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Biomedical subjects

L A Benvenuti

Publications and source records attributed to L A Benvenuti.

At least 19 recordsLinked to original sources

Thyroxine-induced cardiac hypertrophy: influence of adrenergic nervous system versus renin-angiotensin system on myocyte remodeling.

The present study assessed the possible involvement of the renin-angiotensin system (RAS) and the sympathetic nervous system (SNS) in thyroxine (T4)-induced cardiac hypertrophy. Hemodynamic parameters, heart weight (HW), ratio of HW to body weight (HW/BW), and myocyte width were evaluated in absence of thyroid hormone (hypothyroidism) and after T4 administration. Male Wistar rats were used. Some were subjected to thyroidectomies, whereas hyperthyroidism was induced in others via daily intraperitoneal injection of T4 (25 or 100 microg x 100 g BW(-1) x day(-1)) for 7 days. In some cases, T4 administration was combined with the angiotensin I-converting enzyme inhibitor enalapril (Ena), with the angiotensin type 1 (AT1) receptor blocker losartan (Los) or with the beta-adrenergic blocker propanolol (Prop). Hemodynamics and morphology were then evaluated. Systolic blood pressure (SBP) was not altered by administration of either T4 alone or T4 in combination with the specific inhibitors. However, SBP decreased significantly in hypothyroid rats. An increased heart rate was seen after administration of either T4 alone or T4 in combination with either Los or Ena. Although the higher dose of T4 significantly increased HW, HW/BW increased in both T4-treated groups. Ena and Prop inhibited the increase in HW or HW/BW in hyperthyroid rats. Morphologically, both T4 dose levels significantly increased myocyte width, an occurrence prevented by RAS or SNS blockers. There was a good correlation between changes in HW/BW and myocyte width. These results indicate that T4-induced cardiac hypertrophy is associated with both the SNS and the RAS.

Animals↗

Cardiac rhabdomyomas exhibit a fetal pattern of atrial natriuretic peptide immunoreactivity.

Rhabdomyomas are the most common heart tumors seen in infancy. However, whether they represent hamartomas or true neoplasms derived from cardiomyocytes is still controversial. The fetal pattern of atrial natriuretic peptide (ANP) expression (predominant in the atrial and ventricular subendocardium) becomes altered during the early postnatal period to that typical of the adult (all atrial cardiomyocytes and some cells in the ventricular impulse-conducting system). To better comprehend the nature and origin of cardiac rhabdomyomas, we investigated the immunohistochemical expression of ANP in seven surgically excised ventricular specimens and two necropsy cases of multiple, atrial, and ventricular rhabdomyomas in children aged 1 to 34 days. Immunogold labeling for ANP at the ultrastructural level was also performed on three ventricular tumors. Although all atrial tumors were immunoreactive for ANP, these usually showed a variable number of faintly positive cardiomyocytes, contrasting with the diffuse and intense immunoreactivity of the surrounding atrial myocardium. ANP was detected in the ventricular tumors of five (56%) of the nine cases. The positive ventricular tumor cells predominated in the subendocardium and areas with prominent fibrous tissue, usually around blood vessels. Immunoelectron microscopy of the ventricular tumors demonstrated rare, positive cytoplasmic granules surrounded by membranes, usually located near the nuclei. We conclude that cardiac rhabdomyomas exhibit a fetal pattern of ANP immunoreactivity, which suggests delayed maturation of the tumoral cardiomyocytes, reinforcing the notion that cardiac rhabdomyomas are fetal hamartomas.

Atrial Natriuretic Factor↗

Histoplasmosis as a late infectious complication following heart transplantation in a patient with Chagas' disease.

Infectious complications following heart transplantation are an important cause of morbidity and mortality. Generally, bacterial infections are predominant; however, fungal infections can be responsible for up to 25% of infectious events. We report the case of a patient who presented with histoplasmosis as an infectious complication five years after heart transplantation due to a chagasic cardiopathy. This association has rarely been reported in the international literature.

Adult↗

Absence of the aortic valve associated with hypoplastic left-sided heart syndrome.

In this report we describe the twelfth case in the literature of absence of the aortic valve cusps, associated with hypoplastic left-sided heart syndrome in a neonate. Clinical and hemodynamic conditions in our patient resemble the classical features of this syndrome except for a greater development of the ascending aorta and the left ventricular cavity, due to aortic insufficiency. A patch was unsuccessfully inserted at the aortic annulus to exclude the left ventricle from the circulation. In addition the Norwood operation was performed.

Aortic Valve↗

Apical aneurysm and left ventricular hypertrophy.

A 59-year-old woman presented with an embolic transient ischemic attack and a history of controlled hypertension for 16 years. Both echocardiogram and MRI showed severe biventricular hypertrophy and an apical aneurysm with a thrombus. The occurrence of an apical aneurysm in the presence of cardiac hypertrophy is a rare finding and has been described in patients with hypertrophic cardiomyopathy. However, it has not been reported in patients with systemic arterial hypertension. In this patient the lack of a relationship between the severity of the hypertrophy and the levels of blood pressure, together with the presence of histologic disorganization of myocardial cardiac muscle cells by endomyocardial biopsy suggested the diagnosis of hypertrophic cardiomyopathy.

