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Biomedical subjects

M J Tobin

Publications and source records attributed to M J Tobin.

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

Effect of imposed inflation time on respiratory frequency and hyperinflation in patients with chronic obstructive pulmonary disease.

Decreases in ventilator inflation time (TI,vent) can cause tachypnea, probably as a response to lung inflation. The response may differ in chronic obstructive pulmonary disease (COPD) because time-constant inhomogeneities could foster overdistention of some lung units during early inflation, causing neural inspiratory time to be shorter than in healthy subjects. We tested the hypothesis that a decrease in TI,vent causes tachypnea, prolongation of exhalation, and a decrease in intrinsic positive end-expiratory pressure (PEEP(i)). Ten patients with stable COPD received assist-control ventilation through a mouthpiece. Decreases in TI,vent, achieved through increases in flow from 30 to 90 L/min, increased frequency, from 16.1 +/- 1.0 (SE) to 20.8 +/- 1.5 breaths/min (p < 0.001), time for exhalation, from 2.1 +/- 0.2 to 2.3 +/- 0.2 s (p < 0.025), and decreased PEEP(i), from 7.0 +/- 1.3 to 6.4 +/- 1.1 cm H(2)O (p < 0.01). Decreases in TI,vent, achieved by decreasing inspiratory pause from 2 to 0 s, increased frequency, from 12.9 +/- 0.8 to 18.1 +/- 1.6 breaths/min (p < 0.001), time for exhalation, from 2.0 +/- 0.2 to 2.6 +/- 0.3 s (p < 0.001), and decreased PEEP(i), from 6.4 +/- 1.1 to 5.5 +/- 0.9 cm H(2)O (p < 0.01). In both experiments, decreases in TI,vent reduced inspiratory effort (p < 0.01). In conclusion, strategies to reduce TI,vent in patients with COPD caused tachypnea, yet prolonged the time for exhalation with consequent decrease in PEEP(i).

Aged↗
PubMed2001

The voluntary drive to breathe is not decreased in hypercapnic patients with severe COPD.

How do the respiratory centres of patients with chronic obstructive pulmonary disease (COPD) and hypercapnia respond to acute increases in inspiratory load? A depressed respiratory motor output has long been postulated, but studies on this issue have yielded inconsistent results, partly due to limitations of investigative techniques. Many of these limitations can be overcome by the twitch interpolation technique, which is capable of accurately quantifying the degree of diaphragmatic activation, termed the voluntary drive to breathe. The hypothesis that patients with COPD and hypercapnia compensate for an acute increase in mechanical load on the inspiratory muscles with a lower voluntary drive to breathe than is the case with normocapnic patients was tested. Measurements were obtained in 15 patients with COPD, six of whom displayed hypercapnia and nine normocapnia. The maximum degree of diaphragmatic activation, expressed as a voluntary activation index (mean +/- SEM), was higher in hypercapnic than in normocapnic patients (98.7 +/- 0.7 versus 94.5 +/- 0.9% (p = 0.006)), as was the mean value (94.5 +/- 0.7 versus 88.5 +/- 1.9% (p = 0.01)). Within-patient values of the index were also less variable in the hypercapnic patients (coefficients of variation, 3.4 +/- 0.3 versus 6.1 +/- 0.9%, p = 0.01). Multiple regression analysis revealed the ratio of dynamic elastance to maximum transdiaphragmatic pressure, an index of inspiratory muscle loading, and pH as the only variables that correlated with maximum voluntary activation index (r2 = 0.69, p = 0.02 for each variable). Contrary to the hypothesis, it was concluded that voluntary activation of the diaphragm was greater and less variable in hypercapnic patients than normocapnic patients with severe chronic obstructive pulmonary disease during an acute increase in inspiratory mechanical load. Whether greater diaphragmatic recruitment during episodes of a severe exacerbation of chronic obstructive pulmonary disease provides a survival advantage for hypercapnic patients with chronic obstructive pulmonary disease remains to be determined.

Aged↗
PubMed2000

How is mechanical ventilation employed in the intensive care unit? An international utilization review.

