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Biomedical subjects

J H Bates

Publications and source records attributed to J H Bates.

At least 55 records · Page 3Linked to original sources

Effects of cholecystokinin tetrapeptide on respiratory function in healthy volunteers.

OBJECTIVE: The authors evaluated respiratory response to cholecystokinin tetrapeptide (CCK-4) in healthy volunteers. METHOD: Subjects were randomly assigned to either a CCK-4 (N = 15) or placebo (N = 15) challenge under double-blind conditions. RESULTS: Dyspnea was reported by all of the subjects who received CCK-4 but only one subject who received placebo. CCK-4 caused a significant increase in tidal volume and minute ventilation but had no effect on breathing frequency. Placebo had no effect on any of the respiratory measures. CONCLUSIONS: These data indicate that the behavioral effects of CCK-4 are accompanied by changes in respiration in healthy volunteers.

Adult↗

Optic neuritis after influenza vaccination.

PURPOSE: To present evidence for a causal relation between optic neuritis and influenza vaccination. METHODS: Case report. In a 59-year-old woman with bilateral optic neuritis, neuro-ophthalmologic examination, magnetic resonance imaging, fluorescent treponemal antibody absorption test, antinuclear antibodies, and complete blood cell count and chemistry were performed. RESULTS: Our patient developed bilateral optic neuritis on two occasions, 1 year apart. No evidence of neuroretinitis, syphilis, or systemic lupus erythematosus was identified. Influenza vaccination was given 2 weeks before the onset of each episode. CONCLUSION: This case provides compelling clinical evidence that implicates influenza vaccination as a cause of optic neuritis.

Female↗

Antioxidant status and lipid peroxidation in diabetic pregnancy.

Pregnancy in insulin-dependent diabetes mellitus is associated with a greater incidence of fetal abnormality. Animal studies suggest that increased free-radical production and antioxidant depletion may contribute to this risk. The aim of the present study was, therefore, to assess nutritional antioxidant status and lipid peroxidation in diabetic mothers in comparison with a control group. A 7 d dietary history and a food-frequency questionnaire were performed and venous blood collected for biochemical analyses from thirty-eight diabetic mothers and matched control subjects before 12 weeks gestation. Protein intake was significantly greater in diabetic patients (81.4 (SE 14.8) v. 72.7 (SE 15.8) g/d, P = 0.015), while total sugar intake was less (79.5 (SE 13.2) v. 104.8 (SE 28.8) g/d, P < 0.001). There were no significant differences in the intake of the major antioxidant vitamins (retinol, vitamin C or vitamin E) or beta-carotene. However, intakes of a number of other micronutrients (including Se, Zn, Mg, Mn, riboflavin, thiamin, niacin and folate) were greater in diabetic patients. Among the nutritional chain-breaking antioxidants, serum levels of alpha-tocopherol (21.6 (SE 5.7) v. 17.3 (SE 4.7) mumol/, P = 0.0013), beta-carotene (0.27 (SE 0.18) v. 0.14 (SE 0.11) mumol/l, P = 0.003) and lycopene (0.23 (SE 0.17) v. 0.16 (SE 0.13) mumol/l, P = 0.03) were greater in diabetic patients. There was no evidence of greater lipid peroxidation in diabetic patients, and total antioxidant capacity was similar in the two groups. Overall, these results indicate that nutritional antioxidant status is better in this group of diabetic mothers than in control pregnant non-diabetic subjects attending the same maternity hospital.

Adult↗

Interpretation of restriction fragment length polymorphism analysis of Mycobacterium tuberculosis isolates from a state with a large rural population.

