Pathways of protein degradation in L6 myotubes

Sudden unexpected death in young adults of 18-35 years account for an important subset of deaths in our autopsy population. The case notes and autopsy reports in 44 subjects were analysed during the period 1985-94 at the Department of Histopathology, University College Hospital, Galway to establish the underlying cause of death. Subjects who were involved in road traffic accidents, cases of drowning, and patients with known congenital heart disease, chronic renal failure and malignancy were excluded. We found that a large proportion of sudden deaths in young adults were secondary to epilepsy and chemical/drug poisoning, accounting for 34 per cent and 31.8 per cent respectively. Sudden adult death syndrome (SADS) accounted for 9 per cent of the study population. Detailed case history, meticulous post-mortem examination and complete toxicological screening are recommended to arrive at the underlying cause of death.     

Photoperiodic modulation of monoamines and amino-acids involved in the control of prolactin and LH secretion in the ewe: evidence for a regulation of tyrosine hydroxylase activity

The aim of this study was to analyse medico-legal autopsy rates among Norwegian citizens who died in the two northernmost counties of Norway during the 20-year period 1973-1992. Medico-legal autopsy rate was defined as the number of medico-legal autopsies divided by the total number of deaths. The rates were calculated according to year of death, manner of death, sex, age, police district and county. The material included 1539 medico-legal autopsies. In the total 20-year period 37.9% (n = 1113) of the violent deaths and 1.2% (n = 426) of the natural deaths were subjected to medico-legal autopsy. The annual rates increased gradually up to 1987. In the last 5-year period 51.7% of the violent deaths and 2.1% of the natural deaths were subjected to medico-legal autopsy. Among violent deaths in this period the medico-legal autopsy rates were: suicides 65.7%, motor vehicle traffic accidents 58.3%, falls 8.6%, and other violent deaths 77.1%. Females dying after a fall and due to natural causes were significantly less frequently than males subjected to medico-legal autopsy. These two categories of death also revealed a significant decrease in autopsy rate with increasing age (age group 0-29, 30-59 and > or = 60 years) in each 5-year period. In cases of violent death the medico-legal autopsy rate according to police district varied from 24.1% to 88.9% in the last 5-year period. In conclusion, medico-legal autopsy rates depended on manner of death, sex, age and police district, besides changes in legislation.     

Speedballing with needle embolization: case study and review of the literature

Foreign-body embolization is not an uncommon occurrence. However, to our knowledge, there are only ten reported cases of needle embolization associated with intravenous drug use. We report the sudden death of a 49-year-old white male with a known history of crack cocaine abuse. At autopsy, suspicious needle marks were noted on the right lower extremity. The lungs were of increased weight at 1000 and 1090 g and appeared edematous. The heart weighed 520 g and had a normal red-brown myocardium. Upon sectioning, a broken hypodermic needle of very small caliber was identified in the right ventricular myocardium protruding into the right ventricular chamber. This needle apparently traveled from the injection site to the right ventricle. The right ventricle was dilated and hypertrophied, and microscopic examination showed hyperemic myocardium surrounding the needle. Sections of lung showed numerous foreign-body type giant cells containing polarizable foreign material consistent with intravenous drug use. Toxicological analysis revealed the presence of ethanol (36 mg/dL), cocaine (0.098 mg/L), benzoylecgonine (2.16 mg/L), and morphine (0.841 mg/L). Urine and blood were positive for the presence of 6-monoacetylmorphine. Based on the toxicological analysis, the cause of death was determined to be cocaine and heroin toxicity, and the manner accidental. The needle embolus was considered an incidental finding.     

Distribution of tissue plasminogen activator insertion/deletion polymorphism in myocardial infarction and control subjects

The purpose of this study was to determine how drug findings in intracranial hematomas should be assessed in forensic autopsy cases. Six cases in which intracranial hematomas containing drugs and chemicals were detected were examined in this study. Of the six cases, five were positive for drugs and chemicals that had been self-administered by the victims prior to injury. Post-traumatic time interval from injury to death was in the range 10 to 65 h. In two individuals who were positive for norephedrine or toluene, the concentrations of these substances were much higher in the intracranial hematomas than in heart blood. In an individual who was positive for phenobarbital, its concentration was only a little higher in the intracranial hematoma than in heart blood. In the remaining two cases, substantial quantities of ethanol were detected in the intracranial hematomas, but little ethanol was detected in heart blood. In three cases, some drugs were administered at hospital after the injuries. The time interval from the initial drug administration to death was 19 to 60 h. In two individuals given phenytoin and/or lidocaine intravenously, substantial amounts of these drugs were detected in the intracranial hematomas. In an individual given diazepam intravenously, a substantial quantity of diazepam was detected in heart blood, but not in the intracranial hematoma. Toxicological analysis of intracranial hematomas may be useful not only for determining whether individuals were under the influence of ethanol at the time they were injured, but also for detecting pre-traumatic usage of other drugs and chemicals. However, the medical record should be reviewed thoroughly from a toxicological view point if victims underwent medical treatment prior to death because drugs administered for the purpose of medical treatment can disseminate into preexisting intracranial hematomas, depending on the size of the hematomas.     

