Death by anaphylactic shock in an institution: an accident or negligence?

This is a description of a man, institutionalised for learning difficulties, known to have an allergy to seafood. After eating a pie, the patient quickly developed dyspnoea and vomiting. The staff at the institution administered epinephrine and called the emergency services. Despite cardiopulmonary resuscitation, the patient died shortly after being admitted to the emergency department of the University Hospitals of Geneva. In the light of the circumstances of the death and of a discrepancy between the information given to the police by the staff at the institution looking after the patient on the one hand, and the preliminary elements of the investigation on the other hand, it was suspected that there was failure in care of the patient and our institute was asked to carry out an autopsy. Basing on all the investigations carried out, the cause of death was anaphylactic reaction following the ingestion of seafood, contrary to what had been alleged by the staff at the home.

Neurobiology of suicide: do biomarkers exist?

Clinical risk factors have a low predictive value on suicide. This may explain the increasing interest in potential neurobiological correlates and specific heritable markers of suicide vulnerability. This review aims to present the current neurobiological findings that have been shown to be implicated in suicide completers and to discuss how postmortem studies may be useful in characterizing these individuals. Data on the role of the main neurobiological systems in suicidality, such as the neurotransmitter families, hypothalamic-pituitary-adrenal axis, neurotrophic factors, and polyamines, are exposed at the different biochemical, genetic, and epigenetic levels. Some neuroanatomic and neuropathological aspects as well as their in vivo morphological and functional neuroimaging correlates are also described. Except for the serotoninergic system, particularly with respect to the polymorphism of the gene coding for the serotonin transporter (5-HTTLPR) and brain-derived neurotrophic factor, data did not converge to produce a univocal consensus. The possible limitations of currently published studies are discussed, as well as the scope for long-term prospective studies.

Gunshot deaths in Geneva, Switzerland: 2001 to 2010.

We have conducted a retrospective study of all gunshot deaths that occurred in Geneva, Switzerland, over a 10-year period (2001-2010). The 133 cases reviewed were classified according to the manner of death, that is, suicide (106 cases), homicide (25 cases), and accident (2 cases). Various data from police authorities and the medicolegal examinations of the bodies were studied, including the age and sex of the victims, location of the event, type of firearm used, concomitant use or nonuse of alcohol and/or other drugs, seasonality, and entry site. These various elements were compared with data found in the literature.

Fatality in a wine vat.

Intoxication with carbon dioxide (CO2), a nonexplosive, colorless, and odorless gas does not cause any clinical symptoms or signs, with the occasional exception of sudation. Carbon dioxide is principally used in the food industry (70% of CO2 production), in particular to preserve foods and to carbonate beverages. Most fatalities resulting from CO2 intoxication are accidental and occur either in closed spaces or when dry ice is used in the food industry. In this case report, a 42-year-old male winemaker engineer was found dead, his head inside a wine vat that had been filled with grapes on the previous day and supplemented with dry ice to improve the taste of wine.

Debates about assisted suicide in Switzerland.

Assisted suicide is allowed in 3 states of the United States (Oregon, Washington, Montana) but only if performed by a physician.On the opposite, in Switzerland, at the beginning of the 20th century, the Swiss Penal Code referred to assisted suicide in the context of honor or an unhappy love affair. It was only in 1985 that Exit Deutsche Schweiz (Exit for German-speaking Switzerland) "medically" assisted the first patient to end his life.Even if authorized by the Swiss law upon certain conditions, assisted suicide is subject to debates for ethical reasons. The Swiss Academy of Medical Sciences described directives to guide physicians on this difficult subject.Different studies showed an increase in the number of medical-assisted suicide in Switzerland since the 1990s. Now, this number seems to be quite stable. Assisted suicide is authorized in a few hospitals under strict conditions (especially when returning home is impossible).Thus, according to the Swiss law, any person could perform assisted suicide; this is essentially performed by 3 main associations, using pentobarbital on medical prescription as lethal substance.Generally speaking, the Swiss population is rather in favor of assisted suicide. Among politics, the debate has been tough until 2010, when the Federal Council decided not to modify the Swiss Penal Code concerning assisted suicide.

[Sexual assaults in Geneva between 2006 and 2010]. / Sexuelle Ubergriffe in Genf (2006 bis 2010).

