A dissincronia mecânica é semelhante em diferentes padrões do bloqueio de ramo esquerdo

FUNDAMENTOS: O bloqueio do ramo esquerdo (BRE) e a presença de disfunção sistólica são as principais indicações de terapia de ressincronização cardíaca (TRC). A dissincronia ventricular mecânica pela ecocardiografia pode ajudar a identificar pacientes responsivos à TRC. O BRE pode mostrar diferentes padrões em sua morfologia. OBJETIVO: Comparar a prevalência de dissincronia mecânica em diferentes padrões de BRE em pacientes com disfunção sistólica esquerda. MÉTODOS: Analisaram-se 48 pacientes com fração de ejeção (FE) < 40% e BRE referidos consecutivamente para análise de dissincronia. Foram realizados ecocardiograma convencional e análise da dissincronia mecânica, interventricular e intraventricular, por 10 conhecidos métodos, usando modo M, Doppler e Doppler tecidual, sozinhos ou combinados. A morfologia do BRE foi categorizada pelo desvio esquerdo do eixo no plano frontal e duração de QRS > 150 ms. RESULTADOS: Eram 24 homens, com idade 60 ± 11 anos e FEVE de 29 ± 7%. Trinta e dois apresentavam QRS > 150 ms, e 22, ECG eixo entre -30º e +90º. A dissincronia interventricular foi identificada em 73% dos pacientes e a intraventricular em valores entre 37-98%. Portadores de QRS > 150 ms apresentaram maiores dimensões do átrio e ventrículo esquerdos, e menor FE (p < 0,05), e o desvio esquerdo do eixo associou-se a pior função diastólica e maior diâmetro atrial. A presença de dissincronia mecânica interventricular e intraventricular (10 métodos) foi semelhante entre os diferentes padrões de BRE (p = ns). CONCLUSÃO: Nos dois diferentes padrões eletrocardiográficos de BRE analisados, não foram observadas diferenças em relação à presença de dissincronia mecânica.

Left Atrial Volume Determinants in Patients with Non-Ischemic Dilated Cardiomyopathy

Background:Left atrial volume (LAV) is a predictor of prognosis in patients with heart failure.Objective:We aimed to evaluate the determinants of LAV in patients with dilated cardiomyopathy (DCM).Methods:Ninety patients with DCM and left ventricular (LV) ejection fraction ≤ 0.50 were included. LAV was measured with real-time three-dimensional echocardiography (eco3D). The variables evaluated were heart rate, systolic blood pressure, LV end-diastolic volume and end-systolic volume and ejection fraction (eco3D), mitral inflow E wave, tissue Doppler e´ wave, E/e´ ratio, intraventricular dyssynchrony, 3D dyssynchrony index and mitral regurgitation vena contracta. Pearson´s coefficient was used to identify the correlation of the LAV with the assessed variables. A multiple linear regression model was developed that included LAV as the dependent variable and the variables correlated with it as the predictive variables.Results:Mean age was 52 ± 11 years-old, LV ejection fraction: 31.5 ± 8.0% (16-50%) and LAV: 39.2±15.7 ml/m2. The variables that correlated with the LAV were LV end-diastolic volume (r = 0.38; p < 0.01), LV end-systolic volume (r = 0.43; p < 0.001), LV ejection fraction (r = -0.36; p < 0.01), E wave (r = 0.50; p < 0.01), E/e´ ratio (r = 0.51; p < 0.01) and mitral regurgitation (r = 0.53; p < 0.01). A multivariate analysis identified the E/e´ ratio (p = 0.02) and mitral regurgitation (p = 0.02) as the only independent variables associated with LAV increase.Conclusion:The LAV is independently determined by LV filling pressures (E/e´ ratio) and mitral regurgitation in DCM.

