| 1. |
- Bendroth, Peter, et al.
(författare)
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Comparison of ethyl glucuronide in hair with phosphatidylethanol in whole blood as post-mortem markers of alcohol abuse
- 2008
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Ingår i: Forensic Science International. - : Elsevier BV. - 0379-0738 .- 1872-6283. ; 176:1, s. 76-81
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Tidskriftsartikel (refereegranskat)abstract
- Ethyl glucuronide (EtG) is a direct metabolite of ethanol and has been used as a marker of alcohol abuse in both urine and hair. This study investigated the value of EtG testing in post-mortem hair for diagnostic improvement of alcohol abuse in forensic medicine. Material from 70 consecutive medico-legal autopsies was collected in accordance with the recommendations on ethics by the Swedish National Board of Forensic Medicine. A method for determination of EtG in hair samples was developed using ultra performance liquid chromatography/electrospray tandem mass spectrometry (UPLC/ESI-MS/MS; LOQ, 2.5 pg/mg). The result of the EtG analysis was compared with the findings of phosphatidylethanol (PEth) in femoral whole blood, as measured by high performance liquid chromatography with an evaporative light-scattering detector (HPLC–ELSD; LOQ, 0.22 μmol/l). Evaluation of liver histology and anamnestic evidence of alcohol abuse of the deceased were taken in consideration for the interpretation. Measurable levels of EtG were present in 49 of the 70 autopsy cases whereas PEth was present in 36. Thirty-nine cases had EtG levels above the cutoff limit (≥30 pg/mg) compared with 29 for PEth (≥0.7 μmol/l). Fifteen cases had EtG as exclusive indicator for alcohol abuse compared with four cases for PEth. These findings suggest that measurements of EtG in hair may provide improved diagnostic information on alcohol abuse, due to a long retrospective time-window for detection and stability of EtG in hair in the decaying cadaver. However, an EtG level below the cutoff does not completely exclude previous alcohol abuse.
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| 2. |
- Comasco, Erika, et al.
(författare)
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Adolescent alcohol consumption : Biomarkers PEth and FAEE in relation to interview and questionnaire data
- 2009
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Ingår i: Journal of Studies on Alcohol and Drugs. - : ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV. - 1937-1888 .- 1938-4114. ; 70:5, s. 797-804
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE The aim of this study was to investigate the congruence of biomarkers, questionnaires, and interviews as instruments to assess adolescent alcohol consumption. METHOD The methodology used was a cross-sectional study with a randomized sample. Four different methods were used to estimate high adolescent alcohol consumption. The concordance of the results was investigated. Surveys were performed, and biological specimens were collected at all schools in the county of Västmanland, Sweden, in 2001. Eighty-one boys and 119 girls from a population of 16- and 19-year-old adolescents were randomly selected from quartiles of volunteers representing various degrees of psychosocial risk behaviors. Using a questionnaire (for a 1-hour session) and in-depth interviews, subjects were assessed regarding their alcohol-use habits. Blood and hair samples were analyzed for phosphatidylethanol (PEth) and fatty acid ethyl esters (FAEEs), respectively. RESULTS High alcohol consumption was underreported in the questionnaire compared with the interviews. PEth and FAEE analyses weakly confirmed the self-reports, and the results of the two biochemical tests did not overlap. The PEth blood test was the most specific but the least sensitive, whereas the FAEE hair test revealed low specificity and an overrepresentation of positive results in girls. CONCLUSIONS The expected higher self-report of high alcohol consumption by interview rather than by questionnaire was confirmed partly because of the influence of a bogus pipeline procedure. The absence of overlap between PEth and FAEE results and their poor agreement with self-reports suggested that biomarkers are unsuitable as screening tools for alcohol consumption in adolescents.
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| 3. |
- Cooper, Gail, et al.
(författare)
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Current status of accreditation for drug testing in hair
- 2008
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Ingår i: Forensic Science International. - : Elsevier BV. - 0379-0738 .- 1872-6283. ; 176:1, s. 9-12
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Tidskriftsartikel (refereegranskat)abstract
- At the annual meeting of the Society of Hair Testing in Vadstena, Sweden in 2006, a committee was appointed to address the issue of guidelines for hair testing and to assess the current status of accreditation amongst laboratories offering drug testing in hair.A short questionnaire was circulated amongst the membership and interested parties. Fifty-two responses were received from hair testing laboratories providing details on the amount and type of hair tests they offered and the status of accreditation within their facilities.Although the vast majority of laboratories follow current guidelines (83%), only nine laboratories were accredited to ISO/IEC 17025 for hair testing. A significant number of laboratories reporting that they were in the process of developing quality systems with a view to accrediting their methods within 2–3 years. This study provides an insight into the status of accreditation in hair testing laboratories and supports the need for guidelines to encourage best practice.
