Tape stripping of human stratum corneum yields cell layers that originate from various depths because of furrows in the skin

Received: 21 November 1996     

Effects of the long acting beta agonist formoterol on asthma control in asthmatic patients using inhaled corticosteroids. The Netherlands and Canadian Formoterol Study Investigators

BACKGROUND: The long acting beta 2 agonist formoterol has proved to be an effective bronchodilator with a prolonged action of 12-14 hours. However, the precise role of formoterol in the maintenance treatment of asthma is still under debate. A study was performed to investigate the efficacy and safety of treatment with formoterol for six months in subjects with asthma. METHODS: In a multicentre double blind, placebo controlled, parallel group study 239 subjects with mild to moderate asthma were randomly assigned to treatment with either inhaled formoterol 24 micrograms twice daily (n = 125) or placebo (n = 114) during eight months. The study consisted of a four week run in period, a 24 week treatment period, and a four week washout period. All subjects were using regular inhaled corticosteroids (100-3200 micrograms daily) but were still needing at least five inhalations of short acting beta 2 agonist per week for symptom relief. The study was performed in 10 outpatient clinics in Canada, and five outpatient clinics and one coordinating centre for 44 Dutch general practitioners in The Netherlands. Twice daily self-reported peak expiratory flow (PEF) measurements, symptom scores, and rescue beta 2 agonist use during the last 28 treatment days compared with baseline values were used as main outcome measures. Spirometric values were measured at entry, at the start of treatment, after four, 12 and 24 weeks of treatment, and after four weeks washout. RESULTS: One hundred and twenty five subjects received formoterol 24 micrograms twice daily via Turbohaler and 114 received placebo. Baseline FEV1 was 67.1% predicted and mean bronchodilator reversibility was 26%. The mean total asthma symptom score was 3.6 (maximum possible 21). A significant decrease in symptoms in favour of formoterol (difference from placebo -0.64, 95% CI -0.04 to -1.23, p = 0.04) was observed. Compared with placebo, morning PEF increased (difference from placebo 28 l/min, 95% CI 18.3 to 37.7, p = 0.0001) and the use of short acting beta 1 agonists decreased (daytime difference from placebo -1.1 inhalation, 95% CI -1.4 to -0.7, p = 0.0001) in the formoterol group. PEF returned to baseline following discontinuation of formoterol, as did asthma symptom scores. Thirty three patients treated with formoterol and 32 treated with placebo required treatment with prednisolone during the study (58 and 55 courses, respectively). CONCLUSIONS: Adding formoterol 24 micrograms twice daily by Turbohaler to inhaled corticosteroids was effective in improving symptom scores and morning PEF, and decreasing the use of rescue beta 2 agonists. There was no apparent loss of asthma control during 24 weeks of treatment with formoterol.


     

Potential radiopharmaceuticals for the detection of ocular melanoma. Part III. A study with 14C and 11C labelled tyrosine and dihydroxyphenylalanine

In order to investigate the possibility of using [1-11C] labelled 3,4-dihydroxyphenylalanine (DOPA) and tyrosine as radiopharmaceuticals for the detection of eye melanoma, the biodistributions of the same 1- and 3-14C-labelled compounds were investigated in Syrian golden hamsters with Greene melanoma. The results of these investigations were compared with positron emission tomography (PET) images of 11C labelled DOPA and tyrosine. The synthesis of these 11C labelled compounds procures of DL mixture, from which D and L forms can be separated. One h after intravenous injection, both 14C labelled DL-, L- and D-DOPA showed a high uptake in tumour tissue, that of DL- and D-DOPA being the highest. These high uptakes, together with relatively low uptake in bone, skin and eye resulted in high tumour/non tumour ratio (for DL-DOPA 5.9, 4.5 and 6.6 respectively). Extraction of the tumour tissue with trichloroacetic acid showed that L-DOPA was mainly incorporated into melanin, whereas D-DOPA was not. Also, the uptake 1 h after intravenous injection of 1-14C-L- and DL-tyrosine into the tumour were high, but L- and DL- were less different; tumour/non tumour ratios were favorable. PET images of the tumour obtained 40-80 min after injection of the [1-11C] labelled DOPA and tyrosine confirmed that melanoma detection was promising and that D-DOPA produced a better melanoma image than L-DOPA.     

