Clinical value of myocardial performance index in patients with isolated diastolic dysfunction.

AIMS: The Doppler-derived myocardial performance index (MPI) has been considered as a diagnostic and prognostic Doppler marker for many different clinical conditions. The purpose of this study was to determine the diagnostic accuracy of traditional Pulsed-wave Doppler (PWD-MPI) and Pulsed-wave tissue Doppler imaging (TDI-MPI) and the degree of agreement between these methods in patients with grade-I diastolic dysfunction (DDI) and a normal ejection fraction. METHODS: Forty-seven consecutive ambulatory patients with DDI were compared to 51 healthy subjects with normal echocardiograms. All subjects underwent measurement of time intervals and MPI with PWD and pulsed TDI. RESULTS: TDI-MPI and PWD-MPI were significantly higher in patients with DDI than in control subjects: 0.49 ± 0.14 vs. 0.40 ± 0.09 (P < 0.001) and 0.45 ± 0.11 vs. 0.37 ± 0.08 (P < 0.001), respectively. Cutoff values of TDI-MPI > 0.42 and PWD-MPI > 0.40 identified DDI subjects, with sensitivities of 74 and 64%; specificities of 61 and 69%; positive likelihood ratios of 1.9 and 2.0; and negative likelihood ratios of 0.42 and 0.53, respectively; no significant difference was noted between the areas under the ROC curves of TDI-MPI and PWD-MPI (P = 0.77). Bland-Altman plots showed wide limits of agreement between these indices: - 0.17 to 0.23 in healthy subjects and - 0.24 to 0.32 in DDI patients. CONCLUSION: PWD-MPI and TDI-MPI showed poor clinical agreement and were not reliable parameters for the assessment of left ventricular diastolic function.

Variabilidade lipídica e risco cardiovascular / Lipid variability and cardiovascular risk

Introdução: As doenças cardiovasculares são a principal causa de óbito no mundo e geram um importante impacto econômico. Hipertensão arterial, diabetes mellitus, dislipidemia, tabagismo e obesidade são os fatores de risco modificáveis mais implicados no aparecimento de infarto agudo do miocárdio (IAM) e acidente vascular encefálico (AVE). A variabilidade nas medidas de parâmetros cardiovasculares tem surgido nos últimos anos como novo fator de risco cardiovascular. Nesse contexto, estudos têm mostrado que uma maior variabilidade de colesterol ligado à lipoproteína de baixa densidade (LDL-C) e colesterol ligado à lipoproteína de alta densidade (HDL-C) está associada com piores desfechos cardiovasculares. Entretanto, nenhum estudo até o momento avaliou o grupo específico de pacientes submetidos à cirurgia de revascularização miocárdica (CRM). Assim, elaborou-se este estudo com o intuito de avaliar se uma maior variabilidade nas medidas de LDL-C e HDL-C em pacientes submetidos à CRM está associada com eventos cardiovasculares maiores, definidos como: IAM não fatal, AVE não fatal, hospitalização por insuficiência cardíaca, hospitalização por angina, nova revascularização (cirúrgica ou percutânea) e morte. Métodos: A população do estudo foi composta de uma coorte de pacientes que foram submetidos à CRM isolada, no período 01 de janeiro de 2012 a 31 de dezembro de 2012. A variabilidade de LDL-C e HDL-C será avaliada por três índices: desvio padrão, coeficiente de variação e variabilidade corrigida independente da média. Resultados: Dos 568 pacientes submetidos à CRM isolada em 2012, 34 pacientes foram a óbito ainda na mesma internação. Também foram excluídos do estudo 50 pacientes que só tiveram uma coleta, e 133 pacientes que não tiveram nenhuma coleta de lípides séricos no período de seguimento, restando 351 pacientes que foram incluídos. Durante o período de seguimento, os pacientes incluídos tiveram total de 2090 coletas de lípides, sendo a média 5,9 coletas. No total, 46 pacientes tiveram somente 2 coletas, e um paciente teve o número máximo de coletas (18). Na primeira medida após a alta hospitalar, o valor médio de colesterol total foi de 155,7 mg/dL, 84,7 mg/dL para LDL-C, 41,8 mg/dL para HDL-C e 152 mg/dL para triglicerídeos. As análises de variabilidade estão sendo realizadas. Conclusão: Espera-se avaliar se uma maior variabilidade nas medidas de LDL-C e HDL-C em pacientes submetidos à CRM está associado com eventos cardiovasculares maiores.

