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Biomedical subjects

J H Bates

Publications and source records attributed to J H Bates.

At least 19 recordsLinked to original sources

Correcting for the Bernoulli effect in lateral pressure measurements.

Measurement of airway pressure is essential in the study of respiratory mechanics, and is usually done via a lateral tap in the conduit (e.g., endotracheal tube, cannula, or mouthpiece) leading into the subject's airway. Such pressure measurements, however, may be severely affected by the Bernoulli effect if the diameter of the conduit is small and the gas flow through it sufficiently high. We present in this note a simple method of assessing whether or not the Bernoulli effect is important in any particular situation. The technique involves comparing the pressure-flow relationships of the conduit obtained both by blowing air through it from one end and sucking air in the reverse direction by applying negative pressure at the same end. If the resistance of the conduit is the same for gas flow in both directions, then half the magnitude of the difference between the two pressure-flow relationships gives the magnitude of the Bernoulli effect pressure. We give results of an experimental situation in which this was the case. We also show that those conditions under which the Bernoulli effect is likely to be a problem are also those under which the velocity profile is likely to be approximately flat, thereby permitting the magnitude of the Bernoulli effect to be easily calculated.

Air Pressure

A nonstatistical approach to estimating confidence intervals about model parameters: application to respiratory mechanics.

Estimates of parameters obtained by fitting models to physiologic data are of little use unless accompanied by confidence intervals. The standard methods for estimating confidence intervals are statistical, and make the assumption that the fitted model accounts for all the deterministic variation in the data while the residuals between the fitted model and the data reflect only stochastic noise. In practice, this is frequently not the case, as one often finds the residuals to be systematically distributed about zero. In this paper, we develop an approach for assessing confidence in a parameter estimate when the order of the model is clearly less than that of the system being modeled. Our approach does not require a parameter to have a single value located within a region of confidence. Instead, we let the parameter value vary over the data set in such a way as to provide a good fit to the entire data set. We apply our approach to the estimation of the resistance of the respiratory system in which a simple model is fitted to measurements of tracheal pressure and flow by recursive multiple linear regression. The values of resistance required to achieve a good fit are represented as a modified histogram in which the contribution of a particular resistance value to the histogram is weighted by the amount of information used in its determination. Our approach provides parameter frequency distribution functions that convey the degree of confidence one may have in the parameter, while not being based on erroneous statistical assumptions.

Airway Resistance

Factors affecting the accuracy of esophageal balloon measurement of pleural pressure in dogs.

Simultaneous measurement of esophageal and tracheal pressures during an occluded inspiratory effort was used to assess the accuracy of the esophageal balloon for measuring pleural pressure in dogs. Esophageal balloons were inserted in five mongrel dogs, and an occlusion test was performed with the balloon tip 5, 10, 15, 20, and 25 cm above the esophageal sphincter; at lung volumes of functional residual capacity (FRC) and FRC + 600 ml; and in supine and right- and left-side lying postures. The protocol was repeated in paralyzed animals. This time the occlusion test was performed by injecting air into a plethysmograph to change the body surface pressure, simulating pressure changes produced by respiratory efforts in spontaneously breathing animals. In 47% of the tests in spontaneously breathing dogs, the slope of esophageal vs. tracheal pressure varied greater than 10% from unity. After paralysis the slope did not vary greater than 5% from unity under any circumstance. These data indicate that the poorer performance of the occlusion test in nonparalyzed dogs is due to active tension in the walls of the esophagus and stress induced in the intrathoracic soft tissues by the descent of the diaphragm during a breathing effort.

Animals

A comparison of interrupter and forced oscillation measurements of respiratory resistance in the dog.

