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Biomedical subjects

D Navajas

Publications and source records attributed to D Navajas.

At least 37 records · Page 2Linked to original sources
PubMed2001

Measurement of cell microrheology by magnetic twisting cytometry with frequency domain demodulation.

Magnetic twisting cytometry (MTC) (Wang N, Butler JP, and Ingber DE, Science 260: 1124-1127, 1993) is a useful technique for probing cell micromechanics. The technique is based on twisting ligand-coated magnetic microbeads bound to membrane receptors and measuring the resulting bead rotation with a magnetometer. Owing to the low signal-to-noise ratio, however, the magnetic signal must be modulated, which is accomplished by spinning the sample at approximately 10 Hz. Present demodulation approaches limit the MTC range to frequencies <0.5 Hz. We propose a novel demodulation algorithm to expand the frequency range of MTC measurements to higher frequencies. The algorithm is based on coherent demodulation in the frequency domain, and its frequency range is limited only by the dynamic response of the magnetometer. Using the new algorithm, we measured the complex modulus of elasticity (G*) of cultured human bronchial epithelial cells (BEAS-2B) from 0.03 to 16 Hz. Cells were cultured in supplemented RPMI medium, and ferromagnetic beads (approximately 5 microm) coated with an RGD peptide were bound to the cell membrane. Both the storage (G', real part of G*) and loss (G", imaginary part of G*) moduli increased with frequency as omega(alpha) (2 pi x frequency) with alpha approximately equal to 1/4. The ratio G"/G' was approximately 0.5 and varied little with frequency. Thus the cells exhibited a predominantly elastic behavior with a weak power law of frequency and a nearly constant proportion of elastic vs. frictional stresses, implying that the mechanical behavior conformed to the so-called structural damping (or constant-phase) law (Maksym GN, Fabry B, Butler JP, Navajas D, Tschumperlin DJ, LaPorte JD, and Fredberg JJ, J Appl Physiol 89: 1619-1632, 2000). We conclude that frequency domain demodulation dramatically increases the frequency range that can be probed with MTC and reveals that the mechanics of these cells conforms to constant-phase behavior over a range of frequencies approaching three decades.

Algorithms↗
PubMed2001

Relevance of linearizing nasal prongs for assessing hypopneas and flow limitation during sleep.

Respiratory disturbances in patients with the sleep apnea-hypopnea syndrome (SAHS) may be detected by means of nasal prongs (NP) pressure (PNP). Nevertheless, PNP is nonlinearly related to flow (V). Our aim was to demonstrate the relevance of linearizing P NP for assessing hypopneas and flow limitation in SAHS. V was measured with a pneumotachograph during the hypopneas and flow limitation events in a continuous positive airway pressure (CPAP) titration in six patients with severe SAHS. These flow patterns were reproduced by a flow generator through an analog of the nares and recorded by NP. PNP was linearized [V NP = (PNP)1/2] by a specially designed analog circuit. For each event we used V, P NP, and V NP to compute the hypopnea flow amplitude (HFA) and a flow limitation index (FLI). Owing to NP nonlinearity, PNP considerably misestimated HFA and FLI. By contrast, V NP provided HFA and FLI values that were very close to those obtained from V: HFA (V NP) = 1.098. HFA(V) - 0.063 (r2 = 0.98) and FLI(V NP) = 1.044. FLI(V) + 0.004 (r2 = 0.99). Square-root linearization of NP greatly increases the accuracy of quantifying hypopneas and flow limitation. This procedure, which could be readily carried out in routine practice by means of the analog circuit we developed, is of interest in optimizing the assessment of respiratory sleep disturbances in SAHS.

Computers, Analog↗
PubMed2001

Forced oscillation measurements do not affect upper airway muscle tone or sleep in clinical studies.

