| 1. |
|
|
| 2. |
- Eriksson, Per Olof, 1968-
(författare)
-
Developing otitis media : experimental studies in particular regarding inflammatory changes in the tympanic membrane
- 2004
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Otitis media (OM), one of the commonest of childhood diseases, causes much suffering. OM exists in a variety of forms, two of which are acute otitis media (AOM) and otitis media with effusion (OME). The clinical courses of these conditions differ, AOM usually presenting with earache, fever and/or aural discharge, and the OME usually with hearing impairment. The tympanic membrane (TM) mirrors the events in the middle ear cavity, and pars flaccida (PF) is the initial site of inflammatory changes in the TM. PF is rich in mast cells (MCs), which by releasing various mediators, may trigger TM inflammation. The aims of the present studies were to investigate early inflammatory changes in the TM in rat models of OM; after mast cell degranulation, in response to AOM, and OME, after myringotomy in AOM and in normal ears. Furthermore, we developed a new rat AOM model, that excludes surgical trauma and resembles the natural route of infection in man. AOM and OME elicited the first inflammatory response in PF of the TM. The response to OME was discrete, but a slight increase in macrophages was found. During the first 48 hours of AOM, the inflammatory response was intense, following a bimodal pattern. This reaction is similar to that found after MC degranulation. In AOM, macrophages were the predominant cell in PF, while in pars tensa (PT), polymorphonuclear cells (mainly neutrophils) predominated. When myringotomy was performed in AOM ears, the healing time was shorter than that of myringotomy in normal ears. The highly inflamed lamina propria seemed to promote healing. During early AOM, as well as following myringotomy, fibrin extravasates into PF and PT. This fibrin deposition may be involved in regulating the inflammatory response. Repeated nasal challenge with the otitis media pathogen Streptococcus pneumoniae provoked AOM and concomitant TM stimulation reduced the number of AOM cases. This new rat AOM model has the advantage of avoiding trauma in the middle ear cavity, while eliciting an intense inflammatory response in the middle ear cavity (MEC).
|
|
| 3. |
- Harsten, Göran, et al.
(författare)
-
Language-Development In Children With Recurrent Acute Otitis-Media During The 1st 3 Years Of Life - Follow-Up-Study From Birth To 7 Years Of Age
- 1993
-
Ingår i: Journal of Laryngology and Otology. - 1748-5460. ; 107:5, s. 407-412
-
Tidskriftsartikel (refereegranskat)abstract
- From a cohort of 113 children, followed prospectively from birth during the first three years of life regarding different aspects of acute otitis media (AOM), two study groups were selected for the present investigation: 13 children with recurrent AOM (rAOM, i.e. at least six episodes of AOM during a 12–month period), and 29 children without any AOM episode. The purpose of this study was to analyse the possible effects of early onset rAOM on language development as assessed at four and seven years of age at phoniatric and linguistic examinations performed blindly. There were no differences between the two groups on any of the linguistic analyses performed, although the rAOM group manifested a somewhat better performance on auditory discrimination tests at four years of age. The results of the present study show that rAOM during the first three years of life, in otherwise healthy children, does not cause a detectable delay of language development at four and seven years of age.
|
|
| 4. |
- Melhus, Åsa, et al.
(författare)
-
A resolved pneumococcal infection protects against nontypeable Haemophilus influenzae : an evaluation of different routes of whole cell immunization in protection against experimental acute otitis media
- 1997
-
Ingår i: International Journal of Pediatric Otorhinolaryngology. - 0165-5876 .- 1872-8464. ; 39:2, s. 119-131
-
Tidskriftsartikel (refereegranskat)abstract
- A conferred cross-protection between Haemophilus influenzae type b (Hib) and nontypeable H. influenzae (NTHi) was demonstrated in a previous study of experimental recurrent otitis media. To explore cross-protection further, and to compare oral administration of whole cells with two more conventional routes for vaccination against acute otitis media (AOM), a total number of 79 rats were immunized perorally, subcutaneously and intrabullarly with H. influenzae or pneumococci and thereafter challenged in the middle ear with NTHi or Hib 4 or 9 weeks later. Otomicroscopic changes, bacterial cultures, and serum IgG antibody levels were monitored. The study demonstrated that while peroral administration did not elicit any protection, a resolved pneumococcal AOM could reduce the susceptibility to reinfection with NTHi. In the latter case no cross-reacting antibodies were detected, but the protective rate was 50% or more, and it was comparable with that found after subcutaneous or intrabullar immunization with homologous NTHi or Hib strains. The results suggest that the protection of the rat middle ear mucosa may involve unspecific responses.