We compared the values of resistance produced by the forced oscillation technique (FOT) and the flow interruption technique (IT) when applied to six anesthetized paralyzed tracheostomized dogs. The FOT returned values of respiratory system resistance as a function of frequency [Re(f)] between 0.25 and 20 Hz. The IT returned a single value of resistance (Rinit) calculated by dividing the immediate change in tracheal pressure occurring upon interruption by the preinterruption flow. We found Rinit to coincide closely with Re(f) in the frequency range 5-20 Hz. Rinit has previously been interpreted as the high-frequency resistance of a resistance-elastance model of the respiratory system airways and tissues. It has also been shown previously, by direct measurement of alveolar pressure in dogs, that Rinit from the lungs alone is an accurate measure of airways resistance while Rinit obtained from the total respiratory system equals airways resistance plus a modest contribution from the chest wall. Re(f) at a frequency of approximately 10 Hz thus appears to be a useful quantity to measure as an index of airways resistance in the dog.

Airway Resistance

Low-frequency pulmonary impedance in rabbits and its response to inhaled methacholine.

We assessed pulmonary mechanics in six open-chest rabbits (3 young and 3 adult) by the forced oscillation technique between 0.16 and 10.64 Hz. Under control conditions, pulmonary resistance (RL) decreased markedly between 0.16 and 4 Hz, after which it became reasonably constant. Measurements of alveolar pressure from two alveolar capsules in each rabbit showed that the large decrease of RL with increasing frequency below 4 Hz was due to lung tissue rheology and that tissue resistance was close to zero above 4 Hz. Estimates of resistance and elastance, also obtained by fitting tidal ventilation data at 1 Hz to the equation of the linear single-compartment model, gave values for RL motion that were slightly higher than those obtained by forced oscillations at the same frequency, presumably because of the flow dependence of airways resistance. After treatment with increasing doses of aerosolized methacholine, RL and pulmonary elastance between 0.16 and 1.34 Hz progressively increased, as did the point at which the pulmonary reactance crossed zero (the resonant frequency). The alveolar pressure measurements showed the lung to become increasingly inhomogeneously ventilated in all six animals, whereas in the three younger rabbits lobar atelectasis developed at high methacholine concentrations and the alveolar capsules ceased to communicate with the central airways. We conclude that the low-frequency pulmonary impedance of rabbits exhibits the same qualitative features observed in other species and that it is a sensitive indicator of the changes in pulmonary mechanics occurring during bronchoconstriction.

Administration, Inhalation

Time course of respiratory mechanics during histamine challenge in the dog.

We studied the dynamics of respiratory mechanical parameters in anesthetized tracheostomized paralyzed dogs challenged with a bolus of histamine injected either venously (venous group) or arterially (arterial group). The venous group was further divided into two groups: the first was bilaterally vagotomized and received hexamethonium bromide (denervated group), and the second also received atropine sulfate (atropine group). In the venous group, tissue resistance (Rti) and tissue elastance (Eti) increased biphasically, whereas airway resistance was monophasic and synchronized with the second rise of the tissue parameters. In the arterial group, Rti, Eti, and airway resistance increased synchronously. The denervated and atropine groups showed dynamics similar to those of the venous group. We postulate that the first phase observed in Rti and Eti in the venous group is due to constriction of the smooth muscles of the peripheral airways and blood vessels distorting the parenchyma. The second and larger phase is then due to histamine reaching the bronchial circulation and constricting the central airways, again distorting the parenchyma. The results from the arterial group support this hypothesis, whereas those from the denervated group ascertain that none of the phases observed in the venous group was due to nervous reflexes.

Airway Resistance

Microbial etiology of acute pneumonia in hospitalized patients.

The purpose of this study was to determine the microbial etiology of pneumonia by using strict criteria among a group of hospitalized patients. Patients with acute community-acquired or hospital-acquired pneumonia were studied in a systematic and comprehensive manner for bacterial, viral, chlamydial, mycobacterial, and fungal pathogens. A total of 198 patients with 204 episodes of pneumonia were evaluated. Despite 100 percent follow-up of all surviving patients, a specific etiologic agent could be found in only 103 episodes. Among 154 episodes of community-acquired pneumonia, a diagnosis was made in 79; the most common pathogen was from the genus Legionella, followed by various Gram-negative enteric bacteria, Gram-positive cocci, influenza A virus, and Mycoplasma pneumoniae. The etiologic agent was found in 24 of the 50 patients with hospital-acquired pneumonia; no pathogen predominated. We conclude that even when elaborate diagnostic studies are done, including many invasive procedures, the etiology can be determined in only about half of the patients with acute pneumonia. The pathogens of pneumonia in this study are not markedly different between community-acquired and hospital-acquired infection.