Epidemiologic relatedness of Mycobacterium tuberculosis isolates from Arkansas residents diagnosed with tuberculosis in 1992-1993 was assessed using IS6110- and pTBN12-based restriction fragment length polymorphism (RFLP) and epidemiologic investigation. Patients with isolates having similar IS6110 patterns had medical records reviewed and were interviewed to identify epidemiologic links. Complete RFLP analyses were obtained for isolates of 235 patients; 78 (33%) matched the pattern of > or = 1 other isolate, forming 24 clusters. Epidemiologic connections were found for 33 (42%) of 78 patients in 11 clusters. Transmission of M. tuberculosis likely occurred many years in the past for 5 patients in 2 clusters. Of clusters based only on IS6110 analyses, those with > or = 6 IS6110 copies had both a significantly greater proportion of isolates that matched by pTBN12 analysis and patients with epidemiologic connections, indicating IS6110 patterns with few bands lack strain specificity. Secondary RFLP analysis increased specificity, but most clustered patients still did not appear to be epidemiologically related. RFLP clustering in rural areas may not represent recent transmission.

Adolescent↗

Retrospective detection of laboratory cross-contamination of Mycobacterium tuberculosis cultures with use of DNA fingerprint analysis.

In 1992-1993, we investigated possible cross-contamination of Mycobacterium tuberculosis cultures as part of a study of tuberculosis in Arkansas by using DNA fingerprint analysis. Of patients whose isolates were matched, those for whom smears were negative and only one culture was positive were identified from laboratory records. Clinical, laboratory, DNA fingerprint, and epidemiological data were reviewed. Of 259 patients, nine (3.5%) were judged to be due to cross-contamination. None of these patients had a clinical course consistent with tuberculosis. All nine specimens were processed with another isolate with a matching DNA fingerprint, and epidemiological connections were not identified among any of the patients. To avoid erroneous diagnoses and unnecessary therapy and public health investigations, specimens from patients with tuberculosis whose smears are negative and only one culture is positive should be investigated for cross-contamination. An inconsistent clinical course and a DNA fingerprint that matches those of other culture-positive specimens processed concurrently, coupled with the lack of an epidemiological connection, suggest cross-contamination.

Adult↗

A distributed nonlinear model of lung tissue elasticity.

We present a theory relating the static stress-strain properties of lung tissue strips to the stress-bearing constituents, collagen and elastin. The fiber pair is modeled as a Hookean spring (elastin) in parallel with a nonlinear string element (collagen), which extends to a maximum stop length. Based on a series of fiber pairs, we develop both analytical and numerical models with distributed constituent properties that account for nonlinear tissue elasticity. The models were fit to measured stretched stress-strain curves of five uniaxially stretched tissue strips, each from a different dog lung. We found that the distributions of stop length and spring stiffness follow inverse power laws, and we hypothesize that this results from the complex fractal-like structure of the constituent fiber matrices in lung tissue. We applied the models to representative pressure-volume (PV) curves from patients with normal, emphysematous, and fibrotic lungs. The PV curves were fit to the equation V = A--Bexp(-KP), where V is volume, P is transpulmonary pressure, and A, B, and K are constants. Our models lead to a possible mechanistic explanation of the shape factor K in terms of the structural organization of collagen and elastin fibers.

Animals↗

Temporal dynamics of acute isovolume bronchoconstriction in the rat.

The time course of lung impedance changes after intravenous injection of bronchial agonist have produced significant insights into the mechanisms of bronchoconstriction in the dog (J. H. T. Bates, A.-M. Lauzon, G. S. Dechman, G. N. Maksym, and T. F. Shuessler. J. Appl. Physiol. 76: 616-626, 1994). We studied the time course of acute induced bronchoconstriction in five anesthetized paralyzed open-chest rats injected intravenously with a bolus of methacholine. For the 16 s immediately after injection, we held the lung volume constant while applying small-amplitude flow oscillations at 1.48, 5.45, and 19.69 Hz simultaneously, which provided us with continuous estimates of lung resistance (RL) and elastance (EL) at each frequency. This procedure was repeated at initial lung inflation pressures of 0.2, 0.4, and 0.6 kPa. Both RL and EL increased progressively after methacholine administration; however, the rate of change of EL increased dramatically as frequency was increased, whereas RL remained relatively independent of frequency. We interpret these findings in terms of a three-compartment model of the rat lung, featuring two parallel alveolar compartments feeding into a central airway compartment. Model simulations support the notions that both central airway shunting and regional ventilation inhomogeneity developed to a significant degree in our constricted rats. We also found that the rates of increase in both RL and EL were greatly enhanced as the initial lung inflation pressure was reduced, in accord with the notion that parenchymal tethering is an important mechanism limiting the extent to which airways can narrow when their smooth muscle is stimulated to contract.

