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Biomedical subjects

J H Bates

Publications and source records attributed to J H Bates.

At least 145 records · Page 8Linked to original sources
PubMed1989

Correcting for the thermodynamic characteristics of a body plethysmograph.

A constant volume body plethysmograph is used to measure changes in total body volume by relating pressure changes measured inside a closed chamber to changes in its volume. The relationship between pressure and volume, however, is complicated by the fact that rapid changes in pressure are accompanied by changes in the temperature of the gas in the plethysmograph. The rate at which the temperature of the gas subsequently approaches that of the environment affects the frequency response of the plethysmograph as a volume measuring instrument. In this paper it is shown that the transient response in plethysmograph pressure to a step change in volume must be a multi-component function, due to the gas near the walls of the plethysmograph approaching thermal equilibrium with the environment at a faster rate than gas near the center. The step response of a 200 L plethysmograph was determined experimentally and found to be well described empirically by a sum of two decaying exponential functions of time. The fitted exponentials were used to construct an algorithm for digitally correcting a measured pressure signal for the effects of the plethysmograph response. When applied to a hypothetical volume waveform over a single breath, an almost perfect correction was obtained.

Animals↗
PubMed1989

Respiratory mechanics determined by flow interruption during passive expiration in cats.

We used the interrupter technique to measure the resistance Rinit (equal to the initial change delta Pinit in tracheal pressure divided by flow at interruption) during expiration in six normal anaesthetized-paralyzed cats. By performing interruptions at different points in expiration we found Rinit in each cat to be linearly dependent on flow. By allowing the cats to expire through two different resistances we were also able to demonstrate a volume dependence of Rinit in four of the cats. In addition, we obtained a secondary pressure change delta Pdif in each cat, as the magnitude of the slow change in tracheal pressure in the 2 sec following interruption of flow. delta Pdif was approximately constant over most of the expired volume range, and represented the difference between the static elastic recoil pressure of the respiratory system and the pressure driving flow at any volume during a passive expiration. delta Pdif became larger than delta Pinit towards the end of expiration. Since previously used methods for measuring respiratory system resistance have employed varying combinations of delta Pinit and delta Pdif as the resistive pressure drop, it is clear that measurements of resistance must be made with standard techniques under standard conditions if they are to be compared.

Airway Resistance↗
PubMed1989

The low-frequency dependence of respiratory system resistance and elastance in normal dogs.

The resistance (R) and elastance (E) of the respiratory system were determined by fitting the equation: pressure = R x flow + E x volume to data obtained from normal anesthetized/paralyzed dogs during mechanical ventilation at different frequencies (5 to 50 breaths per min) and tidal volumes. R exhibited a 50% decrease with increasing frequency while E showed a less marked but still distinct increase with frequency. Volume-time profiles were also recorded in the same animals during passive expiration, and the frequency dependence of resistance and elastance from 0 to 1 Hz predicted from the bi-exponential curves fitted to the profiles. The way in which resistance and elastance were predicted to vary with frequency was similar to the variations determined from regular ventilation data. There were, however, some systematic differences between the actual values of resistance and elastance obtained by the two methods which may reflect certain nonlinear characteristics of the respiratory system such as static hysteresis. Nonlinearities were also evident in that both the resistances and the elastances at all frequencies showed a slight decrease with increasing tidal volume. We conclude that a large part of the mechanical behaviour of the normal canine respiratory system at low frequencies can be accounted for in terms of a two-compartment model describing a homogeneous alveolar region surrounded by viscoelastic tissue.

Airway Resistance↗
PubMed1989

Measurement of alveolar pressure in closed-chest dogs during flow interruption.

We have developed a technique for installing alveolar capsules in dogs with intact chest wall, by exposing a region of parietal pleura between a pair of ribs and gluing the parietal and visceral pleura together around a small region of lung. This allows the direct measurement of alveolar pressure during spontaneous breathing. We measured alveolar pressure in normal dogs using this technique while suddenly interrupting flow at the trachea during passive expiration. Tracheal pressure exhibited a very rapid rise immediately on interruption that we showed to be composed of two distinct and roughly equal parts: one was the resistive pressure drop across the airways, and the other was a resistive pressure drop across tissues. By simultaneously measuring pleural pressure we showed that the tissues responsible were only in the chest wall and not in the lungs.

