Use of echocardiography for predicting myocardial viability in patients with reperfused anterior wall myocardial infarction

Dobutamine stress echocardiography (DSE), myocardial contrast echocardiography (MCE), and ultrasonic tissue characterization with integrated backscatter are useful methods for assessing myocardial viability in acute myocardial infarction. In this study, we compared the potential of 3 methods for predicting myocardial viability in 38 patients with reperfused anterior wall acute myocardial infarction. We performed MCE shortly after coronary reperfusion with an intracoronary injection of microbubbles. We recorded 2-dimensional integrated backscatter images at rest and, then, performed low-dose (10 microg/kg/min) DSE 3 days later. In integrated backscatter images, we placed the region of interest in the midwall of the myocardial segment to reconstruct the cyclic variation of myocardial integrated backscatter. The myocardial segment was judged viable when it showed active contraction 3 months later. Among 74 segments analyzed, 34 were judged viable. Presence of contractile response during DSE predicted segmental viability with 91% sensitivity and 78% specificity. Intense and homogenous contrast enhancement with MCE predicted viability with 82% sensitivity and 73% specificity. The presence of synchronous contraction of cyclic variation predicted myocardial viability with 79% sensitivity and 83% specificity. There were no differences in sensitivity and specificity among the 3 methods. Thus, MCE and ultrasonic tissue characterization can predict myocardial viability as accurately as DSE in patients with acute myocardial infarction. The logistics of the methods may determine clinical application.     

The effect of heparin on tissue factor and tissue factor pathway inhibitor in patients with acute myocardial infarction

We examined plasma TF and free TFPI levels in 26 consecutive patients with AMI, 26 patients with stable exertional angina, and 25 patients with chest pain syndrome. In patients with AMI, blood samples were obtained immediately after admission and at 4, 8, 16, 24, and 48 h, and the third, fifth, seventh, and fourteenth day after initiation of reperfusion therapy. Plasma TF levels in patients with AMI on admission were significantly higher than in the chest pain syndrome and stable exertional angina groups (248.0+/-117. 4 vs. 179.5+/-29.2 vs. 189.5+/-29.6 pg/ml, P<0.01). In patients with AMI, the level subsequently decreased after heparin administration and was maintained at significantly lower levels compared to those on admission. Plasma free TFPI levels in patients with AMI on admission were significantly higher than in the chest pain syndrome and stable exertional angina groups [33.5+/-12.4 vs. 26.0+/-7.6 ng/ml (P<0.01) vs. 27.5+/-6.3 ng/ml, P<0.05]. In patients with AMI, it reached the maximum level at 4 h after the administration of heparin, and gradually decreased over the time course. These data indicated that continuous administration of a low dose of heparin was effective in decreasing TF levels without affecting TFPI levels. Our results elucidate one of the mechanisms by which the administration of heparin is beneficial in AMI patients undergoing percutaneous revascularization.     

Role of Dok-1 and Dok-2 in myeloid homeostasis and suppression of leukemia

Dok-1 and Dok-2 are closely related rasGAP-associated docking proteins expressed preferentially in hematopoietic cells. Although they are phosphorylated upon activation of many protein tyrosine kinases (PTKs), including those coupled with cytokine receptors and oncogenic PTKs like Bcr-Abl, their physiological roles are largely unidentified. Here, we generated mice lacking Dok-1 and/or Dok-2, which included the double-deficient mice succumbed to myeloproliferative disease resembling human chronic myelogenous leukemia (CML) and chronic myelomonocytic leukemia. The double-deficient mice displayed medullary and extramedullary hyperplasia of granulocyte/macrophage progenitors with leukemic potential, and their myeloid cells showed hyperproliferation and hypo-apoptosis upon treatment and deprivation of cytokines, respectively. Consistently, the mutant myeloid cells showed enhanced Erk and Akt activation upon cytokine stimulation. Moreover, loss of Dok-1 and/or Dok-2 induced blastic transformation of chronic phase CML-like disease in mice carrying the bcr-abl gene, a cause of CML. These findings demonstrate that Dok-1 and Dok-2 are key negative regulators of cytokine responses and are essential for myeloid homeostasis and suppression of leukemia.     

