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Biomedical subjects

A Lockhart

Publications and source records attributed to A Lockhart.

At least 91 records · Page 5Linked to original sources
PubMed1991

The alpha 1-adrenergic agonist methoxamine and the "loop" diuretic frusemide reduce nasal potential difference.

Pretreatment by inhalation with the alpha 1-adrenergic agonist methoxamine and the "loop" diuretic frusemide reduces the bronchial response to certain airway challenges in asthma. To test whether these drugs may act by altering airway epithelial ion and water transport, their effect on nasal potential difference (PD) when applied topically in eight normal volunteers was measured. For comparison, the effect of the Na(+)-channel blocking drug amiloride and the beta 2-adrenergic agonist salbutamol was also tested. Both methoxamine and frusemide significantly reduced PD: at the highest concentration given (10(-3) mol.l-1), there was a mean drop in PD from baseline of 39.5% following methoxamine treatment (p less than 0.05) and a mean drop of 30.2% following frusemide (p less than 0.05). Neither drug was as effective as amiloride, which caused a mean drop in PD of 27.5% from baseline at 10(-6) mol.l-1 and a drop of 71.6% at 10(-3) mol.l-1 (p less than 0.01 for each concentration). Salbutamol had no significant effect on PD (p greater than 0.05). We conclude that methoxamine and frusemide may derive their protective effect on some bronchial challenge, at least in part, from their effect on airway epithelial ion flux.

Adult↗
PubMed1990

Effects of SK&F 104353, a leukotriene receptor antagonist, on the bronchial responses to histamine in subjects with asthma: a comparative study with terfenadine.

We compared the effects of pretreatment of 800 micrograms of inhaled Smith Kline & French (SK&F) 104353, a leukotriene receptor antagonist, and 120 mg of oral terfenadine on the bronchial responses to inhaled histamine in 12 subjects with asthma. The study took place on 3 different days and was conducted according to a double-blind, crossover, double-dummy, randomized, and placebo-controlled design. There was no difference in baseline and prechallenge FEV1 after placebo, SK&F 104353, and terfenadine administration. The median ratio of the provocative dose causing a 20% fall in FEV1 from baseline (PD20) with terfenadine over PD20 with placebo was 12.36 (range, 3.2 to 30.3; p less than 0.01) and that of PD20 with SK&F 104353 over PD20 with placebo was 1.51 (range, 0.8 to 5.9; not significant). Analysis of individual results demonstrated a shift toward the right of the dose-response curves to histamine with SK&F 104353 compared to that with placebo in three subjects, whereas the active compound did not exhibit any protective effect against histamine in the remaining nine subjects. We conclude that there is a leukotriene component to the bronchial responses to histamine in some, but not all, subjects. This component remains, however, small and does not appear to be clinically important in the population of subjects with asthma that was studied.

Adult↗
PubMed1990

Mechanical effects of PEEP in patients with adult respiratory distress syndrome.

In 10 patients with adult respiratory distress syndrome, we studied the effects on respiratory system mechanics of two levels of positive end-expiratory pressure (PEEP), best PEEP (BP) and half of this value (HBP), using a respiratory inductive plethysmograph (RIP) combined with a super syringe. We found the following. 1) Inflation compliance of pressure-volume (PV) curves did not change significantly. 2) End-expiratory volume increased with HBP and further with BP (278 +/- 186 and 464 +/- 313 ml, respectively, P less than 0.01). This increase was positively correlated with inflation compliance for HBP and BP (r = 0.794, P less than 0.01 and r = 0.876, P less than 0.01, respectively). 3) No dynamic hyper-inflation was detected on mechanical ventilation at zero end-expiratory pressure (ZEEP), and the time constant of the respiratory system was in the normal range (0.79 +/- 0.21 s). 4) Hysteresis of PVrip curves, which were corrected for gas exchange, decreased significantly with PEEP (P less than 0.05). We conclude that PEEP does not change inflation PV curve but induces an increase in intrathoracic volume whose magnitude is related to compliance and PEEP level. The reduction of hysteresis with PEEP suggests less gas trapping and thus a functional improvement.

