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BACKGROUND:: Because pulmonary endogenous surfactant is altered during acute respiratory distress syndrome, surfactant replacement may improve clinical outcomes. However, trials of surfactant use have had mixed results. We designed this animal model of unilateral (right) lung injury to explore the effect of exogenous surfactant administered to the injured lung on inflammation in the injured and noninjured lung. METHODS:: Mice underwent hydrochloric acid instillation (1.5 mL/kg) into the right bronchus and prolonged (7 hours) mechanical ventilation (25 mL/kg). After 3 hours, mice were treated with 1 mL/kg exogenous surfactant (Curosurf®) (surf group) or sterile saline (NaCl 0.9%) (vehicle group) in the injured (right) lung or did not receive any treatment (hydrochloric acid, ventilator-induced lung injury). Gas exchange, lung compliance, and bronchoalveolar inflammation (cells, albumin, and cytokines) were evaluated. After a significant analysis of variance (ANOVA) test, Tukey post hoc test was used for statistical analysis. RESULTS:: At least 8 to 10 mice in each group were analyzed for each evaluated variable. Surfactant treatment significantly increased both the arterial oxygen tension to fraction of inspired oxygen ratio and respiratory system static compliance (P = 0.027 and P = 0.007, respectively, for surf group versus vehicle). Surfactant therapy increased indices of inflammation in the acid-injured lung compared with vehicle: inflammatory cells (685 [602-773] and 216 [125-305] × 1000/mL, respectively; P < 0.001) and albumin in bronchoalveolar lavage (BAL) (1442 ± 588 and 743 ± 647 μg/mL, respectively; P = 0.027). These differences were not found (P = 0.96 and P = 0.54) in the contralateral (uninjured) lung (inflammatory cells 131 [78-195] and 119 [87-149] × 1000/mL and albumin 135 ± 100 and 173 ± 115 μg/mL). CONCLUSIONS:: Exogenous surfactant administration to an acid-injured right lung improved gas exchange and whole respiratory system compliance. However, markers of inflammation increased in the right (injured) lung, although this result was not found in the left (uninjured) lung. These data suggest that the mechanism by which surfactant improves lung function may involve both uninjured and injured alveoli.

Saccharomyces boulardii for the Prevention of Antibiotic-Associated Diarrhea in Adult Hospitalized Patients: A Single-Center, Randomized, Double-Blind, Placebo-Controlled Trial

PURPOSE: This study investigates whether positron emission tomography (PET) can be used to monitor the inflammatory response and its correlation with the later fibroproliferative phase in an experimental model of acute lung injury. METHODS: Hydrochloric acid (0.1 N, pH 1, 1.5 ml/kg) was instilled into the right bronchus of mice. A group of mice underwent a micro-computed tomography (CT) scan 1 h after lung injury and a series of 2-[(18)F]fluorine-2-deoxy-D: -glucose (FDG)-PET scans (6, 24 and 48 h and 7 days after surgery). After 21 days respiratory static compliance was assessed and lung tissue was collected in order to measure the hydroxy (OH)-proline content. Other groups of mice underwent micro-CT and micro-PET scans at the same time points, and then were immediately killed to assess arterial blood gases and histology. RESULTS: Histological analysis showed the recruitment of neutrophils and macrophages into the damaged lung, reaching the peak at 24 and 48 h, respectively. The time course of the [(18)F]FDG signal, used as a marker of inflammation, correlated with that of recruited inflammatory cells. In mice killed 21 days after the surgery, a correlation was found between reduced respiratory static compliance and high PET signal 7 days after lung injury. The PET signal also correlated with the OH-proline content. CONCLUSIONS: This study demonstrated that PET imaging is a valid means of tracking the inflammatory response, also in longitudinal studies. Moreover, a correlation was found between persistence of the inflammatory response and fibrotic evolution of the injury.

Evidence of diastolic dysfunction in cirrhosis contributed to the definition of cirrhotic cardiomyopathy. In 109 patients with chronic HCV infection with or without cirrhosis E/A ratio, a Doppler marker of diastolic dysfunction, was decreased in cirrhotics (0.89 ± 0.03 vs controls 1.21 ± 0.07, p < 0.01) and to a lesser extent in patients with advanced liver fibrosis (1.17 ± 0.07, p < 0.01). Left ventricular parietal wall thickness was increased. The nature of this abnormality in human cirrhosis has not been clarified, animal studies reporting cardiac hypertrophy. To this aim we employed the echo- cardiographic integrated backscatter (IBS) technique to obtain an indirect estimate of tissue density (decreased when a higher percentage of muscle fibres is present and increased when fibrosis prevails) to provide myocardial tissue charac- terization in a subset of patients with compensated HCV cirrhosis. The average IBS signal was reduced in cirrhotics at the level of the posterior wall (21.72 ± 1.46 dB versus 30.85 ± 1.40 dB in controls, p < 0.01). Our results confirm diastolic dysfunction in postviral cirrhosis pointing to cardiac hypertrophy as the anatomopathological background in the compen- sated stage of disease.