Effect of pentobarbital on normal brain protection and on the response of 9L rat brain tumor to radiation therapy

The authors attempted to confirm published reports that pentobarbital protects against radiation-induced damage to normal rat brain, as well as enhances radiotherapeutic efficacy in a rat brain tumor model. They evaluated animal survival in 9L gliosarcoma-burdened rats that received whole-brain radiation therapy (16, 24, 32, or 40 Gy) while under intraperitoneal pentobarbital (60 mg/kg) or intramuscular ketamine (60 mg/kg) sedation. The animals were examined at autopsy to attribute death to either intracranial tumor growth or normal brain toxicity in the absence of discernible tumor. There was no difference between the two anesthesia groups regarding the survival of unirradiated animals. Radiation therapy produced a significant dose-dependent prolongation in animal survival, which was limited by the development of normal tissue toxicity at the higher doses. When compared to ketamine anesthesia, pentobarbital anesthesia appeared to offer some protection (not statistically significant) against early (but not late) toxicity at selected radiation doses. A reduction in the number of deaths from tissue toxicity suggested an increased antitumor effect, but again this was not statistically significant. Only in one case was there even a marginal significant difference (p = 0.045) between overall therapeutic efficacy in rats sedated with pentobarbital versus ketamine. While there may be a radioprotective effect of pentobarbital in rat brains without intracranial tumor, there is no conclusive evidence for either radioprotection or significant improvement of radiotherapeutic efficacy in this 9L rat brain tumor model.     

Large-cell change of hepatocytes in cirrhosis may represent a reaction to prolonged cholestasis

The deaths of 10 heroin body packers are reported and contrasted to those of cocaine body packers. Only one was a woman, and all were traveling to or from Colombia. Drug packets deteriorated in the gastrointestinal tract and caused the deaths of eight victims. Accomplices removed drug packets from two of these smugglers after death occurred. One died of peritonitis stemming from a small-bowel obstruction caused by the drug packets, and one died from the recreational use of heroin (nasally ingested). The heroin recovered was < or = 881 g, and the drug purity of the contraband in three cases was between 65% and 73%. Blood concentrations of morphine were < 1.0 mg/L in four victims; no morphine was detected in the smuggler who died of peritonitis. However, two victims had blood morphine concentrations of 4.4 mg/L and 6.7 mg/L, respectively, and three had morphine concentrations of 35.8, 39.4, and 52.6 mg/L, respectively. Fatal heroin body packing differs from cocaine body packing in that individuals may have extremely high drug levels in their blood and their accomplices appear to be more likely to abandon them in a remote location after attempting to remove the drug packets after death has occurred.     

Homicides without clues in children

From 1990 to 1995, 274 deaths of infants (age range 7 days-6 years) were investigated in Münster, where there were no indications of suspicious circumstances. In 167 cases a legal autopsy was carried out and revealed 5 homicides. In 107 cases where an autopsy was not ordered by the prosecutor 3 homicides were discovered. A similar frequency of homicides in both groups indicates that the criteria used to form the basis of a decision by the prosecutor to release the body are insufficient. On average one out of 30 cases was found to be a homicide as the result of the autopsy where the initial assumption was death from natural causes.     

Flush resuscitation for group A streptococcus toxic shock: a possible role for continuous renal replacement therapy and plasmapheresis

Concentrations of citalopram in medicolegal samples from 92 autopsies and 27 living persons are described. In autopsy cases in which citalopram alone was the cause of death, concentrations ranged from 2.0 to 6.2 mg/kg whole blood. In autopsy cases in which citalopram together with other substances was considered to be the cause of death, the concentrations of citalopram ranged from 0.6 to 5.2 mg/kg whole blood. In autopsy cases toxic concentrations ranged from 0.4 to 0.9 mg/kg whole blood and therapeutic concentrations from 0.03 to 0.6 mg/kg whole blood. In samples from living persons the concentrations of citalopram in whole blood were 0.02 to 0.3 mg/kg.     

