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PubMed1984

DNA in cytosol fractions obtained by differential centrifugation of homogenates of rapidly growing liver tumors.

Preliminary work revealed that the cytosol fractions obtained by differential centrifugation of homogenates of the rapidly growing Morris hepatomas 7777 and 7288CTC contained substantially more DNA than could be detected with the more slowly growing hepatoma 5123C or the liver of tumor-bearing rats. The amount of DNA in the cytosol fractions of the rapidly growing hepatomas was decreased by concentrations of cations which are known to promote precipitation of solubilized chromatin. Data on the incorporation of [3H]thymidine into DNA of nuclear and cytosol fractions and the time-dependent effects of hydroxyurea were compatible with initial nuclear synthesis and later release of the DNA seen in the cytosol fractions. The amount of this DNA was increased in larger tumors and was less in isolated cells than in solid tumors. Postmortem changes in the liver and hepatoma 5123C, but not in hepatomas 7777 and 7288CTC, resulted in a large increase in DNA appearing in the cytosol fraction. The results indicated that the measurement of DNA in cytosol fractions may serve as a guide to the existence of necrosis in tumors, but is not always proportional to the degree of necrosis.

Animals↗
PubMed1995

Magnetic resonance axonography of the rat spinal cord: postmortem effects.

The recent development of magnetic resonance (MR) axonography, which uses three-dimensional anisotropy contrast (3DAC), a new algorithm for the treatment of an apparent diffusion tensor, has provided an unprecedented opportunity for visualizing the anatomical details of the spinal cord in live animals. In this study, the authors investigated the sensitivity of the 3DAC method in detecting pathological conditions by obtaining chronological MR axonography of the rat spinal cord immediately after induction of cardiac arrest. The results clearly demonstrated that 3DAC is highly sensitive to any perturbation of physiological conditions. Trichromatic coefficient analyses indicated postmortem changes observed pictorially are indeed due to loss of anisotropy. The study further indicated the presence of at least two independent factors responsible for observed physiological anisotropy. Considering its rather simple implementation process and high anatomical resolution as well as its sensitivity to pathological alteration, MR axonography based on the 3DAC method appears to be the ideal noninvasive imaging technique for assessment of the spinal cord in biomedicine.

Animals↗
PubMed1978

Dopamine metabolites in human brain.

The relationship of human brain levels of 3,4-dihydroxyphenylacetic acid (DOPAC) to cerebrospinal fluid levels of this domapine (DA) metabolite was studied. The effect of postmortem delay was evaluated in the rat. DOPAC was resistant to postmortem changes in brain kept in situ. The level of DOPAC (free and conjugated) determined in DA-rich areas of six human brains amounted to only a fraction of the homovanillic acid (HVA) found in the same regions. The DOPAC/HVA ratio in human brain was similar to that found in CSF. We conclude that HVA is the major DA metabolite in human brain and that DA metabolite levels in CSF reflect DA metabolite levels in brain.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1995

Postmortem degradation of administered ethanol-d6 and production of endogenous ethanol: experimental studies using rats and rabbits.

Deuterium-labeled ethanol-d6 was employed to study the metabolism and postmortem change of ethanol in putrefied organ tissues. First, 4 ml/kg body weight of 25% (w/v) solution of ethanol-d6 was administered orally to each of 15 rats. The heart blood and organs were collected 15-90 min after the administration and the ethanol-d6 was analyzed by head space gas chromatography/mass spectrometry. The ethanol-d6 concentration in the organ tissues reached its maximum at 15 min after the administration and then gradually declined, showing the same pattern as human ethanol metabolism. Ethanol-d6 (3 ml of the same solution/kg body weight) was injected into the vein of a rabbit's ear (total of 12 rabbits). The rabbit was killed with carbon monoxide 30 min after the administration and the carcass was allowed to stand for 1-4 days at 30 degrees C in a moist chamber. The concentration of ethanol-d6 decreased moderately. Postmortem ethanol and 1-propanol concentrations, in contrast, showed marked increases 2.5 days and more after sacrifice in line with the degree of putrefaction of each organ tissue including skeletal muscle. This suggests the postmortem activation of micro-organism activity. These results indicate that ethanol concentrations in cadaver tissues must be carefully assessed with due consideration of postmortem degradation and production.

1-Propanol↗
PubMedDate not supplied

A case of homicidal poisoning involving several drugs.

