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Biomedical subjects

J Verhoef

Publications and source records attributed to J Verhoef.

At least 397 records · Page 22Linked to original sources
PubMed1989

Results of a double-blind placebo-controlled study using ciprofloxacin for prevention of travelers' diarrhea.

To determine the efficacy, safety and effect on fecal flora of ciprofloxacin in the prevention of travelers' diarrhea, 54 volunteers traveling to Tunisia were randomized in a double-blind manner to receive either 500 mg ciprofloxacin or a placebo once daily for one week. Results of 53 volunteers were available for evaluation of efficacy. One of 25 subjects (4%) receiving ciprofloxacin versus 18 of 28 subjects (64%) in the placebo group experienced travelers' diarrhea (p less than 0.0001). The protection offered by ciprofloxacin was 94%. In one volunteer taking ciprofloxacin, prophylaxis was terminated due to sunburn with blistering. Among 41 subjects reporting sunburn, no statistical difference was observed between the two treatment groups in the percentage of body surface area of sunburn. Quantitative feces cultures revealed a marked decrease in the number of gram-negative organisms in volunteers receiving ciprofloxacin and a significant increase in the number of Escherichia coli in the placebo group. Five weeks after return, the aerobic bacterial flora of both treatment groups showed the pre-travel pattern.

Adult↗
PubMed1989

Comparative in vitro antibacterial activity of the new carbapenem meropenem (SM-7338).

The in vitro antimicrobial activity of the new carbapenem meropenem (SM-7338) was determined by an agar dilution method in comparison with imipenem, ticarcillin/calvulanic acid, ceftazidime and the fourth-generation cephalosporin cefepime (BMY 28142). Meropenem showed superior activity against Enterobacteriaceae (MIC90 less than or equal to 0.06 mg/l) and against non-fermentative gram-negative rods, with the exception of Xanthomonas maltophilia. Meropenem had excellent activity against beta-lactamase-producing Haemophilus influenzae and Neisseria gonorrhoeae, and against the Bacteroides fragilis group. Imipenem was slightly more active then meropenem against gram-positive cocci especially Enterococcus faecalis.

Anti-Bacterial Agents↗
PubMed1989

Once-daily aminoglycoside administration: new strategies for an old drug.

Considerable in vitro and clinical research has been conducted concerning once-daily administration of aminoglycosides. Inherent to such regimens are elevated peak concentrations and prolonged periods during which concentrations are below the MIC for the pathogen. High peak concentration to MIC ratios may maximize bactericidal rates but the problem of toxicity remains. Although sustained exposure to sublethal concentrations could undermine efficacy, antimicrobial activity may be prolonged by the post-antibiotic effect. A wide variety of animal toxicity and efficacy models has been investigated. Findings suggest that less frequent administration is associated with less toxicity while efficacy remains unaltered. Elevated doses appeared to be well tolerated in studies in volunteers and patients, however relatively few critically ill patients have been assessed. Efficacy in the treatment of urinary tract, respiratory and other infections appears unaffected by administration frequency. In an attempt to standardize dosage regimens to allow comparisons among diverse patient groups in clinical trials, guidelines for dosage adjustment based on renal function are outlined.

Aminoglycosides↗
PubMed1989

The use of a hybridization assay for the study of host defences against herpes simplex virus.

A rapid and simple hybridization assay was developed as an alternative for virus titration for the investigation of host resistance against HSV-1 infections in vitro. The probe which was constructed for this assay was shown to be HSV-1-specific. When a monolayer of fibroblasts was infected for 24 h before hybridization, 15 PFU were detected reliably. A plateau in hybridization levels was found when the multiplicity of infection reached 1. In order to demonstrate the applicability of the probe for the study of host defences against HSV in vitro, fibroblasts were infected with HSV in the presence of different numbers of adherent cells and different concentrations of serum containing high titres of anti-HSV antibodies and complement. After 20 h of incubation, samples were lysed, spotted on Zetaprobe filter paper and hybridized with a 32P-labelled RNA probe. Spots were counted for radioactivity. The radioactivity was taken as a measure of the success of infection. Results showed that at high (10%) concentrations of serum containing high titres of anti-HSV antibodies and complement neutralization plays an important role. At low (1%) concentrations of serum containing high titres of anti-HSV antibodies and complement the phagocytic role of adherent cells becomes the dominant factor in preventing infection of the fibroblasts. However, when the number of infectious particles is increased, the protection provided by adherent cells is overwhelmed.

