Replication-deficient adenovirus vectors are efficient vehicles for delivering therapeutic genes into mammalian cells. However, the high doses required to produce effective gene transfer in vivo can also cause unwanted cellular toxicity. To improve replication-deficient adenovirus transgene expression while minimizing adverse reactions, we have tested polycationic compounds for their ability to enhance adenovirus adsorption. We demonstrate increased transgene expression after mixing adenovirus preparations with polycations, cationic lipids, and CaCl2 prior to transduction in vitro. An E1-deleted adenovirus vector was admixed with various polycations, and beta-galactosidase (beta-gal) activity was evaluated. The optimal polycation concentrations for augmenting adenovirus-mediated gene transfer were 5-10 microg/mL polybrene, 400 microg/mL protamine sulfate, 10 microg/mL N-(1-[2,3-dioleoyloxy]propyl)-N,N,N-trimethylammonium methylsulfate (DOTAP), 2.5 microg/mL Lipofectamine, and 62.5 mM CaCl2. Polycations enhanced beta-gal expression in three of six established cell lines. Similar results were obtained using primary tumor cell cultures, where beta-gal expression was increased 1.5- to 10.7-fold (mean = 3.6) by polybrene, 1.8- to 7.5-fold (mean = 3.4) by DOTAP, and 2.3- to 10.4-fold (mean = 4.8) by protamine sulfate. Adenovirus transduction efficiency in two primary leukemia isolates was improved by 3- and 4.5-fold. We were unable to demonstrate any benefit when adenovirus was admixed with protamine sulfate prior to intratumoral injection in a xenogeneic severe combined immunodeficient mouse melanoma tumor model. Further studies will determine whether polycations can improve intratumoral gene transfer.

Adenoviridae↗

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Evidence-based nursing practice: a call to action for nursing informatics.

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Evidence-Based Medicine↗

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Flexible monitoring in the management of patient care processes: a pilot study.

This article describes a study conducted on the internal medicine, general surgical, and vascular wards of a large metropolitan hospital to assess the impact of a networked monitoring system and portable patient monitors. This pilot study was developed to address the need of hospital patients who require continuous noninvasive vital signs monitoring (including heart rate, noninvasive blood pressure, pulse oximetry, cardiac waveform monitoring) with the addition of surveillance from a cardiac intensive care area. Data were collected from 114 patients over a 3-month period to identify a patient group that could be managed appropriately under the new system and to determine the effect that flexible monitoring had on patient care management. Findings include identification of a specific patient group that can be managed successfully outside the cardiac intensive care area using this system. Other findings suggest a way to improve the management of patient monitoring in the general ward areas.

Aged↗