Postmortem biochemistry

Postmortem biochemistry may provide significant information in determining the cause of death. Due to the rapid postmortem breakdown of metabolism and active membrane transport only analytes which are stable in blood can be determined on this fluid compartment, other parameters have to be analysed on other fluid compartments like vitreous humor (VH). However, using another fluid compartment as a mirror of blood at the moment of death involves severe methodical problems. The conceptual problems of reference values in vitreous humor as a mirror of blood are addressed. Additionally, the necessary steps to be taken before calculating the discriminating values between "normal" and "diseased" are described. For all chemical determinations, a clear definition of the site of sample acquisition is necessary. Up to now chemical determinations on alternative fluids have mainly been carried out using instruments calibrated for urine or serum. Developing calibrated methods for analysis of alternative fluids is a further task for the future.     

Postmortem skeletal lesions

Postmortem bone alterations are very frequent and can raise the issue of their nature (antemortem, perimortem or postmortem defects). The aim of this work is to study various aspects of defects which were not assessed as perimortem trauma, from a series of 50 defects examined, resulting from 24 forensic cases. This study emphasizes the variability of size, shape and number of postmortem defects. Usually the diagnosis of antemortem defects is helped by a careful examination of some characteristics as the edges of the defects, the areas of discoloration of the edges and of the whole bone. Elsewhere it appears very difficult to know the true nature (antemortem, postmortem, or perimortem alterations) of the bone.     

Postmortem dental radiography

Comparison of postmortem and antemortem dental radiographic films or digital images is a common procedure for establishing identity of human remains. This article describes some problems with producing postmortem dental radiographs in a medical examiner setting and gives methods for circumventing these difficulties. Resection of the jaws, when permitted, significantly simplifies the postmortem radiographic technique. When producing an actual postmortem panoramic dental radiograph (orthopantomogram) from a dry skull, stabilization of the specimen for exposure by the moving beam source may be accomplished simply by placing the specimen upside down on an anthropologist's skull ring. Image "burnout" in the anterior segment, which results from absence of the tissues of the neck, may be avoided by appropriate placement of radiodense objects such as "zippered" plastic bags filled with water or other fluid material, freezer gel packs, or a block of self-polymerizing acrylic. These methods may increase future postmortem dental radiography efficiency.     

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 pink teeth.

A series of cases is reported in which pink teeth were observed during the postmortem period. Most cases were associated with decomposition in a moist environment. Experimental procedures led to the extraction of pink material from dentin and demonstration that hemoglobin and serum proteins were present. The pink-tooth phenomenon was duplicated in human teeth by instilling into the pulp chambers whole blood and blood with the red cells hemolyzed. The change was manifested in teeth of dogs after freezing, heating, and decomposition in a moist environment. The authors postulate that pink teeth occur as a result of breakdown of red blood cells in the pulp chamber of the tooth and diffusion of hemoglobin and other serum proteins into the dentin via the dential tubules. Histochemical studies show that the brown or gray material in some teeth subjected to postmortem aging is probably hemoglobin and serum proteins. Factors of age, vascularity of the pulp chamber, and postmortem conditions are discussed in relation to the postmortem development of pink teeth.     

Postmortem monocular indirect ophthalmoscopy

Postmortem monocular indirect ophthalmoscopy permits examination of the posterior fundus and peripheral retina even if there is less than perfect anterior segment media such as postmortem corneal clouding. Light directed through the decedent's pupil from a bright focal light source illuminates the fundus and reflected light from the retina is then projected out of the eye. An aspheric condensing lens positioned in front of the eye focuses the retinal image at the focal plane of the lens. The real inverted, laterally reversed image comprises a wide field of view permitting evaluation of the decedent's fundus for retinal hemorrhages and other lesions.     

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.     

Postmortem cerebrospinal fluid pleocytosis

We show that postmortem cerebrospinal fluid (CSF) pleocytosis is a common event. Postmortem cerebrospinal or ventricular fluid was obtained from children and adults. The cells were counted and morphologically characterized using several histochemical markers. Infants exhibit a brisk postmortem CSF pleocytosis. Sudden infant death cases have relatively high CSF counts. Typeable cells are mononuclear and consist of approximately 60%-70% lymphocytes and 20%-40% macrophages. When postmortem duration is greater than 12 h, the cells become vacuolated and cannot be identified. The etiology of these findings requires further study.     

