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Developing otitis media: experimental studies in particular regarding inflammatory changes in the tympanic membrane
Umeå University, Faculty of Medicine, Clinical Sciences, Otorhinolaryngology.
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

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).

Place, publisher, year, edition, pages
2004. , 56 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 871
Keyword [en]
Otorhinolaryngology, otitis media with effusion, acute otitis media, myringotomy, tympanic membrane, rat, Streptococcus pneumoniae, compound 48/80, mast cell
Keyword [sv]
Otorhinolaryngologi
National Category
Otorhinolaryngology
Research subject
Oto-Rhino-Laryngology
Identifiers
URN: urn:nbn:se:umu:diva-180ISBN: 91-7305-580-8 (print)OAI: oai:DiVA.org:umu-180DiVA: diva2:142014
Public defence
2004-02-13, Sal D (grå salen), 1D, Tandläkarhögskolan, Norrlands Universitetssjukhus, Umeå, 09:00 (English)
Opponent
Supervisors
Available from: 2004-01-19 Created: 2004-01-19 Last updated: 2010-04-12Bibliographically approved
List of papers
1. Degranulation of mast cells provokes a massive inflammatory reaction in the tympanic membrane.
Open this publication in new window or tab >>Degranulation of mast cells provokes a massive inflammatory reaction in the tympanic membrane.
2001 (English)In: The Laryngoscope, ISSN 0023-852X, E-ISSN 1531-4995, Vol. 111, no 7, 1264-1270 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: The pars flaccida is extremely rich in mast cells. On stimulation the mast cells release preformed and de novo synthesized inflammatory substances. The purpose of this study was to examine how these mast cell substances provoke inflammatory changes in the tympanic membrane. STUDY DESIGN: In vivo, murine model. METHODS: In a rat model, the mast cell secretagogue compound 48/80 was applied locally to the tympanic membrane on 4 consecutive days and the ensuing inflammatory changes were evaluated by otological, light, and electron microscopy 3, 6, 9, 12, 18, 24, 36, and 48 hours and 4, 6, and 8 days later. RESULTS: Degranulation of the mast cells occurred within 3 hours of applying compound 48/80. Release of the mast cell substances coincided with an inflammatory event characterized by a two-stage reaction: an edema stage, peaking 6 hours after application, followed by a massive invasion of inflammatory cells, peaking at 24 and 48 hours. Pars flaccida and pars tensa were both involved, pars flaccida showing the earliest changes. Pars tensa exhibited the same biphasic reaction as pars flaccida, but approximately 6 hours later. CONCLUSIONS: The mast cells of the pars flaccida have the capacity to elicit an intense inflammation of the tympanic membrane. The biphasic reaction pattern resembles that observed in experimental otitis media, suggesting involvement of the mast cells in this inflammatory condition of the middle ear.

Keyword
Tympanic membrane, mast cells, otitis media. inflammation, compound 48/80
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-3347 (URN)10.1097/00005537-200107000-00023 (DOI)11568552 (PubMedID)
Available from: 2004-01-19 Created: 2004-01-19 Last updated: 2017-12-14Bibliographically approved
2. First forty-eight hours of developing otitis media: An experimental study
Open this publication in new window or tab >>First forty-eight hours of developing otitis media: An experimental study
2003 (English)In: Annals of Otology, Rhinology and Laryngology, ISSN 0003-4894, E-ISSN 1943-572X, Vol. 112, no 6, 558-566 p.Article in journal (Refereed) Published
Abstract [en]

The early inflammatory changes in the tympanic membrane were explored in 2 rat models. Acute otitis media was induced by instillation of Streptococcus pneumoniae type 3 into the middle ear cavity, and otitis media with effusion was induced by blockage of the eustachian tube. Otomicroscopic examination was performed before the rats were painlessly sacrificed at 3, 6, 9, 12, 18, 24, or 48 hours after initiation of the otitis media conditions. The tympanic membrane was studied by light and electron microscopy. Both acute otitis media and otitis media with effusion caused early inflammatory changes of the tympanic membrane, and the pars flaccida was the portion that reacted first. The inflammatory alterations were most pronounced in the acute otitis media model. The course of inflammation showed a bimodal pattern with an early deposition of a filamentous material with a band pattern, typical of fibrin. Despite a fluid-filled middle ear cavity, the inflammatory changes in the otitis media with effusion model were moderate, as was consistent with the clinical appearance of the tympanic membrane.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-3348 (URN)12834127 (PubMedID)
Available from: 2004-01-19 Created: 2004-01-19 Last updated: 2017-12-14Bibliographically approved
3. Early structural tympanic membrane ractions to myringotomy: A study in an acute otitis media model.
Open this publication in new window or tab >>Early structural tympanic membrane ractions to myringotomy: A study in an acute otitis media model.
2002 (English)In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 122, no 5, 479-487 p.Article in journal (Refereed) Published
Abstract [en]

