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  • 51.
    Berling Holm, Katarina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Bornefalk Hermansson, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Knutsson, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar. Örebro Univ Hosp, Dept Otolaryngol, Örebro, Sweden.
    von Unge, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar. Akershus Univ Hosp, Dept Otorhinolaryngol, Oslo, Norway; Univ Oslo, Oslo, Norway.
    Surgery for Chronic Otitis Media Causes Greater Taste Disturbance Than Surgery for Otosclerosis.2019Inngår i: Otology and Neurotology, ISSN 1531-7129, E-ISSN 1537-4505, Vol. 40, nr 1, s. e32-e39Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives: Patients with otosclerosis more often complain about postoperative taste disturbance than patients with chronic otitis media, which seems paradoxical. We aim to investigate if and potentially why this seems to be the case, since the chorda tympani nerve (CTN) is thought to be severely traumatized less frequently during surgery in the former than in the latter.

    Study Design: Prospective cohort study.

    Setting: Department of Otorhinolaryngology at Hospital of Vastmanland, Vasteras, Sweden.

    Patients: Sixty-five adults undergoing primary middle ear surgery were included. Thirty-seven were operated on for chronic suppurative otitis media with or without cholesteatoma (CSOM) and 28 for otosclerosis.

    Interventions: Middle ear surgery due to otosclerosis or CSOM. Subjective and objective taste measurements and quality of life (QoL) questionnaire.

    Main Outcome Measures: Taste was assessed using electrogustometry (EGM) and the filter paper disc (FPD) method before and up to 1 year after surgery. Questionnaires on taste disturbance, including a visual analogue scale (VAS), and QoL were completed before and up to 1 year after surgery.

    Results: Subjective taste disturbance anytime during the 1-year follow-up were reported by 62 and 46%, respectively. The difference in EGM 1 week after surgery compared with preoperative EGM was significantly greater among CSOM patients than otosclerosis. One year postoperatively, the difference is non-significant.

    Conclusion: Surgery for CSOM causes greater initial and more long-lasting taste disturbances as compared with surgery for otosclerosis. One-year postoperative taste normalizes for both CSOM and otosclerosis patients according to VAS and EGM measurements. No real change in QoL was seen 1-year postoperatively.

    Level of evidence: Level 2 evidence is prospective observational research with an experimental design.

  • 52.
    Berling Holm, Katarina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Knutsson, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Strömbäck, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Danckwardt-Lillieström, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Papatziamos, Georgios
    Karolinska Univ Hosp, ENT Dept, Stockholm, Sweden.
    Rosenblad, Andreas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    von Unge, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås. Akershus Univ Hosp, Dept Otorhinolaryngol, Lorenskog, Norway; Univ Oslo, N-0316 Oslo, Norway.
    Taste disturbance after stapes surgery: an evaluation of frequency, severity, duration, and quality-of-life2017Inngår i: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 37, nr 1, s. 39-43Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

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

     

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

     

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

     

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

  • 53.
    Berling, Katarina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Mannstrom, Paula
    Ulfendahl, Mats
    Lillieström, Niklas Danckwardt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Von Unge, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    The chorda tympani degenerates during chronic otitis media: an electron microscopy study2015Inngår i: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 135, nr 6, s. 542-548Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

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

  • 54.
    Björck, Martin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kärlkirurgi.
    Bergqvist, David
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kärlkirurgi.
    Engström, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Glomustumörer, en kärlkirurgisk utmaning som kräver ett multidisciplinärt samarbete2009Inngår i: Svensk Kirurgi, ISSN 0346-847X, Vol. 67, nr 3 Suppl., s. 35-Artikkel i tidsskrift (Fagfellevurdert)
  • 55.
    Bohman, Anton
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Juodakis, Julius
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Obstet & Gynecol, Gothenburg, Sweden.
    Oscarsson, Martin
    Skaraborg Hosp, Dept Otorhinolaryngol, Skovde, Sweden.
    Bacelis, Jonas
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Obstet & Gynecol, Gothenburg, Sweden.
    Bende, Mats
    Skaraborg Hosp, Dept Otorhinolaryngol, Skovde, Sweden.
    Naluai, Asa Torinsson
    Univ Gothenburg, Sahlgrenska Acad, Inst Biomed, Dept Microbiol & Immunol, Gothenburg, Sweden.
    A family-based genome-wide association study of chronic rhinosinusitis with nasal polyps implicates several genes in the disease pathogenesis2017Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, nr 12, artikkel-id e0185244Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: The pathogenesis of chronic rhinosinusitis with nasal polyps is largely unknown. Previous studies have given valuable information about genetic variants associated with this disease but much is still unexplained. Our goal was to identify genetic markers and genes associated with susceptibility to chronic rhinosinusitis with nasal polyps using a family-based genome-wide association study.

    Methods: 427 patients (293 males and 134 females) with CRSwNP and 393 controls (175 males and 218 females) were recruited from several Swedish hospitals. SNP association values were generated using DFAM (implemented in PLINK) and Efficient Mixed Model Association eXpedited (EMMAX). Analyses of pathway enrichment, gene expression levels and expression quantitative trait loci were then performed in turn.

    Results: None of the analysed SNPs reached genome wide significant association of 5.0 x 10-(8). Pathway analyses using our top 1000 markers with the most significant association p-values resulted in 138 target genes. A comparison between our target genes and gene expression data from the NCBI Gene Expression Omnibus database showed significant overlap for 36 of these genes. Comparisons with data from expression quantitative trait loci showed the most skewed allelic distributions in cases with chronic rhinosinusitis with nasal polyps compared with controls for the genes HLCS, HLA-DRA, BICD2, VSIR and SLC5A1.

    Conclusion: Our study indicates that HLCS, HLA-DRA, BICD2, VSIR and SLC5A1 could be involved in the pathogenesis of chronic rhinosinusitis with nasal polyps. HLA-DRA has been associated with chronic rhinosinusitis with nasal polyps in previous studies and HLCS, BICD2, VSIR and SLC5A1 may be new targets for future research.

  • 56.
    Bohman, Anton
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Oscarsson, Martin
    Skaraborg Hosp, Dept Otorhinolaryngol, Skovde, Sweden.
    Holmberg, Kenneth
    Univ Gothenburg, Sahlgrenska Acad, Dept Otorhinolaryngol, Gothenburg, Sweden.
    Johansson, Leif
    Skaraborg Hosp, Dept Otorhinolaryngol, Skovde, Sweden.
    Millqvist, Eva
    Univ Gothenburg, Sahlgrenska Acad, Dept Internal Med Resp Med & Allergol, Gothenburg, Sweden.
    Nasic, Salmir
    Skaraborg Hosp, Res & Dev Ctr, Skovde, Sweden.
    Bende, Mats
    Skaraborg Hosp, Dept Otorhinolaryngol, Skovde, Sweden.
    Relative frequencies of symptoms and risk factors among patients with chronic rhinosinusitis with nasal polyps using a case-control study2018Inngår i: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 138, nr 1, s. 46-49Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives: The aim of this study was to investigate the relative frequency of important symptoms of chronic rhinosinusitis with nasal polyps (CRSwNP), the link between CRSwNP and the lower airways and the importance of smoking in CRSwNP.

    Method: Three hundred and sixty-eight patients with CRSwNP and 1349 controls were recruited to the study and underwent a structured interview about symptoms from the upper and lower airways, and about smoking habits. Furthermore, all participants were clinically examined using nasal endoscopy.

    Results: Due to interactions between the outcome variables, a multiple logistic regression model was fitted to the data. Nasal secretions, nasal blockage and impaired sense of smell were symptoms associated with CRSwNP. Furthermore, male gender, increasing age and asthma were also associated with the disease. Current smoking was less frequent among patients with CRSwNP.

    Conclusion: By comparing symptoms and risk factors of patients with CRSwNP with those of a large population-based control group and testing them in a multiple logistic regression model, we have been able to generate data that address key research interests in CRSwNP.

  • 57.
    Bohman, Anton
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Oscarsson, Martin
    Holmberg, Kenneth
    Johansson, Leif
    Millqvist, Eva
    Nasic, Salmir
    Torinsson-Naluai, Asa
    Bende, Mats
    Heredity of nasal polyps2015Inngår i: Rhinology, ISSN 0300-0729, E-ISSN 1996-8604, Vol. 53, nr 1, s. 25-28Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

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

  • 58. Boldrup, L.
    et al.
    Coates, P. J.
    Laurell, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Wilms, T.
    Fahraeus, R.
    Nylander, K.
    Downregulation of miRNA-424: a sign of field cancerisation in clinically normal tongue adjacent to squamous cell carcinoma2015Inngår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 112, nr 11, s. 1760-1765Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

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

  • 59.
    Boldrup, Linda
    et al.
    Umea Univ, Dept Med Biosci Pathol, SE-90185 Umea, Sweden..
    Gu, Xiaolian
    Umea Univ, Dept Med Biosci Pathol, SE-90185 Umea, Sweden..
    Coates, Philip J.
    Masaryk Mem Canc Inst, RECAMO, Brno 65653, Czech Republic..
    Norberg-Spaak, Lena
    Umea Univ, Dept Clin Sci ENT, SE-90185 Umea, Sweden..
    Fahraeus, Robin
    Umea Univ, Dept Med Biosci Pathol, SE-90185 Umea, Sweden.;Masaryk Mem Canc Inst, RECAMO, Brno 65653, Czech Republic.;Univ Paris 07, Hop St Louis, Inst Genet Mol, F-75010 Paris, France..
    Laurell, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar. Umea Univ, Dept Clin Sci ENT, SE-90185 Umea, Sweden.
    Wilms, Torben
    Umea Univ, Dept Clin Sci ENT, SE-90185 Umea, Sweden..
    Nylander, Karin
    Umea Univ, Dept Med Biosci Pathol, SE-90185 Umea, Sweden..
    Gene expression changes in tumor free tongue tissue adjacent to tongue squamous cell carcinoma2017Inngår i: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 8, nr 12, s. 19389-19402Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

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

  • 60.
    Bondza, Sina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för biomedicinsk strålningsvetenskap.
    Stenberg, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för biomedicinsk strålningsvetenskap.
    Nestor, Marika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för biomedicinsk strålningsvetenskap. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Andersson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för biomedicinsk strålningsvetenskap.
    Björkeund, Hanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för biomedicinsk strålningsvetenskap.
    Conjugation Effects on Antibody-Drug Conjugates: Evaluation of Interaction Kinetics in Real Time on Living Cells2014Inngår i: Molecular Pharmaceutics, ISSN 1543-8384, E-ISSN 1543-8392, Vol. 11, nr 11, s. 4154-4163Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

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

  • 61. Borgström, A.
    et al.
    Nerfeldt, P.
    Friberg, Danielle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Adenotonsillotomy Versus Adenotonsillectomy in Pediatric Obstructive Sleep Apnea: An RCT.2017Inngår i: Pediatrics, Vol. 139, nr 7Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Adenotonsillectomy (ATE) is a well-established and effective treatment of pediatric obstructive sleep apnea (OSA). In recent years, a more conservative method, adenotonsillotomy (ATT), has gained popularity because it is associated with less postoperative morbidity. Yet no previous randomized study has compared these 2 methods regarding their effectiveness in treating pediatric OSA in terms of polysomnographic data, which was the primary aim of this study. The hypothesis was that ATT is noninferior to ATE after 1 year.