Antibodies, Viral↗
PubMed1989

Prevention of bacterial and fungal infections in granulocytopenic patients.

Granulocytopenic patients are at high risk for infections caused by gram-negative bacteria mostly originating from the gastro-intestinal tract. Several antimicrobial prophylactic regimens are used for prevention of bacterial infections. Prophylaxis with absorbable antimicrobial agents such as trimethoprim-sulfamethoxazole or new fluorinated quinolones seems to be superior to non-absorbable drugs such as polymyxin, vancomycin and gentamicin. The most promising results are obtained with new quinolones. Use of prophylaxis in neutropenic patients leads to changes in the spectrum of infections from gram-negative towards gram-positive.

Agranulocytosis↗
PubMed1989

Trospectomycin enhances surface phagocytosis of Bacteroides and Staphylococcus by altering the bacterial glycocalyx.

The influence of trospectomycin on phagocytosis of Bacteriodes thetaiotaomicron, Bacteroides fragilis and Staphylococcus epidermidis was studied in the presence or absence of glycocalyx isolated from these microorganisms. Bacteria were grown with or without 0.25 or 0.5 of the minimal inhibitory concentration (MIC) of trospectomycin, a new chemically synthesized analog of spectinomycin. Surface phagocytosis by human polymorphonuclear leukocytes (PMNL) was determined using a modified fluorochrome assay. Subinhibitory concentrations of trospectomycin significantly enhanced surface phagocytosis of Bacteroides and Staphylococcus. When homologous or heterologous isolated glycocalyx was added to trospectomycin treated bacteria prior to incubation with PMNL, phagocytosis was reduced to levels observed in the untreated bacteria. Addition of glycocalyx to untreated strains produced no significant reduction of phagocytosis. The glycocalyx preparations were free of lipopolysaccharide and did not affect PMNL viability.

Anti-Bacterial Agents↗
PubMed1989

The influence of subminimal inhibitory concentrations of netilmicin and ceftriaxone on the interaction of Escherichia coli with host defences.

The effect of sub-MICs of netilmicin and ceftriaxone on the interaction between encapsulated and unencapsulated strains of Escherichia coli and certain host defence mechanisms, i.e. complement activation, opsonization, phagocytosis by human polymorphonuclear leucocytes (PMN), and serum bactericidal activity have been studied. Experiments were carried out testing antibiotics either alone or in combination. Non-capsulated strains of E. coli activated complement rapidly and were easily phagocytosed and killed after opsonization in human pooled serum. Pretreatment of these strains with sub-MICs of antibiotics did not change the rate of opsonization or the degree of uptake by PMN, but did enhance serum sensitivity. Capsulated strains of E. coli were both poorly opsonized and resistant to serum bactericidal activity. Treatment of these strains with sub-MICs of antibiotics enhanced complement consumption as well as phagocytosis by PMN, but did not affect serum-resistance.

Blood Bactericidal Activity↗
PubMed1989

Enhancement of opsonophagocytosis of Bacteroides spp. by clindamycin in subinhibitory concentrations.

Radioactively labelled bacteria were incubated overnight in the presence or absence of one-half the MIC of clindamycin, then preopsonized with normal human serum or homologous rabbit antiserum and incubated with human polymorphonuclear leucocytes. Clindamycin in subinhibitory concentrations significantly enhanced the phagocytosis of all four Bacteroides strains. Complement-dependent as well as antibody-dependent phagocytosis was enhanced by clindamycin in one Bacteroides strain. In the other three strains, only antibody dependent phagocytosis was enhanced by clindamycin. Transmission electron microscopy confirmed phagocytosis of the bacteroides.

Antibodies, Bacterial↗
PubMed1989

The role of glycocalyx in surface phagocytosis of Bacteroides spp., in the presence and absence of clindamycin.

