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Biomedical subjects

B M Andersen

Publications and source records attributed to B M Andersen.

At least 73 records · Page 4Linked to original sources
PubMed1987

Endotoxin release from invasive meningococci related to sulfonamide resistance, serogroup and serotype.

The relationship between endotoxin liberation, sulfonamide resistance, serogroups and serotypes was studied in 28 Neisseria meningitidis strains isolated from patients with meningococcal disease. Sulfonamide resistance was present in 15/28 strains. 22 strains belonged to serogroup B, and 5 to group C; 1 strain was non-groupable. Free endotoxin activity in growing cultures of meningococci with endotoxin titre of greater than or equal to 10(2) was found in 27/28 strains. A high endotoxin activity was present in both sulfonamide-sensitive and -resistant invasive meningococci. A high endotoxin release with titre greater than or equal to 10(3) seemed to be more associated with serogroup C than B, and more to the serotypes 2 and 15/16 than to the non-typable strains.

Drug Resistance, Microbial↗
PubMed1985

Benzylpenicillin in mice. Effect of meningococci on plasma concentrations.

Plasma concentration studies were performed in mice given high intravenous (i.v.) bolus injections or subcutaneous (s.c.) depot doses of benzylpenicillin. There was a marked difference in plasma concentration within and between individuals both after benzylpenicillin (BP) given i.v. and after benzylpenicillin procaine (BPP) given s.c. BP given i.v. resulted in a plasma half-life of 15.2 minutes, while BPP given s.c. resulted in a plasma half-life of 2.7 hours. Infection with an endotoxin-liberating meningococcal strain in BP-treated animals increased the plasma levels of BP compared with uninfected controls.

Animals↗
PubMed1984

Endotoxin liberation and invasivity of Neisseria meningitidis.

The relationship between endotoxin liberation and invasiveness was studied in 50 strains of Neisseria meningitidis isolated from blood or cerebrospinal fluid (CSF) of 16 patients with invasive disease, from nasopharynx of 9 patients with upper respiratory tract symptoms, and from nasopharynx and rectum (1, serogroup W-135) in 25 persons examined for venereal disease. Meningococci varied in their ability to liberate endotoxin. Free endotoxin was partly a function of growth and seemed to be associated with certain properties of the individual strain. Strains isolated for patients with invasive disease liberated significantly more endotoxin than strains isolated from the venereal group (p less than 0.002). All 16 invasive strains were sulfonamide resistant, against 5/9 strains from patients with upper respiratory disease symptoms and only 4/25 strains from the venereal group. The difference between the invasive group and the venereal group was significant (p less than 0.002). Serogroup A, B, C meningococci liberated significantly more endotoxin than non-A, B, C strains (p = 0.01, and serogroup A, B, C strains isolated from nasopharynx tended to have a higher endotoxin release than non-A, B, C strains isolated from the same place (not significant). Serogroup B meningococci were most frequently isolated both from patients with invasive disease and from the nasopharynx of the persons examined for venereal disease. Serogroup B meningococci had significantly more free endotoxin when isolated from blood or CSF than when isolated from nasopharynx of presumably healthy persons (p = 0.002).

Bacteriological Techniques↗
PubMed1984

Effect of benzylpenicillin in mice infected with endotoxin-liberating or non-liberating variant strains of Neisseria meningitidis.

The effect of benzylpenicillin treatment was studied in mice infected intraperitoneally (i.p.) with endotoxin-liberating (E+) and non-liberating (E-) meningococci derived from the same original serogroup B strain. The E+ meningococci were significantly more virulent to mice than the E- variants in untreated animals (p less than 0.001). Large doses of benzylpenicillin given intravenously (i.v.) immediately after i.p. inoculation of E+ or E- meningococci resulted in complete, or almost complete survival. When treatment started later the number of surviving E- infected animals increased in all treatment regimens. By contrast, E+ infected animals had one or more treatment groups in all regimens that did not respond to benzylpenicillin at all. Benzylpenicillin treatment was given over a period of time as intermittent, regular i.v. doses, or as a depot preparation subcutaneously (s.c.). The mortality observed in E+ infected mice after benzylpenicillin i.v. was 75%, after benzylpenicillin procaine s.c. 82.5%, while animals receiving only saline i.v. had a mortality of 67.5%. The corresponding mortalities for E- infected animals were 15% (p = 0.0014), 42.5%, and 42.5%, respectively.

Animals↗
PubMed1984

The virulence in mice of Neisseria meningitidis variants differing in free endotoxin activities and cell envelope properties.