    METHODS: Seventy-nine children, aged 2 to 6 years, with OSA (Apnea-Hypopnea Index [AHI] 5–30) were randomized to ATT (n = 40) or ATE (n = 39). Polysomnography (PSG) and questionnaire OSA-18 were assessed at baseline and 1 year postsurgery.

    RESULTS: Mean difference between groups in the primary outcome, change in AHI, was 0.83, 95% confidence interval –3.2 to 4.9, not exceeding the noninferiority margin of 5. After ATE, AHI decreased from median 12.7 (interquartile range 8.3–19.1) to 2.0 (1.2–3.1) and after ATT from 15.8 (8.5–21.2) to 4.0 (1.2–5.1). For both groups, significant improvements of PSG and OSA-18 questionnaire outcomes were observed, with no significant differences between groups. Five children (13%) in the ATT group needed repeated surgery for tonsil regrowth and recurrence of OSA.

    CONCLUSIONS: The results suggest that ATT is noninferior to ATE in treating pediatric OSA regarding PSG outcomes after 1 year. ATT could be considered an alternative to ATE for treatment of pediatric OSA. However, after ATT, there is a nonnegligible risk of recurrence of OSA, and this should be taken into account when selecting surgical method.

  • 62.
    Borgström, Anna
    et al.
    Karolinska Inst, Dept Clin Sci Intervent & Technol, CLINTEC, Stockholm, Sweden.
    Nerfeldt, Pia
    Karolinska Univ Hosp, Karolinska Inst, Dept Otorhinolaryngol, CLINTEC, Stockholm, Sweden.
    Friberg, Danielle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Postoperative pain and bleeding after adenotonsillectomy versus adenotonsillotomy in pediatric obstructive sleep apnea an RCT2019Inngår i: European Archives of Oto-Rhino-Laryngology, ISSN 0937-4477, E-ISSN 1434-4726, Vol. 276, nr 11, s. 3231-3238Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE: Our previous randomized controlled trial (RCT) of children with obstructive sleep apnea (OSA) showed no significant differences between adenotonsillectomy (ATE) and adenotonsillomy (ATE) in improving nocturnal respiration and symptoms after one year. This is the continuous report with the evaluation of postoperative morbidity concerning bleeding and pain.

    METHODS: A double-blinded RCT including 79 children, aged 2-6 years, with moderate to severe OSA, randomized to either ATE (n = 40) or ATT (n = 39). From one to ten days postoperatively, parents filled in a logbook with six pain-related outcomes (parent and child grading pain at different levels, days of analgesic use and return to normal diet). Peri- and postoperative bleeding were also registered.

    RESULTS: 63 patients (80%) returned the logbook. There were significant differences between groups in only two of the six pain-related outcomes in favor of the ATT group; first day when the children graded themselves as pain free (p = 0.021, Log Rank Test), and first day the caregiver estimated pain VAS ≤ 5 (p = 0.007, Log Rank Test). Two (5%) cases of postoperative bleeding occurred in the ATE group, one of which needed a return to theatre. No case of postoperative bleeding was seen in the ATT group.

    CONCLUSIONS: The results from this RCT are in line with previous comparative studies between ATT and ATE. Children operated with ATT had significantly less postoperative pain in one-third of the outcomes, and less bleeding than ATE. However, as the differences in morbidity between the surgical methods were minor the clinical significance is uncertain.

    TRIAL REGISTRATION: This study was approved by the Swedish Regional Ethics Board in Stockholm, Sweden (Dnr 2011/925-32 and 2013/2274-32) and registered at ClinicalTrials.gov (Trial registration number NCT01676181).

  • 63.
    Borota, Ljubisa
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Mahmoud, Ehab
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Nyberg, Christoffer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Ekberg, Tomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Combined percutaneous and transarterial devascularisation of juvenile nasopharyngeal angiofibroma with protection of internal carotid artery: A modification of the technique2015Inngår i: Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences, ISSN 1591-0199, Vol. 21, nr 3, s. 390-396Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

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

  • 64.
    Boström, Marja
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Plastikkirurgi.
    Khalifa, Shaden
    Boström, Henrik
    Liu, Wei
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Friberg, Ulla
    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.
    Effects of Neurotrophic Factors on Growth and Glial Cell Alignment of Cultured Adult Spiral Ganglion Cells2009Inngår i: Audiology & neuro-otology, ISSN 1420-3030, E-ISSN 1421-9700, Vol. 15, nr 3, s. 175-186Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

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

  • 65.
    Botling, Johan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Edlund, Karolina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Segersten, Ulrika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Tahmasebpoor, Simin
    Engström, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Sundström, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Malmström, Per-Uno
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Micke, Patrick
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Impact of thawing on RNA integrity and gene expression analysis in fresh frozen tissue2009Inngår i: Diagnostic molecular pathology (Print), ISSN 1052-9551, E-ISSN 1533-4066, Vol. 18, nr 1, s. 44-52Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

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

  • 66. Briem, Birgir
    et al.
    Thorvardsson, Ornolfur
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Petersen, Hannes
    Acute epiglottitis in Iceland 1983-20052009Inngår i: Auris, nasus, larynx, ISSN 0385-8146, E-ISSN 1879-1476, Vol. 36, nr 1, s. 46-52Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

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

  • 67. Browaldh, N
    et al.
    Bring, J
    Friberg, Danielle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    SKUP(3) RCT; continuous study: Changes in sleepiness and quality of life after modified UPPP.2016Inngår i: The Laryngoscope, ISSN 0023-852X, E-ISSN 1531-4995, Vol. 26, nr 6Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives/Hypothesis

    Our previous study showed that modified uvulopalatopharyngoplasty (UPPP), including tonsillectomy, significantly improved nocturnal respiration in obstructive sleep apnea syndrome (OSAS) patients. This is a continuous study of changes in daytime sleepiness and quality of life.

    Study Design

    Prospective randomized controlled trial (RCT), two parallel arms.

    Methods

    Sixty‐five patients with apnea‐hypopnea index ≥ 15, body mass index < 36, Epworth Sleepiness Scale (ESS) ≥ 8, Friedman stage I or II, failing nonsurgical treatment. The intervention group (n = 32) underwent surgery, and the controls (n = 33) had no treatment. At baseline and the 7‐month follow‐up, polysomnography, questionnaires, and vigilance tests were implemented.

    Results

    All patients answered the questionnaires, and 48 took the vigilance test. Epworth Sleepiness Scale decreased significantly in the intervention group, from a mean (standard deviation) of 12.5(3.2) to 6.8(3.9), but nonsignificantly in the control group, from 12.9(3.1) to 12.5(3.9), a significant group difference (P < 0.001). The physical and mental component score on the Short Form‐36 questionnaire increased significantly in the intervention group, from a mean 47.8(8.3) to 51.2(8.8) and from 42.1(10.6) to 48.1(9.7), respectively, but with nonsignificant changes in the controls: 49.0(9.0) to 48.3(9.1) and 41.0(10.2) to 42.7(11.5), significant group differences (P = 0.007, P = 0.031), respectively. The sleep latency/vigilance test showed a significant mean increase in the intervention group of 7(12.4) minutes and a decrease in the controls of 2.2(10.6), a significant group difference (P = 0.011). There were significant correlations between changes in subjective outcomes and nocturnal respiration.

    Conclusion

    This RCT shows that modified UPPP was effective in improving daytime sleepiness and quality of life in OSAS patients. It strengthens the body of evidence on the potential effect of surgery offered to selected patients.

  • 68. Brown, Toby D
    et al.
    Edin, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Detta, Nicola
    Skelton, Anthony D
    Hutmacher, Dietmar W
    Dalton, Paul D
    Melt electrospinning of poly(ε-caprolactone) scaffolds: phenomenological observations associated with collection and direct writing.2014Inngår i: Materials science & engineering. C, biomimetic materials, sensors and systems, ISSN 0928-4931, E-ISSN 1873-0191, Vol. 45Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

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

  • 69.
    Bylund, Nina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Jensson, David
    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.
    Berg, T
    Marsk, E
    Hultcrantz, M
    Hadziosmanovic, Nermin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Rodriguez-Lorenzo, Andres
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Plastikkirurgi.
    Jonsson, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Synkinesis in Bell's palsy in a randomised controlled trial2017Inngår i: Clinical Otolaryngology, ISSN 1749-4478, E-ISSN 1365-2273, Vol. 42, nr 3, s. 673-680Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

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

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

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

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

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

  • 70.
    Cai, Bing
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Xia, Wei
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Bredenberg, Susanne
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Li, Hao
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Engqvist, Håkan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Bioceramic microneedles with flexible and self-swelling substrate2015Inngår i: European journal of pharmaceutics and biopharmaceutics, ISSN 0939-6411, E-ISSN 1873-3441, Vol. 94, s. 404-410Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    To reduce the effort required to penetrate the skin and optimize drug release profiles, bioceramic microneedle arrays with higher-aspect-ratio needles and a flexible and self-swelling substrate have been developed. Swelling of the substrate can assist in separating it from the needles and leave them in the skin as a drug depot. The preparation procedures for this bioceramic microneedle are described in the paper. Clonidine hydrochloride, the model drug, was released in a controlled manner by the microneedle device in vitro. Results showed that the microneedle array with a flexible and self-swelling substrate released the drug content faster than the array with a rigid substrate. Disintegration of the needle material and diffusion of the drug molecules are believed as the main control mechanisms of the drug release from these microneedle arrays. Ex vivo skin penetration showed that they can effectively penetrate the stratum corneum without an extra device. This work represents a progression in the improvement of bioceramic microneedles for transdermal drug delivery.

