Preliminary study on diffuse axonal injury by Fourier transform infrared spectroscopy histopathology imaging.

The objective of this study was to evaluate the application of Fourier transform infrared (FTIR) spectroscopy for detecting diffuse axonal injury (DAI) in a mouse model. Brain tissues from DAI mouse model were prepared with H&E, silver, and ß-amyloid precursor protein (ß-APP) immunohistochemistry stains and were also studied with FTIR. The infrared spectrum images showed high absorption of amide II in the subcortical white matter of the experimental mouse brain, while there was no obvious expression of amide II in the control mouse brain. The areas with high absorption of amide II were in the same distribution as the DAI region confirmed by the silver and ß-APP studies. The result suggests that high absorption of amide II correlates with axonal injury. The use of FTIR imaging allows the biochemical changes associated with DAI pathologies to be detected in the tissues, thus providing an important adjunct method to the current conventional pathological diagnostic techniques.

Methylenedioxypyrovalerone ("bath salts"), related death: case report and review of the literature.

Cathinone derivatives (bath salts) have emerged as the latest drugs of abuse. 3,4-methylenedioxypyrovalerone (MDPV) is the primary active ingredient in bath salts used in this country. This article presents the second reported cause of death by MDPV intoxication alone. In April 2011, a delusional man was emergently brought to a hospital, where he self-reported bath salt usage. He became agitated, developed ventricular tachycardia, hyperthermia, and died. Comprehensive alcohol and drug testing was performed. Using the alkaline drug screen, heart blood contained 0.7 mg/L MDPV and peripheral blood contained 1.0 mg/L MDPV. His bizarre behavior with life-threatening hyperthermia was consistent with an MDPV-induced excited delirium state. MDPV is not yet found by routine immunoassay toxicology screens. Testing for MDPV should be considered in cases with a history of polysubstance abuse with stimulant type drugs, report of acute onset of psychogenic symptoms, excited delirium syndrome, or presentation in a hyperthermic state.

Anaphylaxis after the injection of buprenorphine.

Cause of death rulings in cases when the concentration of a drug or drugs is higher than observed following therapeutic use are generally straightforward "drug deaths." However, when toxicology testing identifies drug concentrations consistent with therapeutic use or detects no drugs at all, then the cause of death determination is more complicated. Given the rapidity and protean manifestations of anaphylaxis, it should be considered in deaths where no other cause of death is apparent in a suspected drug death. This article reports two cases where an anaphylactic reaction was observed following either the actual or alleged use of therapeutic formulations of buprenorphine intravenously.

[Correlation between the changes of oxidation reduction potential values and postmortem interval of heart blood in rabbits after death].

OBJECTIVE: To investigate correlation between the changes of oxidation reduction potential (ORP) values of heart blood in rabbits after death and postmortem interval (PMI) at different temperatures. METHODS: Forty-eight rabbits were randomly divided into 6 groups and sacrificed by air embolism. Blood samples were taken from the right ventricle of each rabbit and stored at different temperatures of 10, 15, 20, 25, 30 and 35 degrees C, respectively. Every 4 hours from 0 h to 132 h postmortem, the ORP values of the blood samples were measured at different intervals by PB-21 electrochemical analyzer. The curvilinear regression equation was established by SPSS 17.0 software. The surface equation and 3D surface diagram were established by MATLAB 7.10.0 software. RESULTS: The ORP values at different temperatures of heart blood in rabbits were highly correlated with the PMI. The ORP values rised obviously when the temperature was high and rised slowly when the temperature was low. The surface equation and 3D surface diagram were obtained. CONCLUSION: The surface equation and 3D surface diagram of ORP values and PMI may be used for PMI estimation at different temperatures.

The role of focal myocardial inflammation in sudden unexpected cardiac and noncardiac deaths--a clinicopathological study.

