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Showing papers by "Altran published in 2002"


Journal ArticleDOI
TL;DR: It is suggested that taurolidine-citrate is a promising combination agent for the prevention and treatment of intravascular catheter-related infections.
Abstract: Intravascular catheter-associated bloodstream infections significantly increase rates of morbidity and hospital costs. Microbial colonization and development of biofilms, which are known to be recalcitrant to antibiotic therapy, often lead to the loss of otherwise patent vascular access systems. We evaluated a new taurolidine- and citrate-based catheter lock solution (Neutrolin; Biolink Corporation, Norwell, Mass.) for its activity against planktonic microbes, antimicrobial activity in a catheter model, and biofilm eradication activity. In studies of planktonic microbes, after 24 h of contact, 675 mg of taurolidine-citrate solution per liter caused > 99% reductions in the initial counts of Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Entercoccus faecalis. A solution of 13,500 mg/liter was cidal for Candida albicans. Ports and attached catheters inoculated with 50 to 600 CFU of these bloodstream isolates per ml were locked with heparin or the taurolidine-citrate solution. After 72 h, there was no growth in the taurolidine-citrate-treated devices but the heparin-treated devices exhibited growth in the range of 6 x 10(2) to 5 x 10(6) CFU/ml. Biofilms were developed on silicone disks in modified Robbins devices with broth containing 6% serum (initial counts, 10(6) to 10(8) CFU/cm(2)). The axenic biofilms were treated for 24 h with taurolidine-citrate or heparin. Taurolidine-citrate exposure resulted in a median reduction of 4.8 logs, whereas heparin treatment resulted in a median reduction of 1.7 logs (P < 0.01). No significant differences in the effects of the two treatments against P. aeruginosa and C. albicans were observed. These findings suggest that taurolidine-citrate is a promising combination agent for the prevention and treatment of intravascular catheter-related infections.

187 citations


Journal ArticleDOI
TL;DR: This study focuses on evaluating the enzyme-catalyzed degradation of a degradable polyurethane synthesized with 1,12 diisocyanatododecane as a substitute for 1,6 di isocyanatohexane, which was used in previous work.
Abstract: Biomaterial-related infections continue to represent a significant challenge to the medical community. Several approaches have been utilized to incorporate antimicrobial agents at the surface of implant devices in attempts to delay or eliminate the formation of biofilms. To date, most of these strategies have focused on drug conjugation or diffusion-limited systems for the delivery of such pharmaceutical agents. More recently, work has been presented on the feasibility of incorporating drugs into the backbone of polymers as a main-chain monomer. When sequenced into the backbone of the polymer with other monomers that are hydrolytically sensitive to enzyme-catalyzed breakdown, it is thought that drugs may be able to be selectively released. Specifically, degradable polyurethanes have been synthesized with fluoroquinolone antibiotics and have shown an ability to kill bacteria when released following degradation of the polymer chains by the macrophage-derived enzyme cholesterol esterase. However, specificity of the cleavage sites in the polymer was difficult to control. Since cholesterol esterase has specificity for hydrophobic moieties, it is desirable to alter the formulation of the polyurethanes to incorporate long hydrophobic monomers immediately adjacent to the ciprofloxacin molecule. Hence, the current study focuses on evaluating the enzyme-catalyzed degradation of a degradable polyurethane synthesized with 1,12 diisocyanatododecane as a substitute for 1,6 diisocyanatohexane, which was used in previous work. Validation of specific ciprofloxacin release and the generation of antimicrobial are shown. A preliminary cell study to assess the cytotoxicity of this biodegradable antibiotic polymer shows that the material has no observable effects on cell proliferation or cell membrane structure.

94 citations


Journal ArticleDOI
TL;DR: A new importance sampling Monte Carlo method is proposed based on a recursive use of the state space decomposition methodology of Doulliez and Jamoulle during the simulation process and it is shown theoretically that the resulting estimator belongs to the variance‐reduction family and an upper bound on its variance is given.
Abstract: The exact evaluation of the probability that the maximum st-flow is greater than or equal to a fixed demand in a stochastic flow network is an NP-hard problem. This limitation leads one to consider Monte Carlo alternatives. In this paper, we propose a new importance sampling Monte Carlo method. It is based on a recursive use of the state space decomposition methodology of Doulliez and Jamoulle during the simulation process. We show theoretically that the resulting estimator belongs to the variance-reduction family and we give an upper bound on its variance. As shown by experimental tests, the new sampling principle offers, in many cases, substantial speedups with respect to a previous importance sampling based on the same decomposition procedure and its best performances are obtained when highly reliable networks are analyzed. © 2002 Wiley Periodicals, Inc. Naval Research Logistics 49: 204–228, 2002; DOI 10.1002/nav.10004

18 citations


DOI
01 Jan 2002
TL;DR: The conocimiento se presenta como el recurso mas fecundo a la hora de generar riqueza in la economia moderna as discussed by the authors.
Abstract: El conocimiento se presenta como el recurso mas fecundo a la hora de generar riqueza en la economia moderna. Las empresas lo han comprendido y estan ensayando sistemas con el fin de gestionarlo y sacarle partido. Para lograrlo se precisa que quienes poseen el conocimiento se muestren dispuestos a compartirlo con el resto de la organizacion, pero eso solo sucedera si reina un ambiente de compromiso, confianza mutua y espiritu de cooperacion.

3 citations


Book ChapterDOI
TL;DR: This paper proposes an Ontology for Object Oriented Design Knowledge and a measure of impact for patterns, two key elements to create a method based in knowledge.
Abstract: It has been a long time since appeared of the Object Oriented (OO) paradigm. From that moment, the designers have accumulated much knowledge in design and construction of OO systems. Patterns are the most refined OO Design Knowledge. However, there are many others kinds of knowledge than not yet classified and formalized. We distinguish and classify the following categories: principles, heuristics, patterns and refactorings. In this paper, we propose an Ontology for Object Oriented Design Knowledge and a measure of impact for patterns, two key elements to create a method based in knowledge.

1 citations