Challenges in the diagnosis of acute cyanide poisoning.

OBJECTIVE: The aim of this systematic review was to identify isolated acute cyanide poison cases and to identify reported signs, symptoms, and laboratory findings. METHODS: We searched MEDLINE, Cochrane Reviews, and Web of Science case reports and series using a number of MeSH descriptors pertaining to cyanide, toxicity, and poisonings. We excluded studies on plants, laboratory analyses, smoke inhalation poisonings, animals as well as non-English language articles and those in which data were not available. Data extracted included demographics, exposure characteristics, acute signs/symptoms, and medical management and outcome. RESULTS: From the initial 2976 articles retrieved, 65 articles (52 case reports, 13 case series) met inclusion criteria and described 102 patients. Most patients were unresponsive (78%), hypotensive (54%), or had respiratory failure (73%); other signs and symptoms included cardiac arrest (20%), seizures (20%), cyanosis (15%), cherry red skin (11%), and had an odor present (15%). Medical management included cyanide antidote kit (20%), sodium thiosulfate (40%), and hydroxocobalamin (29%). The majority of cases (66%) required intubation with mechanical ventilation and a substantial number (39%) developed refractory hypotension requiring vasopressor support. CONCLUSIONS: Contrary to general reviews published on cyanide toxicity, reports of cherry red skin and bitter almond odor were rare among published cyanide cases. Consistent with other studies, metabolic acidosis with significant lactic acidosis were the laboratory values consistently associated with cyanide toxicity. Healthcare providers may overlook cyanide toxicity in the differential diagnosis, if certain expected characteristics, such as the odor of almonds or a cherry red color of the skin are absent on physical examination.

Review: experimental manipulations of microglia in mouse models of Alzheimer's pathology: activation reduces amyloid but hastens tau pathology.

The inflammation hypothesis of Alzheimer's pathogenesis has directed much scientific effort towards ameliorating this disease. The development of mouse models of amyloid deposition permitted direct tests of the proposal that amyloid-activated microglia could cause neurodegeneration in vivo. Many approaches to manipulating microglial activation have been applied to these mouse models, and are the subject of this review. In general, these results do not support a direct neuricidal action of microglia in mouse amyloid models under any activation state. Some of the manipulations cause both a reduction in pathology and a reduction in microglial activation. However, at least for agents like ibuprofen, this outcome may result from a direct action on amyloid production, and a reduction in the microglial-provoking amyloid deposits, rather than from reduced microglial activation leading to a decline in amyloid deposition. Instead, a surprising number of the experimental manipulations which increase microglial activation lead to enhanced clearance of the amyloid deposits. Both the literature and new data presented here suggest that either classical or alternative activation of microglia can lead to enhanced amyloid clearance. However, a limited number of studies comparing the same treatments in amyloid-depositing vs. tau-depositing mice find the opposite effects. Treatments that benefit amyloid pathology accelerate tau pathology. This observation argues strongly that potential treatments be tested for impact on both amyloid and tau pathology before consideration of testing in humans.