Total Artificial Heart as Bridge to Heart Transplantation in Chagas Cardiomyopathy: Case Report.

Chagas disease (CD) is becoming an increasingly recognized cause of dilated cardiomyopathy outside of Latin America, where it is endemic, due to population shifts and migration. Heart transplantation (HTx) is a therapeutic option for end-stage cardiomyopathy due to CD, but may be considered a relative contraindication due to potential reactivation of the causative organism with immunosuppression therapy. The total artificial heart (TAH) can provide mechanical circulatory support in decompensated patients with severe biventricular dysfunction until the time of HTx, while avoiding immunosuppressive therapy and removing the organ most affected by the causative organism. We report herein a patient with CD and severe biventricular dysfunction, who had mechanical circulatory support with a TAH for more than 6 months, followed by successful orthotopic HTx and treatment with benznidazole for 3 months. The patient had no evidence of recurrent disease in the transplanted heart based on endomyocardial biopsy up to 1 year post-transplantation, and remains alive more than 30 months after insertion of a TAH and 24 months after HTx.

Dobutamine-induced fever and isolated eosinophilic myocarditis in a 66-year-old male awaiting heart transplantation: a case report.

A 66-year-old male with non-ischemic dilated cardiomyopathy who presented for decompensated heart failure and heart transplant evaluation had to be temporarily delisted from the transplant list due to fever. No infectious source was identified and drug fever was suspected. Dobutamine was discontinued and his fever subsequently defervesced. He eventually received an orthotopic heart transplantation without complication. Explanted heart showed eosinophilic myocarditis with pathologic features consistent with a drug-induced pattern of myocarditis. Throughout the hospital course, he did not develop peripheral blood eosinophilia to suggest eosinophilic myocarditis. The importance of this report is to have a greater awareness of dobutamine-induced fever and eosinophilic myocarditis even in patients without peripheral eosinophilia. In febrile patients receiving prolonged dobutamine infusion with no other evidence of infection, consideration should be given to discontinuing dobutamine or switching to an alternative inotrope such as milrinone.

Heart transplantation for Chagas cardiomyopathy in the United States.

Since an initial case in 2006, we noted multiple patients undergoing heart transplantation (HTx) for Chagas cardiomyopathy (CC) at our transplant program. The clinical characteristics, laboratory results and outcomes of patients with CC undergoing HTx in the United States have not been reported previously. In 2010, we implemented a systematic screening and management program for patients undergoing HTx for CC. Before HTx, all patients with idiopathic dilated cardiomyopathy who were born in a Chagas disease endemic country were screened for Trypanosoma cruzi (TC) infection with serology. After HTx, monitoring for TC reactivation was performed using clinical visits, echocardiography, endomyocardial biopsy and serial whole blood polymerase chain reaction (PCR) testing. Between June 2006 and January 2012, 11 patients underwent HTx for CC. One patient was empirically treated due to the presence of TC amastigotes in explanted cardiac tissue. Two patients experienced allograft dysfunction due to TC reactivation and three patients experienced subclinical reactivation (positive PCR results), which were treated. Chagas disease is a common cause of dilated cardiomyopathy in patients from endemic countries undergoing HTx at a transplant program in the United States. Reactivation is common after transplantation and can cause adverse outcomes.

Toll-like receptor-4 is expressed by macrophages in murine and human lipid-rich atherosclerotic plaques and upregulated by oxidized LDL.

BACKGROUND: Inflammation is implicated in atherogenesis and plaque disruption. Toll-like receptor 2 (TLR-2) and TLR-4, a human homologue of drosophila Toll, play an important role in the innate and inflammatory signaling responses to microbial agents. To investigate a potential role of these receptors in atherosclerosis, we assessed the expression of TLR-2 and TLR-4 in murine and human atherosclerotic plaques. METHODS AND RESULTS: Aortic root lesions of high-fat diet-fed apoE-deficient mice (n=5) and human coronary atherosclerotic plaques (n=9) obtained at autopsy were examined for TLR-4 and TLR-2 expression by immunohistochemistry. Aortic atherosclerotic lesions in all apoE-deficient mice expressed TLR-4, whereas aortic tissue obtained from control C57BL/6J mice showed no TLR-4 expression. All 5 lipid-rich human plaques expressed TRL-4, whereas the 4 fibrous plaques and 4 normal human arteries showed no or minimal expression. Serial sections and double immunostaining showed TLR-4 colocalizing with macrophages both in murine atherosclerotic lesions and at the shoulder region of human coronary artery plaques. In contrast to TLR-4, none of the plaques expressed TLR-2. Furthermore, basal TLR-4 mRNA expression by human monocyte-derived macrophages was upregulated by ox-LDL in vitro. CONCLUSIONS: Our study demonstrates that TLR-4 is preferentially expressed by macrophages in murine and human lipid-rich atherosclerotic lesions, where it may play a role to enhance and sustain the innate immune and inflammatory responses. Moreover, upregulation of TLR-4 in macrophages by oxidized LDL suggests that TLR-4 may provide a potential pathophysiological link between lipids and infection/inflammation and atherosclerosis.