Antigen-triggered interferon-γ and interleukin-10 pattern in cured mucosal leishmaniasis patients is shaped during the active phase of disease.

An exacerbated type 1 response to leishmanial antigens is the basis of tissue destruction observed in mucosal leishmaniasis (ML). After therapy, a persistent production of high levels of inflammatory cytokines can confer a poor prognosis. Herein we investigated whether the clinical conditions defined during the active phase of ML affect the magnitude of long-term anti-Leishmania immune response. Twenty clinically cured ML cases were studied. Peripheral blood mononuclear cells (PBMC) were cultured with L. braziliensis antigens (Lb-Ag), Toxoplasma gondii antigens (Tg-Ag), concanavalin-A (Con-A) or medium alone, and the lymphocyte proliferative response and cytokine secretion were quantified. Medical records were reviewed for Montenegro skin test (MST) during diagnosis, duration of ML disease or time elapsed after clinical cure. The duration of disease was correlated positively with MST (r = 0·61). Lb-Ag induced interferon (IFN)-γ was correlated positively with duration of illness (r = 0·69) as well as the frequency of secreting cells [enzyme-linked immunospot (ELISPOT)] assay. No association was observed for Tg-Ag or Con-A. Disease duration was correlated negatively with interleukin (IL)-10 production (r = -0·76). Moreover, a negative correlation between length of time after clinical cure and TNF levels (r = -0·94) or the IFN-γ : IL-10 ratio (r = -0·89) were also seen. We suggest that the magnitude of the IFN-γ inflammatory response triggered by ML can be driven by the time of leishmanial antigens exposition during the active phase of the disease. This pattern could persist even long-term after cure. However, despite IFN-γ levels, the decrease of the TNF and IFN-γ : IL-10 ratio reflects the control of proinflammatory responses achieved by cure of ML, possibly preventing disease relapses.

Are the severe injuries of cutaneous leishmaniasis caused by an exacerbated Th1 response?

American tegumentary leishmaniasis (ATL) is a disease whose clinical features are strongly related to the type of immune response it induces. Herein we report an atypical presentation of cutaneous leishmaniasis in a woman with a severe and extensive sore located in her leg, and we describe the differences between the usual local immune response in ATL and the local immune response in this patient. We observed an intense inflammatory response characterized by Th1 cells and cytokines with conspicuous expression of Toll-like receptor 3 (TLR-3). Few parasites were present, but there was an extensive tissue damage. We also discuss the immunological factors that could be related to the atypical presentation.

Leishmania (Viannia) braziliensis identification by PCR in the state of Para, Brazil.

The incidence of cutaneous leishmaniasis (CL) is increasing and there is limited surveillance of Leishmania species throughout the world. We identified the species associated with CL in a region of Amazonia, an area recognized for its Leishmania species variability. Clinical findings were analyzed and correlated with the species identified in 93 patients. PCR assays were based on small subunit ribosomal DNA (SSU-rDNA) and G6PD, and were performed in a laboratory located 3,500km away. Leishmania (V.) braziliensis was identified in 53 patients (57%). The other 40 patients (43%) carried a different species (including six cases of L. (L.) amazonensis). Molecular methods can be employed, using special media, to allow transport to distant laboratories. L. (V.) braziliensis is the most common species in the area of Para. The location of ulcers can suggest CL species.

