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Biomedical subjects

D J Turner

Publications and source records attributed to D J Turner.

At least 19 recordsLinked to original sources

The role of endogenous corticosterone in the late-phase response to allergen challenge in the brown Norway rat.

The aim of this study was to assess the role of endogenous corticosterone (CCST) concentrations on the late airway response (LAR) to ovalbumin (OA). Thirty-two Brown Norway (BN) rats were sensitized to OA on Day 0, then divided into three groups. Group 1 (n = 11) received saline (1 ml, subcutaneously) at time (T) = -24, -12, and 0 h prior to a 5% OA challenge on Day 14. Group 2 (n = 11) received metyrapone (MTP), an 11 beta-hydroxylase inhibitor, (10 mg/100 g in 1 ml saline, subcutaneously) at time (T) = -24, -12, and 0 h. Group 3 (n = 10) received MTP on the same schedule as Group 2, plus CCST in the drinking water (16 micrograms/ml) from T = -24 to T = 0 h. Pulmonary resistance (RL) was measured for 8 h following OA challenge to determine early (EAR) and LAR. Blood samples were taken at T = 0 and T = 8 h to determine serum CCST levels. Bronchoalveolar lavage (BAL) fluid was collected at T = 8 h. Serum CCST levels were significantly reduced in the MTP group (235 ng/ml +/- 14 SEM) compared with control (564 +/- 38, p < 0.0001) and MTP+CCST animals (349 +/- 19, p < 0.0005). There were no differences in either baseline RL or EAR between the groups. However, the MTP group had a smaller LAR (6 ml/cm H2O/s*min +/- 2 SEM) than the control group (19 +/- 5, p < 0.02). The effect of MTP on LAR was reversed by treatment with CCST (21 +/- 3, p < 0.005). Total cell counts (p < 0.05) and eosinophils (p < 0.01) were increased in the BAL fluid of MTP rats versus control and MTP+CCST animals. We conclude that depletion of endogenous CCST in the BN rat diminishes the LAR to allergen challenge. These results indicate that physiologic levels of CCST are not necessary for development of the EAR, but they play a permissive role in the LAR to inhaled allergen.

Airway Resistance

A new technique to generate and assess forced expiration from raised lung volume in infants.

We have developed a new technique that allows assessment of infant lung function over an extended volume range. The lungs are rapidly inflated to a predetermined inflation pressure (PP) using a modified diaphragm pump. Forced expiratory flow-volume (FEFV) curves are then generated from raised lung volumes using an inflatable plastic jacket. We studied 26 normal infants with a median age of 14 mo (range, 3 to 23 mo). FEFV curves were obtained in each infant from end-tidal inspiration and from lung volumes set by a range of PP (15 to 20 cm H2O). Mean (SE) volume above FRC was 107 ml (9 ml), and mean forced expiratory time was 0.73 s (0.05 s) at end-tidal inspiration. Both measurements increased progressively with increases in PP to 251 ml (13 ml) and 1.04 s (0.06 s), respectively, at 20 cm H2O PP (p < 0.0001). Mean intrasubject coefficient of variation was 15.5% (95% confidence interval, 12 to 19%) for maximal flow at FRC, but it was less than 6% (95% CI, 4 to 8%) for forced expiratory volume-time (FEVt) measurements at all levels of PP. Twenty-seven recurrently wheezy infants with a median age of 13 mo (range, 6 to 18 mo) were subsequently studied using a PP of 17.5 cm H2O. Wheezy infants had a lower VmaxFRC [mean (1.39 ml/s/cm) and 95% CI (1.15 to 1.63 ml/s/cm)] than did normal infants (1.78 ml/s/cm; CI, 1.51 to 2.05) (p < 0.05). FEV1 measurements were all lower in wheezy infants than in normals infants: mean FEV0.5, 1.86 ml/cm (CI, 1.73 to 1.98) and 2.31 ml/cm (CI, 2.15 to 2.48), respectively (p < 0.0001); FEV0.75, 2.20 ml/cm (CI, 2.07 to 2.32) and 2.72 ml/cm (CI, 2.52 to 2.91), respectively (p < 0.0001); FEV1.0, 2.42 ml/cm (CI, 2.26 to 2.58) and 2.84 ml/cm (CI, 2.63 to 3.06), respectively (p < 0.005). The Ci values of each FEVt measurement did not overlap between the wheezy and normal groups; however, the CI values of VmaxFRC overlapped markedly. In addition, FEVt parameters showed greater sensitivity in detecting reduced lung function (71 to 89%) than did VmaxFRC parameters (56%). We conclude that (1) FEVt measurements derived from a lung volume set by a standardized pressure are more reproducible than flow measurements in the tidal volume range; (2) FEVt measurements are significantly lower in wheezy infants than in normal infants, show less overlap than flow measurements in the tidal volume range, and therefore are better able to separate the two populations.

