Death caused by ingestion of endosulfan

This paper reports the autopsy and toxicological findings of a death caused by ingestion of endosulfan dispersed in a colorless liquid containing about 55% of xylene (w/v). For isolation of endosulfan, the biological material was homogenized and the drug was isolated by extraction with ether. Quantitative determinations were carried out by gas chromatography. The following concentrations of endosulfan were found: Blood 30 mg/L Gastric contents 0.5 g in the total 50 mL Liver 20 mg/kg Kidney 2.0 mg/kg Brain 0.3 mg/kg Xylene (solvent) was detected only in stomach contents (0.4 g in the total 50 mL).     

Pesticide poisoning initially suspected as a natural death

A pesticide poisoning victim suspected initially as having died a natural death was autopsied. The victim was a 47-year-old male. Macroscopically, signs of acute death and, in particular, general erosion in the mucosa of the airways and esophagus were observed. In the gastric contents, which had a pungent smell and a greenish-brown color, 5.00 g/L of propanil, 1.27 g/L of carbaryl, 0.38 g/L of ethylbenzene, and 0.32 g/L of xylene were detected. In the blood (serum), 21.6 mg/L of propanil, 8.1 mg/L of carbaryl, 1.7 mg/L of ethylbenzene, and 4.0 mg/L of xylene were identified. Postmortem methemoglobinemia (45%) was recognized. The cause of death was considered to have been pesticide poisoning; propanil was probably most responsible for his death. The police considered the case to be "death with illness as the suspected cause." By performing an autopsy, however, we were able to clarify that the cause of death was pesticide poisoning.     

Bupropion and alcohol fatal intoxication: case report.

A fatality due to the ingestion of bupropion and ethanol is presented. Bupropion and its metabolites were extracted from several tissues and identified using gas chromatography with nitrogenphosphorus and mass spectrometry detection. The concentrations of bupropion, hydroxybupropion and the erythroamino and threoamino alcohol metabolites in heart blood were 4.2, 5.0, 0.6 and 4.6 mg/l, respectively. The heart blood ethanol concentration was 0.27 g/dl. In addition, bupropion was distributed as follows: subclavian blood, 6.2 mg/l; bile, 1.4 mg/l; kidney, 2.4 mg/l; liver, 1.0 mg/kg; stomach contents, 16 mg and urine, 37 mg/l.     

Biochemical measurements of glucose metabolism in relation to cause of death and postmortem effects

This study was performed to examine the relationship between postmortem biochemical values and cause of death. The follow samples were taken from 399 corpses: cerebrospinal fluid (CSF; n = 376, suboccipital), blood (n = 158, femoral vein), and urine (n = 101, at autopsy). (See Table 1 for causes of death) All samples were stored at -80 degrees C. A further 100 samples of blood were later taken and stored at +4 degrees C before testing. Biochemical determinations made were: glucose in CSF, blood, and urine (hexokinase method); lactate (LDH/GPT) and free acetone (HS-gas chromatography) in CSF; hemoglobin A1 in blood (microcolumn technique). In 34 cases fatal diabetic coma was considered verified by morphological and chemical findings. One hundred cases of sudden cardiac death were chosen as the main control group. In 32 of the 34 cases defined above, the value of the formula of Traub (glucose + lactate in CSF) exceeded 415 mg/dl. It is not influenced significantly by hyperglycemia or hyperlactatemia due to factors other than diabetes (i.e., carbon monoxide, asphyxia). After death the value rose till the 30th hpm, then remained stable for at least 1 week. Fatal coma was defined as the ketoacidotic form if free acetone in CSF ranged above 21 mg/l. In these cases, CSF glucose and free acetone correlated positively. Hemoglobin A1 remained stable after death. Its amount was independent from postmortem blood glucose, postmortem interval and total hemoglobin. Furthermore, the manner of storage (-80 degrees or +4 degrees C) had no significant influence on its values. In 29 of 34 cases of fatal coma, Hb A1 exceeded 12.1%. Analysis of urine glucose showed elevated levels (over 500 mg/dl) in diabetic comas. On conclusion, fatal diabetic coma seems indicated as the cause of death if measured values of postmortem biochemistry exceed the following limits: CSF-Traub 415 mg/dl, free acetone (CSF) 21 mg/l; Hb A1 12.1%; urine glucose 500 mg/dl. Most important are the Traub formula and hemoglobin A1. Usually, in fatal coma both values are elevated. If both of them are normal, diabetic coma can nearly be excluded. Combined evaluation of all values is absolutely necessary. Morphology must also always be taken into account. Consequently, a diagnosis of fatal coma can be obtained by a process of elimination.     

