Role of videofluorography swallow study in management of dysphagia in neurologically compromised patients.

PURPOSE: The aim of this study was to demonstrate the key role of the videofluorography swallow study (VFSS) in the management of patients with dysphagia and varying degrees of neurological deficit. MATERIALS AND METHODS: In 1 year (March 2004-March 2005) 47 patients with oropharyngeal dysphagia due to different types of neurological deficit and who required rehabilitation were studied. All patients underwent: (1) clinical history assessment, (2) speech therapy assessment and (3) VFSS using digital fluoroscopy (25 frames per second). Patients were divided according to the Waxman classification into seven levels of dysphagia, and the most suitable type of feeding was selected (normal diet, restricted diet, artificial nutrition). At discharge, the possibility of changing the dietary regimen followed in hospital was evaluated based on clinical progress, radiological follow-up and the degree of improvement obtained. RESULTS: VFSS confirmed aspiration in 21/47 (44%) patients, of whom four (8%) had not been suspected at clinical-speech therapy assessment. In 13/47 (28%) patients, VFSS identified changes at the oral (three patients) or pharyngeal stage (three patients) or both (seven patients) but with no signs of silent aspiration. In the remaining 13 (28%) patients, VFSS did not show any changes in swallow dynamics. On the basis of these data, together with the follow-up at the end of rehabilitation treatment, different nutritional strategies were adopted: artificial nutrition [percutaneous endoscopic gastrostomy (PEG) or nasogastric tube], a restricted-consistency diet or normal diet. CONCLUSIONS: Our experience shows that VFSS precisely classifies the degree of dysphagia that conditions the dietary management of each neurologically compromised patient.

Evaluation of adaptive support ventilation in paralysed patients and in a physical lung model.

OBJECTIVE: Evaluation of the respiratory pattern selected by the Adaptive Support Ventilation (ASV) in ventilated patients with acute, chronic respiratory failure and normal lungs and in a physical lung model. DESIGN: We tested ASV both on patients and in a physical lung model, with a normal level of minute ventilation and with minute ventilation increased by 30%. In each patient, respiratory pattern, mechanics and blood gases were recorded. SETTING: General ICU of a University Hospital. RESULTS: In patients with normal lungs, mean values+/-SD were: tidal volume (Vt) 558.1+/-142.4 mL, respiratory rate (RR) 12.6+/-1.3b/min and inspiratory time/total time ratio (Ti/Ttot) 42.4+/-4.1%; in COPD, mean values+/-SD were: Vt 724+/-171 mL, RR 9.2+/-2.7b/min and Ti/Ttot 26.6+/-10.5%; in restrictive ones, mean values+/-SD were: Vt 550.2+/-77.0 mL, RR 15.8+/-2.6b/min, Ti/Ttot 47.5+/-2.5%. In the lung model, at a normal setting, mean values+/-SD were: Vt 523+/-18.5 mL, RR 14+/-0.0b/min, Ti/Ttot 44.0%, in COPD, mean values+/-SD were: Vt 678+/-0.0 mL, RR 9+/-0.0b/min, Ti/Ttot 20+/-0.7%, in restrictive one, mean values+/-SD were: Vt 513+/-12.8 mL, RR 15+/-0.0b/min, Ti/Ttot 48+/-1.5%. In model hyperventilation conditions in a normal setting a Vt of 582+/-16.6 mL, RR 16+/-0.0b/min, Ti/Ttot 48+/-0.0% were selected, in the obstructive setting Vt 883+/-0.0 mL, RR 9+/-0.0b/min, Ti/Ttot 20+/-0.0% and in a restrictive one Vt 545+/-8.4 mL, RR 18+/-0.0b/min, Ti/Ttot 50-0.0%. CONCLUSIONS: In normal patients ASV selected a ventilatory pattern close to the physiological one, in COPD almost a high expiratory time pattern and in restrictive ones a reduced tidal volume pattern. In the model the selection was similar. In the hyperventilation test, ASV chose a balanced increase in both Vt and RR.

Induction and transmission of cytogenetic toxic effects of 5-fluorouracil in male germline cells of Swiss mice.

