvulopalatopharyngoplasty.

    Objective: The Friedman staging system is a clinical tool for selecting patients with obstructive sleep apnea who are appropriate for uvulopalatopharyngoplasty. The objective of this study was to evaluate the staging system by determining the inter-examiner agreement of one of its key components, the Friedman tongue position.

    Methods: Eleven residents and four specialists in Otorhinolaryngology were recruited from a course in surgical management of obstructive sleep apnea. They examined each other’s tongue positions, resulting in a total of 210 evaluations. Cohen’s kappa analysis was performed to assess the inter-examiner agreement. The range of kappa is usually between 0–1, where 0 is complete disagreement and 1 is complete agreement.

    Results: The median kappa was 0.36 (1st and 3rd quartile, 0.23 and 0.42), corresponding to only a slight agreement.

  • 196. J, Sundquist
    et al.
    X, Li
    Friberg, Danielle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    K, Hemminki
    K, Sundquist
    Obstructive sleep apnea syndrome in siblings: an 8-year Swedish follow-up study.2008Inngår i: Sleep, ISSN 0161-8105, E-ISSN 1550-9109, Vol. 31, nr 6, s. 817-823Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background:

    Understanding the genetic transmission of obstructive sleep apnea syndrome (OSAS) will help clinicians identify patients at risk and offer opportunities for intervention and treatment at specialist clinics.

    Objective:

    To estimate familial risk of hospitalization for OSAS in the adult population of Sweden, and to determine if there are any differences by age and sex.

    Design, setting, and participants:

    Using the MigMed database at the Karolinska Institute, we divided the population of Sweden into sibling groups based on a shared mother and father and ascertained the presence or absence of a primary hospital diagnosis of OSAS in each individual during the follow-up period, 1997 to 2004. Individuals were categorized as having or not having a sibling with OSAS, based on the presence or absence of the disorder in at least 1 of their siblings. Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were estimated for men and women with a sibling with OSAS, compared with men and women in the reference group (SIR = 1).

    Results:

    After accounting for socioeconomic status, age, geographic region, and period of diagnosis, men with at least 1 sibling who had OSAS had a SIR of 3.42 (95% CI, 2.18–5.36); the corresponding SIR in women was 3.25 (95% CI, 1.84–5.65).

    Conclusions:

    Our results indicate that physicians should consider family history of OSAS when deciding whether to refer a patient for further sleep examinations.

  • 197.
    Jensson, David
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Plastikkirurgi.
    Enghag, Sara
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Bylund, Nina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Jonsson, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Wikström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Grindlund, Margareta E
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Flink, Roland
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Rodriguez-Lorenzo, Andres
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Plastikkirurgi.
    Cranial Nerve Coactivation and Implication for Nerve Transfers to the Facial Nerve.2018Inngår i: Plastic and reconstructive surgery (1963), ISSN 0032-1052, E-ISSN 1529-4242, Vol. 141, nr 4, s. 582e-585eArtikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In reanimation surgery, effortless smile can be achieved by a nonfacial donor nerve. The underlying mechanisms for this smile development, and which is the best nonfacial neurotizer, need further clarification. The aim of the present study was therefore to further explore the natural coactivation between facial mimic muscles and muscles innervated by the most common donor nerves used in smile reanimation. The study was conducted in 10 healthy adults. Correlation between voluntary facial muscle movements and simultaneous electromyographic activity in muscles innervated by the masseter, hypoglossal, and spinal accessory nerves was assessed. The association between voluntary movements in the latter muscles and simultaneous electromyographic activity in facial muscles was also studied. Smile coactivated the masseter and tongue muscles equally. During the seven mimic movements, the masseter muscle had fewer electromyographically measured coactivations compared with the tongue (two of seven versus five of seven). The trapezius muscle demonstrated no coactivation during mimic movements. Movements of the masseter, tongue, and trapezius muscles induced electromyographically recorded coactivation in the facial muscles. Bite resulted in the strongest coactivation of the zygomaticus major muscle. The authors demonstrated coactivation between voluntary smile and the masseter and tongue muscles. During voluntary bite, strong coactivation of the zygomaticus major muscle was noted. The narrower coactivation pattern in the masseter muscle may be advantageous for central relearning and the development of a spontaneous smile. The strong coactivation between the masseter muscle and the zygomaticus major indicates that the masseter nerve may be preferred in smile reanimation.