Caracterização de bactérias dos gêneros Mima e Herella (Tribo Mimeae, DeBord, 1942): 1) Propriedade morfo-bioquímicas e sensibilidade aos antibióticos

No presente trabalho, os autores estudaram as propriedades morfo-bioquímicas e a sinsibilidade aos antibióticos de 19 amostras de bactérias dos gêneros Mima e Herellea isoladas de material clínico e identificadas como Mima polymorpha variedade oxidans, Mima polymorpha e Herellea vaginicola. No estudo bioquímico observou-se que Herellea vaginicola foi oxidase negativa e em meio complexo nitrogenado, consistentemente ataca a glicose, galactose, manose, arabinose, xilose, lactose a 10% e irregularmente ataca a ramnose e a celobiose; em base sintética nitrogenada, além das atividades citadas, consistentemente produziu ácido a partir da lactose. Mima polymopha foi oxidase negativa, não apresentando atividade glicidolítica, quer em meio complexo nitrogenado, quer em base sintética nitrogenada. Mima polymorpha var. oxidans, foi oxidase positiva, não revelando nenhuma atividade glicidolítica. Herellea vaginicola e Mima polymorpha mostraram grande sensibilidade à gabromicina, knamicina, neomicina, colistin, sendo que a última também foi muito sensível ao cloranfenicol e rovamicina. Mima polymorpha var. oxidans, apresentou grande sensibilidade à knamicina, neomicina, colistin, cloranfenicol e wintomylon. A sensibilidade das amostras a 1 a 0,1 unidade de penicilina/ml, nas condições ensaiadas no presente trabalho, não foi absoluta, como a observada por Baumann, Doudoroff & Stanier (1968a) que permitisse uma separação entre amostras oxidase positiva e negativa ou uma diferenciação dentro do grupo das bactérias oxidase positiva.

Isolamento e caracterização de Pseudomonas maltophilia (Hugh & Ryschenkow, 1960) de material clínico humano, na cidade do Rio de Janeiro

Os autores estudaram as propriedades morfo-bioquímicas e a sensibilidade às substâncias antimicrobianas, de uma nova e rara espécie de Pseudomonas, a Pseudomonas maltophilia (Hugh & Ryschenkow, 1960), isolada de secração vaginal. Como características marcantes, dentre mais de 65 testadas, as amostras estudadas mostraram ser: oxidase negativa e lisina descarboxilase positiva; produziram desoxiribonuclease e um pigmento escuro que se difunde no meio; atacaram oxidativamente a maltose tanto em meio complexo nitrogenado como em meio de Hugh & Leifson e hidrolisaram a esculina. As amostras foram sensíveis ao cloranfenicol, gentamicina, kanamicina, colistin e gabromicina.

Long-term miR-669a therapy alleviates chronic dilated cardiomyopathy in dystrophic mice.

BACKGROUND: Dilated cardiomyopathy (DCM) is a leading cause of chronic morbidity and mortality in muscular dystrophy (MD) patients. Current pharmacological treatments are not yet able to counteract chronic myocardial wastage, thus novel therapies are being intensely explored. MicroRNAs have been implicated as fine regulators of cardiomyopathic progression. Previously, miR-669a downregulation has been linked to the severe DCM progression displayed by Sgcb-null dystrophic mice. However, the impact of long-term overexpression of miR-669a on muscle structure and functionality of the dystrophic heart is yet unknown. METHODS AND RESULTS: Here, we demonstrate that intraventricular delivery of adeno-associated viral (AAV) vectors induces long-term (18 months) miR-669a overexpression and improves survival of Sgcb-null mice. Treated hearts display significant decrease in hypertrophic remodeling, fibrosis, and cardiomyocyte apoptosis. Moreover, miR-669a treatment increases sarcomere organization, reduces ventricular atrial natriuretic peptide (ANP) levels, and ameliorates gene/miRNA profile of DCM markers. Furthermore, long-term miR-669a overexpression significantly reduces adverse remodeling and enhances systolic fractional shortening of the left ventricle in treated dystrophic mice, without significant detrimental consequences on skeletal muscle wastage. CONCLUSIONS: Our findings provide the first evidence of long-term beneficial impact of AAV-mediated miRNA therapy in a transgenic model of severe, chronic MD-associated DCM.

