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  • 201.
    Sgaramella, Nicola
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences. Naples, Italy.
    Coates, P. J.
    Dundee, U.K..
    Strindlund, K.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Loljung, Lotta
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Colella, G.
    Naples, Italy.
    Laurell, G.
    Uppsala, Sweden.
    Rossiello, R.
    Naples, Italy.
    Muzio, L. L.
    Foggia, Italy.
    Loizou, Christos
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Tartaro, G.
    Naples, Italy.
    Olofsson, Katarina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Danielsson, Karin
    Umeå University, Faculty of Medicine, Department of Odontology.
    Fåhraeus, R.
    Brno, Czech Republic; Paris, France.
    Nylander, Karin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Expression of p16 in squamous cell carcinoma of the mobile tongue is independent of HPV infection despite presence of the HPV-receptor syndecan-12015In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 113, no 2, p. 321-326Article in journal (Refereed)
    Abstract [en]

    Background: Tongue squamous cell carcinoma (TSCC) is increasing in incidence, especially among young patients and preferably females. Infection with human papilloma virus (HPV) has been suggested as a cause of SCC in the head and neck, and the proportion of oropharyngeal cancers caused by HPV has steadily increased. Methods: Samples from 109 patients with primary TSCC were analysed for the presence of HPV16 by in situ hybridisation and for expression of its surrogate marker p16 and the HPV receptor syndecan-1 by immunhistochemistry. Results: No evidence of HPV16 DNA was observed in the tumours, although one-third showed p16 staining. There was no difference in the expression of the primary HPV receptor, syndecan-1, between TSCC and a group of tonsil SCC. Conclusion: Whereas p16 is expressed in some TSCCs, HPV16 is undetectable, therefore, p16 cannot be used as a surrogate marker for high-risk HPV-infection in this tumour. Despite presence of the HPV-receptor syndecan-1 in TSCC, HPV prefers the tonsillar environment. Lack of p16 associates with worse prognosis primarily in patients aged <= 40 years with tongue SCC. The improved prognosis seen in p16-positive TSCC can be due to induction of a senescent phenotype or an inherent radiosensitivity due to the ability of p16 to inhibit homologous recombination repair.

  • 202.
    Sgaramella, Nicola
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Department of Medical, Surgical and Dental Specialties, Second University of Naples, Multidisciplinary Naples, Italy; Department of Neuroscience Reproductive and Dentistry Sciences, University of Naples Federico II, Naples, Italy.
    Gu, Xiaolian
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Boldrup, Linda
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Coates, Philip J.
    Fåhraeus, Robin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. RECAMO, Masaryk Memorial Cancer Institute, Brno, Czech Republic; University Paris Diderot, INSERM UMRS1162, Paris, France.
    Califano, Luigi
    Tartaro, Gianpaolo
    Colella, Giuseppe
    Norberg-Spaak, Lena
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Strom, Adrian
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Wilms, Torben
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Lo Muzio, Lorenzo
    Orabona, Giovanni Dell'Aversana
    Santagata, Mario
    Loljung, Lotta
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Rossiello, Riccardo
    Danielsson, Karin
    Umeå University, Faculty of Medicine, Department of Odontology.
    Strindlund, Klas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Lillqvist, Sandra
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Nylander, Karin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Searching for new targets and treatments in the battle against squamous cell carcinoma of the head and neck, with specific focus on tumours of the tongue2018In: Current Topics in Medicinal Chemistry, ISSN 1568-0266, E-ISSN 1873-4294, Vol. 18, no 3, p. 214-218Article, review/survey (Refereed)
    Abstract [en]

    Squamous cell carcinoma of the head and neck, SCCHN, is a heterogeneous group of tumours not only concerning the site of origin but also regarding aetiology. The 5-year survival for the whole group of SCCHN tumours has not significantly improved over the last 20-25 years. Apart from tumour spread to lymph nodes, N status, gains and losses of specific chromosomes are the only factors shown to be independent prognostic markers for these tumours. Worldwide, an increasing number of people ≤ 40 years are seen being affected by tongue SCC, the most common tumour within the SCCHN group. Even without any clinical signs of metastasis, up to 30% of all tongue SCC have histologically detectable spread to lymph nodes. In this mini review, field cancerization, tumour microenvironment, the so called EMT (epithelial mesenchymal transition) process and the role of viruses in development of SCCHN are discussed as well as potential new therapeutic targets. For the group of tongue SCC, with the increasing incidence seen in young patients and particularly women, new data with impact on prognosis and treatment are urgently needed. But as long as data from the analyses of several sub sites are presented as valid for the whole group of tumours, this vital point is missed.

  • 203.
    Sgaramella, Nicola
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Second University of Naples, Multidisciplinary Department of Medical, Surgical and Dental Specialties, Naples, Italy; Department of Neuroscience Reproductive and Dentistry Sciences, University of Naples Federico II, Naples, Italy.
    Lindell Jonsson, Eva
    Uppsala university.
    Boldrup, Linda
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Califano, Luigi
    University of Naples, Italy.
    Coates, Philip J
    University of Dundee, UK.
    Tartaro, Gianpaolo
    Second University of Naples, Italy.
    Lo Muzio, Lorenzo
    University of Foggia, Italy.
    Fåhraeus, Robin
    University Paris Diderot, INSERM UMRS1162, Paris, France; RECAMO, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
    Colella, Giuseppe
    Second University of Naples, Italy.
    Dell'Aversana Orabona, Giovanni
    University of Naples, Italy.
    Loljung, Lotta
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Santagata, Mario
    Second University of Naples, Italy.
    Rossiello, Riccardo
    Seconda Universita’ Degli Studi di Napoli, Italy.
    Wilms, Torben
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Danielsson, Karin
    Umeå University, Faculty of Medicine, Department of Odontology.
    Laurell, Göran
    Nylander, Karin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    High expression of podoplanin in squamous cell carcinoma of the tongue occurs predominantly in patients ≤ 40 years but does not correlate with tumour spread2016In: The Journal of Pathology: Clinical Research, ISSN 2056-4538, Vol. 2, no 1, p. 3-8Article in journal (Refereed)
    Abstract [en]

    More than 30% of patients with squamous cell carcinoma (SCC) of the mobile tongue have clinically undetectable lymph node metastasis. Tumour cells can spread as single cells or collectively. A protein known to play a role in both processes is podoplanin, which is expressed in endothelial cells not only in lymph vessels but also in some aggressive tumours with high invasive and metastatic potential. Here we studied samples from 129 patients with primary SCC of the tongue for expression of podoplanin using immunohistochemistry. mRNA levels were analysed in another 27 cases of tongue SCC with adjacent clinically tumour-free tongue tissue and 14 tongue samples from healthy donors. Higher levels of podoplanin were seen in tumours compared to both normal tongue and clinically normal tongue in the tumour vicinity. No association was found between levels of podoplanin, presence of lymph node metastases or other clinical factors. Patients aged 40 or less were more likely to express high levels of podoplanin protein compared to older patients (p 50.027). We conclude that levels of podoplanin in primary tongue SCCs are not associated with lymph node metastases. However, tongue SCCs arising in young patients (40 years of age) are more likely to express high levels of podoplanin than tongue SCCs that arise in the more elderly. The data suggest that podoplanin has a distinctive role in young patients, who are known to have a poor prognosis: these patients may, therefore, benefit from podoplanin inhibitory therapies.

  • 204.
    Sgaramella, Nicola
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Multidisciplinary Department of Medical, Surgical and Dental Specialties, Second University of Naples; 3 Department of Neuroscience Reproductive and Dentistry Sciences, University of Naples Federico II, I-801 38 Naples, Italy.
    Wilms, Torben
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Boldrup, Linda
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Loljung, Lotta
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Gu, Xiaolian
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Coates, Philip J.
    Hassellöf, Petra
    Califano, Luigi
    Lo Muzio, Lorenzo
    Fåhraeus, Robin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. RECAMO, Masaryk Memorial Cancer Institute, 656 53 Brno, Czech Republic; University Paris Diderot, INSERM UMRS1162, Paris 75010, France.
    Spaak, Lena Norberg
    Franco, Renato
    Tartaro, Gianpaolo
    Colella, Giuseppe
    Santagata, Mario
    Orabona, Giovanni Dell'Aversana
    Chirico, Fabrizio
    Danielsson, Karin
    Umeå University, Faculty of Medicine, Department of Odontology.
    Troiano, Giuseppe
    Ardito, Fatima
    Nylander, Karin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Ethnicity based variation in expression of E-cadherin in patients with squamous cell carcinoma of the oral tongue2018In: Oncology Letters, ISSN 1792-1074, E-ISSN 1792-1082, Vol. 16, no 5, p. 6603-6607Article in journal (Refereed)
    Abstract [en]

    The oral tongue is the most common site for tumours within the oral cavity. Despite intense research, there has been no improvement in the survival rate for patients with oral tongue squamous cell carcinoma (OTSCC) during the last decades. Differences between oral cancer patients based on ethno-geographical distribution have been reported. The present study used immunohistochemistry to evaluate commonly used markers of cancer cell phenotypes, E-cadherin, -catenin and cytokeratins 5 and 19, in 120 patients with OTSCC. To evaluate the impact of ethnicity, patients from Sweden and Italy were included. A higher proportion of Swedish patients exhibited high expression of E-cadherin in their tumours (P=0.039), and high levels of E-cadherin in Swedish OTSCC patients that had succumbed to their disease were associated with poor prognosis. These data demonstrated differences in the pathological characteristics of OTSCC between two different European populations. The findings emphasise the need to take ethnicity/geographical location of patients into account when comparing results from different studies of OTSCC.

