Non-hormonal treatment of vulvo-vaginal atrophy-related symptoms in post-menopausal women.

In post-menopausal period vulvo-vaginal atrophy (VVA)-related symptoms may seriously affect women's quality of life. Hormonal replacement therapy effectively relieves these symptoms but it is not always safe or accepted, and a non-hormonal treatment is often needed instead. Over a period of 12 weeks, we tested the effect of a twice-a-week vulvo-vaginal application of a hyaluronic acid, AC collagen, isoflavones and vitamins-based cream (Perilei Pausa) on 35 women in post-menopausal period, reporting VVA-related symptoms. After 12 weeks of treatment with Perilei Pausa a significant improvement in vaginal dryness, vulvo-vaginal itching, dyspareunia (P < 0.001), dysuria (P = 0.02), nocturia (P = 0.009) and pollakiuria (P = 0.005) was reported by the women. Colposcopical score assessing the intensity of atrophic colpitis, cervico-vaginal paleness and petechiae was also reduced (P = 0.037, P = 0.016 and P = 0.032, respectively). No significant difference in terms of maturation value of cervico-vaginal epithelium was observed. In conclusion, Perilei Pausa may represent an effective and safe alternative treatment of symptomatic VVA in post-menopausal women.

Chest MR imaging in the follow-up of pulmonary alterations in paediatric patients with middle lobe syndrome: comparison with chest X-ray.

PURPOSE: The authors evaluated the role of magnetic resonance (MR) imaging of the chest in comparison with chest X-ray in the follow-up of pulmonary abnormalities detected by computed tomography (CT) in paediatric patients with middle lobe syndrome. MATERIALS AND METHODS: Seventeen patients with middle lobe syndrome (mean age 6.2 years) underwent chest CT at the time of diagnosis (100 kV, CARE dose with quality reference of 70 mAs; collimation 24×1.2 mm; rotation time 0.33 s; scan time 5 s); at follow-up after a mean of 15.3 months, all patients were evaluated with chest MR imaging with a respiratory-triggered T2-weighted BLADE sequence (TR 2,000; TE 27 ms; FOV 400 mm; flip angle 150°; slice thickness 5 mm) and chest X-ray. Images from each modality were assessed for the presence of pulmonary consolidations, bronchiectases, bronchial wall thickening and mucous plugging. Hilar and mediastinal lymphadenopathies were assessed on CT and MR images. RESULTS: Baseline CT detected consolidations in 100% of patients, bronchiectases in 35%, bronchial wall thickening in 53% and mucous plugging in 35%. MR imaging and chest X-ray identified consolidations in 65% and 35%, bronchiectases in 35% and 29%, bronchial wall thickening in 59% and 6% and mucous plugging in 25% and 0%, respectively. Lymphadenopathy was seen in 64% of patients at CT and in 47% at MR imaging. CONCLUSIONS: Patients with middle lobe syndrome show a wide range of parenchymal and bronchial abnormalities at diagnosis. Compared with MR imaging, chest X-ray seems to underestimate these changes. Chest MR imaging might represent a feasible and radiation-free option for an overall assessment of the lung in the follow-up of patients with middle lobe syndrome.

Interplay between steroid receptors and neoplastic progression in sarcoma tumors.

Steroid hormones are expressed at low levels in mesenchymal cells and are highly expressed in soft tissue sarcoma. In human soft tissue fibrosarcoma cell line (HT-1080), the epidermal growth factor (EGF) stimulates the express of matrix metal (MMPs) expression through a Src-dependent mechanism. In human fibrosarcomas, increased expression of MMPs correlates with the metastatic progression. Our recent data in human breast cancer cell line MCF-7, demonstrates that EGF stimulates estradiol receptor (ER) phosphorylation on tyrosine at position 537 thereby promoting the association of a complex among EGF receptor (EGFR), androgen receptor (AR), ER, and Src that activates EGF-dependent signaling pathway. In the present study, we demonstrate that, in HT-1080 cells, the Src kinase activity is involved in EGFR phosphorylation and this activity is regulated by an interplay between Src, steroid receptors, and EGFR. In these cells, estradiol (E(2) )/ER and synthetic androgen (R1881)/AR trans-activate EGFR leading to the downstream signaling and to ERK activation. Indeed, the association between ER/AR and EGFR enhances metastatic progression of fibrosarcoma tumors. A population pilot study performed on 16 patients with soft tissue neoplasias highlights that MMPs expression correlates with progression of anaplastic sarcoma as well as overexpression of EGFR. These findings suggest that there is a crosstalk among AR, ER, and EGFR that lead to src activation also in fibrosarcoma cells.

