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Biomedical subjects

D L Maxwell

Publications and source records attributed to D L Maxwell.

At least 19 recordsLinked to original sources
PubMed1991

Compensatory growth in fibrotic lung injury.

We induced severe left-sided lung fibrosis by the unilateral endobronchial instillation of paraquat (1.0 mg/kg) into the left lungs of adult Fischer 344 male rats. Growth of the contralateral lung as well as its proliferative activity were measured 6 or 14 days later. Whereas the left lung underwent severe fibrosis and shrinkage with more than 85% reduction in lung volume, the right lung more than doubled in size. In addition, there was a significant increase in total protein content, DNA content, and DNA synthesis. We conclude that unilateral lung injury resulting in ipsilateral fibrosis and loss of parenchyma is associated with compensatory growth of the contralateral lung.

Animals↗
PubMed1990

Adverse effects of inhaled corticosteroids.

Corticosteroids have a significant role in the management of asthma due to their powerful anti-inflammatory actions. However, when given orally, they cause significant and unwanted side-effects. Early attempts to circumvent these side-effects were largely unsuccessful. Recently, new synthetic corticosteroids have been developed that have powerful topical action but weak generalised effects due to rapid systemic metabolism. These new compounds provide adequate control of airways' obstruction in almost all asthmatics. Oral candidiasis may occur but can generally be controlled by adjusting the frequency of dosage and changing delivery systems. In high doses, there is biochemical evidence of adrenal suppression, but the clinical importance of this is not yet clear and there is no evidence of a significant effect on growth in children. High dose inhaled corticosteroids have been shown to affect biochemical indices of bone turnover in the short term. The long term clinical consequences of this are still under evaluation. Inhaled corticosteroids have provided a significant advance in the management of asthma, but physicians need to remain alert for the possibility of systemic side effects when used in high doses for long periods of time.

Administration, Inhalation↗
PubMed1990

Skin responses to intradermal histamine and leukotrienes C4, D4, and E4 in patients with chronic idiopathic urticaria and in normal subjects.

Mast cell inflammatory mediators, such as histamine, and newly formed compounds, such as the leukotrienes, cause wheal and flare when they are injected intradermally into normal subjects and may therefore play a role in the formation of urticaria. The effects of intradermal injections (50 microliters) of six different concentrations of histamine (range, 3.3 x 10(-4) to 3.3 x 10(-9) mol/L) and the leukotrienes C4, D4, and E4 (range, 2 x 10(-4) to 2 x 10(-9) mol/L) have been compared in 10 normal subjects and in 10 patients with chronic idiopathic urticaria. Wheal-and-flare sizes were measured at timed intervals up to 4 hours, and area under the curve for each response over time was calculated. There were no significant differences in leukotriene-induced responses between groups. Maximum sizes of histamine-induced wheal and flare were similar in each group of subjects. There were, however, significant increases in mean areas under the response curve of histamine wheal and flare in the patients with urticaria (wheal, p less than 0.001; flare, p less than 0.001; analysis of variance). These findings demonstrate a prolongation of skin responses to histamine in patients with urticaria and suggest an impaired clearance of histamine (or other vasoactive agents released by histamine) from the skin of these patients.

Analysis of Variance↗
PubMed1990

Ventilatory effects of substance P, vasoactive intestinal peptide, and nitroprusside in humans.

Animal studies suggest that the neuropeptides, substance P and vasoactive intestinal peptide (VIP), may influence carotid body chemoreceptor activity and that substance P may take part in the carotid body response to hypoxia. The effects of these peptides on resting ventilation and on ventilatory responses to hypoxia and to hypercapnia have been investigated in six normal humans. Infusions of substance P (1 pmol.kg-1.min-1) and of VIP (6 pmol.kg-1.min-1) were compared with placebo and with nitroprusside (5 micrograms.kg-1.min-1) as a control for the hypotensive action of the peptides. Both peptides caused significantly less hypotension than nitroprusside. Substance P and nitroprusside caused significantly greater increases in ventilation and in the hypoxic ventilatory response than VIP. No changes were seen in hypercapnic sensitivity. The stimulation of ventilation and the differential effects on ventilatory chemosensitivity that accompanied hypotension are consistent either with stimulation of carotid body chemoreceptor activity or with an interaction with peripheral chemoreceptor input to the respiratory center, as is seen in animals. The similar cardiovascular but different ventilatory effects of the peptides suggest that substance P may also stimulate the carotid body in a manner independent of the effect of hypotension. This is consistent with a role of substance P in the hypoxic ventilatory response in humans.