Adenomatoid tumor of the heart: report of a case.

We report a case of an adenomatoid tumor involving the heart. The lesion was found incidentally at the time of cardiac surgery, measured 1.0 cm, and was poorly demarcated from the adjacent myocardium. Microscopically, the tumor consisted of aggregates of relatively large, epithelioid cells that coalesced to form tubular spaces and occasionally branched into anastomosing channels. The neoplastic cells were strongly immunoreactive with antibodies against cytokeratin. The pathologic features of this unusual cardiac tumor are diagnostic of an adenomatoid tumor, a relatively rare benign neoplasm of mesothelial origin usually found in association with the genital tract. Although rare cases of adenomatoid tumors found outside of the genital tract have been described, including two recently reported pleural tumors, it has not been described to involve the heart.

Absence of endocardial lymphoid infiltrates (Quilty lesions) in nonheart transplant recipients treated with cyclosporine.

The clinical records and autopsy material from 14 patients treated with cyclosporine who were not recipients of cardiac allografts were reviewed to further study the nature of endocardial lymphoid infiltrates (quilty lesions). Although there was well-documented exposure to cyclosporine, no endocardial lymphoid infiltrates were identified in these cases, providing evidence that the endocardial-based Quilty lesion is not the result of the direct effect of cyclosporine and may represent a localized form of heart rejection confined to the endocardium.

Nature and significance of epicardial lymphoid infiltrates in cardiac allografts.

BACKGROUND: Myocardial lymphocytic infiltration after transplantation is usually a manifestation of acute cellular rejection. However, purely endocardial infiltrates are generally not regarded as rejection (so-called "Quilty lesions"). The nature of epicardial lymphoid infiltration in cardiac allografts and its significance when observed in endomyocardial biopsies or autopsies are uncertain. METHODS: Twenty-seven cases of transplant-associated epicardial lymphoid infiltration were identified; 16 cases were identified from 1602 consecutive transplant biopsy specimens from 125 patients, and 11 from 14 autopsies, ranging from 1 to 35 months (mean 7.8 months) after transplantation. RESULTS: The infiltrates were composed of aggregates of lymphocytes and histiocytes distributed throughout the epicardium. Plasma cells were found in 52% of cases, with occasional eosinophils and rare neutrophils. Most were vascular, and four autopsy cases had follicle formation. Twenty-four cases (93%) showed a mixed population of cells in a random distribution consisting of T cells in association with fewer B cells and histiocytes. Fifteen cases (nine autopsies, six biopsies) had acute rejection, and nine autopsies had chronic vascular rejection. Fourteen of twenty-four cases (58%) showed concurrent Quilty lesion (nine autopsies, five biopsies), and the remainder showed at least one Quilty lesion in an earlier biopsy. CONCLUSION: Epicardial lymphoid infiltrates occur with significant frequency after heart transplantation and can be associated with, and mimic, acute cellular rejection. However, they exhibit morphologic and immunophenotypic features which are distinguishable from rejection-associated infiltrates.

Zonal anatomy of the cervix: correlation of MR imaging and histologic examination of hysterectomy specimens.

High-resolution magnetic resonance (MR) images of nine hysterectomy specimens were correlated with light microscopy, computer-aided image analysis, and immunohistochemical examination to investigate the histologic counterparts of the zonal anatomy of the cervix. A central stripe of high signal intensity, a surrounding middle layer of low signal intensity, and an outer layer of intermediate signal intensity were found in all specimens. Histologic correlation indicated that the central stripe most likely represents the secretions in the canal, the cervical mucosa, and the plicae palmatae; the other two layers represent fibromuscular stroma. The percentage of nuclear area in the inner zone of the fibromuscular stroma is 2.5 times greater than in the outer zone, which may account for the lower signal intensity of the inner zone. No difference in distribution of collagen, laminin, and fibronectin (common components of the extracellular matrix) was found between the two zones of the cervical fibromuscular stroma.

Prognostic significance of tumor proliferative fraction and DNA content in stage I non-small cell lung cancer.

Analyses of tumor DNA content and proliferative fraction by flow cytometry have been useful as prognostic determinants in a variety of solid tumors. The significance of this analysis in Stage I (T1N0M0 and T2N0M0) non-small cell lung carcinoma (NSCC) is unestablished. We determined DNA content (ploidy) and proliferative fraction (percentage S phase) on 44 surgically resected Stage I NSCC specimens obtained between 1977 and 1982. All cases had a minimum follow-up of 5 yr. Of the 44 cases, 27 were adenocarcinomas, 15 squamous cell carcinomas, and 2 large cell carcinomas. Of these, 32 (73%) had T1N0M0 lesions and 12 (27%) had T2N0M0 lesions. Overall 5-yr survival was 70%. All patients surviving 5 yr were free of detectable tumor. Patients with T1N0M0 lesions had an 81% 5-yr survival, but those with T2N0M0 lesions had a 42% 5-yr survival (p = 0.009). Analysis of tumor DNA content revealed 35 diploid tumors (79%) and 9 aneuploid tumors (21%). The 5-yr survival for diploid tumors was 77% compared with a 44% 5-yr survival in aneuploid lesions (p = 0.048). The median proliferative fraction was 6%. All patients with a percentage S phase less than 6% survived 5 yr, and 41% (9 of 22) of those greater than 6% survived 5 yr (p less than 0.001). When 8% S phase was used as a cutoff, 93% (28 of 30) below the cutoff survived 5 yr but only 21% (3 of 14) above the cutoff survived 5 yr (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Autocrine angiotensin system regulation of bovine aortic endothelial cell migration and plasminogen activator involves modulation of proto-oncogene pp60c-src expression.

