Elizabeth Balraj

A Metabolic Basis for Alzheimer Disease

Most studies of Alzheimers disease (AD) have focused on a single precipitating alteration as the etiological event rather than global changes closely linked to aging. Recent evidence suggests that the most significant of these global changes are metabolic. Here we present data indicating that metabolic rate, nutrition, and neuronal size are all early indicators of AD. Understanding the cellular and molecular basis for these changes may open a new dimension to understanding AD.

Autonomic dysreflexia and sudden death in people with traumatic spinal cord injury.

Autonomic dysreflexia (AD) is an uncommon but potentially life-threatening clinical syndrome consisting of acute episodes of excessive, uncontrolled sympathetic output that may occur in quadriplegics and in paraplegics whose spinal cord lesions are above the level of T6. These uncontrolled bouts of sympathetic output can cause transient and pronounced elevations of blood pressure that on occasion can lead to serious sequela such as the precipitation of a hypertensive intracerebral hemorrhage. The episodes of AD are often triggered by some type of noxious stimulus such as a distended urinary bladder or a fecal impaction. We present the case of a 62-year-old man with a history of quadriplegia resulting from a diving accident 40 years ago that was complicated clinically by episodes of autonomic dysreflexia. While hospitalized, he experienced an episode of autonomic dysreflexia with severe hypertension, which was soon followed by neurologic deterioration and death. Antemortem imaging revealed a large hypertensive-type intracerebral hemorrhage originating in his right caudate nucleus. Although his death at first appeared to be a natural death due to a spontaneous hypertensive-type intracerebral hemorrhage, his clinically documented autonomic dysreflexia convincingly linked the remote spinal cord injury and the fatal intracerebral hemorrhage, engendering an accidental manner of death.

Quantitative distribution of monoamine oxidase A in brainstem monoamine nuclei is normal in major depression

An abnormal expression of noradrenergic proteins (e.g., tyrosine hydroxylase, norepinephrine transporters) in the locus coeruleus has recently been demonstrated in subjects with major depression and/or victims of suicide. Monoamine oxidase A (MAO-A) is a key enzyme in the catabolism of biogenic amines and is expressed in brain noradrenergic neurons. In this study, the binding of [3H]Ro41-1049 to MAO-A was measured by quantitative autoradiography at multiple levels along the rostral-caudal axis of the noradrenergic locus coeruleus from subjects with major depression and age- and postmortem interval-matched control subjects who were psychiatrically normal. [3H]Ro41-1049 binding to MAO-A was unevenly distributed along the axis of the locus coeruleus, paralleling an uneven number of neuromelanin-containing (noradrenergic) neurons throughout the nucleus. Accordingly, there was a significant correlation between the number of neuromelanin-containing neurons per section and the specific binding of [3H]Ro41-1049 at any particular level of the locus coeruleus in control subjects (r(2)=0.25; p<0.001) and in subjects with major depression (r(2)=0.14; p<0. 001). Moderate levels of [3H]Ro41-1049 binding were observed in regions surrounding the locus coeruleus, including the central gray and the dorsal and median raphe nuclei. No significant differences in [3H]Ro41-1049 binding to MAO-A were observed at any level of the locus coeruleus, or raphe nuclei, comparing subjects with major depression to psychiatrically normal control subjects. These findings demonstrate that the pathophysiology of major depression is not likely to involve abnormalities in MAO-A.

Indices of Metabolic Dysfunction and Oxidative Stress

Metabolic alterations are a key player involved in the onset of Alzheimer disease pathophysiology and, in this review, we focus on diet, metabolic rate, and neuronal size differences that have all been shown to play etiological and pathological roles in Alzheimer disease. Specifically, one of the earliest manifestations of brain metabolic depression in these patients is a sustained high caloric intake meaning that general diet is an important factor to take in account. Moreover, atrophy in the vasculature and a reduced glucose transporter activity for the vessels is also a common feature in Alzheimer disease. Finally, the overall size of neurons is larger in cases of Alzheimer disease than that of age-matched controls and, in individuals with Alzheimer disease, neuronal size inversely correlates with disease duration and positively associates with oxidative stress. Overall, clarifying cellular and molecular manifestations involved in metabolic alterations may contribute to a better understanding of early Alzheimer disease pathophysiology.