Airway Resistance↗

Effect of stochastic heterogeneity on lung impedance during acute bronchoconstriction: a model analysis.

In a previous study (J. H. T. Bates, A. M. Lauzon, G. S. Dechman, G. N. Makaym, and T. F. Schuessler. J. Appl. Physiol. 76: 616-626, 1994), we investigated the acute changes in isovolume lung mechanics immediately after a bolus injection of histamine. We found that dynamic resistance and elastance increased progressively in the 80-s period after injection, whereas the estimated tissue hysteresivity reached a stable plateau after approximately 25 s. In the present study, we developed a computer model of the lung to investigate the mechanisms responsible for these observations. The model conforms to Horsfield's morphometry, with the addition of compliant airways and structural damping tissue units. Using this model, we simulated the time course of acute bronchoconstriction after intravenous administration of a bolus of bronchial agonist. Heterogeneity was induced by randomly varying the values of the maximal airway smooth muscle contraction and the tissue response to the agonist. Our results demonstrate that much of the increase in lung impedance observed in our previous study can be produced purely by the effects of airway heterogeneity. However, we were only able to reproduce the plateauing of hysteresivity by assigning a minimum radius to each airway, beyond which it would immediately snap completely shut. We propose that airway closure played an important role in our experimental observations.

Airway Resistance↗

A model of the spontaneously breathing patient: applications to intrinsic PEEP and work of breathing.

Intrinsic positive end-expiratory pressure (PEEPi) and inspiratory work of breathing (WI) are important factors in the management of severe obstructive respiratory disease. We used a computer model of spontaneously breathing patients with chronic obstructive pulmonary disease to assess the sensitivity of measurement techniques for dynamic PEEPi (PEEPidyn) and WI to expiratory muscle activity (EMA) and cardiogenic oscillations (CGO) on esophageal pressure. Without EMA and CGO, both PEEPidyn and WI were accurately estimated (r = 0.999 and 0.95, respectively). Addition of moderate EMA caused PEEPidyn and WI to be systematically overestimated by 141 and 52%, respectively. Furthermore, CGO introduced large random errors, obliterating the correlation between the true and estimated values for both PEEPidyn (r = 0.29) and WI (r = 0.38). Thus the accurate estimation of PEEPidyn and WI requires steps to be taken to ameliorate the adverse effects of both EMA and CGO. Taking advantage of our simulations, we also investigated the relationship between PEEPidyn and static PEEPi (PEEPistat). The PEEPidyn/PEEPistat ratio decreased as stress adaptation in the lung was increased, suggesting that heterogeneity of expiratory flow limitation is responsible for the discrepancies between PEEPidyn and PEEPistat that have been reported in patients with severe airway obstruction.

Airway Obstruction↗

Monitoring changes in lung air and liquid volumes with electrical impedance tomography.

Electrical impedance tomography (EIT) uses electrical measurements at electrodes placed around the thorax to image changes in the conductivity distribution within the thorax. This technique is well suited to studying pulmonary function because the movement of air, blood, and extravascular fluid induces significant conductivity changes within the thorax. We conducted three experimental protocols in a total of 19 dogs to assess the accuracy with which EIT can quantify changes in the volumes of both gas and fluid in the lungs. In the first protocol, lung volume increments from 50 to 1,000 ml were applied with a large syringe. EIT measured these volume changes with an average error of 27 +/- 6 ml. In the second protocol, EIT measurements were made at end expiration and end inspiration during regular ventilation with tidal volume ranging from 100 to 1,000 ml. The average error in the EIT estimates of tidal volume was 90 +/- 43 ml. In the third protocol, lung liquid volume was measured by instilling 5% albumin solution into a lung lobe in increments ranging from 10 to 100 ml. EIT measured these volume changes with an average error of 10 +/- 10 ml and was also able to detect into which lobe the fluid had been instilled. These results indicate that EIT can noninvasively measure changes in the volumes of both gas and fluid in the lungs with clinically useful accuracy.