  • 71.
    Cai, Yixiao
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Edin, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Jin, Zhe
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Fysiologi.
    Alexsson, Andrei
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Gudjonsson, Olafur
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    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.
    Karlsson, Mikael
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Li, Hao
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Strategy towards independent electrical stimulation from cochlear implants: Guided auditory neuron growth on topographically modified nanocrystalline diamond2016Inngår i: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 31, s. 211-220Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Cochlear implants (CI) have been used for several decades to treat patients with profound hearing loss. Nevertheless, results vary between individuals, and fine hearing is generally poor due to the lack of discrete neural stimulation from the individual receptor hair cells. A major problem is the deliverance of independent stimulation signals to individual auditory neurons. Fine hearing requires significantly more stimulation contacts with intimate neuron/electrode interphases from ordered axonal re-growth, something current CI technology cannot provide.

    Here, we demonstrate the potential application of micro-textured nanocrystalline diamond (NCD) surfaces on CI electrode arrays. Such textured NCD surfaces consist of micrometer-sized nail-head-shaped pillars (size 5 5 lm2) made with sequences of micro/nano-fabrication processes, including sputtering, photolithography and plasma etching.

    The results show that human and murine inner-ear ganglion neurites and, potentially, neural progenitor cells can attach to patterned NCD surfaces without an extracellular matrix coating. Microscopic methods revealed adhesion and neural growth, specifically along the nail-head-shaped NCD pillars in an ordered manner, rather than in non-textured areas. This pattern was established when the inter-NCD pillar distance varied between 4 and 9 lm.

    The findings demonstrate that regenerating auditory neurons show a strong affinity to the NCD pillars, and the technique could be used for neural guidance and the creation of new neural networks. Together with the NCD’s unique anti-bacterial and electrical properties, patterned NCD surfaces could provide designed neural/electrode interfaces to create independent electrical stimulation signals in CI electrode arrays for the neural population.

  • 72.
    Cai, Yixiao
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    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.
    Karlsson, Mikael
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Ordered auditory neuron growth on micro-structured nanocrystalline diamond surface2015Konferansepaper (Fagfellevurdert)
  • 73.
    Cederblad, Lena
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Johansson, Silvia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Enblad, Gunilla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Engström, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Blomquist, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Cancer of the parotid gland; long-term follow-up: A single centre experience on recurrence and survival2009Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 48, nr 4, s. 549-555Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND:

    The aim of the study was to investigate the results of treatment of malignant parotid gland tumours at a single centre during a 56 year period, focusing on tumour control and survival.

    PATIENTS AND METHODS:

    At Uppsala University Hospital, Sweden, 144 patients (73 male and 71 female) with parotid cancer were treated between 1948 and 2004. The mean and median ages were 62 and 65 years, respectively (range 16-89 years). Surgery was the primary treatment in 113 (78%) patients followed by radiotherapy in 81. Postoperative radiotherapy in doses of 64-66 Gy, where the intention was curative and delivered with either split course or not, was administered to a majority of patients after 1970. The split-course mode was practised between 1970 and 1989. The median follow-up time was 8.3 years for patients still alive. There were 57 (40%) relapses, of which 40 were local recurrences with 26 inside the treatment volume.

    RESULTS:

    The overall 5-year survival was 53%. The majority of tumour-related deaths appeared in the first 3-5 years after diagnosis. Age, co-morbidity, the presence of lymph node metastases, adenoid cystic carcinoma and extent of disease were important for outcome; gender, however, was not. We found no difference in the survival between patients following split course therapy versus continuous fractionation. No difference could be seen in the survival of patients treated in the 1970s versus the 1990s.

    CONCLUSIONS:

    Age, nodal engagement, a higher T-stage, adenoid cystic carcinoma histopathology, facial palsy and intercurrent disease worsen the outcome of patients, whereas gender does not. Treatment principles at our hospital have been surgery followed by radiotherapy since the early 1970s even though a split course technique was practised during a part of this period. Survival has not improved markedly. Thus, there is scope for improvement for this group of patients.

  • 74.
    Cederblad, Lena
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Thunberg, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Engström, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Castro, Juan
    Rutqvist, Lars Erik
    Laytragoon-Lewin, Nongnit
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    The Combined Effects of Single-Nucleotide Polymorphisms, Tobacco Products, and Ethanol on Normal Resting Blood Mononuclear Cells2013Inngår i: Nicotine & tobacco research, ISSN 1462-2203, E-ISSN 1469-994X, Vol. 15, nr 5, s. 890-895Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Introduction: Tobacco and ethanol consumption are crucial factors in the development of various diseases including cancer. In this investigation, we evaluated the combined effects of a number of single nucleotide polymorphisms (SNPs), with ethanol and tobacco products on healthy individuals. Methods: Pure nicotine, cigarette smoke extract, and Swedish snuff (snus) extract were used. The effects were examined by means of in vitro cell cycle progression and cell death of peripheral blood mononuclear cells (PBMCs) obtained from healthy donors. Results: After 3 days, in vitro, resting PBMCs entered the S and G2 stage in the presence of 100 mu M nicotine. The PBMCs only proceeded to S stage, in the presence of 0.2% ethanol. The nicotine- and ethanol-induced normal cell cycle progression correlated to a number of SNPs in the IL12RB2, Rad 52, XRCC2, P53, CCND3, and ABCA1 genes. Certain SNPs in Caspases 8, IL12RB2, Rad 52, MMP2, and MDM2 genes appeared to significantly influence the effects of EtOH-, snus-, and snus + EtOH-induced cell death. Importantly, the highest degree of cell death was observed in the presence of smoke + EtOH. The amount of cell death under this treatment condition also correlated to specific SNPs, located in the MDM2, ABCA1, or GASC1 genes. Conclusions: Cigarette smoke in combination with ethanol strongly induced massive cell death. Long-term exposure to smoke and ethanol could provoke chronic inflammation, and this could be the initiation of disease including the development of cancer at various sites.

  • 75.
    Chacko, L. Johnson
    et al.
    Med Univ Innsbruck, Dept Otorhinolaryngol, Anichstr 35, A-6020 Innsbruck, Austria..
    Blumer, M. J. F.
    Med Univ Innsbruck, Dept Anat Histol & Embryol, Div Clin & Funct Anat, Muellerstr 59, A-6020 Innsbruck, Austria..
    Pechriggl, E.
    Med Univ Innsbruck, Dept Anat Histol & Embryol, Div Clin & Funct Anat, Muellerstr 59, A-6020 Innsbruck, Austria..
    Rask-Andersen, Helge
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Dietl, W.
    Med Univ Innsbruck, Dept Otorhinolaryngol, Anichstr 35, A-6020 Innsbruck, Austria..
    Haim, A.
    Med Univ Innsbruck, Dept Plast Reconstruct & Aesthet Surg, Innerkoflerstr 1, A-6020 Innsbruck, Austria..
    Fritsch, H.
    Med Univ Innsbruck, Dept Anat Histol & Embryol, Div Clin & Funct Anat, Muellerstr 59, A-6020 Innsbruck, Austria..
    Glueckert, R.
    Med Univ Innsbruck, Dept Otorhinolaryngol, Anichstr 35, A-6020 Innsbruck, Austria.;Tirol Kliniken, Univ Clin Innsbruck, Anichstr 35, A-6020 Innsbruck, Austria..
    Dudas, J.
    Med Univ Innsbruck, Dept Otorhinolaryngol, Anichstr 35, A-6020 Innsbruck, Austria..
    Schrott-Fischer, A.
    Med Univ Innsbruck, Dept Otorhinolaryngol, Anichstr 35, A-6020 Innsbruck, Austria..
    Role of BDNF and neurotrophic receptors in human inner ear development2017Inngår i: Cell and Tissue Research, ISSN 0302-766X, E-ISSN 1432-0878, Vol. 370, nr 3, s. 347-363Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The expression patterns of the neurotrophin, brain-derived neurotrophic factor, BDNF, and the neurotrophic receptors-p75NTR and Trk receptors-in the developing human fetal inner ear between the gestational weeks (GW) 9 to 12 are examined via in situ hybridization and immunohistochemistry. BDNF mRNA expression was highest in the cochlea at GW 9 but declined in the course of development. In contrast to embryonic murine specimens, a decline in BDNF expression from the apical to the basal turn of the cochlea could not be observed. p75NTR immunostaining was most prominent in the nerve fibers that penetrate into the sensory epithelia of the cochlea, the urticule and the saccule as gestational age progresses. TrkB and TrkC expression intensified towards GW 12, at which point the BDNF mRNA localization was at its lowest. TrkA expression was limited to fiber subpopulations of the facial nerve at GW 10. In the adult human inner ear, we observed BDNF mRNA expression in the apical poles of the cochlear hair cells and supporting cells, while in the adult human utricle, the expression was localized in the vestibular hair cells. We demonstrate the highly specific staining patterns of BDNF mRNA and its putative receptors over a developmental period in which multiple hearing disorders are manifested. Our findings suggest that BDNF and neurotrophin receptors are important players during early human inner ear development. In particular, they seem to be important for the survival of the afferent sensory neurons.

