V. Fineschi

THE DIAGNOSIS OF AMNIOTIC FLUID EMBOLISM : AN IMMUNOHISTOCHEMICAL STUDY FOR THE QUANTIFICATION OF PULMONARY MAST CELL TRYPTASE

Abstract Recent clinical articles have suggested that amniotic fluid embolism (AFE) may be the result of anaphylactic reactions to fetal antigens and that the major part of this clinical syndrome is the result of mast cell degranulation and of the release of histamine, tryptase and other mediators. Tryptase, a neutral protease, is known to be the dominant protein component of the secretory granules of T and TC mast cells. In this paper we have examined the presence and the pulmonary distribution of mast cell tryptase utilizing specific immunohistochemical studies and morphometric evaluation in six cases of fatal amniotic fluid embolism compared to six subjects who died following anaphylactic shock and two control groups (five and six cases respectively) of traumatic death. The results demonstrate a numerical increase of pulmonary mast cells in the subjects who died of AFE (average cell number 54.095) with values corresponding to those encountered in cases of death due to anaphylactic shock (average cell number 51.378) compared with that of the traumatic control groups (average cell number 24.477 and 9.995 respectively). These results can shed light on additional criteria for the diagnosis of amniotic fluid embolism.

Fatal poisoning by MDMA (ecstasy) and MDEA: a case report

The first observation of lethal recreational use of MDMA (ecstasy) and MDEA in Italy is reported, together with extensive toxicological and histopathological documentation. Findings such as disseminated intravascular coagulation, rarely reported before, are colocated in the framework of the toxic syndrome for a better definition of criteria for forensic diagnosis.

Adam (MDMA) and Eve (MDEA) misuse: an immunohistochemical study on three fatal cases

Three fatal cases of MDMA/MDEA misuse have been examined. These referred to white males between 19 and 20 years of age, in which post-mortem toxicology showed the presence of MDMA (in one case), MDEA (in one case) and both (in one case). The clinical data were analysed and the histopathological findings were studied following immunohistochemical investigations. A complete immunohistochemical study has made it possible to demonstrate rhabdomyolysis and myoglobinuria with alterations of the organs typical of a DIC. Clinical, histopathological and toxicological data suggest that severe or fatal complications following ecstasy ingestion could be related to idiosyncratic response.

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.

Fatal anaphylactic shock during a fluorescein angiography

The Authors describe an extremely rare fatal case (sixth case in the literature) of anaphylactic shock following a fluorescein angiography. This is the first report in which the diagnosis of anaphylactic reaction to the dye was made through laboratory analyses. The diagnosis of fatal shock due to sodium fluorescein was made based on clinical, laboratory and immunohistochemical data. Mast-cell tryptase was dosed in serum and a pulmonary immunohistochemical evaluation was performed. Tryptase, a neutral protease of human mast-cells is a potentially important indicator of mast-cell involvement in anaphylactic events.

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

Myocardial necrosis and cocaine. A quantitative morphologic study in 26 cocaine-associated deaths.

Abstract A quantification of different forms of acute myocardial necrosis, myocardial leukocytic infiltrates and myocardial fibrosis was accomplished in 26 chronic cocaine abusers who died of cocaine intoxication and compared to 45 normal subjects who died from head trauma and 38 who died of acquired immunodeficiency syndrome. The findings were: absence of infarct necrosis, a similar frequency and extent of coagulative myocytolysis (contraction band necrosis) and leukocytic infiltrates in cocaine abusers and normal controls, and an absence of myocardial fibrosis in cocaine abusers. These findings question both the acute and chronic cardiotoxicity of cocaine. The infarct-like pattern in some predisposed subjects may be due to an excess of catecholamine release induced by the drug resulting in coagulative myocytolysis and platelet thrombi.

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. Its 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-1β) 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).

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.

Histological Criteria for Diagnosis of Amanita Phalloides Poisoning

Five fatal cases of poisoning from ingestion of Amanita phalloides, a very common mushroom in central Italy, are reported. The fact that four of the cases occurred simultaneously enabled uniform collection of clinical, pathology and toxicology data, which is presented with particular emphasis on the histological aspects. The fifth case involved a six-year-old girl, and is discussed with reference to differential diagnosis with respect to Reyes syndrome, which was the initial diagnosis, demonstrated incorrect by the histology, pathology and toxicology findings. The typical liver and kidney alterations of Amanita phalloides poisoning, consisting of massive hepatic central lobular cell necrosis and acute tubular necrosis of the kidney are described. Outside the liver, there was often general hemorrhagic diathesis and severe brain edema. Although poisoning by Amanita phalloides is rare, these cases confirm the requirement for as complete a comparison as possible between circumstantial histopathological and toxicological data for the purposes of forensic diagnosis.