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Biomedical subjects

J H Bates

Publications and source records attributed to J H Bates.

At least 37 records · Page 2Linked to original sources

Kinetics of respiratory system elastance after airway challenge in dogs.

We compared the time courses of lung mechanical changes with intravenous (iv) injection vs. aerosol administration of histamine, methacholine, and ACh in dogs. We interpret these results in terms of a spring-and-dashpot model of airway smooth muscle receiving activation via a tissue compartment when agonist is delivered by the iv route and through an additional airway wall compartment when it is delivered by the aerosol route. The model accurately accounts for the principal features of the respiratory system elastance response curves. It also accounts for the differences between iv and aerosol responses, supporting the notion that agonist delivered by aerosol has to traverse a longer pathway to the airway smooth muscle than does agonist delivered iv. The time constants representing diffusive exchange of agonist between compartments were not significantly different for the three agonists, suggesting that the three agonists shared a common principal means of clearance, which was presumably blood flow.

Acetylcholine↗

Bronchial responsiveness among inbred mouse strains. Role of airway smooth-muscle shortening velocity.

To investigate the relationship between bronchial responsiveness and airway smooth-muscle (ASM) contractile properties, we studied inbred mice with known interstrain differences in airway responsiveness. Using oscillatory mechanics, we confirmed that A/J mice were hyperresponsive to methacholine (MCh) as compared with mice of the C3H/HeJ and C57BL/6J strains. Analysis of respiratory system resistance and elastance at different flow oscillation frequencies indicated that interstrain differences in responsiveness are present in both central and peripheral airways of these mice. We used video microscopy to measure the rate of contraction of explanted airways, and found that the airways of A/J mice contracted more rapidly than those of C3H/HeJ or C57BL/6J mice. In studies of a fourth strain (Balb/C) of mice, we found both bronchial hyperresponsiveness and increased ASM shortening velocity. The rank order of responsiveness among strains was the same as that for shortening velocity (A/J > Balb/C > C3H/HeJ > C57BL/6J). Furthermore, in each strain of mice, shortening velocity correlated with the achieved degree of airway narrowing and with a greater likelihood of airway closure in individual airways. In contrast, generation of isometric tension in trachealis, morphometric measurements of tracheal ASM, tracheal myosin content, and dose-response curves for MCh of explanted intraparenchymal bronchi failed to correspond to the in vivo phenotype of airway reactivity. These results indicate that bronchial responsiveness is related to ASM shortening velocity, and underscore the importance of smooth-muscle dynamics in understanding the mechanisms of bronchial responsiveness.

Airway Resistance↗

Effects of cool, dry air stimulation on peripheral lung mechanics in asthma.

We have previously demonstrated that peripheral airway resistance (Rp) rises more in asthmatics than in nonasthmatic control subjects after segmental challenge with cool, dry air. To better understand this rise in Rp, we used a stop-flow method to measure the decay of segment pressure with time that yielded information on airway resistance (Raw), final plateau pressure (Pp), and peripheral lung compliance (Cp). After stop-flow maneuvers in all seven asthmatics and all seven normal subjects, pressure decayed smoothly without an initial sudden drop. This finding suggests that Raw was negligible and that the predominant site of flow resistance was the collateral pathways of the obstructed segment. Asthmatics had a significantly higher Pp and lower Cp at baseline than did normal subjects, but neither Pp nor Cp changed after challenge. Pp and Rp were significantly correlated. When interpreted in terms of a single-compartment nonlinear model, we concluded that Rp is predominantly determined by the resistance of the collateral airways rather than the more proximal airways. We also concluded that, compared with normal subjects, asthmatics have (1) more collateral airway narrowing and closure and lower segmental compliance, and (2) after challenge, increased collateral airway narrowing or closure without a change in compliance of the distal lung parenchyma. These results reflect the fundamental differences in peripheral lung mechanics between asthmatic and nonasthmatic subjects and in their response to directly instilled cool, dry air.

Adult↗

Audit of deep wound infection following hip fracture surgery.

