Clinical and analytical problems of sodium azide poisonings as exemplified by a case of fatal suicidal poisoning.

AIM OF THE STUDY: To present clinical and analytical aspects associated with sodium azide poisoning. The problems were verified on the basis of a case of sodium azide poisoning which was unique due to its circumstances and the development of an analytical method applied for medico-legal practice. MATERIAL AND METHODS: The object of the study was a toxicological analysis of biological specimens collected from a woman who ingested two doses of sodium azide purchased over the Internet, in a suicide attempt. After the ingestion of the first dose, the clinical management in the form of symptomatic treatment indicated a possibility of recovery. However, the ingestion of a second dose of the xenobiotic, already in the hospital, caused death. Toxicological findings were obtained with the dedicated technique of gas chromatography-mass spectrometry (GC-EI-MS-MS) after extraction combined with derivatization using pentafluorobenzyl bromide (PFBBr). RESULTS: Post-mortem toxicological studies demonstrated sodium azide in the blood (0.18 mg/l) and urine (6.50 mg/l) samples collected from the woman. CONCLUSIONS: Cases of sodium azide poisoning are rare and difficult to treat, but a review of the literature over a longer interval of time shows that they continue to occur. Therefore, case studies of sodium azide poisoning, together with descriptions of research methodology, can be useful both in clinical terms and in the preparation of toxicological expert opinions for medico-legal purposes.

"New designer drugs" in aspects of forensic toxicology.

AIM OF THE STUDY: In autumn of 2010, in response to an ever-increasing market of "new designer drugs" and in view of new legal regulations, the Sanitary Inspection inspected numerous so-called "smart shops" where such products were sold. In the course of mass inspections, 3545 packages of various preparations were secured on the market in the Malopolska province. A total of 942 preparations were collected for analysis; of this number, 539 were sold as tablets and pills and 403 as plant-derived substances. The objective of the study was to determine potentially psychoactive components of the investigated preparations. MATERIAL AND METHODS: The prepared samples were identified by employing an analytical procedure where the analytes were investigated by gas chromatography-electron impact mass spectrometry (GC-EI-MS) and thus a library of mass spectra was created. RESULTS: The analysis revealed the following substances in the investigated products: piperazine derivatives (BZP, MPMP, TFMPP), cathinone derivatives (N-ethylcathinone, buthylone, ethylone, methylone, buphedrone, flephedrone), pyrovalerone derivatives (MDPV, naphyrone), and synthetic cannabinoids (AM-694, JWH-019, JWH-073, JWH-081, JWH-122, JWH-200, JWH-250). CONCLUSIONS: An unlimited source, i.e. the Internet, continues to provide the worldwide market with preparations of this type and their composition is constantly modified. The scale and complexity of the problem pose a challenge to forensic and clinical toxicology in the field of new designer drugs.

Medico-legal aspect of amphetamine-related deaths.

The subject of the work included 41 cases of death in which amphetamine was involved as the direct or indirect cause. Identification and determination of xenobiotics in blood samples collected from post-mortem cases were performed by high-performance liquid chromatography coupled with tandem mass spectrometry with electrospray ionisation (HPLC-ESI-MS-MS). Only for two cases was the cause of death amphetamine poisoning. In most of the investigated cases the death was caused by poisoning due to complex amphetamine and other psychoactive substances (e.g. opiates, benzodiazepines, cocaine). In other cases, multi-organ damage (fall from a height, traffic accident), a puncture wound and wound incised, drowning, or asphyxiation by hanging were reported. It can be explained as risky, murderous, or suicidal actions of people who were under the influence of amphetamines. The presented paper focuses on the interpretation of amphetamine concentration in blood samples from the perspective of direct or indirect cause of death.

Analysis of variability of concentrations of valproic acid (VPA) and its selected metabolites in the blood serum of patients treated with VPA and patients hospitalized because of VPA poisoning.

AIM OF THE STUDY: To compare the metabolic profile of valproic acid (VPA) in the studied groups of cases through an analysis of variability of concentrations of VPA with its selected metabolites (2-ene-VPA, 4-ene-VPA, 3-keto-VPA). STUDY MATERIAL: Blood serum samples collected from 27 patients treated with VPA drugs in the Psychiatry Unit and in the Neurology and Cerebral Strokes Unit at the Ludwik Rydygier Provincial Specialist Hospital in Krakow, and blood serum samples collected from 26 patients hospitalized because of suspected acute VPA poisoning at the Toxicology Department, Chair of Toxicology and Environmental Diseases, Jagiellonian University Medical College in Krakow. RESULTS AND CONCLUSIONS: The analysis of concentrations of VPA and its selected metabolites has shown that the metabolic profile of VPA determined in cases of acute poisoning is different from cases of VPA therapy. One of VPA's metabolic pathways - the process of desaturation - is unchanged in acute poisoning and prevails over the process of ß-oxidation. The ingestion of toxic VPA doses results in an increased formation of 4-ene-VPA, proportional to an increase in VPA concentration. Acute VPA poisoning involves the saturation of VPA's metabolic transformations at the stage of ß-oxidation. The process of oxidation of 2-ene-VPA to 3-keto-VPA is slowed down after the ingestion of toxic doses.

