John C. Hunsaker

Induction of Alzheimer-like β-Amyloid Immunoreactivity in the Brains of Rabbits with Dietary Cholesterol

beta-amyloid and ALZ-50 immunocytochemical reactivity were determined in the brains of rabbits fed either a control or 2% cholesterol diet. Control rabbits demonstrated no accumulation of intracellular immunolabeled beta-amyloid within 3 min after death. In animals fed the experimental diet for 4, 6, and 8 weeks (postmortem interval < 3 min), there was an increasingly mild-to-moderate-to-severe accumulation of intracellular immunolabeled beta-amyloid. Whether or not beta-amyloid is causally linked to processes leading to dementia, it is related in some way to the prime cause of human death; heart disease. Hypercholesterolemic rabbits may provide an animal model to study altered beta-APP metabolism leading to Alzheimer-like beta-amyloid accumulation xe03and extracellular deposition in brain.

Cortical senile plaques in coronary artery disease, aging and Alzheimer's disease

Mild alterations in cognitive function are present in normal aging and severe cognitive alterations are a hallmark of Alzheimers disease (AD). The cognitive change in AD has been correlated to the characteristic pathologic lesions in the brain, senile plaques (SP) and neurofibrillary tangles. Senile plaques are the most consistent correlative marker in AD. We present preliminary data indicating that abundant SP are found in the brains of nondemented patients dying with or as a result of critical coronary artery disease (cCAD) compared to nonheart disease (non-HD) subjects; 15 of 20 cCAD patients contained SP and only two of 16 non-HD patients contained SP.

Increased incidence of neurofibrillary tangles (NFT) in non-demented individuals with hypertension.

The incidence rates and numerical densities of argryophilic neurofibrillary tangles (NFT) and senile plaques (SP) were determined in non-demented individuals and subjects with Alzheimers disease (AD). The non-AD subjects were grouped according to cardiac status; those individuals with critical coronary artery disease (cCAD), those hypertensive individuals without cCAD (HyperT), and those without heart disease (non-HD). The incidence and densities of SP and NFT were significantly greater in AD than any of the non-demented groups. The prevalence of SP was increased in both HyperT and cCAD compared to non-HD controls, while NFT occurrence was accentuated in non-demented HyperT subjects only. The densities of SP and NFT in HyperT were elevated compared to cCAD or both cCAD and non-HD controls; NFT densities were similar in cCAD and non-HD. NFT density increased with increasing age in only the non-HD and cCAD groups, suggesting a possible relationship between disease process and NFT formation in the AD and HyperT populations.

Temporal Sequence of Plaque Formation in the Cerebral Cortex of Non-Demented Individuals

One of the hallmarks of Alzheimers disease is the presence of argyrophilic plaques (arg-P) accompanying dementia and other forms of cognitive alterations. In the present investigation 195 non-demented, cognitively normal patients were grouped according to the presence or absence of critical coronary artery disease (cCAD), defined as a 75% or greater stenosis of one of the epicardial arteries. None of the subjects had significant cerebral vascular disease. The parahippocampal gyrus (PHG) and frontal pole were analyzed for the presence of arg-P, A4 deposition, ALZ-50 immunoreactive (IR) neurons and neuropil threads (NT). Individuals with cCAD have a significantly greater incidence of plaques than non-heart disease (non- HD) subjects. Every cCAD subject had ALZ-50 IR neurons in the PHG and a greater incidence of NT as compared to the non-HD subjects. Every subject with plaques also had IR neurons and NT in the PHG. Based on the presumption that early neurodegeneration labeled by ALZ-50 antibody and amyloid deposition are in some way linked, then the sequence of plaque formation is initiated by the presence of ALZ-50 IR neurons followed in order by NT, A4 deposition and diffuse form arg-P.

Methadone Toxicity Fatalities: A Review of Medical Examiner Cases in a Large Metropolitan Area*

Abstract:  Over the past several years, Medical Examiners in Kentucky and around the nation have observed a dramatic rise in drug intoxication deaths involving the prescription medication methadone. This documented rise in methadone‐related deaths requires a better understanding of methadone’s pathophysiology and the ways it contributes to significantly increase morbidity and mortality. This study reviews 176 fatalities ascribed to methadone toxicity by the Office of the Chief Medical Examiner in Kentucky between 2000 and 2004. Postmortem toxicological analysis recorded a more than 10‐fold increase in methadone toxicity fatalities, rising from 6 cases in 2000 to 68 cases in 2003. Of the 176 methadone‐related fatalities, methadone was the only drug detected in postmortem blood and urine toxicological analyses in 11 (6.25%) cases. The mean methadone blood concentration of all 176 cases was 0.535 mg / L (0.02–4.0). The following psychoactive medications were detected: antidepressants (39.8%), benzodiazepines (32.4%), and other opioids in addition to methadone (27.8%). Cannabinoids were detected in 44 (28.4%) cases and cocaine or metabolite in 34 (21.9%) cases. Of the 95 cases with a known history of methadone use, 46 (48.4%) involved prescription by private physician. The interpretation of blood methadone concentrations alone or combined with other psychoactive drugs requires consideration of the subject’s potential chronic use of and tolerance to the drug. A thorough investigation into the practices of procurement and use/abuse of methadone is essential to arrive at the proper designation of the cause of death.

