Multicentric case series of scuba diving fatalities: The role of intracardiac gaseous carbon dioxide in the forensic diagnosis.

Scuba diving fatalities post-mortem diagnosis presents a higher level of forensic complexity because of their occurrence in a non-natural human life environment. Scuba divers are equipped with diving gas to breathe underwater. It is essential for them to be fully trained in order to be able to manage their dive safely despite the varying increase of ambient pressure and temperature decrease. Throughout the dive, the inhaled diving gas is dissolved in the diver's tissues during the descent and if the decompression steps are not respected during the ascent, the balance between the dissolved gas and the tissues (including blood) is disrupted, leading to a gaseous release in the organism. Depending on the magnitude of this gaseous release, free gas can occur in blood and tissue. Venous or arterial gas embolism can also occur as a consequence of decompression sickness or barotraumatism. It can also induce drowsiness that consequently leads to drowning. As a result, the occurrence of gas in dead scuba divers is very complex to interpret, as is the difficulty to distinguish it from resuscitation maneuver artifacts or body decomposition. Although the literature is scarce in this domain, significant work has been done to provide a precise intracadaveric gas sampling method to enlighten the cause and circumstances of death during the dive. The aim of this study is to obtain higher statistical significance by collecting a number of cases to confirm the gas sampling protocol and analysis and gain more information about the cause of death and the events surrounding the fatality through the establishment of clear management guidelines.

Total Blood Carbon Monoxide: Alternative to Carboxyhemoglobin as Biological Marker for Carbon Monoxide Poisoning Determination.

As one of the most abundant toxic contaminants in the atmosphere, carbon monoxide (CO) plays a significant role in toxicology and public health. Every year, around half of the accidental non-fire-related poisoning deaths are attributed to CO in the USA, UK and many other countries. However, due to the non-specificity of the symptoms and often encountered inconsistency of these with the results obtained from measurements of the biomarker for CO poisonings, carboxyhemoglobin (COHb), there is a high rate of misdiagnoses. The mechanism of toxicity of CO includes not only the reduced transport of oxygen caused by COHb but also the impairment of cellular respiration and activation of oxidative metabolism by binding to other proteins. Therefore, in this study we propose the measurement of the total amount of CO in blood (TBCO) by airtight gas syringe-gas chromatography-mass spectrometry (AGS-GC-MS) as an alternative to COHb for the determination of CO exposures. The method is validated for a clinical range with TBCO concentrations of 1.63-104 nmol/mL of headspace (HS) (0.65-41.6 µmol/mL blood). The limit of quantification was found between 2 and 5 nmol/mL HS (0.8 and 2 µmol/mL blood). The method is applied to a cohort of 13 patients, who were exposed to CO under controlled conditions, and the results are compared to those obtained by CO-oximetry. Furthermore, samples were compared before and after a "flushing" step to remove excess CO. Results showed a significant decrease in TBCO when samples were flushed (10-60%), whereas no constant trend was observed for COHb. Therefore, measurement of TBCO by AGS-GC-MS suggests the presence of more dissolved CO than previously known. This constitutes a first step into the acknowledgment of a possibly significant amount of CO present not in the form of COHb, but as free CO, which might help explain the incongruences with symptoms and decrease misdiagnoses.

Carbon monoxide analysis method in human blood by Airtight Gas Syringe - Gas Chromatography - Mass Spectrometry (AGS-GC-MS): Relevance for postmortem poisoning diagnosis.

Carbon monoxide is one of the most abundant toxic air pollutants. Symptoms of a CO intoxication are non-specific, leading to a high number of misdiagnosed CO poisoning cases that are missing in the disease statistics. The chemical nature of the molecule makes it difficult to detect for long periods and at low levels, thus requiring a very accurate and sensitive method. Current methods capable of accurate and sensitive analyses are available, however an inconsistency between results and symptoms are frequently reported. Therefore, an improved method for the analysis of carbon monoxide in blood and in the headspace (HS) of the sampling tube with the use of Airtight Gas Syringe - Gas Chromatography - Mass Spectrometry (AGS-GC-MS) is hereby presented and validated, for CO concentrations in a range of 10-200 nmol/mL HS (2-40 µmol/mL blood). Analytical LOQ is found at 0.9 nmol/mL HS (0.18 µmol/mL blood) and LOD at 0.1 nmol/mL gas. Application to intoxicated samples from autopsies and comparison to previously published methods show that this method is more appropriate, since performed under fully controlled conditions. Results show higher CO concentrations compared to previous approaches, indicating that results might have been underestimating the true blood CO burden. Therefore, this approach has the potential to help reduce the misdiagnosed cases and the gap between measurement and diagnosis of CO poisonings.

