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Biomedical subjects

J R Carpenter

Publications and source records attributed to J R Carpenter.

15 recordsLinked to original sources
PubMed1992

Trials of the bronchodilator activity of the isoenzyme-selective phosphodiesterase inhibitor AH 21-132 in healthy volunteers during a methacholine challenge test.

1. An approximately steady-state reduction of specific airway conductance was induced in normal human subjects by means of a methacholine individualized loading+maintenance dose regime. Tested against this background bronchoconstriction, the mixed type III/IV phosphodiesterase inhibitor AH 21-132, ingested in doses up to 90 mg, had no detectable bronchodilator activity. 2. AH 21-132, infused intravenously over 15 min, evoked short-lived bronchodilatation at doses of 20 and 40 mg, without affecting blood pressure or heart rate. 3. AH 21-132, mixed 1:18.5 by weight with sucrose, dissolved in saline, nebulized and inhaled in doses between 2 and 24 mg of AH 21-132, produced dose-dependent bronchodilation. The ED50 was estimated as 9.2 mg AH 21-132. The peak relief of imposed bronchoconstriction was 80% and the apparent half-time of removal of AH 21-132 from its site of action was 25 min. 4. Inhaled, nebulized, hypertonic sucrose had a minor bronchodilator action. 5. AH 21-132, by intravenous and inhaled routes of administration, provides relief of methacholine-induced bronchoconstriction.

Administration, Inhalation↗
PubMed1991

A method for bioassay of potency and effectiveness of inhaled bronchodilators in normal subjects.

1. Bioassay of inhaled bronchodilator drugs for potency and effectiveness in normal human subjects is rendered difficult and imprecise because bronchomotor tone is low. When attempting to determine log dose-effect relationships for inhaled, nebulised bronchodilator drugs and measuring increased specific airways conductance (sGaw), the coefficient of variation of each mean response is likely to be so large that an intermediate response is not significantly different from either the maximum or no response. 2. A method is described by which inhaled, nebulised bronchodilator drugs can be bioassayed for potency and effectiveness with high precision. The method involves the use of inhaled, nebulised bronchoconstrictor agents (methacholine or histamine) to provide a highly reproducible, near-constant, background reduction in airway conductance in normal human subjects. The activity of bronchodilators is assessed against this background reduction in airway conductance. 3. Log specific airway conductance (log sGaw) was chosen as the response metameter on grounds of normality of distribution and relative homoscedasticity. A central straight line segment of the bronchoconstrictor drug dose-effect curve extending over a 10-fold dose multiple could be found easily; the upper end of this segment occurred near 67-75% reduction in sGaw and was reproducible. 4. The effect of a dose bronchoconstrictor drug causing 67-75% reduction in sGaw waned linearly with time at first, over the effect segment corresponding to the linear segment of the drug's log dose-effect curve. The rate constant of local elimination of bronchoconstrictor drug from its site of action, in inhaled dose equivalents, was deduced from the ratio of the slopes of the linear segments of the log dose-effect and time-effect curves. 5. The maintenance dose rate to maintain the peak effect (67-75% reduction in sGaw) of the loading dose was calculated. The repeated administration of maintenance doses at regular short intervals, at this calculated dose rate, created a steady state of bronchoconstriction equal in extent to the effect of the loading dose. This steady state bronchoconstriction occurred without undue discomfort for the subject and was reproducible. 6. Against this background bronchoconstriction, inhaled, nebulised salbutamol produced a rapidly developing and slowly waning increase in sGaw. Reproducible log dose-effect curves for the bronchodilator drugs salbutamol and reproterol allowed measurement of their potency and effectiveness; the potency of reproterol relative to salbutamol was 0.082 with 95% confidence limits of 0.0504 and 0.131. 7. Estimation of the subject's pharmacodynamic and pharmacokinetic parameters for inhaled methacholine from just three dosage individualising sessions provides estimates accurate enough to be of practical value.

Adult↗
PubMed1987

Effects of spasmogens on relaxant dose-response curves to full or partial agonists at beta-adrenoceptors of guinea pig isolated trachea.