An audit of 171 consecutive hip fractures treated surgically showed a deep wound infection rate of 3.6%. Several shortcomings in the implementation of the infection policy were identified and recommendations to eliminate them introduced. Review of the subsequent 186 patients gave a deep infection rate of 1.1%. Attention to detail and good practice are essential to maintain low wound infection rates.

Aged↗

Complexity of terminal airspace geometry assessed by lung computed tomography in normal subjects and patients with chronic obstructive pulmonary disease.

Increases in the low attenuation areas (LAA) of chest x-ray computed tomography images in patients with chronic obstructive pulmonary disease (COPD) have been reported to reflect the development of pathological emphysema. We examined the statistical properties of LAA clusters in COPD patients and in healthy subjects. In COPD patients, the percentage of the lung field occupied by LAAs (LAA%) ranged from 2.6 to 67.6. In contrast, LAA% was always <30% in healthy subjects. The cumulative size distribution of the LAA clusters followed a power law characterized by an exponent D. We show that D is a measure of the complexity of the terminal airspace geometry. The COPD patients with normal LAA% had significantly smaller D values than the healthy subjects, and the D values did not correlate with pulmonary function tests except for the diffusing capacity of the lung. We interpret these results by using a large elastic spring network model and find that the neighboring smaller LAA clusters tend to coalesce and form larger clusters as the weak elastic fibers separating them break under tension. This process leaves LAA% unchanged whereas it decreases the number of small clusters and increases the number of large clusters, which results in a reduction in D similar to that observed in early emphysema patients. These findings suggest that D is a sensitive and powerful parameter for the detection of the terminal airspace enlargement that occurs in early emphysema.

Forced Expiratory Volume↗

Effects of lung volume on lung and chest wall mechanics in rats.

To investigate the effect of lung volume on chest wall and lung mechanics in the rats, we measured the impedance (Z) under closed- and open-chest conditions at various positive end-expiratory pressures (0-0.9 kPa) by using a computer-controlled small-animal ventilator (T. F. Schuessler and J. H. T. Bates. IEEE Trans. Biomed. Eng. 42: 860-866, 1995) that we have developed for determining accurately the respiratory Z in small animals. The Z of total respiratory system and lungs was measured with small-volume oscillations between 0.25 and 9.125 Hz. The measured Z was fitted to a model that featured a constant-phase tissue compartment (with dissipation and elastance characterized by constants G and H, respectively) and a constant airway resistance (Z. Hantos, B. Daroczy, B. Suki, S. Nagy, and J. J. Fredberg. J. Appl. Physiol. 72: 168-178, 1992). We matched the lung volume between the closed- and open-chest conditions by using the quasi-static pressure-volume relationship of the lungs to calculate Z as a function of lung volume. Resistance decreased with lung volume and was not significantly different between total respiratory system and lungs. However, G and H of the respiratory system were significantly higher than those of the lungs. We conclude that chest wall in rats has a significant influence on tissue mechanics of the total respiratory system.

Airway Resistance↗

Estimating respiratory mechanics in the presence of flow limitation.

Dynamic collapse of the pulmonary airways, leading to flow limitation, is a significant event in a number of respiratory pathologies, including obstructive sleep apnea syndrome and chronic obstructive pulmonary disease. Quantitative evaluation of the mechanical status of the respiratory system in these conditions provides useful insights into airway caliber and tissue stiffness, which are hallmarks of such abnormalities. However, assessing respiratory mechanics in the presence of flow limitation is problematic because the single-compartment linear model on which most assessment methods are based is not valid over the entire breath. Indeed, even deciding which parts of a breath are flow limited from measurement of mouth flow and pleural pressure often proves to be difficult. In this study, we investigated the use of two approaches to assessing the overall mechanical properties of the respiratory system in the presence of inspiratory flow limitation. The first method is an adaptation of the classic Mead-Whittenberger method, and the second method is based on information-weighted histograms obtained from recursively estimated signals of respiratory resistance and elastance. We tested the methods on data simulated by using a computer model of the respiratory system and on data collected from obese sleeping pigs. We found that the information-weighted histograms provided the more robust overall estimates of respiratory mechanics.

Air Pressure↗

Breathing responses to small inspiratory threshold loads in humans.