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 ophthalmologic examination by endoscopy

Abnormal intraocular findings detected during forensic autopsies have generally been ignored. In this study, we assessed the usefulness of postmortem ophthalmologic examination in 46 cases using an endoscope system with a tip diameter of 0.9 mm. This procedure was performed using a portable system, and only 1 assistant was needed. Furthermore, the procedure required only about 5 minutes for both eyes. Abnormal intraocular findings were seen in 22 (47.8%) of 46 cases. Fundus hemorrhages were observed in 4, and papilledema was observed in 3 of 5 cases of death due to head trauma; besides, it was possible to estimate the interval between head trauma and death based on intraocular findings. Seven of 16 cases of death from asphyxia presented abnormal intraocular findings, including retinal splinter hemorrhages. Fundus hemorrhages were observed in 2 of 3 cases of death by drowning, which, to our knowledge, had never been reported to date.Thus, this procedure proved easy to perform, and it may be useful to detect significant abnormal intraocular findings related to the presumed cause of death during autopsies.     

尸体化学的研究进展

近年来,尸体化学在法医病理学的常规检查中发挥着愈发重要的作用并取得了重大的进展,对于玻璃体液、血液、尿液、脑脊液的生化分析可为确定死因或者阐明法医案件提供重要的信息,尤其是当利用形态学的方法无法发现死亡过程中的病理生理改变时(糖尿病、乙醇性酮症酸中毒、电解质紊乱),尸体化学对于法医鉴定实践中的心肌缺血、败血症、炎症、感染、过敏以及激素紊乱也有着较高的应用价值。本文对相关研究成果进行阐述,包括糖代谢、肝功能、肾功能、心功能、败血症、炎症、感染、过敏以及激素等方面的研究和应用。     

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 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.     

Postmortem investigation of lamotrigine concentrations

Lamotrigine is a relatively new anticonvulsant. Therapeutic plasma concentrations generally range from 1 to 4 mg/L, although several studies have shown that good control of epilepsy has been achieved with concentrations reaching 10 mg/L generally, with little toxicity. In overdose, however, the drug has been linked to ECG changes that may suggest a possible arrythmogenic effect and hence cardiac toxicity. Lamotrigine has also been shown to cause encephalopathy and thus neurotoxicity. There is no information concerning postmortem lamotrigine concentrations and their interpretation. We describe lamotrigine concentrations in postmortem specimens including blood, liver, bile, vitreous humour, and urine from eight cases. A high performance liquid chromatography (HPLC) method is described with extraction procedures for the various tissues. Two possible groups were identified. The first being the "broader therapeutic" group with blood concentrations ranging from 0.9 to 7.2 mg/L and corresponding liver concentrations ranging from 16 to 36 mg/kg. The second being a "supratherapeutic" group with blood concentrations ranging from 20 to 39 mg/L and corresponding liver concentrations ranging from 53 to 350 mg/kg. Although none of the eight cases described were attributed to overdose by lamotrigine alone, the cause of death for one of the three cases in the "supratherapeutic" group was given as mixed drug toxicity. Cause of death for the remaining two cases in this group was reported as epilepsy. However, both these cases showed elevated concentrations of lamotrigine and both were co-medicated with valproic acid. Such co-administration has been shown in the literature to lead to elevated lamotrigine concentrations and a reduction in lamotrigine dose has been recommended. With such data, we highlight the importance of monitoring lamotrigine concentrations in cases co-medicated, particularly with valproic acid.     

Postmortem behavior of the rheobase

Own investigations on the postmortem rise of muscular threshold were conducted on 20 bodies with exactly known time of death. Muscular contraction was objectified using a sensitive force transducer. The muscle was excitated using rectangular impulses of 1 second duration of a current intensity which produces a force of muscular contraction of 2.5 mN. These excitations were continued over the postmortem interval until a current intensity of 80 mN doesn't cause a contraction of 2.5 mN any more. Investigations were mainly performed at the thenar muscles. There is a linear relationship between ln of muscular threshold (current intensity) and the time since death (r = 0.965). For any case the linear regression line between ln of muscular threshold and time since death was calculated. With mean values for slope and intercept the time of death was calculated for each measured threshold. Extrapolation of the time since death with mean values also for the slope reveals a much more precise estimation of the time since death than an extrapolation with an individual slope as proposed by Joachim and Feldmann (1980). The method was proved on a random sample of 8 practical cases. The real time since death was always within the 95%-limits of confidence of the extrapolated time since death.