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Biomedical subjects

K Prellner

Publications and source records attributed to K Prellner.

At least 91 records · Page 5Linked to original sources

Comparison of antibody levels and protective efficacy against pneumococci in two immunoglobulin preparations for intravenous use.

Passive immunization with modern intravenous immunoglobulin preparations might be used prophylactically in individuals at extreme risk of contracting postsplenectomy sepsis or therapeutically in established infections. Since pneumococci are the predominant causative organisms, we determined antibodies against 14 pneumococcal serotypes in two commercially available immunoglobulin preparations (two batches of each) using enzyme-linked immunosorbent assay. The four batches were remarkably similar in antibody content. Low levels against some clinically important serotypes, i.e. types 3, 8 and 18C were recorded. The protective effect of one batch of each preparation against type 1 pneumococci was documented in splenectomized rats.

Animals↗

Effect of gamma globulin infusion on type-specific pneumococcal antibody levels in splenectomized adults.

Using an ELISA technique, changes in specific antibody levels against pneumococcal serotypes 1, 4, 7F, 14, 18C and 23F were studied in 8 adults healthy at the time of investigation but splenectomized previously because of hematological disease following infusion of 200 mg/kg body weight of a commercially available immunoglobulin preparation for intravenous use (Sandoglobulin). Among the 4 patients with initially low serum levels of antipneumococcal antibodies, significantly raised antibody levels were demonstrated against type 14 for 8 weeks. On the other hand, the infusion did not lead to increased antibody levels in 3 patients with high preinfusion values for antipneumococcal antibodies. In contrast, a significantly lower antibody value for type 7F was recorded 3 weeks after infusion. Efficacy of immunoglobulin prophylaxis is, therefore, probably doubtful in certain splenectomized patients, and if contemplated should be preceded by analysis of antibody levels against common pathogens.

Adolescent↗

IgG subclasses and antibodies to group B streptococci, pneumococci, and tetanus toxoid in preterm neonates after intravenous infusion of immunoglobulin to the mothers.

High doses of intravenous immunoglobulin were given to seven pregnant women between the 27th and 36th wk of gestation who were at risk for preterm delivery. Determinations of IgG subclasses and of antibodies against group B streptococcal serotypes, pneumococcal polysaccharides, and tetanus toxoid were done in maternal serum before and after intravenous IgG infusion and after delivery in cord serum. Substantial transplacental passage of the infused material could be observed in five cases where delivery occurred at the 34th wk or later. After the 36th wk of gestation, IgG subclass and antibody concentrations in cord serum were increased up to the levels in the maternal serum.

Antibodies↗

Recurrent otitis media: genetic immunoglobulin markers in children and their parents.

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.

Adult↗

A simple method for collecting nasopharyngeal secretions, using cross-linked dextran.

Local immunological defence mechanisms in the human upper respiratory tract are incompletely defined. This is partly due to the absence of simple and reproducible methods for collecting undiluted secretions. The method described in the present study for collecting nasopharyngeal secretion was simple to perform and exploited the absorbing capacity of dextran, by using filterweave sacs containing dry dextran beads applied locally. The method enabled 100-200 microliters undiluted fluid to be sampled from 15 of 20 healthy volunteers. Measurements of albumin, IgG, IgA and complement factor C3 were performed. The absorption procedure per se was demonstrated not to influence the distribution of these proteins.

Adolescent↗

Combined IgG2, IgG4 and IgA deficiency: low C1q concentrations and the presence of excess C1r and C1s in an adult patient with recurrent pneumococcal infections.

The complement (C) profile was investigated in an adult patient with combined IgG2, IgG4 and IgA deficiency and recurrent pneumococcal infections. The analysis revealed no gross impairment of the classic and alternative pathways of C activation. However, the concentrations of circulating C1q were persistently decreased, and the sera contained an excess of C1r-C1s complexes, resembling the C1 aberrations previously found in children with recurrent acute otitis media. The concentrations of C4 in the patient were persistently low. This could be ascribed to partial C4 deficiency with lack of C4A variants. The patient's IgG and IgM antibody responses to pneumococcal capsular polysaccharides and to other bacterial carbohydrate antigens were very poor. Interestingly, pneumococcal C-polysaccharide (CPS) could be detected in serum obtained during infection-free periods. Since CPS has been shown to bind C1q without causing C1 activation, the possibility was considered that the C1 aberrations in serum were due to circulating CPS. After administration of intramuscular gammaglobulin to the patient, the serum C1q levels were observed to return to normal.

