Efficacy of meditation in generalized anxiety disorder.

A study was conducted to compare the efficacy of meditation with that of imipramine and chlordiazepoxide in the treatment of Generalized Anxiety Disorder. At the end of five weeks, meditation was found to be as effective as pharmacotherapy in controlling symptoms of anxiety. It was superior in altering trait anxiety (TMAS Scores).

The pharmacology of oral anticoagulants: implications for therapy.

All oral anticoagulants act by producing a functional deficiency of vitamin K, thereby impairing the normal synthesis of factors II, VII, IX and X. All, except dicumarol, are well absorbed after oral administration. They are highly protein bound and are mainly metabolized in the liver.

Effective reversal of warfarin-induced excessive anticoagulation with low dose vitamin K1.

Reversal of the anticoagulant effect of warfarin in patients with no active haemorrhage can be achieved by administration of intravenous vitamin K1. Currently recommended doses of intravenous vitamin K1, for this purpose often result in subsequent difficulties in anticoagulation. We observed the response to low dose intravenous vitamin K1 in patients requiring reversal of anticoagulant therapy.

Hypernatraemia in an adult in-patient population.

We report a retrospective study of hypernatraemia (serum sodium concentration greater than 150 mmol/l) in an adult in-patient population of a health district during one year. The incidence was 0.3% with at least 60% of cases developing after hospital admission, mainly in elderly patients.

An automatic reaction control chemical ionization technique in ion trap detector for quantitative plasma profding of arecoline in treated alzheimer patients.

An automatic reaction control chemical ionization technique in an ion trap detector (lTD) was used to quantitate the levels of the cholinergic drug, arecoline, in plasma of treated patients with Alzheimer's disease. The chemical ionization reaction was carried out with acetonitrile. The protonated molecules of arecoline (m I z 156) and the internal standard, homoarecoline (m / z 170), were monitored.

Optimising the dose of oral anticoagulants.

Oral anticoagulants, although valuable, can be dangerous if their use is not carefully monitored. Variability in response to warfarin due to a variety of factors means that initial dose is difficult to predict. The fixed dose regime for initiation of anticoagulant therapy (10 mg daily for three days) results in excessive anticoagulation in one third of patients.

Enantioselective and diastereoselective aspects of the oxidative metabolism of metoprolol.

Enantio- and diastereoselective aspects of oxidative metabolism of metoprolol (1) were examined in the presence of rat liver and human liver microsomes using a pseudoracemate of 1, made up of equal molar (2R)-1-d0 and (2S)-1-d2, as substrate. Both O-demethylation and alpha-hydroxylation showed only slight enantioselectivity, 2R/2S ratios being 1.18 and 0.

Clinical presentation and investigation of patients proceeding to isotope lung scanning for suspected pulmonary embolism.

The presenting features of 250 consecutive patients who underwent a ventilation/perfusion lung scan for suspected pulmonary embolus (PE) were analysed. Ninety-six patients had lung scans highly suggestive of PE, with one or more unmatched segmental perfusion defects (scan positive), 86 had low probability scans (scan negative) and 68 an indeterminate scan. Scan positive patients were more likely to have a PaO2 of less than 10.

Brain uptake and anticancer activities of vincristine and vinblastine are restricted by their low cerebrovascular permeability and binding to plasma constituents in rat.

Unidirectional blood-brain barrier transfer of the lipophilic anticancer agents vincristine and vinblastine was studied in anesthetized rats, using an isolated, in situ brain perfusion technique. Drug binding to plasma constituents was also measured. Despite the high lipophilicity of these agents (the log octanol/physiological saline partition coefficient equalled 2.

Anticentromere antibody positive CREST syndrome associated with polyarthritis, renal impairment and mixed cryoglobulinaemia.

We describe a 63-year-old female who developed the CREST syndrome within two years. Even though she was anticentromere antibody positive, her illness followed a very aggressive course and was associated with severe polyarthritis, renal impairment, hypocomplementaemia and mixed cryoglobulinaemia.

Clinical pharmacokinetic considerations in the control of oral anticoagulant therapy.

Aspects of the pharmacokinetics of warfarin that are clinically relevant are reviewed here. Since warfarin is normally completely absorbed, resistance to treatment due to impaired absorption is unusual, even in severe short bowel syndrome. Warfarin is highly albumin-bound; thus, hypoalbuminaemic states result in an increased free fraction of the drug and a decreased half-life but, as might be expected, there is no evidence of altered response at steady-state.

Carotid sinus hypersensitivity and complete heart block in Reiter's syndrome.

We describe a 42-year-old man with Reiter's syndrome who developed complete heart block only 5 weeks after the onset of his illness. He was also noted to have carotid sinus hypersensitivity and evidence of sinoatrial disease. There were no clinical signs or echocardiographic findings to suggest involvement of the aortic root or aortic valve.

Chemical aspects of metoprolol metabolism. Asymmetric synthesis and absolute configuration of the 3-[4-(1-hydroxy-2-methoxyethyl)phenoxy]-1-(isopropylamino)-2-propanols , the diastereomeric benzylic hydroxylation metabolites.

