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J W Paterson

Publications and source records attributed to J W Paterson.

At least 55 records · Page 3Linked to original sources
PubMed1983

Effect of steroids on beta-adrenoceptor-mediated relaxation of pig bronchus.

1--Progesterone, testosterone (40 microM), cortisol and cortisol hemisuccinate (80 microM) caused 6-8 fold potentiations of (+/-)-isoprenaline (Iso)-induced relaxations of pig bronchus while several other steroids caused smaller potentiations or had no effect. 2--17 beta-Oestradiol (40 microM) increased the potency of Iso, (-)-adrenaline (Adr) and (-)-noradrenaline (NA) by 10.6, 2.3 and 2.6 fold respectively but had no significant effect on the potency of fenoterol (Fen). 3--Inhibition of catechol-O-methyl transferase (COMT) with U-0521 (30 microM) caused a 6 fold increase in the potency of Iso but failed to alter the potency of Adr, NA or Fen. The extraneuronal uptake inhibitor normetanephrine (50 microM) caused significant 2 fold increases in the potency of Iso and Adr but did not potentiate the responses to NA or Fen. 4--In preparations where the potency of Iso had already been increased by U-0521 (30 microM) or by normetanephrine, 17 beta-oestradiol produced no significant further increase in potency. These results indicate that steroid-induced increases in the potency of catecholamines in pig bronchus can be explained in terms of inhibition of COMT or extraneuronal uptake or both.

Airway Resistance↗
PubMed1983

Effect of hypothermia on beta 1-adrenoceptor-mediated relaxation of pig bronchus.

The relaxant potencies of (+/-)-isoprenaline and of (-)-noradrenaline (NA) in the pig isolated bronchus were increased 5.4 and 3.1 fold respectively by lowering the organ bath temperature from 37 degrees C to 27 degrees C, whereas the potencies of the non-catecholamine beta-adrenoceptor agonists fenoterol and orciprenaline were not significantly changed. At 37 degrees C, the catechol-O-methyl transferase (COMT) inhibitor U-0521 (30 microM), caused a 7.2 fold increase in the potency of isoprenaline but had no effect on the potency of fenoterol. At 27 degrees C the potency of isoprenaline was similar in the absence or presence of U-0521 (30 microM). Furthermore, in bronchi where extraneuronal uptake was inhibited by phenoxybenzamine, the potency of NA was not significantly altered by reducing bathing temperature from 37 degrees C to 27 degrees C. These results suggest that the hypothermic potentiation of isoprenaline in pig bronchus resulted from inhibition of COMT or of access to COMT, rather than from sensitization of beta 1-adrenoceptors.

Adrenergic beta-Agonists↗
PubMed1983

Classification of beta-adrenoceptors in isolated bronchus of the pig.

1 (+/-)-Isoprenaline (Iso), (-)-adrenaline (Ad), (-)-noradrenaline (NA), the beta 2-selective adrenoceptor agonist (+/-)-fenoterol (Fen) and the beta 1-selective adrenoceptor agonist (+/-)-RO363 caused concentration-dependent relaxation of preparations of pig bronchus pre-contracted with carbachol 40-ng/ml (0.22 microM). Iso, Ad, NA and Fen caused complete relaxation of carbachol-induced tone, but RO363 caused relaxation equivalent to only 59% of the maximal response to Iso. 2 When relaxation responses to these amines were plotted as a % of their maximal effects, comparison of EC50 values showed that the order of potency was RO363 greater than Iso greater than NA greater than Fen greater than Ad (14.4:4.6:1:0.4:0.3). 3 pA2 values determined for the beta-adrenoceptor antagonists propranolol (non-selective) and atenolol (beta 1-selective), or the partial agonist salbutamol (beta 2-selective) using Iso as agonist were 8.3, 7.3 and 4.4 respectively. The pA2 value for atenolol using RO363 as the agonist was 7.6. 4 These results indicate that porcine bronchus contains a homogeneous population of beta 1-adrenoceptors.

Animals↗
PubMed1983

Correlations between pharmacological responses and structure of human lung parenchyma strips.

