Population pharmacokinetics model of THC used by pulmonary route in occasional cannabis smokers.

Cannabis is the most widely used illegal drug in the world. Delta-9-tetrahydrocannabinol (THC) is the main source of the pharmacological effect. Some studies have been carried out and showed significant variability in the described models as the values of the estimated pharmacokinetic parameters. The objective of this study was to develop a population pharmacokinetic model for THC in occasional cannabis smokers. Twelve male volunteers (age: 20-28years, body weight: 62.5-91.0kg), tobacco (3-8 cigarette per day) and cannabis occasional smokers were recruited from the local community. After ad libitum smoking cannabis cigarette according a standardized procedure, 16 blood samples up to 72h were collected. Population pharmacokinetic analysis was performed using a non-linear mixed effects model, with NONMEM software. Demographic and biological data were investigated as covariates. A three-compartment model with first-order elimination fitted the data. The model was parameterized in terms of micro constants and central volume of distribution (V1). Normal ALT concentration (6.0 to 45.0IU/l) demonstrated a statistically significant correlation with k10. The mean values (%Relative Standard Error (RSE)) for k10, k12, k21, k23, k32 and V1 were 0.408h-1 (48.8%), 4.070h-1 (21.4%), 0.022h-1 (27.0%), 1.070h-1 (14.3%), 1.060h-1 (16.7%) and 19.10L (39.7%), respectively. We have developed a population pharmacokinetic model able to describe the quantitative relationship between administration of inhaled doses of THC and the observed plasma concentrations after smoking cannabis. In addition, a linear relationship between ALT concentration and value of k10 has been described and request further investigation.

A review of methods for nematode identification.

Nematodes are non-segmented roundworms found in soil, aquatic environment, plants, or animals. Either useful or pathogenic, they greatly influence environmental equilibrium, human and animal health, as well as plant production. Knowledge on their taxonomy and biology are key issues to answer the different challenges associated to these organisms. Nowadays, most of the nematode taxonomy remains unknown or unclear. Several approaches are available for parasite identification, from the traditional morphology-based techniques to the sophisticated high-throughput sequencing technologies. All these techniques have advantages or drawbacks depending on the sample origin and the number of nematodes to be processed. This review proposes an overview of all newly available methods available to identify known and/or unknown nematodes with a specific focus on emerging high-throughput molecular techniques.

Monitoring of four DNA extraction methods upstream of high-throughput sequencing of Anisakidae nematodes.

Different methods were evaluated to extract DNA from pooled nematodes belonging to Anisakis, Contracaecum, Pseudoterranova and Hysterothylacium genera isolated from edible fish. Pooled DNA extraction is the first and compulsory step to allow the identification of a large number of samples through high-throughput DNA sequencing with drastic time and cost reductions.

[Vagal syncope in young adults: specificity of the tilt-table test]. / Syncope vagale de l'adulte jeune: spécificité du test d'inclinaison.

OBJECTIVE: The head-up tilt test has been used for more than 10 years to reproduce vagal lipothymia. The criteria for a positive test and specificity are however still lacking. METHOD: Thirty male volunteers, age 18 to 35 years, with no past history of lipothymia nor any signs of hypervagotonicity at physical examination, on fasting blood samples or on exercise tests with sudden interruption and Holter recording were selected for the study. Two head-up tilt tests at 60 degrees for 45 minutes were conducted, one with no presensitivisation and the other with a bolus of isoproterenol (2, 4, 6 and 8 micrograms) starting 30 minutes after the beginning of the test. Blood pressure was measured throughout the test. RESULTS: The systolic blood pressure curves showed drops of more than 30 mmHg accompanied by spontaneously resolving clinical signs in 6 of the 30 subjects during the non-sensitized tests and in 14 out of 30 during the sensitized tests. A symptomatic drop in systolic blood pressure of more than 30 mmHg compared to the moment before the malaise accompanied by clinical signs which did not resolve within 1 minute and required returning to the supine position occurred in one volunteer during a non-sensibilized test. This same type of reaction was observed in 4 volunteers during sensitized tests, three times after an isoproterenol bolus. CONCLUSION: Taking this later manifestation as the criteria for a positive head-up tilt test, the specificity of the non-sensitized and isoproterenol-sensitized tests in the young adult are 96.7 and 86.7% respectively. These findings must be considered with caution since there is no proof that these young men with no past history of hypervagotonicity but a positive head-up tilt test may be one day confronted with a situation generating a vagal reaction.

The quinolone, flumequine, has no effect on theophylline pharmacokinetics.

The kinetics of a single i.v. dose of theophylline given either alone or with flumequine was studied in eight healthy volunteers. No statistically significant differences were observed in the pharmacokinetic parameters of theophylline (volume of distribution, elimination half-life, AUC, plasma clearance) following the two treatments. Pretreatment for 5 days with oral flumequine (400 mg, three times daily) had no significant effect on the disposition of a single i.v. dose of theophylline in healthy volunteers.

GABA-ergic control of visual perception in healthy volunteers: effects of midazolam, a benzodiazepine, on spatio-temporal contrast sensitivity.

