Measurement of isoniazid in tuberculosis patients using finger sweat with creatinine normalisation: A controlled administration study.

BACKGROUND: Insufficient exposure and poor compliance with anti-tuberculosis (TB) medications are risk factors for treatment failure and the development of drug resistance. Measurement of drugs in biological samples, such as blood and saliva, can be used to assess adherence and make dose adjustments by therapeutic drug monitoring (TDM). Finger sweat testing is a convenient and non-invasive method to monitor patients. OBJECTIVES: To assess the feasibility of finger sweat testing for medication adherence and as a semi-quantitative tool for TDM analysis. METHODS: Ten patients provided finger sweat, blood and saliva samples following a controlled dose of isoniazid. Samples were analysed by liquid chromatography-mass spectrometry. RESULTS: Isoniazid can be detected in finger sweat 1-6 h following administration at typically prescribed dosages. The normalisation of isoniazid to creatinine increases the correlation between finger sweat and serum isoniazid concentration and provides a means to account for inconsistent sample volumes. CONCLUSION: We describe the time-course measurement of isoniazid (or drug-to-creatinine ratio) in finger sweat compared to the pharmacokinetic profile in blood for the first time. This technique, adaptable for other drugs, could reduce the burden on clinics and improve patient experience.

Noninvasive drug adherence monitoring of antipsychotic patients via finger sweat testing.

Collection of finger sweat is explored here as a rapid and convenient way of monitoring patient adherence to antipsychotic drugs. Finger sweat samples (n = 426) collected from patients receiving treatment with clozapine, quetiapine and olanzapine were analysed by liquid chromatography mass spectrometry, including a subgroup of patients with paired plasma samples. Finger sweat samples were also analysed from a negative control group and patients who had handled antipsychotic medication only. The finger sweat test (based on the detection of parent drug in one donated sample) was 100% effective in monitoring adherence within commonly prescribed dosing ranges. In comparison to participants who handled the medication only, the test could distinguish between contact and administration through monitoring of the drug metabolite, or the level of parent drug. Additionally, in a subgroup of patients prescribed clozapine, a statistically significant correlation was observed between the mass of parent drug in finger sweat and plasma concentration. The finger sweat technology shows promise as a dignified, noninvasive method to monitor treatment adherence in patients taking antipsychotics.

Physiological, environmental and genetic variation in apical dominance as determined by decapitation in Triplochiton scleroxylon.

Patterns of lateral shoot growth following decapitation in 1-meter tall, rooted Triplochiton scleroxylon K. Schum. cuttings varied with clone and in response to a range of environmental conditions and growth regulator treatments. Two phases of bud activity were identified, the Sprouting Phase, in which many buds were released from correlative inhibition, and the Dominance Phase (starting 3-4 weeks after decapitation) in which uppermost laterals began to dominate and suppress growth, and sometimes cause apical abscission of lower lateral shoots. Except in non-erect plants, the most distal lateral to elongate became the new leading shoot. During the Sprouting Phase, the proportion of active buds was increased by removing leaves from the upper part of the stem, and by reducing the photoperiod from 13-15 h to 11 h, particularly at 20 degrees C rather than 25 degrees C. Conversely, the proportion of sprouting buds was decreased by injecting plant stems with NAA (250 microg/plant). During the Dominance Phase, suppression of lateral shoot growth was hastened by stem injection with GA(3) (200 microg/plant), especially when applied to the uppermost shoot at the end of the Sprouting Phase. Reimposition of dominance was delayed, however, by (1) high rates of N:P:K fertilization, (2) low temperature (20 versus 25 degrees C) under relatively long days (13 and 15 h), (3) low photon flux density (160 micromol m(-2) s(-1)) and (4) severe defoliation. Plant orientation had no effect on bud activity of decapitated plants, but affected the relative vigor and orientation of new lateral shoots. High temperature (25 versus 20 degrees C) and injection with GA(3) increased the erectness of newly developing lateral shoots.

Effects of gibberellin A(4 + 7) and bark-ringing on cone initiation in mature Picea sitchensis grafts.

Large numbers of cones (strobili) were induced in a 10-year-old plot of mature grafts of Picea sitchensis (Bong.) Carr. All trees injected with 20 mg GA(4 + 7) in June initiated female and male cones in the same year. This treatment increased the number of female cones per plant 12-fold above the controls, more than doubling the percentage of cones that were female. Complete bark-ringing (done in May of the previous year) showed an additive effect with GA on the number of female cones formed, but a negative interaction on the number of male cones induced. Ringing promoted male cone production most when used alone. Treatments, singly or combined, also increased the proportion of cones that were lateral, compared with the preponderance of terminal male cones in the controls. The effects were apparently not directly associated with alterations in vegetative vigor, although these occurred causing a reduction in the proportion of buds containing vegetative shoots the following year. The clones differed in most characteristics, but both sparse and prolific clones were induced to reproductive activity. Viable seed yields per tree, and notional production from seed-orchards were enhanced almost 10-fold by GA injection, and about 4-fold by bark-ringing and GA + bark-ringing.