Comparison of the effect of histidine-rich glycoprotein and 6-aminohexanoic acid on plasmin production and fibrinolysis in vitro.

Because histidine-rich glycoprotein binds to the kringle 1-3 domain of plasminogen, it may affect fibrinolysis by reducing fibrin-dependent plasmin production, and in this way it could be mechanistically analogous to 6-aminohexanoic acid. We tested this hypothesis by comparing the effects of histidine-rich glycoprotein and 6-aminohexanoic acid in an in vitro assay of fibrin-dependent plasmin production mediated by tissue plasminogen activator. Whereas 1 mM of 6-aminohexanoic acid increased the K(m) of the reaction from approximately 0.22 microM to approximately 1.7 microM, 2 microM of histidine-rich glycoprotein had no discernible effect. Similar results were obtained in an assay based upon fibrin clot lysis. Therefore, we could not document an effect of histidine-rich glycoprotein on the rate of fibrin-dependent plasmin production.

Polar Plasmodium falciparum lipids induce lipogenesis in rat adipocytes in vitro.

Previous studies have shown that 'toxic malarial antigens' released by Plasmodium yoelii can induce hypoglycaemia in mice and act synergistically with insulin in stimulating lipogenesis in rat adipocytes in vitro. In this study, it was shown that similar bioactivity could be detected in Plasmodium falciparum culture supernatant, and the molecular basis of this activity was further investigated. Boiled spent culture medium from P. falciparum cultures ('BS-Pf') (exclusively released into the culture supernatant when schizonts rupture) acts in synergy with insulin to increase lipogenesis in a rat adipocyte assay by more than 250% (P < 0.001). Control preparations prepared from non-parasitized erythrocytes grown under similar conditions had no effect (P < 0.001). While contamination with mycoplasma has previously been shown to interfere with the interpretation of data obtained with other molecules thought to be released from P. falciparum in culture, including those inducing TNF-alpha and NO production by macrophages, such contamination was unequivocally ruled out here. BS-Pf alone did not stimulate the lipogenesis in short-term assays (less than 4 h), while long-term exposure of rat adipocytes to BS-Pf alone (12-24 h) caused a stimulation of lipogenesis at a level comparable to that observed with insulin. Furthermore, lipogenesis-inducing activity was also detected in the serum of squirrel monkeys infected with different species of malaria parasites (P. vivax, P. falciparum and P. brasilianum). Preliminary biochemical characterization showed that the biological activity was found in the solvent-extracted polar lipid fraction of boiled supernatant of P. falciparum cultures. All the different polar lipid fractions, collected from silica gel column chromatography, showed a comparable lipogenesis-inducing activity. Enzymatic treatment by phospholipase C of the lipid fraction, which co-migrated with the phosphatidylcholine standard, showed that the activity of the fraction was associated with the 1,2-diacylglycerol (1,2-DAG) moieties released from polar lipids. When this exogenous 1,2-DAG was added to the adipocyte cultures (short- and long-term cultures), it induced stimulation of lipogenesis in rat adipocytes, while no lipogenic activity was obtained from bacterial polar lipids and 1,2-DAG isolated from unparasitized erythrocytes. The importance of these findings is discussed with reference to other toxic malarial antigens and also to the potential role of these molecules in the induction of hypoglycaemia in the severe forms of malaria.

Dobutamine two-dimensional transesophageal echocardiographic stress testing for detection of coronary artery disease.