In Geneva, all sexual assault victims are examined both by a gynaecologist and a forensic pathologist with special training in clinical forensic medicine. Between 2006 and 2010, 473 victims were examined following such an assault. Over the years, the number of sexual assaults rose steadily. Most victims were aged between 15 and 30 years. The majority of the assaults occurred at night and on the weekend and often happened at the place where the perpetrator or the victim lived. Usually, the offender acted alone and was known to the victim. Many victims hesitate to present for an examination, which makes it difficult to collect evidence. Penetration was usually vaginal and without the use of a condom. Injuries on the body or genitals were seen in only half of the cases for the first ones and in less than one third for the second ones. Quite often (at least in 42 % of the cases), the victim consumed alcohol before the assault and the use of drugs--especially cannabis--was not uncommon either.

Alterations in phosphatidylinositol 3-kinase activity and PTEN phosphatase in the prefrontal cortex of depressed suicide victims.

BACKGROUND: Recent studies have reported alterations in protein kinase B (PKB)/Akt and in its downstream target, glycogen synthase kinase 3ß, in depression and suicide. The aim of the present study was to investigate possible impairment of the upstream regulators, namely phosphatidylinositol 3-kinase (PI3K) and PTEN. METHODS: The ventral prefrontal cortex (Brodmann's area 11) of 24 suicide victims and 24 drug-free nonsuicide subjects was used. The antemortem diagnoses of major depression disorder were obtained from the institutional records or psychological autopsy, and toxicological analyses were performed. Protein levels of PI3K and PTEN were assayed using the immunoblot method, and the kinase activity of PI3K and Akt was determined by phosphorylation of specific substrates. RESULTS: A decrease was observed in the enzymatic activity of PI3K [ANOVA: F(3, 44) = 9.20; p < 0.001] and Akt1 [ANOVA: F(3, 44) = 13.59; p < 0.001], without any change in protein levels, in both depressed suicide victims and depressed nonsuicide subjects (p < 0.01 and p < 0.002, respectively). PTEN protein levels were increased in the same groups [ANOVA: F(3, 44) = 10.5; p < 0.001]. No change was observed in nondepressed suicide victims. CONCLUSION: This study concludes that attenuation of kinase activity of PKB/Akt in depressed suicide victims may be due to the combined dysregulation of PTEN and PI3K resulting in insufficient phosphorylation of lipid second messengers. The effect is associated with major depression rather than with suicide per se. Given the cellular deficits reported in major depression, the study of enzymes involved in cell survival and neuroplasticity is particularly relevant to neurotrophic factor dysregulation in depression.

Simultaneous analysis of serotonin transporter, tryptophan hydroxylase 1 and 2 gene expression in the ventral prefrontal cortex of suicide victims.

Serotonergic signaling abnormalities have been implicated in suicide. Tryptophan hydroxylase (TPH), the rate limiting enzyme of serotonin biosynthesis and the serotonin transporter (SLC6A4), involved in the reuptake of serotonin from the synaptic gap, play major role in serotonergic signaling. In this study, we aimed to compare the levels of expression of these serotonin-related genes between suicide completers and controls and to identify genetic loci involved in their regulation. SLC6A4, TPH1, and TPH2 mRNA levels were measured in the ventral prefrontal cortex (VPFC) of 39 suicide completers and 40 matched controls. To identify the molecular basis of gene expression variation, we performed association studies between cis-acting polymorphisms and SLC6A4, TPH1, and TPH2 transcript levels. Finally, association analyses were carried out between suicide and TPH2 cis-single nucleotide polymorphisms (SNPs) in cohorts of 154 suicide completers and 289 control subjects. Whereas SLC6A4 and TPH1 mRNA expression levels did not differ between suicides and controls, TPH2 levels were found significantly increased (P = 0.003) in suicide completers. We observed that SNP rs10748185 located in the promoter region of TPH2 significantly affect levels of TPH2 mRNA expression. However, we did not find positive association between this eQTL (rs10748185) and suicide. Here, we report the simultaneous analysis of the expression of three serotonin-related genes in the VPFC of suicide victims and controls. This study showed that TPH2 expression levels were increased in the VPFC of suicide victims. Although, we identified a genetic variant that explains variance in TPH2 expression, we did not find evidence associating this cis-regulatory SNP with suicidal behavior.

Female Child and Adolescent Sexual Abuse Cases Reported at the Geneva University Hospitals Between 2006 and 2014: A Retrospective Study.