  • 205.
    Shah, Farhan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Neuromuscular injuries and pharyngeal dysfunction in snorers and sleep apnea patients: a study on pathological changes in the human soft palate and its relationship with swallowing dysfunction2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Obstructive sleep apnea (OSA) is a prevalent progressive sleep disorder with serious negative health consequences. Although several risk factors such as obesity can make an individual vulnerable to develop OSA, the pathophysiological mechanism for the collapse of the upper airway is unclear. Moreover, the etiology of the commonly occurring swallowing dysfunction in snorers and sleep apnea patients is not understood. In the light of this, we aimed to investigate whether muscle and nerve changes in upper airway contributes to pharyngeal dysfunction in snorers and sleep apnea patients.

    Twenty-two patients (1 female, 21 males, mean age 45 years) undergoing soft palate surgery because of snoring and sleep apnea were included in the study. Ten healthy non-snoring males, mean age 38 years, were recruited as controls. Biopsies from the uvula were obtained from both patients and voluntary controls. Control autopsies from both uvula and palatopharyngeus muscles were taken post mortem from 6 previously healthy adult subjects (3 males, 3 females, mean age 52 years) and two male infants (age 4 months and 1.4 years). Overnight sleep registration and videoradiographic examinations of pharyngeal swallowing function were performed in both patients and voluntary controls.

    Enzyme and immunohistochemistry and morphometric techniques were used to investigate cytoskeletal and membrane proteins desmin and dystrophin and two neurotrophins, brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). The nerve fascicles in the soft palate were explored for changes in axon and Schwann cell density and for signs of axon regeneration. 

    All patients were snores, and 14 patients had OSA with a mean apnea-hypopnea index 24, range 5-84. Sixteen of the 22 patients had swallowing dysfunction. None of the 10 voluntary controls had sleep apnea or swallowing dysfunction. In both controls and patients, a subgroup of muscle fibers in the soft palate lacked immunoreaction for desmin and the C-terminus of dystrophin, and these fibers were more common in patients than in controls (p<0.001). Moreover, muscle fibers with disorganized desmin were commonly observed in patients, but not in controls (p<0.001). Thus, overall, desmin abnormalities were significantly more frequent in patients (46 vs. 15%, p<0.001), and some of these fibers showed upregulation of BDNF. In addition, nerve fascicles from the soft palate of patients displayed lower density of axons (p<0.02) and a smaller area occupied by Schwann cells (p=0.001) compared to controls. The axon density within nerve fascicles as well as the cytoskeletal abnormalities in muscles correlated significantly with swallowing dysfunction (rs=0.50 and 0.76, respectively, p≤0.03).

    To conclude, human soft palate muscles seem to be of a unique allotype. In the soft palate of snorers and sleep apnea patients, cytoskeletal myopathy and neuropathy were frequently observed, and these changes correlate significantly with pharyngeal swallowing dysfunction. The upregulation of BDNF in muscle fibers of patients may relate to a regenerative attempt after injury. Consequently, a disturbed sensorimotor function and muscle weakness may contribute to development and progression of swallowing dysfunction and OSA. Traumatic snoring vibrations and muscle overload are plausible causes of the neuromuscular injuries. 

  • 206.
    Shah, Farhan
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Berggren, Diana
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Holmlund, Thorbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Levring Jäghagen, Eva
    Umeå University, Faculty of Medicine, Department of Odontology.
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Unique expression of cytoskeletal proteins in human soft palate muscles2016In: Journal of Anatomy, ISSN 0021-8782, E-ISSN 1469-7580, Vol. 228, no 3, p. 487-494Article in journal (Refereed)
    Abstract [en]

    The human oropharyngeal muscles have a unique anatomy with diverse and intricate functions. To investigate if this specialization is also reflected in the cytoarchitecture of muscle fibers, intermediate filament proteins and the dystrophin-associated protein complex have been analyzed in two human palate muscles, musculus uvula (UV) and musculus palatopharyngeus (PP), with immunohistochenmical and morphological techniques. Human limb muscles were used as reference. The findings show that the soft palate muscle fibers have a cytoskeletal architecture that differs from the limb muscles. While all limb muscles showed immunoreaction for a panel of antibodies directed against different domains of cytoskeletal proteins desmin and dystrophin, a subpopulation of palate muscle fibers lacked or had a faint immunoreaction for desmin (UV 11.7% and PP 9.8%) and the C-terminal of the dystrophin molecule (UV 4.2% and PP 6.4%). The vast majority of these fibers expressed slow contractile protein myosin heavy chain I. Furthermore, an unusual staining pattern was also observed in these fibers for β-dystroglycan, caveolin-3 and neuronal nitric oxide synthase nNOS, which are all membrane-linking proteins associated with the dystrophin C-terminus. While the immunoreaction for nNOS was generally weak or absent, β-dystroglycan and caveolin-3 showed a stronger immunostaining. The absence or a low expression of cytoskeletal proteins otherwise considered ubiquitous and important for integration and contraction of muscle cells indicate a unique cytoarchitecture designed to meet the intricate demands of the upper airway muscles. It can be concluded that a subgroup of muscle fibers in the human soft palate appears to have special biomechanical properties, and their unique cytoarchitecture must be taken into account while assessing function and pathology in oropharyngeal muscles.

  • 207.
    Shah, Farhan
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Holmlund, Thorbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Jaghagen, Eva Levring
    Umeå University, Faculty of Medicine, Department of Odontology.
    Berggren, Diana
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Franklin, Karl A.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Neurotrophic factor BDNF is upregulated in soft palate muscles of snorers and sleep apnea patients2019In: Laryngoscope Investigative Otolaryngology, ISSN 2378-8038, Vol. 4, no 1, p. 174-180Article in journal (Refereed)
    Abstract [en]

    Objectives: Neuromuscular injuries are suggested to contribute to upper airway collapse and swallowing dysfunction in patients with sleep apnea. Neurotrophins, a family of proteins involved in survival, development, and function of neurons, are reported to be upregulated in limb muscle fibers in response to overload and nerve damage. We aimed to investigate the expression of two important neurotrophins, brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), in muscle fibers of uvula from snorers and sleep apnea patients and to compare these findings with pharyngeal function.

    Methods: Uvula muscle biopsies from 22 patients and 10 controls were analyzed for BDNF, NGF, and cytoskeletal protein desmin using immunohistochemistry. Pharyngeal swallowing function was assessed using videoradiography.

    Results: BDNF, but not NGF, was significantly upregulated in a subpopulation of muscle fibers in snoring and sleep apnea patients. Two major immunoreaction patterns for BDNF were observed; a fine grainy point like BDNF staining was displayed in muscle fibers of both patients and controls (41 +/- 23 vs. 25 +/- 17%, respectively, P = .06), while an abnormal upregulated intense-dotted or disorganized reaction was mainly observed in patients (8 +/- 8 vs. 2 +/- 2%, P = .02). The latter fibers, which often displayed an abnormal immunoreaction for desmin, were more frequent in patients with than without swallowing dysfunction (10 +/- 8 vs. 3 +/- 3%, P = .05).

    Conclusion: BDNF is upregulated in the upper airway muscles of snorers and sleep apnea patients, and especially in patients with swallowing dysfunction. Upregulation of BDNF is suggested to be a response to denervation, reinnervation, and repair of injured muscle fibers. Our findings propose that damaged upper airway muscles might heal following treatment for snoring and sleep apnea.

  • 208.
    Shah, Farhan
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Laboratory of Muscle Biology, IMB, Umeå University.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Holmlund, Thorbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Levring Jäghagen, Eva
    Umeå University, Faculty of Medicine, Department of Odontology.
    Berggren, Diana
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Franklin, Karl A.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Upregulated expression of brain-derived neurotrophic factor in soft palate muscles of snorers and obstructive sleep apnea patientsManuscript (preprint) (Other academic)
  • 209.
    Shah, Farhan
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Franklin, Karl A
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Holmlund, Thorbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Levring Jäghagen, Eva
    Umeå University, Faculty of Medicine, Department of Odontology.
    Berggren, Diana
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Desmin and dystrophin abnormalities in upper airway muscles of snorers and patients with sleep apnea2019In: Respiratory Research, ISSN 1465-993X, Vol. 20, article id 31Article in journal (Refereed)
    Abstract [en]

    The pathophysiology of obstruction and swallowing dysfunction in snores and sleep apnea patients remains unclear. Neuropathy and to some extent myopathy have been suggested as contributing causes. Recently we reported an absence and an abnormal isoform of two cytoskeletal proteins, desmin, and dystrophin, in upper airway muscles of healthy humans. These cytoskeletal proteins are considered vital for muscle function. We aimed to investigate for muscle cytoskeletal abnormalities in upper airways and its association with swallowing dysfunction and severity of sleep apnea. Cytoskeletal proteins desmin and dystrophin were morphologically evaluated in the uvula muscle of 22 patients undergoing soft palate surgery due to snoring and sleep apnea and in 10 healthy controls. The muscles were analysed with immunohistochemical methods, and swallowing function was assessed using videoradiography. Desmin displayed a disorganized pattern in 21 +/- 13% of the muscle fibres in patients, while these fibers were not present in controls. Muscle fibres lacking desmin were present in both patients and controls, but the proportion was higher in patients (25 +/- 12% vs. 14 +/- 7%, p = 0.009). The overall desmin abnormalities were significantly more frequent in patients than in controls (46 +/- 18% vs. 14 +/- 7%, p < 0.001). In patients, the C-terminus of the dystrophin molecule was absent in 19 +/- 18% of the desmin-abnormal muscle fibres. Patients with swallowing dysfunction had 55 +/- 10% desmin-abnormal muscle fibres vs. 22 +/- 6% in patients without swallowing dysfunction, p = 0.002. Cytoskeletal abnormalities in soft palate muscles most likely contribute to pharyngeal dysfunction in snorers and sleep apnea patients. Plausible causes for the presence of these abnormalities is traumatic snoring vibrations, tissue stretch or muscle overload.