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| 4. |
- Druid, Henrik, et al.
(författare)
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Evaluation of the role of abstinence in heroin overdose deaths using segmental hair analysis
- 2007
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Ingår i: Forensic Science International. - : Elsevier BV. - 0379-0738 .- 1872-6283. ; 168:2-3, s. 223-226
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Tidskriftsartikel (refereegranskat)abstract
- In the body heroin is rapidly metabolized to 6-acetylmorphine and morphine. Victims of lethal heroin overdose often present with fairly low blood concentrations of morphine. Reduced tolerance due to abstinence has been proposed to account for this finding. The aim of the present study was to examine the role of abstinence in drug-related deaths by comparing recent and past exposure to opioids using segmental hair analysis with the postmortem blood morphine concentrations in deceased heroin users. The study included 60 deceased drug addicts in the Stockholm area, Sweden. In 32 cases, death was not related to heroin intake. In 18 of the 28 heroin fatalities, opioids were absent in the most recent hair segment, suggesting a reduced tolerance to opioids. However, the blood morphine levels were similar to those found in the 10 subjects that showed continuous opioid use. Hair and blood analysis disclosed an extensive use of additional drugs that directly or indirectly may influence the opioid system. The results suggest that abstinence is not a critical factor for heroin overdose death. Obviously tolerant subjects die after intake of similar doses. Other factors, particularly polydrug use, seem to be more causally important for these deaths.
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| 5. |
- Eriksson, Therese, 1979-
(författare)
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Organelle movement in melanophores: Effects of Panax ginseng, ginsenosides and quercetin
- 2009
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Panax ginseng is a traditional herb that has been used for over 2000 years to promote health and longevity. Active components of ginseng include ginsenosides, polysaccharides, flavonoids, polyacetylenes, peptides, vitamins, phenols and enzymes, of which the ginsenosides are considered to be the major bioactive constituents. Although widely used, the exact mechanisms of ginseng and its compounds remain unclear. In this thesis we use melanophores from Xenopus laevis to investigate the effects of Panax ginseng extract G115 and its constituents on organelle transport and signalling. Due to coordinated bidirectional movement of their pigmented granules (melanosomes), in response to defined chemical signals, melanophores are capable of fast colour changes and provide a great model for the study of intracellular transport. The movement is regulated by alterations in cyclic adenosine 3’:5’-monophosphate (cAMP) concentration, where a high or low level induce anterograde (dispersion) or retrograde (aggregation) transport respectively, resulting in a dark or light cell. Here we demonstrate that Panax ginseng and its constituents ginsenoside Rc and Rd and flavonoid quercetin induce a concentration-dependent anterograde transport of melanosomes. The effect of ginseng is shown to be independent of cAMP changes and protein kinase A activation. Upon incubation of melanophores with a combination of Rc or Rd and quercetin, a synergistic increase in anterograde movement was seen, indicating cooperation between the ginsenoside and flavonoid parts of ginseng. Protein kinase C (PKC) inhibitor Myristoylated EGF-R Fragment 651-658 decreased the anterograde movement stimulated by ginseng and ginsenoside Rc and Rd. Moreover, ginseng, but not ginsenosides or quercetin, stimulated an activation of 44/42-mitogen activated protein kinase (MAPK), previously shown to be involved in both aggregation and dispersion of melanosomes. PKC-inhibition did not affect the MAPK-activation, suggesting a role for PKC in the ginseng- and ginsenoside-induced dispersion but not as an upstream activator of MAPK.
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| 6. |
- Forsman, M., et al.