|
|
| 5. |
- Melhus, Åsa, et al.
(författare)
-
Amoxicillin treatment of experimental acute otitis media caused by Haemophilus influenzae with non-beta-lactamase-mediated resistance to beta-lactams : aspects of virulence and treatment
- 1997
-
Ingår i: Antimicrobial Agents and Chemotherapy. - 0066-4804 .- 1098-6596. ; 41:9, s. 1979-1984
-
Tidskriftsartikel (refereegranskat)abstract
- Through alterations primarily in the penicillin-binding proteins, a non-beta-lactamase-mediated resistance to beta-lactams has evolved in Haemophilus influenzae. The virulence of these chromosomally changed strains has been questioned. To ascertain whether these alterations involve a reduction in virulence of H. influenzae and whether they could be advantageous for the bacterium during amoxicillin treatment of acute otitis media, a total of 70 Sprague-Dawley rats were challenged with a susceptible recipient strain or a genetically similar resistant transformant strain. Antibiotic therapy was started on day 3 after inoculation, and the animals were monitored by daily otomicroscopy and analysis of bacterial samples from middle ear effusions obtained on day 8, the last day of observation. The animals were also sacrificed on days 4 and 8 and after 2 months for morphological examination. Compared with the susceptible recipient strain, recovery from infections caused by the resistant transformant strain was delayed, and the late structural changes were more severe in the animals challenged with the latter strain. The results of the study indicate that chromosomal alterations mediating a relatively low level of resistance to beta-lactams may be advantageous for H. influenzae during antibiotic treatment of a local infection in the rat, and the alterations may occur without any significant loss of virulence.
|
|
| 6. |
|
|
| 7. |
- Melhus, Åsa, et al.
(författare)
-
Effect of Haemophilus influenzae type b conjugate vaccine in combination with peroral immunization with Escherichia coli on experimental otitis media
- 1996
-
Ingår i: International Journal of Pediatric Otorhinolaryngology. - : Elsevier BV. - 0165-5876 .- 1872-8464. ; 36:1, s. 1-12
-
Tidskriftsartikel (refereegranskat)abstract
- The protective ability of a conjugated Haemophilus influenzae type b vaccine, ACT-HIB, used singly or in combination with orally administered Escherichia coli, was investigated in a rat model for acute otitis media. The humoral response to ACT-HIB was also analyzed. The study demonstrated that ACT-HIB vaccination resulted in a prompt antibody response, and that ACT-HIB was efficient in preventing middle ear infections caused by Haemophilus influenzae type b. The efficiency increased if the vaccine was combined with Escherichia coli. The results suggest that Escherichia coli could possibly be useful in the future as a vaccine vehicle, and since Haemophilus influenzae acute mastoiditis seems to be almost exclusively due to serotype b, the incidence of this infection may be reduced with the conjugated Haemophilus influenzae type b vaccines.
|
|
| 8. |
- Melhus, Åsa, et al.
