Nebulized and intraperitoneal ketamine have equivalent antidepressant-like effect in the forced swim and tail suspension tests in mice.

Major depressive disorder (MDD) is a debilitating illness that affects millions of people worldwide. Currently available antidepressants often take weeks to months to reach their full effect, which leads to an increased risk of suicidal behavior in patients with MMD. Intranasally, esketamine has emerged as an alternative to current antidepressants because of its rapid onset and long-lasting effects in patients with MDD. Animal models are useful for the initial pharmacological screening and for a better understanding of the mechanisms underlying the effects of new drugs with potential against MDD. There is a lack of data on alternative routes of drug administration, either oral or injectable, that can be used in preclinical studies. This study aimed to test whether ketamine has antidepressant-like effects in mice when administered via nebulization using a low-cost apparatus. When mice whose depressive-like behavior was induced by corticosterone were treated with nebulized ketamine at concentrations of 1.3, 2.6, and 5.2 mg/mL, immobility was reduced by 38.6 %, 62.0 %, and 61.1 %, respectively, in the forced swimming test (FST) and 43.6 %, 42.1 %, and 57.9 %, respectively, in the tail suspension test (TST). When depression-like behavior was induced by dexamethasone, nebulization with ketamine reduced immobility by 79.7 %, 49.2 %, and 44.4 % in the FST and 80.9 %, 71.4 %, and 80.4 %, respectively, in the TST. When depression-like behavior was induced by the association between dexamethasone and unpredictable chronic mild stress (UCMS) exposure, immobility was reduced by 26.1 %, 55.3 %, and 19.1 % in FST. Mice treated with nebulized ketamine did not show significant changes in the distance covered or in the time spent moving in the open field test. The efficacy of intraperitoneal and nebulized ketamine is equivalent, which shows that nebulization can be an alternative inexpensive route of drug administration for behavioral studies in rodents.

Proton pump inhibitors in patients treated with aspirin and clopidogrel after acute coronary syndrome.

INTRODUCTION: Clopidogrel is an antiplatelet agent converted to its active metabolite by cytochrome P-450 isoenzymes. Numerous drugs are known to inhibit P-450 isoenzymes, including proton pump inhibitors (PPIs), which are often associated with aspirin and clopidogrel to prevent adverse gastrointestinal effects. In vitro studies first showed that PPIs reduced the antiplatelet effect of clopidogrel, while recent clinical studies have raised concerns that the addition of a PPI to clopidogrel in acute coronary syndrome (ACS) patients could actually increase the risk of recurrent cardiovascular events. OBJECTIVE: The aim of this study was to evaluate whether the prescription of a PPI conferred a worse prognosis in patients discharged with aspirin and clopidogrel treatment after ACS. METHODS: A total of 876 patients admitted with ACS and discharged with aspirin and clopidogrel, with a planned duration of at least six months, from January 2004 to March 2008, were reviewed. Patients were classified in two groups according to whether or not a PPI was prescribed at discharge. The PPIs considered were those mainly metabolized by cytochrome P-450 2C19. We excluded patients with insufficient information available on either prescription or clinical records that could allow clearly confirm or exclude exposure to a PPI. Primary end points were six-month all-cause mortality and the composite of death, myocardial infarction and unstable angina at six months. RESULTS: Of the 802 patients considered for further analysis, 274 (34.2%) individuals were medicated with a PPI in addition to dual antiplatelet therapy. Patients taking PPIs were older, more often had renal insufficiency and less often had a history of coronary revascularization and smoking. They more often presented with Killip class >I and lower hemoglobin concentration on admission. There were no significant differences between the two groups in terms of medical treatment (during hospital stay and at discharge) or invasive procedures. By multivariate analysis, independent and positive predictors of PPI prescription were older age and lower hemoglobin concentration on admission. Patients taking PPIs had a slightly higher prevalence of six-month mortality (6.5% vs. 3.9%) and of the composite end point (12.9% vs. 9.2%), although without statistical significance. By multivariate analysis including potential confounding variables, the prescription of a PPI on top of aspirin and clopidogrel was still n ot associated with a worse prognosis. CONCLUSIONS: In the present study, PPI precription in addition to aspirin and clopidogrel after ACS was not associated with a worse six-month prognosis.

Echocardiographic assessment of a cardiac lymphoma: beyond two-dimensional imaging.