Adult↗
PubMed1989

The value of ear lobe oximetry in the assessment of disability in asbestos-related disease.

Thirty-four asbestos workers, with either asbestosis, diffuse pleural thickening, calcified pleural plaques, or with comparable asbestos exposure but no evidence of asbestos-related disease and seven normal controls underwent a progressive exercise test. The subjects were categorized on the basis of lung function tests and PA chest X-rays. During the exercise test oxygen saturation was measured continuously by an ear lobe oximeter. The asbestosis and diffuse pleural thickening groups showed significant oxygen desaturation on exertion, confirming that both these conditions give rise to appreciable respiratory disability.

Asbestosis↗
PubMed1989

Atrial natriuretic peptide: physiological release associated with natriuresis during negative pressure breathing in man.

1. Negative pressure breathing was one of the first physiological tools used to study the renal effects of redistribution of the blood volume from the peripheries to the thorax. The recent discovery of a putative natriuretic hormone (atrial natriuretic peptide, ANP) in cardiac atrial tissue has rekindled interest in the effect of the cardiovascular system on renal function. We have therefore studied the effects of this physiological manoeuvre on plasma ANP concentrations and renal responses. 2. Plasma concentrations of ANP, plasma renin activity and plasma aldosterone concentration were measured during an 80 min period of negative pressure breathing at -12 cmH2O pressure in six hydrated normal subjects. Identical control studies were performed in the same subjects at at least 1 week apart. 3. Negative pressure breathing resulted in a natriuresis and diuresis which were associated with a significant rise in plasma ANP concentration. The natriuresis occurred despite an increase in plasma renin activity and in plasma aldosterone concentration. 4. These findings, under specific carefully controlled conditions, support the previously contentious postulate that negative pressure breathing enhances sodium excretion, in addition to its well-recognized diuretic effect. They add further weight to the hypothesis that expansion of the central blood volume is an important stimulus to the release of ANP from the heart (acting by way of atrial distension), and suggest that changes of plasma ANP concentration may have induced the natriuresis which occurred in the face of a modest activation of the sodium-retaining renin-aldosterone system.

Adult↗
PubMed1988

Histamine-induced airway obstruction in infancy: changes in oxygenation.

In seven recurrently wheezy infants who were found to be histamine-responsive during bronchial challenge, changes in oxygenation (by oximeter and transcutaneous PO2 electrode) and carbon dioxide tension (by transcutaneous PCO2 electrode) were concurrently measured. The histamine challenge consisted of doubling concentrations administered by nebulizer for 1 min at 5-min intervals, up to a maximum concentration of 8 g/L. The response was determined from maximum expiratory flow using a squeeze technique. Significant mean reductions in transcutaneous oxygen tension of 0.9 +/- 0.7 kPa and 1.5 +/- 0.9 kPa were seen respectively at half the provoking concentration and at the provoking concentration of histamine that caused a significant reduction in maximum expiratory flow rates. The reduction in oxygen saturation of 4.8 +/- 3% was also significant at the provoking concentration. No significant change in transcutaneous carbon dioxide tension was seen. These results suggest that acute histamine-induced airway obstruction causes significant ventilation/perfusion disturbance in wheezy infants. Oxygen monitoring should be performed during bronchial challenge tests in infancy.

Blood Gas Monitoring, Transcutaneous↗
PubMed1988

Lung volume changes during histamine-induced bronchoconstriction in recurrently wheezy infants.

Respiratory inductance plethysmography was used to estimate changes in functional residual capacity (FRC) in seven recurrently wheezy infants undergoing histamine challenge. Inhalations of normal saline and doubling concentrations of histamine were given up to and including the provoking concentration (PC) that caused a significant fall in maximum flow at FRC (Vmax FRC) as measured using the inflatable jacket technique. Below the PC histamine in general caused small increases in FRC [9.4 +/- 7.6 ml (mean +/- SD) at half the provoking concentration]. However, larger increases were seen at the provoking concentration (26.6 +/- 15.6 ml). Inspection of flow-volume curves obtained before and after the larger changes in FRC suggested that the reduction in airflow measured by the change in Vmax FRC was underestimated.

