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Biomedical subjects

L Gattinoni

Publications and source records attributed to L Gattinoni.

At least 19 recordsLinked to original sources
PubMed2003

Pulmonary and extrapulmonary acute respiratory distress syndrome are different.

Acute respiratory distress syndrome (ARDS) can be derived from two pathogenetic pathways: a direct insult on lung cells (pulmonary ARDS (ARDSp)) or indirectly (extrapulmonary ARDS (ARDSexp)). This review reports and discusses differences in biochemical activation, histology, morphological aspects, respiratory mechanics and response to different ventilatory strategies between ARDSp and ARDSexp. In ARDSp the direct insult primarily affects the alveolar epithelium with a local alveolar inflammatory response while in ARDSexp the indirect insult affects the vascular endothelium by inflammatory mediators through the bloodstream. Radiological pattern in ARDSp is characterised by a prevalent alveolar consolidation while the ARDSexp by a prevalent ground-glass opacification. In ARDSp the lung elastance, while in ARDSexp the chest wall and intra-abdominal chest elastance are increased. The effects of positive end-expiratory pressure, recruitment manoeuvres and prone position are clearly greater in ARDSexp. Although these two types of acute respiratory distress syndrome have different pathogenic pathways, morphological aspects, respiratory mechanics, and different response to ventilatory strategies, at the present, is still not clear, if this distinction can really ameliorate the outcome.

Airway Resistance↗
PubMed2002

Short-term effects of anastrozole treatment on insulin-like growth factor system in postmenopausal advanced breast cancer patients.

Insulin-like growth factors (IGFs) play a fundamental role in cancer development by acting in both an endocrinal and paracrinal manner, and hormone breast cancer treatments affect the IGF system by modifying circulating growth factor levels. We evaluated total IGF-1, IGF-2, IGF binding protein (IGFBP)-1 and IGFBP-3 in the blood of 34 postmenopausal advanced breast cancer patients (median age 63 years, range 41-85) treated with anastrozole, a non-steroidal structure aromatase inhibitor (NSS-AI). The plasma samples were obtained at baseline, and after 2, 4, 8 and 12 weeks of treatment. The IGFs were quantitated by means of sensitive radioimmunoassays (RIAs). IGF-1 significantly increased during anastrozole treatment (baseline versus 12 weeks, P=0.031), IGF-2 showed a trend towards an increase, and IGFBP-1 constantly but not significantly decreased; IGFBP-3 did not seem to be affected at all. The anastrozole-induced changes in IGFs and IGFBP-1 appeared to be different in the patients receiving a clinical benefit from those observed in non-responders. We have previously shown that letrozole (a different type of NSS-AI) modifies blood IGF-1 levels, and the results of this study of the biological effects of anastrozole on the components of the IGF system confirm our previous observations.

Adult↗
PubMed2002

Prone position in acute respiratory distress syndrome.

In the last few years prone positioning has been used increasingly in the treatment of patients with acute respiratory distress syndrome (ARDS) and this manoeuvre is now considered a simple and safe method to improve oxygenation. However, the physiological mechanisms causing respiratory function improvement as well as the real clinical benefit are not yet fully understood. The aim of this review is to discuss the physiological and clinical effects of prone positioning in patients with ARDS. The main physiological aims of prone positioning are: 1) to improve oxygenation; 2) to improve respiratory mechanics; 3) to homogenise the pleural pressure gradient, the alveolar inflation and the ventilation distribution; 4) to increase lung volume and reduce the amount of atelectatic regions; 5) to facilitate the drainage of secretions; and 6) to reduce ventilator-associated lung injury. According to the available data, the authors conclude that: 1) oxygenation improves in approximately 70-80% of patients with early acute respiratory distress syndrome; 2) the beneficial effects of oxygenation reduce after 1 week of mechanical ventilation; 3) the aetiology of acute respiratory distress syndrome may markedly affect the response to prone positioning; 4) extreme care is necessary when the manoeuvre is performed; 5) pressure sores are frequent and related to the number of pronations; 6) the supports used to prone and during positioning are different and nonstandardised among centres; and 7) intensive care unit and hospital stay and mortality still remain high despite prone positioning.

