Oral contraceptive steroids increased the residence time of caffeine in 9 young women by a factor of 2. The effect was already manifested during the first cycle 2 weeks after starting oral contraceptive steroids (OCS) and was slightly increased in the second cycle, after 6 weeks on OCS. Toxic effects attributed to oral contraceptive steroids may in part be indirect and due to prolonged retention of absorbed toxic agents to which women are exposed.

Contrary to our hypothesis, hypoxia does not potentiate the effect of exercise training on physical fitness, vascular function, or glucose homeostasis in type 2 diabetes.

The pharmacokinetics of epidural clonidine 150 micrograms was studied in 13 patients who had undergone abdominal hysterectomy. Plasma clonidine concentrations were measured up to 19 h in eight patients. In another five patients frequent blood sampling was performed only during the first 20 min to define early vascular uptake better. Peak plasma clonidine concentrations of 1.08 +/- 0.35 ng ml-1 (mean +/- s.d.) were reached between 5 and 10 min after injection. Plasma elimination half-life was 829 +/- 157 min and plasma clearance was 177 +/- 28 ml min-1. There was a significant decrease in arterial blood pressure within 10 min of the injection of clonidine. The maximum decrease in systolic blood pressure, from a pre-injection value of 135 +/- 24.7 to 99 +/- 14.4 mmHg (18.0 +/- 3.3 to 13.2 +/- 1.9 kPa), occurred at 60 min. Blood pressure remained significantly lower than the pre-injection value for 4 h. There was no change in heart rate. Verbal analogue pain scores, on a scale 0-10, decreased from a median of 7.6 before clonidine to 5.0 after 30 min (P less than 0.05). The median score at 60 min was 4.3. Thereafter, pain scores were not significantly different from the control score. We conclude that epidural clonidine 150 micrograms produces only moderate and short-lived postoperative analgesia. Absorption of clonidine from the epidural space into the blood is very rapid and may contribute to the hypotension that occurs.

Background and purpose: For irradiation of localized prostate-cancer, moderately-hypofractionated regimens with a variety of dose per fraction are used. We adopted a regimen of 70 Gy in 28 fractions of 2.5 Gy, using state of the art radiotherapy (RT) and closely monitored the efficacy, toxicity and health-related quality of life (HRQoL) in a large cohort, using patient-reported outcomes. Materials and methods: Between 2008 and 2016, 462 patients with intermediate-to high-risk localized prostate cancer were treated with RT, 28 fractions of 2.5 Gy, using IMRT/VMAT, an online fiducialmaker based correction protocol and a daily inserted endorectal balloon. Overall freedom from failure (no biochemical or clinical recurrence) , as well as self-reported genitourinary (GU) and gastrointestinal (GI) related toxicity and HRQoL are reported. Results: Overall freedom from failure rates at 3 and 5 years were 92.0% (89.1-94.9%) and 83.5% (78.6-88.4%), respectively. Prevalence rates of grade 2 GU/GI-toxicity were 16.3%/6.3% and 22,1%/3.2% after 3 and 5 years respectively. The 5-year actuarial incidences of grade 2 GU/GI-toxicity were 43.5%/18.5%. HRQoL worsened during RT and gradually recovered thereafter, In accordance with the prevalence rates. Conclusion: Treatment of intermediate-or high-risk localized prostate cancer with RT to 70 Gy in 28 fractions with IMRT/VMAT, using fiducial markers and an endorectal balloon leads to good long-term tumor control rates and acceptable patient reported toxicity rates. Furthermore, patient-reported outcomes, including HRQoL, are essential for a good comparison between different studies. Finally, prevalence rates show a better correlation with HRQoL than actuarial incidence rates do and might therefore better represent the burden of toxicity.

Acne results from the increased production of sebum and the accumulation of sebum in the sebaceous duct. Androgens have a direct influence on this condition as they stimulate both the formation of sebum and the hyperkeratinisation of the upper part of the duct which leads eventually to its obstruction. Clinical tests have demonstrated that most acne patients do not have an increased level of androgen in the blood. They do, however, show an increased conversion of testosterone to 5-alpha-dihy-drotestosterone (5-alpha-DHT) in the skin. This latter hormone is responsible for the stimulation of the sebaceous gland. The enzymic conversion of testosterone to 5-alpha-DHT can be inhibited by progesterone. Progesterone, when applied topically in an alcohol/water solution, is 80 percent metabolized in the skin and is not converted into androgens in the body. It may therefore be expected that the topical application of progesterone will not give rise to side effects in either men or women. Preliminary trials are in agreement with this expectation. Extensive clinical investigations of an alcohol/ water solution of progesterone are therefore recommended, as this may be the first clinically useful, locally active, antiandrogen to be effective in the treatment of acne.