  • 210.
    Shah, Farhan
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Laboratory of Muscle Biology, IMB, Umeå University.
    Franklin, Karl
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Holmlund, Thorbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Levring Jäghagen, Eva
    Umeå University, Faculty of Medicine, Department of Odontology.
    Berggren, Diana
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Desmin and dystrophin myopathy in the upper airway of snoring and obstructive sleep apnea patientsManuscript (preprint) (Other academic)
  • 211.
    Shah, Farhan
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Holmlund, Thorbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Levring Jäghagen, Eva
    Umeå University, Faculty of Medicine, Department of Odontology.
    Berggren, Diana
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Franklin, Karl A
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Axon and Schwann Cell Degeneration in Nerves of Upper Airway Relates to Pharyngeal Dysfunction in Snorers and Patients With Sleep Apnea2018In: Chest, ISSN 0012-3692, E-ISSN 1931-3543, Vol. 154, no 5, p. 1091-1098Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The pathophysiologic mechanism of nocturnal obstruction and swallowing dysfunction commonly occurring in patients with sleep apnea is unclear. The goal of this study was to investigate whether nerve injuries in the upper airways of snorers and patients with sleep apnea are associated with pharyngeal dysfunction and severity of sleep apnea.

    METHODS: Twenty-two patients undergoing palatal surgery due to snoring and sleep apnea were investigated for a swallowing dysfunction by using videoradiography. Twelve healthy nonsnoring subjects were included as control subjects. Tissue samples from the soft palate at the base of the uvula were obtained in all patients and control subjects. Nerves and muscle were analyzed with immunohistochemical and morphologic methods, and the findings were correlated with swallowing function and degree of sleep apnea.

    RESULTS: In the soft palate of patients, nerve fascicles exhibited a significantly lower density of axons (5.4 vs 17.9 x 10(-3) axons/mu m(2); P = .02), a smaller percentage area occupied by Schwann cells (17.5% vs 45.2%; P = .001) and a larger number of circular shaped Schwann cells lacking central axons (43.0% vs 12.7%; P < 0.001) compared with control subjects. The low density of axons was significantly related to degree of swallowing dysfunction (r = 0.5; P = .03) and apnea-hypopnea index > 5 (P = .03). Regenerating axons were frequently observed in patients compared with control subjects (11.3 +/- 4.2% vs 4.8 +/- 2.4%; P = .02).

    CONCLUSIONS: Axon degeneration in preterminal nerves of the soft palate is associated with pharyngeal dysfunction in snorers and patients with sleep apnea. The most likely cause for the nerve injuries is traumatic snoring vibrations and tissue stretch, leading to swallowing dysfunction and increased risk for upper airway obstruction during sleep.

  • 212.
    Shah, Farhan
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Laboratory of Muscle Biology, IMB, Umeå University.
    Holmlund, Thorbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Levring Jäghagen, Eva
    Umeå University, Faculty of Medicine, Department of Odontology.
    Berggren, Diana
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Franklin, Karl A.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Axon and Schwann cell degeneration in nerves of upper airway relates to pharyngeal dysfunction in snorers and sleep apnea patientsManuscript (preprint) (Other academic)
  • 213. Silvola, Juha T.
    et al.
    Sinkkonen, Saku T.
    Wanscher, Jens
    Westman, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Holm, Niels H.
    Ovesen, Therese
    The status of Eustachian tube balloon dilations in Nordic countries2019In: World Journal of Otorhinolaryngology - Head and Neck Surgery, ISSN 2589-1081, Vol. 5, no 3, p. 148-151Article in journal (Refereed)
    Abstract [en]

    There is no unanimous consensus for indications of eustachian tube balloon dilation (ETBD). Nordic countries have relatively similar hospital organizations and treatment guidelines. Therefore, it was logical to organize a consensus meeting of ETBD. The symposium: Nordic Experiences on Eustachian Tube Balloon Dilation, in Copenhagen, 30-31 March, 2017. The panellists from Denmark, Finland, Norway and Sweden and the attendees of the meeting agreed a consensus on the following issues: Candidates, Definition of Eustachian Tube Dysfunction, Diagnostic Work up, Differential Diagnosis, Contraindications, ETBD Procedure, Complications, Follow-up, and Outcomes. The article also presents the status for ETBD in each of these countries. Thereafter the consensus statement has been discussed in the national societies and meetings for ear surgeons in each of these countries. It can be assumed that surgeons in the hospitals of these Nordic countries generally follow the recommendations from the consensus meeting.

  • 214.
    Sjöström, Björn
    Umeå University, Faculty of Medicine, Clinical Sciences, Otorhinolaryngology.
    Munhåla, svalg2006In: Öron-, näs- och halssjukdomar, huvud- och halskirurgi, Liber AB , 2006, 3, p. 149-198Chapter in book (Other academic)
  • 215. Skjönsberg, Åsa
    et al.
    Bucinskaite, Violeta
    Laurell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Ulfendahl, Mats
    Augmented ototoxic effect of cisplatin in heterozygotes of the German waltzing guinea pig2008In: Audiology & neuro-otology, ISSN 1420-3030, E-ISSN 1421-9700, Vol. 13, no 2, p. 97-104Article in journal (Refereed)
    Abstract [en]

    It has previously been demonstrated that the carriers of the German waltzing guinea pig are less susceptible to noise trauma. To explore whether this represents a general resistance to inner ear trauma, carriers of the German waltzing guinea pig were exposed to the ototoxic agent cisplatin. Two doses of cisplatin were injected intravenously into anesthetized carriers and weight-matched control animals. Prior to and 96 h after the injections hearing thresholds were established by recording the auditory brainstem responses at 3.5, 7, 14, and 28 kHz. The cochleae were harvested to estimate hair cell loss and to analyze total platinum content. The carriers of the German waltzing guinea pig strain suffered from a more pronounced cisplatin-induced hearing loss compared to the control animals. The results suggest that mechanisms responsible for the protection against acoustic stress do not provide any protection against cisplatin in carriers of the German waltzing guinea pig.

  • 216.
    Spandow, Odd
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Gothefors, Leif
    Fagerlund, Markku
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Holm, Stig
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    [A case report of untreated otitis. Headache as a symptom of lateral sinus thrombosis].1997In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 94, no 48, p. 4505-8Article in journal (Refereed)
  • 217.
    Spandow, Odd
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Gothefors, Leif
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Fagerlund, Markku
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Kristensen, Bo
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Holm, Stig
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Lateral sinus thrombosis after untreated otitis media: A clinical problem – again?2000In: European Archives of Oto-Rhino-Laryngology, ISSN 0937-4477, E-ISSN 1434-4726, Vol. 257, no 1, p. 1-5Article in journal (Refereed)
    Abstract [en]

    Antimicrobial agents have greatly reduced the incidence of intracranial complications of infections of the middle ear and mastoid. Too many prescriptions and overconsumption of antibiotics when otitis media is suspected has caused resistance to many antibiotics, leading to a pronounced and justifiable desire to reduce the widespread excessive use of antibiotics. The possible untoward consequences of a too restricted antibiotic policy, however, is illustrated by the following case of a 14-year-old boy who, after non-treatment of an ear infection, fell ill with one-sided headache and vomiting caused by a lateral sinus thrombosis. After intravenous treatment with antibiotics, anticoagulants and ventilation of the middle ear, the infection was cured without complications. This case calls attention to the symptoms of otitic complications arising outside the temporal bone. The physician must always bear in mind the possibility of an unusual event. The general treatment of endocranial complications is outlined, giving details of the treatment given in this special case. We stress that one should not be too cautious in prescribing antibiotics in otitis media.

  • 218.
    Spratley, Jorge
    et al.
    Umeå University, Faculty of Medicine, Clinical Sciences, Otorhinolaryngology.
    Hellström, Sten
    Umeå University, Faculty of Medicine, Clinical Sciences, Otorhinolaryngology.
    Eriksson, Per Olof
    Umeå University, Faculty of Medicine, Clinical Sciences.
    Pais-Clemente, Manuel
    Early structural tympanic membrane ractions to myringotomy: A study in an acute otitis media model.2002In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 122, no 5, p. 479-487Article in journal (Refereed)
    Abstract [en]

    Myringotomy (Myr) is one of the most frequently performed surgical procedures in children. However, events occurring in the early phases, i.e. a matter of hours, following Myr in the acute otitis media (AOM) model have not been described. The aim of the present study was to evaluate the early otomicroscopic and histopathologic reactions of the tympanic membrane (TM) after Myr during the course of AOM (AOM-Myr). The left tympanic bulla from 36 healthy Sprague-Dawley rats was inoculated with Streptococcus pneumoniae type 3. Forty-eight h later, at Day 0, 4 randomized animals were immediately sacrificed and the remaining animals were treated with bilateral Myr. Otomicroscopy and sacrifices were performed in series of 4 animals at 3, 6, 9, 12, 24 and 48 h, and 4 and 7 days. The AOM-Myr TMs were compared to non-infected Myr TMs (non-AOM-Myr). The TMs were then dissected free and routinely processed for light and electron microscopy. AOM developed in all inoculated ears at Day 0. In the pars tensa of the AOM-Myr TMs the reaction of the keratinocyte layer of the perforation border was already evident at 6 h. The lamina propria exhibited a strong inflammatory reaction, which became more organized from 12 h onwards. At Day 4 the perforations were closed in three-quarters of cases. At Day 7 all perforations were healed with a distorted scar. In the non-AOM Myr TMs a strong degranulation of mast cells and edema were found in the pars flaccida at 6 h. A keratin spur at the perforation border was not seen until 24 h. All perforations were patent on Day 7 and myringosclerotic deposits were abundant in these TMs. The infected TMs regenerated faster and closed their perforations at an earlier stage. These findings favor the hypothesis that there is a low risk of chronic perforations when myringotomizing AOM TMs.

  • 219.
    Spratley, Jorge
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Hellström, Sten
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Eriksson, Per-Olof
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Pais-Clemente, Manuel
    Department of Otorhinolaryngology, University of Porto Medical School Hospital, Porto, Portugal.
    Myringotomy delays the tympanic membrane recovery in acute otitis media: a study in the rat model2002In: The Laryngoscope, ISSN 0023-852X, E-ISSN 1531-4995, Vol. 112, no 8 Pt 1, p. 1474-1481Article in journal (Refereed)
    Abstract [en]

    BACKGROUND/HYPOTHESIS: Acute otitis media is a major cause of visits to pediatric health care providers. Myringotomy in uncomplicated acute otitis media is debatable today. The study addressed this problem through the otomicroscopic and histopathological observations of the events occurring in the tympanic membrane during the first week after myringotomy.