(författare)
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Urinary detection times and excretion patterns of flunitrazepam and its metabolites after a single oral dose
- 2009
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Ingår i: Journal of Analytical Toxicology. - 0146-4760 .- 1945-2403. ; 33:8, s. 491-501
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the excretion profiles of flunitrazepam metabolites in urine after a single dose. Sixteen volunteers received either 0.5 or 2.0 mg flunitrazepam. Urine samples were collected after 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 240, and 336 h. Samples were screened using CEDIA (300 µg/L cutoff) and quantitated using liquid chromatography-tandem mass spectrometry. The cutoff was 0.5 µg/L for flunitrazepam, N-desmethylflunitrazepam, 7-aminoflunitrazepam, 7-aminodesmethylflunitrazepam, 7-acetamidoflunitrazepam, and 7-acetamidodesmethylflunitrazepam. None of the subjects receiving 0.5 mg were screened positive, and only 23 of 102 samples from the subjects given 2.0 mg were positive with CEDIA. The predominant metabolites were 7-aminoflunitrazepam and 7-aminodesmethylflunitrazepam. For all subjects given the low dose, 7-aminoflunitrazepam was detected up to 120 h, and for two subjects for more than 240 h. Seven subjects given the high dose were positive up to 240 h for 7-aminoflunitrazepam. We conclude that the ratio 7-aminodesmethylflunitrazepam to 7-aminoflunitrazepam increased with time, independent of dose, and may be used to estimate the time of intake. For some low-dose subjects, the metabolite concentrations in the early samples were low and a chromatographic method may fail to detect the intake. We think laboratories should consider this when advising police and hospitals about sampling as well as when they set up strategies for analysis.
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| 7. |
- Forsman, Åsa, et al.
(författare)
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Förslag till förbättringar av rattfylleristatistiken i Sverige : underlag till uppdrag att förbättra beskrivningen av vägtrafikolyckornas hälsopåverkan
- 2008
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- In June 2006, the Swedish Road Administration was mandated by the Government to improve the description of the health effects of road traffic accidents. Under the terms of this mandate, a proposal was to be made as to how the recording of alcohol and drug related accidents can be improved, and how sample surveys of the prevalence of drivers under the influence of alcohol and/or drugs should be performed. This note describes the data used for these parts of the mandate. One common condition for both these parts is that possible screening methods for drivers under the influence of narcotics should be studied. In order to measure the proportion of traffic mileage travelled by drink/drug drivers, the investigation should be organised as a statistical sample survey where the police check drivers at sites selected at random. As regards selection in time, it may be reasonable to use quota sampling. In the present situation, we do not consider that it is possible to carry out regular surveys of drug driving. If the regulations are amended so that routine controls can be performed, and if the police begin to use screening instruments for drug tests, regular surveys can be performed. These surveys can then be integrated with the investigations regarding alcohol, by requiring the stopped drivers to give samples for both alcohol and for drugs.
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| 8. |
- Hodgins, Sheelagh, et al.
(författare)
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A multisite study of community treatment programs for mentally ill offenders with major mental disorders : Design, measures, and the forensic sample
- 2007
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Ingår i: Criminal justice and behavior. - : SAGE Publications. - 0093-8548 .- 1552-3594. ; 34:2, s. 211-228
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Tidskriftsartikel (refereegranskat)abstract
- This article presents reasons for undertaking ""The Comparative Study of the Prevention of Crime and Violence by Mentally Ill Persons"" and reasons for decisions regarding the study design and choice of measures. A brief portrait of the forensic patients that have been recruited is also presented. Community treatment programs could offer long-term cost-effective care for offenders with major mental disorders (MMDs). The study aims to identify the necessary ingredients of an effective program. Sites are selected in four countries where identification of most, if not all, persons with MMD who commit crimes within the catchment area was possible. Within each site, two samples of patients with MMD are recruited, one from a forensic hospital and one from a general psychiatric hospital. Assessments are completed prior to discharge. Participants are followed during a 5-year period. Comparisons of the forensic patients recruited in the four sites indicate many more similarities than differences.
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| 9. |
- Jones, A Wayne, et al.