Cytogenetic toxicity after a single intraperitoneal exposure of three different doses (5,10 and 15 mg/kg) of 5-fluorouracil (5-FU) and its transmission in the male germline cells of Swiss mice was assessed. At 24 hrs post-treatment each of the doses of 5-FU induced statistically highly significant number of chromosomal aberrations, mostly random chromatid breaks, in the spermatogonial cells with maximum aberrations in the lowest dose. Primary spermatocytic chromosome analysis at week 4 post-treatment showed the presence of a statistically significant number of aberrant spermatocytes with atypical bivalents, mostly with autosomal and/or XY univalents. Sperm morphology assay at week 8 post-treatment exhibited higher percentages of abnormal sperm, but were not statistically significant. This indicated the gradual decline in the transmission of the induced cytogenetic toxic effects of 5-FU from spermatogonia to sperm, which might be because of gradual elimination of the grossly affected spermatogonial cells during the course of spermatogenesis.

S-phase dependent cytogenetic toxicity of 5-fluorouracil in bone marrow cells of mice.

The in vivo cytogenetic toxicity of three different doses (5,10 and 15 mg/kg) of 5-fluorouracil (5-FU) (in Fluracil) was assessed in bone marrow cells of mice. At 24 hrs post-treatment the induced chromosomal aberrations, mostly chromatid breaks and fragments, by all the three different concentrations of 5-FU were found statistically significant. However, mitotic index study at 24 hrs post-treatment indicated it as nonmitotoxic. At 30 hrs posttreatment, all the three doses of 5-FU induced a statistically significant number of micronuclei per thousand polychromatic erythrocytes. This indicated 5-FU as nonmitotoxic but highly clastogenic in bone marrow cells of mice.

Potential transmission of the cytogenetic toxic effects of methotrexate in the male germline cells of Swiss mice.

On testing the cytogenetic toxic effects of methotrexate, a widely prescribed antineoplastic drug, in the male germline cells of Swiss mice, it was found highly clastogenic to the spermatogonial cells at 24-h post-treatment after a single intraperitoneal exposure. The occurrence of significant percentages of aberrant primary spermatocytes with atypical bivalents at week 4 post-treatment and a little higher percentages of sperm with abnormal morphology at week 8 post-treatment indicated the potential transmission of the induced cytogenetic toxic effects of methotrexate from spermatogonia to sperm in the male germline cells of Swiss mice.

Acute effects of inhaled nitric oxide in adult respiratory distress syndrome.

This study evaluated the dose-response effect of inhaled nitric oxide (NO) on gas exchange, haemodynamics, and respiratory mechanics in patients with adult respiratory distress syndrome (ARDS). Of 19 consecutive ARDS patients on mechanical ventilation, eight (42%) responded to a test of 10 parts per million (ppm) NO inhalation with a 25% increase in arterial oxygen tension (Pa,O2,) over the baseline value. The eight NO-responders were extensively studied during administration of seven inhaled NO doses: 0.5, 1, 5, 10, 20, 50 and 100 ppm. Pulmonary pressure and pulmonary vascular resistance exhibited a dose-dependent decrease at NO doses of 0.5-5 ppm, with a plateau at higher doses. At all doses, inhaled NO improved O2 exchange via a reduction in venous admixture. On average, the increase in Pa,O2, was maximal at 5 ppm NO. Some patients, however, exhibited maximal improvement in Pa,O2 at 100 ppm NO. In all patients, the increase in arterial O2 content was maximal at 5 ppm NO. The lack of further increase in arterial O2 content above 5 ppm partly depended on an NO-induced increase in methaemoglobin. Respiratory mechanics were not affected by NO inhalation. In conclusion, NO doses < or =5 ppm are effective for optimal treatment both of hypoxaemia and of pulmonary hypertension in adult respiratory distress syndrome. Although NO doses as high as 100 ppm may further increase arterial oxygen tension, this effect may not lead to an improvement in arterial O2 content, due to the NO-induced increase in methaemoglobin. It is important to consider the effect of NO not only on arterial oxygen tension, but also on arterial O2 content for correct management of inhaled nitric oxide therapy.

FGF-2 stimulates migration of Kaposi's sarcoma-like vascular cells by HGF-dependent relocalization of the urokinase receptor.

