Performance of rest myocardial perfusion imaging in the management of acute chest pain in the emergency room in developing nations (PREMIER trial)

Background. Rest myocardial perfusion imaging (MPI) is effective in managing patients with acute chest pain in developed countries. We aimed to define the role and feasibility of rest MPI in low-to-middle income countries. Methods and Results. Low-to-intermediate risk patients (n = 356) presenting with chest pain to ten centers in eight developing countries were injected with a Tc-99m-based tracer, and standard imaging was performed. The primary outcome was a composite of death, non-fatal myocardial infarction (MI), recurrent angina, and coronary revascularization at 30 days. Sixty-nine patients had a positive MPI (19.4%), and 52 patients (14.6%) had a primary outcome event. An abnormal rest-MPI result was the only variable which independently predicted the primary outcome [adjusted odds ratio (OR) 8.19, 95% confidence interval 4.10-16.40, P = .0001]. The association of MPI result and the primary outcome was stronger (adjusted OR 17.35) when only the patients injected during pain were considered. Rest-MPI had a negative predictive value of 92.7% for the primary outcome, improving to 99.3% for the hard event composite of death or MI. Conclusions. Our study demonstrates that rest-MPI is a reliable test for ruling out MI when applied to patients in developing countries. (J Nucl Cardiol 2012;19:1146-53.)

Assessment of myocardial infarction by CT angiography and cardiovascular MRI in patients with cocaine-associated chest pain: a pilot study

Objectives: Cocaine is a commonly used illicit drug that leads to the most emergency department (ED) visits. Chest pain is the most common presentation, reported in 40% of patients. Our aim was to evaluate the incidence of previous myocardial infarction among young cocaine users (18-40 years) with cocaine-associated chest pain by the assessment of myocardial fibrosis by cardiovascular MRI. Second, we also intended to evaluate the coronary tree by CT angiography (CTA). Methods: 24 cocaine users (22 males) who frequently complained about cocaine-associated chest pain underwent CTA and cardiovascular MRI. Mean age of patients was 29.7 years and most of them (79%) had frequently used inhalatory cocaine. Results: The calcium score turned out to be positive in only one patient (Agatston=54). Among the coronary segments evaluated, only one patient had calcified plaques at the anterior descending coronary artery (proximal and medium segments). Assessment of regional ventricular function by the evaluation of 17 segments was normal in all patients. None of the patients showed myocardial delayed enhancement, indicative of myocardial fibrosis. CTA therefore confirmed the low cardiovascular risk of these patients, since most of them (96%) had no atherosclerosis detected by this examination. Only one patient (4%) had coronary atherosclerosis detected, without significant coronary stenosis. Conclusion: Cardiovascular MR did not detect the presence of delayed enhancement indicative of myocardial fibrosis among young cocaine users with low cardiovascular risk who had complained of cocaine-associated chest pain.

Chest associated to motor physiotherapy improves cardiovascular variables in newborns with respiratory distress syndrome

Background We aimed to evaluate the effects of chest and motor physiotherapy treatment on hemodynamic variables in preterm newborns with respiratory distress syndrome. Methods We evaluated heart rate (HR), respiratory rate (RR), systolic (SAP), mean (MAP) and diastolic arterial pressure (DAP), temperature and oxygen saturation (SO2%) in 44 newborns with respiratory distress syndrome. We compared all variables between before physiotherapy treatment vs. after the last physiotherapy treatment. Newborns were treated during 11 days. Variables were measured 2 minutes before and 5 minutes after each physiotherapy treatment. We applied paired Student t test to compare variables between the two periods. Results HR (148.5 ± 8.5 bpm vs. 137.1 ± 6.8 bpm - p < 0.001), SAP (72.3 ± 11.3 mmHg vs. 63.6 ± 6.7 mmHg - p = 0.001) and MAP (57.5 ± 12 mmHg vs. 47.7 ± 5.8 mmHg - p = 0.001) were significantly reduced after 11 days of physiotherapy treatment compared to before the first session. There were no significant changes regarding RR, temperature, DAP and SO2%. Conclusions Chest and motor physiotherapy improved cardiovascular parameters in respiratory distress syndrome newborns.