Clinical application of dual-source CT in the evaluation of patients with lung cancer: correlation with perfusion scintigraphy and pulmonary function tests.

PURPOSE: This study was done to assess the diagnostic potential of dual-source computed tomography (DSCT) in the functional evaluation of lung cancer patients undergoing surgical resection. The CT data were compared with pulmonary perfusion scintigraphy and pulmonary function tests (PFTs). MATERIALS AND METHODS: All patients were evaluated with DSCT, scintigraphy and PFTs. The DSCT scan protocol was as follows: two tubes (80 and 140 kV; Care Dose protocol); 70 cc of contrast material (5 cc/s); 5- to 6-s scan time; 0.6 mm collimation. After the automatic calculation of lung perfusion with DSCT and quantification of air volumes and emphysema with dedicated software applications, the perfusional CT studies were compared with scintigraphy using a visual score for perfusion defects; CT air volumes and emphysema were compared with PFTs. RESULTS: The values of accuracy, sensitivity, specificity and positive (PPV) and negative (NPV) predictive values of DSCT compared with perfusion scintigraphy as the reference standard were: 0.88, 0.84, 0.90, 0.93 and 0.88, respectively. The McNemar test did not identify significant differences either between the two imaging techniques (p=0.07) or between CT and PFTs (p=0.09). CONCLUSIONS: DSCT is a robust and promising technique that provides important and accurate information on lung function.

A simple device designed to facilitate sternal closure and avoid complications.

We report an easy technique for sternal closure based on the use of a steel spoon. The spoon is placed under the line of the sternotomy where a stainless steel wire is passed through the bone. The tip of the wire passes through the bone and is then placed in the spoon which guides and facilitates the progressive passage of the wire through the bone. Finally, the spoon is symmetrically placed under the sternum on the opposite side.

Behavior profile of family members of donors and nondonors of organs.

UNLABELLED: Organ transplant shortage is a global problem caused by several factors, most of which are related to members of the family, who play a major role in the donation process. OBJECTIVE: We sought to determine the most determinant features in the donor profile that relate to positive decisions versus refusal of donation. MATERIAL AND METHODS: Fifty-six families who were approached by the Organ Procurement Organization (OPO) from November 2004 to April 2006 agreed to participate in this work. To assess donor profiles, we used a structured interview. RESULTS: Parental involvement directly in decisions about donation lead to significantly less frequent consent (P = .005), young donor age was associated with a reduced probability of donation (P = .002), violent death negatively influenced donation consent, excluding suicide (P = .004). CONCLUSION: The present study showed violent death, young patient age, and parental donation consent to be the most important factors that make it harder to obtain consent organ donation. When a collateral relative (sibling/uncle) or children were responsible for the donation decision, there was more success of consent.

Heart transplantation in arrhythmogenic right ventricular dysplasia: case reports.

OBJECTIVE: Arrhythmogenic right ventricular dysplasia (ARVD) is a myocardial disease of familiar, origin where the myocardium is replaced by fibrofatty tissue predominantly in the right ventricle. Herein we have presented the clinical courses of 4 patients with ARVD who underwent orthotopic heart transplantation. PATIENTS AND METHODS: Among 358 adult patients undergoing heart transplantation, 4 (1.1%) displayed ARVD. The main indication for transplantation was the progression to heart failure associated with arrhythmias. All 4 patients displayed rapid, severe courses leading to heart failure with left ventricular involvement and uncontrolled arrhythmias. RESULTS: In all cases the transplantation was performed using a bicaval technique with prophylactic tricuspid valve annuloplasty. One patient developed hyperacute rejection and infection, leading to death on the 7th day after surgery. The other 3 cases showed a good evolution with clinical remission of the symptoms. Pathological study of the explanted hearts confirmed the presence of the disease. CONCLUSIONS: ARVD is a serious cardiomyopathy that can develop malignant arrhythmias, severe ventricular dysfunction with right ventricular predominance, and sudden cardiac death. Orthotopic heart transplantation must always be considered in advanced cases of ARVD with malignant arrhythmias or refractory congestive heart failure with or without uncontrolled arrhythmias, because it is the only way to remit the symptoms and the disease.

