p53 promotes adenoviral replication and increases late viral gene expression.

The tumor suppressor protein, p53, plays a critical role in viro-oncology. However, the role of p53 in adenoviral replication is still poorly understood. In this paper, we have explored further the effect of p53 on adenoviral replicative lysis. Using well-characterized cells expressing a functional p53 (A549, K1neo, RKO) and isogenic derivatives that do not (K1scx, RKOp53.13), we show that virus replication, late virus protein expression and both wtAd5 and ONYX-015 virus-induced cell death are impaired in cells deficient in functional p53. Conversely, by transfecting p53 into these and other cells (IIICF/c, HeLa), we increase late virus protein expression and virus yield. We also show, using reporter assays in IIICF/c, HeLa and K1scx cells, that p53 can cooperate with E1a to enhance transcription from the major late promoter of the virus. Late viral protein production is enhanced by exogenous p53. Taken together, our data suggest that functional p53 can promote the adenovirus (Ad) lytic cycle. These results have implications for the use of Ad mutants that are defective in p53 degradation, such as ONYX-015, as agents for the treatment of cancers.

Profound hypoxemia resulting from shunting across an inadvertent atrial septal tear after left ventricular assist device placement.

UNLABELLED: Defects within the interatrial septum (IAS) can be a source of significant right-to-left shunting and hypoxemia, particularly after placement of a left ventricular assist device (LVAD). We report a case of LVAD placement in which an unrecognized IAS tear occurred intraoperatively, leading to profound arterial desaturation. Transesophageal echocardiography (TEE) was instrumental in making the diagnosis. Certain intraoperative events increased the pressure gradient between the right and left atria, aggravating hypoxemia. We recommend that patients undergoing LVAD placement be screened intraoperatively with TEE for unrecognized IAS defects. Re-examination of the IAS should occur on weaning from cardiopulmonary bypass. IMPLICATIONS: A traumatic atrial septal defect after atrial cannulation caused a right-to-left intracardiac shunt on initiation of left ventricular assist device support that was further aggravated by chest closure and pleural suction, culminating in severe hypoxemia.

Induction of cell death by adenoviruses.

Adenoviruses have proved to be excellent tools for gaining insight into the regulation, and deregulation, of the mammalian cell cycle. With the widespread clinical use of gene therapy fast approaching, there comes a need for a better understanding of how the cell death process is regulated. A greater understanding will allow the development of therapeutic approaches that both maximise transgene expression while minimising cytotoxicity to the target cell. Consequently, much adenovirus research has centered on understanding the mechanisms governing adenovirus induced cell death or apoptosis. This review discusses recent advances in the field of adenovirus cell death regulation and evaluates the roles of implicated gene products and their respective data. The data suggest the existence of multiple virus gene products involved in cell death regulation and point towards several distinct, yet related, cell death pathways. A discussion of the shortcomings of current adenoviral research, along with a proposed model based upon the data is also given.

Unrecognized esophageal perforation in a neonate during transesophageal echocardiography.

Esophageal perforation caused by transesophageal echocardiography in an infant is believed to be extremely rare. If unrecognized, serious morbidity can result. We report a case of pharyngeal perforation in a neonate undergoing an interrupted aortic arch repair.

The adequacy of basic intraoperative transesophageal echocardiography performed by experienced anesthesiologists.

UNLABELLED: Transesophageal echocardiography (TEE) may improve intraoperative decision-making and patient outcome if it is performed and interpreted correctly. After revising our TEE examination to fulfill the published guidelines for basic TEE practitioners, we prospectively evaluated the ability of our cardiac anesthesiologists (all very experienced with TEE) to record and interpret this revised examination. Educational aids and regular TEE performance feedback were provided to the anesthesiologists. Their interpretations were compared with the independently determined results of experts. Compared with their own historical controls (42% recording rate), all anesthesiologists showed significant improvement in their ability to record a basic intraoperative TEE examination resulting in 81% (P < 0.0001) of all required images being recorded: 88% before cardiopulmonary bypass, 77% immediately after bypass, and 64% after chest closure. Seventy-nine percent of the images recorded at baseline were correctly interpreted, 6% were incorrectly interpreted, and 15% were not evaluated. Our attempt to assess compliance with published guidelines for basic intraoperative TEE resulted in a marked improvement in our intraoperative TEE practice. Most, but not all, standard cross-sections are recorded or interpreted correctly, even by highly experienced and motivated practitioners. IMPLICATIONS: Experienced cardiac anesthesiologists can obtain and correctly interpret most basic intraoperative transesophageal echocardiograms.

The safety and efficacy of sevoflurane anesthesia in infants and children with congenital heart disease.

UNLABELLED: We tested the hypothesis that sevoflurane is a safer and more effective anesthetic than halothane during the induction and maintenance of anesthesia for infants and children with congenital heart disease undergoing cardiac surgery. With a background of fentanyl (5 microg/kg bolus, then 5 microg. kg(-1). h(-1)), the two inhaled anesthetics were directly compared in a randomized, double-blinded, open-label study involving 180 infants and children. Primary outcome variables included severe hypotension, bradycardia, and oxygen desaturation, defined as a 30% decrease in the resting mean arterial blood pressure or heart rate, or a 20% decrease in the resting arterial oxygen saturation, for at least 30 s. There were no differences in the incidence of these variables; however, patients receiving halothane experienced twice as many episodes of severe hypotension as those who received sevoflurane (P = 0.03). These recurrences of hypotension occurred despite an increased incidence of vasopressor use in the halothane-treated patients than in the sevoflurane-treated patients. Multivariate stepwise logistic regression demonstrated that patients less than 1 yr old were at increased risk for hypotension compared with older children (P = 0.0004), and patients with preoperative cyanosis were at increased risk for developing severe desaturation (P = 0.049). Sevoflurane may have hemodynamic advantages over halothane in infants and children with congenital heart disease. IMPLICATIONS: In infants and children with congenital heart disease, anesthesia with sevoflurane may result in fewer episodes of severe hypotension and less emergent drug use than anesthesia with halothane.

The effects of inhaled nitric oxide on postoperative pulmonary hypertension in infants and children undergoing surgical repair of congenital heart disease.

UNLABELLED: The role of inhaled nitric oxide in the immediate post-bypass period after surgical repair of congenital heart disease is uncertain. In a controlled, randomized, double-blind study, we tested the hypothesis that inhaled nitric oxide (NO) would reduce pulmonary hypertension immediately after surgical repair of congenital heart disease in 40 patients with preoperative evidence of pulmonary hypertension (mean pulmonary arterial pressure [MPAP] exceeding 50% of mean systemic arterial pressure [MSAP]). Patients were then followed in the intensive care unit (ICU) to document the incidence of severe pulmonary hypertension. Of the patients, 36% (n = 13) emerged from bypass with MPAP > 50% MSAP. In these patients, inhaled NO reduced MPAP by 19% (P = 0.008) versus an increase of 9% in the placebo group. No effect on MPAP was observed in patients emerging from bypass without pulmonary hypertension (n = 23). Inhaled NO was required five times in the ICU, always in the patients who had emerged from cardiopulmonary bypass with pulmonary hypertension (5 of 13 [38%] versus 0 of 23). We conclude that, in infants and children undergoing congenital heart surgery, inhaled NO selectively reduces MPAP in patients who emerge from cardiopulmonary bypass with pulmonary hypertension and has no effect on those who emerge without it. IMPLICATIONS: In a randomized double-blind study, inhaled nitric oxide selectively reduced pulmonary artery pressures in pediatric patients who developed pulmonary hypertension (high blood pressure in the lungs) immediately after cardiopulmonary bypass and surgical repair.