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Biomedical subjects

J W Lammers

Publications and source records attributed to J W Lammers.

136 records · Page 8Linked to original sources

Characterization of the muscarinic receptor in human tracheal smooth muscle.

Muscarinic receptors in human tracheal smooth muscle were characterized by radioligand binding and functional studies. Specific [3H]-(-)-quinuclidinylbenzilate ([3H]-(-)-QNB) binding to tracheal smooth muscle membranes was reversible, stereoselective and of high affinity (Kd = 47 +/- 4 pmol/l; RT = 920 +/- 120 fmol/g tissue). Inhibition of specific [3H]-(-)-QNB binding by the M-1 selective antagonist pirenzepine was found to occur at relative high concentrations classifying the muscarinic receptor population as belonging to the M-2 subclass. Inhibition of specific [3H]-(-)-QNB binding by muscarinic agonists revealed the presence of high and low affinity sites in nearly equal proportions. 5'-Guanylylimidodiphosphate converted high affinity sites into low affinity sites although its effect was minimal. Log dose-contraction curves of methacholine had Hill coefficients of 1.10 +/- 0.04 with pD2-values of 6.75 +/- 0.02. Inhibition of specific [3H]-(-)-QNB binding by methacholine, however, was best described by a two binding site model with pKi-values considerably lower. The difference between these affinity values points to the presence of substantial receptor reserve.

Adolescent↗

Ventilatory effects of atenolol and bevantolol in asthma.

The cardioequipotency of 400 mg bevantolol and 100 mg atenolol was determined by measuring the exercise heart rate in healthy subjects. The beta-blockers were then used in these doses to investigate their ventilatory effects in patients with asthma. The effects of both drugs on forced expiratory flow parameters for large and small airways were assessed at rest and during and after exercise. A dose-response curve was then plotted after inhalation of the beta 2-adrenoceptor agonist terbutaline. Bevantolol significantly decreased the forced expiratory volume in 1 second (FEV1) and the peak expiratory flow rate (PEFR) at rest, while there was no such change with placebo or atenolol. Both beta-blockers decreased the maximal expiratory flow rates at 50% of forced vital capacity (MEF50) and after expiration of 75% of the forced vital capacity (MEF25) at rest; the decrease was larger after bevantolol than after atenolol. During atenolol there was a decrease in FEV1 and in PEFR (P less than 0.01) 15 minutes after exercise in comparison with preexercise values. There was no significant difference between pre- and postexercise values of MEF50 and MEF25 during atenolol dosing. After bevantolol there was only a small change in PEFR after exercise, probably because of the low preexercise values of the ventilatory indices with this drug. Inhalation of terbutaline up to a dose of 2 mg significantly improved all ventilatory indices measured, but with bevantolol the values after 2 mg inhaled terbutaline were lower than the initial values.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Ventilatory effects of long-term treatment with pindolol and metoprolol in hypertensive patients with chronic obstructive lung disease.

Effects of long-term treatment with pindolol (10 mg twice daily) and metoprolol (100 mg twice daily) on lung function and blood pressure were investigated in eight patients with chronic obstructive lung disease and hypertension. After a placebo period, both beta-adrenoceptor blockers were administered double-blind and cross-over for 4 weeks. By assessing parameters of expiratory flow an attempt was made to distinguish between large and small airways function. Diastolic blood pressure decreased significantly during both pindolol and metoprolol (P less than 0.01). Except for a decrease in forced expiratory volume in 1 s (FEV1) during metoprolol treatment, there was no other change in expiratory flow parameters after placebo or both beta-adrenoceptor blockers. Inhalation of terbutaline induced a small improvement in large airways function after placebo and metoprolol, but not after pindolol; there was no effect of terbutaline on parameters of small airways function. If a beta-adrenoceptor blocker is necessary in patients with chronic obstructive lung disease, a beta 1-adrenoceptor selective blocker is preferred in combination with bronchodilator agents.

Adult↗

Ventilatory effects of beta 1-receptor-selective blockade with bisoprolol and metoprolol in asthmatic patients.

In a double blind, placebo-controlled study the ventilatory effects of the beta 1-selective receptor blockers bisoprolol (EMD 33512) and metoprolol and their interactions with the beta 2-adrenoceptor agonist terbutaline were investigated in 8 asthmatic patients. Both beta-blockers, in all the doses given, caused a significant decrease in peak expiratory flow rate (PEFR). Vital capacity (VC) and forced expiratory volume in one second (FEV1) were significantly decreased only after 10 mg bisoprolol. Terbutaline inhalation caused the same significant improvements in FEV1 and PEFR during placebo as during bisoprolol 10 mg, bisoprolol 20 mg and metoprolol 100 mg. Both beta-blockers caused equal changes in heart rate (HR) at rest. Systolic and diastolic blood pressure (BP) decreased significantly after bisoprolol 20 mg and metoprolol 100 mg, but not after bisoprolol 10 mg. Inhalation of terbutaline up to a dose of 3.5 mg had no influence on HR and BP. The results point to good beta 1-selectivity of bisoprolol 10 mg and 20 mg and metoprolol 100 mg in asthmatic patients. No correlation was found between the plasma levels of the beta-blockers and the changes in the ventilatory indices, HR or BP.