The influence of isolated glycocalyx from Bacteroides thetaiotaomicron and B. fragilis on surface phagocytosis of clindamycin-treated and -untreated homologous and heterologous species was studied. When homologous or heterologous isolated glycocalyx was added to clindamycin-treated B. thetaiotaomicron or B. fragilis before incubation with PMNL, phagocytosis was reduced to levels observed in the untreated control bacteria, but addition of glycocalyx to untreated control strains showed no reduction of phagocytosis. When isolated bacteroides-glycocalyx was added to Staphylococcus aureus or S. epidermidis, phagocytosis of both clindamycin-treated and -untreated bacteria was significantly reduced. The isolated glycocalyx preparations were analysed by thin layer and gas-liquid chromatography; these preparations were free of lipopolysaccharides. The isolated glycocalyx did not affect PMNL viability. Our findings suggest that the glycocalyx is an important virulence factor because it impairs phagocytosis of Bacteroides spp. by PMNL. Clindamycin may enhance opsonophagocytosis of bacteroides by altering the glycocalyx.

Bacteroides↗
PubMed1989

Lipid peroxidation of human granulocytes (PMN) and monocytes by iron complexes.

Because the phagocytic function of non-stimulated human polymorphonuclear granulocytes (PMN) is impaired after incubation with either polynuclear Fe(III) or Fe(II), we decided to study lipid peroxidation of PMN and monocytes by these iron complexes. Lipid peroxidation was assessed by measuring thiobarbituric acid reactive substances and fluorescent compounds. In this study we report that monocytes, isolated in the standard way (EDTA-mediated detachment), release significantly more thiobarbituric acid reactive substances after incubation with iron than PMN. Monocytes, however, isolated without EDTA release the same amount after incubation with iron as PMN. The iron complexes shown to impair phagocyte function also stimulated the peroxidation of membrane lipids. Ascorbic acid in high concentrations enhanced iron-induced lipid peroxidation. Lipid peroxidation induced by ferrous ascorbate (1:20) could be inhibited by catalase, the iron chelators deferoxamine and transferrin, and the hydroxyl radical scavenger thiourea. Mononuclear complexes (ferric citrate 1:20) did not impair granulocyte function and did not induce lipid peroxidation. Our results suggest that impaired phagocyte function in patients with iron overload may be due to non-transferrin bound iron-mediated peroxidation of membrane lipids. However, the lowest amount of ferrous ascorbate (1:20) capable of inducing lipid peroxidation (50 microM) was significantly higher than that which impaired phagocyte function (10 microM).

Ferric Compounds↗
PubMed1989

Increased expression of leucocyte adherence-related glycoproteins by polymorphonuclear leucocytes during phagocytosis of staphylococci on an endothelial surface.

Phagocytosis of Staphylococcus aureus by human polymorphonuclear leucocytes (PMN) on the surface of endothelial cells is accompanied by adherence of the PMN to the endothelial surface and detachment of the endothelial cells from the culture monolayer. We studied the role of the leucocyte adherence-related glycoproteins (Leu-CAM: Mo1/LFA-1/150,95 or CD11a-c-CD18 complex) in these processes. Phagocytosis of S. aureus induced increased expression of the common beta chain (CD18) of Leu-CAM as demonstrated by flow cytometric analysis of PMN treated with a monoclonal antibody (MoAb) (CLB-LFA-1/1) directed against CD18 and fluorescein isothiocyanate (FITC)-conjugated anti-MoAb. This same MoAb also inhibited the increased adherence of the PMN to the endothelial cells which occurs during phagocytosis. Blocking of adherence during phagocytosis with MoAb CLT-LFA-1/1 had no effect on the detaching activity of the PMN on the endothelial cells. We conclude that adherence of PMN to endothelial cells during phagocytosis of S. aureus is mediated by the Leu-CAM complex. Adherence through the Leu-CAM, however, is not necessary for endothelial damage by the phagocytosing PMN.

Antibodies, Monoclonal↗
PubMed1989

Influence of fluoroquinolones on expression and function of P fimbriae in uropathogenic Escherichia coli.