The virulence of two serogroup B meningococcal strains (270E+ and 840E+) having a high endotoxin release during in vitro growth, was compared with the virulence of corresponding variants (270E- and 840E-) liberating less endotoxin. The E-variants were isolated during subcultivations from the E+ strains. 270E+ and 840E+ were both serotype 15:P1.16, while 270E- was serotype 15:P1.2 and 840E- was non-typable. The SDS-PAGE patterns of the E+ and E- variants were also dissimilar. The E+ and E- variants differed in several other properties. Groups of mice were inoculated intravenously (i.v.) or intraperitoneally (i.p.) with E+ and E- meningococci. The endotoxin activities of inoculates and mouse blood were assayed by a Limulus lysate test. The mice received a similar infective dose of E+ and E- variants. A higher level of CFU and endotoxin was found in heart blood of E+ than of E-infected mice during the first hours after infection. Both 30h and 72h after inoculation, E+ variants were significantly more lethal to mice than E- variants (p less than 0.01).

Animals↗
PubMed1983

Sulfonamide resistance in Neisseria meningitidis strains liberating various amounts of free endotoxin.

The relationship between sulfonamide susceptibility and the ability to liberate endotoxin was studied in 50 strains of Neisseria meningitidis. The endotoxin activity was investigated by the Limulus lysate test in growing cultures of 25 sulfonamide-resistant and 25 sensitive strains. The sulfonamide-resistant strains tended to have a higher endotoxin activity in cultures grown for 6 h than sensitive ones, and had also a higher amount of free, filtrable endotoxin.

Anti-Bacterial Agents↗
PubMed1982

Effect of penicillin on the morphology of a Neisseria meningitidis strain not liberating free endotoxin. An electron microscopy study.

A strain of Neisseria meningitidis which did not release filtrable endotoxin during in vitro growth was treated with 100 times MIC values of benzylpenicillin. After 2 h of exposure to penicillin, most of the bacterial cells were plasmolysed, and only a few bacteria were alive after 20 h. The peptidoglycan layer could be demonstrated in samples investigated after 2 h of penicillin treatment, but was undetectable after 20 h. Only a few outer cell wall structures, small enough to be filtered through a 0.45 micrometer filter were separated from the bacterial cells. Such structures could be observed in all samples studied, both untreated as well as treated cells cultures. This observation corresponded well to the very low content of free endotoxin in filtrates from the samples. Adhesiveness between completely divided cells and between aggregates of cells and cell wall structures was a characteristic finding in the untreated control cultures, but penicillin treatment seemed to amplify this tendency.

Adhesiveness↗
PubMed1981

Loss of sulfonamide resistance in Neisseria meningitidis.

Four strains of Neisseria meningitidis were studied during serial passage. From two strains which originally were sulfonamide resistant, variants developed that had altered susceptibility to sulfonamides. One of the variants became relatively highly sulfonamide-sensitive, the other exhibited merely reduced sulfonamide resistance. There was a difference in the resistance pattern for two sulfonamides (sulfaisodimidine and sulfamethoxazole), and the effect of inoculum size and growth conditions in three different media could be demonstrated. Although the patterns of susceptibility to other antibacterial agents were different for the strains studied, no further susceptibility alterations occurred in parallel to the sulfonamide sensitivity changes. The variants also lost their ability to liberate free endotoxin.

Anti-Bacterial Agents↗
PubMed1981

Loss of endotoxin liberation in Neisseria meningitidis.

Four strains of Neisseria meningitidis were studied during serial passage. Upon subcultivation, two of them lost the ability to liberate endotoxin. Ultrastructurally, the two parent endotoxin liberating strains exhibited quantitatively more free cell wall membranes and blebs in the medium than their non-liberating variants. Similarly, the endotoxin-releasing original strains exhibited higher sulfonamide resistance than their variants, and had markedly more sticky cells, which showed pronounced adherence to the surfaces of plastic and heated blood agar.

Adhesiveness↗
PubMed1981

Effect of penicillin on the morphology of a Neisseria meningitidis strain liberating free endotoxin. An electron microscope study.

An endotoxin-liberating strain of Neisseria meningitidis plasmolysed extensively after 2 h of exposure to 100 times MIC values of benzypenicillin. The peptidoglycan layer could be demonstrated after 2 h of treatment in places where the cytoplasm still was close to the cell wall. After 20 h, however, this layer was complete undetectable. In untreated cells the peptidoglycan layer could more easily be found in older cultures than in very young cultures. An increased adhesiveness and aggregation to other bacterial cells and to cell wall material could be observed after 2 h of penicillin treatment, and more pronouncedly after 20 h. A high yield of free cell wall material could be demonstrated after 2 h of penicillin treatment. This corresponded well to an increased content of free endotoxin in the filtrates from the cell cultures treated with penicillin, compared to untreated controls. After 20 h of treatment, free cell wall material had formed large aggregates or was adherent to the cell walls of ghost cells. The corresponding endotoxin analysis showed a reduced content of filtrable endotoxin. Possible implications of the structural changes in relation to penicillin treatment of patients are discussed.

Cell Membrane↗
PubMed1980

The endotoxin-liberating effect of antibiotics on meningococci in vitro.