  • 76.
    Cheng, Junping
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Engström, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Ekberg, Tomas
    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 kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Anniko, Matti
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Tolmachev, Vladimir
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    The use of closo-dodecaborate-containing linker improves targeting of HNSCC xenografts with radioiodinated chimeric monoclonal antibody U362010Inngår i: Molecular Medicine Reports, ISSN 1791-2997, Vol. 3, nr 1, s. 155-160Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Radionuclide imaging of head and neck squamous cell carcinoma (HNSCC) using monoclonal antibodies (MAbs) has the potential to contribute to improved diagnosis and staging, thereby making more effective treatment possible. Chimeric monoclonal antibody U36 (cMAb U36), specific to CD44v6 antigen. is a candidate for the targeting of HNSCC. The aim of this study was to compare the influence of indirect iodination via closo-dodecaborate-based linker (DABI) with the influence of direct radioiodination on the biodistribution of the chimeric anti-CD44v6 antibody U36. The study was performed using nude mice bearing UT-SCC7 HNSCC xenografts using the paired-label method. The biodistribution of cMAb U36 labelled directly with I-131 and using DABI with I-125 was compared in the same animals. The influence of DABI on the tumour-to-organ ratio was evaluated. For both conjugates, radioactivity uptake in blood and organs decreased with time, except in tumours and the thyroid. DABI-labelled cMAb U36 was characterised by fast blood clearance and an elevated uptake in the liver and spleen. The use of DABI enabled a 1.5 to 2-fold improvement in the tumour-to-blood and tumour-to-organ ratios in comparison with direct radioiodination, with the exception of the liver and spleen. These results indicate that DABI is a promising linker for the coupling of radioiodine to HNSCC-targeting antibodies.

  • 77.
    Christou, Constantina
    et al.
    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.
    Strömbäck, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Bifurcation of the intratemporal facial nerve: A rare anatomical anomaly2018Inngår i: ACTA OTO-LARYNGOLOGICA CASE REPORTS, ISSN 2377-2484, Vol. 3, nr 1, s. 15-18Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The anatomical position of the facial nerve is a critical factor in determining surgical candidacy in patients with congenital aural atresia (CAA). All patients with CAA must preoperatively be evaluated using a grading score based on information gained from a high resolution CT scan. In patients not suitable for surgical reconstruction, implantation of novel hearing implants is increasingly used for hearing rehabilitation. We, here, describe a bifurcation of the intratemporal part of the facial nerve in a 5-year old boy with CAA undergoing implantation with a bone conductive hearing device.

  • 78.
    Coelho, Ruben
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Plastikkirurgi.
    Ekberg, Thomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Svensson, Malin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Mani, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Plastikkirurgi.
    Rodriguez-Lorenzo, Andres
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Plastikkirurgi.
    Reconstruction of late esophagus perforation after anterior cervical spine fusion with an adipofascial anterolateral thigh free flap: A case report.2017Inngår i: Microsurgery, ISSN 0738-1085, E-ISSN 1098-2752, Vol. 37, nr 6, s. 684-688Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Reconstruction of late esophageal perforation usually requires flap surgery to achieve wound healing. However, restoring the continuity between the digestive tract and retropharyngeal space to allow for normal swallowing remains a technical challenge. In this report, we describe the use of a thin and pliable free adipofascial anterolateral thigh (ALT) flap in a 47-year-old tetraplegic man with a history of C5-C6 fracture presented with a large posterior esophagus wall perforation allowing an easier flap insetting for a successful wound closure. The postoperative course was uneventful and mucosalization of the flap was confirmed by esophagoscopy 4 weeks postsurgery. The patient tolerated normal diet and maintained normal swallowing during a follow-up of 3 years postoperatively. The adipofascial ALT flap may provide easier insetting due to the thin and pliable layer of adipofascial tissue for reconstructing large defects of the posterior wall of the esophagus by filling the retroesophageal space.

  • 79.
    Counter, S. Allen
    et al.
    Harvard Med Sch, Biol Labs, Dept Neurol, 16 Divin Ave, Cambridge, MA 02138 USA.;Massachusetts Gen Hosp, Dept Neurophysiol, Boston, MA 02114 USA..
    Buchanan, Leo H.
    Harvard Univ Hlth Serv, Audiol Clin, Dept Otolaryngol, Cambridge, MA USA..
    Ortega, Fernando
    Univ San Francisco Quito, Galapagos Inst Arts & Sci GAIAS, Colegio Ciencias Salud, Escuela Salud Publ, Quito, Ecuador..
    Jacobs, Anthony B.
    Harvard Biol Labs, Cambridge, MA USA..
    Laurell, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Assessment of the Brainstem- Mediated Stapedius Muscle Reflex in Andean Children Living at High Altitudes2017Inngår i: High Altitude Medicine & Biology, ISSN 1527-0297, E-ISSN 1557-8682, Vol. 18, nr 1, s. 37-45Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This study examined the physiological thresholds, amplitude growth, and contraction duration of the acoustic stapedius reflex (ASR) in Andean children aged 2-17 years living at altitudes of 2850m (Altitude I Group) and 3973m (Altitude II Group) as part of a general medical assessment of the health status of the children. The brainstem-mediated ASR reveals the integrity of the neuronal components of the auditory reflex arc, including the cochlea receptors, eight cranial nerves, and brainstem neural projections to the cochlear nuclei, bilateral superior olivary nuclei, facial nerve nuclei, and facial nerve and its stapedius branch. Uncrossed (ipsilateral) and crossed (contralateral) ASR thresholds (ASRT), ASR amplitude growth (ASRG) function, and ASR muscle contraction duration (decay/ fatigue) (ASRD) were measured noninvasively with 500, 1000 Hz and broadband (bandwidth = 125-4000 Hz) noise stimulus activators using a middle ear immittance system. Oxygen saturation (SaO(2)) level and heart rate were measured in a subsample of the study group. Statistical analyses revealed that the Altitude I and Altitude II groups had ASRT, ASRG function, and ASRD rates comparable to children at sea level and that the two groups were not significantly different for any of the ASR measures. No significant association was found between SaO(2) or heart rate and ASRT, growth, and muscle fatigue rate. In conclusion, the assessment of the ASR in children in the high-altitude groups revealed normal function. Furthermore, the results indicate no adverse oto-physiological effects of altitude on the brainstem-mediated ASR at elevations between 2850 and 4000m and suggest normal middle ear and auditory brainstem function.

  • 80.
    Counter, S. Allen
    et al.
    Harvard Univ, Harvard Med Sch, Dept Neurol, Biol Labs, 16 Divin Ave, Cambridge, MA 02138 USA.;Massachusetts Gen Hosp, Dept Neurophysiol, Boston, MA 02114 USA..
    Buchanan, Leo H.
    Harvard Univ, Dept Otolaryngol, Audiol Clin, Hlth Serv, 16 Divin Ave, Cambridge, MA 02138 USA..
    Ortega, Fernando
    Univ San Francisco Quito, Escuela Salud Publ, Colegio Ciencias Salud, Quito, Ecuador.;Univ San Francisco Quito, Galapagos Inst Arts & Sci GAIAS, Quito, Ecuador..
    Jacobs, Anthony B.
    Harvard Univ, Harvard Biol Labs, 16 Divin Ave, Cambridge, MA 02138 USA..
    Laurell, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Middle Ear Function and Pathophysiology in Andean Children Living at High Altitudes2017Inngår i: High Altitude Medicine & Biology, ISSN 1527-0297, E-ISSN 1557-8682, Vol. 18, nr 2, s. 163-170Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The extent of altitude-related middle ear disorders in children native to high altitudes is unclear. This study examined middle ear pathophysiology in two groups of children living in high-altitude Ecuadorian Andean communities by investigating middle ear pressure (MEP), tympanic membrane compliance (TMC), and ear canal volume (ECV) using tympanometry, and by otological examination. Altitude I Group lived at 2850m, and Altitude II Group resided at around 4000m. The two high-altitude groups were compared with a reference group of children residing at sea level. Mean MEP was -3.6daPa (SD: 39.2), 3.5daPa (SD: 28.7), and 1.3daPa (SD: 13.6) for Altitude I Group, Altitude II Group, and the Sea Level Group, respectively. The MEP was not significantly different among the three groups. Mean TMC was 0.63cm3 (SD: 0.51), 0.60cm3 (SD: 0.43), and 0.60cm3 (SD: 0.24) for Altitude I Group, Altitude II Group, and the Sea Level Group, respectively. The TMC was not significantly different among the three groups. Mean ECV was 1.1 (SD: 0.26), 1.2 (SD: 0.26), and 1.0 (SD: 0.23) for Altitude I Group, Altitude II Group, and the Sea Level Group, respectively. The difference in ECV between Altitude I Group and Altitude II Group was significant (p=0.043), as was the difference between Altitude II Group and the Sea Level Group (p=0.001). ECV did not differ significantly between Altitude I Group and the Sea Level Group. Otological examination revealed a low incidence of ear canal and middle ear pathology. In conclusion, tympanometric and otological findings did not reveal a high incidence of middle ear pathophysiology in children living at altitudes as high as around 4000m.

  • 81. Counter, S Allen
    et al.
    Damberg, Peter
    Aski, Sahar Nikkhou
    Nagy, Kálmán
    Berglin, Cecilia Engmér
    Laurell, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Experimental Fusion of Contrast Enhanced High-Field Magnetic Resonance Imaging and High-Resolution Micro-Computed Tomography in Imaging the Mouse Inner Ear2015Inngår i: The Open Neuroimaging Journal, ISSN 1874-4400, E-ISSN 1874-4400, Vol. 9, s. 7-12Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: Imaging cochlear, vestibular, and 8th cranial nerve abnormalities remains a challenge. In this study, the membranous and osseous labyrinths of the wild type mouse inner ear were examined using volumetric data from ultra high-field magnetic resonance imaging (MRI) with gadolinium contrast at 9.4 Tesla and high-resolution micro-computed tomography (µCT) to visualize the scalae and vestibular apparatus, and to establish imaging protocols and parameters for comparative analysis of the normal and mutant mouse inner ear.

    METHODS: For in vivo MRI acquisition, animals were placed in a Milleped coil situated in the isocenter of a horizontal 9.4 T Varian magnet. For µCT examination, cone beam scans were performed ex vivo following MRI using the µCT component of a nanoScan PET/CT in vivo scanner.

    RESULTS: The fusion of Gd enhanced high field MRI and high-resolution µCT scans revealed the dynamic membranous labyrinth of the perilymphatic fluid filled scala tympani and scala vestibule of the cochlea, and semicircular canals of the vestibular apparatus, within the µCT visualized contours of the contiguous osseous labyrinth. The ex vivo µCT segmentation revealed the surface contours and structural morphology of each cochlea turn and the semicircular canals in 3 planes.