The expression of TLR9 in human cutaneous leishmaniasis is associated with granuloma.

The Toll-like receptor (TLR) signalling pathway is the first system that defends against Leishmania. After recognising Leishmania as nonself, TLRs trigger NF-κB expression.NF-κB proceeds to the nucleus and promotes the transcription of pro-inflammatory cytokines. TLR9 is thus an important factor in the induction of an effective immune response against Leishmania. We examined the pattern of TLR9 expression in 12 patients with cutaneous leishmaniasis caused by Leishmania braziliensis detected by polymerase chain reaction. Normal skin was analysed as a negative control. TLR9 expression was examined in the dermis and epidermis by immunohistochemical analysis of paraffin-embedded biopsy tissue. TLR9 expression was primarily observed in the granuloma. The protein was detected in a few cells in the dermis. A lower expression level was detected in the epidermis of patients with leishmaniasis when compared with normal skin. The presence of TLR9 in the skin of patients with cutaneous leishmaniasis is associated with granuloma and expressed by macrophages.

Doppler-derived myocardial performance index in patients with impaired left ventricular relaxation and preserved systolic function.

BACKGROUND: The Doppler-derived myocardial performance index (MPI) has been used in the evaluation of left ventricular (LV) function in several diseases. In patients with isolated diastolic dysfunction, the diagnostic utility of this index remains unclear. The aim of this study was to determine the diagnostic utility of MPI in patients with systemic hypertension, impaired LV relaxation, and normal ejection fraction. METHODS: Thirty hypertensive patients with impaired LV relaxation were compared to 30 control subjects. MPI and its components, isovolumetric relaxation time (IRT), isovolumetric contraction time (ICT), and the ejection time (ET), were measured from LV outflow and mitral inflow Doppler velocity profiles. RESULTS: MPI was higher in patients than in control subjects (0.45 +/- 0.13 vs 0.37 +/- 0.07 P < 0.0029). The increase in MPI was due to the prolongation of IRT without significant change of ICT and ET. MPI cutoff value of > or =0.40 identified impaired LV relaxation with a sensitivity of 63% and specificity of 70% while an IRT >94 ms had a sensitivity of 67% and specificity of 80%. Multivariate analysis identified relative wall thickness, mitral early filling wave velocity (E), and systolic myocardial velocity (Sm) as independent predictors of MPI in patients with hypertension. CONCLUSIONS: MPI was increase in patients with hypertension, diastolic dysfunction, and normal ejection fraction but was not superior to IRT to detect impaired LV relaxation.

Mucosal leishmaniasis: description of case management approaches and analysis of risk factors for treatment failure in a cohort of 140 patients in Brazil.

BACKGROUND: Mucosal leishmaniasis is caused mainly by Leishmania braziliensis and it occurs months or years after cutaneous lesions. This progressive disease destroys cartilages and osseous structures from face, pharynx and larynx. OBJECTIVE AND METHODS: The aim of this study was to analyse the significance of clinical and epidemiological findings, diagnosis and treatment with the outcome and recurrence of mucosal leishmaniasis through binary logistic regression model from 140 patients with mucosal leishmaniasis from a Brazilian centre. RESULTS: The median age of patients was 57.5 and systemic arterial hypertension was the most prevalent secondary disease found in patients with mucosal leishmaniasis (43%). Diabetes, chronic nephropathy and viral hepatitis, allergy and coagulopathy were found in less than 10% of patients. Human immunodeficiency virus (HIV) infection was found in 7 of 140 patients (5%). Rhinorrhea (47%) and epistaxis (75%) were the most common symptoms. N-methyl-glucamine showed a cure rate of 91% and recurrence of 22%. Pentamidine showed a similar rate of cure (91%) and recurrence (25%). Fifteen patients received itraconazole with a cure rate of 73% and recurrence of 18%. Amphotericin B was the drug used in 30 patients with 82% of response with a recurrence rate of 7%. The binary logistic regression analysis demonstrated that systemic arterial hypertension and HIV infection were associated with failure of the treatment (P < 0.05). CONCLUSION: The current first-line mucosal leishmaniasis therapy shows an adequate cure but later recurrence. HIV infection and systemic arterial hypertension should be investigated before start the treatment of mucosal leishmaniasis. Conflicts of interest The authors are not part of any associations or commercial relationships that might represent conflicts of interest in the writing of this study (e.g. pharmaceutical stock ownership, consultancy, advisory board membership, relevant patents, or research funding).

