Description of Lyme disease-like syndrome in Brazil. Is it a new tick borne disease or Lyme disease variation?

An emerging clinical entity that reproduces clinical manifestations similar to those observed in Lyme disease (LD) has been recently under discussion in Brazil. Due to etiological and laboratory particularities it is named LD-like syndrome or LD imitator syndrome. The condition is considered to be a zoonosis transmitted by ticks of the genus Amblyomma, possibly caused by interaction of multiple fastidious microorganisms originating a protean clinical picture, including neurological, osteoarticular and erythema migrans-like lesions. When peripheral blood of patients with LD-like syndrome is viewed under a dark-field microscope, mobile uncultivable spirochete-like bacteria are observed. PCR carried out with specific or conservative primers to recognize Borrelia burgdorferi sensu stricto or the genus Borrelia has been negative in ticks and in biological samples. Two different procedures, respectively involving hematoxylin and eosin staining of cerebrospinal fluid and electron microscopy analysis of blood, have revealed spirochetes not belonging to the genera Borrelia, Leptospira or Treponema. Surprisingly, co-infection with microorganisms resembling Mycoplasma and Chlamydia was observed on one occasion by electron microscopy analysis. We discuss here the possible existence of a new tick-borne disease in Brazil imitating LD, except for a higher frequency of recurrence episodes observed along prolonged clinical follow-up.

Decrease in sulphated glycosaminoglycans in aortic dissection--possible role in the pathogenesis.

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.

Fatal meningoencephalitis caused by reactivation of Trypanosoma cruzi infection in a patient with AIDS.

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.

Histological evidence of concomitant intramyocardial and epicardial vasculitis in necropsied heart allografts: a possible relationship with graft coronary arteriosclerosis.

BACKGROUND: The significance of medial lymphocytic vasculitis in intramural coronary vessels in heart transplantation is very poorly understood. This study was designed to identify histological evidence of an association between the presence of epicardial coronary lesions and the occurrence of intramyocardial vasculitis and/or myocardial ischemia. METHODS: We analyzed the frequency of medial vasculitis and other myocardial histological alterations in a retrospective study of 24 human cardiac allografts from patients who died of ischemic heart disease and/or myocardial rejection. RESULTS: Medial lymphocytic vasculitis in the myocardium was associated with vasculitis in the vasa vasorum of the epicardial coronary arteries and the presence of microfoci of acute myocardial infarction but was independent of the occurrence of myocardial fiber rejection. Chronic graft epicardial arteriopathy revealed two patterns of lesions. One pattern was similar to that of usual atherosclerosis, compromising mainly the proximal segments of the coronary artery, and was not associated with intramural vasculitis. The other pattern demonstrated diffuse involvement of the epicardial artery associated with vasculitis of its vasa vasorum and lymphocytic vasculitis of the intramural vessels. This second type of epicardial coronary lesion seemed to evolve to fibrotic arteries with thinned walls, frequently demonstrating aneurysmal dilatation with severe fibrosis of the adventitia and poor vasa vasorum. CONCLUSION: Medial vasculitis affecting intramyocardial vessels is associated with adventitial epicardial coronary vasculitis in the transplanted heart. The process of vasculitis may be involved in the development of chronic graft arteriosclerosis and is associated with ischemic myocardial lesions, but seems independent of myocardial fiber rejection.

Gamma delta T cells play no major role in human heart allograft rejection.

To investigate the role of gamma delta T cells in human heart transplantation, we searched for this T cell population in endomyocardial biopsies as well as in T cell lines and clones derived from graft-infiltrating lymphocytes. The number of gamma delta T cells in endomyocardial biopsies from transplanted patients (n = 55) was mostly low and did not differ significantly from nontransplanted patients (n = 21). Moreover, there was no association of gamma delta T cell distribution with rejection status or with time posttransplantation. Graft-derived T cell lines were established in the presence of autologous feeder cells and recombinant interleukin-2 to favor the growth of in vivo-activated T cells. Twenty T cell lines analyzed by flow cytometry showed low percentages of gamma delta T cells, and we were unable to obtain gamma delta T cell clones for functional studies. These results show that gamma delta T cells are poorly expressed on human heart allograft infiltrates and indicate that, when present, they are not activated in the graft. Our data suggest that gamma delta T cells do not have a major role in human heart rejection.

Usefulness of T-cell phenotype characterization in endomyocardial biopsy fragments from human cardiac allografts.