Massive degeneration and atrophy of the native heart after heterotopic transplantation: a case report.

Extreme myocardial degeneration leading to advanced stages of cardiomyopathy with extensive atrophy is rarely observed before patients die. However, heterotopic transplantation is a special situation wherein this phenomenon can be observed. The greater part of the failed heart shows recuperation after receiving circulatory assistance by reduction of myocardial work. Herein we have reported an unusual behavior of degenerative cardiomyopathy associated with intense myocardial apoptosis resulting in extreme ventricular atrophy after heterotopic heart transplantation. An 11-year-old girl with end-stage heart failure due to dilated cardiomyopathy of undetermined etiology without pulmonary hypertension underwent heterotopic cardiac transplantation with an undersized (by weight mismatch) donor heart. After 9 years heart failure reappeared due to native heart enlargement leading to allograft compression. The patient underwent native heart replacement leaving her with 2 donor hearts. Despite normal hemodynamic recuperation, the patient experienced massive arterial microemboli which led to death. Pathological studies showed exuberant myocardial degeneration in the native heart with intense atrophy of the muscle and gigantic ventricular enlargement. The left ventricle wall was extremely thin with rarefaction of cardiomyocytes and replacement by fibrosis. The right ventricle showed old extensive thrombosis. In conclusion, this report is not usual as it is not frequent to observe cardiomyopathy with an intense degree of myocardial degeneration and atrophy, because the patient dies earlier. In special situations it is possible that a recipient may have 2 donor hearts with normal hemodynamics. Heterotopic heart transplantation is a surgical alternative in a priority situation offering excellent outcomes; however, the native heart must be removed when there is compromise of the function of the heterotopic allograft.

Endomyocardial biopsy as risk factor in the development of tricuspid insufficiency after heart transplantation.

OBJECTIVE: Endomyocardial biopsy (EMB), which is used to monitor for rejection, may cause tricuspid regurgitation (TR) after orthotopic heart transplantation (OHT). The purpose of this investigation was to examine the occurrence of tricuspid valve tissue in myocardial specimens obtained by routine EMB performed after OHT. PATIENTS AND METHODS: From January 2000 to July 2008, 125 of the patients who underwent OHT survived more than 1 month. Their follow-up varied from 1 month to 8.5 years (mean, 5.1 +/- 3.7 years). EMB was the gold standard examination and myocardial scintigraphy with gallium served as a screen to routinely monitor rejection. RESULTS: Each of 428 EMB including 4 to 7 fragments, totaling 1715 fragments, were reviewed for this study. The number of EMB per patient varied from 3 to 8 (mean, 4.6 +/- 3.5). Histopathological analysis of these fragments showed tricuspid tissue in 4 patients (3.2%), among whom only 1 showed aggravation of TR. CONCLUSIONS: EMB remains the standard method to diagnose rejection after OLT. It can be performed with low risk. Reducing the number of EMB using gallium myocardial scintigraphy or other alternative methods as well as adoption of special care during the biopsy can significantly minimize trauma to the tricuspid valve.

Autoimmunity in Chagas' disease. Identification of cardiac myosin-B13 Trypanosoma cruzi protein crossreactive T cell clones in heart lesions of a chronic Chagas' cardiomyopathy patient.

