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T Ovesen

Publications and source records attributed to T Ovesen.

At least 19 recordsLinked to original sources
PubMed2001

RANTES in otitis media with effusion: presence, role and correlation with cytokines and microbiology.

Various inflammatory cells and cytokines have been identified in otitis media with effusion (OME). The presence of neutrophils has been linked to interleukin-8, but no chemotactic factor has as yet been identified for monocytes. The chemokine RANTES (Regulated upon Activation, Normal T Expressed and Secreted) attracts and activates primarily monocytes and may contribute to the pathogenesis of middle ear inflammation. We investigated the presence of RANTES by: 1) ELISA measurement in 114 middle ear effusions from children suffering from OME, 2) immunohistochemical localisation in experimental OME rabbit middle ear mucosa, and 3) expression in cultured rabbit middle ear epithelium in response to proinflammatory stimuli. RANTES was detectable in 94 (82%) of 114 effusions with a median concentration of 79.7 pg/mg total protein content. The concentration of RANTES was positively correlated with the endotoxin content. Immunohistochemically, RANTES was localized to the epithelial layer in experimental OME. In vitro, RANTES was expressed in middle ear epithelium in response to proinflammatory stimuli (TNF-alpha) in a dose-dependent manner. The expression of RANTES may explain the recruitment of monocytes in OME, possibly as a result of TNF-alpha-mediated endotoxin stimulation.

Animals↗
PubMed2001

Induction of mucin and adhesion molecules in middle ear mucosa.

We hypothesized that inflammation molecules induce the secretory hyperplasia characteristic of otitis media with effusion (OME). The purpose of the present study was to compare the location of inflammation molecules and mucin in the middle ear mucosa of both normal and OME ears. OME was created by bisection of the tensor veli palatini muscle in germ-free rabbits, and the development of middle ear effusion was confirmed by otomicroscopy and tympanometry. Ventilation tubes (VTs) were inserted in half of the ears. The animals were decapitated after 8 weeks, and serial sections of the middle ear mucosae were either periodic acid-Schiff (PAS)-stained or stained immunohistochemically for inflammation molecules or mucins. The length of stained epithelium was measured and related to the total epithelial length. There was a striking resemblance between mucin-type MUC5B- and PAS-positive epithelium and areas positive for the chemoattractant inflammation molecules intercellular adhesion molecule-1 (ICAM-1) and RANTES (reacted upon activation, normal T expressed and secreted). The percentages of ICAM-1- and PAS-stained epithelium were significantly higher in OME ears than in normal ears. OME ears treated with VTs also contained significantly more PAS-positive epithelium than normal ears, but less than OME ears. Based on the spatial and temporal coincidence between ICAM-1 and mucin, it is suggested that: (i) inflammation may initiate and maintain the hypersecretory state of the middle ear mucosa which is presumably responsible for the chronicity of OME; and (ii) that MUC5B is a major mucin component of OME effusions.

Animals↗
PubMed2001

How does endotoxin trigger inflammation in otitis media with effusion?

OBJECTIVES: The relationship among microorganisms, endotoxin, and inflammatory mediators in otitis media with effusion (OME) was examined. STUDY DESIGN: Analysis of 152 middle ear effusions aspirated at the time of ventilation tube insertion from children with OME. METHODS: Effusion samples were cultured for pathogenic bacteria The two primary cytokines, interleukin-1beta (IL1beta) and tumor necrosis factor (TNFalpha), and the adhesion molecules, intercellular and vascular adhesion molecule (ICAM-1 and VCAM-1), were quantified using the enzyme-linked immunosorbent assay (ELISA) technique. Endotoxin concentration was measured with a limulus amebocyte lysate assay, and total protein concentration was quantified using the Biorad microassay. RESULTS: The cultures of pathogenic bacteria were positive in 33 of the 152 effusions (22%), which contained more endotoxin and more of the primary cytokines than the 119 culture-negative effusions. Endotoxin and the primary cytokines were positively correlated, both in the whole material and in the sterile effusions alone. The adhesion molecules were positively correlated with each other, but not with endotoxin or the primary cytokines. CONCLUSIONS: We found a positive correlation between endotoxin and the primary cytokines TNFalpha and IL1beta in culture-positive OME effusions as well as in culture-negative ones, suggesting endotoxin-induced local production of TNFalpha and IL1beta in the middle ear. ICAM-1 and VCAM-1 were also present in the middle ear, but their concentrations were not directly correlated to endotoxin or the primary cytokines.

Bacterial Infections↗
PubMed2000

Effect of N-acetylcysteine on the incidence of recurrence of otitis media with effusion and re-insertion of ventilation tubes.

