Screening for Corticosteroid Adulterants in Korean Herbal Medicines

The objective of this study was to determine the presence of corticosteroids in illegal herbal medicines using ultra‐high‐performance liquid chromatography–tandem mass spectrometry. We collected 212 herbal medicine samples that were advertised as being effective for treatment of joint pain and bone aches. Samples were from the Korean commercial market during a span of four years (2010–2013), and the method was validated. The limits of quantification ranged from 0.47 to 15.0 ng/mL, and recoveries ranged from 80.6% to 119.5%. The intra‐ and interday precision ranged from 0.18% to 8.82% and from 0.09% to 8.96%, respectively. Among the samples, three samples (1.4%) were identified as adulterants. Dexamethasone was the only compound detected in the adulterated products. As the corticosteroid–adulteration of herbal medicines may become a major problem and lead to side effects, the continued development of screening procedures for herbal medicines is critical.     

Anorectic sibutramine detected in a Chinese herbal drug for weight loss

In the presented case, a young healthy woman had ordered a Chinese herbal medicine, called "LiDa Dai Dai Hua Jiao Nang", via internet. She took this product for approximately 1 week, but on the second day she developed severe headache, vertigo and sensation of numbness. After discontinuing medication, symptoms disappeared within 2 days. For identification of the ingredients, a urine sample as well as a sample of the "LiDa" capsule were analysed by GC-MS and HPLC-DAD. One major ingredient was detected in urine as well as in the "LiDa" capsule and was identified as sibutramine. Quantification by HPLC-DAD yielded 27.4 mg sibutramine base, which is approximately two times the amount of the highest authorized single dose available on the pharmaceutical market in Germany. This case demonstrates a common problem with herbal medicines, where adulterations with synthetic therapeutic substances can lead to severe side effects and/or potentially fatal interactions with conventional medicines.     

Findings in fatal cases of poisoning attributed to traditional remedies in South Africa.

An analysis of the Johannesburg forensic database over the years 1991-1995 revealed 206 cases in which a traditional remedy was either stated to be the cause of death or was found to be present in a case of poisoning with an unknown substance. The range of toxins detected was wide, with herbal materials being found in 43% of cases, and pharmaceutical or agri-chemicals in 20% and 33% respectively. Since there are as yet no standard methods for the detection of many herbal remedies or their metabolites, careful analysis, using methods such as HPLC/MS, are mandatory for the correct identification of the true cause in cases of poisoning ascribed to traditional remedies.     

药物遗传学在法医学中的应用前景

人类因为基因的差异而表现出对某种药物、毒物、外界有害的化学物质、过敏原作出不同的反应.这种遗传背景的差异使一些人可以快速地清除这些物质,而另一些人却因此产生严重的不良反应.甚至死亡.药物遗传学和药物基因组学,通过对人类基因组测序和大规模基因组多态性的鉴别研究,诠释了个体遗传差异与对药物毒物不同反应之间的关系,这为该类案件的法医学鉴定提供了新的理论基础和研究手段.     

Near Infrared Spectroscopy Detection and Quantification of Herbal Medicines Adulterated with Sibutramine

There is an increasing demand for herbal medicines in weight loss treatment. Some synthetic chemicals, such as sibutramine (SB), have been detected as adulterants in herbal formulations. In this study, two strategies using near infrared (NIR) spectroscopy have been developed to evaluate potential adulteration of herbal medicines with SB: a qualitative screening approach and a quantitative methodology based on multivariate calibration. Samples were composed by products commercialized as herbal medicines, as well as by laboratory adulterated samples. Spectra were obtained in the range of 14,000–4000 per cm. Using PLS‐DA, a correct classification of 100% was achieved for the external validation set. In the quantitative approach, the root mean squares error of prediction (RMSEP), for both PLS and MLR models, was 0.2%w/w. The results prove the potential of NIR spectroscopy and multivariate calibration in quantifying sibutramine in adulterated herbal medicines samples.     

Sudden death in hemodialysis patients

Hemodialysis patients may die suddenly and unexpectedly from a number of causes. These may be divided into those deaths due directly to and occurring during hemodialysis, those deaths occurring while the patient is not undergoing dialysis, and those deaths that may occur at any time. The first group includes brain herniation, air embolism, acute hemorrhage as a result of machine malfunction or fistula rupture, electrocution, cardiac arrhythmia caused by hypokalemia, complications of subclavian intravenous catheter insertion, third-degree heart block as a result of triglyceride emulsion, and disseminated intravascular coagulation (DIC) or hyperkalemia caused by overheated dialysate. The second group includes deaths due to pericardial tamponade because of effusion and suicidal causes of death (exsanguination, electrolyte imbalance as a result of excessive intake of salt, fluid, or potassium) as well as more conventional methods of suicide. The last category includes people dying of arteriosclerotic cardiovascular disease, hypertensive cardiovascular disease, and internal hemorrhage. Investigation of these deaths, including pertinent historical, laboratory, and autopsy data and investigation of dialysis equipment, is discussed.     