A 1-d point-prevalence study was performed with the aim of describing the characteristics of conventional mechanical ventilation in intensive care units ICUs from North America, South America, Spain, and Portugal. The study involved 412 medical-surgical ICUs and 1,638 patients receiving mechanical ventilation at the moment of the study. The main outcome measures were characterization of the indications for initiation of mechanical ventilation, the artificial airways used to deliver mechanical ventilation, the ventilator modes and settings, and the methods of weaning. The median age of the study patients was 61 yr, and the median duration of mechanical ventilation at the time of the study was 7 d. Common indications for the initiation of mechanical ventilation included acute respiratory failure (66%), acute exacerbation of chronic obstructive pulmonary disease (13%), coma (10%), and neuromuscular disorders (10%). Mechanical ventilation was delivered via an endotracheal tube in 75% of patients, a tracheostomy in 24%, and a facial mask in 1%. Ventilator modes consisted of assist/control ventilation in 47% of patients and 46% were ventilated with synchronized intermittent mandatory ventilation, pressure support, or the combination of both. The median tidal volume setting was 9 ml/kg in patients receiving assist/control and the median setting of pressure support was 18 cm H(2)O. Positive end-expiratory pressure was not employed in 31% of patients. Method of weaning varied considerably from country to country, and even within a country several methods were in use. We conclude that the primary indications for mechanical ventilation and the ventilator settings were remarkably similar across countries, but the selection of modes of mechanical ventilation and methods of weaning varied considerably from country to country.

Data Collection↗
PubMed2000

Assessment of neural inspiratory time in ventilator-supported patients.

Neural inspiratory time (TI) is a measurement of fundamental importance in studies of patient-ventilator interaction. The measurement is usually based on recordings of flow, esophageal pressure (Pes), and transdiaphragmatic pressure (Pdi), but the concordance of such estimates of neural TI with a more direct measurement of neural activity has not been systematically evaluated. To address this issue, we studied nine ventilator-supported patients in whom we employed esophageal electrode recordings of the diaphragmatic electromyogram (EMG) as the reference measurement of neural TI. Comparison of the indirect estimates of neural TI duration, based on flow, Pes, and Pdi against the reference measurement, revealed a mean difference (bias) ranging from -54 to 612 ms during spontaneous breathing and from -52 to 714 ms during mechanical ventilation; the respective precisions (standard deviations of the differences) ranged from 79 to 175 ms and from 74 to 221 ms. Because an indirect estimate of neural TI duration could be identical to that of the reference measurement and yet be displaced in time, this lag or lead was quantified as the phase angle of neural TI onset. Flow-based estimates of the onset of neural TI displayed a systematic lag, which may be explained at least in part by concurrent intrinsic positive end-expiratory pressure. In conclusion, the indirect estimates of the onset and duration of neural TI in ventilator-dependent patients displayed poor agreement with the diaphragmatic EMG measurement of neural TI.

Aged↗
PubMed2000

Effect of isocapnic hypoxia on variational activity of breathing.

In the presence of either hypocapnia or sleep, hypoxia has been shown to induce periodic breathing and increase the total variational activity of breath components. It is not known whether hypoxia induces alterations in breathing variability during wakefulness and in the absence of hypocapnia. To address this issue, we studied nonobtrusively 14 healthy awake subjects before and during the delivery of a hypoxic gas mixture via a plastic hood; the subjects' oxygen saturation decreased from 98 to 79% and end-tidal carbon dioxide tension was kept constant. Compared with air, isocapnic hypoxia increased the gross variability of minute ventilation (V I), tidal volume (VT), inspiratory time (TI), and expiratory time (TE) (all p < 0.004). Isocapnic hypoxia decreased the autocorrelation coefficient at a lag of one breath for TE (p < 0. 008) and V I (p = 0.07), the number of consecutive breath lags having significant autocorrelation coefficients for TE (p = 0.03), and the cycle time of oscillations in V I (p = 0.03). When partitioned, the increase in total variational activity during isocapnic hypoxia was found to result from increases in the random fractions of V I, VT, TI, and TE (all p < 0.05), and the oscillatory fractions of V I, VT, and TE (all p < 0.03). In conclusion, hypoxia induced hidden oscillations in V I, VT, and TE despite wakefulness and an isocapnic state, suggesting that neural responses may have a more important role in the genesis of hypoxia-induced oscillations than previously reported.