A diflunisal related fatality: a case report

A case is reported where the death of an individual resulted from the ingestion of diflunisal. Diflunisal was identified by a combination of liquid chromatography, UV spectrophotometry and colorimetry. Diflunisal was quantified in blood (260 mg/l), bile (71 mg/l), kidney (350 mg/kg), liver (400 mg/kg), stomach contents (34 mg) and urine (78 mg/l). No previous literature references discussing diflunisal related fatalities were available.     

Chloral hydrate overdose: trichloroethanol detection by gas chromatography/mass spectrometry.

A case is presented where an individual ingested a fatal dose of chloral hydrate. Trichloroethanol (TCE), the metabolite of chloral hydrate, was initially identified by the Fujiwara reaction and quantified by gas chromatography/mass spectrometry in blood )127 mg/l), urine (128 mg/l) and stomach contents (25 mg total).     

Serum C-reactive protein levels in postmortem blood--an analysis with special reference to the cause of death and survival time

We have investigated postmortem serum CRP levels in 408 forensic autopsy cases consisting of 216 acute and 192 non-acute death cases having postmortem interval of less than 48 h. CRP ranged from 0.03 to 66.13 mg/dl with the median of 0.28 mg/dl. In 362 traumatic death, survival time and the presence of severe infection were the major factors contributing to CRP elevation, while postmortem interval, age, gender, hepatic injury and liver cirrhosis was not. In almost all the immediate deaths (15/16) CRP remained at a low level (<0.5 mg/dl). Acute deaths and subacute deaths within 6 h showed lower CRP levels compared to longer survivors, consistent with the clinical and experimental studies. As for natural diseases, the CRP level reflected the pathological findings. The results suggest a possibility of CRP as a forensic diagnostic marker.     

Fatal flecainide intoxication

A fatal case attributed to flecainide acetate (Tambocor), a class Ic antiarrythmic drug, is presented. Flecainide was detected by GC/MS in gastric contents, blood and liver as well. The urine analysis revealed the presence of its dealkylated metabolite. Body fluids and tissue concentrations determined by GC/ECD were 7.7 mg/kg in femoral blood, 0.26 mg/kg in bile, 18 mg/kg in liver, 0.17 mg/kg in cerebrospinal fluid, 0.22 mg/kg in brain cortex and 28.9 mg/kg in urine. The total amount of flecainide in gastric contents was about 43 mg. Even taking into account the postmortem redistribution of flecainide, its blood level still remains in the toxic range.     

Physiological variations in blood ethanol measurements during the post-absorptive state

Specimens of arterial plasma and venous whole blood were obtained at 3-10 min intervals during the post-peak phase of ethanol metabolism in healthy volunteers. The concentrations of ethanol in blood and plasma were determined by headspace gas chromatography. This method had a standard deviation of 0.28 mg/dl for whole blood and 0.26 mg/dl for plasma and the coefficients of variation were 0.43% and 0.79% respectively. The physiological variation from time-to-time, expressed as the residual standard deviation after fitting the ethanol concentration-time regression relationships, ranged from 0.43-3.7 mg/dl (0.65-16%). The time-to-time variations in concentrations of ethanol were maximum when there were problems in getting an unimpeded flow of blood through the indwelling catheters. The results do not support the existence of sporadic fluctuations or spiking in the blood alcohol concentration-time profile during the post-absorptive state. Instead, this study underscores the need to control carefully the method of sampling blood and in this way keep pre-analytical sources of variation to a minimum.     

