The introduction of gas warfare and its medical response in world war one.

The introduction of gas warfare in World War One was impactful, as it both expanded the breadth of warfare and fueled the invention of techniques required to treat these new injuries. Gas injuries were responsible for 91,000 of 1.3 million deaths in World War One. Gassed soldiers had wounds which the world had never seen. They presented in large scale to medical tents and base hospitals across Europe. As gas casualties poured in, doctors and nurses had to treat these conditions in the best way they knew. Gas warfare changed how war was performed and how casualties of this attack were treated. The techniques learned from treating the multitudes of men with gas burns led to advances in the field of burn care, which have helped to improve mortality and reduce morbidity in hospitals across the world.

Methylene Blue Administration During and After Life-Threatening Intoxication by Hydrogen Sulfide: Efficacy Studies in Adult Sheep and Mechanisms of Action.

Exposure to toxic levels of hydrogen sulfide (H2S) produces an acute cardiac depression that can be rapidly fatal. We sought to characterize the time course of the cardiac effects produced by the toxicity of H2S in sheep, a human sized mammal, and to describe the in vivo and in vitro antidotal properties of methylene blue (MB), which has shown efficacy in sulfide intoxicated rats. Infusing NaHS (720 mg) in anesthetized adult sheep produced a rapid dilation of the left ventricular with a decrease in contractility, which was lethal within about 10 min by pulseless electrical activity. MB (7 mg/kg), administered during sulfide exposure, maintained cardiac contractility and allowed all of the treated animals to recover. At a dose of 350 mg NaHS, we were able to produce an intoxication, which led to a persistent decrease in ventricular function for at least 1 h in nontreated animals. Administration of MB, 3 or 30 min after the end of exposure, whereas all free H2S had already vanished, restored cardiac contractility and the pyruvate/lactate (P/L) ratio. We found that MB exerts its antidotal effects through at least 4 different mechanisms: (1) a direct oxidation of free sulfide; (2) an increase in the pool of "trapped" H2S in red cells; (3) a restoration of the mitochondrial substrate-level phosphorylation; and (4) a rescue of the mitochondrial electron chain. In conclusion, H2S intoxication produces acute and long persisting alteration in cardiac function in large mammals even after all free H2S has vanished. MB exerts its antidotal effects against life-threatening sulfide intoxication via multifarious properties, some of them unrelated to any direct interaction with free H2S.

Comparative evaluation of antidotal efficacy of 2-PAM and HNK-102 oximes during inhalation of sarin vapor in Swiss albino mice.

Efficacy of two oximes treatments evaluated during inhalation of sarin vapor (LCt50, 755.9 mg/min/m3) in simulated real scenario in vivo. Majority of mice either became moribund or died within 1-2 min during exposure to multifold-lethal concentrations of sarin vapor. Protection indices were determined by exposing to sarin vapor in two sessions, 1 min exposure followed by treatments with or without HNK-102 (56.56 mg/kg, im) or 2-PAM (30 mg/kg, im) and atropine (10 mg/kg, ip), and again exposed for remaining 14 min. Protection offered by HNK-102 was found to be four folds higher compared to 2-PAM in the same toxic environment. Secondly, sub-lethal concentration of sarin vapor (0.8 × LCt50 or 605 mg/min/m3), 24 h post investigations revealed that the oximes could not reactivate brain and serum acetylcholinesterase (AChE) activity. The treatments prevented increase in protein concentration (p < .05) and macrophages infiltration compared to sarin alone group in broncho-alveolar lavage fluid. Lung histopathology showed intense peribronchial infiltration and edema with desquamating epithelial lining and mild to moderate alveolar septal infiltration in sarin and atropine groups, respectively. Noticeable peeling-off observed in epithelial lining and sporadic mild infiltration of epithelial cells at bronchiolar region in 2-PAM and HNK-102 groups, respectively. The oximes failed to reactivate AChE activity; however, the mice survived up to 6.0 × LCt50, proved involvement of non-AChE targets in sarin toxicity. Atropine alone treatment was found to be either ineffective or increased the toxicity. HNK-102, exhibited better survivability with lung protection, can be considered as a better replacement for 2-PAM to treat sarin inhalation induced poisoning.

Poison gas and thefirst World War: key role ofpharmacists.

Poison gas has been the subject of attention from the French army (Grand Quartier General). The 22sd of April 1915, General Joffre decided that the General Direction for Health Service was in charge of the protection of troops against what he called "this new mode of terror, disease, and death". Actions are been launched to found ways for the protection means and to obtain for the army at least equivalent weapons. Pharmacists will have a leading role thanks to their knowledge in chemistry. Research laboratories were working in two areas: individual protection and production of aggressive agents. Paul Lebeau, Gabriel Bertrand, Alexandre Degrez, Charles Moureu were among many others very committed to fight and remains at the top and to react quickly to ennemy's attacks. At the end of the war, Paul Lebeau received the Legion d'Honneur medal for his contribution to war. The school of pharmacy was recognized as faculty of pharmacy, by a decree of May 14th, 1920. The knowledge that were obtained during this period will be used for the second World War, but the chemical weapon was not much used, as opposed to more recent usage in Vietnam, Irak and Syria.

Therapy against organophosphate poisoning: the importance of anticholinergic drugs with antiglutamatergic properties.

