Lisa B. E. Shields

Induction of immune responses to ovarian tumor antigens by multiparity

Objective: Because epidemiologic data indicate a reduction in ovarian cancer risk with increased parity, the occurrence of maternal immunization against ovarian tumor-associated antigens during pregnancy was investigated. Methods: Sera were obtained from nulligravid and multiparous women and from men. Cellular proteins were isolated from four ovarian tumor cell lines as well as from normal ovaries. These proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and the presence of cellular proteins reactive with each individuals serum was assessed by Westrn immunoblot. Tumor-reactive antibodies from two multiparous women were used to prepare immunoaffinity columns for the isolation of reactive proteins from ovarian turmor cells. These immunoaffinity-purified antigens were transferred electrophoretically to nitrocellulose membranes, stained with Ponceau S, and identified by amino acid sequencing. Results: Western immunoblot analysis of the cellular proteins from four established ovarian tumor cell lines using sera from multiparous women as the primary antibody indicated that these samples recognized multiple bands on ovarian tumors, ranging from 30 to 150 kD. Two commonly recognized proteins were isolated and subjected to microsequencing, which identified the 56-kD band protein as elongation factor-1α and the 38-kD protein as nucleophosmin/B23 protein. Both of these proteins play integral roles in cell growth. Conclusion: These findings suggest that certain antigens expressed by the fetus immunize women during pregnancy. This immune response may protect these women from the subsequent development of cancer.

Alterations in humoral immune responses associated with recurrent pregnancy loss

OBJECTIVE To investigate the reactivity of maternal antibodies with endometrium-derived antigens and to correlate their association with recurrent pregnancy loss (RPL). DESIGN Prevalence study. SETTING Academic research center. PATIENT(S) Nulliparous women (n = 10), women with RPL (n = 15), pregnant women (n = 8), and multiparous women with a normal obstetric history (n = 20). INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Reactive antibodies were analyzed by Western immunoblot techniques and quantitated by densitometry. RESULT(S) Antibodies from women with RPL and multiparous women recognized antigens ranging from 10-120 kd on normal endometrium and endometrial tumors. Antibodies from most women with RPL (10/15) and from multiparous women (15/20) recognized 65-kd and 80-kd proteins in normal endometrium. Antibodies from women with RPL recognized 21-kd and 28-kd antigens (12/15 and 13/15, respectively) in endometrial tumors at a significantly greater rate (than did antibodies from multiparous women (5/20 and 8/20, respectively). Women with RPL had significantly lower levels of asymmetric IgG compared with controls. CONCLUSION(S) Recurrent pregnancy loss may be linked with the failure to elicit asymmetric IgG and a unique immunologic recognition of endometrial antigens.

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.

Benefit of chondroitinase ABC on sensory axon regeneration in a laceration model of spinal cord injury in the rat

BACKGROUND Chondroitin sulfate proteoglycans are up-regulated in the spinal cord after SCI, creating a molecular barrier inhibitory to axon growth. Chondroitinase ABC degrades CSPGs in vitro and in vivo. METHODS We studied whether IT ChABC promotes axonal regeneration in a laceration model of SCI. Three groups of Sprague-Dawley rats were used: control and rats treated with low-dose and high-dose IT ChABC. Chondroitin sulfate proteoglycan breakdown products were measured by 2-B-6 expression, and intact CSPGs by CS-56 expression. Sensory axonal regeneration was traced after CTB injection into the median, ulnar, and sciatic nerves. RESULTS CS-56 expression was down-regulated and 2-B-6 expression was increased in the groups treated with IT ChABC but not in the control. Laminin and GFAP immunoreactivity was unaltered in the ChABC groups. The number of axons growing into the scar was 3.1 times greater (P < .01) in the high-dose ChABC group and 2.1 times greater (P < .01) in the low-dose group compared with the controls. The length of axonal growth after high- and low-dose ChABC was 9.9 (P < .01) and 8.3 (P < .01) times greater, respectively, than in the control group. Axons extended across the lesion gap and into the distal spinal cord stump in 2 of 8 (low dose) and in 3 of 9 (high dose) rats compared with none in the control group. CONCLUSIONS Intrathecal ChABC administration caused a slight decrease in CSPGs in the scar after a laceration SCI with a minimal increase in sensory axonal regeneration into and across the laceration gap.

Use of magnetic stimulation to elicit motor evoked potentials, somatosensory evoked potentials, and H-reflexes in non-sedated rodents

Assessment of locomotor function of rodents may be supplemented using electrophysiological tests which monitor the integrity of ascending and descending tracts as well as the focal circuitry of the spinal cord in non-sedated rodents. Magnetically induced SSEPs (M-SSEPs) were elicited in rats by activating the hindpaw using magnetic stimulation (MS). M-SSEP response latencies were slightly longer than those elicited by electrical stimulation. M-SSEPs were eliminated following selective dorsal column lacerations of the spinal cord, indicating that they were transmitted via this tract. Magnetically induced motor evoked potentials (M-MEPs) were elicited in mice following transcranial MS and recorded from the gastrocnemius muscles. M-MEPs performed on myelin deficient mice demonstrated longer onset latencies and smaller amplitudes than in wild-type mice. Magnetically induced H-reflexes (MH-reflexes) which assess local circuitry in the lumbosacral area of the spinal cord were performed in rats. This response disappeared following an L3 contusion spinal cord injury, however, kainic acid (KA) injection at L3, known to selectively destroy interneurons, caused a shorter latency and an increase in the amplitude of the MH-reflex. M-SSEPs and MH-reflexes in rats and M-MEPs in mice compliment locomotor evaluation in assessing the functional integrity of the spinal cord under normal and pathological conditions in the non-sedated animal.

