Forensic investigation on a combined death by food aspiration and acute escitalopram intoxication occurred to a psychiatric subject in a nursing home.

Food aspiration is one of the major health risks for elderly people in nursing homes which could lead to death. Moreover, misconducts in pharmacotherapy may represent a potential risk of adverse drug reactions. It is reported here the toxicological evaluation of a combined death by food aspiration and acute escitalopram intoxication of a psychiatric subject, occurred in a nursing home. An 89-year-old man, suffering from dysphagia and Alzheimer's, was resident in a nursing home. He was fed with a liquid diet administered directly in mouth using a syringe. The man was also being treated with escitalopram 10 mg tablet. One evening, after receiving the meal in the usual way, the man complained of sudden illness. Carried to the emergency room, the man died about 3 h later with a diagnosis of cardiogenic shock subsequentially to ab ingestis. The histological findings revealed the presence of exogenous material, probably food, up to the finest bronchial branches. The toxicological examination revealed the presence of escitalopram and its main metabolite, desmethylcitalopram: in the blood 1972 ng/ml and 285 ng/ml, in the brain 4657 ng/g and 1025 ng/g, in the gastric content 2317 ng/g and 423 ng/g, in the lung 21,771 ng/g and 468 ng/g, respectively. The bad practice of the nurses to dissolve the escitalopram tablet in the liquefied food and to administer the therapy with a syringe directly into the mouth emerged thanks this investigation. Following food aspiration, escitalopram was absorbed by inhalation route, reaching high concentrations in blood and tissues. The death occurred due to a combined mechanism between food aspiration and the escitalopram toxic action.

Oxidative-Nitrosative Stress and Myocardial Dysfunctions in Sepsis: Evidence from the Literature and Postmortem Observations.

BACKGROUND: Myocardial depression in sepsis is common, and it is associated with higher mortality. In recent years, the hypothesis that the myocardial dysfunction during sepsis could be mediated by ischemia related to decreased coronary blood flow waned and a complex mechanism was invoked to explain cardiac dysfunction in sepsis. Oxidative stress unbalance is thought to play a critical role in the pathogenesis of cardiac impairment in septic patients. AIM: In this paper, we review the current literature regarding the pathophysiology of cardiac dysfunction in sepsis, focusing on the possible role of oxidative-nitrosative stress unbalance and mitochondria dysfunction. We discuss these mechanisms within the broad scenario of cardiac involvement in sepsis. CONCLUSIONS: Findings from the current literature broaden our understanding of the role of oxidative and nitrosative stress unbalance in the pathophysiology of cardiac dysfunction in sepsis, thus contributing to the establishment of a relationship between these settings and the occurrence of oxidative stress. The complex pathogenesis of septic cardiac failure may explain why, despite the therapeutic strategies, sepsis remains a big clinical challenge for effectively managing the disease to minimize mortality, leading to consideration of the potential therapeutic effects of antioxidant agents.

The NADPH oxidase NOX2 as a novel biomarker for suicidality: evidence from human post mortem brain samples.

Recent evidence points towards a role of oxidative stress in suicidality. However, few studies were carried out on the sources of reactive oxygen species (ROS) in subjects with suicidal behaviour. We have previously demonstrated that the NADPH oxidase NOX2-derived oxidative stress has a major role in the development of neuropathological alterations observed in an animal model of psychosis. Here, we investigated the possible increase in NOX2 in post mortem brain samples of subjects who died by asphyctic suicide (AS) compared with controls (CTRL) and subjects who died by non-suicidal asphyxia (NSA). We found that NOX2 expression was significantly higher in the cortex of AS subjects than in the other two experimental groups. NOX2 immunostaining was mainly detected in GABAergic neurons, with a minor presence of NOX2-positive-stained cells in glutamatergic and dopaminergic neurons, as well as astrocytes and microglia. A sustained increase in the expression of 8-hydroxy-2'-deoxyguanosine, an indirect marker of oxidative stress, was also detected in the cortex of AS subjects, compared with CTRL and NSA subjects. A significant elevation in cortical interleukin-6 immunoreactivity in AS subjects suggested an involvement of cytokine-associated molecular pathways in NOX2 elevations. Our results suggest that the increase in NOX2-derived oxidative stress in the brain might be involved in the neuropathological pathways leading to suicidal behaviour. These results may open innovative insights in the identification of new pathogenetic and necroscopic biomarkers, predictive for suicidality and potentially useful for suicide prevention.

