Crossbow injuries: A case report with experimental reconstruction study and a systematic review of literature.

In modern times crossbow - a ranged weapon diffused during Middle Ages - is increasing its popularity in recreational hunting and sports; crossbow bolts have a great penetration capacity, despite their low initial velocity. Great concerns emerge when considering that notwithstanding crossbow is a potentially lethal distance weapon, it is easy to obtain without having to undertake any tests on the buyer's mental or physical health. Although rare, crossbow injuries can be challenging for the forensic pathologist due to great similarities with other wounds pattern (gunshots wounds or injury due to sharp force). Especially when the arrow is removed from its original position or the body is decomposed, identification of the weapon can be difficult. According to forensic literature, suicides, homicides and non-lethal injuries by crossbow have been reported up to the present day. We followed the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) indications in the identification and selection of studies and reviewed a series of cases of both fatal and non-fatal crossbow injuries, according to the manner of death (homicide, suicide, accidental). The casuistic part of this paper deals with an attempted murder of a 21-year old man: a case of non-lethal crossbow injury of the thorax in which an interdisciplinary approach, involving forensic inspection, ballistic and radiology tests, led to solve the case.

An immunohistochemical study of the diagnostic value of TREM-1 as marker for fatal sepsis cases.

Triggering receptor expressed on myeloid cells-1 (TREM-1) is produced and up-regulated by exposure of myeloid cells to lipopolysaccharides or other components of either bacterial or fungal origin, which causes it to be strongly expressed on phagocytes that accumulate in inflamed areas. Because TREM-1 participates in septic shock and in amplifying the inflammatory response to bacterial and fungal infections, we believe it could be an immunohistochemical marker for postmortem diagnosis of sepsis. We tested the anti-TREM-1 antibody in 28 cases of death by septic shock and divided them into two groups. The diagnosis was made according to the criteria of the Surviving Sepsis Campaign. In all cases, blood cultures were positive. The first group was comprised subjects that presented high ante-mortem serum procalcitonin and the soluble form of TREM-1 (s-TREM-1) values. The second group comprised subjects in which s-TREM-1 was not measured ante-mortem. We used samples of brain, heart, lung, liver and kidney for each case to test the anti-TREM-1 antibody. A semiquantitative evaluation of the immunohistochemical findings was made. In lung samples, we found immunostaining in the cells of the monocyte line in 24 of 28 cases, which suggests that TREM-1 is produced principally by cells of the monocyte line. In liver tissue, we found low TREM-staining in the hepatocyte cytoplasm, duct epithelium, the portal-biliary space and blood vessel. In kidney tissue samples, we found the TREM-1 antibody immunostaining in glomeruli and renal tubules. We also found TREM-1 staining in the lumen of blood vessels. Immunohistochemical staining using the anti-TREM-1 antibody can be useful for postmortem diagnosis of sepsis.

Scuba diving death: Always due to drowning? Two forensic cases and a review of the literature.

Scuba diving is an increasingly common recreational activity. We describe the physiopathology of barotrauma in two cases where death was caused by pulmonary barotrauma while diving. An inspection and autopsy were carried out in both cases. The autopsy data were supported by post-mortem radiological investigation. Histological and toxicological analyses were also carried out, and dive computer and tank manometer analysis performed. In both cases, the cause of death was attributable to arterial gas embolism, resulting from pulmonary barotrauma subsequent to pulmonary over-distension. The dive computer analysis and the tank manometer allowed us to understand what happened underwater. In our opinion, a multidisciplinary approach is crucial in order to clarify the cause of death. Some pathological conditions and risk factors should be considered before diving.

What is the present situation of vascular surgery? Considerations and reflections based on real practice.

