Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Beta adrenoceptor function in central airway smooth muscle of patients with chronic airflow obstruction was investigated by radioligand binding studies and isoprenaline relaxation experiments. Receptor characteristics were determined in tracheal smooth muscle preparations obtained at necropsy from 12 patients and in bronchial tissue obtained at thoracototomy from 21 patients with chronic airflow obstruction. Receptor characteristics were compared with those obtained in airway tissue preparations from 65 control subjects without chronic airflow obstruction. The number of beta adrenoceptors, their binding affinity for the radioligand [125I]-(-)-cyanopindolol, and the tissue binding characteristics of isoprenaline were similar in tissue from patients with chronic airflow obstruction and from control subjects. Isoprenaline induced relaxation of tracheal smooth muscle without precontraction by methacholine showed slightly (though not significantly) less sensitivity to isoprenaline in patients with chronic airflow obstruction than in control subjects (mean (SEM) pD2--the negative logarithm of the concentration producing 50% relaxation--6.32 (0.16) v 6.62 (0.15)). The same pattern of pD2 values was found in segmental bronchial strips without precontraction by methacholine (chronic airflow obstruction 6.55 (0.27), control 7.14 (0.12)). Isoprenaline relaxation in segmental bronchial strips when contracted maximally was significantly less in the patients with airflow obstruction than in the control subjects (pD2 value 5.99 (0.18) v 6.45 (0.07)). These results suggest that beta adrenoceptors in airway smooth muscle of patients with chronic airflow obstruction are not abnormal in number or in binding affinity but that there is less effective coupling between components of the relaxant system distal to the beta adrenoceptor. The possibility that the reduced isoprenaline sensitivity is a consequence of previous bronchodilator treatment cannot be excluded.
Thorax 1989 Jan
PMID:Beta adrenoceptor binding and induced relaxation in airway smooth muscle from patients with chronic airflow obstruction. 253 44

Ten patients with exercise induced asthma, in whom inhaled nedocromil sodium 4 mg by metered dose inhaler attenuated the exercise fall in forced expiratory volume in one second (FEV1) by at least 40%, participated in a double blind dose response study to compare the protective effect of nedocromil sodium given 15 minutes before exercise challenge via a nebuliser (Wright) in concentrations of 0.5, 5, 10, and 20 mg/ml with that of placebo (saline). Response was assessed as the maximum fall in FEV1 after the patient had run on a treadmill for six to eight minutes. Plasma concentrations of nedocromil sodium were measured at the time of challenge. After exercise challenge the mean (SEM) maximum percentage falls in FEV1 were 30.3 (1.6) for the control run and 28.0 (4.1) after placebo. The percentage fall was attenuated by pretreatment with all concentrations of nedocromil sodium to 12.8 (2.8), 11.2 (2.1), 12.8 (2.1), and 14.1 (3.5) for the 0.5, 5, 10, and 20 mg/ml concentrations respectively (p less than 0.001). There were no significant differences between the different nedocromil concentrations. Mean plasma concentrations of nedocromil were proportional to dose. Thus concentrations of nebulised nedocromil sodium that ranged from 0.5 to 20 mg/ml gave a similar degree of protection (50-60%) against exercise induced asthma. This appears to be the maximum protection that can be achieved with nedocromil sodium and is similar to the protection obtained with 4 mg nedocromil administered by metered dose aerosol.
Thorax 1989 Oct
PMID:Dose-response study of nebulised nedocromil sodium in exercise induced asthma. 255 7

A radiotracer technique has been used to assess aerosol delivery from a pressurised metered dose inhaler, used both with and without a 10 cm cylindrical spacer attachment (Syncroner), which has an open section in its upper surface. The radionuclide technetium-99m (99mTc) was added to sodium cromoglycate in a canister (Intal inhaler; 1 mg/puff); in vitro studies with a multistage liquid impinger showed that the radiolabel acted as a marker for the presence of drug over a wide range of particle sizes. Ten healthy volunteers were studied after they had inhaled from (1) a metered dose inhaler alone (slow inhaled flow rate, about 25 l/min); (2) metered dose inhaler plus spacer (slow flow rate); and (3) metered dose inhaler plus spacer (fast inhaled flow rate, about 100 l/min). Inhalation was coordinated with firing the spray and was followed by 10 seconds' breath holding. With the metered dose inhaler alone a mean 11.0% (SEM 1.4%) of the dose reached the lungs, compared with significantly higher doses for slow (16.1% (2.2%] and fast (13.3% (1.7%] inhalations through the spacer. The distribution pattern within the lungs was significantly more peripheral after slow inhalation. Oropharyngeal deposition was halved by the spacer. The open spacer should teach patients good coordination and delivers more aerosol to the lungs than a correctly used metered dose inhaler.
Thorax 1989 Sep
PMID:Pressurised aerosol deposition in the human lung with and without an "open" spacer device. 258 5