The significance of focal myocardial inflammation in sudden death is poorly understood, because there are few studies addressing its frequency in noncardiac and cardiac arrhythmic deaths. We prospectively assessed inflammation in 384 consecutive hearts seen in consultation from a single medical examiners' office. Hearts were received intact and sectioned uniformly in five areas and reviewed histologically by a single pathologist. Intrinsic inflammatory diseases of the myocardium were excluded. Infiltrates were classified as lymphocytic without necrosis, lymphocytic with myocyte necrosis, and eosinophilic. Histologic findings were retrospectively correlated with other cardiac findings, history of drug and medication use, postmortem toxicology, and cause of death. In the 384 hearts, any infiltrate was found in 18%. There were multifocal infiltrates in 9%, inflammation with necrosis in 2%, and eosinophilic myocarditis in 4%. Infiltrates were most frequent in natural noncardiac deaths (31%), and least frequent in traumatic deaths (12%). Infiltrates with myocyte necrosis occurred in 4% of arrhythmic deaths with no other cause, 3% of cardiac deaths with cardiomegaly, 3% of traumatic deaths, 2% of natural noncardiac deaths, 2% of other cardiac deaths, and 1% of coronary deaths. Infiltrates were common in patients on antibiotics (54%) or neuroleptic drugs (27%). Eosinophilic infiltrates were especially common in patients on antibiotics (18%). We conclude that incidental cardiac inflammatory infiltrates without necrosis are not uncommon, but focal myocarditis, defined as inflammation with necrosis, occurs in about 5% of hearts, and may be considered a possible contributory factor. Incidental infiltrates are common in patients on medications, especially antibiotics.

Diabetic ketoacidosis: a silent death.

Diabetic ketoacidosis (DKA) results from severe insulin deficiency and can be diagnosed at autopsy despite no known history of the disease. Diabetic ketoacidosis may be the initial manifestation of type 1 diabetes or may result from increased insulin requirement in type 1 diabetic patients. The purpose of this study was to determine the percentage of DKA death investigated by the Office of Chief Medical Examiner that was not associated with a known history of diabetes.Cases investigated by the Office of Chief Medical Examiner during a 6-year period whose cause of death was DKA were identified using a centralized database. To determine the percentage with known history of diabetes, investigation reports were reviewed for any documentation of this history. The toxicology reports of all DKA deaths were reviewed together with histologic slides, if available, for possible microscopic changes. Concentrations of vitreous glucose, vitreous acetone, and blood acetone were used to diagnose DKA in these autopsied cases.Nearly a third of all death from DKA (32 of 92 during a 6-year period) occurred in individuals who had no known history of diabetes, emphasizing the importance of regular physicals that include a check of glucose concentration, and especially if any warning signs are present. In a case of sudden death, it is recommended that the volatile toxicology analysis at a medical examiner's office should include tests for acetone concentration, which when elevated, together with an elevated vitreous glucose, indicates DKA.

Sudden coronary death caused by pathologic intimal thickening without atheromatous plaque formation.

BACKGROUND: Atherosclerotic plaques progress from early lesions with little free cholesterol and lipid to late fibroatheromas with necrotic cores that may rupture. The frequency of severe coronary atherosclerosis without core formation in any artery in sudden coronary death is not known. METHODS: We studied 314 hearts from 253 men and 61 women who died suddenly from severe coronary stenosis (≥ 1 epicardial artery with ≥ 75% luminal area narrowing) and with no other cause of death. If no section demonstrated any necrotic core, the designation was nonatheromatous atherosclerosis; if there was ≥ 1 necrotic core, the designation was atheromatous atherosclerosis. Plaques were scored for the presence of calcification, intimal inflammation, and neovasculature on a 5-point scale. Plaque burden was estimated semiquantitatively. RESULTS: In 22 men (9%) and 14 women (23%), there were no necrotic cores in any plaque (nonatheromatous atherosclerosis). Fourteen of these 36 nonatheromatous atherosclerosis cases had focal acute thrombus due to erosion (39%). Of the remaining 278 cases (atheromatous atherosclerosis), acute erosions were present in 25 (9%; P<.0001). Sudden death due to nonatheromatous atherosclerosis occurred more frequently in women (P<.001), in Blacks (20%; P=.003), and at a younger age (44± 12 years) than atheromatous atherosclerosis (52 ± 12 years; P=.0003). On multivariate analysis, nonatheromatous atherosclerosis was associated with younger age (P=.001), female gender (P=.004), and Black race (P=.006). CONCLUSIONS: Nonatheromatous atherosclerosis constitutes slightly >10% of sudden coronary deaths and is more frequent in young Black women. Nonatheromatous atherosclerosis is a relatively infrequent pathway for coronary plaque progression, leading to severe disease and sudden death that may involve plaque erosion.

