Includes bibliographical references (leaves 49-50).

Includes abstract. / Includes bibliographical references. / Pharyngocutaneous fistula is a common complication of total laryngectomy. We hypothesised that perioperative proton pump inhibitor (PPI) treatment could reduce the incidence of pharyngocutaneous fistulae. This prospective placebo-controlled double-blind randomised controlled trial compared PPI treatment (14 days enteral omeprazole) with a placebo in patients undergoing primary total laryngectomy. The incidence of pharyngocutaneous fistula was recorded.

Includes summary. Includes bibliographical references.

Background: Single-sided deafness is defined as a severe-to-profound hearing loss in one ear and normal or near-normal hearing in the other ear. The handicap experienced by patients with bilateral sensorineural hearing loss is well known, but the consequences of single-sided deafness are often underestimated based on the assumption that a person with normal hearing in the contralateral ear is not likely to face a major handicap. Objectives: To determine the handicap level in patients with single-sided deafness, and compare the handicap between employed and unemployed patients. Also, to investigate the relationship between perceived disability and noise in the workplace. The effect of age and duration of hearing loss on the perceived disability of single-sided deafness was also examined. Methods: Two validated questionnaires (1) Speech, Spatial and Qualities of Hearing Scale (SSQ12); and (2) Hearing Handicap Inventory for adults (HHIA) were handed to participants with SSD. This research was conducted in two tertiary hospitals in Cape Town, namely, Groote Schuur Hospital and Red Cross War Memorial Children's Hospital, over the period from November 2018 to August 2020. Results: Fifty-four participants were included in the study, 44 adults and 10 children. Employing the HHIA questionnaire, the results show that 39% of adult participants have a significant handicap compared to 32% who have a moderate handicap and 30% who have no handicap. Also, there was no significant difference in the total handicap scores between the employed and unemployed groups, and the presence of noise in the workplace did not influence the total handicap score in the employed group. There was no influence on age or duration of hearing loss on the total handicap score. The mean of the responses in the SSQ12 questionnaire was between 3.42 and 7; thus, some participants experience major hearing difficulties, while others have minor difficulties. Most of the participants are struggling to follow a conversation with background noise and have difficulty localizing sounds. They also struggle to identify the sound distance. They report increased effort when listening to someone or something. Conclusions: A majority of the patients with single-sided deafness in our population either have a severe or a mild-moderate handicap. A good assessment of the individual's degree of handicap is required to adequately counsel the patient and assist in the decision regarding treatment options.

<p>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.</p><p>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).</p><p>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.</p><p>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.</p><p>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.</p>

<p>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.</p><p>The aim of the present thesis was to analyze the management and treatment of ISSNHL patients in Sweden with regard to outcome.</p><p>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.</p><p>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.</p><p><em>Conclusion:</em> 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.</p>

