Utilidade de Ecocardiografia da Sobrecarga Farmacológica com Dobutamina nas Cardiomiopatias Dilatadas não Isquémicas

INTRODUCTION: Low-dose dobutamine stress echocardiography is a common and useful technique to assess myocardial viability in patients with ischemic cardiomyopathy. OBJECTIVE: To evaluate the use of low-dose dobutamine stress echocardiography in determining the functional status of patients with idiopathic dilated cardiomyopathy (IDCM). METHODS: Prospective study of 28 patients with IDCM by transthoracic echocardiography (2D), low-dose dobutamine stress echocardiography, cardiopulmonary exercise testing (CPET) and measurement of pro-BNP. RESULTS: The mean age of the population was 50.3 +/- 11.5 years, 9 female and 19 male. Mean ejection fraction was 32.1 +/- 9.8%. All were in sinus rhythm. The following parameters were analyzed in 2D echocardiography and after dobutamine: dimensions of left atrium (LA) and of left ventricle in diastole and systole, shortening fraction (%), left ventricular end-diastolic (EDV) and end-systolic volumes (ESV), ejection fraction (EF), and mitral inflow (E, A, E/A ratio and deceleration time). In CPET, we considered the following parameters: peak VO2 and % maximal peak VO2 attained. We compared echo results with CPET. There was a correlation between age and peak VO2 (r = -0.38 with p = 0.049). In 2D echo, there was a correlation between baseline EF and LA dimensions and peak VO2 (r = 0.45 / p = 0.004 and r = -0.49 / p = 0.014, respectively). After dobutamine echo, there was a correlation between some echo parameters and peak VO2: EF - r = 0.59 / p = 0.001, LA dimensions - r = 0.56 / p = 0.007, and ESV - r = -0.45 / p = 0.026. Percentage maximal peak VO2 attained correlated with LA dimensions measured in 2D echo and after dobutamine (r = -0.398 / p = 0.036 and r = -0.674 / p = 0.02 respectively) and EF after dobutamine (r = -0.389 / p = 0.04). The value of pro-BNP correlated with LA dimensions and baseline EF (r = 0.44 / p = 0.02 and r = -0.57 / p = 0.002, respectively), and the correlation was maintained after inotropic stimulation with dobutamine (r = 0.57 / p = 0.001 and r = -0.55 / p = 0.0039). CONCLUSION: Low-dose dobutamine stress echocardiography showed stronger correlations with cardiopulmonary exercise testing than the parameters evaluated by conventional echocardiography and could be used to determine the functional status of patients with dilated cardiomyopathy; patients with greater ejection fraction after inotropic stimulation had better cardiopulmonary tests.

Valor Prognóstico da Normalização da Resposta Ventilatória ao Exercício para o Consumo Máximo de Oxigénio na Insuficiência Cardíaca

Cardiopulmonary exercise testing (CPET) is an objective method for assessment of functional capacity and for prognostic stratification of patients with chronic heart failure (CHF). In this study, we analyzed the prognostic value of a recently described CPET-derived parameter, the minute ventilation to carbon dioxide production slope normalized for peak oxygen consumption (VE/VCO2 slope/pVO2). METHODS: We prospectively studied 157 patients with stable CHF and dilated cardiomyopathy who performed maximal CPET using the modified Bruce protocol. The prognostic value of VE/VCO2 slope/pVO2 was determined and compared with traditional CPET parameters. RESULTS: During follow-up 37 patients died and 12 were transplanted. Mean follow-up in surviving patients was 29.7 months (12-36). Cox multivariate analysis revealed that VE/VCO2 slope/pVO2 had the greatest prognostic power of all the parameters studied. A VE/VCO2 slope/pVO2 of > or = 2.2 signaled cases at higher risk. CONCLUSION: Normalization of the ventilatory response to exercise for peak oxygen consumption appears to increase the prognostic value of CPET in patients with CHF.

Prognostic Value of a New Cardiopulmonary Exercise Testing Parameter in Chronic Heart Failure: Oxygen Uptake Efficiency at Peak Exercise - Comparison with Oxygen Uptake Efficiency Slope

