liu.seSearch for publications in DiVA
Change search
Refine search result
1234 51 - 100 of 166
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 51.
    Harder, Henrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences.
    Mäki-Torkko, Elina
    Linköping University, Department of Clinical and Experimental Medicine, Technical Audiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology in Linköping.
    Lyxell, Björn
    Linköping University, The Swedish Institute for Disability Research. Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology in Norrköping.
    Speech-perception in elderly implant recipients2010In: 11th International Conference on Cochlear Implants and Other Implantable Auditory Technologies, 2010, p. 339-Conference paper (Other academic)
  • 52.
    Harder, Lena
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of ENT - Head and Neck Surgery UHL.
    Sarberg, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Harder, Henrik
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of ENT - Head and Neck Surgery UHL.
    Relationship between restless legs syndrome and snoring during pregnancy2008In: JOURNAL OF SLEEP RESEARCH,ISSN 0962-1105: Volume 17, 2008, Vol. 17, p. 114-114Conference paper (Refereed)
  • 53.
    Harder, Lena
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of ENT - Head and Neck Surgery UHL.
    Sarberg, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Harder, Henrik
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of ENT - Head and Neck Surgery UHL.
    Snoring during pregnancy and its relation to pre-eclampsia2008In: Journal of Sleep Research, ISSN 0962-1105, E-ISSN 1365-2869, Vol. 17, no Supplements 1, p. 159-159Article in journal (Refereed)
    Abstract [en]

    Objective: Does snoring during pregnancy influence development of pre-eclampsia?

    Method: Five hundred and three pregnant women were presented a questionnaire concerning snoring, daytime sleepiness and edema. Epworth Sleepiness score (ESS) and symptoms of restless legs syndrome were also included. The questionnaire was presented in the 1st, 2nd and 3rd trimester and blood pressure was recorded. Women snoring often-always at visit 2 and/or 3 were denoted habitual snorers, those snoring never-seldom non-snorers and there was also a category occasional snorers. Habitual snorers were offered a sleep respiratory recording (Embletta); 34 volunteered.

    Results: 36/503 women (7,2%) snored habitually already at the first visit. At the end of pregnancy the fraction had increased to 19,5%. At the first visit BMI of habitual snorers was 25,3 compared to 22,9 for non-snorers (s.), but there was no difference concerning increase during pregnancy. Habitual snorers reported more edema at visit 2 and 3, higher scores in morning and daytime tiredness and ESS score compared to non-snorers at all visits (s.). Their systolic blood pressure increased more (s.) already between 1st and 2nd visit. Weight and Apgar scores of the newborns showed no difference. Pre-eclampsia developed in 18 women, twice as common among habitual snorers than in those snoring never-occasionally (n.s.). Their snoring scores were higher at all visits; the greatest difference at visit 3 (P50,058). Their diastolic pressure increased more already at the 2nd visit (s.), they had more edema and higher increase in BMI (s.). ESS and tiredness scores did not differ. 9/34 sleep recordings showed supine AHI 45. Two women who later developed pre-eclampsia were recorded; both had supine AHI 45.

    Conclusions: Habitual snorers had higher BMI from start, more daytime tiredness, higher ESS scores and their diastolic blood pressure increased more already during early pregnancy. Preeclampsia was twice as common among snorers as non-snorers; not significant due to the low number of cases. The relation between pre-eclampsia and snoring therefore remains elusive.

  • 54.
    Hedin-Skogman, Barbro
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Croner, Stefan
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Ödkvist, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of ENT - Head and Neck Surgery UHL.
    Acute facial palsy in children - a 2-year follow-up study with focus on Lyme neuroborreliosis2003In: International Journal of Pediatric Otorhinolaryngology, ISSN 0165-5876, Vol. 67, no 6, p. 597-602Article in journal (Refereed)
    Abstract [en]

    Objective: Acute facial palsy in children is believed to be a rather benign neurological condition. Follow-up-studies are sparse, especially including a thorough otoneurological re-examination. The aim of this study was to examine children with a history of facial palsy in order to register the incidence of complete recovery and the severity and nature of sequelae. We also wanted to investigate whether there was a correlation between sequelae and Lyme Borreliosis, treatment or other health problems.

    Methods: Twenty-seven children with a history of facial palsy were included. A re-examination was performed by an Ear-Nose-Throat (ENT) specialist 1–2.9 years (median 2) after the acute facial palsy. The otoneurological examination included grading the three branches of the facial nerve with the House-Brackman score, otomicroscopy and investigation with Frenzel glasses. A paediatrician interviewed the families. Medical files were analysed.

    Result: The incidence of complete recovery was 78% at the 2-year follow-up. In six out of 27 children (22%), the facial nerve function was mildly or moderately impaired. Four children reported problems with tear secretion and pronunciation. There was no correlation between sequelae after the facial palsy and gender, age, related symptoms, Lyme neuroborreliosis (NB), treatment, other health problems or performance.

    Conclusion: One fifth of children with an acute facial palsy get a permanent dysfunction of the facial nerve. Other neurological symptoms or health problems do not accompany the sequelae of the facial palsy. Lyme NB or treatment seems to have no correlation to clinical outcome. Factors of importance for complete recovery after an acute facial palsy are still not known.

  • 55. Hellquist, Henrik B.
    et al.
    Sundelin, Kaarina
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of ENT - Head and Neck Surgery UHL.
    DiBacco, A.
    Department of Pathology and Laboratory Medicine, European Institute of Oncology, Milan University School of Medicine, Milan, Italy.
    Tytor, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery . Linköping University, Faculty of Health Sciences.
    Manzotti, Michela
    Department of Pathology and Laboratory Medicine, European Institute of Oncology, Milan University School of Medicine, Milan, Italy.
    Viale, Giuseppe J.
    Department of Pathology and Laboratory Medicine, European Institute of Oncology, Milan University School of Medicine, Milan, Italy.
    Tumour growth fraction and apoptosis in salivary gland acinic cell carcinomas: Prognostic implications of Ki-67 and bcl-2 expression and of in situ end labelling (TUNEL)1997In: The Journal of Pathology, ISSN 0031-3025, Vol. 181, no 3, p. 323-329Article in journal (Refereed)
    Abstract [en]

    bcl-2 protein and Ki-67 (MIB-1) were studied in 32 acinic cell carcinomas (ACCs), all with a minimum of 5 years' clinical follow-up. Tumour apoptosis was evaluated by TdT dUTP nick end labelling (TUNEL) and by morphological criteria. Five patients died of their disease. Patients with stage I tumours had significantly better survival compared with other stages (P<0·05). Patients with MIB-1-negative tumours had significantly better survival than patients with MIB-1-positive tumours (P=0·05). This study confirms a previous report that MIB-1 is an independent prognostic factor for survival in patients with ACC. Stage I tumours had high expression of bcl-2 protein, but there was no difference when compared with other stages. TUNEL positivity was most prevalent in stage I tumours, compared with stages II, III, and IV (P<0·05), probably indicating more apoptosis. This could imply a capacity of stage I tumours ('early tumours') for early selection of tumour cells for elimination by apoptosis. There was no significant difference between expression of bcl-2 and TUNEL, between these parameters and clinical outcome, or between any parameter and morphological subclassification. We conclude that MIB-1 has prognostic value in ACC. Clinical staging, bcl-2, and TUNEL are also potentially useful as prognostic markers.

  • 56.
    Hemlin, Claes
    et al.
    Aleris Sabbatsberg Hospital, Stockholm.
    Sunnergren, Ola
    County Hospital Ryhov, Jönköping.
    Hultcrantz, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of ENT - Head and Neck Surgery UHL.
    Ericsson, Elisabeth
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of ENT - Head and Neck Surgery UHL.
    Hessén Söderman, Anne- Charlotte
    Karolinska University Hospital.
    Roos, Kristian
    Capio Lundby Hospital, Göteborg.
    Passmark, H
    Stalfors, Joacim
    Sahlgrenska University Hospital, Göteborg.
    A Patient questionnaire can give valid information on the prescence of morbidity after tonaillar surgery - results of a validation study2012Conference paper (Other academic)
  • 57.
    Hessen Soderman, Anne-Charlotte
    et al.
    Karolinska University Hospital.
    Ericsson, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of ENT - Head and Neck Surgery UHL.
    Hemlin, Claes
    Karolinska Institute.
    Hultcrantz, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of ENT - Head and Neck Surgery UHL.
    Mansson, Ingemar
    Sahlgrens University Hospital.
    Roos, Kristian
    Capio Lundby.
    Stalfors, Joacim
    Sahlgrens University Hospital.
    Reduced Risk of Primary Postoperative Hemorrhage After Tonsil Surgery in Sweden: Results from the National Tonsil Surgery Register in Sweden Covering More Than 10 Years and 54,696 Operations2011In: The Laryngoscope, ISSN 0023-852X, E-ISSN 1531-4995, Vol. 121, no 11, p. 2322-2326Article in journal (Refereed)
    Abstract [en]

    Objectives/Hypothesis: To analyze the incidence of primary bleeding following tonsil surgery and to evaluate risk factors. less thanbrgreater than less thanbrgreater thanStudy Design: Register study of the results from the National Tonsil Surgery Register in Sweden covering the period 1997 to 2008 and 54,696 operations. less thanbrgreater than less thanbrgreater thanMethods: Data were collected by means of three questionnaires, two filled in by professionals and one 6 months post-operatively by the patient/parent. less thanbrgreater than less thanbrgreater thanResults: A total of 719 patients experienced primary postoperative bleeding during the hospital stay (1.3%). A number of independent factors were correlated with decreased risk of post-tonsillectomy hemorrhage: younger age (P andlt; .0001), female sex (P andlt; .0001), type of surgery (tonsillotomy) (P = .0006), and surgery performed on a day-surgery basis (P andlt; .0001). Indication for surgery and number of operations performed at the department did not correlate with postoperative bleeding risk. A significant decrease in primary postoperative hemorrhage rate from 2% to 0.96% was found during the study period. less thanbrgreater than less thanbrgreater thanConclusions: Primary hemorrhage following tonsil surgery is rare. During the study period, a significant decrease in primary bleeding rates occurred. The changes in practice with an increasing proportion of day-surgery cases and tonsillotomy have contributed to the reduced risk, but cannot completely explain the reduction.

  • 58.
    Hessén Söderman, Anne- Charlotte
    et al.
    Karolinska University Hospital.
    Ericsson, Elisabeth
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of ENT - Head and Neck Surgery UHL.
    Hemlin, Claes
    Aleris Sabbatsberg Hospital, Stockholm.
    Hultcrantz, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of ENT - Head and Neck Surgery UHL.
    Roos, Kristian
    Capio Lundby Hospital, Göteborg.
    Sunnergren, Ola
    County Hospital Ryhov, Jönköping.
    Stalfors, Joacim
    Sahlgrenska University Hospital, Göteborg.
    Posttonsillectomy haemorrhage rates related to surgical technique.2012Conference paper (Other academic)
  • 59.
    Hultcrantz, Elisabeth
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery . Östergötlands Läns Landsting, Reconstruction Centre, Department of ENT - Head and Neck Surgery UHL.
    Sudden deafness - A critical evaluation of pathogenesis and 'cure'1999In: OTO-RHINO-LARYNGOLOGIA NOVA, ISSN 1014-8221, Vol. 9, no 5, p. 178-188Article in journal (Refereed)
    Abstract [en]

    Objective: To discuss the possible etiology, pathogenesis and 'cure' of idiopathic sudden deafness (SD). Method: A review was made of different methods for the study of inner-ear physiology, especially its microcirculation, relating them to clinical evaluation and praxis for SD. Results: Cochlear blood flow (CBF) can be measured quantitatively with the microsphere method in animals. Direct qualitative measurements can be performed using the laser Doppler method. The CBF is partly autoregulated, but to a lesser degree than cerebral blood flow. Sympathetic stimulation decreases CBF up to 25%. Noise does not influence total CBF but seems to reduce blood flow in the lateral wall. Nicotinic acid, hemodilution and osmotic drugs increase the CBF proportionally. Carbogen increases the CBF but also creates acidosis. Treating patients with SD in accordance with these findings does not show any convincing effect compared to no treatment. Conclusion: More and more diseases have been identified which can have SD as a symptom. It is important to investigate to identify these treatable cases. Idiopathic cases should not be exposed to hazardous systemic medication or surgery. Local treatment through the round window will be the treatment modality for the future, but more basic research is necessary. Copyright (C) 2000 S. Karger AG, Basel.

