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Biomedical subjects

J Verhoef

Publications and source records attributed to J Verhoef.

At least 415 records · Page 23Linked to original sources

Isolation and chemical analysis of 7-O-(2-amino-2-deoxy-alpha-D-glucopyranosyl)-L-glycero-D-manno-heptose as a constituent of the lipopolysaccharides of the UDP-galactose epimerase-less mutant J-5 of Escherichia coli and Vibrio cholerae.

Methyl 7-O-(2-amino-2-deoxy-alpha-D-glucopyranosyl)-L-glycero-D-manno-hepto+ ++ pyranoside (1) was released from the lipopolysaccharide of the UDP-galactose epimerase-less mutant J-5 of Escherichia coli by methanolysis and isolated by high-voltage paper electrophoresis. Its chemical structure was determined by chemical analysis, deamination with nitrous acid, g.1.c.-m.s., and 1H- and 13C-n.m.r. spectroscopy performed on its acetylated derivative. The disaccharide moiety of 1 was also detected in lipopolysaccharides of Vibrio cholerae.

Carbohydrate Epimerases↗

Comparison of once daily ceftriaxone with gentamicin plus cefuroxime for treatment of serious bacterial infections.

To compare the efficacy of once daily monotherapy with that of standard combination antibiotic therapy for the initial management of patients suspected of serious bacterial infections, 105 patients were randomised to treatment with ceftriaxone alone (53 patients) or to a combination of cefuroxime and gentamicin (52 patients). There was no difference between the groups in proportions responding to therapy or proportions dying from infection, except when non-evaluable patients were excluded from the group with definite bacterial infection, in which case response was better among those treated with ceftriaxone. The groups did not differ in number of side-effects, but therapy had to be discontinued because of treatment failure, an adverse effect, or death in 1 of 53 patients given ceftriaxone and in 11 of 34 given the combination. Use of ceftriaxone was 107.36 pounds ($182.51) cheaper per patient, and saved 40 minutes of nursing and drug administration time per patient per day. Thus 2 g ceftriaxone given once a day is at least as effective and costs less in time and money than gentamicin plus cefuroxime for the initial treatment of patients with serious systemic bacterial infections.

Adult↗

Dialysis fluids and local host resistance in patients on continuous ambulatory peritoneal dialysis.

The ability of polymorphonuclear leukocytes, monocytes and peritoneal macrophages to mount a respiratory burst in continuous ambulatory peritoneal dialysis (CAPD) fluids was tested in a phorbol-myristate acetate stimulated chemiluminescence assay. Fresh CAPD fluids depressed the chemiluminescence response of all three types of phagocytes tested to less than 18% of their chemiluminescence response in control buffer. When tested in spent CAPD fluids the suppression of chemiluminescence was 30-32%. Oxygen consumption of polymorphonuclear leukocytes was depressed in fresh CAPD fluids to below 40%. Both phagocytosis of Escherichia coli by and bactericidal capacity of polymorphonuclear leukocytes and monocytes were suppressed in fresh CAPD fluids but not in spent effluents. The influence of acidic pH and hyperosmolality on phagocytic functions were studied separately by modifying the acidity or the glucose content of the control buffer. pH values below 6.0 significantly inhibited chemiluminescence but not phagocytosis. Under hypertonic conditions, both phagocytosis and chemiluminescence were inhibited. We conclude that the currently available CAPD solutions are beyond the limits of acid and osmotic tolerance of human phagocytic cells, and may thus compromise the peritoneal defenses of CAPD patients.

Escherichia coli↗

Endemic Acinetobacter anitratus in a surgical intensive care unit: mechanical ventilators as reservoir.

Colonization and infection with an endemic multiresistant strain of Acinetobacter calcoaceticus variety anitratus had been observed in the surgical intensive care unit of a university hospital since 1982. An outbreak of infection with this endemic, multiresistant Acinetobacter anitratus strain occurred between January and September, 1984. After initial attempts at identification of environmental reservoirs had been unsuccessful, risk factors for the acquisition of Acinetobacter anitratus were investigated by comparing the epidemiological characteristics of patients who became colonized or infected with those of control patients without colonization. The results of this case-control study and of the ensuing specific cultures indicated that ventilators in use in the unit were the reservoirs of Acinetobacter anitratus, resulting in frequent nosocomial respiratory tract infections. After modification of the mechanical ventilators, colonization and infection rates with Acinetobacter anitratus decreased. Since January 1985, no new cases of colonization or infection with this endemic strain of Acinetobacter anitratus have been recorded.