The relation between pulmonary distensibility, lung volume, and elastic recoil pressure was examined in 45 patients (38 men) with cryptogenic fibrosing alveolitis (mean age 61 (SD 14) years). Exponential analysis of static pressure-volume data obtained during deflation of the lungs gave the exponent K, an index of the distensibility of the remaining inflatable lung tissue. Total lung capacity (TLC) was measured in a body plethysmograph or by nitrogen washout. The results were compared with values obtained in 147 healthy subjects (95 men), of mean age 39 (SD 16) years. Fibrosing alveolitis decreased K by 0.62 (SEM 0.04) kPa-1. This decrease was approximately equal to 2 SD of the regression of log K on age in healthy subjects. TLC was decreased to a mean of 70% (SD 14%) predicted in the patients with fibrosing alveolitis. Lung recoil pressure at maximum inspiration was about twice the expected value and regression analysis showed that most of this increase was related to the decreased K rather than to the decreased TLC. In the men with fibrosing alveolitis the regression of height standardised TLC (TLC/Ht3) on K was significant (p less than 0.02); the regression slope was similar to that for 95 healthy men, but was displaced to a smaller lung volume. The dependence of TLC/Ht3 on K is consistent with the close relation between K and peripheral airspace size found in normal lungs. In fibrosing alveolitis decreased pulmonary distensibility probably reflects a decrease in airspace size, whereas most of the decrease in lung volume reflects the loss of inflatable tissue in the fibrotic process.
Thorax 1989 Sep
PMID:Decreased pulmonary distensibility in fibrosing alveolitis and its relation to decreased lung volume. 258 9

Platelet activating factor, a potent mediator of inflammation, causes a sustained increase in airway responsiveness to methacholine in man and has been implicated in asthma. The effect of the beta 2 agonist salbutamol (200 micrograms by inhalation) on platelet activating factor induced bronchoconstriction and airway hyperresponsiveness was studied in seven normal subjects in a double blind, crossover study. Salbutamol only partially inhibited the platelet activating factor induced fall in partial flow at 30% of vital capacity (Vp30) (mean percentage fall 47.6 (SEM 7.9); p less than 0.001), whereas it completely blocked a similar degree of bronchoconstriction induced by methacholine. Salbutamol did not prevent the accompanying transient flushing and chest irritation and did not affect the transient neutropenia (mean % fall 69.5 (13.6); p less than 0.01) or the rebound neutrophilia (mean % increase 84.7 (24.7); p less than 0.05) that followed platelet activating factor. There was an increase in the airway responsiveness to methacholine following inhalation of platelet activating factor, the maximum mean change being a three fold increase in PC40 (the provocative concentration of methacholine causing a 40% fall in Vp30) on day 3 (p less than 0.01). Salbutamol caused a significant attenuation of this response on day 3 (p less than 0.02) but had no significant effect on days 1 and 7. Thus a therapeutic dose of salbutamol caused partial inhibition of platelet activating factor induced bronchoconstriction and had a minimal effect on the increased bronchial responsiveness following platelet activating factor.
Thorax 1989 Feb
PMID:Effects of salbutamol on bronchoconstriction, bronchial hyperresponsiveness, and leucocyte responses induced by platelet activating factor in man. 264 45

