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Biomedical subjects

M M Moreno

Publications and source records attributed to M M Moreno.

14 recordsLinked to original sources

Synthesis of quinolinyl chalcones and evaluation of their antimalarial activity.

Quinolinyl chalcones were synthesized and evaluated for their inhibition of the Plasmodium falciparum cystein protease falcipain and their activity against cultured P. falciparum parasites. They were also tested for in vivo efficacy in a rodent P. berghei model. Their activity against falcipain and as antimalarials was moderate, but antimalarial activity was probably not due to the inhibition of falcipain and may follow a different mechanism. 1-(2,4-Dichlorophenyl)-3-[3-(2-chloro-6,7-dimethoxiquinolinyl)]-2-propen-1-one 3j was the most promising compound among those here reported (IC50 19.0 microM).

Animals↗

Flow dynamics of stenotic aortic valves assessed by signal processing of Doppler spectrograms.

Clinical assessment of aortic stenosis (AS) is sometimes challenging, because all hemodynamic indexes of severity are modified by flow rate. However, the mechanisms underlying flow dependence remain controversial. Analysis of instantaneous flow dynamics has provided crucial information in a number of cardiovascular disorders and may add new insight into this phenomenon. This study was designed to analyze in vivo the effects of flow interventions on instantaneous valvular dynamics of stenotic valves. For this purpose, a custom algorithm for signal processing of Doppler spectrograms was developed and validated against a control population. Digital Doppler recordings at the aortic valve and left ventricular outflow tract were obtained in 15 patients with AS, at baseline and during low-dose dobutamine infusion; 10 normal subjects were studied as controls. Spectrograms were processed by signal averaging, time alignment, modal-velocity enhancement, envelope tracing, and numerical interpolation. Instantaneous relative aortic valve area (rAVA) was obtained by the continuity equation and plotted against normalized ejection time. Curves were classified as either type A (rapid, early-systolic opening) or type B (slow, end-systolic opening). Curves from controls closely matched prior knowledge of normal valve dynamics, but curves from patients were clearly different: all controls except 2 (80%) had type A, whereas all patients except 3 (80%) had a type B pattern (p = 0.03). Dobutamine infusion in patients increased and slightly anticipated peak rAVA by accelerating valve opening. Despite similar values of area and pressure difference, type B dynamics were associated with lower blood pressure (p = 0.01) and worse long-term outcome (>3 years) than type A flow dynamics (p = 0.02). Signal processing of Doppler spectrograms allows a comprehensive assessment of aortic flow dynamics. Differences in timing of valve aperture and in maximal leaflet excursion account for flow-mediated changes in valve area, suggesting complementary effects of inertia and elasticity on the kinetics of stenotic aortic valves. Flow-dynamic analysis provides novel clinical information regarding physiology of AS unavailable to conventional indexes.

Aged↗

Effects of dobutamine on Doppler echocardiographic indexes of aortic stenosis.

OBJECTIVES: This study sought to assess the diagnostic implications of the flow dependence of Doppler echocardiographic indexes of aortic valve stenosis. BACKGROUND: Although valve area has been shown to change with alterations in flow rate, the diagnostic consequences of this phenomenon remain unknown. Valve resistance has been suggested as a more stable index for evaluating aortic stenosis. METHODS: A low dose dobutamine protocol was performed in 35 patients with aortic stenosis. Hemodynamic indexes were obtained by Doppler echocardiography at baseline and at each dobutamine dose. RESULTS: As a result of the shortening of the systolic ejection period, flow increased from (mean +/- SD) 164 +/- 48 to 229 +/- 102 ml/s (p < 0.0001). At peak flow, valve area increased by 28% (from 0.5 +/- 0.2 to 0.6 +/- 0.3 cm2, p < 0.0001), whereas valve resistance decreased by 4% (from 498 +/- 252 to 459 +/- 222 dynes.s.cm-5, p = 0.04). This observed change in resistance was smaller than that for valve area (p < 0.01). The flow dependence of valve area varied among individual patients (p < 0.0001). Multivariate analysis identified calcific degenerative etiology (beta 0.29, p = 0.002), left ventricular velocity of fiber shortening (beta 0.22, p = 0.01), baseline flow (beta -0.28, p = 0.04) and amount of flow increased induced by dobutamine (beta 0.90, p < 0.0001) as factors related to valve area flow dependence. CONCLUSIONS: Although all Doppler echocardiographic indexes of aortic stenosis are affected by flow, valve resistance is more stable than valve area under dobutamine-induced hemodynamic changes. Baseline valve area may be unreliable in patients with calcific degenerative aortic stenosis and low output states.

