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Biomedical subjects

G Iotti

Publications and source records attributed to G Iotti.

At least 19 recordsLinked to original sources
PubMed2006

Expression of CCL9/MIP-1gamma is repressed by BCR/ABL and its restoration suppresses in vivo leukemogenesis of 32D-BCR/ABL cells.

Transformation of hematopoietic cells by the BCR/ABL oncogene is caused by perturbation of signal transduction pathways leading to altered patterns of gene expression and activity. By oligonucleotide microarray hybridization of polysomal RNA of untreated and STI571-treated 32D-BCR/ABL cells, we identified the beta-chemokine CCL9 as a gene regulated by BCR/ABL in a tyrosine kinase-dependent manner. BCR/ABL repressed CCL9 expression at the transcriptional level by mechanisms involving suppression of p38 MAP kinase, and modulation of the activity of CDP/cut and C/EBPalpha, two transcription regulators of myeloid differentiation. However, repression of C/EBP-dependent transcription did not prevent the induction of CCL9 expression by STI571, suggesting that C/EBPalpha is involved in maintaining rather than in inducing CCL9 expression. Restoration of CCL9 expression in 32D-BCR/ABL cells had no effect on the in vitro proliferation of these cells, but reduced their leukemogenic potential in vivo, possibly by recruitment of CD3-positive immune cells. Together, these findings suggest that downregulation of chemokine expression may be involved in BCR/ABL-dependent leukemogenesis by altering the relationship between transformed cells and the microenvironment.

Animals↗
PubMed1997

[Inhaled nitrous oxide (NO) for the treatment of ARDS].

OBJECTIVE: To investigate the initial longterm effect of inhaled NO on hypoxemia in ARDS patients. DESIGN: Retrospective study. PATIENTS: Nine hypoxemic patients with ARDS (Murray Lung Injury Score, LIS, 2.8 +/- 0.3), treated with conventional mechanical ventilation. INTERVENTIONS: Continuous NO inhalation was started after a test of inhaled NO efficacy on gas exchange and hemodynamics. Long term effects of inhaled NO were evaluated daily in terms of arterial oxygenation and methemoglobin formation. RESULTS: The initial NO inhalation increased the PaO2/FiO2 from 141 +/- 64 mmHg to 216 +/- 70 mmHg (p < 0.0001) and decreased the mean pulmonary pressure from 38 +/- 7 mmHg to 32 +/- 5 mmHg (p < 0.01), the pulmonary venous admixture from 29 +/- 10% to 20 +/- 8% (p < 0.01) and the pulmonary vascular resistance from 325 +/- 97 dyne.s.cm-5 to 238 +/- 48 dyne.s.cm-5 (p < 0.01). Daily withdrawal of inhaled NO, which was administered for 14 +/- 16 days at 8 +/- 2 ppm, was associated with a decrease in PaO2/FiO2 by 61 +/- 32 mmHg (p < 0.0001). During prolonged NO inhalation the FiO2 was decreased, on average, by 0.34 +/- 0.19 (p < 0.01), the positive end-expiratory pressure by 4 +/- 2 cmH2O (p < 0.01) and the peak inspiratory pressure by 7 +/- 4 cmH2O (p < 0.01). Three patients died during the ICU stay. CONCLUSIONS: Our results confirm the interest for inhaled NO as an additional approach for the treatment of hypoxemia in ARDS. Inhaled NO seems to allow for a better control of gas exchange, rather than for a rapid reduction of the ventilatory support.

Adolescent↗
PubMed1996

Bronchoalveolar lavage fluid composition in alveolar proteinosis. Early changes after therapeutic lavage.