    CONCLUSIONS: The fusion of ultra high-field MRI and high-resolution µCT imaging techniques were complementary, and provided high-resolution dynamic and static visualization of the complex morphological features of the normal mouse inner ear structures, which may offer a valuable approach for the investigation of cochlear and vestibular abnormalities that are associated with birth defects related to genetic inner ear disorders in humans.

  • 82. Counter, S Allen
    et al.
    Nikkhou, Sahar
    Brené, Stefan
    Damberg, Peter
    Sierakowiak, Adam
    Klason, Tomas
    Berglin, Cecilia Engmér
    Laurell, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    MRI evidence of endolymphatic impermeability to the gadolinium molecule in the in vivo mouse inner ear at 9.4 tesla2013Inngår i: The Open Neuroimaging Journal, ISSN 1874-4400, E-ISSN 1874-4400, Vol. 7, s. 27-31Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE:

    Previous in vivo experimental magnetic resonance imaging (MRI) investigations of the mammalian inner ear at 4.7 Tesla have indicated that intravenously injected gadolinium (Gd) penetrates the perilymphatic labyrinth, but not the endolymphatic membranous labyrinth. In the present study, high field MRI at 9.4T was used to visualize the in vivo mouse vestibulo-cochlea system, and to determine whether the endolymphatic system is permeable to a Gd complex.

    METHODS:

    A 9.4 T Varian magnet equipped with a 12 cm inner diameter gradient system with maximum gradient strength of 600 mT/m, a millipede coil (Varian design) and a Gd contrast agent were used for image acquisition in the normal C57 BL-6 mouse.

    RESULTS:

    High-resolution 2D and 3D images of the mouse cochlea were acquired within 80 minutes following intravenous injection of Gd. Gd initially permeated the perilymphatic scala tympani and scala vestibuli, and permitted visualization of both cochlear turns from base to apex. The superior, inferior and lateral semicircular canals were subsequently visualized in 3 planes. The membranous endolymphatic labyrinth was impermeable to intravenously injected Gd, and thus showed no apparent uptake of Gd at 9.4T.

    CONCLUSION:

    The 9.4T field strength MRI permitted acquisition of high resolution images of anatomical and physiological features of the normal, wild type mouse perilymphatic inner ear in vivo, and provided further evidence that the endolymphatic system is impermeable to intravenously injected Gd.

  • 83.
    Counter, S. Allen
    et al.
    Harvard Univ, Biol Labs, Dept Neurol, Cambridge, MA 02138 USA..
    Nikkhou-Aski, Sahar
    Karolinska Univ Sjukhuset Solna, Karolinska Expt Res & Imaging Ctr, Stockholm, Sweden.;Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Damberg, Peter
    Karolinska Univ Sjukhuset Solna, Karolinska Expt Res & Imaging Ctr, Stockholm, Sweden.;Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Berglin, Cecilia Engmer
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden..
    Laurell, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Ultra-high-field (9.4 T) MRI Analysis of Contrast Agent Transport Across the Blood-Perilymph Barrier and Intrastrial Fluid-Blood Barrier in the Mouse Inner Ear2017Inngår i: Otology and Neurotology, ISSN 1531-7129, E-ISSN 1537-4505, Vol. 38, nr 7, s. 1052-1059Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Hypothesis: Effective paramagnetic contrast agent for the penetration of the perilymphatic spaces of the scala tympani, scala vestibuli, and scala media of the mouse inner ear can be determined using intravenous injection of various gadolinium (Gd) complexes and ultra-high-field magnetic resonance imaging (MRI) at 9.4 Tesla.

    Background: A number of contrast agents have been explored in experimental high-field MRI to determine the most effective Gd complex for ideal signal-to-noise ratio and maximal visualization of the in vivo mammalian inner ear in analyzing the temporal and spatial parameters involved in drug penetration of the blood-perilymph barrier and intrastrial fluid-blood barrier in the mouse model using MRI.

    Methods: Gadoteric acid (Dotarem), Gadobutrol (Gadovist), Gadodiamide (Omniscan), Gadopent acid (Magnevist), and Mangafodipir (Teslascan) were administered intravenously using the tail vein of 60 Balb/C mice. High-resolution T1 images of drug penetration were acquired with a horizontal 9.4 T Agilent magnet after intravenously injection. Signal intensity was used as a metric of temporal and spatial parameters of drug delivery and penetration of the perilymphatic and endolymphatic spaces.

    Results: ANOVA analysis of the area under the curve of intensity enhancement in perilymph revealed a significant difference (p < 0.05) in the scalae uptake using different contrast agents (F (3,25) = 3.54, p = 0.029). The Gadoteric acid complex Dotarem was found to be the most effective Gd compound in terms of rapid, morphological enhancement for analysis of the temporal, and spatial distribution in the perilymphatic space of the inner ear.

    Conclusion: Gadoteric acid (Dotarem) demonstrated efficacy as a contrast agent for enhanced visualization of the perilymphatic spaces of the inner ear labyrinthine in the mouse, including the scala tympani and scala vestibuli of the cochlea, and the semicircular canals of the vestibular apparatus. These findings may inform the clinical application of Gd compounds in patients with inner ear fluid disorders and vertigo.

  • 84.
    Covaciu, Lucian
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Weis, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Bengtsson, Caroline
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Allers, M
    Lunderquist, A
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Rubertsson, Sten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Brain temperature in volunteers subjected to intranasal cooling2011Inngår i: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 37, nr 8, s. 1277-1284Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Intranasal cooling can be used to initiate therapeutic hypothermia. However, direct measurement of brain temperature is difficult and the intra-cerebral distribution of temperature changes with cooling is unknown. The purpose of this study was to measure the brain temperature of human volunteers subjected to intranasal cooling using non-invasive magnetic resonance (MR) methods. Intranasal balloons catheters circulated with saline at 20A degrees C were applied for 60 min in ten awake volunteers. No sedation was used. Brain temperature changes were measured and mapped using MR spectroscopic imaging (MRSI) and phase-mapping techniques. Heart rate and blood pressure were monitored throughout the experiment. Rectal temperature was measured before and after the cooling. Mini Mental State Examination (MMSE) test and nasal inspection were done before and after the cooling. Questionnaires about the subjects' personal experience were completed after the experiment. Brain temperature decrease measured by MRSI was -1.7 +/- A 0.8A degrees C and by phase-mapping -1.8 +/- A 0.9A degrees C (n = 9) at the end of cooling. Spatial distribution of temperature changes was relatively uniform. Rectal temperature decreased by -0.5 +/- A 0.3A degrees C (n = 5). The physiological parameters were stable and no shivering was reported. The volunteers remained alert during cooling and no cognitive dysfunctions were apparent in the MMSE test. Postcooling nasal examination detected increased nasal secretion in nine of the ten volunteers. Volunteers' acceptance of the method was good. Both MR techniques revealed brain temperature reductions after 60 min of intranasal cooling with balloons circulated with saline at 20A degrees C in awake, unsedated volunteers.

  • 85.
    Covaciu, Lucian
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Weis, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för radiologi.
    Bengtsson, Caroline
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Allers, Mats
    Division of thoracic sciences, Department of clinical sciences, Lund University.
    Lunderquist, Anders
    Department of radiology, Lund University.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för radiologi.
    Rubertsson, Sten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Brain temperature in healthy volunteers subjected to intranasal cooling2011Inngår i: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 37, nr 8, s. 1277-1284Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    Purpose:

    Intranasal cooling can be used to initiate therapeutic hypothermia. However, direct measurement of brain temperature is difficult and the intra-cerebral distribution of temperature changes with cooling is unknown. The purpose of this study was to measure the brain temperature of human volunteers subjected to intranasal cooling using non-invasive magnetic resonance (MR) methods.

    Methods:

    Intranasal balloons catheters circulated with saline at 20 °C were applied for 60 min in 10 healthy, unsedated volunteers. Brain temperature changes were measured and mapped using MR spectroscopic imaging (MRSI) and phase-mapping techniques. Heart rate and blood pressure were monitored throughout the experiment. Rectal temperature was measured before and after the cooling. Mini Mental State Examination (MMSE) test and nasal inspection were done before and after the cooling. Questionnaires about the subjects personal experience were filled after the experiment.

    Results:

    Brain temperature decrease measured by MRSI was -1.7 ± 0.8°C and by phase-mapping -1.8 ± 0.9°C at the end of cooling. Spatial distribution of temperature changes was relatively uniform. Rectal temperature decreased by -0.5 ± 0.3°C. The physiological parameters were stable and no shivering was reported. The volunteers remained alert during cooling and no cognitive dysfunctions were apparent at MMSE test. Postcooling nasal examination detected increased nasal secretion in 9 of the 10 volunteers. Volunteer’s acceptance of the method was good.   

    Conclusion:

    Both MR techniques revealed brain temperature reductions after 60 min intranasal cooling with balloons circulated with saline at 20 °C in healthy and unsedated volunteers.

  • 86. Dammeyer, Pascal
    et al.
    Hellberg, Victoria
    Wallin, Inger
    Laurell, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Shoshan, Maria
    Ehrsson, Hans
    Arner, Elias S. J.
    Kirkegaard, Mette
    Cisplatin and oxaliplatin are toxic to cochlear outer hair cells and both target thioredoxin reductase in organ of Corti cultures2014Inngår i: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 134, nr 5, s. 448-454Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Conclusion: Inhibition of thioredoxin reductase (TrxR) may be a contributing factor in cisplatin- induced ototoxicity. Direct exposure of organ of Corti to cisplatin and oxaliplatin gives equal loss of hair cells. Objectives: Platinum- containing drugs are known to target the anti- oxidant selenoprotein TrxR in cancer cells. Two such anti- cancer, platinum- containing drugs, cisplatin and oxaliplatin, have different side effects. Only cisplatin induces hearing loss, i.e. has an ototoxic side effect that is not seen after treatment with oxaliplatin. The objective of this study was to evaluate if TrxR is a target in the cochlea. Loss of outer hair cells was also compared when cisplatin and oxaliplatin were administered directly to the organ of Corti. Methods: Organ of Corti cell culture was used for direct exposure to cisplatin and oxaliplatin. Hair cells were evaluated and the level of TrxR was assessed. Immunohistochemical staining for TrxR was performed. An animal model was used to evaluate the effect on TrxR after treatment with cisplatin and oxaliplatin in vivo. Results: Direct exposure of cochlear organotypic cultures to either cisplatin or oxaliplatin induced comparable levels of outer hair cell loss and inhibition of TrxR, demonstrating that both drugs are similarly ototoxic provided that the cochlea becomes directly exposed.

