Biomedical subjects
Publications and source records attributed to O Kalm.
A short summary of the middle ear mucosal defence system and the characteristics of the infecting bacteria associated with purulent acute otitis media (AOM) is given. Data on humoral immune factors in middle ear effusions and serum during AOM are presented and the possibility that children with frequent recurrences of AOM exhibit an impaired ability to produce antibodies against AOM-associated antigens is discussed.
The effect of serial intravenous infusion of human immunoglobulin on the frequency of acute otitis media (AOM) episodes and on other upper respiratory tract infections was prospectively studied in a group of 22 otitis-prone children, 1-4 years old. After pair-matching, the children were allocated to immunoglobulin treatment or to a control group. Increased specific IgG antibody activities against pneumococcal types associated with recurrent AOM (rAOM) were generally achieved, but no significant difference was noted in the frequency of AOM attacks or other respiratory tract infections between the immunoglobulin-treated children and their pair-matched untreated controls. The results indicate that, although serum antibody activities against bacteria associated with AOM are increased by immunoglobulin infusions, this does not prevent the development of AOM in children suffering from rAOM.
The effect of a series of five immunoglobulin G infusions--at 3-4 week interval--on serum IgG antibody concentrations against some pneumococcal types commonly associated with acute otitis media (AOM) was studied in 11 children, 1-4 years old, suffering from recurrent AOM. Increase of specific IgG antibody concentrations was observed when the initial concentrations were low. However, once higher antibody concentrations had been achieved as a result of the treatment, subsequent infusions resulted in a decrease of the antibodies. In two children with initially high specific antibody concentrations, antibodies successively decreased in response to repeated immunoglobulin infusions.
The likelihood that hereditary factors play a significant role in the development of recurrent acute otitis media (rAOM) in children has been suggested. The genetically determined immunoglobulin variants, Gm and Km, are useful tools for mapping out the genetic loci involved in antibody responses. Certain Gm and Km types, G2m(23) and Km(1), appear to be linked to genes which regulate the concentrations of antibodies to pneumococcal polysaccharide antigens in adults. Our aim was to identify such immunoglobulin markers in rAOM children, since these children have extremely low concentrations of IgG antibodies against the pneumococcal types associated with this disease. The markers G1m(1), G1m(2), G1m(3), G2m(23) and Km(1) were identified in 20 families, each comprising 1 parent and 1 child with a history of rAOM and 1 parent free from rAOM. In addition, G2m(23) was identified in 47 children without AOM. The distribution of Gm and Km markers between rAOM and healthy subjects did not differ significantly. If anything, rAOM children exhibited a high rate of the G2m(23) marker, whereas earlier observations in adults have demonstrated low responders to polysaccharide antigens to be preferentially G2m(-23). Our findings indicate that mechanisms responsible for the low concentrations of antibodies to pneumococcal polysaccharides in rAOM children may differ from those causing certain adults to be low responders when exposed to pneumococcal polysaccharides.
Streptococcus pneumoniae frequently accounts for acute purulent otitis media (AOM) episodes. Recurrences are common and are most often caused by pneumococci of groups 6, 19 and 23. In 15 two-year-old children with recurrent AOM ( rAOM ) complement (C) components and antibodies against various pneumococcal capsular polysaccharides were analyzed during the acute phase of an AOM episode and 6 years later. Comparison was made with findings in non-otitis-prone children of comparable age. In contrast to non-otitis-prone children, 60% of children with rAOM had no detectable IgG antibodies against the pneumococcal capsular polysaccharides 6A or 19F. Analysis of C1 subcomponent complexes together with the finding of relatively low C1q concentrations gave evidence of disturbed C1 function in the acute phase of rAOM . At the 6-year follow-up antibodies against all the investigated pneumococcal capsular polysaccharides had increased in most of the children, but low IgG antibodies to type 6A polysaccharide were still more frequently found in the former rAOM children than in non-otitis-prone children. The C profiles had normalized at follow-up. These findings indicate a reduced ability in rAOM children to respond adequately with IgG antibodies to pneumococcal types encountered in rAOM . The combination of low antibody concentrations and the interference with the complement system and efficient opsonization through classical pathway activation could possibly contribute to the development of rAOM .