Quantification of fatal helium exposure following self-administration.

Helium is nontoxic at standard conditions, plays no biological role, and is found in trace amounts in human blood. Helium can be dangerous if inhaled to excess, since it is a simple tissue hypoxia and so displaces the oxygen needed for normal respiration. This report presents a fatal case of a middle-aged male victim who died from self-administered helium exposure. For the first time, the quantification of the helium levels in gastric and lung air and in blood samples was achieved using gas chromatography-mass spectrometry after airtight sampling. The results of the toxicological investigation showed that death was caused directly by helium exposure. However, based on the pathomorphological changes detected during the forensic autopsy, we suppose that the fatal outcome was the result of the lack of oxygen after inhalation.

Drug Vaping: From the Dangers of Misuse to New Therapeutic Devices.

Users of e-cigarettes are unwitting volunteers participating in a worldwide epidemiological study. Because of the obvious benefits of e-cigarettes compared with traditional cigarette smoking, these electronic devices have been introduced all around the world to support tobacco smoking cessation. Same potential harm reduction could be considered by cannabis vaping for marijuana smokers. However, the toxicities of liquids and aerosols remain under investigation because although the use of e-cigarettes is likely to be less harmful than traditional cigarette smoking, trace levels of contaminants have been identified. Simultaneously, other electronic devices, such as e-vaporisers, e-hookahs or e-pipes, have been developed and commercialised. Consequently, misuse of electronic devices has increased, and experimentation has been documented on Internet web fora. Although legal and illegal drugs are currently consumed with these e-devices, no scientific papers are available to support the observations reported by numerous media and web fora. Moreover, building on illegal drug vaping and vaporisation with e-devices (vaping misuse), legal drug vaping (an alternative use of vaping) could present therapeutic benefits, as occurs with medical cannabis vaporisation with table vaporisers. This review seeks to synthesise the problems of e-cigarette and liquid refill toxicity in order to introduce the dangers of illegal and legal drugs consumed using vaping and vaporisation for recreational purposes, and finally, to present the potential therapeutic benefits of vaping as a new administration route for legal drugs.

Blood monitoring of perfluorocarbon compounds (F-tert-butylcyclohexane, perfluoromethyldecalin and perfluorodecalin) by headspace-gas chromatography-tandem mass spectrometry.

A headspace-gas chromatography-tandem mass spectrometry (HS-GC-MS/MS) method for the trace measurement of perfluorocarbon compounds (PFCs) in blood was developed. Due to oxygen carrying capabilities of PFCs, application to doping and sports misuse is speculated. This study was therefore extended to perform validation methods for F-tert-butylcyclohexane (Oxycyte(®)), perfluoro(methyldecalin) (PFMD) and perfluorodecalin (PFD). The limit of detection of these compounds was established and found to be 1.2 µg/mL blood for F-tert-butylcyclohexane, 4.9 µg/mL blood for PFMD and 9.6 µg/mL blood for PFD. The limit of quantification was assumed to be 12 µg/mL blood (F-tert-butylcyclohexane), 48 µg/mL blood (PFMD) and 96 µg/mL blood (PFD). HS-GC-MS/MS technique allows detection from 1000 to 10,000 times lower than the estimated required dose to ensure a biological effect for the investigated PFCs. Thus, this technique could be used to identify a PFC misuse several hours, maybe days, after the injection or the sporting event. Clinical trials with those compounds are still required to evaluate the validation parameters with the calculated estimations.

When gas analysis assists with postmortem imaging to diagnose causes of death.