To investiage the effect of inspiratory threshold load (ITL) on breathing, all previous work studied loads that were much greater than would be encountered under pathophysiological conditions. We hypothesized that mild ITL from 2.5 to 20 cmH2O is sufficient to modify control and sensation of breathing. The study was performed in healthy subjects. The results demonstrated that with mild ITL 1) inspiratory difficulty sensation could be perceived at an ITL of 2.5 cmH2O; 2) tidal volume increased without change in breathing frequency, resulting in hyperpnea; and 3) although additional time was required for inspiratory pressure to attain the threshold before inspiratory flow was initiated, the total inspiratory muscle contraction time remained constant. This resulted in shortening of the available time for inspiratory flow, so that the tidal volume was maintained or increased by significant increase in mean inspiratory flow. On the basis of computer simulation, we conclude that the mild ITL is sufficient to increase breathing sensation and alter breathing control, presumably aiming at maintaining a certain level of ventilation but minimizing the energy consumption of the inspiratory muscles.

Adult↗

Automatic control of pressure support mechanical ventilation using fuzzy logic.

There is currently no universally accepted approach to weaning patients from mechanical ventilation, but there is clearly a feeling within the medical community that it may be possible to formulate the weaning process algorithmically in some manner. Fuzzy logic seems suited this task because of the way it so naturally represents the subjective human notions employed in much of medical decision-making. The purpose of the present study was to develop a fuzzy logic algorithm for controlling pressure support ventilation in patients in the intensive care unit, utilizing measurements of heart rate, tidal volume, breathing frequency, and arterial oxygen saturation. In this report we describe the fuzzy logic algorithm, and demonstrate its use retrospectively in 13 patients with severe chronic obstructive pulmonary disease, by comparing the decisions made by the algorithm with what actually transpired. The fuzzy logic recommendations agreed with the status quo to within 2 cm H(2)O an average of 76% of the time, and to within 4 cm H(2)O an average of 88% of the time (although in most of these instances no medical decisions were taken as to whether or not to change the level of ventilatory support). We also compared the predictions of our algorithm with those cases in which changes in pressure support level were actually made by an attending physician, and found that the physicians tended to reduce the support level somewhat more aggressively than the algorithm did. We conclude that our fuzzy algorithm has the potential to control the level of pressure support ventilation from ongoing measurements of a patient's vital signs.

Adult↗

Isovolume bronchoconstriction by vagal stimulation in dogs: effects of lung inflation pressure.

The changes elicited in lung mechanics by a given stimulus to the airway smooth muscle depend significantly on end-expiratory lung volume. However, the precise quantitative relationship between volume (or inflation pressure) and airway responsiveness remains to be elucidated. We measured the changes in lung elastic recoil pressure and impedance at 1 and 8 Hz, produced in anesthetized, paralyzed, open-chest dogs over periods of 32 sec, when the vagus nerves were continuously electrically stimulated at constant lung volume. The increases in lung elastic recoil pressure increased with PEEP, which we interpret as being due to parenchymal distortions produced by the contracting airways acting against parenchymal attachment forces that increase with lung volume. In contrast, the increases in lung resistance at 1 and 8 Hz and elastance at 1 Hz all decreased by several-fold as PEEP was increased, which we interpret as reflecting the decreased airway smooth muscle shortening that was achieved with increasing parenchymal load.

Analysis of Variance↗

Diversity of DNA fingerprints of Mycobacterium tuberculosis isolates in the United States.

To investigate the diversity of IS6110 fingerprints of Mycobacterium tuberculosis isolates in the United States and to determine if matching IS6110 fingerprints represent recent interstate tuberculosis transmission, we performed restriction fragment length polymorphism analysis of M. tuberculosis isolates from 1,326 patients in three geographically separated states. Seven hundred ninety-five different IS6110 fingerprint patterns were generated, and pattern diversity was similar in each state. Ninety-six percent of the fingerprint patterns were observed in only one state, demonstrating that most IS6110 fingerprint patterns are confined to a single geographic location. Of the IS6110 fingerprint patterns that were shared by isolates from more than one state, most isolates with 1 to 5 IS6110 copies were separable by pTBN12 fingerprinting whereas those with > 15 copies were not. One high-copy-number M. tuberculosis strain had identical IS6110 and pTBN12 fingerprints and included 57 isolates from three states. Epidemiological data demonstrated significant recent transmission of tuberculosis within each city but not among the states. This suggests that identical fingerprints of isolates from geographically separate locations most likely reflect interstate tuberculosis transmission in the past, with subsequent intrastate spread of disease. Further evaluation of M. tuberculosis strains that cause outbreaks in different geographic locations will provide insight into the epidemiological and bacteriological factors that facilitate the spread of tuberculosis.