Previous studies have demonstrated the anti-inflammatory, anti-oxidant, and mucolytic nature of N-acetylcysteine (NAC). Theoretically, these properties make the substance ideal for therapeutic use against otitis media with effusion (OME). The disease is characterized as a sustained non-specific inflammation of the middle ear mucosa with secretory transformation of the epithelium resulting in accumulation of fluid in the middle ear space. To investigate the effects of instillation of NAC in the middle ear, a double-blind, placebo-controlled, randomized trial was carried out. A total of 75 children who were undergoing their first bilateral insertion of ventilation tubes (VT) due to OME were randomized to Mucomyst (NAC) or placebo (the vehicle) on one ear in relation to the VT insertion. The contralateral ear underwent VT insertion exclusively. Instillation of Mucomyst or placebo was repeated 3 and 7 days afterwards. The children were followed regularly for 11-39 months. Episodes of otorrhea, recurrence of OME after VT extrusion and re-insertion of VTs were registered as primary outcome parameters. The results demonstrated that Mucomyst significantly reduced the recurrence of OME and re-insertion of VTs (p < 0.025) and significantly increased the time until VT extrusion (p < 0.0167). In addition, the number of episodes of ear problems and visits at the ENT clinic were reduced significantly by NAC (p < 0.0383).

Acetylcysteine↗
PubMed2000

Middle ear epithelium has inflammatory capacity.

Endotoxin, tumour necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and intercellular adhesion molecule-1 (ICAM-1) were detected in 88%, 51%, 58% and 66% of 152 middle ears from patients suffering from otitis media with effusion. In this study the hypothesis that bacterial endotoxin, TNF-alpha, IL-1 beta and ICAM-1 induce the inflammatory process characteristic of otitis media with effusion was tested. Cultures of rabbit middle ear epithelium were exposed to endotoxin, TNF-alpha or IL-1 beta. The expression of ICAM-1 on the cell surfaces was measured with a direct enzyme-linked immunosorbent assay on the cell layer. For TNF-alpha, 5 ng/ml significantly increased ICAM-1 expression, whereas 100 ng/ml had a toxic effect. For IL-1 beta, as little as 1 ng/ml produced a significant increase in ICAM-1 expression. Endotoxin stimulated ICAM-1 expression less strongly in concentrations from 100 ng/ml to 100 micrograms/ml. The findings indicate that stimulation of ICAM-1 by endotoxin is mediated, at least in part, by TNF-alpha and IL-1 beta. It is concluded that endotoxin induces sustained inflammation in OME, and that this inflammation is mediated, at least in part, by the primary cytokines TNF-alpha and IL-1 beta.

Animals↗
PubMed2000

Acute mastoidectomy in a Danish county from 1977 to 1997--operative findings and long-term results.

Data from patients undergoing acute mastoidectomy were examined retrospectively to evaluate if the nature of acute mastoiditis (AM) treated surgically has changed during the last 20 years (1977-97). Moreover, a prevalence study was conducted to clarify the otological and audiological course following acute mastoidectomy. Patients with cholesteatoma and intracranial complications were excluded. Thus, 79 patients with a median age of 16 months were included. Thirty-seven percent had a history of middle ear disease, and the mean duration from onset of symptoms to admission was 9 days. Well-being was affected in 46%, and 82% had fever. The clinical picture was dominated by auricular protrusion (77%) and pathological tympanic membrane (94%). Postauricular oedema, hyperaemia and tenderness were demonstrated in 89%, 78% and 49% of cases, respectively. Peroperatively, purulent middle ear effusion was recognized in 92%, subperiosteal abscess in 66% and pus in the mastoid in 90%. Specimens revealed growth of pathogens in 58%, predominantly Gram-positive bacteria. The observation period was 1-20 years. The findings in operated ears were not significantly different from the contralateral non-operated ears concerning incidence of otitis media, hearing and ear canal volume. Conclusively, acute mastoidectomy is a safe and effective treatment to eliminate infection. The operation can be done with negligible risk and does not leave long-term sequelae.

Acute Disease↗
PubMed1999

Positron emission tomography of cortical centers of tinnitus.

Tinnitus is associated with a wide variety of disorders in the auditory system. Whether generated peripherally or centrally, tinnitus is believed to be associated with activity in specific cortical regions. The present study tested the hypothesis that these cortical centers subserve the generation, perception and processing of the tinnitus stimulus and that these processes are suppressed by lidocaine and masking. Positron emission tomography was used to map the tinnitus-specific central activity. By subtracting positron emission tomography images of regional cerebral blood flow distribution obtained during suppression of the tinnitus from positron emission tomography images obtained during the habitual tinnitus sensation, we were able to identify brain areas concerned with the cerebral representation of tinnitus. Increased neuronal activity caused by tinnitus occurred predominantly in the right hemisphere with significant foci in the middle frontal and middle temporal gyri, in addition to lateral and mesial posterior sites. The results are consistent with the hypothesis that the sensation of tinnitus is associated with activity in cortical regions functionally linked to subserve attention, emotion and memory. For the first time, the functional anatomy of conditions with and without the habitual tinnitus sensation was obtained and compared in the same subjects.

