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Biomedical subjects

N A Saunders

Publications and source records attributed to N A Saunders.

At least 109 records · Page 6Linked to original sources

Bacterial colonisation of the respiratory tract in chronic bronchitis.

One hundred and nine subjects with chronic bronchitis were studied prior to winter and without clinical infection, to determine baseline patterns of bacterial colonisation. Qualitative analysis of cultures of oropharyngeal swabs showed little difference from age matched normal controls (17) except for growth of small numbers of Gram negative coliforms in the chronic bronchitic group. Quantitation of bacteria colonising the oropharynx showed small numbers (mean of 10(5) cfu/ml), with no particular bacteria dominating. Haemophilus influenzae was present in 7.3% of throat swabs from chronic bronchitic patients, but the organism was always less than 10% of the total count. Quantitation of bacteria in sputum showed significantly higher numbers (mean 10(7) cfu/ml). H. influenzae was detected in 25.7% of available specimens, and when present constituted greater than 90% of the total count. Biotyping of H. influenzae isolates demonstrated a separate colonisation of the upper and lower respiratory tracts.

Aged↗

Lack of airway response to nasal irritation in normal and asthmatic subjects.

Twenty two subjects (10 normals, nine asthmatics and three who had suggestive histories for asthma but normal bronchial histamine challenges) underwent nasal challenges with logarithmic incremental doses of histamine or saline on alternate days. Nasal resistance (measured by posterior rhinometry), and forced expiratory volume in one second (FEV1) were assessed after each dose of nasal histamine or placebo. After each nasal challenge (maximum nasal dose of 250 micrograms of histamine or doubling of nasal resistance) bronchial responsiveness was measured with a bronchial histamine challenge. Despite significant changes in nasal resistance with nasal histamine (p less than 0.01) there was no significant change in the forced expiratory volume in one second, or in bronchial responsiveness. We were unable to demonstrate nasobronchial reflexes initiated by acute irritation of the nasal mucosa with histamine in either normal subjects or in those with mild to moderate asthma.

Adolescent↗

Typing of Legionella pneumophila serogroups 2-14 strains by analysis of restriction fragment length polymorphisms.

A typing method based on analysis of restriction fragment length polymorphisms has previously been developed for Legionella pneumophila serogroup 1. Here data are presented demonstrating the utility of this method for typing strains of all other L. pneumophila serogroups described to date. The method, which is highly discriminatory, should be of considerable value in epidemiological investigations of legionella infections.

Bacterial Typing Techniques↗

Analysis of bronchial reactivity in epidemiological studies.

The measurement of bronchial reactivity in epidemiological studies has the advantage of quantifying an objective physiological feature of asthma. Bronchial reactivity was developed in a clinical setting and has been conventionally expressed as the dose of agonist producing a 20% fall in FEV1 (PD20). As PD20 can be estimated for less than 20% of subjects in general community surveys with the doses of agonist that are usually given, data from most subjects must be censored. Thus PD20 alone is a poor index of bronchial reactivity for epidemiological studies. Data from 809 aluminium smelter workers were used to evaluate alternative methods of analysing bronchial reactivity. Dose-response relationships were analysed by four methods: (1) PD20 by the conventional method of interpolating the dose on a logarithmic scale between the last two measurements of FEV1; (2) PD20 (with allowance for extrapolation), estimated by fitting an exponential curve to the dose-response data; (3) the linear regression slope between dose and FEV1 when significant; (4) the dose-response slope obtained in all subjects as the % change in FEV1 from baseline in response to total dose. When each of these measures was related to symptoms, diagnosis, and treatment of asthma, all differentiated between "asthmatic" and "non-asthmatic" subjects. The dose-response slope (method 4) had the advantages of simplicity and no censored data, and was shown to be clinically relevant. It is suggested that the dose-response slope should be used for the analysis of bronchial reactivity in epidemiological studies.

Airway Resistance↗

Estimation of the probability of disturbed breathing during sleep before a sleep study.

We have investigated the ability of a statistical model developed from clinical data and questionnaire responses to predict disturbance of breathing during sleep. Data from 100 consecutive patients referred for sleep study for suspected sleep apnea were used to develop the model using logistic regression analysis. For each subject, the model predicted the probability of having an apnea-hypopnea index (AHI) greater than 15; this probability was compared with the AHI measured from sleep study. A probability cutoff point (= 0.15) was decided on that minimized the number of subjects with false-negative predictions. Four terms--apneas observed by bed partner, hypertension, body mass index, and age--were found to contribute significantly to the model with observed apneas being by far the most predictive term of the four (adjusted odds ratio 19.7). When the model was tested to estimate the probability of an AHI greater than 15 for 105 patients from a second group of consecutive patients referred for sleep study, the model correctly classified 33 of 36 patients with a measured AHI greater than 15 (sensitivity = 92%) and 35 of 69 patients with a measured AHI less than or equal to 15(specificity = 51%). This study shows that analysis of clinical features of patients presenting with suspected sleep apnea may reduce the need for sleep studies by about one-third yet still lead to the identification of the great majority of patients with abnormal breathing during sleep.

