Stephen J. Cina

PRIMARY CARDIAC TUMORS CAUSING SUDDEN DEATH: A REVIEW OF THE LITERATURE

Sudden unexpected death accounts for 200,000-400,000 deaths each year in the United States. Although the vast majority of these fatalities are related to atherosclerotic heart disease, a small percentage (approximately 0.0025%) stem from primary cardiac neoplasms. There have been 120 cases of sudden death attributed to primary cardiac tumors in the (published) literature. Although 103 of these lesions were histologically benign (86%), their intracardiac locations precipitated conductive and hemodynamic abnormalities that resulted in sudden death. These tumors are usually easily recognized at necropsy. The most common intracardiac lesion causing sudden death, endodermal heterotopia of the atrioventricular (AV) node, however, may not be discovered unless the AV node is microscopically examined. Owing to the rarity of these neoplasms, a brief review of their salient gross and microscopic features is in order.

Tissue distribution of tramadol and metabolites in an overdose fatality

Tramadol (Ultram) is a centrally acting, synthetic analgesic agent. Although it has some affinity for the opiate receptors, tramadol is believed to exert its analgesic effect by inhibiting the re-uptake of norepinephrine and serotonin. There are several published cases of tramadols involvement in drug-related deaths and impairment. Reports of deaths involving tramadol alone with associated tissue concentrations are rare. This report documents a case in which tramadol overdose was identified as the cause of death. The following tramadol concentrations were found in various tissues: blood, 20 mg/L; urine, 110.2 mg/L; liver, 68.9 mg/kg; and kidney, 37.5 mg/kg. Tissue distributions of the two primary metabolites, N-desmethyl and O-desmethyl tramadol, are also reported. In each tissue or fluid except urine, the tramadol concentration was greater than either metabolite, consistent with other reports of drug-impaired drivers and postmortem cases. The O-desmethyl metabolite concentration was greater than the N-desmethyl metabolite concentration in all tissues; this is in contrast to other postmortem reports, in which the majority of cases report concentrations of O-desmethyl as less than those of N-desmethyl. This may be useful as an indicator of time lapse between ingestion and death.

Hydrogen peroxide: a source of lethal oxygen embolism. Case report and review of the literature

Hydrogen peroxide is a readily available clear, odorless liquid that is commonly used as an irrigant for superficial wounds. It is not widely thought of as a poison; however, it may rarely be the cause of accidental death. A case of fatal oxygen embolism in a child after ingestion of hydrogen peroxide is reported. A total of five similar cases have been previously described. Morbidity and mortality have also been reported with the use of hydrogen peroxide in hospitals. Gastric catabolism of hydrogen peroxide produces oxygen and water. When the amount of oxygen evolved exceeds its maximal blood solubility, venous embolization occurs. Hydrogen peroxide should not be considered to be innocuous; it should neither be ingested nor used in situations where the evolved oxygen gas cannot dissipate freely. The ubiquitous nature of household peroxide and its erroneous benign reputation suggest that child-resistant containers are in order. A protocol delineating the medicolegal investigation and postmortem examination of fatalities caused by the ingestion of this substance is offered.

Multifactorial analysis of firearm wounds to the head with attention to anatomic location

Firearm wounds to the head are often fatal and are routinely encountered in the practice of forensic pathology in the United States. Often, the anatomic site of the entrance wound is used to support or refute the manner of death indicated by the scene investigation and/or circumstances of the case. The present retrospective study of 120 fatalities resulting from 140 firearm wounds to the head correlates the anatomic region of the entrance wound and range of fire with the manner of death. Other demographic data analyzed include age, race, and gender of the decedents, as well as evidence of drug and/or ethanol use. It is hoped that this study will provide concrete data to support the largely anecdotal associations between the specific site of entry of firearm injuries to the head and the manner of death.

