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Biomedical subjects

J Kraan

Publications and source records attributed to J Kraan.

46 records · Page 3Linked to original sources

Creation of four consecutive instantaneous steady-state plasma concentration plateaus of theophylline and enprofylline by repeated infusions with exponentially decreasing delivery rates.

Repeated exponentially decreasing infusions have been used to administer theophylline and enprofylline to show whether it would be feasible to create consecutive plasma concentration plateaus within a few hours. The infusions were carried out on two separate days in 8 stable asthmatics. Before the infusion experiments, the pharmacokinetics of the substances in the individual subjects were determined on a separate day. Plasma concentration rose to the desired level within 5 min after the start of the infusion at each dose level and a stable plasma concentration plateau was maintained during the following 90 min of the infusion. It was possible to achieve 4 subsequent concentration plateaus within a 6 h period. Use of this infusion method resulted in predictable plasma concentrations at all levels and so the method appears safe when the required plasma concentrations are below the toxic level. Apart from clinical situations where effective dosages of drugs must be administered rapidly, the method showed be useful in pharmacological dose-response studies.

Adult↗

Dosage and time effects of inhaled budesonide on bronchial hyperreactivity.

In a double-blind study of 2 parallel groups of 15 allergic asthmatic patients each, we investigated whether treatment with inhaled budesonide has a dose- and time-dependent effect on the degree of bronchial hyperreactivity. The patients were randomly allocated to treatment with either 200 or 800 micrograms budesonide per day for a period of 8 wk. The active treatment period was preceded by a selection period of 3 wk, and a single-blind placebo period of 2 wk. During these initial 5 wk the maintenance treatment of the patients, including cromolyn sodium and inhaled corticosteroids, was withheld. Spirometry and inhalation provocation tests with methacholine were carried out, and the symptom score was recorded every 2 wk. The methacholine provocation concentrations (geometric mean) causing a decrease in FEV1 of 20% (PC20) in the 200 and 800 micrograms/day treatment groups just before the active treatment period were 0.90 and 0.91 mg/ml, respectively. These values increased significantly to 1.21 and 1.84 mg/ml after 2 wk of treatment (p less than 0.05 and p less than 0.001, respectively) and to 1.55 and 2.74 mg/ml after 8 wk of treatment (p less than 0.01 and p less than 0.001). During the whole study period budesonide in a dosage of 800 micrograms/day induced a significantly larger change in PC20 than in a dosage of 200 micrograms/day. The FEV1 before treatment was 91 +/- 3% (SEM) and 84 +/- 2% of the predicted value in the 200 and 800 micrograms/day treatment groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

Changes in bronchial hyperreactivity induced by 4 weeks of treatment with antiasthmatic drugs in patients with allergic asthma: a comparison between budesonide and terbutaline.

We performed a double-blind crossover study to compare the effects of long-term treatment of inhaled budesonide and terbutaline on bronchial hyperreactivity in 17 patients with allergic asthma. Both drugs were administered for 4 weeks with a placebo-treatment period before and after each active-treatment period. To assess bronchial hyperreactivity, standardized inhalation provocation tests with histamine and propranolol were performed every 2 weeks. Before each inhalation provocation the drugs were withheld for at least 12 hours. Before the budesonide treatment the FEV1 value (percent predicted) was 85.3 +/- 4.1% (mean +/- SEM). After 2 and 4 weeks of treatment with this drug, the value increased significantly to 89.4 +/- 4.1% and 96.2 +/- 3.8%, respectively (p less than 0.05 and p less than 0.005). The histamine provocation concentrations causing a decrease in FEV1 of 20% (PC20) on the same days were 4.0, 7.2, and 9.5 mg/ml, respectively (both p less than 0.001). The PC20 values for propranolol, which were measured 1 hour after the histamine provocation, were 11.7, 13.3, and 14.0 mg/ml (ns). The FEV1 values before and after 2 and 4 weeks of treatment with terbutaline were 86.2 +/- 4.0%, 84.8 +/- 4.1%, and 87.0 +/- 4.6%, respectively. The histamine PC20 values on the same days were 4.7, 3.1 (p less than 0.05), and 3.8 mg/ml, respectively. The propranolol PC20 values were 14.2, 8.7, and 10.1 mg/ml (p less than 0.001 and p less than 0.05, respectively. We conclude that budesonide improves bronchial hyperreactivity, possibly by a dampening of late allergic reactions, whereas treatment with terbutaline may lead to a temporary increase of bronchial hyperreactivity, possibly as a result of beta-receptor desensitization.

Adolescent↗

Three-color flowcytometric analysis of mature and immature hematological malignancies. A guideline of the Dutch Foundation for Immunophenotyping of Hematological Malignancies (SIHON).

Multiparameter flowcytometry offers an insight into differentiation pathways, maturation stages and abnormal features of cell (sub)populations thus helping to establish and classify hematological malignancies. The Dutch Foundation for Immunophenotyping of Hematological Malignancies (SIHON) has formulated a guideline for a rapid screening followed by confirmation and classification in a standardized way. For this aim seven carefully composed monoclonal antibody combinations are elucidated for screening the test sample in a first phase. In this phase a relative frequency distribution of the cells will be established and a decision will be made about abnormal cells present, as well as their mature or immature state and the cell lineage they belong to. In a second phase, panels with cell lineage dependent monoclonal antibody combinations may be used to confirm and classify the abnormal cell population indicated in phase 1, as well as to establish the presence or absence of an abberant immunophenotype.

Flow Cytometry↗