A compilation of postmortem femoral blood concentrations of drugs is presented. The samples are collected from cases in which the cause of death was: A) certified intoxication by one substance alone, B) certified intoxication by more than one substance and/or alcohol, and C) certified other cause of death without incapacitation due to drugs. The concentrations were compared with blood concentrations detected in suspected drugged drivers (D), and with previously published fatal and therapeutic concentrations. The special features of this compilation are: 1) exclusively femoral blood concentrations are quoted, 2) all analyses are based on samples handled according to a standardized, quality-controlled procedure, 3) two control groups are included, and 4) one-substance-only intoxications are separated from other intoxications. The material is based on a selection of 15,800 samples sent to the Department of Forensic Chemistry in Link?ping, Sweden, during 1992 to 1995 from the six forensic pathology units in Sweden, and the list includes 83 drugs. The compilation includes drugs, where previously published data are scarce. Furthermore, the data gathered from cases with other cause of death than intoxication (group C) constitute a new kind of reference information, which probably offers a better estimate of obviously non fatal levels in postmortem blood than any compilation of therapeutic concentrations in living subjects. The possible factors influencing postmortem drug concentrations are discussed.
The increasing contamination of freshwater with pharmaceuticals, surfactants, pesticides and other organic compounds are of major concern. As these contaminants are detected at trace levels in the environment it is important to determine if they elicit biological responses at the observed levels. In addition to chemical pollutants, there is also a concern for increasing levels of bacteria and other microorganisms in freshwater systems. In an earlier study, we observed the activation of inflammatory systems downstream of a wastewater treatment plant (WWTP) in southern Sweden. We also observed that the water contained unidentified components that were pro-inflammatory and potentiated the immune response in human urinary bladder epithelial cells. In order to determine if these effects were unique for the studied site or represent a common response in Swedish water, we have now performed a study on three WWTPs and their recipient waters in central Sweden. Analysis of immune responses in urinary bladder epithelial cells, monocyte-like cells and blood mononuclear cells confirm that these waters activate the immune system as well as induce pro-inflammatory responses. The results indicate that the cytokine profiles correlate to the endotoxin load of the waters rather than to the levels of pharmaceuticals or culturable bacteria load, suggesting that measurements of endotoxin levels and immune responses would be a valuable addition to the analysis of inland waters.
Hypothermia and hyperthermia related cases recorded for the period 1973 to 1984 were collected from the files of the Department of Forensic Medicine, University of Oulu, and the necropsy protocols including toxicological results were analyzed. The fact that similar alcohol concentrations were found in both types of fatalities points to the poikilothermic effect of alcohol in humans, as found in animal studies. Both types of deaths seem to be associated with the alcohol elimination phase. Antidepressants and neuroleptics were most often found in the hypothermia cases, but benzodiazepines were also quite frequently present. In spite of the diminished use of barbiturates, these still appear in hypothermia fatalities. Certain other drugs that affect thermoregulation were also noted in solitary cases. Extended toxicological analysis was seldom made in the cases of hyperthermia deaths, and no firm conclusions on the poikilothermic effect of psychotropic drugs could be reached, for example. Therapeutic drug concentrations did not alone predispose the subjects to hypothermia, but appeared in connection with alcohol consumption or chronic diseases.