Serum concentrations of cardiac troponin I in sudden death: A pilot study

Sudden cardiac death due to lethal arrhythmia may be the initial presenting symptom of ischemic heart disease. In many cases, in the absence of trauma, a majority of these deaths will be visually inspected by a medical examiner and released with death being ascribed to atherosclerotic cardiovascular disease, coronary artery disease, arrhythmia, myocardial infarction, or a similar diagnosis. When an autopsy is performed, there may be significant cardiovascular disease but no gross or histologic evidence of an acute myocardial infarct unless the patient survived for several hours following the event. Biochemical assays of creatine kinase MB fraction (CKMB) performed on serum have been used to document myocardial injury in the absence of morphologic changes. Newly developed assays for cardiac troponin I (cTnI) may detect myocardial injury with a greater sensitivity than CKMB. A prospective study was performed on 28 autopsied patients at the Office of the Chief Medical Examiner of the state of Maryland. Subclavian blood was sampled for subsequent analysis of serum CKMB and cTnI. In 3 cases of cardiac-related death, there was insufficient plasma for analysis of both CKMB and cTnI, and only CKMB was quantitated. In 12 cases, hemolysis rendered interpretation questionable. Of the remaining 16 cases, the mean serum CKMB level was 857.9 ng/ml (n = 7) and the cTnI level was 93.4 ng/ml (n = 4) for cardiac-related deaths, compared with mean CKMB levels of 116.4 ng/ml (n = 9) and mean cTnI levels of 16.6 ng/ml (n = 9) for non-cardiac-related deaths. The differences in serum elevation of both CKMB and cTnI noted between the cardiac- and non-cardiac-related deaths were statistically significant. Serum cTnI concentrations >40 ng/ml were only noted in cardiac-related deaths. These data suggest that an elevated postmortem serum concentration of cTnI reflects ischemic heart disease and supports its use in determining cause of death. Quantitation of this analyte may prove useful when death may be due to an arrhythmia following a morphologically undetectable microinfarct.

A rapid postmortem cardiac troponin T assay: laboratory evidence of sudden cardiac death.

Postmortem examination may be useful in establishing the cause of sudden unexpected death. In many instances, however, limitations of staffing, budget, and time may force the pathologist to triage cases to external examination rather than autopsy. A rapid assay for cardiac troponin T (cTnT) to document suspected cardiac-related deaths may optimize the use of the time and resources of the autopsy pathologist. Peripheral blood was sampled percutaneously before each of 40 autopsies and placed in the well of the Cardiac T Rapid Assay unit in accordance with the included instructions, and the results were read after 15 minutes. The assay result, decedent age, postmortem interval, and evidence of cardiopulmonary resuscitation were tabulated and subsequently correlated with the cause of death. On final sign-out of each of the autopsies, the cause of death was determined to be cardiac-related (n = 20) versus the cause in noncardiac control subjects (n = 20). This determination was made while the investigators were blinded to the cTnT assay result. Of the 20 cardiac deaths, 17 (85%) showed positive results for cTnT compared with 6 (30%) false-positive results among the 20 control cases; this result was statistically significant according to the chi-square test. In the over-50 age group, the sensitivity of this assay in detecting cardiac-related death was 91%, with a specificity of 86%. Perimortem cardiopulmonary resuscitation did not appear to result in false-positive results. In the appropriate setting, this rapid assay for cTnT can provide valuable data supportive of a cardiac-related death. This inexpensive test may best be used in triaging sudden deaths in persons over 50 to external examination versus complete autopsy.

Sudden death due to metronidazole/ethanol interaction.

Metronidazole (Flagyl), a commonly prescribed antimicrobial agent, can produce a reaction similar to that of disulfiram (Antabuse) when administered to patients drinking ethanol. This drug/chemical interaction results in accumulation of acetaldehyde in the blood. Acetaldehyde is hepatotoxic, cardiotoxic, and arrythmogenic; no lethal serum acetaldehyde level has been established. Sudden death has been reported in patients taking disulfiram while using ethanol; no fatalities have been reported due to ethanol/ metronidazole interactions. Described is a case of a 31-year-old woman who died moments after an assault by a male companion, during which he inflicted minor physical trauma to her upper arm. Toxicologic analysis yielded elevated concentrations of serum ethanol (162 mg/d), acetaldehyde (4.6 mg/d), and metronidazole (0.42 mg/L). The cause of death was reported to be cardiac dysrhythmia due to acetaldehyde toxicity due to an ethanol/ metronidazole interaction. Autonomic stress associated with the assault is likely to have contributed to this womans death. The mechanism of death is examined.