Anesthesia↗

The incidence of false-positive cultures for Mycobacterium tuberculosis.

The frequency of false-positive cultures for Mycobacterium tuberculosis due to cross-contamination has been difficult to determine because of the lack of specific strain markers. Isolates collected prospectively over 5 yr from a municipal health department laboratory underwent DNA fingerprinting using the IS6110 and pTBN12 sequences. We reviewed the clinical and laboratory records of all isolates that had matching DNA fingerprints and were processed within 42 d of each other; 8 isolates were classified as probable or definite false-positives, representing 4.0% (8/199) of the culture-positive patients. A convenience sample of 42 isolates from three other mycobacterial laboratories also underwent DNA fingerprinting, and five (12%) were found to be definite or probable false-positives. Cross-contamination during initial processing of specimens was the most common source of false-positive cultures. The source of cross-contamination for three false-positive cultures was a laboratory proficiency survey specimen containing strain H37Ra. Ten of the 13 patients were misdiagnosed as having tuberculosis, and seven received unnecessary multidrug treatment. Clinicians should be aware of the potential for false-positive cultures for M. tuberculosis, and mycobacteriology laboratories need to carefully review procedures to minimize this occurrence. DNA fingerprinting provides a valuable tool for the study of false-positive cultures.

Bacteriological Techniques↗

A longitudinal study of transmission of tuberculosis in a large prison population.

The purpose of this study was to determine the extent of transmission of tuberculosis in a large prison population over an 18-mo period. Restriction-fragment-length polymorphism (RFLP) analysis of isolates of Mycobacterium tuberculosis was performed, using the insertion sequence IS6110 and the plasmid pTBN12. Patients infected with strains having the same fingerprint were grouped in clusters. Medical records were reviewed and movement of inmates among prisons was examined for selected patients. Tuberculosis was diagnosed in 216 inmates (case rate = 2,283 per 100,000 per year). Isolates from 210 (97%) patients were fingerprinted, 155 (74%) were grouped in 25 clusters, and 55 (26%) showed a unique fingerprint. Recent infection was inferred in 62% of these patients. Eighty-four percent (161 of 192) of patients tested were human immunodeficiency virus (HIV)-positive, of whom 121 were in clusters and 40 were not (p = 0.74). Patients in clusters were less adherent with tuberculosis treatment than those not in clusters (p < 0.05), and prison transmission of resistant strains was observed. It is crucial that infection control guidelines be fully implemented in the prison setting to prevent tuberculosis transmission.

Adult↗

DNA fingerprinting with two probes decreases clustering of Mycobacterium tuberculosis.

DNA fingerprinting of Mycobacterium tuberculosis is used to study the epidemiology of tuberculosis, but the specificity of the widely used IS6110 technique has not been validated. Isolates from Denver, Colorado from December 1988 through June 1994 were fingerprinted with the IS6110 technique. Available records were reviewed for patients whose isolates were within IS6110-defined clusters, and these isolates were fingerprinted with an independent technique (pTBN12). Of 189 isolates, 86 (46%) were in IS6110-defined clusters. Clustering was inversely related to the number of copies of IS6110, ranging from 12 of 12 (100%) to 37 of 48 (77%) and 37 of 129 (29%) for isolates having one, two to five, and more than five copies (p < 0.001). Of the 86 isolates clustered with the IS6110 technique, 35 (41%) had unique pTBN12 fingerprints. Discordant results with the two fingerprinting techniques were more common among isolates having five or fewer copies of IS6110. Epidemiologic links were identified among four of 35 (11%) patients whose isolates had discordant fingerprinting results, as compared with 40 of 51 (78%) of those whose isolates matched by both IS6110 and pTBN12. DNA fingerprinting with the IS6110 technique was not a specific marker of DNA clonality, particularly among isolates having fewer than five copies of IS6110. The use of a supplemental DNA fingerprinting technique decreased clustering and improved the correlation between the transmission links predicted by molecular techniques and epidemiologic investigation.

