425 research outputs found

    Future perspectives of aminoglycoside therapy

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    Gentamicin Inactivation in Purulent Exudates: Role of Cell Lysis

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    Factors contributing to the binding and reversible inactivation of gentamicin by purulent exudates were studied in a simplified in vitro model consisting of purified human polymorphonuclear leukocytes (PMNLs). Whereas intact PMNLs (106-108/ml) bound almost no [14C]gentamicin, freeze-thawed PMNLs showed extensive [14C]gentamicin binding, expressed as antibiotic cosedimenting with particulate material from the lysed PMNLs. Antibiotic binding could be related to the concentration of lysed PMNLs and to the amount of [14C]gentamicin added. Binding of [14C]gentamicin by lysed PMNLs was highly sensitive to DNase I but was unaffected by RNase, Triton X-100, or protease. Purified chromatin or DNA from either purulent exudates or lysed PMNLs reproduced the [14C]gentamicin-binding pattern obtained with crude PMNL lysate. These results show that gentamicin inactivation in purulent exudates can be correlated with binding of the antibiotic to lysed PMNLs; PMNL chromatin DNA is identified as one of the major binding factor

    Typhoid fever imported from Mexico to Switzerland. Studies on R factor mediated chloramphenicol resistance

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    A case of typhoid fever caused by Salmonella typhi occurred in Geneva. The patient was probably infected in Mexico City. The strain isolated from this patient corresponds with the description of the Mexican S. typhi strain, since it is a degraded Vi-strain resistant to chloramphenicol, streptomycin, sulphonamides and tetracyclines. It carried an fi− transferable R factor with a CSSuT resistance pattern. It can be accepted that this case forms part of the Mexican outbreak of chloramphenicol-resistant typhoid fever which has already been observed in visitors to Mexico from England and the United State

    Short-Term Administration of Rifampin in the Prevention or Eradication of Infection Due to Foreign Bodies

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    Short-term administration of rifampin was evaluated as a means of preventing or eradicating infection due to foreign bodies. Tissue cages were implanted into guinea pigs and subsequently infected with 103 colony-forming units of Staphylococcus aureus Wood 46. Infection developed in all tissue cages. Rifampin was administered thereafter intraperitoneally at a dosage of 7.5 mg/kg every 12 hr for 48 hr, and the tissue-cage fluid was monitored for possible development of infection by quantitative bacteriologic methods for 15 days. In all cases rifampin prevented or eradicated tissue-cage infection if treatment was initiated either 3 hr before or ⩜12 hr after inoculation of microorganisms but was ineffective if initiated >12 hr after inoculation. In cases of failure of treatment, rifampin-resistant variants could be demonstrated. Rifampin seems to prevent or eradicate tissue-cage infection only if given early after bacterial inoculatio

    Cleavage of C3 by Neutral Proteases from Granulocytes in Pleural Empyema

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    The possibility of direct inactivation of C3 by granular enzymes from polymorphonuclear leukocytes(PMNLs) in pleural empyema was examined. As a group, pleural empyema from 10 patients with purulent effusions and a positive bacteriologic culture cleaved significantly more 125I-labeled C3 bound to Sepharose (18.4% ± 7.3%) than did 19sterile pleural effusions (2.4% ± 0.9%; P << 0.001)and sonicates from bacterial strains commonly found in empyema (1.4% ± 0.2%). Granular enzymesfrom 7 × 106 PMNLs cleaved 78.5% of 125I-labeled C3 bound to Sepharose. When proteolysis of 125I-labeled C3 after incubation with pleural empyema or PMNL granular enzymes was examined with polyacrylamide gel electrophoresis, breakdown products were similar. Granulocyte elastase-like activity was detected in four samples of pleural empyema. Granulocyte elastase inhibitors, as well as 10% human serum, effectively suppressed cleavage of C3 and elastase-like activity. In pleural empyemas, granular enzymes from PMNLs, especially elastase, apparently contribute to low complement-mediated opsonic activity by direct inactivation of C

