PubMed Health⌕ Search

Biomedical subjects

F Musshoff

Publications and source records attributed to F Musshoff.

At least 37 records · Page 2Linked to original sources

Pulmonary edema in fatal heroin overdose: immunohistological investigations with IgE, collagen IV and laminin - no increase of defects of alveolar-capillary membranes.

Pulmonary edema complicating heroin overdosage is a well recognized entity and regarded as the major mechanism contributing to death in heroin addicts. It's pathogenesis is unknown, several mechanisms are discussed: hypoxia-induced increase of pulmonary capillary permeability, depressed myocardial contractility, centrally induced respiratory depression, primary toxic effects on the alveolar capillaries and acute anaphylactic shock. The present study included opiate-related deaths (n=23) and a control group of sudden cardiovascular deaths (n=12) to verify the hypothesis, that defects of the alveolar capillary membranes and/or an acute anaphylactic reaction leads to pulmonary congestion, edema and hemorrhages. Lung specimens were obtained from these 35 autopsies of persons autopsied in the Institute of Forensic Medicine, University of Bonn, in 1997 and 1998. All specimens were examined with hematoxylin-eosin, prussian blue and investigated with immunohistological methods using primary antibodies against collagen IV, laminin and IgE. Defects of the basal laminae of the alveoli were found, demonstrated by laminin and collagen IV, and the number of IgE-positive cells was counted in both groups. There was an increased but not significant number of IgE-positive cells in the heroin-group and defects of the epithelial and endothelial basal laminae were found in both groups without significant differences.

Anaphylaxis↗

[Dangers and risks of black market anabolic steroid abuse in sports --gas chromatography-mass spectrometry analyses].

Anabolic steroids have become increasingly popular among athletes even at subcompetitive or recreational level instead of extensive doping tests, educational campaigns and lethal incidents. Nowadays, the fitness boom has also produced a population of steroid users at high school level and also under non-sports practicing children. After opening the borders to East Europe an explosion of the black-market for anabolic steroids occurred. Beside the well-known side effects of anabolic steroids new problems and risks occurred due to fake drugs from the black market. This review ist subdivided into two parts: We provide a detailed review of the literature an anabolic steroids to the reader the information needed to make an informed decision an the relative risks and benefits of anabolic steroids. Secondly, we evaluated 40 "anabolic steroids" obtained from the black market using mass spectrometry or gas chromatography analysis to evaluate the real pharmacological compounds. As the results of this analysis, we found that 15 (37.5%) these drugs contained different or any pharmacological compounds as labeled. From the external packing, a differentiation between original and the fake drugs was impossible. Therefore, a large information and credibility gap concerning anabolic steroids particular those from the black market exists between the athletes and the medical and scientific communities. We believe that this gap can only be closed if both groups are be better informed about anabolic steroids.

Anabolic Agents↗

Illegal or legitimate use? Precursor compounds to amphetamine and methamphetamine.

The interpretation of methamphetamine and amphetamine positive test results in biological samples is a challenge to clinical and forensic toxicology for several reasons. The effects of pH and dilution of urine samples and the knowledge about legitimate and illicit sources have to be taken into account. Besides a potentially legal prescription of amphetamines, many substances metabolize to methamphetamine or amphetamine in the body: amphetaminil, benzphetamine, clobenzorex, deprenyl, dimethylamphetamine, ethylamphetamine, famprofazone, fencamine, fenethylline, fenproporex, furfenorex, mefenorex, mesocarb, and prenylamine. Especially the knowledge of potential origins of methamphetamine and amphetamine turns out to be very important to prevent a misinterpretation of the surrounding circumstances and to prove illegal drug abuse. In this review, potential precursor compounds are described, including their medical use and major clinical effects and their metabolic profiles, as well as some clues which help to identify the sources.

Amphetamines↗

Fatality caused by a combined trimipramine-citalopram intoxication.