Adolescent↗

Effects of pneumococcal vaccination on tonsillo-pharyngitis and upper respiratory tract flora.

The effect of a 14-valent pneumococcal vaccine on upper respiratory tract infections and carriage of beta-haemolytic streptococci was studied in a double-blind prospective study of 405 children 0.5-5 years of age. In the children under 2 years of age at vaccination, the cases of acute tonsillitis were more frequent among the vaccinees than among the controls (p less than 0.01). In contrast, among the children over 2 years of age at vaccination, fewer episodes of acute tonsillitis were reported among the vaccinees than among the controls (p less than 0.01). In the older age group, the total rate of upper respiratory tract infections was also significantly reduced. Similarly, an increase in asymptomatic carriage of group A streptococci was registered in children vaccinated at 2-5 years of age (p less than 0.01). Inversely, the carriership of group C streptococci diminished among the vaccinated children (p less than 0.05). Some possible mechanisms underlying these unexpected findings, including non-specific mitogenic features and cross-protection due to antigenic similarities, were explored.

Age Factors↗

Phenoxymethylpenicillin and therapeutic failure in acute otitis media.

The aim of the present investigation was to determine to what extent beta-lactamase producing Haemophilus influenzae (H.i.) and Branhamella catarrhalis (B.c.) were isolated in cases of failure of treatment of acute otitis media (AOM) with phenoxymethylpenicillin. Among children with suspected therapeutic failure referred to an ENT specialist altogether 11, 15% of those referred, fulfilled the criteria of AOM. Three of them were on erythromycin, 1 on ampicillin and 7 on phenoxymethylpenicillin. In 5 of the children treated with phenoxymethylpenicillin H.i. was isolated from middle ear exudate and/or the nasopharynx. All H.i. isolates were non-capsulated and beta-lactamase negative. One beta-lactamase producing B.c. was isolated from the nasopharynx in a patient with pure culture of H.i. in the ear exudate. The present investigation did not support the suggestion that beta-lactamase producing H.i. or B.c. are major causative agents in therapeutic failures of AOM treated with phenoxymethylpenicillin and did not produce any evidence supporting a change from the recommended ampicillin esters/amoxycillin in therapeutic failures.

Acute Disease↗

Beneficial effect of pneumococcal vaccination on otitis media in children over two years old.

The effect of immunization with a 14-valent pneumococcal vaccine (Pneumovax) was studied in a double-blind trial in which 405 children between the ages of 6 months and 5 years were matched in vaccine/control pairs according to age and history of otitis media. The fact that all the children attended day-care centres ensured that both vaccinees and controls were similarly exposed to upper respiratory tract pathogens. The total incidence of acute otitis media was reduced during a 2-year follow-up period by 24% (P less than 0.05) among those vaccinated between the ages of 2 and 5. For recurrent episodes a decrease by 40% was noted. Protective efficacy was demonstrable during the first post-vaccinational year, but not when more than 1 year had lapsed after the vaccination. These findings suggest that, while the vaccine had not effect on children under 2 years old, it may be a useful aid in preventing recurrent attacks of otitis media in children between 2 and 5 years of age.

Bacterial Vaccines↗

Pneumococcal antibodies and complement during and after periods of recurrent otitis.

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 .

Antibodies, Bacterial↗

Pneumococcal antibodies in families with recurrent otitis media.

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.

Antibodies, Bacterial↗

Effect of pneumococcal vaccination on upper respiratory tract infections in children. Design of a follow-up study.