  • 60.
    Hultcrantz, Elisabeth
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery . Linköping University, Faculty of Health Sciences.
    Ericsson, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery . Linköping University, Faculty of Health Sciences.
    Pediatric Tonsillotomy with Radiofrequency Technique: Less Morbidity and Pain2004In: The Laryngoscope, ISSN 0023-852X, Vol. 114, no 5, p. 871-877Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To compare two techniques for pediatric tonsil surgery with respect to pain and postoperative morbidity. The two methods were the partial tonsil resection using radiofrequency (RF) technique (tonsillotomy [TT]) versus traditional tonsillectomy (TE).

    STUDY DESIGN: Prospective clinical randomized study in one tertiary care ENT clinic and two secondary care clinics.

    METHOD: One hundred fifty children, between 5 and 15 years of age, were randomized to either TT with RF using the Surgitron Ellman, 1.7 MHz, or regular TE. Randomization was performed from the waiting list, including children with both a history of obstructive problems and recurrent tonsillitis. The TT was performed with a specially made sling electrode using a cut/coagulation mode.

    RESULTS: Forty-nine children were operated on with TT and 43 with TE. There was significantly less bleeding in the TT group, although two cases of primary postoperative bleeding occurred among the TT children and one in the TE group. The pain recordings showed significantly less pain for the TT children from the second hour postoperatively onward, and the TT children were pain free and in school 3 days earlier than the TE group. The TT group had less need of the prescribed drugs (diclofenac and paracetamol). After 9 days, 73% of the TT children were completely healed, but only 31% of the TE children. By that time, the TE children had lost a mean of 660 g, and the TT children had gained 127 g. The effect on snoring was the same for both groups.

    CONCLUSION: RF appears to be a safe and reliable method for tonsil surgery with much less postoperative morbidity than regular TE.

  • 61.
    Hultcrantz, Elisabeth
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of ENT - Head and Neck Surgery UHL.
    Ericsson, Elisabeth
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of ENT - Head and Neck Surgery UHL.
    Hemlin, Claes
    Aleris Sabbatsberg Hospital, Stockholm.
    National Guidelines for Tonsillotomy in children in Sweden.2012Conference paper (Other academic)
  • 62.
    Hultcrantz, Elisabeth
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of ENT - Head and Neck Surgery UHL.
    Ericsson, Elisabeth
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of ENT - Head and Neck Surgery UHL. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Hemlin, Claes
    Aleris specialistvård Sabbatsberg, Stockholm.
    Eggertsen, Robert
    Avd. för Samhällsmedicin och folkhälsa/allmänmedicin, Göteborgs Universitet.
    Lundeborg-Hammarström, Inger
    Linköping University, Department of Clinical and Experimental Medicine, Speech and Language Pathology. Linköping University, Faculty of Health Sciences.
    Marcusson, Agneta
    Östergötlands Läns Landsting, Sinnescentrum, Department of Oral Surgery UHL.
    Proczkowska-Björklund, Marie
    Barn- och ungdomspsykiatri, Psykiatriska kliniken, Höglandet Eksjö/Nässjö.
    Stjernquist-Desatnik, Anna
    Öron-näsa-hals-kliniken, Universitetssjukhuset Lund.
    Zettergren-Wijk, Lena
    Avdelningen för tandreglering, Folktandvården Gävleborg AB, Gävle.
    Moa, Gunnar
    Projektledare Nationella medicinska indikationer.
    Törnqvist, Helene
    Projektledare Nationella medicinska indikationer.
    Indikation för tonsillotomi på barn och ungdomar2011Report (Other academic)
  • 63.
    Hultcrantz, Elisabeth
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of ENT - Head and Neck Surgery UHL.
    Harder, Lena
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of ENT - Head and Neck Surgery UHL.
    Loord, Helena
    Östergötlands Läns Landsting, Reconstruction Centre, Department of ENT - Head and Neck Surgery UHL.
    Käll, Lars-Göran
    Östergötlands Läns Landsting, Reconstruction Centre, Department of ENT - Head and Neck Surgery VHN.
    Ydreborg, Kjell
    ORL-Clinic, Ryhov Hospital, Jönköping.
    Wallberg, Staffan
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences.
    Svanborg, Eva
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Neurophysiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurophysiology UHL.
    Long-term effects of radiofrequency ablation of the soft palate on snoring.2010In: European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery, ISSN 1434-4726, Vol. 267, no 1, p. 137-142Article in journal (Refereed)
    Abstract [en]

    The objective of the study was to evaluate short- and long-term effects of radiofrequency treatment of the soft palate on snoring. Twenty-nine patients with habitual snoring were studied prospectively and treated up to four times at 4-6 week intervals with an Ellman Surgitrone((R)). Electromyography (EMG) of m. palatoglossus was performed in ten patients. Patients and partners evaluated snoring, sleep quality and daytime sleepiness 1 week preoperatively, 6 months and 3-4 years postoperatively. Snoring was reduced postoperatively (P < 0.0001). Sleep time increased, daytime sleepiness was reduced, and the partners slept better after 6 months. However, 3-4 years postoperatively only 25% of patients were satisfied. Another 25% had received additional treatment. EMG was normal in 6/10 patients preoperatively. They all continued to snore postoperatively. Four patients had pathological EMGs; three were responders. In conclusion, radiofrequency treatment for snoring may lead to long-term improvement in one out of four cases. Pre-evaluation with EMG may predict the outcome.

  • 64.
    Hultcrantz, Elisabeth
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of ENT - Head and Neck Surgery UHL.
    Harder, Lena
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of ENT - Head and Neck Surgery UHL.
    Zetterlund, Eva-Lena
    Östergötlands Läns Landsting, Anaesthesiology and Surgical Centre, Department of Anaesthesiology and Intensive Care VHN.
    Roberg, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of ENT - Head and Neck Surgery UHL.
    To treat snoring with nasal steroids - effects on more than one level?2010In: ACTA OTO-LARYNGOLOGICA, ISSN 0001-6489, Vol. 130, no 1, p. 124-131Article in journal (Refereed)
    Abstract [en]

    Conclusion. An inflammatory swelling in the uvula and nose due to vibration might be a contributing factor in snoring. The presence of corticosteroid receptors in the uvula indicates the possibility for treatment with local steroids. Use of mometasone furoate (MF) for 3 months reduced snoring and related symptoms in some patients. Objective. To investigate the effect of a nasal steroid, MF, on snoring and related discomfort. Subjects and methods. In the first part of the study, uvular and nasal biopsies from six patients with social snoring were examined using immunohistochemistry to evaluate whether corticosteroid receptors were present. Then 100 snoring patients were invited to participate in the second part of the study. In all, 72 men and 22 women with a mean age of 47 years and BMI 27 answered a questionnaire about symptoms, had ENT status assessed and reported sleep and related variables for a 7 day period. After randomization to placebo or MF, they used a nasal spray for 3 months at a dosage of 200 mu g. Thereafter the procedure was repeated. Results. Corticosteroid receptors were present in the mucous membranes and around the blood vessels in all uvulas examined. A total of 84 patients were evaluated. No decrease in mean snoring score was seen. Daytime sleepiness showed a slight improvement in the MF group and partners were less disturbed. Minor side effects were equal for both groups.

  • 65.
    Hultcrantz, Elisabeth
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of ENT - Head and Neck Surgery UHL.
    Lofstrand Tidestrom, B
    Uppsala University.
    The development of sleep disordered breathing from 4 to 12 years and dental arch morphology2009In: INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY, ISSN 0165-5876, Vol. 73, no 9, p. 1234-1241Article in journal (Refereed)
    Abstract [en]

    Objective: To track the development of sleep disordered breathing (SDB) as well as dento-facial morphology in cohort of children by having them complete a questionnaire at ages 4, 6 and 12. Clinical examination, sleep studies (at ages 4 and 12) and orthodontic evaluation were carried out on all who were reported to snore regularly and children who did not snore at all. Results: Out of the original group of 615 children, 64% (393) answered the inquiry on all three occasions. Of those, 27 snored regularly and 231 did not snore at all at the age of 12. There were differences between those groups on all answers, especially prevalence of oral breathing: 78% versus 5% (p andlt; 0.001). The prevalence of OSA decreased from 3.1% at the age of 4 to 0.8% at age 12 and the severity decreased from a mean AHI 14.8 at 4 to a mean AHI of 1.95 at age 12. The minimum prevalence of snoring regularly was estimated to 4.2% at 12 years compared to 5.3% at 4, calculated for the original cohort of 644 children. The odds for a child who snored regularly at 4 or 6 years to be snoring regularly also at age 12 was 3.7 times greater than fora not snoring child in spite of surgery (OR 3.7, 95% CI 2.4-5.7). 63 children had undergone surgery due to snoring by age 12. 14 of them never snored and 17 snored regularly at the age 12. The dental arch was narrower in the children snoring regularly at 4, 6 and 12 years compared to not snoring children. Cross-bites were more common among snoring children than among non-snoring children, at 4 and 6 as well as at 12. Conclusion: The prevalence of regular snoring is about the same from 4 to 12 years independent of surgery, but the prevalence of OSA decreased considerably. The children snoring regularly generally have a narrower maxilla compared to children not snoring. Surgery in young children is necessary but "cures" the snoring only temporary.

  • 66.
    Hultcrantz, Elisabeth
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of ENT - Head and Neck Surgery UHL.
    Nosrati-Zarenoe, Ramesh
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of ENT - Head and Neck Surgery UHL.
    Corticosteroid treatment of Idiopathic Sudden Sensorineural Hearing Loss. Part 2: a meta-analysis of a RCT and the Swedish national databaseManuscript (preprint) (Other academic)
    Abstract [en]

    Objective: A randomized placebo-controlled study (paper ON-11-66) has demonstrated no effect of Prednisolone in customary dosage on Idiopathic Sudden Sensorineural Hearing Loss (ISSNHL). The aim of the present paper is to analyze a larger patient group by meta-analysis of data from the RCT together with corresponding material drawn from the Swedish national database for ISSNHL.

    Study design: Meta-analysis of data from a RCT and a Swedish national database for ISSNHL.

    Patients: Data from 192 patients, 18–80 years, with ISSNHL was available. All had a hearing loss of at least 30 dB measured as PTA in the three most affected contiguous frequencies. Patients had been enrolled within one week after onset and evaluated by audiograms after three months.

    Intervention: 45/99 (RCT) and 54/99 (the database) had been treated with Prednisolone in tapering doses from 60 mg daily and 42/93 with placebo (RCT) or 51/93 with no treatment (the database). Primary outcome was the mean hearing improvement on day 90 for the different groups. A mean difference of >10 dB improvement was needed to demonstrate treatment effect of Prednisolone compared to placebo/no treatment.

    Results: No significant difference was seen between the Prednisolone group and placebo/no treatment (p=0.06). Total recovery was 38% in Prednisolone group, 40% in the placebo and 14% in the no treatment group. Vertigo at the onset of hearing loss and age had a negative prognostic value equally in all groups and signs of inflammation had a positive.

