Iron overdose epidemiology, clinical features and iron concentration-effect relationships: the UK experience 2008-2017.

Background: Iron poisoning is potentially serious, but mortality has fallen worldwide since implementation of pack size and packaging restrictions, and changes in iron use during pregnancy. The management of individual cases of overdose remains problematic due to uncertainty about indications for antidote. We examine the epidemiology of iron overdose in hospital cases referred to the UK National Poisons Information Service (NPIS) and evaluate the toxicokinetics of iron in patients ingesting only iron preparations. Methods: Anonymized hospital referral patient data from the NPIS database were collated for the period 1 January 2008 to 31 July 2017. Information was extracted, where recorded, on type of ingestion [iron alone (single), or combined with other agents (mixed)], reported dose, iron salt, timed iron concentrations and symptoms. In single-agent ingestions, the relationships between reported elemental iron dose, early concentrations (4-6 h), and symptoms were evaluated in teenagers and adults (≥13 years) and children (≤12 years) using standard statistical techniques (correlation and unpaired nonparametric comparisons). In those patients with sufficient sample points (three or more), a simple kinetic analysis was conducted. Results: Of 2708 patients with iron overdoses referred by UK hospitals for advice during the 9.7 years study period, 1839 were single-agent ingestions. There were two peaks in age incidence in single-agent exposures; 539/1839 (28.4%) were <6 years (54.1% males) while 675/1839 (36.7%) were between 13 and 20 years (91% females), the latter a substantial excess over the proportion in the totality of hospital referrals to the NPIS in the same period (13-20 years: 23,776/144,268 16.5%; 67.5% female) (p < .0001 overall and for female %). In 475 teenagers and adults and 86 children, with at least one-timed iron concentration available, there was no correlation between stated dose and iron concentration measured 4-6 h post-ingestion. Observed peak iron concentrations were not related to reported symptoms in adults. Initial iron concentrations were significantly higher in 30 patients (25 adults, 5 children) who received desferrioxamine (DFO) compared to those that did not [no DFO: mean 63.8 µmol/L (95% CI 62.1-65.6), median 64; DFO: mean 78.5 µmol/L (95% CI 69.2-87.7), median 78.1; Mann-Whitney p < .0018). No significant differences in symptoms were observed pre-treatment between DFO-treated and untreated groups. No patients died in this cohort. Conclusion: Single-agent iron exposures reported from UK hospitals were most common in children <5 years and young people aged 13-20 years. Poisoning with organ failure was not identified and there were no fatalities. No correlations were observed between reported iron doses and early concentrations, or between iron concentrations and symptoms in this cohort of mild-to-moderate poisoning.

Expertos, juicios y crimen: Pere Mata (1811-1877) y el veneno de María Bonamot / Experts, trials and crimes: Pere Mata (1811-1877) and Maria Bonamot's poison

El siglo XIX fue un periodo en el que se produjo un creciente interés por los venenos y los crímenes por envenenamiento a pesar de no ser formas habituales de homicidio. La nueva toxicología pretendía ofrecer herramientas para combatir este tipo de crímenes. Sin embargo, fueron precisamente los debates surgidos durante los procesos judiciales, los que ayudaron a configurar la toxicología del siglo XIX. Alejados de las pautas ofrecidas en los manuales y ante la necesidad de mostrar a un juez carente de formación en estas materias, la presencia o ausencia del veneno, los toxicólogos del siglo XIX pusieron en juego todas sus estrategias para vencer a otros expertos y convencer a los profanos. A mediados de 1844 se produjo en Madrid un caso de envenenamiento que llamó la atención tanto de la prensa médica como de la prensa periódica española. Dos factores contribuyeron a su popularidad: las fechas en las que se produjo (tan solo un año después de la creación de la cátedra de Medicina Legal en las Facultades de Madrid y Barcelona); y la participación como peritos de algunos de los personajes españoles más influyentes en la medicina legal y toxicología española como es el caso de Pere Mata i Fontanet (1811-1877). Pere Mata desempeñó una labor importante en los tres terrenos que contribuyeron decisivamente a la homogeneidad de la comunidad de toxicólogos: la formación universitaria, la literatura académica y la organización profesional. El análisis de un caso de envenenamiento como el que se desarrolla en este trabajo, permite considerar muchas de las cuestiones relacionadas con la toxicología en el siglo XIX: la constitución de una nueva disciplina académica, la creación de una comunidad de expertos, las controversias públicas y la gestión de las pruebas periciales en los tribunales