    STUDY DESIGN: Randomized study in an experimental animal model.

    METHODS: Under anesthesia, the left middle ear of 36 Sprague-Dawley rats was inoculated with Streptococcus pneumoniae type 3. Forty-eight hours later, at day 0, four animals were immediately killed and the remaining animals were randomly assigned into a myringotomy group (n = 16, myringotomy on the left ear) and a non-myringotomy group (n = 16, otomicroscopy without myringotomy). Otomicroscopy and killings were performed in series of four animals from each group at days 1, 2, 4, and 7 after myringotomy. Tympanic membranes were collected after fixation and processed for light and electron microscopy.

    RESULTS: All inoculated ears showed a manifest acute otitis media at day 0. An intense infiltration by inflammatory cells and edema distorted severely the tympanic membrane structure. These findings decreased the following days. However, inflammation as evaluated by the thickness and the cytoarchitecture of the tympanic membrane layers, recovered significantly faster in the membranes in the non-myringotomy group. At day 7, all tympanic membranes in the myringotomy group were closed by a hypertrophic keratinizing epithelium and a remodeling connective tissue layer, whereas the animals in the non-myringotomy group had a residual edema in the lamina propria.

    CONCLUSIONS: The present infectious model induced an intense inflammatory reaction within the entire structure of the tympanic membrane. Myringotomy provoked a delayed recovery from the inflammatory process within the tympanic membrane. Therefore, if applicable to human conditions, the use of myringotomy in the management of acute otitis media should be restricted to selected cases of acute otitis media.

  • 220.
    Stenfeldt, K
    Umeå University, Faculty of Medicine, Clinical Sciences, Otorhinolaryngology.
    Plastikkirurgi trots normalt utseende - är det försvarbart2004In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, no 50, p. 4140-43Article in journal (Other (popular science, discussion, etc.))
  • 221.
    Stenfeldt, Karin
    Umeå University, Faculty of Medicine, Clinical Sciences, Otorhinolaryngology.
    Retained Tubes2004In: Advanced Therapy of Otitis Media, BC Decker Inc, London , 2004, p. 290-294Chapter in book (Other (popular science, discussion, etc.))
  • 222.
    Stenfeldt, Karin
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Johansson, Cathrine
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Eriksson, Per-Olof
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Hellström, Sten
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Collagen Type II Is Produced in Healing Pars Tensa of Perforated Tympanic Membranes: An Experimental Study in the Rat2013In: Otology and Neurotology, ISSN 1531-7129, E-ISSN 1537-4505, Vol. 34, no 7, p. E88-E92Article in journal (Refereed)
    Abstract [en]

    Hypothesis: Type II collagen is synthesized in the tympanic membrane during healing of a perforation. The time course and appearance of Type II collagen regrowth in the newly healed tympanic membrane is the subject of the present study. Background: The arrangement of Type II collagen fibers in the tympanic membrane gives it a unique tensile strength important for sound conduction. Healing after tympanic membrane perforation can cause the tympanic membrane to lose its characteristic. At what phase Type II collagen in tympanic membrane is replaced during healing of a perforation has previously not been studied. Methods: Rat tympanic membranes were perforated, and the animals were sacrificed 9 to 16 days after perforation. Tympanic membranes were stained with a Type II collagen antibody. Results: At Day 9, a majority of the tympanic membranes had healed. Keratinizing epithelium and connective tissue had formed, but there was no Type II collagen. At Day 10, all tympanic membranes had healed, and staining for Type II collagen appeared. After Day 10, staining was more intense. Newly formed collagen did not show the parallel bundle arrangement seen in normal tympanic membranes but was more scattered in the tissue. Conclusion: Type II collagen was seen in tympanic membranes only after closure of the perforation. The fiber arrangement after healing was disturbed, which presumably has an impact on the function of the tympanic membrane. Understanding the formation of Type II collagen in the healing of tympanic membrane perforations could enable further research toward treating tympanic membrane perforations.

  • 223. Stenfeldt, Karin
    et al.
    Johansson, Cathrine
    Umeå University, Faculty of Medicine, Clinical Sciences, Otorhinolaryngology.
    Hellström, Sten
    Umeå University, Faculty of Medicine, Clinical Sciences, Otorhinolaryngology.
    The collagen structure of the tympanic membrane: collagen types I, II, and III in the healthy tympanic membrane, during healing of a perforation, and during infection.2006In: Archives of Otolaryngology - Head & Neck Surgery, ISSN 0886-4470, E-ISSN 1538-361X, Vol. 132, no 3, p. 293-298Article in journal (Refereed)
  • 224.
    Stenhammar, Christina
    et al.
    Institutionen för kvinnors och barns hälsa, Uppsala universitet.
    Isaksson, Joakim
    Umeå University, Faculty of Social Sciences, Department of Social Work.
    Granström, Brith
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Laurell, Göran
    Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar, Uppsala universitet.
    Tiblom Ehrsson, Ylva
    Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar, Uppsala universitet, Institutionen för folkhälsa- och vårdvetetenskap, vårdvetenskap, Uppsala universitet.
    Changes in intimate relationships following treatment for head and neck cancer: a qualitative study2017In: Journal of psychosocial oncology, ISSN 0734-7332, E-ISSN 1540-7586, Vol. 35, no 5, p. 614-630Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to determine how patients with head and neck cancer experience changes within their intimate relationships at the end of treatment and detect detrimental and facilitating factors in the process of resuming intimate relationships. Interviews were conducted with 131 patients. A core category – "Being open vs. not sharing the cancer journey" – emerged from the patients' narratives and was based on the experiences of engagement/disengagement, openess/fear, and patronising attitudes/sharing the burden. The findings point to the necessity of patients being open about the disease trajectory and might be understood in the light of theories about potential changes in identity and self-concept.

  • 225.
    Stepanidis, Karen
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Kessel, Marie
    Caye-Thomasen, Per
    Stangerup, Sven-Eric
    Socio-demographic distribution of vestibular schwannomas in Denmark2014In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 134, no 6, p. 551-556Article in journal (Refereed)
    Abstract [en]

    Conclusion: Vestibular schwannomas (VSs) are diagnosed less frequently in the remote parts of Denmark, whereas the diagnostic age and tumor size is the same across the different socio-demographic areas of Denmark. Objective: To determine whether VSs are diagnosed equally often in different socio-demographic areas of Denmark and whether a change has occurred during the period 1976-2012. In addition, differences in diagnostic age and tumor size between areas were explored. Methods: Since 1976, all patients diagnosed with a VS in Denmark have been registered in a national database, in which information on, for example, the size of the tumor and the age and address of the patient has been registered. Up to 2012, 2739 patients were diagnosed with a VS. Patient distribution according to area of habitat was determined by subgrouping into urban, suburban, rural, and remote municipalities, using the definitions of socio-demographic areas elaborated by Demarks Statistic. Results: The mean national incidence increased almost linearly over the time period from 6.1 per million per year in the first period from 1976 to 1984, to 22.1 per million per year in the last period from 2003 to 2012. There was a lower incidence at the end of the period in the remote areas compared with the other socio-demographic areas (1976-1984, p = 0.05 and 2003-2011, p = 0.001). The mean age at diagnosis increased during the period, from 52.6 years in the first period to 58.6 years in the last period. There was no significant difference in the age distribution between socio-demographic areas. The mean diagnostic tumor size decreased during the period, from 28.6 mm in the first period to about 10 mm in the last period. There was no significant difference in the size of the tumor between socio-demographic areas.

  • 226.
    Strindlund, Klas
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Troiano, Giuseppe
    Sgaramella, Nicola
    Coates, Philip J.
    Gu, Xiaolian
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Boldrup, Linda
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Califano, Luigi
    Fåhraeus, Robin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. RECAMO, Masaryk Memorial Cancer Institute, Brno, Czech Republic; Institut de Génétique Moléculaire, Hôpital St. Louis, Université Paris 7, Paris, France.
    Muzio, Lorenzo Lo
    Ardito, Fatima
    Colella, Giuseppe
    Tartaro, Gianpaolo
    Franco, Renato
    Norberg-Spaak, Lena
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Saadat, Mohammad
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Nylander, Karin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Patients with high c-MYC-expressing squamous cell carcinomas of the tongue show better survival than those with low- and medium-expressing tumours2017In: Journal of Oral Pathology & Medicine, ISSN 0904-2512, E-ISSN 1600-0714, Vol. 46, no 10, p. 967-971Article in journal (Refereed)
    Abstract [en]

    Backgroundc-MYC is a potent oncoprotein with roles in a wide range of cellular processes such as differentiation, apoptosis and growth control. Deregulation of the MYC gene is commonly seen in human tumours resulting in overexpression of the protein. Here we studied expression of c-MYC in correlation to clinical outcome in patients with primary squamous cell carcinoma of the mobile tongue. MethodsImmunohistochemistry was used to identify c-MYC in a group of 104 tongue squamous cell carcinomas with an antibody directed against the N-terminal part of the protein. Staining was evaluated by multiplying the percentage of c-MYC-expressing cells with staining intensity, giving a quick score for each tumour. ResultsAll 104 tumours expressed c-MYC at varying levels. Quantitation according to per cent of positive cells and staining intensity revealed that most (15/21; 71%) high-expressing tumours were seen in males. Within the group of high c-MYC-expressing tumours, the majority were alive 2 and 5 years after treatment. ConclusionsThe present findings show that expression of c-MYC has prognostic value in squamous cell carcinoma of the tongue, and could be useful in choice of therapy.