Unusual manifestations of tegumentary leishmaniasis in AIDS patients from the New World.

BACKGROUND: Comorbidity from tegumentary leishmaniasis and AIDS is poorly characterized. OBJECTIVES: To describe a series of patients coinfected with Leishmania and human immunodeficiency virus (HIV). METHODS: Clinical records from patients were analysed by demographic data, clinical manifestations, diagnoses, treatments and outcomes. RESULTS: Fifteen cases of AIDS/tegumentary leishmaniasis were found. The diagnosis of leishmaniasis was confirmed by the detection of Leishmania amastigotes or antigens from the cutaneous or mucosal lesions. The mean CD4+ T-cell count was 84 cells mm(-3) (range 8-258) and all patients were classified as having AIDS according to the Centers for Disease Control and Prevention. A wide range of manifestations was found, varying from a single ulcer to multiple and polymorphic lesions. Mucosal lesions were present in 80% and cutaneous lesions in 73% of patients (53% with mucocutaneous form), disseminated lesions in 60% and genital lesions in 27% of patients. All patients received anti-Leishmania therapy and 53% showed relapses. Sixty-seven per cent received highly active antiretroviral therapy but showed no difference in outcomes and relapses compared with those not using medication. Forty per cent died during the study period. In these patients, the anti-Leishmania antibody and Montenegro skin test were useful in the diagnosis of leishmaniasis, probably because leishmaniasis preceded immunosuppression due to HIV infection. CONCLUSIONS: Clinical manifestations of tegumentary leishmaniasis in HIV-infected patients are diverse. Our data emphasize possible unusual manifestations of this disease in HIV-infected patients, particularly in severely immunosuppressed cases (< 200 CD4+ cells mm(-3)).

In situ immune responses to interstitial pneumonitis in human visceral leishmaniasis.

Lung disease during active human visceral leishmaniasis is frequently reported. As such, studies have associated pulmonary symptoms to interstitial pneumonitis with a mononuclear infiltrate. However, the immune response in this condition has never been described before. The aim of this study was to determine the immunophenotypic pattern and cytokine profile of lung involvement (IPL) in human visceral leishmaniasis. Quantitative methods of analysis were performed using immunohistochemistry, and were compared with a control group of normal lung. Interstitial macrophages and cd8 cells were increased in IPL, and IL-4 as well as TNF-alpha displayed increased expression when compared to the control group. This inflammatory process with a Th2 pattern, as suggested by increased IL-4 and low IFN-gamma expression, is consistent with the immune response in other organs of visceral leishmaniasis. The microenvironment of the immune response in this condition is associated with lung disease in patients with interstitial pneumonitis related to visceral leishmaniasis, increasing the chance of bacterial infection.

A quantitative and morphometric study of mast cells in cutaneous leishmaniasis.

Background Mast cells (MCs) are related with healing process in chronic inflammatory diseases, although in cutaneous leishmaniasis (CL) its importance is unknown. The aim of this study was to determine the correlation of MC with clinical findings in patients with the localized form of CL. Methods A cohort of 85 patients with CL was evaluated. MCs count was performed in pre-treatment biopsies and correlation with clinical findings and Leishmania species determined by PCR were performed. Results The MCs count in patients with CL caused by Leishmania (V.) braziliensis was 14.3 +/- 9.8 cells/mm(2), and 7.0 +/- 6.5 cells/mm(2) in patients with L. (L.) amazonensis (P < 0.05). The linear regression of MCs count with the age showed a tendency of cell number decreasing, according to ageing of the patient (r2 = 0.05; P < 0.05). The association of disease's duration and MCs count was positive (r2 = 0.11; P < 0.05). There was not any association of MCs count with number of lesions neither with Leishmania antigen expression. The MCs count was higher in patients with earlier healing after treatment (P < 0.05). Conclusion MC can be important in CL and related with healing lesion.

