47 research outputs found
Forensic Toxicology: Clinico‐pathological Aspects and Medico‐legal Issues
No full textEssential Forensic Medicine covers the broad area of the forensic medical sciences, delivering core knowledge in the biomedical sciences, and the law and ethics surrounding them. Concise, accessible chapters cover a wide range of topics from basic forensic identification and examination techniques to forensic toxicology and psychiatry. Written by internationally-recognized experts in the field, this authoritative guide offers complete chapter coverage of the legal system, courts, and witnesses; investigation of the deceased and their lawful disposal; and the duties of a registered medical practitioner and the General Medical Council. It instructs readers on the general principles of scene examination and the medico-legal autopsy including how to interpret the many kinds of injuries one can suffer—including those from blunt impact and sharp force, firearms and explosives, asphyxia and drowning. Further chapters cover sexual offences, child abuse, and using DNA in human identification, mental health, alcohol and drug abuse. A fresh, accessible, up to date textbook on forensic medicine Written by a well-known experts with decades of experience in the field Includes numerous figures and tables, and detailed lists of key information Features numerous case studies to reinforce key concepts and ideas explored within the book Helps students to prepare for examinations and enables practitioners to broaden their understanding of the discipline Part of the “Essential Forensic Science” series, Essential Forensic Medicine is a highly useful guide for advanced undergraduate students, master’s students, and new practitioners to the field
DOMPERIDONE E MORTE CARDIACA IMPROVVISA: IMPLICAZIONI MEDICOLEGALI
No full textIntroduzione: la morte cardiaca improvvisa (MCI) è definita come una morte naturale per cause cardiache, che si realizza al massimo entro un’ora dalla comparsa della sintomatologia acuta in un soggetto nel quale, indipendentemente dalla conoscenza di una cardiopatia preesistente, il decesso giunga inatteso e per il tempo e per la modalità. La MCI usualmente riconosce il concorso di concause pre-esistenti, a diversa espressione disfunzionale, sulle quali agisce un fattore scatenante, il quale può assumere rilievo forense.Materiali e metodi: è presentato il caso di una donna di 47 anni con storia di dipendenza da alcool e prolasso valvolare mitralico noto, che, senza prescrizione medica, ha assunto per disturbi gastrointestinali 2 compresse da 10 mg di Domperidone (D), alle ore 09.00 e alle ore 12.00 della stessa giornata nella quale, alle ore 17,45 andava incontro a morte improvvisa. Ciò avveniva nel corso di una seduta di psicoterapia. L’esame necroscopico era corredato da prelievi ed esami tossicologici con ricerca di D su sangue e screening “general unknown” su urine (LC-MS/MS).Risultati: l’esame cardiopatologico ha rilevato macroscopicamente lieve ipertrofia cardiaca e minimo prolasso del lembo anteriore della valvola mitrale, ed istologicamente ipertrofia miocitaria, diffusa disorganizzazione delle miofibre, edema e fibrosi perivascolare. A livello epatico steato-cirrosi avanzata. Gli esami tossicologici su sangue hanno accertato una concentrazione ematica di D pari a 36,81 ng/mL (86 nM); la ricerca di xenobiotici su urina ha dato esito negativo.Conclusioni: si tratta di un caso di MCI di tipo aritmico, correlabile sotto il profilo concausale a fattori preesistenti quali il prolasso mitralico1 ed una cardiomiopatia ad eziologia non nota (verosimilmente esotossica), implicanti la sussistenza di un quadro di instabilità elettrica miocardica con conseguente abbassamento della soglia di fibrillazione ventricolare. Il possibile effetto pro-aritmico è stato esercitato, a nostro avviso, dal Domperidone (D), farmaco a rischio di torsione di punta2 e di MCI, agente con un blocco dei canali del potassio della cellula cardiaca (IKr.) e correlata alterazione della fase di ripolarizzazione miocitaria da cui rischio di sviluppo di aritmie3. Le prime segnalazioni di tali effetti avversi risalgono a circa 10 anni or sono, comportando la diffida all’impiego del farmaco da parte della Comunità Scientifica. Studi recenti hanno stabilito, tra l’altro, per il D un basso indice terapeutico, potendosi documentare alterazioni della ripolarizzazione miocitaria già a partire da 30-60 nM (12,8-25.5 ng/mL)4. Inoltre, sebbene i predetti effetti avversi del D siano stati di recente recepiti dall’Agenzia Italiana del Farmaco (AIFA) con la sua nota del 14.11.20115, il D, per dosaggi bassi (5 mg), rimane di libera vendita per automedicazione, nonostante possa essere riconosciuto quale fattore trigger anche letale. Il D è metabolizzato a livello epatico, la sua somministrazione in soggetti epatopatici è pertanto controindicata, implicando il realizzarsi di picchi ematici elevati ed il prolungarsi del tempo di dimezzamento. Nel caso sopra esposto infatti, nonostante l’assunzione di un dosaggio entro il range terapeutico, il farmaco è stato in grado di determinare, in un soggetto epatopatico, l’instaurarsi di concentrazioni ematiche idonee a causare alterazioni della ripolarizzazione miocitaria ad evoluzione letale