    Perioperative Antibiotic Prophylaxis of Wound and Foreign Body Infections: Microbial Factors Affecting Efficacy

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    Numerous microbial factors are responsible for perioperative infections and influence the efficacy of antibiotic prophylaxis. These factors include the staphylococcal carrier state, bacterial adherence to a number of host proteins, the production of glycocalyx by sessile bacteria, and shifts in antibiotic resistance. A full understanding of the mechanisms involved will lead to further reductions in the number of postoperative infections. Unfortunately, the microbial factors affecting prophylaxis cannot be evaluated separately under clinical conditions; they are easier to study under circumstances whose bacteriologic features are well defined and in which the presence of foreign materials (e.g., sutures) greatly potentiates pathogenic mechanisms. Such circumstances exist, for example, in infections developing after "clean” surgery and in experimental models. Since even clean wounds are found to be contaminated when sampled carefully, the control of infection is more a quantitative than a qualitative problem. The critical period for the development of infection is short: an antibiotic course not exceeding 24 hours seems effective in preventing infectio

    Foreign Body Infection: Role of Fibronectin as a Ligand for the Adherence of Staphylococcus aureus

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    Foreign bodies made of polymethylmethacrylate coverslips were implanted subcutaneously into guinea pigs, were explanted four weeks later, and were tested for in vitro adherence of Staphylococcus aureus strain Wood 46. In the presence of serum, the level of staphylococcal adherence to explanted coverslips was 20 times higher than that of adherence to unimplanted coverslips. Adherence to explanted coverslips was caused by fibronectin deposits on the foreign body surface and was inhibited in a dose-related fashion by specific antibodies to fibronecti

    Levels of Free Granulocyte Elastase in Bronchial Secretions from Patients with Cystic Fibrosis: Effect of Antimicrobial Treatment Against Pseudomonas aeruginosa

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    Large amounts of free granulocyte elastase (GE), an enzyme capable of mediating airway damage, have been found in bronchial secretions of patients with cystic fibrosis who are infected with Pseudomonas aeruginosa. This finding indicates an imbalance between GE and its antiproteases, α1-proteinase inhibitor (α1-PI) and bronchial mucosal inhibitor (BMI), in the airways of these individuals. The effect of intravenous antimicrobial treatment against P. aeruginosa on activity and concentration of GE, BMI, and α1-PI was evaluated in 30 treatment courses of 20 patients with cystic fibrosis. Although sputum volume and level of immunoreactive GE decreased and concentrations of α1-PI and BMI increased significantly (P < .05), a high level of free GE persisted. No active α1-PI and BMI were detectable after treatment. High levels of GE correlated with a poor pulmonary condition (rs = .98, P < .001). In vitro, elastolytic activity of bronchial secretions from patients with cystic fibrosis was significantly inhibited by eglin C and an oxidation-resistant variant of α1-PI, both compounds currently produced by recombinant DNA technolog

    Kustaanheimo-Stiefel Regularization and the Quadrupolar Conjugacy

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    In this note, we present the Kustaanheimo-Stiefel regularization in a symplectic and quaternionic fashion. The bilinear relation is associated with the moment map of the S1S^{1}- action of the Kustaanheimo-Stiefel transformation, which yields a concise proof of the symplecticity of the Kustaanheimo-Stiefel transformation symplectically reduced by this circle action. The relation between the Kustaanheimo-Stiefel regularization and the Levi-Civita regularization is established via the investigation of the Levi-Civita planes. A set of Darboux coordinates (which we call Chenciner-F\'ejoz coordinates) is generalized from the planar case to the spatial case. Finally, we obtain a conjugacy relation between the integrable approximating dynamics of the lunar spatial three-body problem and its regularized counterpart, similar to the conjugacy relation between the extended averaged system and the averaged regularized system in the planar case.Comment: 19 pages, corrected versio
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