[Analysis of death cases involved in TASER in the State of Maryland].

OBJECTIVE: To evaluate the features of autopsy cases involved in electronic weapon (TASER) in the State of Maryland, and to discuss the appraisable points. METHODS: Thirteen autopsy cases involving TASER were collected from 2004 to 2011 in the Office of the Chief Medical Examiner, State of Maryland. All the cases include detailed scene investigations, complete autopsy, toxicological analysis and histopathological examination. Statistical analysis were conducted including general information of victim, type of TASER, type of contact, toxicological results, manner and cause of death. RESULTS: Majority of victims were male with an acute onset of agitated and delusional behavior. Drugs were often involved. Deaths were attributed to multiple factors. CONCLUSION: Most of cases involved in TASER resulted from multiple fatal factors. Further researches are needed for the principal mechanism. Thorough scene investigation and complete autopsy examination play crucial role in evaluation of such cases.

Morphologic characteristic of coronary artery disease, with emphasis on thromboses, in patients younger than 40 years of age.

There are few pathologic descriptions of fatal coronary artery disease in the young. The morphologic characteristics of sudden coronary deaths in 47 hearts from patients younger than 40 years were studied. Numbers of plaques with necrotic cores were quantitated in each heart. Compared to 194 sudden coronary deaths >40 years, heart weight was lower, acute plaque erosions more frequent, and extent of disease less in the ≤40 years group. Plaque burden was less in hearts with erosions, and healed infarcts more common in hearts with stable plaque. The numbers of fibroatheromas increased with age until the 6th decade (P < .0001) as well as the proportion of total plaques that were atheromatous. Plaques in younger patients have fewer lipid-rich cores. Most thrombi show areas of organization, with layering frequent in erosions, suggesting a possible method of plaque enlargement in the absence of necrotic core formation.

Morphologic features of exertional versus nonexertional sudden death in patients with hypertrophic cardiomyopathy.

Pathologic features that characterize hypertrophic cardiomyopathy (HC) in exertional versus nonexertional sudden deaths have not been extensively studied. We performed gross measurements and histologic analysis on 103 autopsy cases of HC and correlated these with clinical findings. Pathologic features of the 71 sudden deaths were compared between exertional and nonexertional deaths. Age at death was significantly younger in exertional (27 +/- 13 years) versus nonexertional sudden deaths (40 +/- 16 years, p = 0.0003). Exertional deaths were more likely in women (35 of 37) versus sudden deaths at rest (21 of 34, p = 0.0002). There was no significant difference in the incidence of syncope in the exertional sudden deaths (14%) compared to the nonexertional sudden deaths (9%, p = 0.5) or in the rate of a previous diagnosis of HC (21% vs 21%, respectively). Mean heart weight was significantly decreased in exertional sudden deaths versus nonexertional sudden deaths. There was no difference in the frequency of left ventricular outflow tract plaque (54% exertional vs 46% nonexertional, p = 0.06). By multivariate analysis, including all categories of HC, only decreased heart weight (p = 0.02) and male gender (p = 0.002) were significantly associated with exertional sudden death. In conclusion, there are no pathologic features that would identify patients with HC at risk for exertional death. Because relatively decreased heart weight is strongly associated with exertional death, and because a large proportion of exertional deaths with HC are not associated with significant asymmetry, cardiologists should be careful in excluding the diagnosis of HC in athletes with even mild degrees of cardiomegaly, especially young men.