Female↗

Urinary uric acid:creatinine ratio, serum erythropoietin, and blood 2,3-diphosphoglycerate in patients with obstructive sleep apnea.

A noninvasive, inexpensive method of excluding significant sleep-associated hypoxemia would be desirable for patients being investigated and treated for obstructive sleep apnea (OSA). Sixty-eight such patients provided specimens before and after sleep studies for estimation of urinary uric acid:creatinine ratio (UA:Cr), serum erythropoietin (EPO), and blood 2,3-diphosphoglycerate (2,3-DPG). Mean (SD) morning 2,3-DPG was higher in 26 patients with overnight hypoxemia than in 42 normoxemic patients (2.54 [0.46] versus 2.24 [0.44] mmol/L; p = 0.01). Neither overnight change nor absolute values of serum EPO or urinary UA:Cr were significantly different between hypoxemic and normoxemic groups. There was a diurnal variation in serum EPO in normoxemic patients (P.M. EPO = 14.8 [7.1] mU/ml; A.M. EPO = 10.7 [7.1] mU/ml; p less than 0.05) but not in hypoxemic patients. Eighteen hypoxemic patients were restudied after using nasal continuous positive airway pressure (nCPAP) for at least 4 wk. Seven normoxemic patients not using nCPAP were restudied after a similar time. There were no significant differences between pretreatment and posttreatment nights in absolute values or percentage overnight change of blood 2,3-DPG or serum EPO in either group. In the hypoxemic (nCPAP) group, overnight change in urinary UA:Cr was lower on the second night (p = 0.04); there was no significant change in the control group. We conclude that although urinary UA:Cr, serum EPO, and 2,3-DPG may be physiologically related to hypoxemia, none of these measures can be used to predict accurately the presence of moderate nocturnal hypoxemia in patients with OSA or in monitoring the effect of their therapy.

2,3-Diphosphoglycerate↗

Evaluation of a selective medium for the isolation and differentiation of Haemophilus influenzae and Haemophilus parainfluenzae from the respiratory tract of chronic bronchitics.

Respiratory tract specimens from chronic bronchitic patients were cultured for Haemophilus species on conventional chocolate agar and a modified sucrose medium in order to determine the accuracy of the new medium in differentiating Haemophilus influenzae from Haemophilus parainfluenzae strains. Haemophilus influenzae biotypes II and III and Haemophilus parainfluenzae biotypes I and II were found to be the predominant strains isolated from the respiratory tract. The modified sucrose medium was found to be a rapid and reliable means of differentiating Haemophilus influenzae from Haemophilus parainfluenzae by sucrose fermentation, on initial isolation.

Bronchitis↗

Use of medications by the elderly.

Our study confirms that multiple medications are frequently taken by relatively healthy residents of a retirement village, the more so when they are less socially active during the day, and when they are living in hostel accommodation. There were few drug combinations that caused a potential interaction, suggesting that safe use of medication by the elderly should be an achievable goal.

Aged↗

Evaluating interns' performance using simulated patients in a casualty department.

An observational study examined the care that was provided by 61 interns for three simulated (standardized) patients in a casualty department within a large teaching hospital. The consultations were recorded on videotape and were scored by reference to explicit criteria that were set by an expert panel. The criteria described standards of clinical competence, communication skills and preventive care for each of the three cases. An additional list of the general opportunities for preventive advice that were suggested by the patients' case histories also was compared with the interns' actual behaviour. Clinical competence was not demonstrated uniformly across the three cases. The problem of urinary-tract infection was managed best; 19% of the interns complied with all criteria, and 93% of the interns complied with 75% of the criteria. For tension headache, only 3% of the interns complied with all the criteria but 67% of interns complied with 75% of the criteria. In the case of bronchitis, only 3% of interns complied with all the criteria but 58% of interns met 75% of the criteria. The quality of preventive care also varied from case to case, being best for the patient with bronchitis and worst for the patient with tension headache. Over all, only three of the 13 criteria were met by more than half the interns. The communication-skills criteria identified three behaviours which the interns were most likely to omit: the interns summarized the patients' problems in only 73 of the 173 consultations; they explained the aetiology of the problems in only 127 of the 173 consultations; and they ensured that the patients understood their plan of management in only 21 of the 173 consultations.