The XIXth century saw a growing interest in poisons and crimes by poison although these are not usual ways of murder. New technology aspired to offer tools to combat this type of crimes. However, it was precisely the debates that arose during trials that helped to configure XIXth century toxicology. Far from the guidelines offered in manuals and facing the need to demonstrate to a judge, lacking In training in these subjects the presence or absence of the poison, XIXth century toxicologists used all of their strategies to beat other experts and convince the layperson. In the middle of 1844 there was a case of poisoning in Madrid that caught the attention of both the medical press and the Spanish newspapers. Two factors contributed to its popularity: the date that it happened 8only a year after the creation of the chair of Forensic Medicine at the faculties in Madrid and Barcelona); and the participation as experts of some of the most influential Spaniards in forensic medicine and Spanish toxicology such as Pere Mata I Fontanet (1811-1877). Pere Mata carried out important work in the three fields which decisively contributed to the homogeneity of the community of toxicologists: university training, academic literature and the professional organization. The analysis of a case of poisoning as the one developed in this work permits the consideration of many issues related totoxicology in the XIXth century: the constitution of a new academic subject, the creation of a community of experts, public controversies and the management of expert evidence at trials

Life and death of Vladimir Mikhailovich Bekhterev / Vida e morte de Vladimir Mikhailovich Bekhterev

Vladimir Mikhailovich Bekhterev was a Russian innovative neuroscientist, extraordinary in the study, diagnosis, and research in the fields of neurology, psychology, morphology, physiology, and psychiatry. Considering the ample and multifaceted scientific feats, only some are touched in a very brief manner. However, it is necessary to highlight his contributions to neurology, with the description of structures, signs and syndromes, to physiology, including reflexology, which later underpinned behaviorism, to psychology, including objective psychology and suggestion. His accomplishments and legacy remained until the present days. Some comments about the scenery that involved his death are also presented.

Vladimir Mikhailovich Bekhterev foi um neurocientista russo inovador, extraordinário no estudo, diagnóstico, e pesquisa nas áreas da neurologia, psicologia, morfologia, fisiologia e psiquiatria. Considerando seus feitos científicos amplos e multifacetados, apenas alguns são tocados de um modo muito abreviado. Entretanto, é necessário realçar suas contribuições à neurologia, com a descrição de estruturas, sinais e síndromes, à fisiologia, compreendendo a reflexologia, que mais tarde fundamentou o behaviorismo, à psicologia, incluindo a psicologia objetiva e a sugestão. Suas realizações e legado se mantiveram até a presente data. Alguns comentários sobre o cenário que envolveu sua morte também são apresentados.

Life and death of Vladimir Mikhailovich Bekhterev.

Vladimir Mikhailovich Bekhterev was a Russian innovative neuroscientist, extraordinary in the study, diagnosis, and research in the fields of neurology, psychology, morphology, physiology, and psychiatry. Considering the ample and multifaceted scientific feats, only some are touched in a very brief manner. However, it is necessary to highlight his contributions to neurology, with the description of structures, signs and syndromes, to physiology, including reflexology, which later underpinned behaviorism, to psychology, including objective psychology and suggestion. His accomplishments and legacy remained until the present days. Some comments about the scenery that involved his death are also presented.

[Bull's blood as an ancient poison]. / Bycza krew jako antyczna trucizna.

Article presents ancient tradition about poisoning with bull's blood and the modern attempts of its explanation. Greek and Roman literary sources are compared with the ancient medical texts.

[At the origin of the theriac: the receipt of Andromachus]. / Aux origines de la thériaque: la recette d'Andromaque.