[Two complex suicidal poisonings with drugs and their medicolegal aspects]. / Dwa kompleksowe samobójcze zatrucia lekami w aspekcie orzecznictwa sadowo-lekarskiego.

The main subject of the study was a toxicological investigation of biological specimens coming from two cases of intoxication with mixture of drugs. Two young people decided to commit suicide by the use of mixture of drugs mainly analgesic in approximately equal doses. For one person the dose of drugs administered turned out to be fatal while second person survived with the symptoms of acute intoxication. The analysis carried out with the use of liquid chromatographic method with mass detection (HPLC/MS) confirmed the presence of mixture of drugs in blood of living person and in postmortem specimens of the victim in significant concentrations. The toxicological findings have delivered information for discussion in medico-legal and ethical aspects.

Significance of toxic interactions in medicolegal evidence. Complex fatal poisoning with drugs of abuse in the material of the Chair of Forensic Medicine, Collegium Medicum, Jagiellonian University in Kraków.

The subject of the study was fatal complex poisonings with drugs of abuse in two young men. In the first case, postmortem investigation revealed cardiotoxic death as the result of an interaction between opiates, amphetamine derivatives and oxazepam. In the second case, death followed the administration of amphetamine derivatives and cocaine (xenobiotics known on the illicit drug market as "UFO"). Based on the toxicological postmortem analysis the authors discuss the interpretation of the results in the light of general problems of interactions taking place in toxicokinetic and toxicodynamic phases of intoxication processes.

[Medico-legal certification of fatal cases after drug: abuse in the light of modern toxicological analysis]. / Opiniowanie sadowo-lekarskie w narkomanii w swietle nowoczesnej analityki toksykologicznej.

Introduction of modern instrumental methods for toxicological analysis make possible a detection and identification of xenobiotics in different kind of multicomponents biological samples (plant sources of narcotics, body fluids and tissues of abusers) on a low concentration level. In this way a range of possibilities for the interpretation of toxicological results was enlarged. General medicolegal trends are strictly connected with modern analytics and they can be discussed on the basis of drug--users and fatal cases of intoxications with narcotics. Toxicological findings of these cases were worked out by means of modern analytical method--liquid chromatography with mass detection (LC/MS).

A case of suicide by intravenous injection of pancuronium.

This report details a suicide by pancuronium bromide injection by a 31-year old female anesthesiologist. Pancuronium bromide was identified in the blood and brain by means of ion-pair extraction followed by thin-layer chromatography, spectrophotometry and electrospray ionization/tandem mass spectrometry. After this positive identification, the levels of pancuronium were carefully quantified by spectrophotometry: 1.05 mg/ml in the blood and 0.51 mg/g in the brain. The cause of death was judged to be asphyxia due to respiratory muscle paralysis caused by pancuronium.

Acute poisonings with chemical compounds among adolescent and adult inhabitants of Kraków in the year 1997.

The pattern of adolescent and adult poisonings in Kraków is presented on the basis of the data collected by the Poison Information Centre of the Department of Clinical Toxicology Collegium Medicum of the Jagiellonian University in 1997. This analysis includes 3472 people treated at the Department of Clinical Toxicology and 118 poisoned people who were not given any treatment and died at the scene of the accident. The group of hospitalised persons consisted of 2359 (67.9%) men and 1113 (32.1%) women, and the group of people who died at the scene of the accident consisted of 97 (82.2%) men and of 21 (17.8%) women. The overall coefficient of poisonings in 1997 was 46.9; for men--67.8 and 28.3 for women. Ethanol (39.7%) followed by drugs (20.2%), drugs + ethanol (6.7%), carbon monoxide (6.2%) and drugs of abuse (4.4%) were the most common cause of acute poisonings. The mortality rate of the cases treated was low (0.43%), but while including those people who were not given any treatment and died at the scene of the accident, mostly due to ethanol, carbon monoxide, and drugs poisoning the fatality index rose up to 3.7%.

