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.

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.

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.

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.

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.

Markers of cardiac oxidative stress and altered morphology after intraperitoneal cocaine injection in a rat model.

This study was designed to assess the parameters of myocardial oxidative stress and related cardiac morphological changes following intraperitoneal cocaine exposure in rats. The cardiac levels of reduced glutathione(GSH), oxidised glutathione(GSSG), ascorbic acid (AA), and the production of malondialdehyde (MDA) were measured, as well as the variations of activity in the enzyme systems involved in cell antioxidant defence, glutathione peroxidase (GSH-Px), glutathione reductase (GR) and superoxide dismutase (SOD). After chronic cocaine administration for 30 days GSH was significantly depleted in the heart from 30 min (P < 0.001) to 24 h (P < 0.001) after exposure, and GSSG was increased for a similar time (P < 0.05 at 30 min and P < 0.01 at 24 h). SOD increased during the first hour (P < 0.001), GR and GSH-Px both increased from 30 min to 24 h, and these increases were statistically significant (P < 0.01 and P < 0.001 at 30 min and P < 0.01 and P < 0.001 at 24 h, respectively). The AA levels increased after 1 h (P < 0.01), remaining significantly so for 24 h (P < 0.001) and MDA increased from 30 min to 24 h, all values being highly significant (P < 0.001). The body weight was significantly (P < 0.001) reduced in both cocaine groups (40 mg/kg x 30 days and 40 mg/kg x 10 days + 60 mg/kg x 20 days). The heart weight (P < 0.01) and its percentage of the body weight (P < 0.001) were significantly higher in these two groups than in the controls. Similarly, in the noradrenaline 4 mg/ kg x 30 days group, the body weight was significantly (P < 0.001) reduced and the heart weight (P < 0.01) and its percentage of body weight (P < 0.001) were significantly higher than in the controls. In comparing the cocaine and noradrenaline experiments, the frequency and extent of cardiac lesions obtained with 40 mg/kg x 10 days + 60 mg/kg x 20 days of cocaine were similar to those with 8 mg/kg of noradrenaline at 24 h. In this experimental model, cocaine administration compromised the antioxidant defence system of the heart associated with a significant increase of heart weight and the percentage of body weight.

Myocardial contraction bands. Definition, quantification and significance in forensic pathology.

Pathological contraction bands affecting myocardial cells are observed in many different human conditions and in different experimental models. Their morphology was defined long ago but we need to understand the pathogenesis and functional meaning. A distinction between different histological forms of contraction bands and their quantification in a large spectrum of human diseases (262 cases) and a normal population sample where death was due to various types of accidental death (170 cases) produced the following conclusions: 1) The term "contraction band necrosis", as used presently, is ambiguous and should be reserved for a specific morpho-functional entity induced experimentally by intravenous catecholamine infusion and seen in equivalent human cases with pheochromocytoma. 2) In human pathology it may represent a sign of adrenergic stress linked with malignant arrhythmia/ventricular fibrillation. 3) Beyond a histological threshold of 37+/-7 foci and 322+/-99 myocells/100 mm2, the lesion may indicate sympathetic overdrive in the natural history of a disease and associated arrhythmogenic supersensitivity. 4) The detection of few pathological contraction bands in normal subjects in some types of accidental death correlates with the survival time, suggesting an agonal adrenergic stimulation to promote the cardiac pump.

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

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.