Upper airway obstruction in the sleep apnoea/hypopnoea syndrome (SAHS) can be easily assessed by measuring respiratory impedance with the forced oscillation technique (FOT). This methodology has been proposed as a useful clinical tool both for the diagnosis of sleep breathing disorders and for continuous positive airway pressure (CPAP) titration. However, previous studies suggest that the application of high-frequency pressure oscillation to the upper airway may induce changes in the electroencephalogram (EEG) or upper airway muscle function. The effect of FOT measurements on upper airway muscle tone and EEG in clinical sleep studies was examined. Seven patients with moderate SAHS were included (age: 54+/-11 yrs; apnoea/hypopnoea index: 43+/-21 events x h(-1); body mass index: 30+/-2 kg x m(-2)). Genioglossus surface electromyogram activity (EMGgg) and EEG signal were analysed with and without FOT application (frequency: 5 Hz and 30 Hz; peak-to-peak pressure oscillation: 1 cmH2O) during stable sleep. Measurements were carried out in two different situations. Step 1: applying FOT during episodes of obstructive events or flow limitation; and step 2: during prolonged periods of normal breathing at optimal CPAP. The root mean square of EMGgg activity and fast Fourier analysis (alpha and delta bands) of the EEG signal were performed. The application of FOT did not increase EMGgg activity in any of the situations studied. In addition, no evidence of the effects on EEG was found: alpha/delta relationship: awake:0.70, baseline sleep:0.13, FOT(5 Hz):0.18, FOT(30 Hz):0.11. The presented results suggest that the use of forced oscillation technique over the ranges of frequency and amplitude proposed for clinical sleep studies does not induce changes in upper airway muscle activity and neurological variables in patients with sleep apnoea/hypopnoea syndrome.

Airway Obstruction↗
PubMed2001

Evaluation of a simplified oscillation technique for assessing airway obstruction in sleep apnoea.

The forced oscillation technique (FOT) is a noninvasive method that is useful for assessing airway obstruction and for titrating continuous positive airway pressure (CPAP) in patients with sleep apnoea. The aim was to evaluate the routine applicability of a simplified FOT set-up based on recording pressure and flow at the level of the CPAP device, i.e. obviating the need for connecting the transducers to the nasal mask. A correction to account for the tubing and the exhaust port was applied. This simplified FOT was evaluated on nine patients with moderate or severe sleep apnoea during routine CPAP titration. Patient impedance measured by the simplified FOT ([Z]) was compared with actual patient impedance ([Zrs]) measured simultaneously with a reference FOT based on recording pressure and flow at the nasal mask. An excellent agreement was found between [Z] and [Zrs] over the wide range of airway obstruction explored (4.8-72.1 cmH2O x s x L(-1)): [Z] = [Zrs] x 0.86 + 1.3 cmH2O x s x L(-1) (r = 0.99). Moreover, the simplified and the conventional FOT settings detected the same respiratory events during sleep. These results demonstrate that this simplified FOT is applicable for measuring airway obstruction during routine sleep studies in patients with sleep apnoea.

Airway Obstruction↗
PubMed2001

Performance of nasal prongs in sleep studies : spectrum of flow-related events.

OBJECTIVES: The use of nasal prongs connected to a pressure transducer is a noninvasive, sensitive method to detect respiratory events, and can be easily implemented in routine sleep studies. Moreover, its good time response allows the detection of several flow-related phenomena of high interest, in addition to apnea and hypopnea. The aims of the study were to examine the quality and performance of the nasal prong flow signal, and to describe other flow-related events during full-night polysomnography studies. METHODS: Twenty-seven subjects were studied (16 male subjects; mean +/- SD age, 49 +/- 14 years; mean body mass index, 27 +/- 4 kg/m(2)): 15 subjects recruited from the general population and 12 consecutive patients with suspected sleep apnea/hypopnea syndrome (SAHS). RESULTS: A blind analysis of the respiratory events detected both by nasal prongs and thermistor was done. The quality of the nasal prong signal recordings was considered optimal for scoring purposes in 78% of cases, and no recording was considered uninterpretable. The nasal prong signal detected additional flow-related events not observed by the thermistor: (1) short and long (> 2 min) periods of inspiratory flow limitation morphology without decrease in the amplitude of the signal; (2) periods of mouth expiration; and (3) snoring. The apnea/hypopnea index was significantly higher with the nasal prong scoring (18 vs 11 [p < 0.05] in the general population and 37 vs 27 [p < 0.001] in the group with suspected SAHS). CONCLUSIONS: The incorporation of nasal prongs in routine full-night studies is an attainable technical option that provides adequate recordings in most cases. Additionally, relevant information not scored by thermistors is obtained on flow-related respiratory events, thus increasing diagnostic accuracy.