Adolescent↗
PubMed1990

Inflation of antishock trousers increases bronchial response to methacholine in healthy subjects.

We studied changes in lung volumes and in bronchial response to methacholine chloride (MC) challenge when antishock trousers (AST) were inflated at venous occlusion pressure in healthy subjects in the standing posture, a maneuver known to shift blood toward lung vessels. On inflation of bladders isolated to lower limbs, lung volumes did not change but bronchial response to MC increased, as evidenced by a greater fall in the forced expiratory volume in 1 s (FEV1) at the highest dose of MC used compared with control without AST inflation (delta FEV1 = 0.94 +/- 0.40 vs. 0.66 +/- 0.46 liter, P less than 0.001). Full inflation of AST, i.e., lower limb and abdominal bladder inflated, significantly reduced vital capacity (P less than 0.001), functional residual capacity (P less than 0.01), and FEV1 (P less than 0.01) and enhanced the bronchial response to MC challenge compared with partial AST inflation (delta FEV1 = 1.28 +/- 0.47 liter, P less than 0.05). Because there was no significant reduction of lung volumes on partial AST inflation, the enhanced bronchial response to MC cannot be explained solely by changes in base-line lung volumes. An alternative explanation might be a congestion and/or edema of the airway wall on AST inflation. Therefore, to investigate further the mechanism of the increased bronchial response to MC, we pretreated the subjects with the inhaled alpha 1-adrenergic agonist methoxamine, which has both direct bronchoconstrictor and bronchial vasoconstrictor effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

[Mechanisms of exertion dyspnea in cardiac insufficiency].

Effort dyspnea in cardiac failure corresponds to a subjective perception of difficulty in breathing which is itself secondary to a disproportion between the central bulbar respiratory regulation and the level of pulmonary ventilation attained. In cardiac failure, this situation is the result of dysfunction of both the respiratory apparatus and the skeletal striated muscle during exercise. During exercise a rise in left ventricular end diastolic pressure causes: a reduction in pulmonary compliance. The bronchial and alveolar capillaries drain into the pulmonary veins. The congestion of these capillaries and the resulting oedema makes the lung "stiffer"; an increase in the resistances of the small airways due to direct compression by congested bronchial vessels. The physiological dead space increases: the respiratory muscles ventilate pulmonary zones which are not perfused to no benefit. The reduction of pulmonary compliance, the increased resistances of the airways and of the physiological dead space all contribute to increase the work of the respiratory muscles. In addition to these mechanical phenomena, there is greater stimulation of the respiratory centre in the brain stem by the metabolic abnormalities of the skeletal striated muscles. During effort, they rapidly function under anaerobic conditions and the resulting hyperproduction of lactate and carbon dioxide stimulates the respiratory centres.

Anaerobic Threshold↗
PubMed1990

[Vasomotility of the bronchial circulation in cardiac failure].

The bronchial circulation is a physiological left-to-left shunt; the venous return of the bronchial arteries vascularising the intra-pulmonary bronchi drains directly into the left heart chambers. In cardiac failure, increased left ventricular filling pressures affects the bronchial circulation and causes stasis and congestion. Congestion of the arterial and venous bronchial microcirculation leads to thickening of the bronchial mucosa and submucosa, resulting in a tendency to obstruct small and medium-sized airways. The bronchial circulation can be explored indirectly in cardiac failure by the spirometric response to adrenergic agonists and antagonists administered by inhalation: bronchial vasomotor phenomena explain the symptomatology of cardiac asthma and also seem to play a role in the genesis of the dyspnoea of effort in patients with cardiac failure.

Bronchi↗
PubMed1989

Bronchial effects of alpha 2-adrenoceptor agonists and of other antihypertensive agents in asthma.