"For the best vascular care to every patient, every day" is the goal of our practice, but is it a possible goal? Where are we now? The general idea is that we are pursuing the right way. The evolution of our discipline in the last two decades has been extraordinary and we reaffirm that we are the leaders in diagnose and treatment of the arterial pathology. Unfortunately, we can find some cases in which reality has to be faced as hardly as it can be, remembering us that we still have to go further with our job. The delay in the diagnose and treatment could lead to a permanent deficit and a money loss for the national health system due to prolonged hospitalization, multiple re-hospitalizations, loss of working capacity. This must be avoided. We strongly suggest that a vascular surgeon should be present in all the Emergency Room and should be routinely involved in the management of patients. The routine use of dedicated interdisciplinary protocols should be strongly advocated. Vascular surgery, as medical specialty, should be recognized as single specialty in all countries and as "peculiar" by the National Authority as well as Neurosurgery and Cardiac Surgery.

Side effects of cocaine abuse: multiorgan toxicity and pathological consequences.

Cocaine is a powerful stimulant of the sympathetic nervous system by inhibiting catecholamine reuptake, stimulating central sympathetic outflow, and increasing the sensitivity of adrenergic nerve endings to norepinephrine (NE). It is known, from numerous studies, that cocaine causes irreversible structural changes on the brain, heart, lung and other organs such as liver and kidney and there are many mechanisms involved in the genesis of these damages. Some effects are determined by the overstimulation of the adrenergic system. Most of the direct toxic effects are mediated by oxidative stress and by mitochondrial dysfunction produced during the metabolism of noradrenaline or during the metabolism of norcocaina, as in cocaine-induced hepathotoxicity. Cocaine is responsible for the coronary arteries vasoconstriction, atherosclerotic phenomena and thrombus formation. In this way, cocaine favors the myocardial infarction. While the arrhythmogenic effect of cocaine is mediated by the action on potassium channel (blocking), calcium channels (enhances the function) and inhibiting the flow of sodium during depolarization. Moreover chronic cocaine use is associated with myocarditis, ventricular hypertrophy, dilated cardiomyopathy and heart failure. A variety of respiratory problems temporally associated with crack inhalation have been reported. Cocaine may cause changes in the respiratory tract as a result of its pharmacologic effects exerted either locally or systemically, its method of administration (smoking, sniffing, injecting), or its alteration of central nervous system neuroregulation of pulmonary function. Renal failure resulting from cocaine abuse has been also well documented. A lot of studies demonstrated a high incidence of congenital cardiovascular and brain malformations in offspring born to mothers with a history of cocaine abuse.

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.

Role of oxidative stress in cocaine-induced cardiotoxicity and cocaine-related death.

Cocaine-induced cardiovascular disorders such as hypertension, thrombosis, myocardial dysfunction, cardiac dysrhythmias and endocarditis have received widespread attention in the context of cocaine abuse. The number of sudden deaths from cardiac causes, including myocardial infarction, ventricular tachyarrhythmia or aortic dissection, is also increasing. This manuscript will highlight the recent employment of study about cocaine cardiotoxicity and oxidative stress. Evidence has revealed that cardiac oxidative stress is a prominent early event of cocaine administration, which severely compromises the cardiac antioxidant cellular system and causes cardiac antioxidant cellular system injuries. Oxidative damage such as peroxidation of membrane phospholipids and depletion of nonenzymatic antioxidants such as glutathione have been found in the myocardium of chronic cocaine-treated animals and in patients. The data indicate that cocaine administration compromised the heart's antioxidant defense system. About the mechanisms involved in the cellular damage, the evidence that cocaine causes apoptosis in the heart comes from in vivo study. In animals model after short-term and long term-cocaine administration, the investigators demonstrates the role of Reactive Oxygen Species as a trigger of cardiac injury induced by cocaine. Cocaine also increased infiltration of inflammatory cells in the heart, and apoptotic cells were predominantly found near inflammatory cells. The role of oxidative stress in cocaine-induced apoptosis in the heart is wide studied and documented.

Retrospective analysis of anaesthesia-related deaths during a 12-year period: looking at the data from a forensic point of view.