Influence of chest wall on lung mechanics during inspiration

RATIONALE: The interaction between lungs and chest wall influences lung volume, that determines lung history during respiration cycle. In this study, the influence of chest wall mechanics on respiratory system is assessed by the evaluation of inspiration pressure-volume curve (PV curve) under three different situations: closed-chest, open-chest and isolated lung. The PV curve parameters in each situation allow us to further understand the role played by different chest wall elements in the respiratory function. Methods: Twenty-four male Wistar rats (236 ± 29 g) were used. The animals were weighted and then anesthetized with xylazine 2% (O,SmL/kg) and ketamine 10% (0,9mL/kg), exsanguinated and later tracheostomies with a metallic cannula (14 gauge).The cannula was connected to an automatic small animal insufflator. This setup was connected to a pressure transducer (32 samples/s). The 24 animals were randomly separated in three groups:(i) closed chest,(ii) open chest and (iii) isolated lung. The rats were insufflated with 20mL quasi-statically (constant speed of 0,1mUs). lnsufflated volume and measured pressure data were kept and PV curves were obtained for all animals. The PV curves were fitted (non-linear least squares) against the sigmoid equation (1) to obtain the sigmoid equation parameters (a,b,c,d). Elastance measurements were obtained from linear regression of pressure/volume measurements in a 0,8s interval before and after the calculated point. Results: The parameters a,b and c showed no significant change, but the parameter d showed a significant variation among the three groups. The initial elastance also varied between open and closed chest, indicating the need of a higher pressure for the lung expansion, as can be seen in Table 1. Conclusion: A supporting effect of the chest wall was observed at the initial moments of inspiration, observed as a higher initial elastance in open chest situations than in closed chest situations (p=0,00001). The similar initial elastance for the isolated lung and closed chest may be explained by the specific method used for the isolated lung experiment. As the isolated lung is supported by the trachea vertically, the weight of the tissue may have a similar effect of the residual negative pressure in the thorax, responsible for maintaining the residual volume.

Influence of chest wall on lung mechanics during inspiration.

RATIONALE: The interaction between lungs and chest wall influences lung volume, that determines lung history during respiration cycle. In this study, the influence of chest wall mechanics on respiratory system is assessed by the evaluation of inspiration pressure-volume curve (PV curve) under three different situations: closed-chest, open-chest and isolated lung. The PV curve parameters in each situation allow us to further understand the role played by different chest wall elements in the respiratory function. Methods: Twenty-four male Wistar rats (236 ± 29 g) were used. The animals were weighted and then anesthetized with xylazine 2% (0,5mL/kg) and ketamine 10% (0,9mL/kg), exsanguinated and later tracheostomized with a metallic cannula (14 gauge). The cannula was connected to an automatic small animal insufflator. This setup was connected to a pressure transducer (32 samples/s). The 24 animals were randomly separated in three groups: (i) closed chest, (ii) open chest and (iii) isolated lung. The rats were insufflated with 20mL quasi-statically (constant speed of 0,1mL/s). Insufflated volume and measured pressure data were kept and PV curves were obtained for all animals. The PV curves were fitted (non-linear least squares) against the sigmoid equation (1) to obtain the sigmoid equation parameters (a,b,c,d). Elastance measurements were obtained from linear regression of pressure/volume measurements in a 0,8s interval before and after the calculated point. Results: The parameters a, b and c showed no significant change, but the parameter d showed a significant variation among the three groups. The initial elastance also varied between open and closed chest, indicating the need of a higher pressure for the lung expansion, as can be seen in Table 1. Table 1: Mean and Standard Deviation of parameters obtained for each protocol. Protocol: Closed Chest – a (mL) -0.35±0.33; b (mL) 13.93±0.89; c (cm H2O) 21.28±2.37; d (cm H2O) 6.17±0.84; r²** (%) 99.4±0.14; Initial Elastance* (cm H2)/mL) 12.72±6.66; Weight (g) 232.33±5.72. Open Chest - a (mL) 0.01±0.28; b (mL) 14.79±0.54; c (cm H2O) 19.47±1.41; d (cm H2O) 3.50±0.28; r²** (%) 98.8±0.34; Initial Elastance* (cm H2)/mL) 28.68±2.36; Weight (g) 217.33±7.97. Isolated Lung - a (mL) -0.09±0.46; b (mL) 14.22±0.75; c (cm H2O) 21.76±1.43; d (cm H2O) 4.24±0.50; r²** (%) 98.9±0.19; Initial Elastance* (cm H2)/mL) 7.13±8.85; Weight (g) 224.33±16.66. * Elastance measures in the 0-0,1 mL range. ** Goodness of sigmoid fit versus measured data Conclusion: A supporting effect of the chest wall was observed at the initial moments of inspiration, observed as a higher initial elastance in open chest situations than in closed chest situations (p=0,00001). The similar initial elastance for the isolated lung and closed chest may be explained by the specific method used for the isolated lung experiment. As the isolated lung is supported by the trachea vertically, the weight of the tissue may have a similar effect of the residual negative pressure in the thorax, responsible for maintaining the residual volume.

