Alkoholist, psühhotroopsetest ja muudest ainetest põhjustatud surmad Eestis: kohtuarstlikel lahangutel põhinev tõendus

Väitekirja elektrooniline versioon ei sisalda publikatsiooneLiigne alkoholi tarvitamine on üheks enneaegse suremuse põhjuseks nii nagu on välditavaks surmapõhjuseks mürgistused psühhotroopsete ainetega. Oluline on välja selgitada alkoholi roll inimese organismi kahjusta¬misel ning selle suurusjärk rahvastiku tervise mõjutamisel. Lahanguleidudel baseeruv uuring on üks viis selle teostamiseks. Sellised väärtuslikku informatsiooni andvad uuringud on keerukad ning seetõttu pole neid palju läbi viidud. Selleks, et tuua välja alkoholi roll surmade põhjustajana ning selle kajastumine rahvastiku surmade statistikas, on omakorda oluline hinnata ja vajadusel parendada surmapõhjuste kodeerimist. Antud uuring oli Eestis esimene, kus kasutati detailset kohtuarstlikku lahangut alkoholi rolli uurimiseks enneaegses suremuses. Uurimistöö eesmärk oli anda tõenduspõhine ülevaade tööealiste meeste alkoholist põhjustatud surmadest, kasutades selleks süvitsi minevat kohtuarstlike lahangute analüüsi, uurida põhihaiguse kodeerimisega seotud probleeme hulgiorganite alkoholist põhjustatud kahjustuse korral ning kirjeldada surmaga lõppenud alkoholi, psühhotroopsete ja muude ainete mürgistusi Eesti kogurahvastikus aastatel 2000-2009 ja 2010-2019. Uuringu tulemused näitasid, et Eestis kohtuarstlikule lahangule suunatud tööealistel meestel esinevad sageli alkoholist põhjustatud haiguslikud muutused siseorganites, mis viitab selles vanuserühmas alkoholi tervistkahjustavale tarvitami¬sele. Uuringu tulemustest nähtus, et osad alkoholi biomarkerid (PEth, EtG ja EtS) on kasutatavad surmajärgses diagnostikas ning neid võiks enam kasutada tavapraktikas ja lahanguid hõlmavates uuringutes, eriti kui puuduvad andmed lahkunu alkoholi tarvitamise harjumuste kohta. Lahanguleiuna hulgiorganite alkoholkahjustuse esinemise korral oli raske diagnoosida põhihaigust Rahvusvahelises Haiguste Klassifikatsioonis puuduvate võimaluste tõttu. Mürgistussurmade uuringu põhjal olid aastatel 2000–2009 esikohal alkoholi¬mürgistused, kuid aastatel 2010–2019 mürgistused narkootiliste ja psühhotroopsete ainetega. Uuringust saadavad teadmised on vajalikud alkoholistrateegia ja -poliitika kujunda¬jatele ning Eesti Kohtuekspertiisi Instituudile kui kohtu¬arstlikke lahanguid teostavale asutusele.Excessive alcohol consumption has been implicated as a major cause of premature mortality. Other preventable causes of death are poisonings with psychotropic substances. It is important to find out the role of alcohol in causing damage to human body as well as the magnitude of it affecting population health. One of the ways of doing that is to carry out an autopsy-based study. Because of the complicated nature of such study they are quite rare, but still produce valuable information. Similarly, it is important to assess and improve ways of coding causes of death to reveal the role of alcohol in causing deaths, and how this reflects in mortality statistics at population level. This study was the first in Estonia to use in-depth forensic autopsy to explore the role of alcohol in premature mortality. The aim of the study was to give an evidence-based overview of deaths among working-aged men caused by alcohol using an in-depth forensic autopsy analysis, to explore the coding problems of underlying cause of death in presence of multiple alcohol-related pathologies of internal organs, and to describe fatal poisonings by alcohol, psychotropic and other substances among general population in 2000–2009 and in 2010–2019. This study showed that alcohol-related pathologies were common among working age men subject to forensic autopsy in Estonia, indicating harmful alcohol consumption in this age group. The study showed that several of the novel alcohol biomarkers appeared to perform well in post mortem samples and could be more widely used in forensic practise. At the same time, in case of multiple alcohol-related pathologies it was not possible to allocate underlying cause of death because of rigidity of classification. Among poisoning deaths, ethanol was the most frequent substance causing death in 2000–2009, but in 2010–2010 narcotic and psychotropic substances prevailed in poisoning deaths in Estonia. The findings of the study are useful for policy makers and for Estonian Forensic Science Institute as the institution where forensic autopsies are carried out.https://www.ester.ee/record=b549826

Prevalence of alcohol-related pathologies at autopsy: Estonian Forensic Study of Alcohol and Premature Death.

