Caffeine. cognitive and physical performance enhancer or psychoactive drug?

Caffeine use is increasing worldwide. The underlying motivations are mainly concentration and memory enhancement and physical performance improvement. Coffee and caffeine-containing products affect the cardiovascular system, with their positive inotropic and chronotropic effects, and the central nervous system, with their locomotor activity stimulation and anxiogenic-like effects. Thus, it is of interest to examine whether these effects could be detrimental for health. Furthermore, caffeine abuse and dependence are becoming more and more common and can lead to caffeine intoxication, which puts individuals at risk for premature and unnatural death. The present review summarizes the main findings concerning caffeine's mechanisms of action (focusing on adenosine antagonism, intracellular calcium mobilization, and phosphodiesterases inhibition), use, abuse, dependence, intoxication, and lethal effects. It also suggests that the concepts of toxic and lethal doses are relative, since doses below the toxic and/or lethal range may play a causal role in intoxication or death. This could be due to caffeine's interaction with other substances or to the individuals' preexisting metabolism alterations or diseases

A proposed role for sepsis in the pathogenesis of myocardial calcification

Myocardial calcification is a rare and life-threatening condition that is a recognised complication of ischaemic heart disease, cardiac surgery, rheumatic fever and myocarditis. It is distinct from coronary artery or valvular calcification, and can be seen in patients with abnormal calcium metabolism1 . Its presence in the context of sepsis is less well recognised and the mechanisms responsible are poorly understood. We review the relevant literature and propose a mechanistic theory for its pathogenesi

Main features and control strategies to reduce overcrowding in emergency departments. A systematic review of the literature

Purpose: Overcrowding is a problem that affects emergency departments (ED) all over the world; it occurs due to a disproportion between user demand and the physical, human and structural resources available. Essential prerequisites to assessing and managing the phenomenon are its accurate measurement and an understanding of its impact. The objective of this systematic review is to identify the characteristics of the problem, analyzing the proposed strategies aimed at improving patient flow, delay in services provided and overcrowding of emergency departments. Methods: To achieve our objectives, a manual computerized search was performed in the bibliographic databases using as keywords “Emergency Department”, “Overcrowding”, “Emergency Room”, “Emergency Service”, “Emergency Unit”“,Emergency Ward”, “Emergency Outpatient Unit”, “Emergency Hospital”, “Crowding”, “Mass Gathering”, “Management” and “Comprehensive Health Care”. Two independent reviewers analyzed abstracts, titles and full text articles for admissibility, according to the selected inclusion and exclusion criteria. Results: The process lead to include 19 articles. It was possible to group the solutions proposed in five categories: work organization, investment in primary care, creation of new dedicated professional figures, work and structural modifications and implementation of predictive simulation models using mathematical algorithms. Conclusion: The most effective measures to guarantee an improvement in the flow of patients are represented by both improving the efficiency of human resources and by developing predictive mathematical models, regardless of the type of hospital and its location. Considering the complexity of EDs and the multiple characteristics of overcrowding and that the causes of crowding are different and site-specific, a careful examination of the specifics of each ED is necessary to identify improving fields

Sodium Nitrite Intoxication and Death: Summarizing Evidence to Facilitate Diagnosis

Background: Over the years, forensic pathology has registered the spread of new methods of suicide, such as the ingestion of sodium nitrite. Sodium nitrite causes increased methemoglobin, resulting in systemic hypoxia, metabolic acidosis, and cyanosis. Since sodium nitrite is a preservative, the ingestion of foods containing an excessive amount of this substance can also cause acute intoxication up to death. The present review is aimed at guiding health professionals in the identification and management of sodium-nitrite-related intoxications and deaths. Methods: A systematic literature search was carried out on PubMed by following the PRISMA statement’s criteria. A total of 35 studies with 132 cases were enrolled, and the data were cataloged in Microsoft Excel. To establish the causal correlation between sodium nitrite ingestion and death, the Naranjo Adverse Drug Reaction Probability Scale was used. Results: In addition to the small number of cases that have currently been published, the study demonstrated that there was a general methodological discrepancy in the diagnostic process. However, some interesting results have emerged, especially in post-mortem diagnostics. Conclusion: Sodium-nitrite-related deaths represent a challenge for forensic pathologists; therefore, it is important to promptly recognize the essential features and perform the necessary and unrepeatable examinations for the correct diagnosis of the cause of death

Takotsubo cardiomyopathy and sepsis: a systematic review

Takotsubo cardiomyopathy (TTC) is characterized by a systolic dysfunction localized in the apical and medial aspect of the left ventricle. It is usually related to physical or emotional stress. Recent evidence highlighting the role of infection led us to analyze the links between TTC and sepsis. A systematic review of the literature was undertaken to assess any trends in clinical findings, diagnosis, and outcomes in such patients. We identified 23 selected papers reporting a total of 26 patients, having sepsis, in whom TTC occurred. For each case, we collected data identifying population characteristics, source of sepsis, clinical disease description, and the results of cardiovascular investigations. The majority of patients were females (n = 16), mean age was 62.8 (14.0 standard deviation) years, and clinical outcome was favorable in 92.3% of the cases once the management of sepsis was initiated. A better understanding of the mechanisms of sepsis-associated TTC may generate novel strategies to treat the complications of this cardiomyopathy and may even help predict and prevent its occurrence

New "lethal highs": a case of a deadly cocktail of GHB and Mephedrone.

