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.

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.

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.

Evaluation of the usefulness of the immunoradiometric method for post-mortem measurement of insulin concentration in the intraocular fluid: preliminary results.

INTRODUCTION: In medicolegal practice, rare cases associated with suicidal, criminal or accidental overdose of insulin are both analytically and forensically challenging. The determination of insulin in post-mortem blood has limited diagnostic value, mainly on account of post-mortem chemical degradation processes (particularly hemolysis), and hence is not useful in medicolegal practice. AIM OF THE STUDY: The aims of the study were: 1) to assess the usefulness of the immunoradiometric method, used in clinical practice, for post-mortem measurement of insulin concentration in the intraocular fluid, 2) to preliminarily evaluate the usefulness of the obtained results for toxicological and medicolegal assessment, and 3) to verify on the basis of our own material the validity of the cited literature data on the effect of hemolysis on the result of insulin level determination in post-mortem blood. MATERIAL AND METHODS: The study material consisted of 93 samples of intraocular fluid collected during consecutive medicolegal autopsies performed in the Department of Forensic Medicine and Forensic Toxicology, Medical University of Silesia in Katowice. In addition, 10 samples of peripheral blood taken from living people (5 women and 5 men) for clinical and diagnostic purposes were analyzed. Insulin(e) IRMA KIT from IMMUNOTECH was used for the analyses. RESULTS: In 86 (92.5%) samples, the insulin concentration was below the analytical sensitivity of the method (less than 0.5 µIU/ml), while in 7 cases it was in the range of 1.42-24.42 µIU/ml. CONCLUSIONS: Determination of the insulin level in the intraocular fluid by the immunoradiometric method provides an opportunity for objective verification of poisoning, however this claim requires further research.

Nonfatal and fatal intoxications with pure caffeine - report of three different cases.

Caffeine is not usually perceived as a drug by most people because it is found in many foods and drinks, including caffeinated energy drinks, as well as in over the counter analgesics and cold preparations. Recently in Poland it has become increasingly common to take pure caffeine, bought through online stores, as a psychoanaleptic. This creates a much higher risk of severe and even fatal poisoning in comparison with the risk associated with the abuse of food products and non-prescription medicines containing low doses of caffeine. This paper presents three different cases of poisoning that occurred when pure caffeine was taken as psychostimulant; in cases 1 and 2 poisoning was the result of a single overdose, while in the case 3 poisoning resulted from a cumulative overdose. In the case 1 there was a severe intoxication (persistent vomiting, hypotension, tremor), and the concentration of caffeine in the blood was found to be 80.16 µg/mL. The patient was treated using hemodialysis, which caused a rapid decrease in blood levels of caffeine and relief of the clinical symptoms of poisoning. Cases 2 and 3 were fatal poisonings, and recorded levels of caffeine in post mortem blood samples were 140.64 µg/mL and 613.0 µg/mL. In case 2 the patient died 10 min after admission to hospital as a result of sudden cardiac arrest, which was preceded by an attack of convulsions, and in case 3 death occurred in home and was also sudden in nature. Taking pure caffeine as a stimulant is associated with a high risk of overdose and the development of serious and even fatal poisoning, and those using pure caffeine are generally completely unaware of these risks. In such cases, death is usually sudden due to functional mechanisms.

Patient's death as a result of mistakenly injection of pancuronium.

Pancuronium is a typical non-depolarizing, curare-mimetic, very potent muscle relaxant. Besides application in anesthesiology and intensive care, it is used in execution as a part of lethal injection. In medico-legal practice, there are cases of using this substance in order to commit suicide or to deprive other people of their lives. Accidental pancuronium intoxications are very rare. The authors present such case ended in sudden death of hospitalized woman after mistakenly injection of the drug. 57-year-old female alcoholic was admitted to the Acute Poisoning Centre after ethylene glycol ingestion. During the fifth day of treatment the nurse by mistake, instead of furosemide, intravenously administered her pancuronium. Sudden respiratory and circulatory arrest occurred, so she was intubated and resuscitation with artificial ventilation were undertaken, however within 1 hour and 45 minutes the patient died. Due to the vague background of a sudden deterioration in the patient's condition, the case was brought for prosecution. The autopsy and histopathological studies did not reveal the cause of death, but undertaken chemico-toxicological examinations identified the presence of pancuronium in blood, liver and kidney (190 ng/ml, 70 ng/g and 125 ng/g, respectively). Chemico-toxicological analysis proved that the cause of death of the 57-year-old hospitalized woman was pancuronium intoxication due to evident medical error during drug administration. In our case the concentration of pancuronium in blood was in therapeutic range (200-600 ng/ml). However, even a therapeutic pancuronium dose administered to patient the breath of whom is not supported and monitored can be a threat to his life.