Three strains of Neisseria meningitis (two endotoxin-liberating and one in vitro variant non-liberating) were studied during treatment with MIC and 100 times MIC values of benzylpenicillin and chloramphenicol in a chemically-defined, protein-free medium. Treatment with the highest dose of benzylpenicillin had the most rapid effect on meningococci, although the antibacterial effect was the same for the two penicillin concentrations after 20 h. Chloramphenicol treatment showed a much slower antibacterial effect. After 2 h of antibacterial treatment, an increase of filtrable endotoxin in the medium was found for the endotoxin-ligerating strains only when the highest penicillin dose was used. During the same period there was a rapid cell death. After 20 hours of treatment, however, the endotoxin-liberating strains treated with high and low concentrations of penicillin had a markedly reduced content of filtrable endotoxin, compared to the controls and to the cultures treated with chloramphenicol. Antibacterial treatment had no, or only minimal, effect on the total content of endotoxin in the cultures, compared to the untreated controls. The endotoxin non-liberating strain had about the same total content of endotoxin as the liberating strains, but did not liberate filtrable endotoxin into the medium unless filtered with a much higher pressure through a filter with smaller pore size.

Chloramphenicol↗
PubMed1980

Release of endotoxin from Neisseria meningitidis. A short survey with a preliminary report on virulence in mice.

Gram-negative bacteria release various amounts of cell wall fragments containing endotoxin into the surroundings. The authors demonstrated that liberation of endotoxin from Neisseria meningitidis during growth varied with strain and growth conditions and was dependent on whether the strains released large quantities of cell wall fragments into the medium or not. The ability to liberate endotoxin could be lost upon subcultivation and was associated with certain traits. The experiments indicated that short-lasting therapy with a penicillin dose big enough to give a rapid bactericidal effect increased the release of free, filtrable endotoxin from endotoxin liberating meningococci, but not from a non-liberating variant. This effect was not found when the meningococci were treated with chloramphenicol. The endotoxin liberating meningococcal strains were more virulent for mice than the non-liberating variants, indicating that the tendency to liberate cell wall fragments containing endotoxin may be a factor in the pathogenesis of meningococcal disease in mice.

Animals↗
PubMed1979

The interaction of penicillin and chloramphenicol against meningococci in vitro.

Combinations of penicillin and chloramphenicol are frequently used initially in the treatment of bacterial meningitis. The simultaneous effects against meningococci of these two drugs were examined in vitro in a chemically defined, proteinfree medium. The investigation was performed with different combinations of the antibiotics, including optimal concentrations. In most instances, penicillin and chloramphenicol seemed to have an additive, but not an iso-additive, effect. No antagonism was found, and only one out of nine strains showed indifference.

Chloramphenicol↗
PubMed1979

Electron microscopical study of Neisseria meningitidis releasing various amounts of free endotoxin.

A study has been made of the ultrastructure of four strains of Neisseria meningitidis which liberate varying amounts of free endotoxin in a chemically-defined, protein-free medium. The two strains which did not release detectable or only sparse amounts of free, filtrable endotoxin were rather uniform in cell size. Their cells appeared to be intact and showed a low tendency to aggregate, In addition cells of these strains showed only sporadic loose, trilaminar membranes and blebs, and free membranous structures were sparse in the medium. The endotoxin releasing strains liberated a high yield of free structures from the outer cell wall into the medium. These structures may represent the lipopolysaccharide (LPS).

Bacteriological Techniques↗
PubMed1978

Liberation of endotoxin during growth of Neisseria meningitidis in a chemically-defined medium.

Modified medium 199 is well suited to the growth of meningococci if rich growth is not necessary. The bacteria were very sensitive to changes in pH and needed a good buffer capacity of the medium. Four strains of Neisseria meningitidis were studied. After the stationary phase had been reached, the vital cell count decreased relatively slowly. However, the total cell count remained unchanged for at least 12 hours. The standardized E. coli endotoxin could be detected easily by the Limulus lysate test in different protein-free, pH-adjusted and ion-balanced liquids, and the determination of endotoxin was reproducible. The Limulus lysate test was more sensitive than the rabbit pyrogen test as regards meningococcal endotoxin. Liberation of endotoxin during growth in modified medium 199 varied with strain and growth conditions. Repeated investigations showed the same pattern of growth and endotoxin liberation for each strain, also under other growth conditions. When sonicating the bacteria, high yields of endotoxin were obtained from each strain.

Culture Media↗
PubMed1978

Mortality in meningococcal infections.

Among 124 patients with meningococcal infections between 1966-1976, 108 had meningitis with a fatality rate of 7.4%, and 16 septicaemia with 18.8% fatality. High risk patients (more than 3 prognostically unfavourable characteristics) increased from 3.5% 1966-1970 to 15.6% 1971-1976, and the total mortality from 3.6 to 10.4%. The most unfavourable prognostic factor was low blood pressure at admission. High risk patients were more common among those who had meningococci with complete or partial sulfonamide resistance (25.7%) than among those having sensitive meningococci (11.9%). When the meningococci were at least partially sulfonamide-resistant, initial therapy with the combination of benzylpenicillin, sulfaisodimidine and chloramphenicol seemed to be more successful than benzylpenicillin alone in patients above 10 years. Ampicillin was used only in children, and these all survived.

Adolescent↗