The mean numbers of cytotoxic/suppressor (CD8+) and helper/inducer (CD4+) T cells were determined in 111 successive endomyocardial biopsy fragments from eight cardiac allograft patients in an attempt to define their significance in the rejection process. Endomyocardial fragments from autopsy or donor hearts without myocarditis were evaluated as controls. The mean numbers of CD8+ and CD4+ T cells in the control group were 0.8 and 0.5 cells/field at x400 magnification, respectively. The mean numbers of CD8+ T cells per field in the cardiac allograft biopsies were 2.4, no rejection group; 5.4 mild rejection group; 11.1, moderate rejection group; and 4.9, resolving rejection group. The mean numbers of CD4+ T cells per field for the same groups were slightly lower than those of the CD8+ T cells. The number of CD8+ T cells per field reliably indicated the severity of rejection. Patients with normal numbers of CD8+ T cells and no evidence of rejection had better long-term outcomes (two or fewer moderate rejection episodes) than those with higher numbers. Analysis of the data suggests that the presence of two or fewer CD8+ T cells/field may be considered normal in the myocardial interstitium. The diagnosis of no evidence of rejection should be coupled to the presence of a normal number of CD8+ T cells. High numbers (greater than 10) of CD8+ T cells, even in absence of myocytolysis, should be treated more assertively, including the use of high doses of prednisone, because all our cases with high numbers showed a worse histologic picture at the subsequent biopsy.(ABSTRACT TRUNCATED AT 250 WORDS)

Higher incidence of malignant neoplasms after heart transplantation for treatment of chronic Chagas' heart disease.

BACKGROUND: Heart transplantation is a new therapeutic procedure to treat heart failure resulting from Chagas' disease. Experimental studies have demonstrated neoplastic effects of benznidazole, which is used for treatment of Trypanosoma cruzi infection. We compared the incidence and characteristics of neoplasia after heart transplantation for treatment of chronic Chagas' disease with those of other diseases. METHODS: Sixteen patients with Chagas' disease and 75 patients with other diseases underwent heart transplantation. Benznidazole was administered to 14 patients with Chagas's disease either for prophylaxis (4 patients) or for treatment of Chagas' disease reactivation (10 patients). RESULTS: The survival rate of patients in the nonchagasic group was 90% at 1 year and 82.4% at 2 years, and the survival rate in the chagasic group was 63% at 1 year and 57% at 2 years. Six of 16 patients (37.5%) with Chagas' disease had malignant tumors after a mean follow-up time of 25.3+/-2.1 months in contrast to 2 of 75 patients (2.7%) in the nonchagasic group after 34.6+/-3.6 months of follow-up. In the chagasic group, lymphoproliferative disorder was diagnosed in three patients, Kaposi's sarcoma in two, and squamous cell carcinoma in one patient. Reactivation of T. cruzi infection was diagnosed in all patients who had lymphoproliferative disorder. One patient without Chagas' disease had lymphoproliferative disorder in the lung, and another had malignant schwannoma affecting the skin. CONCLUSIONS: We found a higher incidence of malignant neoplasia after heart transplantation for treatment of chronic Chagas' disease. It is likely that the neoplasia is the result of chronic infection with an immunomodulator protozoan, immunosuppression, reactivation of the T. cruzi infection, or the toxicity of therapeutic intervention with benznidazole.

Acute myocardial infarction with diffuse endarteritis, contraction bands, and distal thrombosis of the coronary arteries in a heart transplant patient.

The case history of a heart transplant patient who died of an acute myocardial infarction 6 months after the procedure is described. The finding of contraction bands and thrombosis associated with endarteritis suggests that coronary vasospasm may have contributed to the acute myocardial infarction during an episode of vascular rejection.

Upregulation of adhesion molecules and class I HLA in the myocardium of chronic chagasic cardiomyopathy and heart allograft rejection, but not in dilated cardiomyopathy.

