Postmortem absorption of drugs and ethanol from aspirated vomitus--an experimental model.

Using human cadavers an experimental model was developed to simulate the agonal aspiration of drug- and alcohol-laden vomitus. By needle puncture, an acidified (N/20 HCl) 60-ml slurry of drugs (paracetamol 3.25 g, dextropropoxyphene 325 mg) and ethanol 3% w/v was introduced into the trachea. After 48 h undisturbed at room temperature, blood samples were obtained from ten sites. Ethanol and drug concentrations were highest in the pulmonary vessels in all five cases studied. Pulmonary vein mean ethanol was 58 mg% (range 13-130), paracetamol 969 mg/l (range 284-1934), propoxyphene 70 mg/l (range 11-168). Pulmonary artery mean ethanol was 53 mg% (range 10-98), paracetamol 476 mg/l (range 141-882), propoxyphene 29 mg/l (range 7.6-80). Ethanol and drug concentrations in aortic blood were higher than in the left heart and concentrations in the superior vena cava were higher than in the right heart, suggesting direct diffusion into these vessels rather than diffusion via the pulmonary and cardiac blood. Potential interpretive problems arising from this phenomenon can be avoided by using femoral vein blood for quantitative toxicological analysis.     

Components of paint thinner in body fluids clearly detected using the salting-out technique

For a more sensitive detection of paint thinner components in body fluids, we made use of a salting-out technique, with sodium chloride added to blood samples followed by gas chromatography, using the headspace method. The detection of ethyl acetate and isobutanol was considerably enhanced using these approaches.     

Postmortem diffusion of drugs from the bladder into femoral venous blood.

We describe significantly elevated drug concentrations in the femoral venous blood due probably to postmortem diffusion from the bladder. A 16-year-old deceased male was found in a shallow ditch in winter. The estimated postmortem interval was 9 days and putrefaction was not advanced. The cardiac chambers contained fluid and coagulated blood and a small amount of buffy coat clots. Diffused hemorrhages were found in the gastric mucosa. The bladder contained approximately 600 ml of clear urine. Gas chromatographic-mass spectrometric analysis of the urine disclosed allylisopropylacetylurea (a fatty acid ureide sedative), diphenhydramine, chlorpheniramine and dihydrocodeine. The cause of death was considered to be drowning due to a drug overdose and cold exposure. The concentrations of diphenhydramine, free dihydrocodeine and total dihydrocodeine in the femoral venous blood (1.89, 3.27 and 3.30 microg/ml, respectively) were much higher than those in blood from the right cardiac chambers (0.294, 0.237 and 0.240 microg/ml, respectively). Urine concentrations of diphenhydramine, free dihydrocodeine and total dihydrocodeine were 22.6, 37.3 and 43.1 microg/ml, respectively. The stomach contained negligible amounts of diphenhydramine, free dihydrocodeine and total dihydrocodeine (0.029, 0.018 and 0.024 mg, respectively); concentrations of these drugs in the femoral muscle were 0.270, 0.246 and 0.314 microg/g, respectively. These results indicate that postmortem diffusion of diphenhydramine and dihydrocodeine from the bladder resulted in the elevated concentrations of these drugs in the femoral venous blood. Not only high urinary drug concentrations but also a large volume of urine in the bladder might accelerate the postmortem diffusion.     

Postmortem stability of DNA

High-molecular-weight DNA was recovered postmortem in sufficient quantities from various human organ tissues as well as from blood, although not all organs were equally well suitable. Good DNA stability was found in brain cortex, lymph nodes and psoas muscle over a period of three weeks postmortem. Spleen and kidney showed good DNA stability up to five days postmortem but after longer periods, rapid degradation was observed. Yields of DNA from blood were not consistent because of the non homogeneity of samples. Blood clots were rich with DNA. Generally, the amount of degraded DNA correlated directly with the duration of the postmortem period. However in some cases, DNA degradation was already prominent after a short period. However in some cases, DNA degradation was already prominent after a short period. Case histories showed that high environmental temperature at the site of death and/or infectious diseases prior to death were the main factors for rapid autolysis. Gradual disappearance to complete loss of the long fragments (15-23 kb) was observed in DNA fingerprinting using the minisatellite probe 33.15. No extra-bands were noted, thus excluding erroneous conclusions. However, evidentiary value of older samples was lower.     

