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Search Results: 1 - 10 of 32251 matches for " Antonio Pedotti "
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Chest wall mechanics during pressure support ventilation
Andrea Aliverti, Eleonora Carlesso, Raffaele Dellacà, Paolo Pelosi, Davide Chiumello, Antonio Pedotti, Luciano Gattinoni
Critical Care , 2006, DOI: 10.1186/cc4867
Abstract: In nine patients four different levels of PSV (5, 10, 15 and 25 cmH2O) were randomly applied with the same level of positive end-expiratory pressure (10 cmH2O). Flow, airway opening, and oesophageal and gastric pressures were measured, and volume variations for the entire chest wall, the ribcage and abdominal compartments were recorded by opto-electronic plethysmography. The pressure and the work generated by the diaphragm, rib cage and abdominal muscles were determined using dynamic pressure-volume loops in the various phases of each respiratory cycle: pre-triggering, post-triggering with the patient's effort combining with the action of the ventilator, pressurization and expiration. The complete breathing pattern was measured and correlated with chest wall kinematics and dynamics.At the various levels of pressure support applied, minute ventilation was constant, with large variations in breathing frequency/ tidal volume ratio. At pressure support levels below 15 cmH2O the following increased: the pressure developed by the inspiratory muscles, the contribution of the rib cage compartment to the total tidal volume, the phase shift between rib cage and abdominal compartments, the post-inspiratory action of the inspiratory rib cage muscles, and the expiratory muscle activity.During PSV, the ventilatory pattern is very different at different levels of pressure support; in patients with acute lung injury pressure support greater than 10 cmH2O permits homogeneous recruitment of respiratory muscles, with resulting synchronous thoraco-abdominal expansion.In intensive care pressure support ventilation (PSV), a form of assisted mechanical ventilation, is among the modes most commonly employed to decrease the patient's work of breathing without neuromuscular blockade [1]. It is known that for optimal unloading of the respiratory muscles, the ventilator should cycle in synchrony with the activity of the patient's respiratory rhythm. Patient-ventilator asynchrony frequently occ
Changes in the mechanical properties of the respiratory system during the development of interstitial lung edema
Raffaele L Dellacà, Emanuela Zannin, Giulio Sancini, Ilaria Rivolta, Biagio E Leone, Antonio Pedotti, Giuseppe Miserocchi
Respiratory Research , 2008, DOI: 10.1186/1465-9921-9-51
Abstract: We studied 17 paralysed and mechanically ventilated closed-chest rats (325–375 g). Total input respiratory system impedance (Zrs) was derived from tracheal flow and pressure signals by applying forced oscillations with frequency components from 0.16 to 18.44 Hz distributed in two forcing signals. In 8 animals interstitial lung edema was induced by intravenous infusion of saline solution (0.75 ml/kg/min) for 4 hours; 9 control animals were studied with the same protocol but without infusion. Zrs was measured at the beginning and every 15 min until the end of the experiment.In the treated group the lung wet-to-dry weight ratio increased from 4.3 ± 0.72 to 5.23 ± 0.59, with no histological signs of alveolar flooding. Resistance (Rrs) increased in both groups over time, but to a greater extent in the treated group. Reactance (Xrs) did not change in the control group, while it decreased significantly at all frequencies but one in the treated. Significant changes in Rrs and Xrs were observed starting after ~135 min from the beginning of the infusion. By applying a constant phase model to partition airways and tissue mechanical properties, we observed a mild increase in airways resistance in both groups. A greater and significant increase in tissue damping (from 603.5 ± 100.3 to 714.5 ± 81.9 cmH2O/L) and elastance (from 4160.2 ± 462.6 to 5018.2 ± 622.5 cmH2O/L) was found only in the treated group.These results suggest that interstitial edema has a small but significant impact on the mechanical features of lung tissues and that these changes begin at very early stages, before the beginning of accumulation of extravascular fluid into the alveoli.The functional organisation of the lung extracellular matrix comprises basically two large macromolecular families. The fibrillar components, including collagen I and III and elastic fibers, provide the elasticity of the lung tissue on stretching and de-stretching which is mechanically defined as lung compliance, that is the ratio be
Rational Engineering of a Human Anti-Dengue Antibody through Experimentally Validated Computational Docking
Luca Simonelli, Mattia Pedotti, Martina Beltramello, Elsa Livoti, Luigi Calzolai, Federica Sallusto, Antonio Lanzavecchia, Luca Varani
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0055561
Abstract: Antibodies play an increasing pivotal role in both basic research and the biopharmaceutical sector, therefore technology for characterizing and improving their properties through rational engineering is desirable. This is a difficult task thought to require high-resolution x-ray structures, which are not always available. We, instead, use a combination of solution NMR epitope mapping and computational docking to investigate the structure of a human antibody in complex with the four Dengue virus serotypes. Analysis of the resulting models allows us to design several antibody mutants altering its properties in a predictable manner, changing its binding selectivity and ultimately improving its ability to neutralize the virus by up to 40 fold. The successful rational design of antibody mutants is a testament to the accuracy achievable by combining experimental NMR epitope mapping with computational docking and to the possibility of applying it to study antibody/pathogen interactions.