In patients with idiopathic alveolar proteinosis, the alveoli are filled with materials rich in surfactant components, especially surfactant protein A (SP-A). The anomaly could be caused by either increased secretion, decreased clearance, or both. To clarify this point, we studied five patients who underwent therapeutic lavage and then were ventilated mechanically for 24 h. During the first 8 h of mechanical ventilation, a surfactant-depleted lung was lavaged at selected intervals, and the bronchoalveolar lavage fluid was analyzed. We observed that, after lavage, various surfactant components accumulated in the airways with different time courses. We also observed that SP-A increased until the second hour and then dropped rapidly, suggesting the existence of an efficient mechanism of removal. These findings suggest that idiopathic alveolar proteinosis might be caused by a primary defect in a slow mechanism of removal or by the presence of factor(s) that interfere with the clearance of surfactant and that can be removed by lavage. It seems clear, however, that an increased secretion rate is unlikely to be the major cause of idiopathic alveolar proteinosis.

Adult↗
PubMed1995

Elevated static compliance of the total respiratory system: early predictor of weaning unsuccess in severed COPD patients mechanically ventilated.

OBJECTIVE: To assess in a group of COPD patients mechanically ventilated for an episode of acute respiratory failure the respiratory mechanics with a simple and non invasive method at the bedside in order to evaluate if these parameters may be predictive of weaning failure or success. DESIGN: A prospective study. SETTING: Intensive care and intermediate intensive care units. PATIENTS: 23 COPD patients ventilated for acute respiratory failure and studied within 24 hours from intubation. METHODS: Using end-expiratory and end-inspiratory airway occlusion technique, we measured PEEPi, static compliance of the respiratory system (Crs, st) maximum respiratory resistance (Rrsmax) and minimum respiratory resistance (Rrsmin). MEASUREMENTS AND RESULTS: The weaned group (A) and the not weaned group (B) were not different regarding to static PEEPi (group A 8.5 +/- 4.0 vs group B 8.9 +/- 2.6 cmH2O), TO Rrsmax (22.4 +/- 5.3 versus 22.2 +/- 9.0 cmH2O/1/s) and to Rrsmin (17.6 +/- 5.5 versus 17.9 +/- 8.0 cmH2O/1/s), while a significant difference (p < 0.001) has been found in Cst, rs (62.7 +/- 17.% versus 111.6 +/- 18.0 ml/cm H2O). The threshold value of 88.5 ml/cmH2O was identified by discriminant analysis and provided the best separation between the two groups, with a sensitivity of 0.85 and a specificity of 0.87. CONCLUSION: Cst, rs measured non invasively in the first 24 h from intubation, provided a good separation between the patients who were successfully weaned and those who failed.

Acute Disease↗
PubMed1995

Respiratory response and inspiratory effort during pressure support ventilation in COPD patients.

OBJECTIVE: Pressure Support Ventilation (PSV) is now widely used in the process of weaning patients from mechanical ventilation. The aim of this study was to evaluate the effects of various levels of PS on respiratory pattern and diaphragmatic efforts in patients affected by chronic obstructive pulmonary disease (COPD). SETTING: Intermediate intensive care unit. PATIENTS: We studied ten patients undergoing PSV and recovering from an episode of acute respiratory failure due to exacerbation of COPD. METHODS: Three levels of PSV were studied, starting from the lowest (PSb) one at which it was possible to obtain an adequate Vt with a pH > or = 7.32 and an SaO2 > 93%. Then, PS was set at 5 cmH2O above (PSb + 5) and below (PSb-5) this starting level. Ventilatory pattern, transdiaphragmatic pressure (Pdi), the pressure-time product of the diaphragm (PTPdi), the integrated EMG of the diaphragm, static PEEP (PEEPi, stat), dynamic PEEP (PEEPi, dyn), and the static compliance and resistance of the total respiratory system were recorded. RESULTS: Minute ventilation did not significantly change with variations in the level of PS, while Vt significantly increased with PS (PS-5 = 6.3 +/- 0.5 ml/kg vs. PSb = 10.1 +/- 0.9 [p < 0.01] and vs. PS + 5 = 11.7 +/- 0.6 [p < 0.01]), producing a reduction in respiratory frequency with longer expiratory time. The best values of blood gases were obtained at PSb, while at PSb-5, PaCO2 markedly increased. During PSb and PSb + 5 and to a lesser extent during PSb-5, most of the patients made several inspiratory efforts that were not efficient enough to trigger the ventilator to inspire; thus, the PTPdi "wasted" during these inefficient efforts was increased, especially during PS + 5. The application of an external PEEP (PEEPe) of 75% of the static intrinsic PEEP during PSb caused a significant reduction in the occurrence of these inefficient efforts (p < 0.05). Minute ventilation remained constant, but Vt decreased, together with Te, leaving the blood gases unaltered. The PTPdi per breath and the dynamic PEEPi were also significantly reduced (by 59% and 31% of control, respectively, p < 0.001) with the application of PEEPe. CONCLUSION: We conclude that in COPD patients, different levels of PSV may induce different respiratory patterns and gas exchange. PS levels capable of obtaining a satisfactory equilibrium in blood gases may result in ineffective respiratory efforts if external PEEP is not applied. The addition of PEEPe, not exceeding dynamic intrinsic PEEP, may also reduce the metabolic work of the diaphragm without altering gas exchange.

