[Chagas disease. Importance of the parasite in the pathogenesis of the cardiac chronic disease].
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Biomedical subjects
Publications and source records attributed to M L Higuchi.
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PURPOSE: To analyze macro and microscopic features of atherosclerotic plaques located in bifurcation of coronary arteries, defining their spatial disposition in those sites. METHODS: We studied 38 bifurcations of coronary arteries of patients whose cause of death was related to coronary artery disease. Histologic sections of 0.5mm were sequentially made from the main artery to the secondary branches. They were stained with hematoxilin-eosin technique. Histological analysis evaluated: a) morphologic composition of the plaques, b) degree of obstruction and c) plaque's disposition. RESULTS: a) Plaque's composition: fibrolipid plaques constituted 80% of the cases and mingled focal atrophy of the media at the base of the plaque in 61% with spots of total destruction and rupture of the elastic layers in 30%; b) degree of obstruction: ranged from 20% to 95%, with average 60 +/- 28%; c) disposition of plaques: we verified morphologic variation along the plaque, most of them (71%) being eccentric at bifurcation and not reaching the beginning of flow divider walls. CONCLUSION: Atherosclerotic plaques located in bifurcation of coronary arteries of adults are often fibrolipid plaques, eccentric, and their spatial disposition on those sites spare the beginning of the inner walls, reaching the outer walls.
The infection developed by Wistar Furth rats inoculated with the Y strain of Trypanosoma cruzi was the experimental model used in our study. The results showed that this infection altered considerably the CD4/CD8 lymphocyte subset ratio and the natural cytotoxic activity of mononuclear cells in the spleen, blood, and myocardial tissue. Concomitantly, an expansion of the number of cells expressing major histocompatibility complex (MHC) class II antigens was observed, as well as spontaneous development of high levels of blast cells, mainly in the spleen. The inflammatory infiltration of the myocardium, made up essentially of CD8+ cells (cytotoxic/suppressor T cells, natural killer cells), was initially found at 9 days postinfection, spread continuously, and was observed until the death of the animals at about 18 days postinfection. T. cruzi infection also enhanced the natural killer activity of mononuclear cells in the blood, spleen, and myocardium. Sorting these cells by affinity columns showed that the natural killer function was performed exclusively by the CD8+ population, which did not express MHC class II antigens. It was shown that the polyclonal T-lymphocyte activation induced by T. cruzi infection results in a wide distribution of CD8+ cells with enhanced natural cytotoxic activity in the spleen, blood, and cardiac tissue.
We report a case of fatal chagasic meningoencephalitis in an AIDS patient. Acute exacerbation of chronic Chagas' disease with involvement of the CNS is uncommon and occurs only in immunocompromised patients. This is the third such reported reactivation and it underscores the importance of considering Chagas' disease in HIV-positive patients from endemic regions.
STUDY OBJECTIVE: The aim was to investigate alterations in sulphated glycosaminoglycans in aortic dissection. DESIGN: Aortic fragments were taken from 10 patients within the first 3 d after onset of symptoms of aortic dissection and from nine age matched patients with no aortic disease. Sulphated glycosaminoglycans were analysed and quantified by agarose gel electrophoresis and densitometry after degradation with specific enzymes. MEASUREMENTS AND MAIN RESULTS: The amount of chondroitin sulphate was similar (7.14 v 7.60 mg.g-1 of dry tissue, n = 10, p greater than 0.5) in patients with dissection and in the control group. Total sulphated glycosaminoglycan content was decreased (11.51 v 14.26 mg.g-1 of dry tissue, n = 10, p less than 0.001). This difference was due to heparan sulphate (1.79 v 2.48 mg.g-1 of dry tissue, n = 10, p less than 0.05) and mainly to dermatan sulphate (2.58 v 4.18 mg.g-1 of dry tissue, n = 10, p less than 0.001). The ratio of 6-/4-sulphated disaccharides after chondroitinase ABC digestion was increased in the affected group. No correlation between these biochemical results and a histological evaluation of mucoid content was found. On the other hand, a significant increase in chondroitin sulphate could be observed related to aging. CONCLUSIONS: The diminution in sulphated glycosaminoglycans and its possible relationship with fat, collagen, and other extracellular matrix molecules could lead to a weakness in the aortic wall related to the dissection.