STUDY OBJECTIVE: To provide an objective quantification of the demographic characteristics and clinical findings related to female child and adolescent sexual abuse cases reported at the Geneva University Hospitals. DESIGN: Retrospective study. SETTING: Obstetrics and gynecology emergency unit. PARTICIPANTS: Female children (0-12 years old) and adolescents (13-20 years old) seeking primary care after sexual assault. INTERVENTIONS: None, observational study. MAIN OUTCOME MEASURES: Delay from assault to time of presentation to primary care presentation, type of perpetrators, and the presence gynecological and bodily lesions. RESULTS: Compared with children, a significantly higher proportion of adolescents presented to the hospital within 24 hours (134/289 (46.4%) vs 7/33 (21.2%); P = .006). Perpetrators were family members in 15/36 (41.7%) of children and in only 14/304 (4.6%) of adolescent patients (P < .00001); perpetrators were unfamiliar/nonrelated people in 8/36 (22.2%) of children and in 166/304 (54.6%) of adolescent patients (P < .0003). We did not find a significant difference between the 2 age groups with regard to the presence of gynecological lesions (15/35 (42.9%) of children and 91/298 (30.5%) of adolescent patients). However, we found a significant difference in the proportion of patients with bodily lesions such that 11/36 (30.6%) of children and 175/300 (58.3%) of adolescents (P = .002) were afflicted with bodily lesions. CONCLUSION: To our knowledge this is the first study to evaluate child and adolescent sexual abuse cases on the basis of real-life data collected in Switzerland. Our results highlight important differences in child and adolescent sexual assault in terms of delay in presentation to primary care, perpetrator's relation to the victim, and presence of bodily lesions. This study confirms that gynecological findings alone are not consistently present in the patients who seek primary care after sexual assault.

[Post-mortem partial skeletization of the face and neck by an Appenzell mountain dog]. / Postmortale Teilskelettierung der Gesichts- und Halsregion durch einen Appenzeller Sennenhund.

An 81-year-old man died unexpectedly from a cardiac cause. His wife, who lived in the same house and suffered from Alzheimer's disease, did not realize his death. When the body was found at the foot of the stairs 2-3 days afterwards, extensive soft tissue defects with notched wound edges, but no signs of vitality, were observed on the head and neck. The site where the body was found showed almost no traces of blood. In view of the injuries and their obviously post-mortem origin it was assumed that they had been caused by the man's Appenzell mountain dog which also lived in the house. By means of DNA typing, swabs from the wound edges of the soft-tissue defects could be assigned to the deceased's dog.

Genetic and epigenetic analysis of SSAT gene dysregulation in suicidal behavior.

It has recently been proposed that the SSAT gene plays a role in the predisposition to suicidal behavior. SSAT expression was found to be down-regulated in the brain of suicide completers. In addition, a single nucleotide polymorphism (SNP) rs6526342 was associated both with variation in SSAT expression and with suicidal behavior. In this study, we aimed to characterize the relationship between SSAT dysregulation and suicide behavior. To this end, we measured SSAT expression levels in the ventral prefrontal cortex (VPFC) of suicide completers (n = 20) and controls (n = 20) and found them to be significantly down-regulated in suicide victims (P = 0.007). To identify the basis of the regulation of SSAT expression, we performed an association analysis of 309 SNPs with SSAT transcript levels in 53 lymphoblastoid cell lines from the CEPH collection. We then examined the methylation status of the SSAT promoter region in males and females suicide completers and control subjects whose SSAT brain expression had been measured. We found no evidence to support a role for SNPs in controlling the level of SSAT expression. SSAT promoter methylation levels were not different between suicide completers and controls and did not correlate with SSAT expression levels. In addition, we found no indication of a genetic association between suicidal behavior and SNPs located within the SSAT gene. Our study provides new results which show that dysregulation of SSAT expression does play a role in suicide behavior. However, our data do not support any association between rs6526342 and variation in SSAT expression or suicidal behavior.

Factors Influencing the Filing of Complaints, Their Investigation, and Subsequent Legal Judgment in Cases of Sexual Assault.

In Geneva, examination of victims of sexual assault is performed by a gynecologist and a medical examiner. 48% of the victims file a complaint and we wanted to investigate the factors leading to file a complaint, those leading the Prosecutor to go to trial, and those influencing a conviction. Between 2006 and 2012, 676 victims of sexual assault were investigated (averaged age 26 year, mean 22). Information on injuries, perpetrators, and circumstances of the assault was collected and analyzed. The attacker being the ex-spouse or a friend and the presence of semen were factors leading to file a complaint. The assailant being a family member or ex-spouse and the presence of genital/anal lesions were factors influencing the Prosecutor. The presence of nongenital lesions, the assailant being known by the victim, influenced conviction. This study shows that the medical examiner plays a vital role in the investigation of cases of sexual assault.