The conduction system of the heart in mice chronically infected with Trypanosoma cruzi: histopathological lesions and electrocardiographic correlations

Chronic focal and diffuse myiocarditis with interstitial fibrosis developed in Swiss outbred mice and in the inbred AKR and A/J strains of mice which were chronically infected with several Trypanosoma cruzi strains belonging to three biological types (Type I, II and III). High incidence of electrocardiographic changes with predominance of intraventricular conduction disturbances, 1st. and 2nd. degree AV block, arrhythmias, comparable with those found in human Chagas' disease, were also present. Morphological study of the conduction tissue of the heart revealed inflammatory and fibrotic changes. The presence of inflammation in the inter-atrial septum almost always coincided with the inflammatory involvement of the ventricular conduction system. Focal inflammation was associated with vacuolization and focal necrosis of the specific fibers. Most of the lesions were seen affecting the His bundel (76.3% of the cases), the right bundle branch (73.3%), AV node (43.9%) and left bundle branch (37.5%). Correlation between morphological changes in the conduction tissue and electrocardiographic alteration occured in 53.0 to 62.5% of the cases, according to the experimental groups.

Dietary fish oil is antihypertrophic but does not enhance postischemic myocardial function in female mice.

Clinically and experimentally, a case for omega-3 polyunsaturated fatty acid (PUFA) cardioprotection in females has not been clearly established. The goal of this study was to investigate whether dietary omega-3 PUFA supplementation could provide ischemic protection in female mice with an underlying genetic predisposition to cardiac hypertrophy. Mature female transgenic mice (TG) with cardiac-specific overexpression of angiotensinogen that develop normotensive cardiac hypertrophy and littermate wild-type (WT) mice were fed a fish oil-derived diet (FO) or PUFA-matched control diet (CTR) for 4 wk. Myocardial membrane lipids, ex vivo cardiac performance (intraventricular balloon) after global no-flow ischemia and reperfusion (15/30 min), and reperfusion arrhythmia incidence were assessed. FO diet suppressed cardiac growth by 5% and 10% in WT and TG, respectively (P < 0.001). The extent of mechanical recovery [rate-pressure product (RPP) = beats/min x mmHg] of FO-fed WT and TG hearts was similar (50 +/- 7% vs. 45 +/- 12%, 30 min reperfusion), and this was not significantly different from CTR-fed WT or TG. To evaluate whether systemic estrogen was masking a protective effect of the FO diet, the responses of ovariectomized (OVX) WT and TG mice to FO dietary intervention were assessed. The extent of mechanical recovery of FO-fed OVX WT and TG (RPP, 50 +/- 4% vs. 64 +/- 8%) was not enhanced compared with CTR-fed mice (RPP, 60 +/- 11% vs. 80 +/- 8%, P = 0.335). Dietary FO did not suppress the incidence of reperfusion arrhythmias in WT or TG hearts (ovary-intact mice or OVX). Our findings indicate a lack of cardioprotective effect of dietary FO in females, determined by assessment of mechanical and arrhythmic activity postischemia in a murine ex vivo heart model.

Solitary fibrous tumor of the lateral ventricle: CT appearances and pathologic correlation with follow-up.

Intracranial solitary fibrous tumors are rare, and intraventricular fibrous tumors are even more unusual. We report a case of solitary fibrous tumor in the region of trigone and body of the left lateral ventricle and discuss the clinical presentation, CT characteristics, and histopathologic features with 1-year follow-up. We speculate that the tumor arose from the perivascular connective tissue of the choroid plexus.