Anaesthesia-related death is one of the most complex events to be studied in forensic pathology because of its rarity and its doubtful presentation. Particularly, the difficulties in assessing the cause of deaths in such circumstances are underlined. A scale must be considered in order to determine the causal role of anaesthesia in the process leading to death. Indeed, beyond deaths exclusively explained by anaesthetic care, there are deaths that are not anaesthesia-related and deaths explained by surgery and co-morbidities in which the role of anaesthetic care has to be carefully investigated. A retrospective analysis of 3138 autopsies is presented with the aim of better understanding the patho-physiological process of anaesthesia-related mortality and to determine the causal role of anaesthesiological care in the process leading to death, thus assessing the real incidence of deaths due to anaesthesia (0.16%). In the present study, the number of deaths generically anaesthesia-related (33 cases) accounts for 2.06% of autopsies due to medical malpractice claims and 1.05% of all autopsies. The number of deaths totally related to anaesthesic care is rather low with 0.32% of autopsies due to medical malpractice claims and 0.16% of all autopsies. Anaesthesia-related deaths were due to lack of or delay in intubation (2 cases), acute cardio-respiratory failure (2 cases) and anaesthetic-induced hepatotoxicity (1 case). The importance of a careful forensic investigation (clinical and familial history, medical records, complete autopsy and toxicology), which can lead to a clear understanding of anaesthesia-related deaths, is also stressed.

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.

Immunohistochemical characterisation and TNF-α expression of the granulomatous infiltration of the brainstem in a case of sudden death due to neurosarcoidosis.

Neurosarcoidosis carries a mortality of 10%, over twice that of sarcoidosis overall, although it has been rarely reported as a cause of sudden death. The current evidence suggests that sarcoidosis results from an enhanced immune reaction to a variety of antigens, non-self or self which causes CD4 (helper-inducer) T-cell accumulation with a ratio of helper-inducer T cells to suppressor-cytotoxic T cells usually high in affected organs, activation and release of inflammatory cytokines, and formation of granulomatous lesions. Numerous cytokines and other mediators are produced by both activated macrophages and T lymphocytes bearing the CD4-helper phenotype during the granuloma responses. A number of data suggest that interferon-gamma (IFN-gamma) and cytokines such as TNF-α, IL-2, and IL-18 play a critical role in the formation of granulomas. In this article, we describe the clinical and pathological characteristics of a patient who suddenly died due to acute respiratory failure. Neurosarcoidosis with massive and extensive involvement of the brainstem was established as the cause of death. Western blot analysis in the patient demonstrated the TNF-α presence as a 51-kDa protein in the brain tissue. The immunohistochemical analysis showed a poor positiveness for CD4 in all samples around the granulomas, as well as moderate positiveness for CD8, CD15, and CD20; CD45 and CD68 showed a strong positiveness in all the brain samples. Histological findings, immunohistochemical analysis, and proteomic studies addressed the diagnosis of neurosarcoidosis with involvement of the nucleus of the solitary tract in the brainstem and central hypoventilation as the cause of death.

Anabolic androgenic steroids abuse and liver toxicity.

In the athletes the wide use of Anabolic Androgenic Steroids (AAS) cause series damage in various organs, in particular, analyzing the liver, elevation on the levels of liver enzymes, cholestatic jaundice, liver tumors, both benign and malignant, and peliosis hepatis are described. A prolonged AAS administration provokes an increase in the activities of liver lysosomal hydrolases and a decrease in some components of the microsomal drug-metabolizing system and in the activity of the mitochondrial respiratory chain complexes without modifying classical serum indicators of hepatic function. Liver is a key organ actively involved in numerous metabolic and detoxifying functions. As a consequence, it is continuously exposed to high levels of endogenous and exogenous oxidants that are by-products of many biochemical pathways and, in fact, it has been demonstrated that intracellular oxidant production is more active in liver than in tissues, like the increase of inflammatory cytokines, apoptosis and the inhibitors of apoptosis NF- κB and Heat Shock Proteins.

Heart disease induced by AAS abuse, using experimental mice/rats models and the role of exercise-induced cardiotoxicity.

