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Biomedical subjects

A Rassi

Publications and source records attributed to A Rassi.

At least 37 records · Page 2Linked to original sources

Comparison of effects of dobutamine and ouabain on left ventricular contraction and relaxation in closed-chest dogs.

Because catecholamines and digitalis have different effects on the time course of myocardial intracellular calcium concentration, their effects on the time course of left ventricular contraction and relaxation may also be different. To study this question, dogs were instrumented to measure left ventricular pressure and determine left ventricular volume from three ultrasonic dimensions. After full recovery from the instrumentation, the effects of dobutamine (2-10 micrograms/kg), ouabain (0.5 mg i.v.) alone, and ouabain given after propranolol (2 mg/kg i.v.), or phentolamine (5 mg i.v.) and incremental doses of ouabain (0.25-0.75 mg i.v.) were assessed on different days. Left ventricular pressure and volume were varied by caval occlusions. Dobutamine significantly increased the slope of the left ventricular end-systolic pressure-volume relation (Emax) and the slope of the dP/dtmax-end-diastolic volume relation (dE/dtmax), while significantly decreasing the time from end-diastole to end-systole (tmax) and the time constant (T) of the isovolumic fall in left ventricular pressure. Ouabain also increased Emax and dE/dtmax but did not alter tmax or T. Dobutamine produced a greater increase in dE/dtmax than in Emax, whereas ouabain produced similar increases in both. These effects of ouabain were not altered by pretreatment with propranolol or phentolamine. We conclude that although dobutamine and ouabain are both positive inotropes that increase Emax, dobutamine speeds the rate of left ventricular contraction (tmax) and relaxation (T), whereas ouabain does not. These effects of ouabain and dobutamine on global parameters of left ventricular chamber performance mirror their influence on intracellular calcium availability. Furthermore, these observations are consistent with the predictions of the time-varying elastance model of the left ventricle and support its usefulness as a conceptual framework to understand and link events occurring during isovolumic contraction, end-systole, and isovolumic relaxation.

Animals↗

Trypanosoma cruzi: zymodemes associated with acute and chronic Chagas' disease in central Brazil.

The clinical characteristics of acute and chronic Chagas' disease in central Brazil are described (29 acute cases and 111 chronic cases). The geographical distribution of Trypanosoma cruzi zymodemes in this region was mapped. Zymodeme (Z) 1 was identified in 12 acute cases, Z2 in 13 and repeated xenodiagnosis gave the same zymodeme identification. The clinical pictures of the Z1 and Z2 acute phases were similar. Resistance to benznidazole treatment occurred after either Z1 or Z2 acute infections. Only 14 positive xenodiagnosis were obtained from the 111 chronic phase patients examined. For 12 of these 14 patients the zymodeme was identified. All 12 carried Z2, 10 of whom had mega involvement. There were several possible explanations for the failure to detect T. cruzi Z1 in chronic Chagas' disease with mega syndromes: suggestions were made for follow-up investigations.

Adolescent↗

[Peripheral polyneuropathy induced by benzonidazole in the treatment of Chagas' disease].

Neurophysiological examination before and after the administration of benzonidazole, has shown peripheral polyneuropathy induced by this drug in most of the patients treated for chronic Chagas' disease. The polyneuropathy was mostly axonal and it was dose dependent being more severe in patients who had denervation of skeletal muscles before receiving the drug.

Adult↗

Further evaluation of lectin affinity purified glycoprotein (GP90) in the enzyme linked immunosorbent assay (ELISA) for diagnosis of Trypanosoma cruzi infection.

Sera from 143 patients considered to be infected with Trypanosoma cruzi on the basis of epidemiological, clinical and standard serological evidence gave positive results in the enzyme-linked immunosorbent assay (ELISA) using a lectin affinity purified 90,000 molecular weight glycoprotein (GP90) antigen preparation. Levels of antibody did not discriminate between clinically classified groups of patients in the chronic phase of infection. The GP90 preparation was found to be heterogeneous.

