Background Swallowing problems are common in Parkinson’s disease, and these affect morbidity and mortality largely due to aspiration-induced pneumonia. Even mild dysphagia affects patient Quality of Life. Deep Brain Stimulation (DBS), a surgical treatment for Parkinson’s disease, improves overall motor function, though the effect of DBS on swallowing function is not clear. The aim of the studies in this thesis was to improve our understanding of the effect from DBS of caudal zona incerta and subthalamic nucleus on pharyngeal swallowing function. Specific aims were to compare DBS effects over time postoperatively (6 & 12 months) for swallowing function, on and off stimulation, with a preoperative baseline assessment in order to identify possible negative swallowing effects of DBS. Methods Eight patients with DBS in caudal zona incerta and eleven patients with DBS in subthalamic nucleus were included in the two studies. The effect of DBS on swallowing function was evaluated by self-estimation on a visual analogue scale and fiberoptic endoscopic evaluation of swallowing function with a predefined swallowing protocol including Rosenbek’s Penetration/Aspiration Scale, Secretion Severity Scale,preswallow spillage, pharyngeal residue and pharyngeal clearance. The patients with caudal zona incerta DBS also answered questions regarding swallowing-related Quality of Life. All patients received L-dopa treatment during postoperative assessments. Results There was no clear effect of DBS on swallowing function in the two samples. The occurrence of aspiration, secretions, pharyngeal residue or clearance was not affected by the surgery or the stimulation. In the subthalamic nucleus DBS sample, self-estimations revealed an improvement with stimulation turned on. For the caudal zona incerta DBS patients, no effect of DBS was seen on the results from the swallowing-related QOL questions. Conclusion Subthalamic nucleus DBS and caudal zona incerta DBS did not appear to have a negative effect on swallowing function in this cohort. Patients with subthalamic nucleus DBS reported a self-perceived improvement in swallowing function after DBS. There appears to be no increased risk for aspiration or penetration due to surgery or stimulation regardless of stimulation site. Since the sample sizes in these cohorts are small, the findings need to be confirmed in larger studies.

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King-Kopetzkys syndrom (KKS) beskrivs som när en person upplever svårigheter med att uppfatta tal, speciellt i bullriga miljöer, men har normala tontrösklar. Orsaken till syndromet är fortfarande oviss och detta gör att de som jobbar inom hörselvården ställs inför ett val då de möter dessa patienter. Patienten kan antingen avfärdas då denne anses höra normalt, eller så tas problemet på allvar och vidare utredning utförs. Genom att göra en systematisk litteraturstudie belyses och förklaras syndromet och syftet har varit att göra en sammanställning och ge en översikt över KKS utifrån de vetenskapliga artiklar som berör ämnet. Målet med detta arbete är att öka förståelsen för KKS. Resultatet pekar på att det är fler kvinnor än män som drabbas och att medelåldern för de med syndromet är ganska låg, runt 32 år. Det finns många olika teorier till orsaken och ingen är i dagsläget mer rätt än den andra. Detsamma gäller mätningar som använts för att försöka utreda syndromet, här framkommer många olika förslag på vägen till diagnostisering. Slutsatsen som dras är att mer forskning kring ämnet är nödvändigt för att få en förklaring och ett tillvägagångssätt för diagnostisering av syndromet.

digitalisering@umu.se

No description available.

Idiopathic Sudden Sensorineural Hearing Loss (ISSNHL) is a rapid loss of hearing caused by damage to the cochlea (inner ear) or auditory nerve. Spontaneous recovery has been seen in 32% - 81%. The incidence of the ISSNHL has been estimated to be between 5 and 20 per 100,000 per year. Different theories (infections, vascular catastrophes, immunologic damage or intracochlear membrane break) about the etiology have resulted in different treatment policies. The effect of therapy is difficult to evaluate for a single physician who sees just a few patients annually. The aim of the present thesis was to analyze the management and treatment of ISSNHL patients in Sweden with regard to outcome. A national database was developed for Sweden with half of all ENT clinics in Sweden participating by submitting a questionnaire for each patient with SSNHL. The questionnaire covered the patient’s background, current disorder, past and family history of different diseases, examinations and treatment. Audiograms at the onset of SSNHL and after three months were requested. All results were analyzed using ordinal logistic regression looking for interactions with hearing recovery and remaining hearing loss as dependent variables. Independent of treatment or no therapy heredity for hearing loss (I, II), older age (I, II) and presence of vertigo (II) was significantly associated with negative outcome. 40% of all patients had an MRI or CT, where 3 – 4% had acoustic neuroma. 24% of patients with ISSNHL who had hematological tests taken had one or more pathological findings. Blood screening varied from simple routine tests to a complete analysis with such tests as HSP70, Anti-Neutrophilic Cytoplasmic Antibodies (ANCA) and Borrelia tests. There was no association between any of these laboratory tests and either hearing improvement or remaining hearing loss evaluating the tests separately (I, II) or after categorization in comparison with those who had normal laboratory findings (II). Patients with hearing loss in the mid-frequency region had significantly better odds for hearing improvement compared to the other three frequency regions (low, high and “flat loss”). Almost 60% of patients with ISSNHL were medically treated, of which nearly 90% got corticosteroids. The medication had no association with either hearing improvement or remaining hearing loss. However, patients who were prescribed rest or sick leave had higher odds for hearing improvement regardless of other treatment. Those patients who did not receive any treatment at all also came significantly later to the ENT clinics than those treated medically and consequently had worse prognosis. Conclusion: There is no standard program for management or treatment of ISSNHL in Sweden. The diagnostic protocol varies. MRI is an underused resource to get specific diagnoses for the condition especially acoustic neuromas. Regardless of pathological findings, treatment is mainly limited to corticosteroids or no medication with no difference in outcome. A randomized placebo controlled study is necessary to evaluate whether there is an effect of corticosteroids on ISSNHL.

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.

Sammanfattning: Ljudlokalisering är en viktig hörselfunktion och fungerar bäst med en god binaural hörsel. För att kunna lokalisera ljud använder hörselsystemet ett antal faktorer. Vid en sensorineural hörselskada påverkas förmågan att uppfatta de här faktorerna. Syftet med studien var att förklara de faktorer som inverkar vid ljudlokalisering och hur riktningshörseln påverkas vid en sensorineural hörselskada. Det här utfördes genom att granska och sammanställa aktuell forskning i en forskningsöversikt. Resultatet visar att de viktigaste faktorerna vid ljudlokalisering i det horisontella och vertikala planet är interaural tidsskillnad, interaural styrkeskillnad och olika spektrala faktorer. Andra faktorer av vikt vid ljudlokalisering är ljudets amplitud, konkurrerande ljud, ljudkällans placering och avståndet till ljudkällan. Vid avståndsbedömning är den viktigaste akustiska faktorn ljudets amplitud, men de spektrala faktorerna har en viss inverkan även här. Resultatet visar att sensorineuralt hörselskadade personer överlag har en sämre förmåga att tillgodogöra sig de akustiska faktorer som påverkar lokalisering av ljud jämfört med normalhörande personer.