Rapid endothelial cell migration and inhibition of thrombosis are critical for the resolution of denudation injuries to the vessel wall. Inhibition of the endothelial cell autocrine angiotensin system, with either the angiotensin-converting enzyme inhibitor lisinopril or the angiotensin II receptor antagonist sar1, ile8-angiotensin II, leads to increased endothelial cell migration and urokinase-like plasminogen activator (u-PA) activity (Bell, L., and J. A. Madri. 1990. Am. J. Pathol. 137:7-12). Inhibition of the autocrine angiotensin system with the converting-enzyme inhibitor or the receptor antagonist also leads to increased expression of the proto-oncogene c-src: pp60c-src mRNA increased 7-11-fold, c-src protein 3-fold, and c-src kinase activity 2-3-fold. Endothelial cell expression of c-src was constitutively elevated after stable infection with a retroviral vector containing the c-src coding sequence. Constitutively increased c-src kinase activity reconstituted the increases in migration and u-PA observed with angiotensin system interruption. Antisera to bovine u-PA blocked the increase in migration associated with increased c-src expression. These data suggest that increases in endothelial cell migration and plasminogen activator after angiotensin system inhibition are at least partially pp60c-src mediated. Elevated c-src expression with angiotensin system inhibition may act to enhance intimal wound closure and to reduce luminal thrombogenicity in vivo.

Junctional zone of the uterus: correlation of MR imaging and histologic examination of hysterectomy specimens.

High-resolution magnetic resonance (MR) images of 12 hysterectomy specimens were correlated with results of light microscopy, image analysis, and immunohistochemical studies to investigate the histologic counterpart of the low-signal-intensity band, or junctional zone (JZ), that surrounds the bright central uterine stripe. All specimens were imaged with a 1.5-T superconducting magnet within 21/2 hours (on average) after hysterectomy. Comparison of histologic findings with measurements obtained at MR imaging indicates that the JZ represents the innermost layer of the myometrium. A threefold increase in percentage of nuclear area was found in the JZ in comparison with the outer myometrium, reflecting an increase in both size and number of nuclei. No difference in distribution of common components of the extracellular space (collagen, laminin, and fibronectin) was found between the two layers.

A distinctive cardiovascular lesion resembling histiocytoid (epithelioid) hemangioma. Evidence suggesting mesothelial participation.

This paper presents 14 examples of a distinctive cardiovascular lesion. The patients' ages ranged from 5 to 76 years (mean, 51 years). There were seven male patients and seven female patients. All of the lesions were small and represented incidental surgical findings. Ten were attached to the endocardium, three were free-floating in the pericardial cavity, and one was inside a dissecting aneurysm of the ascending aorta. Microscopically, the lesions were enclosed in a fibrinous network and composed of a solid proliferation of round to polygonal cells with centrally located nuclei. Immunohistochemically, the cells were negative for FVIII-related antigen and lysozyme, but they stained positively for keratin, especially when clustered in small micropapillary or tubule-like formations. The nature and pathogenesis of these lesions are uncertain. Their location and some of their microscopic features originally suggested a relationship with the entity described as histiocytoid (epithelioid) hemangioma. However, their intense immunoreactivity for keratin, occasional presentation in the pericardial sac, and marked morphologic similarities with nodular mesothelial hyperplasia as sometimes seen in hernia sacs point toward the alternative possibility of a reactive mesothelial nature. A possible pathogenetic mechanism for the endocardial cases is ingrowth of pericardial mesothelial cells along a perforation tract that may have developed at the time of a cardiac catheterization. There were no recurrences or metastases in any of the cases.

A rapid method for the production of erythrocytes in the state "EC4" and "EC43".

The present report describes simple methods for preparing red blood cells coated with complement components. Erythrocytes coated strongly with C4 and C3 (EC43 cells) can be prepared using the standard sucrose hemolysis reaction system. Erythrocytes coated with C4 but not C3 (EC4 cells) can be prepared by a slight modification (addition of EDTA to sucrose prior to adding serum). Occasional sera (especially from black subjects) produced weak C3 coating of red blood cells in the modified sucrose hemolysis reaction. This C3 coating could be entirely abolished (without reducing C4 coating) by using Mg++ poor serum produced by dialyzing serum against Mg++ free barbital buffer. The EC43 and EC3 cells are extremely useful in analysis of anticomplement antiglobulin sera.