Adult↗

Uvulopalatopharyngoplasty as a treatment for snoring.

Uvulopalatopharyngoplaty was performed in 18 consecutive patients (15 men and three women; mean +/- standard deviation [SD] age, 46.3 +/- 7.5 years) who presented for the treatment of heavy habitual snoring. No attempt was made to select patients who were ideal anatomically for palatal modification. The loudness of snoring was measured during sleep by integrating the output of a calibrated microphone. An assessment before operation showed that nine patients had obstructive sleep apnoea; four patients had an apnoea index of greater than or equal to 25 apnoeas per hour. The patients were overweight and consumed, on average, 38 g of alcohol per day, but these variables did not change after the operation. The postoperative assessment was performed 138 +/- 44 days after uvulopalatopharyngoplasty. Fourteen patients showed a reduction in the loudness of their snoring, although snoring was abolished in one patient only (average snoring loudness in arbitrary units/min of sleep, 2.8 +/- 2.1 before operation compared with 1.4 +/- 1.5 units/min of sleep after the operation; P less than 0.05. The loudest snore in arbitrary units measured 7.1 +/- 3.3 units compared with 4.8 +/- 3.3 units, respectively; P less than 0.05). The percentage of the sleep time that was spent at an arterial oxygen saturation of less than 90% was reduced after uvulopalatopharyngoplasty (28% +/- 32% of total sleep time compared with 17% +/- 24% of total sleep time, respectively; P less than 0.05). There was no change in the apnoea index. The diastolic blood pressure was lower at the postoperative assessment (94 +/- 11 mmHg compared with 87 +/- 8 mmHg; P less than 0.05); six of 10 subjects whose diastolic blood pressures were greater than or equal to 95 mmHg before the operation had a diastolic blood pressure of less than 95 mmHg after uvulopalatopharyngoplasty (P less than 0.02). Computed tomographic scans showed an increase in the upper airway cross-sectional area at 3 cm and 4 cm above the hyoid bone after uvulopalatopharyngoplasty (P less than 0.05). We conclude that uvulopalatopharyngoplasty is an effective treatment for habitual, heavy snoring in many patients, but it is not the treatment of choice for patients with clinically-significant obstructive sleep apnoea.

Adult↗

Pulmonary alveolar macrophages express a polyamine transport system.

Polyamine transport is an important mechanism by which cells regulate their intracellular polyamine content. It is well established that the lung has a high capacity for polyamine transport, and recently the polyamine putrescine has been shown to be selectively accumulated into the type II pneumocyte of rabbit lung slices (Saunders et al.: Lab. Invest., 95:380-386, 1988). In addition, it has been suggested that there may be more than one polyamine transport system in lung tissue (Byers et al.: Am. J. Physiol., 252:C663-C669, 1987). In the present study, we have examined whether there are differences in the distribution of putrescine and spermidine uptake activities in isolated rabbit lung cells. We report that pulmonary alveolar macrophages have a greater rate of uptake of both putrescine and spermidine than the total lung cell population. Kinetic analysis of the polyamine uptake system present in macrophages showed putrescine uptake consisted of a saturable (Km = 2.1 microM) and nonsaturable component whilst spermidine uptake consisted of both a high- and a low-capacity saturable component (Km = 0.16 microM and 1.97 microM, respectively). The rate of polyamine transport was similar to those reported for many proliferative or tumor cell-lines and appears to be greater than any other major lung cell type. Inhibition studies of the transport of polyamines into pulmonary alveolar macrophages suggested that the uptake of both putrescine and spermidine was mediated by the same system, which could not be described by simple Michaelis-Menten kinetics. The transport appears to be reversible due to significant efflux. This is the first study to describe the presence of multiple polyamine transport systems in pulmonary alveolar macrophages.

Animals↗

Relation between plasma beta-endorphin and the ventilatory response to hypercapnia in humans.