Bronchial Provocation Tests↗
PubMed1988

The effect of almitrine bismesylate on the steady-state responses of arterial chemoreceptors to CO2 and O2 in the cat.

The interaction between almitrine bismesylate, a pharmacological stimulant of peripheral chemoreceptors, and varying levels of oxygen (PO2 50-600 Torr) and carbon dioxide (PCO2 10-65 Torr) on steady state carotid chemoreceptor discharge was investigated in pentobarbitone-anaesthetised cats. Almitrine was given as constant intravenous (50 micrograms/kg per min for 4 min) and intracarotid infusions (4-16 micrograms/kg per min) at different levels of alveolar PO2 and PCO2. Almitrine always excited discharge. The intracarotid infusions at the lower infusion rate (4-8 micrograms/kg per min) and the i.v. infusions increased the slope of the isoxic response to CO2. This effect could be reversed by raising PO2 to high levels. Higher infusion rates of almitrine (16 micrograms/kg per min) displaced the CO2 response curve upwards but did not increase its slope above that obtained in control conditions at end-tidal PO2 of 50 Torr. However, as these higher infusion rates caused levels of discharge greater than those achieved during control conditions, their effects on control CO2 sensitivity could not be ascertained. Our results suggest that almitrine excites carotid body chemoreceptors by a mechanism similar to that of hypoxia and not like that of carbon dioxide.

Almitrine↗
PubMed1987

Ventilatory effects of inhaled capsaicin in man.

Nebulised capsaicin (10(-7) M) was inhaled by 8 normal subjects to study its effects on the pattern of breathing. When compared to the diluent alone capsaicin increased mean inspiratory flow, a reflection of central inspiratory drive (mean increase: 25 +/- 6%, SEM, p less than 0.01), with a trend to increasing ventilation through more rapid but not more shallow breathing. If capsaicin selectively stimulates non-myelinated fibres in the lung in man as it does in dogs, these results suggest that such stimulation in man can alter the pattern of breathing.

Adult↗
PubMed1987

Autoregulation of retinal blood flow in diabetic retinopathy measured by the blue-light entoptic technique.

Autoregulation of retinal blood flow was measured in 23 diabetic patients, 9 with nonproliferative retinopathy, 9 with proliferative retinopathy, and 5 with photocoagulated retinopathy. Three of the proliferative patients were studied on two occasions, at the proliferative stage and after photocoagulation. The stimuli to autoregulation used were isocapnic hyperoxia and hypoxia. Flow velocity of leukocytes in the perifoveal circulation was measured using the blue-field entoptic technique, and retinal artery and vein diameters were measured using a computerized digitizing system. Results under conditions of isocapnic hypoxia showed a mean increase in flow velocity of 41.0 +/- 33.0% (P less than 0.05) in nonproliferative retinopathy, 3.5 +/- 17.0% (not significant) in proliferative retinopathy, and 30.0 +/- 17.0% (P less than 0.05) after photocoagulation. In hyperoxia, flow velocity fell by a mean of 21.0 +/- 21.6% (P less than 0.05) in nonproliferative retinopathy, 33.0 +/- 19.9% (P less than 0.005) in proliferative retinopathy, and 21.0 +/- 26.0% (not significant) in photocoagulated retinopathy. The results are compared with a group of nondiabetic subjects reported previously.

Adult↗
PubMed1987

Acute ventilatory changes during i.v. induction of anaesthesia with thiopentone or propofol in man. Studies using inductance plethysmography.

We have compared the acute ventilatory changes during induction of anaesthesia with equipotent doses of thiopentone and propofol in 12 premedicated female patients. Using ventilatory inductance plethysmography we have shown that both agents depress respiration to a similar and significant degree (P less than 0.001). However, although the functional residual capacity was reduced in patients receiving propofol, it increased slightly after induction with thiopentone (P less than 0.05).

Adult↗
PubMed1987

Circulatory and respiratory effects of infused adenosine in conscious man.

1. The nucleoside, adenosine, was infused into six conscious healthy male subjects at rates up to 100 micrograms kg-1 min-1. 2. Compared with a control 0.9% saline infusion, adenosine in all subjects caused dose dependent increases in heart rate, skin temperature and minute ventilation with corresponding falls in PaCO2, estimated transcutaneously. 3. There were no changes in systemic blood pressure, airways resistance (measured by forced partial expiratory manoeuvres), or plasma catecholamines. At the top infusion rates subjects experienced tolerable chest and abdominal discomfort. 4. These findings conflict with some previous studies in anaesthetised man and animals, in which higher doses of adenosine and its long acting analogues have caused hypotension and central respiratory depression. 5. Although some of these changes may have been due to symptoms, the cardiovascular changes may have been due to a vasodilator action and the respiratory stimulation may have been due to an action on peripheral chemoreceptors.

