Death of Socrates: a likely case of poison hemlock (Conium maculatum) poisoning.

INTRODUCTION: The death of Socrates in 399 BCE is described in Plato's dialogue, the Phaedo, written an unknown time afterwards from accounts by others. THE EVIDENCE: Socrates' death has almost always been attributed to his drinking an extract of poison hemlock, Conium maculatum, despite apparent discrepancies between the clinical features described in classical translations of the Phaedo and general clinical experience of poisoning with the toxic alkaloids it contains. EVALUATION: Recent acute philological analysis of the original Greek text has resolved many of the discrepancies by showing that the terms used in the classical translations were misinterpretations of the clinical signs described. It is also likely that the unpleasant clinical effects, such as vomiting, abdominal pain, diarrhoea and muscle fasciculation commonly described in modern reports of poison hemlock poisoning, were not mentioned to present the death of Socrates in a way consistent with his philosophical ideals and those of his pupil Plato. CONCLUSIONS: Seen in this way, the death of Socrates can be accepted as a limited case report of Conium maculatum poisoning. Even after reaching that conclusion, intriguing scientific questions remain about the toxicity of the coniine alkaloids and the mechanisms of their effects.

The role of inhaled methoxyflurane in acute pain management.

Methoxyflurane is an inhaled analgesic administered via a disposable inhaler which has been used in Australia for over 40 years for the management of pain associated with trauma and for medical procedures in children and adults. Now available in 16 countries worldwide, it is licensed in Europe for moderate to severe pain associated with trauma in conscious adults, although additional applications are being made to widen the range of approved indications. Considering these ongoing developments, we reviewed the available evidence on clinical usage and safety of inhaled analgesic methoxyflurane in trauma pain and in medical procedures in both adults and children. Published data on methoxyflurane in trauma and procedural pain show it to be effective, well tolerated, and highly rated by patients, providing rapid onset of analgesia. Methoxyflurane has a well-established safety profile; adverse events are usually brief and self-limiting, and no clinically significant effects on vital signs or consciousness levels have been reported. Nephrotoxicity previously associated with methoxyflurane at high anesthetic doses is not reported with low analgesic doses. Although two large retrospective comparative studies in the prehospital setting showed inhaled analgesic methoxyflurane to be less effective than intravenous morphine and intranasal fentanyl, this should be balanced against the administration, supervision times, and safety profile of these agents. Given the limitations of currently available analgesic agents in the prehospital and emergency department settings, the ease of use and portability of methoxyflurane combined with its rapid onset of effective pain relief and favorable safety profile make it a useful nonopioid option for pain management. Except for the STOP! study, which formed the basis for approval in trauma pain in Europe, and a few smaller randomized controlled trials (RCTs), much of the available data are observational or retrospective, and further RCTs are currently underway to provide more robust data.

Investigating a toxic risk (self-inflicted) the example of conventional and advanced studies of a novel Tobacco Heating System.

This special issue of Regulatory Toxicology and Pharmacology contains 9 scientific papers from Philip Morris International about the laboratory and 1 about early clinical investigation of a novel 'Tobacco Heating System'. The studies have employed conventional and a wide range of newer 'omics and bioinformatics techniques to seek and explore potential toxic actions of the inhalable vapour it generates. The methods of study and display of results employed are considered to be a valuable guide and model for wider application in other toxicological investigations because they are directed more to proximal causes of effects than to the cruder distal end points revealed by conventional, empirical procedures. As such they should be regarded as a paradigm for the applicability and accuracy of the testing and prediction of toxic risks.

Hot dog? Toxicological concerns and The Hound of the Baskervilles.

The terrifying dog in the Hound of the Baskervilles is described as having 'blazing eyes' and a 'luminous muzzle', appearances attributed by Watson and Holmes to the application of phosphorus. Review of the toxicity and flammability of white phosphorus make this improbable. It is suggested that Conan Doyle's description was probably influenced by knowledge of the recent and much publicized discovery of luminescence due to the radioactivity of uranium salts.

Toxicity testing of a novel riboflavin-based technology for pathogen reduction and white blood cell inactivation.

The Mirasol PRT System (Gambro BCT, Lakewood, CO) for platelets and plasma uses riboflavin and UV light to reduce pathogens and inactivate white blood cells in donated blood products. An extensive toxicology program, developed in accordance with International Organisation for Standardisation (ISO) 10993 guidelines, was performed for the Mirasol PRT system. Test and control articles for most of the reported studies were treated (test) or untreated (control) blood products. For some studies, pure lumichrome (the major photoproduct of riboflavin) or photolyzed riboflavin solution was used. Systemic toxicity was evaluated with in vivo animal studies in the acute and subchronic settings. Developmental toxicity was evaluated with an in vivo animal study. Genotoxicity and neoantigenicity were evaluated with in vitro and in vivo tests. Hemocompatibility and cytotoxicity were assessed with standard, in vitro assays. The pharmacokinteics, excretion, and tissue distribution of (14)C-riboflavin and its photoproducts was evaluated with an in vivo animal study. The possible presence of leachable or extractable compounds (from the disposable set) was evaluated with novel assays for measuring these compounds in blood. No treatment-related toxicity was observed in any of the studies.