Pictorial review of the postmortem computed tomography in neonaticide cases.

Neonaticide is defined by the deliberate killing or homicide of a child within 24 h of its birth. In this context, three fundamental questions are generally asked of the forensic pathologist: what is the cause of death of the neonate? Was the child viable (i.e., what is the gestational age of the neonate)? Finally, was the neonate stillborn or liveborn?Postmortem imaging can help answer these questions by conducting (1) a complete lesional analysis of the body and the placenta, (2) an estimation of the gestational age by measuring the lengths of the diaphyseal long bones, and (3) an analysis of the aeration of the lungs and intestines. Using the details of 18 cases, we illustrate aspects of neonaticide cases in postmortem computed tomography (PMCT), offering detailed examples of notable postmortem changes and abnormalities, especially in the analysis of the pulmonary parenchyma. This article presents a useful iconography for the radiologist confronted with this rare yet complex forensic situation.

Cyanide Suicide After Deep Web Shopping: A Case Report.

Cyanide is a product that is known for its use in industrial or laboratory processes, as well as for intentional intoxication. The toxicity of cyanide is well described in humans with rapid inhibition of cellular aerobic metabolism after ingestion or inhalation, leading to severe clinical effects that are frequently lethal. We report the case of a young white man found dead in a hotel room after self-poisoning with cyanide ordered in the deep Web. This case shows a probable complex suicide kit use including cyanide, as a lethal tool, and dextromethorphan, as a sedative and anxiolytic substance. This case is an original example of the emerging deep Web shopping in illegal drug procurement.

Involvement of UDP-glucuronosyltransferases UGT1A9 and UGT2B7 in ethanol glucuronidation, and interactions with common drugs of abuse.

Ethyl glucuronide (EtG) determination is increasingly used in clinical and forensic toxicology to document ethanol consumption. The enzymes involved in EtG production, as well as potential interactions with common drugs of abuse, have not been extensively studied. Activities of human liver (HLM), kidney (HKM), and intestinal (HIM) microsomes, as well as of 12 major human recombinant UDP-glucuronosyltransferases (UGTs), toward ethanol (50 and 500 mM) were evaluated in vitro using liquid chromatography-tandem mass spectrometry. Enzyme kinetic parameters were determined for pooled microsomes and recombinant UGTs with significant activity. Individual contributions of UGTs were estimated using the relative activity factor approach, proposed for scaling activities obtained with cDNA-expressed enzymes to HLM. Interaction of morphine, codeine, lorazepam, oxazepam, nicotine, cotinine, cannabinol, and cannabidiol (5, 10, 15 mg/l) with ethanol (1.15, 4.6, 11.5 g/l; i.e., 25, 100, 250 mM) glucuronidation was assessed using pooled HLM. Ethanol glucuronidation intrinsic clearance (Cl(int)) was 4 and 12.7 times higher for HLM than for HKM and HIM, respectively. All recombinant UGTs, except UGT1A1, 1A6, and 1A10, produced EtG in detectable amounts. UGT1A9 and 2B7 were the most active enzymes, each accounting for 17 and 33% of HLM Cl(int), respectively. Only cannabinol and cannabidiol significantly affected ethanol glucuronidation. Cannabinol increased ethanol glucuronidation in a concentration-dependent manner, whereas cannabidiol significantly inhibited EtG formation in a noncompetitive manner (IC(50) = 1.17 mg/l; inhibition constant (K(i)) = 3.1 mg/l). UGT1A9 and 2B7 are the main enzymes involved in ethanol glucuronidation. In addition, our results suggest that cannabinol and cannabidiol could significantly alter ethanol glucuronidation.

Fatal Overdose of Gamma-hydroxybutyrate Acid After Ingestion of 1,4-Butanediol.

We report a case of fatal intoxication from 1,4-butanediol (1,4-BD), which was ingested by a young and "naïve" gamma-hydroxybutyrate (GHB) consumer during a party with the co-ingestion of alcohol, cannabis, and methylene-dioxy-methamphetamine. The following drug concentrations were found using gas chromatography coupled with mass spectrometry on autopsy samples and on a cup and a glass found at the scene: 20,350 mg/L (bottle) for 1,4-BD; 1020 mg/L (femoral blood), 3380 mg/L (cardiac blood), 47,280 mg/L (gastric content), and 570 mg/L (vitreous humor) for GHB. The concentration of GHB is difficult to interpret in forensic cases due to the possibility of an endogenous production of GHB. The variable tolerance of the user may also modify the peri- and postmortem GHB concentrations. This case underscores the need to have many different sources of toxicology samples analyzed to avoid the hypothesis of endogenous production of GHB.