INTRODUCTION: A growing body of evidence shows the prognostic value of oxygen uptake efficiency slope (OUES), a cardiopulmonary exercise test (CPET) parameter derived from the logarithmic relationship between O(2) consumption (VO(2)) and minute ventilation (VE) in patients with chronic heart failure (CHF). OBJECTIVE: To evaluate the prognostic value of a new CPET parameter - peak oxygen uptake efficiency (POUE) - and to compare it with OUES in patients with CHF. METHODS: We prospectively studied 206 consecutive patients with stable CHF due to dilated cardiomyopathy - 153 male, aged 53.3±13.0 years, 35.4% of ischemic etiology, left ventricular ejection fraction 27.7±8.0%, 81.1% in sinus rhythm, 97.1% receiving ACE-Is or ARBs, 78.2% beta-blockers and 60.2% spironolactone - who performed a first maximal symptom-limited treadmill CPET, using the modified Bruce protocol. In 33% of patients an cardioverter-defibrillator (ICD) or cardiac resynchronization therapy device (CRT-D) was implanted during follow-up. Peak VO(2), percentage of predicted peak VO(2), VE/VCO(2) slope, OUES and POUE were analyzed. OUES was calculated using the formula VO(2) (l/min) = OUES (log(10)VE) + b. POUE was calculated as pVO(2) (l/min) / log(10)peakVE (l/min). Correlation coefficients between the studied parameters were obtained. The prognosis of each variable adjusted for age was evaluated through Cox proportional hazard models and R2 percent (R2%) and V index (V6) were used as measures of the predictive accuracy of events of each of these variables. Receiver operating characteristic (ROC) curves from logistic regression models were used to determine the cut-offs for OUES and POUE. RESULTS: pVO(2): 20.5±5.9; percentage of predicted peak VO(2): 68.6±18.2; VE/VCO(2) slope: 30.6±8.3; OUES: 1.85±0.61; POUE: 0.88±0.27. During a mean follow-up of 33.1±14.8 months, 45 (21.8%) patients died, 10 (4.9%) underwent urgent heart transplantation and in three patients (1.5%) a left ventricular assist device was implanted. All variables proved to be independent predictors of this combined event; however, VE/VCO2 slope was most strongly associated with events (HR 11.14). In this population, POUE was associated with a higher risk of events than OUES (HR 9.61 vs. 7.01), and was also a better predictor of events (R2: 28.91 vs. 22.37). CONCLUSION: POUE was more strongly associated with death, urgent heart transplantation and implantation of a left ventricular assist device and proved to be a better predictor of events than OUES. These results suggest that this new parameter can increase the prognostic value of CPET in patients with CHF.

Reliability of Two Methods for Identifying the Postural Phase of Gait Initiation in Healthy and Post-stroke Subjects

This study aims to compare two methods of assessing the postural phase of gait initiation as to intrasession reliability, in healthy and post-stroke subjects. As a secondary aim, this study aims to analyse anticipatory postural adjustments during gait initiation based on the centre of pressure (CoP) displacements in post-stroke participants. The CoP signal was acquired during gait initiation in fifteen post-stroke subjects and twenty-three healthy controls. Postural phase was identified through a baseline-based method and a maximal displacement based method. In both healthy and post-stroke participants higher intra-class correlation coefficient and lower coefficient of variation values were obtained with the baseline-based method when compared to the maximal displacement based method. Post-stroke participants presented decreased CoP displacement backward and toward the first swing limb compared to controls when the baseline-based method was used. With the maximal displacement based method, there were differences between groups only regarding backward CoP displacement. Postural phase duration in medial-lateral direction was also increased in post-stroke participants when using the maximal displacement based method. The findings obtained indicate that the baseline-based method is more reliable detecting the onset of gait initiation in both groups, while the maximal displacement based method presents greater sensitivity for post-stroke participants.

Leukopenia in Kidney Transplant Patients with the Association of Valganciclovir and Mycophenolate Mofetil

Cytomegalovirus (CMV) is the most common viral infection after transplantation. Valganciclovir (VGC) is established for prophylaxis and treatment of CMV infections, but leukopenia which appears in 10% to 13% (severe in 4.9%) is the principal side effect. We have recently noted an increased incidence of leukopenia and severe neutropenia among our renal transplant patients and thought to identify the associated factors. We conducted a retrospective analysis of all kidney transplantations performed between January 2005 and December 2006. All patients received mycophenolate mofetil (MMF), tacrolimus, and steroids. VGC was used for targeted prophylaxis and preemptive therapy of CMV infection, with doses adjusted to renal function. Of the 64 patients undergoing renal transplantation 13 (20.3%) developed leukopenia within 3 +/- 2 months after transplantation with severe neutropenia in 5 (7.8%). All patients were on MMF and VGC (VGC 605 +/- 296 mg/d). Leukopenia was significantly associated with simultaneous liver-kidney transplantation and with second kidney transplantations (P < .01). The incidence of leukopenia was higher among patients under VGC since day 1 of transplantation (P = .008) with maximal incidence observed among patients prescribed 900 mg/d as opposed to those on lower doses (P < .01). There was no increase in CMV infection among patients with a low dose of VGC. No patient developed clinical CMV disease. In conclusion, VGC prophylaxis was associated with an increased frequency of leukopenia on MMF-tacrolimus treated patients or regimens. Low-dose VGC for CMV prophylaxis appeared to be as effective as high-dose treatment, and associated less frequently with leukopenia and neutropenia.