Biopsy↗

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.

Acute Disease↗

Reactivation of Chagas' disease in a human immunodeficiency virus-infected patient leading to severe heart disease with a late positive direct microscopic examination of the blood.

We report a human immunodeficiency virus (HIV)-infected man with chronic Chagas' disease who developed a congestive heart failure that could not be clinically controlled. Endomyocardial biopsy revealed severe myocarditis and the xenodiagnosis result was positive, but Trypanosoma cruzi by direct microscopic examination of the blood was found only four months after the symptoms had started. Treatment with benznidazole was effective in reducing parasitemia, stabilizing the clinical status, and controlling tissue damage related to the parasite. Although the finding of T. cruzi trypomastigotes by direct microscopic examination of the blood has been considered the mark of Chagas' reactivation in immunocompromised patients with chronic disease, in this case it was a late finding.

AIDS-Related Opportunistic Infections↗

An in situ quantitative immunohistochemical study of cytokines and IL-2R+ in chronic human chagasic myocarditis: correlation with the presence of myocardial Trypanosoma cruzi antigens.

Inflammatory cells positive for the cytokines IL-2, IL-4, IL-6, TNF-alpha, and IFN-gamma and for IL-2R, as well as CD8+ and CD4+ T cells and B cells were quantified using an immunoperoxidase technique in 25 fresh myocardial fragments from patients presenting with chronic chagasic cardiomyopathy. The presence of Trypanosoma cruzi antigens (Ags) in the myocardium was also investigated. The cases were grouped into group A (no Ag), group B (scarce extramyocardial fiber Ags), and group C (intramyocardial pseudocysts and extramyocardial fiber Ags). IL-2 was detected in very few cells (0.30 +/- 0.40 positive cells/hpf), suggesting immunological imbalance in chronic chagasic patients. IFN-gamma+ was the cytokine most frequently demonstrated (7.52 +/- 5.87 positive cells/hpf) and there was a good correlation between the number of IFN-gamma+ cells and CD8+ T cells in group A. IL-4+ cells were present in higher numbers in group C (2.78 +/- 1.49 positive cells/hpf). TNF-alpha+ (1.59 +/- 1.68 positive cells/hpf) and IL-6+ (2.76 +/- 2.32 positive cells/hpf) cells were present in moderate numbers. Fewer B cells were present, not related with the intensity of T. cruzi Ags. These results suggest that cytokines, as they occur in other infectious diseases, play a fundamental role in the control of T. cruzi in chronic human chagasic disease. A fatal outcome seems to be associated with the increased production of cytokines derived from the Th2 subpopulation of the CD4+ T cells.

Animals↗

Immunohistochemical expression of atrial natriuretic peptide (ANP) in the conducting system and internodal atrial myocardium of human hearts.

Expression and distribution of atrial natriuretic peptide (ANP) were studied immunohistochemically in the conducting system and internodal atrial myocardium of 5 adult human hearts. Myocytes from the sinus node and compact atrioventricular node were usually ANP-negative; only a very few cells exhibited ANP immunoreactivity. These ANP-positive myocytes were small and did not appear to be trapped working atrial myocytes which are larger than nodal cells. The transitional cell zones of the sinus node and the atrioventricular node were composed of bundles of ANP-positive myocytes, intermingled with non-reactive myocytes. The internodal atrial myocardium exhibited a comparable intensity of myocyte staining in each case examined. Thus, morphologically distinct connecting pathways between the sinus node and the atrioventricular node with regard to myocyte ANP immunoreactivity could not be demonstrated, reinforcing the notion that they actually do not exist. The penetrating bundle, branching bundle and bundle branches were usually composed of ANP-negative myocytes although some ANP-positive myocytes were observed in the branching bundle and bundle branches in 4 cases. Myocytes from the ventricular conducting tissue presenting ANP immunoreactivity have been designated Purkinje fibers and have been found in several mammalian species.

Adult↗

Association of an increase in CD8+ T cells with the presence of Trypanosoma cruzi antigens in chronic, human, chagasic myocarditis.