Correlations were sought between responses of human lung parenchyma strip to 5-hydroxytryptamine (5-HT) and (-)-noradrenaline (NA) and the proportions of the three major, potentially contractile components within the strip, namely smooth muscle in airways proximal to alveolar ducts, vascular smooth muscle and contractile cells in alveolar septa. After the isometric measurement of responses to 5-HT or to NA, lung strips were processed for stereological examination at the light microscopic level. On average, approximately 46% of the total volume of the lung strip was tissue and the remainder was air space. Tissue contained blood vessels (16.8%), airways proximal to alveolar ducts (4.8%) and alveolar parenchyma (78.4%). Human lung parenchyma strips relaxed, contracted or failed to respond to 5-HT or NA. Results indicated that these agonists caused simultaneous contraction of blood vessels and relaxation of airways proximal to alveolar ducts. The size and type of responses to 5-HT or NA was significantly correlated with the ratio of the volume of blood vessels and larger airways. Conversely, the proportion of alveolar tissue in lung strips was not significantly correlated with responses to 5-HT or NA.

Humans↗
PubMed1982

Catecholamine transport in isolated lung parenchyma of pig.

1 Lung parenchyma strips of the pig incubated at 37 degrees C with [(3)H]-(-)-noradrenaline ([(3)H]-NA) or [(3)H]-(+/-)-isoprenaline ([(3)H]-Iso), accumulated radioactivity via saturable, high affinity uptake processes. Apparent saturation constants (K(m)) for [(3)H]-NA and [(3)H]-Iso were 1.34 x 10(-6) M and 1.63 x 10(-6) M respectively, while apparent transport maxima (V(max)) were 4.86 and 1.63 x 10(-9) mol min(-1) g(-1) respectively.2 Cellular accumulation of radioactivity from radiolabelled catecholamines was greatly reduced by lowering the temperature to 7 degrees C, pretreatment with ouabain (100 muM), phentolamine (15 muM) or phenoxybenzamine (80 muM). However, accumulation of radioactivity derived from ((3)H]-NA was inhibited selectively by cocaine (10 muM) and desipramine (1 muM), while normetanephrine (80 muM) and 3-O-methylisoprenaline (50 muM) caused much greater reductions in cellular radioactivity from [(3)H]-Iso than from ((3)H]-NA. Taken together with information from kinetic studies, the results indicate that these amines are transported by separate uptake processes.3 Cocaine (50 muM) which selectively reduced [(3)H]-NA transport, had no significant effect on the sensitivity (EC(50)) of isolated parenchyma lung strips of the pig to the contractile effects of cumulative concentrations of NA. The catechol-O-methyl transferase (COMT) inhibitor, U-0521 (60 muM), also failed to alter the potency of NA, while normetanephrine (80 muM) caused a 2 fold decrease in potency.4 Phentolamine (15 muM), which reduced the cellular accumulation of radioactivity derived from [(3)H]-Iso by 64%, caused a small potentiation of Iso-induced relaxations of porcine lung strips. Normetanephrine (80 muM) and 3-O-methylisoprenaline (50 muM), which also depressed the accumulation of cellular radioactivity from [(3)H]-Iso by > 50%, caused rightward shifts in Iso concentration-effect curves as a result of beta-adrenoceptor blockade. In sharp contrast, cortisol (80 muM) and U-0521 (60 muM), which caused smaller reductions in the cellular accumulation of radioactivity derived from [(3)H]-Iso, both caused an approximately 9 fold potentiation of responses to Iso in isolated lung strips.5 The results indicate that the major sites of uptake and metabolism of NA in porcine parenchyma strip are remote from alpha-adrenoceptors mediating NA-induced contraction. Similarly, some major sites of uptake of Iso are remote from beta-adrenoceptors mediating Iso-induced relaxation. However, beta-adrenoceptors are apparently in close proximity to a compartment containing COMT activity.

Animals↗
PubMed1982

Pharmacological responses of human and porcine lung parenchyma, bronchus and pulmonary artery.

1 Responses of preparations of human and porcine isolated bronchus and pulmonary artery to carbachol (CCh), methacholine, histamine, 5-hydroxytryptamine (5-HT), (-)-noradrenaline (NA), (-)adrenaline (Adr) and (+/-)-isoprenaline (Iso) were compared with responses to the same agonists in isolated lung parenchyma strips. 2 All preparations from both human and porcine lung contracted in response to histamine and all, except preparations of porcine pulmonary artery, contracted in response to CCh. Human and porcine pulmonary artery and parenchyma strip contracted in response to NA while bronchial preparations invariably relaxed. Iso caused relaxation of human and porcine bronchus and parenchyma strip. Although 5-HT was completely inactive in tissues isolated from pig lung, this amine was a powerful spasmogen in human pulmonary artery, relaxed human bronchus and caused variable responses in human parenchyma. 3 Results indicate that the pharmacological characteristics of human and porcine parenchyma strips may be explained in terms of responses of vascular or airways smooth muscle.

Animals↗
PubMed1982

A comparative study of beta-adrenoceptors in human and porcine lung parenchyma strip.