Accidental or suicidal poisonings due to benzodiazepines have been previously reported. A case of fatal, homicidal poisoning with benzodiazepines, antipyretic analgesics (anti-inflammatory drugs), and beer is described here. In this homicidal poisoning, the drugs and beer were given to the decedent by his wife. Autopsy findings showed no clinically significant macroscopic findings except for slight postmortem change. Capillary gas chromatography coupled to mass spectrometry was employed to quantitate the drugs in biological fluids and stomach contents. Six drugs (brotizolam, triazolam, ibuprofen, dihydrocodeine, phenylpropanolamine, and chlorpheniramine) were identified and quantitated in blood, urine, and stomach contents. Although each drug was present in a very small quantity, the cause of death was determined to be the combination of these drugs and alcohol poisoning.

Adult↗
PubMed1982

Lead burden in prehistorical, historical and modern human bones.

From archaeological findings it is well known that, in the past, lead has been intensively used by man. The toxicological aspects of increased lead exposure are perceived onward from the 2nd century B.C.; between 90 and 95% of the absorbed lead is stored in bone. Therefore measurement of lead levels in ancient bones seemed to be a suitable approach to determine the real body burdens at different periods of time and to compare the results with the present situation. Approximately 650 bones from a total of 332 individuals of the following epochs were analysed: prehistorical Peruvians, prehistorical Teutons, late Romans, Middle Age (further differentiated), present time Germans. The determination of lead was made by graphite furnace atomic absorption spectroscopy. The possibilities of postmortem alterations of lead concentrations were thoroughly investigated. For this purpose the dependence of the lead concentrations found were compared with the age, sex, type of bone, conditions of preservation and storage. It is concluded that only the series "prehistorical Teutons" may be exposed to levels which are relevant to postmortem changes. The lead concentration of the group "prehistorical Peruvians" can be taken as the "physiological zero point"; from this culture no use of lead is known. The present body burden for lead in germany is about 20 times greater than this "physiological zero point". In the late Roman epoch, but also in the Middle Age the lead concentrations and body burden was 41-47% of that today. Only at the time after the Barbarian Invasions did this value drop to 13% as a result of a lower living standard. The different sources of lead exposure during Roman times, the Middle Age and today are discussed.

Adolescent↗
PubMed2000

Automated determination of carboxyhemoglobin contents in autopsy materials using head-space gas chromatography/mass spectrometry.

To establish a method for the routine analysis of carboxyhemoglobin (COHb) in autopsy materials including those which have undergone postmortem changes, e.g. thermo-coagulation, putrifaction and contamination, an automated head-space gas chromatography/mass spectrometry (GC/MS) analysis was utilized. The procedure consisted of preparation of the sample in a vial and a carbon monoxide (CO) saturated sample, for estimation of hemoglobin content, in another vial, the addition of n-octanol, potassium ferricyanide and an internal standard (t-butanol), GC separation and determination of CO using a GC/MS system equipped with an automated head-space gas sampler. The method was practical not only with the blood and bone marrow aspirates to confirm the findings on the CO-oximeter system, but also with the thermo-coagulated and putrified blood.

Automation↗
PubMed1991

Microscopic and chemical examinations for estimating the time since death of skeletal remains--its application to forensic cases.

Postmortem changes in human compact bones were examined by microradiography and electron microscopy, simultaneously with an examination of UV-fluorescence in the cross-section of bones by microscopic spectrophotometry. Total protein content in bones were also examined. No significant morphological changes were found in compact bones exposed to the open air for less than 10 years since death. In bones buried in the soil, vacuolation of bone tissues generally began around 5 years since death. This histological changes extended into the mid zone of the substantia compacta in bones of 6 years or more. In bones left in the sea for 4 or 5 years, vacuoles with 5-10 microns in diameter were observed in the outer peripheral zone of the substantia compacta. The relative intensity of UV-fluorescence in the peripheral zone of the substantia compacta dwindled with time since death and their correlation coefficient was considerably high. Although the correlation coefficient of protein content with time since death of bones was significant, it was too low for forensic science application. These microscopic methods were applied to the estimation of bone date in 5 actual criminal cases and the reliability of the determination of time since death based on the present data were evaluated. The results obtained provided good estimations of the bone date.

Bone and Bones↗
PubMed2004

Transcriptional profile of postmortem skeletal muscle.

