Sedation and analgesia in interventional radiology: Where do we stand, where are we heading and why does it matter?

The aims of this review were to describe the rationale and the techniques of sedation in interventional radiology, and to compile the safety and efficacy results available so far in the literature. A systematic MEDLINE/PubMed literature search was performed. Preliminary results from several studies demonstrated the feasibility, the efficacy and the safety of using sedative techniques in interventional radiology. Beyond pharmacological sedation and clinical hypnosis, digital sedation could reduce the anxiety and pain associated with interventional radiology procedures.

Positron emission tomographic studies of [11C]MDL 72222, a potential 5-HT3 receptor radioligand: distribution, kinetics and binding in the brain of the baboon.

The drug MDL 72222, a selective 5-HT3 receptor antagonist, was labelled with 11C and evaluated for distribution kinetics in brain and in vivo binding to 5-HT3 receptors using cold MDL 72222 challenge and positron emission tomography (PET), in three anaesthetized baboons. After tracer doses of [11C]MDL 72222 (i.v. bolus), 11C radioactivity was equally partitioned between plasma and blood cells and readily crossed the blood-brain barrier; it was distributed heterogeneously into 17 different structures of the brain. The kinetic curves for 11C in tissue showed a rapid initial uptake, followed by a slower ascending phase, up to about the twentieth minute and by a plateau, until the end of experiment (90 min). The plateau values indicated marked uptake in brain which, however, varied according to the region considered. In inhibition studies with cold MDL 72222 (1 mg.kg-1) as pretreatment, co-injection or displacement, no clear-cut effects on the kinetics of [11C] MDL 72222 in brain were detected in any region, including those known to be rich in 5-HT3 receptors. These observations suggest that specific binding to 5-HT3 receptors was not detectable in brain in vivo, because of the high lipophilicity (thus a great capacity for non-specific binding) of MDL 72222. These negative findings may also result from both the possible suboptimal affinity of MDL 72222 for 5-HT3 receptors in vivo and the relatively low density of 5-HT3 receptors present only in selected areas of the mammalian brain. This study is a step in the search of selective 5-HT3 receptor radioligands, adequate for in vivo applications. Slow clearance of [11C]MDL 72222 from brain tissue in baboons, should be accounted for in clinical pharmacokinetic investigations for optimal posology considerations.

Clinical pharmacokinetics after repeated intrapleural bupivacaine administration.

Patients (n = 14) who underwent thoracotomy during surgery of the oesophagus for cancer received an initial intrapleural dose of 10 ml bupivacaine hydrochloride 2.5 mg/ml followed by repeated administration every 8 hours from the first to the fourth postoperative day. The mean (+/- SD) peak plasma drug concentration (Cmax) [352 +/- 120 micrograms/L], time to peak (tmax) [0.83 +/- 0.51 h], and first-order absorption rate constant (ka) [5.46 +/- 4.95 h-1] after the twelfth dose were significantly different from the Cmax (206 +/- 81 micrograms/L), tmax (1.8 +/- 1.2h), and ka (1.8 +/- 1.47 h-1) determined after the first dose. Half-life (3.5 +/- 2.2h) and mean concentration (204 +/- 105 micrograms/L) were not significantly different on the fourth day from those on the first (4.1 +/- 2.6h and 142 +/- 71 micrograms/L, respectively). No sharp peak corresponding to systemic toxicity and no accumulation could be expected with these low doses, administered at short intervals and providing good pain relief in this surgical series.

Serum level monitoring and therapeutic effect of haloperidol in schizophrenic patients.

Haloperidol serum concentrations were determined after IM or oral treatment in 15 schizophrenic patients. No correlation was found between drug levels and therapeutic effect. However, a good relationship was found between the half-life calculated after the first IM injection and the BPRS decrease after 3 weeks. Therefore a serum level study to the first day may forecast the therapeutic response.

A gas-liquid chromatographic method for the quantitative determination of quinidine in blood.

A gas-liquid chromatographic method, using chloroquine as internal standard, for quinidine evaluation in serum is described. Prior to acidic delipidation, chloroquine is added to the serum sample and an alkaline extraction is used. Direct gas-liquid chromatographic analysis of unaltered forms using a nitrogen detector is performed. The sensitivity limit of this method is 0.5 microng/ml, i.e. sufficient for therapeutic quinidine blood level determinatin (1 to 5 microng/ml).

A practical proposal for arginine-vasopressin radioimmunoassay.

This work proposes the use of (a) a commercially available homologous system AVP antibody-AVP (Arginine Vasopressin) standard and (b) new acquisitions for the improvement of sensitivity for AVP radioimmunoassay by separate or simultaneous use of two-phase sequential incubation and epsilon-aminocaproic acid (EACA). The antiserum used in the system described is very specific since none even cross-reacted with lysine vasopressin (LVP) and has an apparent affinity constant (K) of 0.909 +/- 0.047 X 10(12) l/mol. This is sufficiently high to detect 0.5 +/- 0.2 pg/tube, which is theoretically expected of biological AVP. The total assay time is less than 48 h.