  • 87.
    Danckwardt-Lillieström, Niklas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Friberg, Ulla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Kinnefors, Anders
    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.
    "Endolymphatic sacitis" in a case of active Menière's disease: an ultrastructural histopathologic investigation1997Inngår i: Annals of Otology, Rhinology and Laryngology, ISSN 0003-4894, E-ISSN 1943-572X, Vol. 106, nr 3, s. 190-198Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    An ultrastructural analysis of an entire intraosseous endolymphatic sac (ES) from a patient with active, well-documented Menière's disease was performed for the first time. The results were compared with those obtained from ES biopsy material from patients with acoustic neuromas. The ES was small in size and showed signs of focal inflammation with intraepithelial invasion by mononuclear cells. At these places the normal fine structure, including the vascular anatomy, was altered. The possible relationship between these changes and Meniere's disease is discussed.

  • 88.
    Danckwardt-Lillieström, Niklas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Friberg, Ulla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Kinnefors, Anders
    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.
    Steriocilia-like structures in the endolymphatic sac in Ménière's disease and acoustic neuroma1998Inngår i: Journal for Oto-Rhino-Laryngology, ISSN 0301-1569, E-ISSN 1423-0275, Vol. 60, nr 4, s. 190-197Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The vestibular aqueduct was surgically removed in 3 patients undergoing labyrinthectomy due to severe Ménière's disease (MD). Stereocilia-like structures were found in the luminal contents of the endolymphatic sac (ES) in all of these patients. The ES from 18 patients with acoustic neuroma were used as controls. In 1 of these, numerous stereocilia-like structures were found in the ES and in 3 additional patients, a few isolated cilia-like structures were disclosed. The findings may suggest an ongoing hair cell degeneration in the inner ear that is more advanced in patients with MD. The data also suggest that the endolymphatic duct is patent and that a longitudinal flow of endolymph also occurs in patients with MD.

  • 89.
    Danckwardt-Lillieström, Niklas
    et al.
    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.
    Friberg, Ulla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Kinnefors, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Ultrastructure of the endolymphatic sac in three patients with Meniere's disease. A preliminary report. 16th Danavox Symposium on Meniere's disease.Kolding, Denmark1995Inngår i: Ménière's disease: Proceedings of the 16th Danavox Symposium, September 19-22, 1995, Scanticon, Kolding, Denmark / [ed] Søren Vesterhauge, Morten Katholm & Pernille Mikines, 1995Konferansepaper (Annet vitenskapelig)
  • 90.
    Di Stazio, Mariateresa
    et al.
    Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy.
    Collesi, Chiara
    Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy;Int Ctr Genet Engn & Biotechnol ICGEB, Mol Med Lab, I-34149 Trieste, Italy.
    Vozzi, Diego
    IRCCS Burlo Garofolo, Med Genet, Trieste, Italy;Qatar Fdn, Sidra Med & Res Ctr, Div Expt Genet, POB 26999, Doha, Qatar.
    Liu, Wei
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Myers, Mike
    Int Ctr Genet Engn & Biotechnol ICGEB, Mol Med Lab, I-34149 Trieste, Italy.
    Morgan, Anna
    Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy.
    D' Adamo, Pio Adamo
    Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy.
    Girotto, Giorgia
    Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy.
    Rubinato, Elisa
    Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy.
    Giacca, Mauro
    Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy;Int Ctr Genet Engn & Biotechnol ICGEB, Mol Med Lab, I-34149 Trieste, Italy.
    Gasparini, Paolo
    Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy.
    TBL1Y: a new gene involved in syndromic hearing loss2019Inngår i: European Journal of Human Genetics, ISSN 1018-4813, E-ISSN 1476-5438, Vol. 27, nr 3, s. 466-474Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Hereditary hearing loss (HHL) is an extremely heterogeneous disorder with autosomal dominant, recessive, and X-linked forms. Here, we described an Italian pedigree affected by HHL but also prostate hyperplasia and increased ratio of the free/ total PSA levels, with the unusual and extremely rare Y-linked pattern of inheritance. Using exome sequencing we found a missense variant (r.206A>T leading to p.Asp69Val) in the TBL1Y gene. TBL1Y is homologous of TBL1X, whose partial deletion has described to be involved in X-linked hearing loss. Here, we demonstrate that it has a restricted expression in adult human cochlea and prostate and the variant identified induces a lower protein stability caused by misfolded mutated protein that impairs its cellular function. These findings indicate that TBL1Y could be considered a novel candidate for HHL.

  • 91. E, Pajediene
    et al.
    I, Bileviciute-Ljungar
    Friberg, Danielle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Sleep patterns among patients with chronic fatigue: A polysomnography-based study.2018Inngår i: The clinical respiratory journal, Vol. 12, nr 4Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives

    The purpose of this study was to detect treatable sleep disorders among patients complaining of chronic fatigue by using sleep questionnaires and polysomnography.

    Methods

    Patients were referred to hospital for investigations and rehabilitation because of a suspected diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The criteria for further referral to full‐night polysomnography (PSG) were symptoms of excessive daytime sleepiness and/or tiredness in the questionnaires.

    Results

    Of a total of 381 patients, 78 (20.5%) patients underwent PSG: 66 women and 12 men, mean age 48.6 years, standard deviation ±9.9 years. On the basis of the PSG, 31 (40.3%) patients were diagnosed with obstructive sleep apnoea, 7 (8.9%) patients with periodic limb movement disorder, 32 (41.0%) patients with restless legs syndrome and 54 (69.3%) patients had one or more other sleep disorder. All patients were grouped into those who fulfilled the diagnostic criteria for ME/CFS (n = 55, 70.5%) and those who did not (n = 23, 29.5%). The latter group had significantly higher respiratory (P = .01) and total arousal (P = .009) indexes and a higher oxygen desaturation index (P = .009).

    Conclusions

    More than half of these chronic fatigue patients, who also have excessive daytime sleepiness and/or tiredness, were diagnosed with sleep disorders such as obstructive sleep apnoea, periodic limb movement disorder and/or restless legs syndrome. Patients with such complaints should undergo polysomnography, fill in questionnaires and be offered treatment for sleep disorders before the diagnose ME/CFS is set.

  • 92. Eckhard, A
    et al.
    Dos Santos, A
    Liu, Wei
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Bassiouni, M
    Arnold, H
    Gleiser, C
    Hirt, B
    Harteneck, C
    Müller, M
    Rask-Andersen, Helge
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Löwenheim, H
    Regulation of the perilymphatic-endolymphatic water shunt in the cochlea by membrane translocation of aquaporin-52015Inngår i: Pflügers Archiv: European Journal of Physiology, ISSN 0031-6768, E-ISSN 1432-2013, Vol. 467, nr 12, s. 2571-2588Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Volume homeostasis of the cochlear endolymph depends on radial and longitudinal endolymph movements (LEMs). LEMs measured in vivo have been exclusively recognized under physiologically challenging conditions, such as experimentally induced alterations of perilymph osmolarity or endolymph volume. The regulatory mechanisms that adjust LEMs to the physiological requirements of endolymph volume homeostasis remain unknown. Here, we describe the formation of an aquaporin (AQP)-based "water shunt" during the postnatal development of the mouse cochlea and its regulation by different triggers. The final complementary expression pattern of AQP5 (apical membrane) and AQP4 (basolateral membrane) in outer sulcus cells (OSCs) of the cochlear apex is acquired at the onset of hearing function (postnatal day (p)8-p12). In vitro, hyperosmolar perfusion of the perilymphatic fluid spaces or the administration of the muscarinic agonist pilocarpine in cochlear explants (p14) induced the translocation of AQP5 channel proteins into the apical membranes of OSCs. AQP5 membrane translocation was blocked by the muscarinic antagonist atropine. The muscarinic M3 acetylcholine (ACh) receptor (M3R) was identified in murine OSCs via mRNA expression, immunolabeling, and in vitro binding studies using an M3R-specific fluorescent ligand. Finally, the water shunt elements AQP4, AQP5, and M3R were also demonstrated in OSCs of the human cochlea. The regulation of the AQP4/AQP5 water shunt in OSCs of the cochlear apex provides a molecular basis for regulated endolymphatic volume homeostasis. Moreover, its dysregulation or disruption may have pathophysiologic implications for clinical conditions related to endolymphatic hydrops, such as Ménière's disease.

  • 93. Eckhard, A
    et al.
    Müller, M
    Salt, A
    Smolders, J
    Rask-Andersen, Helge
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Löwenheim, H
    Water permeability of the mammalian cochlea: functional features of an aquaporin-facilitated water shunt at the perilymph-endolymph barrier2014Inngår i: Pflügers Archiv: European Journal of Physiology, ISSN 0031-6768, E-ISSN 1432-2013, Vol. 466, nr 10, s. 1963-1985Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The cochlear duct epithelium (CDE) constitutes a tight barrier that effectively separates the inner ear fluids, endolymph and perilymph, thereby maintaining distinct ionic and osmotic gradients that are essential for auditory function. However, in vivo experiments have demonstrated that the CDE allows for rapid water exchange between fluid compartments. The molecular mechanism governing water permeation across the CDE remains elusive. We computationally determined the diffusional (P D) and osmotic (P f) water permeability coefficients for the mammalian CDE based on in silico simulations of cochlear water dynamics integrating previously derived in vivo experimental data on fluid flow with expression sites of molecular water channels (aquaporins, AQPs). The P D of the entire CDE (P D = 8.18 × 10(-5) cm s(-1)) and its individual partitions including Reissner's membrane (P D = 12.06 × 10(-5) cm s(-1)) and the organ of Corti (P D = 10.2 × 10(-5) cm s(-1)) were similar to other epithelia with AQP-facilitated water permeation. The P f of the CDE (P f = 6.15 × 10(-4) cm s(-1)) was also in the range of other epithelia while an exceptionally high P f was determined for an epithelial subdomain of outer sulcus cells in the cochlear apex co-expressing AQP4 and AQP5 (OSCs; P f = 156.90 × 10(-3) cm s(-1)). The P f/P D ratios of the CDE (P f/P D = 7.52) and OSCs (P f/P D = 242.02) indicate an aqueous pore-facilitated water exchange and reveal a high-transfer region or "water shunt" in the cochlear apex. This "water shunt" explains experimentally determined phenomena of endolymphatic longitudinal flow towards the cochlear apex. The water permeability coefficients of the CDE emphasise the physiological and pathophysiological relevance of water dynamics in the cochlea in particular for endolymphatic hydrops and Ménière's disease.