The effects of inhaled platelet activating factor were compared with those of inhaled methacholine (control) on airway calibre, airway responsiveness to methacholine and isoprenaline, and circulating cells in eight subjects with mild, stable asthma. Platelet activating factor was given in six doses at 15 minute intervals and airway response measured as change in partial expiratory flow at 30% of vital capacity (Vp30). Platelet activating factor caused a fall in Vp30, the mean (SEM) maximum percentage fall being 28.9 (4.2) five minutes after the first dose (12 micrograms) and 50.9 (8.0) after the second dose (24 micrograms). Tachyphylaxis occurred, however, with the four subsequent doses of inhaled platelet activating factor. There was transient neutropenia after the first dose, from a mean of 3.6 (0.2) x 10(9) to 2.2 (0.5) x 10(9) neutrophils/l; this response also showed tachyphylaxis with subsequent doses. The mean PC40 (the concentration of methacholine needed to cause a 40% fall in Vp30) was unchanged one, three, and seven days after administration of platelet activating factor. There was no significant correlation between baseline PC40 methacholine and the maximal fall in Vp30 after either the first (12 micrograms) or the second dose (24 micrograms) of platelet activating factor. The control challenge with methacholine produced a degree of bronchoconstriction similar to that of platelet activating factor but was not associated with any significant change in bronchial responsiveness or in circulating cells. The bronchodilator response to inhaled isoprenaline measured three days after inhalation of platelet activating factor and of methacholine was similar after the two challenges. Thus asthmatic subjects who are hyperresponsive to methacholine show a similar bronchoconstrictor response to platelet activating factor, as has been observed in normal subjects; overall this did not cause airway hyperresponsiveness to methacholine.
Thorax 1989 Feb
PMID:Effects of platelet activating factor on airway calibre, airway responsiveness, and circulating cells in asthmatic subjects. 264 46

Lung volumes and arterial blood gas tensions in patients undergoing coronary artery surgery were compared in 77 patients given an internal mammary artery graft (group 1) and 33 patients given a saphenous vein graft only (group 2). Patients in both groups developed a severe restrictive ventilatory defect after surgery, more pronounced in those receiving an internal mammary artery graft. Mean (SEM) vital capacity in groups 1 and 2 was reduced to 36% (1.2%) and 45% (2.0%) of preoperative values on the second postoperative day (1.56 and 1.85 1 respectively), with some recovery by day 4 to 56% (1.2%) and 63% (2.1%) of preoperative values. The mean (SEM) arterial oxygen tension was 7.34 (0.13) kPa for group 1 and 7.46 (0.20) kPa for group 2 on day 2, rising to 8.39 (0.13) and 9.01 (0.23) kPa on day 4. Analgesic requirements were greater in the group receiving an internal mammary artery graft. Possible explanations for the differences between the effects of the two grafts include the higher frequency of pleurotomy, the placing of pleural drains, and additional surgical trauma when internal mammary artery grafts are used.
Thorax 1989 Mar
PMID:Lung function after coronary artery surgery using the internal mammary artery and the saphenous vein. 270 51

Ventilation-perfusion (VA/Q) relationships and gas exchange were studied by the multiple inert gas technique in 19 patients admitted to hospital with acute severe asthma (FEV1 41% predicted) before and during the administration of intravenous salbutamol, inhaled salbutamol, or 100% oxygen. Eight patients received a continuous intravenous infusion of salbutamol (4 micrograms/min, total dose 360 micrograms) and were studied before treatment, after 60 and 90 minutes of treatment, and one hour after treatment had been discontinued. Six patients had measurements before and 15 minutes after inhaling 300 micrograms salbutamol from a metered dose inhaler on two occasions (total dose 600 micrograms) and one hour after the last dose. Measurements were also made in five patients before and while they breathed 100% oxygen for 20 minutes. At baseline (fractional inspired oxygen (FiO2) 21%) all patients showed a broad unimodal (n = 10) or bimodal (n = 9) distribution of blood flow with respect to VA/Q. A mean of 10.5% of the blood flow was associated with low VA/Q units without any appreciable shunt. One of the best descriptors of VA/Q inequality, the second moment of the perfusion distribution on a log scale (log SD Q), was moderately high with a mean of 1.18 (SEM 0.08) (normal less than 0.6). Measures of VA/Q inequality correlated poorly with spirometric findings. After salbutamol the increase in airflow rates was similar regardless of the route of administration. Intravenous salbutamol, however, caused a significant increase in heart rate, cardiac output, and oxygen consumption (VO2); in addition, both perfusion to low VA/Q areas and log SD Q increased significantly. Inhaled salbutamol caused only minor changes in heart rate, cardiac output, VO2, and VA/Q inequality. Arterial oxygen tension (PaO2) remained unchanged during salbutamol administration, irrespective of the route of administration. During 100% oxygen breathing there was a significant increase in log SD Q (from 1.11 to 1.44). It is concluded that patients with acute severe asthma show considerable VA/Q inequality with a high level of pulmonary vascular reactivity. Despite similar bronchodilator effects from inhaled and intravenous salbutamol, VA/Q relationships worsened only during intravenous infusion. PaO2 remained unchanged, however, because the change in VA/Q relationships was associated with an increase in metabolic rate and cardiac output.
Thorax 1989 Apr
PMID:Ventilation-perfusion mismatching in acute severe asthma: effects of salbutamol and 100% oxygen. 276 27