[Fast and accurate method for theophylline analysis in preterm babies using gas chromatography and nitrogen selective detector (NFID) (author's transl)]. / Méthode de chromatographie en phase gazeuse-NFID pour la détermination rapide de la théophylline sanguine chez les enfants prématures.

The combined utilization of (a) a weak polar OV-1 phase, (b) an on-column methylation using a methylating agent commercially available, (c) a nitrogen selective detector (NFID) and (d) a small volume of sample, allows the development of a fast (less than 20 min) and accurate method for theophylline analysis in preterm babies. With 50 microliter of capillary whole blood sample, its limit of sensitivity was 0.5 microgram/ml of theophylline. This method is most desirable for theophylline monitoring in treating apnea of premature infants.

Simultaneous GLC determination of phenylpropanolamine and chlorpheniramine in urine using a nitrogen selective detector.

A simple, rapid, and sensitive simultaneous quantitative determination of phenylpropanolamine and chlorpheniramine in human urine by GLC, using a nitrogen specific detector, is described. After alkaline extraction from urine, phenylpropanolamine and chlorpheniramine are analyzed directly by GLC, without a derivatization step. Promethazine was used as the internal standard. The total assay time is less than 30 min. The method is useful in studies of pharmacokinetic and pharmacological interactions of drug combinations.

Improved electron-capture GLC determination of alprenolol and oxprenolol in serum using a wall-coated open tubular column.

An accurate, rapid, and sensitive GLC determination of alprenolol and oxprenolol in serum is described. This method combines an electron-capture detector with a wall-coated open tubular column. The lowest detectable amount of the halogenated (heptafluoroacyl) derivatives of alprenolol and oxprenolol is 2 pg. The high resolving power and the rapid elution time of the wall-coated open tubular column dramatically improve the performance (accuracy and sensitivity) of the conventional electron-capture detector and packed column system in these determinations. This method allows the use of small volumes of sample (100-200 microliter), does not require redistilled reagents, and has a simplified extraction procedure.

Wall-coated open tubular column coupled with nitrogen-selective detector for routine GLC determination of diazepam, meprobamate, phenylbutazone, and thioridazine in serum.

The selectivity and sensitivity provided by a wall-coated open tubular column coupled with a nitrogen-selective detector allowed rapid, accurate determination of diazepam, meprobamate, phenylbutazone, and thioridazine in serum in the same chromatographic system using 100--200 microliters of sample.

Liquid chromatographic determination of noxytiolin and 1-methyl-2-thiourea in serum: application to pharmacokinetic studies in rabbits and humans.

A high-performance liquid chromatographic method is described which determines noxytiolin and 1-methyl-2-thiourea concentrations in serum. Valid determination requires immediate ultracentrifugation of blood samples, rapid serum freezing, and injection into the chromatograph within 6 h. A number of pharmacokinetic parameters were calculated from serum concentration data in rabbits and humans. An unknown metabolite was detected in both species but its structure was not identified.

[Therapeutic potential of Ro 5-3335. New active benzodiazepine in vitro against HIV-1 viruses resistant or non-resistant to AZT]. / Potentiel thérapeutique du Ro 5-3335. Une nouvelle benzodiazépine active in vitro contre les virus HIV-1 résistants ou non à l'AZT.

Ro 5-3335 is a new benzodiazepine highly active in vitro (IC50 = 0.1-1.0 microM [corrected]) against HIV-1 viruses of AIDS resistant or non-resistant to zidovudine (AZT). It is also active against HIV-2. Ro 5-3335 is original by its mechanism of action, acting on the trans-activation factor of transcription (TAT) and non on the reverse transcriptase. Such as, it could prevent proviral DNA to express in both evolutive and silent AIDS resistant or non-resistant to AZT or to other anti-reverse transcriptase series. In addition, in antagonizing extracellular TAT's actions, Ro 5-3335 could alleviate the syndrome commonly associated with AIDS as Kaposi's syndrome. In rodent test, Ro 5-3335 has no diazepam-like central effects and presents in comparison to AZT a more favorable therapeutic index. In dog, the elimination half-life, peak concentration and availability are 2 h, 0.8 microM and 85% respectively, after a 1 mg.kg-1 oral dose of Ro 5-3335. Theoretically, Ro 5-3335 and now its analogue Ro 24-7429 seem to possess all virtues to antagonize evolutive and latent AIDS. Its arrival is timely to cope with the ever increasing resistance phenomena, lengthy development of AIDS vaccines, exponential contamination of populations worldwide and last but not least possibly to impede evolutions of the disease. Ability to manipulate TAT-mediated activation of HIV-1 genes paves the ways to study conceivable corrections of abnormal gene expressions of neurotransmitters, hormones, oncogenes and key enzymes.