Acinetobacter↗

Surface hydrophobicity and opsonic requirements of coagulase-negative staphylococci in suspension and adhering to a polymer substratum.

The opsonic requirements for phagocytosis in suspension of 38 clinical isolates of coagulase-negative staphylococci recovered from neonates with septicemia were found to be related to the degree of surface hydrophobicity of these strains. Sixteen isolates were adequately opsonized only in the presence of complement; this group was significant more hydrophobic (p less than 0.001) than the 22 strains not requiring complement for efficient uptake in suspension. Evidence showed that hydrophobic groups present on the bacterial surface may interfere with IgG opsonization. In contrast, IgG sufficed as an opsonin without complement being required for the efficient uptake of these hydrophobic strains when adhering to a polymer surface.

Bacterial Adhesion↗

Host defence to bacterial infection in the neonate.

Host defence to bacterial infection is mainly determined by opsonins, i.e., IgG antibodies and complement, and phagocytic cells, which co-operate to remove bacterial invaders from host tissues. Various studies have clearly documented distinct defects in both arms of host defence in the newborn period. Chemotaxis, i.e., directed migration of polymorphonuclear leukocytes (PMN) is impaired in the neonate. Phagocytosis of bacteria by neonatal PMN is normal, but post-phagocytic events, particularly metabolic activation and bacterial killing are impaired, the latter defect apparently due to diminished generation of reactive oxygen species. Both classical and alternative pathway activity of complement are mildly diminished (50-80% of adult values) in the term newborn, but are more severely decreased in the premature infant (20-40% of adult values in 28 to 36 weeks prematures). Opsonic activity of transplacentally-derived IgG when compared to maternal IgG is strikingly deficient against staphylococci and group B streptococci (GBS), in the latter case depending on the GBS serotype. Since opsonization is a key process in antibacterial defence, it is speculated that these opsonic defects of IgG may be an essential determinant of the neonate's susceptibility to disease due to these bacteria.

Bacterial Infections↗

Treatment of gram-negative septic shock with human IgG antibody to Escherichia coli J5: a prospective, double-blind, randomized trial.

In a randomized, double-blind, multicenter trial we compared the efficacy of a preparation of human IgG antibody to Escherichia coli J5 (J5-IVIG) with that of a standard IgG preparation (IVIG) for the treatment of gram-negative septic shock. At study entry, patients received a single intravenous dose of 200 mg/kg of body weight (maximal dose, 12 g) of either J5-IVIG or IVIG. Of the 100 patients randomized, 71 (30 receiving J5-IVIG and 41 receiving IVIG) had a documented gram-negative infection. Mortality from gram-negative septic shock was 50% (15 of 30) in J5-IVIG recipients and 49% (20 of 41) in IVIG recipients. In addition, treatment with J5-IVIG did not reduce the number of systemic complications of shock and did not delay the occurrence of death due to septic shock. Thus we conclude that J5-IVIG was not superior to IVIG in reducing mortality or in reversing gram-negative septic shock.

Adolescent↗

Prevention of colonization and infection in critically ill patients: a prospective randomized study.

In a prospective randomized study to determine whether prevention of colonization of Gram-negative bacteria results in prevention of Gram-negative bacterial infections, 96 intensive care patients were randomly allocated into a control group and a study group. The study group received oral nonabsorbable antimicrobial agents (i.e., tobramycin, amphotericin B, and polymyxin E) in addition to parenteral antibiotics. Colonization with Gram-negative microorganisms in the oropharynx, and respiratory and digestive tracts increased in the control group during their stay, while the study group did not tend to colonize with Gram-negative bacteria. In the control group, 107 nosocomial infections were diagnosed, vs. 42 nosocomial infections in the study group. Nosocomial infections caused by Gram-negative bacteria were significantly less frequent in the study group. Mortality due to an acquired infection was significantly less frequent in the study group. We conclude that colonization, infection, and subsequent mortality by nosocomial Gram-negative bacteria can be prevented by a regime of topically applied nonabsorbable antibiotics.