Flow cytometric evaluation of DNA degradation: a predictor of postmortem interval?

The time of death of an individual can easily be determined if the postmortem interval can be assessed. Although livor mortis, rigor mortis, and, to a lesser degree, algor mortis have been used to estimate the postmortem interval, most experienced forensic pathologists agree that these characteristics provide, at best, “postmortem windows.” Quantitation of the vitreous fluid potassium level has been of some value in evaluating the early postmortem interval, but the accuracy of this method is dependent on external conditions, the availability of vitreous fluid (e.g., burned bodies, head trauma), and the purity of the sample. A simple, relatively inexpensive assay performed on readily available tissues, less dependent upon external factors, and providing data that could be plotted on a reproducible control curve would be of value in determining the postmortem interval accurately. This office is currently investigating flow cytometric DNA content analysis performed on splenic tissue harvested from a series of autopsies with known postmortem intervals. Preliminary data suggest that DNA degradation occurs in a predictable pattern over the intermediate postmortem period. A graph is being generated that will plot the degree of DNA fragmentation with respect to the postmortem interval. It is hoped that sections of spleen from “unknown” cases could be submitted for flow cytometric analysis of DNA content and plotted on the curve to estimate the postmortem interval and, thus, determine the time of death.

Stereolithography: a potential new tool in forensic medicine.

Stereolithography is a computer-mediated method that can be used to quickly create anatomically correct three-dimensional epoxy and acrylic resin models from various types of medical data. Multiple imaging modalities can be exploited, including computed tomography and magnetic resonance imaging. The technology was first developed and used in 1986 to overcome limitations in previous computer-aided manufacturing/milling techniques. Stereolithography is presently used to accurately reproduce both the external and internal anatomy of body structures. Current medical uses of stereolithography include preoperative planning of orthopedic and maxillofacial surgeries, the fabrication of custom prosthetic devices; and the assessment of the degree of bony and soft-tissue injury caused by trauma. We propose that there is a useful, as yet untapped, potential for this technology in forensic medicine.

Isolation and identification of female DNA on postcoital penile swabs.

After sexual assault, cells originating from the assailant may be recovered from the victim. Through polymerase chain reaction (PCR)-based technology, positive scientific identification of the assailant may be made from these cells. Described is a prospective study describing a method for positively identifying cells from a female sex partner obtained from postcoital swabs of the penis of the male sex partner. Swabs were taken from the penis of a man at 1- to 24-hour intervals after coitus. DNA was isolated from each swab through standard organic extraction methods. The presence of female DNA was detected using the gender-specific amelogenin marker. Extracted DNA was amplified for eight different genetic loci using the Promega PowerPlex kit (Promega) and Amplitaq Gold (Perkin Elmer). Amplified samples were electrophoresed on precast sequencing gels (Hitachi) and were analyzed fluorescently using Hitachis FMBIO 2 fluorescent scanner and software. Each sample obtained from a penile swab or condom was compared to male and female buccal controls. Female DNA was isolated from all postcoital penile swabs as determined by exclusive amplification of the X-chromosome specific 212 base pair amelogenin marker. In all cases, scientific identification of the female DNA from the swabs was determined by coamplification of eight STR loci (PowerPlex) and was compared to female and male control profiles. Cells shed from a female victim during sexual intercourse can be retrieved from the penis of a male offender after sexual intercourse during a 1- to 24-hour postcoital interval. DNA can be extracted from these cells and can be used to scientifically identify the female sexual participant through PCR-based technology. It is suggested that penile swabs be taken from alleged perpetrators of sexual assaults to associate them with a female victim.