On the Shift from Anticipatory Heart Rate Deceleration to Acceleratory Recovery: Revisiting the Role of Response Factors

The influence of inducing motor responses of low and high force at different times in the cardiac cycle was examined. A handgrip response was used which allowed the separation of response initiation from response completion. Based on earlier work, we expected initiation, rather than completion, to initiate poststimulus cardiac acceleration. We also thought that preparation for a high force response might alter preparatory changes of interbeat interval differently from preparation for a low force response. Fifteen college-aged male subjects performed a warned reaction time task in which a visual stimulus signalled a handgrip requiring either a high or a low force to close. NoGo trials in which an inhibit signal was presented occurred on 12% of the trials. Stimuli occurred either on the R-wave of the electrocardiogram or 300 ms later. Reaction speed was varied in different trial blocks by rewarding response times of 200 ms (+/- 50 ms), 300 ms, or 400 ms. Results based on the timing of response initiation were essentially identical to those based on the timing of response completion. High force relative to low force was associated with both earlier response initiation and earlier cardiac acceleration. Force did not alter preparatory cardiac deceleration. Force and response speed did, however, alter the level of heart rate after response occurrence. Thus, response initiation (or an earlier response process) appears to induce a cardiac acceleration whose level is influenced by the speed and force of the motor response.     

Prolactin concentration in plasma and susceptibility to mammary tumors in female rats from different strains treated chronically with estradiol-17β

Summary Prolactin is associated with the development of mammary tumors in rats. The aim of the present study was to evaluate whether strain differences in susceptibility to the development of mammary tumors could be explained by genetic differences in the response of the pituitary to chronic stimulation by estrogens. Prolactin levels were measured in plasma from rats of the Sprague-Dawley, Wistar WAG/Rij and Brown Norway BN/BiRij strains before and at different times after subcutaneous implantation of estradiol-17 in cholesterol/paraffin pellets. In all strains plasma prolactin was elevated from the second week after implantation of the pellet, although there were quantitative differences between the responses. At 32 weeks after implantation of the pellets the plasma level of prolactin in Sprague-Dawley rats was 1247 ± 367 ng NIAMDD prolactin RP-1/ml (mean ± S.E.M), whereas Wistar WAG/Rij and Brown Norway BN/BiRij had plasma prolactin levels of 679 ± 211 and 182 ± 19 ng/ml respectively. Between 52 and 104 weeks after implantation these values rose to 4016 ± 1116, 5004 ± 1053 and 808 ± 129 ng/ml respectively. The plasma concentration of prolactin of rats in this age group was strongly associated with the occurrence of pituitary adenomas in all three strains. In untreated rats, the concentration of prolactin in the plasma increased with age to only 200–400 ng/ml at 12–24 months of age but no significant differences were observed between the three rat strains. It is concluded that observed differences in spontaneous and estrogen-mediated mammary tumor development in these rat strains cannot be explained by genetic differences in the plasma concentration of prolactin. The development of malignant mammary tumors after estrogen treatment appears to be associated with the extent of the increase in plasma prolactin induced by the estrogen.     

Development of a primary-care tool to assess treatment success in COPD: consensus report from a closed meeting of respiratory and primary-care specialists.

A 1-day meeting, attended by invited respiratory and primary-care specialists all of whom had an international profile and a specific interest in Chronic Obstructive Pulmonary Disease (COPD), considered specific research recommendations from the Global Initiative in Obstructive Lung Disease (GOLD) workshop report. Attendees discussed developing a tool to complement spirometry and help primary-care physicians assess treatment success in patients with chronic obstructive pulmonary disease. Discussion focused on the requirement of such a tool, and the limitations of existing tools. Proposals followed for a simple, cost-effective checklist for primary-care. This paper is a consensus report of the discussions from the meeting. Decisions reached on the proposed questionnaire were unanimous.