A Pathophysiological Insight into Sepsis and Its Correlation with Postmortem Diagnosis.

BACKGROUND: Sepsis is among the leading causes of death worldwide and is the focus of a great deal of attention from policymakers and caregivers. However, sepsis poses significant challenges from a clinical point of view regarding its early detection and the best organization of sepsis care. Furthermore, we do not yet have reliable tools for measuring the incidence of sepsis. Methods based on analyses of insurance claims are unreliable, and postmortem diagnosis is still challenging since autopsy findings are often nonspecific. AIM: The objective of this review is to assess the state of our knowledge of the molecular and biohumoral mechanisms of sepsis and to correlate them with our postmortem diagnosis ability. CONCLUSION: The diagnosis of sepsis-related deaths is an illustrative example of the reciprocal value of autopsy both for clinicians and for pathologists. A complete methodological approach, integrating clinical data by means of autopsy and histological and laboratory findings aiming to identify and demonstrate the host response to infectious insults, is mandatory to illuminate the exact cause of death. This would help clinicians to compare pre- and postmortem findings and to reliably measure the incidence of sepsis.

Use of contrast media in diagnostic imaging: medico-legal considerations.

Contrast media (CM) are used in imaging techniques to enhance the differences between body tissues on images. The ideal contrast medium should achieve very high concentration in the tissues without producing any adverse effects. Unfortunately, this has not been possible so far and all CM have adverse effects. The increasing use of CM is likely to give rise to a wide range of pitfalls, including compliance with and appropriateness of indications for the use of CM themselves, the choice of the 'best' contrast agent, off-label use, evaluation of special populations of patients, and competence to tackle emergency scenarios following the administration of CM. Even more prominent, and potentially more important, is the issue of informed consent which brings with it a duty to inform patients awaiting the administration of CM with regard to the nature of the procedure, the existence of alternative procedures, the extent of the risks relating to the use of CM and, finally, the risks relating to refusal of the procedure. All these issues may give rise to concerns about liability for failure to offer adequate information to patients or to carefully evaluate and balance the potential risks and benefits of the procedure or, finally, for being unprepared in the event of adverse reactions to CM, especially when these are severe and life-threatening. Educational and training programmes for radiologists are likely to shape change in the medical liability environment in the coming years.

A rare case of a scuba diver's death due to propeller injuries of a desalination pump.

Water skiing, boat racing, skin and scuba diving, as well as pleasure boat cruising are becoming increasingly popular hobbies. As a result, the incidence of injuries secondary to motor propellers is becoming more frequent. Injuries by propellers, amputation, death by drowning, and bleeding are rare reported events in forensic literature. The most common circumstances surrounding boat-propeller-related injuries are concerned with getting into or out of the boat, personal watercraft use or water skiing, and falling or being thrown from the boat. A case of a scuba diver's death that occurred during an illegal scuba fishing trip around a desalination plant is presented. A complete autopsy and histological study of all organs and surfaces of dismembered cadaveric sections, performed in order to determine the phases of death, are reported. An underwater scene investigation was conducted by an engineering team studying the mouth of the pump and the dynamic characteristic of rotating propeller blades.

Gua Sha a traditional Chinese healing technique that could mimick physical abuse: a potential issue with forensic implications. A case study.

Gua Sha (press-stroking) is a traditional Chinese healing technique utilized to combat pain, common cold, heatstroke, and respiratory problems. Patterned ecchymoses may appear due to the action of scraping and scratching repeatedly in a unidirectional manner, with a smooth edge over a lubricated area. They may be very informative, since they, generally, reproduce the shape of the injurious agent. However, many confounding factors can make the identification of the lesions difficult. A case of a 43 year-old Chinese woman, hospitalized for abdominal pain, is reported. An unusual pattern of reddish ecchymoses on the back was present. After a careful investigation, ecchymoses were attributed to Gua Sha. The case demonstrated that clinicians and forensic pathologists should also consider press-stroking, and other similar techniques in adults who present scratch-like marks or ecchymoses on various body districts, even if they have an unusual pattern.