Acute Disease

Temperature dependence of melphalan efflux kinetics in Chinese hamster ovary cells.

The temperature dependence of the kinetics of efflux of melphalan from Chinese hamster ovary (CHO) cells was studied from 4 degrees to 47 degrees. Time courses for melphalan efflux showed an initial rapid phase of efflux followed by a plateau. The data for melphalan concentration (c) versus efflux time (t) were described by the equation c(t) = A + B exp(-kt), where A is the final steady-state melphalan concentration, B is the total change in melphalan concentration from time zero until steady-state conditions are reached, and k is the rate constant for the efflux process. The plateau level obtained was not dependent on temperature and corresponded to 22 +/- 3.2% of the drug remaining in the cells after efflux. The time for melphalan efflux to reach the plateau level was dependent on temperature. This was reflected by an increase in the rate constants for melphalan efflux with increasing temperature from 30 degrees to 47 degrees. The rate constant for melphalan efflux at 37 degrees was 0.045 +/- 0.002 min-1. Efflux of melphalan occurred much more slowly at lower temperatures such as 4 degrees and 20 degrees. An Arrhenius plot for melphalan efflux showed a linear and decreasing trend at temperatures between 30 degrees and 47 degrees with an activation energy of 1.046 x 10(3) J/mol.

Animals

Gas physical properties and respiratory system resistance measured by flow interruption.

If the flow of gas at the airway opening of a tracheostomized dog is suddenly interrupted during expiration, the airway pressure exhibits a sudden very rapid rise, called delta Pinit, which has been shown previously to equal the resistive pressure drop across the airways in open-chest dogs, and to have a significant additional contribution from the tissues of the chest wall in intact dogs. In the present study we attempted to separate the contributions of airways and tissues to delta Pinit in intact dogs by performing flow interruptions with the lungs full of gas mixtures having different physical properties. A Moody plot (the Friction coefficient calculated using delta Pinit versus the Reynolds number) had a marked negative slope at Reynolds numbers up to 5 x 10(4), whereas the plot is predicted to have a slope close to zero at Reynolds numbers greater than 4 x 10(3) on the basis of purely fluid dynamic considerations. Assuming delta Pinit to be the result of a linear dependence of airway resistance on flow and a constant tissue resistance, we were able to account for the negative slope of the Moody plot. We also found that the values of airway and tissue resistances estimated from the data were very close to those estimated by more direct means in a previous study of delta Pinit. We conclude that it is possible to discern the separate effects of airway and tissue resistances in delta Pinit at high Reynolds numbers.

Airway Resistance

IS6110: conservation of sequence in the Mycobacterium tuberculosis complex and its utilization in DNA fingerprinting.

Multiple copies of an insertion sequence, IS6110, were shown to be present in the genome of members of the Mycobacterium tuberculosis complex (M. tuberculosis and M. bovis). Ten to 12 copies are present in various strains of M. tuberculosis, while strains of M. bovis contain only one to three copies. IS6110 was not detected in the DNA of other species of mycobacteria. Restriction endonuclease analysis indicated that the sequence of IS6110 is conserved across strain and species lines. Hybridization to the insertion sequence can be used to detect restriction fragment length polymorphism reflecting divergence in the sequence of regions flanking the various copies of IS6110. These differences were used to fingerprint various strains of the M. tuberculosis complex.

Autoradiography

Deconvolution of tracer and dilution data using the Wiener filter.