Effective swimmer’s action during the grab start technique

The external forces applied in swimming starts have been often studied, but using direct analysis and simple interpretation data processes. This study aimed to develop a tool for vertical and horizontal force assessment based on the swimmers' propulsive and structural forces (passive forces due to dead weight) applied during the block phase. Four methodological pathways were followed: the experimented fall of a rigid body, the swimmers' inertia effect, the development of a mathematical model to describe the outcome of the rigid body fall and its generalization to include the effects of the inertia, and the experimental swimmers' starting protocol analysed with the inclusion of the developed mathematical tool. The first three methodological steps resulted in the description and computation of the passive force components. At the fourth step, six well-trained swimmers performed three 15 m maximal grab start trials and three-dimensional (3D) kinetic data were obtained using a six degrees of freedom force plate. The passive force contribution to the start performance obtained from the model was subtracted from the experimental force due to the swimmers resulting in the swimmers' active forces. As expected, the swimmers' vertical and horizontal active forces accounted for the maximum variability contribution of the experimental forces. It was found that the active force profile for the vertical and horizontal components resembled one another. These findings should be considered in clarifying the active swimmers' force variability and the respective geometrical profile as indicators to redefine steering strategies.

The relationship of cardiorespiratory fitness, birth weight and parental BMI on adolescents’ obesity status

The aims of this study were as follows: (1) to analyze differences in cardiorespiratory fitness (CRF), parents' body mass index (BMI) and birth weight (BW) between non-overweight (NOW) and overweight/obese (OV/OB) adolescents, and (2) to investigate the association of those variables with the risk of their biological offspring being OV/OB. This study comprised 788 adolescents (477 girls and 311 boys), aged between 12 and 18 years. CRF was predicted by maximal multistage 20-m shuttle-run test according to the procedures described in FITNESSGRAM. Children's BMI was classified according to the International Obesity Task Force. Adolescents' BW was assessed from each child's pediatric record at birth. Parents' OV/OB status was defined and classified according to the World Health Organization. Socioeconomic status was defined by parental education. The prevalence OV/OB was 21.4 and 5.3%, respectively, and there were no gender differences. The OV/OB adolescents (girls and boys) had significantly (P

Automatic syllabification for danish text-to-speech systems

In this paper, a rule-based automatic syllabifier for Danish is described using the Maximal Onset Principle. Prior success rates of rule-based methods applied to Portuguese and Catalan syllabification modules were on the basis of this work. The system was implemented and tested using a very small set of rules. The results gave rise to 96.9% and 98.7% of word accuracy rate, contrary to our initial expectations, being Danish a language with a complex syllabic structure and thus difficult to be rule-driven. Comparison with data-driven syllabification system using artificial neural networks showed a higher accuracy rate of the former system.

Disturbance in hemoglobin metabolism and in vivo antimalarial activity of azole antimycotics

Plasmodium parasites degrade host hemoglobin to obtain free amino acids, essential for protein synthesis. During this event, free toxic heme moieties crystallize spontaneously to produce a non-toxic pigment called hemozoin or ß-hematin. In this context, a group of azole antimycotics, clotrimazole (CTZ), ketoconazole (KTZ) and fluconazole (FCZ), were investigated for their abilities to inhibit ß-hematin synthesis (IßHS) and hemoglobin proteolysis (IHbP) in vitro. The ß-hematin synthesis was recorded by spectrophotometry at 405 nm and the hemoglobin proteolysis was determined by SDS-PAGE 12.5%, followed by densitometric analysis. Compounds were also assayed in vivo in a malaria murine model. CTZ and KTZ exhibited the maximal effects inhibiting both biochemical events, showing inhibition of β-hematin synthesis (IC50 values of 12.4 ± 0.9 µM and 14.4 ± 1.4 µM respectively) and inhibition of hemoglobin proteolysis (80.1 ± 2.0% and 55.3 ± 3.6%, respectively). There is a broad correlation to the in vivo results, especially CTZ, which reduced the parasitemia (%P) of infected-mice at 4th day post-infection significantly compared to non-treated controls (12.4 ± 3.0% compared to 26.6 ± 3.7%, p = 0.014) and prolonged the survival days post-infection. The results indicated that the inhibition of the hemoglobin metabolism by the azole antimycotics could be responsible for their antimalarial effect.

