Comparative analysis of post-mortem drug concentrations in cerebrospinal fluid and blood.

This study aimed to compare the concentration of various xenobiotics in both cerebrospinal fluid (CSF) and blood. We examined 175 autopsy cases covering a wide range of ages, causes of death, and drug ingestion histories, with cerebrospinal fluid and blood samples available for toxicological testing. Analytes studied included opioids, benzodiazepines, antidepressants, antipsychotics, and illicit substances such as cannabinoids, stimulants and new psychoactive substances, including synthetic cathinones and synthetic cannabinoids. We found that concentrations in CSF were generally lower than in blood. A significant correlation was observed between drug concentrations in CSF and blood for many analytes (p < 0.05). However, the strength and direction of the correlation varied considerably depending on the physicochemical properties of the drugs, suggesting that a 'one size fits all' model may not be applicable. The results indicate that cerebrospinal fluid (CSF) can be used to detect a variety of xenobiotics, particularly amphetamines, synthetic cathinones and synthetic cannabinoids, in cases where conventional biological materials are not available. Additionally, using the results obtained in the future can lead to a better understanding of pharmacokinetic processes and the effect of post-mortem redistribution. Further research is needed to refine our understanding of these relationships.

A fatal case of poisoning with a cathinone derivative: α-PiHP and its postmortem distribution in body fluids and organ tissues.

New psychoactive substances continue to appear on the drug market, and alpha-pyrrolidinoisohexanophenone (α-PiHP) is one of the most popular cathinone derivatives. In this article, we report a case of death caused by α-PiHP. Based on the toxicological results of the studied case along with autopsy, histopathological findings and crime-scene information, fatal intoxication with α-PiHP was accepted as the final cause of death. α-PiHP and its metabolite (OH-α-PiHP) were detected and quantified in all postmortem materials (blood collected from the heart, the femoral vein and the dural venous sinuses; vitreous humor; cerebrospinal fluid; cerebral cortex; brainstem; cerebellum; bile; liver; kidney; heart; pancreas; spleen; thyroid gland; lung; adipose tissue; stomach and intestine). To date, this is the first case of determination of α-PiHP and its metabolite in postmortem specimens. In our opinion, α-PiHP and its metabolite concentration database can be helpful in the interpretation of fatal cases.

Toxicological Analysis of Cases of Mixed Poisonings with Synthetic Cathinones and Other Drugs of Abuse.

Some of the most commonly used new psychoactive substances (NPSs) are synthetic cathinones (SCs). The literature increasingly indicates that SCs have a significant addictive potential and pose a high risk to human health and life. The vast majority of SC users take a number of substances simultaneously. This article lists the detected concentrations in 26 fatal and 2 non-fatal real cases, in which SCs or an SC along with other substances were determined in blood and other biological materials. The following SCs were found most often: α-pyrrolidinohexiophenone, α-pyrrolidinopentiophenone, N-ethylpentedrone (NEP), 4-methyl-α-ethylaminopentiophenone and N-ethylhexedrone. In addition to detected SCs, the analyzed samples showed the presence of conventional drugs such as methamphetamine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxyamphetamine, amphetamine and NPSs from groups other than SCs, such as synthetic cannabinoids (UR-144 and 5F-AMB), synthetic opioids (AH-7921, U-47700 and 4-fluorobutyrfentanyl) and others (desoxypipradrol and etizolam). The quantitative analyses were carried out by liquid chromatography with tandem mass spectrometry (LC-MS-MS). This study presents pioneering data on concentrations and effects of 4-ethylmethcathinone, NEP, N-ethylbuphedrone and mexedrone. Also noteworthy are the data on SCs that until now have rarely been described in the literature together with specified blood concentrations. The analyzed cases of taking SCs were associated with fatal intoxication (n = 26), driving under the influence of drugs (n = 2) and death caused by beating (n = 1). Taking SCs has serious side effects that can lead to multiple organ failure and death. The use of more than one psychoactive substance simultaneously (including at least one SC) contributes to increased SC toxicity. These data could be valuable for further interpretation of other results from toxicological analyses.