(författare)
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Concentration-Time Profiles of Gamma-Hydroxybutyrate in Blood After Recreational Doses are Best Described by Zero-Order Rather Than First-Order Kinetics
- 2009
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Ingår i: Journal of Analytical Toxicology. - 0146-4760 .- 1945-2403. ; 33:6, s. 332-335
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Tidskriftsartikel (refereegranskat)abstract
- The recreational drug gamma-hydroxybutyrate (GHB) has a short plasma elimination half-life (t(1/2)) reported to be about 30-50 min. However, this represents a terminal half-life and therefore might not necessarily apply after large (abuse) doses are taken. Clinical studies with sodium oxybate (sodium salt of GHB) suggest that zero-order rather than first-order kinetics are more appropriate to describe post-peak concentration-time (C-T) profiles. We report the case of a 23-year-old male found unconscious by the police and a blood sample contained 100 mg/L GHB and 0.14 g% ethanol. On regaining consciousness the man admitted drinking alcohol about 6 h earlier but claimed that his drink must have been spiked with GHB. The police wanted to know how much GHB had been administered to account for the man's clinical condition. A back-calculation for 6 h, assuming a GHB half-life of 40 min, gives a very high concentration in blood of approximately 900 mg/L, which would probably have proven fatal. Back-calculating using zero-order kinetics and a proposed elimination rate of 18 mg/L per hour leads to a GHB concentration of 208 mg/L, which is much more realistic. Toxicologists should not arbitrarily apply the principles of first-order kinetics after abuse doses of drugs, when zero-order or saturation kinetics (Michaelis-Menten) are more appropriate.
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| 10. |
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| 11. |
- Nilsson, Kent W, et al.
(författare)
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Smoking as a product of gene-environment interaction
- 2009
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Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 114:2, s. 100-107
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Tidskriftsartikel (refereegranskat)abstract
- A strong hereditary influence on smoking has been demonstrated. As one of the candidate genes in relation to smoking, the serotonin transporter gene (5-HTTLPR) has been suggested, however with conflicting results. In recent studies, it has been shown that genotypic and environmental (G*E) factors interact in the shaping of a variety of phenotypic expressions. The objective of the present study was to investigate the interaction between a variation in the 5-HTTLPR and family environment in relation to smoking habits, nicotine dependence, and nicotine and cotinine levels in hair samples. A random Swedish adolescent population sample (n = 785), from which 200 individuals were stratified regarding behaviour, was genotyped for 5-HTTLPR and assessed with semi-structured interviews, a questionnaire, and hair analyses of nicotine and cotinine. The 5-HTTLPR gene interacted with a poor family environment to predict smoking habits, as well as nicotine and cotinine levels. The risk of being a smoker was increased 13 times for an individual with a combination of the 5-HTTLPR LS genotype and a poor family environment in comparison with the Homozygous Long-Long (LL) genotype and a good family environment.
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| 12. |
- Nyström, Ingrid, et al.
(författare)
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Quantitation of R-(−)- and S-(+)-Amphetamine in Hair and Blood by Gas Chromatography-Mass Spectrometry : An Application to Compliance Monitoring in Adult-Attention Deficit Hyperactivity Disorder Treatment
- 2005
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Ingår i: Journal of Analytical Toxicology. - : Oxford University Press (OUP). - 0146-4760 .- 1945-2403. ; 29:7, s. 682-688
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Tidskriftsartikel (refereegranskat)abstract
- Amphetamine has been used in Attention Deficit Hyperactivity Disorder (ADHD), narcolepsy, and as an appetite suppressant either as the racemate or in different proportions of its enantiomers. In Linköping, Sweden, the Department for Drug Dependence has successfully treated drug abusers also diagnosed with Adult ADHD with Metamina® [S-(+)-amphetamine]. Because of the high risk of relapse into drug abuse, a strategy involving the analysis of amphetamine enantiomers in blood and hair was investigated for the assessment of compliance as well as abstinence from street amphetamine. Four patients were included: one patient was treated with racemic amphetamine, and three with Metamina. Blood and hair samples were obtained as a part of the treatment. A basic extraction of the analytes into iso-octane was used. Hair was dissolved in sodium hydroxide before extraction. Chiral derivatization was performed by reaction with S-(−)-N-(trifluoroacetyl)prolyl chloride. Quantitation of R-(−)- and S-(+)-amphetamine was performed by gas chromatography-mass spectrometry in selected ion monitoring. Both blood and hair sample results showed good compliance for patients 1 and 2. Patient 3 and 4 showed different percentages of S-(+)-amphetamine in hair together with varying total concentrations, suggesting intake of additional racemic illicit amphetamine. During treatment, these patients also showed other signs of noncompliance, and one was temporarily withdrawn from treatment. We conclude that the method is suitable to detect therapeutic concentrations of R-(−)- and S-(+)-amphetamine in both blood and hair and that hair reveals noncompliance not shown by concentrations or enantiomer ratios in blood.
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| 13. |
- Roman, M., et al.