Adenosine↗
PubMed1987

Contrasting effects of two xanthines, theophylline and enprofylline, on the cardio-respiratory stimulation of infused adenosine in man.

Six normal male subjects, ages 28-40 years, were studied on separate days during increasing infusions with adenosine, 40-120 micrograms kg-1 min-1, before and during infusions of two xanthine derivatives, theophylline (mean plasma concentration 9 mg l-1) and enprofylline (mean plasma concentration 3 mg l-1). The study was double-blind, randomized, placebo controlled. Cardio-respiratory variables were measured non-invasively. Adenosine by itself increased heart rate (P less than 0.05), skin temperature (P less than 0.05), resting minute ventilation (P less than 0.01) and decreased estimated Pa, CO2 (P less than 0.01). Compared with placebo enprofylline increased heart rate (P less than 0.05) and shifted the heart rate and ventilation dose-response curves of adenosine upwards (P less than 0.05 and P less than 0.02, respectively). Theophylline did not by itself affect heart rate but significantly (P less than 0.05) reduced the heart rate response to adenosine. Compared with placebo theophylline caused a small increase in minute ventilation (P less than 0.05) and flattened the dose-response curves of the effects of adenosine on ventilation (P less than 0.01) and Pa, CO2 (P less than 0.01). Theophylline also reduced abdominal and chest discomfort caused by adenosine permitting significantly (P less than 0.05) higher infusion rates of adenosine. These findings suggest that, with equipotent bronchodilating plasma concentrations, theophylline can inhibit while enprofylline augments some cardio-respiratory stimulant effects of infused adenosine in man.

Adenosine↗
PubMed1987

Hypoxaemia in wheezy infants after bronchodilator treatment.

The response of the bronchi to nebulised salbutamol was measured in five recurrently wheezy infants. Changes in oxygenation (measured by pulse oximeter and transcutaneous PO2 electrodes) and carbon dioxide (measured by transcutaneous PCO2 electrode) were recorded at the same time. Neither nebulised saline nor salbutamol caused any changes in the measurements of airway function. A significant drop in mean oxygen saturation of 2% and of transcutaneous oxygen tension of 1.3 kPa occurred after nebulised salbutamol. No significant change occurred in measurements of transcutaneous carbon dioxide tension, nor was there any significant change in any of these measurements after 2.5 ml of nebulised saline had been given as a control. These results suggest that nebulised salbutamol may cause significant hypoxaemia, in wheezy infants probably by inducing ventilation/perfusion disturbance.

Albuterol↗
PubMed1987

Effect of substance P on cardiovascular and respiratory function in subjects.

The effect of substance P (SP), administered both intravenously and by inhalation, has been studied in normal and asthmatic humans. Intravenous infusion of SP (0.2-3.3 pmol X kg-1 X min-1) achieving a plasma concentration of SP between 5 and 25 pM produced vasodilatation (mean +/- SD), maximal increase in skin temperature (0.9 +/- 0.3 degree C) (P less than 0.05), and fall in diastolic blood pressure (8.5 +/- 2.9 mmHg) (P less than 0.05) associated with an increase in heart rate (15 +/- 10 beats/min) (P less than 0.05). All subjects had a fall in Vp30 (airflow at 70% of forced vital capacity measured from total lung capacity after a forced partial expiratory flow maneuver) at low infusion rate (P less than 0.05) and a significant rise at the highest infusion rate (P less than 0.05). Ventilation at rest and when stimulated by transient hypoxia increased (mean increase in resting ventilation 0.73 +/- 0.4 l/min and mean percent increase in transient ventilatory hypoxic response 41 +/- 27%). There was a small nonsignificant increase in plasma norepinephrine but no change in epinephrine or histamine. Inhaled SP, up to 0.7 mumol, caused a small nonsignificant fall in airway function in asthmatic subjects. SP has demonstrable effects on vascular smooth muscle and control of ventilation but at the doses studied had little effect on airway function.

Adult↗