The spindle-shaped cell line TTB was recently isolated from highly vascularized skin lesions of BKV/HIV-1 tat transgenic mice and shown to possess an autocrine loop for hepatocyte growth factor (HGF). We show that fibroblast growth factor-2 (FGF-2) stimulates TTB cell migration and promotes polarization of uPAR at the leading edge of migrating cells. FGF-stimulated TTB cells presented the typical migratory phenotype, with a triangular cell shape and concomitant breakdown of actin stress fibers and smooth muscle-specific actin isoform. FGF-2-stimulated migration was blocked by antibodies against urokinase-type plasminogen activator (uPA) or uPA receptor (uPAR) and by neutralizing anti-HGF antibodies. The latter also inhibited uPAR relocalization at the cell surface of FGF-2-treated TTB cells. This points to a crosstalk between FGF-2 and HGF that might mediate TTB cell migration by modulating the localization of cell surface uPAR.

Unfavorable mechanical effects of heat and moisture exchangers in ventilated patients.

OBJECTIVE: To investigate the mechanical effects of artificial noses. SETTING: A general intensive care unit of a university hospital. PATIENTS: 10 patients in pressure support ventilation for acute respiratory failure. INTERVENTIONS: The following three conditions were randomly tested on each patient: the use of a heated humidifier (control condition), the use of a heat and moisture exchanger without filtering function (HME), and the use of a combined heat and moisture exchanger and mechanical filter (HMEF). The pressure support level was automatically adapted by means of a closed-loop control in order to obtain constancy, throughout the study, of patient inspiratory effort as evaluated from airway occlusion pressure at 0.1 s (P0.1). Patient's ventilatory pattern, P0.1, work of breathing, and blood gases were recorded. MEASUREMENTS AND MAIN RESULTS: The artificial noses increased different components of the inspiratory load: inspiratory resistance, ventilation requirements (due to increased dead space ventilation), and dynamic intrinsic positive end-expiratory pressure (PEEP). The additional load imposed by the artificial noses was entirely undertaken by the ventilator, being the closed-loop control of P0.1 effective to maintain constancy of patient inspiratory work by means of adequate increases in pressure support level. CONCLUSIONS: The artificial noses cause unfavorable mechanical effects by increasing inspiratory resistance, ventilation requirements, and dynamic intrinsic PEEP. Clinicians should consider these effects when setting mechanical ventilation and when assessing patients' ability to breathe spontaneously.

[Inhaled nitrous oxide (NO) for the treatment of ARDS]. / Ossido nitrico (NO) per via inalatoria nel trattamento dell'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.

[Therapeutic alternatives in the treatment of class T1N0 squamous cell carcinoma of the penis: indications and limitations]. / Alternative terapeutiche nel trattamento del carcinoma spinocellulare del pene di categoria T1N0: indicazioni e limiti.

At INT of Milan between 1964 and 1990, 204 consecutive native patients suffering from penile cancer have been treated. 101 (59%) patients out of 171 with invasive cancer (23 affected with Tis were excluded) have been classified T1N0M0. 74 patients have been treated with penis conserving methods, such as circumcision, radiotherapy, laser excision and primary chemotherapy + conserving surgery. Overall local failure and/or nodal relapses occurred in 27% (20/74). Relapses are significantly related with grading but there isn't any relationship with macroscopical aspect or size of the tumor. The conservative treatment had been possible in 80% of patients. In our experience T1N0 clinical stage conservative therapy does not worsen the prognosis.

Closed-loop control of airway occlusion pressure at 0.1 second (P0.1) applied to pressure-support ventilation: algorithm and application in intubated patients.

OBJECTIVE: Airway occlusion pressure at 0.1 sec (P0.1) is an index of respiratory center output. During pressure-support ventilation, P0.1 correlates with the mechanical output of the inspiratory muscles and has an inverse relationship with the amount of pressure-support ventilation. Based on these observations, we designed a closed-loop control which, by automatically adjusting pressure-support ventilation, stabilizes P0.1, and hence patient inspiratory activity, at a desired target. The purpose of the study was to demonstrate the feasibility of the method, rather than its efficacy or even its influence on patient outcome. DESIGN: Prospective, randomized trial. SETTING: A general intensive care unit of a university hospital in Italy. PATIENTS: Eight stable patients intubated and ventilated with pressure-support ventilation for acute respiratory failure. INTERVENTIONS: Patients were transiently connected to a computer-controlled ventilator on which the algorithm for closed-loop control was implemented. The closed-loop control was based on breath by breath measurement of P0.1, and on comparison with a target set by the user. When actual P0.1 proved to be higher than the target value, the P0.1 controller automatically increased pressure-support ventilation, and decreased it when P0.1 proved to be lower than the target value. For safety, a volume controller was also implemented. Four P0.1 targets (1.5, 2.5, 3.5, and 4.5 cm H2O) were applied at random for 15 mins each. MEASUREMENTS AND MAIN RESULTS: The closed-loop algorithm was able to control P0.1, with a difference from the set targets of 0.59 +/- 0.27 (SD) cm H2O. CONCLUSIONS: The study shows that P0.1 can be automatically controlled by pressure-support ventilation adjustments with a computer. Inspiratory activity can thus be stabilized at a level prescribed by the physician.