Acute Disease↗
PubMed2002

Different modes of assisted ventilation in patients with acute respiratory failure.

The aim of the present study was to verify that the patient/ventilator interaction is similar, regardless of the mode of assisted mechanical ventilation (i.e. pressure- or volume-limited) used, if tidal volume (VT) and peak inspiratory flow (PIF) are matched. Therefore, the authors compared the effects of three different modes of assisted ventilation on the work of breathing (WOB) and gas exchange in patients with acute respiratory failure. For Protocol 1, in seven patients, the authors compared pressure support, assist pressure control and assist control (with square and decelerating wave inspiratory flow pattern) set to deliver the same VT and PIF. For Protocol 2, in another 10 patients, the authors compared pressure support and assist control with high (0.8 L x s(-1)) and low (0.6 L x s(-1)) PIFs set to deliver the same VT. In Protocol 1, there was no difference in WOB and gas exchange between the three modes of assisted ventilation tested. In Protocol 2, the decrease of PIFs during assist control significantly increased WOB. In conclusion, different modes of assisted ventilation similarly reduce work of breathing and provide adequate gas exchange at fixed tidal volume and peak inspiratory flow only. During assist control, tidal volume and peak inspiratory flow (set by the physician) are the main determinants of the patient/ventilator interaction.

Acute Disease↗
PubMed2001

A blunt complex abdominal trauma: total hepatectomy and liver transplantation.

A victim of a motor accident was referred to the Emergency Department. He was unconscious, breathing was rapid and shallow, and had a mean arterial pressure of 60 mmHg with a distended abdomen. A peritoneal lavage was positive for blood. An immediate laparotomy showed a massive hepatic injury with bilobar disruptions. After an unsuccessful hepatorrhaphy an extensive perhepatic gauze packing was done. During the operation the patient was massively transfused and high doses of dopamine were used. At the end a relative stability was reached, but a few hours later, due to the high risk of sepsis and abdominal compartment syndrome, a second laparotomy was performed. Despite efforts to reach a good hemostasis, it was decided to perform a total hepatectomy and portocaval shunt. The patient was put on the waiting list for a compatible liver. After 36 h in this anhepatic state, the patient received the new graft. The graft showed immediate recovery. In cases of severe and complex liver trauma, performing a total hepatectomy followed by liver transplantation is justified.

Accidents, Traffic↗
PubMed2001

Effect of prone positioning on the survival of patients with acute respiratory failure.

BACKGROUND: Although placing patients with acute respiratory failure in a prone (face down) position improves their oxygenation 60 to 70 percent of the time, the effect on survival is not known. METHODS: In a multicenter, randomized trial, we compared conventional treatment (in the supine position) of patients with acute lung injury or the acute respiratory distress syndrome with a predefined strategy of placing patients in a prone position for six or more hours daily for 10 days. We enrolled 304 patients, 152 in each group. RESULTS: The mortality rate was 23.0 percent during the 10-day study period, 49.3 percent at the time of discharge from the intensive care unit, and 60.5 percent at 6 months. The relative risk of death in the prone group as compared with the supine group was 0.84 at the end of the study period (95 percent confidence interval, 0.56 to 1.27), 1.05 at the time of discharge from the intensive care unit (95 percent confidence interval, 0.84 to 1.32), and 1.06 at six months (95 percent confidence interval, 0.88 to 1.28). During the study period the mean (+/-SD) increase in the ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen, measured each morning while patients were supine, was greater in the prone than the supine group (63.0+/-66.8 vs. 44.6+/-68.2, P=0.02). The incidence of complications related to positioning (such as pressure sores and accidental extubation) was similar in the two groups. CONCLUSIONS: Although placing patients with acute respiratory failure in a prone position improves their oxygenation, it does not improve survival.

Female↗
PubMed2001

Recruitment and derecruitment during acute respiratory failure: an experimental study.