Consultation interface between Pathologist and Forensic Science Experts for histopathology examination
No full textDebate remains to how much the magnitude of histopathologic examination may be of benefit to medicolegal purposes. We sought to address the question after reviewing consultation cases requested to pathologists from forensics
A Mechanism for Altered Polyunsaturated Fatty Acid Biosynthesis in Cystic Fibrosis
No full textCystic fibrosis (CF) is a debilitating, multi-organ, autosomal recessive disease caused by mutations leading to absence of functional cystic fibrosis transmembrane conductance regulator (CFTR) in epithelial cells. Chronic pulmonary disease, characterized by excessive inflammation and recurrent infections, is the primary source of morbidity and mortality in individuals with CF. Altered polyunsaturated fatty acid (PUFA) biosynthesis, resulting in increased metabolism of linoleic acid (LA) to arachidonic acid (AA), plays a key role in CF pathophysiology. Increased AA biosynthesis contributes to excessive inflammation in the lungs of individuals with CF. The mechanism by which absence of functional CFTR leads to aberrant PUFA biosynthesis has been elusive. This dissertation is the first delineation of a pathway linking PUFA metabolism to CFTR. Through studies in human bronchial epithelial cells, this dissertation demonstrates that absence of functional CFTR leads to increased activation of AMP-activated protein kinase (AMPK) by calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ). Elevated AMPK activity leads to increased expression and activity of Δ6-desaturase (Δ6D) and Δ5-desaturase (Δ5D). Increased activity of Δ6D and Δ5D results in increased metabolism of LA to AA
Transiently Increased Variation Between a Point-of-Care and Laboratory INR Method After a Long Period of Correlation
No full textThe role of polyunsaturated fatty acid and eicosanoid biosynthesis in the pathogenesis of cystic fibrosis
No full textThe primary cause of morbidity and mortality in cystic fibrosis is progressive pulmonary disease, an important component of which is a hyperactive inflammatory response, the mechanisms of which are not completely understood. Previous studies have highlighted alterations in polyunsaturated fatty acid and eicosanoid metabolism in cystic fibrosis airway epithelial cells leading to increased arachidonic acid and its metabolites, the pro-inflammatory leukotrienes and prostaglandins. This work tests the hypothesis that these underlying metabolic abnormalities play an important role in the excessive inflammatory response. Using airway epithelial cell culture models of cystic fibrosis, we demonstrate that there is increased release of AA in response to stimulation in CF cells. Additionally, we show that enzymes of fatty acid and eicosanoid metabolism, including Δ6-desaturase, cytosolic phospholipase A2, cyclooxygenase-2, microsomal PGE2 synthase, and 5-lipoxygenase, are upregulated in cystic fibrosis cells compared to wild-type counterparts. These increases are exaggerated when the cells are stimulated with products of Pseudomonas aeruginosa culture, leading to increased production of PGE2 and LTB4 and the pro-inflammatory cytokines IL-6 and IL-8. Inhibition of the LTB4 synthesis pathway at any of multiple points results in blunting of both cyclooxygenase-2 expression and IL-6 and IL-8 production, while inhibition of cyclooxygenase-2 itself results in only minor suppression of cytokine production. Similar results are seen with docosahexaenoic acid, an anti-inflammatory n-3 fatty acid. Taken together, these results indicate that fatty acid and eicosanoid metabolic abnormalities that are intrinsic to epithelial cells in cystic fibrosis, particularly the LTB4 synthesis pathway, may play an important role in the hyperactive inflammatory response characteristic of this disease
The role of polyunsaturated fatty acid and eicosanoid biosynthesis in the pathogenesis of cystic fibrosis
No full textDHA and EPA reverse cystic fibrosis-related FA abnormalities by suppressing FA desaturase expression and activity
No full textUse of acetyl chloride/methanol for assumed selective methylation of plasma nonesterified fatty acids results in significant methylation of esterified fatty acids
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