The immunohistochemical expression of adhesion molecules and class I HLA in chronic chagasic cardiomyopathy were compared with heart allograft rejection and dilated cardiomyopathy, to obtain new knowledge on the occurrence of autoimmunity and inflammation in the pathogenesis of chronic chagasic cardiomyopathy. Semiquantitative immunohistochemistry was performed for CD8+ T cells, ICAM-1, VCAM-1, LFA-1, and class I HLA in frozen sections of myocardial biopsies from patients presenting chronic chagasic cardiomyopathy (group I, n = 12), heart allograft rejection (group II, n = 9) or dilated cardiomyopathy (group III, n = 9). A high mean number of CD8+ T cells/mm(2) was present in group I (18.26) and group II (28.60), but not in group III (0.83). The frequency of high expression for ICAM-1 and VCAM-1 on the endothelial and interstitial cells, and for class I HLA on the cardiomyocytes was greater in group I (100%, 33.3%, and 83.3%, respectively) and group II (100%, 66.7%, and 77.8%, respectively), compared to group III (66.7%, 0%, and 0%, respectively). ICAM-1 and VCAM-1 probably participate in the development of the lymphocytic inflammatory infiltrate present in chronic chagasic cardiomyopathy, as seen in heart allograft rejection. The overexpression of adhesion molecules and the induction of class I HLA on the cardiomyocytes are probably related to the high cytokine levels at the inflammatory sites in chronic chagasic cardiomyopathy. Although the induction of class I HLA on the cardiomyocytes is consistent with an autoimmune reaction, it should not be considered as irrefutable evidence for autoimmunity in chronic chagasic cardiomyopathy. The differential expression of adhesion molecules and class I HLA in dilated cardiomyopathy compared to chronic chagasic cardiomyopathy suggests differences in the pathogenesis of these cardiomyopathies.

Atheromas that cause fatal thrombosis are usually large and frequently accompanied by vessel enlargement.

Several lines of clinical evidence show that AMI frequently occurs at sites with mild to moderate degree of coronary stenosis. The degree of luminal stenosis depends on plaque deposition and degree of vessel remodeling, features poorly assessed by coronary angiography. This postmortem study tested the hypothesis that the size of coronary atheroma and the type of remodeling distinguish culprit lesion responsible for fatal AMI from equi-stenotic nonculprit lesion in the same coronary tree. The main coronary branches from 36 consecutive patients with fatal AMI were studied. The culprit lesion (Group 1) and an equi-stenotic nonculprit segment (Group 2) obtained in measurements of another coronary branch from the same patient were compared. Morphometry and plaque composition was assessed in both groups. Compared to Group 2, Group 1 had larger areas of: plaque 9.6 vs. 4.7 mm(2), vessel 12.7 vs. 7.4 mm(2) and lumen 1.7 vs. 1.2 mm(2); (P< .01). Positive remodeling was more frequent in Group 1 than Group 2: 21/30 (70%) vs. 8/26 (31%). Plaque area correlated positively with lipid core and macrophages and negatively with fibrosis and smooth muscle cells. Atherosclerotic plaques that cause fatal thrombosis are more frequently positively remodeled and tend to be larger than nonculprit plaques with the same degree of cross-sectional stenosis. We tested whether arterial remodeling and plaque size vary between segments containing a fatal thrombosed plaque versus an equi-stenotic nonculprit plaque. Culprit vessel segments had higher cross-sectional areas of intimal plaque and of vessel wall than equi-stenotic nonculprit plaques. The cross-sectional area of the vessel correlated positively with both the lipid core area and CD68(+) macrophage content, and negatively with fibrosis area and smooth muscle cell content. These results add elements explaining limitations of angiography in identifying plaques and provide new insights into the role of remodeling in plaque instability.

Autopsy findings in early and late postoperative death after partial left ventriculectomy.

BACKGROUND: Partial left ventriculectomy (PLV) is an alternative to heart transplantation for patients with severe heart failure. However, this procedure is accompanied by high morbidity and mortality. Therefore, we studied the hearts of 12 patients who underwent this procedure to increase our understanding of the causes of bad outcome. METHODS: We analyzed the autopsy hearts of 11 of 16 patients who died after PLV, and one heart from a patient who underwent heart transplantation. RESULTS: Six patients died less than 30 days postoperatively, 4 of cardiogenic shock, 1 of arrhythmia, and 1 of coagulopathy. Five patients died from 36 to 120 days after the procedure, 4 of cardiogenic shock and 1 of arrhythmia. The patient who underwent heart transplantation had a cardiogenic shock 230 days after PLV. Ten hearts weighed more than 500 g and nine had myocardial infarction that extended to the papillary muscles. Four patients had infarction of both papillary muscles and 3 of them had episodes of arrhythmia, suggesting some relation between these events. CONCLUSIONS: We found several important morphologic clues for bad outcome: infarction of both papillary muscles, which may be associated with the development of arrhythmia, and myocardial infarction and pericardial hemorrhage, which may contribute to the outcome of heart failure.

Determinants of midterm outcome of partial left ventriculectomy in dilated cardiomyopathy.