Histopathology of mast cells and cytokines during healing of human mucosal leishmaniasis.

Mast cells (MCs) are associated with chronic inflammatory diseases. However, there is no study evaluating the importance of MCs in the mucosal leishmaniasis (ML). The aim of this study was to quantify the most important cytokines associated with mucosal leishmaniasis, before and after disease treatment, correlating with the healing. A cohort of 12 patients with ML was evaluated, and biopsies were taken before and after the treatment. A quantitative estimation of MCs and some cytokines was analysed by density of the labelled cells through immunohistochemistry. The MCs count in the tissue from patients with ML before treatment showed a mean of 29.3 +/- 37.9 cells/mm(2). The MCs count in patients with ML after healing decreased to 14.8 +/- 23.9 cells/mm(2). There was an inverse relation of MCs with IFN-gamma and IL-4 expression (r2 = 29.4 and r2 = 22.3 with P < 0.05). The expression of IL-10 and TNF-alpha was not related with MCs count. MCs decrease after treatment associated with decrease of IL-4 and IFN-gamma. The explanations of cytokine correlation are discussed in the article.

Mecanismos das arritmias cardíacas: fundamentos para o cardiologista clínico / Basic mechanisms of arrhythmia: essentials for clinical cardiologists

Atualmente, são muitas as possibilidades de tratamento para a população de pacientes acometidos por taquiarritmias supraventriculares e ventriculares, incluindo a ablação por cateter, as drogas antiarrítmicas e os dispositivos implantáveis. Além disso, o avanço no campo das terapias moleculares tem revelado a importância dos fatores genéticos no desenvolvimento e tratamento das arritmias. A utilização clínica desse amplo arsenal diagnóstico e terapêutico pode ser muito facilitada pelo entendimento dos mecanismos fundamentais as arritmias cardíacas. Este artigo descreve sucintamente os mecanismos básicos das arritmias cardíacas com ênfase em seus aspectos relevantes à prática clínica.

Can interferon-gamma and interleukin-10 balance be associated with severity of human Leishmania (Viannia) braziliensis infection?

Suitable levels of interferon (IFN)-gamma and interleukin (IL)-10 seem to favour the outcome of cutaneous leishmaniasis (CL), while high IFN-gamma and low IL-10 production are associated with severity of mucosal leishmaniasis (ML). Considering that cytokine balance is important for the maintenance of protective responses in leishmaniasis, our aim was to investigate leishmanial antigens-induced IFN-gamma and IL-10 levels maintained in healed individuals who had different clinical outcomes of Leishmania infection. Thirty-three individuals who recovered from L. braziliensis infection were studied: cured CL (CCL), cured ML (CML), spontaneous healing of CL (SH) or asymptomatic individuals (ASY). Cytokines were quantified by enzyme-linked immunosorbent assay (ELISA) in culture supernatants of L. braziliensis-stimulated peripheral blood mononuclear cells (PBMC). IFN-gamma levels were higher in CML (7593 +/- 5994 pg/ml) in comparison to SH (3163 +/- 1526 pg/ml), ASY (1313 +/- 1048 pg/ml) or CCL (1897 +/- 2087 pg/ml). Moreover, cured ML cases maintained significantly lower production of IL-10 (127 +/- 57.8 pg/ml) in comparison to SH (1373 +/- 244 pg/ml), ASY (734 +/- 233 pg/ml) or CCL (542 +/- 375 pg/ml). Thus, a high IFN-gamma/IL-10 ratio observed in CML can indicate unfavourable cytokine balance. On the other hand, no significant difference in the IFN-gamma/IL-10 ratio was observed when CCL individuals were compared to SH or ASY subjects. In conclusion, even after clinical healing, ML patients maintained a high IFN-gamma/IL-10 secretion profile in response to leishmanial antigens. This finding can explain a delayed down-modulation of exacerbated inflammatory responses, which can be related in turn to the necessity of prolonged therapy in ML management. Conversely, lower IFN-gamma/IL-10 balance observed in CCL, SH and ASY individuals can represent a better-modulated immune response associated with a favourable prognosis.