Potent cholinesterase inhibitors (e.g., soman, sarin), induce a wide range of deleterious effects including convulsions, behavioral impairments and ultimately, death. Due to the likelihood of various scenarios of military or terrorist attacks by these and other chemical weapons, research has to be aimed at finding optimal therapies. Early accumulation of acetylcholine in synaptic clefts was suggested to trigger an array of toxic events including an excessive release of glutamate, culminating in the activation of its receptors. Stimulation of the N-Methyl-D-Aspartate (NMDA) subtype of these receptors was associated with the neuronal injury that initiates organophosphate-induced brain damage. The notion of a stepwise mechanism yielded treatments based on a combination of an immediate administration of enzyme reactivators and anticholinergic drugs. This strategy dramatically increased survival rates but did not abolish convulsions and failed to prevent the ensuing cognitive dysfunction. Efforts to improve this paradigm by adding anticonvulsants or antiglutamatergic drugs with anti-epileptic characteristics produced dubious results. Under these conditions, benactyzine and caramiphen, agents with anticholinergic and antiglutamatergic properties, provided improved protection when introduced as adjunct agents to oximes, reversible cholinesterase inhibitors and/or specific antimuscarinic drugs such as atropine. In contrast, the specific antimuscarinic drug scopolamine failed to block soman-induced changes in glutamatergic and behavioral parameters even when given prophylactically. These findings along with a large number of additional reports led towards the conclusion that the therapeutic advantage of drugs such as benactyzine and caramiphen could derive from their ability to modulate central cholinergic and glutamate neurotransmission.

Suicide prevention through means restriction: assessing the risk of substitution. A critical review and synthesis.

The effectiveness of restricting access to certain means of committing suicide has been demonstrated, at least as regards toxic domestic gas, firearms, drugs and bridges. At the individual level, studies tend to indicate that many persons have a preference for a given means, which would limit the possibility of substitution or displacement towards another method. Similarly, the fact that suicidal crisis are very often short-lived (and, what is more, influenced by ambivalence or impulsiveness) suggests that an individual with restricted access to a given means would not put off his plans to later or turn to alternative methods. This has been more difficult to demonstrate scientifically in population studies. Nevertheless, it appears that, should such a shift occur towards other means, it would be put into effect only in part and over a longer term.

[Nerve gas--guidelines for care of victims of terrorism]. / Nervegass--retningslinjer ved terror.

The threat from chemical warfare agents such as nerve agents against civilians has traditionally been considered irrelevant. Following the recent terrorist attacks in the US on 11 September 2001 and in Madrid, Spain on 11 March 2004, the threat from such weapons is taken seriously. Hospitals must therefore be prepared to take care of civilian victims. Emergency preparedness implies education and training of healthcare professionals, stocking of antidotes, and training of personnel. This involves decontamination of patients, establishment of routines to avoid contamination of hospitals, and the ability to determine if patients and first responders are contaminated with chemicals and to avoid such contamination. Treatment against nerve agents includes atropine, acetylcholinesterase reactivators (obidoxime or pralidoxime) and benzodiazepines (diazepam). Because these drugs are not sufficiently effective in protecting the brain, new and more effective countermeasures must be developed.

Operational atmospheric modeling system CARIS for effective emergency response associated with hazardous chemical releases in Korea.

The Chemical Accidents Response Information System (CARIS) was developed at the Center for Chemical Safety Management in South Korea in order to track and predict the dispersion of hazardous chemicals in the case of an accident or terrorist attack involving chemical companies. The main objective of CARIS is to facilitate an efficient emergency response to hazardous chemical accidents by rapidly providing key information in the decision-making process. In particular, the atmospheric modeling system implemented in CARIS, which is composed of a real-time numerical weather forecasting model and an air pollution dispersion model, can be used as a tool to forecast concentrations and to provide a wide range of assessments associated with various hazardous chemicals in real time. This article introduces the components of CARIS and describes its operational modeling system. Some examples of the operational modeling system and its use for emergency preparedness are presented and discussed. Finally, this article evaluates the current numerical weather prediction model for Korea.

Respiratory illness in agricultural workers.

Respiratory diseases have long been recognized in association with work in farming. Overall, only a small proportion of the population is employed in agriculture, so respiratory disease in farmers is not a major public health issue. However, farmers are known to have high morbidity and mortality from certain respiratory diseases, as shown by routinely collected statistics. Despite this, knowledge of the frequency, nature and risk factors for some respiratory disorders in agricultural workers is incomplete. Multiple exposures are common and some exposures can give rise to more than one specific disease. Moreover, the most common respiratory symptoms reported by farm workers (wheeze, dyspnoea and cough) are relatively non-specific and can be associated with several occupational respiratory disorders. This review describes the main occupational respiratory illnesses in farming and summarizes the current literature about epidemiology and prevention. The most important diseases are rhinitis and asthma, which, although common, are not usually fatal. Some non-allergic conditions, e.g. asthma-like syndrome and organic toxic dust syndrome, are not yet fully understood, but appear to be common among farm workers. The most serious respiratory diseases are hypersensitivity pneumonitis and respiratory infections, but these are rare. Most importantly, respiratory diseases are preventable by controlling harmful exposures to organic dust, toxic gases and chemicals on farms through improvements in animal rearing techniques, ventilation of animal accommodation, careful drying and storage of animal feed-stuffs, crops and other products, and use of personal protective equipment.