Airway Resistance↗
PubMed1989

A comparison of the dose-response behavior of canine airways and parenchyma.

We compared the histamine responsiveness of canine airways and parenchymal tissues in six anesthetized paralyzed open-chest mongrel dogs, partitioning total lung resistance (RL) into airway resistance (Raw) and tissue viscance (Vti). Pressure was measured during tidal breathing (frequency was 0.3 Hz) at the trachea and in three alveolar regions by use of alveolar capsules. Measurements were taken before and after the delivery of increasing concentrations of aerosolized histamine (0.1-30 mg/ml). We found that Vti accounted for 78 +/- 8% of RL under base-line conditions; this proportion remained relatively constant throughout the histamine concentration-response curve. There was a significant correlation between percent change in Vti and percent change in Raw at all levels of histamine-induced constriction (P less than 0.001). Moreover, the sensitivity of the tissues and airways (defined as the concentration of histamine required to double resistance) was remarkably similar. We conclude that, at this frequency of ventilation, Vti accounts for the major portion of RL both under base-line conditions and after histamine-induced constriction. Although increases in RL cannot be attributed solely to events occurring in the airways, the close correlation between changes in Raw and Vti and the similar sensitivities of the two support the use of indexes reflecting changes in airway caliber as an indicator of overall lung histamine responsiveness.

Aerosols↗
PubMed1989

Viscoelastic behavior of lung and chest wall in dogs determined by flow interruption.

Pulmonary and chest wall mechanics were studied in six anesthetized paralyzed dogs, by use of the technique of rapid airway occlusion during constant flow inflation. Analysis of the pressure changes after flow interruption allowed us to partition the overall resistance of the lung (Rl) and chest wall (Rw) and total respiratory system (Rrs) into two components, one (Rinit) reflecting in the lung airway resistance (Raw), the other (delta R) reflecting primarily the viscoelastic properties of the pulmonary and chest wall tissues. The effects of varying inspiratory flow and inflation volume were interpreted in terms of frequency dependence of resistance, by using a spring-and-dashpot model previously proposed and substantiated by Bates et al. (Proc. 9th Annu. Conf. IEEE Med. Biol. Soc., 1987, vol. 3, p. 1802-1803). We observed that 1) Raw and Rw,init were nearly equal and small relative to Rl and Rw (both were unaffected by flow); 2) Rrs,init decreased slightly with increasing volume; 3) both delta Rl and delta Rw decreased with increasing flow and increased with increasing lung volume. These changes were manifestations of frequency dependence of delta R, as it is predicted by the model; 4) Rrs, Rl, and Rw followed the same trends as delta R. These results corroborate data previously reported in the literature with the use of different techniques to measure airways and pulmonary tissue resistances and confirm that the use of Rl to assess bronchial reactivity is problematic. The interrupter techniques provides a convenient way to obtain Raw values, as well as analogs of lung and chest wall tissue resistances in intact dogs.

Airway Resistance↗
PubMed1989

Respiratory mechanics in the normal dog determined by expiratory flow interruption.

We recently proposed an eight-parameter model of the respiratory system to account for its mechanical behavior when flow is interrupted during passive expiration. The model consists of two four-parameter submodels representing the lungs and the chest wall, respectively. The lung submodel consists of an airways resistance together with elements embodying the viscoelastic properties of the lung tissues. The chest wall submodel has similar structure. We estimated the parameters of the model from data obtained in four normal, anesthetized, paralyzed, tracheostomized mongrel dogs. This model explains why lung tissue and chest wall resistances should be markedly frequency dependent at low frequencies and also permits a physiological interpretation of resistance measurements provided by the flow interruption method.

Airway Resistance↗
PubMed1989

Diagnosis of tuberculosis: present and future.

Current methods used worldwide for diagnosis of tuberculosis (TB) are not markedly different from those used 50 years ago. The standard has been to demonstrate microbiologically the presence of Mycobacterium tuberculosis in secretions and/or tissue from the patient. Improvements have been made that permit greater sensitivity for the examination of stained smears and for more rapid detection of growth of the organism using radiometric techniques. New methods for diagnosis that may well eliminate the need for smear and culture of specimens are under varying stages of development. These new methods are based on the detection of specific components of the organisms or on detection of specific antibodies produced by the patient. Some of these methods will require expensive and sophisticated equipment, and this will make them much less available in developing countries. The use of gene probes for diagnosis of TB is in use now on a limited scale. For the near future, we predict that nucleic acid techniques will be developed for use worldwide. These techniques will have a sensitivity and specificity never before achieved; they should be less expensive than standard methods, and the time required for analysis of a sample and the reporting of results will be reduced to 1 day.