Adult↗

Effect of iron on polymorphonuclear granulocyte phagocytic capacity: role of oxidation state and effect of ascorbic acid.

It has been shown that iron (III) impairs the function of polymorphonuclear granulocytes (PMN). We have studied the effect of iron (II), on the membrane function of PMN, by assessing the uptake of radiolabelled Staphylococcus aureus by these cells. Iron (II), significantly impaired PMN phagocytic function. Addition of ascorbic acid reduced uptake further. Ferrous ascorbate, molar ratio 1:20, impaired phagocytic capacity of PMN significantly at iron concentrations as low as 1-10 microM. The toxic effect of iron (II) was not observed when desferrioxamine or transferrin was present in the incubation medium. The oxygen-free radical scavengers thiourea, mannitol and catalase prevented toxicity mediated by ferrous ammoniumsulphate but not by ferrous ascorbate (molar ratio of 1:20). Although high concentrations of ascorbic acid inhibited the generation of .OH and also the formation of the DMPO-.OH adduct by zymosan stimulated PMN, toxicity of iron increased. Iron (II) impaired the uptake of S. aureus by PMN of a patient with chronic granulomatous disease while iron (III) did not. Iron mediated impairment of PMN function is not only a result of the generation of toxic oxygen metabolites but also of direct interaction of iron (II) or an iron (II)-oxygen intermediate with molecules of the cell membrane.

Adult↗

Polynuclear iron complexes impair the function of polymorphonuclear granulocytes.

In a previous study we showed that the phagocytic function of non-stimulated PMN was impaired after incubation with high concentrations (200 microM) of polynuclear Fe(III), probably as a result of continuous generation of small amounts of superoxide and subsequent formation of hydroxyl radicals (Van Asbeck et al, 1984b). Because polynuclear Fe(III) complexes may not be available for biological reactions we have studied the effects of polynuclear and mononuclear iron(III) on the PMN. Fe(III) in its polynuclear form (Fe:citrate 1:1) was deleterious for the phagocytic function of PMN, while the mononuclear form (Fe:citrate 1:20) was not toxic. Binding affinity of polynuclear Fe(III) for PMN was higher than of mononuclear Fe(III), and a considerable amount of bound Fe(III) was found in the cytosolic fraction of non-stimulated PMN. Limit dilution analysis of polynuclear complexes revealed that concentrations as low as 25 microM Fe(III) significantly impaired phagocytic function. The molecular weight of these complexes is similar to that of the non-transferrin plasma iron found in the serum of patients with iron overload. The toxic effects of small polynuclear non-transferrin plasma Fe(III) complexes on PMN function may contribute to the development of infections in patients with iron overload.

Adult↗

Carumonam (Ro 17-2301; AMA-1080) compared with gentamicin for treatment of complicated urinary tract infections.

Carumonam and gentamicin were compared in a prospective, randomized study of 52 patients with complicated urinary tract infections. Patients were treated with either carumonam (1 g every 8 h) or gentamicin (1 mg/kg every 8 h). The mean duration of therapy (carumonam, 8.5 days; gentamicin, 8.5 days) was similar for both groups. A total of 45% of patients treated with carumonam and 48% of those receiving gentamicin were cured, as defined by a negative culture 1 to 2 weeks after therapy. After 4 to 6 weeks, the figures were 27% for carumonam and 38% for gentamicin. In the carumonam group, there were 6 relapses and 11 reinfections. In the gentamicin group, there were eight relapses and five reinfections. Adverse effects in the carumonam group were limited to phlebitis at the intravenous infusion site in two patients; another patient developed bloody diarrhea. Nephrotoxicity was documented in two patients in the gentamicin treatment group (9%), and another patient developed minor liver function disturbances. Three patients with gentamicin-resistant carumonam-susceptible isolates were treated with carumonam, and two were cured. Urinary colonization with group D streptococci occurred in 7 of 27 (26%) carumonam-treated patients compared with 7 of 19 (37%) gentamicin-treated patients; no one required treatment. A significant correlation was found between colonization with group D streptococci and neurogenic bladder dysfunction (P less than 0.007). It is concluded that the use of the carumonam is as effective as the gentamicin regimen in the treatment of complicated urinary tract infections.

