New Methods of Reconstruction for Old Challenges: The Use of the Integra Graft in Necrotizing Soft Tissue Infections of the Male Genitalia.

In this paper, we describe two cases of Fournier's gangrene (FG) in which Integra grafting was used for reconstruction. FG is a progressive necrotizing infection occurring in the perineal region and on the external genitalia. Reconstructive options using local tissue are limited due to the destruction this infection imposes on the soft tissue.

Parathyroid surgery in renal failure patients.

The treatment of hyperparathyroidism secondary to renal failure is a complex clinical dilemma. No simple optimal approach to patient selection and stratification for surgical intervention is available at this time. The goals of this publication are to review the pathophysiology of parathyroid gland function in patients with impaired renal function, make recommendations for how to proceed with a parathyroidectomy in these patients, and to provide some guidelines for preoperative and postoperative management.

Overexpression of the Na-K-ATPase alpha2-subunit improves lung liquid clearance during ventilation-induced lung injury.

Mechanical ventilation with high tidal volumes (HV(T)) impairs lung liquid clearance (LLC) and downregulates alveolar epithelial Na-K-ATPase. We have previously reported that the Na-K-ATPase alpha(2)-subunit contributes to LLC in normal rat lungs. Here we tested whether overexpression of Na-K-ATPase alpha(2)-subunit in the alveolar epithelium would increase clearance in a HV(T) model of lung injury.

High CO2 levels impair alveolar epithelial function independently of pH.

Background: In patients with acute respiratory failure, gas exchange is impaired due to the accumulation of fluid in the lung airspaces. This life-threatening syndrome is treated with mechanical ventilation, which is adjusted to maintain gas exchange, but can be associated with the accumulation of carbon dioxide in the lung. Carbon dioxide (CO2) is a by-product of cellular energy utilization and its elimination is affected via alveolar epithelial cells.

Interdependency of beta-adrenergic receptors and CFTR in regulation of alveolar active Na+ transport.

Beta-adrenergic receptors (betaAR) regulate active Na+ transport in the alveolar epithelium and accelerate clearance of excess airspace fluid. Accumulating data indicates that the cystic fibrosis transmembrane conductance regulator (CFTR) is important for upregulation of the active ion transport that is needed to maintain alveolar fluid homeostasis during pulmonary edema. We hypothesized that betaAR regulation of alveolar active transport may be mediated via a CFTR dependent pathway.

Hypocapnic but not metabolic alkalosis impairs alveolar fluid reabsorption.

Acid-base disturbances, such as metabolic or respiratory alkalosis, are relatively common in critically ill patients. We examined the effects of alkalosis (hypocapnic or metabolic alkalosis) on alveolar fluid reabsorption in the isolated and continuously perfused rat lung model. We found that alveolar fluid reabsorption after 1 hour was impaired by low levels of CO2 partial pressure (PCO2; 10 and 20 mm Hg) independent of pH levels (7.

Upregulation of alveolar epithelial active Na+ transport is dependent on beta2-adrenergic receptor signaling.

Alveolar epithelial beta-adrenergic receptor (betaAR) activation accelerates active Na+ transport in lung epithelial cells in vitro and speeds alveolar edema resolution in human lung tissue and normal and injured animal lungs. Whether these receptors are essential for alveolar fluid clearance (AFC) or if other mechanisms are sufficient to regulate active transport is unknown. In this study, we report that mice with no beta1- or beta2-adrenergic receptors (beta1AR-/-/beta2AR-/-) have reduced distal lung Na,K-ATPase function and diminished basal and amiloride-sensitive AFC.

Augmentation of endogenous dopamine production increases lung liquid clearance.

We have previously reported that dopamine increased active Na+ transport in rat lungs by upregulating the alveolar epithelial Na,K-ATPase. Here we tested whether alveolar epithelial cells produce dopamine and whether increasing endogenous dopamine production by feeding rats a 4% tyrosine diet (TSD) would increase lung liquid clearance. Alveolar Type II cells express the enzyme aromatic-L-amino acid decarboxylase (AADC) and, when incubated with the dopamine precursor, 3-hydroxy-L-tyrosine (L-dopa), produce dopamine.

Na,K-ATPase gene transfer increases liquid clearance during ventilation-induced lung injury.

Mechanical ventilation with high tidal volumes (HVT) downregulates alveolar Na,K-ATPase function and impairs lung liquid clearance. We hypothesized that overexpression of Na,K-ATPase in the alveolar epithelium could counterbalance these changes and increase clearance in a rat model of mild ventilation-induced lung injury. We used a surfactant-based system to deliver 4 x 10(9) plaque-forming units of E1a-/E3- recombinant adenovirus containing either a rat beta1 Na,K-ATPase subunit cDNA (adbeta1) or no cDNA (adnull) to rat lungs 7 days before ventilation with a VT of approximately 40 ml/kg (peak airway pressure of less than 35 cm H2O) for 40 minutes.

In vivo timing of onset of transgene expression following adenoviral-mediated gene transfer.

Recombinant adenoviruses are efficient gene transfer vehicles that could be used for treatment of acute diseases. However, the time required for adenoviruses to produce physiologically relevant levels of transgene in vivo is unknown. To address this question rat lungs were infected with an E1a(-)/E3a(-) adenovirus that contains an hCMV-driven human beta(2)-adrenergic receptor (beta(2)AR) cDNA.

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.

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.

Acute hyperoxic lung injury does not impede adenoviral-mediated alveolar gene transfer.

The transfer of protective genes to the alveolar epithelium can attenuate lung injury if accomplished before its onset. The pathobiology of acute lung injury (ALI) includes formidable hurdles to gene transfer, including alveoli filled with fluid, inflammatory cells, and cytokines, all of which may impair gene transfer after the onset of injury. We tested the hypothesis that adenovectors could efficiently transduce injured alveoli by exposing adult, male Sprague-Dawley rats to 100% oxygen for 48 or 60 h before endotracheal instillation of either 1 x 10(9) or 4 x 10(9) plaque-forming units of an adenovirus that expresses an Escherichia coli lac Z gene (adbeta-gal) in a surfactant-based vehicle (Survanta).

Na,K-ATPase overexpression improves alveolar fluid clearance in a rat model of elevated left atrial pressure.

Background: Acute elevation of left atrial pressure (LAP) increases extravascular water and impairs active Na(+) transport in rat lungs. We have reported that overexpression of Na,K-ATPase subunit genes in the alveolar epithelium increases alveolar fluid clearance (AFC) in normal and injured rat lungs with normal LAP. We reasoned that adenovirus-mediated transfer of an Na,K-ATPase beta-subunit gene to the alveolar epithelium could improve AFC in rat lungs in the presence of acutely elevated LAP.