Autopsy specimens are often used in molecular biological studies of disease pathophysiology. However, few analyses have focused specifically on postmortem changes in skeletal muscles, and almost all of those investigate protein or metabolic changes. Although some structural and enzymatic changes have been described, the sequence of transcriptional events associated with these remains unclear. We analyzed a series of new and preexisting human skeletal muscle data sets on approximately 12,500 genes and expressed sequence tags (ESTs) generated by the Affymetrix U95Av2 GeneChips from seven autopsy and seven surgical specimens. Remarkably, postmortem specimens (up to 46 h) revealed a significant and prominent upregulation of transcripts involved with protein biosynthesis. Additional upregulated transcripts are associated with cellular responses to oxidative stress, hypoxia, and ischemia; however, only a subset of genes in these pathways was affected. Overexpression was also seen for apoptosis-related, cell cycle regulation/arrest-related, and signal transduction-related genes. No major gene expression differences were seen between autopsy specimens with <20-h and 34- to 46-h postmortem intervals or between pediatric and adult cases. These data demonstrate that, likely in response to hypoxia and oxidative stress, skeletal muscle undergoes a highly active transcriptional, and possibly, translational phase during the initial 46-h postmortem interval. Knowledge of these changes is important for proper interpretation of gene expression studies utilizing autopsy specimens.

Gene Expression Profiling↗
PubMed2001

Factors affecting decomposition and Diptera colonization.

Understanding the process of corpse decomposition is basic to establishing the postmortem interval (PMI) in any death investigation even using insect evidence. The sequence of postmortem changes in soft tissues usually gives an idea of how long an individual has been dead. However, modification of the decomposition process can considerably alter the estimate of the time of death. A body after death is sometimes subject to depredation by various types of animals among which insects can have a predominant role in the breakdown of the corpse thus, accelerating the decomposition rate. The interference of the insect community in the decomposition process has been investigated by several experimental studies using animal models and very few contributions directly on cadavers. Several of the most frequent factors affecting PMI estimates such as temperature, burial depth and access of the body to insects are fully reviewed. On account of their activity and world wide distribution, Diptera are the insects of greatest forensic interest. The knowledge of factors inhibiting or favouring colonization and Diptera development is a necessary pre-requisite for estimating the PMI using entomological data.

Animals↗
PubMed1997

Epicoprostanol found in adipocere from five human autopsies.

Adipocere formation is well known as a later postmortem change. We collected adipocere from five male victims which had been submerged under the sea or fresh water for 1 mon to 4 yr. Fresh subcutaneous fat of a male victim who died from a cerebral contusion was used as the control. The samples were homogenized, and the lipids were extracted with chloroform and methanol followed by injection into a gas chromatograph and a gas chromatograph-mass spectrometer. We detected hydroxy fatty acids (10-hydroxyoctadecanoic acid and 10-hydroxyhexadecanoic acid) as well as 10-ketooctadecanoic acid in adipocere, but not in the control. In addition, we found for the first time a cholesterol-related peak with a molecular ion of 388 in adipocere and identified it as epicoprostanol, suggesting not only oxidation but also reduction had occurred during the formation of adipocere. In addition, we showed the time-course of epicoprostanol accumulation. The relationship between the time of adipocere formation and the characteristic lipid composition is discussed.

Adipose Tissue↗
PubMed2004

Characterization of soils containing adipocere.

The formation of adipocere (commonly known as grave wax), a spontaneous inhibition of postmortem changes, has been extensively analyzed in forensic science. However, soils in which adipocere formation occurs have never been described in detail. Therefore, this study is intended as a first step in the characterization of soils containing adipocere. Two grave soils (Gleyic Anthrosols) that prevent the timely reuse of graves due to the occurrence of adipocere and a control soil (Gleyic Luvisol) were selected from a cemetery in the Central Black Forest (Southwest Germany). Descriptions of soil morphology and a wide assay of physical, chemical, and microbiologic soil characteristics were accomplished. In contrast to the control soil, the grave soils were characterized by lower bulk density and pH. The degradation of the soil structure caused by digging led to a higher water table and the expansion of the reducing conditions in the graves where the prevalent absence of oxygen in range of the coffins inhibited decomposition processes. Although the formation of adipocere led to the conservation of the buried corpses, phosphorus, dissolved organic carbon, and cadavarine leaching from the graves was observed. Microbial biomass and microbial activity were higher in the control soil and hence reflected the inert character of adipocere. The study results clearly show the need for additional approaches in forensic, pedologic, and microbiologic research.

