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Cooper G.A.A.,University of Glasgow | Kronstrand R.,National Board of Forensic Medicine | Kintz P.,Linköping University
Forensic Science International | Year: 2012

The Society of Hair Testing (SoHT) Guidelines for Drug Testing in Hair provide laboratories with recommended best practice guidelines whether they are currently offering drug testing in hair, or plan to offer a hair testing service in the future. The guidelines include reference to recommended sample collection and storage procedures, through sample preparation, pre-treatment and analysis and the use of cut-offs. © 2011.

Edston E.,National Board of Forensic Medicine
Forensic Science, Medicine, and Pathology | Year: 2013

Death in anaphylactic shock cannot be diagnosed by autopsy alone. Morphological diagnosis of anaphylactic death by counting mast cells in the lung and airways have failed to give consistent results. Previously it has been observed that eosinophils seem to accumulate in the spleen in anaphylaxis. The purpose of this study was to investigate if it is possible to safely diagnose anaphylactic deaths by counting eosinophils, mast cells, and basophils in the spleen. In 43 forensic autopsy cases specific antibodies to mast cells, eosinophil-, and basophil granulocytes were used on sections from lung and splenic tissue. The cells were counted in 20 × 40 fields in a Leica photo-microscope. Presumed deaths in anaphylaxis were compared with sudden deaths after intravenous injection of opiates, and sudden cardiac deaths (control group). The main result was that significant (p < 0.05)increases of both eosinophil granulocytes (mean 26.6 ± 17.8/SD/)and mast cells (3.2 ± 2.0/SD/) versus controls (eosinophils mean 7.0 ± 10.5 and mast cells mean 0.9 ± 1.1) were seen in splenic tissue in anaphylactic deaths. Comparing cases with high and low concentrations of mast cell tryptase in serum showed a similar increase in eosinophils and mast cells in the spleen in cases with elevated tryptase, but not in the lung. The numbers of pulmonary mast cells and eosinophils were not different in anaphylactic deaths compared with controls. It is concluded that by quantifying eosinophil granulocytes and mast cells in the spleen in combination with tryptase measurements in serum it is possible to diagnose anaphylaxis with a high degree of certainty. © 2013 Springer Science+Business Media New York.

Jones A.W.,National board of Forensic Medicine | Holmgren A.,National board of Forensic Medicine
Forensic Science International | Year: 2012

The concentrations of zolpidem and zopiclone were determined in peripheral blood samples in two forensic materials collected over a 10-year period (2001-2010). The z-hypnotics were determined in venous blood from living subjects (impaired drivers) and in femoral blood from deceased persons (forensic autopsies), with the latter classified as intoxication or other causes of death. The z-hypnotics were determined in blood by capillary column gas chromatography (GC) with a nitrogen-phosphorous (N-P) detector after solvent extraction with n-butyl acetate. The analytical limit of quantitation (LOQ) was 0.02. mg/L for zopiclone and 0.05. mg/L for zolpidem and these have remained unchanged throughout the study. When death was attributed to drug intoxication (N=918), the median concentration of zopiclone in blood was 0.20. mg/L compared with 0.06. mg/L for other causes of death (N=1215) and 0.07. mg/L in traffic offenders (N=691) (p<0.001). Likewise, a higher median concentration (0.30. mg/L) was found in intoxication deaths involving zolpidem (N=357) compared with 0.13. mg/L for other causes of death (N=397) or 0.19. mg/L in impaired drivers (N=837) (p<0.001). Median concentration in blood of both z-hypnotics were appreciably higher in intoxication deaths when no other substances were identified; 0 70. mg/L (N=12) for zopiclone and 1.35. mg/L (N=12) for zolpidem. The median concentrations of z-hypnotics in blood decreased as the number of co-ingested substances increased for intoxication deaths but not other causes of death. The most prevalent co-ingested substances were ethanol in autopsy cases and diazepam in the motorists. This large compilation of forensic cases should prove useful when toxicologists are required to interpret concentrations of z-hypnotics in blood samples in relation to cause of death. © 2012 Elsevier Ireland Ltd.