When guinea pig isolated trachea is contracted with either carbachol or methacholine, relaxant concentration-response curves to isoprenaline, salmefamol and fenoterol were shifted to the right, compared with curves obtained with either spontaneous or histamine-induced tone. Carbachol and methacholine also reduced the maximal relaxation to fenoterol and abolished relaxations to the partial agonist pindolol. It is concluded that the processes linking receptor to contractile response in trachea are different for histamine receptors and muscarinic cholinoceptors.

Adrenergic beta-Agonists↗
PubMed1986

A method for presenting and comparing dose-response curves.

When dose-response curves are replicated, averaging the responses to each dose of drug reduces the slope of the mean curve. The shape of the curve can be preserved, however, by first normalizing each dose-response curve and then interpolating log concentrations that induce predetermined responses. These log concentrations are averaged, and then the responses are scaled to the mean maximal response. Mean dose-response curves obtained using this method were compared with mean curves obtained by the conventional method. It was found that this method did not distort the slope of the curve, and smaller differences were detected as significant. Neither method was found to be satisfactory for obtaining a truly representative mean curve for biphasic dose-response curves. The nature of the distribution of EC50 and maximal response was investigated, and it was confirmed that EC50 are log-normally distributed, whereas maximal responses are normally distributed.

Adrenergic beta-Antagonists↗
PubMed1977

Survival in polymyositis: corticosteroids and risk factors.

Thirty-one polymyositis patients treated with low-dose corticosteroid were age and sex matched with 31 polymyositis patients treated with high-dose corticosteroid. Although disease severity at onset of the study was similar in the groups, no statistically significant difference in survival was found. The death rate in each group was greater than normal. The presence of dysphagia or severe muscle weakness lessened the chances of survival. Controlled trials with other drugs should be carried out.

Adrenal Cortex Hormones↗
PubMed1976

Release of [3H]noradrenaline from perfused rat hearts by potassium and its modifications by 6-hydroxydopamine and reserpine.

The sources of noradrenaline (NA) released by excess potassium from isolated perfused rat hearts were investigated by labelling the hearts from normal, reserpine-treated, and 6-hydroxydopamine-treated (6-OHDA-treated) rats with [3H]HA, and measuring the increased rate of efflux induced by perfusion with a Krebs solution containing varying amounts of excess potassium. The [3H]NA and its metabolites in the effluent were separated by adsorption on alumina and a cation-exchange resin (Dowex-50). The release induced by potassium was a linear function of the log of the increased potassium concentration. Following a 1-h efflux period after labelling with [3H]NA, the hearts from reserpine-treated rats retained 1/5 as much [3H]NA, and released, in response to a 56mM elevation in the potassium concentration, less than 1/6 as much tritium label as the hearts from untreated (control) animals. In contrast, the hearts form 6-OHDA-treated animals retained 1/15 of the amount of [3H]NA and released 1/50 of the 3H label as did the control hearts. The potassium-induced increase of 3H-labelled substances in the effluent from the control hearts showed a large (threefold) percentage increase in the [3H]NA fraction, whereas the effluents from the hearts of reserpine- and 6-OHDA-treated animals contained only small increases in the [3H]NA fraction. Based on the assumptions that reserpine prevented retention of NA in the storage granules whereas 6-OHDA prevented almost all neuronal storage, it was concluded that more than 80% of the NA released by potassium excess from perfused normal hearts originated from the storage vesicles of the nerves, the remainder being largely from the cytoplasm of the nerves, with only a small portion from extraneuronal sources.

Animals↗
PubMed1976

Ultrasound evaluation of the popliteal space. Comparison with arthrography and physical examination.

Ultrasound scanning techniques were used to examine the popliteal space in 102 knees. In 30 of 34 knees in which arthrograms were also obtained, the information obtained from both tests was the same. In two instances in which there were different results, the presence of palpable popliteal cysts was confirmed by ultrasound scans but not by arthrography, and in two other cases, small asymptomatic cysts were seen on arthrograms but not on ultrasound scans. In the 68 other knees, ultrasound scans were helpful in the differential diagnosis of popliteal cysts, popliteal artery aneurysms, thrombophlebitis, and a solid poplitieal mass. The results indicate that ultrasound scanning is a valuable, rapid, safe, accurate technique in evaluating patients with symptoms or findings related to the popliteal space.

Aneurysm↗