Rib Cage Deformities Alter Respiratory Muscle Action and Chest Wall Function in Patients with Severe Osteogenesis Imperfecta
Antonella LoMauro, Simona Pochintesta, Marianna Romei, Maria Grazia D'Angelo, Antonio Pedotti, Anna Carla Turconi, Andrea Aliverti
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0035965
Abstract: Background Osteogenesis imperfecta (OI) is an inherited connective tissue disorder characterized by bone fragility, multiple fractures and significant chest wall deformities. Cardiopulmonary insufficiency is the leading cause of death in these patients. Methods Seven patients with severe OI type III, 15 with moderate OI type IV and 26 healthy subjects were studied. In addition to standard spirometry, rib cage geometry, breathing pattern and regional chest wall volume changes at rest in seated and supine position were assessed by opto-electronic plethysmography to investigate if structural modifications of the rib cage in OI have consequences on ventilatory pattern. One-way or two-way analysis of variance was performed to compare the results between the three groups and the two postures. Results Both OI type III and IV patients showed reduced FVC and FEV1 compared to predicted values, on condition that updated reference equations are considered. In both positions, ventilation was lower in OI patients than control because of lower tidal volume (p<0.01). In contrast to OI type IV patients, whose chest wall geometry and function was normal, OI type III patients were characterized by reduced (p<0.01) angle at the sternum (pectus carinatum), paradoxical inspiratory inward motion of the pulmonary rib cage, significant thoraco-abdominal asynchronies and rib cage distortions in supine position (p<0.001). Conclusions In conclusion, the restrictive respiratory pattern of Osteogenesis Imperfecta is closely related to the severity of the disease and to the sternal deformities. Pectus carinatum characterizes OI type III patients and alters respiratory muscles coordination, leading to chest wall and rib cage distortions and an inefficient ventilator pattern. OI type IV is characterized by lower alterations in the respiratory function. These findings suggest that functional assessment and treatment of OI should be differentiated in these two forms of the disease.
The Abdominal Circulatory Pump
Andrea Aliverti, Dario Bovio, Irene Fullin, Raffaele L. Dellacà, Antonella Lo Mauro, Antonio Pedotti, Peter T. Macklem
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0005550
Abstract: Blood in the splanchnic vasculature can be transferred to the extremities. We quantified such blood shifts in normal subjects by measuring trunk volume by optoelectronic plethysmography, simultaneously with changes in body volume by whole body plethysmography during contractions of the diaphragm and abdominal muscles. Trunk volume changes with blood shifts, but body volume does not so that the blood volume shifted between trunk and extremities (Vbs) is the difference between changes in trunk and body volume. This is so because both trunk and body volume change identically with breathing and gas expansion or compression. During tidal breathing Vbs was 50–75 ml with an ejection fraction of 4–6% and an output of 750–1500 ml/min. Step increases in abdominal pressure resulted in rapid emptying presumably from the liver with a time constant of 0.61±0.1SE sec. followed by slower flow from non-hepatic viscera. The filling time constant was 0.57±0.09SE sec. Splanchnic emptying shifted up to 650 ml blood. With emptying, the increased hepatic vein flow increases the blood pressure at its entry into the inferior vena cava (IVC) and abolishes the pressure gradient producing flow between the femoral vein and the IVC inducing blood pooling in the legs. The findings are important for exercise because the larger the Vbs the greater the perfusion of locomotor muscles. During asystolic cardiac arrest we calculate that appropriate timing of abdominal compression could produce an output of 6 L/min. so that the abdominal circulatory pump might act as an auxiliary heart.