Lymphoma is usually recognized as the third most frequent metastatic malignancy involving the heart. In recent years, the incidence of cardiac lymphoma has increased, mainly because of HIV-infected patients. We present a case of secondary cardiac lymphoma in an HIV patient presenting with heart failure. Transthoracic echocardiography showed increased left ventricular (LV) wall thickness and an extensive mass in the right cavities with involvement of the tricuspid annulus (Figure 1). Doppler tissue imaging (DTI) showed reduced systolic and diastolic velocities at mitral and tricuspid annulus, compatible with systolic and diastolic myocardial dysfunction, likely owing to infiltration. After 2 weeks of chemotherapy, repeated exam showed significant reduction of the tumour mass and of the LV wall thickness, as well as normalized systolic and diastolic velocities at mitral and tricuspid annulus, as assessed by DTI. Use of transthoracic echocardiography, mostly two-dimensional imaging, has been described for several years for the diagnosis of cardiac involvement as well as for the assessment of tumour regression in response to chemotherapy. The present case report highlights the potential utility of other echocardiographic modalities, particularly DTI, for the assessment of cardiac lymphoma but also for monitoring the tumour response to adequate therapy.

Smoking in acute coronary syndromes--the "smoker's paradox" revisited.

INTRODUCTION: Although a well-known risk factor for coronary disease, smoking has long been associated with lower short-term mortality in acute coronary syndromes (ACS). There are few recent works on Portuguese populations examining all aspects of smoking in ACS, particularly the interaction between smoking and other risk factors, and the management and prognosis of patients according to smoking status. OBJECTIVE: We sought to examine clinical characteristics, presentation, in-hospital treatment, angiographic features and prognosis of patients with and without smoking history admitted with ACS. METHODS: A total of 1228 patients consecutively admitted with ACS from January 2004 to March 2007 were analyzed. Patients were classified into two groups, those with present or past smoking habits (n=450) making up Group I and those without smoking habits (n=778), Group II. The main outcome analyzed was overall mortality during hospital stay and at 6 months. RESULTS: Smokers and former smokers were younger and more frequently male (odds ratio [OR] = 22.46; 95% confidence interval [CI]: 12.94-38.96), and less often had diabetes (OR = 0.41; 95% CI: 0.30-0.54), hypertension (OR = 0.31; 95% CI: 0.24-0.39) and renal insufficiency (OR = 0.26; 95% CI: 0.18-0.36). Patients with smoking habits more frequently presented with ST elevation (OR = 1.32; 95% CI: 1.04-1.67), more often received evidence-based medical therapy, namely beta blockers (during hospital stay, OR = 2.42; 95% CI: 1.63-3.56 and at discharge, OR = 1.45; 95% CI: 1.03-2.1) and statins (at discharge, OR = 2.48; 95% CI: 1.2-6.1), and more frequently underwent coronary angiography (OR = 2.15; 95% CI: 1.63-2.84). Although smokers and former smokers had lower in-hospital mortality on univariate analysis (OR = 0.54; 95% CI: 0.31-0.96), this association was not confirmed on multivariate analysis, with adjustment for known short-term mortality predictors (OR = 1.25; 95% CI: 0.61-2.54). Similarly, multivariate analysis failed to confirm lower 6-month mortality for smokers and former smokers (OR = 2.0; 95% CI: 1.17-3.41). CONCLUSIONS: Clinical characteristics and management options differed between ACS patients with and without smoking habits. These differences explained the lower shortterm mortality initially observed between the two groups. In our population of patients admitted with ACS, we did not find a real "smoker's paradox".

Coexistence of coronary cameral fistulae and cor triatriatum sinister in an elderly patient.

Coronary cameral fistulae are unusual congenital or acquired anomalous communications between an epicardial coronary artery and a cardiac chamber. There are no reported cases of the association of coronary cameral fistulae and cor triatriatum, a rare congenital cardiac anomaly in which a fibromuscular membrane divides the left atrium into two chambers. We report the case of an 82-year-old man presenting with recurrent anterior chest pain. Echocardiographic examination identified non-obstructive cor triatriatum, mitral valve prolapse resulting in significant mitral regurgitation, dilated coronary arteries, and established the entry site of coronary artery fistulae at the apex of the left ventricle (Figure 1). Coronary angiography confirmed the existence of a plexiform fistula between the left anterior descending coronary artery and the left ventricle. Tetrofosmine scintigraphy revealed the presence of stress-induced ischaemia in the apex. To our knowledge, we report the oldest person with coronary cameral fistulae presenting with angina only at this stage, and the interesting case of the coexistence of two, although unconnected, congenital conditions in an elderly patient. In addition, this report highlights the important role of transthoracic and transoesophageal echocardiography to the characterization of these unusual anomalies, and the complementary information offered by three-dimensional transthoracic echocardiography.