Postmortem increase in potassium in the vitreous humor. Which parameters are suitable as indicators of antemortem agonal electrolyte imbalance?

The relationship between a rise in the potassium concentration in the vitreous humor and the time of death has been established by several authors. Sturner (1963) and Adelson (1963) have been able to demonstrate a more precise relationship between potassium and the time of death in cases of sudden death and death occurring within 6 h as opposed to death after a chronic, lingering disease. However, the duration of the terminal episode cannot always be assessed in forensic medicine. Therefore, it would be valuable if other parameters could also be established that would indicate an agonal dysregulation of electrolytes. Our study revealed that sodium, urea, chloride, and calcium are of great value in indicating antemortem electrolyte imbalance because of their stability in the vitreous humor after death. The first results established that urea may be a suitable internal standard.     

A Rare Presentation of Sudden Death due to Pulmonary Thromboembolism Possibly as a Result of Giant Hepatic Hemangioma

Hepatic hemangiomas are usually detected incidentally when investigating for other nonrelated pathologies. When symptomatic, they are usually large and cause symptoms such as abdominal discomfort or other digestive issues. Occasionally, uncommon presentations such as bleeding with coagulopathy (Kasabach–Merritt syndrome) or even fever of unknown origin may occur. As hepatic hemangiomas are benign, they do not result in tumor emboli and pulmonary thromboembolism due to hepatic hemangiomas is extremely rare. This is a case report of a rare case of a female with no known past medical history who presented with sudden death due to pulmonary thromboembolism, possibly as a result of an underlying giant hepatic hemangioma. Incidentally, she also had three other tumors—pancreatic cystic lymphangioma, cerebral capillary telangiectasia, and papillary thyroid carcinoma, and their potential contribution to the cause of death will be discussed.     

Suicide Case Due to Phosphoric Acid Ingestion: Case Report and Review of Literature

Ingesting caustic substances represents a common event which may result in serious injuries of the gastrointestinal system. Severity of injury depends on the type of ingested substance: Caustic burns are more frequently associated with acid ingestion and their severity depends on type, concentration, time of exposure, and amount of the ingested substance. We report a case of phosphoric acid ingestion leading to death in a patient with depressive disorder. While reports ingestion of other acids and organophosphates can be found in the literature, there are no reports detailing a death due to phosphoric acid ingestion. We hope that presenting the findings in this case can aid death investigators in future cases that may involve ingestion of such a substance. After autopsy pH, phosphate and calcium ions concentration in the blood were analyzed. The cause of death was due to systemic effects: metabolic acidosis, hypophosphatemia, hypocalcemia, and hyperkalemia.     

Investigations of clobazam (Frisium) by combined gas chromatography/mass spectrometry (author's transl)

Clobazam (Frisium) was hydrolyzed according to three methods commonly used in the determination of 1.4-benzo-diazepines; the reaction products were analyzed by gas chromatography/mass spectrometry and thin-layer chromatography. Five degradation products were obtained for which structure proposals are discussed. After oral intake two of these substances were also detected in human urine. It should be recognized that some of the above mentioned substances may be on-column degradation products of artifacts occurring during hydrolyzation and/or sample clean-up.     

Medicines and psychoactive agents in traffic users—the medico-legal problem in Poland

The increasing number of traffic accidents connected with rapid development of motorization makes us think of their causes. Regulations by law binding in Poland demand traffic users to be checked up on the presence of agents similar ethyl alcohol. Commonly abused medicines, especially sedative and psychotropic but also hypnotic and analgesic are a great traffic problem. Up to the present analytical procedures and a model medico-legal opinion on the influence of medicines on psychophysical efficiency have not been standardised.In the paper the authors have presented the results of their research on agents negatively influencing the human psychophysical efficiency carried out in the Forensic Medicine Department, Silesian University of Medicine, Katowice. The research comprised individuals involved in both traffic crashes and accidents who (as checked) either where not under the influence of ethyl alcohol or the concentration of ethanol was low (1‰). Positive cases most often showed only one sort of medicines (barbiturates, benzodiazepines or opiates). In other cases barbiturates and benzodiazepines, benzodiazepines and opiates as well as derivatives of benzodiazepine and tricyclic antidepressants were determined. Blood concentrations of all these substances were in a wide range of therapeutic doses.     

