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To optimize appropriate antimicrobial use in a university hospital and identify barriers hampering implementation strategies, physicians were interviewed regarding their opinions on antimicrobial policies. Results indicated that effective strategies should include regular updates of guidelines that incorporate the views of relevant departments and focus on addressing senior staff and residents because residents do not make independent decisions in a teaching-hospital setting.

Objective: To investigate whether the health-economics research published in Dutch journals is in agreement with the guidelines for pharmaco-economic research as published in 1999 by the Dutch 'College voor zorgverzekeringen' [Healthcare Insurance Board]., Design: Descriptive., Method: A literature search was performed for health-economic evaluations published during 1990-1999 in Dutch journals such as Nederlands Tijdschrift voor Geneeskunde (NTvG), Pharmaceutisch Weekblad and Tijdschrift voor Gezondheidswetenschappen. The resulting 19 studies, primarily published in the NTvG, were compared with the pharmaco-economic guidelines, summarised in 9 criteria., Results: The social perspective was taken in 5 studies (26%), non-related medical costs were excluded in 19 (100%), relevant subgroup analyses were performed in 16 (84%), effectiveness was explicitly differentiated from efficacy in 15 (79%), incremental analysis was performed in 18 (95%), an adequate period of analysis was chosen in 16 (84%), costs, benefits and health gains were discounted in 13 (68%), sensitivity analysis was included in the investigation in 10 (53%), and estimated cost prices were used in 9 (47%)., Conclusion: The methodology in recently published Dutch health-economics research was partly in agreement with the later official guidelines for pharmaco-economic studies in the Netherlands.

An in vitro/in vivo study was carried out with different rectal formulations of temazepam. Pharmacokinetic data were determined in a cross-over study in 10 volunteers after rectal administration of 10 mg temazepam as a polyethylene glycol based suppository (selected from in vitro data), a liquid-filled capsule and a micro-enema respectively, using oral administration of a liquid-filled capsule as a reference. Serum levels of temazepam indicate an instantaneous and complete release from the micro-enema (Frel = 0.94 +/- 0.21, Cmax 205 +/- 36.9 micrograms/l, tmax 0.49 +/- 0.31 hour) and a slower but complete release of temazepam from the suppository (Frel = 1.10 +/- 0.25, Cmax 202 +/- 41.3 micrograms/l, tmax 1.48 +/- 0.41 hour). A high interindividual variation in absorption profiles was observed after rectal administration of the liquid-filled capsule (Frel 0.72 +/- 0.36, Cmax 182 +/- 122 micrograms/l, tmax 4.08 +/- 4.28 hour), which makes it less suitable for rectal use. The micro-enema and suppository appear to be useful as rectal formulations for temazepam.

A simple extraction system for the selective and quantitative isolation of apomorphine from human plasma is described. Apomorphine and N-n-propylnorapomorphine were isolated by complex formation between a borate group and the diol group of the apomorphines in an alkaline medium, this in combination with ion-pair formation. The reproducibility and linearity of this extraction method combined with high-performance liquid chromatography with electrochemical detection is excellent. The absolute mean recovery of apomorphine was 100%, the recovery of N-n-propylnorapomorphine was 98%. The detection limit of apomorphine in human plasma in the described system is approximately 0.5 ng/ml.

A hypothesis to explain the stimulatory role of cyclic AMP (adenosine 3':5'-monophosphate) in pancreatic enzyme secretion. has been tested. In this hypothesis cyclic AMP would activate a phospholipase activity, which would lead to a locally increased lysophospholipid formation, resulting in a fusion between the zymogen granule membrane and the apical plasma membrane. Cyclic AMP added to isolated pig pancreatic zymogen granules leads to an increased lysis of these granules, but the slowness of this effect makes its physiological significance dubious. In pancreatic homogenates or zymogen granules no stimulating effect of cyclic AMP on lipase of phospholipase activity could be demonstrated. Isolated zymogen granules have a high lysophospholipid content (27% of total phospholipids), consisting of the 1-acyl and 2-acyl forms of lysophosphatidylcholine and lysophosphatidylethanolamine. Experiments with radioactive phosphatidylcholine indicate that the lysophospholipids are due to the action of endogenous (phospho)lipases during the isolation procedure. It is concluded that these experiments do not lend support to the above hypothesis for the mechanism of action of cyclic AMP in pancreatic enzyme secretion