In the study of living systems it is often necessary to inject or infuse a substance into the peripheral circulation and monitor its subsequent concentration in the plasma with time. Examples abound in the pharmacokinetic study of drugs and in the use of the indicator dilution technique for measuring blood flow. Furthermore, it is often necessary to deconvolve one such measured, and hence noisy, data set with another. One of the standard methods for deconvolving noisy signals is the Wiener filter, which is generally derived as a real window in the frequency domain such that the mean squared error between the estimated deconvolved function and the truth, on average, is minimized. Application of the Wiener filter requires some (often crude) model of the noise-to-signal power ratio as a function of frequency. In the pharmacokinetic and indicator dilution situations, however, one invariably has a good model of the actual function to be deconvolved in the form of a sum of decaying exponential functions. Such a model may be employed to calculate the signal-to-noise power ratio for use in the Wiener filter, or alternatively may be directly deconvolved itself. It is shown that better results are achieved with the Wiener filter if the model of the signal is not particularly accurate, whereas with a very accurate model it is better to deconvolve the model itself. The point at which the two deconvolution approaches perform comparably occurs when the error in the model is of a similar magnitude to the noise.

Mathematical Computing

Chromosomal DNA fingerprint patterns produced with IS6110 as strain-specific markers for epidemiologic study of tuberculosis.

Mycobacterium tuberculosis isolates were studied by comparing chromosomal DNA fingerprint patterns produced by digestion of chromosomal DNA with BamHI, followed by agarose electrophoresis and hybridization with radiolabeled probes of insertion sequence IS6110. DNA fingerprints of 14 isolates from separate members of five households or closely associated individuals were compared. Marked differences were observed when unrelated isolates were compared. There were no or minimal differences in the restriction fragment patterns generated from isolates of any one household or associated group. Among related isolates, the only noticeable difference was an additional fragment of IS6110 in the fingerprint pattern of one isolate. Insertional activity was also suggested when restriction fragment patterns of H37Rv DNA isolated in 1987 and 1990 were compared. In a similar manner, M. tuberculosis reference strain Erdman was compared to a clinical isolate from an individual working with that strain. These isolates had identical DNA fingerprints which were distinct from all other isolates, verifying laboratory-acquired infection. Chromosomal DNA fingerprint patterns produced with IS6110 are excellent stain-specific markers for the epidemiologic study of tuberculosis.

DNA Fingerprinting

Low-frequency respiratory system resistance in the normal dog during mechanical ventilation.

The low-frequency resistances of the respiratory system, lung, and chest wall were investigated in four anesthetized paralyzed dogs mechanically ventilated at various frequencies between 0.08 and 0.83 Hz. The resistances were calculated by three different methods: 1) as the real part of the complex impedance obtained from regular ventilation data, 2) as the effective resistance of a two-compartment model fitted to the same data, and 3) as the resistance of a single-compartment model fitted to data obtained during sinusoidal ventilation at various frequencies. Alveolar pressures were measured by a closed-chest alveolar capsule technique and afforded a direct measure of airways resistance. All three resistance estimates were very similar and decreased markedly with frequency between 0 and 1 Hz. The real part of lung impedance at the higher frequencies investigated (around 5 Hz) closely approximated airways resistance, as predicted by the eight-parameter viscoelastic model of respiratory mechanics proposed by Bates et al. (J. Appl. Physiol. 67:2276-2285, 1989).

Airway Resistance

Histamine-induced constriction of canine peripheral lung: an airway or tissue response?

We compared the histamine responsiveness of peripheral airways (less than 6.0 mm diam) and parenchymal tissues in eight anesthetized paralyzed open-chest mongrel dogs. We measured pressure in a peripheral bronchus by using an antegrade wedged catheter and pressure in the alveolar region subtended by the wedged bronchus by using an alveolar capsule. Sinusoidal volume oscillations at a frequency of 0.5 Hz were delivered by a linear motor pump into the segment through the wedged catheter. We calculated the resistance of the segment (Rseg) and partitioned Rseg into tissue viscance (i.e., proportional to the resistive pressure drop between the alveolus and the pleura) and peripheral airway resistance. Measurements were taken under baseline conditions and after delivery of increasing concentrations of aerosolized histamine (0.1 micrograms/ml to 100.0 mg/ml) into the segment. We found that the histamine responsiveness of the peripheral airways and lung tissues varied markedly within a given dog. In four of eight dogs the airways were more responsive to histamine, in three of eight the tissues were more responsive, and in one of eight the response was equivalent at the two sites. We conclude that in a given animal, there is marked heterogeneity in the histamine responsiveness of the peripheral airways and parenchymal tissues and that either may dominate responsiveness in the peripheral lung.