Adolescent↗

Chagas' disease: serodiagnosis with purified Gp25 antigen.

Development of a highly specific test system for the diagnosis of Chagas' disease (CD) was sought using Gp25, a surface glycoprotein recently isolated from Trypanosoma cruzi culture forms. Radioimmunoprecipitation assays were performed to screen 567 sera for IgG antibodies to Gp25. Correct diagnosis was attained in 97.8% of the 321 sera collected from chagasic patients in several endemic areas of South America. Sera from patients with various clinical forms of chronic disease displayed similar levels of antibodies (Abs) to Gp25. Moreover, there was little cross-reactivity when assayed against 246 sera from non-chagasic individuals, including 105 samples from individuals infected with unrelated trypanosomatids. Cross-reactivity was found in two such sera; these were used to identify a minor protein contaminant as the nonspecific antigen. Residual cross-reactive molecules were eliminated from Gp25 by affinity purification on Concanavalin A (Con A) columns. We recommend this antigen-antibody system for use in routine screening of blood donors.

Adult↗

Enhancement of the autologous mixed lymphocyte reaction in patients with Chagas' heart disease.

Autologous mixed lymphocyte reactions (AMLR) were studied in 18 individuals chronically infected with Trypanosoma cruzi. These individuals were further classified into three clinical groups: the asymptomatic indeterminate form (n = 5); the mega disease form (n = 5); and the cardiomyopathy form (n = 8). While patients with mega disease showed a normal proliferative response when compared with normal controls, the indeterminate group showed a lowered response in sharp contrast with the heart disease group, which presented a very high proliferative response to autologous non-T cells. These abnormal AMLR represent direct evidence for an immunoregulatory malfunction which may be involved in the inflammatory cardiac damage in chronic Chagas' disease.

Adult↗

Specific and non-specific lymphocyte blastogenic responses in individuals infected with Trypanosoma cruzi.

Lymphocyte blastogenic response to various parasite-specific and non-parasite antigens was measured in 31 Trypanosoma cruzi-infected individuals representing the indeterminate, megadisease and cardiomyopathy forms of Chagas' disease. The non-parasite antigens and mitogens stimulated responses in the peripheral blood mononuclear cell (PBMC) cultures of the infected individuals to levels not different than the stimulation seen in PBMC of the normal control group (n = 10). The cell culture antigen (CC-Ag) derived from trypomastigote-amastigote forms of T. cruzi and the epimastigote antigen (EPI-Ag) elicited a strong response among all infected individuals in contrast to virtually no response among the normal controls. Comparisons among the individuals with T. cruzi infection stimulated with EPI-Ag showed no significant difference between the clinical groups. However, stimulus with CC-Ag showed the megadisease group response to be greater than the response of the indeterminate group, but not different than than of the cardiomyopathy group. The possible biological implications of these findings are discussed.

Adolescent↗

Antibody levels to Trypanosoma cruzi in infected patients with and without evidence of chronic Chagas' disease.

Antibody levels to Trypanosoma cruzi were compared in asymptomatic individuals infected with the parasite as well as those with different forms of chronic Chagas' disease of varying severity. The following three serologic tests were used: complement fixation, direct agglutination with previous treatment of the serum with 2-mercaptoethanol, and the enzyme-linked immunosorbent assay. The clinical groups tested included individuals with (a) a positive serology but no symptoms and without evidence of chronic disease (indeterminate form); (b) mega disease (groups I, II, III, and IV); (c) cardiomyopathy (mild, moderate, and severe); and (d) those with both mega disease and cardiomyopathy (combined form). The mean enzyme-linked immunosorbent assay and complement fixation antibody levels among the various clinical groups showed no statistical differences. With the direct agglutination test patients with mega disease and those with severe cardiomyopathy had slightly higher mean titers than patients in the indeterminate group and those with mild or moderate cardiomyopathy. While there may be possible reasons for these differences, the biological relevance of the findings was concluded to be of dubious significance.