Adult↗
PubMed2001

[Neuromuscular syndromes of the critically ill].

With the continuous improvement in the survival of critical patients, new neuromuscular syndromes are being described. The clinical finding is an acute-subacute onset of generalised weakness with difficulty in weaning the patient from the ventilator, due to polyneuropathy, myopathy, prolonged neuromuscular blockade or a combination of these disorders. Although having a multifactorial ethiopathology, the major risk factors in the development of these disorders are multiple organ failure and sepsis for polyneuropathy; corticosteroids and neuromuscular junction blocking agents (NMB) for myopathy; and NMB and renal and liver failure for prolonged neuromuscular blockade. No specific treatment exists, which is why--due to the high incidence of these syndromes and their poor prognosis, with a mortality rate higher than 50%--we should recognise, diagnose and avoid, where possible, the conditions that help the development of these disorders.

English Abstract↗
PubMed2001

Forced oscillation technique: from theory to clinical applications.

The forced oscillation technique (FOT) allows the noninvasive assessment of the mechanical properties of the respiratory system. Given that the technique does not require patient cooperation, it is suitable for the routine evaluation of respiratory function in a variety of clinical applications. In this paper, the rationale and the most conventional equipment and data processing of the technique are described. A number of clinical applications of FOT are briefly reviewed. One common use of the technique is to assess respiratory function in patients with different pathologies and in epidemiology. One of the most referenced applications of FOT is in tests of airway responsiveness to inhaled agents (bronchoprovocation and bronchodilatation). Finally, two recent promising applications of FOT are described: monitoring respiratory resistance during invasive and noninvasive mechanical ventilation, and detection of upper airway obstruction during sleep.

Humans↗
PubMed2000

Forced oscillation assessment of respiratory mechanics in ventilated patients.

The forced oscillation technique (FOT) is a method for non-invasively assessing respiratory mechanics that is applicable both in paralysed and non-paralysed patients. As the FOT requires a minimal modification of the conventional ventilation setting and does not interfere with the ventilation protocol, the technique is potentially useful to monitor patient mechanics during invasive and noninvasive ventilation. FOT allows the assessment of the respiratory system linearity by measuring resistance and reactance at different lung volumes or end-expiratory pressures. Moreover, FOT allows the physician to track the changes in patient mechanics along the ventilation cycle. Applying FOT at different frequencies may allow the physician to interpret patient mechanics in terms of models with pathophysiological interest. The current methodological and technical experience make possible the implementation of portable and compact computerised FOT systems specifically addressed to its application in the mechanical ventilation setting.

Humans↗
PubMed2000

Noninvasive assessment of respiratory resistance in severe chronic respiratory patients with nasal CPAP.

Noninvasive measurement of respiratory resistance during nasal ventilatory support could be useful to assess the mechanical status of the patient and to optimize the ventilator settings. The aim was to investigate whether the forced oscillation technique (FOT) applied through a nasal mask allows reliable noninvasive estimation of respiratory resistance (Rrs) in patients with severe chronic respiratory disease. FOT Rrs (5 Hz) and lung resistance (R(L)) measured simultaneously from spontaneous breathing signals by an oesophageal balloon were compared in eight patients with chronic obstructive pulmonary disease and in six patients with a restrictive ventilatory defect due to chest wall disease. Measurements were performed in sitting and supine postures during application of nasal continuous positive airway pressure (CPAP): 4, 8 and 12 cmH2O in obstructive patients and 4 cmH2O in restrictive patients. In the restrictive patients Rrs and R(L) (in cmH2O x s x L(-1)) were virtually coincident: mean+/-SD, 12.6+/-6.1 and 11.6+/-6.6 (r=0.96) in sitting and 9.7+/-3.1 and 10.2+/-3.3 (r=0.92) in supine posture, respectively. In the obstructive patients (CPAP = 4 cmH2O), Rrs slightly underestimated R(L): mean+/-SD, 11.5+/-5.9 and 14.4+/-16.8 (r=0.92) in sitting and 15.0+/-9.8 and 21.1+/-12.6 (r=0.96) in supine posture, respectively. Similar results were found at CPAP = 8 and 12 cmH2O. The results obtained in patients with resistance values in the range typically found in nasal ventilatory support suggest that forced oscillation technique could be valuable to noninvasively estimate a patient's respiratory mechanical resistance.