Data available on the extent of cocaine use and dependence: biochemistry, pharmacologic effects and global burden of disease of cocaine abusers.

Drug use is seen more as an individualistic behaviour and is therefore not readily conceived of from a population perspective. There is general recognition of several phases and degrees of drug abuse, from initiation and early-use patterns to long-term chronic use. Cocaine and its derivative "crack" cocaine provide an example of both the globalization of substance use and the cyclical nature of drug epidemics. Cocaine is a powerful CNS (Central Nervous System) stimulant but exerts its action in a several types of adverse health effects, including acute toxic effects (i.e. overdose, accidental injury and violence), dependence, cardiovascular disease, cirrhosis, bloodborne bacterial and viral infections, and mental disorders. Of interest, many people who use Cocaine will use also other drugs; therefore, ascribing adverse health effect to a certain drug might be difficult. Any mucous membrane can act as a port of entry for cocaine and the systemic effect is greatly influenced by the route and speed of administration. The effects of Cocaine mainly depend on the user's addiction, the dose received and the mode of assumption. Laws restricting the availability of cocaine saw a decrease in consumption in these countries until the 1960s. The number of cocaine users worldwide ranged from 14 million to 21 million (0.3-0.5% of the population aged 15-64 years). The largest market was North America, then western and central Europe and South America.

Cardiovascular effects of cocaine: cellular, ionic and molecular mechanisms.

Cocaine is a widely abused drug responsible for the majority of deaths ascribed to drug overdose. Many mechanisms have been proposed in order to explain the various cocaine associated cardiovascular complications. Conventionally, cocaine cardiotoxicity has been thought to be mediated indirectly through its sympathomimetic effect, i.e., by inhibiting the reuptake and thus increasing the levels of neuronal catecholamines at work on adrenoceptors. Increased oxidative stress, reactive oxygen species, and cocaine-induced apoptosis in the heart muscle have suggested a new way to understand the cardiotoxic effects of cocaine. More recent studies have led the attention to the interaction of cocaine and some metabolites with cardiac sodium, calcium and potassium channels. The current paper is aimed to investigate the molecular mechanisms of cocaine cardiotoxicity which have a specific clinical and forensic interest. From a clinical point of view the full knowledge of the exact mechanisms by which cocaine exerts cardio - vascular damage is essential to identify potential therapeutic targets and improve novel strategies for cocaine related cardiovascular diseases. From a forensic point of view, it is to be underlined that cocaine use is often associated to sudden death in young, otherwise healthy individuals. While such events are widely reported, the relationship between cardiac morphological alterations and molecular/cellular mechanisms is still controversial. In conclusion, the study of cocaine cardiovascular toxicity needs a strict collaboration between clinicians and pathologists which may be very effective in further dissecting the mechanisms underlying cocaine cardiotoxicity and understanding the cardiac cocaine connection.

Acute administration of 3,4-methylenedioxymethamphetamine (MDMA) induces oxidative stress, lipoperoxidation and TNFα-mediated apoptosis in rat liver.