Postmortem imaging consists in the non-invasive examination of bodies using medical imaging techniques. However, gas volume quantification and the interpretation of the gas collection results from cadavers remain difficult. We used whole-body postmortem multi-detector computed tomography (MDCT) followed by a full autopsy or external examination to detect the gaseous volumes in bodies. Gases were sampled from cardiac cavities, and the sample compositions were analyzed by headspace gas chromatography-mass spectrometry/thermal conductivity detection (HS-GC-MS/TCD). Three categories were defined according to the presumed origin of the gas: alteration/putrefaction, high-magnitude vital gas embolism (e.g., from scuba diving accident) and gas embolism of lower magnitude (e.g., following a traumatic injury). Cadaveric alteration gas was diagnosed even if only one gas from among hydrogen, hydrogen sulfide or methane was detected. In alteration cases, the carbon dioxide/nitrogen ratio was often >0.2, except in the case of advanced alteration, when methane presence was the best indicator. In the gas embolism cases (vital or not), hydrogen, hydrogen sulfide and methane were absent. Moreover, with high-magnitude vital gas embolisms, carbon dioxide content was >20%, and the carbon dioxide/nitrogen ratio was >0.2. With gas embolisms of lower magnitude (gas presence consecutive to a traumatic injury), carbon dioxide content was <20% and the carbon dioxide/nitrogen ratio was often <0.2. We found that gas analysis provided useful assistance to the postmortem imaging diagnosis of causes of death. Based on the quantifications of gaseous cardiac samples, reliable indicators were determined to document causes of death. MDCT examination of the body must be performed as quickly as possible, as does gas sampling, to avoid generating any artifactual alteration gases. Because of cardiac gas composition analysis, it is possible to distinguish alteration gases and gas embolisms of different magnitudes.

Validation of an analytical method for nitrous oxide (N2O) laughing gas by headspace gas chromatography coupled to mass spectrometry (HS-GC-MS): forensic application to a lethal intoxication.

Drug abuse is a widespread problem affecting both teenagers and adults. Nitrous oxide is becoming increasingly popular as an inhalation drug, causing harmful neurological and hematological effects. Some gas chromatography-mass spectrometry (GC-MS) methods for nitrous oxide measurement have been previously described. The main drawbacks of these methods include a lack of sensitivity for forensic applications; including an inability to quantitatively determine the concentration of gas present. The following study provides a validated method using HS-GC-MS which incorporates hydrogen sulfide as a suitable internal standard allowing the quantification of nitrous oxide. Upon analysis, sample and internal standard have similar retention times and are eluted quickly from the molecular sieve 5Å PLOT capillary column and the Porabond Q column therefore providing rapid data collection whilst preserving well defined peaks. After validation, the method has been applied to a real case of N2O intoxication indicating concentrations in a mono-intoxication.

Gas analysis of exhumed cadavers buried for 30 years: a case report about long time alteration.

Due to important alteration caused by long time decomposition, the gases in human bodies buried for more than a year have not been investigated. For the first time, the results of gas analysis sampled from bodies recently exhumed after 30 years are presented. Adipocere formation has prevented the bodies from too important alteration, and gaseous areas were identified. The sampling was performed with airtight syringes assisted by multi-detector computed tomography (MDCT) in those specific areas. The important amount of methane (CH4), coupled to weak amounts of hydrogen (H2) and carbon dioxide (CO2), usual gaseous alteration indicators, have permitted to confirm methanogenesis mechanism for long period of alteration. H2 and CO2 produced during the first stages of the alteration process were consumed through anaerobic oxidation by methanogenic bacteria, generating CH4.

New trends in the kitchen: propellants assessment of edible food aerosol sprays used on food.