Adult↗

[The mitral valve apparatus in hypertrophic myocardiopathy: observations by transesophageal echocardiography].

INTRODUCTION AND OBJECTIVES: We analyzed the characteristics of mitral valve apparatus by transesophageal echocardiography in a consecutive series of patients with hypertrophic cardiomyopathy. METHODS: We performed a transesophageal study in 60 patients; 35 of them had intraventricular obstruction at basal state. The following measurements and observations were made in the frontal long-axis transesophageal plane: a) length of both mitral leaflets and dimensions of left ventricular outflow tract that were compared with those obtained from 25 normal subjects; b) structure involved in the systolic anterior mitral motion; c) mechanism of mitral regurgitation, and d) sequence of systolic events. RESULTS: Compared with control subjects (anterior mitral leaflet: 2.86 +/- 0.3 cm, posterior mitral leaflet: 1.62 +/- 0.2 and 1.7 +/- 0.2 cm, respectively; the mitral leaflets were longer in patients with and without subaortic obstruction (anterior leaflet: 2.3 +/- 0.1; posterior leaflet: 1.07 both, p < 0.01). Systolic anterior motion was observed in 49 patients, with mitral leaflet-septal contact in 87% of patients with obstruction and in 11% of nonobstructive patients (p < 0.01). Structures participating in this phenomenon were: distal portion of the anterior mitral leaflet (77.5%), of both mitral leaflets (18.4%) and anomalous chordae (4.1%); in 5 patients the obstruction was located at a more distal level. Mitral regurgitation was observed in 43 patients; in 37 of them the jet was posteriorly directed in late systole. Patients with hypertrophic cardiomyopathy have longer mitral leaflets with frequent associated abnormalities suggesting that this disease is not confined to myocardium and that leaflet length is not the sole determinant of the obstruction; 2) in almost 80% of patients the systolic anterior motion was produced by the distal anterior mitral leaflet resulting in incomplete coaptation in mid-systole; 3) the sequence of systolic events was ejection/obstruction/leak.

Adult↗

[Accuracy and clinical applicability of the echocardiographic automated endocardial boundary detection system: correlation and bias analysis].

INTRODUCTION AND OBJECTIVES: Automated edge detection of endocardial borders is a new echo system that permits on-line delineation and tracking of blood-tissue interface and offers promise for measuring cyclic changes in cavity area and the assessment of left ventricular function on-line. Its accuracy has only been analyzed by linear regression and its applicability in unselected patients is not clearly established. METHODS: We analyzed the accuracy and clinical applicability of the system in 150 patients. Its accuracy was assessed not only by linear regression but also by bias analysis by comparing the results of the system with those obtained by manual tracing from parasternal short-axis and apical 4 chamber views. RESULTS: We obtained satisfactory studies with this system in at least one of the two echo views in 66% of patients: 47% from 4-chambers view, 43% from parasternal short-axis view and 24.6% from both echo views. A visual semiquantitative assessment of left ventricular function could be performed in 88.6% of patients (p < 0.001). On-line and hand-traced left ventricular areas there well correlated, but fractional area change values from both methods correlated less closely. 95% limits of agreement between both methods were: 2.8 +/- 5.5 cm2 (end-diastolic area), 1 +/- 4.4 cm2 (end-systolic area) and 1.2 +/- 23% (fractional area change) in short-axis parasternal view; in apical 4-chambers view these limits were: 1.16 +/- 6.4 cm2,--1.1 +/- 6 cm2 and 7.3 +/- 16%, respectively. CONCLUSIONS: Although the correlations between left ventricular areas from both methods were close the limits of agreement exceeded our acceptable range of reproducibility. Fractional area change showed only moderate correlations and a lack of agreement with off-line method. Poor image quality of the conventional echo still limits the clinical applicability of the current automated edge detection system.