Adult↗

Tissue-reacting immunoglobulins in patients with different clinical forms of Chagas' disease.

Antibodies against endocardium, blood vessels, interstitium, and plasma membrane of skeletal and heart muscle cells (EVI), as well as antibodies against structures from peripheral nerve (PN), were studied in serum samples from 27 individuals with negative Trypanosoma cruzi serology and 102 seropositive individuals with or without Chagas' disease from the State of Goiás, Brazil. Although significantly higher titers of EVI and PN antibodies were found in some of the seropositive individuals their presence was not correlated with the clinical symptoms and signs which characterize the chronic stage of the disease, nor with the severity of the disease.

Antibodies↗

Mechanisms of tachycardia on standing: studies in normal individuals and in chronic Chagas' heart patients.

The reflex tachycardia induced by change from the supine position to a 70 degree head-up tilt was studied in conscious normal individuals and in patients with chronic Chagas' heart disease, known to constitute a model of parasympathetic denervation of the sinus node, in the absence of cardiac failure. Chagas' patients showed markedly decreased heart rate responses during the initial 10 s following tilt to upright posture. A similar response was obtained in normals after parasympathetic blockade with atropine. beta-Adrenergic blockade failed to produce a significant effect on the initial heart rate response of normals, but heart rate increment, at 1 and 5 min of tilt, was significantly reduced in normals and abolished in patients. These results indicate a biphasic mode of tachycardia elicited by the upright posture; initially it depends on parasympathetic withdrawal, sympathetic stimulation becoming the predominant mechanism when stabilisation is attained in the orthostatic position.

Adult↗

Abnormal heart rate responses during exercise in patients with Chagas' disease.

Normal subjects and cardiac chagasic patients without previous history of congestive failure or actual evidences of cardiac decompensation were exercised on a treadmill or a bicycle ergometer. Patients with less than the expected increase in heart rate during exercise were found to exhibit also an abnormal heart rate response to pharmacologic blockade and acute alterations in systemic vascular resistance. These results are in agreement with previous observations showing neuronal degeneration and autonomic impairment in chronic Chagas' heart disease.

Chagas Disease↗

Postural reflexes in chronic Chagas's heart disease. Heart rate and arterial pressure responses.

Studies of heart rate and blood pressure responses to 70 degrees head-up tilt and 30 degrees head-down tilt were conducted in normal subjects and in chronic cardiac chagasic patients without past or present cardiac decompensation. During steady state of tilt, heart rate alterations were less marked in the chagasic than in the control group. Vasodepressor syncope supervened in three cardiac chagasic patients, two of whom showed the distinctive feature of hypotension without reflex bradycardia. In these patients, vagal control of cardiac rate could not be demonstrated either following a full blocking dose of atropine or during sudden elevation of systemic arterial blood pressure. These results are interpreted in the context of the pathologic and functional derangements of autonomic control which occur in Chagas' heart disease.

Adult↗

Specific chemotherapy of Chagas disease: a comparison between the response in patients and experimental animals inoculated with the same strains.

Eleven strains of Trypanosoma cruzi were isolated from patients with Chagas disease in central Brazil by xenodiagnosis and inoculation into newborn mice. Biological characterization and isoenzyme analysis showed that 6 strains were type II (zymodeme 2) and 5 were type III (zymodeme 1). Patients were treated with benznidazole or benznidazole plus nifurtimox. Mice infected with each isolated strain were treated for comparison with the results obtained in the respective patient. Evaluation of cure of the patients was based on the indirect immunofluorescence test, complement fixation reaction and xenodiagnosis. For the mice, haemoculture, indirect immunofluorescence testing, xenodiagnosis and inoculation of blood into newborn mice were used. Tests were performed 3-6 months after the end of treatment. The cure rate was 66-100% in mice infected with type II strains and 0-9% in those infected with type III strains. The correlation between treatment results in patients and mice was 81.8% (9 of 11 cases). Type II strains were more susceptible to treatment, in contrast to type III strains which yielded the majority of therapeutic failures.

Adolescent↗