Postmortem diagnosis of sepsis

Human sepsis is a spectrum of pathophysiological changes in the host system resulting from a generalized activation and systemic expression of the host's inflammatory pathways in response to infection. Since autopsy findings and routine histology in cases of suspected fatal sepsis are most often unspecific and unconvincing, a number of studies has recently dealt with different methods and markers to better define criteria for the postmortem diagnosis of sepsis. Research carried out on specimens obtained postmortem from sepsis-associated fatalities is an important tool to improve our understanding of inflammatory organ changes and the associated underlying pathophysiological mechanisms. One pitfall the investigator has to be aware of is how to select appropriate case material that constitutes the basis for the setting-up of reference values that derive from such studies. Since no scientific studies have investigated the value of cardiac blood samples in the present context, autopsy blood samples for the determination of biochemical sepsis markers have to derive from the femoral vein. In both sepsis cases as well as controls, the time of death has to be well defined.     

Postmortem concentrations of citalopram

The postmortem concentrations of citalopram in blood, bile, liver, and vitreous humour were investigated in 14 cases using a specially developed high performance liquid chromatography assay. Concentrations from drug and non-drug related deaths were categorized to determine a postmortem therapeutic and toxic range. Therapeutic citalopram concentrations for blood, bile, liver, and vitreous humour ranged to 0.4 mg/L, 2.1 mg/l, 6.6 mg/kg, and 0.2 mg/L, respectively. In one potentially fatal response to citalopram, concentrations were 0.8 mg/L, 6.0 mg/L, 0.3 mg/L for blood, bile and vitreous humour, respectively.     

从医疗纠纷法医学尸体检验看纠纷的原因及防范措施

自我单位接受全市医疗纠纷的尸体检验以来,案件数呈逐年上升趋势。本文从医疗纠纷法医学尸体检验角度,总结医疗纠纷的形成原因并对医疗单位提出建议,以期限防范和减少医疗事故的发生。     

Postmortem oxycodone and hydrocodone blood concentrations

There is limited data on postmortem oxycodone concentrations, consisting of three published reports with a total of 11 cases, many of which were polypharmacy cases. This report presents the results of a review of autopsy and coroner's reports from 10 counties for the years 2000 and 2001 to locate cases with oxycodone or hydrocodone exposure as a leading cause of death. Eighty-eight cases were located. Twenty-four deaths were attributed to oxycodone alone. Mean and median postmortem oxycodone blood concentrations were 1.23 mg/L and 0.43 mg/L, respectively. The range was 0.12 to 8.0 mg/L, with 13 cases (54%) < or = 0.5 mg/L. Seventeen deaths were attributed to hydrocodone alone. Mean and median postmortem hydrocodone blood concentrations were 0.53 mg/L and 0.40 mg/L, respectively. The range was 0.12 to 1.6 mg/L, with 11 cases (65%) < or = 0.5 mg/L. There were seven cases where the cause of death was attributed to the effects of a combination of hydrocodone and oxycodone. Mean oxycodone and hydrocodone blood concentrations were 0.34 mg/L and 0.14 mg/L, respectively. Forty cases involved polysubstance overdoses with significant involvement of other drugs and ethanol. Mean oxycodone and hydrocodone blood concentrations were 0.18 mg/L and 0.29 mg/L, respectively. The list of other substances involved was extensive but included ethanol, amitriptyline, methadone, codeine, propoxyphene, and acetaminophen. The findings of this study report oxycodone values associated with a fatality at blood concentrations lower than previously reported. This may represent enhanced information because of the larger sample group. Hydrocodone values associated with a fatality were similar to previously published values.     