We aimed to elucidate the relationships between pleural (Ppl), esophageal (Pes), and superimposed gravitational pressures in acute lung injury, and to understand the mechanisms of recruitment and derecruitment. In six dogs with oleic acid respiratory failure, we measured Pes and Ppl in the uppermost, middle, and most dependent lung regions. Each dog was studied at positive end-expiratory pressure (PEEP) of 5 and 15 cm H2O and three levels of tidal volume (VT; low, medium, and high). For each PEEP-VT combination, we obtained a computed tomographic (CT) scan at end-inspiration and end-expiration. The variations of Ppl and Pes pressures were correlated (r = 0.86 +/- 0.07, p < 0.0001), as was the vertical gradient of transpulmonary (PL) and superimposed pressure (r = 0.92, p < 0.0001). Recruitment proceeded continuously along the entire volume-pressure curve. Estimated threshold opening pressures were normally distributed (mode = 20 to 25 cm H2O). The amount of end-expiratory collapse at the same PEEP and PL was significantly lower when ventilation was performed at high VT. End-inspiratory and end-expiratory collapse were highly correlated (r = 0.86, p < 0.0001), suggesting that as more tissue is recruited at end-inspiration, more remains recruited at end-expiration. When superimposed pressure exceeded applied airway pressure (Paw), collapse significantly increased.

Animals↗
PubMed2001

Recruitment and derecruitment during acute respiratory failure: a clinical study.

In a model of acute lung injury, we showed that positive end-expiratory pressure (PEEP) and tidal volume (VT) are interactive variables that determine the extent of lung recruitment, that recruitment occurs across the entire range of total lung capacity, and that superimposed pressure is a key determinant of lung collapse. Aiming to verify if the same rules apply in a clinical setting, we randomly ventilated five ALI/ARDS patients with 10, 15, 20, 30, 35, and 45 cm H2O plateau pressure and 5, 10, 15, and 20 cm H2O of PEEP. For each PEEP-VT condition, we obtained computed tomography at end inspiration and end expiration. We found that recruitment occurred along the entire volume-pressure curve, independent of lower and upper inflection points, and that estimated threshold opening pressures were normally distributed (mode = 20 cm H2O). Recruitment occurred progressively from nondependent to dependent lung regions. Overstretching was not associated with hyperinflation. Derecruitment did not parallel deflation, and estimated threshold closing pressures were normally distributed (mode = 5 cm H2O). End-inspiratory and end-expiratory collapse were correlated, suggesting a plateau-PEEP interaction. When superimposed gravitational pressure exceeded PEEP, end-expiratory collapse increased. We concluded that the rules governing recruitment and derecruitment equally apply in an oleic acid model and in human ALI/ARDS.

Adult↗
PubMed2001

Effects of different continuous positive airway pressure devices and periodic hyperinflations on respiratory function.

OBJECTIVE: To compare the effect on respiratory function of different continuous positive airway pressure systems and periodic hyperinflations in patients with respiratory failure. DESIGN: Prospective SETTING: Hospital intensive care unit. PATIENTS: Sixteen intubated patients (eight men and eight women, age 54 +/- 18 yrs, PaO2/FiO2 277 +/- 58 torr, positive end-expiratory pressure 6.2 +/- 2.0 cm H2O). INTERVENTIONS: We evaluated continuous flow positive airway pressure systems with high or low flow plus a reservoir bag equipped with spring-loaded mechanical or underwater seal positive end-expiratory pressure valve and a continuous positive airway pressure by a Servo 300 C ventilator with or without periodic hyperinflations (three assisted breaths per minute with constant inspiratory pressure of 30 cm H2O over positive end-expiratory pressure). MEASUREMENTS AND MAIN RESULTS: We measured the respiratory pattern, work of breathing, dyspnea sensation, end-expiratory lung volume, and gas exchange. We found the following: a) Work of breathing and gas exchange were comparable between continuous flow systems; b) the ventilator continuous positive airway pressure was not different compared with continuous flow systems; and c) continuous positive airway pressure with periodic hyperinflations reduced work of breathing (10.7 +/- 9.5 vs. 6.3 +/- 5.7 J/min, p <.05) and dyspnea sensation (1.6 +/- 1.2 vs. 1.1 +/- 0.8 cm, p <.05) increased end-expiratory lung volume (1.6 +/- 0.8 vs. 2.0 +/- 0.9 L, p <.05) and PaO2 (100 +/- 21 vs. 120 +/- 25 torr, p <.05) compared with ventilator continuous positive airway pressure. CONCLUSIONS: The continuous flow positive airway pressure systems tested are equally efficient; a ventilator can provide satisfactory continuous positive airway pressure; and the use of periodic hyperinflations during continuous positive airway pressure can improve respiratory function and reduce the work of breathing.