Adult↗
PubMed1999

Stimulus-dependent central processing of auditory stimuli: a PET study.

Positron emission tomography (PET) was used to investigate the neural systems involved in the central processing of different auditory stimuli. Noise, pure tone and pure-tone pulses, music and speech were presented monaurally. O-15-water PET scans were obtained in relation to these stimulations presented to five normal hearing and healthy subjects. All stimuli were related to a basic scan in silence. Processing of simple auditory stimuli, such as pure tones and noise, predominantly activate the left transverse temporal gyrus (Brodmann area [BA] 41), whereas sounds with discontinued acoustic patterns, such as pure-tone pulse trains, activated parts of the auditory association area in the superior temporal gyri (BA 42) in both hemispheres. Moreover, sounds with complex spectral, intensity, and temporal structures (words, speech, music) activated spatially even more extensive associative auditory areas in both hemispheres (BA 21, 22). PET has revealed a remarkable potential to investigate early central auditory processing, and has provided evidence of the coexistence of functionally linked, but individually active parallel and serial auditory networks.

Acoustic Impedance Tests↗
PubMed1998

Acute mastoidectomy in a Danish county from 1977 to 1996 with focus on the bacteriology.

To evaluate if the nature of acute mastoiditis (AM) treated surgically has changed during the last 20 years (1977-1996), the data from patients undergoing acute mastoidectomy were examined retrospectively. Cases with cholesteatomas and intracranial complications were excluded, while 79 patients (48% male) with a median age of 16 months were included. There was a history of infectious middle ear disease in 37% and the mean duration from onset of symptoms to admission was 9 days. The well-being was affected in 46 and 82% had fever. Purulent middle ear effusion was recognized in 92%. A subperiosteal abscess in 66% of the ears peroperatively. Specimens yielded growth of pathogens in 58%, predominantly gram positive bacteria, fully or partially sensitive to penicillin. Antimicrobial treatment before admittance masked or reduced more symptoms significantly. The patients from the last 10-year-period had less frequently acute otitis media in their history, shorter duration of hospitalization, and more frequently haemolytic Streptococcus group A. Conclusively, AM affects especially infants without previous middle ear disease. The clinical picture has become more subtle in time, probably due to antibiotics, and concomitantly the bacteriological pattern has changed.

Acute Disease↗
PubMed1998

New aspects of secretory otitis media, eustachian tube function and middle ear gas.

The insertion of ventilation tubes to equalize pressure in the middle ear is the most common procedure used to treat otitis media. This article evaluates the advantages and drawbacks of ventilation and explores the various roles of the components of middle ear pressure, with special emphasis on oxygen-derived free radicals.

Carbon Dioxide↗
PubMed1997

Influence of hyperoxia on in vitro growth of rabbit middle ear epithelium and auditory meatal epithelium.

The oxygen partial pressure of middle ear gas increases more than 3-fold upon insertion of ventilation tubes, while the carbon dioxide partial pressure decreases. Whereas the middle ear gas is normally equilibrated to venous gases and has an oxygen partial pressure of 43 mmHg, 138 mmHg is measured in ventilated ears. The present study was undertaken to compare the effects of these oxygen tensions on in vitro growth and glycoprotein secretion of rabbit middle ear epithelium and for comparison auditory meatal epithelium. Cultures were incubated in atmospheres of 7, 21 or 75% O2 in 5% CO2 and the remnant N2. The cell layer protein mass, [3H]thymidine-incorporation, DNA content and [3H]glucosamine-incorporation was measured in identical subcultures every third day during a 15-day period. In middle ear epithelium the DNA content, DNA synthesis and cell layer protein mass were significantly higher at 7% oxygen compared to 21% and 75%. In conclusion hyperoxia leads to decreased growth of middle ear epithelium in vitro. If applicable to in vivo conditions, this might contribute to the mechanism of action of ventilation tubes. Moreover the proliferation rate of auditory meatal epithelium exceeds that of middle ear epithelium both at 7 and 21% oxygen, an interesting point with regards to cholesteatoma pathogenesis.

Animals↗
PubMed1997

Precision of tympanometric measurements.