Aims Mitral regurgitation (MR) confers independent risk in patients with acute myocardial infarction. We utilized data from the VALsartan In Acute myocardial iNfarcTion echo study to relate baseline MR to left ventricular (LV) size, shape, and function, and to assess the relationship between baseline MR and progression of MR and cardiovascular (CV) outcomes. Methods and results We studied 496 patients with heart failure (HF) and/or systolic dysfunction after MI who underwent echocardiography at a median of 5 days after MI. MR severity, quantified as the regurgitant jet area/left atrial area ratio, was assessed at baseline, one and 20 months post-MI and related to LV size, shape, function, and clinical outcomes. Increased MR at baseline was associated with larger LV end-diastolic and end-systolic volumes, increased sphericity index, and reduced ejection fraction ( P trend < 0.001). Moderate–severe MR was an independent predictor of total mortality [adjusted hazard ratio (HR) 2.4 (1.1–5.3)], CV mortality [adjusted HR 2.7 (1.2–6.1)], hospitalization for HF [adjusted HR 2.5 (1.1–5.5)], or death or HF hospitalization [adjusted HR 2.5 (1.4–4.6)]. Patients with progression of MR during the first post-MI month were substantially more likely to die or develop HF (adjusted HR per increased MR grade 3.0, 95% CI 1.8–4.9). Progression of MR over 20 months in survivors was associated with increased hospitalizations for HF ( P < 0.001). Conclusion Following high-risk myocardial infarction, baseline mitral regurgitant severity is associated with larger LV volumes and worse LV function. Both baseline MR severity and progression of MR are associated with an increased likelihood of adverse outcomes.

Background High dosage anthracyclines in pediatric patients with acute lymphoblastic leukemia (ALL) is associated with cardiotoxicity. However, data on the cardiac effects of lower cumulative doses of these drugs are not conclusive. The aim of this study was to assess the cardiac effects of low cumulative anthracycline doses in long-term survivors of ALL. Procedure Echocardiograms were performed on 62 long-term ALL survivors, without any overt or sub-clinical signs or symptoms of heart failure. The interval after stopping therapy was 12.6 ± 4.3 years; the mean cumulative dose of anthracyclines was 228.2 ± 42.3 mg/m2. Left ventricular (LV) structure and function were studied by echocolor-Doppler. An age, gender and body surface area (BSA) matched group of healthy subjects was used as controls. Cardiac data were analyzed before and after BSA normalization. Results Long term survivors of ALL, showed a lower LV mass index, interventricular septal and posterior wall thickness, which were independently related to gender and to age at which the ALL diagnosis was made. Data analyzed according to gender showed that abnormalities were confined to the female group. No alterations were observed in the ALL male group versus the corresponding control group. No relationship was observed between the echocardiografic abnormalities and the duration of follow-up or the anthracycline mean dose employed. Conclusions In the absence of any signs or symptoms of heart failure, female ALL survivors treated with low cumulative anthracycline doses, showed a reduced LV mass and wall thickness. This suggests that in female ALL survivors an echocardyographic follow-up should be recommended. Pediatr Blood Cancer. 2010;55:1343–1347. © 2010 Wiley-Liss, Inc.

Aims To assess the relationship between left atrial (LA) size and outcome after high-risk myocardial infarction (MI) and to study dynamic changes in LA size during long-term follow-up. Methods and results The VALIANT Echocardiography study prospectively enrolled 610 patients with left ventricular (LV) dysfunction, heart failure (HF), or both following MI. We assessed LA volume indexed to body surface area (LAVi) at baseline, 1 month, and 20 months after MI. Baseline LAVi was an independent predictor of all-cause death or HF hospitalization ( P = 0.004). In patients who survived to 20 months, LAVi increased a mean of 3.00 ± 7.08 mL/m2 from baseline. Hypertension, lower estimated glomerular filtration rate, and LV mass were the only baseline independent predictors of LA remodelling. Changes in LA size were related to worsening in MR and increasing in LV volumes. LA enlargement during the first month was significantly greater in patients who subsequently died or were hospitalized for HF than in patients without events. Conclusion Baseline LA size is an independent predictor of death or HF hospitalization following high-risk MI. Moreover, LA remodelling during the first month after infarction is associated with adverse outcome.

Diabetes is associated with a reduction of arterial distensibility. Limited information exists regarding whether or how early this appears in the course of the disease. We studied 54 normoglycemic, normotensive, healthy offspring of 2 parents with type 2 diabetes mellitus and 55 age- and sex-matched healthy control subjects. Carotid diastolic diameter and systodiastolic change were measured by echo tracking (Wall Track System) and wall thickness by echocolor Doppler (Sonos 5500, Philips). Pulse pressure was measured by a semiautomatic device positioned on the brachial artery and arterial distensibility calculated by Reneman formula. Blood pressure, blood glucose, glycohemoglobin, and insulin sensitivity (homeostasis model assessment index) were normal or only slightly elevated and by and large similar in the 2 groups. Compared with control subjects, offspring of diabetic parents showed similar carotid diameters at diastole and a reduced increase in carotid diameter at systole (−16%), a reduced carotid artery distensibility (−30%), and an increased pulse pressure (+21.8%), all differences being statistically significant ( P 2 ). Carotid artery wall thickness was not different between the 2 groups. Thus, subjects with predisposition to diabetes show carotid artery stiffening even in the absence of blood pressure alterations, as well as substantial alterations of glucose metabolism, body mass index, and changes in carotid wall thickness. This suggests that, in diabetes, alterations in arterial mechanical properties represent an early phenomenon, which may occur in the absence of metabolic and blood pressure alterations.