Adult↗

[T-cell-rich B-cell lymphoma: multifactorial study of 4 cases].

PURPOSE: With the correlational study of four cases in several areas (clinic, morphoimmunologycal, ultrastructural and genetic) we try to valorate the still controversial entity known as T-cell rich B-cell lymphoma (TRBL), and stablish some useful clues in order to settle down the differential diagnosis between TRBL, Hodgkin's disease (HD), and T-cell non-Hodgkin's lymphomas (TNHL). PATIENTS AND METHODS: Cases proceeded from Oncology Department, and had been firstly misdiagnosed either as HD (3 cases) or as TNHL (1 case). Biopsies were processed and stained in routine way, H&E, Giemsa and Wilder. Immunohystological study, using monoclonal antibodies against B-cells, T-cells, histiocytes, activation and proliferation markers, was also performed with avidin biotine peroxidase (ABC) method. Ultrastructural study was performed in three of the cases; two patients were studied by PCR and Southern blot. RESULTS: All of the cases showed a diffuse hystological pattern, with variable fibrosis, and proliferation of venules and capillaries. Small lymphoid cells, being positive for CD3, were dominant. Large blastic cells, positive for CD20, some of them with a Sternberg-like appearance, could be found, in a spitty pattern. Histiocytes were abundant and positive to CD68. Proliferation index (Ki-67) ranged between 13 and 24.5% being the stain mainly positive for B-cells and in a certain extent, also for T-cells. Ultrastructural features were closer to those of the NHL than to the ones found in HD. Molecular study failed to prove any rearrangement. CONCLUSIONS: TRBL is a rare entity between B-cell NHL group. Diagnosis and differential diagnosis (mostly with HD and T-cell NHL) have to be properly made, because of the very distinct prognosis and therapy.

Adult↗

Left atrial appendage Doppler flow patterns: implications on thrombus formation.

The characteristics and clinical implications of left atrial appendage (LAA) flow have not been clearly analyzed. Thirty-nine consecutive patients underwent a transesophageal echocardiographic (TEE) color Doppler study to correlate the LAA pulsed Doppler flow pattern with echocardiographic variables and the cardiac rhythm of each patient. Three different LAA flow patterns were identified. Type I flow, characterized by a biphasic pattern (waves of filling and emptying), was found in 17 patients, all in sinus rhythm; it was not associated with LAA spontaneous contrast or thrombus. Mean peak velocities of the filling and emptying waves were, respectively: 28 +/- 12 cm/sec and 31 +/- 9 cm/sec. Type II sawtooth active flow (eight patients) (mean peak velocity: 49 +/- 12 cm/sec) was only detected in atrial fibrillation (AF) and dilated LAA (LAA area: 421 +/- 40 mm2) but without thrombus or significant LAA spontaneous echocardiographic contrast. Type III flow pattern was noted in 14 patients with AF and a very dilated LAA (LAA area: 619 +/- 96 mm2). This flow pattern was characterized by the absence of identifiable flow waves and was associated with the presence of LAA spontaneous contrast; the majority (six of seven) had evidence of thrombus. We concluded that the LAA is a dynamic structure in which TEE study identified three flow patterns with different implications. AF is associated with two LAA flow types (II and III) with a larger LAA size as well as a higher incidence of LAA clots in type III flow.

Atrial Fibrillation↗

[Characterization of Doppler flow of the left atrial appendage and its relation to thrombi. A transesophageal echocardiographic study].

OBJECTIVE: The characteristics and clinical implications associated with Left Atrial Appendage (LAA) flow have not been clearly analyzed. The purpose of this transesophageal pulsed doppler study was to evaluate the importance of rhythm and echo doppler parameters on LAA thrombus formation. DESIGN: Prospective study. SETTING: Patients in a follow-up transesophageal echocardiographic study at Gregorio Maranon General Hospital, Madrid. PATIENTS: Through a transesophageal echocardiographic color Doppler prospective study we evaluated 44 consecutive patients. INTERVENTIONS: In each patient we measured presence of atrial fibrillation, presence of LAA thrombi and LAA doppler flow pattern parameters (peak velocity and area enclosed by the pulsed doppler filling and emptying waves). MEASUREMENTS: We identified three types of LAA doppler flow: Type I, clearly defining biphasic flow, was present only in sinus rhythm patients and not associated to LAA thrombus; Type II saw-fish active flow pattern was detected only in atrial fibrillation patients not associated also with LAA thrombus. Type III low flow pattern occurred only in atrial fibrillation patients and is associated to the majority of LAA thrombus. CONCLUSIONS: These findings document the importance of LAA doppler factors when transesophageal echocardiography is used to study LAA thrombus formation.

Adult↗

[Echocardiographic quantification of mitral regurgitation. Comparative study with transthoracic and transesophageal Doppler color echocardiography].

The quantification of mitral regurgitation by means of colour coded Doppler echocardiography still is a controversial issue. A prospective study on 86 consecutive patients with mitral regurgitation diagnosis was carried out by means of conventional transthoracic colour coded Doppler echocardiography in order to make a comparative study with results obtained by means of transoesophageal colour coded Doppler echocardiography. A systematic measurement of the following parameters was carried out in each patient: Colour coded area or mitral regurgitation jet, auricular depth of mitral regurgitation jet, severity degree of mitral regurgitation, left auricular area, mitral regurgitation ratio and transthoracic crossection plan of largest regurgitation area. Both echocardiographic techniques had the first three parameters in common. The mitral regurgitation area by transthoracic echocardiography was 370 +/- 41 mm2 and by transoesophagial technique 558 +/- 43 mm2 (p less than or equal to 0.001 - r = 0.71). The depth of mitral regurgitation by transthoracic path was 31 +/- 2.7 mm and by transoesophageal path 37 +/- 25 mm (p less than or equal to 0.01 - r = 0.74). The existing correlation between the mitral regurgitation area obtained by both techniques improved (r = 0.84) when a four camera apical transthoracic plan was used and worsened (r = 0.45) when the longitudinal parasternal path was used. We came to the conclusion that the valorization of mitral regurgitation made by both techniques is not accurately comparable, existing undervaluation in transthoracic echocardiography. The discrepancies between the two techniques are more patent and statistically more significant when longitudinal parasternal plan is used for transthoracic quantification of severity degree of mitral regurgitation.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Antibody dependent cell-mediated cytotoxicity of Trypanosoma cruzi: the release of tritium-labelled RNA, DNA and protein.

The cytotoxicity of normal rat spleen cells to antibody-coated Trypanosoma cruzi epimastigotes has been studied by assaying the release of [3H]-labelled macromolecules from the parasites. The release of thymidine (DNA) is slower than the release of uridine (RNA), suggesting that the nucleus is broken down more slowly than the cytoplasmic membrane. Less than 50% of the leucine (protein) is released when the parasites are lysed, whereas uridine (RNA) is almost totally released. In practical terms these results show that the release of incorporated radioisotope-labelled uridine can be used as a sensitive assay for cytotoxicity of T. cruzi. Cytotoxicity by normal rat spleen cells is antibody dependent and proportional to the logarithm of effector cell number. The lag phase and the rate of RNA release is not altered by centrifuging the parasites and effector cells to enhance contacts between them.

Animals↗