P fimbriae are the major adhesins mediating attachment of pyelonephritogenic Escherichia coli to urinary tract tissues, and they therefore constitute a recognized virulence factor. In this work, the effect of fluoroquinolones on P fimbria expression and function in E. coli SS142 and C1212 was assessed. Ciprofloxacin, fleroxacin, and norfloxacin were compared with their precursor nalidixic acid and with trimethoprim in sublethal concentrations ranging from 1/32 to 1/4 of the MIC. Fimbria function was assessed in a standard hemagglutination assay and in a parallel hemagglutination inhibition assay in which the tier of antifimbrial antiserum necessary to inhibit hemagglutination by SS142 was determined. Adhesion of antibiotic-exposed bacteria to human uroma T24 cells in suspension was also measured. Fimbria production was quantitated in an inhibition enzyme-linked immunosorbent assay. Trimethoprim produced a dose-dependent decrease of three to four hemagglutination titers for both strains and a decline in the antiserum titer from 1:16 (control) to 1:128 (1/4 MIC) for E. coli SS142. Adherence exhibited similar decrements from 130 +/- 28 (control) to 16 +/- 3 (1/4 MIC) and from 83 +/- 19 (control) to 30 +/- 11 (1/4 MIC) E. coli cells per uroepithelial cell (mean +/- standard error) for SS142 and C1212, respectively (P less than 0.015). By enzyme-linked immunosorbent assay, the inhibition following exposure decreased in a dose-dependent manner from 31% (control) to 8% (1/4 MIC). By contrast, none of the quinolones produced significant changes in the parameters assessed above. At sublethal concentrations, trimethoprim decreased fimbria production. Following exposure to fluoroquinolones, however, E. coli expressed morphologically and functionally intact P fimbriae.

4-Quinolones↗
PubMed1989

Complement-mediated phagocytosis of herpes simplex virus by granulocytes. Binding or ingestion.

The role of complement receptors in phagocytosis of herpes simplex virus (HSV) by PMN was examined. Complement components were deposited on the surface of the virus particle in the presence or absence of specific anti-HSV antibodies. Flow cytometry was used to analyze the phagocytosis of fluorescence-labeled viruses and demonstrated that although a virion is able to associate with PMN in the presence of complement alone, the granulocyte is not triggered to mount a metabolic burst. Efficient stimulation of PMN occurs when complexes are formed consisting of virus, specific antibodies, and complement. To address the question whether the viruses were inside or outside the cell, a combined enhancement/quenching method was developed using ammonium chloride as a lysosomotropic agent and trypan blue as a quenching dye. The data indicate that Fc receptor-mediated phagocytosis by PMN results in the ingestion of all cell-associated herpes virions. Interactions of virions through PMN-complement receptors CR1 and CR3 results solely in binding to the PMN but not in internalization. Interactions via both complement and Fc receptors cause synergistic stimulation of the PMN and result in very efficient association of viruses, greater than 80% of which were inside the cell.

Complement System Proteins↗
PubMed1989

Cytotoxic effects of commercial continuous ambulatory peritoneal dialysis (CAPD) fluids and of bacterial exoproducts on human mesothelial cells in vitro.

Cultured human mesothelial cells were exposed to peritoneal dialysis fluids, supernatants from cultures of Staphylococcus aureus and S. epidermidis, and antibiotics. Mesothelial cell monolayer cultures were derived from surgically removed omentum. The cytotoxicity of various agents for the cultured mesothelial cells was measured by a 51 Cr-release assay. All brands of fresh peritoneal dialysis fluids induced a more than 50% 51 Cr-release after 18 h. Morphological changes observed included retraction and shrinking of cells, pyknosis of the nuclei and, finally, detachment of cells over an 18-h period. Neutralization of the acid (pH 5.2-5.5) fluids to pH 7.3 did not abolish the cytotoxicity. In contrast, effluent dialysis fluids were not toxic for mesothelial cells; neither was acid (pH 5.5) culture medium nor culture medium with glucose up to 2%. However, higher glucose concentrations induced increasing 51 Cr-release. Furthermore, filter-sterilized supernatants of S. aureus were cytotoxic for mesothelial cell monolayers in 4/7 (57%) strains of S. aureus tested. In contrast, only 4/29 (14%) strains of S. epidermidis produced cytotoxic exoproducts (p = 0.03). Antibiotics were not found to be cytotoxic, with the possible exception of erythromycin. We conclude that currently available peritoneal dialysis fluids are cytotoxic for mesothelial cells in vitro and that during episodes of peritonitis exoproducts of some bacterial strains may further reduce mesothelial cell viability.