BACKGROUND: Partial left ventriculectomy has been proposed for treatment of severe cardiomyopathies. This study reports midterm results of this procedure in 37 patients with dilated cardiomyopathy. METHODS: All patients were in New York Heart Association class III (16) or IV (21). Partial ventriculectomy was associated with mitral annuloplasty in 27 patients and with mitral replacement in 2. RESULTS: There were seven operative deaths (18.9%). During a mean follow-up of 18.2+/-9.3 months, 9 more patients died. Actuarial survival was 56.7%+/-8.1% at 6 and 24 months. Analysis of factors influencing outcome showed that midterm survival was significantly affected only by myocardial cell diameter. Otherwise, functional class improved from 3.5+/-0.5 to 1.8+/-0.9 in the survivors (p < 0.001). Furthermore, left ventricular diastolic volume decreased from 523+/-207 to 380+/-148 mL (p < 0.001), and left ventricular ejection fraction increased from 17.1%+/-4.6% to 23%+/-8% (p < 0.001), whereas significant changes in cardiac index, stroke index, and pulmonary pressures were found at 1 month of follow-up. Although left ventricular diastolic volume tended to increase in the late postoperative period, left ventricular ejection fraction and hemodynamic variables did not change significantly. CONCLUSIONS: Partial ventriculectomy improves left ventricular function and congestive heart failure in patients with dilated cardiomyopathy for up to 24 months of follow-up. Nevertheless, this procedure's clinical application is limited by the high mortality observed in the first postoperative months. Otherwise, new perspectives may be advised by the identification that partial ventriculectomy results seem to be influenced by compromised myocardial cells.

Heart transplantation for chronic Chagas' heart disease.

BACKGROUND: Chagas' disease has been considered a contraindication to heart transplantation as Trypanosoma cruzi infection could recur after immunosuppression. METHODS: We report the follow-up of 22 patients who underwent orthotopic heart transplantation for treatment of end-stage chronic Chagas' heart disease, divided in two groups. Group 1 consisted of 9 patients operated on from September 1985 to June 1991, and group 2 patients underwent transplantation from July 1991 to June 1995. After our early experience with group 1, we attempted to use a lower cyclosporine dosage in group 2. RESULTS: Total actuarial survival at 24 months was 60%, and it was better for group 2 (33% for group 1, 80% for group 2, p = 0.008). Parasitemia occurred similarly in both groups, but Chagas' disease reactivation was seen in 5 group 1 patients and in 1 group 2 member (p < 0.002). Neoplasia developed in 5 group 1 patients and 1 group 2 patient, and contributed to death in 3 of them. CONCLUSIONS: These data demonstrate satisfactory outcome of cardiac transplantation in patients with end-stage Chagas' heart disease in the second phase of our experience. Further progress is necessary to improve the results and evaluate its proper role in the management of this disease.

Correlation between gallium-67 imaging and endomyocardial biopsy in children with severe dilated cardiomyopathy.

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.

The role of active myocarditis in the development of heart failure in chronic Chagas' disease: a study based on endomyocardial biopsies.

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.

Thin-section and freeze-fracture study of post-mortem changes in dog myocardium.

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.

Detection of Mycoplasma pneumoniae and Chlamydia pneumoniae in ruptured atherosclerotic plaques.

This paper reports what is apparently the first observation of Mycoplasma pneumoniae in association with Chlamydia pneumoniae in thrombosed ruptured atheromas. We performed electron microscopy and in situ hybridization in specimens from three patients who died of acute myocardial infarction. These patients had typical symptoms of acute ischemic syndrome. Mycoplasmas were present mainly in the lipid core of the ruptured thrombosed plaque. Vulnerable atheromas are rich in cholesterol and may favor the growth of mycoplasmas, the only microorganisms that require cholesterol for survival. We suggest that the association of Mycoplasma pneumoniae and Chlamydia pneumoniae may increase the virulence of these microorganisms, favoring proliferation, plaque inflammation and possibly plaque rupture.

[Analysis of the composition and spatial disposition of atherosclerotic plaques localized in epicardial coronary artery bifurcations in adults]. / Análise da composição e disposição espacial de placas ateroscleróticas localizadas em bifurcações das artérias coronárias epicárdicas de adultos.

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.

[Lymphocytic myocarditis. Response to treatment with immunosuppressive drugs]. / Miocardite linfocitária. Resposta ao tratamento com drogas imunossupressoras.

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.

[Comparison of histologic changes in Chagas' cardiomyopathy and dilated cardiomyopathy]. / Comparação entre alterações histológicas da miocardiopatia da doença de Chagas e cardiomiopatia dilatada.

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.