Bacteria↗
PubMed1975

The neuropathological findings in irreversible coma. A critque of the "respirator".

1. Postmortem examinations were made on 240 of the 459 cases succumbing (52 percent of the deaths) in the Collaborative Study on Cerebral Survival; the central nervous system was examined in 226 cases. 2. The autopsy was performed on an average of 15.3 hours after death. 3. The mean weight of the brains was 1450 plus or minus 196 grams; the mean weight of the brains of patients on whom resuscitation was stopped, presumably on the basis of "cerebral death," was greater than that of the patients succumbing to cardiac failure. There was a tendency for the brain to increase in weight about 24 hours after the initiation of resuscitative measures. At that time, swelling, discoloration, softening, congestion, and brain herniations also became more prominent. 4. On the basis of a survey of American neuropathologists and the data from this study, the entity commonly termed "respirator brain" may be confirmed. This is a dynamic process that is complicated by concurrent postmortem changes. The respirator brain requires time (approximately 24 hours) for maturation; many patients die a cardiac death during the metamorphosis. If the patient survives for 3 to 4 days, the percentage dying with typical respirator brains is less, and more patients have electroencephalograms with biological activity. 5. The following clinical factors tend to be associated with an increased number of respirator brains: A. Cerebral trauma B. Subnormal body timperature C. Low systolic blood pressure D. Dilated pupils E. Pupils unresponsive to light F. Absence of cephalic reflexes G. Electrocerebral Silence (ECS) 6. The following factors have no apparent effect on the number of respirator brains or tend to be associated with fewer respirator brains: A. Severe drug intoxications B. Small reacting pupils C. Medications D. Presence of spinal reflexes E. Presence of biological activity (BA) in the electroencephalogram 7. A set of common criteria for a respirator brain was used to test the following: A. The local and consultant neuropathologist's diagnosis of respirator brain B. The significance of critical perfusion pressure and critical oxygen tension in respirator brain C. The role of cardiac output in the production of a respirator brain 8. Since a respirator brain is an imperfectly defined entity, an exact correlation with any combination of clinical and EEG findings could not be expected. The use of a standardized measurement of CBF seems a logical and promising confirmatory test for respirator brain.

Adult↗
PubMed2004

Interstitial infusion of IL13-PE38QQR in the rat brain stem.

Interstitial infusion of IL13-PE38QQR, a tumor specific, chimeric cytotoxin, into the rat brain stem was performed in an effort to assess safety. Six rats underwent stereotaxic cannula placement into the pontine segment of the brain stem followed by a 24-h infusion of IL13-PE38QQR (volume of infusion (Vi) 200 microl) at a concentration of 10 microg/ml. The animals were assessed neurologically and then sacrificed either immediately or after 2 weeks. All animals tolerated the infusions without exhibiting any neurological changes. Postmortem examination of the brains revealed no significant histological changes beyond the site of the cannula tract. These findings indicate that supratherapeutic concentrations of IL13-PE38QQR administered by interstitial infusion into the rat brain stem is well tolerated and may serve as a potential therapeutic strategy for children with diffuse pontine gliomas.

ADP Ribose Transferases↗
PubMedDate not supplied

Time after excision and temperature alter ex vivo tissue relaxation time measurements.

Previously unreported effects of tissue storage were recently observed in the authors' experimental magnetic resonance (MR) studies. To evaluate the effect of elapsed time after excision and storage temperature on tissue relaxation time measurements, tissue samples from the liver, pancreas, kidney, testis, spleen, and brain were obtained in rats. T1 and T2 were first measured within 5 minutes of excision, and between subsequent measurements, tubes were kept in a water bath at 40 degrees C, at room temperature (28 degrees C), or in an ice bath (4 degrees C). Cellular and organellar integrity was assessed with electron microscopy and correlated with the MR findings. At 40 degrees C (20-MHz spectrometer), the T1 of liver decreased from 280 msec +/- 8 to 212 msec +/- 10 during the first 60 minutes; the T1 of pancreas decreased from 276 msec +/- 3 to 208 msec +/- 2. Other tissues showed less than a 5% decrease in T1. T2 changes were smaller than T1 changes in all tissues. Electron microscopy of pancreatic acinar cells showed postmortem changes in mitochondria evolving over the first 60 minutes after death. Manganese loading experiments implicated mitochondrial manganese stores in the observed enhanced postmortem decrease in T1. This study calls into question reported relaxation time data for liver and pancreas. MR studies of excised tissues must account for time and temperature to prevent systematic experimental errors.