In a recent study it was found that children with recurrent acute otitis media (rAOM), in contrast to healthy children, frequently lack detectable antipneumococcal IgG antibodies against capsular types 6A and 19F. In children with rAOM, the concentrations of antibodies against type 6A polysaccharide remained low even after the period of rAOM had ceased. Antibody levels against various pneumococcal capsular polysaccharides were determined in otitis-prone and healthy members of 19 families. 25 children with a history of rAOM (mean age 7.2 years) and their parents, one of whom in each family had had rAOM during childhood, were investigated. Compared to the parents, the rAOM children had lower concentrations of IgG antibodies against the pneumococcal types 6A, 14, 19F and 23F and of IgA antibodies against type 23F. Compared to their parents, the rAOM children had higher concentrations of IgM antibodies against types 3 and 23F. 'Healthy parents' did not differ from 'rAOM parents' in IgG antibody levels against any of the pneumococcal capsular polysaccharides investigated. The findings indicate that rAOM occurs in individuals with a delayed rather than with a persisting inability to mount an adequate antibody response against the offending pneumococci.
76 patients with acute maxillary sinusitis were treated with oral erythromycin stearate (500 mg twice or 3 times a day for 10 days). The mean concentration of erythromycin in the sinus secretion after 3-5 days' treatment was 0.6 mug/ml with the lower dosage and 1.3 mug/ml with the higher. The concentration of erythromycin in the sinus secretion was, on the average, 10-20 times higher than the minimum inhibitory concentration (MIC) for group A streptococci and pneumococci, and reached MIC values for 15-30% of 100 examined strains of Haemophilus influenzae. 81% of the patients given the smaller and 94% of those given the larger dose improved or recovered. Radiological improvement was demonstrated in both groups. The infections with H. influenzae tended to respond somewhat less to the treatment than those with pneumococci. Comparisons of the roentgen findings and the findings at aspiration showed good agreement. An extra projection taken with the patient recumbent and the affected side downwards gave no information above that obtained from the routine projections. The large dose caused side effects more often (in 17/41 patients) than the smaller one (4/35 patients). In 10 patients treatment was discontinued because of side effects; 8 of them had received the larger dose.
The antibody activity of the IgM class and subclasses of IgG and IgA against pneumococcal bacteria of types 3, 6A and 19F was studied before and after administration of a pneumococcal vaccine (Pneumovax) in a group of children with recurrent acute otitis media (rAOM) and in groups of non-otitis-prone children. Only occasionally was there a significant rise in antibody activity after vaccination in any of the groups. There was no difference in the response to vaccination between rAOM children and healthy children. However, rAOM children exhibited lower antibody activities in most Ig subclasses against pneumococcus type 6A--a common causative agent in AOM--before as well as after vaccination compared with the healthy children. The results indicate that the response to vaccination is equally poor in all children, irrespective of whether they have a history of frequent attacks of acute otitis media, but, in contrast to healthy children, the rAOM children seem to have an inability to mobilize antibodies in response to infections with some pneumococcal types.
Although little is known about the occurrence of treatment failure in acute otitis media (AOM), available data suggest that it may be over-diagnosed. In the present study the frequency of treatment failure in AOM was determined in 113 children followed for 3 years from birth. Of 300 AOM episodes, 293 (in 70 children) were treated with oral antibiotics, and children under 10-11 months of age usually underwent myringotomy as well. During the observation period, there were 22 instances (in 16 children) of failure to respond to the primary antibiotic treatment of the AOM episodes. The annual frequency of treatment failure was 18.5%, 4.5% and 4.2% during the first, second and third years of life, respectively. The risk of failure to respond to antibiotic treatment was greater during the first year of life than during the following 2 years. The bacteria isolated and the choice of drug seemed to be of secondary importance.
To evaluate possible risk factors for developing recurrent acute otitis media (rAOM), 113 children were followed prospectively from birth to the age of 3 years. One of the aims was to determine whether such risk factors could be identified before the onset of the recurrences, so that optimal care and prophylactic measures could be made available at an early stage in such cases, on the basis of continuous follow-up by an ENT specialist. During the follow-up, 13 children developed rAOM, defined as six or more episodes of acute otitis media (AOM) during a 12-month period, 57 children had occasional episodes of AOM, and 43 children had no AOM at all. Of the children with onset of AOM before 6 months of age, 80% developed frequent episodes of AOM. The frequency of other respiratory tract infections and of family histories of otitis-proneness was higher among rAOM children than among the other children. The development of rAOM was unrelated to such factors as sex, familial history of allergy, duration of breast-feeding, or domestic environment. Nor could attendance at day-care centres be concluded as constituting a risk factor for the development of rAOM. An onset of AOM before 6 months of age was highly predictive of subsequent recurrent bouts of AOM, which emphasizes the importance of correct diagnosis in infants.