Acute Disease↗
PubMed1995

Simple method to measure total expiratory time constant based on the passive expiratory flow-volume curve.

OBJECTIVE: In intubated, mechanically ventilated patients, inspiration is forced by externally applied positive pressure. In contrast, exhalation is passive and depends on the time constant of the total respiratory system. The expiratory time constant is thus an important determinant of mechanical ventilation. The aim of this study was to evaluate a simple method for measuring the expiratory time constant in ventilated subjects. DESIGN: Prospective study using a lung simulator and ten dogs. SETTING: University hospital. SUBJECTS: Commercially available lung simulator and ten greyhound dogs. INTERVENTIONS: Different expiratory time constants were set on the lung simulator. In the dogs, the endotracheal tube was clamped to increase airways resistance by 22.5 cm H2O/(L/sec) and the lungs were injured with hydrochloric acid to decrease total respiratory compliance by 16 mL/cm H2O. This procedure resulted in a wide range of expiratory time constants. MEASUREMENTS AND MAIN RESULTS: Pneumotachography was used to measure flow and volume. The ratio of exhaled volume and peak flow was calculated from these signals, corrected for the limited exhalation time yielding the "calculated expiratory time constant" and compared with the actual expiratory time constant. The typical error was +/- 0.19 sec for the lung simulator and +/- 0.15 sec for the dogs. CONCLUSIONS: The volume and peak flow corrected for limited exhalation time is a good estimate of the total expiratory time constant in passive subjects and may be useful for the titration of mechanical ventilation.

Airway Resistance↗
PubMed1995

[Nitric oxide inhalation test in patients with ARDS: preliminary assessment of the effect on arterial oxygenation].

OBJECTIVE: Inhaled NO can improve arterial oxygenation in ARDS. We evaluated the incidence and the magnitude of this effect during a short test of NO inhalation. This was performed in 24 consecutive mechanically ventilated patients with ARDS in order to assess the interest of NO for the therapy of hypoxemia in each case. DESIGN: Retro-spective study. SETTING: ICU in a University Hospital. PATIENTS: 24 hypoxemic patients with ARDS (lung injury score, LIS, 2.9 +/- 0.52), treated with conventional mechanical ventilation. INTERVENTIONS: Tests were performed using a mean inhalatory NO dose of 14 +/- 6 ppm. A pair of PaO2 data was obtained for each patient from two blood gas analysis, performed one just before and one 15 min after the start of NO inhalation. RESULTS: The mean baseline PaO2 was 76 +/- 21 mmHg and significantly increased with NO inhalation to 97 +/- 34 mmHg (p = 0.0001). Considering the individual response to NO, patients were arbitrarily classified as responders when the increase of PaO2 from baseline was > or = 10%. Sixteen patients were identified as responders, showing a mean increase of PaO2 from baseline by 40 +/- 26%, while the remaining 8 patients resulted non responders (mean change 1 +/- 5.7%). In no case a clinically significant decrease of PaO2 was observed during NO inhalation. The response to NO did not correlate with the LIS (r = 0.019) and with baseline PaO2 (r = 0.31). CONCLUSIONS: Inhaled NO doses of 14 +/- 6 ppm increased on the average the PaO2 in a group of ARDS patients, the individual response being however variable. A deterioration of arterial oxygenation was never observed. Even if the criteria for predicting the response to NO still remain to be defined, a short test seems to reliably provide a first estimate of the magnitude of the response.

