Plasma fluphenazine concentrations in outpatients receiving fluphenazine decanoate (Modecate)

Plasma fluphenazine concentrations were measured by neuroleptic radioreceptor assay in 17 outpatients receiving chronic treatment with intramuscular fluphenazine decanoate. The range of concentrations was 0.5–2.4 μg/L over the dosage range of 0.30–3.2 mg/d. Age, sex and smoking status had no influence on plasma fluphenazine concentrations, which were not correlated with dose (expressed as mg/kg/d). There was no significant correlation between plasma concentration and clinical status of the patients. No difference in plasma concentration between patients with extrapyramidal signs or tardive dyskinesia and those without signs were observed.     

An investigation of the actions of diltiazem on rat aorta exposed to acute hypoxia followed by re-oxygenation.

1 The effects of diltiazem and removal of extracellular Ca2+ were examined on contractions, of the rat isolated aorta, to noradrenaline (NA) and high K+, during exposure to oxygenated conditions and hypoxia followed by re-oxygenation. 2 Exposure to hypoxia caused a similar reduction of contractile responses to NA and KCl, while re-oxygenation restored contractile activity. 3 Ca2+-free conditions abolished responses to KCl but a transient response to NA remained which was resistant to hypoxia. 4 Diltiazem produced similar reductions of responses to NA during both oxygenated conditions and hypoxia, whereas during re-oxygenation the effects of diltiazem upon responses to NA were enhanced. 5 Diltiazem produced a more pronounced reduction of responses to KCl than of responses to NA. However, the reduction of responses to KCl by diltiazem was not modified by the changes in PO2 examined in the present study. 6 The present study indicates that contractions of the rat aorta mediated by intracellular Ca2+ are resistant to the hypoxic conditions studied in the present investigation, whereas those responses mediated by an influx of Ca2+ are reduced. The increase in the contractile response to NA following re-oxygenation may result from an increased influx of extracellular Ca2+ since such responses show an enhanced sensitivity to diltiazem.     

6-L-18F-fluorodihydroxyphenylalanine PET in neuroendocrine tumors: basic aspects and emerging clinical applications.

In recent years, 6-l-18F-fluorodihydroxyphenylalanine (18F-DOPA) PET has emerged as a new diagnostic tool for the imaging of neuroendocrine tumors. This application is based on the unique property of neuroendocrine tumors to produce and secrete various substances, a process that requires the uptake of metabolic precursors, which leads to the uptake of 18F-DOPA. This nonsystematic review first describes basic aspects of 18F-DOPA imaging, including radiosynthesis, factors involved in tracer uptake, and various aspects of metabolism and imaging. Subsequently, this review provides an overview of current clinical applications in neuroendocrine tumors, including carcinoid tumors, pancreatic islet cell tumors, pheochromocytoma, paraganglioma, medullary thyroid cancer, hyperinsulinism, and various other clinical entities. The application of PET/CT in carcinoid tumors has unsurpassed sensitivity. In medullary thyroid cancer, pheochromocytoma, and hyperinsulinism, results are also excellent and contribute significantly to clinical management. In the remaining conditions, the initial experience with 18F-DOPA PET indicates that it seems to be less valuable, but further study is required.     

Lead generation using pharmacophore mapping and three-dimensional database searching: application to muscarinic M(3) receptor antagonists.

By using a pharmacophore model, a geometrical representation of the features necessary for molecules to show a particular biological activity, it is possible to search databases containing the 3D structures of molecules and identify novel compounds which may possess this activity. We describe our experiences of establishing a working 3D database system and its use in rational drug design. By using muscarinic M(3) receptor antagonists as an example, we show that it is possible to identify potent novel lead compounds using this approach. Pharmacophore generation based on the structures of known M(3) receptor antagonists, 3D database searching, and medium-throughput screening were used to identify candidate compounds. Three compounds were chosen to define the pharmacophore: a lung-selective M(3) antagonist patented by Pfizer and two Astra compounds which show affinity at the M(3) receptor. From these, a pharmacophore model was generated, using the program DISCO, and this was used subsequently to search a UNITY 3D database of proprietary compounds; 172 compounds were found to fit the pharmacophore. These compounds were then screened, and 1-[2-(2-(diethylamino)ethoxy)phenyl]-2-phenylethanone (pA(2) 6.67) was identified as the best hit, with N-[2-(piperidin-1-ylmethyl)cycohexyl]-2-propoxybenz amide (pA(2) 4. 83) and phenylcarbamic acid 2-(morpholin-4-ylmethyl)cyclohexyl ester (pA(2) 5.54) demonstrating lower activity. As well as its potency, 1-[2-(2-(diethylamino)ethoxy)phenyl]-2-phenylethanone is a simple structure with limited similarity to existing M(3) receptor antagonists.     

Power versus participation in health service teams: a delicate balance.

The purpose of this paper is to critically review the effectiveness of a participative management approach within health service teams. It questions the reality of staff empowerment as an essential product of this approach, and examines the influence of power issues on the degree of empowerment that the organization may allow. The benefits and challenges of staff participation are highlighted, with reference to the manager's role in the participation process. The article concludes by advocating the positive use of power in order to maintain the integrity and effectiveness of a participative management approach.     

Use of paramagnetic chelated metal derivatives of polysaccharides and spin-labeled polysaccharides as contrast agents in magnetic resonance imaging.

Soluble and insoluble polysaccharides were derivatized with diethylenetriaminepentaacetic acid (DTPA) and/or spin-labeled with 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO). Polysaccharides derivatized with DTPA were prepared via cyanogen bromide activation, coupling to a diamine linker, and to DTPA anhydride. Spin-labeled polysaccharides were also prepared via cyanogen bromide activation. The extent of derivatization for dextran (18 kDa) was about 120 glucose units per DTPA, and for cellulose and starch about 15-30 units per DTPA. For spin-labeled polysaccharides, the average loading ranged from 1 nitroxide per 16 glucose units for starch to 181 for dextran (82 kDa). These derivatized paramagnetic polysaccharides were shown to be more effective relaxants than the small paramagnetic molecules alone. Both soluble and insoluble polysaccharide-linker-DTPA-Gd(III) complexes were effectively cleared from the body (rats) after oral administration. After intravenous administration, the biodistribution of dextran-linker-DTPA-Gd(III) complexes differed significantly from that of GdDTPA. Reduction of the nitroxide by ascorbic acid was retarded in the polysaccharide derivatives, particularly in starch derivatized with both nitroxide and linker-DTPA-Cu(II). These agents showed contrast enhancement in the gastrointestinal tract of rabbits.     

An assessment of the accuracy of electrolyte concentrations in neonatal parenteral nutrition

Over a six‐week period in January and February 2002, 2ml samples were removed from all neonatal PN bags dispensed Samples were submitted for analysis of sodium, potassium and magnesium in triplicate by the hospital's clinical chemistry department using a Vitros Codac 950AT, dry slide, automated analyser Only 19.3, 7.1 and 30.4 per cent of measured sodium, potassium and magnesium concentrations respectively deviated by £5 per cent from stated bag concentrations The results indicate that it is possible that some electrolyte concentrations included in neonatal PN vary significantly from stated values