Forced Expiratory Flow Rates

Pressure transmission across the respiratory system at raised lung volumes in infants.

Forced expiratory flow-volume (FEFV) curves can be generated from end-tidal inspiration in infants with use of an inflatable jacket. We have developed a technique to raise lung volume in the infant before generation of FEFV curves. Measurements of pressure transmission to the airway opening by use of static maneuvers have shown no change with increasing lung volume above end-tidal inspiration. The aim of this study was to determine, under dynamic conditions (i.e., during rapid thoracic compression), whether the efficiency of pressure transmission across the chest wall is altered by raising lung volume above the tidal range. Dynamic pressure transmission (Ptx,dyn) was measured in five infants (age 6-17 mo). Jacket pressure (Pj), esophageal pressure, and volume were measured throughout passive and FEFV curves at lung volumes set by 10, 15, and 20 cmH2O preset pressure. The group mean Ptx,dyn was 37 +/- 6% (SE) of Pj at end-tidal inspiration, and no change was seen with further increases in lung volume. However, a mean decrease in Ptx,dyn of 42% was evident throughout the tidal volume range (i.e., from end-tidal inspiration to end expiration). Isovolume static pressure transmission (Ptx,st) was measured in three of the five infants by inflation of the jacket in a stepwise manner with the airway closed. Measurements were made at end-tidal inspiration and lung volumes at 10, 15, and 20 cmH2O preset pressure. Resulting changes in Pj, esophageal pressure, and airway opening pressure were compared using linear regressions to determine Ptx,st.(ABSTRACT TRUNCATED AT 250 WORDS)

Cystic Fibrosis

Improved detection of abnormal respiratory function using forced expiration from raised lung volume in infants with cystic fibrosis.

The raised volume rapid thoracic compression (RVRTC) technique is a recently developed method of measuring lung function in infants. The measurements of forced expiratory volume-time (FEVt) parameters from raised lung volumes have been shown to be less variable than maximal flow at functional residual capacity (VmaxFRC), obtained from the conventional rapid thoracic compression (RTC) technique. Measurements of VmaxFRC are highly variable, and may not be sensitive enough to detect a difference between normal infants and infants with cystic fibrosis (CF). The aim of this study was to determine whether the raised volume rapid thoracic compression technique could detect abnormal lung function in a group of CF infants with no current respiratory symptoms. Twelve CF infants were studied (median age 10.5 months, range 3-18 months), and compared to normative data collected previously on 26 healthy infants (median age 14 months, range 3-23 months). We found that VmaxFRC failed to detect any difference between the two groups. CF infants had significantly smaller FEV0.5 and FEV0.75 measurements at a lung volume set by 17.5 cmH2O predetermined inflation pressure (PP) both as raw values and when expressed as percentage predicted. We conclude that the raised volume rapid thoracic compression technique is a sensitive tool, able to detect abnormal lung function in infants with cystic fibrosis. This abnormality was not demonstrated by measurements derived from the conventional rapid thoracic compression technique in the tidal volume range.

Cystic Fibrosis

The effect of age on bronchodilator responsiveness.

The relationship between age and bronchodilator responsiveness (BDR) in children has not been studied using objective parameters. The aim of this study was to seek such a relationship in young asthmatic children using dose-response curves (DRC). Fourteen asthmatic subjects (age 3-9 years) with a forced expiratory volume in 1 sec (FEV1) less than 80% predicted were studied after being trained to use a spirometer reliably. Each subject completed a DRC by inhaling 5 doses of salbutamol (albuterol) at 15 min intervals until a cumulative total of 6.84 mg of salbutamol had been administered. FEV1, forced vital capacity (FVC), and forced expiratory flow at mid vital capacity (FEF25-75) were measured before and after each nebulization. In addition, arterial oxygen saturation (SaO2) and heart rate (HR) were measured in some of the subjects. All lung function parameters, SaO2 and HR increased significantly between baseline and completion of the DRC. A significant age effect on BDR was detected in FEV1 and FVC, with older children showing a greater response than young ones. The response had plateaued after the maximum dose in the younger but not in the older children. These findings suggest that the level of response to a bronchodilator increases significantly with increasing age in young asthmatics.