Adult↗
PubMed2000

Bone lead levels and language processing performance.

The relation between bone lead absorption and language processing abilities in 156 randomly selected 11- to 14-year-old boys who were asymptomatic for lead toxicity is examined. Tibial lead concentrations were measured by X-ray fluorescence spectroscopy. The language processing outcome variables consisted of the least and most difficult subtests from the Nonword Repetition Task, Competing Language Processing Task, and the Revised Token Test. Participants were classified by quartiles according to bone lead concentrations, and analysis of variance and analysis of covariance measured the impact on language processing scores. Results showed that children in the highest bone lead quartile displayed decreased language processing performance on the most difficult language processing tasks but not on the easier tasks.

Adolescent↗
PubMed2000

Real-time studies of the interactions between epidermal growth factor and its receptor during endocytic trafficking.

The interactions of growth factors with cell surface receptors regulate fundamental cell processes, such as growth, differentiation and transformation. Understanding the nature of these interactions at the molecular level is of fundamental importance in cell biology. This is not only from the point of view of basic science, but also because of the repercussions such knowledge might have in understanding the mode of action of drugs in cells. Receptor mediated endocytosis has been implicated in the downregulation of the mitogenic signal. However, no data are thus far available on how growth factor/receptor interactions might control endocytic trafficking. Here we show that information on modes of binding and receptor conformational changes can be obtained using time-resolved fluorescence methods. We have found that fluorescent probes bound to epidermal growth factor (EGF) show dynamic fluorescence quenching when EGF is bound to internalising EGF receptors (EGFR). We propose that this dynamic quenching takes place because EGF-bound probes interact with tryptophan residues in the extracellular domain of the EGF-EGFR complex. Real-time accumulation of fluorescent decays has also allowed us to follow the time course of a conformational change in EGFR occurring during endocytosis, and correlate this information with endosomal trafficking and EGFR recycling.

Cell Line↗
PubMed1999

Reconciling in vitro and in vivo measurements of aerosol delivery from a metered-dose inhaler during mechanical ventilation and defining efficiency-enhancing factors.

We attempted to resolve the discrepancies in reported data on aerosol deposition from a chlorofluorocarbon (CFC)-propelled metered-dose inhaler (MDI) during mechanical ventilation, obtained by in vivo and in vitro methodologies. Albuterol delivery to the lower respiratory tract was decreased in a humidified versus a dry circuit (16.2 versus 30.4%, respectively; p < 0.01). In 10 mechanically ventilated patients, 4.8% of the nominal dose was exhaled. When the exhaled aerosol was subtracted from the in vitro delivery of 16.2% achieved in a humidified ventilator circuit, the resulting value (16.2 - 4.8 = 11.4%) was similar to in vivo estimates of aerosol deposition. Having reconciled in vitro with in vivo findings, we then evaluated factors influencing aerosol delivery. A lower inspiratory flow rate (40 versus 80 L/min; p < 0.001), a longer duty cycle (0.50 versus 0.25; p < 0.04), and a shorter interval between successive MDI actuations (15 versus 60 s; p < 0.02) increased aerosol delivery, whereas use of a hydrofluoroalkane (HFA)-propelled MDI decreased aerosol delivery compared with the CFC-propelled MDI. A MDI and actuator combination other than that designed by the manufacturer altered aerosol particle size and decreased drug delivery. In conclusion, aerosol delivery in an in vitro model accurately reflects in vivo delivery, providing a means for investigating methods to improve the efficiency of aerosol therapy during mechanical ventilation.

Aerosols↗
PubMed1999

Effect of spontaneous breathing trial duration on outcome of attempts to discontinue mechanical ventilation. Spanish Lung Failure Collaborative Group.