Molecular analysis of the CYP2F1 gene: identification of a frequent non-functional allelic variant.

The CYP2F1 is a human cytochrome P450 that is selectively expressed in lung tissue and involved in the metabolism of various pneumotoxicants with potential carcinogenic effects. In the present study, we report the first systematic investigation of the genetic polymorphism of this enzyme. We analyzed the nucleotidic sequence of the CYP2F1 gene in DNA samples from 90 French Caucasians consisting in 44 patients with lung cancer and 46 control individuals, using single-strand conformation polymorphism analysis of PCR products (PCR-SSCP). We identified 24 novel mutations distributed in the promoter region of the gene, as well as in the coding regions and their flanking intronic sequences. In addition to the wild-type CYP2F1*1 allele, seven allelic variant, CYP2F1*2A, *2B, *3, *4, *5A, *5B and *6, were characterized. The most frequent allelic variant, CYP2F1*2A (25.6%), harbors a combination of 9 mutations, including 2 missense mutations (Asp218Asn and Gln266His) and a 1-bp insertion (c.14_15insC) that creates a premature stop codon in exon 2, probably leading to the synthesis of a severely truncated protein with no catalytic activity. The identification of around 7% of homozygotes for the frameshift mutation in our Caucasian population suggests the existence of an interindividual variation of the CYP2F1 activity and, consequently, the possibility of interindividual differences in the toxic response to some pneumotoxicants and in the susceptibility to certain chemically induced diseases. However, our preliminary results did not show any evidence that the CYP2F1 genetic polymorphism has implications in the pathogenesis of lung cancer.

Suicidal hanging resulting in complete decapitation--forensic, radiological, and anthropological studies: a case report.

The authors report a case of complete posthanging decapitation. The decapitated corpse lay against a pillar of a road bridge. The head had rolled 5 m from the trunk. The bridge was 7.2 m above the road level. The rope was 3.6 m long, its lower end was 3.6 m from the ground and its diameter was 10 mm. The noose used was a slip knot. Plain X-rays of the skull and cervical spine were obtained. The skull X-rays showed air in the meningeal spaces, in both lateral and third ventricles. The severance plane of the cervical spine was between the third and the fourth cervical vertebrae. No other cervical vertebral injuries were noted. At autopsy, the brain was macroscopically unremarkable except for air in the meningeal veins. The decapitation injuries of the head and the torso corresponded perfectly, without apparent loss of substance. The severance plane was confirmed. Dry bone study was carried out. Except for fractures of the extremities of the spinous processes of the second and third cervical vertebrae, no other bone injury of the spine was seen. The cervical vertebrae displayed numerous osteoarthritic lesions. The traditional hangman's fracture was not found. To the best of our knowledge, this is the first report of complete posthanging decapitation with a severance plane between the third and fourth cervical vertebrae.

Fatal accidental intrathecal injection of vindesine.

A 25-year-old woman being treated for non-Hodgkin's lymphoma was accidentally given vindesine intrathecally. The error was recognized immediately and a spinal cord washing was performed through syringing with isotonic saline. However, the patient died 6 weeks later with increasing paralysis, which was followed by neurologic failure. The deceased was autopsied and the central nervous system was removed for a microscopic examination. The results showed microscopic lesions extending from the lumbar to the thoracic portion of the spinal cord, which included pseudocystic transformation of the cells, degeneration of myelin, and microhemorrhages. The brain was edematous and, in the cerebellum, the vermis showed a loss of granule and Purkinje cells. The authors compare this report on vindesine toxicity with cases in the literature involving vincristine. The treating physician admitted responsibility and was sentenced to both a fine and imprisonment.

Extensive Necrotic Purpura in Levamisole-Adulterated Cocaine Abuse - A Case Report.