Noninvasive positive-pressure ventilation in clinical practice at a large university-affiliated Brazilian hospital

OBJECTIVES: To describe noninvasive positive-pressure ventilation use in intensive care unit clinical practice, factors associated with NPPV failure and the associated prognosis. METHODS: A prospective cohort study. RESULTS: Medical disorders (59%) and elective surgery (21%) were the main causes for admission to the intensive care unit. The main indications for the initiation of noninvasive positive-pressure ventilation were the following: post-extubation, acute respiratory failure and use as an adjunctive technique to chest physiotherapy. The noninvasive positive-pressure ventilation failure group was older and had a higher Simplified Acute Physiology Score II score. The noninvasive positive-pressure ventilation failure rate was 35%. The main reasons for intubation were acute respiratory failure (55%) and a decreased level of consciousness (20%). The noninvasive positive-pressure ventilation failure group presented a shorter period of noninvasive positive-pressure ventilation use than the successful group [three (2-5) versus four (3-7) days]; they had lower levels of pH, HCO3 and base excess, and the FiO(2) level was higher. These patients also presented lower PaO2:FiO2 ratios; on the last day of support, the inspiratory positive airway pressure and expiratory positive airway pressure were higher. The failure group also had a longer average duration of stay in the intensive care unit [17 (10-26) days vs. 8 (5-14) days], as well as a higher mortality rate (9 vs. 51%). There was an association between failure and mortality, which had an odds ratio (95% CI) of 10.6 (5.93 - 19.07). The multiple logistic regression analysis using noninvasive positive pressure ventilation failure as a dependent variable found that treatment tended to fail in patients with a Simplified Acute Physiology Score II >= 34, an inspiratory positive airway pressure level >= 15 cmH2O and pH<7.40. CONCLUSION: The indications for noninvasive positive-pressure ventilation were quite varied. The failure group had a longer intensive care unit stay and higher mortality. Simplified Acute Physiology Score II >= 34, pH<7.40 and higher inspiratory positive airway pressure levels were associated with failure.

The effects of high-intensity resistance exercise on the blood lipid profile and liver function in hypercholesterolemic hamsters

It is well established that atherogenic dyslipidemia, characterized by high levels of triglycerides (TG), total cholesterol (TC), and low-density lipoprotein (LDL) cholesterol and low levels of high-density lipoprotein (HDL) cholesterol, constitutes important risk factors for cardiovascular disease. Regular exercise has been associated with a reduced risk for metabolic diseases. However, studies supporting the concept that resistance exercise is a modifier of blood lipid parameters are often contradictory. The aim of this study was to investigate the effects of high-intensity resistance exercise on the serum levels of TG, TC, HDL and non-HDL cholesterol, glucose, and the liver function enzymes alanine aminotransferase (ALT, EC 2.6.1.2) and aspartate aminotransferase (AST, EC 2.6.1.1) in golden Syrian hamsters (Mesocricetus auratus (Waterhouse, 1839)) fed a hypercholesterolemic diet. Sedentary groups (S) and exercise groups (E) were fed a standard diet (SS and ES) or a cholesterol-enriched diet (standard plus 1% cholesterol, SC and EC). Resistance exercise was performed by jumps in the water, carrying a load strapped to the chest, representing 10 maximum repetitions (10 RM, 30 s rest, five days per week for five weeks). Mean blood sample comparisons were made by ANOVA + Tukey or ANOVA + Kruskal-Wallis tests (p < 0.05) to compare parametric and nonparametric samples, respectively. There were no differences in blood lipids between the standard diet groups (SS and ES) (p > 0.05). However, the EC group increased the glucose, non-HDL, and TC levels in comparison with the ES group. Moreover, the EC group increased the TG levels versus the SC group (p < 0.05). In addition, the ALT levels were increased only by diet treatment. These findings indicated that high-intensity resistance exercise contributed to dyslipidemia in hamsters fed a hypercholesterolemic diet, whereas liver function enzymes did not differ in regards to the exercise protocol.