Aged↗
PubMed2000

Evaluation of a method for assessing respiratory mechanics during noninvasive ventilation.

Noninvasive assessment of respiratory resistance (Rrs) and elastance (Ers), which is not easy with conventional methods, could be useful in the optimization of pressure support ventilation. The aim of this study was to evaluate a simple noninvasive method (Delta-inst) of measuring Rrs during nasal pressure support ventilation. Rrs and Ers (Delta-inst) were computed from inspiratory mask pressure, flow and volume recorded during pressure support ventilation. The Delta-inst method was compared with the forced oscillation technique (FOT) in seven patients with chronic obstructive pulmonary disease (COPD) and in eight healthy subjects without and with added resistance (3.1 cmH2O x s x L(-1)). Rrs measured by Delta-inst (5.2+/-1.7, 7.2+/-0.5 and 6.9+/-1.2 cmH2O x s x L(-1)) and by FOT (5.0+/-0.7, 7.6+/-0.9 and 8.1+/-2.7 cmH2O x s x L(-1)) in healthy subjects without and with added resistance and COPD, respectively, were not significantly different (p>0.05). Rrs measured by both techniques showed a significant coefficient of linear correlation (r=0.70 s) (p<0.01). In the COPD patients, the variability of Delta-inst Rrs (30%) was greater than that of FOT Rrs (21%). The agreement between Ers obtained by Delta-inst and by FOT was less than that found for Rrs. Delta-inst is a noninvasive and simple method for reliably assessing resistance. Therefore, it is useful for monitoring airway obstruction and is potentially helpful in adapting the settings for pressure support ventilation in accordance with patient mechanics.

Adult↗
PubMed2000

Mechanical properties of cultured human airway smooth muscle cells from 0.05 to 0.4 Hz.

We investigated the rheological properties of living human airway smooth muscle cells in culture and monitored the changes in rheological properties induced by exogenous stimuli. We oscillated small magnetic microbeads bound specifically to integrin receptors and computed the storage modulus (G') and loss modulus (G") from the applied torque and the resulting rotational motion of the beads as determined from their remanent magnetic field. Under baseline conditions, G' increased weakly with frequency, whereas G" was independent of the frequency. The cell was predominantly elastic, with the ratio of G" to G' (defined as eta) being approximately 0. 35 at all frequencies. G' and G" increased together after contractile activation and decreased together after deactivation, whereas eta remained unaltered in each case. Thus elastic and dissipative stresses were coupled during changes in contractile activation. G' and G" decreased with disruption of the actin fibers by cytochalasin D, but eta increased. These results imply that the mechanisms for frictional energy loss and elastic energy storage in the living cell are coupled and reside within the cytoskeleton.

Cell Movement↗
PubMed2000

A simplified method for monitoring respiratory impedance during continuous positive airway pressure.

The forced oscillation technique is useful in detecting changes in upper airway obstruction in patients with sleep apnoea undergoing continuous positive airway pressure (CPAP) ventilation. The aim of this study was to implement and evaluate a method for estimating respiratory impedance (Zrs) from the pressure and flow recorded at the inlet of the CPAP tubing. The method is based on correcting impedance measured at the inlet of the CPAP tubing (Zi) for the effect of the tubing and the exhalation port. The method was evaluated in mechanical analogues and in a healthy subject. Sinusoidal oscillation of 5, 10 and 20 Hz were superimposed on CPAP (5-15 cmH2O). At 5 Hz, the changes in airflow obstruction were substantially underestimated by Zi. Furthermore, Zi exhibited a negative dependence on Zrs at 20 Hz. The assessment of Zrs was greatly improved after correcting Zi for the effects of the CPAP tubing and the exhalation port. Zrs was well estimated at low frequencies, reaching very high values during total occlusion (>60 cmH2O x s x L(-1) at 5-10 Hz). These results indicate that changes in airflow obstruction can be detected using the forced oscillation technique from pressure and flow recorded on the continuous positive airway pressure device. This facilitates the clinical application of the forced oscillation technique for monitoring upper airway patency during sleep.