Does restricted distribution limit access and coverage of yellow fever vaccine in the United States?

BACKGROUND: While human immunodeficiency virus (HIV)-related causes of death have been well documented in developed countries, in Africa data are scanty and mainly based on autopsy studies from city hospitals which are highly selective and may not represent causes of HIV-associated deaths in the general population. This study, from a rural population, describes the causes of death in HIV-positive people and their HIV-negative controls. METHODS: A natural history cohort comprising HIV-1 infected participants and HIV-negative controls was established in rural Uganda in 1990. Causes of death were determined by reviewing the premorbid clinical and laboratory findings and from information obtained from relatives. Blindness to the deceased's HIV serostatus was maintained throughout. RESULTS: In all, 78 deaths occurred over a 6-year period: 63 deaths occurred in the HIV-positive cases (53 prevalent and 10 incident cases) and 15 deaths in the HIV-negative controls. Of the prevalent cases, 56%, and 9% the incident cases enrolled died, compared with 7% of the HIV-negative controls. Of the 55 HIV-positive cases with sufficient data to establish cause of death, 52 (95%) were assessed as having HIV-associated deaths and 48 (87%) died in WHO stage 4 (AIDS). The main causes of death were wasting syndrome (31%), chronic diarrhoea (22%), cryptococcal meningitis (13%) and chest infection (11%). CONCLUSIONS: Our results represent an unbiased selection of deaths in a rural area. The HIV-positive cases have high death rates and die of HIV-related pathologies. The main causes of death reflect the WHO clinical case definition of AIDS. Cryptococcal meningitis is also a common cause of death in this population.     

Evidence that loss of chromosome 18q is associated with tumor progression

Toxicological investigation of suspected cocaine-related deaths routinely involves the identification of cocaine (COC) and its metabolites including benzoylecgonine (BE) and ecgonine methyl ester (EME) in postmortem specimens. We utilized solid-phase extraction followed by gas chromatography/mass spectrometry for the qualitative and quantitative analysis of cocaine and eight cocaine-related analytes. These analytes included anhydroecgonine methyl ester (AEME), a unique product formed during cocaine smoking, and cocaethylene (CE), formed by transesterification of cocaine in the presence of ethanol. Thirteen pairs of postmortem heart blood and urine specimens were analyzed from cases of death due to acute cocaine intoxication, multiple drug intoxication, or other non-drug related causes. COC, EME, and BE were detected in all specimens. The range of concentrations in blood were: COC, 23-2088 ng/mL; BE, 215-9195 ng/mL; and EME, 220-7275 ng/ mL. AEME was identified in 2 blood and 10 urine specimens, and CE was identified in 1 blood specimen and 4 urine specimens. The identification of AEME in the specimens indicated that "crack" cocaine had been smoked, and the presence of CE indicated co-administration of cocaine and ethanol. The presence of these unique cocaine analysis in postmortem specimens provides valuable information regarding the cause and manner of death.     

High postmortem concentrations of hypoxanthine and urate in the vitreous humor of infants are not confined to cases of sudden infant death syndrome

OBJECTIVE: High concentrations of hypoxanthine and urate have been found in the blood of rats who died suddenly during induced respiratory alkalosis as well as in cases of sudden death in malignant hyperthermia-susceptible pigs challenged with halothane. The origin of these metabolites is the excessive hydrolysis of adenine nucleotides, which is associated with the production of free radicals. We wished to establish whether high levels of these compounds were also to be found in sudden infant death syndrome (SIDS) victims, compared with other causes of death. DESIGN: Vitreous humor samples were analysed for hypoxanthine and urate by high-performance liquid chromatography. SETTING: Forensic Laboratories, Salt River, Cape Town. PARTICIPANTS: Vitreous humor samples were collected from 91 infants presented for postmortem examination. MAIN OUTCOME AND RESULTS: From autopsy reports, cause of death was classified as: (i) SIDS (N = 50); (ii) acute sudden death (N = 5); and (iii) all other causes of death (N = 36). There were no differences in the hypoxanthine or urate levels of groups (i) and (iii) over the first 5 days of the postmortem period. Group (ii) levels were lower than those of both (i) and (iii). CONCLUSION: Adenine nucleotide hydrolysis is not only a feature of SIDS, and possibly results from antemortem hypoxia in most deaths. The lower concentrations found in cases of acute sudden death probably resulted only from postmortem hydrolysis of the nucleotides.     