Adventitial lymphocytic inflammation in human coronary arteries with intimal atherosclerosis.

BACKGROUND: The relationship between adventitial inflammation, plaque type, and culprit plaque morphology in the epicardial arterial circulation has not been studied in detail. METHODS: We studied semiserial sections of coronary arteries at autopsy from patients dying with severe coronary disease, 81 men (age 50 + or - 12 years) and 13 women (age 52 + or - 13 years). Lesions were classified at 3- to 5-mm segments according to modified AHA criteria. Adventitial lymphocyte aggregates were assessed at every 5-mm interval and graded semiquantitatively. Macrophage density in the adventitial fat and intima was assessed with anti-CD68 staining. RESULTS: Adventitial lymphocytic inflammation increased with percent stenosis (P<.0001) and not calcification (P>.2). Hemorrhage into late core, rupture, erosion, and thin caps all had greater adventitial lymphocytic inflammation independent of percent stenosis (P<.0001). Peri-adventitial adipose macrophage density was increased in plaques with atheromas (206 + or - 22 mm(2) vs. 121 + or - 15 mm(2) in fibrous plaques; P=.02) and correlated positively with adventitial lymphocytes (P<.0001) and intimal macrophage content (P<.0001). CONCLUSIONS: Features associated with plaque instability are associated with significantly greater degrees of adventitial lymphocytic inflammation, both as lymphocyte aggregates and as adipocyte-derived macrophages. Further study is required to determine the nature of the association between intimal and adventitial lymphocytic inflammation.

Immunolocalisation of fibrin in coronary atherosclerosis: implications for necrotic core development.

BACKGROUND: Intraplaque haemorrhage has been shown to be important in necrotic core enlargement. Immunolocalisation of fibrin within progressive stages of plaque progression has not been extensively studied. METHODS: Histological sections (n = 74) of human coronary arteries were stained immunohistochemically for fibrin II, red blood cell antigen (glycophorin A), and CD31. Plaques were chosen to represent a range of lesions [6 adaptive intimal thickening, AIT (AHA grade I); 4 intimal xanthomas (AHA grade II), 19 pathologic intimal thickening, PIT (AHA grade III, or pre-atheroma); 34 fibroatheromas, FA (AHA grade IV and V); and 11 thin cap fibroatheromas (TCFA, AHA grade IV)]. RESULTS: Fibrin was generally absent in the intima of AIT and PIT, with moderate staining in cores of early FA (2.6 +/- 0.3). All late FA and TCFA demonstrated intracore fibrin, with mean scores of 2.9 +/- 0.3 and 3.0 +/- 0.3, respectively. Intimal vasa vasorum counts increased with intimal fibrin score (p < 0.0001); in 68% of cores with fibrin staining, there was minimal or no evidence of red cell breakdown. CONCLUSIONS: Fibrin in necrotic cores is present proportional to intraplaque vasa vasorum and before red cells, suggesting leakage of vessels before frank intraplaque haemorrhage. Fibrin may play a role in the bridge between pre-atheroma and atheroma.

Comparison of necropsy findings in patients with sarcoidosis dying suddenly from cardiac sarcoidosis versus dying suddenly from other causes.