Alteration in kinase activity but not in protein levels of protein kinase B and glycogen synthase kinase-3beta in ventral prefrontal cortex of depressed suicide victims.

BACKGROUND: Past studies in the neurobiology of suicide have reported alterations in serotonin and downstream effectors, such as Akt/protein kinase B. In this study, we aimed to examine possible abnormality in the Akt/glycogen synthase kinase-3beta (GSK-3beta) axis of depressed suicide victims' brains. METHODS: Twenty suicide victims and 20 drug-free non-suicide subjects were included for a postmortem study. The ventral prefrontal cortex area (BA'11) was used, and antemortem diagnoses of major depression disorder (MDD) (DSM-IV) were made from Institution's records. The protein levels of GSK-3alpha/beta and Akt-1 were assayed with the Western blot method, and the kinase activity of Akt and GSK-3alpha/beta were determined by phosphorylation of specific substrates. RESULTS: There was no change either in GSK-3alpha/beta and Akt-1 protein levels or in lithium-inhibitable total GSK-3alpha/beta enzyme activity of the ventral prefrontal cortex. The enzyme activity of Akt decreased significantly [analysis of variance (ANOVA): F(3,36)=5.372; p= .003], whereas GSK-3beta activity increased significantly [ANOVA: F(3,36)=8.567; p= .002] in depressed suicide victims and non-suicide subjects but not in non-depressed suicide victims. CONCLUSIONS: This study indicated that the activity rather than the protein levels of Akt and GSK-3beta was altered. The alteration was associated with MDD rather than with suicide per se.

Unplanned complex suicide by self-strangulation associated with multiple sharp force injuries: a case report.

In cases of ligature strangulation, the importance of distinguishing self-inflicted death from homicide is crucial. This entails objective scene investigation, autopsy and anamnesis in order to elucidate the manner of death correctly. The authors report a case of unplanned complex suicide by means of self-strangulation and multiple sharp force injury. The use of more than one suicide method, consecutively--termed unplanned complex suicide--gives this case particular significance. A brief discussion on this uncommon method of suicide is presented, particularly relevant to the attending forensic physician. In addition, a short overview of the entity of complex suicide is given.

Upregulation of IRAS/nischarin (I1-imidazoline receptor), a regulatory protein of µ-opioid receptor trafficking, in postmortem prefrontal cortex of long-term opiate and mixed opiate/cocaine abusers.

Imidazoline receptor antisera-selected (IRAS)/nischarin, a putative I1-imidazoline receptor, has recently been shown to regulate µ-opioid receptor (OR) trafficking and resensitisation. To study a possible involvement of this µ-OR regulator in opiate dependence, the present study assessed by Western blot analysis the contents of IRAS/nischarin and µ-OR in total homogenates and subcellular preparations of postmortem human prefrontal cortex (PFC/BA9) of long-term opiate and mixed opiate/cocaine abusers as well as of matched healthy control subjects. In the PFC/BA9 of long-term opiate/cocaine abusers (all subjects together) IRAS/nischarin content was increased (+67%, p < 0.01, n = 11) when compared with matched controls (n = 10). Similar increases were found for the subgroups of opiate (+72%, n = 6) and mixed opiate/cocaine (+61%, n = 5) abusers. IRAS/nischarin immunocontents were also found increased in subcellular membrane preparations (+61%, p < 0.05, n = 10) of PFC/BA9 from opiate addicts. In the same brain samples, the levels of µ-OR were not different to those in control subjects. Based on the increased contents in brains of opiate abusers and the reported function as µ-OR regulator, IRAS/nischarin could represent a new promising target for treatment of opiate use disorder.

Suicides in the young people of Geneva, Switzerland, from 1993 to 2002.

Suicides in Geneva in those less than 25 years old, from 1993 to 2002, were reviewed. Scenes investigations, autopsy findings, toxicology results, and psychiatric history (when available) were examined. There were 65 cases. The average annual suicide rate was 11/100,000. Seventy-seven percent were male, and 23% were female. The youngest was 12 years old and most of the victims were 18 years old and over (89%). For men, the use of firearms was the most common method (38%), followed by fall from height (16%) and drowning (10%). For women, fall from height was the most frequent (40%), followed by firearms and medication overdoses (20% each), hanging (13%), and drowning (7%). Toxicological analysis was performed in 41% of the cases and showed that alcohol was present in 26% and other drugs in 67% of these cases. The most common drugs present were benzodiazepines, cannabis, and cocaine.

