Maria J Ramos — Page 2

PubMed2004

Periodically changing ventilator circuits is not necessary to prevent ventilator-associated pneumonia when a heat and moisture exchanger is used.

OBJECTIVE: To analyze the efficacy of periodically changing ventilator circuits for decreasing the rate of ventilator-associated pneumonia when a heat and moisture exchanger (HME) is used for humidification. The Centers for Disease Control and Prevention recommended not changing the circuits periodically. DESIGN: Randomized, controlled trial conducted between April 2001 and August 2002. SETTING: A 24-bed, medical-surgical intensive care unit in a 650-bed, tertiary-care hospital. PATIENTS: All patients requiring mechanical ventilation during more than 72 hours from April 2001 to August 2002. INTERVENTIONS: Patients were randomized into two groups: (1) ventilation with change of ventilator circuits every 48 hours and (2) ventilation with no change of circuits. Throat swabs were taken on admission and twice weekly until discharge to classify pneumonia as endogenous or exogenous. RESULTS: Three hundred four patients (143 from group 1 and 161 from group 2) with similar characteristics (age, gender, Acute Physiology and Chronic Health Evaluation II score, diagnostic group, and mortality) were analyzed. There was no significant difference in the rate of pneumonia between the groups (23.1% vs 23.0% and 15.5 vs 14.8 per 1,000 ventilator-days). There was no significant difference in the incidence of exogenous pneumonia per 1,000 days of mechanical ventilation (1.71 vs 1.25). There was no difference in the distribution of microorganisms causing pneumonia. CONCLUSIONS: Circuit change using an HME for humidification does not decrease pneumonia and represents an unnecessary cost.

Costs and Cost Analysis↗

PubMed2003

A molecular modeling study of inhibitors of nuclear factor kappa-B (p50)--DNA binding.

Nuclear Factor-kappa B (NF-kappaB) is an inducible transcription factor of the Rel family, and is sequestered in the cytoplasm by the IkappaB family of proteins. NF-kappaB can exist in several dimeric forms, but the p50/p65 heterodimer is the predominant one. Activation of NF-kappaB by a range of stimuli including viral products, and oxidative stress, leads to phosphorylation and proteasome dependent degradation of IkappaB, leading to the release of free NF-kappaB. This free NF-kappaB then binds to its target sites (KB sites in the DNA) to initiate transcription. These kappaB sites are also present in the Long Terminal Repeat (LTR) of HIV-1, and hence NF-kappaB (p50 subunit) binding to LTR-DNA is critical in viral replication. Targeting direct p50-DNA binding, in this regard, is a novel approach to design anti-HIV gene expression inhibitors, which do not have the problem of resistance unlike in other anti-HIV strategies. The present study is a part of our search for leads for the specific inhibition of p50-DNA binding. We have been experimentally studying different types of these inhibitors, and in this work, we attempted to get a common definition of their structural mechanism onto p50-DNA binding. Using three different classes of inhibitors, we modelled their association with the DNA-Binding Region (DBR) of the p50 subunit of NF-kappaB. Docking studies were carried out using a genetic algorithm based program (GOLD). Further, to compare electrostatic complementarity in the association of the inhibitors with the DBR, Molecular Electrostatic Potentials (MEPs) were generated for the DBR and each inhibitor. The results of docking revealed a strong network of hydrogen bonding interactions for every active inhibitor, and the contrary for the less active ones. Further, the MEPs revealed that the DBR of p50 represents a surface of electropositive potential, and the active inhibitors represent a complementary electronegative surface. With the present modelling study we conclude that the principal properties to be possessed by the new leads against p50-DNA binding should be that of having the ability to make a strong network of hydrogen bonds with the DBR of p50, and preferably, having electronegative potentials in their peripheral surface.

Computer Simulation↗