The aim of this thesis was two-fold: first, to evaluate four different functional aspects of the speech and language spectrum; oral-motor function, voice, /s/-articulation and phonology in preschool children with tonsillar hypertrophy before and after surgical treatment. The second aim was to investigate weather the outcome of surgery was equal for two surgical techniques; tonsillectomy or tonsillotomy combined with adenoidectomy when necessary. In all included publications (I-IV), 67 children on waiting list for tonsil surgery and randomized to either tonsillectomy (33) or tonsillotomy (34) participated. The children were assessed and audio-recorded within a month before surgery and six months postoperatively. Results were compared to age-matched control groups. In the first study, oral motor function was assessed using the Nordic Orofacial Test-Screening, NOT-S, consisting of a structured interview and a clinical examination. Before surgery, the children in the study group differed in all domains of the structured interview in comparison to age-matched controls and in the clinical examination regarding the parameters deviant lip position and trouble nose-breathing. Postoperatively oral motor functions were normalized in both surgical groups and no differences to age matched controls were observed. In study two, recordings of three sustained vowels (/α , u, i/) and 14 words elicited by picture naming were analysed both perceptually and acoustically. Compared to the controls, significant differences were found in the study group preoperatively with higher ratings on Visual Analogue Scales (VAS) for the voice quality parameters “hyponasality” and “compressed/throaty” and also lower for pitch. Significantly higher values on all studied perturbation measures (jitter, shimmer and Noise to Harmonics Ratio) were found. Regarding center frequencies of formants, the study groups had lower F3 values for /u / and also lower F2 and F3 for / i / compared to age-matched controls. After surgery there were no significant differences between the perceptual ratings of voice quality of the two surgical groups and there were no significant differences between the children in the surgical groups and the corresponding controls. The acoustic analyses showed a decrease in all the measures of perturbation for the study group after surgery with a slight difference between the two surgical groups. The children in the tonsillotomy group had higher shimmer value for /u/ and higher NHR for /α/. In comparison to the older controls significantly higher values were found an all perturbation measures and the difference seen regarding formant frequencies for the /i/-sound in comparison to controls still remained. The significantly lower third formant (F3) of the /u/-sound also remained. When comparing pre- versus postoperative results for the surgical group as a whole, a decrease was found on all perturbation measures postoperatively, however the differences were not statistically significant. A significant increase was found in formant 3 for /α/ and /u/ was found. The material used in the third study were speech samples containing the /s/-sound and elicited by picture naming and sentence repetition. Before surgery the study group was rated to have more indistinct /s/-sounds than agematched controls. The acoustic analyses showed that the study group had lower spectral peak values for the /s/-sound than controls. After surgery the operated children’s /s/-production did not differ perceptually from the older controls, neither as a whole group nor when divided according to surgical methods. Regarding the acoustic analyses however, the study groups differed from the age-matched control group showing that noise duration was longer and the peak location higher in the study groups. In study four, a Swedish phonology test was performed and transcribed phonetically. The transcription of each child was analyzed in terms of phonological processes and categorized into one of six developmental stages according to the model developed by Nettelbladt (1983) and adapted by Sahlén, Reuterskiold-Wagner, Nettelbladt &amp; Radeborg (1999). A majority of the children in the study group (62.7 %) showed a slowed phonological development preoperatively (developmental stages 0-4), compared to the age-matched control group. Postoperatively the children in both surgical groups had improved their phonological skills. However, they were still behind in comparison to age-matched controls and the difference was even larger than before surgery. The results of this thesis project have clinical relevance for both speech and language pathologists (SLP’s) and ear-nose and throat-surgeons (ENT-surgeons). SLP’s must be aware of the potential impact of tonsillar hypertrophy on oral-motor function and the speech and language spectrum to be able to help affected children adequately and ENT- surgeons should include oral motor and speech and language problems as additional indications for tonsillar surgery.

Early identification of hearing impairment in children is essential to avoid potentially disabling effects of hearing loss or deafness. This necessitates effective screening measures appropriate to the community in question. Current methods used in South Africa, especially for pre-school and school going children have resulted in poor coverage as they are designed for the more developed countries. There is thus a need to devise a screening method that is appropriate to our local conditions. In this study, a free-field live voice test was developed based on three levels: whisper, conversational and loud. This was evaluated against pure tone audiometry for sensitivity, specificity, cost and ease of application in two studies: hospital and school- based. A total of 394 children were tested; 189 in hospital-based study and 205 in school based study. 378 of the total were eligible for analysis. In the hospital-based study, the results of 177 children were analysed. The age range was 3 - 12 years with a mean of 5.8 years. The sensitivity (ability of the test to detect hearing impairment) was 80.0%; and the specificity (ability to identify children with normal hearing) was 95.0%. In the school-based study, done after modification and standardisation of the test set, the sensitivity and specificity were 83.3% and 97.8% respectively. Age range was 3 - 8 years with 79% being 4- 6 years. In both studies, the voice test was simpler to perform, easily understood and acceptable to the children and the testers; and considerably cheaper as the only equipment required was picture/toy set. The main limitation was non-standardisation of the test set. This was rectified in the school-based study. The drawbacks noted were the inability of the voice test to detect unilateral hearing loss/deafness and high frequency hearing loss. The voice test generally correlated well with pure tone audiometry and could be used as alternative for screening for hearing impairment in the community especially for pre-school and school going children. However, it is recommended to repeat the study in actual community settings using Community Health Care Workers as the testers. This would also determine the reliability of the voice test, as this cannot be reliably established at this stage.