The respective prevalence of hypertension and asthma is sufficient for their combined existence to be far from rare. The effects of certain antihypertensive drugs, e.g., alpha 2-adrenoceptor agonists, on the bronchi may be either harmful or beneficial. When inhaled, alpha 2-agonists reduce the immediate bronchial response to allergens, whereas when ingested they aggravate the bronchial response to histamine and all the more so when their effect on the central nervous system is greater. Therefore, there has been much interest in agents such as the new oxazoline derivative, rilmenidine, which has less central effects than clonidine, an imidazoline compound of reference. Calcium antagonists inhibit smooth muscle contraction and release of mast cell inflammatory mediators. In asthmatic subjects, their short-term administration leads to a modest improvement in spontaneous bronchial obstruction, has only a partial protective action against various nonspecific or allergenic stimuli, and slightly reinforces the beneficial effect of beta 2-agonists. Beta-adrenoceptor antagonists aggravate bronchial obstruction and nonspecific bronchial hyperreactivity in asthmatic subjects. These harmful effects are dose-dependent, have even been reported after the administration of eyedrops, and are common to all beta-blockers. Angiotensin-converting enzyme inhibitors increase bronchial hyperreactivity in patients who develop cough during treatment and may, in certain cases, worsen or even induce asthma, probably by opposing inactivation by hydrolysis of tachykinins and of bradykinins.

Adrenergic alpha-Agonists↗
PubMed1989

Bronchial hyperresponsiveness to methacholine in patients with impaired left ventricular function.

To elucidate the pathogenesis of bronchospasm in congestive heart failure, we studied 23 patients with chronic impairment of left ventricular function due to coronary artery disease or dilated cardiomyopathy. In 21 of them we found marked bronchial hyperresponsiveness to methacholine. The mean dose (+/- SD) of methacholine that elicited a 20 percent decrease in the forced expiratory volume in one second (FEV1) was 421 +/- 298 micrograms, nearly the same as in patients with symptomatic asthma. In contrast, there was no bronchial response to methacholine in 9 of 10 patients who had coronary artery disease but normal left ventricular function. Administration of the bronchodilator albuterol led to a partial (43 percent) reversal of the methacholine-induced bronchial obstruction. In 12 patients, pretreatment with the alpha-adrenergic agonist methoxamine (10 mg by inhalation), a potent vasoconstrictor, fully prevented the methacholine-induced decrease in FEV1. The protective effect of methoxamine was blocked by the alpha-adrenergic antagonist phentolamine in all six patients who received this agent. We conclude that bronchial hyperresponsiveness to cholinergic agonists is frequent in patients with impaired left ventricular function and may contribute to the wheezy dyspnea commonly observed in such patients. The bronchoconstriction may be mediated at least in part by dilatation of the bronchial vessels.

Adult↗
PubMed1989

[Polyendocrinopathy combined with primary pulmonary arterial hypertension].

We report the case of a woman who had premature menopause, adrenal insufficiency and hypothyroidism by peripheral gland lesion, all most probably due to an autoimmune disorder, and who subsequently developed primary pulmonary arterial hypertension. The causes of this hypertension are ill-defined, but an autoimmune origin has often been envisaged since primary pulmonary arterial hypertension is not unfrequently associated with connective tissue diseases. Its association with an autoimmune polyendocrinopathy has only been reported, to our knowledge, on four occasions; in all 4 cases the thyroid gland was involved, and a connective tissue disease was present in 3 of them. Our case, which includes adrenal insufficiency and premature menopause is, as far as we know, unique. The possible link between these various diseases is their autoimmune nature, in which case primary pulmonary arterial hypertension would belong to the category of organ-specific autoimmune diseases. Our case supports the hypothesis that a number of isolated primary pulmonary arterial hypertensions could be of autoimmune origin.

Autoimmune Diseases↗
PubMed1989

Serum thymic hormone thymulin activity is normal in children with asthma.