Invasive Assessment of the Coronary Microcirculation Using the Index of Microcirculatory Resistance: Description and Validation of an Animal Model

INTRODUCTION: The index of microcirculatory resistance (IMR) enables/provides quantitative, invasive, and real-time assessment of coronary microcirculation status. AIMS: The primary aim of this study was to validate the assessment of IMR in a large animal model, and the secondary aim was to compare two doses of intracoronary papaverine, 5 and 10 mg, for induction of maximal hyperemia and its evolution over time. METHODS: Measurements of IMR were performed in eight pigs. Mean distal pressure (Pd) and mean transit time (Tmn) were measured at rest and at maximal hyperemia induced with intracoronary papaverine, 5 and 10 mg, and after 2, 5, 8 and 10 minutes. Disruption of the microcirculation was achieved by selective injection of 40-μm microspheres via a microcatheter in the left anterior descending artery. RESULTS: In each animal 14 IMR measurements were made. There were no differences between the two doses of papaverine regarding Pd response and IMR values - 11 ± 4.5 U with 5 mg and 10.6 ± 3 U with 10 mg (p=0.612). The evolution of IMR over time was also similar with the two doses, with significant differences from resting values disappearing after five minutes of intracoronary papaverine administration. IMR increased with disrupted microcirculation in all animals (41 ± 16 U, p=0.001). CONCLUSIONS: IMR provides invasive and real-time assessment of coronary microcirculation. Disruption of the microvascular bed is associated with a significant increase in IMR. A 5-mg dose of intracoronary papaverine is as effective as a 10-mg dose in inducing maximal hyperemia. After five minutes of papaverine administration there is no significant difference from resting hemodynamic status.

Lack of Spontaneous Venous Pulsation: Possible Risk Indicator in Normal Tension Glaucoma?

PURPOSE: Recently, the absence of spontaneous venous pulsation (SVP) has been suggested as a vascular risk factor for primary open-angle glaucoma (POAG). As the mechanism behind this phenomenon is still unknown, the authors have studied this vascular component using colour Doppler imaging (CDI). METHODS: A total of 236 patients were divided into three diagnostic groups: healthy controls (81), POAG (86) and normal tension glaucoma (NTG; 69). All subjects were submitted to CDI studies of the retrobulbar circulation, intraocular pressure measurements and assessment of SVP existence. Mann-Whitney, chi-square contingency tables and Spearman correlations were used to explore differences and correlations between variables in the diagnostic groups. RESULTS: Eighty-two percent of healthy controls had SVP (66/81), while a smaller numbers were registered in both glaucoma groups: POAG - 50% (43/86); NTG - 51% (35/69). In NTG patients, but not in POAG patients, the prevalence of the SVP phenomenon decreases with increased glaucoma damage (p = 0.04; p = 0.55, respectively). Overall glaucoma patients from both groups had lower central retinal vein (CRV) velocities than the healthy controls (p < 0.05). NTG patients with SVP had less severe visual field defects (mean defect -6.92 versus -11.1, p < 0.05), higher [correction added after online publication 21 September 2012; the word 'higher' has been inserted to replace the word 'lower'] peak systolic and mean flow velocities in the central retinal artery (p < 0.01; p < 0.05, respectively) as well as higher [correction added after online publication 21 September 2012; the word higher has been inserted to replace the word lower] maximal velocities and RI of the CRV (p < 0.02; p < 0.05, respectively). CONCLUSIONS: Glaucoma patients have a decrease in CRV velocities. SVP is less prevalent in glaucoma patients than in healthy individuals. This phenomenon apparently reflects different hemodynamic patterns in the central retinal vessels. This variable may be of particular importance in NTG patients, where it may be associated with more advanced functional damage.

Intracoronary Delivery of Human Mesenchymal/Stromal Stem Cells: Insights from Coronary Microcirculation Invasive Assessment in a Swine Model