Respiratory rehabilitation: a physiotherapy approach to the control of asthma symptoms and anxiety

OBJECTIVES: The objectives of this study were to verify the degree of anxiety, respiratory distress, and health-related quality of life in a group of asthmatic patients who have experienced previous panic attacks. Additionally, we evaluated if a respiratory physiotherapy program (breathing retraining) improved both asthma and panic disorder symptoms, resulting in an improvement in the health-related quality of life of asthmatics. METHODS: Asthmatic individuals were assigned to a chest physiotherapy group that included a breathing retraining program held once a week for three months or a paired control group that included a Subtle Touch program. All patients were assessed using the Diagnostic and Statistical Manual of Mental Disorders IV, the Sheehan Anxiety Scale, the Quality of Life Questionnaire, and spirometry parameter measurements. RESULTS: Both groups had high marks for panic disorder and agoraphobia, which limited their quality of life. The Breathing Retraining Group program improved the clinical control of asthma, reduced panic symptoms and agoraphobia, decreased patient scores on the Sheehan Anxiety Scale, and improved their quality of life. Spirometry parameters were unchanged. CONCLUSION: Breathing retraining improves the clinical control of asthma and anxiety symptoms and the health-related quality of life in asthmatic patients.

Pleural tuberculosis: is radiological evidence of pulmonary-associated disease related to the exacerbation of the inflammatory response?

OBJECTIVE: Pleural tuberculosis is the most frequently occurring form of extra pulmonary disease in adults. In up to 40% of cases, the lung parenchyma is concomitantly involved, which can have an epidemiological impact. This study aims to evaluate the pleural and systemic inflammatory response of patients with pleural or pleuropulmonary tuberculosis. METHODS: A prospective study of 39 patients with confirmed pleural tuberculosis. After thoracentesis, a high resolution chest tomography was performed to evaluate the pulmonary involvement. Of the 39 patients, 20 exhibited only pleural effusion, and high resolution chest tomography revealed active associated-pulmonary disease in 19 patients. The total protein, lactic dehydrogenase, adenosine deaminase, vascular endothelial growth factor, interleukin-8, tumor necrosis factor-alpha, and transforming growth factor-beta(1) levels were quantified in the patient serum and pleural fluid. RESULTS: All of the effusions were exudates with high levels of adenosine deaminase. The levels of vascular endothelial growth factor and transforming growth factor-beta(1) were increased in the blood and pleural fluid of all of the patients with pleural tuberculosis, with no differences between the two forms of tuberculosis. The tumor necrosis factor-alpha levels were significantly higher in the pleural fluid of the patients with the pleuropulmonary form of tuberculosis. The interleukin-8 levels were high in the pleural fluid of all of the patients, without any differences between the forms of tuberculosis. CONCLUSION: Tumor necrosis factor-alpha was the single cytokine that significantly increased in the pleural fluid of the patients with pulmonary involvement. However, an overlap in the results does not permit us to suggest that cytokine is a biological marker of concomitant parenchymal involvement. Although high resolution chest tomography can be useful in identifying these patients, the investigation of fast acid bacilli and cultures for M. tuberculosis in the sputum is recommended for all patients who are diagnosed with pleural tuberculosis.