1. Responses to (+/-)-isoprenaline (Iso), (-)-adrenaline (Adr) and (-)-noradrenaline (NA) were compared in isolated preparations of human and porcine lung parenchyma strip. 2. The order of relaxant potencies of these catecholamines in both human and porcine lung parenchyma was Iso greater than Adr greater than NA (1:0.24:0.01, human; 1:0.21:0.01.pig). These results suggest that beta 2-adrenoceptors predominate in both types of lung parenchyma strip. 3. pA2 values for the beta-adrenoceptor antagonist, propranolol (non-selective), with Iso as the agonist, in human and porcine lung strips were 7.84 and 7.83 respectively and for atenolol were 6.50 and 5.35 respectively. Taken as a whole results indicate the existence of an apparently homogeneous population of beta 2-adrenoceptors in porcine parenchyma strip, while both beta 1 and beta 2-adrenoceptors were revealed in human lung parenchyma.

Animals↗
PubMed1981

Effect of intravenous injection of rimiterol in asthma.

1 The effect of i.v. rimiterol was compared with aerosol rimiterol in twelve asthmatic patients. 2 A cumulative dose of rimiterol (1050 microgram) given in six separate injections over 90 min resulted in a mean increase in peak expiratory flow rate (PEFR) of 50.6% and FEV1 of 53.7%. 3 Comparison of the degree of bronchodilation to the same dose of rimiterol administered intravenously or by aerosol, suggested that on average the potency ratio was 10:1, i.e. ten times the aerosol dose was required to produce the equivalent bronchodilator effect. 4 Palpitations, tremor and postural hypotension were common during the first minute after the drug was injected intravenously, but did not occur after aerosol administration. 5 It is suggested that rimiterol by intravenous injection is a useful addition to the treatment of acute asthma.

Adult↗
PubMed1981

Plasma theophylline assay service for outpatients.

It is generally agreed that the bronchodilator response to theophylline can be directly related to plasma concentration and that the efficacy of theophylline therapy can be improved if plasma concentrations are monitored. However, it is not known whether this improvement is realised in routine clinical practice. In this study, theophylline plasma concentrations were measured in 359 outpatients attending a teaching hospital respiratory medicine clinic. In nearly three-quarters of these patients (73.2%), the plasma concentration of theophylline was below the recommended therapeutic range of 55-110 mumoles/liter (10-20 mg/liter). These results were made available to the medical staff at the patient consultation. One hundred and seventy-seven patients reattended for a second visit and their plasma concentrations remeasured. At this visit, 63.2% of plasma levels were below the therapeutic range of 55-110 mumoles/liter; the percentage of patients in this therapeutic range had risen from 25.6% at the first visit to 33.9% at the second. Concentrations in excess of 110 mumoles/liter were rare and accounted for only 1.1-2.8% of sample assayed. The increase in the percentage of patients whose plasma concentration was in the therapeutic range may have been due to a better patient compliance resulting from provision of the "on-line" plasma monitoring service. The data suggest that physicians are conservative in their use of theophylline and may be maintaining the patients at a therapeutic range of 28-55 mumoles/liter, particularly when the drug is given with other therapeutic agents such as the beta 2-adrenoceptor agonists.

Adolescent↗
PubMed1980

Effect of restrictions on prescribing patterns for dextropropoxyphene.

Prescribing of compound analgesics containing dextropropoxyphene was limited to consultants only in a teaching hospital. Inpatient prescribing (mainly by junior staff) fell immediately to very low levels but outpatient prescribing (by consultants) fell more slowly to about one-third of the original level, suggesting that patients and doctors find dextropropoxyphene compounds useful. Prescriptions for paracetamol increased but so did those for other compound analgesics, particularly those containing high doses of codeine, indicating a belief that compound analgesics have a role in treatment. Restrictions may produce unexpected results and monitoring is essential, but the method of audit used by pharmacies is not suitable for detailed analysis.

Acetaminophen↗
PubMed1980

A hand-held calculator program for individualized dosage adjustment of intravenous theophylline in acute asthma.