Adult↗

Attachment of human polymorphonuclear leukocytes to herpes simplex virus-infected fibroblasts mediated by antibody-independent complement activation.

Herpes simplex virus (HSV)-infected cells can activate the human complement system without interference of specific anti-HSV antibodies. Analysis by flow cytometry showed that C3-like molecules were deposited on the membrane of the infected cell when incubated with human serum without specific antibodies. Depletion of calcium to block the classical pathway of the complement system had no effect on fluorescence intensity. The complement activation could be blocked by chelating both calcium and magnesium or by heating the serum. Furthermore, in the fluid phase C3 was converted to C3b by infected cells and not by uninfected cells. The antibody-independent activation did not lead to lysis of the virus-infected fibroblasts, indicating that the complement cascade is abrogated before formation of the membrane attack complex. This was also confirmed by measurement of the 50% hemolytic complement activities for total and alternative pathways. Polymorphonuclear leukocytes attached to infected fibroblasts after incubation of these fibroblasts with intact complement. This is most probably mediated by complement receptor binding of C3b and C3bi which is deposited on the membrane of the HSV-infected cell. Both type 1 and type 2 HSVs showed the same characteristics in complement activation and thereby mediated polymorphonuclear leukocyte adherence.

Calcium↗

Comparative study of ceftriaxone monotherapy versus a combination regimen of cefuroxime plus gentamicin for treatment of serious bacterial infections: the efficacy, safety and effect on fecal flora.

To assess the efficacy of once daily monotherapy relative to standard combination antibiotic therapy for the initial management of patients suspected of serious bacterial infections, we conducted a randomized trial comparing ceftriaxone (Rocephin) with a combination of cefuroxime plus gentamicin. Of 105 patients, 53 were treated with ceftriaxone alone and 52 with the combination; 13 patients were considered not evaluable. 42 of 53 patients given ceftriaxone and 33 of 52 given cefuroxime plus gentamicin responded to treatment (p = 0.07). Three patients given ceftriaxone and 6 who received gentamicin plus cefuroxime died (p = 0.28). Definite bacterial infections were identified in 67 patients; of the evaluable patients with a definite infection 27 of 29 who received ceftriaxone and 21 of 31 who were treated with the combination were cured (p = 0.01). No difference was found in the number of side effects. However, therapy had to be discontinued due to treatment failure, an adverse effect or death in 1 of 33 patients given ceftriaxone and in 11 of 34 given the combination (p = 0.002). Ceftriaxone was found to have an impact on the count of E. coli in intestinal microflora. Changes in normal bacterial composition did not lead to the overgrowth with resistant Enterobacteriaceae or Pseudomonas, however, colonization by yeast was observed. Using ceftriaxone reduced the cost of antimicrobial therapy per patient by 107 pounds (US$ 183). Moreover, the total time save per patient due to decreased nursing and drug administration time per day was 40 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial Infections↗

Monobactam antibiotics in subinhibitory concentrations enhance opsonophagocytosis and serum bacteriolysis in certain Escherichia coli strains.

Capsular polysaccharides are known to protect Gram-negative bacteria from complement-mediated killing and opsonophagocytosis. Monobactam antibiotics selectively inhibit penicillin-binding protein 3 (PBP3), resulting in abnormally structured peptidoglycan, causing defective cell surface structures. The authors studied the influence of subinhibitory concentrations of the monobactam antibiotics aztreonam and carumonam on serum bacteriolysis and opsonophagocytosis of four K-encapsulated and five non-K-encapsulated Escherichia coli strains. It was observed that monobactam antibiotics in subinhibitory concentrations enhanced opsonophagocytosis of the four K-encapsulated and one non-K-encapsulated E. coli strains tested. Opsonophagocytosis of the other four non-K-encapsulated E. coli strains was not enhanced. Serum bacteriolysis studies revealed that of the four K-encapsulated strains tested only one strain showed a significant enhancement of bacteriolysis after treatment with subinhibitory concentrations of monobactam antibiotics. None of the unencapsulated strains showed a significant change in percentage lysis after treatment with either aztreonam or carumonam.

Anti-Bacterial Agents↗