Toxicologic aspects of deaths due to falls from height

A prospective study of 161 victims of falls from height is reported. The aim was to determine the interest of systematic qualitative and quantitative toxicological analysis in such fatalities. The primary cause of death was suicide (84.5%), followed by accidents (7%) and homicide (1%). In the remaining 7.5%, cause of death was undetermined. In the suicides, there was evidence of psychotropic medicines in 57% of the observations, with a much higher proportion of benzodiazepines and antidepressants in women than in men. Quantitative toxicologic analysis showed overdosing on medication in 16 suicide victims, with toxic levels in 11 of these. Systematic qualitative and quantitative toxicologic analysis made a significant contribution to the diagnosis of suicide by revealing either an unknown psychiatric treatment or a toxic level.     

The influence of ethanol on the level of ketone bodies in hypothermia

Presently available possibilities of macro- and microscopic diagnosis of death from hypothermia are very limited as the changes observed are either weakly specific (ecchymoses in the mucous membrane of the stomach, histological features of haemorrhagic pancreatic necrosis, cardiomyocyte necrosis or decreased content of glycogen in hepatocytes) or represent only local action of low temperatures (frostbites, violet patches in the region of knees and elbows, red livores) and they may not be present in cases of death from cooling at environmental temperature close to zero or higher.The study evaluated the usefulness of acetoacetic acid (Ac-Ac), beta-hydroxybutyric acid (beta-HBA) and acetone determinations in blood, urine and vitreous humour for diagnosis of death from hypothermia. These three substances called ketone bodies, are easily assimilated energetic substrates that get oxidized preferentially before glucose and fatty acids. In hypoglycaemia (also hypothermia-induced one), the tissues dependent on glucose (e.g. the brain) cover most of their energetic needs from oxidation of these compounds.The analysis of 16 cases of death in circumstances suggesting hypothermia (mainly of the alcohol abusers) showed that the degree of ketosis was inversely proportional to the blood ethanol concentration. This relation may result from stimulation of insulin release and a decrease in the release of its antagonists by ethanol, as well as from inhibition of free fatty acid (FFA) beta-oxidation due to increase in the NADH/NAD ratio. So, the antiketonaemic effects of ethanol (together with its influence on the dilatation of the peripheral vessels and inhibition of shivering thermogenesis by muscle relaxation), explain increased sensitivity of intoxicated persons to low temperatures.     

Death certification of "suicide by cop"

Death certification of "suicide by cop" is controversial among some medical examiners and coroners. We present five such deaths that were certified as suicides and discuss the medico-legal issues involved with these certifications. To certify such a death as a suicide, certain criteria should be met. Suicide by cop is a circumstance that involves competing intentional acts that may result in dichotomous determinations of the manner of death. Despite the absence of direct self-infliction, there is overwhelming evidence that these five individuals intended to end their own lives. Their use of an unusual method to accomplish this goal may inappropriately result in a reflexive certification of homicide. All of the decedents possessed weapons or a facsimile of a weapon. We present five instances of suicide by cop and contend that these types of deaths are best certified as suicides.     

Death of an 89-year-old man during autosexual activity

Autoerotic fatalities are accidental deaths occurring as a direct result of autosexual activities, mostly involving men in the 2nd to 8th decade of life. Death most often occurs in the domestic environment due to strangulation or asphyxia. However, fatalities related to autosexual activity in a wider sense may also be caused by an accident or sudden death from an internal cause. We report the case of an aged man who died while engaged in outdoor autosexual activities due to a combination of a pre-existing internal disease and an accident (drowning).     

Mechanical airway obstruction caused by accidental aspiration of part of a ballpoint pen

The authors present three cases of death in children aged 4, 9, and 10 years, respectively, that were first thought to be caused by herbal or other poisonings but at autopsy were found to be caused by airway obstruction from aspiration of ballpoint pen parts. Aspiration of a foreign body is a leading cause of accidental death in children, but the circumstances in these cases were unique. In the first case, a 4-year-old child died shortly after a visit to a traditional healer. The child's mother blamed him for the death and fatally assaulted him. The second case was a 9-year-old who died at school. Case 3 was a 10-year-old who collapsed while playing with a ballpoint pen in her mouth. In the latter two cases, the relatives alleged poisoning. At autopsy, there was no evidence of trauma, disease, or poisoning in all three cases. Ballpoint pen parts were present in the larynx, carina, and left main bronchus, respectively. Features of "asphyxial" death were present, and included subconjunctival hemorrhages, subendocardial hemorrhages, and congestion of the face and internal organs. These deaths are preventable by education of children, parents, and teachers. Ballpoint pen manufacturers should also modify the design of these pens to improve their safety.     