Despite general development of drug assay services and increasing interest in pharmacokinetics, proper dosage regimen calculations are not often made in routine clinical practice. This could be due, in part, to unfamiliarity with pharmacokinetic theory, the consequent difficulty of collaboration and the inevitable delay while data are processed on a computer. The present program for a hand-held calculator (TI-59) was written to minimize these problems, and was designed for the use of intravenous theophylline in the management of acute asthma, where there is a need for individualisation of dosage. Calculations are based on the one compartment open model. With 3--4 plasma drug concentrations taken early in the treatment, the program gives a measure of goodness of fit, the elimination rate constant (kel), the volume of distribution (Vd) and the suggested infusion rate to achieve a given steady-state level. Data from 10 severe acute asthmatic patients were used to test the model and the estimated parameters were: Vd = 0.26 +/- 0.029l/kg (mean +/- SEM) and Kel = 0.20 +/- 0.045 h(-1). The average standard deviation (s) for differences between the model and observations was 0.96 +/- 0.21 mg/l, of which at least 0.5 mg/l was due to assay error. In seven patients where the infusion period was extended, the predicted steady state plasma concentration agreed reasonably with that observed (r = 0.83, df = 5, 0.01 < p < 0.05).

Acute Disease↗
PubMed1980

Comparative efficacy of salbutamol by pressurized aerosol and wet nebulizer in acute asthma.

1 Cumulative dose-response curves (FEV1) to pressurized aerosol salbutamol were established in 17 patients admitted to hospital with acute severe asthma. After the maximal pressurized aerosol effect had been achieved, a further dose (5 mg) of salbutamol was given by wet nebulizer and any further increment recorded. 2 Baseline FEV1 was 1.16 +/- 0.55 (mean +/- s.d.), an average of 36% of predicted, and the maximal aerosol induced change in FEV1 was 0.435 +/- 0.330 1 (t = 5.72, P < 0.01). There was an additional, small increment in FEV1 after nebulizer of 0.043 +/- 0.085 1 (t = 2.26, P < 0.05). 3 Detailed analysis of the data according to a theoretical dose-response relationship showed that the nebulizer-aerosol increment was unrelated to asthma severity.

Acute Disease↗
PubMed1980

An in vitro study of various drugs on central and peripheral airways of the rat: a comparison with human airways.

1 The effect of histamine and other drugs on the central and peripheral airways of the rat was studied by applying them directly to isolated tracheal and lung strip preparations. These effects were then compared with those observed on human isolated bronchial muscle preparations. 2 Acetylcholine and 5-hydroxytryptamine (5-HT) both contracted the lung strip and trachea of the rat, and both were more potent on the trachea than the lung strip. 3 Histamine and prostaglandins E2 (PGF2) or F2 tau (PGF2 tau) produced no effect on either the lung strip or trachea of the rat. 4 On the human isolated bronchial preparation, in contrast to the rat airways, both histamine and PGF2 tau produced marked concentration-dependent contractions and 5-HT either produced no response or a slight relaxation. 5 In view of these results, the use of anaphylactic bronchoconstriction in the rat as a model for the study of asthma in man is questioned.

Acetylcholine↗
PubMed1979

Cross-over study of the efficacy of four beta 2-sympathomimetic bronchodilator aerosols.

1 Bronchodilator efficacy of four beta 2-sympathomimetic aerosols, fenoterol, orciprenaline, salbutamol and terbutaline has been compared in nine patients with chronic stable reversible airways obstruction using a double-blind placebo controlled cross-over design. Two puffs of each agent were given on two separate occasions to each of the patients and the forced expiratory volume in one second (FEV1) and the vital capacity (VC) were measured before and 30, 90, 150 and 210 min after administration. 2 Multivariate analysis of the data at 30 min showed FEV1 and VC in these patients to be so highly correlated that they could be considered as a single variable. 3 When absolute change in VC at 30 min was used as the response criterion, efficacy of the four drugs was significantly better than placebo (P < 0.01). It was not possible to rank all four drugs in order of effectiveness; fenoterol and salbutamol were significantly better than terbutaline and orciprenaline (P < 0.01) but this was complicated by a significant interaction effect between drugs and patients (P < 0.01). 4 Similar results were obtained when absolute and relative changes in FEV1 and VC and area under the curve were used as response variables. 5 The study demonstrates that important individual differences in patient response may be concealed if only average drug effects are considered.

Adrenergic beta-Agonists↗
PubMed1979

Bronchodilator drugs.

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Adrenergic alpha-Agonists↗
PubMed1978

Clinical trial experience by simulation: a workshop report.

A new computer program for experimental design simulation was used in a three-day postgraduate workshop on clinical trials. Participants were given information on a fictitious new drug and asked to design a trial to evaluate it. On the first day they reviewed the data and designed a protocol, and results for these specifications were generated on the computer. The second day was spent analysing results, and on the last day the findings of the different studies were presented at a symposium. Flexibility of the program ensured a high degree of realism in all trials and emphasised the influence of design on results and conclusions.

Adolescent↗