1. Endogenous opioids have been implicated in the control of breathing in neonates, but their role in ventilatory control in adults remains unclear. 2. We studied the relationship between circulating immunoreactive beta-endorphin and the ventilatory and mouth occlusion pressure responses to hypercapnia in 12 healthy male subjects. In addition, we examined the effect of repetitive hypercapnia on plasma beta-endorphin and cortisol levels. 3. A weak but significant negative relationship between the ventilatory response to hypercapnia and basal plasma beta-endorphin levels was observed (r = -0.35, P less than 0.01). A similar negative relationship was noted between mouth occlusion pressure response to hypercapnia and basal plasma beta-endorphin levels (r = -0.36, P less than 0.01). 4. Repetitive hypercapnia prevented the fall in plasma cortisol that occurred under control conditions (P less than 0.02) but had no effect on plasma beta-endorphin. 5. We conclude that plasma beta-endorphin may play a role in the central chemical control of breathing in man.

Adult↗

Interrater reliability of computer-assisted scoring of breathing during sleep.

Twenty-six records of sleep and breathing obtained with a portable monitoring system from elderly subjects were scored by three raters with computer assistance to examine interrater reliability of scoring. Raters were a medical student, a nurse practitioner, and a family physician, all of whom had at least one month's experience with the equipment. Agreement among raters was measured with the unweighted kappa statistic. Significant agreement was observed for all variables, although agreement was better for variables describing breathing (range of kappa 0.71-0.87) than for those describing sleep (range of kappa 0.34-0.57). Complete agreement among the three raters on diagnostic classification occurred in 17 cases. In the remaining 9 cases, 2 raters agreed, whereas the third differed by not more than one category for type of disturbance (e.g., normal versus hypopnea, hypopnea versus apnea) or severity (e.g., mild versus moderate). There was only one disagreement among raters for the 9 subjects with severe respiratory disturbance. We conclude that interrater reliability of identifying and characterizing breathing disturbance during sleep as recorded by portable monitoring is high among trained raters using computer assistance.

Aged↗

Supplemental oxygen and quality of sleep in patients with chronic obstructive lung disease.

The hypothesis that supplemental oxygen could improve the quality of sleep was tested in 23 consecutive patients (14 male, nine female; age 42-74 years) with chronic obstructive lung disease (mean (SD) FEV1 0.81 (0.32) litre, FEV1/FVC 37% (12%). Patients breathed compressed air or supplemental oxygen via nasal cannulas on consecutive nights in a randomised, double blind, crossover trial. Quality of sleep was assessed by questionnaire and by electroencephalographic sleep staging. The study had a power of 80% to detect, at the 0.05 level, a 20% improvement in total sleep time. Seventeen patients slept for two nights in the laboratory. Oxygenation during sleep was improved by oxygen administration, but there was no improvement in quality of sleep. There was an acclimatisation effect with better sleep on the second night. Six patients spent an additional acclimatisation night in the laboratory as well as the two study nights. There was no difference in sleep quality between the second and third nights or between the compressed air and the oxygen nights in these patients. Subgroups of patients with an arterial carbon dioxide tension of over 43 mm Hg (5.7 kPa) (n = 12) and arterial oxygen saturation of less than 90% (n = 11) while awake did not show any improvement in quality of sleep on the oxygen night. It is concluded that supplemental oxygen improves nocturnal oxygenation but does not immediately improve the quality of sleep in the laboratory in patients with chronic obstructive lung disease.

Adult↗

Localization of spermidine uptake in rabbit lung slices.

The lungs have a high polyamine transport capability, and the type II pneumocyte has recently been identified as a major site of putrescine uptake and localization (N. A. Saunders, P. J. Rigby, K. F. Ilett, and R. F. Minchin. Lab. Invest. 59: 380-386, 1988). However, recent evidence suggests that multiple polyamine transport systems exist. In the present study, localization of spermidine uptake in rabbit lung was investigated. Although [14C]spermidine was rapidly accumulated by lung slices, it was not significantly metabolized, and no efflux of the accumulated polyamine was apparent. Autoradiographs prepared after [3H]spermidine transport revealed a localization of uptake activity to cells identified by electron microscopy as type II pneumocytes. Spermidine uptake occurred in all type II cells examined and thus appeared to be a characteristic function of this cell type. In contrast, spermidine uptake was virtually absent in the major airways and blood vessels, whereas moderate uptake was associated with pulmonary alveolar macrophages and alveolar tissue. Subsequent purification and culture of type II pneumocytes showed these cells to have significant polyamine uptake activity. In addition, spermidine uptake activity was positively correlated with the proportion of type II cells present at the various stages of their purification. In other studies, cultured pulmonary alveolar macrophages possessed similar uptake activity to that of cultured type II cells. Combined, these data suggest that both type II cells and pulmonary alveolar macrophages may represent major sites of spermidine uptake in vivo. We also suggest that the transport of polyamines by type II cells may reflect a critical role for polyamines in a characteristic function of this cell type.

