Role of EUS Gan, S. Ian, MD; Rajan, Elizabeth, MD; Adler, Douglas G., MD ...
Gastrointestinal endoscopy,
09/2007, Letnik:
66, Številka:
3
Journal Article
Patients with end-stage heart failure are at high risk for sudden cardiac death. However, implantable cardioverter-defibrillator (ICD) is not routinely implanted given the high competing risk of pump ...failure. A unique population worth separate consideration are patients with end-stage heart failure awaiting heart transplantation, as prolonged survival improves the chances of receiving transplant.
To compare clinical outcomes of heart failure patients with and without an ICD awaiting heart transplant.
We performed an extensive literature search and systematic review of studies that compared end-stage heart failure patients with and without an ICD awaiting heart transplantation. We separately assessed the rates of total mortality, sudden cardiac death, nonsudden cardiac death, and heart transplantation. Risk ratio (RR) and 95% confidence intervals were measured using the Mantel-Haenszel method. The random effects model was used owing to heterogeneity across study cohorts.
Ten studies with a total of 36,112 patients were included. A total of 62.5% of patients had an ICD implanted. Patients with an ICD had decreased total mortality (RR 0.60, 95% CI 0.51–0.71, P < .00001) and sudden cardiac death (RR 0.27, 95% CI 0.11–0.66, P = .004) and increased rates of heart transplantation (RR 1.09, 95% CI 1.05–1.14, P < .0001). There was no difference in prevalence of nonsudden cardiac death (RR 0.68, 95% CI 0.44–1.04, P = .07).
ICD implantation is associated with improved outcomes in patients awaiting heart transplant, characterized by decreased total mortality and sudden cardiac death as well as higher rates of heart transplantation.
Role of endoscopy in the management of GERD Lichtenstein, David R., MD; Cash, Brooks D., MD; Davila, Raquel, MD ...
Gastrointestinal endoscopy,
08/2007, Letnik:
66, Številka:
2
Journal Article
Endoscopic electronic medical record systems Conway, Jason D., MD; Adler, Douglas G., MD; Diehl, David L., MD ...
Gastrointestinal endoscopy,
2008, Letnik:
67, Številka:
4
Journal Article
Cytosolic phospholipase A2alpha (cPLA2alpha) hydrolyzes arachidonic acid from cellular membrane phospholipids, thereby providing enzymatic substrates for the synthesis of eicosanoids, such as ...prostaglandins and leukotrienes. Considerable understanding of cPLA2alpha function has been derived from investigations of the enzyme and from cPLA2alpha-null mice, but knowledge of discrete roles for this enzyme in humans is limited. We investigated a patient hypothesized to have an inherited prostanoid biosynthesis deficiency due to his multiple, complicated small intestinal ulcers despite no use of cyclooxygenase inhibitors. Levels of thromboxane B2 and 12-hydroxyeicosatetraenoic acid produced by platelets and leukotriene B4 released from calcium ionophore-activated blood were markedly reduced, indicating defective enzymatic release of the arachidonic acid substrate for the corresponding cyclooxygenase and lipoxygenases. Platelet aggregation and degranulation induced by adenosine diphosphate or collagen were diminished but were normal in response to arachidonic acid. Two heterozygous single base pair mutations and a known SNP were found in the coding regions of the patient's cPLA2alpha genes (p.Ser111Pro+Arg485His; Lys651Arg). The total PLA2 activity in sonicated platelets was diminished, and the urinary metabolites of prostacyclin, prostaglandin E2, prostaglandin D2, and thromboxane A2 were also reduced. These findings characterize what we believe is a novel inherited deficiency of cPLA2.
Cytosolic phospholipase A.sub.2α (cPLA.sub.2α) hydrolyzes arachidonic acid from cellular membrane phospholipids, thereby providing enzymatic substrates for the synthesis of eicosanoids, such as ...prostaglandins and leukotrienes. Considerable understanding of cPLA.sub.2α function has been derived from investigations of the enzyme and from cPLA.sub.2α-null mice, but knowledge of discrete roles for this enzyme in humans is limited. We investigated a patient hypothesized to have an inherited prostanoid biosynthesis deficiency due to his multiple, complicated small intestinal ulcers despite no use of cyclooxygenase inhibitors. Levels of thromboxane B.sub.2 and 12-hydroxyeicosatetraenoic acid produced by platelets and leukotriene B.sub.4 released from calcium ionophore--activated blood were markedly reduced, indicating defective enzymatic release of the arachidonic acid substrate for the corresponding cyclooxygenase and lipoxygenases. Platelet aggregation and degranulation induced by adenosine diphosphate or collagen were diminished but were normal in response to arachidonic acid. Two heterozygous single base pair mutations and a known SNP were found in the coding regions of the patient's cPLA.sub.2α genes (p.Ser111Pro+Arg485His; Lys651Arg). The total PLA.sub.2 activity in sonicated platelets was diminished, and the urinary metabolites of prostacyclin, prostaglandin E.sub.2, prostaglandin D.sub.2, and thromboxane A.sub.2 were also reduced. These findings characterize what we believe is a novel inherited deficiency of cPLA.sub.2.
Mitochondrial quality control is critical for cardiac homeostasis as these organelles are responsible for generating most of the energy needed to sustain contraction. Dysfunctional mitochondria are ...normally degraded via intracellular degradation pathways that converge on the lysosome. Here, we identified an alternative mechanism to eliminate mitochondria when lysosomal function is compromised. We show that lysosomal inhibition leads to increased secretion of mitochondria in large extracellular vesicles (EVs). The EVs are produced in multivesicular bodies, and their release is independent of autophagy. Deletion of the small GTPase Rab7 in cells or adult mouse heart leads to increased secretion of EVs containing ubiquitinated cargos, including intact mitochondria. The secreted EVs are captured by macrophages without activating inflammation. Hearts from aged mice or Danon disease patients have increased levels of secreted EVs containing mitochondria indicating activation of vesicular release during cardiac pathophysiology. Overall, these findings establish that mitochondria are eliminated in large EVs through the endosomal pathway when lysosomal degradation is inhibited.
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