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The usefulness and cost of echocardiography was evaluated in 133 consecutive patients admitted to the Coronary Care Unit. A useful echocardiogram was one that provided new information, which influenced diagnosis, prognosis, or treatment. The cost of a useful echocardiogram was defined as the unit cost ($476 the Medicare global fee) x units (i.e., total echocardiograms / useful echocardiograms). Admission diagnoses were unstable angina (34%), arrhythmia (14%), congestive heart failure (8%), postprocedure monitoring (7%), acute myocardial infarction (6%), and miscellaneous (20%). The echocardiogram provided new information in 29% of patients. Patients without a recent echocardiogram (within 3 months) were twice as likely to have a useful echocardiogram (33 of 99, 33%) as those with a recent echocardiogram (5 of 34, 15%, p <0.05). A cardiologist predicted the overall usefulness of echocardiography with a positive predictive accuracy of 52% and a negative predictive accuracy of 94% (p < 0.0001). The overall cost of a useful echocardiogram of 3.5 units or $1,666 per useful study was decreased to $904 (1.9 units) if only studies predicted to be useful were considered. The usefulness of echocardiography varied significantly (p <0.02) within the admitting diagnostic categories. The usefulness of an echocardiogram was underestimated in patients with congestive heart failure, where it was found to be most useful (64%; $762 or 1.6 units). Thus, usefulness relates to the admission diagnosis, the availability of a recent echocardiogram, and to clinical judgment. [ABSTRACT FROM AUTHOR]

Tumor necrosis factor (TNF) promotes immunity and modulates cell viability, in part, by promoting alterations of cellular gene expression. The mechanisms through which TNF communicates with the nucleus and alters gene expression are incompletely understood. Incubation of human umbilical vein endothelial cells (HUVEC) with TNF induces phosphorylation of the CRE-binding protein (CREB) transcription factor on serine 133 and increases CREB DNA binding and transactivation. Dominant negative CREB, an antagonist antibody directed against the type 1 TNF receptor, or pharmacological inhibition of p38 MAPK signaling blocked TNF-induced CREB activation as determined by phosphorylation and gene reporter assays. From among the kinases that can activate CREB, we found that downstream of p38 MAPK, MSK1 is activated by TNF to promote CREB activation. These observations show that CREB is activated by TNF/TNFR1 signaling through a p38MAPK/MSK1 signaling pathway.

Vascular endothelial cell growth factor (VEGF) plays a crucial role in the development of the cardiovascular system and in promoting angiogenesis associated with physiological and pathological processes. Although a great deal is known of the cytoplasmic signaling pathways activated by VEGF, much less is known of the mechanisms through which VEGF communicates with the nucleus and alters the activity of transcription factors. Binding of VEGF to the KDR/Flk1 receptor tyrosine kinase induces phosphorylation of the CRE-binding protein (CREB) transcription factor on serine 133 and increases CREB DNA binding and transactivation. p38 MAPK/MSK-1 and protein kinase C/p90RSK pathways mediate CREB phosphorylation. Confocal microscopy shows that VEGF-induced phosphorylation of nuclear CREB is blocked by pharmacological inhibition of protein kinase C and p38 mitogen-activated protein kinase signaling. Thus, KDR/Flk1 uses multiple pathways to transmit signals into the nucleus where CREB becomes activated. These results suggest that CREB may play a role in alterations of gene expression important to angiogenesis.

Vascular endothelial cell growth factor (VEGF) binds to and promotes the activation of one of its receptors, KDR. Once activated, KDR induces the tyrosine phosphorylation of cytoplasmic signaling proteins that are important to endothelial cell proliferation. In human umbilical vein endothelial cells (HUVECs), tumor necrosis factor (TNF) inhibits the phosphorylation and activation of KDR. The ability of TNF to diminish VEGF-stimulated KDR activity was impaired by sodium orthovanadate, suggesting that the inhibitory activity of TNF was mediated by a protein-tyrosine phosphatase. KDR-initiated responses specifically associated with endothelial cell proliferation, mitogen-activated protein kinase activation and DNA synthesis, were also inhibited by TNF, and this was reversed by sodium orthovanadate. Stimulation of HUVECs with TNF induced association of the SHP-1 protein-tyrosine phosphatase with KDR, identifying this phosphatase as a candidate negative regulator of VEGF signal transduction. Heterologous receptor inactivation mediated by a protein-tyrosine phosphatase provides insight into how TNF may inhibit endothelial cell proliferative responses and modulate angiogenesis in pathological settings.

A protein that binds the intracellular domain of KDR (KDR-IC), a receptor for vascular endothelial cell growth factor (VEGF), was identified by two-hybrid screening. Two-hybrid mapping showed that the VEGF receptor-associated protein (VRAP) interacted with tyrosine 951 in the kinase insert domain of KDR. Northern blot analysis identified multiple VRAP transcripts in peripheral leukocytes, spleen, thymus, heart, lung, and human umbilical vein endothelial cells (HUVEC). The predominant VRAP mRNA encodes a 389-amino acid protein that contains an SH2 domain and a C-terminal proline-rich motif. In HUVEC, VEGF promotes association of VRAP with KDR. Phospholipase C gamma and phosphatidylinositol 3-kinase, effector proteins that are downstream of KDR and important to VEGF-induced endothelial cell survival and proliferative responses, associate constitutively with VRAP. These observations identify VRAP as an adaptor that recruits cytoplasmic signaling proteins to KDR, which plays an important role in normal and pathological angiogenesis.

