BackgroundDietary and illness factors affect risk of growth faltering; the role of enteropathogens is less clear. As part of the Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) study, we quantify the effects of enteropathogen infection, diarrhoea and diet on child growth.MethodsNewborns were enrolled and followed until 24 months. Length and weight were assessed monthly. Illnesses and breastfeeding practices were documented biweekly; from 9 to 24 months, non-breast milk intakes were quantified monthly. Routinely collected non-diarrhoeal stools were analysed for a broad array of enteropathogens. A linear piecewise spline model was used to quantify associations of each factor with growth velocity in seven of eight MAL-ED sites; cumulative effects on attained size at 24 months were estimated for mean, low (10th percentile) and high (90th percentile) exposure levels. Additionally, the six most prevalent enteropathogens were evaluated for their effects on growth.ResultsDiarrhoea did not have a statistically significant effect on growth. Children with high enteropathogen exposure were estimated to be 1.21±0.33 cm (p<0.001; 0.39 length for age (LAZ)) shorter and 0.08±0.15 kg (p=0.60; 0.08 weight-for-age (WAZ)) lighter at 24 months, on average, than children with low exposure. Campylobacter and enteroaggregativeEscherichia coli detections were associated with deficits of 0.83±0.33 and 0.85±0.31 cm in length (p=0.011 and 0.001) and 0.22±0.15 and 0.09±0.14 kg in weight (p=0.14 and 0.52), respectively. Children with low energy intakes and protein density were estimated to be 1.39±0.33 cm (p<0.001; 0.42 LAZ) shorter and 0.81±0.15 kg (p<0.001; 0.65 WAZ) lighter at 24 months than those with high intakes.ConclusionsReducing enteropathogen burden and improving energy and protein density of complementary foods could reduce stunting.

Objectives To characterize an experimental model of pulmonary embolism by studying hemodynamics, lung mechanics and histopathologic derangements caused by pulmonary microembolism in pigs. To identify lung alterations after embolism that may be similar to those evidenced in pulmonary inflammatory conditions. Materials and methods Ten Large White pigs (weight 35-42 kg) were instrumented with arterial and pulmonary catheters, and pulmonary embolism was induced in five pigs by injection of polystyrene microspheres (diameter ~300 µM), in order to obtain a pulmonary mean arterial pressure of twice the baseline value. Five other animals injected with saline served as controls. Hemodynamic and respiratory data were collected and pressure x volume curves of the respiratory system were performed by a quasi-static low flow method. Animals were followed for 12 hours, and after death lung fragments were dissected and sent to pathology. Results Pulmonary embolism induced a significant reduction in stroke volume (71 ± 18 ml/min/bpm pre vs 36 ± 9 ml/min/bpm post, P < 0.05), an increase in pulmonary mean arterial pressure (27 ± 4 mmHg pre vs 39 ± 6 mmHg post, P < 0.05) and pulmonary vascular resistance (193 ± 122 mmHg/l/min pre vs 451 ± 149 mmHg/l/min post, P < 0.05). Respiratory dysfunction was evidenced by significant reductions in the PaO 2 /FiO 2 ratio (480 ± 50 pre vs 159 ± 55 post, P < 0.05), the dynamic lung compliance (27 ± 6 ml/cmH 2 O pre vs 19 ± 5 ml/cmH 2 O post, P < 0.05), the increase in dead space ventilation (20 ± 4 pre vs 47 ± 20 post, P < 0.05) and, the shift of pressure x volume curves to the right, with reduction in pulmonary hysteresis. Pathology depicted inflammatory neutrophil infiltrates, alveolar edema, collapse and hemorrhagic infarctions. Conclusion This model of embolism is associated with cardiovascular dysfunction, as well as respiratory injury characterized by a decrease in oxygenation, lung compliance and hysteresis. Pathology findings were similar to those verified in inflammatory pulmonary injury conditions. This model may be useful to study pathophysiology, as well as pharmacologic and ventilatory interventions useful to treat pulmonary embolism. P6 Hemodynamic and metabolic features of a porcine systemic low flow state model