Assessing the applicability of cerebrospinal fluid collected from the spinal cord for the determination of ethyl alcohol in post-mortem toxicology.

This paper presents the results of a study on the applicability of cerebrospinal fluid (CSF) collected from the spinal canal in the post-mortem determination of ethyl alcohol. The present study reviewed data of autopsy cases (n = 45), in which ethyl alcohol was detected in CSF using gas chromatography with a flame ionization detector (HS-GC-FID), to investigate ethyl alcohol concentrations in CSF, compared with blood. As a result of statistical analysis of the obtained data, a high positive correlation was found between blood ethanol concentration and cerebrospinal fluid collected from the spinal canal ethanol concentration. The Pearson correlation coefficient was statistically highly significant (p < 0.001) (r = 0.9503). The data obtained allowed us to conclude that cerebrospinal fluid collected from the spinal canal can be collected during an autopsy as an alternative biological specimen to assess the ethanol content. Cerebrospinal fluid collected from the spinal canal can corroborate and lend credibility to the results obtained for blood and, in special cases, when blood is drawn from putrefied bodies and may even be a superior specimen to blood for assessing ethyl alcohol intoxication status.

Suicide using an electric drill - case report and literature review. / Samobójstwo z uzyciem wiertarki elektrycznej ­ opis przypadku i przeglad pismiennictwa.

The use of an electric drill to commit suicide is rare in forensic practice. The aim of the work is to present the first case of this kind from the Upper Silesia. The results of post-mortem examinations and the results of prosecutor's examination of case files containing medical documentation from the patient's treatment were analyzed. People with mental disorders and diseases may choose unusual methods of taking their own lives, such as using an electric drill. This may cause investigators a lot of doubt as to whether the event was really a suicide. In addition to full post-mortem diagnostics, it is particularly important in such cases to assess the medical history of the deceased, often with the participation of a psychiatrist as a consultant.

[The use of clinical molecular and genetic tests in forensic medical opinions]. / Wykorzystanie klinicznych badan molekularno-genetycznych w opiniowaniu sadowo-lekarskim.

Modern molecular biology and clinical genetics have the ability to diagnose many diseases, the presence or absence of which is important in various areas of forensic medical opinion. The aim of the study is to present examples of possible non-standard application of clinical molecular-genetic tests in forensic medicine. From among all the opinions prepared so far at the Department of Forensic Medicine in Katowice, three were selected two of which concerned post-autopsy conclusions relating to the cause of death, and in one case - opinion based on the files of a case related to the suspicion of a maltreated child syndrome in an infant. In all these cases, the results of the molecular and genetic tests were negative, which was taken into account by the experts when formulating the final conclusions of the opinion. The use of clinical molecular and genetic tests in forensic medicine is possible and always brings important additional information that broadens the possibilities of opinion-making and facilitates diagnosis. The areas in which this type of research may be particularly useful are: diagnostics of the basis of thromboembolic complications, modern integrated morphological and molecular diagnostics of neoplasms and diagnostics of genetic defects of connective tissue in children suspected of having abused child syndrome.

Sudden death during methadone replacement therapy - case report and literature review. / Nagly zgon w trakcie terapii zastepczej metadonem ­ opis przypadku i przeglad literatury.

Methadone is a diphenylpropylamine derivative that binds to opioid receptors and has been used in drug abstinence and substitution treatment programs. The aim of the study is to describe a case of sudden death of a prisoner during methadone substitution therapy from the authors' medico-legal consulting practice and to review the literature. A 41-year-old male with a long history of abuse of psychoactive substances, especially heroin, serving a prison sentence, after consultation in the addiction treatment clinic, started methadone substitution therapy. In the following days he took two doses of the drug (50 mg each). The prisoner was pronounced dead during the night. Blood toxicology tests showed the presence of methadone at the therapeutic concentration of 816 ng/ml. Currently, it is believed that even the therapeutic concentration of methadone increases the risk of sudden cardiac death, especially in predisposed patients (e.g. with structural pathologies of the myocardium, cardiac arrhythmias, hypokalemia, and liver failure).

Immunohistochemical detection of insulin at the injection site in a case of suspected murder with the suicide of the perpetrator.

