Thesis (doctoral)--Lund University, 1997. / Added t.p. with thesis statement inserted.

Thesis (doctoral)--Lund University, 1997. / Added t.p. with thesis statement inserted.

No description available.

Otitis Media is one of the most common childhood diseases. Recurrent acute otitis media RAOM is characterized by repeated episodes of inflammation of the middle ear in conjunction with middle ear fluid, and often with an inflamed or bulging eardrum. Defective clearance by the Eustachian tube results in mucus build-up and is characteristic of otitis media with effusion (OME). Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, respiratory syncytial virus, and rhinovirus are the most common contributors to otitis media pathogenesis. In New Zealand, OME has been implicated with conductive hearing loss in childhood and has been shown to significantly impact on speech and language development. New Zealand Māori and Polynesian children have displayed significantly higher hearing test failure rates than European-Caucasian children. The collectins, Surfactant Protein (SP)-A and -D are encoded by three genes (SP-A1, SP-A2, and SP-D) and are host defense proteins present in the middle ear and Eustachian tube. Single nucleotide polymorphisms (SNPs) in SP-A1 and SP-A2 have been associated with increased or decreased susceptibility to otitis media, meningococcal disease, and range of respiratory diseases. Using allele-specific primers and real-time PCR with SYBR Green I melting curve analysis, four groups of individuals were genotyped for eleven SP-A1, SP-A2, and SP-D SNPs: European-Caucasian individuals with RAOM/OME; New Zealand Māori/Polynesian individuals with RAOM/OME; individuals with meningococcal disease; and a control group. The computer program, Haploview, was employed to perform χ2 analyses and identify statistically significant associations of alleles/haplotypes with RAOM/OME or meningococcal disease. In the European-Caucasian population, two SP-A1 alleles, one SP-A2 allele, and four haplotypes (CGAGC, 1A3, 1A9, and 1A10) were found to be associated with increased risk of RAOM/OME (P lt; 0.05). Conversely, haplotypes 6A2 and 1A2 were found to be protective against susceptibility to RAOM/OME (P lt; 0.05). In New Zealand Māori and Polynesian individuals, two SP-A1 alleles, three SP-A2 alleles, one SP-D allele, and four haplotypes (6A8, 6A10, 1A3, and 1A10) were found to be associated with increased risk of RAOM/OME (P lt; 0.05). An additional four haplotypes (6A2, 1A0, 1A2, and TA) were determined to be protective against susceptibility to RAOM/OME (P lt; 0.05). However, protective SPA1/SPA2/SPD haplotype 6A2-1A0-TA was significantly under-represented in the New Zealand Māori and Polynesian population (P lt; 0.05). A single allele and haplotype were associated with increased risk of meningococcal disease (P lt; 0.05). The findings of this study confirm that specific genetic variants of SP-A and SP-D are associated with either increased or decreased risk of developing RAOM and/or OME. Furthermore, it was demonstrated that New Zealand Māori and Polynesian individuals appear to exhibit more haplotypes susceptible to RAOM/OME. This may provide a partial explanation for the higher RAOM/OME-related failure rates of hearing tests in New Zealand Māori and Polynesian children. However, there are numerous socio-economic and environmental factors that also contribute to otitis media pathogenesis which were not considered in this study. The effects of the SP-A1, SP-A2, and SP-D alleles and haplotypes on the bacterial/viral binding efficiencies of SP-A and SP-D need to be investigated by further research, using a large population, to confirm the association with susceptibility or resistance with RAOM/OME.

Diss. (sammanfattning) Linköping : Linköpings universitet, 2008. / Härtill 4 uppsatser.

Thesis (M.S.)--Oregon State University, 2010. / Printout. Includes bibliographical references (leaves 73-76). Also available on the World Wide Web.

Thesis (Ph. D.)--School of Biology, Georgia Institute of Technology, 2005. Directed by Paul Edmonds. / Paul Edmonds, Committee Chair ; Steve Harvey, Committee Member ; Igor Zhulin, Committee Member ; Yury Chernoff, Committee Member ; Mostafa El-Sayed, Committee Member. Includes bibliographical references.

Thesis (doctoral)--University of Lund, 1981.

Abstract The purpose was to evaluate the microbiological mechanism of action of xylitol and to assess its use in clinical practice for preventing acute otitis media (AOM). To test whether the effect of xylitol on S. pneumoniae is inhibited by fructose, a total of 20 strains of S. pneumoniae were exposed to xylitol in the presence of fructose and other carbon sources. Addition of 5% xylitol to the media resulted in marked growth inhibition, an effect which was totally eliminated in the presence of 1%, 2.5% or 5% fructose but not in the presence of 1% or 5% glucose, 1% galactose or 1% sucrose. The inhibition of pneumococcal growth is probably mediated via a fructose phosphotransferase system in a similar manner to that seen in mutans streptococci. Sorbitol alone did not affect the growth of pneumococci, and thus sorbitol is unlikely to provide any clinical benefit in the prevention of AOM. To evaluate the effect of xylitol on the ultrastructure of S. pneumoniae and Haemophilus influenzae (H. influenzae) and on the pneumococcal phenotype, five strains of S. pneumoniae and one strain of H. influenzae were examined by electron microscopy after xylitol exposure. Xylitol damaged the ultrastructure of the pneumococci. Some of the bacteria were lysed and the cell wall of the remaining ones became more diffuse and the polysaccharide capsule was ragged. The resulting morphology was identical to that of the transparent pneumococcal phenotypic variant. The properties of the transparent variants of pneumococci could explain the clinical efficacy of xylitol in preventing AOM despite the lack of effect on the nasopharyngeal carriage of pneumococci. The cell wall of H. influenzae became slightly thicker, but the morphology remained otherwise unchanged. To evaluate the pharmacokinetics of xylitol locally in the nasopharynx, xylitol concentrations were measured in the saliva of 65 children by enzymatic assay after giving them xylitol chewing gum or syrup at doses equal to those used in clinical trials. Concentrations high enough to have an antimicrobial effect were attained, but the xylitol disappeared from the saliva within 15 minutes, which indicates that high peak concentrations may be more important for efficacy than the time for which the concentration exceeds the level needed for an antimicrobial effect. To find a more convenient dosing regime for xylitol prophylaxis, xylitol was administered to 1277 children only during an acute respiratory infection (ARI) in a randomised placebo-controlled trial. The occurrence of AOM during ARI was 34/166 (20.5%) in the xylitol mixture group as compared with 32/157 (20.4%) among the children receiving the control mixture. Among older children receiving control chewing gum, xylitol chewing gum or xylitol lozenges, AOM was experienced by 24/218 (11.0%), 31/220 (14.1%) and 34/219 (15.5%) respectively. None of the differences between the groups was statistically significant. Xylitol should be used continuously in AOM prophylaxis, as it proved ineffective when used only during URI.

Abstract This study was undertaken to improve the diagnosis of otitis media and to investigate possible hearing loss caused by middle ear effusion (MEE) in small children. The accuracy of minitympanometry in detecting MEE was evaluated in 162 children. The finding was compared with the amount of effusion found in myringotomy. Minitympanometry proved to be an accurate method to detect MEE in young children, the sensitivity and specificity values being 79% and 93% in cooperative children but it had no value in non-cooperative children. Minitympanometric examination could be performed successfully with good cooperation in 87% of a total of 206 children in paediatric outpatient clinic. Impaired mobility of the tympanic membrane (TM) was the best sign of MEE in pneumatic otoscopy of 76 children, with sensitivity and specificity values of 75% and 90%, respectively. The influence of nitrous oxide (N2O) on MEE was tested by weighting the effusion found in myringotomy during general anaesthesia with and without N2O in 39 and 37 children, respectively. The mean weight of the effusion in the oxygen-air group did not differ from the weight in the N2O group, and thus peroperative findings in myringotomy are reliable. Studies on symptomatology and the temporal development of acute otitis media (AOM) during upper respiratory tract infection (URI) were based on three-month follow-up of 857 children. Symptoms of URI only were compared with symptoms of URI complicated by AOM in the same child in 138 children. The most important symptom associated with AOM was earache, with a relative risk of 21.3. Sore throat, night restlessness and fever at days 3-6 were also significantly associated with AOM, with relative risks of 3.2, 2.6 and 1.8, respectively. In 44 children under two years of age, earache, conjunctival symptoms and cloudy rhinitis were significantly associated with AOM. Temporal development of AOM was assessed from 250 episodes in 184 children. Sixty-three per cent of cases of AOM occurred during the first week after the onset of URI, peaking on days 2 to 5. The onset of AOM in children with a history of recurrent episodes of AOM did not differ from that in those who had experienced only a few episodes of AOM. No individual tendency was noticed among children suffering more than one AOM episode during follow-up. To assess the influence of the quantity and quality of MEE on hearing in small children, transient evoked otoacoustic emission (TEOAE) was performed under general anaesthesia before myringotomy in 185 ears of 102 children. Reduced TEOAEs indicating hearing loss were found in 83% of the ears with mucoid effusion and in 56% of the ears with non-mucoid effusion, the difference being statistically significant (p < 0.01). A significant negative correlation between the reproducibility of TEOAE responses and the amount of effusion was found (Spearman rank correlation coefficient r = -0.589, p < 0.001). Findings in minitympanometry correlated with the responses of TEOAE. Although parents are able to predict AOM quite reliably, various symptoms and the duration of URI seems to be of little value in helping the diagnosis of AOM. Detection of effusion in OM may be improven by minitympanometry in cooperative children. Any kind of effusion may cause hearing loss in small children, which must be considered when treating OM.