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Biomedical subjects

J Morley

Publications and source records attributed to J Morley.

At least 37 records · Page 2Linked to original sources
PubMed1998

The pursuit of precision pharmaceuticals: divergent effects of beta2 agonist isomers.

Beta2 agonists are the most commonly used treatment for acute bronchoconstriction. However, during regular use there is a progressive decline of protective efficacy of bronchodilators. This progressive decline has long been considered anomalous because with short-acting beta agonists, there is no corresponding change in bronchodilator efficacy. Airway hyper-responsiveness is itself a feature of asthma and there maybe however, there may be an increase in airway hyper-responsiveness following regular use of beta2 agonist. Airway hyperresponsiveness could diminish the capacity of beta agonists to protect from or result in paradoxical bronchospasm and there effects of racemic salbutamol. There have been reports of increased morbidity and mortality associated with excessive use of beta(2) agonists. As all beta agonists used clinically are racemates composed of 1:1 mixtures of R and S isomers, conducted on the possible involvement of the isomers in hyper-responsiveness. Hyper-responsiveness cannot be attributed to the R isomer, whose capacity to activate beta adrenoceptors will nullify this effect. In contrast, extensive evidence indicated that the S isomer might cause hyper-responsiveness and potential airway inflammation. Further, the S isomer shows a propensity to activate human eosinophils and alter muscarinic M(2) receptor functions. The S isomer, which makes no contribution to therapeutic efficacy and may exacerbate asthma, might therefore be excluded from asthma therapy.

Journal Article↗
PubMed1998

Levalbuterol hydrochloride.

Racemic salbutamol (racemic albuterol) ameliorates symptoms of asthma by activating beta-adrenoceptors on nerve, smooth muscle and inflammatory cells within the airways. Racemic salbutamol comprises equal proportions of 2 isomers: (S)-salbutamol and (R)-salbutamol, with the latter being exclusively responsible for activation of beta-adrenoceptors. Accordingly, within racemic salbutamol it is (R)-salbutamol that efficiently relieves obstruction of asthmatic airways and affords highly effective protection from bronchoconstrictor stimuli, including allergens. During regular use of racemic salbutamol, there is a progressive decline of protective efficacy and a corresponding intensification of airway responsiveness. This decline is largely absent during regular use of (R)-salbutamol. Consequently, bronchodilator responses to sub-maximal doses of (R)-salbutamol exceed responses to the equivalent dose of (R)-salbutamol given as the racemate. For example, in asthmatics with baseline FEVs <or= 60%, 1.25 mg of nebulised (R)-salbutamol achieved a maximal 52% change in FEV while 2.5 mg of racemic salbutamol only achieved a 38% change in FEV. Since extrapulmonary effects (e.g., tremor, heart rate) of beta agonists are related to dose and limit the use of beta agonist therapy, (R)-salbutamol at 0.63 mg provides uncompromised efficacy with marked reduction of side-effects. In addition to quantitative differences, the constituent isomers of salbutamol also exhibit qualitative differences. Thus, (R)-salbutamol inhibits activation of human eosinophils in vitro whereas, under the same conditions and concentrations, (S)-salbutamol augments activation of these cells. This property of (S)-salbutamol may explain why eosinophilia in induced sputum from subjects with allergic asthma is increased by regular use of racemic salbutamol. Similarly, the capacity of (R)-salbutamol to suppress hyperresponsiveness of the airways can be contrasted with the capacity of (S)-salbutamol to intensify hyperresponsiveness. This action of (S)-salbutamol would explain why regular use of racemic salbutamol intensifies the bronchoconstrictor response to antigen in subjects with allergic asthma. Taken together, these findings imply that replacement of racemic salbutamol by (R)-salbutamol will diminish, or even eliminate, the anomalous actions that have curtailed the efficacy of racemic salbutamol. Pharmacokinetically, (R)-salbutamol exhibits near absolute conformational stability (i.e., no conversion to (S)-salbutamol). If in vitro anti-inflammatory actions of (R)-salbutamol are also manifest in asthmatic airways, (R)-salbutamol could provide a novel approach to asthma therapy which combines bronchodilation and bronchoprotection with anti-inflammatory efficacy.

Journal Article↗
PubMed1997

Decreased glucose utilisation does not increase food intake in the marsupial Sminthopsis crassicaudata.