  • 94. Eckhard, Andreas
    et al.
    Gleiser, Corinna
    Arnold, Heinz
    Rask-Andersen, Helge
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Kumagami, Hidetaka
    Müller, Marcus
    Hirt, Bernhard
    Löwenheim, Hubert
    Water channel proteins in the inner ear and their link to hearing impairment and deafness2012Inngår i: Molecular Aspects of Medicine, ISSN 0098-2997, E-ISSN 1872-9452, Vol. 33, nr 5-6, s. 612-637Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The inner ear is a fluid-filled sensory organ that transforms mechanical stimuli into the senses of hearing and balance. These neurosensory functions depend on the strict regulation of the volume of the two major extracellular fluid domains of the inner ear, the perilymph and the endolymph. Water channel proteins, or aquaporins (AQPs), are molecular candidates for the precise regulation of perilymph and endolymph volume. Eight AQP subtypes have been identified in the membranous labyrinth of the inner ear. Similar AQP subtypes are also expressed in the kidney, where they function in whole-body water regulation. In the inner ear, AQP subtypes are ubiquitously expressed in distinct cell types, suggesting that AQPs have an important physiological role in the volume regulation of perilymph and endolymph. Furthermore, disturbed AQP function may have pathophysiological relevance and may turn AQPs into therapeutic targets for the treatment of inner ear diseases. In this review, we present the currently available knowledge regarding the expression and function of AQPs in the inner ear. We give special consideration to AQP subtypes AQP2, AQP4 and AQP5, which have been studied most extensively. The potential functions of AQP2 and AQP5 in the resorption and secretion of endolymph and of AQP4 in the equilibration of cell volume are described. The pathophysiological implications of these AQP subtypes for inner ear diseases, that appear to involve impaired fluid regulation, such as Menière's disease and Sjögren's syndrome, are discussed.

  • 95. Eckhard, Andreas
    et al.
    Gleiser, Corinna
    Rask-Andersen, Helge
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Arnold, Heinz
    Liu, Wei
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Mack, Andreas
    Müller, Marcus
    Löwenheim, Hubert
    Hirt, Bernhard
    Co-localisation of Kir4.1 and AQP4 in rat and human cochleae reveals a gap in water channel expression at the transduction sites of endocochlear K+ recycling routes2012Inngår i: Cell and Tissue Research, ISSN 0302-766X, E-ISSN 1432-0878, Vol. 350, nr 1, s. 27-43Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Sensory transduction in the cochlea depends on perilymphatic-endolymphatic potassium (K+) recycling. It has been suggested that the epithelial supporting cells (SCs) of the cochlear duct may form the intracellular K+ recycling pathway. Thus, they must be endowed with molecular mechanisms that facilitate K+ uptake and release, along with concomitant osmotically driven water movements. As yet, no molecules have been described that would allow for volume-equilibrated transepithelial K+ fluxes across the SCs. This study describes the subcellular co-localisation of the Kir4.1 K+ channel (Kir4.1) and the aquaporin-4 water channel (AQP4) in SCs, on the basis of immunohistochemical double-labelling experiments in rat and human cochleae. The results of this study reveal the expression of Kir4.1 in the basal or basolateral membranes of the SCs in the sensory domain of the organ of Corti that are adjacent to hair cells and in the non-sensory domains of the inner and outer sulci that abut large extracellular fluid spaces. The SCs of the inner sulcus (interdental cells, inner sulcus cells) and the outer sulcus (Hensen’s cells, outer sulcus cells) display the co-localisation of Kir4.1 and AQP4 expression. However, the SCs in the sensory domain of the organ of Corti reveal a gap in the expression of AQP4. The outer pillar cell is devoid of both Kir4.1 and AQP4. The subcellular co-localisation of Kir4.1 and AQP4 in the SCs of the cochlea described in this study resembles that of the astroglia of the central nervous system and the glial Mueller cells in the retina.

  • 96.
    Edfeldt, Lennart
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Middle Ear Cholesteatoma: Surgical Treatment, Follow-up and Hearing Restoration2013Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Although middle-ear cholesteatoma is a major topic in otological research, its etiology and pathogenesis remain unclear. Pediatric cholesteatoma is considered more aggressive than adult cholesteatoma, as it has a higher rate of growth, is more often infected and exhibits wider extension. Higher incidence of residual and recurrent disease after surgical treatment of pediatric cholesteatoma has been observed in most studies. In this study, the results are presented from a canal wall down (CWD) obliteration technique used in 330 adult patients (Paper I) with cholesteatoma, evaluated at 1, 3 and 6 years following surgery. Additionally, results are offered from 57 pediatric patients (Paper II) using identical surgical technique and compared with adults. The surgical and hearing outcomes in both groups showed a low incidence of residual and recurrent disease and a high rate of ear water resistance without infection. The results were unrelated to the severity and extension of disease, as well as to age and previous surgery. No differences were found in outcomes between adult and pediatric cholesteatoma patients.

    The thesis also describes the use of diffusion-weighted magnetic resonance imaging (DW-MRI) (Paper III) in follow-up examinations of adult cholesteatoma patients undergoing surgical treatment. Non-echo planar diffusion-weighted imaging (Non-EPI DW-MRI)increased the accuracy of clinical examinations. It is concluded that the use of non-EPI DW-MRI should be mandatory in clinical follow-ups after cholesteatoma surgery. In Paper IV a relatively new mode of hearing rehabilitation was investigated, with an active middle ear implant (AMEI), in patients with chronically disabled ears. Functional hearing results were compared with the previous use of conventional hearing aids before and after AMEI implantation. Moreover, the consequences of positioning of the implant in the middle ear were evaluated using cone beam computed tomography (CBCT), a modification of conventional computed tomography. The hearing results, assessed with AMEI, were found to be less dependent on the precise positioning of the floating mass transducer(FMT) against the round window membrane (RWM) than was anticipated. Further, the hearing results were noted to be comparable with those with conventional hearing aids and even superior at high frequencies.

     

     

    Delarbeid
    1. Surgical treatment of adult cholesteatoma: long-term follow-up using total reconstruction procedure without staging
    Åpne denne publikasjonen i ny fane eller vindu >>Surgical treatment of adult cholesteatoma: long-term follow-up using total reconstruction procedure without staging
    2013 (engelsk)Inngår i: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 133, nr 1, s. 28-34Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Conclusions:

    A total of 330 cases of adult cholesteatoma were operated with canal-wall down (CWD) and total reconstruction procedure (TRP) without staging. Independent of preoperative middle ear conditions, cholesteatoma extent and localization, long-term improvement of hearing with a low incidence of residual and recurrent disease were achieved.

    Objectives:

    To evaluate long-term surgical and hearing results using a well-defined surgical technique without staging in adult cholesteatoma.

    Methods:

    The same CWD surgical technique, including obliteration of the mastoid cavity, reconstruction of the canal wall, and ossiculoplasty with autologous bone, was used by three senior surgeons (1982-2004). Preoperative and postoperative pure tone average (PTA) for air conduction (AC), bone conduction (BC), and air-bone gap (ABG) were assessed and compared 1, 3, and 6 years after surgery. Various prognostic factors with potential influence on long-term hearing outcome were evaluated.

    Results:

    Recurrence of AC occurred in 10%, residual disease in 3%. Six years after surgery all patients except one had a dry ear and over 92% of all cases were water resistant. Three patients developed complete deafness. Long-lasting improvement and/or preservation of hearing, with maintenance of PTA-ABG closure in 68% of all cases within 20 dB, were obtained. Sixty-four (19%) ossicular revisions were performed.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-188875 (URN)10.3109/00016489.2012.707333 (DOI)000312525800004 ()23113656 (PubMedID)
    Tilgjengelig fra: 2012-12-20 Laget: 2012-12-20 Sist oppdatert: 2017-12-06bibliografisk kontrollert
    2. Surgical treatment of paediatric cholesteatoma: Long-term follow up in comparison with adults
    Åpne denne publikasjonen i ny fane eller vindu >>Surgical treatment of paediatric cholesteatoma: Long-term follow up in comparison with adults
    Vise andre…
    2012 (engelsk)Inngår i: International Journal of Pediatric Otorhinolaryngology, ISSN 0165-5876, E-ISSN 1872-8464, Vol. 76, nr 8, s. 1091-1097Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Objective: This study was designed to analyse long-term results after surgery of acquired (ACH) and congenital cholesteatoma (CCH) of the middle ear in children and compare these with adults.

    Methods: Computer-based analysis of consecutively operated paediatric patients for ACH and CCH in a tertiary referral centre was made in 57 cases under the age of 12 operated 1983-2004 by three surgeons using identical technique. A canal wall down and total reconstruction procedure (TRP) with obliteration of the mastoid cavity, canal wall reconstruction, ossiculoplasty with consistent use of autologous bone and an "aeration enhancement procedure" (AEP) with silicon sheet in selected cases were used. Pre- and post-operative PTA (0.5-3 kHz) and pure-tone average air-bone gap (PTA-ABG) together with surgical parameters were assessed 1, 3 and 6 years following surgery.

    Results: Results showed stable hearing over 6 years with low incidence of persistent and recurrent disease comparable with results from adult patients. In nearly half of the cases, silastic sheeting was used. In 21 cases, stapes was eroded. Bone conduction thresholds levels remained unaffected 6 years after surgery. No deaf ears, postoperative facial dysfunction or other lesions related to surgery were observed. Six years after surgery every evaluated ear was found to be water-resistant and infection-free.