New products available for food creations include a wide variety of "supposed" food grade aerosol sprays. However, the gas propellants used cannot be considered as safe. The different legislations available did not rule any maximum residue limits, even though these compounds have some limits when used for other food purposes. This study shows a preliminary monitoring of propane, butane and dimethyl ether residues, in cakes and chocolate after spraying, when these gases are used as propellants in food aerosol sprays. Release kinetics of propane, butane and dimethyl ether were measured over one day with sprayed food, left at room temperature or in the fridge after spraying. The alkanes and dimethyl ether analyses were performed by headspace-gas chromatography-mass spectrometry/thermal conductivity detection, using monodeuterated propane and butane generated in situ as internal standards. According to the obtained results and regardingthe extrapolations of the maximum residue limits existing for these substances, different delays should be respected according to the storage conditions and the gas propellant to consume safely the sprayed food.

Indirect hydrogen analysis by gas chromatography coupled to mass spectrometry (GC-MS).

Gas chromatography (GC) is an analytical tool very useful to investigate the composition of gaseous mixtures. The different gases are separated by specific columns but, if hydrogen (H2 ) is present in the sample, its detection can be performed by a thermal conductivity detector or a helium ionization detector. Indeed, coupled to GC, no other detector can perform this detection except the expensive atomic emission detector. Based on the detection and analysis of H2 isotopes by low-pressure chemical ionization mass spectrometry (MS), a new method for H2 detection by GC coupled to MS with an electron ionization ion source and a quadrupole analyser is presented. The presence of H2 in a gaseous mixture could easily be put in evidence by the monitoring of the molecular ion of the protonated carrier gas.

Innovative method for carbon dioxide determination in human postmortem cardiac gas samples using headspace-gas chromatography-mass spectrometry and stable labeled isotope as internal standard.

A novel approach to measure carbon dioxide (CO2) in gaseous samples, based on a precise and accurate quantification by (13)CO2 internal standard generated in situ is presented. The main goal of this study was to provide an innovative headspace-gas chromatography-mass spectrometry (HS-GC-MS) method applicable in the routine determination of CO2. The main drawback of the GC methods discussed in the literature for CO2 measurement is the lack of a specific internal standard necessary to perform quantification. CO2 measurement is still quantified by external calibration without taking into account analytical problems which can often occur considering gaseous samples. To avoid the manipulation of a stable isotope-labeled gas, we have chosen to generate in situ an internal labeled standard gas ((13)CO2) on the basis of the stoichiometric formation of CO2 by the reaction of hydrochloric acid (HCl) with sodium hydrogen carbonate (NaH(13)CO3). This method allows a precise measurement of CO2 concentration and was validated on various human postmortem gas samples in order to study its efficiency.

Accuracy profile validation of a new analytical method for butane measurement using headspace-gas chromatography-mass spectrometry.

The aim of our study was to provide an innovative HS-GC/MS method applicable to the routine determination of butane concentration in forensic toxicology laboratories. The main drawback of the GC/MS methods discussed in literature concerning butane measurement was the absence of a specific butane internal standard necessary to perform quantification. Because no stable isotope of butane is commercially available, it is essential to develop a new approach by an in situ generation of standards. To avoid the manipulation of a stable isotope-labelled gas, we have chosen to generate in situ an internal labelled standard gas (C(4)H(9)D) following the basis of the stoichiometric formation of butane by the reaction of deuterated water (D(2)O) with Grignard reagent butylmagnesium chloride (C(4)H(9)MgCl). This method allows a precise measurement of butane concentration and therefore, a full validation by accuracy profile was presented.

Confirmation of natural gas explosion from methane quantification by headspace gas chromatography-mass spectrometry (HS-GC-MS) in postmortem samples: a case report.

A new analytical approach for measuring methane in tissues is presented. For the first time, the use of in situ-produced, stably labelled CDH(3) provides a reliable and precise methane quantification. This method was applied to postmortem samples obtained from two victims to help determine the explosion origin. There was evidence of methane in the adipose tissue (82 nmol/g) and cardiac blood (1.3 nmol/g) of one victim, which corresponded to a lethal methane outburst. These results are discussed in the context of the available literature to define an analysis protocol for application in the event of a gas explosion.

Monitoring of aglycons of yew glycosides (3,5-dimethoxyphenol, myrtenol and 1-octen-3-ol) as first indicator of yew presence.