Strategies of use of a specific immunoglobulin-rich egg yolk powder in weaning piglets

Two experiments were performed to determine the best strategy of use of the product TRACTcare® 4P (ITPSA) (TC, specific immunoglobulin-rich egg yolk powder within an energetic fatty acid matrix) in piglets from weaning and for 6 weeks, in diets without or with inclusion of antibiotics. Each trial was performed with 144 piglets in 24 pens, in a completely randomized design blocked by initial body weight. Feeds were formulated according to animal requirements in two periods. In the first trial no antibiotics were included in the feeds and no room disinfection from previous trial was performed; treatments were: 1) Negative control (NC); 2) NC+TC on top of the feed within the hopper for the first 3 days on trial (30 g/pig×day), and eventually if diarrhea appeared (TCOT); 3) NC+TC ad libitum provided in an extra hopper within the pen (TCAL); and 4) NC+TC at 5 g/kg added to the feed in the mixer (TC5). In the second trial, treatments were: 1) Positive control: basal diet that included 250 mg/kg amoxiciline (BD)+100 mg/kg colistine (AC); 2) BD+2 g/kg TC (TC2A); 3) BD+5 g/kg TC (TC5A); and 4) BD+8 g/kg TC (TC8A). In diets without antibiotics, the product TC at 5 g/kg in the feed numerically improved BW by 8% compared to Control animals, while G:F was almost identical between both groups. When antibiotics were used in the feed, replacement of colistin at 100 mg/kg for TC at 2 g/kg in feed numerically improved the performance compared to Positive control animals (for the whole trial period ADG 8% better: 390 g vs. 361 g; G:F 1% better: 0.748 kg/kg vs. 0.742 kg/kg), possibly due to the stimulation of feed consumption at weaning. In both trials, the lower number of dead and culled animals from TC5 and TC2A together with higher BW represented an advantage over Control treatments of 6% to 10% animals more and 15% to 17% total BW more at the end of the trial.

Neuroprotective role of lactate after cerebral ischemia.

It is well established that lactate can be used as an energy substrate by the brain by conversion to pyruvate and a subsequent oxidation in the mitochondria. Knowing the need for readily metabolizable substrates directly after ischemia and the protective effect of lactate after excitotoxicity, the aim of this study was to investigate whether lactate administration directly after ischemia could be neuroprotective. In vitro, the addition of 4 mmol/L L-lactate to the medium of rat organotypic hippocampal slices, directly after oxygen and glucose deprivation (OGD), protected against neuronal death, whereas a higher dose of 20 mmol/L was toxic. In vivo, after middle cerebral artery occlusion in the mouse, an intracerebroventricular injection of 2 microL of 100 mmol/L L-lactate, immediately after reperfusion, led to a significant decrease in lesion size, which was more pronounced in the striatum, and an improvement in neurologic outcome. A later injection 1 h after reperfusion did not reduce lesion size, but significantly improved neurologic outcome, which is an important point in the context of a potential clinical application. Therefore, a moderate increase in lactate after ischemia may be a therapeutic tool.

A CMR study of the effects of tissue edema and necrosis on left ventricular dyssynchrony in acute myocardial infarction: implications for cardiac resynchronization therapy.

