The effect of nicotine on perceptual, ocular motor, postural, and vegetative functions at rest and in motion.

Nicotine has wellknown, unpleasant side effects, e.g., transient dizziness, nausea, and nicotine-induced nystagmus (NIN). To investigate factors influencing these effects, we addressed three questions: (1) Is the intensity of dizziness, nausea, NIN, and unsteadiness dependent on nicotine dosage? (2) Does the intensity of perceptual, ocular motor, vegetative effects, and postural imbalance correlate? (3) Do visual or vestibular motion stimuli produce and/or aggravate distressing dizziness and nausea? Sixty healthy non-smokers or occasional smokers participated; 40 were tested once before and six times after application of a nicotine nasal spray in doses of 1 mg or 2 mg with or without motion stimulation; 20 received a placebo nasal spray. Plasma nicotine concentrations were significantly related to nicotine dosage. Dizziness, nausea, NIN, and unsteadiness also depended on the nicotine dosage (p < 0.01).Nicotine blood concentration was a better predictor for the temporal dependence of nystagmus than nicotine dosage. Dizziness correlated highly with nausea (R = 0.63, p < 0.001). The degree of nicotine-induced nausea significantly correlated with postural imbalance. The time course of postural sway differed according to nicotine dosage and gender: for women, there was no clear relationship between sway magnitude and nicotine dosage, while men showed increased sway with higher dosage. Motion stimulation increased nicotine-induced dizziness and nausea, but did not significantly influence NIN or postural imbalance. Our data support the view that all measured adverse effects reflect dose-dependent nicotine-induced vestibular dysfunction. Additional motion stimulation aggravates dizziness and nausea, i.e., nicotine increases sensitivity to motion sickness.

Influence of halothane on the effect of cAMP-dependent and cAMP-independent positive inotropic agents in human myocardium.

Volatile anaesthetics have a variety of effects on the myocardium, namely a negative inotropic effect and a catecholamine sensitizing effect. The present study was designed to see if the hydrocarbon anaesthetics interact specifically with subcellular targets of the myocardial cell, by examining the effects of halothane in the presence of positive inotropic agents with different mechanisms of action. Experiments were performed in isolated electrically driven left ventricular preparations (1 Hz, 37 degrees C, Ca2+ 1.8 mmol litre-1) from human hearts obtained at cardiac surgery. The concentration-response curves of noradrenaline, milrinone, BayK 8644 and Ca2+ were investigated in the absence and in the presence of halothane. Halothane enhanced the efficacy of noradrenaline and milrinone but not of Ca2+ or BayK 8644. The potency of milrinone was also increased by halothane, whereas the potency of BayK 8644 was decreased and those of noradrenaline and Ca2+ were unchanged. Halothane differentially influences the effects of agents with different positive inotropic mechanisms. This experimental approach can be taken as a functional method to localize the mechanisms of action of the inhalation anaesthetics in human myocardium, namely sensitization of cAMP formation and interaction with L-type Ca2+ channels.

[Unusual injection site in a drug fatality in prison]. / Bemerkenswerte Lokalisation von Einstichstellen bei einem Drogentodesfall in der Haftanstalt.

A lethal heroin-intoxication of a prisoner with localization of hardly detectable injection marks on the frenulum praeputii is reported. An extensive external examination in particular in cases of death in jail or of drug addicts is necessary to detect unusual signs of intravenous drug addiction.

[Isopropanol and acetone level in serum after preoperative surface disinfection with antiseptics containing isopropanol]. / Isopropanol- und Acetonspiegel im Serum nach präoperativer Flächendesinfektion mit isopropanolhaltigen Antiseptika.

After preoperative skin disinfection in pediatric surgery, serum levels of isopropanol up to 12.2 mg/l (MW 5.0 mg/l +/- 3.37, n = 26) were found. They result from a rapid and prolonged but uncharacteristic percutaneous resorption of the isopropanol-containing disinfectant. In about 50% of the cases, serum levels of acetone showed an increase up to 82 mg/l already before skin disinfection, presumably caused by preoperative starvation. After skin disinfection, raised acetone levels were found in 19 of 26 cases. As increased isopropanol and acetone levels are discussed as alcoholism markers, a falsification of congener analysis after skin disinfection, e.g. in cases of adult victims of accidents, has to be taken into consideration. Endogenous serum levels of methanol (0.87 mg/l +/- 0.49), ethanol (0.32 mg/l +/- 0.09), acetaldehyde (0.31 mg/l +/- 0.10) and others remained unaffected. Some uncharacteristic elevations of propanol-1 levels are caused by contaminated rubber caps.

[Change in congener analysis caused by percutaneous absorption of propanol-containing antiseptics]. / Veränderung von Begleitstoffanalysen durch percutane Resorption propanolhaltiger Antiseptika.

According to the forensic literature, an alteration of blood alcohol concentration through alcohol disinfection before venepuncture is unlikely, however, percutaneous resorption of alcohol containing antiseptics is well documented. There are no investigations available, elucidating to what extent this is also correct for congener alcohols, particularly propanol-1/-2, which have serum levels in range of mg/l. In experiments with surgical hand and local skin disinfection, carried out with and without oral alcohol, relevant levels of propanol-1/-2 between 0.2 and 2 mg/l were measured. We conclude, that the routine clinical use of antiseptics is able to alterate and to falsify congener levels and can lead to incorrect interpretation of congener analysis.

Reduced binocular depth inversion as an indicator of cannabis-induced censorship impairment.

Measurements of binocular depth inversion using a stereoscopic slide projection with polarized light were performed in healthy volunteers before and after cannabis intake. Since binocular depth inversion represents an illusion occurring in the perception of semantically meaningful objects projected in a 3-D inverted fashion, the hypothesis can be tested that cannabis-induced "psychedelic states" represent a condition in which the human CNS is unable to correct implausible perceptual hypotheses. The data demonstrate a strong cannabis-induced impairment of binocular depth inversion.