AIMS: Alcohol can induce diverse serious pathologies, yet this complexity may be obscured when alcohol-related deaths are classified according to a single underlying cause. We sought to quantify this issue and its implications for analysing mortality data. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional study included 554 men aged 25-54 in Estonia undergoing forensic autopsy in 2008-09. MEASUREMENTS: Potentially alcohol-related pathologies were identified following macroscopic and histological examination. Alcohol biomarkers levels were determined. For a subset (26%), drinking behaviour was provided by next-of-kin. The Estonian Statistics Office provided underlying cause of death. FINDINGS: Most deaths (75%) showed evidence of potentially alcohol-related pathologies, and 32% had pathologies in two or more organs. The liver was most commonly affected [60.5%, 95% confidence interval (CI) = 56.3-64.6] followed by the lungs (18.6%, 95% CI = 15.4-22.1), stomach (17.5%, 95% CI = 14.4-20.9), pancreas (14.1%, 95% CI = 11.3-17.3), heart (4.9%, 95% CI = 3.2-7.0) and oesophagus (1.4%, 95% CI = 0.6-2.8). Only a minority with liver pathology had a second pathology. The number of pathologies correlated with alcohol biomarkers (phosphatidylethanol, gamma-glytamyl transpeptidase in blood, ethylglucuronide, ethylsulphate in urine). Despite the high prevalence of liver pathology, few deaths had alcoholic liver disease specified as the underlying cause. CONCLUSION: The majority of 554 men aged 25-54 undergoing forensic autopsy in Estonia in 2008-09 showed evidence of alcohol-related pathology. However, the recording of deaths by underlying cause failed to capture the scale and nature of alcohol-induced pathologies found

La Forme naturelle

65aastane naine leiti kodust surnuna, eelmisel päeval oli leitud samast tema abikaasa – 62aastane mees. Mõlema surnukeha kohtuarstlikul lahangul jäi kahtlus raskmetallimürgistuse suhtes. Vere analüüsides leiti mõlema lahkunu vereproovis toksilistes väärtustes seleenisisaldus, mis oli otsene surmapõhjus. Lahanguleid oli mehel ja naisel sarnane: suu limaskestal oranžikaspunane õlijas aine, sarnane aine maos ja kaksteistsõrmikus, siseelundite oranžikas värvus ning dehüdreerunud välimus. Kohtuarstlikul lahangul sedastati lisaks veel mehel maksatsirroos ja hepatiit, alkoholi kontsentratsioon veres oli 1,56 mg/g (‰). Päev hiljem surnud naisel esines rasvmaks ja steatohepatiit, alkoholi kontsentratsioon veres oli 0,34 mg/g (‰).Kirjanduse andmetel esineb inimestel ägedat seleenimürgistust äärmiselt harva ja teadaolevalt pole seda varem Eestis diagnoositud. Ägeda seleenimürgistuse korral võivad esineda tugev kõhuvalu, profuusne diarröa ja oksendamine ning küüslaugu lõhn suust.Eesti Arst 2016; 95(2):109–11

Alcohol and premature death in Estonian men: a study of forensic autopsies using novel biomarkers and proxy informants.

BACKGROUND: Alcohol makes an important contribution to premature mortality in many countries in Eastern Europe, including Estonia. However, the full extent of its impact, and the mechanisms underlying it, are challenging issues to research. We describe the design and initial findings of a study aimed at investigating the association of alcohol with mortality in a large series of forensic autopsies of working-age men in Estonia. METHODS: 1299 male deaths aged 25-54 years were subject to forensic autopsy in 2008-2009. The routine autopsy protocol was augmented by a more systematic inspection of organs, drug testing, assay of liver enzymes and novel biomarkers of alcohol consumption (EtG, EtS and PEth), together with proxy interviews with next of kin for deaths among men who lived in or close to a major town. RESULTS: 595 augmented autopsies were performed. Of these, 66% were from external causes (26% suicide, 25% poisoning). 17% were attributed to circulatory system diseases and 7% to alcoholic liver disease. Blood alcohol concentrations (BAC) of ≥ 0.2 mg/g were found for 55% of deaths. Interviews were conducted with proxy informants for 61% of the subjects who had resided in towns. Of these, 28% were reported in the previous year to have been daily or almost daily drinkers and 10% had drunk non-beverage alcohols. Blood ethanol and the liver enzyme GGT were only associated with daily drinking. However, the novel biomarkers showed a more graded response with recent consumption. In contrast, the liver enzymes AST and ALT were largely uninformative because of post-mortem changes. The presence of extremely high PEth concentrations in some samples also suggested post-mortem formation. CONCLUSION: We have shown the feasibility of deploying an extended research protocol within the setting of routine forensic autopsies that offer scope to deepen our understanding of the alcohol-related burden of premature mortality. The most unique feature of the study is the information on a wide range of informative alcohol biomarkers, several of which have not been used previously in this sort of post-mortem research study. We have demonstrated, for the first time, the epidemiological value and validity of these novel alcohol biomarkers in post-mortem samples