Children, aged 6 months to 5 years, were pair-matched with respect to age and history of otitis media acuta. The 405 children received either a subcutaneous injection of Pneumovax (a 14-valent pneumococcal vaccine) or of saline, in a double-blind fashion. The follow-up period for each child was 1 1/2 years. In children younger than 2 years at vaccination no difference was recorded between vaccinees and controls concerning the number of consultations due to otitis media acuta or to other upper respiratory tract infections. In children older than 2 years at vaccination a reduction in the overall frequency of visits due to upper respiratory tract infections was observed after vaccination. The incidence of otitis media acuta was reduced during the first postvaccinal year while visits due to tonsillitis and pharyngitis were reduced during the whole follow-up period in vaccinees as compared to controls.

Acute Disease↗

C1q binding and complement activation by capsular and cell wall components of S. pneumoniae type XIX.

Cell wall components (purified cell walls, teichoic acid and residual cell walls) from S. pneumoniae type XIX showed antibody independent C1q binding capacity, as assessed by C1q deviation test, with teichoic acid being the most efficient. Specific capsular substance did not bind C1q. All substances tested produced C1 activation in normal human serum, but not in hypo-gamma-globulinemic serum. Thus, teichoic acid showed high C1q binding capacity but did not activate C1 in the absence of antibodies. Teichoic acid was an effective activator of alternative pathway. Specific capsular substance did not activate the alternative pathway in C1q deficient serum or in Mg2+ -EGTA chelated normal serum.

Cell Wall↗

Complement in pneumococcal infections with varying degrees of severity.

Complement component levels (Clq, Cls, C4, C3, factor B and properdin) and C1 subcomponent complexes (C1r-C1s, C1-r-C1-, C1-r-C1-s-C1 inactivator, 1A) were studied in 16 adults with pneumococcal infections varying severity. Patients with fulminant disease and signs of septic shock showed pronounced hypocomplementemia. In patients with pneumococcal pneumonia or meningitis elevated levels of C1-r-C1-s-C1- IA complexes indicated activation of C1, despite normal levels of C1q, C1s, C4 and C3. Moderately decreased properdin values suggested involvement of the alternative pathway. In adults with pneumococcal otitis no changes in the complement profile was found. In contrast, pronounced aberrations of the C1 subcomponents were earlier demonstrated in children with otitis.

Adolescent↗

Bacteria associated with acute otitis media have high Clq binding capacity.

A simple, rapid and sensitive radioimmunologic method for demonstrating Clq binding to bacteria is described. Various bacteria were shown to bind Clq without the participation of antibodies. Great differences in Clq binding levels between different types and strains of S. pneumoniae were found. A high uptake of Clq was observed for many pneumococcal strains of type VI, XIX and XXIII and also for non-typable strains of H. influenzae and B. catarrhalis. Other bacteria tested, including H. influenzae types a-f, demonstrated less capacity to bind Clq.

Antibodies, Bacterial↗

Complement activation by pneumococci associated with acute otitis media.

Pneumococci (types, I, III, VI, XIV, XVIII, XIX and XXIII) associated with acute otitis media were shown to activate complement in normal human serum by the classical as well as by the alternative pathway. In serum incubated with pneumococci classical pathway activation was demonstrated by decreased C4 values and the appearance of C1r-C1s-C1 IA complexes. Pneumococci caused C3 conversion in C2-deficient serum and in serum chelated with Mg++ EGTA showing activation of the alternative pathway without participation of the C42 convertase. Complement activation was more efficient when both pathways were intact. This was evident from a more pronounced C3 conversion and a greater reduction of the values for properdin and factor B in non-chelated serum as compared to Mg++ EGTA chelated serum.

Acute Disease↗

Purification of C-reactive protein on DEAE-cellulose by a simple two-step procedure utilizing the calcium-dependency of the protein.

A simple procedure for isolating C-reactive protein is presented. The method consists of two chromatographic separations on diethylaminoethyl (DEAE)-cellulose columns and utilized the difference between the binding of C-reactive protein to DEAE in the presence and absence of calcium. Electrophoretically pure C-reactive protein can be recovered from serum or ascitic fluid with a yield of approx. 50--60% within one day.

C-Reactive Protein↗