    Conclusion: Prednisolone in customary dosage does not influence recovery after ISSNHL.

  • 67.
    Hydén, Dag
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of ENT - Head and Neck Surgery UHL.
    Arlinger, Stig
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery . Linköping University, Faculty of Health Sciences.
    On light-induced sneezing2009In: EYE, ISSN 0950-222X, Vol. 23, no 11, p. 2112-2114Article in journal (Refereed)
    Abstract [en]

    Purpose To investigate whether the tickling inside the nose before a light-induced sneeze in susceptible individuals is correlated to a recordable local activity or not. Methods Seven healthy volunteers, three with a history of light-induced sneezing, were stimulated with stroboscopic light or a strong halogen lamp. Recording was done with an evoked potential averaging technique via intranasal electrodes placed in such a way that they substantially reduced the strong electrical response from the retina. Results Despite an adequate light stimulus, no reproducible electrical activity could be recorded from any of the members in any experiment. Conclusion Light-induced sneezing is presumably a central phenomenon. The electrical activity travels through the optic pathways straight to the trigeminal nucleus and the tickling is a referred sensation. A genetic variation in the distance between the optic pathways (colliculus superior) and the mesencephalic part of the trigeminal nucleus may explain why light-induced sneezing is more common in certain families and races.

  • 68.
    Hällgren, Mathias
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Technical Audiology. Linköping University, Faculty of Health Sciences.
    Larsby, Birgitta
    Linköping University, Department of Clinical and Experimental Medicine, Technical Audiology. Linköping University, Faculty of Health Sciences.
    Lyxell, Björn
    Linköping University, Department of Behavioural Sciences and Learning. Linköping University, Faculty of Arts and Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of ENT - Head and Neck Surgery UHL.
    Arlinger, Stig
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences.
    Cognitive effects in dichotic speech testing in elderly persons2001In: Ear and Hearing, ISSN 0196-0202, Vol. 22, no 2, p. 120-129Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To study the effect of chronologic age on central auditory functions using dichotic speech tests and to study whether and how the age effect in dichotic listening is related to cognitive ability.

    DESIGN: Dichotic speech tests and cognitive tests were performed on 30 bilaterally hearing-impaired subjects, with a pure-tone average better than 50 dB HL. They were between 42 and 84 yr of age and were divided into an older and a younger group comprising 15 subjects each. The dichotic test material were digits, low-redundancy sentences and consonant-vowel syllables. The subjects reported stimuli heard in both ears (free report) or in one ear (directed report to left or right ear). The cognitive test battery comprised tests focusing on short-term memory, verbal information-processing speed and phonologic processing.

    RESULTS: A decreased overall performance in all dichotic speech tests was observed in the older group. In the syllable test the older subjects showed poorer results when focusing on the stimuli heard in the left ear, as compared with when focusing on stimuli heard in the right ear, whereas the younger group showed almost equal results for left- and right ear-focusing conditions. An age effect was also seen in reaction times recorded in the cognitive tests and in the scores of the reading span test. These cognitive parameters correlate with the results of the dichotic test when focusing to the left, but not when focusing to the right in the directed report condition. In the free report condition the overall performance showed a high correlation with cognitive test parameters.

    CONCLUSIONS: Effects of chronologic age in dichotic speech tests in the elderly have been verified. The degree of effect is dependent on test material, way of reporting and focusing condition. The different listening tasks in dichotic tests put different demands on cognitive ability shown by a varying degree of correlations between cognitive function and dichotic test parameters. Also, the results indicate a strong connection between age-related cognitive decline in the elderly and problems to perceive stimuli presented to the left ear.

  • 69.
    Hällgren, Mathias
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Technical Audiology . Linköping University, Faculty of Health Sciences.
    Larsby, Birgitta
    Linköping University, Department of Clinical and Experimental Medicine, Technical Audiology . Linköping University, Faculty of Health Sciences.
    Lyxell, Björn
    Linköping University, Department of Behavioural Sciences and Learning. Linköping University, Faculty of Arts and Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of ENT - Head and Neck Surgery UHL.
    Arlinger, Stig
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery . Linköping University, Faculty of Health Sciences.
    Evaluation of a cognitive test battery in young and elderly normal-hearing and hearing-impaired persons2001In: Journal of the American Academy of Audiology, ISSN 1050-0545, Vol. 12, no 7, p. 357-370Article in journal (Refereed)
    Abstract [en]

    A cognitive test battery sensitive to processes important for speech understanding was developed and investigated. Test stimuli are presented as text or in an auditory or audiovisual modality. The tests investigate phonologic processing and verbal information processing. Four subject groups, young/elderly with normal-hearing and young/elderly with hearing impairment, each including 12 subjects, participated in the study. The only significant effect in the text modality was an age effect in the speed of performance, seen also in the auditory and audiovisual modalities. In the auditory and audiovisual modalities, the effects of hearing status and modality were seen in accuracy parameters. Interactions between hearing status and modality, both in accuracy and in reaction times, show that hearing-impaired subjects have difficulties without visual cues. Performing the test battery in noise made the tasks more difficult, especially in the auditory modality and for the elderly, affecting both accuracy and speed. Test-retest measurements showed learning effects and a modality-dependent variability. The test battery has proven useful in assessing the relative contribution of different input signals and the effects of age, hearing impairment, and visual contribution on functions important for speech processing.

  • 70.
    Jain, Mayur Vilas
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Paczulla, Anna M.
    University of Tubingen, Germany .
    Klonisch, Thomas
    University of Manitoba, Canada .
    Dimgba, Florence N.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Rao, Sahana
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Roberg, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology in Linköping.
    Schweizer, Frank
    University of Manitoba, Canada .
    Lengerke, Claudia
    University of Tubingen, Germany .
    Davoodpour, Padideh
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Palicharla, Vivek R.
    Centre DNA Fingerprinting and Diagnost CDFD, India .
    Maddika, Subbareddy
    Centre DNA Fingerprinting and Diagnost CDFD, India .
    Los, Marek Jan
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Interconnections between apoptotic, autophagic and necrotic pathways: implications for cancer therapy development2013In: Journal of Cellular and Molecular Medicine (Print), ISSN 1582-1838, E-ISSN 1582-4934, Vol. 17, no 1, p. 12-29Article, review/survey (Refereed)
    Abstract [en]

    The rapid accumulation of knowledge on apoptosis regulation in the 1990s was followed by the development of several experimental anticancer- and anti-ischaemia (stroke or myocardial infarction) drugs. Activation of apoptotic pathways or the removal of cellular apoptotic inhibitors has been suggested to aid cancer therapy and the inhibition of apoptosis was thought to limit ischaemia-induced damage. However, initial clinical studies on apoptosis-modulating drugs led to unexpected results in different clinical conditions and this may have been due to co-effects on non-apoptotic interconnected cell death mechanisms and the yin-yang role of autophagy in survival versus cell death. In this review, we extend the analysis of cell death beyond apoptosis. Upon introduction of molecular pathways governing autophagy and necrosis (also called necroptosis or programmed necrosis), we focus on the interconnected character of cell death signals and on the shared cell death processes involving mitochondria (e.g. mitophagy and mitoptosis) and molecular signals playing prominent roles in multiple pathways (e.g. Bcl2-family members and p53). We also briefly highlight stress-induced cell senescence that plays a role not only in organismal ageing but also offers the development of novel anticancer strategies. Finally, we briefly illustrate the interconnected character of cell death forms in clinical settings while discussing irradiation-induced mitotic catastrophe. The signalling pathways are discussed in their relation to cancer biology and treatment approaches.

  • 71.
    Jedlinski, Adam
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of ENT - Head and Neck Surgery UHL.
    Ansell, Anna
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences.
    Johansson, Ann-Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of ENT - Head and Neck Surgery UHL.
    Roberg, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of ENT - Head and Neck Surgery UHL.
    EGFR status and EGFR ligand expression influence the treatment response of head and neck cancer cell lines2013In: Journal of Oral Pathology & Medicine, ISSN 0904-2512, E-ISSN 1600-0714, Vol. 42, no 1, p. 26-36Article in journal (Refereed)
    Abstract [en]

    Background: Combination treatment (chemoradiotherapy) is the standard treatment for locally advanced head and neck squamous cell carcinoma (HNSCC); however, treatment resistance and local recurrence are significant problems. A high level of epidermal growth factor receptor (EGFR) has been associated with a more aggressive phenotype as well as decreased responsiveness to radio- or chemotherapy. We examined the role of EGFR status and EGFR ligand expression for the treatment response. Methods: Intrinsic sensitivity to radiotherapy, cisplatin, and cetuximab treatments was investigated in 25 HNSCC cell lines. EGFR gene copy number, mRNA and protein expression, EGFR and Akt phosphorylation status, and mRNA expression of the EGFR ligands were analyzed using quantitative PCR and ELISA and assessed for their impact on treatment sensitivity. Results: Different treatment modalities yielded great diversity in outcome; of note, cetuximab treatment stimulated growth in one cell line. When treatments were combined primarily additive effects were observed. While radioresistance tended to be associated with a high level of phosphorylated EGFR (pEGFR; P = 0.09), cetuximab-resistant cells had low levels of pEGFR (P = 0.13). The three most cetuximab-sensitive cell lines had high EGFR gene copy numbers. Furthermore, cetuximab treatment response was significantly correlated with epiregulin mRNA expression (r = -0.408, P = 0.043). Cisplatin-resistant tumor cells expressed significantly lower levels of EGFR protein (P = 0.04) compared to cisplatin-sensitive cells and tended to have lower levels of phosphorylated Akt (pAkt; P = 0.13) and lower expression levels of amphiregulin (P = 0.18). Conclusions: Epidermal growth factor receptor status and ligand expression influence the treatment sensitivity of HNSCC cells and may be useful as predictive markers.

  • 72.
    Jerhammar, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery . Linköping University, Faculty of Health Sciences.
    On Predictive Factors of Treatment Response in Head and Neck Squamous Cell Carcinoma2008Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer and yearly include 500 000 new cases worldwide. The outcomes for these patients have not been significantly improved over the last decades and the five year survival is still around 50 %. Establishing predictive markers of treatment response will have great impact on the clinical management of this disease.

    The aim of this thesis was to elucidate markers of intrinsic response to radiotherapy and cisplatin. Combining expression patterns of 14 proteins and identifying mutations in the p53 gene, we were able to incorporate both protein and genetic changes to create a predictive model termed Number of Negative Points (NNP). We used the NNP model to statistically calculate the combination of factors that had the best correlation to intrinsic radiosensitivity (IR). We established that a panel of three markers, epidermal growth factor receptor (EGFR), survivin and splice site/missence mutations of p53, had the best correlation to IR (R=0.990, p<0.0001).

    We also conducted gene expression analysis to investigate what genes and gene ontologies that are different between cell lines with varying IR. Furthermore, we wanted to identify key regulator genes with central positions of molecular networks, which were generated from the transcripts included in the deregulated gene ontologies. A transcriptional profile of 28 key regulator genes was generated. Immunoblot analysis supported deregulation at the protein level of three markers implicated from the transcriptional profile. We propose that these proteins, notch1, thrombospondin 1, and pai‐1 are predictive markers of IR.

    Finally, on a subset of cell lines with sensitivity or resistance to cisplatin, we performed gene expression analysis. Markers of intrinsic cisplatin sensitivity (ICS) such as gene ontologies and key regulators of molecular networks were proposed and five genes, APOE, CTNNB1, MMP7, MMP13, and THBS1 were selected for further analysis. Quantitative polymerase chain reaction (qPCR) analysis of these genes in 25 cell lines established that MMP7 (p=0.0013) and MMP13 (p=0.058) are possible predictive markers of ICS.