Optimizing positive end-expiratory pressure by oscillatory mechanics minimizes tidal recruitment and distension: an experimental study in a lavage model of lung injury
Emanuela Zannin, Raffaele L Dellaca, Peter Kostic, Pasquale P Pompilio, Anders Larsson, Antonio Pedotti, Goran Hedenstierna, Peter Frykholm
Critical Care , 2012, DOI: 10.1186/cc11858
Abstract: We studied six pigs in which lung injury was induced by bronchoalveolar lavage. The animals were ventilated with a tidal volume of 6 ml/kg. Forced oscillations at 5 Hz were superimposed on the ventilation waveform. Pressure and flow were measured at the tip and at the inlet of the endotracheal tube respectively. Respiratory system reactance (Xrs) was computed from the pressure and flow signals and expressed in terms of oscillatory elastance (EX5). Positive end-expiratory pressure (PEEP) was increased from 0 to 24 cm H2O in steps of 4 cm H2O and subsequently decreased from 24 to 0 in steps of 2 cm H2O. At each PEEP step CT scans and EX5 were assessed at end-expiration and end-inspiration.During deflation the relationship between both end-expiratory and end-inspiratory EX5 and PEEP was a U-shaped curve with minimum values at PEEP = 13.4 ± 1.0 cm H2O (mean ± SD) and 13.0 ± 1.0 cm H2O respectively. EX5 was always higher at end-inspiration than at end-expiration, the difference between the average curves being minimal at 12 cm H2O. At this PEEP level, CT did not show any substantial sign of intra-tidal recruitment/derecruitment or expiratory lung collapse.Using FOT it was possible to measure EX5 both at end-expiration and at end-inspiration. The optimal PEEP strategy based on end-expiratory EX5 minimized intra-tidal recruitment/derecruitment as assessed by CT, and the concurrent attenuation of intra-tidal variations of EX5 suggests that it may also minimize tidal mechanical stress.Current strategies for mechanical ventilation of patients with acute respiratory distress syndrome (ARDS) include low tidal volumes and increased positive end-expiratory pressure (PEEP) [1]. The physiological basis for these strategies is still under debate, but may involve the reduction of forces of stress and strain on the parenchyma [2]. The ARDSNet protocol is a table-based approach of setting PEEP and the fraction of inspired oxygen (FIO2) levels to achieve an oxygenation target [3]. The a
Intra-fraction setup variability: IR optical localization vs. X-ray imaging in a hypofractionated patient population
Maria Spadea, Barbara Tagaste, Marco Riboldi, Eleonora Preve, Daniela Alterio, Gaia Piperno, Cristina Garibaldi, Roberto Orecchia, Antonio Pedotti, Guido Baroni
Radiation Oncology , 2011, DOI: 10.1186/1748-717x-6-38
Abstract: We analyzed data coming from 87 patients treated with hypo-fractionated radiotherapy at cranial and extra-cranial sites. Patient setup was realized through the ExacTrac X-ray 6D system (BrainLAB, Germany), consisting of 2 infrared TV cameras for external fiducial localization and X-ray imaging in double projection for image registration. Before irradiation, patients were pre-aligned relying on optical marker localization. Patient position was refined through the automatic matching of X-ray images to digitally reconstructed radiographs, providing 6 corrective parameters that were automatically applied using a robotic couch. Infrared patient localization and X-ray imaging were performed at the end of treatment, thus providing independent measures of intra-fraction motion.According to optical measurements, the size of intra-fraction motion was (median ± quartile) 0.3 ± 0.3 mm, 0.6 ± 0.6 mm, 0.7 ± 0.6 mm for cranial, abdominal and lung patients, respectively. X-ray image registration estimated larger intra-fraction motion, equal to 0.9 ± 0.8 mm, 1.3 ± 1.2 mm, 1.8 ± 2.2 mm, correspondingly.Optical tracking highlighted negligible intra-fraction motion at both cranial and extra-cranial sites. The larger motion detected by X-ray image registration showed significant inter-patient variability, in contrast to infrared optical tracking measurement. Infrared localization is put forward as the optimal strategy to monitor intra-fraction motion, featuring robustness, flexibility and less invasivity with respect to X-ray based techniques.Over the last few years, the development of Image Guided Radiation Therapy (IGRT) technologies has resulted in the design and realization of systems allowing precise patient setup and monitoring at each therapy fraction [1-3]. The rationale is related to dose escalation and hypo-fractionated protocols, which require the precise localization of the target throughout the treatment. Morphological changes, tumor shrinkage and organ motion effects lead
Positive end-expiratory pressure optimization with forced oscillation technique reduces ventilator induced lung injury: a controlled experimental study in pigs with saline lavage lung injury
Peter Kostic, Emanuela Zannin, Marie Andersson Olerud, Pasquale P Pompilio, G?ran Hedenstierna, Antonio Pedotti, Anders Larsson, Peter Frykholm, Raffaele L Dellaca
Critical Care , 2011, DOI: 10.1186/cc10236