Autoerotic asphyxia: Part I

Fatal autoerotic asphyxia refers to death during solitary sexual activity with self-induced asphyxiation meant to be brief and reversible. However, an unexpected fatality results from a failure of a release mechanism apparatus. The large majority of victims of autoerotic death are Caucasian males between the second and fourth decade. While autoerotic death may encompass a myriad of other means of achieving sexual gratification, which includes asphyxia by plastic bag or inhalation of noxious chemicals, the most common method is by ligature about the neck. This study presents a 9-year retrospective review of deaths due to autoerotic asphyxia, specifically ligature asphyxia, in Kentucky between 1993 and 2001. Of the sixteen victims, all were Caucasian males between the ages of 14 and 59 years, with a mean age of 38.3 years. Cross-dressing was a feature in 4 cases. A thorough review of the decedents background, meticulous scene investigation, and complete postmortem examination may shed light on the mechanism and psychosocial predisposition associated with autoerotic asphyxia.

Atypical autoerotic death. Part II

Autoerotic fatalities encompass a wide array of means and mechanisms used to attain sexual gratification. The most commonly encountered autoerotic practice, specifically, autoerotic asphyxia, denotes death resulting from failure of a release mechanism of the apparatus designed to attain cerebral hypoxia for heightened arousal. Historically, the majority of victims of autoerotic death are Caucasian males under the age of 30. While autoerotic death is most often associated with a constrictive cervical ligature tied to either other parts of the victims body or to an inanimate object such as a door, several other methods have been reported. These modalities include ligature around the thorax or abdomen, plastic bags covering the face, electrical current, inhalation of a toxic gas or chemicals, or partial or total submersion, known as aquaerotic asphyxiation. This study highlights 11 cases of atypical autoerotic death, including asphyxia with a plastic bag, electrocution, and inhalation of butane and nitrous oxide (N2O). Whereas the manner of death in the majority of autoerotic death cases is deemed accidental, we present and analyze unique and equivocal cases representing 4 different manners of death: accident, natural, suicide, and homicide. The 11 victims were all Caucasian and between the ages of 17 and 55. Ten decedents were males, 1 female. A comprehensive investigation incorporating a thorough scene analysis, gathering of the victims history, and complete postmortem examination is necessary to elucidate both the cause and manner of death in these atypical cases.

Nonterrorist suicidal deaths involving explosives.

Suicidal deaths involving explosives unconnected to terrorism are rare. The investigation of deaths from explosive devices requires a multidisciplinary collaborative effort, as demonstrated in this study. Reported are 2 cases of nonterrorist suicidal explosive-related deaths with massive craniocerebral destruction. The first case involves a 20-year-old man who was discovered in the basement apartment of his father’s home seconds after an explosion. At the scene investigators recovered illegal improvised power-technique explosive devices, specifically M-100s, together with the victim’s handwritten suicide note. The victim exhibited extensive craniofacial injuries, which medicolegal officials attributed to the decedent’s intentionally placing one of these devices in his mouth. The second case involves a 46-year-old man who was found by his wife at his home. In the victim’s facial wound, investigators recovered portions of a detonator blasting cap attached to electrical lead wires extending to his right hand. A suicide note was discovered at the scene. The appropriate collection of physical evidence at the scene of the explosion and a detailed examination of the victim’s history is as important as documentation of injury patterns and recovery of trace evidence at autopsy. A basic understanding of the variety of explosive devices is also necessary. This investigatory approach greatly enhances the medicolegal death investigator’s ability to reconstruct the fatal event as a means of separating accidental and homicidal explosive-related deaths from this uncommon form of suicide.

Dog Bite-related Fatalities: A 15-year Review of Kentucky Medical Examiner Cases

A human dog bite-related fatality generally refers to death proximately caused by trauma from a dogs teeth and jaws. According to The Humane Society of the United States, more than 300 individuals died of dog attacks in the United States between 1979 and 1996. Children <12 and elders >70 years represent the typical victims. Pit bull-type dogs, Rottweilers, and German Shepherds constitute the majority of canines implicated in these fatalities. This is a 15-year (1991–2005) retrospective review of dog bite-related fatalities undergoing medicolegal investigation in Kentucky. Of the 11 deaths, 10 consisted of multiple bite marks and blunt force injuries of the head and neck, trunk, and extremities. In 1 case, an asplenic victims immediate cause of death was bacterial sepsis secondary to a dog bite. Individuals ranged between 14 months and 87 years; 7 (63.6%) were ≤6 years; 10 (90.9%) individuals were white, and 8 (72.7%) were male. Forensic odontological examinations were performed on the dogs in 4 cases. The requisite multidisciplinary investigation includes a detailed assessment of the scene, the victim, and dog or dogs suspected in the attack.