Levamisole, which is used as an adulterated compound of cocaine, is currently being seen year after year in cocaine intoxication. For a few cases in the last decade, necrotic purpura and neutropenia after levamisole/cocaine intoxication have been described in the medical community. Herein, we present an original case of levamisole intoxication of a 40-year-old woman who smoked heroin and cocaine few during a month. She rapidly presented an extensive necrotic purpura of the nose, cheeks and extremities (lower and upper), and immunologic reactions (positive anti-MPO and anti-HNE). Levamisole was detected on hairs with ultra-high performance liquid chromatography and tandem mass spectrometry. The case reports also a probable cocaine supplier deceit, which bring pure drug for hospital investigation after the intoxication of his client. The intoxicated woman had survived with several skin and chronic pain complications. That case recalls the knowledge about levamisole with a short review of the forensic literature.

False positive aortic dissection on postmortem computed tomography.

UNLABELLED: Post-mortem CT-scan (PMCT) has become increasingly useful as a diagnostic tool. However, certain normal postmortem changes may mimic the appearance of pathologic findings. We report two cases of false positive aortic dissection. METHODS: Non-contrast PMCT was performed on a sixty-four-detector row scanner. Each PMCT examination was assessed and reported by two independent radiologists. Autopsies were performed according European recommendations. CASES: In two corpses, a false positive DeBakey type I aortic dissection was detected. Autopsies confirmed that CT findings were artifactual. For each case the cause of the mistake was individually discussed and mainly based on the abnormalities observed during the autopsy. In fact, in our series (750 PMCT) a true aortic dissection was detected in two corpses during the same period. CONCLUSION: When a PMCT is performed, false positive aortic dissection can occur, which confirms the interest in combining opacification.

Human CYP4F12 genetic polymorphism: identification and functional characterization of seven variant allozymes.

The human cytochrome CYP4F12 has been shown to be metabolically active toward inflammatory mediators and exogenous compounds such as antihistaminic drugs. We recently identified a genetic polymorphism within the promoter region, associated with a decreased level of enzyme expression. In the present study, we report the further identification of single nucleotide polymorphisms in the coding sequence of the CYP4F12 gene. A polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) analysis of DNA samples from 53 unrelated French Caucasians, allowed the identification of ten mutations, comprising seven missense mutations, 31C>T (Leu11Phe), 38C>T (Pro13Leu), 47C>T (Met16Thr), 4759G>A (Asp76Asn), 4801G>A (Val90Leu), 8896C>T (Arg188Cys) and 23545G>A (Gly522Ser). Their functional impact toward ebastine hydroxylation was evaluated using heterologous expression in Saccharomyces cerevisiae cells of site-directed mutated cDNA variants. Five out seven variants did not exhibit any significant difference in CYP4F12 catalytic activity, whereas two variants, Val90Ile and Arg188Cys, displayed significant changes in their Michaelis-Menten (Km, Vm) parameters. These data on CYP4F12 genetic polymorphism provide tools for further studies of association with pathological processes involving an inflammatory component and with variations in anti-histaminic drug response.

Functional characterization of genetic polymorphisms identified in the human cytochrome P450 4F12 (CYP4F12) promoter region.

The human cytochrome CYP4F12 has been shown to be active toward inflammatory mediators and exogenous compounds such as antihistaminic drugs. In the present study, we report the first investigation of polymorphisms in the human CYP4F12 gene. A screening for sequence variations in the 5'-flanking region was performed by a Polymerase Chain Reaction-Single Strand Conformational Polymorphism (PCR-SSCP) strategy, using DNA samples from 53 unrelated French individuals of Caucasian origin. Several polymorphisms were identified, comprising a large deletion located in intron 1 (CYP4F12*v1), two isolated substitutions -402G>A (CYP4F12*v3) and -188 T>C (CYP4F12*v4) and nine combined mutations, -474T>C, -279A>C, -224A>G, -173G>A, -145C>G, -140T>C, -126T>C, -56T>C, and -21T>G (CYP4F12*v2). Considering the nature and location of the polymorphisms characterizing the CYP4F12*v1 and *v2, the functional relevance of those two allelic variants was further examined by transfecting different cell lines with constructs of the related region of the CYP4F12/luciferase reporter gene. Both alleles lead to a significant decrease of CYP4F12 gene expression in HepG2 cell line and, therefore, are likely to determine interindividual differences in CYP4F12 gene expression.

Use of hair testing to determine methadone exposure in pediatric deaths.