Reducing the amount of monomers in intraocular lenses through sterilization by gamma radiation.

Sterile inflammatory reactions of varying degrees are a rare, but not uncommon, complication after intraocular lens implantation. At present we still do not know the cause of these processes, but we consider two chemical substances contained in the lens at least as risk factors for them: monomeric methyl methacrylate, which is present in any lens made from polymethyl methacrylate (Perspex), and ethylene oxide, an extremely toxic agent, which is absorbed by the lens during sterilization with this gas. Gas chromatographic investigations show that under sterilization of intraocular lenses by 60Co radiation the amount of monomeric methyl methacrylate in the lens can be reduced drastically. Also, any contamination of the lens by ethylene oxide is avoided. Therefore, at least two important arguments speak in favor of this alternative sterilization technique.

Concentrations of mustard gas [bis(2-chloroethyl)sulfide] in the tissues of a victim of a vesicant exposure.

An Iranian soldier died at a toxicological intensive care unit at Munich seven days after a vesicant exposure. At the autopsy the typical symptoms of mustard gas intoxication were found. The vesicant was detected qualitatively by gas chromatography-mass spectrometry (GC-MS) in the abdominal fat and quantified in the tissues and in the body fluids by the following method: (1) extraction by dichloromethane, (2) cleanup of the extracts by thin-layer chromatography (TLC) on silica plates, (3) extractive derivatization with gold-chloride, and (4) quantitative determination by electrothermal atomic absorption spectrometry (ET-AAS). The equal extracts, after heating, served for blanks. The following concentrations were found (milligrams of mustard gas/kilograms of tissue wet weight): brain 10.7, cerebrospinal fluid 1.9, liver 2.4, kidney 5.6; spleen 1.5, lung 0.8, muscle 3.9, fat 15.1, skin 8.4, skin with subcutaneous fatty tissue 11.8, liquid from a skin blister: below detection limit, blood 1.1, and urine: below detection limit.

[Enzyme immunochemical detection of the use of hashish and confirmation by thin-layer chromatography]. / Zum enzymatisch-immunochemischen Nachweis des Haschischkonsums und seiner dünnschichtchromatographischen Absicherung.

The EMIT cannabinoid assay was used for screening blood and urine after smoking tetrahydrocannabinol (THC; 10 mg) or ingestion of THC (30 mg). Cannabinoid levels in urine remain detectable up to 1 week. Confirmation was done by adsorption of the THC carboxylic acid onto a C18 extraction column and elution with acetone and TLC. The method is simple and sensitive and is applicable with common laboratory equipment. The detection limit is 10 ng/ml, using 10 ml urine.

Cadmium body burden of an occupationally non burdened population in southern Bavaria (FRG).

The cadmium body burden of the occupationally non-burdened population in the southern Bavarian area was estimated from the cadmium concentrations in liver and renal cortex, determined by ET-AAS of 263 autopsy cases. A mean value of 17.9 mg cadmium was calculated for all cases and 21.9 mg cadmium for all adults. The body burdens found do not depend on sex but greatly on smoking habits. Mean values for non-smokers are 13.5 mg, for moderate smokers 22.5 mg and for heavy smokers 33.2 mg. The dependence on age is similar to that of the cadmium concentration in the kidney cortex: an increase up to an age of approximately 50 years and a decrease at higher ages. Between the average value we found and the critical body burden calculated by Roels et al. (1983) is a safety factor of 8 to 10, but in some of our cases of middle-aged, heavy smokers this safety factor drops to a value lower than 1. It is concluded that it seems to be imperative to control the further trend of the cadmium body burden in occupationally non-burdened populations.

[A gas chromatographic determination of 6-mercaptopurine in the serum of immunosuppressed transplantation patients]. / Ein gaschromatographischer Nachweis von 6-Mercaptopurin im Serum von immunsupprimierten Transplantationspatienten.

The knowledge of serum levels of azathioprine or its metabolite 6-mercaptopurine is important for the monitoring of the immunosuppressive therapy after kidney transplantation, especially when kidney function is low. For this reason, the work of Bailey et al. was modified. 6-Mercaptopurine was extracted from the serum with a mixture of isopropanol-ethylacetate (1:1 v:v), derivatized with trimethylaniliniumhydroxyde and measured gaschromatographically. Sulfhydryl-protecting reagents were added to prevent loss of substance. Oxyethyltheophylline was used as the internal standard. The extraction and clean-up method recovered 80% of the 6-mercaptopurine present, the lower limit of sensitivity was 20 ng/ml, i.e., ten times lower than that of Bailey et al. The method could be realized on eight patients treated with azathioprine, the half life of the drug was about 20-40 min within the first hour i.v. application.

[Investigations of guaifenesine metabolism with gas chromatography-mass spectrometry]. / Unersuchungen zum Metabolismus von Guaifenesin mit Hilfe der Gaschromatographie-Massenspektrometrie.

Recently the authors about toxicological investigations after uptake of guaiacol glyceryl ether containing drugs. There had been detected two intensive pink spots on the TLC from urine samples after detection with Marquis-reagent. It is reported about the identification of Catechol glyceryl ether and Hydroxyguaifenesine via Gas Chromatography Mass Spectrometry. Until today only the oxidation of guaiacol glyceryl ether to beta-(2-methoxyphenoxy)lactic acid is described. The demethylation of G. is performed by O-Demethylase localized in liver microsomes. This enzyme seems to be the main enzyme for the metabolism of G. It is pointed out to a pharmacologically interesting relationship between the chemical structure of guaiacol glyceryl ether and codeine.