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The article discusses a study on the rapid removal of symptomatic trees in Manitoba and its impact on Dutch elm disease (DED) infection rates. Selected areas were coupled on the basis of geographic proximity, population size, and area under DED management. To select a treed urban region within each community as a study area, aerial imagery was used. The rate of compliance with the target time of removal of infected trees was found to be quite high in all communities from 2004 to 2009.

A method is described for the quantitative analysis of terbutaline in human tissues. Gas chromatography and chemical ionization mass fragmentography are used for selective and sensitive detection. A detection limit of 1.5 ng of the free drug per gram tissue is observed when 0.5 g of the dry tissue is used. No interference from the major metabolite, the sulphate conjugate of terbutaline, is found. Finally the method is applied to the post mortem tissues of two persons who used terbutaline frequently.

Continued exposure of target cells to a hormonal agonist frequently leads to a blunted response to that agonist. This process has been termed desensitization, refractoriness, tolerance or tachyphylaxis. The receptor involved in case of beta-sympathomimetics is the beta-adrenergic receptor. When the clinical aspects of beta-adrenergic receptor desensitization are considered, a number of points need serious attention: 1) the route of administration of the drug and the concentration of the drug reached at the receptor site; 2) other factors which may cause reduced responsiveness of the beta-adrenergic receptor besides beta-sympathomimetics and interfere with this process; 3) the different cell-types which are studied and thought to be representative for processes taking place at lung tissue level; 4) the in vivo parameter(s) chosen to describe desensitization; 5) the difference between normal and asthmatic subjects; 6) the mechanism behind desensitization. The paper concerns a review of these points. Since the clinical findings with respect to the induction of desensitization by beta-sympathomimetics are rather controversial, the therapeutic advice should be: use it with caution.

A sensitive method for the qualitative and semiquantitative determination of terbutaline in plasma and urine has been developed. After a single oral dose of 5 mg terbutaline sulphate the drug could be analysed easily. The detection limit in plasma is less than 1 ng ml-1.

Repeated finger tremor measurements have been performed in six normal and eight asthmatic subjects after subcutaneous and oral administration of terbutaline. Prior to the investigations the patients had not used bronchodilators for 10-14 days. The finger tremor pattern showed a striking parallelism with the terbutaline serum concentrations and with the cAMP plasma levels. After subcutaneous administration the increase in tremor values in asthmatic subjects was significantly less than in normals. This suggests a beta-blockade in skeletal muscle of asthmatics. The difference after oral administration was not statistically significant.

The pharmacokinetics of terbutaline has been studied after subcutaneous adminsitration of a therapeutic dose of 250 microgram in 14 patients. Short absorption half-lives of about 7 min resulted in a fast uptake of the drug. Serum concentrations of terbutaline were measured up to 10 hr after administration, depending on the individual. An open one-compartment model appeared adequate for the mathematical description of the kinetics in most patients. Elimination constants of 0.27 +/- 0.07 hr-1 were observed. The elimination process was biphasic in 5 patients with a mean elimination constant of the second phase of 0.10 +/- 0.04 hr-1. This resulted in a comparatively high concentration of 0.7 ng/ml 10 hr after administration. Regular use of terbutaline did not influence the pharmacokinetic data in a significant way.

An interactive computer programme was written for a small computer to perform curve fitting in pharmacokinetic analyses. The programme can handle data with or without an absorption phase. It considers, however, the absorption process to be of first-order kinetics. If necessary a lag time is incorporated in the absorption phase. Results are compared with programmes running only on large computer systems.

Over the past 6 years, several gas chromatography-mass spectrometry (GC-MS) methods for terbutaline have been developed, each with certain advantages and disadvantages. They all involve monitoring of an ion selected from the mass spectrum of a suitable terbutaline derivative. This technique, often referred to as mass fragmentography or selected ion monitoring, reduces the interference from other drugs and endogenous compounds. Different ionization techniques have been employed to obtain high sensitivity, viz. electron impact and chemical ionization. Typically, the methods can be used to measure terbutaline concentrations down to 0.1-0.3 ng/mL in plasma or serum. Isolation of terbutaline from biological materials is complicated by the low partition of the drug from water to organic solvents. Extraction with a large volume of ethyl acetate, ion pair extraction, or isolation on a cation exchange column have been used. These methods are time consuming, and attempts have therefore been made to modify them. Rapid extraction can be achieved on a disposable reversed-phase octadecylsilyl column with unimpaired sensitivity and selectivity. Preliminary results indicate that negative ion chemical ionization of a fluorine-containing derivative can further increase the sensitivity of the terbutaline assays.