(författare)
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Quantitation of seven low-dosage antipsychotic drugs in human postmortem blood using LC-MS-MS
- 2008
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Ingår i: Journal of Analytical Toxicology. - : Preston Publications Inc. - 0146-4760 .- 1945-2403. ; 32:2, s. 147-155
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Tidskriftsartikel (refereegranskat)abstract
- In forensic toxicology, antipsychotic drugs are of considerable interest because of their abuse potential and their involvement in intoxications and suicides. In recent years, several new drugs dosed at low levels have entered the market and have put further demands on assays used. The aim of this work was to develop a validated liquid chromatography-tandem mass spectrometry assay for the quantitation of the low-dosage antipsychotic drugs buspirone, fluphenazine, flupenthixol, perphenazine, risperidone, ziprasidone, and zuclopenthixol in human postmortem blood. After liquid-liquid extraction using methyl t-butyl ether, compounds were separated on a Zorbax SB-CN column. Calibration curves were linear in the range 0.8-100 microg/L (r > 0.998) for all drugs. Both within- and between-day coefficients of variation were lower than 25% for all drugs at the LOQ, and extraction recoveries ranged between 58 and 112%. The possible presence of matrix effects was closely investigated. Fifty-four authentic samples were analyzed within the routine postmortem investigation, which resulted in the diagnosis of three fatal intoxications. Even though only a few intoxications were identified, the assay may present valuable information on suicidal deaths in psychotic patients where a true negative result implies noncompliance and a higher susceptibility for suicide. Without a sensitive enough method, this conclusion cannot be drawn. Therefore, we believe that antipsychotic drugs must be measured not only in toxic concentrations but also in therapeutic levels in postmortem cases
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| 14. |
- Stephanson, Nikolai, et al.
(författare)
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Accurate identification and quantification of 11-nor-Delta(9)-tetrahydrocannabinol-9-carboxylic acid in urine drug testing: Evaluation of a direct high efficiency liquid chromatographic-mass spectrometric method
- 2008
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Ingår i: Journal of chromatography. B. - : Elsevier Science B.V., Amsterdam.. - 1570-0232 .- 1873-376X. ; 871:1, s. 101-108
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Tidskriftsartikel (refereegranskat)abstract
- A direct liquid chromatographic-tandem mass spectrometric (LC-MS/MS) method for measurement of urinary Delta(9)-tetrahydrocannabinol carboxylic acid (THCA) was developed. The method involved dilution of the urine sample with water containing H-2(9)-deuterated analogue as internal standard, hydrolysis with ammonia, reversed phase chromatography using a Waters ultra-performance liquid chromatography (UPLC (TM)) equipment with gradient elution, negative electrospray ionization, and monitoring of two product ions in selected reaction monitoring mode. The measuring range was 2-1000 ng/mL for THCA, and the intra- and inter-assay imprecision, expressed as the coefficient of variation, was below 5%. Influence from urine matrix on ionization efficiency was noted in infusion experiments, but was compensated for by the internal standard. Comparison with established gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry methods in authentic patient samples demonstrated accuracy in both qualitative and quantitative results. A small difference in mean ratios (similar to 15%) may be explained by the use of different hydrolysis procedures between methods. In conclusion, the high efficiency LC-MS/MS method was capable of accurately identify and quantify THCA in urine with a capacity of 14 samples per hour.
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| 15. |
- Vikingsson, Svante, et al.
(författare)
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Retention of opioids and their glucuronides on a combined zwitterion and hydrophilic interaction stationary phase
- 2008
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Ingår i: Journal of Chromatography A. - : Elsevier Science B.V., Amsterdam.. - 0021-9673 .- 1873-3778. ; 1187:01-Feb, s. 46-52
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Tidskriftsartikel (refereegranskat)abstract
- A stationary phase combining zwitterionic ion chromatography and hydrophilic interaction chromatography (ZIC-HILIC) from SeQuant was evaluated for the chromatography of some opiates and their polar metabolites. The effects of mobile phase constitution on retention and resolution were extensively evaluated. Different aspects of mobile phase constitution such as ion strength and type of buffer, type and amount of organic modifier and pH were examined. The selectivity and retention of the opiates compared to their glucuronides could be substantially altered with small changes of the mobile phase, especially when the type of buffer, i.e., formate, or acetate and organic modifier, i.e., acetonitrile or methanol were changed. The retention on the ZIC-HILIC was dominated by hydrophilic interaction chromatography (HILIC) but considerable effects on the selectivity was observed, possibly caused by an ion exchange mechanism due to interactions with the charges on the stationary phase.
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