DNA analysis of ingested tomato and pepper seeds

Ingested food is one of the important types of forensic evidence obtained during a medicolegal autopsy. Many materials containing seeds pass through the human digestive system and are still recognizable; thus, they can be valuable for providing investigative leads. Currently, the identification of seeds relies on microscopic and morphologic examination. However this method sometimes can be problematic. For example, the microscopic appearance of the ingested tomato and pepper seeds is very similar; thus, it is not always easy to distinguish these seeds by comparing their physical characteristics. Tomato and pepper seeds were selected as a model system to assess the value of performing DNA analysis as an alternate and/or complimentary means of seed identification. Results of blind testing indicate that the deoxyribonucleic acid-amplified fragment length polymorphism (DNA-AFLP) results were able to discriminate between pepper and tomato seed samples after they passed through the digestive system.     

Postmortem methemoglobin concentrations and their significance

Small concentrations of methemoglobin are present in the blood of normal individuals. Increased concentrations of methemoglobin can be formed by the action of certain chemicals or drugs, or in individuals with specific genetic defects. There is little information available concerning the validity of postmortem methemoglobin concentration as an indicator of antemortem methemoglobinemia. We measured blood concentrations of methemoglobin in 49 autopsy specimens. We conclude that postmortem methemoglobin concentrations are not valid indicators of antemortem methemoglobinemia.     

MDMA的死后再分布及其机制

对MDMA死后再分布及其发生机制进行的动物实验和案例研究的文献,阐述MDMA死后心血浓度升高、死后通过胃肠道和气管内MDMA的再分布、MDMA在死后代谢再分布中的作用,以及死后再分布的发生机制与死后血液流动、顺浓度梯度扩散、毒物的代谢等有关的问题。     

Postmortem redistribution of morphine and its metabolites

The postmortem redistribution of morphine, morphine-3-glucuronide, morphine-6-glucuronide and total morphine was assessed in 40 heroin-related deaths. In blood taken from subclavian, heart, and femoral regions, concentrations of morphine and its metabolites were similar. While there was a trend for higher concentrations in heart blood, when compared with femoral or subclavian blood, this was not significant. There was also no significant difference in concentrations between admission and autopsy blood in which the postmortem interval was on average 59 h. From our observations, significant postmortem redistribution of morphine and its metabolites seems unlikely.     

尸体血管造影技术的发展和趋势

尸体血管造影技术是一种有效的血管检查手段,对探查尸体血管,尤其是心脏、脑部血管的情况具有重要意义。该技术起源于15世纪,发展于18、19世纪。尤其是在发现X线之后,该技术进入了快速发展阶段,无论是在对比剂、灌注方法,还是在成像方法上都取得了巨大的发展。目前,该技术已被广泛应用于实践中。但该技术仍存在一些瑕疵,首先,对比剂仍无法克服渗透弥散、栓塞血管等问题,最理想的对比剂仍未发现;其次,目前的灌注方法仍无法模拟生理血液流动状态。在＂保全尸＂的宗教和传统观念的指引下,有必要进一步提高目前的造影技术,以满足实践需求。     

Postmortem sera and cerebrospinal fluid enzymes

Antemortem and postmortem sera from 60 dogs were evaluated for lipase, amylase, alkaline phosphatase, gamma-glutamyltransferase, and alanine aminotransferase (AAT); cerebrospinal fluid was examined for AAT and alkaline phosphatase. The postmortem intervals were 3, 6, 12, 24, and 48 h at temperatures of 4, 20, and 37 degrees C. Amylase levels remained stable at 4 and 20 degrees C and may be beneficial for diagnosing pancreatitis. Lipase levels may be useful as an adjunct to amylase values. Serum alkaline phosphatase values increased with postmortem interval; values were higher at 37 degrees C than at 4 degrees C. Other enzymes were of little value for diagnosis.     