In asthma, it has been hypothesized that suppressor T-lymphocytes play a protective role and have been reported to be functionally abnormal. Thymic hormone thymulin plays a role in the differentiation of T-lymphocytes and plasmatic thymulin concentration and is related to the functional state of the thymus. To assess the participation of the thymus in the impairment of T-lymphocyte function, we measured plasma thymulin activity in children with allergic asthma (N = 40). The plasma thymulin activity was compared with plasma thymulin activity of children with nonallergic asthma (N = 6), children with atopic dermatitis (N = 9) or allergic rhinitis (N = 7), and in age-matched healthy control children (N = 18) (age range of children studied, 2 to 19 years). Thymulin activity was found within the normal range (1/16 to 1/64) in all control children and in all children with allergic asthma and allergic rhinitis, as well as in all children with intrinsic asthma and atopic dermatitis. Our findings are at variance with the low thymulin activity previously reported in allergic asthma, and we could not explain these discrepancies. (Both studies used the same bioassay, and the population studied did not appear to be different.) T-lymphocyte abnormalities in subjects with asthma must be assessed by other means than measurement of thymic function.

Adolescent↗
PubMed1989

Chronobiological study of the relationship between dyspnoea and airway obstruction in symptomatic asthmatic subjects.

1. We performed a chronobiological study of the relationship between peak expiratory flow rate (PEFR) and magnitude of dyspnoea in 35 symptomatic asthmatic patients to determine how accurately asthmatic subjects assess spontaneous airway obstruction and whether this accuracy varies throughout the 24 h period and depends on characteristics of the subjects or asthma. 2. At 07.00, 11.00, 15.00, 19.00 and 23.00 hours on 8 consecutive days in their ordinary environment and under their usual drug regimen, the subjects first rated their dyspnoea with a visual analogue scale and immediately after recorded their PEFR. 3. The linear regression coefficients between dyspnoea score and PEFR for the 35 subjects were continuously distributed between -0.93 and +0.21, with most r values ranging from -0.9 to -0.5. The group median r values calculated at each time point showed that strongest correlation between dyspnoea score and PEFR occurred at 7 h. which coincided with the lowest PEFR values. 4. We chose r = -0.7 (r2 = 0.5) as a limit to distinguish good perceivers (-1 less than r less than or equal to -0.7) from bad perceivers of airway obstruction. These two populations differed only by a higher variability of both PEFR and dyspnoea score in good than in bad perceivers, but not for severity, duration or treatment of asthma, absolute value of dyspnoea score, age or sex. 5. Our study quantified an important intra- and between-subject variability in the accuracy of perception of spontaneous airway obstruction in asthmatic subjects which seems to be unrelated to most characteristics of asthma.

Adult↗
PubMed1989

Ventilatory response to carbon dioxide during extradural anaesthesia with lignocaine and fentanyl.

Twenty-seven patients undergoing extracorporeal shock-wave lithotripsy or knee arthroscopy received extradural anaesthesia with 2% lignocaine plus adrenaline 1 in 200,000. They were allocated randomly to three groups, one receiving no fentanyl (n = 6), the two others receiving fentanyl 50 micrograms either extradurally (n = 15) or i.v. (n = 6). Three tests of sensitivity to carbon dioxide (Read's method) were performed successively on each patient: before operation and at 1 and 2 h after the extradural injection. Whereas lignocaine and adrenaline alone had no significant effects on basal ventilation and the ventilatory response to carbon dioxide, extradural fentanyl caused a slight reduction in resting ventilatory rate and ventilation at 1 and 2 h with no change in resting end-tidal carbon dioxide concentration. In addition, the slope of the ventilatory response to carbon dioxide was reduced slightly at 1 h and ventilation at end-tidal PCO2 of 7.3 kPa was reduced also at 1 and 2 h. Conversely, the same dose of fentanyl i.v. had lesser and shorter effects on ventilation at rest and during carbon dioxide rebreathing. Our results show that fentanyl 50 micrograms given extradurally caused slight ventilatory depression which is probably clinically unimportant.

Adult↗
PubMed1989

[Sulfidopeptide leukotrienes and asthma].