Cluster Analysis↗

The effect of delay in treatment on local control by radiotherapy.

PURPOSE: The objective of this study was to estimate the effect of delay in initiation of treatment on rates of local control by radiotherapy. METHODS AND MATERIALS: A model of the effects of delay was developed based on the following assumptions: (a) that tumor growth rate is exponential, (b) that a predetermined radiotherapy regimen will kill the same fraction of clonogenic cells in a given tumor whether it is administered early or late, and (c) that the absolute number of cells surviving in a tumor is determined by Poisson statistics. Monte Carlo simulation was used to estimate the expected rate of decrease in local control associated with delay in a population of tumors, which was heterogeneous with respect to doubling time and initial volume. The model was applied to carcinoma of the tonsillar region. RESULTS: It was shown that at some point in the evolution of every case, the probability of local control decreases sharply over a relatively short period of time. The maximum rate of decrease in the probability of local control occurs at the 37% local control level when it reaches 25.5% per tumor doubling time. When heterogeneity with respect to doubling time and stage was taken into account, it was estimated that the local control rate would decrease by approximately 10% per month in a typical series of patients with carcinoma of the tonsillar region. CONCLUSIONS: It was concluded that delay in initiation of radiotherapy may be associated with a clinically important deterioration in local control rates. We recommend that waiting times for radiotherapy should be As Short As Reasonably Achievable (ASARA).

Algorithms↗

Temporal response of lung impedance after i.v. oleic acid in dogs.

We measured total and regional lung impedances in six anaesthetized, paralysed dogs every min for 1 hour immediately following i.v. oleic acid administration. Total lung impedance was assessed from pressure and flow data collected at the airway opening during conventional mechanical ventilation. We obtained regional lung impedance at two sites simultaneously using our recently developed alveolar capsule oscillator technique (Davey, B.L.K. and J.H.T. Bates, 1993, Respir. Physiol. 91:165-182). We found that total lung resistance (RL) increased for the first 15 min in a manner suggestive of an initial bronchoconstrictive event, and then remained stable for the remainder of the hour. EL continued to increase throughout the entire period. In contrast, regional alveolar resistance (RA) increased initially and then returned to baseline, while regional alveolar elastance (EA) remained unchanged. We interpret these results as reflecting an initial transient bronchoconstriction together with a progressive accumulation of oedema in the dependent regions of the lung. This implies that the changes in EL were due mostly to increased heterogeneity of regional ventilation, and that non-dependent lung regions may remain virtually unaffected mechanically even when the overall oedematous changes in lung mechanics are severe.

Airway Resistance↗

Strand displacement amplification and the polymerase chain reaction for monitoring response to treatment in patients with pulmonary tuberculosis.

Specific amplification of Mycobacterium tuberculosis DNA was investigated as an alternative to conventional microbiologic follow-up in 31 cases of smear- and culture-positive pulmonary tuberculosis. Strand displacement amplification (SDA) and the polymerase chain reaction (PCR) were applied to 438 sequential sputum specimens: 67 (15%) were positive by culture, 248 (57%) by SDA, and 231 (53%) by PCR (chi2=3.94, P=.05). Of 200 specimens collected >180 days after treatment started, none yielded positive cultures, while 50 (25%), representing 16 patients, were positive by both DNA assays. A weak correlation was demonstrated between DNA persistence in sputum and duration of culture positivity (r=0.45, P=.01), although no correlation was found with the radiographic extent of disease. The inability to distinguish live and dead organisms precludes DNA amplification from use in therapeutic monitoring. For this purpose, quantitative RNA assays are needed if such techniques are to supplant conventional microbiology.

Base Sequence↗

Specificity of IS6110-based amplification assays for Mycobacterium tuberculosis complex.

The specificity of IS6110 for the Mycobacterium tuberculosis complex has recently been questioned. We observed no cross-reaction with 27 nontuberculous mycobacteria using strand displacement- and PCR-based amplification of the nucleotide 970 to 1026 and 762 to 865 regions of IS6110. These data support use of selected regions of IS6110 as M. tuberculosis complex-specific targets.

Bacteriological Techniques↗