Fourty-four patients (aged 10 months to 15 years) were assessed in a double-blind study to observe the correlation between myocardial uptake of 67-gallium and endomyocardial biopsy in the detection of moderate to severe myocardial inflammation. The sensitivity and specificity of gallium-67 imaging were 87 and 81%, respectively. Based on these findings, immunosuppressive therapy can be assigned to children with dilated cardiomyopathy and positive myocardial uptake, since moderate and severe myocardial inflammation may be detected by this non-invasive method.
PURPOSE: To analyse hemodynamic parameters (left ventricles ejection fraction, cardiac index, mean pulmonary wedge pressure and left ventricle diastolic diameter, in a group of children with active myocarditis (diagnosed by endomyocardial biopsy) pre and post treatment with conventional therapy and immunosuppressive drugs (isolated prednisone or prednisone associated with azathioprine or cyclosporine). PATIENTS AND METHODS: Forty-four pediatric patients with active myocarditis were studied. Twenty males and 24 females from 10 months to 15 years old (median = 1.3 years). All patients were submitted to hemodynamic study and endomyocardial biopsy. The hemodynamic parameters mentioned above were analysed before and after the proposed therapy. The patients were distributed in group according to the admission in the protocol, group I (9 pts)--conventional therapy (CT); group II (12 pts)--CT plus prednisone; group III (16 pts)--CT plus prednisone plus azathioprine; group IV (13 pts)--CT plus prednisone plus cyclosporine. RESULTS: Forty-four patients were submitted to four different groups of therapeutic protocol. The hemodynamic parameters were analysed in each of them. Left ventricle ejection fraction were no significantly different in the pre and post therapeutic scheme in group I and II, they were significantly higher (p less than 0.05) in group III and IV. The same happened with cardiac index. The mean pulmonary wedge pressure no presented statistical differences in group I and II before and after treatment but significantly lower lends were observed in group III and IV. The same behavior were noted in the left ventricle end diastolic diameter. CONCLUSION: The association of azathioprine or cyclosporine to prednisone presented better results in the left ventricle function, when compared with conventional drugs or isolated use of prednisone, based in the analysis of same hemodynamic parameters.
PURPOSE: To evaluate immunosuppressive drugs on the treatment of myocarditis. PATIENTS AND METHODS: Right ventricular endomyocardial biopsy was performed in 102 patients with dilated cardiomyopathy. According to histopathologic aspect the patients were divided into two groups: I--with active lymphocytic myocarditis (ALM); II--without ALM: 51 patients. Ten patients from group I (Ib), with moderate or intense myocarditis were treated with prednisone and azathioprine during six months. RESULTS: After six months of observation, in group Ia (41 patients): 41 improved, 22% worsened and 12% died; in group Ib (10 patients): 60% improved, 10% worsened and 30% died; 51 patients in group II: 59% improved, 17% worsened and 10% died. Control biopsy on group Ib showed decrease of myocarditis in 62%. CONCLUSION: Immunosuppressive drugs do not always improve quality of life, or increase the survival, although in more than 50% of the cases it was possible to control inflammatory process.
The authors present the case of a 9-month-old child with clinical dilated cardiomyopathy that at necropsy showed myocardial cells with volumous, bizarre, and pleomorphic nuclei. These nuclear alterations were also found in other tissues. The myocardial ultrastructural studies revealed degenerative cytoplasmatic changes, nuclear membrane invaginations forming tubules, vesicles, and cytoplasmatic pseudoinclusions, and intranuclear vermicelar bodies, which all suggest virus-induced lesions. Although the ultrastructural studies and immunoperoxidase tests for virus identification were negative, the authors believe that a virus is most probably the agent of these alterations. This case seems to be the first reported on dilated cardiomyopathy with bizarre nuclear alterations in the myocardial fibers having strong evidence pointing to viral etiology.
The authors describe the clinical-pathologic findings in four patients with myocardial infarct (MI) associated with Chagas' disease, found among 181 autopsies of chronic congestive cardiac chagasic patients. Organized thrombo-embolus was found in the epicardial portion of a coronary artery in one instance and thrombosis in the apex of the left ventricle as well as systemic infarcts were found in all cases. These data suggest thrombo-embolism, probably from the apex of the left ventricle, as a possible cause for the regional (large; transmural) MI in chronic Chagas' heart disease. The mechanism usually operative in MI, i.e. complicated atherosclerosis, was not present in the patients of this series. Moreover, our data do not support either small artery disease or heart denervation as etiologic factors for regional MI.