The role of sulfidopeptide leukotrienes in asthma alone or in association with other mediators is still debated. Sulfidopeptide leukotrienes (s-LT) C4, D4 and E4 are 5-lipoxygenase derivatives of membrane arachidonic acid. All s-LT contract bronchial smooth muscle in vitro and provoke an acute bronchial obstruction in vivo in both healthy and asthmatic subjects. Numerous cells, including mast cells, alveolar macrophages, polynuclear basophils and eosinophils, are capable of secreting s-LT following such diverse stimuli as allergen exposure, platelet activating factor and calcium ionophore A 23187. In addition to constricting bronchial smooth muscle, s-LT promote the occurrence of mucosal oedema increase micro-vascular permeability in the bronchial wall, and cause hypersecretion of mucus by tracheo-bronchial glands. These effects lead to worsening of airways obstruction. s-LT increase non specific bronchial hyper-responsiveness. Clinical trials aiming to test the efficacy of new anti-leukotrienes are currently under way. In general these products have a real antagonistic effect on exogenous s-LT. Their efficacy vis-a-vis other types of stimulus such as allergens, histamine and exercise does not seem to be constant and depends largely on the composition and perhaps the route of administration (inhaled versus oral). The contribution of s-LT as part of the therapeutic arsenal for the long term treatment of asthma remains to be established.

Asthma↗
PubMed1989

[Current data on non-specific bronchial hyperreactivity].

It is not necessary to have excessive shortening of smooth muscle to cause the disproportionate bronchial obstruction which is a characteristic of bronchial hyperresponsiveness (HRB). There are also no convincing arguments favouring increased contractility in vivo of airway smooth muscle in subjects having HRB in vivo. Excessive bronchial obstruction seems to be linked to factors increasing the effects of smooth muscle contraction: hypertrophy of smooth muscle, excessive thickening of the wall linked to pre-existing bronchial lesions, vasodilatation and acute parietal oedema caused by stimuli used to demonstrate HRB. Activation of effectors involved in HRB may be by direct through action on the post junctional receptors, indirect through local liberation of paracrine mediators, or stimulation of bronchial receptors causing a reflex increase in vagal tone. Various techniques have been used to cause HRB in man and in different of animal species. Whether the method employed damages the epithelium, causes an inflammatory infiltrate or interfere with the degradation of paracrine mediators, HRB is both transient and weak. Thus experimental HRB does not open pathways for the research into the cause of asthma. On the other hand these studies permit a better understanding of factors which aggravate human asthma. Even the causes of human HRB are poorly understood. The prevalence of HRB is greater than of asthma, there is no narrow correlation between the severity of asthma and the intensity of HRB and there are arguments in favour of the familial segregation of HRB. The question is posed, therefore, whether HRB is similar to atopy with a genetic factor determining the predisposition to the expression of asthma under the influence of environmental factors.

Airway Obstruction↗
PubMed1989

Diagnostic value of reversibility of chronic airway obstruction to separate asthma from chronic bronchitis: a statistical approach.

Our aim was to assess the usefulness of tests of reversibility of airways obstruction (AO) in the differential diagnosis of asthma (A) and chronic bronchitis (CB). We selected on strict clinical criteria 20 CB and 32 A patients with stable AO and measured maximal forced expiratory flows before and after increasing doses of inhaled salbutamol. The highest sensitivity (Se), specificity (Sp) and likelihood ratio (L) were obtained when the improvement in forced expiratory volume in one second (FEV1) was expressed as a percentage of predicted FEV1. Se, Sp and L were 0.97, 0.95 and 19.3 (highest possible L: 20) for an increase of 10% of predicted FEV1 on 0.2 mg of salbutamol, and 1.0, 1.0 and 20, respectively, for an increase of 15% on 1 mg of salbutamol. Conversely, L was only 2.8 when the widely used increase in FEV1 of 20% over baseline was tested. In a second group of 42 unselected patients, who were referred to the laboratory for routine lung function testing with a presenting diagnosis of A or CB, L was only 5.5 when the 10% increase in predicted FEV1 was used and even lower for the classical 20% increase over baseline FEV1. We submit that routine tests of reversibility of AO have little diagnostic usefulness in unselected patients with AO and that the commonly used criteria of 15 or 20% increase in FEV1 over baseline are of no value in separating A from CB.

Albuterol↗