Heart tissue destruction in chronic Chagas' disease cardiomyopathy (CCC) may be caused by autoimmune recognition of heart tissue by a mononuclear cell infiltrate decades after Trypanosoma cruzi infection. Indirect evidence suggests there is molecular mimicry between T. cruzi and heart tissue. In murine models of CCC, antibodies and CD4+ T cells recognize myosin, the major heart protein. We recently identified a heart-specific epitope of cardiac myosin heavy chain (residues 1442-1447, AAALDK) that is crossreactive with a homologous sequence (AAAGDK) of the immunodominant T. cruzi antigen B13. Furthermore, cardiac myosin-B13 crossreactive antibodies are present in 100% CCC patients vs 14% asymptomatic T. cruzi-seropositive individuals (P = 2.3 x 10(-6)), suggesting a role for molecular mimicry between cardiac myosin and B13 in CCC pathogenesis. In this paper, we obtained heart-infiltrating T cell clones from CCC patients to assess whether molecular mimicry between cardiac myosin and B13 is directly involved in the genesis of heart lesions. We identified T cell clones derived from CCC heart lesions simultaneously responsive to cardiac myosin heavy chain (but not skeletal myosin heavy chain) and B13 T. cruzi protein, but could not find T cell clones primarily reactive to any T. cruzi antigen. Together with the association of myosin-B13 crossreactive antibodies with CCC, the present data strongly suggest the relevance of molecular mimicry between cardiac myosin and the T. cruzi protein B13 in the pathogenesis of heart lesions in chronic Chagas' disease cardiomyopathy.

Prophylactic donor tricuspid annuloplasty in orthotopic bicaval heart transplantation.

OBJECTIVE: The objective of this study was to evaluate the effects of prophylactic heart donor tricuspid annuloplasty to improve the degree of valvar regurgitation and the hemodynamic performance after orthotopic heart transplantation using bicaval anastomosis. METHODS: From March 1985 to December 2005, of the 368 patients undergoing orthotopic heart transplantation, 20 patients were selected because they survived more than 6 months. They were divided into 2 groups: group I-10 patients underwent prophylactic heart donor tricuspid annuloplasty by the De Vega technique; group II-10 patients did not receive a graft with this procedure. Their presurgical clinical characteristics were the same. In the postsurgical period, tricuspid regurgitation degree evaluated by transthoracic Doppler echocardiography was qualified from 0 to 3: 0 = absent; 1 = mild; 2 = moderate; and 3 = severe. Myocardial performance was evaluated by the ventricular ejection fraction and by an invasive hemodynamic study, performed during routine endomyocardial biopsies. RESULTS: At a follow-up of 14.6 +/- 4.3 months (6 and 16 months), group I showed no mortality, whereas group II had 10% (P > .05). However, it was not related to the annuloplasty. The mean degree of tricuspid regurgitation in group I was 0.4 +/- 0.6; in group II, 1.6 +/- 0.8 (P < .05). There was a significant difference between the 2 groups in the right atrium pressure, which was higher in group II. CONCLUSIONS: Prophylactic tricuspid annuloplasty in the heart donor significantly reduced the degree of valvular regurgitation after heart transplantation using a bicaval anastomosis without significantly interfering with the hemodynamic performance of the allograft.

Methotrexate associated to lipid core nanoparticles improves cardiac allograft vasculopathy and the inflammatory profile in a rabbit heart graft model.

Coronary allograft vasculopathy is an inflammatory-proliferative process that compromises the long-term success of heart transplantation and has no effective treatment. A lipid nanoemulsion (LDE) can carry chemotherapeutic agents in the circulation and concentrates them in the heart graft. The aim of the study was to investigate the effects of methotrexate (MTX) associated to LDE. Rabbits fed a 0.5% cholesterol diet and submitted to heterotopic heart transplantation were treated with cyclosporine A (10 mg·kg-1·day-1 orally) and allocated to treatment with intravenous LDE-MTX (4 mg/kg, weekly, n=10) or with weekly intravenous saline solution (control group, n=10), beginning on the day of surgery. Animals were euthanized 6 weeks later. Compared to controls, grafts of LDE-MTX treated rabbits showed 20% reduction of coronary stenosis, with a four-fold increase in vessel lumen and 80% reduction of macrophage staining in grafts. Necrosis was attenuated by LDE-MTX. Native hearts of both LDE-MTX and Control groups were apparently normal. Gene expression of lipoprotein receptors was significantly greater in grafts compared to native hearts. In LDE-MTX group, gene expression of the pro-inflammatory factors tumor necrosis factor-α, monocyte chemoattractant protein-1, interleukin-18, vascular cell adhesion molecule-1, and matrix metalloproteinase-12 was strongly diminished whereas expression of anti-inflammatory interleukin-10 increased. LDE-MTX promoted improvement of the cardiac allograft vasculopathy and diminished inflammation in heart grafts.