The marsupial Sminthopsis crassicaudata increases food intake following a fast. However, the role of metabolic fuel availability, in particular glucose, in the regulation of food intake in this animal is unknown. In this study, we have demonstrated that neither insulin-induced hypoglycaemia nor metabolic blockade of glucose utilisation with 2-deoxy-D-glucose effects food intake compared to saline-treated controls, suggesting that mechanisms other than glucose availability are important in the regulation of food intake in this marsupial. These data are discussed in the context of the role of glucoprivation in feeding in other mammals.

Animals↗
PubMed1997

Sublingual absorption of salbutamol in the guinea-pig.

Clinical observations both claim and refute sublingual absorption of salbutamol. To resolve this issue, the capacity of salbutamol to inhibit substantial bronchoconstrictor responses to histamine has been defined for both intravenous injection of saline in the anaesthetized ventilated guinea-pig. Substantial sublingual absorption was observed. It is suggested that low dose sublingual formulations might have advantage over inhalation forms of sympathomimetics.

Administration, Sublingual↗
PubMed1997

Smile design--specific considerations.

Smile design is a new discipline that has come to the forefront with the recent popularity of cosmetic dentistry techniques. This article explores some of the principles used in smile design that can enhance the esthetics of any anterior restorative procedure.

Age Factors↗
PubMed1997

The esthetics of anterior tooth aging.

As generations proceed to reinvent themselves in an effort to achieve and maintain youth, cosmetic dentistry faces one of its greatest and most persistent challenges: the restoration of an aging smile. Although the need for this restorative therapy has not yet been adequately studied, the momentum continues to build as aging teeth exhibit physical characteristics that affect their function as well as appearance. This review presents the most common factors influencing the esthetics of anterior tooth aging: coloration; wear and the effects of erosion, attrition, abrasion, and abfraction; and position of teeth relative to each other and surrounding tissues. While dental science seeks to understand how well age-specific restorative procedures can affect patients, the question of the necessity of this therapy remains. Should a healthy smile require treatment? Only time will reveal at what cost and to what extent a younger appearance plays a role in dental science.

Adult↗
PubMed1996

Atrial fibrillation, anticoagulation, and stroke.

There is a demonstrated statistical association between atrial fibrillation, rheumatic valvular disease, and embolic stroke. This article assesses the results of 6 major clinical trials (AFASAK, BAATAF, SPINAF, SPAF [parts I and II], CAFA and EAFTA--see text for trial names). Multivariate analysis revealed 4 independent clinical features that identified patients with atrial fibrillation at an increased risk for stroke: hypertension, increasing age, previous transient ischemic attack, and diabetes mellitus. Without anticoagulation therapy, patients with any of these risk factors had a 4% annual risk of stroke. Patients with cardiac disorders such as congestive heart failure and coronary artery disease have a stroke rate 3 times higher than patients without any risk factors; patients with atrial fibrillation but no concomitant risk factors or structural heart disease seemed to have little concomitant risk for stroke. Meta-analysis revealed a 64% reduction of risk for stroke in patients treated with warfarin, as compared with placebo. The value of warfarin therapy in patients > 75 years old is less clear because of a high risk of hemorrhagic complications.

Aged↗
PubMed1995

Zaditen SRO permits once-daily dosing with superior efficacy in the prophylaxis of asthma.

This international, multicenter clinical trial was designed to compare the efficacy and safety of two different formulations of ketotifen: Zaditen SRO and Zaditen Standard Form. In a randomized double-blind study over a 12-week treatment period, 3 parallel groups of asthmatic subjects received Zaditen SRO (2 mg once daily), Zaditen SRO (4 mg once daily), or Zaditen Standard Form (1 mg twice daily). Asthmatic subjects (362 evaluable cases, aged 6-29 years) kept daily records of clinical symptoms, use of concomitant medication, and peak flow recordings and were examined at 2-week intervals up to the end of the study. Zaditen SRO 4 mg administered once a day at night showed a statistically significant faster onset of action and was more clinically effective than Zaditen Standard Form. The Zaditen SRO 4-mg and 2-mg formulations were at least as well tolerated as the standard form, with somnolence occurring equally after both formulations. In conclusion, Zaditen SRO (4 mg once daily) was found to be equally safe and more effective in the prophylactic treatment of mild and moderate bronchial asthma than Zaditen Standard Form (1 mg twice daily).

Adolescent↗
PubMed1994

Asthma control.

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Albuterol↗