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Biomedical subjects

R van Furth

Publications and source records attributed to R van Furth.

At least 163 records · Page 9Linked to original sources
PubMed1989

Clinical evaluation of pneumococcal meningitis in adults over a twelve-year period.

A retrospective study was performed to review the clinical features and outcome of 39 episodes of pneumococcal meningitis in 36 adult patients over a 12-year period. Overall mortality was 33.3%. Only a few of the deaths were directly related to the central nervous system disease and most of them were due to cardiorespiratory failure. Univariate analysis showed that death was more likely to occur in patients with advanced age, an absence of neck stiffness, a high pulse rate, an associated pneumonia, internal complications, or a long duration of the disease (greater than 7 days) before treatment was started. Patients who died had a higher erythrocyte sedimentation rate and serum bilirubin level and a lower serum sodium level than those who survived. Discriminant analysis showed the development of internal complications to be the strongest predictive factor of a poor outcome of illness. Two other important predictors of a poor outcome were the absence of neck stiffness and associated pneumonia. The history of a skull fracture or head surgery was significantly correlated with a better than average prognosis. The incidence of sequelae in survivors at the time of discharge amounted to 72%. None of the clinical features were significantly correlated with the development of sequelae, except a higher cerebrospinal fluid protein content.

Adolescent↗
PubMed1989

Decontaminating efficacy of ciprofloxacin in an animal model.

A study was performed to assess the suppressive effect of ciprofloxacin on the aerobic gram-negative flora of the gastrointestinal tract in mice in relation to its effect on colonization resistance. Ciprofloxacin exhibited a potent decontaminating effect, with the maximum effect being reached at a dose of 8 mg/kg/day. At this dose aerobic gram-negative rods were eliminated from the gastrointestinal tract within 24h without any adverse influence on the parameters of colonization resistance measured.

Animals↗
PubMed1989

Modulation of the host flora.

Modulation of the bacterial flora of patients with a high risk of acquiring an infection can be achieved in several ways. The approach used in the Leiden University Hospital is based on selective elimination of the aerobic bacteria in the oropharyngeal cavity and intestinal tract, leaving the anaerobic flora intact. This kind of selective modulation of the host flora has an advantage in that it does not affect the colonization resistance provided by bacterial antagonism, which prevents colonization by resistant but potentially pathogenic bacteria or fungi. The elimination of aerobic bacteria combined with nursing in protective isolation and consumption of food with few bacteria has led to a significant reduction of the incidence of major and fatal infections in patients during episodes of severe granulocytopenia. From these results it may be concluded that the objective of selective antibiotic modulation, namely, the prevention of infections, can be achieved with this approach.

Animals↗
PubMed1989

Is the conventional doctrine about macrophage activation still true?

The present results challenge the view that macrophage activation leads to a general, non-specific increase of microbicidal activity of these cells. Instead, it was found that the interactions between activated macrophages and micro-organisms are dependent on the kind of activation and the type of target micro-organism.

Animals↗
PubMed1989

Comparison of the efficacies of amphotericin B, fluconazole, and itraconazole against a systemic Candida albicans infection in normal and neutropenic mice.

We compared the efficacies of the new triazole antifungal drugs fluconazole and itraconazole with that of amphotericin B in vitro and in an animal model of systemic candidiasis in normal and neutropenic mice. Antifungal treatment with fluconazole (2.5 to 20 mg/kg orally twice daily), itraconazole (10 to 40 mg/kg orally twice daily), or amphotericin B (0.1 to 4 mg/kg intraperitoneally once daily) was started 1 day after intravenous injection of 10(4) Candida albicans into normal mice or 10(3) C. albicans into neutropenic mice; the drugs were administered for 2 days. In normal mice the efficacy of treatment, which was assessed on the basis of the number of C. albicans cultured from the kidney, was greater for amphotericin B than for the triazoles. Fluconazole was more potent than itraconazole on the basis of equivalent doses, although itraconazole was more potent on the basis of the amount of free drug that was available. In neutropenic mice amphotericin B was less effective than it was in normal mice, whereas the triazoles were equally effective in normal and neutropenic mice. This was not expected, since in vitro data showed that amphotericin B was highly fungicidal, whereas both fluconazole and itraconazole had only a minimal effect on the growth of C. albicans in vitro.