Abstract: 17 pigs, in which acute lung injury (ALI) was induced by saline lavage, were studied. Animals were randomized into two groups: in the first PEEP was titrated according to Xrs (FOT group), in the control group PEEP was set according to the ARDSNet protocol (ARDSNet group). The duration of the trial was 12 hours. In both groups recruitment maneuvers (RM) were performed every 2 hours, increasing PEEP to 20 cmH2O. In the FOT group PEEP was titrated by monitoring Xrs while PEEP was reduced from 20 cmH2O in steps of 2 cmH2O. PEEP was considered optimal at the step before which Xrs started to decrease. Ventilatory parameters, lung mechanics, blood gases and hemodynamic parameters were recorded hourly. Lung injury was evaluated by histopathological analysis.The PEEP levels set in the FOT group were significantly higher compared to those set in the ARDSNet group during the whole trial. These higher values of PEEP resulted in improved lung mechanics, reduced driving pressure, improved oxygenation, with a trend for higher PaCO2 and lower systemic and pulmonary pressure. After 12 hours of ventilation, histopathological analysis showed a significantly lower score of lung injury in the FOT group compared to the ARDSNet group.In a lavage model of lung injury a PEEP optimization strategy based on maximizing Xrs attenuated the signs of ventilator induced lung injury. The respiratory system reactance measured by FOT could thus be an important component in a strategy for delivering protective ventilation to patients with ARDS/acute lung injury.Mechanical ventilation is a mainstay of intensive care for patients with acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS). A ventilation strategy based on tidal volumes of 6 ml.kg-1 and pre-defined positive end-expiratory pressure (PEEP) settings has been shown to reduce morbidity and mortality probably due to less ventilation-induced lung injury (VILI) [1-3]. Various protocols using higher levels of PEEP in combination
Mast Cells in the Pathogenesis of Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis
Massimo Costanza,Mario P. Colombo,Rosetta Pedotti
International Journal of Molecular Sciences , 2012, DOI: 10.3390/ijms131115107
Abstract: Mast cells (MCs) are best known as key immune players in immunoglobulin E (IgE)-dependent allergic reactions. In recent years, several lines of evidence have suggested that MCs might play an important role in several pathological conditions, including autoimmune disorders such as multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), an animal model for MS. Since their first description in MS plaques in the late 1800s, much effort has been put into elucidating the contribution of MCs to the development of central nervous system (CNS) autoimmunity. Mouse models of MC-deficiency have provided a valuable experimental tool for dissecting MC involvement in MS and EAE. However, to date there is still major controversy concerning the function of MCs in these diseases. Indeed, although MCs have been classically proposed as having a detrimental and pro-inflammatory role, recent literature has questioned and resized the contribution of MCs to the pathology of MS and EAE. In this review, we will present the main evidence obtained in MS and EAE on this topic, and discuss the critical and controversial aspects of such evidence.
Computational Docking of Antibody-Antigen Complexes, Opportunities and Pitfalls Illustrated by Influenza Hemagglutinin
Mattia Pedotti,Luca Simonelli,Elsa Livoti,Luca Varani
International Journal of Molecular Sciences , 2011, DOI: 10.3390/ijms12010226
Abstract: Antibodies play an increasingly important role in both basic research and the pharmaceutical industry. Since their efficiency depends, in ultimate analysis, on their atomic interactions with an antigen, studying such interactions is important to understand how they function and, in the long run, to design new molecules with desired properties. Computational docking, the process of predicting the conformation of a complex from its separated components, is emerging as a fast and affordable technique for the structural characterization of antibody-antigen complexes. In this manuscript, we first describe the different computational strategies for the modeling of antibodies and docking of their complexes, and then predict the binding of two antibodies to the stalk region of influenza hemagglutinin, an important pharmaceutical target. The purpose is two-fold: on a general note, we want to illustrate the advantages and pitfalls of computational docking with a practical example, using different approaches and comparing the results to known experimental structures. On a more specific note, we want to assess if docking can be successful in characterizing the binding to the same influenza epitope of other antibodies with unknown structure, which has practical relevance for pharmaceutical and biological research. The paper clearly shows that some of the computational docking predictions can be very accurate, but the algorithm often fails to discriminate them from inaccurate solutions. It is of paramount importance, therefore, to use rapidly obtained experimental data to validate the computational results.
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