    The markers of IR and ICS presented here could, if confirmed in a clinical setting, guide clinicians in the choice of treatment and thus give a more individualized and effective therapy for patients with HNSCC.

    List of papers
    1. Number of negative points: a novel method for predicting radiosensitivity in head and neck tumor cell lines.
    Open this publication in new window or tab >>Number of negative points: a novel method for predicting radiosensitivity in head and neck tumor cell lines.
    Show others...
    2008 (English)In: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 20, no 2, p. 453-461Article in journal (Refereed) Published
    Abstract [en]

    The present study was aimed at establishing a method that combines multiple factors of protein and genetic changes that enables prediction of radiosensitivity in the head and neck squamous cell carcinoma (HNSCC) cell lines. In nine HNSCC cell lines, the quantity of protein expression and the type of genetic alterations were translated into a point system, called the Number of Negative Points. The expression of 14 proteins involved in growth control and/or apoptosis was quantified using a densitometric assessment of Western blots. The blots were adjusted to actin and standardised to normal oral keratinocytes classifying them into four groups depending on the amount of protein expressed (0-3 points). Mutations of the p53 gene were classified into three groups and each mutation was given one point. Since the cell lines each had a known intrinsic radiosensitivity, a multivariate statistical calculation could then be performed to select for the combination of factors having the strongest correlation to radiosensitivity. The strongest correlation of the investigated factors was the combination of epidermal growth factor receptor, survivin and splice site/missense p53 mutations (R=0.990 and P<0.0001). No single factor had a significant correlation to the intrinsic radiosensitivity. Since a significant correlation to the intrinsic radiosensitivity was achieved only when two or more factors were combined, we conclude that a method such as the Number of Negative Points is necessary for prediction of treatment response. We present a novel method to combine factors which enables the prediction of radiosensitivity of HNSCC cell lines.

    Keywords
    Predictive markers, p53, epidermal growth factor receptor, survivin, squamous cell carcinoma
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-19558 (URN)10.3892/or_00000028 (DOI)18636211 (PubMedID)
    Available from: 2009-06-26 Created: 2009-06-26 Last updated: 2018-09-11Bibliographically approved
    2. Identification of Key Regulator Genes Linked to Radioresistance in Head and Neck Squamous Cell Carcinoma by Bioinformatic Processing of Transcript Data
    Open this publication in new window or tab >>Identification of Key Regulator Genes Linked to Radioresistance in Head and Neck Squamous Cell Carcinoma by Bioinformatic Processing of Transcript Data
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Purpose: We analyzed basal expression patterns of cell lines with different intrinsic radiosensitivity to discover predictive markers of radiotherapy response.

    Experimental Design: Five head and neck squamous cell carcinoma (HNSCC) cell lines were selected for microarray analysis. Two cell lines showed high resistance to radiation, two cell lines showed an intermediate resistance and one cell line was sensitive and therefore used as reference to other cell lines. Three gene lists were generated from this analysis; one list with commonly deregulated genes in all cell lines compared to the reference and two lists with deregulated genes for the intermediate and highly resistant cell lines compared to the reference, respectively. Gene Ontology enrichment profiling and Ingenuity Pathway Analysis was applied on all gene lists. Key transcript findings were verified at the protein level by Western blot.

    Results: Expression analysis of the high and intermediate resistant cell lines compared to the reference resulted in approximately 1300 significantly altered transcripts, respectively; 552 transcripts were found commonly differently expressed. The deregulated transcripts enriched several GO-categories under biological process, cellular component and molecular function as well as multiple molecular networks in Ingenuity Pathway Analysis. A transcriptional profile of 28 key-regulator genes from the molecular networks was generated from the four resistant lines compared to the reference. Finally, immunoblot analysis supported deregulation at the protein level of markers implicated from the transcriptional-profile.

    Conclusions: Novel markers for prediction of radiation sensitivity could be proposed from bioinformatic processing of gene-expression profiles in HNSCC carcinoma cells.

    Keywords
    Microarray, Radiotherapy, Predictive biomarkers, Gene Ontology, Pathway analysis
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-19570 (URN)
    Available from: 2009-06-29 Created: 2009-06-29 Last updated: 2010-01-14Bibliographically approved
    3. Matrix metalloproteinase-7 and -13 predict response to cisplatin in head and neck cancer
    Open this publication in new window or tab >>Matrix metalloproteinase-7 and -13 predict response to cisplatin in head and neck cancer
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Purpose: To identify gene ontology categories and key regulators with impact on the intrinsic cisplatin sensitivity (ICS) in head and neck squamous cell carcinoma (HNSCC).

    Experimental design: The ICS was determined in 35 HNSCC cell lines. Three of these cell lines, one sensitive and two resistant, were selected for microarray analysis. Gene Ontology (GO) categories were assessed using the gene ontology tree machine (GOTM) tool, and transcripts included in these categories were further analyzed using Ingenuity Pathway Analysis (IPA) for detection of key regulator genes. A group of key regulators were verified at protein level by Western blot analysis and on mRNA level using quantitative real-time PCR (qPCR).

    Results: 781 transcripts were detected as significantly differently expressed for the resistant cell lines compared to the sensitive cell line. A total of ten different categories were enriched in GOTM by these transcripts and a transcriptional profile was made from the 20 key regulators identified in the IPA analysis. Five key regulator genes, apolipoprotein E (APOE), catenin beta1 (CTNNB1), matrix metalloproteinase-7 (MMP-7), matrix metalloproteinase-13 (MMP-13), and thrombospondin 1 (THBS1), were verified in 25 HNSCC cell lines on mRNA level using qPCR. The results confirmed MMP-7 (p=0.0013) and implied MMP-13 (p=0.058) as potential biomarkers of ICS.

    Conclusions: We conclude that genome-wide transcriptional analysis and appropriate bioinformatics enable the identification of genes with impact on treatment response. Furthermore, we propose MMP-7 and MMP-13 as predictive markers of cisplatin resistance in HNSCC.

    Keywords
    Predictive markers, chemotherapy, microarray and intrinsic cisplatin resistance
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-19571 (URN)
    Available from: 2009-06-29 Created: 2009-06-29 Last updated: 2010-01-14Bibliographically approved
  • 73.
    Jerhammar, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences.
    Predictive Markers of Treatment Resistance in Head and Neck Squamous Cell Carcinoma2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Head and neck cancer is a common malignancy with approximately 600 000 new cases yearly. Disappointingly, the overall survival has not increased over the last decades. The concept of personalized medicine, i.e. to treat every patient with an individually planned treatment regime has gathered increased interest, but requires the establishment of novel biomarkers that can predict treatment response.

    The aim of this thesis is to propose novel predictive single markers or combinations of markers of response to radiation, cisplatin and cetuximab. The general methodology is to evaluate common differences of cell lines resistant to radiation, cisplatin or cetuximab compared to sensitive counterparts.

    In paper I, we analysed the expression of 14 proteins involved in growth control and/or apoptosis by western blot and related them to intrinsic radiosensitivity (IR) in nine cell lines. No factor had a significant correlation to IR on its own. A combination of EGFR, survivin, Bak, Smad4, and Hsp70 had the best correlation to IR (R=0.886, p=0.001). Additionally, we analysed the presence of p53 mutations in the cell lines. All cell lines had at least one missense, splice site or loss of transcript mutation. To be able to combine protein expression and presence of p53 mutations we created a system designated the number of negative points (NNP). With this system we could extract that expression of EGFR, survivin, and p53 missense or splice site mutations had the best correlation to IR (R=0.990, p<0.001).

    In paper II we conducted a gene expression microarray analysis of three cell lines, from which common deregulations in two cisplatin resistant cell lines was compared to a cisplatin sensitive cell line. From a bioinformatic approach of gene ontology and molecular network analysis, we defined a transcriptional profile of 20 genes. Finally, key findings were analysed in a larger panel of cell lines, where high MMP-7 expression correlated with higher cisplatin resistance.

    Paper III compared 4 cell lines with high IR to a radiosensitive equivalent. Using a similar bioinformatic approach as paper II, we established a transcriptional profile of 14 genes. Analysis in a larger panel of cell lines revealed that FN1 expression predicts higher IR.

    Paper IV establishes the cetuximab sensitivity of 35 cell lines of which 12 were resistant and five were sensitive to cetuximab. After whole genome gene copy number analysis of five cetuximab resistant and five cetuximab sensitive cell lines, and verification of key findings in a larger cell line panel, the results show that the amplification of the YAP1 gene is coupled to cetuximab resistance.

    In summary, this thesis proposes a number of novel markers of resistance to radiation, cisplatin, and cetuximab which could influence treatment choice in the future, following verifications in primary tumor material.

    List of papers
    1. Number of negative points: a novel method for predicting radiosensitivity in head and neck tumor cell lines.
    Open this publication in new window or tab >>Number of negative points: a novel method for predicting radiosensitivity in head and neck tumor cell lines.
    Show others...
    2008 (English)In: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 20, no 2, p. 453-461Article in journal (Refereed) Published
    Abstract [en]

    The present study was aimed at establishing a method that combines multiple factors of protein and genetic changes that enables prediction of radiosensitivity in the head and neck squamous cell carcinoma (HNSCC) cell lines. In nine HNSCC cell lines, the quantity of protein expression and the type of genetic alterations were translated into a point system, called the Number of Negative Points. The expression of 14 proteins involved in growth control and/or apoptosis was quantified using a densitometric assessment of Western blots. The blots were adjusted to actin and standardised to normal oral keratinocytes classifying them into four groups depending on the amount of protein expressed (0-3 points). Mutations of the p53 gene were classified into three groups and each mutation was given one point. Since the cell lines each had a known intrinsic radiosensitivity, a multivariate statistical calculation could then be performed to select for the combination of factors having the strongest correlation to radiosensitivity. The strongest correlation of the investigated factors was the combination of epidermal growth factor receptor, survivin and splice site/missense p53 mutations (R=0.990 and P<0.0001). No single factor had a significant correlation to the intrinsic radiosensitivity. Since a significant correlation to the intrinsic radiosensitivity was achieved only when two or more factors were combined, we conclude that a method such as the Number of Negative Points is necessary for prediction of treatment response. We present a novel method to combine factors which enables the prediction of radiosensitivity of HNSCC cell lines.

    Keywords
    Predictive markers, p53, epidermal growth factor receptor, survivin, squamous cell carcinoma
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-19558 (URN)10.3892/or_00000028 (DOI)18636211 (PubMedID)
    Available from: 2009-06-26 Created: 2009-06-26 Last updated: 2018-09-11Bibliographically approved
    2. Matrix metalloproteinase-7 and -13 expression associate to cisplatin resistance in head and neck cancer cell lines.
    Open this publication in new window or tab >>Matrix metalloproteinase-7 and -13 expression associate to cisplatin resistance in head and neck cancer cell lines.
    Show others...
    2009 (English)In: Oral Oncology, ISSN 1368-8375, E-ISSN 1879-0593, Vol. 45, no 10, p. 866-871Article in journal (Refereed) Published
    Abstract [en]

    Concomitant chemoradiotherapy is a common treatment for advanced head and neck squamous cell carcinomas (HNSCC). Cisplatin is the backbone of chemotherapy regimens used to treat HNSCC. Therefore, the aim of this study was to identify predictive markers for cisplatin treatment outcome in HNSCC. The intrinsic cisplatin sensitivity (ICS) was determined in a panel of tumour cell lines. From this panel, one sensitive and two resistant cell lines were selected for comparative transcript profiling using microarray analysis. The enrichment of Gene Ontology (GO) categories in sensitive versus resistant cell lines were assessed using the Gene Ontology Tree Machine bioinformatics tool. In total, 781 transcripts were found to be differentially expressed and 11 GO categories were enriched. Transcripts contributing to this enrichment were further analyzed using Ingenuity Pathway Analysis (IPA) for identification of key regulator genes. IPA recognized 20 key regulator genes of which five were differentially expressed in sensitive versus resistant cell lines. The mRNA level of these five genes was further assessed in a panel of 25 HNSCC cell lines using quantitative real-time PCR. Among these key regulators, MMP-7 and MMP-13 are implicated as potential biomarkers of ICS. Taken together, genome-wide transcriptional analysis identified single genes, GO categories as well as molecular networks that are differentially expressed in HNSCC cell lines with different ICS. Furthermore, two novel predictive biomarkers for cisplatin resistance, MMP-7 and MMP-13, were identified.