The "golden sniff": suicide by sniffing heroin

The best known but apparently rare method to commit suicide by the intake of drugs is the 'golden shot'. As a result of a criminalistic scrutiny in combination with an exploration of the medical history, the findings of the autopsy and the toxicological analysis it is often not possible to discriminate between an accidental and a suicidal intoxication. The manner of death is therefore in most cases undeterminable. The presented unusual suicide by a letal opiate intoxication do to sniffing the drug would not have been clarified, neither with a complete examination of the history, an entirely performed autopsy, the determination of the way of ingestion of the drug nor with a complete toxicological analysis. The diagnosis is based primarily on the availability of a farewell letter. This case demonstrates that it is very difficult to determine the manner of death. Examining drug addicts it is exceedingly important to perform an overall examination by visiting the scene, by inspecting there the corps and the environment and by performing a complete autopsy with toxilogical examinations.     

Fatal heroin 'overdose': a review

The current paper examines critically the literature on deaths attributed to heroin overdose, and examines the characteristics and circumstances of such deaths. In particular, the dominance of the widely held belief that heroin-related fatalities are a consequence of overdose is challenged. Deaths attributed to overdose represented in the literature are typically older, heroin-dependent males not in drug treatment at the time of death. Fatalities involving only heroin appear to form a minority of overdose occasions, the presence of other drugs (primarily central nervous system depressants such as alcohol and benzodiazepines) being commonly detected at autopsy. Furthermore, deaths attributed to overdose are likely to have morphine levels no higher than those who survive, or heroin users who die from other causes. It is concluded that the term overdose is, in many cases, a misleading term, since it implies the same mechanism of death in all cases, an implication that is neither clinically useful nor consistent with published data. Implications for the prevention of heroin-related deaths are discussed.     

A prototype Internet autopsy database. 1625 consecutive fetal and neonatal autopsy facesheets spanning 20 years

OBJECTIVE: To demonstrate that cause-of-death statements can be generated by a computer algorithm from an autopsy database composed of diagnostic terms. DATA SOURCES: Over 49 000 autopsy facesheets contributed by over a dozen institutions were collected from a publicly accessible Internet autopsy database. This database is available at the following web site: http:@www.med.jhu.edu/pathology/iad.html STUDY SELECTION: To test the feasibility of creating and using a publicly available autopsy database, and to identify the technical and medicolegal problems that may arise with such a novel resource, a prototype study was designed by selecting autopsy facesheets from fetal and neonatal deaths. An algorithm was developed to determine the cause of death from the listing of anatomic diagnoses. DATA EXTRACTION: One thousand six hundred twenty-five fetal and neonatal autopsy facesheets were selected encompassing fetal and neonatal deaths occurring up to 28 days after birth. DATA SYNTHESIS: The algorithm determined causes of death from autopsy facesheet data in all cases. On review by an experienced pediatric pathologist, these automatically generated cause-of-death statements required no modification or only slight modification in over 90% of cases. CONCLUSIONS: A large multi-institutional autopsy database composed of demographic and diagnostic information has been deposited on the Internet. This information can be freely downloaded and used by any researcher without violating patient confidentiality. As a demonstration of one possible application of the database, fetal and neonatal autopsies generated cause-of-death statements using a computer algorithm. One can anticipate that the wealth of information contained in autopsy facesheets can be assembled into a database that will serve the public interest.     

Acute ischaemic lesions in death due to ischaemic heart disease. An autopsy study of 333 cases of out-of-hospital death

The frequency of acute coronary artery thrombus and myocardial infarction in subjects dying suddenly or unexpectedly from ischaemic heart disease (IHD) is still unclear, with previous autopsy studies reporting an incidence between 4% and 100%. In this study of 333 randomly selected out-of-hospital deaths, detailed autopsy showed IHD as the sole cause of death in 206 (62%). One hundred and seventeen acute coronary thrombi were present in 96 cases whilst four had an established acute infarct without an identifiable coronary thrombus. Thus 100 (48.5%) IHD deaths had evidence of an acute ischaemic lesion. Acute lesions were equally prevalent among males and females, but the incidence declined with increasing age and they were less frequent among those with a prior clinical history of heart disease. One hundred and forty-seven IHD deaths were witnessed. The proportion of cases with an acute ischaemic lesion increased with the duration of pre-morbid symptoms. Of those with an acute lesion, only 17% died without symptoms compared to 63% of those without an acute lesion. All cases with symptoms lasting more than 3.5 h had an acute lesion. Overall, almost half out-of-hospital IHD deaths in this study were related to an acute ischaemic lesion. Differences in the detail of the pathological examination and examination of differing sub-groups of the out-of-hospital death population probably account for the differing results of previous studies.     