Exhaled Acetone as a New Biomarker of Heart Failure Severity

Background: Heart failure (HF) is associated with poor prognosis, and the identification of biomarkers of its severity could help in its treatment. In a pilot study, we observed high levels of acetone in the exhaled breath of patients with HF. The present study was designed to evaluate exhaled acetone as a biomarker of HF diagnosis and HF severity. Methods: Of 235 patients with systolic dysfunction evaluated between May 2009 and September 2010, 89 patients (HF group) fulfilled inclusion criteria and were compared with sex- and age-matched healthy subjects (control group, n = 20). Patients with HF were grouped according to clinical stability (acute decompensated HF [ADHF], n = 59; chronic HF, n = 30) and submitted to exhaled breath collection. Identification of chemical species was done by gas chromatography-mass spectrometry and quantification by spectrophotometry. Patients with diabetes were excluded. Results: The concentration of exhaled breath acetone (EBA) was higher in the HF group (median, 3.7 mu g/L; interquartile range [IQR], 1.69-10.45 mu g/L) than in the control group (median, 0.39 mu g/L; IQR, 0.30-0.79 mu g/L; P < .001) and higher in the ADHF group (median, 7.8 mu g/L; IQR, 3.6-15.2 mu g/L) than in the chronic HF group (median, 1.22 mu g/L; IQR, 0.68-2.19 P < .001). The accuracy and sensitivity of this method in the diagnosis of HF and ADHF were about 85%, a value similar to that obtained with B-type natriuretic peptide (BNP). EBA levels differed significantly as a function of severity of HF (New York Heart Association classification, P < .001). There was a positive correlation between EBA and BNP (r = 0.772, P < .001). Conclusions: EBA not only is a promising noninvasive diagnostic method of HF with an accuracy equivalent to BNP but also a new biomarker of HF severity. CHEST 2012; 142(2):457-466

A direct D-bar reconstruction algorithm for recovering a complex conductivity in 2D

A direct reconstruction algorithm for complex conductivities in W-2,W-infinity(Omega), where Omega is a bounded, simply connected Lipschitz domain in R-2, is presented. The framework is based on the uniqueness proof by Francini (2000 Inverse Problems 6 107-19), but equations relating the Dirichlet-to-Neumann to the scattering transform and the exponentially growing solutions are not present in that work, and are derived here. The algorithm constitutes the first D-bar method for the reconstruction of conductivities and permittivities in two dimensions. Reconstructions of numerically simulated chest phantoms with discontinuities at the organ boundaries are included.

Does videothoracoscopy improve clinical outcomes when implemented as part of a pleural empyema treatment algorithm?

OBJECTIVE: We aimed to evaluate whether the inclusion of videothoracoscopy in a pleural empyema treatment algorithm would change the clinical outcome of such patients. METHODS: This study performed quality-improvement research. We conducted a retrospective review of patients who underwent pleural decortication for pleural empyema at our institution from 2002 to 2008. With the old algorithm (January 2002 to September 2005), open decortication was the procedure of choice, and videothoracoscopy was only performed in certain sporadic mid-stage cases. With the new algorithm (October 2005 to December 2008), videothoracoscopy became the first-line treatment option, whereas open decortication was only performed in patients with a thick pleural peel (>2 cm) observed by chest scan. The patients were divided into an old algorithm (n = 93) and new algorithm (n = 113) group and compared. The main outcome variables assessed included treatment failure (pleural space reintervention or death up to 60 days after medical discharge) and the occurrence of complications. RESULTS: Videothoracoscopy and open decortication were performed in 13 and 80 patients from the old algorithm group and in 81 and 32 patients from the new algorithm group, respectively (p < 0.01). The patients in the new algorithm group were older (41 +/- 1 vs. 46.3 +/- 16.7 years, p=0.014) and had higher Charlson Comorbidity Index scores [0(0-3) vs. 2(0-4), p = 0.032]. The occurrence of treatment failure was similar in both groups (19.35% vs. 24.77%, p= 0.35), although the complication rate was lower in the new algorithm group (48.3% vs. 33.6%, p = 0.04). CONCLUSIONS: The wider use of videothoracoscopy in pleural empyema treatment was associated with fewer complications and unaltered rates of mortality and reoperation even though more severely ill patients were subjected to videothoracoscopic surgery.

The Role of Target Therapies in Schistosomiasis-Associated Pulmonary Arterial Hypertension