    Place, publisher, year, edition, pages
    Elsevier, 2009
    Keywords
    Predictive markers; Gene Ontology; Head and neck cancer; Cisplatin; Microarray; MMPs
    National Category
    Cancer and Oncology
    Identifiers
    urn:nbn:se:liu:diva-21436 (URN)10.1016/j.oraloncology.2009.02.008 (DOI)000270022000005 ()19442568 (PubMedID)
    Available from: 2009-10-01 Created: 2009-10-01 Last updated: 2017-12-13Bibliographically approved
    3. Fibronectin 1 is a potential biomarker for radioresistance in head and neck squamous cell carcinoma
    Open this publication in new window or tab >>Fibronectin 1 is a potential biomarker for radioresistance in head and neck squamous cell carcinoma
    Show others...
    2010 (English)In: CANCER BIOLOGY and THERAPY, ISSN 1538-4047, Vol. 10, no 12, p. 1244-1251Article in journal (Refereed) Published
    Abstract [en]

    Radiotherapy remains the backbone of head and neck cancer therapy but response is sometimes impeded by tumor radioresistance. Identifying predictive biomarkers of radiotherapy response is a crucial step towards personalized therapy. The aim of this study was to explore gene expression data in search of biomarkers predictive of the response to radiotherapy in head and neck squamous cell carcinoma (HNSCC). Microarray analysis was performed on five cell lines with various intrinsic radiosensitivity, selected from a panel of 29 HNSCC cell lines. The bioinformatics approach included Gene Ontology (GO) enrichment profiling and Ingenuity Pathway Analysis (IPA). The GO-analysis detected 16 deregulated categories from which development, receptor activity and extracellular region represented the largest groups. Fourteen hub genes (CEBPA, CEBPB, CTNNB1, FN1, MYC, MYCN, PLAU, SDC4, SERPINE1, SP1, TAF4B, THBS1, TP53 and VLDLR) were identified from the IPA network analysis. The hub genes in the highest ranked network, (FN1, SERPINE1, THBS1 and VLDLR) were further subjected to qPCR analysis in the complete panel of 29 cell lines. Of these genes, high FN1 expression associated to high intrinsic radiosensitivity (p = 0.047). In conclusion, gene ontologies and hub genes of importance for intrinsic radiosensitivity were defined. The overall results suggest that FN1 should be explored as a potential novel biomarker for radioresistance.

    Place, publisher, year, edition, pages
    Landes Bioscience, 2010
    Keywords
    head and neck cancer, predictive markers, radiotherapy, microarray, gene ontology, pathway analysis, fibronectin 1
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-64243 (URN)10.4161/cbt.10.12.13432 (DOI)000285388400007 ()
    Available from: 2011-01-17 Created: 2011-01-17 Last updated: 2012-03-29Bibliographically approved
    4. YAP1 Gene Amplification is a Marker for Cetuximab Resistance in Head and Neck Cancer
    Open this publication in new window or tab >>YAP1 Gene Amplification is a Marker for Cetuximab Resistance in Head and Neck Cancer
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    The epidermal growth factor receptor (EGFR) is commonly overexpressed in head and neck squamous cell carcinomas (HNSCC). The monoclonal antibody cetuximab (Erbitux®) inhibits its signaling and has been approved for treatment of HNSCC. However, since many patients do not benefit from cetuximab treatment, predictive biomarkers of cetuximab response are required. The present study aims at finding novel markers of cetuximab resistance.

    The intrinsic cetuximab sensitivity of 35 HNSCC cell lines was determined, and revealed a great variation in the response between cell lines. Five cell lines (14%) were cetuximab sensitive, and 12 (34%) were resistant. Interestingly, two cell lines proliferated after cetuximab treatment.

    10 cell lines (five cetuximab sensitive and five cetuximab resistant) were selected for gene copy number array analysis on the Affymetrix SNP 6.0 platform. 39 protein coding genes were amplified in cetuximab resistant cells and normal in sensitive cells, all present on genomic regions 11q22.1 or 5p13-15. Five genes were selected for quantitative PCR  verification, namely, YAP1 and TRPC6 (11q22.1) and PDCD6, TPPP, and PTGER4 (5p13-15). An extended panel of totally 10 cetuximab resistant and 10 sensitive cell lines verified that YAP1 amplified cells are cetuximab resistant.

    YAP1 gene amplification was highly correlated to the YAP1 mRNA expression, which was significantly higher in cetuximab resistant cells than in sensitive. YAP1 downregulation resulted in increased cetuximab sensitivity in one of two cetuximab resistant cell lines investigated and growth inhibition in another. We conclude that YAP1 is a marker for cetuximab resistance in head and neck cancer.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-76151 (URN)
    Available from: 2012-03-29 Created: 2012-03-29 Last updated: 2012-03-29Bibliographically approved
  • 74.
    Jerhammar, Fredrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences.
    Ceder, Rebecca
    Karolinska Institute, Stockholm.
    Garvin, Stina
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    Grenman, Reidar
    Turku University Hospital, Finland.
    C Grafstrom, Roland
    Karolinska Institute, Stockholm.
    Roberg, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of ENT - Head and Neck Surgery UHL.
    Fibronectin 1 is a potential biomarker for radioresistance in head and neck squamous cell carcinoma2010In: CANCER BIOLOGY and THERAPY, ISSN 1538-4047, Vol. 10, no 12, p. 1244-1251Article in journal (Refereed)
    Abstract [en]

    Radiotherapy remains the backbone of head and neck cancer therapy but response is sometimes impeded by tumor radioresistance. Identifying predictive biomarkers of radiotherapy response is a crucial step towards personalized therapy. The aim of this study was to explore gene expression data in search of biomarkers predictive of the response to radiotherapy in head and neck squamous cell carcinoma (HNSCC). Microarray analysis was performed on five cell lines with various intrinsic radiosensitivity, selected from a panel of 29 HNSCC cell lines. The bioinformatics approach included Gene Ontology (GO) enrichment profiling and Ingenuity Pathway Analysis (IPA). The GO-analysis detected 16 deregulated categories from which development, receptor activity and extracellular region represented the largest groups. Fourteen hub genes (CEBPA, CEBPB, CTNNB1, FN1, MYC, MYCN, PLAU, SDC4, SERPINE1, SP1, TAF4B, THBS1, TP53 and VLDLR) were identified from the IPA network analysis. The hub genes in the highest ranked network, (FN1, SERPINE1, THBS1 and VLDLR) were further subjected to qPCR analysis in the complete panel of 29 cell lines. Of these genes, high FN1 expression associated to high intrinsic radiosensitivity (p = 0.047). In conclusion, gene ontologies and hub genes of importance for intrinsic radiosensitivity were defined. The overall results suggest that FN1 should be explored as a potential novel biomarker for radioresistance.

  • 75.
    Jerhammar, Fredrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery . Linköping University, Faculty of Health Sciences.
    Ceder, Rebecca
    Institute of Environmental Medicine, Division of Biochemical Toxicology and Experimental Cancer Research, Karolinska Institute, Stockholm, Sweden.
    Grénman, Reidar
    Department of Otorhinolaryngology-Head and Neck Surgery, Turku University Central Hospital, University of Turku, Turku, Finland/Department of Medical Biochemistry, University of Turku, Turku, Finland.
    Grafström, Roland C.
    Institute of Environmental Medicine, Division of Biochemical Toxicology and Experimental Cancer Research, Karolinska Institute, Stockholm, Sweden.
    Roberg, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of ENT - Head and Neck Surgery UHL.
    Identification of Key Regulator Genes Linked to Radioresistance in Head and Neck Squamous Cell Carcinoma by Bioinformatic Processing of Transcript DataManuscript (preprint) (Other academic)
    Abstract [en]

    Purpose: We analyzed basal expression patterns of cell lines with different intrinsic radiosensitivity to discover predictive markers of radiotherapy response.

    Experimental Design: Five head and neck squamous cell carcinoma (HNSCC) cell lines were selected for microarray analysis. Two cell lines showed high resistance to radiation, two cell lines showed an intermediate resistance and one cell line was sensitive and therefore used as reference to other cell lines. Three gene lists were generated from this analysis; one list with commonly deregulated genes in all cell lines compared to the reference and two lists with deregulated genes for the intermediate and highly resistant cell lines compared to the reference, respectively. Gene Ontology enrichment profiling and Ingenuity Pathway Analysis was applied on all gene lists. Key transcript findings were verified at the protein level by Western blot.

    Results: Expression analysis of the high and intermediate resistant cell lines compared to the reference resulted in approximately 1300 significantly altered transcripts, respectively; 552 transcripts were found commonly differently expressed. The deregulated transcripts enriched several GO-categories under biological process, cellular component and molecular function as well as multiple molecular networks in Ingenuity Pathway Analysis. A transcriptional profile of 28 key-regulator genes from the molecular networks was generated from the four resistant lines compared to the reference. Finally, immunoblot analysis supported deregulation at the protein level of markers implicated from the transcriptional-profile.

    Conclusions: Novel markers for prediction of radiation sensitivity could be proposed from bioinformatic processing of gene-expression profiles in HNSCC carcinoma cells.

  • 76.
    Jerhammar, Fredrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences.
    Johansson, Ann-Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences.
    Jansson, Agneta
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    Welander, Jenny
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Roberg, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of ENT - Head and Neck Surgery UHL.
    YAP1 Gene Amplification is a Marker for Cetuximab Resistance in Head and Neck CancerManuscript (preprint) (Other academic)
    Abstract [en]

    The epidermal growth factor receptor (EGFR) is commonly overexpressed in head and neck squamous cell carcinomas (HNSCC). The monoclonal antibody cetuximab (Erbitux®) inhibits its signaling and has been approved for treatment of HNSCC. However, since many patients do not benefit from cetuximab treatment, predictive biomarkers of cetuximab response are required. The present study aims at finding novel markers of cetuximab resistance.

    The intrinsic cetuximab sensitivity of 35 HNSCC cell lines was determined, and revealed a great variation in the response between cell lines. Five cell lines (14%) were cetuximab sensitive, and 12 (34%) were resistant. Interestingly, two cell lines proliferated after cetuximab treatment.

    10 cell lines (five cetuximab sensitive and five cetuximab resistant) were selected for gene copy number array analysis on the Affymetrix SNP 6.0 platform. 39 protein coding genes were amplified in cetuximab resistant cells and normal in sensitive cells, all present on genomic regions 11q22.1 or 5p13-15. Five genes were selected for quantitative PCR  verification, namely, YAP1 and TRPC6 (11q22.1) and PDCD6, TPPP, and PTGER4 (5p13-15). An extended panel of totally 10 cetuximab resistant and 10 sensitive cell lines verified that YAP1 amplified cells are cetuximab resistant.

    YAP1 gene amplification was highly correlated to the YAP1 mRNA expression, which was significantly higher in cetuximab resistant cells than in sensitive. YAP1 downregulation resulted in increased cetuximab sensitivity in one of two cetuximab resistant cell lines investigated and growth inhibition in another. We conclude that YAP1 is a marker for cetuximab resistance in head and neck cancer.