  • 227.
    Sundstedt, Stina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Swallowing and deep brain stimulation: swallowing function in Parkinson's disease after subthalamic nucleus and caudal zona incerta deep brain stimulation2014Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background Swallowing problems are common in Parkinson’s disease, and these affect morbidity and mortality largely due to aspiration-induced pneumonia. Even mild dysphagia affects patient Quality of Life. Deep Brain Stimulation (DBS), a surgical treatment for Parkinson’s disease, improves overall motor function, though the effect of DBS on swallowing function is not clear. The aim of the studies in this thesis was to improve our understanding of the effect from DBS of caudal zona incerta and subthalamic nucleus on pharyngeal swallowing function. Specific aims were to compare DBS effects over time postoperatively (6 & 12 months) for swallowing function, on and off stimulation, with a preoperative baseline assessment in order to identify possible negative swallowing effects of DBS.

    Methods Eight patients with DBS in caudal zona incerta and eleven patients with DBS in subthalamic nucleus were included in the two studies. The effect of DBS on swallowing function was evaluated by self-estimation on a visual analogue scale and fiberoptic endoscopic evaluation of swallowing function with a predefined swallowing protocol including Rosenbek’s Penetration/Aspiration Scale, Secretion Severity Scale,preswallow spillage, pharyngeal residue and pharyngeal clearance. The patients with caudal zona incerta DBS also answered questions regarding swallowing-related Quality of Life. All patients received L-dopa treatment during postoperative assessments.

    Results There was no clear effect of DBS on swallowing function in the two samples. The occurrence of aspiration, secretions, pharyngeal residue or clearance was not affected by the surgery or the stimulation. In the subthalamic nucleus DBS sample, self-estimations revealed an improvement with stimulation turned on. For the caudal zona incerta DBS patients, no effect of DBS was seen on the results from the swallowing-related QOL questions.

    Conclusion Subthalamic nucleus DBS and caudal zona incerta DBS did not appear to have a negative effect on swallowing function in this cohort. Patients with subthalamic nucleus DBS reported a self-perceived improvement in swallowing function after DBS. There appears to be no increased risk for aspiration or penetration due to surgery or stimulation regardless of stimulation site. Since the sample sizes in these cohorts are small, the findings need to be confirmed in larger studies.

  • 228.
    Sundstedt, Stina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Swallowing function in patients with Parkinson’s disease and Deep Brain Stimulation2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background

    Parkinson’s disease (PD) is one of the most common neurodegenerative diseases in Europe. Besides motor dysfunction, PD is characterized by several non-motor and secondary motor features, such as weight change, sialorrhea, constipation and swallowing problems. Of these, swallowing is one of the most critical, as it is associated with aspiration pneumonia and consequently is the comorbidity with the highest mortality rate. Swallowing problems affect four of every five patients with PD, and even mild swallowing problems have notable psychosocial effects for patients and their caregivers. Consequently, it is essential to find treatment strategies for PD that may alleviate symptoms for patients with swallowing problems and their potential consequences.

    Deep Brain Stimulation (DBS) is a surgical treatment option for PD, which improves overall motor function and quality of life, but its effect on swallowing function is not clear.

    The purpose of this thesis was to contribute to the understanding of the effect of deep brain stimulation in the subthalamic nucleus (STN DBS) and the caudal zona incerta (cZI DBS) on pharyngeal swallowing function and on swallow-specific quality of life in patients with PD.

    The specific aims were to assess longitudinally the effect of STN DBS and cZI DBS on swallowing at 6 and 12 months postoperatively, in order to identify possible effects of the DBS on swallowing function. In addition, the effects of cZI DBS on ratings of swallowing-related non-motor and secondary motor features such as body weight changes, sialorrhea and speech problems were to be assessed.

    Methods

    Eleven PD patients with STN DBS (Paper I) and seventeen patients with cZI DBS (Paper II-IV) were included in this thesis. All patients were evaluated preoperatively and 6 and 12 months postoperatively. The effect of STN DBS and cZI DBS on swallowing was assessed with Fibreoptic-Endoscopic Evaluation of Swallowing (FEES) according to a predefined protocol including Penetration-Aspiration scale, Secretion Severity scale, preswallow spillage, pharyngeal residue, and pharyngeal clearance. Self-assessments were addressed using a visual analogue scale. The cZI DBS patients also completed the Swallowing Quality of Life (SWAL-QOL) questionnaire. Weight changes measured by Body Mass Index, and specific items from the Unified Parkinson’s Disease Rating Scale were also examined. Nine controls without PD were included in Paper IV, by answering the SWAL-QOL questionnaire.

    Results

    No clear effect of DBS on swallowing function or swallow-specific quality of life could be observed. There was no effect of DBS on the occurrence of aspiration, secretion, pharyngeal residue or clearance in the study groups with STN DBS or cZI DBS. Patients with STN DBS reported a subjective improvement in swallowing function with DBS stimulation turned on at 6 and 12 months after surgery.

    In patients with cZI DBS, the median body mass index was postoperatively increased with 1.1kg/m2 and the median increase in weight were +3.0 kg after 12 months with cZI DBS.

    The scores from the SWAL-QOL questionnaire were high overall in the group with cZI DBS, and the scores were unaffected by the cZI DBS surgery and stimulation. The SWAL-QOL total score was not significantly different between the PD patients and the controls, but the scores from the ‘burden’ and the ‘symptom’ subscales were worse in PD patients.

    Conclusions

    STN DBS or cZI DBS did not have a negative effect on swallowing function or ratings of swallow-specific ‘quality of life’ aspects in this cohort. Patients with STN DBS reported a self-perceived improvement in swallowing function when DBS was turned on. With regard to swallowing, patients with cZI DBS had an overall good quality of life throughout the conduct of the study and their swallow-specific quality of life was not negatively affected by cZI DBS. There seems to be no increased risk for aspiration or penetration due to surgery or stimulation for either the STN DBS or the cZI DBS groups. cZI DBS caused weight gain postoperatively. Since the sample sizes in these cohorts are small, the findings need to be confirmed in larger studies.

  • 229.
    Sundstedt, Stina
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Holmén, Lina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Speech and Language Therapy.
    Rova, Elin
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Speech and Language Therapy.
    Linder, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Nordh, Erik
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Olofsson, Katarina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Swallowing safety in Parkinson's disease after zona incerta Deep Brain Stimulation2017In: Brain and Behavior, ISSN 2162-3279, E-ISSN 2162-3279, Vol. 7, no 6, article id e00709Article in journal (Refereed)
    Abstract [en]

    Objectives: The objective of this study was to examine swallowing function in patients with Parkinson's disease before and after caudal zona incerta deep brain (cZI DBS) surgery. The aims were to examine the effect of cZI DBS on swallowing safety regarding liquid and solid food, as well as to identify the effect of cZI DBS on body mass index (BMI) and specific items from part II of the Unified Parkinson's Disease Rating Scale (UPDRS).

    Materials and Methods: The median age of the 14 patients was 57 years (range 46–71), with a median disease duration of 6 years (range 2–13). The present sample is an extension of a previous report, into which six additional patients have been added. Fiber endoscopic examinations of swallowing function, measures of BMI, and evaluation of UPDRS part II items were made before and 12 months after surgery, with and without activated DBS.

    Results: There were no significant changes due to cZI DBS regarding penetration/aspiration, pharyngeal residue or premature spillage (> .05). Median BMI increased by +1.1 kg/m2 12 months after surgery (= .01, = .50). All reported specific symptoms from the UPDRS part II were slight or mild. A significant improvement regarding handling of utensils was seen 12 months postoperatively (= .03, = −.42).

    Conclusions: Caudal zona incerta DBS was found not to have a negative impact on swallowing safety. A significant increase in postoperative weight was observed, and speech seemed to be slightly negatively affected, whereas handling of utensils was improved with cZI DBS.

  • 230.
    Sundstedt, Stina
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Nordh, Erik
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Linder, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Hedström, Johanna
    Department of Otorhinolaryngology, Head and Neck Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Sweden.
    Finizia, Caterina
    Department of Otorhinolaryngology, Head and Neck Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Sweden.
    Olofsson, Katarina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    ­­Swallowing quality of life after zona incerta Deep brain stimulation2017In: Annals of Otology, Rhinology and Laryngology, ISSN 0003-4894, E-ISSN 1943-572X, Vol. 126, no 2, p. 110-116Article in journal (Refereed)
    Abstract [en]

    Objectives: The management of Parkinson’s disease (PD) has been improved, but management of features like swallowing problems is still challenging. Deep Brain Stimulation (DBS) alleviates the cardinal motor symptoms and improves quality of life, but its effect on swallowing is not fully explored. The purpose of this study was to examine self-reported swallowing specific quality of life, before and after caudal zona incerta DBS (cZI DBS), in comparison with a control group.

    Methods: Nine PD patients (2 women and 7 men) completed the self-report Swallowing Quality of Life questionnaire (SWAL-QOL) before and 12 months after cZI DBS surgery. The postoperative data were compared to nine controls. Median ages were 53 years (range 40-70) for patients and 54 years (range 42-72) for controls.

    Results: No significant differences were found between the pre-, or postoperative scores. The SWAL-QOL total scores did not differ significantly between PD patients and controls. PD patients reported significantly lower scores in the 'burden' subscale and in the 'symptom' scale.

    Conclusions: PD patients selected for cZI DBS showed a good self-reported swallowing specific quality of life, in many aspects equal to controls. CZI DBS did not negatively affect swallowing specific quality of life in this study.

  • 231.
    Sundstedt, Stina
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Speech and Language Therapy.
    Olofsson, Katarina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    van Doorn, Jan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Speech and Language Therapy.
    Linder, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Nordh, Erik
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neurophysiology.
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Swallowing function in Parkinson’s patients following Zona Incerta deep brain stimulation2012In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 126, no 5, p. 350-356Article in journal (Refereed)
    Abstract [en]

    Objective The purpose of the present study was to examine if there was a negative effect of caudal Zona Incerta deep brain stimulation (cZI DBS) on pharyngeal swallowing function in Parkinson’s patients (PD). There are no former reports on swallowing and cZI DBS.