BACKGROUND: Mesenchymal stem/stromal cells have unique properties favorable to their use in clinical practice and have been studied for cardiac repair. However, these cells are larger than coronary microvessels and there is controversy about the risk of embolization and microinfarctions, which could jeopardize the safety and efficacy of intracoronary route for their delivery. The index of microcirculatory resistance (IMR) is an invasive method for quantitatively assessing the coronary microcirculation status. OBJECTIVES: To examine heart microcirculation after intracoronary injection of mesenchymal stem/stromal cells with the index of microcirculatory resistance. METHODS: Healthy swine were randomized to receive by intracoronary route either 30x106 MSC or the same solution with no cells (1% human albumin/PBS) (placebo). Blinded operators took coronary pressure and flow measurements, prior to intracoronary infusion and at 5 and 30 minutes post-delivery. Coronary flow reserve (CFR) and the IMR were compared between groups. RESULTS: CFR and IMR were done with a variance within the 3 transit time measurements of 6% at rest and 11% at maximal hyperemia. After intracoronary infusion there were no significant differences in CFR. The IMR was significantly higher in MSC-injected animals (at 30 minutes, 14.2U vs. 8.8U, p = 0.02) and intragroup analysis showed a significant increase of 112% from baseline to 30 minutes after cell infusion, although no electrocardiographic changes or clinical deterioration were noted. CONCLUSION: Overall, this study provides definitive evidence of microcirculatory disruption upon intracoronary administration of mesenchymal stem/stromal cells, in a large animal model closely resembling human cardiac physiology, function and anatomy.

Growth and differentiation on a trypanosome of the subgenus Schizotrypanum from the bat Phyllostomus hastatus

The effects of temperature, pH, osmolarity and aeration on the growth and differentiation of a trypanosome ofthe subgenus Schizotrypanum isolatedfrom the bat Phyllostomus hastatus were studied. In general, the growth characteristics ofthe flagellate were similar to those of Trypanosoma (Schizotrypanum) cruzi. However, the parasite did not growth at 33 or 37C. Increase in the osmolarity and aeration promoted growth at 33C. Significant metacyclogenesis was detected only in the growth condition where maximal growth occured (28C, pH 7.3, 380m0s/kg, in tissue cullure flasks), at the end ofthe exponential growth phase. The begining of the metacyclogenesis process was coincident with most glucose utilization and lowest pH. During metacyclogenesis both culture medium pH and osmolarity increased steadly.

Comparison of the fluorescent polarization (TDx) and the enzymatic competitive (EMIT 2000) immune assays for the measurement of cyclosporin A blood concentration

Evaluation of Cyclosporin A (CyA) blood concentration is imperative in solid organ transplantation in order to achieve maximal immunosuppression with the least side effects. We compared the results of whole blood concentrations of CyA in 50 blood samples simultaneously evaluated by the fluorescent polarization immune assay (TDx) and the enzymatic competitive immune assay (EMIT 2000). There was a strong correlation between both kits for any range of CyA blood concentration (R=0.99, p<0.001). The within-run and between-days coefficient of variation were less than 4% for both assays. The cost for each CyA measurement was 50% lower for the EMIT assay when compared to the TDx assay. We concluded that the EMIT is as accurate as the TDx in measuring CyA blood concentration and has the advantage of a lower cost, as well as the possibility of widespread access to the EMIT methodology in contrast to the TDx equipment, allowing the laboratory to perform several routines within a working day.

Pulmonary function and aerobic capacity in asymptomatic bariatric candidates with very severe morbid obesity

PURPOSE: Aerobic capacity and respiratory function may be compromised in obesity, but few studies have been done in highly obese bariatric candidates. In a prospective study, these variables were documented in the preoperative period, aiming to define possible physiologic limitations in a apparently healthy and asymptomatic population. METHOD: Forty-six consecutively enrolled adults (age 39.6 ± 8.4 years, 87.0% females, body mass index /BMI 49.6 ± 6.3 kg/m² ) were analyzed. Ventilatory variables were investigated by automated spirometry, aerobic capacity was estimated by a modified Bruce test in an ergometric treadmill, and body composition was determined by bioimpedance analysis. RESULTS: Total fat was greatly increased (46.4 ± 4.6% of body weight) and body water reduced (47.3 ± 4.6 % body weight), as expected for such obese group. Spirometric findings including forced vital capacity of 3.3 ± 0.8 L and forced expiratory volume-1 second of 2.6 ± 0.6 L were usually acceptable for age and gender, but mild restrictive pulmonary insufficiency was diagnosed in 20.9%. Aerobic capacity was more markedly diminished, as reflected by very modest maximal time (4.5 ± 1.1 min) and distance (322 ±142 m) along with proportionally elevated maximal oxygen consumption (23.4 ± 9.5 mL/kg/min) achieved by these subjects during test exercise. CONCLUSIONS: 1) Cardiopulmonary evaluation was feasible and well-tolerated in this severely obese population; 2) Mean spirometric variables were not diminished in this study, but part of the population displayed mild restrictive changes; 3) Exercise tolerance was very negatively influenced by obesity, resulting in reduced endurance and excessive metabolic cost for the treadmill run; 4) More attention to fitness and aerobic capacity is recommended for seriously obese bariatric candidates;