The duration of spontaneous breathing trials before extubation has been set at 2 h in research studies, but the optimal duration is not known. We conducted a prospective, multicenter study involving 526 ventilator-supported patients considered ready for weaning, to compare clinical outcomes for trials of spontaneous breathing with target durations of 30 and 120 min. Of the 270 and 256 patients in the 30- and 120-min trial groups, respectively, 237 (87.8%) and 216 (84.8%), respectively, completed the trial without distress and were extubated (p = 0.32); 32 (13.5%) and 29 (13.4%), respectively, of these patients required reintubation within 48 h. The percentage of patients who remained extubated for 48 h after a spontaneous breathing trial did not differ in the 30- and 120-min trial groups (75.9% versus 73.0%, respectively, p = 0.43). The 30- and 120-min trial groups had similar within-unit mortality rates (13 and 9%, respectively) and in-hospital mortality rates (19 and 18%, respectively). Reintubation was required in 61 (13.5%) patients, and these patients had a higher mortality (20 of 61, 32.8%) than did patients who tolerated extubation (18 of 392, 4.6%) (p < 0.001). Neither measurements of respiratory frequency, heart rate, systolic blood pressure, and oxygen saturation during the trial, nor other functional measurements before the trial discriminated between patients who required reintubation from those who tolerated extubation. In conclusion, after a first trial of spontaneous breathing, successful extubation was achieved equally effectively with trials targeted to last 30 and 120 min.

Aged↗
PubMed1999

Can diaphragmatic contractility be assessed by twitch airway pressures in patients with chronic obstructive pulmonary disease?

In healthy subjects and in patients without lung diseases, twitch airway pressure (Paw(tw)) responses to phrenic nerve stimulation can be used to predict twitch esophageal pressure (Pes(tw)) and twitch transdiaphragmatic pressure (Pdi(tw)), thus overcoming the need for placement of esophageal and gastric balloons. The aim of this study was to determine whether measurements of Paw(tw) combined with simple maneuvers could be used to predict Pes(tw), and possibly Pdi(tw), in patients with severe chronic obstructive pulmonary disease (COPD) (n = 12). Stimulations delivered at relaxed FRC produced a correlation coefficient (r) between Paw(tw) and Pes(tw) of 0.44 (p < 0.001) and of 0.62 (p < 0.001) during stimulations while patients performed a gentle exhalation from FRC. Stimulations performed during a gentle inhalation produced a good correlation between Paw(tw) and Pes(tw) (r = 0.92, p < 0.001); however, the limits of agreement between Paw(tw) and Pes(tw) were wide. Correlations between Paw(tw) and Pdi(tw) during the three experimental conditions were weak. In conclusion, during a gentle inspiratory effort in patients with severe COPD the correlation between Paw(tw) and Pdi(tw) was weak, whereas the correlation between Paw(tw) and Pes(tw) was good, but it was not sufficient to allow the prediction of Pes(tw) from Paw(tw) in all patients.

Action Potentials↗
PubMed1999

Preferential pulmonary retention of (S)-albuterol after inhalation of racemic albuterol.

The (R)-enantiomer of racemic albuterol produces bronchodilation, whereas the (S)-enantiomer may increase airway reactivity. After oral or intravenous administration of racemic albuterol, the (R)- enantiomer is metabolized several times faster than the (S)-enantiomer; however, enantiomer disposition after inhaling racemic albuterol with a metered-dose inhaler (MDI) is not known. Accordingly, 10 healthy subjects inhaled racemic albuterol with a MDI alone and with a MDI and holding chamber. We measured plasma levels of unchanged (R)- and (S)-albuterol before and up to 4 h after inhalation of racemic albuterol, and determined the unchanged R/S ratio in urine before and at 0.5, 4, 8, and 24 h later. The disposition of albuterol's enantiomers with a MDI and holding chamber was similar to that with a MDI alone. The area under the curve (AUC) of the plasma levels over time was significantly lower for the (S)- than for the (R)-enantiomer-395.5 +/- 141.0 (SE) versus 882.7 +/- 126.4 ng. ml(-)(1). min (p < 0.05)-indicating preferential retention of (S)-albuterol in the lung. The R/S ratio in urine at 0. 5 h after albuterol was > 1, reflecting the higher plasma level of the (R)-enantiomer. In conclusion, preferential retention of the (S)- compared with the (R)-enantiomer in the lung could lead to accumulation of the (S)-enantiomer after long-term use of racemic albuterol.

Administration, Inhalation↗