[The role of laboratory methods in clinical and forensic toxicology]. / Rola metodyki laboratoryjnej w toksykologii klinicznej i sadowej.

In the present work problems of differences between laboratory methods used in contemporary toxicological clinical and forensic analysis. The significance of instrumental methods as a factor quarantined proper level of scientific investigation has been underlined. A role of an analyst in clinical laboratory and an expert in toxicological forensic areas has been discussed.

A chemical and physicochemical study of an Egyptian mummy 'Iset Iri Hetes' from the Ptolemaic period III-I B.C.

Chemical and physicochemical examinations of the fragments of an Egyptian mummy dated between the 3rd and 1st century B.C. were performed. The chemical examinations indicated the presence of resin in the skull and in the fragments of bandages wrapped around the mummy. An analysis of the infrared spectra of the fragments indicated a type of resin originating from the Copal group. Physicochemical investigations showed that main chemical elements such as Ca, Mg, Na, K, P and trace chemical elements such as Fe, Zn, Cu, and Pb occurred in bone fragments in proportions typical for people living today. In tooth fragments, values were similar to normal except for K, P, and Zn, which were lower, and Pb, which was absent. In the fingernails, most elements were found in much higher concentrations except for Cu and Pb, which were lower. The results of the study in terms of their implications on mummification are discussed.

A serological and histological study of the Egyptian mummy 'Iset Iri Hetes' from the Ptolemaic period III-I B.C.

Serological and histological examinations of the muscles of the calf of an Egyptian mummy dated between the third and first centuries B.C. were performed. Human protein was identified, the ABO phenotype was determined as type B, and morphological disruption of the cells was observed.

[Evaluation of the treat of acute poisoning with chemical compounds among adult inhabitants of Krakow in 1995]. / Ocena zagrozenia ostrymi zatruciami substancjami chemicznymi wsród doroslych mieszkanców Krakowa w 1995 roku.

The goal of this study is to evaluate the number and the reasons (poison and structure) of acute poisonings which occurred among Kraków adult inhabitants in the year 1995. Under analysis there were 3003 people treated at the Department of Clinical Toxicology and 210 poisoned who died at the place of accident prior to any treatment was conducted. The group of hospitalized persons consisted of 63.7% men and 36.3% women, and the group of people who died at the place of accident consisted of 89.5% men and of 10.5% women. The overall coefficient of poisonings during the year 1995 was 48.3; for men was 66.7 and 32.5 for women. A drugs (45.1%) followed by ethanol (42.8%) were the most common cause of acute poisonings. The mortality rate of the treated patients was low (0.7%), but while including those people who died at the place of accident prior to any treatment, the mortality rate rose up to 7.2%. That increase in the mortality rate was caused mainly by fatal cases due to ethanol and carbon monoxide poisonings.

[Selected medico-legal problems in cases of poisoning with substances of abuse]. / Wybrane problemy orzecznictwa medycznoprawnego w zatruciach substancjami uzalezniajacymi.

In toxicological examinations of substances of abuse with respect to medico-legal purposes many problems have been discussed. A selection of biological material and proper analytical methods in confrontation with interpretation of results in reference to the subject in question seems to be a central toxicological issue. Blood and urine samples are usually used in cases of human. The problem is more complicated if it concerns dead subjects on the account of postmortem processes in a body. From this point of view, in fatal cases of poisonings experience proves, besides blood and urine also other body fluids such as: cerebrospinal fluid, vitreous humor, perilymph and bile turned out to be usefull for examinations of various xenobiotics. The analytical methods (FPIA, HPLC, GC-MS) have been used for qualitative and quantitative evaluation in wide range of xenobiotic concentration in biological matrix. Interpretation of the results including such problems as toxic interaction, metabolism, data base has been discussed in the study on the basis of intoxication cases with substances of abuse.

Pesticides poisonings in clinical and medicolegal aspect.

In the course of time, progress in knowledge, after many years of a widespread use of pesticides, it is necessary to evaluate negative results they cause. Poisonings with these xenobiotics have claimed new tasks and problems for toxicology. The present study comprises some complex problems of pesticides poisonings on the basis of examinations referring to non-fatal and fatal cases of poisonings in clinical and medicolegal aspects. They include cholinesterase inhibitor poisonings, dipyridil herbicides and chlorphenoxyacetate as well. On the basis of quantitative determinations of cholinesterase inhibitors relations between blood concentration and toxic effects were considered. Moreover, an elimination of inhibitors from blood in relation to the method of treatment and kind of pesticide was observed. In fatal cases of intoxication morphological changes in tissues, pesticides distribution and antemortem-postmortem relations were discussed. Toxicological findings in the cases examined constitute a data library for complex clinical and medicolegal purposes.