Evisceration and intestine damage as a rare form of suicide in forensic and psychiatric practice - description of two cases.

Suicide is a major public health problem around the world. Case reports include extreme suicidal self-inflicted injuries, in which extensive damage to the abdominal wall associated with injury or even excision of fragments of the intestine and its fragmentation are present. These cases usually give rise to doubts of investigators as to the course of the incident, the circumstances of death and the possibility of participation of other people. At the same time they are interesting from the medico-legal and psychiatric perspective. The aim of this study is the presentation of two extremely rare cases of suicides through evisceration and intestinal injury from the clinical and opinioning practice of the authors, one of which ended with survival and the second one with death. Regardless of the final result of the suicide attempt (death or survival), good practice of the investigative teams in such cases should include a detailed examination of the place of the suicide attempt, obtaining opinion of an expert in the field of forensic medicine with full post-mortem diagnosis, and in-depth forensic psychological and psychiatric analysis of, among others, lifeline, mental state and suicidal motivation (so-called psychological autopsy).

Histopathological changes in lungs of the mountain snow avalanche victims and its potential usefulness in determination of cause and mechanism of death

On 28 January 2003 snow avalanche in the Polish Tatras happened, in which 8 people died and 5 were injured. We tried to determine cause and manner of death in 6 fatal victims instead of advanced late post mortem changes in internal organs. Taking into consideration the circumstances of death, we paid special attention to histopathological examination of lungs, extended by Gomori's and AZAN staining. Pattern of the changes was similar to those observed in forensic medicine in cases of asphyxia due to airway obstruction and/or immobilization of chest and abdomen (Perthes' syndrome). Histopathological study with the use of more specific staining methods has a significant diagnostic value during establishing the cause and mechanism of death of the deceased snow avalanche victims with advanced post mortem changes.

Traumatic basal subarachnoid haemorrhage or ruptured brain aneurysm in 16-year-old boy? - case report

Traumatic basal subarachnoid haemorrhage (TBSAH) represents only 1.8% of all subarachnoid haemorrhage cases diagnosed during autopsy. This report presents such a case from the current practice of the authors. Sixteen-year-old boy was beaten by the aggressors. Suddenly he lost his consciousness and fall after he received a single blow in the neck. He was resuscitated immediately, but died at the scene. During the external examination we did not find any significant external injuries. Autopsy revealed large contusion of right sternocleidomastoid muscle. In the cranial cavity we found extensive subarachnoid haemorrhage, located mainly on brain basis, in the posterior cranial fossa and covering the subtentorial structures. During the preparation of blood vessels we noticed a slight change of morphology suggesting damaged vessel or aneurysm, or vascular malformation located in the basilar artery bifurcation, which was taken to detailed microscopic evaluation using the special stainings. Histological examination showed vital interruption of the basilar artery wall with massive haemorrhage, without the presence of general microscopic pathology. From the medico-legal viewpoint, to determine traumatic background of haemorrhage it is necessary to find the coexistence of the following circumstances: a sustained trauma, post-mortem findings consistent with a time of injury, the presence of temporal relationship between injury and death, and morphological vital injury of the brain vessel, as well as the absence of prior vascular malformations. For this purpose Verhoeff-van Gieson's, Masson's, Turnbull's and Gomori' histological stainings may be successfully used.

Dual orexin receptor antagonists - promising agents in the treatment of sleep disorders.

Insomnia is a serious medical and social problem, its prevalence in the general population ranges from 9 to 35% depending on the country and assessment method. Often, patients are subject to inappropriate and therefore dangerous pharmacotherapies that include prolonged administration of hypnotic drugs, benzodiazepines and other GABAA receptor modulators. This usually does not lead to a satisfactory improvement in patients' clinical states and may cause lifelong drug dependence. Brain state transitions require the coordinated activity of numerous neuronal pathways and brain structures. It is thought that orexin-expressing neurons play a crucial role in this process. Due to their interaction with the sleep-wake-regulating neuronal population, they can activate vigilance-promoting regions and prevent unwanted sleep intrusions. Understanding the multiple orexin modulatory effects is crucial in the context of pathogenesis of insomnia and should lead to the development of novel treatments. An important step in this process was the synthesis of dual antagonists of orexin receptors. Crucially, these drugs, as opposed to benzodiazepines, do not change the sleep architecture and have limited side-effects. This new pharmacological approach might be the most appropriate to treat insomnia.