Liver toxicity is one of the consequences of ecstasy (3,4-methylenedioxymethamphetamine MDMA) abuse and hepatocellular damage is reported after MDMA consumption. Various factors probably play a role in ecstasy-induced hepatotoxicity, namely its metabolism, the increased efflux of neurotransmitters, the oxidation of biogenic amines, and hyperthermia. MDMA undergoes extensive hepatic metabolism that involves the production of reactive metabolites which form adducts with intracellular nucleophilic sites. MDMA-induced-TNF-α can promote multiple mechanisms to initiate apoptosis in hepatocytes, activation of pro-apoptotic (BID, SMAC/DIABLO) and inhibition of anti-apoptotic (NF-κB, Bcl-2) proteins. The aim of the present study was to obtain evidence for the oxidative stress mechanism and apoptosis involved in ecstasy-induced hepatotoxicity in rat liver after a single 20 mg/kg, i.p. MDMA administration. Reduced and oxidized glutathione (GSH and GSSG), ascorbic acid (AA), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and malondialdehyde (MDA), an indicator of lipid peroxidation, were determined in rat liver after 3 and 6h after MDMA treatment. The effect of a single MDMA treatment included decrease of GR and GPx activities (29% and 25%, respectively) and GSH/GSSG ratio (32%) with an increase of MDA (119%) after 3h from ecstasy administration compared to control rats. Liver cytosolic level of AA was increased (32%) after 6 h MDMA treatment. Our results demonstrate a strong positive reaction for TNFα (p<0.001) in hepatocytes and a diffuse apoptotic process in the liver specimens (p<0.001). There was correlation between immunohistochemical results and Western blotting which were quantitatively measured by densitometry, confirming the strong positivity for TNF-α (p<0.001) and NF-κB (p<0.001); weak and intense positivity reactions was confirmed for Bcl-2, SMAC/DIABLO (p<0.001) and BID reactions (p<0.001). The results obtained in the present study suggest that MDMA induces loss of GSH homeostasis, decreases antioxidant enzyme activities, and lipoperoxidation that causes an oxidative stress that accompaines the MDMA-induced apoptosis in liver cells.

Lethal injuries following building collapse: comparison between autopsy and radiographic findings.

PURPOSE: The aim of this study was to evaluate the impact of conventional radiology on the assessment of causes of death of human beings after a building collapse and to establish whether the radiographic approach is useful and justifiable. MATERIALS AND METHODS: Eight victims of a building collapse were subjected to autopsy, toxicology and radiographic examinations of the entire body. The autopsy findings, classified into three groups according to the New Injury Severity Score (NISS), were compared with radiographic findings. RESULTS: The death of the three individuals in group 1 was ascribed to mechanical asphyxia. Costal fractures, pneumothorax and subcutaneous emphysema were detected in one case only. The three individuals in group 2 died of mechanical asphyxia associated with cerebral injuries in all cases, abdominal injuries in two and cardiac injuries in one. Plain films showed skull fracture in one case, air within the cardiac chambers in another and diaphragmatic injuries in the third. The two individuals in group 3 died of injuries not compatible with life at the cardiac and abdominal level in both cases and at the cerebral level in one. Radiography showed multiple fractures of the cranium associated with diaphragmatic injuries in one case only. No significant pleuropulmonary radiographic findings were detected in any of the eight victims. Paralytic ileus, identified in all patients, is not strictly correlated to abdominal injuries. Skeletal injuries were all confirmed at conventional radiography. CONCLUSIONS: Conventional radiography allows for the overall assessment of skeletal injuries. Radiographic findings provide limited information about the causes of death, whereas findings related to the concomitant causes of death are more frequent. Conventional radiography should be considered inadequate, especially if the potential of the modern software tools available on current computed tomography and magnetic resonance images is considered.

Renal heat shock proteins over-expression due to anabolic androgenic steroids abuse.

Chronic use of anabolic adrogenic steroids (AAS) has been known to cause serious adverse effects. While the effects of AASs on cardiovascular system are well known, toxicity on other organs has received less attention. A doserelated nephrotoxic effect has been proposed and a wide variety of morpho-functional damages have been observed, but the exact pathophysiological mechanism of action is still not well known. In the present minireview, we highlight the remaining issues through an analysis of the pertinent literature. As with HSPs toxic agents their overexpression could be considered a protective reaction against AAS abuse however, comprehensive studies concerning the whole range of Hsps/chaperones expressions in all organs after long term use of AAS are needed.

C3a, TNF-alpha and interleukin myocardial expression in a case of fatal sudden cardiac failure during clinic reactivation of systemic lupus erythematosus.