DNA Fingerprinting↗

Electrical impedance tomography can monitor dynamic hyperinflation in dogs.

We assessed in eight dogs the accuracy with which electrical impedance tomography (EIT) can monitor changes in lung volume by comparing the changes in mean lung conductivity obtained with EIT to changes in esophageal pressure (Pes) and to airway opening pressure (Pao) measured after airway occlusion. The average volume measurement errors were determined: 26 ml for EIT; 35 ml for Pao; and 54 ml for Pes. Subsequently, lung inflation due to applied positive end-expiratory pressure was measured by EIT (delta VEIT) and Pao (delta VPAO) under both inflation and deflation conditions. Whereas delta VPAO was equal under both conditions, delta VEIT was 28 ml greater during deflation than inflation, indicating that EIT is sensitive to lung volume history. The average inflation delta VEIT was 67.7 +/- 78 ml greater than delta VPAO, for an average volume increase of 418 ml. Lung inflation due to external expiratory resistance was measured during ventilation by EIT (delta VEIT,vent) and Pes (delta VPes,vent) and at occlusion by EIT (delta VEIT,occl), Pes, and Pao. The average differences between EIT estimates and delta VEIT,occl were 5.8 +/- 44 ml for delta VEIT,vent and 49.5 +/- 34 ml for delta VEIT,occl. The average volume increase for all dogs was 442.2 ml. These results show that EIT can provide usefully accurate estimates of changes in lung volume over an extended time period and that the technique has promise as a means of conveniently and noninvasively monitoring lung hyperinflation.

Airway Resistance↗

Airway-parenchymal interdependence after airway contraction in rat lung explants.

The constriction of pulmonary airways is limited by the tethering effect exerted by parenchymal attachments. To characterize this tethering effect at the scale of intraparenchymal airways, we studied the pattern of parenchymal distortion due to bronchoconstriction in a rat lung explant system. First, we measured the elastic modulus under tension for 2% (wt/vol) agarose alone (37.6 +/- 1.5 kPa) and for agarose-filled lung (5.7 +/- 1.3 kPa). The latter is similar to the elastic modulus of air-filled lung at total lung capacity (4.5-6 kPa) (S. J. Lai-Fook, T. A. Wilson, R. E. Hyatt, and J. R. Rodarte. J. Appl. Physiol. 40: 508-513, 1976), suggesting that explants can be used as a model of lung tissue distortion. Subsequently, confocal microscopic images of fluorescently labeled 0.5-mm-thick explants prepared from agarose-filled rat lungs inflated to total lung capacity (48 ml/kg) were acquired. Images were taken before and after airway constriction was induced by direct application of 10 mM methacholine, and the pattern of parenchymal distortion was measured from the displacement of tissue landmarks identified in each image for 14 explants. The magnitude of the radial component of tissue displacement was calculated as a function of distance from the airway wall and characterized by a parameter, b, describing the rate at which tissue movement decreased with radial distance. The parameter b was 0.994 +/- 0.19 (SE), which is close to the prediction of b = 1 of micromechanical modeling (T. A. Wilson. J. Appl. Physiol. 33: 472-478, 1972). There was significant variability in b, however, which was correlated with the fractional reduction in airway diameter (r = 0.496). Additionally, parenchymal distortion showed significant torsion with respect to the radial direction. This torsion was similar in concentric zones around the airway, suggesting that it originates from inhomogeneity in the parenchyma rather than inhomogeneous airway constriction. Our results demonstrate the significance of the nonlinear mechanical properties of alveolar walls and the anisotropy of the parenchyma in determining the nature of airway-parenchymal interdependence.