Impact of effective valvotomy in mitral stenosis on pulmonary venous flow pattern.

AIMS: Transesophageal Doppler echocardiography (TEE) is a useful tool to investigate pulmonary venous flow (PVF) velocity, which is altered in patients with mitral stenosis (MS). This study used TEE to analyze the variations in the PVF pattern after successful valvar dilatation in MS patients. METHODS/RESULTS: A total of 15 MS patients, mean age 27.2 years, underwent effective percutaneous balloon valvotomy (PBV). All were submitted to TEE before and after PBV. TEE assessed systolic (SPFV) and diastolic (DPFV) peak flow velocities and their ratio (SPFV/DPFV), time-velocity integrals (STVI and DTVI) and their ratio, and diastolic flow deceleration (DFD). Valvotomy yielded statistically significant increases (P < or = 0.05) in the SPFV: increase on average by 67% and STVI by 120%, as well as in the diastolic component: increased on average by 35%, DTVI by 33%, and DFD by 75%. CONCLUSION: TEE demonstrated that PBV induced a global increase in velocities of PVF, probably related to improvement of left atrial emptying.

Padrões de pressão e de velocidade de fluxo num modelo in vitro de anastomose sistêmico-pulmonar. Importância para análise do estado funcional / Patterns of pressure and flow velocity distribution in a in vitro model of systemic to pulmonary artery anastomosis. Importance for functional evaluation

A função das anastomoses sistêmicos-pulmonares(S-P) e a detecção de obstrução parcial são dificeis pela ecocardiografia. Objetivo: Analisar os padrões de pressão e de distribuição espacial da velocidade do fluxo num modelo in vitro de S-P com ou sem obstrução parcial. Método: Foi utilizado um modelo de fluxo contínuo: dois tubos - circulações sistêmica(S) e pulmonar(P), foram conectados por outro - anastomose sistêmico-pulmonar (S-P). O modelo foi estudado sem obstrução e com uma obstrução longa na S-P, com medida direta das pressões em S,P e na S-P antes e após a obstrução, e análise simultânea com Doppler contínuo (DC) e mapeamento de fluxo em cores (MFC). Resultados: Sem obstrução a pressão de 5 (36,6 mmHg) foi maior do que em P(9,4mmHg) e S-P(6,3 mmHg)(p menor 0,05), sem diferença significante entre S-P e P. O maior gradiente de pressão por cateter (30,4mmHg) e por DC(27,9mmHg) foi na junção de S com S-P com sinais de aceleração de fluxo proximal ao MFC. Com obstrução, as pressões em S(95,8 mmHg) e S-P(75,4 mmHg) antes da obstrução não foram diferentes entre si, mas maiores do que as pressões de P(35,9 mmHg) e S-P(33 mmHg) após a obstrução (p menor 0,05), com gradientes de pressão pelo DC semelhantes e com sinais de aceleração proximal à junção de S com S-P, e antes da abstrução em S-P ao MFC. Conclusão: Com obstrução de S-P observou-se gradiente de opressão baixo ao DC na junção de S com S-P, e altos no trajeto da S-P com sinais de aceleração de fluxo, sem obstrução os maiores gradientes de pressão e aceleração de fluxo ocorreram na junção de S com S-P.

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.