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Biomedical subjects

K Prellner

Publications and source records attributed to K Prellner.

At least 37 records · Page 2Linked to original sources

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.

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.

Acute Disease↗

Effect of Haemophilus influenzae type b conjugate vaccine in combination with peroral immunization with Escherichia coli on experimental otitis media.

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.

Acute Disease↗

Pathogenesis of middle ear adhesions.

Middle ear adhesions are well-known to the ear surgeon, although data on etiology, pathogenesis, and significance are lacking in current literature. This study on experimental acute otitis media presents histopathological data on these aspects. Pneumococci were inoculated in the right middle ear bulla of 25 rats; the left ear served as control. At days 4, 8, 16, 90, and 180, respectively, 5 rats were decapitated, and the bullae were removed, opened, and stained with periodic acid-Schiff (PAS)/alcian blue. The entire middle ear mucosae were dissected from the bone, embedded as whole mounts in colophonium chambers, and examined by light microscopy. Representative parts of the mucosae were sectioned and examined in the same way. All inoculated ears from day 8 and later (20 in total), contained mucosal adhesions of various sizes, shapes, and locations. None were found in control ears. The site of predilection for the development of adhesions was the hypotympanum, followed by the anterior epitympanum, the attic, the drum, the interossicular spaces, and the tubal orifice. Based on present histopathological findings, we conclude that the middle ear adhesion is a pathological phenomenon caused by infection, and we propose a six-stage hypothesis of pathogenesis: 1. Localized epithelial rupture; 2. Prolapse of subepithelial tissue; 3. Epithelialization of the prolapse; resulting in a polypous/fold-like prominence; 4. Growth and elongation of the prominence; 5. Fusion of the end/tip of the prominence with another part of the mucosa; 6. Formation of an adhesion.

Acute Disease↗

Incidence, aetiology, and prognosis of acute epiglottitis in children and adults in Sweden.

A retrospective study of the incidence, aetiology and case fatality rate of acute epiglottitis in children and adults was performed. The study covered the whole of Sweden (population 8.4 million) during the years 1987-89, before general vaccination against Haemophilus influenzae (Hi) type b was started. Patients were included if it was documented that they fulfilled all 3 of the following criteria: (a) red and swollen epiglottis visualized by indirect laryngoscopy, (b) inspiratory stridor or difficulties in swallowing, and (c) a temperature > or = 38 degrees C. A total of 306 children and adolescents (0-19 years) and 502 adults (> or = 20 years) were found. The age-specific incidence was highest in children aged 0-4 years, (14.7/100,000 per year). The total incidence was 3.2/100,000 per year. In the age group 0-19 years, blood cultures had been obtained from 195 (64%) and Hi was isolated from 154 (79%). In adults (> or = 20 years), 114 of 298 blood cultures yielded Hi, while pneumococci were isolated from 5 and group A streptococci from 3 patients. A total of 220 children (72%) and 114 adults (23%) needed an artificial airway. Five children and 12 adults died. In conclusion, the incidence of acute epiglottis in Sweden is very high. Compared to a previous country-wide study covering the years 1981-83 that used the same methods for case finding and case definition, the incidence in children had decreased while the incidence in adults had increased.

Adolescent↗

Penicillin reduces secretory capacity in rat middle ear mucosa in acute otitis media.