In medicolegal practice, rare cases involving suicidal, criminal, or accidental insulin overdose are both analytically and forensically challenging. The aim of this study is to present a model procedure in such cases, developed at the Department of Forensic Medicine and Toxicology of the Medical University of Silesia in Katowice, with particular emphasis on the possibility of additional confirmation of insulin intake by its immunohistochemical detection at the injection site. In the example case presented here, an immunohistochemical examination using FLEX Polyclonal Guinea Pig Anti-Insulin antibody (code IR002, Dako) confirmed the presence of insulin in the subcutaneous tissue of the victims. In our opinion, the method of immunohistochemical detection of insulin at the injection site can and should be used routinely in such cases.

Medico-legal analysis of cases of children who died suddenly due to pneumonia undiagnosed in their lifetime. / Sadowo-lekarska analiza przypadków dzieci zmarlych nagle z powodu nierozpoznanego za zycia zapalenia pluc.

Pneumonia is one of the most common causes of children's hospitalization and death. The aim of the study was a medico-legal analysis of children who died suddenly due to pneumonia undiagnosed in their lifetime. The research was of a retrospective character and consisted in an analysis of prosecution files. The study included 47 children who died between 2011-2018 in whom pneumonia after post-mortem examination was indicated as the cause of death, as well as children in whom the cause of death, despite additional post-mortem examinations, including histopathological tests, was not established. In some cases, under additional post-mortem examinations, additional targeted immunohistochemical staining of selected lung sections was performed to establish the diagnosis. In children with prodromal symptoms, histopathological examination showed significantly more frequent atelectasis than in children without prodromal symptoms. Pneumonia is a significant clinical problem. Especially in young children, it may proceed with- out any symptoms that would cause such a diagnosis to be made. A properly conducted post-mortem diagnosis supplemented by immunohistochemical examinations allows to reduce the number of unexplained deaths in children.

Toxicological Analysis of Intoxications with Synthetic Cathinones.

Synthetic cathinones (SCs) are currently the second largest and the second most frequently seized group of new psychoactive substances. They are sold as replacements for controlled stimulants such as amphetamine, cocaine and 3,4-methylenedioxymethamphetamine. Administration of low doses of SCs can cause euphoria and increased alertness, and administration of high doses or chronic use of cathinones can cause serious adverse effects such as hallucinations, delirium, hyperthermia and tachycardia. In the years 2013-2019 in our practice, as many as 16 different SCs were detected in biological materials. This article lists the observed concentrations in 39 fatal and 18 non-fatal cases, in which a single SC as well as an SC in combination with amphetamine or ethyl alcohol were detected and quantified in biological materials. The quantitative analyses were carried out by liquid chromatography with tandem mass spectrometry. The analyzed cases of taking SCs were associated with intoxication (2 cases), fatal intoxication (36), driving under the influence of drugs (10) and other circumstances (9) such as violence, insulting an officer and holding a hostage. Taking SCs has serious side effects that can lead to multiple organ failure and death. Screening for the presence of SCs in biological materials should be part of the routine course of treatment in intoxication cases, both at the stage of clinical diagnosis and at the stage of forensic toxicological analysis. Ethyl alcohol and amphetamine may contribute to increased SC toxicity. These data could be valuable for further interpretation of other results from toxicological analyses.

A rare case of fatal poisoning during long-term therapy with lithium carbonate - chronic poisoning, suicide or psychiatric malpractice? / Rzadki przypadek smiertelnego zatrucia w trakcie dlugotrwalej terapii weglanem litu ­ samobójstwo, przewlekle zatrucie czy blad medyczny psychiatry?