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.

Noninvasive evaluation of instantaneous total mechanical activity of the respiratory muscles during pressure support ventilation.

OBJECTIVE: The measurement of esophageal pressure (Pes) is the conventional method for the evaluation of the forces applied to the respiratory system by the respiratory muscles. As an alternative to Pes measurement, we propose the calculation of the instantaneous net pressure applied by the respiratory muscles [Pmusc(t)]. DESIGN: Prospective, randomized study. SETTING: A general ICU of a university hospital. PATIENTS: Eight intubated patients submitted to pressure support ventilation for acute respiratory failure. INTERVENTIONS: Four different levels of pressure support were used to unload progressively the respiratory muscles. Pmusc(t) was calculated at all levels of pressure support and compared with Pes corrected for chest wall load as a reference. Pmusc(t) was further used to calculate inspiratory work of breathing, which in turn was compared with data obtained with the conventional method. MEASUREMENTS AND RESULTS: Airway pressure, airflow, and Pes were measured. Both for amplitude and for timing, Pmusc(t) showed good agreement with reference measurements. Work of breathing as calculated from Pmusc(t) agreed well with the measurement obtained with the conventional method (mean difference, 0.057 +/- 0.157 J). CONCLUSIONS: Noninvasive evaluation of Pmusc(t) allows extended monitoring of mechanical ventilation, which is particularly interesting for pressure preset ventilation modes.

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.

Respiratory mechanics by least squares fitting in mechanically ventilated patients: applications during paralysis and during pressure support ventilation.

OBJECTIVE: To evaluate a least squares fitting technique for the purpose of measuring total respiratory compliance (Crs) and resistance (Rrs) in patients submitted to partial ventilatory support, without the need for esophageal pressure measurement. DESIGN: Prospective, randomized study. SETTING: A general ICU of a University Hospital. PATIENTS: 11 patients in acute respiratory failure, intubated and assisted by pressure support ventilation (PSV). INTERVENTIONS: Patients were ventilated at 4 different levels of pressure support. At the end of the study, they were paralyzed for diagnostic reasons and submitted to volume controlled ventilation (CMV). MEASUREMENTS AND RESULTS: A least squares fitting (LSF) method was applied to measure Crs and Rrs at different levels of pressure support as well as in CMV. Crs and Rrs calculated by the LSF method were compared to reference values which were obtained in PSV by measurement of esophageal pressure, and in CMV by the application of the constant flow, end-inspiratory occlusion method. Inspiratory activity was measured by P0.1. In CMV, Crs and Rrs measured by the LSF method are close to quasistatic compliance (-1.5 +/- 1.5 ml/cmH2O) and to the mean value of minimum and maximum end-inspiratory resistance (+0.9 +/- 2.5 cmH2O/(l/s)). Applied during PSV, the LSF method leads to gross underestimation of Rrs (-10.4 +/- 2.3 cmH2O/(l/s)) and overestimation of Crs (+35.2 +/- 33 ml/cmH2O) whenever the set pressure support level is low and the activity of the respiratory muscles is high (P0.1 was 4.6 +/- 3.1 cmH2O). However, satisfactory estimations of Crs and Rrs by the LSF method were obtained at increased pressure support levels, resulting in a mean error of -0.4 +/- 6 ml/cmH2O and -2.8 +/- 1.5 cmH2O/(l/s), respectively. This condition was coincident with a P0.1 of 1.6 +/- 0.7 cmH2O. CONCLUSION: The LSF method allows non-invasive evaluation of respiratory mechanics during PSV, provided that a near-relaxation condition is obtained by means of an adequately increased pressure support level. The measurement of P0.1 may be helpful for titrating the pressure support in order to obtain the condition of near-relaxation.

[Nitric oxide inhalation test in patients with ARDS: preliminary assessment of the effect on arterial oxygenation]. / Test di inalazione di ossido nitrico (NO) in pazienti con ARDS: valutazione preliminare dell'effetto sull'ossigenazione arteriosa.

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.