Antibodies, Bacterial↗
PubMed1988

Computer analysis of physical factors affecting the use of the interrupter technique in infants.

The interrupter technique involves measuring pressure changes at the airway opening following abrupt interruption of airflow, and relies on rapid equilibration of alveolar and airway opening pressures. Following airway occlusion one generally sees a rapid change in airway opening pressure, Pinit, which reflects the resistive pressure drop across the system, followed by a secondary, slower pressure change, Pdif, which reflects the tissue visco-elastic properties together with any redistribution of gases occurring between lung units at different pressure at the time of interruption. Physical factors in the measuring equipment, i.e., the time taken for valve closure and the presence of a proximal compliant compartment, can cause errors in the calculation of resistance and elastance using the interrupter technique. A computer model was used to determine the effects of these factors on the calculation of resistance and elastance in normal infants, premature infants, and infants with bronchopulmonary dysplasia. The elastance from 25 ml of dead space gas did not introduce significant errors into the measurements in any group of infants, but the presence of an unsupported upper airway caused errors of up to 245%. Increasing valve closure time introduced progressively larger errors into the calculation of resistance and elastance. To keep these errors acceptably small, an occlusion valve should close in 20 ms or less.

Airway Resistance↗
PubMed1988

A subtractive method for decomposing muscle tension into individual twitches.

When an isolated strip of skeletal muscle tissue is held at fixed length and stimulated electrically with a very brief pulse of electricity it responds with a transient increase in tension known as a twitch. If the same strip is stimulated repetitively with short pulses it produces a tension that can be considered to be composed of individual twitches arising from each stimulus. We present a subtractive method for decomposing a muscle tension curve into individual twitches of various heights. The locations of the twitches are known a priori from the times at which each stimulus was applied to the muscle. The shape of each twitch is assumed the same as that of a single twitch obtained just prior to the repetitive stimulation tension signal. We therefore find the heights of the individual twitches composing a tension curve. We find that most of a tension signal from isolated dog diaphragm strips can be accounted for as the sum of twitches of the same shape but different heights. We also derive a refractory factor, for stimulation at a given frequency, that describes how the heights of the twitches in a tension curve are attenuated as a function of stimulation frequency.

Animals↗
PubMed1988

Repetitive DNA sequences as probes for Mycobacterium tuberculosis.

Three cloned segments of Mycobacterium tuberculosis DNA which are promising as clinical probes were identified. An MboI digest of DNA from a clinical isolate of M. tuberculosis was cloned into bacteriophage M13. To identify recombinants specific for the M. tuberculosis complex, plaque lifts were hybridized with M. bovis and M. kansasii DNA. Recombinants which selectively hybridized with M. bovis DNA were characterized by probing slot blots and restriction digests of DNA from various mycobacteria. Three recombinants that did not hybridize to a significant extent with DNA from nontuberculous mycobacteria were identified. These three probes are of special interest because they are each repeated multiple (10 to 16) times in the M. tuberculosis chromosome. These probes were also shown to be useful for fingerprinting strains for epidemiological studies.

Blotting, Southern↗
PubMed1988

Effect of lung volume on interrupter resistance in cats challenged with methacholine.

To examine the effects of changes in lung volume on the magnitude of maximal bronchoconstriction, seven anesthetized, paralyzed, tracheostomized cats were challenged with aerosolized methacholine (MCh) and respiratory system resistance (Rss) was measured at different lung volumes using the interrupter technique. Analysis of the pressure changes following end-inspiratory interruptions allowed us to partition Rss into two quantities with the units of resistance, one (Rinit) corresponding to the resistance of the airways and the other (Rdif) reflecting the viscoelastic properties of the tissues of the respiratory system as well as gas redistribution following interruption of flow. Rinit and Rdif were used to construct concentration-response curves to MCh. Lung volume was increased by the application of 5, 10, and 15 cmH2O of positive end-expiratory pressure. The curve for Rinit reached a plateau in all cats, demonstrating a limit to the degree of MCh-induced bronchoconstriction. The mean value of Rinit (cmH2O.ml-1.s) for the group under control conditions was 0.011 and rose to 0.058 after maximal bronchoconstriction; the volume at which the flow was interrupted was 11.5 +/- 0.5 (SE) ml/kg above functional residual capacity (FRC). It then fell progressively to 0.029 at 21.2 +/- 0.8 ml/kg above FRC, 0.007 at 35.9 +/- 1.3 ml/kg above FRC, and 0.005 at 52.0 +/- 1.8 ml/kg above FRC. Cutting either the sympathetic or parasympathetic branches of the vagi had no significant effect on the lung volume-induced changes in MCh-induced bronchoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗
PubMed1988