Postmortem forensic toxicology of trazodone

Trazodone is a popular antidepressant medication that has been available for approximately 30 years. It has a reputation as a safe drug with relatively few reported fatalities attributed solely to it. We review the pharmacology and forensic toxicology of trazodone and report toxicology and cause and manner of death in a series of 37 deaths in which trazodone was detected. Although the normal upper therapeutic blood concentration for trazodone is about 2 mg/L, fatalities are rarely attributed solely to it at blood concentrations below 9 mg/L. Considering the pharmacology of the drug, potential interactions between other drugs with serotonin reuptake properties need to be considered, as does the increased susceptibility to the toxic effects in patients with pre-existing heart disease. In the cases reviewed, none were attributed solely to trazodone, although trazodone was frequently present together with other serotonergic drugs, such as the selective serotonin reuptake inhibitors like fluoxetine and sertraline. Ten cases had blood trazodone concentrations above 2 mg/L. Of these cases, trazodone played a primary role in the death of three subjects, with blood concentrations all greater than 9 mg/L. We confirm the conclusions of others that trazodone is a relatively safe drug except in massive overdose, although its toxicity may be influenced by the presence of other drugs and underlying pathophysiology.     

Postmortem detection of hemp intoxication

The diagnostic tools applicable to the forensic medical expertise of cadavers in cannabinoid intoxication (CI) were evaluated. Histochemistry with incubation of stable blue "B" (SBB) were used for the detection of cannabinoids in the bronchi and lungs. Hyperemia and capillarostasis in the mucous tunics of the mouth and stomach as well as hyperemia and edema in the lungs and brain were histochemically detected in CI. The histochemical activity of aldehyde dehydrogenase (AlDG) was most essentially decreasing in the adrenal glands and brain of younger persons. The SBB reaction in the bronchial and alveolar epithelia was positive in 85% of cases. A high proof value of the CI diagnostics was pointed out in cadaver expertise.     

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.     

Postmortem diagnosis of cerebral malaria

Human cerebral malaria is a frequent encephalopathy that occurs in the endemic tropical-subtropical zones. There are a smaller number of imported cases in continental zones where the diagnosis sometimes remains difficult to establish. Fifteen days after the death of a 36-year-old male French citizen in Africa, an investigation to determine the cause of death was conducted. Histologic examination of the brain permitted the diagnosis of cerebral malaria. Because of the popularity of overseas tourism and because this disorder may appear as "sudden death," these victims may be referred to a forensic pathologist. This case demonstrates the role a forensic pathologist may play in determining the cause of death in cerebral malaria.     

Postmortem diagnosis of hypertonic dehydration

Beside morphological signs of hypertonic dehydration as tinting of skin, sunken eyes, dry surface of the galea or dry cutting areas of organs, a chemical profile of vitreous humor was proposed as a diagnostic tool for the diagnosis of hypertonic dehydration. The profile consists of an elevation of sodium >155 mmol/l, chloride >135 mmol/l and urea >40 mg/dl. This profile was named dehydration pattern. The value of this dehydration pattern for the diagnosis of hypertonic dehydration will be discussed by a short review of the literature and case reports. So far, the published literature on the dehydration pattern is not a sound scientific basis for the diagnosis of dehydration.     

Postmortem evaluation of barbiturate poisonings

The evaluation of barbiturate intoxication as the cause of death is often difficult when the concentration in body fluids and organs is not extremely high. The problem arises because of the great capacity of barbiturates to produce tolerance after chronic use, a property that is often unknown. Therefore, the most abused barbiturates were studied to assess whether chronic intake causes morphological liver changes or not. It was found that the chronic abuse of drugs containing seco-, cyclo-, brallo-, and/or pentobarbital produces hypertrophy of the smooth endoplasmic reticulum of hepatocytes corresponding to that of phenobarbital. Neither acute barbiturate overdose (without a history of abuse) nor chronic abuse of opiates causes similar liver changes. In conclusion, barbiturate tolerance can be evaluated postmortem by light microscopic examination of the liver.