Proteomic inventory of myocardial proteins from patients with chronic Chagas' cardiomyopathy.

Chronic Chagas' disease cardiomyopathy (CCC) is an often fatal outcome of Trypanosoma cruzi infection, with a poorer prognosis than other cardiomyopathies. CCC is refractory to heart failure treatments, and is the major indication of heart transplantation in Latin America. A diffuse myocarditis, plus intense myocardial hypertrophy, damage and fibrosis, in the presence of very few T. cruzi forms, are the histopathological hallmarks of CCC. To gain a better understanding of the pathophysiology of CCC, we analyzed the protein profile in the affected CCC myocardium. Homogenates from left ventricular myocardial samples of end-stage CCC hearts explanted during heart transplantation were subjected to two-dimensional electrophoresis with Coomassie blue staining; protein identification was performed by MALDI-ToF mass spectrometry and peptide mass fingerprinting. The identification of selected proteins was confirmed by immunoblotting. We demonstrated that 246 proteins matched in gels from two CCC patients. They corresponded to 112 distinct proteins. Along with structural/contractile and metabolism proteins, we also identified proteins involved in apoptosis (caspase 8, caspase 2), immune system (T cell receptor ss chain, granzyme A, HLA class I) and stress processes (heat shock proteins, superoxide dismutases, and other oxidative stress proteins). Proteins involved in cell signaling and transcriptional factors were also identified. The identification of caspases and oxidative stress proteins suggests the occurrence of active apoptosis and significant oxidative stress in CCC myocardium. These results generated an inventory of myocardial proteins in CCC that should contribute to the generation of hypothesis-driven experiments designed on the basis of the classes of proteins identified here.

Recommendations for use of everolimus after heart transplantation: results from a Latin-American Consensus Meeting.

Despite improvements during the last decades, heart transplantation remains associated with several medical complications, which limit clinical outcomes: acute rejection with hemodynamic compromise, cytomegalovirus (CMV) infections, allograft vasculopathy, chronic renal failure, and neoplasias. Everolimus, a proliferation signal inhibitor, represents a new option for adjunctive immunosuppressive therapy. Everolimus displays better efficacy in de novo heart transplant patients than azathioprine for prophylaxis of biopsy-proven acute rejection episodes of at least ISHLT grade 3A (P < .001), of allograft vasculopathy (P < .01), and of CMV infections (P < .01). These findings suggest that everolimus potentially play an important role as part of immunosuppressive therapy in heart transplant recipients. Heart transplant investigators from Latin America produced recommendations for everolimus use in daily practice based on available data and their own experience.

Percutaneous dilatational tracheostomy using a tracheoscopic ventilation tube in an experimental ex vivo animal model.

The ETView(®) tube is a standard endotracheal tube with an embedded miniature video camera that permits real-time video imaging of the tracheal lumen. We evaluated its use when performing percutaneous dilatational tracheostomy (PDT) in an ex vivo animal model. The model consisted of a pig larynyx and trachea. The ETView tube was used as an alternative to bronchoscopy, to see all manoeuvres of PDT in real time. At the end of the PDT, operative time and any complications such as trauma to the cricoid cartilage, tracheal wall or tube cuff were assessed. Nine PDT procedures were performed by two experienced operators. The mean operative time was 7.1 ± 0.9 minutes. No complications were observed. Our study supports the use of the ETView tube as a suitable alternative to bronchoscopy when performing PDT, although clinical studies are required to confirm our experimental results. .

Later evolution after cardiac transplantation in Chagas' disease.