Background: Schistosomiasis-associated pulmonary arterial hypertension (Sch-PAH) may be one of the most prevalent forms of pulmonary arterial hypertension (PAH) worldwide. However, the clinical and hemodynamical response to specific PAH therapy in Sch-PAH is not known. Methods: We retrospectively analyzed the charts of all patients with Sch-PAH who initiated specific PAH treatment between June 2003 and June 2010 in a single PAH reference center in Sao Paulo, Brazil. Clinical and hemodynamical data were retrospectively collected and evaluated in two periods: baseline and posttreatment. Results: The study population consisted of 12 patients with Sch-PAH. They were treated with phosphodiseterase-5 inhibitors (seven patients), endothelin receptor antagonists (four patients), or combination therapy (one patient). Mean treatment period was 34.9 +/- 15.5 months. Patients with Sch-PAH presented significant improvements in terms of functional class, 6-min walk test distance (439 +/- 85 to 492 +/- 79 m, P = .032), cardiac index (2.66 +/- 0.59 to 3.08 +/- 0.68 L/min/m(2), P = .028), and indexed pulmonary vascular resistance (20.7 +/- 11.6 to 15.9 +/- 9 W/m(2), P = .038) with the introduction of specific PAH treatment. Conclusions: We conclude that specific PAH therapy may be of benefit to patients with Sch-PAH, considering clinical, functional, and hemodynamic parameters. CHEST 2012; 141(4):923-928

CPAP Has No Effect on Clearance, Sputum Properties, or Expectorated Volume in Cystic Fibrosis

BACKGROUND: Positive expiratory pressure (PEP) is used for airway clearance in cystic fibrosis (CF) patients. Hypertonic saline (HTS) aerosol increases sputum expectoration volume and may improve respiratory secretion properties. CPAP may also be used to maintain airway patency and mobilize secretions. To evaluate if CPAP would increase the beneficial clearance effect of HTS in subjects with CF, we investigated the effects of CPAP alone and CPAP followed by HTS on sputum physical properties and expectoration volume in CF subjects. METHODS: In this crossover study, 15 CF subjects (mean age 19 y old) were randomized to interventions, 48 hours apart: directed coughs (control), CPAP at 10 cm H2O, HTS 7%, and both CPAP and HTS (CPAP+HTS). Sputum collection was performed at baseline and after interventions. Expectorated volume was determined and in vitro sputum properties were analyzed for contact angle and cough clearability. RESULTS: There were no significant differences between any treatment in arterial blood pressure, heart rate, or pulse oximetry, between the 2 time points. HTS and CPAP+HTS improved cough clearability by 50% (P = .001) and expectorated volume secretion by 530% (P = .001). However, there were no differences between control and CPAP on sputum contact angle, cough clearability, or volume of expectorated secretion. CONCLUSIONS: CPAP alone had no effect on mucus clearance, sputum properties, or expectorated volume, and did not potentiate the effect of HTS alone in CF subjects.

Proinflammatory and Antiinflammatory Cytokine Levels in Complicated and Noncomplicated Parapneumonic Pleural Effusions

Objectives: This study aimed to evaluate a panel of proinflammatory and antiinflammatory cytokines in noncomplicated and complicated parapneumonic pleural effusions and to correlate their levels with pleural fluid biochemical parameters. Methods: Serum and pleural effusion were collected from 60 patients with noncomplicated (n = 26) or complicated (n = 34) parapneumonic effusions and assayed for cytologic, biochemical, and proinflammatory and antiinflammatory cytokines. Student t test was used to compare serum and pleural fluid values, Spearman correlation to analyze the relationship between pleural fluid cytokines and biochemical parameters, and accuracy of pleural fluid cytokine levels to determine the optimal cutoff value for identification of complicated effusions. Corrections for multiple comparisons were applied and a P value < .05 was accepted as significant. Results: Serum and pleural fluid cytokine levels of IL-8, vascular endothelial growth factor (VEGF), IL-10, and tumor necrosis factor (TNF) soluble receptor (sR) II were similar between groups. In contrast, complicated effusions had higher levels of pleural fluid IL-1 beta, IL-1 receptor antagonist (ra), and TNF sRI. Negative correlations were found between pleural fluid glucose with IL-1 beta and TNF sRI and positive correlations between lactic dehydrogenate (LDH) with IL-1 beta, IL-8, and VEGF. Pleural fluid levels of IL-1 beta, IL-1ra, and TNF sRI were more accurate than IL-8, VEGF, IL-10, and TNF sRII in discriminating complicated effusions. Conclusions: Both proinflammatory and antiinflammatory cytokine levels in pleural fluid are elevated in complicated in comparison with noncomplicated parapneumonic pleural effusions, and they correlate with both pleural fluid glucose and LDH levels. IL-1 beta, IL-1ra, and TNF sRI had higher sensitivity and specificity than IL-8, VEGF, IL-10, and TNF sRII in discriminating complicated effusions. CHEST 2012; 141( 1):183-189