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Biomedical subjects

J E Pérez

Publications and source records attributed to J E Pérez.

At least 19 recordsLinked to original sources

Double modulation of 5-fluorouracil by trimetrexate and leucovorin in patients with advanced colorectal carcinoma.

The purpose of this report is to evaluate the efficacy and toxicity (Tx) of a double modulation of 5-fluorouracil (5-FU) by trimetrexate (TMTX) and leucovorin (LV) in patients with advanced recurrent (inoperable) or metastatic colorectal cancer (ACC). Between December 1997 and August 2000, 36 patients were entered in this phase II study. Median age was 61 years, and 18 patients (50%) were female. Median performance status was 0 (range: 0-1), whereas primary tumor location was colon in 21 patients (58%) and rectum in 15 patients (42%). The number of metastatic sites was 1:29 patients (81%); 2:6 patients (17%) and 3:1 patient (3%). Hepatic involvement was observed in 33 patients (92%). Treatment consisted of TMTX 110 mg/m2 IV over 1 hour at hour (H) 0; LV 50 mg/m2 IV over 2 hours IV infusion starting at H 18; and 5-FU 900 mg/m2 IV bolus at H 20. LV (rescue) 15 mg/m2 orally was administered every 6 hours (total 6 doses) beginning at H 24. Cycles were repeated every 2 weeks until progressive disease (PD) or severe Tx. Thirty-four patients are assessable for response (R) (two patients refused further treatment after the first course of therapy), whereas all patients were assessable for Tx. Complete response: 1 patient (3%); partial response: 4 patients (12%), with an overall objective response rate of 15% (95% CI, 1%-25%); no change: 12 patients (35%); and progressive disease: 17 patients (50%). The median time to treatment failure was 4 months and median survival was 11 months. Tx was within acceptable limits. The dose-limiting side effect was mucositis. Eight episodes of grade II or III stomatitis were observed and were responsible for dosage modifications of TMTX and 5-FU. Leukopenia was observed in 16 patients (44%); neutropenia was registered in 19 patients (53%); anemia was seen in 18 patients (50%); emesis in 22 patients (61%); and dermatitis in 3 patients (8%). There were no therapy-related deaths. The double modulation of 5-FU by TMTX and LV showed modest antitumoral activity with mild to moderate Tx.

Aged↗

[Genetic and morphological characteristics of the populations of Cyprinodon dearborni (Atherinomorpha: Cyprinodontidae) in Chacopata and Laguna de los Patos, Venezuela].

Two populations of the fish Cyprinodon dearborni were compared, one from Laguna de Chacopata and the other from Laguna de los Patos, Cumaná, Venezuela. The morphometric method of the Box Truss was used; the organisms were photographed with a digital camera. In the images 18 measures were made to each organism, with the MOCHA 1.2 program. The tendencies of morphologic variation among populations were analyzed by main components using STATGRAPHICS 2.0 and SHEAR programs. The first four main components in males and females explained 88% of the total variation. The components two, three and four separate the two populations based on the body form of the animals. For the electrophoretic study, 13 enzymatic systems were analyzed in starch gels. The variation and genetic distance were calculated with the program GENES 2.0. Differences were observed in the systems G6PDH, GPI; ES and GLUD, that which can be used as isoenzimatic markers. Genetic diversity of Chacopata (H = 0.086, p = 0.079) was higher than in Laguna de los Patos (H = 0.029, p = 0.028), but both are within the average in populations of fish. The two populations presented a Nei distance of 0.058. The genetic and morphologic differentiation suggests an incipient process of separation whose causes could be the ecological conditions of their habitat, or processes of vicariant speciation.

Animals↗

Ultrasonic tissue characterization: review of an approach to assess hypertrophic myocardium.

It is well known that left ventricular hypertrophy is associated with increased cardiovascular morbidity and mortality. Recently, there has been considerable interest in the application and refinement of noninvasive diagnostic techniques for identification of myocardial tissue composition to permit differentiation between left ventricular hypertrophy that may be associated with irreversible, and therefore, possibly adverse, collagen accumulation ("pathological hypertrophy") as opposed to the type of possibly "benign" hypertrophy devoid of such characteristics (i.e., "physiological hypertrophy"). We review the current state of knowledge in the application of ultrasonic tissue characterization that addresses this question with respect to left ventricular myocardium.