Atrial pacing and dipyridamole transesophageal echocardiography have been shown to be sensitive and specific tests for the detection of coronary artery disease. However, the sensitivity and specificity of dobutamine transesophageal echocardiography have not been reported. The purpose of this study was to determine the feasibility, sensitivity, and specificity of dobutamine transesophageal echocardiography for the detection of coronary artery disease. Transesophageal echocardiographic assessment of left ventricular function was performed in 81 adult patients aged 62 +/- 12 years during stepwise infusion of dobutamine from 5.0 to 40 micrograms/kg/min. Ischemia was diagnosed by the development of severe hypokinesis, akinesis, or dyskinesis of a previously contractile left ventricular segment. Coronary artery disease was defined by angiography as a reduction in luminal diameter of > or = 70% of an epicardial or > or = 50% of the left main coronary artery. In patients who had undergone coronary artery bypass graft surgery, a stenotic bypass graft was defined as a reduction in luminal diameter of > or = 70%. In patients without previous CABG, significant coronary artery disease was present in 21 patients: 5 with single-vessel disease, 7 double-vessel disease, 8 triple-vessel disease, and 1 left main coronary disease. Dobutamine transesophageal echocardiography had a sensitivity of 90% (19 of 21) and specificity of 94% (49 of 52) for the detection of coronary artery disease. In patients with previous CABG (n = 8), the sensitivity and specificity for the detection of bypass graft stenosis were 100% (4 of 4) and 75% (3 of 4), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Two-dimensional transesophageal echocardiographic determination of mitral valve area in adults with mitral stenosis.

Two-dimensional transthoracic echocardiography has been shown to be a reliable and accurate method of measuring stenotic mitral valve orifice area. Little data exist on the role of two-dimensional transesophageal echocardiography for this purpose. Thus in 45 adult patients with mitral stenosis mitral valve area was determined by direct planimetry with the use of two-dimensional transesophageal and transthoracic echocardiography. Transesophageal was less feasible than transthoracic echocardiography in the 45 patients (69% vs. 89%, p < 0.025). In 14 patients, two-dimensional transesophageal echocardiography was not feasible, primarily because of leaflet dropout. In 30 patients, transesophageal and transthoracic echocardiography were feasible, and measurements of mitral valve area by the two techniques correlated well (r = 0.91, SEE = 0.33 cm2, p < 0.0001). Mean mitral valve orifice area determined by transesophageal echocardiography (1.54 +/- 0.75 cm2; range 0.56 to 3.49 cm2) and by transthoracic echocardiography (1.55 +/- 0.78 cm2; range 0.62 to 3.68 cm2) did not differ (p = NS). The absolute (0.24 +/- 0.22 cm2) and percent (19% +/- 21%) differences between mitral valve area determined by transesophageal versus transthoracic echocardiography were small. These data show that mitral valve area in patients with mitral stenosis can be accurately measured by direct planimetry with two-dimensional transesophageal echocardiography. Technical refinements such as lateral-gain-compensation features may improve the feasibility of two-dimensional transesophageal echocardiography for measurements of mitral stenosis area, and this technique may become an adjunct to transthoracic echocardiography in the assessment of severity of mitral stenosis.

Pulsed Doppler transesophageal echocardiographic determination of cardiac output in human beings: comparison with thermodilution technique.

Measurement of cardiac output is a clinically valuable and widely used index of cardiac function. Although transesophageal echocardiography has been used to assess left ventricular function, little data exist on the accuracy of this technique in the measurement of cardiac output. Therefore cardiac output derived by pulsed Doppler transesophageal echocardiography and thermodilution methods were compared in adult patients being mechanically ventilated. The left ventricular outflow tract diameter was determined from a transgastric long-axis view of the left ventricle by using the transverse plane and longitudinal plane of the transesophageal scope. The cross-sectional area of the left ventricular outflow tract was calculated from the diameter assuming a circular shape. Pulsed Doppler recordings were obtained at the left ventricular outflow tract. Doppler time-velocity integrals were measured from the leading edge of the velocity curve. Cardiac output derived by transesophageal echocardiography was calculated as time-velocity integral multiplied by left ventricular outflow tract area and heart rate. Cardiac output derived by transesophageal echocardiography from the transverse plane (n = 26) and longitudinal plane (n = 22) were correlated with simultaneous thermodilution measurements. Thermodilution-derived cardiac output demonstrated excellent correlation with cardiac output measured by using transesophageal echocardiography from the transverse plane (r = 0.97, SEE = 0.84 L/min; p < 0.0001) and longitudinal plane (r = 0.95, SEE = 0.97 L/min; p < 0.0001). Transesophageal echocardiography is a promising technique in the measurement of cardiac output and expands the clinical use of this modality in the assessment of cardiac function.