OBJECTIVES The purpose of this study was to understand the reason for variation in the sensitivity of different methods of detecting right-to-left shunts (RLS). BACKGROUND Patent foramen ovale (PFO) is implicated in the pathogenesis of cryptogenic stroke, decompression illness, and migraine headaches. Intravenous agitated saline injections with tomographic imaging (transthoracic, transesophageal, and intracardiac echocardiography) has been used for detecting intracardiac shunts. Some patients with a high clinical suspicion of PFO have inconclusive echocardiographic study results. Transcranial Doppler (TCD) is an alternative method for detecting RLS that is not dependent on tomographic imaging. METHODS Thirty-eight consecutive patients who were undergoing PFO closure had simultaneous transcranial Doppler and intracardiac echocardiography performed. Agitated saline injections were performed at rest, with Valsalva maneuver, and with forced expiration into a manometer to 40 mm Hg before and after closure, as well as 3 or more months after closure. Right atrial pressures were measured in the periprocedural period, and RLS were graded according to standard methods during these maneuvers. RESULTS Right atrial pressures were significantly higher with Valsalva maneuver compared with rest (before closure 21.6 ± 11.9 mm Hg vs. 6.6 ± 2.6 mm Hg, p < 0.001; after closure 28.4 ± 13.9 mm Hg vs. 6.8 ± 2.6 mm Hg, p < 0.001) and with manometer compared with Valsalva maneuver (before closure 38.7 ± 6.6 mm Hg vs. 21.6 ± 11.9 mm Hg, p < 0.001; after closure 44.0 ± 9.5 mm Hg vs. 28.4 ± 13.9 mm Hg, p < 0.001). Intracardiac echocardiography underestimated shunting in 34% of patients with Valsalva maneuver or manometer after closure compared with TCD. CONCLUSIONS Transcranial Doppler with immediate feedback provided by forced expiration against a manometer to 40 mm Hg is more sensitive than echocardiographic imaging for the detection of RLS. These observations have significant implications for determining the incidence of RLS in patients with stroke or migraine.

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Percutaneous coronary intervention (PCI) has traditionally not been an option for patients with end-stage liver disease (ESLD) and coronary artery disease (CAD). This retrospective study was designed to demonstrate the feasibility and safety of PCI in liver transplant candidates. Patients with ESLD and hemodynamically significant CAD who were otherwise deemed to be acceptable candidates for liver transplantation underwent PCI. The procedural success rates, mortality and myocardial infarction rates, and bleeding outcomes were examined. Sixteen patients with ESLD underwent PCI: 15 with bare-metal stents (1.3 stents per patient on average) and 1 with balloon angioplasty alone. The median diameter stenosis per lesion was 80%, the median platelet count was 68 Â 10 9 /L, the median international normalized ratio was 1.3, and the median Model for End-Stage Liver Disease score was 13. PCI was successful in 94% of the patients. One patient had a suboptimal residual stenosis of 50% after stenting. There were no in-hospital or 30-day deaths or myocardial infarctions, and no patients developed hematomas. One patient required a 1-U platelet transfusion, and another required 1 U of packed red blood cells. All patients remained clinically stable 1 month after PCI. Nine of the 16 patients were listed for liver transplantation, and 3 patients underwent liver transplantation. In conclusion, we have demonstrated the safety and feasibility of PCI in a small cohort of patients with ESLD and hemodynamically significant CAD, the majority of whom had significant thrombocytopenia. Larger studies are required to determine whether PCI is an effective treatment strategy for patients with ESLD and hemodynamically significant CAD who otherwise would not be candidates for liver transplantation. End-stage liver disease (ESLD) is associated with increased cardiovascular risk. 1 Although the prevalence of coronary artery disease (CAD) was previously thought to be lower in patients with ESLD versus the general population, multiple studies have demonstrated an increased prevalence of CAD in this subset of patients. [2][3][4][5][6] The overall prevalence of CAD in patients with ESLD has been reported to be 20% to 28%, with the highest prevalence being reported in patients over the age of 50 years. 2,6,7 The ideal management strategy for liver transplant candidates with CAD remains unknown. The 3-year mortality rate of patients with CAD undergoing orthotopic liver transplantation (OLT) has been reported to be 26% to 50% whether medical management or surgical revascularization is pursued. 8,9 Coronary artery bypass grafting before OLT can accelerate or exacerbate liver failure 10 and has been associated with increased morbidity and mortality. 11 Percutaneous coronary intervention (PCI) with stenting has Abbreviations: CAD, coronary artery disease; ESLD, end-stage liver disease; INR, international normalized ratio; MELD, Model for End-Stage Liver Disease; OLT, orthotopic liver transplantation; PCI, percutaneous coronary intervention; PTCA, percutaneou...

Bcl-2-related proteins (i.e. Bcl-2 and Bax) regulate the effector stage of apoptosis and can modulate the entry of quiescent cells into the cell cycle. Phosphorylation of Bcl-2 is presumed to modify its apoptosis-inhibitory function. By utilizing an interleukin-3 (IL-3)-dependent hematopoietic cell line, we examined the structural requirements of Bcl-2 phosphorylation and the correlation of this post-translational modification with its function. In the presence of IL-3, constitutively expressed Bcl-2 was phosphorylated on serine residue(s), and phosphorylated Bcl-2 lost its capacity to heterodimerize with Bax. Whereas the majority of Bcl-2 resided in mitochondria, phosphorylation only affected a minor pool of total Bcl-2 that selectively partitioned into a soluble fraction. Cytosolic targeting of Bcl-2 greatly increased its ratio of phosphorylation. Bcl-2 phosphorylation was reduced during IL-3 deprivation, and its phosphorylation was also delayed after transient cytokine deprivation. This pattern of phosphorylation temporally correlated with the accelerated exit and delayed reentry of Bcl-2-expressing cells into the cell cycle upon transient IL-3 deprivation and subsequent cytokine restimulation. Thus, IL-3-induced phosphorylation of a distinct pool of Bcl-2 may contribute to the inactivation of its antiproliferative function.

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