In this study the histopathologic features of Chagas' disease and idiopathic dilated cardiomyopathy were compared in 38 patients with congestive heart failure, classes II or III. Biopsy specimens were obtained with the Stanford model needle for right ventricle. Twenty-two patients presented non-chagasic dilated cardiomyopathy, and 16 were carriers of Chagas' disease. Twenty-three were male and 15 were female; their ages varied 18 and 49 years (mean 35.5). Fibrosis was slightly more frequently and intense in Chagas' disease than in dilated cardiomyopathy. Myocarditis aspect also was more frequent in Chagas' disease than in dilated cardiomyopathy (62.4% vs. 50%), with all cases showing a chronic form; acute myocarditis was observed only in dilated myocardiopathy. These differences, however, did not reach statistical significance. In conclusion, the presence of fibrosis, hypertrophy and moderate to severe degrees of chronic inflammatory infiltrate are suggestive of but not pathognomonic of Chagas' disease. On the other hand, dilated myocardiopathies are more frequently associated with less fibrosis or hypertrophy and the presence of mild degree of inflammatory infiltrate. The arrangement of this inflammatory infiltrate tends to be diffuse in dilated cardiomyopathy and in chagasic myocarditis it is multifocal, very similar to the histopathological aspect found in myocardial rejections episodes of transplanted hearts.
1. Fragments of dog hearts submitted to 1, 6, 10, 24 and 48 h of autolysis at 20 degrees C were studied with freeze-fracture and thin-section techniques under the transmission electron microscope. 2. The freeze-fracture replicas revealed maximal reduction in the mean number and clustering of intramembrane particles at 6 h post mortem, indicating irreversible cellular damage. However, signs of lethal damage (intramitochondrial amorphous dense bodies) were not observed in thin sections of the same material. 3. The present study indicates that signs of irreversible damage similar to that occurring in in vivo ischemic alterations can be detected earlier by the freeze-fracture technique than by the thin-section technique.
The first case of a hyperacute rejection of a human cardiac allograft in Brazil is reported. The histopathological aspects of hyperacute cardiac rejection in its earlier moments are described when degenerative and necrotic features of the cardiac fibers are not totally developed. The authors believe that neutrophilic exudation and lesion of the vessel wall are good signs for a correct diagnosis of hyperacute rejection. Furthermore, they observed that the process is diffuse enough to justify the indication of endomyocardial biopsy when there are reasons to suspect this diagnosis. Presence of IgM and complement (C3) are also useful.
The authors analyze the presence of active myocarditis in endomyocardial biopsies from 38 patients with chronic Chagas' disease diagnosed serologically. The patients were divided into three clinical groups of increasing severity. Group I: 13 patients with normal electrocardiograms, normal chest x-rays, and no symptoms; Group II: 13 patients with abnormal electrocardiograms and no cardiomegaly; and Group III: 12 patients with abnormal electrocardiograms, cardiomegaly and heart failure. In order to diagnose myocarditis activity, two sets of criteria were used: one mainly observing histopathologic aspects of inflammatory cells aggressing cardiac fibers; and the other counting the mean number of lymphocytes per high power microscopic field. The results of both methods showed a higher incidence of active myocarditis in the clinical group with heart failure. The present report clearly shows the important role played by activity of myocarditis in the development of heart failure in chronic Chagas' disease. Therefore, the possibility of using drugs to control early stages of the activity of the inflammatory process is suggested. On the other hand, endomyocardial biopsy (EMB) seems to be an adequate method to evaluate the intensity of the cardiac inflammatory process in Chagas' heart disease.
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Right ventricular endomyocardial biopsy was used to study myocardial involvement in 42 patients with chronic Chagas' disease. Patients were divided into three groups: group A included 16 patients with normal ECGs, normal chest x-rays, and no symptoms; group B included 15 patients with abnormal ECGs and no cardiomegaly; and group C included 11 patients with abnormal ECGs and cardiomegaly. Biopsy fragments were analyzed for hypertrophy, degeneration of myocardial fibers, and interstitial changes such as edema, fibrosis, and inflammatory infiltrate. In group A, 5 of 16 biopsies exhibited none of the previously mentioned alterations. The frequencies pathologic alterations in groups A, B, and C, respectively, were: hypertrophy 31%, 66%, and 100%; degeneration 50%, 86%, and 81%; edema 43%, 46%, and 36%; fibrosis 12%, 33%, and 54%; and inflammatory infiltrate 37%, 66%, and 65%. These data suggest that myocardial lesions of Chagas' disease represent a continuous progression from fiber destruction to substitution by fibrosis, with compensatory hypertrophy; these data also suggest that cardiac dilatation occurs when the extent of fibrosis no longer allows for efficient compensatory hypertrophy.
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