Neurotrophin levels in postmortem brains of suicide victims and the effects of antemortem diagnosis and psychotropic drugs.

Suicide is a major public health problem but the neurobiological factors of risk are poorly understood. Recent studies have mentioned changes in the serotoninergic system and in neuronal plasticity, as well. The present investigation was undertaken to examine whether there is an abnormality in brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) proteins in suicide victims. The effect of diagnosis and drug treatments on the neurotrophins was also assessed. Thirty suicide victims (11 F/19 M) and twenty-four (10 F/14 M) drug-free non-suicide subjects, devoid of psychiatric or neurological disease, were examined. Antemortem diagnoses and toxicological analyses had been performed. The ventral prefrontal cortex (PFC), the hippocampus, and the entorhinal cortex were selected. BDNF and NT-3 levels were assayed either with the Western blot or with the ELISA method. Results indicated a significant decrease in BDNF and NT-3 levels in the hippocampus and PFC (only BDNF) but not in the entorhinal cortex, of suicide victims who were drug-free compared with non-suicide controls. The decrease was observed in all suicide victims, regardless of diagnosis. In drug-treated suicide victims, neurotrophin levels were not significantly different from non-suicide controls. This study supports a role of BDNF and NT-3 neurotrophin, in the pathophysiology of suicidal behavior. Anatomically, this role may implicate the hippocampus and the PFC but not the entorhinal cortex. The absence of change in BDNF and NT-3 levels of drug-treated suicide victims suggests that both neurotrophins are mediators of psychotropic drugs. A better understanding of the neurobiology of suicide could help detect populations at risk.

BDNF promoter I methylation correlates between post-mortem human peripheral and brain tissues.

Several psychiatric disorders have been associated with CpG methylation changes in CG rich promoters of the brain-derived neurotrophic factor (BDNF) mainly by extracting DNA from peripheral blood cells. Whether changes in peripheral DNA methylation can be used as a proxy for brain-specific alterations remains an open question. In this study we aimed to compare DNA methylation levels in BDNF promoter regions in human blood cells, muscle and brain regions using bisulfite-pyrosequencing. We found a significant correlation between the levels of BDNF promoter I methylation measured in quadriceps and vPFC tissues extracted from the same individuals (n = 98, Pearson, r = 0.48, p = 4.5 × 10(-7)). In the hippocampus, BDNF promoter I and IV methylation levels were strongly correlated (Pearson, n = 37, r = 0.74, p = 1.4 × 10(-7)). We found evidence for sex-dependent effect on BDNF promoter methylation levels in the various tissues and blood samples. Taken together, these data indicate a strong intra-individual correlation between peripheral and brain tissue. They also suggest that sex determines methylation patterns in BDNF promoter region across different types of tissue, including muscle, brain, and blood.

Up-regulated 14-3-3ß and 14-3-3ζ proteins in prefrontal cortex of subjects with schizophrenia: effect of psychotropic treatment.

14-3-3 is a family of conserved regulatory proteins that bind to a multitude of functionally diverse signalling proteins. Various genetic studies and gene expression and proteomic analyses have involved 14-3-3 proteins in schizophrenia (SZ). On the other hand, studies about the status of these proteins in major depressive disorder (MD) are still missing. Immunoreactivity values of cytosolic 14-3-3ß and 14-3-3ζ proteins were evaluated by Western blot in prefrontal cortex (PFC) of subjects with schizophrenia (SZ; n=22), subjects with major depressive disorder (MD; n=21) and age-, gender- and postmortem delay-matched control subjects (n=52). The modulation of 14-3-3ß and 14-3-3ζ proteins by psychotropic medication was also assessed. The analysis of both proteins in SZ subjects with respect to matched control subjects showed increased 14-3-3ß (Δ=33±10%, p<0.05) and 14-3-3ζ (Δ=29±6%, p<0.05) immunoreactivity in antipsychotic-free but not in antipsychotic-treated SZ subjects. Immunoreactivity values of 14-3-3ß and 14-3-3ζ were not altered in MD subjects. These results show the specific up-regulation of 14-3-3ß and 14-3-3ζ proteins in PFC of SZ subjects and suggest a possible down-regulation of both proteins by antipsychotic treatment.