Postmortem Fluid Concentrations of Heroin Biomarkers and Their Metabolites

Only limited data exist concerning the utility of complementary specimens in heroin-related deaths. As such, this report employed a validated LC-MS-MS method to quantify 6-monoacetylmorphine (6-MAM), 6-acetylcodeine (6-AC), and their metabolites morphine and codeine in blood with (BN) and without preservative (B) and the additional unpreserved specimens of vitreous humor, urine, stomach contents, and bile from 20 postmortem cases in which heroin was the primary cause of death. The median concentration of 6-MAM in BN was 0.011 mg/L, B was 0.008 mg/L, urine was 0.186 mg/L, vitreous humor was 0.022 mg/L, stomach contents was 0.147 mg/L, and bile was 0.012 mg/L. Only one case was found to be positive for 6-AC in B (case 6, 0.002 mg/L), and the median concentration of 6-AC was 0.002 mg/L in BN, 0.012 mg/L in urine, 0.003 mg/L in vitreous humor, 0.057 mg/L in stomach contents, and 0.004 mg/L in bile. These findings present new information on the distribution of these analytes in complementary matrices and support their inclusion for accurately determining the role of heroin in opioid-related deaths.     

Morbus Fahr--considerations on a case of sudden death

This paper presents 21 cases related to cyanide intoxication by oral ingestion. Cyanide concentrations in biological specimens are especially different from the type of postmortem specimens, and very important in interpreting the cause of death in postmortem forensic toxicology. Besides the detection of cyanide in autopsy specimens, the autopsy findings were unremarkable. Biological samples (0.2mL or equal to less than 10μg of cyanide) were analyzed colorimetrically for cyanide. In a series of 21 cyanide fatalities, the concentration ranges (mean±SD) of cyanide in heart blood, peripheral blood and gastric contents were 0.1-248.6mg/L (38.1±56.6mg/L), 0.3-212.4mg/L (17.1±45.1mg/L) and 2.0-6398.0mg/kg (859.0±1486.2mg/kg), respectively. The ranges of the heart/peripheral blood concentration ratio and gastric contents/peripheral blood concentration ratio were 0.3-10.6 (mean 3.4) and 3.4-402.4 (mean 86.0), respectively. From the difference of cyanide concentration and the concentration ratio of cyanide in different types of postmortem specimens, the possibility of the postmortem redistribution of cyanide and death by oral ingestion of cyanide could be confirmed. We reported cyanide fatal cases along with a review of literature.     

Identification of human urinary stains by the quotient uric acid/urea nitrogen

Uric acid (UA) and urea nitrogen (UN) were determined in urinary stains and the UA/UN x 20 values were calculated. The values in human urinary stains were 1.11-4.21, while those in other mammals except some of chimpanzees, were under 0.7, and those in fecal stains of birds were over 80. Most of the stains of other human body fluids or plant juices tested contained neither UA nor UN, and some contained one, but never the other. Ascorbic acid (AS) of up to 100 mg/dl in urine did not interfere with UA determination when dried human urinary stains were analyzed. It was also found that the contents of UA were very low at the peripheral parts of urinary stains. The present results indicate that the quotient UA/UN is useful for identification of human urinary stains in forensic practice provided that the peripheral part of the stain is not used.     

Comparative evaluation of postmortem serum concentrations of neopterin and C-reactive protein

The cellular immune response is accompanied by the release of neopterin. The level of neopterin in serum is increased in patients suffering from viral infections, autoimmune diseases, systemic inflammation, allograft rejection and malignant diseases, while that of C-reactive protein (CRP) is known to rise during inflammatory diseases and traumas. To investigate postmortem neopterin and CRP concentrations with regard to the cause of death, we examined cardiac and peripheral blood samples in 474 autopsy cases without advanced decomposition (0-96 years of age, 343 males and 131 females), 2.8 h to 3 days (median, 18.0 h) after death. Survival time was 0.1 h to 5 months (median, 3.0 h) for traumatic death, and 0.1-1, 440 h (median, 2.5 h) for natural death. In autopsied subjects, neopterin concentrations were higher than the clinical reference, independent of the time after death, and depended on the survival time. In cases of acute and subacute death due to trauma, the neopterin level in right heart blood was mildly to moderately elevated (about 50-200 nmol/l) except for sharp instrument injury, whereas the CRP concentration usually remained low (<1 mg/dl). However, a moderate rise in the CRP level (around 1-10 mg/dl) was observed in fatal cases of hypothermia (cold exposure). Markedly elevated serum CRP and neopterin levels (>10 mg/dl and >500 nmol/l, respectively) were detected in cases of delayed death due to trauma involving systemic inflammatory response syndrome (SIRS) and of fatal bacterial infections. For sepsis, the serum CRP level was markedly elevated but the neopterin level was low in some cases. Fatal viral infections usually resulted in a marked elevation in the serum neopterin level (>500 nmol/l) with a mild to moderate rise in the CRP level. Combined analyses of neopterin and CRP may be useful to investigate viral infections and delayed traumatic death involving SIRS to support pathological findings.     

