Irene Riezzo

Sudden cardiac death during anabolic steroid abuse: morphologic and toxicologic findings in two fatal cases of bodybuilders.

We report two cases of sudden cardiac death (SCD) involving previously healthy bodybuilders who were chronic androgenic–anabolic steroids users. In both instances, autopsies, histology of the organs, and toxicologic screening were performed. Our findings support an emerging consensus that the effects of vigorous weight training, combined with anabolic steroid use and increased androgen sensitivity, may predispose these young men to myocardial injury and even SCD.

Correlation between cardiac oxidative stress and myocardial pathology due to acute and chronic norepinephrine administration in rats

Background: To investigate the cardiotoxic role of reactive oxygen species (ROS) and of products derived from catecholamines auto‐oxidation, we studied: (1) the response of antioxidant cardiac cellular defence systems to oxidative stress induced by norepinephrine (NE) administration, (2) the effect of NE administration on cardiac β1‐adrenergic receptors by means of receptor binding assay, (3) the cellular morphological alterations related to the biologically cross‐talk between the NE administration and cytokines [tumor necrosis factor‐alpha (TNF‐α), monocyte chemotactic protein‐1 (MCP‐1), interleukins IL6, IL8, IL10]Methods and Results: A total of 195 male rats was used in the experiment. All animals underwent electrocardiogram (EKG) before being sacrificed. The results obtained show that NE administration influences the antioxidant cellular defence system significantly increasing glutathione peroxidase (GPx) activity, glutathione reductase (GR) and superoxide dismutase (SOD). The oxidized glutathione (GSH/GSSG) ratio significantly decreases and malondialdehyde (MDA) levels increase showing a state of lipoperoxidation of cardiac tissue. We describe a significant apoptotic process randomly sparse in the damaged myocardium and the effect of ROS on the NE‐mediated TNF‐α, MCP‐1, and IL6, IL8, IL10 production. Conclusions: Our results support the hypothesis that catecholamines may induce oxidative damage through reactive intermediates resulting from their auto‐oxidation, irrespective of their interaction with adrenergic receptors, thus representing an important factor in the pathogenesis of catecholamines‐induced cardiotoxicity. The rise of the cardioinhibitory cytokines may be interpreted as the adaptive response of jeopardized myocardium with respect to the cardiac dysfunction resulting from NE injection.

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.

Histological age determination of venous thrombosis: A neglected forensic task in fatal pulmonary thrombo-embolism

The histological age determination of venous thromboses in fatal pulmonary embolism cases is an important task of forensic medicine and requires thorough knowledge of the general and specific pathology of pulmonary thromboembolism (PTE). The aim of our investigation was to carry out a chronological evaluation of the deep venous thrombosis (DVT) phenomenon, to assess the chronological transformation of the thrombus and to determine the causal relationship with PTE as cause of death. The clinical data and the autopsy records of the 2843 autopsies performed over the period 1 November 1998 to 31 December 2007 were retrospectively evaluated, and 140 cases in which PTE was pointed out as cause of death were selected. The dissection of the deep veins of the legs has been performed systematically to search for the starting point of venous embolism. 4.5% of pulmonary embolisms originated in the in iliac veins, 20.7% in the femoral veins, and 74.8% in the deep crural veins. In the venous sites of thrombosis, the histological assessment has been performed in conjunction with the surrounding vascular wall of uncut blood vessel with at least three to six different transverse incisions. Histological assessment of the embolus samples was also performed in conjunction with the venous sites of thrombosis. In our selected 140 cases of PTE, the DVT was classified as phase 1 in 48 cases (34.29%), as phase 2 in 70 cases (50%), and 22 cases (15.71%) were evaluated as older than 2 months (phase 3). The observed transformation of the thrombus by organization is suitable for a forensically utilizable age determination. However, only three chronological stages can be distinguished with any degree of certainty using immunohistochemistry and CLSM.

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.

Insight into stress-induced cardiomyopathy and sudden cardiac death due to stress. A forensic cardio-pathologist point of view.

Emotional, physiological and physical stress is associated with increased rates of cerebrovascular events and sudden deaths. The pathophysiology of stress-induced cardiomyopathy is not well understood. Proposed mechanisms for catecholamine-mediated stunning in stress cardiomyopathy include epicardial vasospasm, microvascular dysfunction, hyperdynamic contractility with midventricular or outflow tract obstruction, and direct effects of catecholamines on cardiomyocytes. Studies show evidence of significant heritable influences on individual responses to adrenergic stimulation. Data from such studies may be of help for a more accurate comprehension of clinical and morphological alterations of the heart. Irrespective of the cause, patients with the classic stress-induced cardiomyopathy morphology deserve special attention because this extensive distribution of wall motion abnormalities has implications for potential associated complications. Cardiac response may be significantly coupled to genetic differences at candidate loci that encode components of catecholamine biosynthesis, storage, and metabolic pathway. Given the role of the sympathetic nervous system in responses to acute stress, it is reasonable to explore whether genetically determined alterations in catecholamine system functions contribute to acute and chronic cardiovascular disorders such as stress-induced cardiomyopathy.