    Methods Eight patients (aged 49 to 71 years; median 62) were evaluated pre- and postoperatively, at six and 12 months after DBS surgery. Evaluation tools were Fiberoptic Endoscopic Evaluation of Swallowing examinations and patients’ self-assessments of the swallowing function including a visual analogue scale and quality of life related questions. The swallowing protocol included Rosenbeck’s Penetration-Aspiration Scale, Secretion Severity Scale and parameters for pre-swallow spillage, pharyngeal residue and pharyngeal clearance.

    Results There was no clear-cut effect of neurostimulation postoperatively at six and 12 months on any of the swallowing parameters except for pre-swallow spillage which was slightly worsened in the stimulation on condition 12m postoperatively. The answers to the self assessment questions did not vary significantly.

    Conclusions The effect of the stimulation on swallowing function varied among individuals but the overall outcome was that cZI DBS did not seem to have a negative influence on swallowing function in the eight patients studied.

  • 232.
    Sundström, Gunnel
    et al.
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Dahl, Inger Marie S
    Hultdin, Magnus
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Lundström, Berit
    Umeå University, Faculty of Medicine, Clinical Sciences, Otorhinolaryngology.
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Engström Laurent, Anna
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Bone marrow hyaluronan distribution in patients with acute myeloid leukemia.2005In: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 22, no 1, p. 71-78Article in journal (Refereed)
    Abstract [en]

    The present study investigated potential age-related changes in human muscle spindles with respect to the intrafusal fiber-type content and myosin heavy chain (MyHC) composition in biceps brachii muscle. The total number of intrafusal fibers per spindle decreased significantly with aging, due to a significant reduction in the number of nuclear chain fibers. Nuclear chain fibers in old spindles were short and some showed novel expression of MyHC α-cardiac. The expression of MyHC α-cardiac in bag1 and bag2 fibers was greatly decreased in the A region. The expression of slow MyHC was increased in nuclear bag1 fibers and that of fetal MyHC decreased in bag2 fibers whereas the patterns of distribution of the remaing MyHC isoforms were generelly not affected by aging. We conclude that aging appears to have an important impact on muscle spindle composition. These changes in muscle spindle phenotype may reflect an age-related deterioration in sensory and motor innervation and are likely to have an impact in motor control in the elderly.

  • 233.
    Söderberg, Ove
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Transmyringeal middle ear ventilation: an experimental approach to evaluation of its benefits and consequences1985Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    A prerequisite for a functioning middle ear is an air-filled middle ear cavity. Aeration of the middle ear cavity is controlled by the Eustachian tube. Dysfunction of the Eustachian tube has long been acknowledged as a significant etiological factor in disorders of the middle ear, especially middle ear effusions. Artificial ventilation of the middle ear through the tympanic membrane has been practised for almost two centuries, but with varying degrees of success. In 1954, Armstrong reintroduced the method of inserting a transmyringeal tympanostomy tube into the ear drum. Since that time this ventilatory device has gained wide popularity and several types of tube have been designed. However, an increasing number of clinical reports have shown treatment with tympanostomy tubes to be followed by complications such as tympanosclerosis, atrophy, persistent perforations and cholesteatomas.

    In the present thesis, experiments were outlined in which the tympanostomy tube - tympanic membrane interaction was studied and in which tympanostomy tubes were also applied in a well-defined type of otitis media. Furthermore, alternative transmyringeal ventilatory procedures such as myringotomies with a delayed healing time were investigated. The results were evaluated with morphological and microbiological methods.

    Repeated tympanostomy tube insertions in ears of healthy rats caused a remarkable thickening (about 30-fold) of the tympanic membrane of the tubulated quadrants, but even the untouched quadrants were affected. The thickened areas were characterized mainly by an increase in dense connective tissue which also contained sclerotic plaques. The structural changes in the tympanic membrane were still present 3 months after the final ventilation episode.

    Cleavage of the rat soft palate caused an immediate accumulation of effusion material in the tympanic cavity due to disturbance of Eustachian tube function. The fluid turned purulent within one to two weeks. The microbial flora of the middle ear cavity correlated well with that of the nasopharynx, indicating an ascending infection. Insertion of a tympanostomy tube could prevent the accumulation of effusion material in the meso- and hypotympanon and significantly suppress bacterial growth in the middle ear cavity.

    Thermal energy-inflicted myringotomies were tested as an alternative method for establishing transmyringeal ventilation. Myringotomies performed either with a CCL-laser or by diathermy showed a delayed healing pattern, most probably due to widespread destruction of the outer keratinized squamous epithelium and damage to the vascular supply. Upon comparison, laser myringotomies appeared more favourable due to their longer closure times, whereas the perforations accomplished by diathermy were often complicated by otorrhea and showed more advanced structural changes.

  • 234.
    Tano, Krister
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    von Essen, Robert
    Eriksson, P O
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Sjöstedt, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Alloiococcus otitidis--otitis media pathogen or normal bacterial flora?2008In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 116, no 9, p. 785-90Article in journal (Refereed)
    Abstract [en]

    During the last decade a new potential otitis media pathogen, Alloiococcus otitidis, has been studied. It is still not clear whether this bacterium really is a pathogen, although it has been found in a high percentage of middle ear effusions in children. The present study aimed to investigate the presence of A. otitidis in the nasopharynx and outer ear canals, and to develop a culture method that would make it possible to isolate A. otitidis from these locations. Nasopharyngeal samples (n = 129) from children below 6 years were investigated by conventional culture on blood agar plates with 6% saline and rabbit antisera against A. otitidis, and by a PCR method. In the same way, we investigated 10 samples from vestibulum nasi of healthy persons, 68 samples from outer ear canals of patients with acute or chronic ear problems, and 24 samples from outer ear canals of healthy persons. In a rat model of acute otitis media, we instilled living A. otitidis into rat middle ears through the tympanic bulla and evaluated the outcome clinically by otomicroscopy at days 3, 6 and 14. Of the 129 nasopharyngeal cultures, 9 were positive for A. otitidis by PCR, but none by the culture method. Of the 68 samples from patients with running ears, 4 were positive for A. otitidis by PCR, but none by the culture method. Of the 24 healthy ear canals, 7 were positive for A. otitidis by PCR and 3 of them also by the culture method. No A. otitidis could be found from the vestibulum nasi. The rat experiment showed that the reactions in the middle ears were mild; we could not provoke a purulent acute otitis media in any of the rats. There was a 7% prevalence of A. otitidis in children below 6 years. The highest prevalence (29%) was found in outer ear canals of healthy persons, which strongly suggests that A. otitidis is part of the normal bacterial flora of the outer ear canal. The doubtful pathogenicity is also confirmed by the fact that--in the rat model--A. otitidis elicited only a mild response in the middle ear. It was possible to isolate A. otitidis using a blood agar plate with 6% saline.

  • 235. Tano, Liselott
    et al.
    Tano, Krister
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology. Department of Otolaryngology, Sunderby Hospital, Luleå, Sweden.
    A daily nasal spray with saline prevents symptoms of rhinitis2004In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 124, no 9, p. 1059-1062Article in journal (Refereed)
    Abstract [en]

    Objective: To ascertain whether a daily nasal spray with physiological saline could prevent symptoms of common cold in a population of otherwise healthy adults.

    Material and Methods: This was study involving 10 weeks of daily use of a nasal saline spray and 10 weeks of only recording symptoms. Young adults eligible for military service at an army barrack in Boden, Sweden were invited to participate in the study and 108 healthy conscripts aged approximate to 20 years agreed to do so. Data were recorded by the participants in a diary at home. In the diary the participants noted symptoms such as rhinitis, blocked nose, cough, fever and sore throat (pharyngeal pain). They also recorded inability to perform their duties due to the symptoms, and any medication or antibiotics necessitated by upper respiratory tract infection.

    Results: A total of 69 subjects completed the 20-week diary period. For 60 of them, compliance during the spray period exceeded 60% and their data were used in the statistical calculations. During the spray period the number of days with nasal secretion and/or blocked nose (mean 6.4 days) was significantly (p= 0.027) lower than that during the observation period (mean 11 days). Furthermore, the participants had a mean of 0.7 episodes of upper respiratory tract infection during the spray period, compared with 1.0 episodes during the observation period (p= 0.05).

    Conclusion: A daily nasal spray with saline can prevent nasal symptoms of common cold in a population of otherwise healthy adults.

  • 236.
    Thore, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Studies on experimental anaerobic infections of the middle ear and on the polymorphonuclear leukocyte function under anaerobic conditions1984Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Despite the clinical importance of anaerobic bacteria in otitis media and the uncertainty regarding the proper treatment of the anaerobic focal infection, few experimental studies focused upon the role of these microorganisms in otitis media have been publis­hed. In the present investigation a guinea-pig model for the induc­tion of anaerobic monoinfections in the middle ear was described. Bacteroides fragilis and Propionibacterium acnes (4.0-10x10 colony forming units) injected via the tympanic membrane were capable of inducing clinical and histological otitis media with persistent seguele in the middle ear cavity. Bacteroides asacc-harolyticus, Peptostreptococcus micros and Peptost repto- coccus anaerobius failed to induce otitis media.

    B. fragilis otitis was accompanied by increased serum IgG and IgM antibody titres against the challenge organism, whereas P. acnes and P. anaerobius did not induce a humoral immune response. The results suggested true virulence of B. fragilis in guinea-pig middle ear monoinfections.

    Metronidazole was found to accelerate the elimination of B.fragilis from the middle ear. However, even high doses of metro­nidazole were nojt fully effective perhaps reflecting an incomplete anaerobiosis at the site of infection in some instances. At pre­sent, nitroimidazoles in chronic otitis media must be regarded as a possible alternative reguiring further study, particularly with regard to the dosage.

