MOR1 receptor mRNA expression in human brains of drug-related fatalities-a real-time PCR quantification

The expression of the human micro-opiate receptor (MOR1) in post mortem human brain tissue was examined using real-time PCR technology. Tissue samples from 11 fatalities due to opiate overdose and five normal subjects with different causes of death were analysed in order to elucidate whether chronic opiate abuse is followed by a regulation of MOR1 expression. In each case nine selected brain regions (thalamus, caudate nucleus, hypothalamus, ventral tegmentum, hippocampus, amygdala, frontal cortex, nucleus accumbens, putamen) were evaluated. The MOR1-mRNA level was determined relative to the housekeeping gene beta2-microglobulin. While in most regions the MOR mRNA levels in the brain of addicts were not different from the control group-with varying levels between 0 and 15% of housekeeping gene level-in the brains of three drug-related fatalities an enormous increase was encountered in the thalamus where the MOR-mRNA level amounted for up to 10,000% of the measured housekeeping gene level. The results obtained by toxicological hair analysis in the group of drug-related fatalities indicate that the enormous thalamic MOR1-expression is primarily found in individuals who died from acute heroin overdose but did not show signs of a substantial chronic administration of the drug. Further studies have to be performed to evaluate if the observed MOR1-mRNA up-regulation in the thalamus in a subpopulation of acute lethal intoxications mirrors a state of functional hypersensitivity associated with the occurrence of death.     

Histopathological findings in 851 autopsies of drug addicts, with toxicologic and virologic correlations

This investigation was carried out on 851 consecutive judicial autopsies of drug addicts who died mostly of heroin overdose from 1977 to 1996. Research of anti-HIV/HBV/HCV antibodies was performed, and histologic sections were retrospectively reviewed. More than 65% were HBV/HCV-positive and about 17% HIV-positive; females were HIV-positive more often than males. Intracranial microhemorrhages were frequently found; cerebral infectious diseases were rare. Inflammatory heart lesions, myocardial fibrosis, and acute ischemia were common. Interstitial nephritis (found in about 8%) was more frequent in females, in older patients, and in those carrying HIV infection; glomerular sclerosis was detected in about 12%. Acute bronchitis and/or pneumonia was demonstrated in 12%, without significant association with HIV infection; pulmonary hemorrhages, foreign body granulomas, and food aspiration were also commonly seen; hyperplasia of pulmonary perivascular lymphatic tissue was rather characteristic. Liver was carrying steatosis in 66.3% and/or hepatitis in 64.5%; acute hepatitis was more frequent in females, chronic hepatitis in older subjects and in those proven positive for hepatotropic viruses; cirrhosis occurred more often in older patients, in those carrying virus infection, and in consumers of nonnarcotics drugs such as ethanol. No pathologic finding was clearly related to drug abuse; therefore, during autopsy, drug addiction can be suspected, but anamnestic and circumstantial data are needed to lead pathologists to request toxicologic analysis to ascertain the cause of death. The present investigation emphasizes that, in addition to the risk of death by overdose, the high incidence of acute and chronic diseases could seriously undermine the health status of heroin and/or other drug consumers.     

Unexpected death as a result of infective endocarditis

Thirteen cases of infective endocarditis (IE) diagnosed for the first time at autopsy or, in those patients with a previous diagnosis of IE, not thought to be active at the time of death, are presented. Of the six patients who died within 24 h of the onset of symptoms, two died of obstruction of a valve orifice, two died of sepsis, one died of sepsis and alcoholic cardiomyopathy, and one died of a coronary artery embolus. Of the five patients with symptoms lasting more than 24 h, three died of sepsis and congestive heart failure. One died from sepsis alone and one died from congestive heart failure (CHF). In two patients whose duration of symptoms is unknown, one died of sepsis and CHF, and in the other the mechanism of death is unknown. Predisposing factors present in 11 of 13 patients included alcoholism (three), intravenous (IV) drug abuse (three), prosthetic valves (three), aortic stenosis (two), past rheumatic fever (one), and nonstenotic congenitally bicuspid valves (two). The reasons for no antemortem diagnosis were a missed or incorrect clinical diagnosis in three patients seen by a physician shortly before death, no signs or symptoms or found dead (four), non-specific signs and symptoms (three), refusal of medical treatment (one), and a solitary lifestyle (one); there was insufficient information about one patient. Individuals with needle tracks, generalized petechiae. Osler's nodes, splinter hemorrhages, intravenous catheters, pacemaker wires, and infected aortic-valve (A-V) shunts are at risk of IE. Blood and the vegetations should be cultured. The attending physician should be notified of the diagnosis in such cases.     