A 53-year-old woman who was diagnosed as suffering from depression was found dead in her bed. The autopsy revealed no morphological changes sufficient to explain death. Toxicological analysis was performed and the drugs trimipramine (2.33 mg/l), citalopram (4.81 mg/l) and zolpidem (0.07 mg/l) were identified in the femoral blood. A combined drug intoxication resulting in synergistic effects to cardiovascular disorders was proposed as the cause of death. An acute overdose and suicide was suggested by calculation of the parent drug to main metabolite ratios in femoral blood and liver tissue. The trimipramine to desmethyltrimipramine ratios were calculated to be 2.06 and 3.18, the citalopram to desmethylcitalopram ratios were 1.96 and 2.02.

Antidepressive Agents, Second-Generation↗

A systematic regional study of dopamine and dopamine-derived salsolinol and norsalsolinol levels in human brain areas.

Dopamine and the dopamine-derived tetrahydroisoquinoline alkaloids salsolinol and norsalsolinol were measured by high-performance liquid chromatography with electrochemical detection in 15 regions of the human brain. The regional distribution of dopamine in 32 brains was similar to previous reports with highest concentrations in the basal ganglia, especially in the striatum, followed by the substantia nigra and the hypothalamus. Significant amounts of salsolinol and norsalsolinol were only found in these dopamine-rich areas, whereas in the other regions no alkaloids were detected. These findings suggest that the concentration of the substrate dopamine may determine the alkaloid level during in vivo formation.

Adult↗

Homicidal poisoning with halothane.

A double homicide by smothering with halothane-moistened towels is described and the blood and tissue concentrations of halothane are discussed in comparison to the literature.

Aged↗

Rapid analysis of parathion in biological samples using headspace solid-phase micro-extraction (HS-SPME) and gas chromatography/mass spectrometry (GC/MS).

A simple and rapid method for the analysis of parathion in biological samples is presented. The method consists of the extraction of parathion from blood samples by headspace solid-phase micro-extraction (SPME), followed by capillary gas chromatography and mass spectrometry detection. The recoveries in the blood samples after addition of ammonium sulphate and sulphuric acid were between 85% and 89% compared to samples prepared in water. Linearity was established over a concentration range of 0.1-5 microg/g blood with acceptable coefficients of correlation and limits of detection reached 0.02-0.05 microg/g. The time for an analysis is 57 minutes for one sample, including the extraction step. In conclusion, HS-SPME in combination with GC/MS is an effective method for the determination and quantification of parathion-ethyl and parathion-methyl in biological material.

Calibration↗

Determination of biological markers for alcohol abuse.

Alcoholism is one of the most frequent addictions and an important subject in forensic medicine and clinical toxicology. Several laboratory abnormalities are associated with excessive alcohol consumption. They are useful in the diagnosis of alcoholism especially during the follow-up of various treatment programs. The biological markers mostly used for diagnosis of alcoholism are presented. Especially, methods for the determination of the following diagnostic tools are reviewed: congener alcohols, gamma-glutamyltransferase, aspartate and alanine aminotransferase, beta-hexosaminidase, erythrocyte aldehyde dehydrogenase, alpha-amino-n-butyric acid to leucine ratio, macrocytosis, carbohydrate-deficient transferrin, (apo)lipoproteins, fatty acid ethyl esters, blood acetate, acetaldehyde adducts, 5-hydroxytryptophol, dolichol and condensation products. No laboratory test exists that is reliable enough for the exact diagnosis of alcoholism. The combination of physician interview, questionnaire and laboratory markers is necessary for the diagnosis of alcoholism.

Alcoholism↗

Suicide with moclobemide and perazine.

A 51-year-old woman who was diagnosed as suffering from depression was found dead in her flat. The autopsy revealed no morphological changes sufficient to explain death. Toxicological analysis was performed and the drugs moclobemide (49.9 mg/l), perazine (1.27 mg/l) and some metabolites were identified in the blood. A combined drug intoxication resulting in synergistic effects to cardiovascular disorders was proposed as the cause of death.

Antipsychotic Agents↗

Identification of famprofazone ingestion.