IDENTIFICATION OF A UNIVERSAL B CELL EPITOPE ON DNA TOPOISOMERASE I,AN AUTOANTIGEN ASSOCIATED WITH SCLERODERMA

Objective. To investigate the distribution of B cell autoepitopes of human DNA topoisomerase I (topo I), an autoantigen associated with scleroderma. Methods. A complementary DNA clone, T1B, was used to produce recombinant proteins of topo I as β-galactosidase fusion proteins. Immunoreactivity to these fusion proteins was then tested in 35 anti–topo I–positive sera from patients with scleroderma, by immunoblotting, enzyme-linked immunosorbent assay, and double immunodiffusion. Results. One epitope was found to be universally recognized by all sera tested. Thirty-two of the samples recognized multiple antigenic regions, but sera from the remaining 3 patients recognized only this universal epitope, and in longitudinal studies of 1 of these 3 patients, the serum recognized only this epitope for more than 2 years, even though multiple, potent, antigenic regions were found on topo I. Conclusion. Recognition of multiple epitopes in most patients suggests that the topo I molecule itself would drive the autoimmunity on topo I. However, antigen-driven autoimmunity could not explain the production of the monoreactive anti–topo I antibody seen in the 3 patients. We thus hypothesize that there is a process whereby recognition of the universal epitope by cross-reaction develops into antigen-driven autoimmunity.     

Columnar metaplasia in the remnant esophagus is a long-term indicator for pneumonia after radical esophagectomy

Background

This study investigated the long-term risk factors for pneumonia after esophageal reconstruction using a gastric tube via the posterior mediastinal route following esophagectomy for esophageal cancer. The influence of columnar metaplasia in the remnant esophagus was specifically assessed.

Methods

Among 225 patients who underwent esophagectomy between January 2004 and December 2010, the subjects were 54 patients who could be followed up for more than 5 years. Routine oncologic follow-up consisted of CT scanning of the abdomen and chest every 4–6 months and annual endoscopy. Data on the occurrence of pneumonia were collected by retrospective review of chest CT scans. Risk factors for pneumonia investigated by univariate and multivariate analyses included the age, gender, diameter of the stapler, length of the intrathoracic remnant esophagus, anastomotic stricture, and presence of columnar metaplasia in the remnant esophagus.

Results

The median age was 62.4 years (interquartile range: 55.8–68.0 years). Forty-three patients were men. Pneumonia was detected in 39 patients (72.2%). The incidence of columnar metaplasia in the remnant esophagus increases with time. Anastomotic stricture was significantly related to the absence of columnar metaplasia on endoscopy in the first year after esophagectomy (p = 0.013). Univariate analysis showed that the frequency of pneumonia was significantly related to the intrathoracic remnant esophagus length ≥4.4 cm (p = 0.014), age over 65 years (p = 0.014), and the presence of columnar metaplasia in the remnant esophagus in the fifth year after esophagectomy (p = 0.005). Among them, age over 65 years and the presence of columnar metaplasia in the remnant esophagus in the fifth year after esophagectomy were found to be independent indicators of the postoperative pneumonia by multivariate analysis.

Conclusion

Pneumonia occurred in 72.2% (39/54) of patients after esophagectomy for esophageal cancer. The presence of columnar metaplasia after esophagectomy is an indicator for pneumonia over the long term.

     

Multiple comet tail artifacts in the liver: a case of congenital hepatic fibrosis showing unusual biliary appearance

Congenital hepatic fibrosis (CHF) is a form of autosomal recessive polycystic kidney disease. Because of the common underlying pathophysiology of ductal plate malformation, CHF can be accompanied by an abnormal biliary appearance, which is characterized by a saccular or fusiform dilatation of the bile ducts. We encountered the case of a 35-year-old man suffering from CHF concomitant with esophageal varices, which were treated by endoscopic sclerotherapy. The patient had elevated serum concentrations of alkaline phosphatase and γ-glutamyl transpeptidase without apparent biliary disease, including hepatolithiasis or a history of cholangitis. Magnetic resonance cholangiography showed an abnormal biliary appearance, which was not saccular or fusiform but had multiple stenosis with unknown causes. B-mode sonogram showed multiple comet tail artifacts in the liver parenchyma, probably corresponding to the compact fibrosis bands and bile in the bile duct as well as peripheral bile duct dilatation, which was proven pathologically. We propose that multiple comet tail artifacts in the liver may suggest the presence of a bile duct abnormality in patients with CHF, suggesting the potential risk for developing biliary complications.