Sudden death in the alcoholic

A study of victims of alcohol abuse was performed on the case files of the Office of the Medical Examiner of Metropolitan Dade County in Miami, Florida. During the year 1983, all cases in which alcoholism, either acute or chronic, was the cause of death primarily or contributory in a natural or accidental manner of death were collected. These 118 cases were then analyzed as to the age, race, sex, and cause of death of the victim along with the blood alcohol content, the drugs detected at autopsy, the scene circumstances, the geographic location of the terminal incident, noting whether or not there was a history of drinking prior to the terminal incident, the average weights of key target organs, and the histopathology of the liver. The most common victim is an older (greater than 50 years) white male who dies from "chronic alcoholism" with a terminal negative blood alcohol. This victim is usually "found dead" at home with a past history of drinking, and histopathologically the liver depicts fatty metamorphosis rather than cirrhosis.     

Fatal intravenous drug abuse secondary to streptomycin overdose

A fatal case of chronic intravenous drug abuse involving the injection of a nonpsychoactive veterinary combination of penicillin G and streptomycin is reported. The circumstances surrounding the death indicate that the decedent died as a result of streptomycin induced paralytic neuromuscular blockade.     

Oral abuse of fentanyl patches (Duragesic): seven case reports

In order to increase the understanding regarding the oral abuse and potential toxicity of fentanyl patches seven cases were identified over a 3-year period where fentanyl, either alone or in combination with other factors, contributed to death following the oral abuse of Duragesic patches. The decedents comprised three females and four males with ages ranging from 20 to 51 years. Postmortem blood fentanyl concentrations were determined in all cases and ranged from 7 to 97 ng/mL. Two deaths were classified as a fentanyl overdose, three deaths were classified as a fentanyl and ethanol overdose, one death was considered a mixed drug intoxication and the remaining death was determined to be a combination of fentanyl and medical causes. These cases represent the largest reported series of deaths following the oral administration of transdermal fentanyl patches and provide detailed information on the potential for the abuse of transdermal Duragesic patches via this route. The postmortem blood fentanyl concentrations detected for each of the decedents demonstrate the potentially fatal blood concentrations that can arise after this relatively rare route of administration.     

Amitriptyline abuse and misuse

Deaths related to amitriptyline toxicity are relatively common and are typically related to suicidal overdose. A less well-recognized situation of amitriptyline intoxication occurs when the drug is abused for its euphorigenic effects. An amitriptyline-related death due to a mixed drug intoxication is presented. Death investigation revealed that the death was accidental rather than suicidal. The case serves to remind forensic investigators that not all amitriptyline overdose deaths represent suicides. A segment of the population is known to abuse amitriptyline.     

Increased risk of fatal intoxication and polypharmacy among psychiatric patients at death

Patients suffering from psychiatric disorders have an excess mortality and a shorter life span expectancy compared to the general population. Furthermore, they are treated with multiple drugs and are known to have an increased risk of drug abuse. In this study, we aimed at investigating the pharmaceutical drug and drug of abuse profiles of the deceased included in the Danish prospective autopsy‐based forensic study on psychiatric patients, SURVIVE. Using the postmortem systematic toxicological analysis results, we identified 129 different consumed compounds in our population (n = 443). Polypharmacy (≥5 compounds) was detected in 39.5% of the deceased. Deceased with a psychiatric diagnosis or who died from a fatal intoxication had significantly more compounds at the time of their death compared to having either no psychiatric diagnosis or another cause of death, respectively. Evidence of drug abuse was present, as 29.8% of our total population had consumed either methadone or illicit drugs of abuse, excluding tetrahydrocannabinol. Of those deceased with a psychiatric diagnosis, 33.6% had either consumed methadone or illicit drugs of abuse, a greater number than those without a psychiatric diagnosis. Fatal intoxication was the most frequent cause of death (40.6%) with methadone as the major intoxicant. Here, we found that those without a psychiatric diagnosis had fewer fatal pharmaceutical drug intoxications compared to the psychiatric diagnosis groups. Our findings add further context to understanding the excess mortality of psychiatric patents, since there is an increased occurrence of fatal intoxication, polypharmacy, and drug abuse in this population.     

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.     

HIV-infection in forensic autopsy cases

Sudden and unexpected death and violent death of persons with a high risk of acquiring HIV-infections, especially homosexual males and intravenous drug abusers, have to be investigated by forensic autopsies. Therefore every forensic pathologist has to be aware of this infection and should try to make the proper diagnosis. Three typical cases are described: (1) suicide by hanging, (2) homicide by cutting the throat and (3) intravenous heroin overdose. Merely retrospectively it could be cleared up that the deceased were homosexual but did not manifestly suffer from AIDS. The morphological findings in the lymph nodes and the postmortem serological findings are described in detail.     