The study aims to present a case of atypical poisoning with lithium carbonate in a 57-year-old woman treated for bipolar affective disorder with lithium carbonate for about 30 years. The patient was admitted to the hospital with significant agitation. An important finding obtained from the family interview was the patient's significant weight loss over the past year. In the hospital, the patient received haloperidol and clonazepam. Laboratory tests showed a very high blood lithium concentration of 3.79 mmol/l [N: 0.6─1.2 mmol/l] and elevated serum concentrations of creatinine (3.6 mg/dl) and urea (110 mg/dl). The patient was transferred to the toxicology department, where hemodialysis was performed and intensive treatment initiated. Despite the rapid decrease in lithium levels, her condition gradually deteriorated. The patient died on the fifth day of hospitalization. The autopsy revealed polycystic kidney disease (PKD). During the preparation of the medico-legal report on the correctness of the medical treatment, it was assumed that the cause of death was lithium carbonate poisoning in the course of advanced chronic kidney disease due to PKD, probably a consequence of long-term lithium therapy. The analysis of medical records revealed that despite her psychiatrist's recommendation, the patient had been refusing the monitoring of lithium levels for the past 18 years. This case demonstrates that both psychiatrists and toxicologists should be aware of possible lithium poisoning upon the deterioration of renal function. Therefore, assessment of renal function should be an integral part of monitoring lithium therapy.

Cerebrospinal fluid in forensic toxicology: Current status and future perspectives.

In forensic toxicology, alternative biological materials are very useful and important, e.g. in the case of lack of basic body fluids. One alternative biological material is cerebrospinal fluid (CSF). The procedures of the collection of biological material during the autopsy are performed in accordance with local, usually national recommendations, which most often require updating. It is very difficult to assess the possibility of using CSF as an alternative biological material for toxicological studies for the presence of drugs, intoxicants, including new psychoactive substances (commonly known as designer drugs), psychotropic substances, and ethyl alcohol, based on current data. Previous research suggests that CSF may be useful in toxicological studies, but these aspects need to be investigated more carefully because studies have collected CSF from different sites and often the results of different authors are not comparable. It would be necessary to prepare guidelines, e.g. the site of CSF collection that may influence the results of quantitative analysis. It would also be necessary to replicate some studies with a different collection site or a more recent analytical technique, e.g. for comparative testing of blood ethanol and cerebrospinal fluid. Cerebrospinal fluid can be a valuable information carrier in the absence of classic biological material from an autopsy. Investigating these aspects in more detail could allow the future use of this alternative material for routine toxicology analyzes in a forensic laboratory.

DNA Barcoding Identifies Unknown Females and Larvae of Fannia R.-D. (Diptera: Fanniidae) from Carrion Succession Experiment and Case Report.

Application of available keys to European Fanniidae did not facilitate unequivocal species identification for third instar larvae and females of Fannia Robineau-Desvoidy, 1830 collected during a study of arthropod succession on pig carrion. To link these samples to known species, we took the advantage of molecular identification methods and compared newly obtained cytochrome oxidase subunit I (COI) barcode sequences against sequences deposited in reference databases. As an outcome of the results obtained, we describe for the first time a third instar larva of Fannia nigra Malloch, 1910 and Fannia pallitibia (Rondani, 1866) and a female of Fannia collini d'Assis-Fonseca, 1966. We provide combinations of characters allowing for discrimination of described insects from other Fanniidae. We provide an update for the key by Rozkosný et al. 1997, which allows differentiation between females of F. collini and other species of Fanniidae. Additionally, we provide a case of a human cadaver discovered in Southern Poland and insect fauna associated with it as the first report of F. nigra larvae developing on a human body.

When DNA profiling is not enough? A case of same-sex siblings identification by odontological assessment after gas explosion-related building collapse.

We aimed to show the usefulness of odontological assessment in forensic investigation. Charred remains of two female siblings were found in a collapsed building after a gas explosion. Due to thermal damage of the bodies, the facial characteristics, fingerprints, height and weight could not be used to distinguish between siblings. Since the victims, 4 and 10-year-old, died simultaneously and all personal belongings were lost, DNA profiling performed with their parents only confirmed the relationship. As dental charts of siblings were not found, we could not easily discriminate which remains would be of the elder and which of the younger sister. The odontological examination enabled us to discriminate between the siblings based on differences in deciduous and permanent dentition. We conclude that although DNA profiling is becoming a standard method of personal identification in some cases it should be supported by additional methods to deliver comprehensive forensic reports.

Concentrations of volatile substances in costal cartilage in relation to blood and urine - preliminary studies.