Altered Expression Profile of IgLON Family of Neural Cell Adhesion Molecules in the Dorsolateral Prefrontal Cortex of Schizophrenic Patients

Neural adhesion proteins are crucial in the development and maintenance of functional neural connectivity. Growing evidence suggests that the IgLON family of neural adhesion molecules LSAMP, NTM, NEGR1, and OPCML are important candidates in forming the susceptibility to schizophrenia (SCZ). IgLON proteins have been shown to be involved in neurite outgrowth, synaptic plasticity and neuronal connectivity, all of which have been shown to be altered in the brains of patients with the diagnosis of schizophrenia. Here we optimized custom 5′-isoform-specific TaqMan gene-expression analysis for the transcripts of human IgLON genes to study the expression of IgLONs in the dorsolateral prefrontal cortex (DLPFC) of schizophrenic patients (n = 36) and control subjects (n = 36). Uniform 5′-region and a single promoter was confirmed for the human NEGR1 gene by in silico analysis. IgLON5, a recently described family member, was also included in the study. We detected significantly elevated levels of the NEGR1 transcript (1.33-fold increase) and the NTM 1b isoform transcript (1.47-fold increase) in the DLPFC of schizophrenia patients compared to healthy controls. Consequent protein analysis performed in male subjects confirmed the increase in NEGR1 protein content both in patients with the paranoid subtype and in patients with other subtypes. In-group analysis of patients revealed that lower expression of certain IgLON transcripts, mostly LSAMP 1a and 1b, could be related with concurrent depressive endophenotype in schizophrenic patients. Additionally, our study cohort provides further evidence that cannabis use may be a relevant risk factor associated with suicidal behaviors in psychotic patients. In conclusion, we provide clinical evidence of increased expression levels of particular IgLON family members in the DLPFC of schizophrenic patients. We propose that alterations in the expression profile of IgLON neural adhesion molecules are associated with brain circuit disorganization in neuropsychiatric disorders, such as schizophrenia. In the light of previously published data, we suggest that increased level of NEGR1 in the frontal cortex may serve as molecular marker for a wider spectrum of psychiatric conditions

Characteristics of cardiovascular deaths in forensic medical cases in Budapest, Vilnius and Tallinn.

Evaluation of the pathomorphological characteristics of cases involving natural and sudden cardiovascular death is essential for the determination of the cause of death. The main purpose of this study is to investigate sudden unexpected cardiovascular death and to study how different geographical climatic influences may affect cardiac mortality in three capitals: Budapest, Vilnius and Tallinn. There were 8482 (5753 male, 2729 female) cardiovascular deaths between 2005 and 2009. The highest rate was observed in the age group between 71 and 80 years (35.17%) and 51-60 years (24.45%). The highest number of cardiovascular deaths occur in January (805/9.49%) and December (770/9.07%). Seasonal distribution was observed, with winter prevalence in Tallinn (279/3.20%) and spring prevalence in Vilnius (760/8.90%). Though in Vilnius and Budapest a great number of deaths occurred in winter and spring, any correlation with other factors (e.g. age, gender, BAC) was not statistically significant. Based on our results we can conclude that environmental-geographical parameters may affect natural cardiovascular death. Examination of pathological patterns and predisposing environmental parameters may help to improve prevention strategies

Guidelines on the Methods of Ascertainment of Whiplash-Associated Disorders

This chapter presents the International Guidelines developed by the Working Group on Personal Injury and Damage under the patronage of the International Academy of Legal Medicine (IALM) regarding the Methods of Ascertainment of any suspected Whiplash-Associated Disorders (WAD). This chapter includes a detailed description of the logical and methodological steps of the ascertainment process as well as a synoptic diagram in the form of a flow-chart. This chapter represents a slightly modified version of an article published in the International Journal of Legal Medicine