Cell Survival↗
PubMed1989

Are intracellularly penetrating antibiotics warranted in CAPD-related peritonitis?

Survival and growth of bacteria within peritoneal macrophages has been implicated as causes of recurrences and relapses of Staphylococcus epidermidis peritonitis. We compared the effect of cephradine--known not to penetrate into peritoneal macrophages--with that of clindamycin--known to concentrate in phagocytes--on the intracellular killing of S. epidermidis by human peritoneal macrophages. Clindamycine (q.i.d. 300 mg) or cephradine (q.i.d. 250 mg) was taken orally for one day in a randomized cross-over setting by 8 stable CAPD patients. On both days peritoneal macrophages were isolated from the overnight effluents and their capacity to phagocytize and kill S. epidermidis was measured. Phagocytes isolated from and incubated in effluents containing clindamycin, showed better bacterial uptake (32 vs 17%, p less than 0.01) and killing (70 vs 42%, p less than 0.01) compared to cephradine. Moreover, clindamycin prevented S. epidermidis to multiply intracellularly (-0.33 decrease in log colony forming units (cfu)/ml after 18 h). In sharp contrast, phagocytes incubated with cephradine allowed S. epidermidis to increase over 18 h (+1.48 increase in log cfu/ml; p less than 0.01 compared to clindamycin). We conclude that antibiotics with the ability to suppress intracellular bacterial growth may provide a more optimal treatment of CAPD-related peritonitis.

Administration, Oral↗
PubMed1989

The influence of cefepime on opsonophagocytosis of bacteria.

The effect of subminimal inhibitory concentrations (sub-MICs) of a semi-synthetic beta-lactam antibiotic, cefepime (BMY 28142), was studied on the opsonophagocytosis by human polymorphonuclear leukocytes (PNMs) of strains of Escherichia coli, Klebsiella oxytoca and Staphylococcus aureus. Cefepime-treated Gram-negative bacteria were not better phagocytosed by PMNs; however the uptake of one of three S. aureus strains was enhanced. The effect of cefepime on the uptake of strains of E. coli was compared to that of two other beta-lactam antibiotics, mecillinam and ceftriaxone. Exposure of E. coli to sub-MICs of mecillinam and ceftriaxone enhanced phagocytosis by PMNs.

Amdinocillin↗
PubMed1989

Heterogeneity in opsonic requirements of Staphylococcus epidermidis: relative importance of surface hydrophobicity, capsules and slime.

The opsonic requirements of 65 strains of Staphylococcus epidermidis were compared in fresh and in heated normal human serum. The strains were isolated from patients with CAPD peritonitis (n = 26), neonatal septicaemia (n = 24) and nasal cultures (n = 15). A wide variation was observed in opsonic requirements between the different strains, both with fresh and with heated serum. Opsonization in heated serum proceeded less efficiently and higher concentrations (mean three-fold compared to fresh serum) were needed for adequate phagocytosis. However, a highly significant correlation was found between the minimal opsonic concentrations of fresh and of heated serum (r = 0.84, P less than 0.0005). In addition, S. epidermidis can become opsonized in agammaglobulinaemic serum. Thus, opsonization of S. epidermidis can be mediated by antibodies alone and by complement alone. Slime-producing strains and encapsulated strains did not require higher concentrations of serum to become opsonized. Opsonic requirements were highly significantly correlated with surface hydrophobicity. Enzymatic treatment rendered the strains more hydrophilic and decreased their opsonic requirements. Isolates from nasal cultures required significantly higher concentrations of both fresh and heated serum to become adequately phagocytozed, whereas isolates from CAPD peritonitis required higher concentrations of heated serum only compared to blood isolates. The uptake of S. epidermidis preopsonized in heated serum as determined in our direct phagocytosis assay did not result in a comparable chemiluminescence response.

Antibodies, Bacterial↗