1. We studied the effects of midazolam (MDZ), a benzodiazepine, on spatio-temporal contrast sensitivity, choice reaction time, and mood visual analogue scales in healthy volunteers. 2. Eight extensively trained, healthy volunteers were included in a placebo-controlled cross-over double-blind trial of MDZ (0.15 mg kg-1). Treatments were injected intramuscularly and evaluations were performed before and 0.5, 1, 2, 3 and 4 h after drug administration. Spatio-temporal contrast sensitivity was measured using a micro-computer with appropriate software. Stimuli were vertical gratings with adjustable contrast, with spatial frequencies of 0.25, 1 and 4 cpd. Four conditions of temporal modulation were used: the grating was either static or drifting laterally with temporal frequencies of 1, 3 and 9 Hz. 3. An analysis of variance was performed on the data. As compared with placebo, MDZ induced an increase in choice reaction time and sedation (as assessed on visual analogue scales). From 0.5-4 h after the injection, MDZ produced an overall decrease in visual sensitivity, as compared with placebo. More specifically, MDZ preferentially affected medium to high spatial frequencies and low temporal frequencies. Several non-exclusive hypotheses may account for the results: 1) an increase in the size of the receptive fields, 2) a preferential effect on the visual parvocellular pathways which mediate the sensitivity to high spatial and low temporal frequencies.

Influence of food on the tyramine pressor effect during chronic moclobemide treatment of healthy volunteers.

An open study was carried out to examine the effect of moclobemide, a new antidepressant reversible inhibitor of MAO-A, on the pressor response induced by oral tyramine added to meals of different lipid and protein composition, and to correlate the blood pressure increase in the tyramine test with that obtained during an exercise test. Eight healthy volunteers of both sexes participated in the study. A tyramine sensitivity and an exercise test were performed beforehand. Subjects were included if, under fasting condition, their systolic blood pressure (SBP) increased by more than 30 mmHg after administration of 400 or 600 mg tyramine. Exercise tests were performed to determine the grade of effort that corresponded to a rise in SBP of 30 mmHg. Subjects received moclobemide 600 mg/d. Starting on Day 7, each subject consumed a standardized meal (52 g lipids, 43 g proteins, 86 g carbohydrates) just before taking moclobemide. Tyramine was added to these meals in daily increasing doses of 50, 100, 150...mg until an increase in SBP > or = 30 mmHg was obtained. On moclobemide treatment, an average dose of 250 mg tyramine (range 150-400 mg) increased SBP by 36.6 mmHg. The time to reach peak SBP was longer (175 min) than in the fasting condition before the trial (40.6 min).(ABSTRACT TRUNCATED AT 250 WORDS)

[Inflammatory joint disease as a manifestation of Toxocara canis larva migrans]. / Arthropathies inflammatoires révélatrices d'une larva migrans à Toxocara canis.

We report a case of migrating joint involvement occurring as the first manifestation of Toxocara canis larva migrans. We also reviewed the literature on joint disease caused by parasitic infections. Diagnostic criteria are described. We suggest that an immunoallergic mechanism is involved. Furthermore, the therapeutic trial with thiabendazole contributed usefully to the diagnosis in our patient.

[Late potentials in patients with hypertension]. / Etude des potentiels tardifs chez l'hypertendu.

UNLABELLED: The presence of late potentials (LP) is considered as the evidence of an anatomical and electrophysiological condition which can give rise to life threatening ventricular arrhythmias. The aim of this work has been to study the incidence of LP in the setting of hypertension and to study their relation to ventricular hypertrophy on one hand and to ventricular arrhythmias on the other. Our study was conducted in 45 hypertensive patients (mean age +/- SD = 53 +/- 12). None of them had clinical evidences of a coronaropathy and only 5 had never been treated. For every patient we carried out a signal averaged electrocardiogram to detect LP, an echocardiogram to determine the myocardial mass index and 48 hours Holter monitoring to record ventricular arrhythmias filed according to the Lown classification. RESULTS: LP have been found in 13 patients. The following table summaries relations between LP, ventricular arrhythmias and myocardial hypertrophy: [table: see text] CONCLUSION: LP are frequently found in hypertensive patients (29%); their incidence is not higher in patients with left ventricular hypertrophy although they more frequently have serious ventricular arrhythmias; the severity of ventricular arrhythmias is not correlated with the presence of LP.

Treatment of mucoid cysts of fingers and toes by injection of sclerosant.

Mucoid cysts of the fingers and toes may be cured by injection of a sclerosant such as sodium tetradecyl sulfate. Easy to perform and inexpensive, this technique appears to be without complications. Most patients are cured after a single injection. Very few need a second or third injection. Relapses are uncommon.

[Professional eczema of trawlermen by contact with bryozoaires in the "baie de scine" (first French cases 1975-1977) (author's transl)]. / Eczéma professionnel du marin pêcheur par contact de bryozoaires en Baie de Seine (premiers cas Français 1975-1977).

Since 1972 in the "Baie de Seine" trawlermen have been affected with a particular eczema of hands and forearms. It is caused by repeated contact with a bryozoaire, Alcyonidium gelatinosum and patch-tests are positive. A survey of 120 trawlermen in Le Havre has shown 13 cases.