Fatal intoxication with a selective serotonin reuptake inhibitor, lorazepam, and codeine

Selective serotonin reuptake inhibitors were introduced in 1987 as an alternative treatment option for patients with depression or certain anxiety disorders. Unfortunately, this greater use has prompted a corresponding increase in reports of more severe side effects and fatalities, with a majority of fatalities occurring due to coingestion of selective serotonin reuptake inhibitors with other substances or serotonergic drugs. We report a case which exemplifies one such fatality related to sertraline, lorazepam, and codeine coingestion. A brief discussion of the presumed mechanism by which death occurred will be offered.     

Field-portable detection of fentanyl and its analogs: A review

The need to detect fentanyl and its analogs in the field is an important capability to help prevent unintentional exposure or overdose on these substances, which may result in death. Many portable methods historically used in the field by first responders and other field users to detect and identify other chemical substances, such as hazardous materials, have been applied to the detection and identification of these synthetic opioids. This paper describes field portable spectroscopic methods used for the detection and identification of fentanyl and its analogs. The methods described are automated colorimetric tests including lateral flow assays; vibrational spectroscopy (mid-infrared and Raman); gas chromatography–mass spectrometry; ion mobility spectrometry, and high-pressure mass spectrometry. In each case the background and key details of these technologies are outlined, followed by a discussion of the application of the technology in the field. Attention is paid to the analysis of complex mixtures and limits of detection, including the required spectral databases and algorithms used to interrogate these types of samples. There is also an emphasis on providing actionable information to the (likely) non-scientist operators of these instruments in the field.     

Can we handle the truth? Legal fictions in the determination of death

Advances in life-saving technologies in the past few decades have challenged our traditional understandings of death. People can be maintained on life-support even after permanently losing the ability to breathe spontaneously and remaining unconscious and unable to interact meaningfully with others. In part because this group of people could help fulfill the growing need for organ donation, there has been a great deal of pressure on the way we determine death. The determination of death has been modified from the old way of understanding death as occurring when a person stops breathing, her heart stops beating, and she is cold to the touch. Today, physicians determine death by relying on a diagnosis of total brain failure or by waiting a short while after circulation stops. Evidence has emerged that the conceptual bases for these approaches to determining death are fundamentally flawed and depart substantially from our biological and common-sense understandings of death. We argue that the current approach to determining death consists of two different types of unacknowledged legal fictions. These legal fictions were developed for practices that are largely ethically legitimate but need to be reconciled with the law. However, the considerable debate over the determination of death in the medical and scientific literature has not informed the public of the fact that our current determinations of death do not adequately establish that a person has died. It seems unlikely that this information can remain hidden for long. Given the instability of the status quo and the difficulty of making the substantial legal changes required by complete transparency, we argue for a second-best policy solution of acknowledging the legal fictions involved in determining death. This move in the direction of greater transparency may someday result in allowing us to face squarely these issues and effect the legal changes necessary to permit ethically appropriate vital organ transplantation. Finally, this paper also provides the beginnings of a taxonomy of legal fictions, concluding that a more systematic theoretical treatment of legal fictions is warranted to understand their advantages and disadvantages across a variety of legal domains.     

Fatality of 33‐Year‐Old Man Involving Kratom Toxicity

Kratom is an herbal product commonly used for its effects which are similar to opioids and stimulants. Few studies demonstrate the dangers and lethality of Kratom, and most fatalities from Kratom involve other abused substances. In the current case report, a 33‐year‐old white man with a known history of opioid abuse and mental illnesses was found unresponsive in his basement with no obvious signs of trauma. After resuscitative efforts, he was pronounced dead and taken for autopsy evaluation. Blood from the inferior vena cava was analyzed for common abused substances. The laboratory toxicology work‐up revealed positive findings of caffeine, cotinine, and naloxone with low levels of Δ‐9 tetrahydrocannabinol. However, a marked level of mitragynine at 1.9 mg/L was observed, the highest reported to date. Given the facts and evidence, the medical examiner certified the cause of death as “mitragynine toxicity” and the manner of death was classified as an “accident.”