Administration, Inhalation↗
PubMed1995

Whole lung lavage.

Bronchoalveolar lavage is universally employed as a diagnostic procedure and also, both in the massive (whole lung) and limited forms, has important therapeutic applications. Since the second half of the century whole lung lavage (WLL) has been applied in patients with pulmonary alveolar proteinosis and has proved successful. The procedure has improved over the years in terms of safety and efficacy, whilst indications and methods for WLL are not yet completely defined and standardized. In this paper, we summarize the history of the development of WLL, and describe the procedure used eight times in five patients in our department.

Adult↗
PubMed1989

Body iron status in critically ill patients: significance of serum ferritin.

Serial measurements of blood haemoglobin, serum iron, serum transferrin, total iron-binding capacity, transferrin per cent saturation and serum ferritin were determined in 51 post-operative critically ill patients to investigate body iron status in severely stressed patients. The results showed decreased blood haemoglobin, serum iron, serum transferrin and transferrin saturation compared to an increase in serum ferritin levels. These results indicate that there is inadequate availability of iron to tissues (secondary to rearrangement of body iron to the advantage of the iron storage compartment), which is often present in severely critically ill patients. A positive correlation was found between the initial (ferritin) levels and SAPS (r = 0.41, p less than 0.01). In addition, the increase of ferritin concentration parallels a worsening of the clinical status in severely ill patients. This is due to enhanced release by the macrophage system. From this, we consider serum ferritin as an acute-phase protein and a useful marker of the severity of the clinical status. It appears to be useful in predicting the patient's outcome, but is not reliable in evaluating iron stores in stressed patients.

Adolescent↗
PubMed1987

Bedside evaluation of right ventricular performance using a rapid computerized thermodilution method.

In 34 patients, we assessed the reproducibility and accuracy of a new, computerized, thermodilution method that determines right ventricular ejection fraction (RVEF). We compared the results from this new algorithm with simultaneous results from the conventional plateau thermodilution method and from both first-pass and gated nuclear techniques. Using this new method improved the reproducibility of thermal determinations of RVEF. Although the thermal values were lower, the correlations between thermal and nuclear measurements were close [r = .92 (first-pass technique), r = .81 (gated technique)]. This new method seems particularly appropriate for serial monitoring of RV performance.

Adult↗
PubMed1987

A continuous flow intermittent mandatory ventilation with continuous positive airway pressure circuit with high-compliance reservoir bag.

Unstable inspiratory pressure may reduce the benefits of intermittent mandatory ventilation and impose a greater work of breathing than some patients can tolerate. The authors evaluated a continuous flow intermittent mandatory ventilation with continuous positive airway pressure apparatus provided with a 10-L high compliance reservoir bag, separated from the ventilator circuit by a one-way valve. A pulmonary simulator was tested to generate a wide range of inspiratory peak flow rates. Pressures and flow rates were examined in different sections of the system, using PEEP levels up to 15 mm Hg and different fresh gas flow rates. The circuit offers many advantages, particularly considering the low inspiratory pressure drop and the low fresh gas flow rates needed for optimal function.

Equipment Design↗