A case of death attributed to methadone acute poisoning in an infant aged 11 months is reported. A sudden infant death syndrome (SIDS) was suspected, whereas a traumatic cause of death was excluded regarding autopsy findings. Specimens were submitted to a large toxicological analysis, which included ethanol measurement by HS-GC-FID, a targeted screening for drugs of abuse and various prescription drug classes followed by quantification using UPLC-MS/MS methods. Methadone and its metabolite (EDDP) were detected in all the tested fluids, as well as in hair, with a blood concentration of methadone considered as lethal for children (73 ng/mL). The cause of death was determined to be acute "methadone poisoning", and the manner of death was "accidental". A discussion of the case circumstances, the difficulties with the interpretation of toxicological findings in children (blood concentration and hair testing), and the origin of exposure are discussed.

[Body's integumentary restoration after autopsy: legislative, technical and ethical issues]. / Restauration des corps après autopsies : aspects législatifs, techniques et éthiques.

In France, families of the deceased raised concerns as regards to the conditions of restoration of body. If scientists hospital autopsies are organized by the Bioethics Law of August 6, 2004, the forensic autopsies were so far not provided with such a legal framework. The legislator has proposed the creation of a new chapter in the Code of Criminal Procedure institutionalizing forensic activities. This legislative evolution allows the harmonization of practices; forensic pathologists must be involved in these changes by bringing their scientific expertise, notably through improving their autopsy techniques.

Skull wounds linked with blunt trauma (hammer example). A report of two depressed skull fractures--elements of biomechanical explanation.

The lesions of the skull following perforating traumas can create complex fractures. The blunt traumas can, according to the swiftness and the shape of the object used, create a depressed fracture. The authors describe through two clinical cases the lesional characteristic of the blunt traumas, perforating the skull using a hammer. In both cases the cranial lesions were very typical: they were geometrical, square shaped, of the same size than the tool (head and tip of the hammer). On the outer table of the skull, the edges of the wounds were sharp and regular. On the inner table, the edges of the wounds were beveled and irregular. The bony penetration in the depressed fracture results from a rupture of the outer table of the bone under tension, in periphery, by the bend of the bone to the impact (outbending) and then, from the inner table with comminuted bony fragmentation. Breeding on the fractures of the size and the shape of the blunt objects used is inconstant and differs, that it is the objects of flat surface or wide in opposition to those of small surface area. Fractures morphologies depend on one hand on these extrinsic factors and on the other hand, of intrinsic factors (structure of the bone). To identify them, we had previously conducted experimental work on cranial bone samples. The bone was submitted to a device for three-point bending. This work had shown properties of thickness and stiffness of the various areas of the vault. Our cases are consistent with these results and illustrate the variability of bone lesions according to region and mode of use of blunt weapons. Many studies have identified criteria for identification of the weapons and the assistance of digital and biomechanical models will be an invaluable contribution with this aim in the future.

[Evaluating the functional impairment of assault survivors in a judicial context: frequency of aggravating factors according to the French Penal Code and evidence for heterogeneous medical practice]. / Examen médical des personnes victimes de violence : fréquence des facteurs aggravants au sens du Code pénal, hétérogénéité des pratiques.

OBJECTIVES: In cases of assault and battery, the French Penal Code considers some aggravating factors. No data are available on the frequency of aggravating factors. Our main objective was to determine this frequency. A secondary objective was to present the evaluation in several forensic medicine units of the duration of the victims' inability to fulfil their usual daily activities, in days of "Total incapacity to work" (TIW). METHODS: Data were collected from six forensic medicine units on 300 evaluations of assaults survivors: aggravating factors, characteristics of the victims and of the assaults, results of medical examination, and determinants of TIW. RESULTS: Aggravating factors were present in most cases (232 of 300, 77%). Median duration of TIW was 2 days (range: 0-60). Medical evaluation ended in the absence of TIW in 0 to 56% of cases in the 6 units (Chi(2), P<0.0001). Forensic physicians considered that they had not evaluated the victims' mental state in 63 of 300 cases (21%). This rate varied significantly from one unit to another (P<0.0001). Determinants of TIW were primarily traumatic injuries in 45% of cases and functional impairment in 55%. Such proportions varied from one unit to another (P=0.01). Mental state impairment was the main determinant of TIW in 0 to 23% of cases (P=0.009). DISCUSSION: The present study documented the high frequency of aggravating factors and the heterogeneity of forensic evaluation in cases of assault and battery. Identifying determinants of TIW in everyday practice can participate in the development of national guidelines.

Acute arsenic poisoning: clinical, toxicological, histopathological, and forensic features.