After a traffic accident a 32-year-old man was suspected of having previously taken an illegal drug. An immunochemical screening procedure revealed positive results for amphetamines in both urine and blood samples. The preliminary test was confirmed by GC/MS and both amphetamine and methamphetamine were found in both body fluids. However, the man denied any use of drugs but claimed to have taken four tablets of Gewodin. One of the ingredients, famprofazone, undergoes metabolic conversion to amphetamine and methamphetamine. Using GC/ MS the ingestion of famprofazone was verified by identification of the unchanged parent compound in the urine sample.

Adult↗

Medico-legal aspects of doping.

Abuse of anabolic steroids is an increasing problem not only among athletes but also body-builders and teenagers. A fast-developing black market has been established since the opening of the borders to eastern Europe. Medico-legal aspects of doping are addressed with particular reference to toxicology and pathology. Constituents of anabolic steroids bought on the black market were identified using gas chromatography/mass spectrometry; the products did not contain the expected ingredients in 35% of cases. Long-term effects and fatalities because of anabolic steroid abuse are reported here based on our own case material and a literature review. In our own cases, severe cardiovascular side-effects developed after long-term abuse of Dianabol (methandrostenolone) and Oral-Turinabol (chlordehydromethyltestosterone), i.e. myocardial infarction, stroke, organomegaly and/or severe atherosclerosis. The pathogenesis of cardiovascular complications (cardiotoxic effect, risk of atherosclerosis, thrombogenic risk) is discussed based on the available literature reports following fatal outcome after the abuse of anabolic steroids.

Journal Article↗

First experience with the REMEDi HS urine benzodiazepine assay.

Ninety eight urine samples were analysed with an immunoassay benzodiazepine kit. A total of 68 urine specimens that were presumptively positive for benzodiazepines were evaluated by the REMEDi HS urine benzodiazepine assay (BIO-RAD, Munich, Germany). Of this number, 53 (78%) specimens were found by REMEDi to contain one or more benzodiazepines or their metabolites, and 15 (22%) were found to be negative. From the discordant group of 15 samples, eight were found to be negative using conventional chromatographic procedures (HPLC or GC/MS), while seven contained one or more benzodiazepines or metabolites, each of which were below the individual cut-off level specified by the manufacturer. Additionally 30 urine specimens that were negative for benzodiazepines using immunoassay were also tested by REMEDi. Two samples were found to be positive. These results could not be confirmed by other chromatographic techniques. The REMEDi HS benzodiazepine assay can be a very useful complementary technique in the clinical/forensic toxicology laboratory, especially for the identification of the parent benzodiazepines administered. The assay provides a rapid result in emergency situations and is useful in confirmation of preliminary positive immunoassay results.

Automation↗

Gas chromatographic/mass spectrometric determination of lysergic acid diethylamide (LSD) in serum samples.

A sensitive method for the detection and quantification of lysergic acid diethylamide (LSD) in serum samples is described. After liquid-liquid extraction the trimethylsilyl derivative of LSD is detected by gas chromatography-mass spectrometry. Experiments with spiked samples resulted in a recovery of 76%, the coefficient of variation was 9.3%. Excellent linearity was obtained over the range 0.1-10 ng ml-1. Additionally experiments demonstrating the light sensitivity of LSD are presented together with casuistics.

Adolescent↗

Salsolinol and norsalsolinol in human urine samples.

The tetrahydroisoquinoline alkaloids salsolinol and norsalsolinol were found in human urine samples in concentrations ranging from 0.1 to 29.5 ng/ml. Great interindividual variation was found in urine levels of these alkaloids in a collection of chronic alcoholics and in a group of nonalcoholics. Thus, levels of the individual alkaloids are insufficient markers for distinguishing between alcoholics and nonalcoholics. However, by using the concentration ratio of norsalsolinol and salsolinol, the so-called dopamine-aldehyde adduct ratio (DAAR), significant differences between alcoholics (median 1.3) and nonalcoholics (median 0.6) were detected. This concentration ratio could serve as a marker for the processor state of the dopaminergic system.