(författare)
-
Experimental recurrent otitis media induced by Haemophilus influenzae : protection and serum antibodies
- 1995
-
Ingår i: American Journal of Otolaryngology. - : Elsevier BV. - 0196-0709 .- 1532-818X. ; 16:6, s. 383-390
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To study whether acute otitis media caused by encapsulated or nontypeable Haemophilus influenzae confers cross-reactive protective immunity in an animal model system and to explore the possible involvement of various humoral specific antibodies in protection. MATERIALS AND METHODS: Rats were intrabullarly challenged with H influenzae type b and two different nontypeable H influenzae strains. One month after the initial infection, the animals were rechallenged ipsilaterally or contralaterally with either a homologous or heterologous strain, and the susceptibility to reinfection was investigated by otomicroscopy. RESULTS: The animals challenged and rechallenged with the type b strain were well-protected ipsilaterally and contralaterally, while the protection after homologous rechallenge with a nontypeable strain was partial in the ipsilateral ear and very poor in the contralateral ear. Middle ears previously infected with a nontypeable strain remained fully susceptible to infections with heterologous strains, but there was an indication of cross-protection in the animal groups where the first episode of acute otitis media was caused by type b and the second by a nontypeable strain. Using the Western blot technique and an enzyme linked immunosorbant assay, the serological response to different outer membrane proteins, especially protein D, of H influenzae during and after middle ear infection were investigated. The serological response from the type b infected animals were generally more distinct, while the antibody levels against protein D were lower in these groups compared with the groups infected with nontypeable strains. CONCLUSIONS: These data indicate that H influenzae type-b-induced experimental otitis media results in a better protection than a nontypeable-induced, and H influenzae b confers a cross protection.
|
|
| 9. |
- Melhus, Åsa, et al.
(författare)
-
Intra- and interstrain differences of virulence among nontypeable Haemophilus influenzae strains
- 1998
-
Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - 0903-4641 .- 1600-0463. ; 106:9, s. 858-868
-
Tidskriftsartikel (refereegranskat)abstract
- Nontypeable Haemophilus influenzae (NTHi) is sometimes the causative agent of invasive diseases, and it has been suggested that there may be differences in virulence among NTHi strains. Whilst studying clinical isolates of NTHi in a rat model of acute otitis media, intra- and interstrain differences in virulence were observed. Two strains with suddenly reduced capacity to cause middle ear infections and one highly virulent strain with dose requirements comparable only to encapsulated H. influenzae strains were further investigated, together with 15 other H. influenzae strains. The strains were characterized by analyzing the lipopolysaccharide, the outer membrane proteins, the hemagglutinating ability, and the polymerase chain reaction products after amplification of a gene sequence associated with encapsulation. The pathogenic capacity was assessed in two different in vivo models. It was found that the two strains with reduced pathogenic capacity could regain their virulence after animal passage. The LPS analysis and the results from the chicken embryo model suggested that the observed change in virulence might be associated with the lipopolysaccharide. For the non-animal-passaged strain 3655 there were indications that an undefined factor(s) contributed to its relatively potent virulence. As all three strains lacked genes necessary for encapsulation, in no case could any part of the increased virulence be attributed to the expression of small amounts of capsule.
|
|
| 10. |
- Melhus, Åsa, et al.
(författare)
-
Nontypeable and encapsulated Haemophilus influenzae yield different clinical courses of experimental otitis media
- 1994
-
Ingår i: Acta Oto-Laryngologica. - 0001-6489 .- 1651-2251. ; 114:3, s. 289-294
-
Tidskriftsartikel (refereegranskat)abstract
- Middle ears of male Sprague-Dawley rats were injected with suspensions of thirteen Haemophilus influenzae strains of different sero- and biotypes and at various concentrations. Systemic and local changes were monitored by clinical observations, otomicroscopy, and analysis of bacterial samples from blood and middle ears. Two patterns of response were recognized, a nontypeable and an encapsulated pattern. The nontypeable H. influenzae middle ear infection required a high bacterial dose and was well past its peak 8 days after challenge, when the encapsulated H. influenzae otitis media was still purulent. The most severe infections were caused by H. influenzae type b strains. The overall mortality rate was zero and the animals recovered without permanent deterioration or otomicroscopically discernable changes. The results of this study show the rat to be a suitable animal model for the study of H. influenzae otitis media.
|
|