BACKGROUND: Oral fluid is an alternative matrix with potential applications in road-side drug screening, work-place testing, drug treatment programs, and epidemiological surveys. Development of methods for extensive drug screening in oral fluid is warranted. METHODS: We developed a liquid chromatography- tandem mass spectrometry (LC-MS/MS) method for drug screening of preserved oral fluid collected with the Intercept collection device. Samples were prepared by liquid-liquid extraction with ethylacetate/heptane (4:1). LC-separation was achieved with an Atlantis dC18-column (2.1 x 50 mm, 3 microm particle). Mass detection was performed by positive ion mode electrospray LC-MS/MS and included the following drugs/metabolites: morphine, 6-monoacetylmorphine, codeine, buprenorphine, methadone, amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxyethylamphetamine, cocaine, benzoylecgonine, Delta-9-tetrahydrocannabinol, lysergic acid diethylamide, alprazolam, bromazepam, clonazepam, 7-aminoclonazepam, diazepam, N-desmethyldiazepam, 3-OH-diazepam, fenazepam, flunitrazepam, 7-aminoflunitrazepam, lorazepam, nitrazepam, 7-aminonitrazepam, oxazepam, zopiclone, zolpidem, carisoprodol, and meprobamat. RESULTS: Screening of 32 drugs was performed with a run time of 14 min. Within- and between-day relative CVs varied from 2.0% to 31.8% and from 3.6% to 39.1%, respectively. Extraction recoveries were >50% except for morphine (30%) and benzoylecgonine (0.2%). The concentrations of the lowest calibrator were 1 nmol/L (0.28 microg/L) to 500 nmol/L (68 microg/L), depending on the drug. CONCLUSION: The method allowed rapid and sensitive oral fluid screening for the most commonly abused drugs in Norway and will be used for a road-side survey of drug use in normal traffic.
The main aim of the present population-based study was to compare drugs in fall versus non-fall accidents causing major trauma, including both clinical and medico-legal autopsy data.
All individuals with accidents resulting in major trauma, a new injury severity score (NISS)>15 or lethal outcome was identified at hospital and/or the Department of Forensic Medicine between 2011 and 2013. Modified Downton Fall Risk Index ranged from 0 to 7, and was based on specific pharmaceuticals (max 5 points), previous fall (1 point) and cognitive impairment (1 point).
One hundred and four individuals with major traumatic accidents were identified, 38 (36.5%) died. The median modified Downton Fall Risk Index was 2 for fall accidents and 0 for non-fall accidents (p?
An environmental risk assessment is presented for the 25 most used pharmaceuticals in the primary health sector in Denmark. Predicted environmental concentrations (PECs) for the aquatic environment were calculated using conservative assumptions and all PECs exceeded 1 ng/l. Measured concentrations were in general within a factor of 2-5 of PECs and ranged from approximately 0.5 ng/l to 3 micrograms/l for nine of the pharmaceuticals reported in literature. The calculation of predicted no-effect concentration (PNEC) based on aquatic ecotoxicity data was possible for six of the pharmaceuticals. PEC/PNEC ratio exceeded one for ibuprofen, acetylsalicylic acid, and paracetamol. For estrogens the PEC/PNEC ratio approached one when non-standard test was used. The ratio was below one for estrogens (standard test), diazepam and digoxin. For the terrestrial compartment, toxicity data were not available, and no assessment was carried out. Comparisons of predicted concentrations of furosemide, ibuprofen, oxytetracycline and ciprofloxacin in sludge based on either preliminary experimental sludge-water partition coefficients (Kd), octanol-water coefficients (Kow) or acid-base constants (pKa) revealed large variations.
An emissions inventory for top consumed human pharmaceuticals in Sweden was done based on national consumption data, human metabolic rates and wastewater treatment removal rates. Concentrations of pharmaceuticals in surface waters in Swedish river basins were predicted using estimated emissions from the inventory and river discharges. Our findings indicate that the top ten emitted pharmaceuticals in our study set of 54 substances are all emitted in amounts above 0.5ton/y to both surface waters and soils. The highest emissions to water were in decreasing order for Metformin, Furosemide, Gabapentin, Atenolol and Tramadol. Predicted emissions to soils calculated with the knowledge that in Sweden sludge is mostly disposed to soil, point to the highest emissions among the studied drugs coming from, in decreasing order, Metformin, Paracetamol, Ibuprofen, Gabapentin and Atenolol. Surface water concentrations in Sweden's largest rivers, all located in low density population zones, were found to be below 10ng/L for all substances studied. In contrast, concentrations in surface waters in Stockholm's metropolitan area, the most populous in Sweden, surpassed 100ng/L for four substances: Atenolol, Metformin, Furosemide and Gabapentin.
Surface water concentrations of 54 pharmaceuticals were predicted for seven major Swedish rivers and the Stockholm City area basins using the STREAM-EU model. These surface water concentrations were used to predict the ecotoxicological impact resulting from the exposure of aquatic organisms to this mixture of 54 pharmaceuticals. STREAM-EU model results indicated that