The clinical diagnosis of cardiac sarcoidosis can be difficult and is largely dependent on newer imaging modalities. A retrospective search of sudden cardiac deaths was performed from a reference laboratory and statewide medical examiner system for a 12-year period. Planimetry was performed on gross photographs of transverse short-axis sections, and the phase of the lesion and the portion of myocardium extent was estimated histologically. Lesions were classified histologically as early (primarily lymphocytic), intermediate (primarily granulomatous), and late (primarily scar). A total of 41 cases were found, including 25 in which the death was ascribed to sarcoidosis of the heart (group 1) and 16 in which sudden death was due to other findings (group 2). No significant differences were found in age or activity at death, although gross scars and epicardial nodules were more frequent in group 1 (p <0.0001). In the hearts with gross scars, the ventricular septum had the largest percentage of involvement (32%) followed by the posterior wall (25%). Histologically, the intermediate phase predominated in group 1, and the late phase predominated in group 2. Approximately 50% of the cases in group 1 had involvement in the right ventricular apex and septum, suggesting a positive yield by biopsy. In conclusion, cardiac sarcoidosis causing sudden death is characterized by extensive active granulomas with a predilection for the subepicardium and ventricular septum.

Monocytes and neutrophils expressing myeloperoxidase occur in fibrous caps and thrombi in unstable coronary plaques.

BACKGROUND: Myeloperoxidase (MPO) -containing macrophages and neutrophils have been described at sites of plaque rupture. The presence of these cells in precursor lesions to acute rupture (thin cap atheroma, or vulnerable plaque) and within thrombi adjacent to ruptures has not been described, nor an association with iron-containing macrophages within unstable plaques. METHODS: We studied 61 acute ruptures, 15 organizing ruptures, 31 thin cap fibroatheromas, and 28 fibroatheromas from 72 sudden coronary death victims by immunohistochemical and histochemical techniques. Inflammatory cells were typed with anti-CD68 (macrophages), anti-BP-30 (neutrophil bactericidal glycoprotein), and anti-MPO. Iron was localized by Mallory's Prussian blue stain. In selected plaques alpha smooth muscle actin (DAKO, Carpinteria, CA, clone M0851) was performed. RESULTS: MPO positive cells were present in 79% of ruptured caps, 28% of thin cap fibroatheroma, and no fibroatheromas; neutrophils were present in 72% of ruptures, 8% of thin cap fibroatheromas, and no fibroatheromas. Iron containing foam cells were present in the caps of 93% of acute ruptures, of 85% of organizing ruptures, 20% of thin cap atheromas, and 10% of fibroatheromas. MPO positive cells were more frequent in occlusive than non-occlusive thrombi adjacent to ruptures (p = .006) and were more numerous in diabetics compared to non-diabetics (p = .002) CONCLUSION: Unstable fibrous caps are more likely to contain MPO-positive cells, neutrophils, and iron-containing macrophages than fibrous caps of stable fibroatheromas. MPO-positive cells in thrombi adjacent to disrupted plaques are associated with occlusive thrombi and are more numerous in diabetic patients.

Evaluation of aortic injury in driver fatalities occurring in motor vehicle accidents in the State of Maryland for 2003 and 2004.

Incorporating epidemiological and pathologic factors, a retrospective analysis of aortic injury and driving fatalities was conducted. To better understand the mechanism of injury, data were compiled for decedent demographics, autopsy and toxicology findings, and accident circumstances, with emphasis on directional impact. Review of the autopsy files of the Office of the Chief Medical Examiner in the State of Maryland in 2003 and 2004, identified 150 cases of aortic injury recorded in 537 autopsied drivers. Aortic lacerations occurred in 96% of the cases with aortic injury, two thirds of which were complete or near complete transections. A large percentage of cases involved a side impact collision. Consistent with extant research on frontal and lateral impacts, the majority of aortic injuries occurred at the ligamentum arteriosum. Also, the mechanism of aortic injury seems to be similar for side and frontal impact collisions, involving a combination of rapid deceleration forces along with chest and/or upper abdominal compression. This study emphasizes the importance of side impact collisions as a cause of aortic injury. Aortic lacerations have a high mortality rate and better motor vehicle design may prevent this type of injury.

Fatal dog maulings associated with infant swings.