Methylephedrine concentrations in blood and urine specimens

Methylephedrine is a sympathomimetic amine that appears in many over-the-counter cough and cold medications throughout the world. The abuse of methylephedrine-containing medications has been reported in Japan. Although methylephedrine is not available in the United States, it was identified in 15 cases received by the Forensic Toxicology Laboratory, Division of Forensic Toxicology, Office of the Armed Forces Medical Examiner, Armed Forces Institute of Pathology over a two-year period; 12 of the 15 cases were collected from patients or decedents located within the confines of the continental United States. Methylephedrine was identified in each case by gas chromatography-nitrogen-phosphorus detection following an alkaline extraction and subsequently confirmed using full scan electron impact mass spectrometry. Quantitation of underivatized methylephedrine was performed using the same technique. Blood methylephedrine concentrations ranged from less than 0.05 to 0.28 mg/L (n = 14), and the mean methylephedrine concentration in urine was 1.6 mg/L (range, 0.15-6.8, n = 11 [excluding case 6]). A literature search revealed little information pertaining to the interpretation of methylephedrine concentrations in the blood. Six of the 15 cases presented here were positive for methylephedrine in the blood. Three of these cases were postmortem cases, and the other three cases were nonfatal aircraft mishaps. There is no evidence in any of these cases that methylephedrine was present at toxic concentrations; therefore, it appears from the cases reviewed in this study that blood methylephedrine concentrations less than 0.3 mg/L are not associated with significant toxicity.     

Factors associated with the decline in cirrhosis death rates among young adults in Allegheny County, Pennsylvania, 1973-1985

From 1973 to 1985, the age-adjusted death rate from liver cirrhosis (International Classification of Diseases, Ninth Revision, code 571) dropped by 62.7% among adults aged 25-54 years in Allegheny County, Pennsylvania. The authors investigated factors associated with this decline by verifying causes of death on death certificates from medical records, coroner's reports, and autopsy reports. Although death rates from cirrhosis were slightly underestimated from death certificates, the underestimation did not alter the declining mortality trend. This decline in rates was significant after adjustment of the age, sex, and race effect using statistical modeling. No significant variability in the time trends was noted between sexes, races, and age groups. Neither did the trends in alcohol-related and "unspecified" cirrhosis differ. However, the trends varied significantly between the cirrhosis deaths certified by the coroner and by noncoroner physicians. From 1973-1975 to 1976-1978, the rate initially dropped by 51% among the coroner cases, whereas it dropped by only 9% among the noncoroner cases. By the period 1982-1985, the death rates of both coroner and noncoroner cases declined to approximately 50% of their 1973-1975 rates. These results suggest that the decline during the years 1973-1985 was real and that the trend was initiated by the pronounced decline during the early years in the coroner-certified cirrhosis deaths.     

Evaluation of the critical body burden concept based on inorganic and organic mercury toxicity to rainbow trout (Oncorhynchus mykiss)

Subadult rainbow trout (Oncorhynchus mykiss) were exposed to four waterborne concentrations each of 64-426 microg/L mercuric chloride (HgCl2) and 4-34 microg/L methylmercury chloride (CH3HgCl) until death to evaluate the critical body burden concept. Mean days to death for fish exposed to the highest and lowest concentrations of HgCl2 were 1 and 58 d, and 2 and > 100 d for fish exposed to CH3HgCl. Time to death was an important factor that influenced Hg tissue concentration, and was most evident among fish that died within a few days of exposure. Critical body burdens for Hg could be difficult to establish at the tissue level because no threshold concentrations were clearly indicated among the liver, kidney, spleen, brain, muscle, and gill that were monitored in this study. A critical burden for Hg was derived on a whole body basis for Hg in its organic form. An evaluation of this and other studies suggests whole body concentrations of 10-20 mg/kg Hg could be lethal to fish. Extrapolation from other studies indicate whole body concentrations of 1-5 mg/kg Hg could have chronic effects on fish and possibly other aquatic organisms. This concept could be used to assess the toxicological significance of chemical concentrations that are monitored in feral aquatic organisms. The tissue-based approach appears to have some advantages over current assessment protocols that focus on waterborne concentrations.