Animals↗

Influence of muscle activity on the elastance of the upper airway of rabbits.

This study sought to assess the effect of variations in upper airway muscle activity on upper airway pressure-volume properties. Upper airway elastance, closing pressure, and reserve volume were measured in the isolated upper airways of anesthetized rabbits under control conditions and after administration of gallamine (2 mg/kg iv) or after 10 min of spontaneous respiration of 7% CO2 in O2. Administration of gallamine to seven animals was associated with a fall in reserve volume from 0.94 +/- 0.24 to 0.69 +/- 0.17 (95% confidence interval) ml (P less than 0.01) and of closing pressure from -7.53 +/- 0.23 to -5.75 +/- 1.05 cmH2O (P less than 0.01), but airway elastance did not change significantly. Hypercapnia in seven animals was associated with a rise in elastance from 7.06 +/- 0.91 to 7.67 +/- 0.86 cmH2O/ml (P less than 0.001) and in reserve volume from 0.68 +/- 0.06 to 0.86 +/- 0.13 ml (P less than 0.05). Closing pressure also changed from -5.88 +/- 0.94 to -7.92 +/- 1.85 cmH2O. This change was correlated with the change in reserve volume but not with the change in elastance. In three animals exposed to hypercapnia, return to room air breathing was associated with return of elastance, reserve volume, and closing pressure to control levels. It is concluded that muscle activity in the upper airway affects both the size and elastance of the airway, but the dominant mechanism by which upper airway muscles increase the resistance of the upper airway to collapse is by increasing airway volume.

Airway Resistance↗

Pressure-volume properties of the upper airway of rabbits.

In 10 anesthetized rabbits the upper airway cephalad of the vocal cords was isolated from the distal airway and sealed. Static deflation pressure-volume data were recorded from the isolated upper airway. The relationship between pressure and volume in the upper airway was a straight line; the correlation coefficient (r) ranged from 0.97 to 1.00. The following quantities were derived from the data: the pressure-volume ratio (upper airway elastance, cmH2O/ml), the pressure in the airway at airway closure (closing pressure, cmH2O), and the airway volume at zero airway pressure (reserve volume, ml). Mean upper airway elastance was 8.13 +/- 1.45 [95% confidence intervals (CI)] cmH2O/ml, closing pressure was -6.93 +/- 1.53 (95% CI) cmH2O, and reserve volume was 0.74 +/- 0.15 (95% CI) ml. There was no significant correlation between elastance and closing pressure (r = 0.47, P greater than 0.1), but closing pressure and reserve volume were significantly correlated (r = 0.77, P less than 0.01). Pressure-volume data recorded from newly dead animals exhibited the same linear relationship between pressure and volume observed in living animals. It is concluded that the pressure-volume properties of the isolated upper airway of the rabbit can be expressed as a single value for airway elastance, that estimation of pressure-volume properties over part of the volume range is representative of the whole volume range, and that pressure-volume properties are determined by passive elastic properties of the airway tissues. It appears that the resistance of the upper airway to collapse by negative intraluminal pressure is more dependent on the initial size of the airway than on its elastance.

Airway Resistance↗

Does aluminum smelting cause lung disease?

The evidence concerning a relationship between work in the aluminum industry and lung disease has been reviewed using epidemiologic criteria. Adequate data on environmental exposure are rarely presented. Case series on aluminum potroom workers over the past 50 years have identified an asthmalike syndrome that appears to be due to an irritant rather than an allergic mechanism. These studies have been supported by evidence of within shift variability of measures of lung function. However, to date, there is inadequate evidence to resolve the question of whether potroom exposure initiates asthma or merely precipitates asthmalike symptoms in a predisposed individual. Cross-sectional studies have demonstrated evidence of reduced lung function, consistent with chronic airflow limitation. In exposed aluminum smelter workers compared to unexposed control subjects. Cigarette smoking, the major potential confounding variable, has been measured and accounted for in multivariate analyses. To date, evidence is lacking from longitudinal studies about the development of disabling chronic obstructive lung disease. Exposure to coal tar pitch volatiles in the production and consumption of anodes has biologic plausibility for an association of lung cancer with work in an aluminum smelter. Although retrospective mortality studies have failed to account for the probable high prevalence of smoking in blue collar workers, the relative risk of lung cancer is very low if present at all. Pulmonary fibrosis has not been shown to be a significant problem in aluminum smelter workers. Future research in the aluminum industry needs to concentrate on longitudinal studies, preferably with an inception cohort for the investigation of potroom asthma.

Aluminum↗