Adult↗
PubMed2001

Estimation of end-expiratory lung volume variations by optoelectronic plethysmography.

OBJECTIVE: To test the capability of optoelectronic plethysmography (OEP) to monitor positive end-expiratory pressure (PEEP)-induced changes of end-expiratory lung volume (EELV) changes in mechanically ventilated paralyzed patients. DESIGN: Laboratory and clinical investigation. SETTING: Intensive care unit of the Ospedale Maggiore Policlinico di Milano. PATIENTS: A total of eight patients with respiratory failure of various degrees, sedated and paralyzed. INTERVENTIONS: PEEP variations (+/-5 cm H2O) relative to the baseline PEEP of 10 cm H2O. MEASUREMENTS AND MAIN RESULTS: In the model protocol, we tested the reproducibility of the OEP by repeating volume measurements of a plastic torso model over a 21-hr period, every 30 mins. The variations of OEP measurements of the torso model (9337 mL value) were encountered in a range of 16 mL (sd = 4 mL). In the patient protocol, we measured the end-expiratory volume of the chest wall (EEVCW) breath-by-breath by OEP before, during, and after the PEEP increase/decrease and we compared its variations with the corresponding variations of EELV measured by helium dilution technique. The regression line between EELV changes measured by helium and EEVCW changes measured by OEP resulted very close to the identity line (slope 1.06, intercept -0.02 L, r(2) = 0.89) and their difference was not related to their absolute magnitude. After PEEP increase, the new steady state of EEVCW was reached approximately in 15 breaths; and, after PEEP decrease, in 3-4 breaths. The slow increase in EEVCW was mainly because of the abdominal compartment. CONCLUSION: OEP measurements of EEVCW accurately reflect the changes of EELV. Furthermore, OEP allows a continuous compartmental analysis, even during unsteady conditions.

Adult↗
PubMed2001

The effects of pressurization rate on breathing pattern, work of breathing, gas exchange and patient comfort in pressure support ventilation.

The aim of this study was to investigate the effects of different pressurization rates during pressure support ventilation on breathing pattern, work of breathing, gas exchange and patient comfort in patients with acute lung injury. The pressurization rate modifies the initial pressure ramp by changing the initial peak flow rate: the increase in pressurization rate is associated with a decrease in the time to reach the level of pressure support ventilation by increasing the peak flow rate. Ten intubated patients (age 64+/-17 yrs, body mass index 24+/-17 Kg x m(-2), arterial oxygen tension/inspired oxygen fraction 214+/-59) were studied in random order varying the pressurization rate at 5 and 15 cmH2O of pressure support ventilation. Breathing comfort was evaluated by a visual analogue scale. Increasing the pressurization rate caused an increase of peak flow rate from 473+/-141 mL x s(-1) to 758+/-302 mL x s(-1) at pressure support ventilation 5 (p<0.05) and from 481+/-126 mL x s(-1) to 1,121+/-175 mL x s(-1) at pressure support ventilation 15 (p<0.05). At the lowest pressurization rate the tidal volume was the lowest, the respiratory rate and the work of breathing were the highest (p<0.05) compared with other pressurization rates. Excluding the lowest pressurization rate, in all the other pressurization rates tested the breathing pattern and the work of breathing did not change. The lowest and the highest pressurization rates caused the worst patient comfort (p<0.05). The gas exchange was stable throughout the study. The presented results suggest: 1) the lowest pressurization rate caused the lowest tidal volume, highest respiratory rate and highest work of breathing; 2) at the other pressurization rates no differences in breathing pattern and work of breathing were observed; and 3) the patient's comfort was worse at the lowest and highest pressurization rates.