Aim: The study aimed to examine whether volatile substances (ethanol, isopropanol, and acetone) can be detected in costal cartilage and also if concentrations of detected substances reliably reflect their concentrations in the peripheral blood - the standard forensic material for toxicological analyses. Such knowledge can be useful in cases when a cadaver's blood is unavailable or contaminated. Material and methods: Ethanol, isopropanol, and acetone concentrations were determined in samples of unground costal cartilage (UCC), ground costal cartilage (GCC), femoral venous blood, and urine. The samples were analysed by gas chromatography (GC) with a flame ionization detector using headspace analysis. Results: Volatile substances were detected in 12 out of 100 analysed samples. There was a strong positive correlation between ethanol concentration in the blood and urine (r = 0.899, p < 0.001), UCC (r = 0.809, p < 0.01), and GCC (r = 0.749, p < 0.01). A similar strong correlation was found for isopropanol concentration in the blood and urine (r = 0.979, p < 0.001), UCC (r = 0.866, p < 0.001), and GCC (r = 0.942, p < 0.001). Acetone concentration in the blood strongly correlated only with its concentration in urine (r = 0.960, p < 0.001). Conclusions: We demonstrated for the first time the possibility of detecting volatile substances: ethanol, isopropanol and acetone in a human costal cartilage. Also, the study showed that higher volatiles concentrations were better determined in ground samples.

Synthetic cathinones - From natural plant stimulant to new drug of abuse.

As recreational substances, synthetic cathinones started to be used at the beginning of the 21st century. There is still limited data on these compounds, introduced to the illicit drug market for the most part after 2009. Considering that synthetic cathinones are currently the second largest group of new psychoactive and dangerous substances among over 670 new psychoactive substances identified in Europe and monitored by the EMCDDA, research on them should be regarded as extremely important. This review focuses on the availability of synthetic cathinones on the illicit drug market, presentation of current trends in the use of these substances, and their mechanisms of action and toxicity. The authors discuss cases of intoxication with synthetic cathinones and post-mortem diagnostics as well as the problem of combined used of synthetic cathinones with other psychoactive substances. Literature as well as clinical and forensic data indicate the need for further research on the metabolism, toxicokinetics, toxicodynamics, clinical effects, and addictive potential of synthetic cathinones, especially in the context of potential threats caused by increased consumption of this group of drugs in future.

Molecular neurochemistry of the lanthanides.

Lanthanides, once termed rare-earth elements, are not as sparce in the environment as their traditional name suggests. Mean litospheric concentrations are in fact comparable to the physiologically fundamental elements such as iodine, cobalt, and selenium. Recent advances in medical technology have resulted in accumulation of lanthanides presenting potential exposure to both our central and peripheral nervous systems. Extensive and detailed studies on these peculiar active metals in the context of their influence on neural functions are therefore urgently required. Almost all neurochemical effects of trivalent lanthanide ions appear to result from the similarity of their radii to the key signaling ion calcium. Lanthanides, especially La3+ and Gd3+ block different types of calcium, potassium, and sodium channels in human and animal neurons, regulate neurotransmitter turnover and release, as well as synaptic activity. Lanthanides also act as modulators of several ionotropic receptors, e.g., GABA, NMDA, and kainate and can also affect numerous signaling mechanisms including NF-κB and apoptotic-related endoplasmic reticulum IRE1-XBP1, PERK, and ATF6 pathways. Several lanthanide ions may cause oxidative neuronal injuries and functional impairment by promoting reactive oxygen species production. However, cerium and yttrium oxides have some unique and promising neuroprotective properties, being able to decrease free radical cell injury and even alleviate motor impairment and cognitive function in animal models of multiple sclerosis and mild traumatic brain damage, respectively. In conclusion, lanthanides affect various neurophysiological processes, altering a large spectrum of brain functions. Thus, a deeper understanding of their potential mechanistic roles during disease and as therapeutic agents requires urgent elucidation.

Letter to Editor. Thromboembolic complications in psychiatry from the perspective of legal claims. / List do redakcji. Powiklania zakrzepowo-zatorowe w psychiatrii z perspektywy roszczen prawnych.

no summary.