The anabolic-androgenic steroids (AAS) are all synthetic derivates of testosterone and are commonly used as sport performance enhancers in athletes. The heart is one of the organs most frequently affected by administration of anabolic steroids. A direct myocardial injury caused by AAS is supposed to determine marked hypertrophy in myocardial cells, extensive regional fibrosis and necrosis. A number of excellent studies, using animal models, were performed to evaluate the cardiac effects of AAS. It is known that exogenous administration induced cardiac hypertrophy in vitro and in vivo, and when combined with exercise, anabolic steroid use has been shown to change exercise-induced physiological cardiac hypertrophy to pathophysiological cardiac hypertrophy. However the molecular mechanisms are still poorly understood. It's described that sudden cardiac death, myocardial infarct; ventricular remodelling and cardiomyopathy do to AAS is related to apoptosis and oxidative stress when associated with exercise. Mechanical stimuli and circulating humoral factors (TNF-α, HSP-70, IL-1ß) released by the heart and peripheral organs are responsible. Testosterone and derivates can work through genomic (activation of specific androgen receptor, interaction with coactivators and co-repressors transcription factors, gene regulation) and non-genomic mechanism (membrane-receptor-second messenger cascades). Chronic AAS abuse results in different patterns of pathologic alterations, which depend on type, dose, frequency, and mode of use. The difficulty in interpreting experimental data on animals (mice and rats) lies in the diversity of experiments (the diversity of substances, which show different properties, different mice / rats by sex and age, duration of treatment with AAS, dosages used, type, scope and exercise duration).

Side effects of AAS abuse: an overview.

Anabolic - androgenic steroids (AAS) were originally developed to promote growth of skeletal muscle. AAS abuse is commonly associated with bodybuilders, weightlifters, and other athletes. The issue of AAS toxicity is not yet completely understood since the adverse effects outline a varied scenario with side effects reported affecting many organs and systems in humans. The true incidence of AAS related medical problems is not known, due to several drawbacks in human studies. The entity of side effects depends on the sex, the dose, the duration of treatment, whether they are taken during exercise training or under sedentary conditions, and the susceptibility of the individuals themselves to androgen exposure partly depending on genetic factors. Both the acute and the chronic effects can lead to toxicity, but generally the serious and even fatal effects depend on the time and the duration of AAS administration. A limitation of human studies is represented by the fact that information about the intake of steroids are, generally, self reported and it is hardly possible to assess the exact dosage. AAS are often used in combination with other dugs or substances, so it is difficult to separate their toxic effects from those caused by the other drugs abused. Hence experimental studies conducted on animal models are mandatory to investigate the mechanisms underlying to AAS toxicity and the organ alterations due to these substances. Finally, clinicians should be aware of the complex and varied pattern of toxicity so as to be able to perform correct diagnoses and treatments.

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.

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.

Preimplantation genetic diagnosis: a step by step guide to recent Italian ethical and legislative troubles.

OBJECTIVE: To analyse legislation and medical professionals' position concerning the doctor's role in assisted reproduction techniques in Italy, and to discuss the implications for physicians of preimplantation genetic diagnosis (PGD). BACKGROUND: Until recently a strict interpretation of the assisted reproduction law (40/2004) and the guidelines subsequently issued, lead to denying infertile couples affected by genetic diseases the right to resort to PGD. In October 2006 the Constitutional Court ruled regarding the question of the constitutional legitimacy of the prohibition of PGD. DISCUSSION: The Constitutional Court declared the manifest inadmissibility of the question of the constitutional legitimacy of article 13 of law 40/2004. The debate has become very animated since the ruling. After the negative sentence of the Constitutional Court, three further sentences recognised the right of couples to obtain PGD, representing a hard blow to law 40/2004 and to the ministerial guidelines; a further confirmation of the untenability of a law that violates fundamental principles such as the right to healthcare for women and the unborn child, the right to responsible motherhood and to informed consent. CONCLUSION: It seems that in Italy the legislative inadequacy for medically assisted procreation is reprieved by the courageous decisions of the judges, which refer to the values of the Italian Constitution, in defence of the fundamental rights of the citizens.

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.