Cardiomyopathies↗

Assessment of myocardial perfusion by contrast echocardiography.

Contrast echocardiography delineates myocardial perfusion and has the potential for quantitating coronary flow and assessing myocardial viability. These applications add important physiologic information to the anatomic information readily available from conventional echocardiography. Because it can be rapidly performed at the bedside, contrast echocardiography may be valuable tool for the use in acute myocardial ischemia. When contrast echocardiography has been used after recanalization of occluded coronary arteries, the assessment of myocardial salvage conveys information concerning reflow, stunning, and prognosis, and in the case of angioplasty it provides immediate information regarding the success of the procedure. Contrast echocardiography can also assess myocardial areas at risk of irreversible damage and the presence or absence of collateral flow. Myocardial contrast echocardiography is a rapidly changing field and with the continued development of newer contrast agents and refinement of ultrasound imaging equipment, the applications of contrast echocardiography will continue to grow.

Coronary Circulation↗

Effects of inotropic stimulation on segmental left ventricular relaxation quantified by color kinesis.

Although myocardial ischemia impairs left ventricular (LV) relaxation before contractile function, regional LV diastolic dysfunction is difficult to evaluate by conventional echocardiography. Because beta-adrenergic stimulation enhances myocardial relaxation, we sought to characterize segmental LV diastolic function (by color kinesis) during dobutamine stress echocardiography and compare it with independently assessed segmental systolic function. We studied 22 patients with suspected coronary artery disease with color kinesis by acquiring digital images with endocardial motion display throughout diastole. Quantification of LV segmental diastolic peak filling rate (SPFR, normalized to segmental end-diastolic area/s) was obtained at rest, low-dose, and peak dobutamine infusion in myocardial segments visualized from the short-axis and/or apical 4-chamber views. In patients with resting normal LV systolic function and a dobutamine-induced hypercontractile response (group I, n = 13 patients; 102 segments), progressive increases in SPFR (p <0.001) were seen in all segments. However, in LV segments with resting systolic wall motion abnormalities (group II, n = 9 patients; 74 segments) SPFR measured at rest was significantly lower than that in group I (p <0.005) and did not increase significantly in response to dobutamine. In both groups of patients, LV myocardial segments (n = 528; rest and after dobutamine)-systolic and quantitative diastolic function-were concordant in 84% and 77% as viewed from short-axis and apical views, respectively. Thus, segmental LV diastolic function can be measured with color kinesis at rest and after inotropic stimulation, allowing comparison with segmental systolic function during pharmacologic stress testing.

Aged↗

Defining left ventricular segmental and global function by echocardiographic intraventricular contrast flow patterns.

Contrast echocardiography improves left ventricular (LV) endocardial border delineation by enhancement of the blood-tissue interface. In particular, the contrast appearing within the LV chamber exhibits characteristic flow patterns over the cardiac cycle, which may be related to the surrounding myocardial wall motion. To determine the relation between the LV intracavitary contrast flow pattern and surrounding wall motion, we reviewed the contrast-enhanced images of 348 consecutive patients studied at rest. We defined 2 different patterns of intracavitary contrast flow as visualized from apical views: a swift, vertical, and homogeneous flow towards the apex (pattern A), and a distinctly protracted, swirling, and heterogeneous flow (pattern B). Images recorded on videotapes were reviewed and the type of pattern (A or B) was determined within the initial 30 to 45 seconds of contrast appearance in the left ventricle. Contrast flow patterns interpreted by independent reviewer were then compared with the interpretation of the LV segmental and global function in each patient. Results demonstrate that 224 of 245 (91%) patients exhibiting pattern A had normal LV segmental function. Furthermore, all but 1 patient (102 of 103) with pattern B had > or =1 wall motion abnormality (p <0.0001). Contrast flow pattern B was observed irrespective of the location of LV wall motion abnormality. Global LV function was normal in 93% of patients exhibiting pattern A, whereas varying degrees of LV dysfunction were noted in 83% of patients with pattern B (p <0.0001). The presence of mitral regurgitation (p = 0.46), aortic insufficiency (p = 0.066), or mitral inflow Doppler abnormality (p = 0.102) was not significantly associated with either pattern. Thus, during contrast echocardiography, the LV intracavitary contrast flow pattern complements the assessment of global and segmental LV function.

Adult↗

Apical hypertrophic cardiomyopathy: echocardiographic diagnosis with the use of intravenous contrast image enhancement.

Echocardiographic image enhancement with an intravenous second-generation contrast agent established the diagnosis of apical hypertrophic cardiomyopathy in 2 patients initially thought to have left ventricular apical thrombus. Image enhancement with contrast agent obviated the need for invasive diagnostic tests, underscoring its applicability in patients with suspected left ventricular masses.

Aged↗

Diagnosis of cardiac rupture with the use of contrast-enhanced echocardiography.

We describe 3 patients with suspected subacute cardiac rupture in whom contrast-enhanced echocardiography played a key role in the diagnosis. In 2 patients, extravasation of the contrast material into the extracardiac space provided direct evidence of subacute cardiac rupture. Absence of this feature helped to exclude cardiac rupture with active hemorrhage into the pericardial space in the third patient. These 3 cases illustrate the safety and applicability of contrast echocardiography in patients with suspected cardiac rupture.

Adult↗

Neoadjuvant chemotherapy with ifosfamide, cisplatin, and vinorelbine in advanced squamous cell carcinoma of the cervix.

A phase II trial was performed to assess the efficacy and toxicity of a combination of ifosfamide (IFX), cisplatin (CDDP), and vinorelbine (VNB) as neoadjuvant chemotherapy (NAC) for untreated advanced cervical carcinoma (ACC). Between October 1995 and February 1998, 40 patients were entered in this study. Their median age was 43 years (range: 23-74 years). International Federation of Gynecology and Obstetrics stages were: IIB, 23; IIIB, 13; and IVA, 4. Therapy consisted of: IFX 2,000 mg/m2 1-hour (H) IV infusion days 1 to 3; 2-mercaptoethanesulfonic acid sodium salt (mesna) 400 mg/m2 IV bolus H 0 and 4, and 800 mg/m2 by mouth H 8, days 1 to 3; VNB 25 mg/m2 20-minute IV infusion days 1 and 8; and CDDP 75 mg/m2 IV day 3. Cycles were repeated every 28 days for a total of three courses. Both staging and response (R) assessment were performed by a multidisciplinary team. An objective response (OR) was observed in 24 of 40 patients (60%; 95% confidence interval, 45-75%). Four patients achieved complete response (CR) (10%); 20 partial response (50%); 12 patients stable disease (30%); and 4 progressive disease (10%). Eight of 24 patients (33%) with OR underwent radical surgery, and histologic CRs were recorded in 2 of them. The remaining patients received definitive radiotherapy after NAC. The dose-limiting toxicity was myelosuppression. Leukopenia occurred in 32 patients (80%) and was grade III or IV in 14 patients (36%). Peripheral neuropathy occurred in 9 patients (22%), whereas myalgias occurred in 10 (25%). Constipation was observed in 9 patients (23%); emesis occurred in 35 patients (88%). There were no therapy-related deaths. These results indicate that IFX/CDDP/VNB is an active combination for ACC with moderate toxicity. Implementation of this regimen in a multimodal therapy protocol deserves further study.

Adult↗

Cyclic variation of integrated backscatter: dependence of time delay on the echocardiographic view used and the myocardial segment analyzed.

To determine the influence of myocardial anisotropy in ultrasonic tissue characterization, we measured the time delay (and magnitude) of the cyclic variation of myocardial integrated backscatter from specific segments visualized in the 4 standard transthoracic echocardiographic views. The cyclic variation data in 10 myocardial regions were obtained from analyses of 2-dimensional integrated backscatter images from 23 healthy subjects. Resultant values (mean +/- SD) for the time delay were as follows: parasternal long-axis view: 1.08 +/- 0.17 (septum) and 1.00 +/- 0.14 (posterior wall); parasternal short-axis view: 1.03 +/- 0.16 (anterior septum), 1.03 +/- 0.14 (posterior wall), 2.22 +/- 0.71 (lateral wall), and 1.65 +/- 0.66 (posterior septum); apical 4-chamber view: 1.08 +/- 0.31 (septum) and 2.20 +/- 0.79 (lateral wall); and apical 2-chamber view: 1.68 +/- 0.62 (inferior wall) and 2.04 +/- 0.72 (anterior wall). Hence, results of this study indicate that myocardial ultrasonic characterization that uses the cyclic variation is influenced by the echocardiographic view and the specific segment of the left ventricle.

Adult↗

Polymorphisms of octopine dehydrogenase (Odh) in mollusks and implications for the neutralism-selectionism hypothesis.

Octopine dehydrogenase (Odh) was examined in several species of bivalves and gastropods and complemented with bibliographic data, to assess the controversy between neutralism and selectionism in explaining the maintenance of genetic variation in natural populations. This debate was the center of the molecular evolution and population genetic research in the 1970s and 1980s, but waned thereafter, without resolution. Although DNA data have been produced, implications are not understood. We examined the polymorphims of Odh in several species of bivalves and gastropods, and the kinetic properties (apparent Km) of the different isozymes in the scallop Euvola ziczac that indicates an apparent case of overdominance of the heterozygous individuals. The question "which of the two hypothesis is correct" has shifted with time to "how much influence did each factor have in the maintenance of genetic variation".

Amino Acid Oxidoreductases↗

[Characterization of myocardial tissue by ultrasound: backscatter].

One of the most important goals in Cardiology is to identify, noninvasively, the normal as well as pathological changes in structure and function of myocardial tissue in order to recognize their etiology and severity. Ultrasonic Tissue Characterization is an approach to define the physical state of the heart by the analysis of the pathological changes that modify cardiac tissue physical properties, therefore generating an ultrasonic signal alteration. Among the most practical types of analysis of this data is the acoustic parameters measurement, and measurements based on integrated backscatter have been utilized the most. Backscatter is the ultrasonic quantification reflected back to the transducer, therefore emanating from myocardial structures or "scatterers". This method has been used to study many patients with hypertrophy, cardiomyopathies, cardiac allograft rejection. But is the investigation of myocardial ischemia-viability one of the most clinically relevant applications because of the importance of selecting, non-invasively, and at a relatively low cost those patients with coronary artery disease in whom myocardial asynergy is noted by conventional echocardiography and/or angiography. The magnitude of alterations in backscatter measurements such as the cyclic variation of integrated backscatter are markers of myocardial viability and could better identify patients who stand to benefit the most revascularization procedures.

Animals↗

Dependence of "apparent" magnitude on the time delay of cyclic variation of myocardial backscatter.

The goal of this study was to determine if the "apparent" magnitude of the cyclic variation, defined as the difference between the values of integrated backscatter at end-diastole and end-systole, was dependent on the corresponding time delay. We measured the cyclic variation in four myocardial segments of the parasternal short-axis view in 23 healthy subjects. The "apparent" magnitude, actual magnitude, and time delay were compared for each segment. Measured time delays were: 2.22+/-0.71 (lateral wall); 1.65+/-0.66 (inferior septum); and approximately 1.0 for the anterior septum and posterior wall. Segments exhibiting large time delays (> 1.0) resulted in a reversal in sign of the "apparent" magnitude of cyclic variation in one instance, and underestimated the true magnitude in both cases. Thus, estimates of the "apparent" magnitude of the cyclic variation are dependent on the associated time delay, whereas a properly defined magnitude is not.

Adult↗

Limited myocardial contractile reserve and chronotropic incompetence in patients with chronic Chagas' disease: assessment by dobutamine stress echocardiography.

OBJECTIVES: To determine whether dobutamine stimulation in patients with Chagas' disease may uncover abnormal contractile responses as seen in ischemic myocardium. BACKGROUND: Segmental left ventricular (LV) dysfunction in the absence of coronary atherosclerosis is frequently seen in patients with chronic Chagas' heart disease. Myocardial ischemia and coronary microcirculation abnormalities have been found in animal models and in humans with Chagas' disease. In addition, chagasic sera may contain autoantibodies against human beta-adrenergic receptors. METHODS: Two groups of patients with Chagas' disease were studied by echocardiography: group 1 (n = 12) without and group 2 (n = 14) with LV segmental wall motion abnormalities (mostly apical aneurysm). Ten normal subjects served as control subjects. We performed qualitative assessment of wall motion and quantitative evaluation of LV cavity under baseline conditions and after dobutamine stimulation. RESULTS: Patients with Chagas' disease exhibited a blunted inotropic and chronotropic response to dobutamine stimulation. After dobutamine, fractional area change in Chagas' group 1 (54.7+/-6.6%; SD) and in group 2 (35.1+/-12.1%) were significantly lower than control group (66.7+/-2.5%; p < 0.001). In addition, in 6 of 14 group 2 patients, dobutamine induced a biphasic response with improvement at low dose and deterioration at peak dose, as seen in patients with coronary artery disease. Although the three groups had similar basal mean heart rates and attained a similar mean peak dobutamine doses, both groups of patients with Chagas' disease had a significantly blunted mean heart rate effect after dobutamine (p < 0.0001). CONCLUSIONS: Thus, dobutamine stimulation unmasks a chronotropic incompetence and a blunted myocardial contractile response in chagasic patients, even in those with no overt manifestation of heart disease.

Cardiotonic Agents↗

Effects of tissue anisotropy and contrast acoustic properties on myocardial scattering in contrast echocardiography.

In this study we explored the potential effects that tissue anisotropy, in conjunction with the acoustic properties of contrast, may have on quantitative measurements of myocardial perfusion with the use of ultrasonic contrast agents. We used a computer simulation of the parasternal short-axis view, based on previously measured values for the anisotropy of backscatter and attenuation of myocardium, to predict the backscattered energy from 18 specific regions within the heart before and after myocardial contrast perfusion. Results demonstrated a regional variation of contrast enhancement in the short-axis view and variations caused by incremental increases in contrast level for specific myocardial regions. Thus quantitative assessment of myocardial perfusion with contrast echocardiography is influenced by the anisotropic properties of the myocardium, and the resulting postcontrast image will depend on the interaction between tissue properties and contrast acoustic properties. The degree of myocardial enhancement caused by the presence of contrast may depend on the spatial position of the specific region investigated with respect to the transducer and the amount of contrast in the myocardium.

Anisotropy↗

Improved echocardiographic delineation of left ventricular thrombus with the use of intravenous second-generation contrast image enhancement.

Transthoracic echocardiography is the most widely used diagnostic test for left ventricular (LV) thrombus, which must be distinguished from other intraventricular structures and image artifacts. To determine whether second-generation intravenous echocardiographic contrast agents provide better delineation of LV thrombus, we reviewed the results of 2-dimensional echocardiographic studies that were performed in 409 patients over a 1-year period to detect LV thrombus. Studies of 190 (46%) patients were interpreted as nondiagnostic for this purpose, of which 48 patients underwent an additional study after intravenous injection of 0.5 to 2 mL of human albumin microspheres within 1 to 4 days. In 43 (90%) of these 48 patients the contrast-enhanced study was definitive and diagnostic for either the presence or absence of an LV thrombus (P <.0001). Of the initial total of 409 patients, 81 had been studied at the bedside in intensive care units. The bedside studies were nondiagnostic for LV thrombus in 51 (63%) of these 81 patients. Of these 51 patients, 14 underwent additional imaging with contrast enhancement, and the contrast-enhanced images became diagnostic (P =. 004) in 11 (79%) of them. Thus intravenous contrast image enhancement improves the diagnostic yield of echocardiography in patients in whom initial images are nondiagnostic for LV thrombus.

Albumins↗