OBJECTIVE: This research reported the accumulated experience with cardiac transplantation in Chagas' disease, emphasizing reactivation, immunosuppression, and mortality. METHODS: Fifty-nine patients undergoing cardiac transplantation had Chagas' disease with classically accepted recipient selection criteria. In this series, 84.7% of the patients were functional class IV; 36.0% used vasopressor support; and 13.5% mechanical circulatory assistance. One patient received a heart and kidney transplantation. RESULTS: After the initial experience the doses of immunosuppressants were significantly reduced with improvement in outcomes. The diagnosis of the reactivation of disease was documented by the identification of parasite in the myocardium, or on subcutaneous or serological exams. Reactivation of disease was significantly reduced by decreasing the immunosuppression. Immediate mortality occurred in 10 cases: three infections, two allograft dysfunction, two rejections, and two sudden deaths. Subsequent mortality happened in 14 patients: four by lymphoma, three by infection, two by Kaposi's sarcoma two by rejection, two by constrictive pericarditis, and one by reactivation of disease in the brain. CONCLUSIONS: There's no correlation between the disease and pre- or postoperative prophylaxis. The early diagnosis and specific treatment of reactivation did not leave functional sequelae in the myocardium. Reduction in immunosuppression significantly reduced reactivation of disease and neoplasms. The combined transplantation can be realized safely with more care about the immunosuppressants.

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.

The Brazilian experience with heart transplantation: a multicenter report.

BACKGROUND: The results of heart transplantation in developing countries are influenced by the high incidence of marginal donors and the large number of recipients with characteristics of alternative list. The purpose of this multicenter report was to determine the rate of survival after heart transplantation in a developing country. Also we studied the causes of death, the results based on the year of transplant, the influence of gender and age, the numbers of transplants per year, and the etiology of the cardiomyopathy causing the heart failure. METHODS: We studied 792 (632 male) patients who underwent orthotopic heart transplantation at 16 centers. The mean age of the patients was 42 +/- 16 years. Etiology included idiopathic dilated cardiomyopathy in 407 patients, ischemia in 196 patients, Chagas disease in 117 patients, and various other in 72 patients. Cyclosporine was the cornerstone of the immunosuppression administered. RESULTS: Survival for the entire population at 3 months and 1, 4, 8, and 12 years was 72%, 66%, 54%, 40%, and 27%, respectively. There was an improvement in survival from 1991 to 1995 compared with before 1991. Age and gender did not influence the results. Unexpected early mortality was observed, but the late results were satisfactory. The most prevalent causes of death were infection in 23%, acute graft failure in 19%, and rejection in 18%. CONCLUSIONS: Heart transplantation has become feasible in developing countries and the survival rate has improved without the influence of gender and age recipients. A chagasic etiology was found to be the third-leading indication for heart transplantation. The impact of increment of donors with appropriate care for reduction of marginal donors, perhaps associated with better recipient selection and postoperative care, should be investigated for improving early results.

Low doses of inhaled nitric oxide in heart transplant recipients.

BACKGROUND: The purpose of this study was to assess the hemodynamic effects of low doses of inhaled nitric oxide in patients after orthotopic heart transplantation. METHODS: Two hours after the operation 10 adult patients who were still under anesthetic effects and undergoing mechanical ventilation inhaled, during 60 minutes, a mixture of nitrogen, oxygen, and nitric oxide (20 ppm). A standard profile of hemodynamic data was collected at baseline, at 30 minutes, at 30 more minutes of inhalation, and at the same points after nitric oxide suspension. RESULTS: A significant decrease was found from baseline to 60 minutes, immediately after nitric oxide inhalation in the following: systemic vascular resistance index 1268 +/- 409 to 1090 +/- 354 (p = 0.0161); pulmonary vascular resistance index 252 +/- 124 to 154 +/- 98 (p < 0.05); pulmonary vascular resistance index/systemic vascular resistance index ratio 0.21 +/- 0.09 to 0.14 +/- 0.08 (p = 0.0025); transpulmonary gradient 12 +/- 3 to 9 +/- 3 (p = 0.05). A significant increase was also found in cardiac index from 4.2 +/- 1.1 to 4.9 +/- 1.4 (p = 0.0007). Other parameters such as mean pulmonary, systemic, wedge and right atrial pressures, in addition to intrapulmonary shunting, heart rate, and oxygen extraction ratio, did not present any significant changes. The procedure was well tolerated by all patients, and no undesirable effects such as methemoglobin elevation or worsening of pulmonary hypertension after nitric oxide suspension were observed. CONCLUSIONS: The beneficial effects observed by inhaled nitric oxide in the pulmonary vascular resistance index/systemic vascular resistance index ratio, transpulmonary gradient, and cardiac index suggest that nitric oxide acts mainly in pulmonary territory and could be a possible pulmonary vasodilator agent used to control central hemodynamics after heart transplantation.

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.