HIV-related deaths outside medical institutions in Stockholm

During a 3-year period (August 1st, 1985 to July 31st, 1988) a systematic investigation of medico-legal autopsy cases with regard to the presence of antibodies for HIV-virus was carried out at the Department of Forensic Medicine in Stockholm, Sweden. Prior to autopsy, blood samples were taken from femoral or subclavian veins and were investigated by use of ELISA-screening and Western blotting test. During the first year of study, HIV infection was demonstrated in 11 out of 3464 deaths (0.32%), during the second year in 29 out of 3483 deaths (0.83%), and during the last year in 13 out of 3107 deaths (0.42%). It was shown that 48 out of the total of 53 HIV positive cases were previously registered, but information about the infection was available to the autopsist in only 27 cases. Drug addicts dominated 41 of 53 cases. There were only eight homo- and bisexual males, two non drug addict Central Africans and two persons who received blood transfusions. Eight of the 53 persons died of natural causes whereas 45 deaths were due to violence and drugs. The causes of death of the HIV positive drug addicts were compared to the causes of death of the HIV negative addicts. The HIV positive drug addicts tended to die suddenly in connection with the intravenous administration of heroin and at lower blood concentrations of morphine more often than the HIV-negative addicts. No increase in the suicide frequency was noted in drug addicts in Stockholm during the studied period.     

Plastic bag asphyxia in southeast Scotland

Death resulting from plastic bag asphyxia has been recognized for >40 years, but relatively little is known about either its epidemiology or its pathophysiology. Over 15 years (1984-1998), 30 deaths were attributed to plastic bag asphyxia among the 14,560 autopsies performed in the Forensic Medicine Unit in Edinburgh. These 30 deaths involved 20 male and 10 female subjects, with an age range of 13 to 81 years. Eleven had some alcohol measurable in the blood, with four having levels >80 mg/dl. Only one individual appeared to have ingested a drug overdose, but inhaled substances within the plastic bag may have contributed to death in five cases. The absence of childhood accidental deaths may reflect successful preventive measures. The 3 accidental deaths involved adults (including 2 who died of autoerotic asphyxia), and the remaining deaths were 27 suicides. Of those who committed suicide, most (59%) had chronic psychiatric illness rather than chronic debilitating or terminal physical illness. In contrast with reports from the United States, publicity associated with "self-deliverance" did not result in an increased number of deaths from plastic bag asphyxia (4 deaths in this series). Analysis of the circumstances of all the deaths revealed them to be difficult to predict and hence prevent.     

Relationships between the deinstitutionalization of healthcare for patients with mental disorder, substance abuse, and isolated death

Isolated death (ID) (i.e., dying alone without anyone noticing for several days) has been suggested to be related to social isolation, mental disorder, and alcohol and/or drug abuse. A major transfer of patients with a mental disorder and/or alcohol and/or drug abuse from institutionalized care to treatment as outpatients has been enacted in Sweden during the past decade. On the basis of the assumption that such deinstitutionalization is likely to result in increased social isolation, our working hypothesis was that the incidence of ID among patients belonging to these categories has increased in Sweden. The present study involved all deaths subjected to a medicolegal examination in Stockholm County (with a population of approximately 1.9 million people) during the period 1992-2000. The pattern of ID (defined as cases involving a postmortem delay between death and discovery of at least 1 week), as well as the incidence of fatalities subjected to medicolegal examination with a record of mental disorder and/or alcohol and/or drug abuse was evaluated. Throughout this period, the proportion of the deceased with a record of a mental disorder was high among all the cases examined and higher still among the cases of ID, especially among those younger than 65 years of age. There was a rather limited increase in the incidence of ID and a much more pronounced increase in the number of former psychiatric patients whose deaths were subjected to medicolegal examination, but did not satisfy the criteria for ID. A record of alcohol and/or drug abuse was more common than a diagnosis of mental disorder among both the males and females who died at an age of less than 65, with a clear difference between the cases of ID and non-ID in the case of men. There was no significant increase in incidence over the course of this study. Thus, this study reveals a slight increase in the number of IDs and a more pronounced increase in the number of medicolegal examination of non-IDs of individuals with a record of a mental disorder.     

Investigations on the cause of death in a polytoxicomanic patient treated with wires and intermaxillary fixation for a chronic, infected mandibular fracture

The case of a 36-year-old male and former patient is presented who died for initially unknown reasons, with intermaxillary wire fixation for the treatment of an infected mandibular fracture still in place. The combined investigation of forensic experts and maxillofacial surgeons excluded aspiration and asphyxia as cause of death. Evidence was found for lethal methadone concentrations after intravenous drug abuse and a broncho pneumonia. Despite the clear evidence of a fatal intoxication in this case, caution must be exercised when dealing with individuals carrying intermaxillary fixation.     