In the United States, antibiotic treatment of acute otitis media is almost mandatory, whereas several other western countries are more reticent. Most clinical trails on antibiotic effect have important methodologic flaws, making an overall interpretation quite difficult. This study determined the effect of penicillin V administration on the secretory capacity of rat middle ear mucosa, during and after acute pneumococcal otitis media, by quantitative studies of the goblet cell density. The right middle ear bullae of 25 rats were inoculated with type 3 pneumococci. Beginning 2 days after inoculation, penicillin V 100 mg/kg/day was administered orally for 5 days. After inoculation, five randomly selected rats were killed on days 4, 8, 16, 90, and 180. The middle ear bullae were removed, split in half, stained with periodic acid-Schiff (PAS)-alcian blue, and the mucosae dissected from the bone. Whole mounts were prepared and the goblet cell density determined in 24 well-defined localities, making a total of 160 counts per ear and covering the entire bulla mucosa. Goblet cell densities were compared with those of 25 normal ears and 25 inoculated, untreated ears. Except on day 4, the penicillin V-treated ears had a significantly lower goblet cell density in almost all localities, on all days of death, when compared with untreated ears. Six months after the acute incident, the goblet cell density was almost normal. However, the enlargement of the mucosal area containing goblet cells seen in untreated ears was unaffected by penicillin V administration. We conclude that administration of penicillin V reduces the increase in secretory capacity of rat middle ear mucosa during and 6 months after acute pneumococcal otitis media.

Acute Disease↗

Clinical aspects on antibiotic resistance: upper respiratory tract infections.

In view of the increased resistance to antibiotics in several upper airway pathogens, the clinical rationale for use of antimicrobial therapy in various upper respiratory tract infections is discussed. The diagnostic skill and the clinical significance of various bacteria are taken into account and strategies for treatment of the different infections, with focus on acute otitis media, are discussed.

Drug Resistance, Microbial↗

Polyp pathogenesis--a histopathological study in experimental otitis media.

We examined the mucosa of 50 rat middle ears in an experimental model of acute otitis media, in order to obtain information on the mechanisms of polyp formation. The right middle ear of 25 rats was inoculated with type 3 pneumococci, and the left ear served as a control. The animals were killed, the middle ear bulla removed, and the mucosa was dissected from the bone, stained PAS-alcian blue and embedded as a whole-mount. The whole-mounts were examined in a light microscope for polypous mucosal prominences. Serial sections were made of all polyps, and of relevant parts of the mucosa. 15 polyps were found in 11 (44%) of 25 infected ears; none were found in normal control ears. Goblet cell density was increased in polyps and the surrounding epithelium. Epithelial microruptures were seen in areas with widespread intra-epithelial liquid vacuoles and subepithelial accumulation of liquids, luminally migrating inflammatory cells, increased vascularization and edema. Connective tissue of the lamina propria was prolapsed through most ruptures. Some prolapses showed signs of re-epithelialization, while others had a full epithelial lining that resembled a fully developed polyp. Our findings support our earlier theory on nasal polyp pathogenesis, based on the following stages: i) Localized rupture of the epithelial lining. ii) Luminal protrusion of the lamina propria through the epithelial defect. iii) Re-epithelialization of protruded tissue, and formation of a polyp.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Changes in goblet cell density in rat middle ear mucosa in acute otitis media.

This study was undertaken to determine quantitative histologic changes after a single episode of acute suppurative otitis media in the rat middle ear mucosa, with special reference to goblet cell density, and to determine the persistency of these changes. Drum vascularization, purulent effusion, mucosal thickness, bone and subepithelial gland formation was assessed. Twenty-five rats were inoculated with viable pneumococci type 3 through the right, bony middle ear bulla. The left bulla served as control. At days 4, 8, 16, 90, and 180 after inoculation, five rats were sacrificed on each occasion; the bullae were removed, opened, and divided into two halves, which were stained according to the periodic acid-Schiff (PAS)-alcian blue method. The stained mucosa was dissected from the bone and placed in an anise oil-colophonium chamber, for determination of interindividual median density and range of goblet cells by light microscopy. Counting was performed in 24 well-defined localities, covering the entire bulla mucosa and the drum. Areas normally containing goblet cells were extended. Goblet cell density was significantly (Mann-Whitney, p < .05) increased in almost all localities, reaching a maximum at day 16, whereafter the mucosa normalized. All changes quantitated, except drum vascularization and purulent effusion, were persisting at day 180. Cobblestone appearance of the epithelial surface and polypous mucosal prominences were found. Mucosal thickening was prominent in areas covered with flat epithelium, less so in other areas. Local differences in the degree of increased mucosal thickness were preventing intrinsic tubal occlusion. Enhanced secretory ability of the middle ear mucosa was persisting 6 months after a single episode of acute suppurative otitis media, perhaps predisposing secretory otitis media.