Myringotomy (Myr) is one of the most frequently performed surgical procedures in children. However, events occurring in the early phases, i.e. a matter of hours, following Myr in the acute otitis media (AOM) model have not been described. The aim of the present study was to evaluate the early otomicroscopic and histopathologic reactions of the tympanic membrane (TM) after Myr during the course of AOM (AOM-Myr). The left tympanic bulla from 36 healthy Sprague-Dawley rats was inoculated with Streptococcus pneumoniae type 3. Forty-eight h later, at Day 0, 4 randomized animals were immediately sacrificed and the remaining animals were treated with bilateral Myr. Otomicroscopy and sacrifices were performed in series of 4 animals at 3, 6, 9, 12, 24 and 48 h, and 4 and 7 days. The AOM-Myr TMs were compared to non-infected Myr TMs (non-AOM-Myr). The TMs were then dissected free and routinely processed for light and electron microscopy. AOM developed in all inoculated ears at Day 0. In the pars tensa of the AOM-Myr TMs the reaction of the keratinocyte layer of the perforation border was already evident at 6 h. The lamina propria exhibited a strong inflammatory reaction, which became more organized from 12 h onwards. At Day 4 the perforations were closed in three-quarters of cases. At Day 7 all perforations were healed with a distorted scar. In the non-AOM Myr TMs a strong degranulation of mast cells and edema were found in the pars flaccida at 6 h. A keratin spur at the perforation border was not seen until 24 h. All perforations were patent on Day 7 and myringosclerotic deposits were abundant in these TMs. The infected TMs regenerated faster and closed their perforations at an earlier stage. These findings favor the hypothesis that there is a low risk of chronic perforations when myringotomizing AOM TMs.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-3349 (URN)12206255 (PubMedID)
Available from: 2004-01-19 Created: 2004-01-19 Last updated: 2017-12-14Bibliographically approved
4. Inflammatory cells during developing otitis media.: An experimental sequential study.
Open this publication in new window or tab >>Inflammatory cells during developing otitis media.: An experimental sequential study.
Manuscript (Other academic)
Identifiers
urn:nbn:se:umu:diva-3350 (URN)
Available from: 2004-01-19 Created: 2004-01-19 Last updated: 2010-01-13Bibliographically approved
5. Acute otitis media develops in the rat after intranasal challenge of Streptococcus pneumoniae.
Open this publication in new window or tab >>Acute otitis media develops in the rat after intranasal challenge of Streptococcus pneumoniae.
2003 (English)In: The Laryngoscope, ISSN 0023-852X, E-ISSN 1531-4995, Vol. 113, no 11, 2047-2051 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES/HYPOTHESIS: The rat is a frequently used animal model for middle ear research. To date, acute otitis media (AOM) has been evoked after instillation of bacteria directly into the middle ear cavity or after traumatizing the tympanic membrane. The purpose of the study was to examine whether, with an intact tympanic membrane and middle ear cavity, intranasally deposited bacteria cause AOM and how tympanic membrane stimulation influences this procedure. STUDY DESIGN: In vivo, murine model. METHODS: In a rat model, Streptococcus pneumoniae, type 3, was intranasally inoculated for 5 consecutive days. The tympanic membrane was treated with saline or with compound 48/80 or was left untreated. The development of AOM was evaluated by otomicroscopy, light microscopy, and middle ear culture. RESULTS: Ninety percent of the ears developed AOM. However, when the tympanic membranes were treated with saline or compound 48/80, only 40% and 57%, respectively, developed AOM. In all, 23 of 40 ears developed AOM and 20 ears showed growth of bacteria. CONCLUSION: Repeated intranasal deposition of S. pneumoniae, type 3, causes AOM in the rat. The development of AOM can be influenced by tympanic membrane stimulation.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-3351 (URN)14603072 (PubMedID)
Available from: 2004-01-19 Created: 2004-01-19 Last updated: 2017-12-14Bibliographically approved

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