Agranulocytosis↗
PubMed1989

Influence of etoposide and cyclophosphamide on the efficacy of cloxacillin and erythromycin in an experimental staphylococcal infection.

The effect of monocytopenia and granulocytopenia on the outgrowth of Staphylococcus aureus as well as on antibiotic efficacy was studied in an experimental thigh infection in mice. Pretreatment with etoposide reduced monocyte numbers in blood to 14% and those of granulocytes to 54% at the time of infection. Monocytopenia did not affect the proliferation of bacteria in the infected thigh or the reduction of bacterial numbers after treatment with cloxacillin or erythromycin. Pretreatment with cyclophosphamide reduced monocyte numbers to 15% and granulocyte numbers to 3%. This resulted in a marked increase in the number of bacteria at the site of infection and a decrease in the efficacy of antibiotic treatment.

Animals↗
PubMed1989

Deficient intracellular killing of bacteria by murine alveolar macrophages.

Microbiologic methods were used to assess the in vitro phagocytosis and intracellular killing of various species of bacteria by freshly isolated murine peritoneal and alveolar macrophages. Peritoneal macrophages showed effective phagocytosis of opsonized Streptococcus pneumoniae, Streptococcus pyogenes, Pseudomonas aeruginosa, Staphylococcus epidermidis, and Listeria monocytogenes, and moderate ingestion of Staphylococcus aureus and Escherichia coli. Alveolar macrophages were poor in phagocytosing opsonized S. pyogenes, S. aureus, and E. coli; ingestion of S. pneumoniae, P. aeruginosa, and S. epidermidis was moderate. Peritoneal macrophages killed 40 to 80% of these bacteria intracellularly, but alveolar macrophages showed almost no intracellular killing of bacteria. To find out whether there is a correlation between the poor bactericidal activity of alveolar macrophages and the oxygen-dependent microbicidal mechanisms of these cells, we determined the uptake of oxygen and the release of superoxide anion and hydrogen peroxide by macrophages at rest and after stimulation with phorbol myristate acetate (PMA) or opsonized S. aureus. Upon exposure to these stimuli, peritoneal macrophages, but not alveolar macrophages, showed an increased uptake of oxygen and release of superoxide anion and hydrogen peroxide. Because alveolar macrophages contain surface active material (SAM), we investigated the phagocytosis and intracellular killing of bacteria and the release of hydrogen peroxide by peritoneal macrophages pretreated with SAM. The results showed reduced phagocytosis and impaired intracellular killing of S. epidermidis by these macrophages. The release of hydrogen peroxide by SAM-pretreated peritoneal macrophages upon stimulation with PMA or opsonized S. aureus was equal to that of the control peritoneal macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Comparison of in vivo and in vitro activities of antibiotics with different modes of action against a tolerant and a non-tolerant Staphylococcus aureus strain.

The antibacterial efficacies of 4 antibiotics with different modes of action against a penicillin-tolerant and a non-tolerant strain of Staphylococcus aureus were investigated. For the in vitro studies the minimum inhibitory concentration (MIC) and the minimum bacterial concentration (MBC) were determined and short-term growth experiments at different antibiotic concentrations were performed. For the in vivo studies, antibacterial efficacy in an experimental infection in normal and granulocytopenic mice was evaluated. For erythromycin, rifampicin and ciprofloxacin, there was no difference in the MIC and MBC values for the 2 strains. Benzylpenicillin had an MBC value for the tolerant strains which was 256 times higher than the MIC; with the non-tolerant strain there was no difference. EC50 values, calculated from the in vitro short-term growth curves, gave similar results. Only benzylpenicillin exhibited a difference in activity against the tolerant strain, as reflected by the EC50 that was 290 times the EC50 for the non-tolerant strain. Studies in normal and granulocytopenic mice gave similar results: benzylpenicillin was 268 times less active against the tolerant strain than against the non-tolerant strain. Erythromycin, rifampicin and ciprofloxacin were 2-3 times less active against the tolerant strain than against the non-tolerant strain. The presence of granulocytes is important for the antibacterial effect of all antibiotics studied, since in the absence of granulocytes higher doses of the antibiotics are needed in order to obtain the same antibacterial effect as when granulocytes are present.