O'Connor K.L.,U.S. National Institute of Standards and Technology | Tillmar A.O.,National Board of Forensic Medicine
Forensic Science International: Genetics | Year: 2012

Ideally for use in forensic analyses, genetic markers on the same chromosome should be more than 50 Mb in physical distance to ensure full recombination and thus independent inheritance. The forensic community has given attention to two STR markers, D12S391 and vWA, that are 6.3 megabases (Mb) apart on chromosome 12. Recent studies have shown no significant linkage disequilibrium between vWA and D12S391 in U.S. and worldwide populations, although genetic linkage has been identified. It is important to evaluate the impact of linkage effects on kinship analysis. In this study, we aimed to determine a more precise measurement of the recombination frequency between vWA and D12S391 based on a larger number of informative meiosis than has been studied previously. We estimated the recombination frequency (θ) to 0.089 (95% CI 0.044-0.158). Using pedigrees simulated under specific kinship scenarios where recombination was expected to affect the likelihood ratio (LR), we evaluated the impact on LR values of including or ignoring linkage between vWA and D12S391. For all pedigree scenarios considered, on average, LR values ignoring linkage were slightly underestimated than when linkage was considered. However, in the incest scenario considered, LR values could be overestimated up to 25-30 times when linkage was ignored. We demonstrate that the effect of ignoring linkage in the likelihood ratio calculation can be considerable. These results suggest that linkage should be considered during kinship analysis when vWA and D12S391 are tested for pedigrees where a recombination could impact the LR value. © 2012 Elsevier Ireland Ltd. All rights reserved.

Jones A.W.,National Board of Forensic Medicine
Forensic Science International | Year: 2010

Reliable information about the elimination rate of alcohol (ethanol) from blood is often needed in forensic science and legal medicine when alcohol-related crimes, such as drunken driving or drug-related sexual assault are investigated. A blood sample for forensic analysis might not be taken until several hours after an offence was committed. The courts usually want to know the suspect's blood-alcohol concentration (BAC) at some earlier time, such as the time of driving. Making these back calculations or retrograde extrapolations of BAC in criminal cases has many proponents and critics. Ethanol is eliminated from the body mainly by oxidative metabolism in the liver by Class I isoenzymes of alcohol dehydrogenase (ADH). Ethanol is an example of a drug for which the Michaelis-Menten pharmacokinetic model applies and the Michaelis constant (km) for Class I ADH is at a BAC of 2-10mg/100mL. This means that the enzyme is saturated with substrate after the first few drinks and that zero-order kinetics is adequate to describe the declining phase of the BAC profile in most forensic situations (BAC>20mg/100mL). After drinking on an empty stomach, the elimination rate of ethanol from blood falls within the range 10-15mg/100mL/h. In non-fasted subjects the rate of elimination tends to be in the range 15-20mg/100mL/h. In alcoholics during detoxification, because activity of microsomal enzyme (CYP2E1) is boosted, the ethanol elimination rate might be 25-35mg/100mL/h. The slope of the BAC declining phase is slightly steeper in women compared with men, which seems to be related to gender differences in liver weight in relation to lean body mass. The present evidence-based review suggests that the physiological range of ethanol elimination rates from blood is from 10 to 35mg/100mL/h. In moderate drinkers 15mg/100mL/h remains a good average value for the population, whereas in apprehended drivers 19mg/100mL/h is more appropriate, since many of these individuals are binge drinkers or alcoholics. In preparing this article, a large number of peer-reviewed publications were scrutinized. Only those meeting certain standards in experimental design, dose of alcohol and blood-sampling protocol were used. The results presented can hopefully serve as best-practice guidelines when questions arise in criminal and civil litigation about the elimination rate of ethanol from blood in humans. © 2010 Elsevier Ireland Ltd.

Using a forensic toxicology database, the authors investigated cases of driving under the influence of drugs (DUID) if methamphetamine (MA) was identified in the blood samples (N = 9,310). The concentrations of MA and amphetamine (AM) in blood were determined after liquid-liquid extraction by gas chromatography-mass spectrometry at limits of quantitation of 0.03 mg/L for both stimulants. In 814 cases, AM was negative in blood and MA was positive at mean (median) and highest concentrations of 0.19 mg/L (0.11 mg/L) and 3.4 mg/L, respectively. Both amines were present in blood in 8,496 cases at concentrations of 0.54 mg/L (0.35 mg/L) and 10.4 mg/L for AM and 0.41 mg/L (0.22 mg/L) and 5.6 mg/L for MA. However, the correlation between AM and MA was low and insignificant (r = -0.13) in the whole material. The coefficient of correlation increased to r = 0.41 (P < 0.001) when the MA/AM concentration ratio was >1. When MA/AM ratios were selected at intervals of 1.0 (e.g., >3.0 and <4.0 up to >9.0 and <10.0), the correlation between AM and MA was r = 0.99 (P < 0.001). Such cases represent the use of MA without contamination from AM, and the mean (median) and highest concentrations of this secondary amine in blood of DUID suspects were 0.72 mg/L (0.56 mg/L) and 4.2 mg/L, respectively.