The effect of flurbiprofen, a potent cyclo-oxygenase inhibitor, on histamine and methacholine reactivity was assessed in seven atopic subjects with asthma. Flurbiprofen 150 mg daily for three days displaced the histamine-FEV1 concentration-response curve to the right by 1.5 doubling doses, whereas no effect was observed on the response to methacholine. Subsequently the effects of flurbiprofen and terfenadine, a specific H1 histamine receptor antagonist, on allergen induced bronchoconstriction were studied in seven atopic but non-asthmatic subjects. The subjects inhaled the concentration of grass pollen allergen that had previously been shown to produce a 20% fall in FEV1 on separate occasions after prior treatment with placebo, flurbiprofen 150 mg daily for three days, terfenadine 180 mg three hours before challenge, and the combination of flurbiprofen and terfenadine. After placebo, allergen challenge caused a mean (SEM) maximum fall in FEV1 of 37.6% (2.6%) after 20 (3.7) minutes, followed by a gradual recovery to within 15% of baseline at 60 minutes. Terfenadine reduced the maximum allergen provoked fall in FEV1 to 21.5% (2.2%) and reduced the area under the time-response curve (AUC) by 50% (6%). Flurbiprofen alone reduced the mean maximum fall in FEV1 to 29.6% (3.2%) and reduced the AUC by 26%. The effect of the combination of flurbiprofen and terfenadine did not differ significantly from that of terfenadine alone. We conclude that histamine and prostaglandins contribute to immediate allergen induced bronchoconstriction and that a complex interaction occurs between the two classes of mediators.
Thorax 1987 Dec
PMID:Effects of a cyclo-oxygenase inhibitor, flurbiprofen, and an H1 histamine receptor antagonist, terfenadine, alone and in combination on allergen induced immediate bronchoconstriction in man. 289 81

Formyl-methionyl-leucyl-phenylalanine (FMLP), a synthetic, acylated tripeptide analogous to bacterial chemotactic factors, has been shown to cause bronchoconstriction in guinea pig, rabbit, and human airways in vitro. To determine whether FMLP causes bronchoconstriction in man in vivo, a preliminary study was undertaken in which five non-smokers (mean age 35 years, FEV1 94% (SEM 5%) predicted) and five smokers (mean age 34 years, FEV1 93% (6%) predicted) inhaled aerosols of FMLP. None of the subjects showed airway hyperresponsiveness to histamine (the provocative concentrations of histamine causing a fall of greater than or equal to 20% in FEV1 (PC20) were over 8 mg/ml). FMLP dissolved in 50% dimethylsulphoxide and 50% saline in concentrations of 0, 0.06, 0.12, 0.25, 0.5, 1.0, 2.0, and 4.0 mg/ml was administered to the subjects by means of a French-Rosenthal dosimeter, FEV1 being recorded after inhalation of each concentration. Dose dependent falls in FEV1 occurred in five non-smokers (geometric mean 1.76, 95% confidence limits 0.87-3.53 mg/ml) and three smokers (0.23, 0.07-0.78 mg/ml), with two smokers not responding by 20% to the highest concentration of FMLP. On a separate day the FMLP dose-response curves were repeated after nebulisation of 500 micrograms of ipratropium bromide. The PC20 FMLP in the responders more than doubled. In six additional normal subjects a histamine inhalation test was performed before and four and 24 hours after inhalation of FMLP. All subjects remained unresponsive to histamine. These results show that FMLP is a potent bronchoconstrictor in some non-asthmatic individuals in vivo and this may be important in bronchoconstriction related to infection in patients with chronic obstructive lung disease.
Thorax 1988 Jan
PMID:Effect of inhaled formyl-methionyl-leucyl-phenylalanine on airway function. 296 25


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