This report describes a suicide case by acute arsenic intoxication via intravenous injection. A 30-year-old woman injected arsenic As (V) (sodium arseniate disodique: Disodium Hydrogena Arsenik RP) in a successful suicide attempt. Three hours following administration, the woman developed severe digestive symptoms. She was admitted to a hospital and transferred to the intensive care unit within 12 h of the massive administration of arsenic. Despite therapeutic efforts, over the next 2 h she developed multiorgan failure and died. A postmortem examination was performed. Pulmonary edema and congestion of liver were apparent. As (V) and As (III) were determined by high performance liquid chromatography and inductively coupled plasma mass spectrometry after mineralization of samples by concentrated nitric acid. Toxicological analysis revealed high concentrations of arsenic in biological fluids as well as in organs. Histopathological examination showed a typical indication of myocarditis. These findings were in agreement with acute arsenic poisoning. The symptoms developed by this young woman (intoxication by intravenous administration) were comparable to oral intoxication. The clinical signs, survival time, and administration type are discussed in light of the literature on acute and chronic arsenic poisoning.

Profiling gene expression of whole cytochrome P450 superfamily in human bronchial and peripheral lung tissues: Differential expression in non-small cell lung cancers.

Susceptibility to lung diseases, such as lung cancer and chronic obstructive pulmonary disease, is largely influenced by the metabolic capacity of lung tissues. This capacity is partly determined by the expression profile of the cytochromes P450 (CYPs), a superfamily of enzymes that have relevant catalytic properties toward exogenous and endogenous compounds. Using quantitative real-time RT-PCR, we conducted a comprehensive analysis of the expression profile of the 57 human CYP genes in non-tumoral (bronchial mucosa and pulmonary parenchyma) and tumoral lung tissues of 18 patients with non-small cell lung cancer. This study highlights (i) inter-individual variations in lung expression for some CYPs, (ii) different CYP expression patterns between bronchial mucosa and pulmonary parenchyma, that indicate distinctive susceptibility of these tissues toward the deleterious effects of inhaled chemical toxicants and carcinogens, (iii) high intertumoral variability, that could have major implications on lung tumor response to anti-cancer drugs.

An apple a day does not always keep the doctor away....

The authors describe a case of suicide in the workplace. A 45-year-old man employed by a fruit and vegetable packing company was found dead in a room containing a modified atmosphere for the packaging of fruits and vegetables. The rescue team measured the carbon monoxide (CO) concentration of the ambient air with a digital CO tester and found a level higher than 600 particles per million. Analysis of an arterial blood sample taken with an airtight syringe revealed the absence of CO but high levels of carbon dioxide (CO(2)). Autopsy revealed no significant injury and police investigators found a handwritten note of intent, describing a recent personal crisis. The authors concluded that the cause of death was suicide by asphyxiation secondary to CO(2) intoxication and notably oxygen (O(2)) depletion. This manner of suicide is rare and most cases previously described in the literature were accidental intoxications. To the best of our knowledge, this is the first case of suicide by CO(2) intoxication and O(2) depletion in a room with a modified atmosphere.

Unusual suicide with a chainsaw.

Described here is a case of suicide with the use of a chainsaw. A female suffering from schizophrenia committed suicide by an ingenious use of a chainsaw that resulted in the transection of her cervical spine and spinal cord. The findings of the resulting investigation are described and the mechanism of suicides with the use of a chainsaw is reviewed. A dry bone study was realized to determine the bone sections, the correlation between anatomic lesions and characteristics of chainsaw. The damage of organs and soft tissues is compared according to the kinds of chainsaw used.

Entomofauna of buried bodies in northern France.

Autopsies of exhumed cadavers can reveal important evidence for clarification of medical insurance and social issues. This study concerns insects sampled on 22 exhumed cadavers in the Lille area. For each corpse, the species and the stages of development were noted, as well as the time elapsed after burial, the location of the cemetery, the stage of decay and possible preservation treatment. A total of eight Diptera and two Coleoptera species were sampled on the corpses. The relationships between entomofauna and conditions of burial are discussed. Three species were regularly found because of their preference for underground environments or closed environments: Conicera tibialis, typically associated with buried bodies, Leptocera caenosa which is known to be associated with human faeces, water closets, caves and cracked soil pipes, and Ophyra capensis, sometimes found on human bodies kept indoors for several months, where blowflies have not had access. Triphleba hyalinata, which is associated with human bodies in wooden coffins, was found only twice.