Drug scenes within several countries have changed in recent years to incorporate a range of licit psychoactive products collectively known as ‘‘legal highs’’: these in combination with substances already in use can cause major health problems and even death. Consumption of Gammahydroxybutyric acid (GHB) spread from 1980s to 2000s, when several nations have enacted laws that have made it illegal. Cases of GHB-caused or related deaths are often described in association with alcohol or traditional drugs (heroin, cocaine, amphetamine); few cases of acute lethal toxicity due to Mephedrone have been recently reported; we describe the first case of fatality due to concomitant consumption of GHB and Mephedrone. A 43 years old man died during a drugs-based party: the two substances were not detected at toxicological screening, but were identified by further analysis on the basis of circumstantial data reported by a survivor. Through our work we aim to bring to the attention in the emerging rol

A lethal case of hoarding due to the combination of traumatic and confined space asphyxia.

Hoarding is defined as the acquisition of, and failure to discard, possessions of little use or value to others, usually associated with a significant degree of clutter in the individual's home. We describe a case of a woman who died from a combined traumatic and confined space asphyxia, after being trapped under some of the objects amassed in her apartment. The event was considered to be accidental; by taking into account the information gathered during assessment of the scene, we believe that the accident took place while entering or exiting the apartment. It appears that the woman, who was trying to open or close the door, could have been using her leg to keep the objects piled behind the door from falling. Unfortunately the pile of hoarded objects collapsed and the woman was fatally trapped underneath them. The age and strength of the woman played an important role in the fatal incident, she was too old and weak to remove the items that had collapsed over her body. The scarcity of space between the collapsed objects and the woman, as well as the absence of external or internal signs of violent asphyxiation, or other causes of death, allowed us to establish that the death resulted from a combined mechanism of both the traumatic and the confined space asphyxiation

Intrauterine fetal decapitation after a high-speed car crash

Motor vehicle collisions are an important cause of blunt abdominal trauma in pregnant woman. Among the possible outcomes of blunt abdominal trauma, placental abruption, direct fetal trauma, and rupture of the gravid uterus are described. An interesting case of complete fetal decapitation with uterine rupture due to a high-velocity motor vehicle collision is described. The external examination of the fetus showed a disconnection between the cervical vertebrae C3 and C4. The autopsy examination showed hematic infiltration of the epicranic soft tissues, an overlap of the parietal bones, and a subarachnoid hemorrhage in the posterior part of interparietal area. Histological analysis was carried out showing a lack of epithelium and hemorrhages in the subcutaneous tissue, a hematic infiltration between the muscular fibers of the neck and between the collagen and deep muscular fibers of the tracheal wall. Specimens collected from the placenta and from the uterus showed a hematic infiltratio

Molecular analysis of different classes of RNA molecules from formalin-fixed paraffin-embedded autoptic tissues: a pilot study

For a long time, it has been thought that fresh and frozen tissues are the only possible source of biological material useful to extract nucleic acids suitable for downstream molecular analysis. Recently, for forensic purpose such as personal identification, also fixed tissues have been used to recover DNA molecules, whereas RNA extracted from such material is still considered too degraded for gene expression studies. In the present pilot study, we evaluated the possibility to use forensic formalin-fixed paraffin-embedded (FFPE) samples, collected at autopsy at different postmortem intervals (PMI) from four individuals, to perform advanced molecular analyses. In particular, we performed qualitative and quantitative analyses of total RNAs extracted from different FFPE tissues and put expression profiles in relation with the organ type and the duration of PMI. Different classes of RNA molecular targets were studied by real-time quantitative RT-PCR. We report molecular evidence that small RNAs are the only RNA molecules still detectable in all the FFPE autoptic tissues. In particular, microRNAs (miRNAs) represent a consistent, stable, and well-preserved molecular target detectable even from tissue sources displaying signs of ongoing putrefaction at autopsy. In this pilot study, we show that miRNAs could represent a highly sensitive and potentially useful forensic marker. Amplification of specific miRNAs using paraffin-embedded blocks could facilitate retrospective molecular analysis using specific forensic-archived tissues chosen as most suitable according to PMI, and this approach would address molecular evidence in forensic cases in which fresh or frozen material is no longer available

Methadone Related Deaths: Identifying the Vulnerable Patients.

Methadone has been used in opioid dependence treatment since the 1960s and is now prescribed also as a chronic pain treatment. Even though its effectiveness has been worldwide assessed, literature reports several cases of death associated with the administration of this drug. Risk factors are still uncertain and the frequent combination with other substances of abuse makes it even more difficult to determine the exact role of methadone in the pathogenesis of fatalities. In this paper the authors present the autopsy findings in a subset of deaths characterized by blood being positive for the methadone only at a therapeutic dose in order to point out those pre-existent pathologic conditions that seem to increase the risk of death in methadone treatment. A routine screening test for a broad spectrum of drugs in urine samples (including methadone, benzodiazepines, cocaine, amphetamines/ methamphetamines, opioids, barbiturates, tetrahydrocannabinol, tricyclic antidepressants) using the ASCENDTM Multi-immunoassay kit (TriageTM8 - Merk®) was performed in all cases of suspected drug-related death, which occurred in the East side of Rome during 2011 (a total of 104 subjects; 73 % male; 27 %female; mean age 32 years old). Among all the subjects examined, 51 were positive for methadone but only 8 belonging to this subset were negative for any other tested drug. A complete autopsy and histological examination was performed in cases where methadone was detected alone and the results were analysed. The histological findings and our observations demonstrated pre-existing conditions affecting the heart and lungs and/or the liver suggesting the importance of an accurate screening/follow up focused on these organs prior to and during treatment in order to promptly identify the presence/onset of clinical conditions increasing the patient’s vulnerability to methadone treatment