[Atypical case of teenager fatal poisoning by butane as a result of gas for lighters inhalation against his will]. / Nietypowy przypadek smiertelnego zatrucia nastolatka butanem na skutek inhalacji gazu do zapalniczek wbrew jego woli.

Inhalatomania with volatile organic compounds is a still present phenomenon among Polish young adolescents. Conscious, voluntary exposition on such substances may result in serious health consequences, including sudden death in the course of acute intoxication. In this paper, atypical case of death of 16-year-old teenager as a result of complications of physically forced inhalation of gas for lighters is presented. According to testimonies of witnesses, the container was placed in the mouth of victim and the gas was introduced directly to his throat. Autopsy revealed small damage of tooth with corresponding bruising of lower lip; brain and lung oedma; single bruisings in the upper respiratory tract and subpleural. Chemical-toxicological analysis of blood, brain and lung samples taken during autopsy revealed in all of them the presence of n-butan--a component of gas for lighters (the greatest in brain and lung tissues). Additionally, in blood the presence of carboxyhemoglobin (COHb) in concentration 7% was confirmed. Based on the results of analyses, acute intoxication with n-butan was estimated as a cause of death; however the key role played the information obtained during the investigation. This case shows, that deaths resulting from gas for lighters inhalation may be a consequence of forced exposition--against victim's will. So medical staff should always check, if on the body of patient there are any signs of physical constraint (the presence of bruisings in the area of viscerocranium and oral cavity, teeth damages, etc.).

[Virological tests in diagnostic management of sudden unexpected deaths in children]. / Badania wirusologiczne w diagnostyce naglych niespodziewanych zgonów dzieci.

Based on the present knowledge, the review paper attempts to answer the general question whether virological tests are justified in cases of sudden deaths in children. In particular, the question addresses their importance in establishing the cause of death. The authors also attempt to answer additional questions, namely: (1) whether histopathology provides an adequate basis for establishing the cause of death, (2) whether extending histological evaluation to exclude immunohistochemistry is warranted, and (3) whether there is a correlation between detection of a virus and "intensity" of inflammatory infiltration detected by histology. At the same time, the present paper is an introduction to discussing the results of research in the above field carried out by the authors. In cases of sudden deaths of chil- dren, numerous investigators point to a viral infection as a significant etiopathogenic factor. Nevertheless, no uniform strategy has been developed to date in post-mortem diagnostic management in this field. This is also true with respect to answering what viruses should be isolated and by what techniques when sudden infant death syndrome (SIDS) and/or sudden unexpected death in infancy (SUDI) are suspected. The review of the literature on the subject allows for stating that virological tests are not justified in all cases of SIDS/SUDI, the more so that these tests are not commonly available and inexpensive. Detection of a virus rarely allows for determining the cause of death, demonstrating only the presence of the virus in the tested material. On numerous occasions, demonstrating the presence of a virus by polymerase chain reaction (PCR) has not been in any way reflected in basic and extended histology. In the opinion of the authors, in cases of SIDS/SUDI suspicion, while determining the cause of death, primarily basic histological tests are recommended, as they are the most valuable screening tests. In justified cases basic tests should be extended to include additional immunohistochemical tests, and in exceptional cases--PCR to isolate a virus. PCR may be performed both in frozen and in formalin/paraffin fixed material.

Trial helplessness of defendant healthcare facilities in cases concerning nosocomial infections / Nieporadnosc procesowa pozwanych jednostek ochrony zdrowia w sprawach o zakazenia szpitalne.

The number of pecuniary cases involving patient claims due to nosocomial infections has been increasing for many years, and with it, the amount of adjudged compensations has also been increasing. In this situation, it is important for defendant healthcare facilities to implement a proper policy, both before the trial and during the court proceedings. Unfortunately, as a rule, defendant facilities commit a variety of errors, such as: wrong strategy, inability to cooperate on the part of those involved in the matter and improper preparation and usage of evidence. The result is that the risk of unfavorable assessment of the case increases significantly.

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.

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.