Isolated myocarditis, or dilated cardiomyopathy, is a rare and usually late clinical manifestation of systemic lupus erythematosus (SLE). Increased levels of complement split products are associated with disease activity. Injury of the vascular endothelium due to complement activation and immune complexes may contribute to the vasculopathy in SLE. We present a case of sudden cardiac failure and death in a 28-year-old Caucasian man, during reactivation of SLE. To explain the sudden cardiac failure, we looked for anti-tumour necrosis factor (TNF)- proportional, variant and anti-interleukin (IL) expression in cardiac cells, and anti-complement (anti-C)3a in small cardiac vessels. The immunohistochemical examination of heart specimens revealed a strong positive reaction in cardiac myocytes for antibodies anti-TNF- proportional, variant and IL-8, and a milder positive reaction for antibodies anti-IL-15 and IL-10. A strong positive reaction of C3a in small cardiac vessels was observed in all specimens. Furthermore, the expression of CD4 and CD8 showed a strong positive reaction in pericardium and valvular endocardium, and a lesser positivity in myocardial specimens. TNF appears to have played a major proinflammatory role in this fatal case.

MDMA administration and heat shock proteins response: foreseeing a molecular link.

Molecular and cellular mechanisms of MDMA-induced toxicity have been extensively studied in a number of experimental models. Nevertheless, only few studies investigated the involvement of HSPs ("molecular chaperones") in MDMA organs toxicity. In the present minireview we highlight this subject analysing the results of these studies conducted especially on brain tissue. Despite of it seems obvious that HSPs overexpression is a protective reaction against MDMA treatment, the molecular mechanisms for exerting their action are far to be undiscovered. At the same time, we need of comprehensive studies concerning the whole range of Hsps/chaperones expressions in all organs after acute and chronic administration of MDMA.

Virtopsy versus digital autopsy: virtual autopsy.

Multislice computed tomography (MSCT) and magnetic resonance imaging (MRI) are being increasingly implemented in forensic pathology. These methods may serve as an adjuvant to classic forensic autopsies. Imaging of the interior of corpses is performed using MSCT and/or MRI. MRI, in addition, is also well suited to the examination of surviving victims of assault, especially choking, and helps visualise internal injuries sometimes not seen on external examination of the victim. Various postprocessing techniques can provide strong forensic evidence for use in legal proceedings. The documentation and analysis of postmortem findings with MSCT and MRI and postprocessing techniques (virtopsy) is investigator independent, objective and noninvasive and will lead to qualitative improvements in forensic pathologic investigation. Apart from the accuracy and three dimensionality that conventional documentations lack, these techniques allow for the re-examination of the corpse and the crime scene even decades later, after burial of the corpse and liberation of the crime scene. We believe that this virtual, noninvasive or minimally invasive approach will improve forensic medicine in the near future.

Anaphylactic latex reaction during anaesthesia: the silent culprit in a fatal case.

The true incidence of anaphylactic latex reactions and their associated morbidity and mortality remain poorly defined. It is noteworthy that a number of groups of individuals are at risk for anaphylactic reactions to latex during surgical and medical procedures; one of these groups is represented by the obstetric and gynaecologic population. A case of unrecognized first anaphylactic reaction to latex in a pregnant woman patient who underwent a caesarean section is presented. The diagnosis of latex allergy was missed and the following day the woman underwent a surgical re-exploration complicated by fatal cardiovascular arrest. At post-mortem examination, pulmonary mast cells in the bronchial walls and capillary septa were identified and a great number of degranulating mast cells with tryptase-positive material outside the cells was documented. A post-mortem latex-specific IgE test showed a high titre (14.00 U/I). Latex-induced fatal anaphylactic shock was recorded as the cause of death. This case highlights some of the practical difficulties in the initial diagnosis and subsequent investigation of fatal anaphylactic reaction during anaesthesia. Anaphylaxis is often misdiagnosed because many other pathologic conditions may present identical clinical manifestations, so anaphylactic shock must be differentiated from other causes of circulatory collapse. Although latex allergy usually has a delayed onset after the start of the surgery and most often a slow onset too, it should be always suspected if circulatory collapse and respiratory failure occur during surgery, even if the patient does not belong to a risk group; in the presence of identified risk factors for latex allergy a well-founded suspicion must be stronger, leading to an immediate discontinuation of the potential trigger.

An unusual case of crossbow homicide.