Suicide: a ten-year retrospective review of Kentucky medical examiner cases

Suicide, a manner of death, ranked as the eleventh leading cause of death in the United States and accounted for approximately 30,000 deaths in 2001. A host of biological and psychosocial components interplay in a suicide investigation. Precipitating factors may include domestic quarrels, loss of employment, financial difficulties, substance abuse, chronic disease, or mental illness. The authors conducted a ten-year (1993--2002) retrospective review of suicide from all Medical Examiners' Offices in Kentucky. There were 2,864 suicides ranging between 11 and 96 years (average age 42.0 years). The majority of victims were males (81.7%) and Caucasian (94.8%). African-American females comprised the smallest group, consisting of only 0.59%. The preferred mode of death was by firearm (67.5%), followed by hanging (13.7%), overdose (9.9%), and carbon monoxide poisoning (4.4%). This comprehensive study discusses the trends of suicide in the United States during the twentieth century and underscores the importance of a multidisciplinary approach to the investigation and prevention of suicide.     

Analysis of cocaine-positive fatalities

A review of all autopsy and toxicology reports for persons dying in New York City in an 11-month period found 935 persons dying with cocaine in their bodies. Cocaine-positive fatalities were more likely in the young black and Hispanic and male population. In addition to cocaine and its metabolites, heroin and other opiates were found in 39% of persons and ethanol in 33% and barbiturates and minor tranquilizers in only 2% of the deceased. Cocaine overdose was responsible for 4% of the deaths and overdose with heroin and cocaine for 12% of the deaths. Violence was often the cause of death. Thirty-eight percent died of homicide, seven percent of suicide, and eight percent from accidents. Of particular interest were 6 persons who died of acute cardiac events directly related to cocaine as well as 4 cases of ruptured dissections of the ascending aorta, and 9 cases of cerebral hemorrhage. Autopsy findings for these individuals are described, and possible mechanisms of death are discussed.     

The Importance of Microscopic Examination of the Lungs in Decedents with Sustained Central Intravascular Catheters: A Nine‐Case Series

Indwelling intravascular catheters provide convenient access to healthcare personnel and also recreational intravenous drug users who inject suspensions of oral medications. A nine‐case series of autopsies of clinically stable decedents with indwelling catheters and sudden death is herein presented. Pulmonary histologic findings were consistent with intravenous administration of oral medications in all cases. In eight, the mechanism of death was directly attributed to occlusive vascular embolization of foreign material, with or without contribution of acute drug toxicity. In one, the mechanism of death was solely attributed to acute drug toxicity. Acute, massive embolization of foreign material may explain sudden death by vascular obstruction, whereas chronic repeated injections lead to obliteration of the pulmonary vasculature, increased pulmonary vascular resistance, and cardiac failure. Therefore, a complete autopsy with histologic examination of the lungs and toxicology testing is recommended in patients with indwelling catheters to determine the cause and mechanism of death.     

Fentanyl concentrations in 23 postmortem cases from the hennepin county medical examiner's office

The purpose of this study was to compare blood fentanyl concentrations in fentanyl-related deaths with fentanyl concentrations found incidentally at autopsy, as well as with fentanyl concentrations found in hospitalized patients receiving fentanyl. Between the years 1997 to 2005, 23 fentanyl-positive postmortem cases were identified. Nineteen of 23 (82.6%) cases were deemed to be drug overdoses. Fentanyl alone was responsible for 8 of the 19 (42.1%) overdose deaths. Mean and median fentanyl concentrations were 36 (SD 38) microg/L and 22 microg/L, respectively, range 5-120 microg/L. Seven of the cases were accidental, one undetermined. The remaining 11 of the 19 (57.9%) cases were mixed drug overdoses. Fentanyl concentrations in these cases were 31 (SD 46) microg/L, range 5-152 microg/L. All of the mixed drug overdoses were determined to be accidental. Four cases where fentanyl was considered an incidental postmortem finding were determined to be natural deaths. In hospitalized inpatients (n = 11) receiving fentanyl 2 of the patients receiving fentanyl for chronic pain for more than 3 months had concentrations of 8.5 microg/L and 9.9 microg/L. The other nine inpatient concentrations were less than 4 microg/L. In conclusion, blood fentanyl concentrations found in cases where fentanyl alone was determined to be the cause of death were similar to cases where fentanyl was part of a mixed drug overdose. There was also considerable overlap between fentanyl concentrations in fentanyl-related overdose deaths compared to hospitalized patients being treated for chronic pain. Fentanyl concentrations in postmortem cases must be interpreted in the context of the deceased's past medical history and autopsy findings.