Acute pesticides poisonings in pregnant women.

44 pregnant women were treated at the Department of Clinical Toxicology in years 1986-1996 as a result of acute poisonings with different xenobiotics. Acute pesticide poisoning that involved 4 cases were always severe and had dramatic clinical course. Carbofuran intoxication stated in a 17-year-old woman (18 weeks of pregnancy) resulted in fetus death. Toxicological findings revealed that the level of the poison in the mothers blood was comparable to that in the fetus. Carbofuran evidently passed the placental barrier in concentration which was sufficient to cause the fetus death. In the second woman (20-year-old, 12 weeks pregnant) who was classified as severely poisoned on admission to the clinic a spontaneous abortion was stated on 27th day after poisoning. The highest level of carbofuran in the blood of the mother was 9.71 micrograms/g. A 30-year-old woman, 10 weeks pregnant took formothion (50 ml) per vaginam in order to provoke abortion. She was classified as moderately poisoned. Gynecological examination and ultrasonography confirmed the pregnancy. The fetus heart tones were audible. The patient was discharged from hospital after 3 days at her own request in a good general condition. The concentration of formothion in washings from vagina was similar to the levels observed in blood serum on the patient admission to the Clinic, and 24 hour later. A 21-year-old woman, 5 month pregnant ingested an unknown amount of endosulfan to provoke abortion. Gynecological examination and abdominal ultrasonography revealed longitudinal pelvic presentation of fetus. Neither fetal movement nor heart tones were audible as early as four hours after the clinical symptoms occurred. Such low concentration of endosulfan in the blood of the mother as 0.47 microgram/g of the poison caused relatively quick fetus death. The highest levels of endosulfan were found in the liver and in the fetus kidneys.

Intermediate syndrome in acute fenitrothion poisoning.

Fenitrothion has been reported as one of the organophosphates causing so called "intermediate syndrome"--clinical entity of still unclear reasons. That is why we decided to perform a retrospective examination of oral intoxication with this compound. Clinical course of 16 cases were analysed. Clinical state on admission, AChE activity and pesticide concentration in blood were considered. Gastric lavage, atropine and oximes were included in the treatment. 6 patients died in the period of 5 to 22 days (mean 11.8) from poison intake. All 6 revealed slight signs of poisoning at the time of admission (first 24th). AChE was moderately inhibited. Patients' clinical state was deteriorating and AChE activity was decreasing during next 48 h even though oximes therapy was applied. Intubation and mechanical ventilation was required. Fenitrothion concentration in blood varied from 470 to 8350 ng/ml (mean 2823 ng/ml). In 3 fatal cases toxicological examination of autopsy tissue was done. High fenitrothion concentration was found in adipose tissue and also in the brain. In the group of 10 recovered patients "intermediate syndrome" was not observed in 3 only. AChE activity returned to normal quickly. Fenitrothion concentration ranged from 96 to 360 ng/ml (mean 202 ng/ml). In the remaining 7 clinical state became worse during next 48-72 hours after temporary improvement. Respiratory failure and increasing AChE activity inhibition were major signs. Fenitrothion concentration varied from 180 to 3020 ng/ml (mean 1690 ng/ml). AChE inhibition persisted even for 30 days from poisoning.

Determination of deslanoside in antemortem and postmortem specimens. Unusual case report.

One case of the erroneous administration of deslanoside and high level of drug in antemortem plasma and postmortem specimens has been reported owing to the unusual surrounding circumstances. Deslanoside in antemortem plasma was determined by FPIA and the analysis was done by HPLC in the postmortem tissue samples. The analytical results and methods used in the examinations are discussed in the following paper.

Carbofuran poisoning of pregnant woman and fetus per ingestion.

A case of carbamate pesticide poisoning of a pregnant woman by carbofuran ingestion is presented. The mother recovered from the poisoning in the hospital but necrosis of the fetus was found. Toxicological findings of the liver, brain, and kidney of the fetus revealed carbofuran in concentrations comparable with the mother's blood. Our findings in the case contribute to the research on permeation of the placental barrier by chemical substances.

The evidence of a null allele in the esterase D in the Polish population.

The existence of the allele EsD degree in mother and her child, expressed phenotypically as EsD 2-0 and EsD 1-0 has been found. The enzymatic activity was reduced to about 50 per cent of the normal values of these phenotypes.