Terbutaline serum levels, c-AMP plasma levels and percentage improvement in FEV1, were strongly correlated after subcutaneous administration of terbutaline to normals (n = 6) and to asthmatics (n = 5). Changes in c-AMP plasma levels were similar in both normals and asthmatics after subcutaneous administration, denying a systemically beta-adrenergic defect to be present in asthmatics.

The mass spectra of some butyrophenones are presented. Electron impact ionization and chemical ionization with isobutane as the reagent gas are compared. The chemical ionization spectra show the quasi molecular ion (M + H)+ to be the most abundant ion. Important fragments in the electron impact spectra are discussed for easy determination of other similar compounds.

The pharmacokinetics of 1-(35-dihydroxyphenyl)-2-(tert.butylamino)ethanol (terbutaline, Bricanyl) after i.v. and s.c. injection to normal humans and after s.c. and p.o. administration to patients was studied. The kinetic measurements showed that the standard deviations of the respective parameters were not excessively large. Therefore a reasonable production of the behaviour of terbutaline in man is possible. Some important parameters are the biological half-life at 3.6 h (SD = 1.0), the body clearance at 0.26 l/(kg x h) (SD = 0.09), the volume of the reference compartment at 0.47 l/kg (SD = 0.10) and the volume in the steady state at 1.01 l/kg (SD = 0.14). The absolute bioavailability is calculated at 10%.

In eight asthmatic and six normal subjects serum terbutaline concentrations were correlated with changes in FEV1, MEF50%, Gaw, sGaw, and plasma cAMP concentrations after administration of 0.5 mg terbutaline subcutaneously, 5 mg orally, and an oral placebo. In asthmatics and normals the changes in serum terbutaline levels and plasma cAMP levels were closely correlated and in the same range. No change in lung function parameters was registered in normals, whereas in asthmatics a significant improvement was shown. In asthmatics all lung function parameters closely parallelled the changes in serum terbutaline concentrations and cAMP plasma concentrations, the FEV1 being the least variable lung function parameter. The maximal effect in FEV1 occurred 30-60 min after the subcutaneous dose and 2-4 h after the oral dose. The FEV1 improvement showed a linear relationship with the serum terbutaline concentration between 1.6 and 6 ng/ml. In contrast with theophyllines and anticholinergics, serum terbutaline concentrations showed a very low interindividual variance. Nevertheless it appeared that prediction of a certain improvement in lung function was not possible on the basis of the serum concentration. Since changes in plasma cAMP values after terbutaline therapy were similar in normals and asthmatics, the lung function improvement in the asthmatics suggests that if a beta-adrenergic defect exists, this must be mainly situated in the lung tissue.

In 8 asthmatic subjects, serum concentrations of terbutaline were correlated with changes in volume of air expelled in the first second of forced expiration (FEV1), other parameters of lung function, c-AMP plasma concentrations and finger tremor values after administration of either 5 mg terbutaline sulphate orally, 0.5 mg terbutaline sulphate subcutaneously or an oral placebo. Prior to the investigation, the patients had not used bronchodilators for 10-14 days. All lung function parameters and tremor values showed a significant correlation with the terbutaline (serum) concentrations in the central compartment and with the c-AMP plasma concentrations. FEV1 was the least variable lung function test. The maximal effect on FEV1 occurred 30-60 min after the subcutaneous dose and 2-4 h after the oral dose, corresponding with the maximal terbutaline serum concentrations and c-AMP plasma levels. In this study, the FEV1 improvement showed a linear relationship with the terbutaline serum concentrations between 1.6 and 6 ng/mL. Three out of 8 asthmatics showed an increase in tremor of more than 6 dB after subcutaneous administration, which corresponded with the awareness of this side-effect. In contrast to theophylline and anticholinergic agents, terbutaline serum concentrations showed a very low interindividual variance. As a consequence, the serum terbutaline concentration was almost predictable. However, the lung function improvement was not predictable since there seems to exist an individual sensitivity for this agonist.