  • 77.
    Jerhammar, Fredrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences.
    Roberg, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of ENT - Head and Neck Surgery UHL. Östergötlands Läns Landsting.
    Variation of intrinsic cetuximab sensitivity in head and neck squamous cell carcinomas in EJC SUPPLEMENTS, vol 8, issue 5, pp 50-502010In: EJC SUPPLEMENTS, Elsevier Science B.V., Amsterdam. , 2010, Vol. 8, no 5, p. 50-50Conference paper (Refereed)
    Abstract [en]

    n/a

  • 78.
    Jerhammar, Fredrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences.
    Welander, Jenny
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Johansson, A C
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Roberg, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of ENT - Head and Neck Surgery UHL.
    Gene Copy Number as Predictive Marker for Cetuximab Resistance in Head and Neck Squamous Cell Carcinomas in EUROPEAN JOURNAL OF CANCER, vol 47, issue , pp S571-S5712011In: EUROPEAN JOURNAL OF CANCER, Elsevier , 2011, Vol. 47, p. S571-S571Conference paper (Refereed)
    Abstract [en]

    n/a

  • 79.
    Johansson, A
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences.
    Ansell, Anna
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences.
    Ostman, A
    Karolinska Institute.
    Roberg, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of ENT - Head and Neck Surgery UHL. Östergötlands Läns Landsting.
    Cancer-associated fibroblasts desensitizes head and neck squamous cell carcinoma cells to epidermal growth factor receptor-targeted therapy in EJC SUPPLEMENTS, vol 8, issue 5, pp 134-1342010In: EJC SUPPLEMENTS, Elsevier Science B.V., Amsterdam. , 2010, Vol. 8, no 5, p. 134-134Conference paper (Refereed)
    Abstract [en]

    n/a

  • 80.
    Johansson, Ann-Charlotte
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences.
    Ansell, Anna
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences.
    Jerhammar, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences.
    Bradic Lindh, Maja
    Östergötlands Läns Landsting, Sinnescentrum, Department of ENT - Head and Neck Surgery UHL.
    Grenman, Reidar
    Turku University Hospital, Finland University of Turku, Finland .
    Munck-Wikland, Eva
    Karolinska University Hospital, Sweden .
    Ostman, Arne
    Karolinska Institute, Sweden .
    Roberg, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of ENT - Head and Neck Surgery UHL.
    Cancer-Associated Fibroblasts Induce Matrix Metalloproteinase-Mediated Cetuximab Resistance in Head and Neck Squamous Cell Carcinoma Cells2012In: Molecular Cancer Research, ISSN 1541-7786, E-ISSN 1557-3125, Vol. 10, no 9, p. 1158-1168Article in journal (Refereed)
    Abstract [en]

    A growing body of evidence suggests that components of the tumor microenvironment, including cancer-associated fibroblasts (CAF), may modulate the treatment sensitivity of tumor cells. Here, we investigated the possible influence of CAFs on the sensitivity of head and neck squamous cell carcinoma (HNSCC) cell lines to cetuximab, an antagonistic epidermal growth factor receptor (EGFR) antibody. Cetuximab treatment caused a reduction in the proliferation rate of HNSCC cell lines, whereas the growth of HNSCC-derived CAF cultures was unaffected. When tumor cells were cocultured with CAFs in a transwell system, the cetuximab-induced growth inhibition was reduced, and a complete protection from growth inhibition was observed in one of the tumor cell lines investigated. Media that had been conditioned by CAFs offered protection from cetuximab treatment in a concentration-dependent manner, suggesting that the resistance to treatment was mediated by CAF-derived soluble factors. The coculture of HNSCC cell lines with CAFs resulted in an elevated expression of matrix metalloproteinase-1 (MMP-1) in both the tumor cells and CAFs. Moreover, the CAF-induced resistance was partly abolished by the presence of an MMP inhibitor. However, CAFs treated with siRNA targeting MMP-1 still protected tumor cells from cetuximab treatment, suggesting that several MMPs may cooperate to facilitate resistance or that the protective effect is mediated by another member of the MMP family. These results identify a novel CAF-dependent modulation of cetuximab sensitivity and suggest that inhibiting MMPs may improve the effects of EGFR-targeted therapy.

  • 81.
    Johansson, Ann-Charlotte
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences.
    Appelqvist, Hanna
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences.
    Nilsson, Cathrine
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences.
    Kågedal, Katarina
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Faculty of Health Sciences.
    Roberg, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of ENT - Head and Neck Surgery UHL.
    Öllinger, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Regulation of apoptosis-associated lysosomal membrane permeabilization2010In: APOPTOSIS, ISSN 1360-8185, Vol. 15, no 5, p. 527-540Article in journal (Refereed)
    Abstract [en]

    Lysosomal membrane permeabilization (LMP) occurs in response to a large variety of cell death stimuli causing release of cathepsins from the lysosomal lumen into the cytosol where they participate in apoptosis signaling. In some settings, apoptosis induction is dependent on an early release of cathepsins, while under other circumstances LMP occurs late in the cell death process and contributes to amplification of the death signal. The mechanism underlying LMP is still incompletely understood; however, a growing body of evidence suggests that LMP may be governed by several distinct mechanisms that are likely engaged in a death stimulus- and cell-type-dependent fashion. In this review, factors contributing to permeabilization of the lysosomal membrane including reactive oxygen species, lysosomal membrane lipid composition, proteases, p53, and Bcl-2 family proteins, are described. Potential mechanisms to safeguard lysosomal integrity and confer resistance to lysosome-dependent cell death are also discussed.

  • 82.
    Johansson, Ann-Charlotte
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology . Linköping University, Faculty of Health Sciences.
    Norberg-Spaak, Lena
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery . Linköping University, Faculty of Health Sciences.
    Roberg, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery . Linköping University, Faculty of Health Sciences.
    Role of lysosomal cathepsins in naphthazarin- and Fas-induced apoptosis in oral squamous cell carcinoma cells2006In: Acta Oto-Laryngologica, ISSN 0001-6489, Vol. 126, no 1, p. 70-81Article in journal (Refereed)
    Abstract [en]

    Conclusion. Intracellular cysteine cathepsins are pro-apoptotic factors involved in activation of caspases in two oral squamous cell carcinoma (SCC) cell lines.

    Objective. To study the possible involvement of lysosomal cathepsins in oral SCC cell apoptosis.

    Material and methods. Apoptosis was induced in the two human oral SCC cell lines UT-SCC-20A and UT-SCC-24A using naphthazarin or anti-Fas antibodies, and was studied by analysis of caspase activity and nuclear morphology. Involvement of lysosomal cathepsins was investigated using the cysteine cathepsin inhibitor z-FA-FMK and the cathepsin D inhibitor pepstatin A. The amounts of cellular and soluble Fas death receptor were determined by ELISA.

    Results. Release of cathepsins from the lysosomes to the cytosol was observed early in apoptosis. Cysteine cathepsins were found to be involved in activation of caspases in response to treatment with naphthazarin or anti-Fas antibodies, but inhibition of cysteine cathepsin activity was not sufficient to prevent cell death. Moreover, inhibition of cysteine cathepsin activity resulted in increased expression of the Fas death receptor, suggesting involvement of extracellular cysteine cathepsins in death receptor shedding.

  • 83.
    Johansson, Ann-Charlotte
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology . Linköping University, Faculty of Health Sciences.
    Steen, Håkan
    Öllinger, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Roberg, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of ENT - Head and Neck Surgery UHL.
    Cathepsin D mediates cytochrome c release and caspase activation in human fibroblast apoptosis induced by staurosporine2003In: Cell Death and Differentiation, ISSN 1350-9047, Vol. 10, no 11, p. 1253-1259Article in journal (Refereed)
    Abstract [en]

    There is increasing evidence that proteases other than caspases, for example, the lysosomal cathepsins B, D and L, are involved in apoptotic cell death. In the present study, we present data that suggest a role for cathepsin D in staurosporine-induced apoptosis in human foreskin fibroblasts. Cathepsin D and cytochrome c were detected partially released to the cytosol after exposure to 0.1 µM staurosporine for 1 h. After 4 h, activation of caspase-9 and -3 was initiated and later caspase-8 activation and a decrease in full-length Bid were detected. Pretreatment of cells with the cathepsin D inhibitor, pepstatin A, prevented cytochrome c release and caspase activation, and delayed cell death. These results imply that cytosolic cathepsin D is a key mediator in staurosporine-induced apoptosis. Analysis of the relative sequence of apoptotic events indicates that, in this cell type, cathepsin D acts upstream of cytochrome c release and caspase activation.

  • 84.
    Johansson, Magnus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Technical Audiology . Linköping University, Faculty of Health Sciences.
    Arlinger, Stig
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery . Linköping University, Faculty of Health Sciences.
    Hearing threshold levels for an otologically unscreened, non-occupationally noise-exposed population in Sweden2002In: International Journal of Audiology, ISSN 1499-2027, Vol. 41, no 3, p. 180-194Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to investigate the hearing threshold levels (HTL) of an otologically unscreened population in Sweden. The results are compared to other studies of otologically unscreened populations, and a new mathematical model of hearing threshold levels as a function of age is presented. The subjects were males and females aged from 19 to 81 years, selected from the province of ╓sterg÷tland in Sweden. The test battery included otoscopy, tympanometry, pure-tone audiometry, and a questionnaire. Subjects exposed to occupational noise were excluded, and in total 603 persons were included in the analysis. The regression analysis resulted in different hyperbolic tangent functions with four parameters: HTL = A + B ╫ tanh(C ╫ age + D).

  • 85.
    Johansson, Magnus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Technical Audiology. Linköping University, Faculty of Health Sciences.
    Arlinger, Stig
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences.
    Otoacoustic emissions and tympanometry in a general adult population in Sweden2003In: International Journal of Audiology, ISSN 1499-2027, Vol. 42, no 8, p. 448-464Article in journal (Refereed)
    Abstract [en]

    The present study concerns a general adult population in Sweden, not exposed to hazardous occupational noise. Tympanometry and spontaneous (SOAE), transient evoked (TEOAE) and distortion-product (DPOAE) otoacoustic emissions were investigated in 493 randomly selected men and women aged from 20 to 79 years. Effects of gender, age, ear side and middle ear state were determined, with and without adjusting for hearing threshold level. No statistically significant effects on middle ear pressure or compliance were present. For TEOAEs and DPOAEs, the effect of gender and age was statistically significant (p < 0.01), with larger signal levels for female subjects and young subjects, even after adjusting for hearing threshold level. No effect of middle ear pressure on otoacoustic emissions was present, but high middle ear compliance was associated with low emission levels (p < 0.01). Reference data for middle ear compliance and pressure and prevalence data on SOAEs, TEOAEs and DPOAEs for male and female subjects in different age groups were determined. Mean signal levels of TEOAEs and DPOAEs are presented.

  • 86.
    Johansson, Magnus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Technical Audiology . Linköping University, Faculty of Health Sciences.
    Arlinger, Stig
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery . Linköping University, Faculty of Health Sciences.
    Prevalence of hearing impairment in a population in Sweden2003In: International Journal of Audiology, ISSN 1499-2027, Vol. 42, no 1, p. 18-28Article in journal (Refereed)
    Abstract [en]

    An epidemiological study was carried out, based on 590 randomly selected subjects, aged from 20 to 80 years, in the province of Ostergötland in Sweden. The results obtained were similar to published results from other countries, with an overall prevalence of subjects with average hearing threshold levels over the frequencies 0.5, 1, 2 and 4 kHz (M4) equal to or exceeding 25 dB HL for the better ear (BE) of 16.9% (95% CI: 13.819.9%). For M4 BE > or = 35 dB HL, the prevalence was 7.7% (95% CI: 5.5-9.8%), for M4 BE > or = 45 dB HL, the prevalence was 3.3% (95% CI: 1.9-4.8%), and for M4 BE > or = 65 dB HL, the prevalence was 0.2% (95% Cl: 0.0-0.6%). The overall prevalence of reported tinnitus was 13.2% (95% CI: 10.5-16.0%). In the population under study, 7.7% of the subjects were estimated to benefit from a hearing aid, while the prevalence of hearing aid users was 2.4%.