Agranulocytosis↗
PubMed1989

Immunocytochemical analysis of cellular responses to BCG.

The study reported here was performed to find out whether changes in the number of mycobacteria in various organs of BCG-infected mice can be related to changes in the phenotype of monocytes, macrophages and lymphocytes in the blood, various tissues, and peritoneal cavity and to the formation of granulomas in the spleen, liver and lungs. The relative amounts of various antigens on the leukocytes were assessed semi-quantitatively after immunocytochemical detection of the binding of monoclonal antibodies. Granuloma formation was determined after immunocytochemical staining of cells in sections of liver and lung tissue with a monoclonal antibody against the common leukocyte antigen and in sections of the spleen with a monoclonal antibody against the Mac-2 antigen. The results showed that during the first week of infection the number of BCG in spleen, liver and lungs declined considerably. Multiplication of mycobacteria during the second week of infection was associated with decreased expression of antigen F4/80 and increased expression of Ia antigen and Mac-2 antigen by blood monocytes and macrophages. Reduction of the numbers of BCG in the spleen and liver during the third week after i.v. injection of BCG and in lungs during the fourth week of the infection was found to be correlated with the degree of granuloma formation in these organs. After intravenous injection of killed BCG no changes were observed in the phenotype of monocytes and the macrophages in spleen, liver, lungs and peritoneal cavity. These mice showed considerably less granuloma formation than BCG-infected mice. The present results indicate that live but not killed mycobacteria induce macrophage activation.

Animals↗
PubMed1989

Elimination of soluble 123I-labelled aggregates of human immunoglobulin G in humans; the effect of splenectomy.

To study the role of the spleen in the elimination of immune complexes we examined mononuclear phagocyte system function in eight healthy controls and eight splenectomized patients, with soluble 123I-labelled aggregates of human immunoglobulin G (AIgG). No differences were found between the two groups in elimination and degradation of AIgG. The loss of splenic function was compensated for by increased uptake of AIgG by the liver. With the dose of 123I-AIgG used in this study (10 micrograms/kg body weight), significant generation of C3a was observed. No correlation was found between erythrocyte CR1 number and the fraction of aggregates that bound to erythrocytes.

Adult↗
PubMed1988

Decreased gastrin secretion in patients with late-onset hypogammaglobulinemia.

We undertook this study to determine whether patients with late-onset hypogammaglobulinemia, who are at very high risk for gastric cancer, have a reduced secretion of gastrin after stimulation with food or bombesin, a potent gastrin-releasing stimulus. We compared the plasma gastrin responses to bombesin and to a standard test meal in 18 patients with late-onset hypogammaglobulinemia with those in patients with X-linked agammaglobulinemia, early-onset hypogammaglobulinemia, or hypogammaglobulinemia due to lymphoproliferative cancer, and in 30 normal control subjects. Thirteen of 18 patients with late-onset hypogammaglobulinemia (72 percent) had an abnormally low gastrin response to bombesin, as compared with none of 21 patients with other forms of hypogammaglobulinemia (P less than 0.05). After a test meal, abnormally low gastrin secretion was found in 6 of 14 patients with late-onset hypogammaglobulinemia (43 percent) and in 1 of 18 patients with other forms of the disease (6 percent) (P not significant). The plasma gastrin responses to stimulation with bombesin or food distinguished late-onset hypogammaglobulinemia from other forms, with sensitivities of 72 and 43 percent and specificities of 100 and 94 percent, respectively. Stimulated gastrin response can therefore be used as a marker for this type of immunodeficiency. The test responses also showed heterogeneity among patients with late-onset hypogammaglobulinemia and may help to identify patients with an increased risk for gastric cancer.

Adolescent↗