Objectives To characterize an experimental model of pulmonary embolism by studying hemodynamics, lung mechanics and histopathologic derangements caused by pulmonary microembolism in pigs. To identify lung alterations after embolism that may be similar to those evidenced in pulmonary inflammatory conditions. Materials and methods Ten Large White pigs (weight 35-42 kg) were instrumented with arterial and pulmonary catheters, and pulmonary embolism was induced in five pigs by injection of polystyrene microspheres (diameter ~300 µM), in order to obtain a pulmonary mean arterial pressure of twice the baseline value. Five other animals injected with saline served as controls. Hemodynamic and respiratory data were collected and pressure x volume curves of the respiratory system were performed by a quasi-static low flow method. Animals were followed for 12 hours, and after death lung fragments were dissected and sent to pathology. Results Pulmonary embolism induced a significant reduction in stroke volume (71 ± 18 ml/min/bpm pre vs 36 ± 9 ml/min/bpm post, P < 0.05), an increase in pulmonary mean arterial pressure (27 ± 4 mmHg pre vs 39 ± 6 mmHg post, P < 0.05) and pulmonary vascular resistance (193 ± 122 mmHg/l/min pre vs 451 ± 149 mmHg/l/min post, P < 0.05). Respiratory dysfunction was evidenced by significant reductions in the PaO 2 /FiO 2 ratio (480 ± 50 pre vs 159 ± 55 post, P < 0.05), the dynamic lung compliance (27 ± 6 ml/cmH 2 O pre vs 19 ± 5 ml/cmH 2 O post, P < 0.05), the increase in dead space ventilation (20 ± 4 pre vs 47 ± 20 post, P < 0.05) and, the shift of pressure x volume curves to the right, with reduction in pulmonary hysteresis. Pathology depicted inflammatory neutrophil infiltrates, alveolar edema, collapse and hemorrhagic infarctions. Conclusion This model of embolism is associated with cardiovascular dysfunction, as well as respiratory injury characterized by a decrease in oxygenation, lung compliance and hysteresis. Pathology findings were similar to those verified in inflammatory pulmonary injury conditions. This model may be useful to study pathophysiology, as well as pharmacologic and ventilatory interventions useful to treat pulmonary embolism. P6 Hemodynamic and metabolic features of a porcine systemic low flow state model

Introduction Cardiac surgery with cardiopulmonary bypass (CPB) is a recognized trigger of systemic inflammatory response, usually related to postoperative acute lung injury (ALI). As an attempt to dampen inflammatory response, steroids have been perioperatively administered to patients. Macrophage migration inhibitory factor (MIF), a regulator of the endotoxin receptor, is implicated in the pathogenesis of ALI. We have previously detected peak circulating levels of MIF, 6 hours post CPB. Experimental data have shown that steroids may induce MIF secretion by mononuclear cells. This study aims to correlate levels of MIF assayed 6 hours post CPB to the intensity of postoperative pulmonary dysfunction, analysing the impact of perioperative steroid administration. MethodsWe included patients submitted to cardiac surgery with CPB, electively started in the morning, performed by the same team under a standard technique except for the addition of methylprednisolone (15 mg/kg) to the CPB priming solution for patients from group MP (n = 37), but not for the remaining patients -group NS (n = 37). MIF circulating levels were assayed at the anesthesia induction, 3, 6, and 24 hours after CPB. A standard weaning protocol with fast track strategy was adopted, and indicators of organ dysfunction and therapeutic intervention were registered during the first 72 hours postoperative.Results Levels of MIF assayed 6 hours post CPB correlated directly to the postoperative duration of mechanical ventilation (P = 0.014, rho = 0.282) and inversely to PaO 2 /FiO 2 ratio (P = 0.0021, rho = -0.265). No difference in MIF levels was noted between the groups. The duration of mechanical ventilation was higher (P = 0.005) in the group MP (7.92 ± 6.0 hours), compared with the group NS (4.92 ± 3.6 hours). ConclusionCirculating levels of MIF assayed 6 hours post CPB are correlated to postoperative pulmonary performance. Immunosuppressive doses of methylprednisolone