Animals↗

Force heterogeneity in a two-dimensional network model of lung tissue elasticity.

We have developed a model of forces developed in lung tissue in which the stress-bearing units are heterogeneous. Each element of the fiber network is composed of an idealized elastin and collagen element in parallel. Elastin is represented by linear springs and collagen by stiff strings that extend without resistance until taut. The model can quantitatively account for the nonlinear shape of the length-tension curve of lung tissue strips when the knee lengths of the collagen fibers are distributed according to an inverse power law. The novel feature of this model is that as macroscopic strain increases the load is carried by progressively fewer elements with progressively higher forces, and preferential pathways of force transmission emerge within the matrix. The topology of these self-organizing pathways of force transmission takes the rough appearance of cracks, but, unlike real cracks, they represent the locus of force concentration rather than force release.

Collagen↗

Effect of time-varying load on degree of bronchoconstriction in the dog.

It is well established that the degree of airway smooth muscle shortening produced by a given dose of bronchial agonist is greatly affected by lung volume. The airways are tethered by parenchymal attachments, the tension of which increases progressively with lung volume, thereby presenting a commensurately increasing hindrance to smooth muscle contraction. Earlier studies (P. F. Dillon, M. O. Aksoy, S. P. Driska, and R. A. Murphy. Science 211: 495-497, 1981) presented evidence that smooth muscle contraction initially involves rapidly cycling cross bridges, which then change to noncycling (latch) bridges. They also suggested that most of the muscle shortening occurs during the early rapid cross-bridge phase. This implies that smooth muscle subject to a given load early in contraction should shorten less than when it is subject to the same load later on. An in vitro study (W. Li and N. L. Stephens. Can. J. Physiol. Pharmacol. 72: 1458-1463, 1994) obtained support for this notion. To test this hypothesis in vivo, we measured the changes in lung impedance at 1 and 6 Hz produced in dogs by a bolus intravenous injection of methacholine when lung volume was increased for 10 s at different times after injection. We found that the changes in mechanics were greatly inhibited, whereas lung volume was elevated. However, when lung volume was returned to its initial level, the lung mechanics continued to change at a rate unaffected by the preceding volume change. We conclude that temporary mechanical inhibition of airway smooth muscle shortening in the normal dog in vivo merely delays an otherwise normal course of contraction.

Animals↗

Polymerase chain reaction to detect Mycobacterium tuberculosis in histologic specimens.

There is a need for rapid and sensitive detection of Mycobacterium tuberculosis in tissue specimens. A polymerase chain reaction (PCR)-based assay for the diagnosis of tuberculosis was evaluated in 60 formalin-fixed tissue specimens, the target for the amplification being a segment of IS6110 in the M. tuberculosis chromosome. Of the 60 formalin-fixed, paraffin-embedded tissue specimens studied, 57 showed granulomatous inflammation and 53 had been cultured for mycobacteria; 10 were positive for M. tuberculosis and three were positive for other mycobacteria. Of 60 samples, 15 showed acid-fast bacilli on special staining. When done comparatively on a positive culture for M. tuberculosis, PCR for M. tuberculosis DNA in 60 tissue samples was 100% sensitive and 93% specific, having a positive predictive value of 76.9% and negative predictive value of 100%. PCR for M. tuberculosis DNA done on tissue samples was positive for 14 of 19 patients who had a clinical diagnosis of tuberculosis, negative for all six patients with nontuberculous mycobacterial infections, and negative for all 33 patients who had a diagnosis of a disease other than mycobacterial infection. When compared with the clinical diagnosis of tuberculosis, PCR for M. tuberculosis DNA in these patients' tissues was 73.6% sensitive and 100% specific, having a positive predictive value of 100% and negative predictive value of 88.6%. These data indicate that PCR amplification is useful for detecting M. tuberculosis DNA in formalin-fixed tissue specimens, and that it can be used to increase diagnostic accuracy in patients who have perplexing diagnostic problems associated with a granulomatous tissue response.

Bacteriological Techniques↗