Aging

Assessment of forced expiratory volume-time parameters in detecting histamine-induced bronchoconstriction in wheezy infants.

A new technique recently introduced allows the measurement of infant lung function from lung volumes raised by a pump prior to generation of forced expiratory flow-volume (FEFV) curves. Forced expiratory volume-time (FEV1) parameters rather than traditional flow parameters are used. The aim of this study was to assess the usefulness of FEV1 parameters in detecting airway responsiveness to histamine in recurrently wheezy infants. Ten infants (age 7-18 months) sedated with 80 mg/kg chloral hydrate underwent a histamine inhalation challenge. Throughout the challenge FEFV curves were generated from end-tidal inspiration. Raised FEFV curves, from a lung volume preset by 15 cmH2O inflation pressure, were gathered at baseline and after the final concentration of histamine. The mean fall from baseline was 47% in maximal flow at functional residual capacity (VmaxFRC) (P < 0.0005), 15.5% in FEV0.5 (P < 0.0001), 13.5% in FEV0.75 (P < 0.005), and 11.0% in FEV1.0 (P = 0.057), after the final concentration of histamine delivered. Tidal volume and inspiratory volume reached above FRC between pre- and posthistamine did not change. Mean oxygen saturation fell significantly from 97 to 93%. We conclude that FEV1 parameters adequately detect reduced lung function during histamine-induced bronchoconstriction and appear suitable for histamine challenge testing in infants.

Bronchoconstriction

Lung function and bronchial challenges in infants: repeatability of histamine and comparison with methacholine challenges.

UNLABELLED: Limited information exists regarding the repeatability of lung function and bronchial challenge tests using the rapid thoracic compression technique (RTC) in infants. AIMS: To determine the repeatability of lung function and histamine challenge test results using the RTC technique and to compare the results obtained for bronchial challenges using histamine (H) and methacholine (M). METHODS: Twelve infants [7 healthy, 5 with cystic fibrosis (CF) had pairs of H challenges 1 week apart. Eleven infants (7 healthy, 4 CF) had one H and one M challenge a week apart. The provocative concentration of H or M to cause a 40% fall in maximum flow at functional residual capacity (PC40) was determined using the RTC technique. Twenty-three comparisons were possible between maximal expiratory flow at functional residual capacity (VmaxFRC) measurements made 1 week apart. RESULTS: The mean difference between pairs of VmaxFRC measurements was 6.4% of baseline, and the coefficient of repeatability was 31.1% of baseline. The mean difference between PC40(H) measurements was 0.163 doubling concentrations, with a coefficient of repeatability of 1.66 doubling concentrations. The mean difference between PC40(H) and PC40(M) was 0.75 doubling concentrations, with 95% of PC40(H) between -0.18 to 1.69 doubling concentrations of the PC40(M). CONCLUSIONS: Although the repeatability of VmaxFRC using the RTC technique is less than for voluntary forced expiratory flow parameters in older children, similar results were obtained for infants as observed in older subjects for repeatability of H challenges and agreement between measures of bronchial responsiveness using H or M.

Bronchial Provocation Tests

Bronchial responsiveness and lung function in recurrently wheezy infants.

Although most wheezy infants are considered asthmatic, they generally respond poorly to antiasthma treatment, and there is inadequate knowledge about the pathologic mechanisms that cause wheezing at this age. The aim of this study was to determine whether the strong association between wheezing and bronchial responsiveness (BR) seen in older subjects was also present in infants. We compared BR with inhaled histamine in 19 recurrently wheezy infants with a group of age-, height-, weight-, and sex-matched control infants. Maximal flow at FRC (VmaxFRC) was determined from partial expiratory flow-volume curves generated using the "squeeze" technique. Histamine was delivered during 1 min of tidal breathing in doubling concentrations from 0.125 g/L to a maximum of 8 g/L or until VmaxFRC fell by 40% (PC40). The median baseline VmaxFRC for the wheezy infants was 100.0 ml/s compared with 182.0 ml/s for the control infants (p less than 0.01). However, there was no significant difference in the PC40 between the two groups (2.1 versus 2.3 g/L).