In both scientific and clinical investigations, precision of instruments is demanded. Precision of tympanometric measures has been reported in the literature rarely, and studies are generally not comparable. This study introduces a new method of determining precision of tympanometric variables. Forty-three participants in good health were investigated. Static compliance, middle ear pressure, and gradient were recorded in test-retest design. Plots of test versus retest measurements were constructed for each variable, after which differences between measurements were plotted against their means. The standard deviation of the distribution of differences provides a measure of precision: the coefficient of repeatability. Static compliance showed a significant disagreement between measurements; hence repeatability was poor, which can be explained by preconditioning of the tympanic membrane. Middle ear pressure and gradient showed good agreement between measurements, and comparable measures of precision are reported. The method is simple and based on two repeated measurements in each subject; the design is ethical and practical in clinical investigations.

Acoustic Impedance Tests↗
PubMed1997

Chlamydia pneumoniae in children with otitis media.

In this study the polymerase chain reaction was used to test for the presence of Chlamydia pneumoniae DNA in 118 middle-ear aspirates from 20 children with acute otitis media (AOM) and 53 children with otitis media with effusion (OME). C. pneumoniae was detected in 8 samples obtained from 5 children with OME and, together with Streptococcus pneumoniae, in a sample from 1 child with AOM. The mean age of these five children (6.6 +/- 1.4 years) was significantly higher than that of the 48 children with OME in whom C. pneumoniae could not be detected (4.3 +/- 1.9 years). The presence of C. pneumoniae in 9.4% of the examined children with OME suggests that C. pneumoniae might be a significant supplementary factor in the etiology of this common children's disease.

Acute Disease↗
PubMed1997

Interleukin-8 and chemotactic activity of middle ear effusions.

The importance of interleukin (IL)-8 in the chemotactic activity of middle ear effusions (MEEs) was evaluated. There was a significantly higher IL-8 concentration in MEEs of children with acute otitis media (AOM) (n = 17; 136 ng/mL) than in children with otitis media with effusion (OME) (n = 28; 65 ng/mL). The IL-8 concentration in MEEs with bacteria (149 ng/mL) was significantly higher than in MEEs without bacteria (66 ng/mL). MEEs from children with AOM and OME had equally higher chemotactic activity than the diluent alone (23.3% and 24.8% vs. 9.2%). The chemotactic activity was not altered by the presence of bacteria nor did it correlate with IL-8 concentration. Fractionation of MEEs by gel chromatography demonstrated that the main chemotactic activity could clearly be separated from the IL-8 activity, thus excluding IL-8 as a main chemotactic component in MEEs.

Bacterial Infections↗
PubMed1996

Quantification of in vitro growth and synthesis in rabbit middle ear epithelial cells.

The purpose of the present study was a quantitative description of middle ear epithelial cell reactions in a standardized model system under controlled conditions. The model is based on a newly developed culture method for rabbit middle ear epithelial cells. The growth pattern of identical subcultures was determined by measurement of total cell protein, DNA synthesis and DNA amount during a 15-day period. The secretory product was quantified by means of 3H-glucosamine incorporation. Epithelial cells from the auditory meatus were examined by identical methods. The results proved the method to be reproducible regarding all parameters. The DNA amount and total cell protein increased throughout the period, whereas DNA synthesis remained constant. Secretion increased linearly for 9 days and then diminished. All parameters were without significant changes when related to DNA amount, reflecting a uniform cellular activity throughout the period. The DNA amount was the most precise parameter with a mean variation coefficient of 6.0% (SD 3.1%). With the baseline values found to be reproducible for the parameters chosen, our model system is considered to be usable for quantifying various factors influencing the proliferation and activity of middle ear epithelium.

Animals↗
PubMed1995

Culture of rabbit middle ear epithelial cells. A method for primary culture and subculture with identification, characterization and growth specification.

During the last decade middle ear epithelium has been cultured from various species. Until now, subcultivation has been achieved only with the use of a feeder-cell layer or conditioned medium. These factors are possible confounders in the in vitro model. On the other hand, subcultivation is necessary for exact quantitative studies. We present a reproducible culture method allowing subcultivation without feeder-cells or conditioned medium. The main features in our method are a low-serum, hormone-supplemented medium, an incubation temperature of 34 degrees C, fixation of explants, gentle trypsinization and replating with high cell density. Cells were identified by immunohistochemistry through a battery of monclonal antibodies. The percentage of epithelial cells in the subculture was 99.2%. To our knowledge, this is the first report describing subcultivation of middle ear epithelial cells exclusively in a completely controlled environment. These are optimal circumstances for future investigation and quantification of various factors influencing proliferation and differentiation of middle ear epithelium.

Animals↗