The toxicity of yew (Taxus spp) is well known from ancient times and is mainly due to taxins acting as inhibitors of calcium and sodium transport across the cell membrane of cardiac myocytes. The confirmation of yew taxins in body fluids can be carried out by liquid chromatography-tandem mass spectrometry (LC-MS/MS). However, before selecting this precise but expensive technique, an orientation test should be done to ascertain yew presence as toxic agent in the organism. As the 3,5-dimethoxyphenol (3,5-DMP), myrtenol and 1-octen-3-ol appear as glycosidically bound volatile compounds and are very yew specific, the detection of 3,5-DMP and the measurement of 1-octen-3-ol / myrtenol concentration ratio constitute reliable indicators of yew presence in forensic cases. The detection of these compounds is easily performed by gas chromatography-mass spectrometry (GC-MS) (SIM) after an enzymatic hydrolysis (ß-glucosidase) allowing the release of volatile compounds from yew glycosides.

[Temporomandibular joint diseases]. / Pathologies temporo-mandibulaires: répercussions générales.

Why are patients liable to suffer from craniomandibular disorders? What are the various local and global consequences? What is the part played by bruxism and craniofacial traumas in the aetiology of cranio-mandibular disorders? What is the contribution that can be expected from MI in this diagnosis? What are the various treatments that can be taken into consideration? These are all questions that the GPs could ask themselves concerning TMJ and related disorders.

Accuracy profile validation of a new method for carbon monoxide measurement in the human blood using headspace-gas chromatography-mass spectrometry (HS-GC-MS).

The aim of our study was to provide an innovative headspace-gas chromatography-mass spectrometry (HS-GC-MS) method applicable for the routine determination of blood CO concentration in forensic toxicology laboratories. The main drawback of the GC/MS methods discussed in literature for CO measurement is the absence of a specific CO internal standard necessary for performing quantification. Even if stable isotope of CO is commercially available in the gaseous state, it is essential to develop a safer method to limit the manipulation of gaseous CO and to precisely control the injected amount of CO for spiking and calibration. To avoid the manipulation of a stable isotope-labeled gas, we have chosen to generate in a vial in situ, an internal labeled standard gas ((13)CO) formed by the reaction of labeled formic acid formic acid (H(13)COOH) with sulfuric acid. As sulfuric acid can also be employed to liberate the CO reagent from whole blood, the procedure allows for the liberation of CO simultaneously with the generation of (13)CO. This method allows for precise measurement of blood CO concentrations from a small amount of blood (10 µL). Finally, this method was applied to measure the CO concentration of intoxicated human blood samples from autopsies.

Review. Sulfur-containing volatile compounds in seafood: occurrence, odorant properties and mechanisms of formation.

An inventory of the most part of sulfur-containing volatile compounds (SCVCs) present in seafood was carried out. These molecules constitute key compounds to understand and improve seafood quality. According to their nature, concentration and environmental parameters (temperature), they can move the overall seafood odor from desirable to rotten. Sulfury odors can also indicate problems in sanitary quality. Thus, it is essential to monitor the generation of these compounds to better control the organoleptic and sanitary quality of seafood. SCVC were divided in two categories: aliphatic compounds and cyclic compounds. Among cyclic SCVC, several families of compounds can be distinguished as thiophenes, thiazoles and their respective derivatives. The main pathways of formation of SCVC in seafood are investigated in order to better understand their presence in seafood aroma. Microbial mediated enzymatic reactions are mainly implied in the generation of aliphatic SCVC whereas Maillard reactions are involved in the generation of cyclic SCVC. A small part of SCVC could also derive from the environment by direct bioaccumulation of S-containing molecules or precursors. Then, the occurrence of SCVC in seafood is discussed according to the extraction methods, analysis methods - sometimes olfactometric methods and the species - the state and the average biochemical composition of the seafood matrix in which they were recovered. Finally, among the identified SCVC, the odorant properties of odor-active volatile compounds were investigated. Aromatic notes and odorant thresholds for odorant SCVC of seafood aroma are listed. Both pathways of formation and lists of SCVC linked to their odorant properties constitute important indicators to optimise seafood quality from an organoleptic and sanitary point of view.