This study was initiated to identify signaling proteins used by the receptors for vascular endothelial cell growth factor KDR/Flk1, and Flt1. Two-hybrid cloning and immunoprecipitation from human umbilical vein endothelial cells (HUVEC) showed that KDR binds to and promotes the tyrosine phosphorylation of phospholipase Cgamma (PLCgamma). Neither placental growth factor, which activates Flt1, epidermal growth factor (EGF), or fibroblast growth factor (FGF) induced tyrosine phosphorylation of PLCgamma, indicating that KDR is uniquely important to PLCgamma activation in HUVEC. By signaling through KDR, VEGF promoted the tyrosine phosphorylation of focal adhesion kinase, induced activation of Akt, protein kinase Cepsilon (PKCepsilon), mitogen-activated protein kinase (MAPK), and promoted thymidine incorporation into DNA. VEGF activates PLCgamma, PKCepsilon, and phosphatidylinositol 3-kinase independently of one another. MEK, PLCgamma, and to a lesser extent PKC, are in the pathway through which KDR activates MAPK. PLCgamma or PKC inhibitors did not affect FGF- or EGF-mediated MAPK activation. MAPK/ERK kinase inhibition diminished VEGF-, FGF-, and EGF-promoted thymidine incorporation into DNA. However, blockade of PKC diminished thymidine incorporation into DNA induced by VEGF but not FGF or EGF. Signaling through KDR/Flk1 activates signaling pathways not utilized by other mitogens to induce proliferation of HUVEC.

Transesophageal echocardiography (TEE) has provided an accurate new window for the evaluation of diseases of the thoracic aorta. Experience with TEE has led to an increased recognition of atherosclerosis of the thoracic aorta as a source of cerebral and systemic embolism. Certain features of aortic plaque morphology detected by TEE may prove to have prognostic and therapeutic significance. The intraoperative assessment of thoracic aortic atherosclerosis by TEE may guide modifications in surgical techniques and aortic manipulations that reduce the incidence of perioperative neurologic complications. TEE has also become a valuable tool for the diagnostic evaluation of patients with blunt chest trauma. The precise role of TEE in the management of these disorders is currently under investigation.

The epidemiology of ventricular tachycardia/fibrillation (VT/VF) and sudden cardiac death (SCD) must be explored from multiple aspects, each of which contributes insights into the problem and no one of which exerts exclusive dominance for preventive or therapeutic strategies. These include: (1) population dynamics, using conventional epidemiologic approaches; (2) risk as a function of time from an index event; (3) conditioning risk factors, based on the presence of underlying disease states; (4) transient risk factors that are dynamic and trigger a potentially fatal event at a specific point in time; and (5) "response risk," which refers to individual susceptibility (possibly determined genetically) to the adverse effects of longitudinal and/or dynamic risk factors. Major inroads into profiling individual or population risk of SCD will require better understanding of each of these epidemiologic-clinical-physiologic interactions. The disciplines range from epidemiology, through clinical medicine, to membrane channel physiology, genetic determinants, and molecular biology.

A patient with a large saphenous vein graft aneurysm is described. This case illustrates the role of magnetic resonance imaging and cardiac catheterization in patients with a mediastinal mass and history of coronary bypass surgery.

Diastolic Doppler filling parameters were measured before and after hemodialyses, performed once with and once without fluid removal. Changes occurred only with fluid removal and correlated with weight loss, indicating that they are the result of reduction in preload.

The role of anticoagulation in the blue toe syndrome is unresolved. We describe the sonographic appearance of atherosclerotic plaques in the thoracic aorta imaged by transesophageal echocardiography in 2 patients with blue toe syndrome who had reembolization while taking therapeutic levels of anticoagulants. The findings of complex atheromas associated with mobile highly echodense linear structures by transesophageal echocardiography may be predictive of reembolization in patients with blue toe syndrome who are taking anticoagulants.

Heart rate variability (HRV) was evaluated during the first 24 hours of hospitalization in 36 patients with acute myocardial infarction. Reperfusion was achieved by 60 minutes in 21 patients (group M1) and by 130 minutes in the remaining 15 (group M2). Mean 24-hour HRV measures were not significantly different between groups M1 and M2. Hourly spectral analysis revealed a decrease in total power (0.01 to 1.0 Hz) from 0 to 8 hours to 9 to 16 and 17 to 24 hours in groups M1 (7.04 +/- 0.27 to 6.94 +/- 0.28 and 6.52 +/- 0.18; p = 0.0006) and in group M2 (6.88 +/- 0.30 to 6.57 +/- 0.23 and 6.40 +/- 0.15; p = 0.002). Total power decreased immediately after reperfusion: in group M1 it decreased during the second hour (7.32 +/- 0.96 to 6.42 +/- 1.2; p = 0.001) and in group M2 during the third (7.47 +/- 1.2 to 6.73 +/- 1.4; p = 0.049) and fourth hours (7.47 +/- 1.2 to 6.48 +/- 1.4; p = 0.029). Mean change in total power in the second hour was -11.6% in group M1 and +3.9% in group M2 (p = 0.0001) and in the third hour, +14.5% in group M1 and -8.6% in group M2 (p = 0.006). During the remaining 21 hours, there was no significant difference in hourly change in total power between groups. Similar changes were noted in high-frequency power, but the ratio of low-frequency to high-frequency power was unchanged. In acute myocardial infarction, HRV is higher during the early phase and decreases as hours progress. Reperfusion causes an immediate, transient, and seemingly paradoxic decrease in HRV, probably because of an abrupt decrease in parasympathetic tone.

Atrial septal aneurysm and a dilated sinus of Valsalva were noted on echocardiography in a 30-year-old male with Wolff-Parkinson-White syndrome. The relative low probability of all three coexisting by chance alone suggests the possibility of a common developmental origin. (ECHOCARDIOGRAPHY, Volume 13, January 1996)