Animals

Estimation of time-varying respiratory mechanical parameters by recursive least squares.

Continuous estimation of time-varying respiratory mechanical parameters is required to fully characterize the time course of bronchoconstriction. To achieve such estimation, we developed an estimator that uses the recursive linear least-squares algorithm to fit the equation Ptr = RV + EV + K to measurements of tracheal pressure (Ptr) and flow (V). The volume (V) is obtained by numerical integration of V. The estimator has a finite memory with length into the past at each point in time that varies inversely with the difference between the current measurement of Ptr and that predicted by the model, to allow the algorithm to track rapidly varying parameters (R, E, and K). V usually exhibits significant drift and must be corrected. Of the several correction methods investigated, subtraction of the recursively weighted average of V before integration to V was found to perform best. The estimator was tested on simulated noisy data where it successfully followed a fivefold increase in R and a twofold increase in E occurring over 10 s. Three dogs and two cats were anesthetized, paralyzed, tracheostomized, and challenged with a bolus of methacholine (approximately 13 mg/kg iv). Increases of 3- to 10-fold were observed in R and 2- to 3-fold in E, beginning within 10-40 s after the bolus injection. In some animals we found that the increase in E occurred more slowly than that in R, which the V signal suggested was due to dynamic hyperinflation of the lungs. These results demonstrate that our recursive estimator is able to track rapid changes in respiratory mechanical parameters during bronchoconstrictor challenge.

Airway Resistance

A nonlinear viscoelastic model of lung tissue mechanics.

There have been a number of attempts recently to use linear models to describe the low-frequency (0-2 Hz) dependence of lung tissue resistance (Rti) and elastance (Eti). Only a few attempts, however, have been made to account for the volume dependence of these quantities, all of which require the tissues to be plastoelastic. In this paper we specifically avoid invoking plastoelasticity and develop a nonlinear viscoelastic model that is also capable of accounting for the nonlinear and frequency-dependent features of lung tissue mechanics. The model parameters were identified by fitting the model to data obtained in a previous study from dogs during sinusoidal ventilation. The model was then used to simulate pressure and flow data by use of various types of ventilation patterns similar to those that have been employed experimentally. Rti and Eti were estimated from the simulated data by use of four different estimation techniques commonly applied in respiratory mechanics studies. We found that the estimated volume dependence of Rti and Eti is sensitive to both the ventilation pattern and the estimation technique, being in error by as much as 217 and 22%, respectively.

Airway Resistance

Partitioning of respiratory mechanics in mechanically ventilated patients.

In ten mechanically ventilated patients, six with chronic obstructive pulmonary disease (COPD) and four with pulmonary edema, we have partitioned the total respiratory system mechanics into the lung (l) and chest wall (w) mechanics using the esophageal balloon technique together with the airway occlusion technique during constant-flow inflation (J. Appl. Physiol. 58: 1840-1848, 1985). Intrinsic positive end-expiratory pressure (PEEPi) was present in eight patients (range 1.1-9.8 cmH2O) and was due mainly to PEEPi,L (80%), with a minor contribution from PEEPi,w (20%), on the average. The increase in respiratory elastance and resistance was determined mainly by abnormalities in lung elastance and resistance. Chest wall elastance was slightly abnormal (7.3 +/- 2.2 cmH2O/l), and chest wall resistance contributed only 10%, on the average, to the total. The work performed by the ventilator to inflate the lung (WL) averaged 2.04 +/- 0.59 and 1.25 +/- 0.21 J/l in COPD and pulmonary edema patients, respectively, whereas Ww was approximately 0.4 J/l in both groups, i.e., close to normal values. We conclude that, in mechanically ventilated patients, abnormalities in total respiratory system mechanics essentially reflect alterations in lung mechanics. However, abnormalities in chest wall mechanics can be relevant in some COPD patients with a high degree of pulmonary hyperinflation.

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