    Conclusion: Our results suggest that one-stage eradication of ACH and CCH in children using total reconstruction procedure (TRP) provide long-term improvement or preservation of hearing, with a low incidence of persistent or recurrent disease. No difference in surgical outcome between children and adults was found.

    Emneord
    Cholesteatoma surgery, Children, Silastic sheeting, Hearing results, Surgical results, Staging, Long-time follow-up
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-179557 (URN)10.1016/j.ijporl.2012.04.006 (DOI)000306449300005 ()
    Tilgjengelig fra: 2012-08-20 Laget: 2012-08-20 Sist oppdatert: 2017-12-07bibliografisk kontrollert
    3. Non-echo planar diffusion-weighted MRI increases follow-up accuracy after one-step step canal wall-down obliteration surgery for cholesteatoma
    Åpne denne publikasjonen i ny fane eller vindu >>Non-echo planar diffusion-weighted MRI increases follow-up accuracy after one-step step canal wall-down obliteration surgery for cholesteatoma
    Vise andre…
    2013 (engelsk)Inngår i: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 133, nr 6, s. 574-583Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Conclusion:

    Non-echo planar (non-EPI) diffusion-weighted (DW) magnetic resonance imaging (MRI) increases the number of detected cholesteatoma after one-step canal-wall down (CWD) obliteration surgery for cholesteatoma compared with clinical evaluation alone.

    Objective:

    To evaluate the use of DW-MRI for detection of cholesteatoma after surgical treatment using CWD obliteration technique.

    Methods:

    Thirty-eight adult patients (41 ears) treated with identical one-step canal-wall down obliteration surgical technique were included in a prospective and blinded study. All patients were investigated with non-EPI and EPI DW-MRI 1-9 months after the clinical examination. Follow-up time after primary surgery varied between 10 and 234 months. DW-MRI were assessed by two neuroradiologists and compared with clinical results. Inter-rater agreement was calculated. Positive non-EPI DW-MRI cases underwent revision surgery within 18-159 days after imaging.

    Results:

    Out of 41 cases seven were evaluated as positive for cholesteatoma on non-EPI DW-MRI. Since one patient refused surgery six of these seven cases underwent surgical revision and all were verified. There was agreement between clinical and non-EPI findings in five of eight cases. EPI findings correlated poorly with non-EPI and clinical findings. Inter-rater agreement (Cohen´s kappa) was 0.91 for non-EPIDW-MRI (p<0.001) and -0.062 for EPI DW-MRI (p=0.43)

     

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-198119 (URN)10.3109/00016489.2012.762118 (DOI)000319011800003 ()23675808 (PubMedID)
    Tilgjengelig fra: 2013-04-09 Laget: 2013-04-09 Sist oppdatert: 2017-12-06bibliografisk kontrollert
    4. Round window vibroplasty in chronic ear surgery: Comparison with conventional hearing rehabilitation
    Åpne denne publikasjonen i ny fane eller vindu >>Round window vibroplasty in chronic ear surgery: Comparison with conventional hearing rehabilitation
    2013 (engelsk)Inngår i: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 138, nr 8, s. 814-825Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Conclusion:

    Functional hearing results with round window vibroplasty in chronically disabled middle ears were comparable and, at high frequencies, superior to the results achieved with previously used conventional hearing aids even after extended surgery. Soft tissue transfer appears to be more important than floating mass transducer (FMT) alignment with the round window membrane (RWM) for efficient coupling or sonoinversion.

    Objectives:

    To evaluate the functional hearing results of an active middle ear implant (AMEI) to the round window niche (RWN). The results were compared with previously used conventional hearing aids. The position of the FMT was determined by cone-beam computed tomography (CBCT).

    Study design:

    Prospective cohort study

    Setting:

    Tertiary referral center

    Material and Methods:

    Seven patients with severe middle ear disease were implanted with an AMEI with round window application. The postoperative hearing outcome was compared with preoperative hearing using unaided and conventionally aided conditions. The results were correlated with the physical/geometric relation of the FMT to the RWM as determined with CBCT.

    Results:

    Dislocation of the FMT was not observed. One patient was re-implanted due to accidental damage to the electrode. In all patients, the pertinent functional hearing results were achieved and were comparable to previous rehabilitation results.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-198120 (URN)10.3109/00016489.2013.780294 (DOI)000321791700004 ()
    Tilgjengelig fra: 2013-04-09 Laget: 2013-04-09 Sist oppdatert: 2017-12-06bibliografisk kontrollert
  • 97.
    Edfeldt, Lennart
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Kinnefors, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Strömbäck, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Köbler, Susanne
    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.
    Surgical treatment of paediatric cholesteatoma: Long-term follow up in comparison with adults2012Inngår i: International Journal of Pediatric Otorhinolaryngology, ISSN 0165-5876, E-ISSN 1872-8464, Vol. 76, nr 8, s. 1091-1097Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: This study was designed to analyse long-term results after surgery of acquired (ACH) and congenital cholesteatoma (CCH) of the middle ear in children and compare these with adults.

    Methods: Computer-based analysis of consecutively operated paediatric patients for ACH and CCH in a tertiary referral centre was made in 57 cases under the age of 12 operated 1983-2004 by three surgeons using identical technique. A canal wall down and total reconstruction procedure (TRP) with obliteration of the mastoid cavity, canal wall reconstruction, ossiculoplasty with consistent use of autologous bone and an "aeration enhancement procedure" (AEP) with silicon sheet in selected cases were used. Pre- and post-operative PTA (0.5-3 kHz) and pure-tone average air-bone gap (PTA-ABG) together with surgical parameters were assessed 1, 3 and 6 years following surgery.

    Results: Results showed stable hearing over 6 years with low incidence of persistent and recurrent disease comparable with results from adult patients. In nearly half of the cases, silastic sheeting was used. In 21 cases, stapes was eroded. Bone conduction thresholds levels remained unaffected 6 years after surgery. No deaf ears, postoperative facial dysfunction or other lesions related to surgery were observed. Six years after surgery every evaluated ear was found to be water-resistant and infection-free.

    Conclusion: Our results suggest that one-stage eradication of ACH and CCH in children using total reconstruction procedure (TRP) provide long-term improvement or preservation of hearing, with a low incidence of persistent or recurrent disease. No difference in surgical outcome between children and adults was found.

  • 98.
    Edfeldt, Lennart
    et al.
    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.
    Round window vibroplasty in chronic ear surgery: Comparison with conventional hearing rehabilitation2013Inngår i: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 138, nr 8, s. 814-825Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Conclusion:

    Functional hearing results with round window vibroplasty in chronically disabled middle ears were comparable and, at high frequencies, superior to the results achieved with previously used conventional hearing aids even after extended surgery. Soft tissue transfer appears to be more important than floating mass transducer (FMT) alignment with the round window membrane (RWM) for efficient coupling or sonoinversion.

    Objectives:

    To evaluate the functional hearing results of an active middle ear implant (AMEI) to the round window niche (RWN). The results were compared with previously used conventional hearing aids. The position of the FMT was determined by cone-beam computed tomography (CBCT).

    Study design:

    Prospective cohort study

    Setting:

    Tertiary referral center

    Material and Methods:

    Seven patients with severe middle ear disease were implanted with an AMEI with round window application. The postoperative hearing outcome was compared with preoperative hearing using unaided and conventionally aided conditions. The results were correlated with the physical/geometric relation of the FMT to the RWM as determined with CBCT.

    Results:

    Dislocation of the FMT was not observed. One patient was re-implanted due to accidental damage to the electrode. In all patients, the pertinent functional hearing results were achieved and were comparable to previous rehabilitation results.

  • 99.
    Edfeldt, Lennart
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Strömback, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Grendin, Joakim
    Bunne, Marie
    Harder, Henrik
    Peebo, Markus
    Eeg-Olofsson, Mans
    Petersson, Carl-Magnus
    Konradsson, Konrad
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Evaluation of cost-utility in middle ear implantation in the 'Nordic School': a multicenter study in Sweden and Norway2014Inngår i: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 134, nr 1, s. 19-25Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Conclusion: Hearing restoration using an active middle ear implant (AMEI) is a highly cost-effective treatment for a selected group of patients with no other possibilities for auditory rehabilitation. Objectives: To evaluate the cost-utility of using an AMEI for hearing rehabilitation. Methods: This was a prospective, multicenter, single-subject repeated study in six tertiary referral centers. Twenty-four patients with sensorineural (SNHL), conductive (CHL), and mixed hearing loss (MHL) were implanted with the AMEI Vibrant Soundbridge (R) (VSB) for medical reasons. All patients were previously rehabilitated with conventional hearing aids. Multiple validated quality of life patient questionnaires, Health Utilities Index (HUI 2 and 3), and Glasgow Hearing Aid Benefit Profile (GHABP) were used to determine the utility gain and quality adjusted life years (QALY). Directly related treatment costs for the implantation were calculated and related to utility gain and QALY. Results: The cost/QALY for patients with SNHL was estimated at (sic)7260/QALY, and for patients with C/MHL at (sic)12 503/QALY.

  • 100.
    Edfeldt, Lennart
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Strömbäck, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Surgical treatment of congenital aural atresia - is it still justified?2015Inngår i: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 135, nr 3, s. 226-232Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Conclusion: Surgery candidacy based on the surgical accessibility of the middle ear seems more valuable than the use of a preoperative grading system. Also patients with severe malformations can benefit from surgical reconstruction. Objective: To evaluate the long-term results of the primary surgical treatment of patients with congenital auricular atresia (CAA). Methods: One hundred patients with CAA underwent surgical reconstruction between 1985 and 2010. The mean follow-up time was 40 months. All patients were retrospectively scored using the Jahrsdoerfer grading scale and divided into two groups according to the grade of their malformation. Group 1 included 20 patients with scores of 4-6 and group 2 included 80 patients with scores of 7-10. Pre- and postoperative air conduction (AC), bone conduction (BC), pure-tone average 'air-bone gap' (PTA(4)-ABG), surgical findings, postoperative complications, and revision surgeries performed were determined and compared between the two groups. Results: For 90% of the patients in group 1 and 79% of the patients in group 2, the postoperative ABG was within 0 and 30 dB. The most common complications were recurrent infection, lateralization of the tympanic membrane, and restenosis of the ear canal.

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