did not affect circulating levels of MIF and may be related to prolonged mechanical ventilation. ResultsFourteen patients (12 males, 56.9 ± 10 years) with severe HF (LV EF 30 ± 6%) were enrolled. All patients had triple-vessel disease and 64% had previous myocardial revascularization. A total of 30 × 10 6 BM-MNC were injected at 15 sites. All patients were discharged from hospital 48 hours after the procedure. The estimated LV ischemic area on MIBI SPECT was measured by percentual of myocardial defect reverse, 14.8 ± 15% of LV mass at baseline that was reduced to 5 ± 11% (P = 0.009) at 8 weeks after S2 procedure. EF increased 16% (P = 0.03) at 8 weeks. The number of PVC was reduced at 24 hours (483 ± 4598 versus 236 ± 6243, P = not significant) and at 8 weeks (483 ± 4598 versus 191 ± 1236, P = not significant). No MA were documented at 24 hours or at 8 weeks. QT dispersion decreased from 63 ± 24 ms at baseline to 54 ± 16 ms (P = 0.3) at 2 months of follow-up.Conclusion BM-MNC transplantation into myocardium of patients with severe heart failure was safely performed and short term follow-up...

Introduction Cardiac surgery with cardiopulmonary bypass (CPB) is a recognized trigger of systemic inflammatory response, usually related to postoperative acute lung injury (ALI). As an attempt to dampen inflammatory response, steroids have been perioperatively administered to patients. Macrophage migration inhibitory factor (MIF), a regulator of the endotoxin receptor, is implicated in the pathogenesis of ALI. We have previously detected peak circulating levels of MIF, 6 hours post CPB. Experimental data have shown that steroids may induce MIF secretion by mononuclear cells. This study aims to correlate levels of MIF assayed 6 hours post CPB to the intensity of postoperative pulmonary dysfunction, analysing the impact of perioperative steroid administration. MethodsWe included patients submitted to cardiac surgery with CPB, electively started in the morning, performed by the same team under a standard technique except for the addition of methylprednisolone (15 mg/kg) to the CPB priming solution for patients from group MP (n = 37), but not for the remaining patients -group NS (n = 37). MIF circulating levels were assayed at the anesthesia induction, 3, 6, and 24 hours after CPB. A standard weaning protocol with fast track strategy was adopted, and indicators of organ dysfunction and therapeutic intervention were registered during the first 72 hours postoperative.Results Levels of MIF assayed 6 hours post CPB correlated directly to the postoperative duration of mechanical ventilation (P = 0.014, rho = 0.282) and inversely to PaO 2 /FiO 2 ratio (P = 0.0021, rho = -0.265). No difference in MIF levels was noted between the groups. The duration of mechanical ventilation was higher (P = 0.005) in the group MP (7.92 ± 6.0 hours), compared with the group NS (4.92 ± 3.6 hours). ConclusionCirculating levels of MIF assayed 6 hours post CPB are correlated to postoperative pulmonary performance. Immunosuppressive doses of methylprednisolone did not affect circulating levels of MIF and may be related to prolonged mechanical ventilation. P2Immediate and short-term safety of catheter-based autologous bone marrow-derived mononuclear cell transplantation into myocardium of patients with severe ischemic heart failure Background Bone marrow-derived mononuclear cell (BM-MNC) transplantation into the myocardium has been proposed as a new therapy for ischemic heart failure (HF). Successful cellular therapy for HF using myoblast transplantation has been reported previously but malignant arrhythmias (MA) were an issue. We investigated the safety of BM-MNC transplantation into the myocardium for MA.Methods A prospective study to evaluate the safety of autologous BM-MNC transplantation in patients with severe ischemic HF not amenable to myocardial revascularization was conducted. Bone marrow was harvested from the iliac crest and BM-MNCs were selected by Ficoll gradient. Hibernating myocardium areas were targeted using electromechanical mapping in catheter-based subendocardial injections (MyoStar, Cordis, Miami Lakes, FL, USA). All patien...