Cardiac pathology in death from electrocution

To better characterize the morphologic changes in electrocution, morphologic changes in the hearts of 21 subjects, who died instantaneously of electrocution, were compared to the hearts of decedents with different types of death. Sixteen myocardial samples per heart were processed for histological examination, and sections were prepared with a variety of specific stains. The frequency, location and extent of myocellular segmentation (stretching and/or rupture) of intercalated discs and associated changes of myocardial bundles and single myocells [myofibre break-up (MFB)] were recorded, quantitatively analysed and statistically evaluated. The frequency of MFB was maximal in cases of electrocution (90%). The findings show that MFB is an ante-mortem change and may be a distinct finding in electrocution.

MDMA Toxicity and Pathological Consequences: A Review About Experimental Data and Autopsy Findings

Studies conducted in humans or in animals explored the presence, nature and potential causes of 3,4-methylenedioxymethamphetamine (MDMA) toxicity. According to literature, there are four principal types of such serious toxicity: hepatic, cardiovascular, cerebral and hyperpyrexic. The molecular mechanisms involved in the genesis of these toxic effects are not yet fully clarified, but the oxidative stress, excitotoxicity, and mitochondrial dysfunction appear to be causal events that converge to mediate MDMA-induced toxicity. Studies conducted on animals demonstrated that the acute administration of MDMA elicits cardiovascular responses that are similar to those elicited by d-amphetamine, and that these responses appear to involve catecholaminergic and non-catecholaminergic-dependent mechanisms. Although there is undeniable evidence of MDMA-induced cardiac toxicity, the mechanism responsible remains to be clarified. While many reports both in humans and in animals have demonstrated MDMA-induced liver damage, the underlying mechanism accounting for hepatic toxicity is poorly understood. Various mechanisms may contribute to MDMA-induced liver toxicity, including the metabolism of MDMA, the increased efflux of neurotransmitters, the oxidation of biogenic amines, and hyperthermia. The molecular mechanisms involved in the genesis of these toxic effects are not yet fully clarified, but the oxidative stress, excitotoxicity, and mitochondrial dysfunction appear to be causal events that converge to mediate MDMA-induced neurotoxicity, as measured by loss of various markers of dopaminergic and serotonergic terminals. The evidence is overwhelming that MDMA produces acute and long-lasting toxic anatomic effects in animals and humans. Anatomical and functional MDMA consequences must be better understood.

Complement C3a expression and tryptase degranulation as promising histopathological tests for diagnosing fatal amniotic fluid embolism.

To date, the most recent specific diagnostic investigations for amniotic fluid embolism have been unable to conclusively identify any mechanism of disease other than a physical block to the circulation. We selected eight fatal cases in previously healthy women with uneventful singleton term pregnancies who presented to tertiary care centers in Italy for delivery. Pathologic features were assessed immunohistochemically using anti-fibrinogen, anti-tryptase, anti-C3a, and anti-cytokeratin antibodies. AE1/AE3 cytokeratin stains proved positive, and tryptase-positive material was documented outside pulmonary mast cells. In all studied cases, expression of complement C3a was twofold lower than in the control group, suggesting a possible complement activation in AFE, initiated by fetal antigen leaking into the maternal circulation.

Ceftriaxone intradermal test-related fatal anaphylactic shock: a medico-legal nightmare.

Allergic reactions to betalactams are the most common cause of adverse drug reactions mediated by specific immunological mechanisms (1). The diagnosis of betalactam allergic reactions is now well established and can be determined using the standardized diagnostic procedures of the European Network for Drug Allergy (ENDA) (2). Intradermal testing is done by the injection of 0.02–0.05 ml of the hapten solution, raising a small bleb that is marked initially. It should be performed on the volar forearm, although other skin areas can be used. Particular caution and testing, starting with 1000-fold dilutions of the stock reagents, should be used in patients who have experienced severe or life-threatening reactions such as anaphylaxis. Skin testing with betalactams should be performed under controlled conditions with emergency treatment available, as systemic side-effects may occur up to 10% of the patients being tested for drug allergy (3). Oral provocation tests are inducing far more systemic reactions than skin tests (4, 5). A 59-year-old man was admitted to the Emergency Department for blunt chest and abdominal trauma. The clinical examination was negative. Medical history was positive for type 2 diabetes and pathological obesity. Patient’s wife referred about an allergic reaction to a cephalosporin (ceftriaxone), 1 month before. An intradermal skin test with ceftriaxone was immediately performed and 5 min after the injection of an undetermined diluted ceftriaxone solution in the left forearm, the patient experienced severe bronchospasm, dyspnoea, restlessness and generalized pruritus. Corticosteroid therapy and continuous fluid replacement were started. The patient required tracheal intubation. Vasoactive drugs (adrenaline and atropine) were administered only 15 min after presentation of the symptoms. Cardio-pulmonary resuscitation was unsuccessful and the man was declared dead. A postmortem examination was performed. On external examination, a small wheal (3 mm in diameter) with