Airway Resistance↗
PubMed1999

Assessment of bronchial reactivity by forced oscillation admittance avoids the upper airway artefact.

The forced oscillation technique (FOT) allows easy assessment of bronchial reactivity. The use of a standard FOT generator (SG) results in changes in respiratory system resistance (delta Rrs,SG) which are affected by an artefact caused by the extrathoracic upper airway (EUA). The aim was to improve the FOT assessment of bronchial reactivity with the SG by computing the change in FOT admittance (delta Ars,SG), which is theoretically unaffected by this artefact. Delta Rrs,SG and delta Ars,SG after bronchial challenge in 17 children were compared with the values measured with a head generator (HG) FOT setup (delta Rrs,HG and delta Ars,HG, respectively), which were taken as a reference, since HG provides data virtually freed from the EUA artefact. At 10 Hz, the SG significantly underestimated the resistance change: delta Rrs,SG=1.77+/-0.62 versus delta Rrs,HG=6.09+/-1.23 hPa x L(-1) x s. Delta Rrs,SG and delta Rrs,HG did not show a significant correlation. By contrast, the amplitude of the change in admittance measured by SG was close to the one obtained with the reference HG: /delta Ars,SG/=29.5+/-4.6 versus /delta Ars,HG/=32.7+/-3.9 mL x hPa(-1) x s(-1). /Delta Ars,SG/ and /delta Ars,HG/ showed a significant correlation (r=0.65, p>0.01). Similar results were found up to 20 Hz. The extrathoracic upper airway artefact was minimized when computing the change in admittance with the standard generator. This forced oscillation technique index may improve the sensitivity in assessing bronchial reactivity with the standard generator setup, which is the most common and easiest to use method for routine lung function testing.

Airway Resistance↗
PubMed1999

Forced oscillation total respiratory resistance and spontaneous breathing lung resistance in COPD patients.

Forced-oscillation total respiratory resistance (Rrs) has been shown to underestimate spontaneous breathing lung resistance (RL,sb) in patients with airway obstruction, probably owing to upper airway shunting. The present study reinvestigates that relationship in seven severely obstructed chronic obstructive pulmonary disease patients using a technique that minimizes that artefact. Rrs at 8 and 16 Hz was computed for each successive forced oscillation cycle. Inspiratory and expiratory RL,sb were obtained by analysing transpulmonary pressure (Ptp) with a four-coefficient model, and compared to Rrs over the same periods. "Instantaneous" values of RL,sb were also obtained by computing the dynamic component of Ptp, and compared to simultaneous values of Rrs. In both respiratory phases, good agreement between Rrs and RL,sb was observed up to RL,sb values of approximately 15 hPa x s(-1) x L(-1) at 8 Hz and 10 hPa x s(-1) x L(-1) at 16 Hz. Instantaneous Rrs and RL,sb varied systematically during the respiratory cycle, exhibiting various amounts of flow- or volume-dependence in the seven patients; the amplitudes of their variations were significantly correlated, but Rrs was much more flow-dependent than RL,sb in three patients. Also, Rrs exceeded RL,sb at end-expiration in three instances, which could be related to expiratory flow limitation. In conclusion, total respiratory resistance is reliable up to much higher levels of airway obstruction than previously thought, provided upper airway shunting is avoided.

Adult↗
PubMed1999

Clinical application of the forced oscillation technique for CPAP titration in the sleep apnea/hypopnea syndrome.