Thrombosed aneurysm of the left sinus of Valsalva.

The authors present the case of a 57-year-old asymptomatic woman, in whom a large left coronary sinus of Valsalva aneurysm was incidentally diagnosed on a routine echocardiogram in 1998. The case was initially presented to cardiac surgery consultants, and since there were no signs of rupture and the patient was asymptomatic, it was decided to keep her in close clinical and echocardiographic follow-up. Eight years later, and with no clinical manifestation in the meantime, a transesophageal echocardiogram (TEE) showed that the aneurysm was filled with swirling spontaneous echo contrast ("smoke") overlying a thrombus, which was not detected by transthoracic echocardiography. The patient then underwent surgical treatment with aortic root and aortic valve replacement and coronary reimplantation, with an excellent result. Although the need for early surgical intervention in patients with ruptured sinus of Valsalva aneurysms is well established, the optimal management of an asymptomatic, unruptured aneurysm is less clear, due to the absence of a precise natural history. The follow-up of our patient clearly demonstrated that it is mandatory to assess unruptured sinus of Valsalva aneurysms by TEE, particularly to exclude thrombotic complications. Such complications are one of the possible paths of the natural history of unruptured sinus of Valsalva aneurysms, and support the indication for early surgical treatment to avoid future complications.

Congenitally corrected transposition of the great arteries and aortic coarctation--an uncommon association.

Congenitally corrected transposition of the great arteries, L-TGA, is a rare abnormality accounting for less than 0.5% of clinically apparent congenital heart disease. Age at time of diagnosis and survival rate are variable and depend mostly on associated anomalies. The authors present a clinical case of a twenty-four-year-old woman in whom, in a routine echocardiogram, congenitally corrected transposition of the great arteries and aortic coarctation were diagnosed, an unusual association. They describe the results of complementary exams (echocardiography, chest X-ray, electrocardiogram and cardiac angiography) that they believe to be useful for the correct diagnosis of this clinical situation. Additionally, the authors make a brief review of the literature relevant to the case.

[Role of transesophageal echocardiography in the assessment and therapeutic management of patients with acute ischemic cerebral events before the age of 65]. / Papel do ecocardiograma transesofágico na avaliação e orientação terapêutica dos doentes com evento cerebral isquémico agudo até aos 65 anos de idade.

INTRODUCTION: Ischemic stroke is the leading cause of mortality in Portugal, with around 30 to 50 % of cases being of cardioembolic etiology. Transesophageal echocardiography (TEE) has assumed growing importance in the detection of cardiac sources of embolism. However, there is controversy regarding the implications of TEE findings for the therapeutic approach to patients with ischemic stroke. OBJECTIVES: To analyze TEE findings in the diagnostic work-up of patients with ischemic cerebral events and to determine their influence on therapeutic strategy. METHODS: We retrospectively studied patients with stroke or transient ischemic attack (TIA) before the age of 65, of no apparent cause after carotid ultrasound, electrocardiogram and transthoracic echocardiography, who underwent TEE between 1992 and 2009. The following diagnoses on TEE were considered as potential embolic sources: atrial septal defect; patent foramen ovale (PFO); atrial septal aneurysm (ASA); vegetations; tumors; intracavitary thrombi; and aortic plaques >2mm (ascending aorta and arch). RESULTS: We analyzed 294 patients, mean age 45 years, 56.8 % men. TEE revealed a potential cardioembolic source in 36.7 % of the patients, PFO and ASA being the most frequent. Throughout the period considered, there was an increase in the number of exams performed, as well as in diagnoses, mainly PFO and ASA. Comparison of patients with and without a diagnosis on TEE showed that the former were older and were more often prescribed oral anticoagulation. By multivariate analysis, the presence of a positive TEE finding was shown to be an independent predictor of treatment with oral anticoagulation (OR=2.48; CI 95%: 1.42-4.34; p=0.001). CONCLUSION: In the population under analysis, TEE was useful in identifying potential cardioembolic sources and influenced the therapeutic strategy.