Acute Disease↗

HLA frequency in patients with chronic secretory otitis media.

It is well established that relationships exist between the frequencies of certain HLA antigens and various disease entities. In an earlier study we found a significant correlation between the frequency of HLA-A2 and HLA-A3 and recurrent acute otitis media (rAOM). Of 34 HLA antigens analysed, HLA-A2 occurred in 80.0% and HLA-A3 in only 11.1% of children with rAOM as compared to 55.9% and 27.5%, respectively, in healthy controls. In the present study we investigated the frequencies of the same 34 HLA antigens in 40 children who had been regularly controlled at our clinic for chronic secretory otitis media (SOM) for at least 6 years. HLA-A2 was found in 52.0% (21/40) and HLA-A3 in 27.5% (11/40) of these children, figures on a par with those of healthy controls. The HLA-A2 frequency was significantly lower in chronic SOM patients than in rAOM children. Some other non-significant differences were also found between these two groups. The results indicate a difference in hereditary influence on the pathogenesis of rAOM and that of chronic SOM.

Acute Disease↗

Prevention of recurrent acute otitis media in otitis-prone children by intermittent prophylaxis with penicillin.

The question whether penicillin V (pcV) given intermittently upon signs of upper respiratory tract infections (URTI) in otitis-prone children might prevent recurrent bouts of acute purulent otitis media (AOM) is addressed. As compared with continuous long-term antibiotic treatment as prophylaxis in otitis-prone children, intermittent administration would reduce the overall consumption of antibiotics. Seventy-six otitis-prone children less than 18 months of age were included in this double-blind, randomized, placebo-controlled multicentre study. Follow-up was from January till June. One hundred and twenty-three episodes of AOM occurred. The number of AOM episodes was reduced by 50% in the children on pcV during URTI episodes as compared with those on placebo. No obvious ecological drawbacks were noted. Thus, the described mode of pcV administration seems to be a rational and safe way to reduce the number of AOM episodes in otitis-prone children.

Acute Disease↗

Nontypeable and encapsulated Haemophilus influenzae yield different clinical courses of experimental otitis media.

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.

Acute Disease↗

Active immunisation and resistance to experimental acute pneumococcal otitis media.

The middle ear mucosal system and the humoral systemic immune factors are the two immunological systems whose involvement in the defence against acute otitis media (AOM) have been most intensively studied. However, their respective importance and their mutual influence is not clear. In the present study, a rat model for pneumococcal AOM was used to further elucidate the involvement of systemic immunity in protection against pneumococcal AOM. Six groups of male Sprague-Dawley rats were immunised with pneumococcal vaccine (PneumovaxRN) or live pneumococci (type 3) via one of three different routes: intraperitoneally, into the gastrointestinal tract (GIT) or into the right middle ear. A subsequent middle ear challenge (re-challenge in one group) with the same pneumococcal strain was performed after 4 days to 8 weeks in the different groups. Systemic immunity was found to be triggered, not only by systemic immunisation, but also by antigenic stimulation of the mucosa in the middle ear and in the GIT. In all groups but that immunised in the GIT, no new peak of specific IgG antibody response was demonstrated in serum after middle ear challenge/re-challenge. In contrast, half of the rats immunised in the GIT showed such a response not only after the inoculation into the GIT but also after a later performed middle ear challenge. Though a faster resolution of pus from the middle ear was observed in rats from all but one group, a significant reduction in the number of rats who developed AOM occurred exclusively among those rats that had previously manifested serological response to immunisation in the GIT.

Animals↗

Language development in children with recurrent acute otitis media during the first three years of life. Follow-up study from birth to seven years of age.

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.

Acute Disease↗