We present three cases of fatal dog maulings of infants placed in mobile infant swings, a phenomenon not previously described in the literature. In each case, the victim was left in a mobile swing, unsupervised by an adult, and the attacking dog was a family pet. Case 1 involved an 18-day-old male infant attacked by a pit bull; Case 2 involved a 3-month-old male infant attacked by a Chow Chow and/or a Dachshund, and Case 3 involved an 18-day-old female infant attacked by a Labrador-pit bull mix. These cases not only underscore the importance of not leaving young children unattended in the presence of pet dogs, but also raise the possibility that mobile swings may trigger a predatory response in dogs and thus may represent an additional risk factor for dog attack.

Simultaneous quantification of methamphetamine, cocaine, codeine, and metabolites in skin by positive chemical ionization gas chromatography-mass spectrometry.

A positive chemical ionization gas chromatography-mass spectrometric method was validated to simultaneously quantify drugs and metabolites in skin collected after controlled administration of methamphetamine, cocaine, and codeine. Calibration curves (2.5-100 ng/skin biopsy) for methamphetamine, amphetamine, cocaine, norcocaine, benzoylecgonine, cocaethylene, norcocaethylene, anhydroecgonine methyl ester, morphine, codeine, and 6-acetylmorphine (5-100 ng/skin biopsy for ecgonine methyl ester and ecgonine ethyl ester) exhibited correlation coefficients >0.999 and concentrations +/-20% of target. Intra- and inter-run precisions were <10%. This procedure should be useful for postmortem analysis; data are included on drug concentrations in skin after controlled drug administration.

Investigation of sudden infant deaths in the State of Maryland (1990-2000).

The Office of the Chief Medical Examiner (OCME) has recorded a significant decline in the deaths of sudden infant death syndrome (SIDS) in the state of Maryland since 1994. However, infants who died of accidental or non-accidental injuries remained consistent during the same time period. This report focuses on the epidemiological characteristics and scene investigation findings of infant victims who died suddenly and unexpectedly in Maryland between 1990 and 2000. A retrospective study of OCME cases between 1990 and 2000 yielded a total of 1619 infant fatalities. 802 infant deaths were determined to be SIDS, which represented 50% of the total infant deaths in our study population. Five hundred and twenty-three (31.8%) deaths were due to natural diseases, 128 (7.9%) deaths were accidents, and 74 (4.6%) were homicides. The manner of death could not be determined after a thorough scene investigation, review of history and a complete postmortem examination in 92 (5.7%) infants. SIDS deaths most often involved infants who were male and black. The peak incidence of SIDS was between 2 and 4 months of age. The majority of SIDS infants (60%) were found unresponsive on their stomach. Among SIDS infants, 269 (33.4%) were found in bed with another person or persons (bed sharing). Of the bed-sharing SIDS cases, 182 (68%) were African-American. In the past 11 years, 52 infants died of asphyxia due to unsafe sleeping environment, such as defective cribs, ill-fitting mattresses, inappropriate bedding materials. Of the 74 homicide victims, 53 (70%) involved infants less than 6 months of age. Twenty (27%) exhibited the classical abuse syndrome characterized by repeated acts of trauma to the infants.

Mesencephalic cryptococcal abscesses presenting with parkinsonism as an initial manifestation of AIDS.

Parkinsonism has been associated with HIV/AIDS and cerebral cryptococcal disease, but to date there has been no report of histological cryptococcal lesions in the substantia nigra (SN) in a patient with parkinsonism. We report on a case of a 63-year-old man who presented with tremor, gait disturbance, and mask-like facies, and showed cryptococcal meningoencephalitis with cryptococcal abscesses in the SN at autopsy, without Lewy bodies or significant degeneration of the SN neurons. Parkinsonism also represented the first manifestation of AIDS in this previously undiagnosed patient. This case highlights the importance of considering infectious etiologies in patients presenting with parkinsonism, and underscores the need for autopsy in evaluation of patients with new or unexplained movement disorders. Movement disorders in association with AIDS and mesencephalic mass lesions are discussed.