  • 87.
    Johansson, Magnus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Technical Audiology . Linköping University, Faculty of Health Sciences.
    Arlinger, Stig
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery . Linköping University, Faculty of Health Sciences.
    The development of noise-induced hearing loss in the Swedish County of Östergötland in the 1980s and the 1990s2001In: Noise & Health, ISSN 1463-1741, Vol. 3, no 10, p. 15-28Article in journal (Refereed)
    Abstract [en]

    This retrospective cross-sectional study of median hearing threshold levels of males employed in two specific occupations shows that the trend with decreasing noise-induced hearing loss in Sweden during the 1970s and 1980s continues into the 1990s. In the occupational categories mechanical work and wood processing men in age groups 30-39, 40-49 and 50-59 years old examined during the time period 1971-76, 1981-86 and 1991-96 were compared. Possible explanations to the improvement might be a wider use of hearing protectors at work and less exposure to noise during military service. The results show that the awareness of noise-induced occupational hearing loss has improved but the hearing conservation programs are still necessary as hearing threshold levels in these occupational groups continue to be poorer than expected in relation to age.

  • 88.
    Kammerlind, Ann-Sofi C.
    et al.
    Ryhov County Hospital.
    Ledin, Torbjörn
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of ENT - Head and Neck Surgery UHL.
    Ödkvist, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of ENT - Head and Neck Surgery UHL.
    Skargren, Elisabeth
    Linköping University, Department of Medical and Health Sciences, Physiotherapy. Linköping University, Faculty of Health Sciences.
    Recovery after acute unilateral vestibular loss and predictors for remaining symptoms2011In: American Journal of Otolaryngology, ISSN 0196-0709, E-ISSN 1532-818X, Vol. 32, no 5, p. 366-375Article in journal (Refereed)
    Abstract [en]

    Purpose: The aims of this study were to follow recovery during the first 6 months after acute unilateral vestibular loss (AUVL) and to determine predictors for self-rated remaining symptoms. Materials and methods: Forty-two subjects were included less than 10 days after AUVL. Static and dynamic clinical balance tests, visual analogue scales, University of California Los Angeles Dizziness Questionnaire, Dizziness Beliefs Scale, European Quality of Life questionnaire, Dizziness Handicap Inventory, and Hospital Anxiety and Depression Scale were performed at inclusion and at 7 follow-ups over 6 months. Subjects rated their symptoms on visual analogue scales daily at home. Videonystagmography was performed in the acute stage and after 10 weeks. Results: Decrease of symptoms and improvement of balance function were larger during the first compared with the latter part of the follow-up period. Visual analogue scale ratings for balance problems were higher than those for dizziness. A prediction model was created based on the results of 4 tests in the acute stage: standing on foam with eyes closed, standing on 1 leg with eyes open, visual analogue scale rating of vertigo at rest, and European Quality of Life questionnaire rating of health-related quality of life. The prediction model identified subjects at risk of having remaining symptoms after 6 months with a sensitivity of 86% and a specificity of 79%. Conclusions: Recovery mainly takes place during the first weeks after AUVL. Subjects rate more balance problems than dizziness. Self-rated remaining symptoms after 6 months may be predicted by clinical balance tests and subjective ratings in the acute stage.

  • 89. Kiessling, J
    et al.
    Pichora-Fuller, MK
    Gatehouse, S
    Stephens, D
    Arlinger, Stig
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery .
    Chisolm, T
    Davis, AC
    Erber, NP
    Hickson, L
    Holmes, A
    Rosenhall, U
    von Wedel, H
    Candidature for and delivery of audiological services: special needs of older people2003In: International Journal of Audiology, ISSN 1499-2027, E-ISSN 1708-8186, Vol. 42, p. S92-S101Article in journal (Refereed)
  • 90.
    Kovacsovics, Bea
    et al.
    Linköping University, Department of Medicine and Health Sciences. Linköping University, Faculty of Health Sciences.
    Davidsson, L
    Linköping University, Department of Medicine and Care, Radiology. Linköping University, Faculty of Health Sciences.
    Harder, Henrik
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of ENT - Head and Neck Surgery UHL.
    Magnuson, Bengt
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Ledin, Torbjörn
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of ENT - Head and Neck Surgery UHL.
    MRI screening of the cerebellopontine angle and inner ear with fast spin-echo T2 technique2000In: Archives Italiennes de Biologie, ISSN 0003-9829, Vol. 138, no 1, p. 87-92Article in journal (Refereed)
    Abstract [en]

    In patients with unilateral hearing loss and dizziness it is important to rule out a cerebellopontine angle process. This is often done by audiological and otoneurological investigations. However, in many cases we must rely on the imaging of the temporal bone and the cerebello-brainstem area. The paper has presented the three dimensional (3D) Fast Spin-Echo (FSE) T2 weighted, 0.7 mm thick MR images, which in addition to being quick, does not require the use of expensive contrast material. Between September 1996 and November 1997, 152 patients with unilateral hearing loss and/or balance disorders were investigated. In normal cases the 7th and 8th nerves could be followed accurately from the brainstem to the internal auditory meatus. The found tumors were hypointense compared to the cerebrospinal fluid and could be outlined with reasonable accuracy even without gadolinium contrast. The inner ear had high signal, like cerebrospinal fluid. The patency of the cochlea could be estimated accurately. Thus, 3D FSE T2 weighted images can reliably differentiate between patients with and without pathologies of the cerebellopontine angle. The use of gadolinium contrast could be avoided in most of the cases, but contrast is necessary for differential diagnostic purposes in patients with alterations in the cerebellopontine angle or in doubtful cases.

  • 91.
    Kågedal, Katarina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences.
    Johansson, Ann-Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences.
    Johansson, Uno
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences.
    Heimlich, Gerd
    Institute for Medical Microbiology, Immunology and Hygiene, University of Köln, Köln, Germany.
    Roberg, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences.
    Wang, Nancy S.
    Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
    Jürgensmeier, Juliane M.
    Institute for Medical Microbiology, Immunology and Hygiene, University of Köln, Köln, Germany.
    Öllinger, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences.
    Lysosomal membrane permeabilization during apoptosis: Involvement of Bax?2005In: International journal of experimental pathology (Print), ISSN 0959-9673, E-ISSN 1365-2613, Vol. 86, no 5, p. 309-321Article in journal (Refereed)
    Abstract [en]

    Bcl-2 family members have long been known to control permeabilization of the mitochondrial membrane during apoptosis, but involvement of these proteins in lysosomal membrane permeabilization (LMP) was not considered until recently. The aim of this study was to investigate the mechanism underlying the release of lysosomal proteases to the cytosol seen during apoptosis, with special emphasis on the role of Bax. In human fibroblasts, exposed to the apoptosis-inducing drug staurosporine (STS), the release of the lysosomal protease cathepsin D to the cytosol was observed by immunocytochemistry. In response to STS treatment, there was a shift in Bax immunostaining from a diffuse to a punctate pattern. Confocal microscopy showed co-localization of Bax with both lysosomes and mitochondria in dying cells. Presence of Bax at the lysosomal membrane was confirmed by immuno-electron microscopy. Furthermore, when recombinant Bax was incubated with pure lysosomal fractions, Bax inserted into the lysosomal membrane and induced the release of lysosomal enzymes. Thus, we suggest that Bax is a mediator of LMP, possibly promoting the release of lysosomal enzymes to the cytosol during apoptosis.

  • 92.
    La Fleur, Linnea
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences.
    Johansson, Ann-Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences.
    Roberg, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of ENT - Head and Neck Surgery UHL.
    A CD44(high)/EGFR(low) Subpopulation within Head and Neck Cancer Cell Lines Shows an Epithelial-Mesenchymal Transition Phenotype and Resistance to Treatment2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 9Article in journal (Refereed)
    Abstract [en]

    Mortality in head and neck squamous cell carcinoma (HNSCC) is high due to emergence of therapy resistance which results in local and regional recurrences that may have their origin in resistant cancer stem cells (CSCs) or cells with an epithelial-mesenchymal transition (EMT) phenotype. In the present study, we investigate the possibility of using the cell surface expression of CD44 and epidermal growth factor receptor (EGFR), both of which have been used as stem cell markers, to identify subpopulations within HNSCC cell lines that differ with respect to phenotype and treatment sensitivity. Three subpopulations, consisting of CD44(high)/EGFR(low), CD44(high)/EGFR(high) and CD44(low) cells, respectively, were collected by fluorescence-activated cell sorting. The CD44(high)/EGFR(low) population showed a spindle-shaped EMT-like morphology, while the CD44(low) population was dominated by cobblestone-shaped cells. The CD44(high)/EGFR(low) population was enriched with cells in G0/G1 and showed a relatively low proliferation rate and a high plating efficiency. Using a real time PCR array, 27 genes, of which 14 were related to an EMT phenotype and two with stemness, were found to be differentially expressed in CD44(high)/EGFR(low) cells in comparison to CD44(low) cells. Moreover, CD44(high)/EGFR(low) cells showed a low sensitivity to radiation, cisplatin, cetuximab and gefitinib, and a high sensitivity to dasatinib relative to its CD44(high)/EGFR(high) and CD44(low) counterparts. In conclusion, our results show that the combination of CD44 (high) and EGFR (low) cell surface expression can be used to identify a treatment resistant subpopulation with an EMT phenotype in HNSCC cell lines.

  • 93.
    Landtblom, Anne-Marie
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Lindvall, Björn
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Neurology . Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Ledin, Torbjörn
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery . Östergötlands Läns Landsting, Reconstruction Centre, Department of ENT - Head and Neck Surgery UHL.
    Berlin, Gösta
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    A case report of plasmapheresis treatment in a patient with paraneoplastic cerebellar degeneration and high anti-Yo antibody titers2008In: Therapeutic Apheresis and Dialysis, ISSN 1744-9979, Vol. 12, no 1, p. 82-85Article in journal (Refereed)
    Abstract [en]

    A patient with paraneoplastic cerebellar degeneration due to anti-Purkinje cell antibodies (anti-Yo) arising from ovarian carcinoma with metastases was treated with three plasmapheresis (PP) series (a total of 22 PP treatments) over one year and was monitored by repeated otoneurological testing, balance tests and clinical investigations. Blood samples for antibody titers were checked on several occasions. Initially there was a weak clinical response and significantly improved test results regarding the caloric response, as well as a possible effect on visual suppression of the vestibulo-ocular reflex after caloric ear irrigation. After the first series of PP treatment, new metastases were found. A half year later there was a progressive course with increasing general symptoms. Serology tests showed continuously high titers of anti-Yo antibody, although somewhat lower after PP. We thus report a minor and short-lived effect of PP, possibly inhibited by the natural course of metastatic disease. © 2008 International Society for Apheresis.