Asthma

Methodological aspects of flow-volume studies in infants.

Although valuable information is being obtained using new techniques to assess infant respiratory mechanics, there have been several concerns about the methodology. These relate to the possibility that chloral hydrate may affect flow-volume measurements by altering upper airway caliber. There is also the possibility that physiological changes may be induced by inhalation of non-pharmacologic and pharmacologic nebulized solutions. The aim of this study was to investigate these phenomena in a group of normal infants. Thoracic gas volume was determined and respiratory mechanics measured using the passive and forced expiratory flow-volume techniques. Respiratory function was assessed in infants before and after 1) sleep was induced by administration of chloral hydrate (n = 10, mean age, 21 weeks); 2) inhalation of nebulized saline (n = 10, mean age, 19 weeks); 3) inhalation of nebulized salbutamol (n = 7, mean age, 22 weeks). A fall in tidal volume was found following administration of chloral hydrate but no significant change was seen in any other respiratory parameter. In addition, no change was seen in any parameter post-saline or salbutamol nebulization. This study provides data which support several basic assumptions made about the infant flow-volume techniques and should provide useful background information for future studies using these techniques.

Albuterol

Response of normal infants to inhaled histamine.

The age at which nonspecific bronchial hyperresponsiveness (BHR) is first seen in humans is unknown, though both genetic and environmental factors have been implicated in its development. The current study aimed to establish whether BHR to histamine can be demonstrated in normal infants. Twelve infants, mean age of 7.8 months (range, 3 to 18 months), were studied. None had any history of a previous significant respiratory illness. Respiratory function was monitored using the maximal flow at function residual capacity (VmaxFRC) obtained with the forced expiratory flow-volume technique. Histamine was inhaled in doubling concentrations from 0.125 to 8 g.L-1. A greater than 30% fall in VmaxFRC was considered a response. All infants responded to histamine, the geometric mean concentration for their response being 1.4 g.L-1. Associated transient changes for the group were an increase in respiratory rate (p less than 0.02) and a fall in SaO2 (p less than 0.001). Forced expiratory flow-volume curves were concave in all infants after the last dose of histamine. We speculate that humans are born with "bronchial hyperresponsiveness" and that genetic or environmental factors determine which infants lose it thereafter.

Bronchi

Effect of diazepam on pancuronium-induced neuromuscular blockade maintained by a feedback system.

The possibility of an interaction between diazepam and pancuronium bromide was investigated in six patients undergoing general anaesthesia maintained with fentanyl, droperidol and nitrous oxide. Neuromuscular blockade was controlled using a feedback mechanism which automatically adjusted the rate of injection of pancuronium to maintain between 71.4 and 72.9% blockade. Diazepam 0.14 mg kg-1 i.v. produced blood concentrations within the therapeutic range, but did not produce consistent changes in the level of blockade, pancuronium concentration in the blood or pancuronium consumption measured over 20 min.

Adolescent

Behavioral treatment for depression: an evaluation of therapeutic components.

Designed study to determine the "active ingredients" in Lewinsohn's behavioral treatment for depression. Fifty-six men and women were screened for significant depression and were assigned to four experimental treatment groups: (1) an activities-increase group instructed to increment participation in reinforcing activities; (2) an expectancy-control group that participated in a fitness program; (3) a self-monitoring control that simply recorded activities and mood daily; and (4) an attention-control group. Consistent with an operant model of depression, the resulted indicated that increases in activities that Ss had rated as pleasureable alleviated depressed mood over a 30--day time period. While all Ss evidenced some improvement in mood, the activities-increase group showed significantly greater improvement than Ss in groups that did not increase their activity levels. Correlational analyses of daily activity and Depression Adjective Check List Scores proved additional support for the behavioral model of depression. The outcome for the four experimental groups was not different on a measure of belief in internal vs. external control of reinforcement.

Activities of Daily Living