Determination of Nicotine,Cotinine and Trans‐3′‐Hydroxycotinine using LC/MS/MS in Forensic Samples of a Nicotine Fatal Case by Oral Ingestion of e‐cigarette Liquid,

Nicotine is a potent neurotoxin alkaloid and is used in e‐cigarette liquid. The LC/MS/MS method was linear over 0.01–1.0 mg/L (r² = 0.992–0.995). Limit of detection and limit of quantitation were 0.001 mg/L (S/N = 3) and 0.003 (S/N = 10). The inaccuracy and imprecision were <13.2%. The recoveries were >99.3%. A 39‐year‐old dentist was found dead lying on the floor under the couch in his dental clinic. The concentration of nicotine, cotinine, and trans‐3′‐hydroxycotinine (heart blood/peripheral blood) was analyzed as follows: 87.2/85.2 mg/L (ratio 1.0), 1.4/1.1 mg/L (ratio 1.3), and 0.012/0.0089 mg/L (ratio 1.3), respectively. The concentration of nicotine was determined to be 6734.8 mg/kg in gastric contents and 7262.0 mg/L in remaining e‐liquid. Only, high concentration of nicotine was detected in the gastric contents as well as the two pieces of evidence collected from the death scene. This fatal case resulted from oral ingestion of e‐cigarette liquid. It is estimated that at least 714 mg of nicotine was orally ingested.     

A case of death from prothiophos poisoning

A 62-year-old male, a farmer, who had ingested prothiophos (Tokuthion), died after 21 h of intensive care. Prothiophos in the tissues of the victim was extracted and purified by Extrelut column extraction. A gas chromatograph equipped with a flame photometric detector, and a gas chromatograph-mass spectrometer were used to detect prothiophos. The concentration of prothiophos was 10.9 micrograms/g in the brain, 8.6 micrograms/g in the kidney, 418 micrograms/g in the liver, 2.96 mg/g in the gastric contents and 4.69 mg/g in the intestinal contents. The case history and the distribution of prothiophos indicated that the cause of death was acute prothiophos poisoning.     

Elevated creatinine levels in rape assault survivors

Urine specimens were collected from alleged rape survivors. In 13 of the 29 survivors, creatinine levels were over 150 mg/dl, and nine of these were over 200 mg/dl. These elevated urine creatinine levels persisted for some time after the alleged rape attacks. Various controls yielded overall levels below those of the alleged rape assault survivors. When control values of creatinine and osmolality of pre- and postintercourse samples were plotted and compared by linear regression covariance analysis to the data on alleged rape survivors, the levels of urinary creatinine in the alleged rape survivors were higher than would have been expected from urine osmolality increases. The dissimilarity of the two sets of data has a p value less than 0.0001. These findings might serve as supplemental objective evidence of rape (or terror) that could be used medicolegally.     

Tissue distribution of olanzapine in a postmortem case

Olanzapine is a relatively new antipsychotic drug used in the United States for the treatment of schizophrenia. Since its release in the United States market in 1996, few cases of fatal acute intoxication have been reported in the literature. This article describes the case of a 25-year-old man found dead at home who had been prescribed olanzapine for schizophrenia. This case is unique because of the measurement of olanzapine in brain tissue obtained from seven regions in addition to the commonly collected biologic matrices. Olanzapine was detected and quantitated by basic liquid-liquid extraction followed by dual-column gas chromatographic analysis with nitrogen phosphorus detection. The assay had a limit of detection of 0.05 mg/L and an upper limit of linearity of 2 mg/L. The presence of olanzapine was confirmed by gas chromatography-mass spectrometry by use of electron impact ionization. The concentrations of olanzapine measured in this case were as follows (mg/L or mg/kg): 0.40 (heart blood), 0.27 (carotid blood), 0.35 (urine), 0.61 (liver), negative (cerebrospinal fluid), 0.33 mg in 50 ml (gastric contents). In the brain, the following distribution of olanzapine was determined (mg/kg): negative (cerebellum), 0.22 (hippocampus), 0.86 (midbrain), 0.16 (amygdala), 0.39 (caudate/putamen), 0.17 (left frontal cortex), and 0.37 (right frontal cortex). The cause of death was determined to be acute intoxication by olanzapine, and the manner of death was accidental.     