We have previously demonstrated that upper airway obstruction in sleep apnea/hypopnea syndrome (SAHS) can be accurately assessed in real-time by measuring respiratory impedance (|Z|) with the forced oscillation technique (FOT). The aims of the present study were: (1) to determine the feasibility of identifying the optimal continuous positive airway pressure (CPAP) for patients with SAHS based on analysis of the |Z| signal during conventional polysomnographic CPAP titration studies; and (2) to evaluate practical issues involved in the application of FOT during CPAP titration. We performed CPAP titration in 28 patients with SAHS during polysomnography (PSG) (14 nap and 14 full overnight studies) using a FOT system applied continuously to obtain an on-line measurement of |Z|. FOT was easily implemented and was well-tolerated by the patients. Optimal CPAP levels were determined both in the conventional manner from the standard PSG titration record and during a separate blinded analysis using the FOT signal alone. The mean conventional versus FOT-based optimal CPAP values were similar for both nap studies (10.6 +/- 0.6 [mean +/- SEM] versus 11.1 +/- 0.6 cm H(2)O, respectively, p = 0. 054) and overnight studies (9.9 +/- 0.7 versus 9.9 +/- 0.6 cm H(2)O, respectively, p = 1.00). Subsequent analysis of the PSG record with the FOT signal incorporated demonstrated that artefacts in the |Z| tracing occurred during mask leak, mouth breathing, and movement during arousal. Such abnormalities were readily identified from the flow tracing. These results indicate that, for adequate interpretation, the tracing and values of respiratory impedance obtained by FOT should be evaluated in conjunction with the flow signal. Continuous FOT-guided CPAP titration is feasible and may be a useful adjunct during manual titration. FOT could also potentially serve as the basis for automated CPAP in SAHS.

Humans↗
PubMed1998

Importance of the pulse oximeter averaging time when measuring oxygen desaturation in sleep apnea.

The accuracy of pulse oximeters in measuring transient changes in oxygen saturation (SaO2) may be affected by the oximeter time response. The aim of this study was to assess the effect of modifying the pulse oximeter averaging time (T) on the measurement of SaO2 in patients with the sleep apnea-hypopnea syndrome (SAHS). Twelve patients with severe SAHS were studied during a nap with conventional oximeters: Ohmeda 3740 and Criticare 501. We compared the readings of each patient's oxygen desaturation measured simultaneously with two identical pulse oximeters. One oximeter was the control (T = 3 seconds), and in the other T was set from 3 seconds to 21 seconds. No significant differences in SaO2 were found when both oximeters were set to the same T (3 seconds). In contrast, increasing T to 12 seconds and 21 seconds in one of the oximeters resulted in considerable and significant differences in the measured SaO2: oxygen desaturation was underestimated by up to 60% when compared with the control. The misestimation of SaO2 induced by settings of T which are within the range selectable in conventional oximeters may be of epidemiological significance when pulse oximetry is used as a complementary diagnostic tool to classify sleep events in SAHS.

Adult↗
PubMed1998

Assessment of airflow obstruction during CPAP by means of forced oscillation in patients with sleep apnea.

The forced oscillation technique (FOT) is a noninvasive method to measure respiratory resistance (Rrs) potentially useful for monitoring upper airway obstruction in patients with obstructive sleep apnea/hypopnea syndrome (SAHS). The aim of this work was to test the clinical suitability of FOT in assessing dynamic changes in airflow obstruction in patients with SAHS during continuous positive airway pressure (CPAP) and to investigate the CPAP dependence of Rrs. Forced oscillation (5 Hz) was applied to six male patients with SAHS submitted to CPAP titration procedure. Esophageal pressure was measured with a balloon-tipped catheter. Mid-inspiratory resistance (Rrs,i), mid-expiratory resistance (Rrs,e), and esophageal pressure swings (deltaPes) were computed for the respiratory events recorded at each CPAP level. Rrs,i decreased markedly and significantly from 36.0 +/- 4.0 cm H2O x s/L (mean +/- SEM) at baseline CPAP (4 cm H2O) to 13.1 +/- 2.8 cm H2O x s/L at optimal CPAP (11.3 +/- 0.4 cm H2O). Rrs,e showed a faster decrease with increasing CPAP reaching normal values at approximately 8 cm H2O. Rrs,i was strongly correlated (r2 = 0.94) with deltaPes. Our results suggest that FOT can be used as an alternative to the esophageal balloon for assessing airflow obstruction in patients with SAHS and for CPAP titration. Moreover, FOT allows us to detect phasic changes in resistance within the breathing cycle.

Adult↗