Increased density of senile plaques (SP), but not neurofibrillary tangles (NFT), in non-demented individuals with the apolipoprotein E4 allele: comparison to confirmed Alzheimer's disease patients

The apolipoprotein E genotype and cortical senile plaque (SP) and cortical and hippocampal neurofibrillary tangle (NFT) densities were determined in non-demented individuals and neuropathologically confirmed AD patients. The non-demented population was further subdivided according to presence or absence of pathologically established critical coronary artery disease (cCAD), hypertension (HyperT), or neither (non-heart disease; non-HD). The apolipoprotein E4 (APOE4) allele incidence and dose frequencies were increased in the AD, cCAD and HyperT groups compared to the non-HD controls. The mean number of SP and NFT was significantly increased with the presence of the APOE4 allele within the entire population. After grouping the non-demented subjects according to cardiac status, SP but not NFT density was increased among those individuals with the APOE4 genotype. In HyperT, the increased density of SP also correlated to the APOE4 allele dose frequency. The density of SP and NFT was increased in all regions of AD brain compared to all other non-demented groups, but no significant difference was found between AD patients with or without an APOE4 allele. These two AD groups were age-matched, but could not be matched for disease duration. The data suggest a relationship between heart disease, APOE4 genotype and the presence of SP regardless of cognitive status.

Hypothermia and hyperthermia medicolegal investigation of morbidity and mortality from exposure to environmental temperature extremes.

CONTEXT The determination of the cause of death from exposure to extreme temperatures is a diagnosis of exclusion. Because both clinical and autopsy findings are nonspecific, a thorough investigation of the background and scene, evaluation of temporally relevant environmental conditions, and assessment of the victims underlying state of health with appropriate laboratory studies, which frequently include autopsy, are essential to establish the cause of injury and/or death with reasonable medical probability. Individuals may encounter environmental extremes in many settings during any season. Both constitutional and external factors exacerbate the stress brought about by extreme temperature. OBJECTIVE This article reviews guidelines for forensic investigation into environmental temperature extremes that contribute to an important seasonal grouping of morbidity and mortality in the United States. DATA SOURCES Articles on clinical and pathologic aspects of hyperthermia and hypothermia were collected and reviewed. CONCLUSIONS Recognition of multiple risk factors predisposing humans to both cold-related and heat-related morbidity and mortality enhances prevention. Awareness of the susceptibility of these exposed at-risk individuals is crucial to investigations by both clinicians and medicolegal death investigators.

Spontaneous Coronary Arterial Dissection and Isolated Eosinophilic Coronary Arteritis: Sudden Cardiac Death in a Patient With a Limited Variant of Churg-Strauss Syndrome

Isolated eosinophilic coronary arteritis expressed as a limited variant of the Churg-Strauss syndrome (allergic granulomatosis and angiitis) is a rare condition. Equally as rare is the entity of isolated spontaneous coronary arterial dissection associated with eosinophilic arteritis. A 57-year-old woman with a history of asthma and recurrent hypersensitivity (anaphylactoid) reactions to various exogenous allergens was found dead in her home; no premonitory complaints had been noted during the preceding days. Autopsy revealed focal occlusion of the left anterior descending and first diagonal coronary arteries by discrete dissecting hematomas of the media as the cause of sudden and unexpected death. Histologically, the affected arterial wall showed eosinophilic inflammation characteristic of this limited expression of the Churg-Strauss syndrome. To our knowledge, sudden cardiac death caused by arterial dissection in isolated eosinophilic coronary arteritis has not previously been reported.

Abuse and neglect: A ten-year review of mortality and morbidity in our elders in a large metropolitan area

Elder abuse and neglect refers to an act or omission resulting in harm, including death, or threatened harm to the health or welfare of an elderly person. Between one and two million elderly Americans experience some form of mistreatment annually. A ten-year (1992-2001) retrospective case review of morbidity and mortality among elders (age > 60 years) was conducted at a State Medical Examiners Office serving a major metropolitan region in Kentucky and Indiana. This study addresses cases of two categories: 1) medicolegal autopsies and 2) examinations of living subjects pursuant to a Clinical Forensic Medicine Program. The authors present 74 postmortem cases, in which 52 deaths were attributed to a homicidal act and 22 deaths were suspicious for neglect. Of the 22 living victims of elder abuse and neglect, 19 cases constituted physical and/or sexual assault and three individuals suffered from neglect. This study summarizes the characteristic features of elder abuse in both postmortem and living cases and underscores the necessity for multi-agency collaboration in order to reach an accurate conclusion in case work. Policies established by a well-established elder abuse task force promote the collaborative interaction necessary to formulate criteria for prevention of abuse and death within this vulnerable population.

Toxicologic Findings in Suicide A 10-Year Retrospective Review of Kentucky Medical Examiner Cases

Toxicologic analysis is an integral component in the investigation of suicide and requires correlation with a detailed scene inspection, with an extensive exploration into the decedents medical and social background to uncover suicidal ideation or intent and a postmortem examination of the body. In this review, the authors analyzed 2864 cases classified as suicide upon autopsy and toxicologic examinations between 1993 and 2002 in the Kentucky Division of Medical Examiners Services. Blood and urine were collected in 95.0% and 72.3% of cases, respectively. A total of 32.5% of the victims had negative blood toxicologic results, and 52.7% of urine toxicology screens yielded no drugs. Analysis of the data indicated that 3 times as many women had taken antidepressants and more than twice as many had consumed opioids. Drug toxicity (“overdose”) ranked as the third (9.9%) leading cause of suicide after firearm injury (67.5%) and hanging (13.7%). Women succumbed to drug toxicity more than men (27.5% versus 5.9%). Of the overdose deaths, 66.5% had a negative blood alcohol concentration (BAC), while antidepressants, opioids, and benzodiazepines were detected in blood in 54.4%, 37.4%, and 29.2% of the subjects, respectively. The collection of these data serves the goals of public health and clinicians in devising strategies for suicide prevention.