Development of Rapid and Economical Colorimetric Screening Method for p‐Phenylenediamine in Variety of Biological Matrices and its Application to Eleven Fatal Cases of p‐Phenylenediamine Poisoning

A rapid colorimetric method for detection of p‐phenylenediamine (PPD) in various biological samples is developed. The o‐cresol test for acetaminophen detection has been modified to detect PPD in blood, urine, gastric contents, and liver. After precipitating protein with trichloroacetic acid solution (2 mL, 10% w/v), biological specimens were required to convert PPD metabolites to PPD by acid hydrolysis. Finally, o‐cresol solution (1 mL, 1% w/v), hydrogen peroxide (200 μL, 3%v/v), and concentrated ammonium hydroxide (0.5 mL) were added in the biological samples. The presence of PPD was indicated by formation of violet color which was turned to bluish green color within 10–15 min. The limit of detection was found to be 2 mg/L in blood, urine, and gastric contents and 2 mg/Kg in liver. This method is also free from any potential interference by p‐aminophenol, acetaminophen, and other amine drugs under test conditions. This method was successfully employed to thirteen fatal cases of PPD poisoning.     

Evaluation of death from hypoglycemia

Hypoglycemia involving a serum glucose of 40 mg/dl or less may lead to death from hypoglycemic coma. Hypoglycemia may be a factor in sudden or unexpected deaths investigated by a medical examiner. We reviewed the data from 54,850 autopsies in a large acute-care medical center to investigate the range of underlying conditions leading to hypoglycemic coma and found 123 cases, which included complications of alcoholism in 41 (33%), drugs in 26 (21%), neoplasia in 26 (21%), conditions producing chronic passive congestion of liver in eight (7%), debilitating neurologic disease in eight (7%), endocrine disorders in four (3%), and a variety of miscellaneous conditions in ten (8%) cases. The commonest mechanisms producing hypoglycemia included liver disease with impaired carbohydrate metabolism, endogenous or exogenous drug or hormonal effect, and inanition from decreased intake of food.     

Postmortem tissue concentrations of venlafaxine

Venlafaxine is a phenethylamine antidepressant which inhibits both serotonin and norepinephrine reuptake and is structurally unrelated to the serotonin reuptake inhibitors (SSRIs). Its major metabolite, O-desmethylvenlafaxine (ODV), also inhibits serotonin reuptake. Although metabolized by the cytochrome P-450 (CYP) system, venlafaxine inhibits CYP 2D6 and 3A4 to a far lesser extent than do the SSRIs. Mechanisms of drug action are reviewed and evaluated in the investigation of 12 fatalities occurring over a 6-month-period where venlafaxine was detected.Venlafaxine and ODV were identified by liquid chromatography-mass spectrometry (LC-MS) using atmospheric pressure ionization (API) electrospray in positive mode following an n-butyl chloride extraction. Postmortem tissue concentrations studied in each of 12 postmortem cases for venlafaxine and ODV, were 0.1-36 and <0.05-3.5mg/l (peripheral blood), <0.05-22 and <0.05-9.9mg/kg (liver), <0.05-10 and <0.05-1.5mg/l (vitreous), <0.05-53 and <0.05-6.8mg/l (bile), <0.05-55 and <0.05-21mg/l (urine), respectively, and 0.1-200mg of venlafaxine in the gastric contents. Venlafaxine was typically present with other drugs, including other antidepressants, alcohol, and benzodiazepines. The potential for interaction with each drug is discussed. Over the 6-month-period of this study, there were no deaths ascribed solely to venlafaxine intoxication.