Zackrisson A.L.,National Board of Forensic Medicine | Lindblom B.,National Board of Forensic Medicine | Ahlner J.,National Board of Forensic Medicine
Clinical Pharmacology and Therapeutics | Year: 2010

In Sweden, about 550 individuals die every year of drug intoxication. Many of these drugs are metabolized by CYP enzymes such as CYP2D6 and CYP2C19. A lack of these enzymes, resulting in poor metabolism, can lead to adverse reactions and even to fatality. On the other hand, an ultrarapid metabolism can lead to insufficient drug plasma concentration, resulting in failure of treatment, or it can lead to high concentrations of active/toxic metabolites. The aim of this project was to study the genetic profile of individuals with regard to the presence of CYP2D6 and CYP2C19 genes, in cases of fatal intoxication (242), suicide (intoxications excluded) (262), and natural death (212). PCR, followed by pyrosequencing, was used for all the analyses. We found that, among those who died of suicide (suicide cases), there was a higher number carrying more than two active CYP2D6 genes (corresponding to the phenotype of ultrarapid metabolizer) as compared with those who died of natural causes (natural-death cases) (P = 0.007). © 2010 American Society for Clinical Pharmacology and Therapeutics.

Reis M.,National Board of Forensic Medicine | Kllen B.,Lund University
Psychological Medicine | Year: 2010

Background Concerns have been expressed about possible adverse effects of the use of antidepressant medication during pregnancy, including risk for neonatal pathology and the presence of congenital malformations. Method Data from the Swedish Medical Birth Register (MBR) from 1 July 1995 up to 2007 were used to identify women who reported the use of antidepressants in early pregnancy or were prescribed antidepressants during pregnancy by antenatal care: a total of 14 821 women with 15 017 infants. Maternal characteristics, maternal delivery diagnoses, infant neonatal diagnoses and the presence of congenital malformations were compared with all other women who gave birth, using the Mantel-Haenszel technique and with adjustments for certain characteristics. Results There was an association between antidepressant treatment and pre-existing diabetes and chronic hypertension but also with many pregnancy complications. Rates of induced delivery and caesarean section were increased. The preterm birth rate was increased but not that of intrauterine growth retardation. Neonatal complications were common, notably after tricyclic antidepressant (TCA) use. An increased risk of persistent pulmonary hypertension of the newborn (PPHN) was verified. The congenital malformation rate was increased after TCAs. An association between use of paroxetine and congenital heart defects was verified and a similar effect on hypospadias was seen. Conclusions Women using antidepressants during pregnancy and their newborns have increased pathology. It is not clear how much of this is due to drug use or underlying pathology. Use of TCAs was found to carry a higher risk than other antidepressants and paroxetine seems to be associated with a specific teratogenic property. © Cambridge University Press 2010.

Jones A.W.,National Board of Forensic Medicine
Drug Testing and Analysis | Year: 2011

Studies in the field of forensic pharmacology and toxicology would not be complete without some knowledge of the history of drug discovery, the various personalities involved, and the events leading to the development and introduction of new therapeutic agents. The first medicinal drugs came from natural sources and existed in the form of herbs, plants, roots, vines and fungi. Until the mid-nineteenth century nature's pharmaceuticals were all that were available to relieve man's pain and suffering. The first synthetic drug, chloral hydrate, was discovered in 1869 and introduced as a sedative-hypnotic; it is still available today in some countries. The first pharmaceutical companies were spin-offs from the textiles and synthetic dye industry and owe much to the rich source of organic chemicals derived from the distillation of coal (coal-tar). The first analgesics and antipyretics, exemplified by phenacetin and acetanilide, were simple chemical derivatives of aniline and p-nitrophenol, both of which were byproducts from coal-tar. An extract from the bark of the white willow tree had been used for centuries to treat various fevers and inflammation. The active principle in white willow, salicin or salicylic acid, had a bitter taste and irritated the gastric mucosa, but a simple chemical modification was much more palatable. This was acetylsalicylic acid, better known as Aspirin®, the first blockbuster drug. At the start of the twentieth century, the first of the barbiturate family of drugs entered the pharmacopoeia and the rest, as they say, is history. © 2011 John Wiley & Sons, Ltd.

Algenas C.,National Board of Forensic Medicine | Tillmar A.O.,National Board of Forensic Medicine
International Journal of Legal Medicine | Year: 2014

In this study, allele frequencies for 29 autosomal short tandem repeats (STRs) and haplotype frequencies for 17 Y-chromosomal STRs of an Afghan population have been generated. Samples from 348 men and women originating from Afghanistan were analysed for the autosomal STRs, and the combined match probability was estimated to be 7.5 × 10-37. One hundred and sixty-nine men were analysed for the Y-chromosomal STRs, which resulted in 132 different haplotypes and a haplotype diversity of 0.995. © 2013 Springer-Verlag Berlin Heidelberg.

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