Biomedical subjects

Phillip Factor

Publications and source records attributed to Phillip Factor.

25 records · Page 2Linked to original sources

PubMed2002

Comparison of surfactant and perfluorochemical liquid enhanced adenovirus-mediated gene transfer in normal rat lung.

Both surfactant- and perfluorochemical (PFC)-based vehicles enhance adenovirus-mediated gene transfer in the lung. To compare the relative effects of surfactant and PFC liquid, we infected orotracheally intubated Sprague-Dawley rats with 4 x 10(9) pfu of an E1a(-)/E3(-) adenovirus expressing either an Escherichia coli lacZ (AdlacZ) mini-gene or no cDNA (Adnull). Surfactant-mediated delivery was achieved via instillation of four, 200-microl aliquots of virus suspended in a 50% surfactant (Survanta) vehicle over a 15-minute period. PFC rats received virus in 100 microl of saline followed by instillation of the PFC liquid FC-75 (10 cc/kg body weight) over a 2- to 3- minute period. Lungs were collected 3 days later for measurement of beta-galactosidase (beta-gal) expression and indices of inflammation. Both PFC liquid and surfactant-based vehicles produced widespread beta-gal expression and increased total beta-gal activity over that observed with instillation of vector alone. Both vehicles comparably increased bronchoalveolar lavage fluid (BALF), total cell counts, neutrophils, total protein, and IFN(gamma). FC-75 was also associated with increased BALF IL1beta. In conclusion, surfactant and FC-75 are similarly effective vehicles for adenovirus-mediated gene transfer to the lung.

Adenoviridae↗

PubMed2002

Effects of beta2-adrenergic receptor overexpression on alveolar epithelial active transport.

beta-Adrenergic receptor (betaAR) agonists accelerate the clearance of edema from the alveolar airspace by increasing the function of epithelial transport proteins, including epithelial Na(+) channels and Na,K-adenosinetriphosphatases. To improve our understanding of the role of the beta(2)AR in regulating alveolar fluid clearance, we used an adenoviral-mediated gene transfer strategy to effect significant increases in membrane-bound beta(2)AR number and function in the alveolar epithelium of normal rats. Alveolar fluid clearance in beta(2)AR-overexpressing lungs, measured by means of an isolated lung model in the absence of catecholamine supplementation, was 100% greater than in controls. These findings were associated with significant increases of epithelial Na(+) channel function and Na,K-adenosine triphosphatase function in the peripheral lung. Experiments performed with adrenalectomized rats, a beta(2)-agonist (procaterol), and a nonspecific beta-antagonist (propranolol) indicate that overexpression maximally up-regulates beta(2)-adrenergic-responsive alveolar fluid clearance and improves responsiveness to endogenous catecholamines. Mechanistic studies in human lung epithelial cells (A549) indicate that receptor overexpression prevents homologous receptor desensitization, possibly by overwhelming endogenous regulatory pathways. Our studies demonstrate that overexpression of beta(2)AR in lung epithelial cells can be used to study the role and regulation of alveolar beta(2)ARs. They also suggest a therapeutic role for the beta(2)AR in the treatment of pulmonary edema.

Animals↗

PubMed2002

Severe status asthmaticus: management with permissive hypercapnia and inhalation anesthesia.

OBJECTIVE: To describe the difficulties that can be encountered during mechanical ventilation of severe status asthmaticus and to discuss the safety of permissive hypercapnia as a ventilatory strategy and the role and limitations of inhalation anesthesia in the treatment of refractory cases. DESIGN: Case series and review of literature. SETTING: Intensive care unit of a tertiary care hospital. PATIENTS: Two patients with severe status asthmaticus. INTERVENTIONS: Administration of inhalational anesthetics. MEASUREMENTS AND MAIN RESULTS: Both patients had respiratory failure secondary to status asthmaticus requiring mechanical ventilation and permissive hypercapnia. They also received inhalational anesthetics because of refractory bronchoconstriction. Levels of PaCO(2) in each case were among the highest and most prolonged elevations (>150 mm Hg for several hours) reported to date. In one case, life-threatening difficulties with ventilation were encountered related to the use of an anesthesia ventilator. Although they had complications related to the severity of their illnesses, both were treated to recovery. CONCLUSIONS: Mechanical ventilation in severe status asthmaticus can be challenging. Permissive hypercapnia is a relatively safe strategy in the ventilatory management of asthma. High levels of hypercapnia and associated severe acidosis are well tolerated in the absence of contraindications (i.e., preexisting intracranial hypertension). Inhalation anesthesia may be useful in the treatment of refractory cases of asthma but should be used carefully because it may be hazardous owing to poor flow capabilities of most anesthesia ventilators.

Adult↗

PubMed2002