The authors report the case of a man found unresponsive in a wooded area with injuries on the face, eyes, shoulders and back, probably produced by caustic agents. A penetrating wound was noted in the left occipital region. Four days after admission to an Intensive Care Unit he died. No weapon was found at the crime scene. Autopsy revealed an occipital bone defect in the wound area, and cerebral haemorrhage in the left hemisphere in the absence of an exit wound. Immunohistochemical staining of brain samples for ß-APP were critical establishing the extent of the injury. The peculiarity of the wound and the lack of circumstantial evidence made it necessary to conduct a careful investigation to identify the weapon. Firing tests performed on experimental cranial models established the use of a crossbow weapon as a cause of the observed wound.

A systematic study of a myocardial lesion: colliquative myocytolysis.

BACKGROUND: The term "myocytolysis" was first used to define the repair process of contraction band necrosis associated with an acute myocardial infarction. On the other hand, in the latter condition a "myofibrillolysis," presenting edematous myocardial cells not involved by infarct necrosis, and without evidence of repair process was reported. The objective of this study is to establish the frequency, extent and meaning of this myocardial lesion. MATERIALS AND METHODS: In 12 groups of patients for a total of 432 cases with and without coronary heart disease, "colliquative myocytolysis"--i.e., progressive vacuolization by loss of myofibrils until their total or subtotal disappearance associated with intramyocellular edema in absence of any cellular reaction--was graded in 16 histological slides of the different cardiac regions in each pathological case. RESULTS: Colliquative myocytolysis (CM) was present in more than 90% with a maximal extent in cases of irreversible congestive heart failure followed by transplanted heart cases (67%) with a survival greater than 1 week. In all other groups, the lesion was absent or minimal. CONCLUSIONS: No correlation was found between CM and contraction band necrosis, gender, age, heart weight, myocardial fibrosis, coronary artery stenosis, clinical data. Colliquative myocytolysis is a specific histological marker of congestive heart failure, without relation to coronary blood flow, heart weight and myocardial fibrosis. Vacuolization of myocardial cells may be due to other causes (e.g., storage disease, etc.) or may be an artifact. There is no support for the belief that coronary ischemia or myocardial hypoxia is its causes.

Myocardial disarray: an architectural disorganization linked with adrenergic stress?

BACKGROUND: Myocardial disarray is a structural abnormality found in specific zones of the normal heart. In some conditions, such as hypertrophic cardiomyopathy (HCM), its occurrence represents a pathological process leading to myocardial asynergy. The incidence of "pathological" myocardial disarray in humans is still not known. It has been suggested that a link exists between adrenergic overactivity and myocardial disarray. The aim of the present study is to compare heart findings in conditions with and without chronic sympathetic overtone for evidence of possible linkage in humans. MATERIALS AND METHODS: A total of 340 hearts were studied. They were divided into seven groups: sudden/unexpected coronary death; sudden/unexpected death in silent Chagas' disease; brain haemorrhage following berry aneurysm rupture; transplanted hearts; congestive heart failure, AIDS and cocaine abuse. Findings in these hearts were compared with anatomic changes in 92 control hearts, where the decedent had died from head trauma, electrocution, or carbon monoxide intoxication. The frequency and presence of myocardial disarray were recorded and correlated to heart weight, extent of myocardial fibrosis, and contraction band necrosis (CBN). RESULTS: Hearts from patients with conditions that increased sympathetic tone showed an association of myocardial disarray and contraction band necrosis without any relationship to heart weight. CONCLUSIONS: Myocardial disarray was observed in cardiac areas where it is not found normally. It was associated with adrenergic myocardial stress morphologically expressed by a higher number of foci (p<0.01) and myocells (p<0.001) with CBN versus findings in normal subjects. The condition deserves further study as a possible myocardial asynergic and arrhythmogenic factor especially in sudden/unexpected death.

Age-related changes in skeletal muscle fiber composition in two swine muscles.

This study focuses the aging-related modification of skeletal fiber types in two skeletal muscles of different-age swine (6 and 18 month). Rectus abdominis and vastus medialis were employed. It was performed an immunohistochemical staining for slow fibers and it was made a quantitative evaluation, using an automatic interactive image analysis system. The percentage of slow fibers decreased in adult swine. Moreover, slow fibers in rectus abdominis were less numerous than in vastus medialis. Aging and muscle function are two important factors able to modify fiber types. Morphometric analyses can ascertain this modification for diagnostic or nourishmental purposes.