The role of Trypanosoma cruzi in the pathogenesis of myocarditis in the chronic phase of Chagas' disease is still controversial, with autoimmune mechanisms frequently being proposed. In the present work, we demonstrate that higher numbers of CD8+ T cells are correlated with the presence of parasite antigens, suggesting an important role for the parasite in the development of myocardial inflammation. Quantification of the mean numbers of CD8+ and CD4+ T cells per 400x microscopic field was performed in myocardial specimens from 33 chronic chagasic patients with heart failures (nine biopsies and 24 necropsies), using an immunoperoxidase technique. The cases were grouped according to a semiquantitative score of the relative amounts of T. cruzi antigens: group 1 = absent (14 cases); group 2 = scarce extracellular or intramacrophagic antigens (12 cases); group 3 = many extracellular or intramacrophagic antigens plus T. cruzi intramyocytic pseudocysts (seven cases). The mean numbers of CD8+ and CD4+ T cells in groups 1,2, and 3 were 6.94 and 3.79, 13.89 and 6.24, and 17.91 and 5.97, respectively. The numbers of CD8+ T cells in groups 2 and 3 were significantly higher compared with group 1 (no T. cruzi antigens), but were not different from each other. Scarce, extramyocytic T. cruzi antigens were associated with an intense inflammatory infiltrate, suggesting that delayed-type hypersensitivity immune mechanism is induced by the parasite; intact myocardiocytes containing parasites did not show an inflammatory reaction around them. A poor inflammatory response was frequently associated with many extramyocytic antigens and myocardial parasite pseudocysts, suggesting that active proliferation and dissemination of the parasites occur when the immunologic response is diminished. The number of CD4+ T cells did not vary significantly among the three groups. We conclude that the CD8+ T cell is the main cell type responsible for immune activation in chronic, human, chagasic myocarditis and is probably activated by the presence of T. cruzi antigens associated with internal myocytic host antigens. The absence of a significant member of CD4+ T cells in the presence of T. cruzi antigens suggests inhibition of CD4+ T cell activation or the lack of a class II major histocompatibility complex molecule presentation mechanism.

Antigens, Protozoan↗

Immunohistochemical detection of atrial natriuretic peptide (ANP) in the chief cells of human carotid bodies.

The presence of atrial natriuretic peptide (ANP) was investigated in human carotid bodies using an immunoperoxidase technique. Immunoreactivity was observed in the chief cells alone, distributed in a homogeneous cytoplasmic pattern, quite different from the granular cytoplasmic pattern known for atrial myocytes. We conclude that ANP is present in human carotid bodies, where it may be synthesized or internalized by the chief cells.

Adult↗

Primary lipomatous tumors of the cardiac valves.

A tricuspid valve mass was identified on echocardiogram in a 69-year-old man with ischemic heart disease, chronic obstructive pulmonary disease, pulmonary embolism, and pneumonia; he died with progressive respiratory insufficiency. The abnormal mass was ascribed initially to infective endocarditis, and the diagnosis at autopsy was fibrolipoma, a benign tumor. Although rare, valve tumors should be included in the differential diagnosis of abnormal valve masses identified on echocardiogram.

Aged↗

Regression of ST segment elevation after thrombolysis in acute aortic dissection.

A 55-year-old man was admitted to the hospital with chest pain and electrocardiogram consistent with the diagnosis of evolving myocardial infarction. Treatment with streptokinase was administered, resulting in clinical and electrocardiographic signs of reperfusion. Hypotension and ST segment elevation occurred 2 hours later and cardiac catheterization was done. At catheterization the diagnosis of aortic dissection was made, but the patient died before surgery. Thus, clinical and electrocardiographic signs of reperfusion after streptokinase may occur in patients with aortic dissection and myocardial infarction.

Acute Disease↗

Severe and fatal mass attacks by 'killer' bees (Africanized honey bees--Apis mellifera scutellata) in Brazil: clinicopathological studies with measurement of serum venom concentrations.

In São Paulo State, Brazil, five males, aged between 8 and 64 years, were attacked by 'Africanized' honey bees (Apis mellifera scutellata). The estimated number of stings received by each patient ranged from > 200 to > 1000. All five were transferred to intensive care units in São Paulo City. Clinical features included intravascular haemolysis, respiratory distress with ARDS, hepatic dysfunction, rhabdomyolysis (with myoglobinaemia and myoglobinuria), hypertension and myocardial damage (perhaps explained by release of endogenous catecholamines by venom phospholipase A2 and mellitin), shock, coma, acute renal failure and bleeding. Laboratory findings included gross neutrophil leucocytosis, elevated serum enzymes [AST, ALT, LDH, CPK (predominantly CPK-MM)] and creatinine. Clotting times were slightly prolonged. Despite treatment with antihistamines, corticosteroids, bronchodilators, vasodilators, bicarbonate, mannitol and mechanical ventilation, three of the patients died between 22 and 71 h after the attacks, with histopathological features of ARDS, hepatocellular necrosis, acute tubular necrosis, focal subendocardial necrosis and disseminated intravascular coagulation. Whole bee venom and phospholipase A2 (PLA2) antigen concentrations were measured in serum and urine for the first time, using enzyme immunoassay. High venom and PLA2 concentrations were detected in serum and urine for more than 50 h after the stings in two fatal cases, in one of which the total circulating unbound whole venom was estimated at 27 mg, one hour after the attack. An antivenom should be developed to treat the increasing numbers of victims of mass attacks by Africanized 'killer' bees in USA, Middle and South America.

Adolescent↗