  • 94.
    Ledin, Torbjörn
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences.
    Kammerlind, Ann-Sofi
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences. Ryhov County Hospital, Jönköping, Sweden.
    Dizziness and disequlibrium2010In: Physical activity in the prevention and treatment of disease: Professional Associations for Physical Activity, Stockholm: Swedish National Institute of Public Health , 2010, p. 356-366Chapter in book (Other academic)
    Abstract [en]

    Svimmelhet er en vanlig forekommende tilstand, og forekomsten øker med stigendealder. Nedsatt, mistet eller forstyrret funksjon i en eller flere av delene ibalansesystemet kan forårsakes av aldring samt av mange forskjellige sykdommerog skader og kan føre til forstyrret balansefunksjon og bevegelsesillusjoner(svimmelhet). Diagnostikken består blant annet av nøyaktig anamnese, tester avvestibulær funksjon, posisjonstester og vurdering av postural kontroll. Denneframstillingen behandler noen svimmelhetstilstander der bevegelsestrening erviktig for å oppnå størst mulig grad av tilheling.Akutt perifert vestibulært tap av balansenervens funksjon på den ene siden girrask og kraftig svimmelhet og balanseforstyrrelser. Tilheling kan påskyndes ved åstimulere sentral kompensasjon med øyebevegelser, hodebevegelser og balanseøvelserav gradvis økende intensitet. Ved godartet posisjonssvimmelhet, det vil sibenign paroksysmal posisjonell vertigo (BPPV), har noen otolitter løsnet og flyttetseg fra hinnesekk til buegang i det indre øret, noe som gir svimmelhet ved hodebevegelserog endringer i kroppsstilling. Ved BPPV brukes to forskjellige behandlingsprinsipper,habitueringstrening og manøverbehandling. Skader i sentralnervesystemetog aldersrelatere forandringer av balansesystemets funksjon kan også føretil svimmelhet og balanseforstyrrelser. Svimmelhet og balansevanskeligheter hoseldre er en stor risikofaktor for fall og påfølgende fraktur. Ved skade på sentralnervesystemetog ved aldersrelatert svimmelhet skal treningen forbedre balanse,koordinasjon og styrke, redusere bevegelsesfrykten og øke aktivitetsgraden.

  • 95.
    Ledin, Torbjörn
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences.
    Kammerlind, Ann-Sofi
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences. Sjukgymnastiken, Länssjukhuset Ryhov, Jönköping.
    Svimmelhet og Balanseforstyrrelser2009In: Aktivitetshåndboken: fysisk aktivitet i forebygging og behandling / [ed] Roald Bahr, Helsedirektoratet , 2009, p. 610-620Chapter in book (Other academic)
    Abstract [no]

    Svimmelhet er en vanlig forekommende tilstand, og forekomsten øker med stigendealder. Nedsatt, mistet eller forstyrret funksjon i en eller flere av delene ibalansesystemet kan forårsakes av aldring samt av mange forskjellige sykdommerog skader og kan føre til forstyrret balansefunksjon og bevegelsesillusjoner(svimmelhet). Diagnostikken består blant annet av nøyaktig anamnese, tester avvestibulær funksjon, posisjonstester og vurdering av postural kontroll. Denneframstillingen behandler noen svimmelhetstilstander der bevegelsestrening erviktig for å oppnå størst mulig grad av tilheling.Akutt perifert vestibulært tap av balansenervens funksjon på den ene siden girrask og kraftig svimmelhet og balanseforstyrrelser. Tilheling kan påskyndes ved åstimulere sentral kompensasjon med øyebevegelser, hodebevegelser og balanseøvelserav gradvis økende intensitet. Ved godartet posisjonssvimmelhet, det vil sibenign paroksysmal posisjonell vertigo (BPPV), har noen otolitter løsnet og flyttetseg fra hinnesekk til buegang i det indre øret, noe som gir svimmelhet ved hodebevegelserog endringer i kroppsstilling. Ved BPPV brukes to forskjellige behandlingsprinsipper,habitueringstrening og manøverbehandling. Skader i sentralnervesystemetog aldersrelatere forandringer av balansesystemets funksjon kan også føretil svimmelhet og balanseforstyrrelser. Svimmelhet og balansevanskeligheter hoseldre er en stor risikofaktor for fall og påfølgende fraktur. Ved skade på sentralnervesystemetog ved aldersrelatert svimmelhet skal treningen forbedre balanse,koordinasjon og styrke, redusere bevegelsesfrykten og øke aktivitetsgraden.

  • 96.
    Ledin, Torbörn
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences.
    Kammerlind, Ann-Sofi
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences.
    Yrsel och balansrubbningar2009In: Ordination motion, Bromberg , 2009, 1, p. 162-165Chapter in book (Other academic)
    Abstract [sv]

    Visste du att svenska läkare allt oftare skriver ut motion på recept? Att vi mår bättre när vi rör på oss och att det kan förebygga många skador är ett obestritt faktum, men att fysisk aktivitet även kan lindra och behandla krämpor och sjukdomar som redan har uppstått är ny kunskap. Det är inte farligt att vara fysiskt aktiv då man drabbats av sjukdom bara man undviker för hög belastning. Det kan dock vara svårt att veta vilka träningsformer som är bra och vilka man ska undvika. I boken Ordination:motion förmedlar svenska experter, främst läkare och sjukgymnaster, fakta på ett ingående och lättförståeligt sätt. Boken består av två delar - en »friskdel« för att förebygga sjukdom och en »sjukdel« som visar hur vi kan lindra vissa sjukdomar med hjälp av vardagsmotion och därmed uppnå bättre hälsa. Boken bygger på FYSS 2008, som är skriven av en rad medicinska experter och används inom sjukvården.

  • 97.
    Lidman, Disa
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Surgery . Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Niklasson, Magnus
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery . Östergötlands Läns Landsting, Reconstruction Centre, Department of ENT - Head and Neck Surgery UHL.
    Survival and function in patients with tumours of the head and neck operated on and reconstructed with free flaps2008In: Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery, ISSN 2000-656X, E-ISSN 2000-6764, Vol. 42, no 2, p. 77-85Article in journal (Refereed)
    Abstract [en]

    From 1983 to 2003, 131 patients were operated on in the head and neck region with 139 free flaps. They were operated on using a team approach of ear, nose, and throat surgeons and plastic surgeons, and sometimes maxillofacial surgeons. The tumours were squamous cell carcinoma (SCC) 104 (80%), salivary gland cancer 13 (10%), sarcoma 5 (4%), basal cell carcinoma 4 (3%), and others 4 (3%). The staging of the primary intraoral SCC tumours (n=79) was 42% in stage II, 28% in stage III, and 30% in stage IV. The survival of patients with primary oral SCC was compared with a previously treated previous series that gave an increase in tumour-related five-year survival from 48% to 58%. Most flaps were radial forearm flaps (73%). Fifteen percent were vascularised bone transfers. A questionnaire was sent to patients who had had oral/oropharyngeal tumours to measure function and satisfaction, to which 47/49 responded. The results including ability to chew and swallow, speech was good, with a median score of 0.78 (range 1-0).

  • 98.
    Lindgren, Stefan
    et al.
    Lund University.
    Brannstrom, Thomas
    Umeå University.
    Hanse, Eric
    University of Gothenburg.
    Ledin, Torbjörn
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of ENT - Head and Neck Surgery UHL.
    Nilsson, Gunnar
    Karolinska Institute.
    Sandler, Stellan
    Uppsala University.
    Tidefelt, Ulf
    University of Örebro.
    Donner, Jakob
    Lund University.
    Medical education in Sweden2011In: Medical teacher, ISSN 0142-159X, E-ISSN 1466-187X, Vol. 33, no 10, p. 798-803Article in journal (Refereed)
    Abstract [en]

    Undergraduate medical education in Sweden has moved from nationally regulated, subject-based courses to programmes integrated either around organ systems or physiological and patho-physiological processes, or organised around basic medical science in conjunction with clinical specialities, with individual profiles at the seven medical schools. The national regulations are restricted to overall academic and professional outcomes. The 51/2 year long university undergraduate curriculum is followed by a mandatory 18 months internship, delivered by the County Councils. While quality control and accreditation for the university curriculum is provided by the Swedish National Agency for Higher Education, no such formal control exists for the internship; undergraduate medical education is therefore in conflict with EU directives from 2005. The Government is expected to move towards 6 years long university undergraduate programmes, leading to licence, which will facilitate international mobility of both Swedish and foreign medical students and doctors. Ongoing academic development of undergraduate education is strengthened by the Bologna process. It includes outcome (competence)-based curricula, university Masters level complying with international standards, progression of competence throughout the curriculum, student directed learning, active participation and roles in practical clinical education and a national assessment model to assure professional competence. In the near future, the dimensioning of Swedish undergraduate education is likely to be decided more by international demands and aspects of quality than by national demands for doctors.

  • 99.
    Lofstrand-Tidestrom, Britta
    et al.
    Uppsala University.
    Hultcrantz, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of ENT - Head and Neck Surgery UHL.
    Development of craniofacial and dental arch morphology in relation to sleep disordered breathing from 4 to 12 years. Effects of adenotonsillar surgery2010In: INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY, ISSN 0165-5876, Vol. 74, no 2, p. 137-143Article in journal (Refereed)
    Abstract [en]

    Objectives: To study the development of craniofacial and dental arch morphology in children with sleep disordered breathing in relation to adenotonsillar surgery. Subjects and methods: From a community-based cohort of 644 children, 393 answered questionnaires at age 4,6 and 12 years. Out of this group, 25 children who were snoring regularly at age 4 could be followed up to age 12 together with 24 controls not snoring at age 4, 6 and 12 years. Study casts were obtained from cases and controls and lateral cephalograms from the cases. Analysis regarding facial features and dento-alveolar development was performed. Results: Children snoring regularly at age 4 showed reduced transversal width of the maxilla and more frequently had anterior open bite and lateral cross-bite than the controls. These conditions persisted for most cases at age 6, by which time 18/25 had been operated for snoring. In most of the cases, surgery cured the snoring temporarily, but their width of the maxilla was still smaller by age 12-even when nasal breathing was attained. At age 12, the frequency of lateral cross-bite was much reduced and anterior open bite was resolved, both in cases and controls. The children who snored regularly at age 12 operated or not operated, showed a long face anatomy and were oral breathers (this applied even to those who were operated). The seven cases who were not operated and the five who were still snoring in spite of surgery at age 12, did not have reduced maxillary width as compared to the controls. Conclusion: Dento-facial development in snoring children is not changed by adenotonsillar surgery regardless of symptom relief. If snoring persists or relapses orthodontic maxillar widening and/or functional training should be considered. Collaboration between otorhinolaryngologist, orthodontists and speech and language pathologists is strongly recommended.

  • 100.
    Lundeborg Hammarström, Inger
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Speech and Language Pathology.
    Ericsson, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of ENT - Head and Neck Surgery UHL.
    Hultcrantz, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of ENT - Head and Neck Surgery UHL.
    McAllister, Anita
    Linköping University, Department of Clinical and Experimental Medicine, Speech and Language Pathology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre. Östergötlands Läns Landsting, Sinnescentrum, Department of ENT - Head and Neck Surgery UHL.
    Influence of adenotonsillar hypertrophy on /s/-articulation in children-effects of surgery2011In: Logopedics, Phoniatrics, Vocology, ISSN 1401-5439, E-ISSN 1651-2022, Vol. 36, no 3, p. 100-108Article in journal (Refereed)
    Abstract [en]

    Tonsillar hypertrophy is common in young children and affects several aspects of the speech such as distortions of the dento-alveolar consonants. The study objective was to assess s-articulation, perceptually and acoustically in children with tonsillar hypertrophy and compare effects of two types of surgery, total tonsillectomy and tonsillotomy. Sixty-seven children, 50-65 months, on waiting list for surgery, were randomized to tonsillectomy or tonsillotomy. The speech material was collected pre-operatively and six months post-operatively.  Two groups of age-matched children were controls. /S/-articulation was affected acoustically with lower spectral peak locations and perceptually with less distinct /s/-production before surgery, in comparison to controls.  After surgery /s/-articulation was normalized perceptually, but acoustic differences remained. No significant differences between surgical methods were found.

1234 51 - 100 of 166
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf