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Biomedical subjects

J E Perez

Publications and source records attributed to J E Perez.

17 recordsLinked to original sources

Aphid derived sugars in the neotropical sandfly--Lutzomyia peruensis.

It is known that a sugar meal is a prerequisite for the transmission of Leishmania by sandflies in the laboratory. Lutzomyia peruensis the proven vector of Leishmania peruviana, was caught by aspiration from crevices in rocks near Chaute in the Rimac Valley, Peru, cryopreserved and analysed for sugars using HPLC. The major sugars present are glucose and fructose as well as smaller amounts of sucrose, maltose, melibiose, turanose and a trisaccharide, probably raffinose. The results indicate that the major carbohydrate sugar meal of Lutzomyia peruensis is aphid honeydew. This is the first report of such behaviour in Neotropical sandflies.

Animals

Phase II trial of cytarabine, cisplatin and vindesine for advanced non-small cell lung cancer.

Thirty-two patients with advanced non-small cell lung cancer (NSCLC) were entered in this study to evaluate the efficacy and toxicity of a chemotherapy schedule including cisplatin (C) 40 mg/m2 intravenously (i.v.) on days 1-3; vindesine (V) 3 mg/m2 i.v. on day 1, and cytarabine (ara-C) 15 mg/m2 subcutaneously every 12 hours on days 1-3 (total dose: 90 mg/m2). Cisplatin was administered simultaneously with one dose of ara-C. Cycles were repeated every 28 days. Five patients out of 28 (18%) fully evaluable for response presented partial remissions. No complete response was observed. Median survival was 8 months and median duration of response was 4 months. Hematologic toxicity was severe in 3 patients. There were no toxicity-related deaths. Other adverse reactions included nausea and vomiting, alopecia and peripheral neuropathy. We conclude that this chemotherapy combination is marginally effective against NSCLC showing in this group of patients a low number of responses of short duration without a significant impact on survival.

Antineoplastic Combined Chemotherapy Protocols

Normal left ventricular performance in children with X-linked hypophosphatemic rickets: a Doppler echocardiography study.

To determine if chronic hypophosphatemia causes myocardial dysfunction, we explored one model for this metabolic derangement by prospectively investigating 11 patients (aged 5-18 years) with X-linked hypophosphatemic rickets (XLH) by M-mode, two-dimensional, and Doppler echocardiography. Inorganic phosphate and calcitriol (1,25-dihydroxyvitamin D3) treatment was withheld 72 h prior to study. None of the patients had cardiovascular symptoms. Fasting serum inorganic phosphate concentrations were subnormal in all: 2.6 +/- 0.5 mg/dl (SD). Serum total and ionized calcium, magnesium, sodium, potassium, and creatine kinase myocardial fraction (CK-MB) levels were unremarkable. Electrocardiograms revealed early repolarization abnormalities in 3 of the 11 patients: 1 had significant QT prolongation (corrected for heart rate), and 2 had T wave abnormalities. Exaggerated U waves occurred in 4 subjects. Resting echocardiograms were normal in 9 patients. In 1 subject there was mitral valve prolapse, and 1 patient possibly had an atrial septal defect (these findings were considered unrelated to hypophosphatemia). All M-mode measurements were normal. The two-dimensionally derived end-diastolic and end-systolic left ventricular volumes were 60.3 +/- 18.0 and 20.5 +/- 6.9 ml, respectively. Left ventricular ejection fraction was 66.1 +/- 4.7%, and the cardiac index by Doppler study was 4.1 +/- 0.8 liters/min per m2 (both values were within normal limits). Although the precise pathogenesis of XLH is unknown and our findings suggest that some electrocardiographic abnormalities may be common in this disorder, we found no evidence for left ventricular dysfunction in this human model of clinically significant long-standing hypophosphatemia.

Adolescent

Bone-only versus visceral-only metastatic pattern in breast cancer: analysis of 150 patients. A GOCS study. Grupo Oncológico Cooperativo del Sur.

The medical records of 510 patients with metastatic breast cancer were retrospectively reviewed. Seventy-seven patients with metastases confined to skeleton and 73 patients bearing visceral-only disease were identified. All patients had a disease-free interval greater than or equal to 6 months and received systemic therapy with any of the following modalities: chemotherapy, hormonotherapy, or chemohormonotherapy. The clinical features, response to treatment, and survival were analyzed and compared for both groups. Median survival of patients with osseous metastases was 28 months, while it was 13 months for those patients with a visceral pattern (p less than 0.001). Response rates to first and second line systemic therapy for both metastatic patterns showed no significant differences, suggesting a similar degree of sensitivity or resistance in both groups. Objective regression to first therapy was 45% in the group with bony disease and 41% among patients with visceral involvement; median duration of response was 16 months and 13 months, respectively. In both groups progressive disease conserved the original metastatic pattern in most patients. We conclude that although a superiority in survival was evident for the osseous metastatic pattern, for these patients efforts should be made to select the least aggressive therapy in order to avoid excessive toxicity. Further studies are needed to confirm our findings.

Adenocarcinoma

Normal left ventricular performance documented by Doppler echocardiography in patients with long-standing hypocalcemia.

INTRODUCTION: Several reports suggest significantly reduced left ventricular performance in subjects with chronic hypocalcemia. We prospectively investigated eight patients, aged 13 to 31 years, with long-standing hypocalcemia due to idiopathic hypoparathyroidism or pseudohypoparathyroidism by echocardiography. PATIENTS AND METHODS: Six subjects had symptomatic hypocalcemia manifested as recurrent tetany (four), seizures (four), mental retardation (three), behavior disorder (one), and skeletal abnormalities (four); three subjects were untreated when studied. None had cardiovascular symptoms. Each patient underwent clinical, biochemical, and cardiac studies, including Doppler, two-dimensional, and M-mode echocardiography, on the same day. RESULTS: In serum, both total and ionized calcium concentrations were reduced and averaged 7.2 mg/dl (range: 5.3 to 8.5 mg/dl; normal: 9.0 to 10.3 mg/dl) and 3.6 mg/dl (range: 3.0 to 3.9 mg/dl; normal: 4.5 to 5.3 mg/dl), respectively. Electrocardiograms revealed prolonged QTc intervals in six patients. Also noted were prominent U waves (five), T-wave abnormalities (four), and right-axis deviation (one). Resting echocardiography, however, demonstrated normal left ventricular function in all subjects. All M-mode measurements were normal. Two-dimensional-derived left ventricular end-diastolic and end-systolic volumes were 87.1 +/- 20.1 ml and 30.2 +/- 9.7 ml (mean +/- SD), respectively. Left ventricular ejection fraction was 65 percent (61.2 to 74.7 percent). Doppler-derived cardiac output and cardiac index averaged 5.1 liters/minute (2.9 to 6.7 liters/minute) and 3.0 liters/minute/m2 (1.7 to 4.3 liters/minute/m2), respectively. CONCLUSION: Our prospective study of eight subjects with functional hypoparathyroidism demonstrated that, despite electrocardiographic abnormalities, long-standing hypocalcemia was not associated with left ventricular dysfunction.

Adolescent

Differentiation between acutely ischemic myocardium and zones of completed infarction in dogs on the basis of frequency-dependent backscatter.

The goal of this work was to determine whether the frequency dependence of apparent backscatter coefficient (not corrected for attenuation within the myocardium) could differentiate completed, remote infarction from acute myocardial injury in vivo. Myocardial infarcts were produced in six dogs by coronary artery occlusion. One to 12 months later, acute ischemic injury was induced in each dog by ligation of a coronary artery that supplied a region of myocardium adjacent to the established infarct. Infarct, ischemic, and normal regions were interrogated with a 5-MHz, circular, 0.5-in. diam, broadband, focused, piezoelectric transducer mounted in a water-filled stand-off device placed against the exposed, beating heart. Apparent backscatter coefficients were measured over the range of frequencies from 3-7 MHz. The frequency dependence was obtained from the slope of log apparent backscatter coefficient versus log frequency. No significant difference in frequency dependence was found between normal and acutely ischemic myocardium for periods of up to 2 h of ischemia. In contrast, frequency dependence in regions of remote infarct (1.8 +/- 0.1, mean +/- standard error) was significantly lower than that in acutely ischemic or nonischemic regions (2.3 +/- 0.1) (p less than 0.01). These results suggest that remote myocardial infarction can be differentiated from acutely injured but still potentially salvageable myocardium in vivo on the basis of the frequency dependence of backscatter.

Animals

Contraction-related variation in frequency dependence of acoustic properties of canine myocardium.

Results of experiments performed in several laboratories indicate that contracting myocardium exhibits a cyclic variation of the magnitude of ultrasonic backscatter, with maxima occurring at end-diastole and minima at end-systole. The mechanisms responsible for this variation are not well understood. The purpose of the present study was to determine whether the frequency dependence of backscatter exhibits systematic variation throughout the cardiac cycle, analysis of which may facilitate improved understanding of biologic factors responsible for the cyclic variation of the magnitude of backscatter. In this study, the myocardial backscatter coefficient, as a function of frequency, was measured throughout the cardiac cycle in nine open-chest dogs. The frequency dependence of the backscatter coefficient was computed from a least-squares linear fit to log backscatter coefficient versus log frequency data. A cyclic variation of frequency dependence of backscatter was found with maximum near end-diastole (f2.6 +/- 0.1) and minimum near end-systole (f2.2 +/- 0.1), a significant variation (p less than 0.01). These results suggest that mechanisms responsible for the cyclic variation of backscatter may include changes in the effective size of the dominant scatterers throughout the cardiac cycle. An alternative explanation for the observed variation is an increase in the myocardial attenuation coefficient during systole followed by a decrease in diastole.

Animals

Automated determination of the magnitude and time delay ("phase") of the cardiac cycle dependent variation of myocardial ultrasonic integrated backscatter.

An algorithm for quantitative description of cardiac cycle dependent variation of integrated backscatter (cyclic variation) has been developed and is shown to be suitable for analysis of nonsinusoidal data typical of ultrasonic tissue characterization measurements from myocardium in vivo. The algorithm produces estimates of the magnitude of variation and of the time delay relative to the electrocardiographically recorded QRS-complex. To validate the algorithm, 246 integrated backscatter measurements were analyzed both manually and by the automated method. The magnitude and time delay estimates from the two methods correlated closely. With a separate set of data, the algorithm produced reasonable descriptions of the cyclic variation for 89 of 101 integrated backscatter measurements. Only modest computational power is required for effective implementation of this algorithm, facilitating inclusion of online automated analysis capabilities in quantitative ultrasonic tissue characterization systems.

Algorithms

Stage IV breast cancer: clinical course and survival of patients with osseous versus extraosseous metastases at initial diagnosis. The GOCS (Grupo Oncológico Cooperativo del Sur) experience.

The medical records of 414 patients with metastatic breast carcinoma treated between 1978 and 1986 were reviewed and 44 women were identified as having stage IV disease when the primary breast lesion was detected. Of these 44 women, 25 had metastatic disease limited to the skeleton while 19 had extraosseous lesions only. The clinical features, response to therapy, and survival were analyzed and compared for both groups. The median survival of those patients with bone-only metastases was 52 months as compared with 13 months for those with extraskeletal lesions (p = 0.0025). The response rate to first-line systemic therapy was similar for both groups (47% for bone metastases and 44% for extraosseous metastases). The median duration of response was 14 months (range, 3-55 months) for patients with bone disease and 8 months (range, 4-43 months) for those with extraskeletal lesions. We conclude that patients with metastatic breast cancer confined to the skeleton at initial diagnosis tend to follow an indolent, chronic course with prolonged survival. Therefore the increase in response rate with aggressive chemotherapy should be balanced against its higher morbidity. Further studies are needed to confirm whether the better prognosis of these patients is determined by the anatomical confinement of the disease to the skeleton or merely reflects the influence of other prognostic factors.

Bone Neoplasms

Sensitive detection of the effects of reperfusion on myocardium by ultrasonic tissue characterization with integrated backscatter.

We have shown recently that tissue characterization of myocardium with ultrasound reflects changes associated with contractile function throughout the cardiac cycle. To determine whether ultrasonic tissue characterization can sensitively detect the impact of ischemic injury and reperfusion on contractile properties of the heart, we studied the time course of change of backscatter after 5, 20, and 60 min of coronary occlusion followed by reperfusion in 15 dogs. The time-averaged integrated backscatter (IB) and the amplitude and phase of cyclic variation of IB (phase relative to the left ventricular pressure waveform) were measured. A novel ultrasonic index of acute injury was identified, the phase-weighted amplitude of cyclic variation, and calculated by weighting the amplitude of cyclic variation of IB with respect to the phase. We hypothesized that backscatter variables would change dramatically after occlusion and that their restitution after reperfusion would sensitively reflect the extent and time course of reversibility of ischemic injury. After coronary occlusion, segmental wall thickening decreased from approximately 55% to 5% regardless of the duration of ischemia. Changes in backscatter associated with this decrease included an increase in time-averaged IB of approximately 5 dB, a 5 dB decrease in cyclic variation, an 80 degree phase shift, and a 7 dB decrease in phase-weighted amplitude. Wall thickening after reperfusion immediately after the 5, 20, or 60 min occlusions recovered to 45%, 27%, and 12% of baseline values, respectively. Within 3 hr it recovered to 53%, 44%, and 22%. Time-averaged IB recovered initially by 89%, 61%, and 44% (all p less than .05) and continued to recover subsequently although more slowly. Ultimate recovery was virtually complete. In contrast to the rapid recovery of time-averaged IB, phase-weighted amplitude recovered initially to only 72%, 41%, and -7% of baseline (all p less than .05) and manifested slower and incomplete recovery when ischemia had been present for 20 or 60 min. After reperfusion, the time course of both cyclic variation and phase were reflected by changes in the phase-weighted amplitude. The backscatter variables assessed appear to sensitively delineate the duration, time course of recovery, and reversibility of ischemic injury in response to reperfusion. The results suggest that early recovery of time-averaged IB corresponds in part to the restoration of tissue ultrastructural integrity.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Cardiac dysfunction during acute lung injury induced by oleic acid in dogs.

Circulatory abnormalities are common during the adult respiratory distress syndrome and contribute importantly to the high mortality seen with this illness, but what causes them is not well characterized. Oleic acid-induced acute lung injury is an experimental model of the human syndrome in which hemodynamic changes are also common. To characterize a possible link between lung injury and cardiac dysfunction in this model, we evaluated cardiac function in mongrel dogs after oleic acid administration. Stroke volume index decreased, the radionuclide ventriculographically determined ejection fraction decreased, and end-diastolic volume increased after oleic acid. These results suggested a decrease in myocardial contractility, a conclusion confirmed when other experiments demonstrated a consistent rightward displacement of the end-systolic pressure-diameter relationship after oleic acid. Histologic examination of the myocardium showed little evidence of vascular injury, and myocardial tissue wet-to-dry weight ratios were normal. Thus, although the pulmonary effects of oleic acid are due to microvascular injury, similar mechanisms are not responsible for the depression in myocardial contractility.

Acute Disease

Sequential therapy with methotrexate and 5-fluorouracil in the treatment of advanced colorectal carcinoma.

Twenty-nine patients with advanced colorectal carcinoma were entered in this study to evaluate the efficacy and toxicity of a sequential chemotherapeutic schedule with methotrexate (MTX), 200 mg/m2 intravenously (IV) (push injection) and 5-fluorouracil (5-FU), 1,200 mg/m2 in continuous IV infusion, using a 20-hour time interval. All patients received calcium leucovorin (LV), 25 mg, intramuscularly (IM) every six hours for eight doses beginning 24 hours after methotrexate administration. Courses were administered every 15 days. Of the 24 patients evaluable for response, 11 (46%) had major objective regressions (one complete remission [CR] and ten partial remissions [PR]). The survival rate of patients who responded to treatment was 60% at 16 months, whereas patients with no change and those in whom the disease progressed had a median survival of 9 months and 3 months, respectively. The median duration of response has not yet been reached in patients who presented objective tumor regression, and was 7.5 months in those with no change. Significant differences were found between objective regression and no change (P less than .0005) and between no change and tumor progression (P less than .05). All patients were evaluable for toxicity. There were three toxic-related deaths (10%) because of severe myelosuppresion, sepsis, and hemorrhage. These promising results, despite important toxicity, reveal the synergism between the two chemotherapeutic agents and also indicate that the response rate achieved could be a consequence of the 20-hour interval and high dose of 5-FU. Further studies are necessary to determine the optimal time interval and the adequate 5-FU dose.

Adult

High-dose alpha-tocopherol as a preventive of doxorubicin-induced alopecia.

The effectiveness of alpha-tocopherol acetate as a preventive of doxorubicin-induced alopecia was evaluated in 20 patients with different types of solid tumors. All received therapy containing doxorubicin in a dose range of 50-60 mg/m2/cycle of treatment. The observed hair loss was severe in 90% and moderate in 10% of the patients. No protective activity of alpha-tocopherol was demonstrated in this trial.

Adult

A relationship between ultrasonic integrated backscatter and myocardial contractile function.

We have shown previously that the physiologic, mechanical cardiac cycle is associated with a parallel, cardiac cycle-dependent variation of integrated backscatter (IB). However, the mechanisms responsible are not known. The mathematical and physiological considerations explored in the present study suggest that the relationship between backscatter and myocardial contractile function reflects cyclic alterations in myofibrillar elastic parameters, with the juxtaposition of intracellular and extracellular elastic elements that have different intrinsic acoustic impedances providing an appropriately sized scattering interface at the cellular level. Cardiac cycle-dependent changes in the degree of local acoustic impedance mismatch therefore may elicit concomitant changes in backscatter. Because acoustic impedance is determined partly by elastic modulus, changes in local elastic moduli resulting from the non-Hookian behavior of myocardial elastic elements exposed to stretch may alter the extent of impedance mismatch. When cardiac cell mechanical behavior is represented by a three-component Maxwell-type model of muscle mechanics, the systolic decrease in IB that we have observed experimentally is predicted. Our prior observations of regional intramural differences in IB and the dependence of IB on global contractile function are accounted for as well. When the model is tested experimentally by assessing its ability to predict the regional and global behavior of backscatter in response to passive left ventricular distention, good concordance is observed.

Animals

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Adolescent