ABSTRACT: BACKGROUND: In acute myocardial infarction (AMI), both tissue necrosis and edema are present and both might be implicated in the development of intraventricular dyssynchrony. However, their relative contribution to transient dyssynchrony is not known. Cardiovascular magnetic resonance (CMR) can detect necrosis and edema with high spatial resolution and it can quantify dyssynchrony by tagging techniques. METHODS: Patients with a first AMI underwent percutaneous coronary interventions (PCI) of the infarct-related artery within 24 h of onset of chest pain. Within 5-7 days after the event and at 4 months, CMR was performed. The CMR protocol included the evaluation of intraventricular dyssynchrony by applying a novel 3D-tagging sequence to the left ventricle (LV) yielding the CURE index (circumferential uniformity ratio estimate; 1 = complete synchrony). On T2-weighted images, edema was measured as high-signal (>2 SD above remote tissue) along the LV mid-myocardial circumference on 3 short-axis images (% of circumference corresponding to the area-at-risk). In analogy, on late-gadolinium enhancement (LGE) images, necrosis was quantified manually as percentage of LV mid-myocardial circumference on 3 short-axis images. Necrosis was also quantified on LGE images covering the entire LV (expressed as %LV mass). Finally, salvaged myocardium was calculated as the area-at-risk minus necrosis (expressed as % of LV circumference). RESULTS: After successful PCI (n = 22, 2 female, mean age: 57 ± 12y), peak troponin T was 20 ± 36ug/l and the LV ejection fraction on CMR was 41 ± 8%. Necrosis mass was 30 ± 10% and CURE was 0.91 ± 0.05. Edema was measured as 58 ± 14% of the LV circumference. In the acute phase, the extent of edema correlated with dyssynchrony (r2 = -0.63, p < 0.01), while extent of necrosis showed borderline correlation (r2 = -0.19, p = 0.05). PCI resulted in salvaged myocardium of 27 ± 14%. LV dyssynchrony (=CURE) decreased at 4 months from 0.91 ± 0.05 to 0.94 ± 0.03 (p < 0.004, paired t-test). At 4 months, edema was absent and scar %LV slightly shrunk to 23.7 ± 10.0% (p < 0.002 vs baseline). Regression of LV dyssynchrony during the 4 months follow-up period was predicted by both, the extent of edema and its necrosis component in the acute phase. CONCLUSIONS: In the acute phase of infarction, LV dyssynchrony is closely related to the extent of edema, while necrosis is a poor predictor of acute LV dyssynchrony. Conversely, regression of intraventricular LV dyssynchrony during infarct healing is predicted by the extent of necrosis in the acute phase.

Multiple courses of antenatal corticosteroids for preterm birth (MACS): a randomised controlled trial.

BACKGROUND: One course of antenatal corticosteroids reduces the risk of respiratory distress syndrome and neonatal death. Weekly doses given to women who remain undelivered after a single course may have benefits (less respiratory morbidity) or cause harm (reduced growth in utero). We aimed to find out whether multiple courses of antenatal corticosteroids would reduce neonatal morbidity and mortality without adversely affecting fetal growth. METHODS: 1858 women at 25-32 weeks' gestation who remained undelivered 14-21 days after an initial course of antenatal corticosteroids and continued to be at high risk of preterm birth were randomly assigned to multiple courses of antenatal corticosteroids (n=937) or placebo (n=921), every 14 days until week 33 or delivery, whichever came first. The primary outcome was a composite of perinatal or neonatal mortality, severe respiratory distress syndrome, intraventricular haemorrhage (grade III or IV), periventricular leucomalacia, bronchopulmonary dysplasia, or necrotising enterocolitis. Analysis was by intention to treat. All patients and caregivers were unaware of the treatment given. This trial is registered as number ISRCTN2654148. FINDINGS: Infants exposed to multiple courses of antenatal corticosteroids had similar morbidity and mortality to those exposed to placebo (150 [12.9%] vs 143 [12.5%]). Those receiving multiple doses of corticosteroids also weighed less at birth than those exposed to placebo (2216 g vs 2330 g, p=0.0026), were shorter (44.5 cm vs 45.4 cm, p<0.001), and had a smaller head circumference (31.1 cm vs 31.7 cm, p<0.001). INTERPRETATION: Multiple courses of antenatal corticosteroids, every 14 days, do not improve preterm-birth outcomes, and are associated with a decreased weight, length, and head circumference at birth. Therefore, this treatment schedule is not recommended. FUNDING: Canadian Institutes of Health Research.

CXCR4-activated astrocyte glutamate release via TNFalpha: amplification by microglia triggers neurotoxicity.