Drug prevalence in drowning deaths in Cuyahoga county, Ohio: a ten-year retrospective study

Previous studies have shown that up to 50% of adult drownings are related to the consumption of alcohol. Little information is available in the literature regarding the possible contribution of ethanol and other drugs to drownings. All records of deaths occurring in Cuyahoga County, Ohio, from 1994–2003, in which drowning was listed as the cause of death, were reviewed. Toxicology analysis was performed on cases where specimens were submitted. Review of the 187 cases showed that the majority (78%) of drowning deaths were ruled as accidents, 26 (14%) as suicide, 5 (3%) as homicide, and 11 (6%) as undetermined. Among the accidental deaths (n = 141), 97 (69%) were negative for all drugs, including ethanol, and 30 cases (21%) were positive for ethanol only. Illicit drugs were detected in 4 of the cases (3%). In the suicides (n = 26), 16 (62%) were negative for all drugs, including ethanol, and 7 cases (27%) were positive for ethanol only (mean blood alcohol concentration [BAC] 0.03 g/dL). Illicit drugs were detected in 3 of the cases (12%). Two of the 5 homicide cases (40%) were positive for ethanol. There were no cases in which the victim tested positive for illicit drugs. Of the 11 cases ruled as undetermined, 64% (n = 7) were negative for all drugs, including ethanol. The remainder of the cases tested positive for ethanol only. There were no cases in which illicit drugs were detected. This study demonstrates that the majority of drowning deaths in Cuyahoga County, Ohio, were not drug related. Deaths in which drugs were detected were typically accidental deaths, with ethanol the most common drug detected.

Sudden Death Due to Ventricular Septal Defect

ABSTRACT Ventricular septal defects (VSD) are usually considered non-life-threatening, usually closing spontaneously or causing symptoms of congestive heart failure, which can be surgically treated in time to save the patients life. Despite the usually benign clinical course of VSD, serious arrhythmias occur in 16–31% of patients. Sudden death accounted for one-third of all deaths in a series of medically managed patients and occurred in 4.2% of patients in a study of VSD and arrhythmias. Cardiac hypertrophy is the common denominator in all cases reported in detail of VSD-associated sudden death. We have encountered four cases of sudden unexpected death from VSD in infants ranging in age from 1 week to 3 and ½ months. In each case there was cardiomegaly and in one case there was pulmonary arteriolar medial thickening, with extension of smooth muscle into small intralobular vessels. In half of our cases the attending physician was sued for malpractice. We believe that VSD in infants and young children are potentially life-threatening malformations which warrant careful clinical follow-up.

Homicidal ethylene glycol intoxication: a report of a case.

We report a case of a 75-year-old hypertensive, diabetic man who presented to the emergency room with symptoms and signs of nausea, acute intoxication, significant alteration in mental status with rapid neurologic deterioration, and blunt impact injuries sustained during a recent altercation with a 36-year-old female companion-caretaker. He denied a history of ethanol abuse or other recent toxic ingestion and had not been diagnosed with or treated for depression. Hospital laboratory tests revealed a metabolic acidosis and a negative urine toxicology screen. He was diagnosed with toxic encephalopathy with metabolic acidosis secondary to metformin. Despite treatments including hemodialysis, he expired after approximately 28 hours of hospitalization. A postmortem anatomic examination revealed recent blunt-impact injuries and cardiac and renal pathology. A subsequent histologic examination revealed the presence of calcium oxalate crystals in the kidneys and brain, in addition to cardiac and renal pathology. Comprehensive forensic toxicologic testing was performed on antemortem and postmortem samples and revealed lethal levels of ethylene glycol. The cause of death was as a result of acute intoxication by ethylene glycol with another condition of multiple blunt impacts to the head, trunk, and extremities. The manner of death was ruled as homicide. A trial by jury, involving the female companion-caretaker, resulted in her conviction, and she was sentenced to 23 years to life in prison. In this report, we present an unusual case of homicidal ethylene glycol intoxication in which legal proceedings have occurred.

DNA Typing of Samples for Polymarker, DQA1, and Nine STR Loci from a Human Body Exhumed After 27 Years

A body was exhumed from the ground after 27 years. Samples of femur bone, tooth, and a fingernail were collected and successfully subjected to DNA extraction, quantitation, amplification, and subsequently typed for DQA1, polymarker, and nine STR loci. All three types of samples were typed for D3S1358, vWA, FGA, D8S1179, D21S11, D18S51, D5S818, D13S17, D7S820, and amelogenin using ABI Prism 377 DNA sequencer.

Atherosclerotic Coronary Artery Disease and “Low” Levels of Carboxyhemoglobin; Report of Fatalities and Discussion of Pathophysiologic Mechanisms of Death

Levels of carboxyhemoglobin that would ordinarily cause little or no noticeable symptoms or other effects proved fatal in individuals suffering from atherosclerotic coronary artery disease. All such deaths that occurred in the Cuyahoga County during a period of 23 years were studied. The pathophysiologic mechanisms that may be operative in these deaths are discussed. The importance of being aware of this fact, while one determines the cause and manner of such deaths, is stressed.