A theoretical analysis of interrupter technique for measuring respiratory mechanics.

The application of the flow interrupter technique to series and parallel models of the respiratory system is examined theoretically, assuming instantaneous transmission of pressures and incompressible gases in the lung air spaces. The initial pressure change observed immediately after occlusion divided by the preocclusion flow gives an initial resistance (Rinit) equal to that of the airway tree when the model consists of compartments connected in parallel. When the compartments are connected in series, Rinit is the resistance of the most proximal airway only. In general, the initial pressure change is followed by a second slower change, reflecting equilibration of pressures between the compartments. The total postocclusion pressure change divided by the flow gives a steady-state resistance (Rss) whose value depends on the ventilation history before occlusion. When this history consists of a relaxed expiration Rss asymptotes from Rinit to a value higher than the zero-frequency resistance of the model as the expiratory time increases. However, the relative contributions of serial and parallel pendelluft and viscoelasticity to Rss cannot be determined from pressure and flow measurements made at the airway opening. Therefore in disease, the interrupter method does not permit one to say whether ventilation inhomogeneity or alteration in lung tissue properties is the predominant abnormality.

Airway Resistance↗
PubMed1988

Interrupter resistance elucidated by alveolar pressure measurement in open-chest normal dogs.

The interrupter method for measuring respiratory system resistance involves rapidly interrupting flow at the mouth while measuring the pressure just distal to the point of interruption. The pressure signal observed invariably exhibits two distinct phases. The first phase is a very rapid jump, designated delta Pinit, which occurs immediately on interruption of flow. The second phase is designated delta Pdif and is a further pressure change in the same direction as delta Pinit but evolving over several seconds. The physiological interpretations of delta Pinit and delta Pdif have been somewhat unclear. Delta Pinit has been taken to equal the pressure drop across the pulmonary airways, possibly with a contribution from the tissues of the respiratory system. Delta Pdif can arise, in principle, from two sources: gas redistribution throughout the lung after interruption of flow and stress recovery within the tissues. To resolve these issues we performed interruption experiments on anesthetized paralyzed, tracheotomized, open-chest normal dogs during passive expiration while measuring alveolar pressures at three sites with alveolar capsules. We found that, in the absence of the chest wall, delta Pinit reflects only the resistance of the airways and that delta Pdif can be ascribed almost entirely to the stress recovery properties of lung tissues.

Airway Resistance↗
PubMed1988

Association of plasmids and virulence of Mycobacterium avium complex.

Mycobacterium avium complex strain LR25, which carries 3 plasmids, was shown to be of high virulence in beige mice as judged by high mortality and a progressive increase in organisms in the spleen and lungs determined by counting the number of colony-forming units. Strain LR163, a "cured" derivative of LR25 that lacks all 3 plasmids, was of low virulence as judged by these criteria. The relative virulence of the strains was confirmed by studies of oxygen metabolite (superoxide anion and hydrogen peroxide) release from resident and BCG-activated mouse peritoneal macrophages. In contrast to loss of virulence, no significant change was seen in drug susceptibility.

Animals↗
PubMed1987

On the difficulties of fitting the double Michaelis-Menten equation to kinetic data.

The double Michaelis-Menten equation describes the reaction kinetics of two independent, saturable uptake mechanisms. The use of this equation to describe drug uptake has been reported several times in the literature, and several methods have been published to fit the equation to data. So far, however, confidence intervals on the fitted kinetic parameters have not been provided. We present a grid-search method for fitting the double Michaelis-Menten equation to kinetic uptake data, and a Monte-Carlo procedure for estimating confidence intervals on the fitted parameters. We show that the fitting problem is extremely ill-conditioned, and that very accurate data are required before any confidence can be placed in the fitted parameters.

Algorithms↗