Adrenergic beta-Antagonists↗

Calcium in tears, lacrimal gland fluid, and fluid from the other orbital glands.

Abnormal tear calcium concentrations, which might be expected in ocular and systemic disorders,may be obscured if tear calcium concentration varies with flow rate. The results of the present study indicated that tear calcium concentration is independent of flow rate with rates faster than those which occur with stimulated overflow tearing (i.e., 2 mu1 per minute), but with slower flow rates such as would be encountered with basal, nonstimulated tear flow, tear calcium concentration increases as flow rate decreases. In addition, at given flow rates, tear calcium concentration is the same as that in at least two components of tears, i.e., lacrimal gland fluid, uncontaminated by fluid from the other orbital glands, and fluid from the other orbital glands, uncontaminated by lcarimal gland fluid. It is apparent that only if calcium concentration is correlated with fluid flow rate will determination of calcium in tears and in the components of tears produce valid information not only about tear calcium levels in the presence of ocular and systemic diseases but also about the mechanism of secretion of calcium by the orbital glands.

Animals↗

Assessment of bronchiectasis: comparison of HRCT and spiral volumetric CT.

OBJECTIVE: Our goal was to ascertain the sensitivity of spiral CT for the detection of bronchiectasis in comparison with high resolution CT (HRCT). MATERIALS AND METHODS: Thirty-one patients with a suspected clinical diagnosis of bronchiectasis were evaluated with spiral CT (slice thickness 5 mm, pitch 1, reconstruction index 2 mm, 1 s rotation) and HRCT (1.5 mm, interval 10 mm). Analysis of the presence, type, and severity of bronchiectasis was performed for each bronchopulmonary lobe. RESULTS: In 30 patients, 177 lobes were evaluated. At HRCT 14 patients showed signs of bronchiectasis in 32 lobes. Spiral CT confirmed the presence in 29 lobes. In one lobe spiral CT was false positive. The severity score was the same in 23 lobes, in 4 lobes higher at HRCT, and in 2 lobes higher at spiral CT. Spiral CT has a high sensitivity of 91% to detect bronchiectasis with a specificity of 99.3%. Spiral CT demonstrates adequately lack of tapering of the bronchus. CONCLUSION: In patients with suspected bronchiectasis, HRCT is the method of first choice based on greater sensitivity and lower radiation dose. However, spiral CT done for other indications is a reliable method for assessment of bronchiectasis. Inability of patients to hold their breath did not prove to interfere with diagnostic reliability.

Adult↗

Muscarinic receptor sensitivity in airway smooth muscle of patients with obstructive airway disease.

The hypothesis of an increased muscarinic receptor sensitivity in airway musculature of patients with asthma, chronic obstructive bronchitis and emphysema was investigated through methacholine-induced contraction of isolated airway smooth muscle strips. Contractile responses were recorded isotonically in tracheal smooth muscle preparations of 5 patients with chronic obstructive bronchitis, 2 patients with emphysema and 1 patient with allergic asthma, as well as in bronchial tissue preparations of 7 patients with chronic obstructive bronchitis. The responses were compared to those obtained in airway tissue preparations of 25 control subjects. The sensitivity to methacholine was normal in all groups of patients. This suggests that muscarinic receptor behaviour is normal in airway smooth muscle of patients with obstructive airway disease.

Aged↗

The search for prejunctional inhibitory muscarinic receptors in human bronchus.

The purpose of our study was to search for and classify prejunctional inhibitory muscarinic receptors in human bronchus with a wide range of muscarinic antagonists. Human bronchial airway smooth muscle strips, collected at thoracotomy from 54 subjects, 31 patients with chronic airway obstruction and 23 control subjects, were suspended in organ baths and stimulated by electrical field stimulation. The stimulation parameters were: frequency: 32 Hz; Grass reading voltage: 70 V (voltage between the electrodes: 15 V); pulse duration: 0.5 msec and train duration: 10 sec, every minute. Twitch responses of smooth muscle strips of 27 subjects (14 with and 13 without chronic airway obstruction) were sufficiently stable to search for the effects of M1-, M2- and M3-selective antagonists. All antagonists were added to the bath in a cumulative manner and decreased twitch contraction. No convincing evidence was found for the presence of prejunctional inhibitory muscarinic receptors of the M2-subtype, reasons for this obvious absence are discussed. Anaesthetical drugs for example, may mask the prejunctional inhibitory muscarinic receptors. The question remains whether the used electrical field stimulation experiments are suitable to point out prejunctional inhibitory muscarinic receptors. It is concluded that additional experiments with other experimental methods and in patients with different anaesthetical treatment are needed.

Airway Obstruction↗