    In order to gain further knowledge of the interaction between poly­morphonuclear leukocytes and bacteria under anaerobic conditions an in vitro model was established. It was shown that P. acnes was readily phagocytosed with the aid of C3 activated either via the classical or alternative pathway and that killing of P. acnes was inefficient during anaerobiosis. The results suggest that P.acnes is maintained in the pus in chronic otitis media because it sur­vives phagocytosis.

    Finally, the interaction between the most common pathogen in acute purulent otitis media, Streptococcus pneumoniae, and human poly­morphonuclear leukocytes under anaerobic conditions was studied. Since purulent maxillary sinus effusion (and probably also purulent middle ear effusion), invariably has a pO^ approaching zero, such studies are highly relevant with regard to the host defence in sinuitis and perhaps also in otitis media.

    S. pneumoniae was killed by the phagocytes under anaerobic condi­tions although at a slower rate than in air. Degradation of pneumo­coccal teichoic acid, DNA and RNA took place after phagocytosis under aerobic as well as anaerobic conditions, whereas degradation of unsaturated cell membrane lipids took place only under aerobic conditions. Furthermore, the pneumococcal autolytic system did not participate in the killing or the degradation of the bacteria.

  • 237.
    Thurfjell, Niklas
    et al.
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Coates, Philip J
    Boldrup, Linda
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Lindgren, Britta
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Bäcklund, Bodil
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Uusitalo, Tony
    Mahani, David
    Dabelsteen, Erik
    Dahlqvist, Åke
    Umeå University, Faculty of Medicine, Clinical Sciences, Otorhinolaryngology.
    Sjöström, Björn
    Umeå University, Faculty of Medicine, Clinical Sciences, Otorhinolaryngology.
    Roos, Göran
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Vojtesek, Borek
    Nenutil, Rudolf
    Nylander, Karin
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Function and importance of p63 in normal oral mucosa and squamous cell carcinoma of the head and neck.2005In: Advances in Oto-Rhino-Laryngology, ISSN 0065-3071, E-ISSN 1662-2847, Vol. 62, p. 49-57Article in journal (Refereed)
    Abstract [en]

    BACKGROUND/AIMS: Squamous cell carcinoma of the head and neck (HNSCC) is the 6th most common malignancy worldwide with a 5-year survival that has not improved over the last 20-25 years. Factors of prognostic significance for this tumour type include the presence of regional lymph node metastasis and amplification of chromosome 3q21-29, where the p63 gene is located. This gene encodes 6 proteins and is crucial for formation of the oral mucosa, teeth, salivary glands and skin. Each of the 6 different p63 proteins has different characteristics and functions, where some resemble the tumour suppressor protein p53, whilst others have functions that oppose p53. METHODS: To understand the function and importance of p63 in oral mucosa and tumour development we have studied protein as well as mRNA expression in normal oral mucosa and tumours. RESULTS/CONCLUSION: Expression of p63 proteins differs between the cell layers in normal oral mucosa, and primary HNSCC has a high expression level of p63 isoforms normally expressed in basal cells. Data suggest that p63 expression in HNSCC influences tumour cell differentiation.

  • 238.
    Thurfjell, Niklas
    et al.
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Coates, Philip J
    Uusitalo, Tony
    Mahani, David
    Dabelsteen, Erik
    Dahlqvist, Ake
    Umeå University, Faculty of Medicine, Clinical Sciences, Otorhinolaryngology.
    Sjöström, Björn
    Umeå University, Faculty of Medicine, Clinical Sciences, Otorhinolaryngology.
    Roos, Göran
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Nylander, Karin
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Complex p63 mRNA isoform expression patterns in squamous cell carcinoma of the head and neck.2004In: International Journal of Oncology, ISSN 1019-6439, Vol. 25, no 1, p. 27-35Article in journal (Refereed)
  • 239.
    Tylstedt, Sven
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    The Human Spiral Ganglion2003Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Our knowledge of the fine structure of the Human Spiral Ganglion (HSG) is still inadequate and new treatment techniques for deafness using electric stimulation, call for further information and studies on the neuronal elements of the human cochlea. This thesis presents results of analyses of human cochlear tissue and specimens obtained during neurosurgical transpetrosal removal of life-threatening meningeomas. The use of surgical biopsies produced a well-preserved material suitable for ultrastructural and immunohistochemical studies on the human inner ear. The SG was studied with respect to fine structure, using TEM technique and the immunostaining pattern of synaptophysin, which is an integral membrane protein of neuronal synaptic vesicles. The immunostaining patterns of the tight junctional protein ZO-1 and the gap junctional proteins Cx26 and Cx43 in the human cochlea were also studied. The ultrastructural morphology revealed an absence of myelination pattern in the HSG, thus differing from that in other species. Furthermore, formation of structural units as well as signs of neural interaction between the type 1 neurons could be observed. Type 1 cells were tightly packed in clusters, sharing the ensheathment of Schwann cells. The cells frequently made direct physical contact in Schwann cell gaps in which membrane specializations appeared. These specializations consisted of symmetrically or asymmetrically distributed filamentous densities along the apposed cell membranes. The same structures were also present between individual unmyelinated nerve fibres and the type 1 cells. Synapses were observed on the type 2 neurons, with nerve fibres originating from the intraganglionic spiral bundle. Such synapses, though rare, were also observed on the type 1 cells. The ultrastructural findings were confirmed by the synaptophysin study. A 3-D model of a Schwann cell gap between two type 1 cells was constructed, describing the distribution pattern of membrane specializations. In the immunohistochemical studies on the human cochlea, ZO-1 was expressed in tissues lining scala media, thus contributing to the formation of a closed compartment system, important for the maintenance of the specific ionic composition of the endolymph. Protein Cx26 could be identified in non-sensory epithelial cells of the organ of Corti, in connective tissue cells of the spiral ligament and spiral limbus, as well as in the basal and intermediate cell layers of stria vascularis. Cx26 in this region may be involved in the recycling of potassium. Protein Cx43 stained weakly in the spiral ligament, but intense staining in the SG may indicate that gap junctions exist between these neurons. A different functional role for the HSG can be assumed from the morphological characteristics and the signs of a neural interaction between the SG cells. This might be relevant for neural processing mechanisms in speech coding and could have implications for cochlear implant techniques.

  • 240.
    Tärnvik, Arne
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Sundqvist, G
    Gothefors, Leif
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Gustafsson, H
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Meningitis caused by Fusobacterium necrophorum.1986In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 5, no 3, p. 353-355Article in journal (Refereed)
  • 241.
    Vallgren, Valentina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Utvärdering av ETDQ-7 formuläret vid uppföljning av ballong dilatering av Örontrumpeten i en svensk studie2018Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 242. van der Wal, Jacqueline E.
    et al.
    Sgaramella, Nicola
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Norberg-Spaak, Lena
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Zborayova, Katarina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Nylander, Karin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    High podoplanin and low E-cadherin levels correlate with better prognosis in adenoid cystic carcinoma2019In: Clinical and Experimental Dental Research, ISSN 2057-4347, Vol. 5, no 4, p. 350-355Article in journal (Refereed)
    Abstract [en]

    Objectives: As tumour spread is a complicating event for malignant salivary gland tumours, we decided to study factors related to cell adhesion and lymph vessel formation in two of the three most common malignant salivary gland tumours, mucoepidermoid carcinoma (MEC) and adenoid cystic carcinoma (ACC), to clarify the clinical relevance and potential usefulness of these factors. We also included a group of polymorphous adenocarcinoma (PAC) as this tumour, in common with ACC often shows perineural growth, but in contrast to ACC has an overall good prognosis.

    Material and methods: Eighteen patients with ACC, 15 with MEC, and six with PAC were included. Protein expression of podoplanin and E‐cadherin was evaluated as percentage of cells expressing the protein and intensity of expression. Ki‐67 expression was included in the study as a marker of proliferative activity.

    Results: Looking at podoplanin, significantly more ACCs were high expressing compared with both MECs (P = .001) and PACs (P = .028). Also when looking at Ki‐67 expression, significantly more ACCs were high expressing compared with MECs (P = .003). Significantly better survival was also seen for ACCs with high podoplanin (P = .022) and low E‐cadherin expression (P = .021), respectively.

    Conclusions: Our findings show that ACCs express significantly higher levels of podoplanin compared with both MECs and PACs and that high levels are correlated to better survival. Even though the group of PACs analysed was small, these tumours, despite their tendency to perineural spread, which they have in common with ACC, differ from ACCs concerning expression of factors with a known connection to tumour spread.

  • 243.
    Vancea, Mihai
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Intrakutana- och enstaka suturersärrläkning i huvud-halsregionen:En analys av kosmetiskt utfall 12 månader efter operation2016Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 244.
    Vestin Fredriksson, Malin
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Öhman, Anders
    Flygare, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Tano, Krister
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    When Maxillary Sinusitis Does Not Heal: Findings on CBCT Scans of the Sinuses With a Particular Focus on the Occurrence of Odontogenic Causes of Maxillary Sinusitis2017In: Laryngoscope Investigative Otolaryngology, E-ISSN 2378-8038, Vol. 2, no 6, p. 442-446Article in journal (Refereed)
    Abstract [en]

    Objectives: This study sought to investigate the proportion of patients with suspected sinusitis referred for radiological examination who have radiologically verified sinusitis of odontogenic origin and to describe this type of sinusitis. Study Design: This investigation is a retrospective study. Methods: A total of 303 sinus examinations involving cone beam computed tomography (CBCT) performed at Sunderby Hospital, Lulea, Sweden in 2012 were independently reviewed by two radiologists. The number of cases of maxillary sinusitis and the correlation between maxillary sinusitis and odontogenic infections were determined. Results: Overall, 24% of the verified cases of sinusitis were odontogenic. An odontogenic origin was identified in 40% of unilateral maxillary sinusitis cases but only 6% of bilateral maxillary sinusitis cases (p=0.0015). Forty-nine out of 54 patients with periapical destruction had adjacent mucosal swelling in the maxillary sinus, but only 15 of these patients satisfied the criteria for sinusitis. Conclusion: The present study confirms the close relationship between odontogenic infections and unilateral maxillary sinusitis.