  • 198.
    Jensson, David
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Plastikkirurgi.
    Weninger, Wolfgang J
    Center of Anatomy and Cell Biology, Medical University of Vienna, Vienna, Austria.
    Schmid, Melanie
    Division of Plastic and Reconstructive Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria.
    Meng, Stefan
    Center of Anatomy and Cell Biology, Medical University of Vienna, Vienna, Austria.
    Jonsson, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Tzou, Chieh-Han John
    Department of Surgery, Plastic and Reconstructive Surgery, Hospital of Divine Savior, Vienna, Austria.
    Rodriguez-Lorenzo, Andres
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Plastikkirurgi.
    Oculo-zygomatic nerve transfer for facial synkinesis: An anatomical feasibility study2019Inngår i: Microsurgery, ISSN 0738-1085, E-ISSN 1098-2752, Vol. 37, nr 7, s. 629-633Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Patients with severe oro-ocular synkinesis often present with concomitant inefficient smile excursion on the affected site. In theory, oculo-zygomatic nerve transfer may decrease synkinesis and improve smile by redirecting nerve fibers to their target muscle. The aim of this study was to explore the feasibility of nerve transfer in human cadavers between a caudal branch innervating the orbicularis oculi to a cephalad branch innervating the zygomaticus major muscles.

    METHODS: Eighteen hemi-faces were dissected. Reach for direct coaptation of a caudal nerve branch innervating the orbicularis oculi muscle to a cephalad nerve branch innervating the zygomaticus major muscle was assessed. Measurements included total number of nerve branches as well as maximum dissection length. Nerve samples were taken from both branches at the site of coaptation and histomorphometric analysis for axonal count was performed.

    RESULTS: The number of sub-branches to the orbicularis oculi muscle was 3.1 ± 1.0 and to the zygomaticus major muscle 4.7 ± 1.2. The maximal length of dissection of the caudal nerve branch to the orbicularis oculi muscle was 28.3 ± 7.3 mm and for the cranial nerve branch to the zygomaticus major muscle 23.8 ± 6.5 mm. Transection and tension-free coaptation was possible in all cases but one. The average myelinated fiber counts per mm2 was of 5,173 ± 2,293 for the caudal orbicularis oculi branch and 5,256 ± 1,774 for the cephalad zygomaticus major branch.

    CONCLUSION: Oculo-zygomatic nerve transfer is an anatomically feasible procedure. The clinical value of this procedure, however, remains to be proven.

  • 199.
    Johansson, Henrik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Lung- allergi- och sömnforskning.
    Emtner, Margareta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Lung- allergi- och sömnforskning.
    Janson, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Lung- allergi- och sömnforskning.
    Malinovschi, Andrei
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi.
    Norlander, Katarina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Nordang, Leif
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Exercise induced dyspnea among adolescents - prevalence and incidence, a five-year follow-up2018Inngår i: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 52Artikkel i tidsskrift (Annet vitenskapelig)
  • 200.
    Johansson, Henrik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Fysioterapi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Lung- allergi- och sömnforskning.
    Ersson, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Lung- allergi- och sömnforskning.
    Malinovschi, Andrei
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi.
    Mallmin, Elisabet
    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.
    Nordang, Leif
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Prevalence of exercise-induced bronchoconstriction and exercise-induced laryngeal obstruction in adolescents attending national sports high school2018Inngår i: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 52Artikkel i tidsskrift (Annet vitenskapelig)
1234567 151 - 200 of 463
RefereraExporteraLink til resultatlisten
Permanent link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf