| 1. |
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| 2. |
- Janson, Håkan, et al.
(författare)
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Protein D, the glycerophosphodiester phosphodiesterase from Haemophilus influenzae with affinity for human immunoglobulin D, influences virulence in a rat otitis model
- 1994
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Ingår i: Infection and Immunity. - 0019-9567 .- 1098-5522. ; 62:11, s. 4848-4854
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Tidskriftsartikel (refereegranskat)abstract
- A mutant lacking the ability to express the surface-exposed lipoprotein protein D was constructed by linker insertion and deletion mutagenesis of a cloned DNA insert containing the protein D structural gene from a nontypeable Haemophilus influenzae strain (NTHi). An isogenic NTHi mutant was isolated after transformation of genetically competent bacteria. The transformant was unreactive to a protein D-specific monoclonal antibody in a colony immunoassay. In addition, the mutant lacked the ability to synthesize detectable levels of protein D by protein staining, immunoblot methods, glycerophosphodiester phosphodiesterase activity, and binding studies of radiolabelled immunoglobulin D. The isogenic protein D-deficient mutant was compared with its parental strain for its ability to induce experimental otitis media in rats challenged with bacteria. An approximately 100-times-higher concentration of the mutant compared with that of the wild-type strain was required in order to cause otitis among all rats challenged with that given dose. The protein D mutant exhibited a generation time that was equal to that of the wild-type strain in complex broth medium. No difference in lipopolysaccharide expression was found between the mutant and the parental strain. These results suggest that protein D may influence the pathogenesis of NTHi in the upper respiratory tract.
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| 3. |
- Foglé-Ansson, Margaretha, et al.
(författare)
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Otomicroscopic findings and systemic interleukin-6 levels in relation to etiologic agent during experimental acute otitis media
- 2006
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Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : Wiley. - 0903-4641 .- 1600-0463. ; 114:4, s. 285-291
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study was to explore whether it was possible to differentiate the clinical course and the otomicroscopic appearance of acute otitis media (AOM) caused by common otitis pathogens in an animal model. Systemic interleukin (IL)-6 levels as early markers for bacterial AOM were also studied. Four groups of rats were inoculated with either Streptococcus pneumoniae, Streptococcus pyogenes, non-typeable Haemophilus influenzae or Moraxella catarrhalis. The animals were monitored by otomicroscopy, photos of the tympanic membrane, cultures and IL-6 detection in serum the following 4 days. The gram-positive S. pneumoniae and S. pyogenes induced severe AOM with opaque effusion behind the tympanic membrane, pronounced dilation of the vessels and spontaneous perforations. The gram-negative H. influenzae and M. catarrhalis induced a less severe infection with cloudy, sometimes foamy effusion, and no spontaneous perforations. With the otomicroscopic findings it was possible to distinguish between infections induced by gram-positive bacteria and gram-negative bacteria. Detection of interleukin-6 in serum appeared to be of limited use for all infections except the pneumococcal AOM, but this needs to be further investigated.
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| 4. |
- Magnuson, Karin, et al.
(författare)
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The tympanic membrane and middle ear mucosa during non-typeable Haemophilus influenzae and Haemophilus influenzae type b acute otitis media : a study in the rat
- 1997
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Ingår i: Acta Oto-Laryngologica. - : Informa UK Limited. - 0001-6489 .- 1651-2251. ; 117:3, s. 396-405
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Tidskriftsartikel (refereegranskat)abstract
- Non-typeable Haemophilus influenzae (NTHi) and encapsulated Haemophilus influenzae type b (Hib) were inoculated into the middle ears of Sprague-Dawley rats. Tympanic membrane (TM) status was assessed otomicroscopically and specimens from various middle ear areas were prepared for light microscopy at various times during the acute phase and up to 6 months after inoculation. Irrespective of bacteria strain, acute otitis media (AOM) was present in all ears 4 days after inoculation. The Hib-infected ears showed initially a severe course of AOM, but all were otomicroscopically resolved by day 12, at which time a few NTHi-inoculated ears still exhibited middle ear effusion. The TMs infected with Hib had normalized without scar formation, whereas NTHi induced a persistent thickening of the TMs in half of all cases. The middle ear mucosa of NTHi-infected ears initially showed vigorous activity among the goblet cells, but the mucosa normalized after the acute phase. Hib, by contrast, induced prominent changes in the middle ear mucosa. Initially, no goblet cell granules or ciliated cells could be observed in the mucosa. Later on, the epithelium contained large, active goblet cells. Glands appeared beneath the mucosa which persisted as streaks of epithelial cells throughout the study period. The findings show that NTHi and Hib both induce AOM but with differing clinical courses, and affect different targets in the middle ear.
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| 5. |
- Westman, Eva, 1966-
(författare)
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Experimental acute otitis media : aspects on treatment, protection and structural changes
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Acute otitis media (AOM) is a common disease in childhood and is one of the most common causes for outpatient antibiotic treatment. The major aetiological agents of AOM have varied over the decades. Now the three most common pathogens are Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. The resistance patterns of these organisms have also varied from the beginning of the antibiotic era to the situation we have today with an increasing incidence of penicillin-resistant S. pneumoniae and a moderate to high frequency of beta-lactamase production in H. influenzae and M. catarrhalis. In Sweden we have continued to use the Scandinavian treatment policy of penicillins as the first-line antibiotic treatment of AOM, which has been implemented with good results in the past. The question is if this policy will continue to have acceptable treatment results. In order to investigate aspects of treatment, protection and structural changes in AOM, an animal model was used. Amoxicillin treatment of AOM caused by H. influenzae was studied. Amoxicillin treatment was shown to shorten the duration of the infection and to reduce the morphological changes normally observed after an untreated AOM. The influence of antibiotic treatment on recurrent AOM was evaluated. Amoxicillin treatment did not lead to less protection against reinfection. Abstaining from antibiotics did not improve the levels of serum IgG antibodies. The IgG levels were significantly higher in treated animals after rechallenge. AOM caused by H. influenzae with a non-beta-lactamase-mediated resistance to beta-lactams was investigated and it was observed that during amoxicillin treatment the chromosomal changes mediating resistance were possibly advantageous for the bacterium. In cultures from children with AOM, there is sometimes growth of several bacteria. The possibility of a sheltering effect of beta-lactamase-producing H. influenzae on a penicillin-sensitive S. pneumoniae in a mixed infection was investigated, and amoxicillin was shown to eradicate the pneumococci from the middle ear despite the presence of beta-lactamase. An increasingly cultured bacterium in nasopharynx and in AOM is M. catarrhalis. It is now beta-lactamase-producing in almost 100% of cases and is thus not eradicated by penicillins. An animal model of AOM caused by beta-lactamase-producing M. catarrhalis was established to study the course of this infection with the possibility of evaluating aspects of virulence between AOM pathogens. The AOM observed was a self-limiting disease. The results obtained in this study in a rat model support the continuing use of penicillins as first-line drugs in the treatment of AOM. Penicillins are not sufficient to treat all causative agents, but the majority of pathogens including the most virulent bacteria are eradicated from the middle ear.
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| 6. |
- Berggren, Diana, et al.
(författare)
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Öron-, näs- och halssjukdomar hos barn
- 2020. - 5
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Ingår i: Barnmedicin. - Lund : Studentlitteratur AB. - 9789144129563 ; , s. 881-887
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 7. |
- Gisselsson-Solen, Marie, et al.
(författare)
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Individual-level effects of antibiotics on colonizing otitis pathogens in the nasopharynx
- 2016
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Ingår i: International Journal of Pediatric Otorhinolaryngology. - : Elsevier BV. - 0165-5876 .- 1872-8464. ; 88, s. 17-21
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although there is evidence of an association between antibiotic consumption and resistant bacteria on a population level, the relationship on an individual level has been less well studied, particularly in terms of nasopharyngeal colonization. We have therefore analysed this association, using data from a closely followed cohort of children taking part in a vaccination trial. Methods: 109 children with early onset of acute otitis media (AOM) were randomised to heptavalent pneumococcal conjugate vaccine (PCV7) or no vaccination. They were followed for three years with scheduled appointments as well as sick visits. Nasopharyngeal cultures were obtained at all visits. Antibiotic treatments were recorded, as were risk factors for AOM, including siblings, short breast-feeding and parental smoking. Data were entered into a Cox regression model, and the findings of Streptococcus pneumoniae and Haemophilus influenzae with reduced susceptibility to the penicillin group were related to the number of previous courses of antibiotics. Results: There was evidence of an association between the amount of previously consumed betalactams and colonization with beta-lactamasenegative ampicillin-resistant (BLNAR) H. influenzae (RR 1.21; 95% CI 1.03-1.43; p = 0.03), and also with the most commonly prescribed drug; amoxicillin (RR 1.39; 95% CI 1.09-1.76; p = 0.01). There was no evidence for an association between antibiotic consumption and betalactamase producing H. influenzae or S. pneumoniae with reduced susceptibility to penicillin. Furthermore, there was no evidence of an association between resistant bacteria and AOM risk factors or PCV7. Conclusion: In this subgroup of children, most of whom were given several courses of antibiotics in early childhood, there was evidence of an association between betalactam/amoxicillin consumption and nasopharyngeal colonization with BLNAR strains, bacteria that have increased in prevalence during the last 10-15 years, and that are notoriously difficult to treat with oral antibiotics.
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| 8. |
- Preciado, Diego, et al.
(författare)
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Panel 8 : Report on Recent Advances in Molecular and Cellular Biochemistry
- 2017
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Ingår i: Otolaryngology - Head and Neck Surgery. - : Wiley. - 0194-5998 .- 1097-6817. ; 156:4_suppl, s. 106-113
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To update the medical literature on recent cellular and molecular advances in otitis media disease models with a principal focus on developments in the past 5 years. We also aim to explain recent translational advances in cellular and molecular biology that have influenced our understanding and management of otitis media. Data Sources: PubMed-indexed peer-reviewed articles. Review Methods: A comprehensive review of the literature was conducted with the term otitis media and the following search terms: molecular biology, cell biology, innate immunity, oxidative stress, mucins, molecular diagnostics. Included articles were published in the English language from January 1, 2010, to July 31, 2015. Implications for Practice: The molecular understanding of otitis media disease progression has rapidly advanced over the last 5 years. The roles of inflammation, mucins, and cell signaling mechanisms have been elucidated and defined. Advances in the field provide a plethora of opportunities for innovative molecular targeting in the development of novel therapeutic strategies for otitis media.
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| 9. |
- Alzbutiene, Giedre, et al.
(författare)
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Tympanic membrane changes in experimental acute otitis media and myringotomy
- 2008
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Ingår i: Medicina. - 1648-9144. ; 44:4, s. 313-321
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Tidskriftsartikel (refereegranskat)abstract
- Objective. The present experimental study explored pathomorphological changes and calcium depositions in the tympanic membrane during experimental acute otitis media caused by nontypeable Haemophilus influenzae in myringotomized and nonmyringotomized ears. Material and methods. A rat model of experimental acute otitis media caused by nontypeable Haemophilus influenzae was employed Sixteen Sprague-Dawley rats were used. Four days following middle ear inoculation, a bilateral myringotomy was performed in six randomly selected animals. Another group of 10 animals was inoculated only. On days 4, 7, 14, and 28, after inoculation, two animals from each group were sacrificed The temporal bones were removed and the tympanic membranes were dissected, followed by paraffin embedding. Adjacent sections were stained with PAS-alcian blue for basic histopathological observations and by von Kossa method for determination of calcium phosphate depositions. Results. Particularly intense invasion of polymorphonuclear neutrophil leukocytes was, seen on day 4 after inoculation. The highest infiltration of macrophages was observed on day 7. The peak number of lymphocytes was seen on day 14. No difference occurred in the number of polymorphonuclear leukocytes in myringotomized and nonmyringotomized tympanic membranes. The infiltration with lymphocytes and activated macrophages in all parts of the myringotomized tympanic membranes was statistically significantly higher than in the nonmyringotomized animals. The total amount of interstitial calcium phosphate depositions during days 7, 14, and 28 of study was statistically higher in the sections of pars tensa from myringotomized membranes compared to the nonmyringotomized membranes. Conclusion. Nontypeable Haemophilus influenzae-induced acute otitis media and myringotomy provoke more extensive inflammatory reaction with microcalcification in the tympanic membranes.
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| 10. |
- Caye-Thomasen, P, et al.
(författare)
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Depletion of mucosal substance P in acute otitis media
- 2004
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Ingår i: Acta Oto-Laryngologica. - : Informa UK Limited. - 1651-2251 .- 0001-6489. ; 124:7, s. 794-797
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Tidskriftsartikel (refereegranskat)abstract
- Objective-The neuropeptide substance P (SP) is an inducer of neurogenic inflammation and bone resorption in the middle ear. Resorption of the bone tissue structures surrounding the middle ear cavity is a distinct feature of the initial stage of acute otitis media (AOM), which may be due to nerve fiber release of SP. Material and Methods-To investigate possible release of SP in the middle ear mucosa during AOM, we used a well-established rat model of AOM caused by Streptococcus pneumoniae. Following tissue extraction on Days 1, 3 and 6 post-inoculation, the mucosal concentration of SP was measured using a radioimmunoassay. Results-Compared to sham-inoculated control ears, the concentration of SP was significantly reduced on Day 1 and even further reduced on Day 3, whereas partial replenishment was found on Day 6. Conclusion-SP seems to be depleted in the rat middle ear mucosa in the hyperacute phase of AOM. This depletion is followed by replenishment and the concentration of SP approaches its normal level 6 days post-inoculation. The release of SP may be the trigger of the concurrent bone resorption and may further augment the inflammatory response to the bacterial colonization.
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