Astrocytes actively participate in synaptic integration by releasing transmitter (glutamate) via a calcium-regulated, exocytosis-like process. Here we show that this process follows activation of the receptor CXCR4 by the chemokine stromal cell-derived factor 1 (SDF-1). An extraordinary feature of the ensuing signaling cascade is the rapid extracellular release of tumor necrosis factor-alpha (TNFalpha). Autocrine/paracrine TNFalpha-dependent signaling leading to prostaglandin (PG) formation not only controls glutamate release and astrocyte communication, but also causes their derangement when activated microglia cooperate to dramatically enhance release of the cytokine in response to CXCR4 stimulation. We demonstrate that altered glial communication has direct neuropathological consequences and that agents interfering with CXCR4-dependent astrocyte-microglia signaling prevent neuronal apoptosis induced by the HIV-1 coat glycoprotein, gp120IIIB. Our results identify a new pathway for glia-glia and glia-neuron communication that is relevant to both normal brain function and neurodegenerative diseases.

Nosocomial Outbreak of Infection With Pan-Drug-Resistant Acinetobacter baumannii in a Tertiary Care University Hospital

OBJECTIVE To describe what is, to our knowledge, the first nosocomial outbreak of infection with pan-drug-resistant (including colistin-resistant) Acinetobacter baumannii, to determine the risk factors associated with these types of infections, and to determine their clinical impact. DESIGN Nested case-control cohort study and a clinical-microbiological study. SETTING A 1,521-bed tertiary care university hospital in Seville, Spain. PATIENTS Case patients were inpatients who had a pan-drug-resistant A. baumannii isolate recovered from a clinical or surveillance sample obtained at least 48 hours after admission to an intensive care unit (ICU) during the time of the epidemic outbreak. Control patients were patients who were admitted to any of the "boxes" (ie, rooms that partition off a distinct area for a patient's bed and the equipment needed to care for the patient) of an ICU for at least 48 hours during the time of the epidemic outbreak. RESULTS All the clinical isolates had similar antibiotic susceptibility patterns (ie, they were resistant to all the antibiotics tested, including colistin), and, on the basis of repetitive extragenic palindromic-polymerase chain reaction, it was determined that all of them were of the same clone. The previous use of quinolones and glycopeptides and an ICU stay were associated with the acquisition of infection or colonization with pan-drug-resistant A. baumannii. To control this outbreak, we implemented the following multicomponent intervention program: the performance of environmental decontamination of the ICUs involved, an environmental survey, a revision of cleaning protocols, active surveillance for colonization with pan-drug-resistant A. baumannii, educational programs for the staff, and the display of posters that illustrate contact isolation measures and antimicrobial use recommendations. CONCLUSIONS We were not able to identify the common source for these cases of infection, but the adopted measures have proven to be effective at controlling the outbreak.

Intravenous iron in inflammatory bowel disease

The prevalence of anemia across studies on patients with inflammatory bowel disease (IBD) is high (30%). Both iron deficiency (ID) and anemia of chronic disease contribute most to the development of anemia in IBD. The prevalence of ID is even higher (45%). Anemia and ID negatively impact the patient's quality of life. Therefore, together with an adequate control of disease activity, iron replacement therapy should start as soon as anemia or ID is detected to attain a normal hemoglobin (Hb) and iron status. Many patients will respond to oral iron, but compliance may be poor, whereas intravenous (i.v.) compounds are safe, provide a faster Hb increase and iron store repletion, and presents a lower rate of treatment discontinuation. Absolute indications for i.v. iron treatment should include severe anemia, intolerance or inappropriate response to oral iron, severe intestinal disease activity, or use of an erythropoietic stimulating agent. Four different products are principally used in clinical practice, which differ in their pharmacokinetic properties and safety profiles: iron gluconate and iron sucrose (lower single doses), and iron dextran and ferric carboxymaltose (higher single doses). After the initial resolution of anemia and the repletion of iron stores, the patient's hematological and iron parameters should be carefully and periodically monitored, and maintenance iron treatment should be provided as required. New i.v. preparations that allow for giving 1000-1500 mg in a single session, thus facilitating patient management, provide an excellent tool to prevent or treat anemia and ID in this patient population, which in turn avoids allogeneic blood transfusion and improves their quality of life.