Breathing disorders can potentially influence craniofacial development through interactions between the respiratory flow and genetic and environmental factors. It has been suggested that certain medical conditions such as persistent rhinitis and renal insufficiency may have an influence on face shape. The effects of these conditions are likely to be subtle; otherwise they would appear as an obvious visible facial feature. The use of three-dimensional imaging provides the opportunity to acquire accurate and high resolution facial data to explore the influence of medical condition on facial morphology. Therefore, the aim of the present study is to investigate the influence of breathing disorders (asthma, atopy, allergic rhinitis and sleep disordered breathing) on face shape in children. The study sample, comprising of 4784 British Caucasian children of which 2922 (61.1%) were diagnosed with a breathing disorder, was selected from the Avon Longitudinal Study of Parents and Children (ALSPAC), which had been conducted to investigate the genetic and environmental determinants of development, health and disease. Three-dimensional surface laser scans were conducted on the children when they were 15 years old. A total of 21 reproducible facial landmarks (x, y, z co-ordinates) were identified. Average facial shells were constructed for each of the different disease groups and compared to facial shells of healthy asymptomatic children. Face-shape variables (angular and linear measurements) were analysed with respect to the different breathing disorders by employing a variety of statistical methods, including t-tests, chi-square tests, principal component analysis, binary logistic regression and analysis of variance (ANOVA). The results reveal that individual breathing disorders have varying influences on facial features, including increased anterior lower face height, a more retrognathic mandible and reduced nose width and prominence. The study also shows that the early removal of adenoids and tonsils can have a significant effect on obstructive breathing, resulting in the restoration of the facial morphology to its normal shape. This was particularly evident in children with normal BMIs. Surprisingly, no significant differences in face shape were detected in children with multiple diseases (combinations of asthma, allergic rhinitis, atopy and sleep-disordered breathing) when compared to healthy children. This may indicate the multifactorial, complex character of this spectrum of diseases. The findings provide evidence of small but potentially real associations between breathing disorders and face shape. This was largely attributable to the use of high-resolution and reproducible three-dimensional facial imaging alongside a large study sample. They also provide the scientific community with a detailed and effective methodology for static facial modelling that could have clinical relevance for early diagnosis of breathing disorders. Furthermore, this research has demonstrated that the ALSPAC patient archive offers a valuable resource to clinicians and the scientific community for investigating associations between various breathing disorders and face shape.

Ménière’s disease affects 1 in 1000 people and produces vertigo and hearing loss (Morrison, 1981). Endolymphatic sac decompression has been advocated on the basis that endolymphatic hydrops is the underlying pathology. The endolymphatic sac is said to be the terminal dilatation of the membranous labyrinth. It has been proposed that endolymph flows from the semicircular canals and cochlea to the endolymphatic sac. Portman (1927) devised a procedure for ‘decompressing’ the endolymphatic sac by removal of the bone from the posterior cranial fossa to relieve the symptoms of Ménière’s disease. Surgery on the endolymphatic sac remains controversial. Shea (1979) and Bagger-Sjöbäck et al (1990, 1993) have studied the endolymphatic sac using different techniques. There are discrepancies in the results between the two studies. The hypothesis that the endolymphatic sac can be safely approached and decompressed by a transmastoid route was tested. A total of thirteen cadaver heads and ten isolated temporal bones were used. A series of dissections were performed to examine the endolymphatic sac, perform measurements and analyse surgical approaches to the sac. Histological and electron microscopic study were performed. The lumen of the endolymphatic sac was not always identifiable in the dura of the posterior cranial fossa or it frequently lay over the sigmoid sinus. In the dura of the posterior cranial fossa where the endolymphatic sac is located was a thickening of the dura. This thickening was present even in the absence of the endolymphatic sac. The endolymphatic sac can be safely approached by a transmastoid approach, if there is an extraosseous component to the endolymphatic sac. The proximal endolymphatic sac can be approached by posterior cranial fossa route.