Alcoholism↗

Formaldehyde-derived tetrahydroisoquinolines and tetrahydro-beta-carbolines in human urine.

Human urine samples were examined for the occurrence of formaldehyde-derived tetrahydroisoquinolines and tetrahydro-beta-carbolines generated by condensation of the methanol oxidation product with biogenic amines. Positive results were obtained for the tryptamine condensation product 1,2,3,4-tetrahydro-beta-carboline and the serotonine condensation product 6-hydroxy-1,2,3,4-tetrahydro-beta-carboline as well as for the condensation products with tyramine, dopamine, adrenaline and noradrenaline 1,2,3,4-tetrahydroisoquinoline, 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, N-methyl-4,6,7-trihydroxy-1,2,3,4-tetrahydroisoquinoline, 4,6,7-trihydroxy-1,2,3,4-tetrahydroisoquinoline, and the metabolite 6-methoxy-7-hydroxy-1,2,3,4-tetrahydroisoquinoline. Negative results were obtained for N-methyl-1,2,3,4-tetrahydroisoquinoline and 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline, N-methyl-1,2,3,4-tetrahydro-beta-carboline, 6-methyl-1,2,3,4-tetrahydro-beta-carboline, and 6-methoxy-1,2,3,4-tetrahydro-beta-carboline in samples of chronic alcoholics as well as in the urine of healthy volunteers. No correlation between alcohol ingestion or state of alcoholization could be demonstrated.

Alcoholism↗

[Ethanol-independent methanol elimination in chronic alcoholics].

72% of a collective of chronic alcoholics (DSM-III-R, ICD 9), who were admitted under the influence of alcohol in order to undergo alcohol withdrawal, showed a serum methanol concentration (SMC) above 10 mg/l. This level is usually considered to be the one for the detection of regular alcohol consumption. The SMC values were considerably higher in cases where alcoholic beverages with a higher methanol content were consumed rather than the ones lower in methanol. In the majority of patients a decrease of the methanol concentration could only be detected once an individually varying limit concentration of ethanol (0-0.62 g/kg) was reached. There were, however, a few exceptions where the elimination of methanol independent from the ethanol concentration could be seen. Contrasting the general collective, these 'ethanol independent' methanol eliminators showed a much higher serum level of ethanol and methanol at the time of admission. As a sign of addiction, all patients showed increased beta 60 values for ethanol and preferred high proof beverages, which at the same time have high methanol contents.

Adult↗

Gas chromatographic-mass spectrometric screening procedure for the identification of formaldehyde-derived tetrahydroisoquinolines in human urine.

A gas chromatographic-mass spectrometric method has been developed for the identification of 1,2,3,4-tetrahydroisoquinoline and six metabolites extracted from urine in the picogram range. The derivatization procedure for the substances, formed by reaction of formaldehyde with biogenic amines, employs propionic anhydride and can take place in aqueous medium. In this way artificial formation of these compounds via condensation of biogenic amines with aldehydes or alpha-keto acids during the work-up procedure is eliminated. The procedure results in hydrophobic compounds, which are quantitatively extractable by liquid-liquid extraction with organic solvents. Further clean-up was performed by solid-phase extraction on C18 sample preparation columns.

Formaldehyde↗

Gas chromatographic-mass spectrometric screening procedure for the identification of formaldehyde-derived tetrahydro-beta-carbolines in human urine.

A gas chromatographic-mass spectrometric method for the identification of 1,2,3,4-tetrahydro-beta-carboline and four metabolites extracted from urine is described. In a first step the substances, formed by reaction of formaldehyde with biogenic amines, were derivatized in aqueous solution with methyl chloroformate to eliminate an artificial formation of these compounds via condensation of endogenous indole ethylamines with aldehydes or alpha-keto acids during the work-up procedure. This initial derivatization formed stable hydrophobic compounds and improved the extractability for a liquid-liquid extraction. Further clean-up was performed by solid-phase extraction on C18 sample preparation columns. The method can identify these compounds in the picogram range.

Carbolines↗