Adult↗
PubMed2000

Identification of tumor antigen-specific cytotoxic T lymphocytes cross-recognizing allogeneic major histocompatibility class I molecules.

Adoptive immunotherapy of cancer utilizes tumor antigen-specific cytotoxic T lymphocytes (CTL) as mediators of a targeted anti-tumor effect. In this study, we show that such CTL can be able to cross-recognize allogeneic major histocompatibility complex (MHC) molecules in a phenomenon of molecular mimicry. A self histo-leukocyte antigen (HLA) A*0201-restricted CTL specific for peptide MT27-35 from the human differentiation antigen Melan-A/MART-1 was shown to cross-recognize allogeneic A*0220 molecules which differ from syngeneic A*0201 for a single amino acid substitution at position 66 of the antigen-binding groove. A*0220 molecules were recognized on a variety of human cells of different histological origin but not on COS-7 cells. A second self-A*0201-restricted CTL, specific for peptide D10/6-271 encoded by the tumor-specific DAM-gene family, was shown to cross-recognize allogeneic B*3701 molecules which differ from syngeneic A*0201 by 32 amino acids in the peptide antigen-binding cleft. B*3701 molecules were recognized on a variety of cell types including COS-7 cells. These data raise new safety issues for clinical trials of cancer immunotherapy using adoptive transfer of in vitro generated, allogeneic CTL with specific anti-tumor activity.

Antigens, Neoplasm↗
PubMed2000

Plasma concentrations and anti-L-cytokine effects of alpha-melanocyte stimulating hormone in septic patients.

OBJECTIVES: The aim of this research was to investigate endogenous concentrations and anti-cytokine effects of the antiinflammatory peptide alpha-melanocyte stimulating hormone (alpha-MSH) in patients with systemic inflammation. The objectives were to determine the following: changes over time of plasma alpha-MSH and relationship with patient outcome, correlation between plasma alpha-MSH and tumor necrosis factor (TNF)-alpha plasma concentration and production in whole blood samples, and influences of alpha-MSH on production of TNF-alpha and interleukin (IL)-1beta in whole blood samples stimulated with lipopolysaccharide (LPS). DESIGN: Prospective, nonrandomized, clinical study. SETTING: Intensive care unit of a university hospital. PATIENTS: A total of 21 patients with sepsis syndrome/septic shock and an equal number of healthy volunteers. INTERVENTIONS: Circulating alpha-MSH and TNF-alpha concentrations and TNF-alpha production in supernatants of LPS (1 ng/mL)-stimulated whole blood were measured repeatedly. To determine whether alpha-MSH can modulate production of TNF-alpha and IL-1 beta, these cytokines were measured in whole blood samples stimulated with LPS (1 ng/mL) in the presence or absence of concentrations of the peptide. MEASUREMENTS AND MAIN RESULTS: Plasma alpha-MSH was low in early samples and gradually increased in patients who recovered but not in those who died. There was a negative correlation between plasma concentrations of alpha-MSH and TNF-alpha. In blood samples taken at early phases of sepsis syndrome, production of TNF-alpha was reduced relative to control values; such production increased in patients who recovered but not in those who died. Addition of alpha-MSH to LPS-stimulated whole blood samples inhibited production of TNF-alpha and IL-1beta in a concentration-dependent manner. CONCLUSIONS: In patients with systemic inflammation, there are substantial changes over time in plasma concentrations of alpha-MSH that are reduced in early phases of the disease. Reduction of this endogenous modulator of inflammation could be detrimental to the host. Addition of alpha-MSH to LPS-stimulated blood samples reduces production of cytokines involved in development of septic syndrome. This inhibition by alpha-MSH, a peptide that is beneficial in treatment of experimental models of sepsis, might therefore be useful to treat sepsis syndrome in humans.

Adult↗