The Greek physician Galen of Pergamum (129-c. 210) has preserved in his two tracts De antidotis and De theriaca ad Pisonem the original recipe of the theriac under the name of Andromachus. Galen specifies that Andromachus was the first to add flesh of vipers in this pharmacological preparation. This paper intends to study the real originality of Andromachus compared with his predecessors and to examine in which sense he can really be considered as the inventor of the theriac.

Solanaceae III: henbane, hags and Hawley Harvey Crippen.

Hyoscyamus, the henbane, is one of the drugs of the ancients. Initially used both as a poison and narcotic, it was widely adopted by witches, wizards and soothsayers as a component of their hallucinatory and flying ointments. It was also used by notorious poisoners such as Madame Voisin in France. Eventually, in the nineteenth century its active principle was isolated by Ladenburg and called l-hyoscine. It proved to be a tropane alkaloid very similar to atropine. These two alkaloids proved to be very important in the study of the parasympathetic component of the autonomic nervous system, and together with physostigmine, allowed the major neurotransmitter acetylcholine to be isolated and its mechanisms of action to be characterised. The Crippen murder case in 1910 gave hyoscine further fame, indeed, notoriety. The unassuming homeopathic doctor murdered his wife with the alkaloid and then decamped for Canada with his mistress Ethel Le Neve. The case became a worldwide sensation for several reasons: the arrest of the fugitive couple by wireless telegraphy (Marconigram) and the extensive chemical and histological evidence presented by Willcox and Spilsbury. Some authorities claim that this was the beginning of the science of forensic medicine in Britain. Hyoscine is now hardly ever used in modern therapeutics but its history from antiquity to the witches and on to Dr Crippen is both bizarre and fascinating.

Toxicology in the Old Testament. Did the High Priest Alcimus die of acute aconitine poisoning?

The Bible contains several interesting contributions to the history of neurology, as is the case of the High Priest Alkimos, who died suddenly in 159 BC. He was regarded as a stereotypical stroke victim for a long time. The reports on his death in the Septauginta and the later 'Jewish Antiquities' of Flavius Josephus present some typical symptoms of stroke (collapse, loss of speech and death within a short time), but they also describe severe pains, which are very unusual among patients with stroke. Similar symptoms can be found in the case of the Roman emperor Claudius, who was poisoned by his spouse Agrippina. It was thought that she used aconitine, an ingredient of the monkshood plant (Aconitum napellus L.), which imitates an apoplectic insult, but also causes vehement pains. It was therefore possible that something similar had happened to Alkimos, as aconitine was a common poison in ancient times and the surroundings of his death may confirm the suspicion. Reigning during a time of great upheaval, Alkimos was able to maintain his high office chiefly because of the help of the Seleucides. He has just begun construction work on the temple of Jerusalem, an order, which was regarded as a sacrilege by his foes. This impression was enhanced by his subsequent illness which could be considered as a divine punishment.

Why did the 5th Earl of Derby die?

The unexpected death of Ferdinando Stanley, 5th Earl of Derby, on April 16, 1594 was an event of major political importance in the later years of Queen Elizabeth I of England. When he had succeeded his father at the age of 38 he became head of one of the most influential families in the country. He also had a claim to the throne if Elizabeth died without naming a successor. Yet within seven months of entering into his inheritance, this previously fit man was suddenly taken ill and died a fortnight later. His death was so significant that the historian John Stow recorded his illness in great detail (Fig. 1).(1) Stow's remarkable account is compatible with a sinister interpretation of the cause.

[Doctor of medicine Awit Reniger (1853-1907) and his doctorate dissertation]. / Awit Reniger (1853-1907) i jego rozprawa na stopien doktora medycyny.

The author announced main details of Awit Reniger's life, main thesis and conclusions of his doctorate dissertation. Doctor's Thesis concerning: Pathological changes in the anatomy of marrow in cases of the phosphorus intoxication. This dissertation is not reported in S. Konopka's: Polish medical bibliography of the nineteenth century (1801-1900).