  • 245. Videhult, Pernilla
    et al.
    Laurell, Göran
    Umeå University, Faculty of Medicine, Clinical Sciences, Otorhinolaryngology.
    Wallin, Inger
    Ehrsson, Hans
    Kinetics of Cisplatin and its monohydrated complex with sulfur-containing compounds designed for local otoprotective administration2006In: Experimental biology and medicine (Maywood, N.J.: Print), ISSN 1535-3702, E-ISSN 1535-3699, Vol. 231, no 10, p. 1638-45Article in journal (Refereed)
  • 246. Videhult Pierre, Pernilla
    et al.
    Engmér, Cecilia
    Wallin, Inger
    Laurell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Ehrsson, Hans
    High concentrations of thiosulfate in scala tympani perilymph after systemic administration in the guinea pig2009In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 129, no 2, p. 132-137Article in journal (Refereed)
    Abstract [en]

    CONCLUSION: High concentrations of the antioxidant thiosulfate reach scala tympani perilymph after i.v. administration in the guinea pig. Thiosulfate concentrations in perilymph remain elevated longer than in blood. This warrants further studies on the possibility of obtaining otoprotection by thiosulfate administration several hours before that of cisplatin without compromising the anticancer effect caused by cisplatin inactivation in the blood compartment.

    OBJECTIVE: Thiosulfate may reduce cisplatin-induced ototoxicity, presumably by oxidative stress relief and formation of inactivate platinum complexes. This study aimed to explore to what extent thiosulfate reaches scala tympani perilymph after systemic administration in the guinea pig.

    MATERIALS AND METHODS: Scala tympani perilymph (1 microl) was aspirated from the basal turn of each cochlea up to 3 h after thiosulfate administration (103 mg/kg b.w., i.v.). Blood samples were also taken. Thiosulfate was quantified by HPLC and fluorescence detection.

    RESULTS: Substantial thiosulfate concentrations were found in perilymph. The area under the concentration-time curve for thiosulfate in perilymph and blood was 3100 microMxmin and 6300 microMxmin, respectively. The highest thiosulfate concentrations in perilymph were found at the first sampling at about 10 min. Due to a more rapid elimination from blood, perilymph concentrations exceeded those of blood towards the end of the experiment.

  • 247.
    Werner, Mimmi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Hair cell regeneration in vestibular epithelia: a study in an in vitro model2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background

    Hair cells (HCs) are the sensory receptors in both the auditory and the vestibular organs of the inner ear. Supporting cells (SCs) are non-sensory cells embracing the HCs. Injuries of the HCs by aging, acoustic trauma or ototoxic drugs (mainly aminoglycosides, e.g. gentamicin) and cisplatin, often cause permanent impairment of hearing and balance. Birds and amphibians can regenerate their auditory and vestibular HCs after injury through proliferation of SCs or direct transdifferentiation of a SC into a HC. For mammals this ability is limited and spontaneous HC regeneration occurs only in the vestibular sensory epithelia. The utricle is one of the five vestibular organs and contributes to our balance by registering linear acceleration and head tilts. The aim of this PhD thesis was to investigate morphological and morphometric events during spontaneous HC regeneration following gentamicin exposure in neonatal rat utricular explants.

    Methods

    Long-term organ culture of macula utriculi, which is stable and reproducible for up to 28 days in vitro (DIV), was used in all papers in the thesis. HC damage was induced by gentamicin. On 2 DIV the explanted utricular maculae were divided into two groups, a control group and a gentamicin-exposed group. In the latter group macular explants were exposed to gentamicin for 48 hours during 2-3 DIV and then allowed to recover. Morphologic and morphometric evaluations were done from utricles harvested at various time points during 28 DIV. Imaging techniques used were light microscopy, including immunohistochemistry, and transmission electron microscopy.

    Results

    In the control group the epithelia were well preserved with a slight decline in HC density after 14 DIV. In the gentamicin-exposed group there was an initial substantial decline in HC density and thereafter the proportion of HCs in relation to SCs increased significantly. Using BrdU as a proliferation marker and myosin 7a as a HC marker, we found no cells that were double marked. At the ultrastructural level, the apical occlusion of the explanted epithelia was intact in both the control and the gentamicin exposed group during the entire in vitro period. Cells that seemed to be in a transitional state, transforming from SCs into HCs were observed in the gentamicin-exposed group. These cells had cytoplasmic extensions basally i.e. foot processes, an assembly of mitochondria basally in the cell or in these foot processes, and often apical SC extensions covering the HC. HCs classified as transitional cells had an increased number of SC connections to their basal parts compared to mature HCs.

    Conclusions 

    In these neonatal rat utricular explants:

    - The morphological structure of the sensory epithelia was well preserved during long-term culture.

    - The renewal of hair cells after gentamicin exposure occurred through direct transdifferentiation of supporting cells into hair cells.

    - There was also a proliferative response by the supporting cells, but this supporting cell proliferation did not contribute to the generation of new hair cells.

    - Cells in a transitional state, showing a characteristic morphology, were observed during the process of transdifferentiation from supporting cells into hair cells.

    - The tight junctional seal of the epithelia stayed morphologically intact also after gentamicin exposure.

    - Gap junctions were observed in between supporting cells but not found in between hair cells and supporting cells or between transitional cells and supporting cells.

  • 248.
    Werner, Mimmi
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Canlon, Barbara
    Viberg, Agneta
    Van De Water, Thomas R.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Berggren, Diana
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Role of Transdifferentiation/Proliferation in Vestibular Hair Cell Renewal within Ototoxin-challenged Utricle ExplantsManuscript (preprint) (Other academic)
  • 249.
    Werner, Mimmi
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Van De Water, Thomas R.
    Andersson, Therese
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Arnoldsson, Göran
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Berggren, Diana
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Morphological and morphometric characteristics of vestibular hair cells and support cells in long term cultures of rat utricle explants2012In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 283, no 1-2, p. 107-116Article in journal (Refereed)
    Abstract [en]

    A method for long term culture of utricular macula explants is demonstrated to be stable and reproducible over a period of 28 days in vitro (DIV). This culture system for four-day-old rat utricular maculae is potentially suitable for studies of hair cell loss, repair and regeneration processes as they occur in post-natal mammalian inner ear sensory epithelia. The cellular events that occur within utricular macula hair cell epithelia during 28 days of culture are documented from serial sections. Vestibular hair cells (HCs) and supporting cells (SCs) were systematically counted using light microscopy (LM) and the assistance of morphometric computer software. Ultrastructural observations were made with transmission electron microscopy (TEM) for describing the changes in the fine detailed morphological characteristics that occurred in the explants related to time in vitro. After 2 DIV the density of HCs was 77%, at 21 DIV it was 69%, and at 28 DIV it was 52% of HCs present at explantation. Between 2 DIV and 28 DIV there was a 1.7% decrease of the vestibular macula HC density per DIV. The corresponding decrease of SC density within the utricular explants was less than 1% per DIV. The overall morphology of the epithelia, i.e. relationship of HCs to SCs, was well preserved during the first two weeks in culture. After this time a slight deterioration of the epithelia was observed and although type I and type II HCs were identified by TEM observations, these two HC types could no longer be distinguished from one another by LM observations. In preparations cultured for 21 DIV, SC nuclei were located more apical and further away from the basal membrane compared to their position in macula explants fixed immediately after dissection. The loss of cells that occurred was probably due to expulsion from the apical (i.e. luminal) surface of the sensory epithelia, but no lesions of the apical lining or ruptures of the basal membrane were observed. There were no significant changes in the volume of the vestibular HC comprising macular epithelium during the observation period of 28 DIV.

  • 250.
    Werner, Mimmi
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Van De Water, Thomas R.
    Hammarsten, Peter
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Arnoldsson, Göran
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Berggren, Diana
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Morphological and morphometric characterization of direct transdifferentiation of support cells into hair cells in ototoxin-exposed neonatal utricular explants2015In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 321, p. 1-11Article in journal (Refereed)
    Abstract [en]

    We have studied aminoglycoside-induced vestibular hair-cell renewal using long-term culture of utricular macula explants from 4-day-old rats. Explanted utricles were exposed to 1 mM of gentamicin for 48 h, during 2nd and 3rd days in vitro (DIV), and then recovering in unsupplemented medium. Utricles were harvested at specified time points from the 2nd through the 28th DIV. The cellular events that occurred within hair cell epithelia during the culture period were documented from serial sectioned specimens. Vestibular hair cells (HCs) and supporting cells (SCs) were systematically counted using light microscopy (LM) with the assistance of morphometric software. Ultrastructural observations were made from selected specimens with transmission electron microscopy (TEM). After 7 DIV, i.e. four days after gentamicin exposure, the density of HCs was 11% of the number of HCs observed in non-gentamicin-exposed control explants. At 28 DIV the HC density was 61% of the number of HCs observed in the control group explant specimens. Simultaneously with this increase in HCs there was a corresponding decline in the number of SCs within the epithelium. The proportion of HCs in relation to SCs increased significantly in the gentamicin-exposed explant group during the 5th to the 28th DIV period of culture. There were no significant differences in the volume estimations of the gentamicin-exposed and the control group explants during the observed period of culture. Morphological observations showed that gentamicin exposure induced extensive loss of HCs within the epithelial layer, which retained their intact apical and basal linings. At 7 to 14 DIV (i.e. 3-11 days after gentamicin exposure) a pseudostratified epithelium with multiple layers of disorganized cells was observed. At 21 DIV new HCs were observed that also possessed features resembling SCs. After 28 DIV a new luminal layer of HCs with several layers of SCs located more basally characterized the gentamicin-exposed epithelium. No mitoses were observed within the epithelial layer of any explants. Our conclusion is that direct transdifferentiation of SCs into HCs was the only process contributing to the renewal of HCs after gentamicin exposure in these explants of vestibular inner ear epithelia obtained from the labyrinths of 4-day-old rats.

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