Animals↗
PubMed2003

Changes in rates of autopsy-detected diagnostic errors over time: a systematic review.

CONTEXT: Substantial discrepanies exist between clinical diagnoses and findings at autopsy. Autopsy may be used as a tool for quality management to analyze diagnostic discrepanies. OBJECTIVE: To determine the rate at which autopsies detect important, clinically missed diagnoses, and the extent to which this rate has changed over time. DATA SOURCES: A systematic literature search for English-language articles available on MEDLINE from 1966 to April 2002, using the search terms autopsy, postmortem changes, post-mortem, postmortem, necropsy, and posthumous, identified 45 studies reporting 53 distinct autopsy series meeting prospectively defined criteria. Reference lists were reviewed to identify additional studies, and the final bibliography was distributed to experts in the field to identify missing or unpublished studies. STUDY SELECTION: Included studies reported clinically missed diagnoses involving a primary cause of death (major errors), with the most serious being those likely to have affected patient outcome (class I errors). DATA EXTRACTION: Logistic regression was performed using data from 53 distinct autopsy series over a 40-year period and adjusting for the effects of changes in autopsy rates, country, case mix (general autopsies; adult medical; adult intensive care; adult or pediatric surgery; general pediatrics or pediatric inpatients; neonatal or pediatric intensive care; and other autopsy), and important methodological features of the primary studies. DATA SYNTHESIS: Of 53 autopsy series identified, 42 reported major errors and 37 reported class I errors. Twenty-six autopsy series reported both major and class I error rates. The median error rate was 23.5% (range, 4.1%-49.8%) for major errors and 9.0% (range, 0%-20.7%) for class I errors. Analyses of diagnostic error rates adjusting for the effects of case mix, country, and autopsy rate yielded relative decreases per decade of 19.4% (95% confidence interval [CI], 1.8%-33.8%) for major errors and 33.4% (95% [CI], 8.4%-51.6%) for class I errors. Despite these decreases, we estimated that a contemporary US institution (based on autopsy rates ranging from 100% [the extrapolated extreme at which clinical selection is eliminated] to 5% [roughly the national average]), could observe a major error rate from 8.4% to 24.4% and a class I error rate from 4.1% to 6.7%. CONCLUSION: The possibility that a given autopsy will reveal important unsuspected diagnoses has decreased over time, but remains sufficiently high that encouraging ongoing use of the autopsy appears warranted.

Autopsy↗
PubMed1993

An animal model of postmortem amitriptyline redistribution.

An experimental rat model was developed to study postmortem changes of drug concentration after an acute overdose. Overnight fasted rats were fed 75 mg of amitriptyline (AMI). Two h after dosing, the rats were anaesthetized and blood samples were drawn from the femoral vein (peripheral blood--PB) and the heart (HB). The rats were sacrificed by CO2 and left at room temperature for either 0.1, 0.5, 1, 2, 5, 10, 24, 48, or 96 hours, when samples of heart blood, blood from the inferior vena cava (PB) and tissue samples from different liver lobes, heart, lungs, kidney, thigh muscle, and brain were taken. Samples were analyzed by high performance liquid chromatography. The AMI concentration in HB increased fairly rapidly within the first 2 h postmortem and from then the average ratio was 6.4 +/- 0.8 (mean +/- sem) (n = 31). In PB, the post/antemortem AMI concentration ratio followed an approximately exponential rise; at 2 h postmortem the ratio was 1.6 +/- 0.3 (n = 5), and at 96 h 55.1 +/- 23.8 (n = 4). For the main metabolite nortriptyline (NOR), the concentration changes followed the same pattern, but to a lesser extent. Among the tissues, the liver lobes had high, but variable drug concentrations; lobes lying closest to the stomach had the highest drug concentrations. The drug concentration in the lungs declined significantly. This animal model demonstrates postmortem drug concentration changes similar to those described in humans. Probable mechanisms include drug diffusion from the stomach and GI tract to the surrounding tissues and blood; and postmortem drug release from the lungs and possibly other drug-rich tissues into the blood.

Amitriptyline↗