Asymmetric synthesis of 3-[4-(1-hydroxy-2-methoxyethyl)phenoxy]-1-(isopropylamino)-2-propanol (2), the benzylic hydroxylation metabolite of metoprolol (1), is described, and the absolute configurations of the diastereoisomers were assigned. Ketone 3, prepared in a multistep synthesis, was reduced with a complex of (2S)-(-)-2-amino-3-methyl-1,1-diphenylbutan-1-ol (9) and borane, yielding 2, with a ratio of 82:18 for the diastereomers. The absolute configurations 1'S,2S and 1'S,2R were assigned for the diastereomers formed in excess on the basis of reductions on closely related alkyl phenyl ketones and the circular dichroism spectrum.

Chemical and stereochemical aspects of propranolol metabolism. Diastereomeric 1-(1-hydroxy-2-propylamino)-3-(1-naphthoxy)-2-propanols produced by rat liver microsomal omega-hydroxylation.

A new metabolic pathway of terminal hydroxylation (omega-hydroxylation) of the N-isopropyl group of propranolol (1) was established. Selected ion-monitoring GC-MS analysis, based on use of the synthesized mixture of diastereoisomers of 1-(1-hydroxy-2-propylamino)-3-(1-naphthoxy)-2-propanol (2) as a standard, established formation of both diastereoisomers of 2 as metabolites of 1. These diastereoisomers were formed in unequal amounts when 1, its hexadeuterated analogue 8 or heptadeuterated analogue 9, were incubated in the presence of the rat liver microsomal fraction.

Attempts to use cyanide ion to trap imine intermediates in the microsomal N-dealkylation of propranolol: formation of alpha-aminonitriles as artifacts when using ether for extraction.

Cyanide anion was used to attempt to trap possible imine intermediates in the oxidative N-dealkylation of propranolol (1). Reaction of 3-(1-naphthoxy)-1-amino-2-propanol (desisopropylpropranolol, 2) with acetone provided this expected intermediate in an approximately 7:1 ratio of oxazolidine 6 to imine 5, as determined by 1H NMR. The mixture when treated with sodium cyanide gave the expected alpha-aminonitrile 7.

Radioimmunoassay for psychotropic drugs. III: Synthesis and properties of haptens for trifluoperazine and fluphenazine.

For the development of radioimmunoassay procedures for trifluoperazine and fluphenazine, three haptens, N-(2-carboxyethyl)desmethyltrifluoperazine, N-(4-carboxybutyl)desmethyltrifluoperazine, and 10-[3-(4-carboxyethylpiperazinyl)-3-oxopropyl]-2-trifluoromethyl-+ ++10H- phenothiazine, were synthesized and characterized. Each hapten was coupled to bovine serum albumin, and the number of hapten residues per mole of bovine serum albumin was calculated by UV spectrophotometric methods. Antibodies to each hapten-protein conjugate were developed in rabbits, and titers of the antisera were checked by evaluating their binding characteristics to the tritiated drug.

Synthesis of deuterium-labeled fluphenazine.

The propylpiperazine side chain of fluphenazine has been labeled with two, four, and six deuterium atoms by lithium aluminum deuteride reduction of the appropriate ester or imide. The gamma-carbon of the propyl group was labeled with two deuterium atoms by reduction of 10- (2-methoxycarbonylethyl) -2-trifluoromethyl-10H-phenothiazine, while four deuterium atoms were incorporated into the piperazine ring by reduction of 10-[3-(3,5-dioxo-1-piperazinyl)propyl]-2-trifluoromethyl-10H-pheno thiazine. The latter reduction gave the d4-labeled N-deshydroxyethyl metabolite of fluphenazine.

Synthesis of deuterium-labeled prochlorperazine.

The propylpiperazine side chain of prochlorperazine was labeled with two, four, or six deuterium atoms by lithium aluminum deuteride reduction of the appropriate amide. The isotopic purity of the products after correcting for chlorine isotopes was greater than 95.7%.

Development of radioimmunoassays for trifluoperazine and their application to metabolic studies of the drug.

Antisera to trifluoperazine have been raised in New Zealand white rabbits to several different types of immunogens, where there was variation in the length and nature of the side chain attached to the phenothiazine nucleus, as well as in the number of hapten residues coupled to bovine serum albumin. A radioimmunoassay for trifluoperazine has been developed which is capable of quantitating 0.3125 ng ml-1 in a 200 microliter plasma sample, with cross-reactivities to the sulfoxide, 7-hydroxy, and N-desmethyl metabolites of trifluoperazine of the order of less than 1, 11, and 12%, respectively.

Radioimmunoassay for prochlorperazine in human plasma.

A new sensitive, specific, and rapid radioimmunoassay procedure for the determination of plasma concentrations of the antiemetic drug prochlorperazine is described. The assay enables the quantitation of 31 pg of the drug in 200 microliters of plasma with a coefficient of variation of approximately 2%. Except for N-desmethylprochlorperazine, the antiserum did not cross-react with the available metabolites tested.