Laurent Fanton

Human Atlas of the Cardiac Fiber Architecture: Study on a Healthy Population

Cardiac fibers, as well as their local arrangement in laminar sheets, have a complex spatial variation of their orientation that has an important role in mechanical and electrical cardiac functions. In this paper, a statistical atlas of this cardiac fiber architecture is built for the first time using human datasets. This atlas provides an average description of the human cardiac fiber architecture along with its variability within the population. In this study, the population is composed of ten healthy human hearts whose cardiac fiber architecture is imaged ex vivo with DT-MRI acquisitions. The atlas construction is based on a computational framework that minimizes user interactions and combines most recent advances in image analysis: graph cuts for segmentation, symmetric log-domain diffeomorphic demons for registration, and log-Euclidean metric for diffusion tensor processing and statistical analysis. Results show that the helix angle of the average fiber orientation is highly correlated to the transmural depth and ranges from -41° on the epicardium to +66° on the endocardium. Moreover, we find that the fiber orientation dispersion across the population (13°) is lower than for the laminar sheets (31°). This study, based on human hearts, extends previous studies on other mammals with concurring conclusions and provides a description of the cardiac fiber architecture more specific to human and better suited for clinical applications. Indeed, this statistical atlas can help to improve the computational models used for radio-frequency ablation, cardiac resynchronization therapy, surgical ventricular restoration, or diagnosis and followups of heart diseases due to fiber architecture anomalies.

Heart lesions associated with anabolic steroid abuse: Comparison of post-mortem findings in athletes and norethandrolone-induced lesions in rabbits

Among 15,000 forensic post-mortem examinations performed on the coroners order over a 24-year period (January 1981-December 2004) in the area of Lyon, France (population: 2,000,000), 2250 cases of unexpected cardiac sudden death were identified retrospectively according to WHO criteria. Of these, 108 occurred during recreational sport and 12 occurred in athletes. In the latter category, a history of anabolic steroid abuse was found in 6 cases, whereas pre-existing ordinary cardiac lesions were observed in the 6 remaining cases. To shed light on the possible role of anabolic steroids in the induction of cardiac lesions, an experimental study was conducted in rabbits that were treated orally with norethandrolone 8mg/kg/day for 60 days, and sacrificed at day 90. The histopathological examination of the heart from treated animals showed coronary thrombosis associated with left ventricle hypertrophy in 3 cases, and lesions analogous to toxic or adrenergic myocarditis in all other treated animals. These findings were very similar to those observed after cardiac sudden death in the 6 athletes with a history of anabolic steroid abuse. In addition, elevated caspase-3 activity in the heart of treated rabbits as compared to controls suggests that apoptosis is involved in the induction of norethandrolone-induced cardiac lesions. These results confirm the cardiotoxic potential of anabolic steroid abuse.

Statistical analysis of the human cardiac fiber architecture from DT-MRI

A statistical atlas of the cardiac fiber architecture is built for the first time with a human dataset of 10 healthy ex vivo hearts acquired using DT-MRI. The atlas is constructed using an efficient semiautomated method where limited interactions are only required to segment the myocardium. All hearts are registered automatically by an efficient and robust non linear registration method. The statistical atlas gives a better understanding of the human cardiac fiber architecture. The study on the global variability of the human cardiac fiber architecture reveals that the fiber orientation is more stable than the laminar sheet orientation. The variability is also consistent across the left ventricular AHA segments. Moreover this atlas could be used for cardiac electromechanical modeling as well as a basis for more precise extrapolation models, essential for in vivo cardiac DT-MRI acquisition.

Fatal intoxication due to ackee (Blighia sapida) in Suriname and French Guyana. GC-MS detection and quantification of hypoglycin-A.

Between 1998 and 2001 the deaths of 16 Surinamese children were recorded along the Maroni River, which forms the border between Suriname and French Guyana. After a metabolic origin was eliminated, ethnobotanical research in the field led to a hypothesis of intoxication through the ingestion of ackee. Ackee (Blighia sapida) is a large green leafy tree of West African origin. Its unripe fruit contains large quantities of two toxic molecules: hypoglycin-A and hypoglycin-B, the former being the more toxic. We have developed a GC-MS procedure allowing us to demonstrate the presence of hypoglycin-A in the gastric fluid of one of the deceased children, and to compare the content of hypoglycin-A in fruit collected on the road to Paramaribo in Suriname (5.1mg/g) with samples from Burkina Faso (8.1mg/g) and Jamaica (9.2mg/g). Field research showed the misuse of this little-known plant by Maroon witch doctors. The Bushinengue witch doctors were informed about the dangers of ackee, and no new cases have been reported to date.

A validated method for quantifying hypoglycin A in whole blood by UHPLC–HRMS/MS

Hypoglycin A (HGA) is the toxic principle in ackee (Blighia sapida Koenig), a nutritious and readily available fruit which is a staple of the Jamaican working-class and rural population. The aril of the unripe fruit has high concentrations of HGA, the cause of Jamaican vomiting sickness, which is very often fatal. HGA is also present in the samara of several species of maple (Acer spp.) which are suspected to cause seasonal pasture myopathy in North America and equine atypical myopathy in Europe, often fatal for horses. The aim of this study was to develop a method for quantifying HGA in blood that would be sensitive enough to provide toxicological evidence of ackee or maple poisoning. Analysis was carried out using solid-phase extraction (HILIC cartridges), dansyl derivatization and UHPLC-HRMS/MS detection. The method was validated in whole blood with a detection limit of 0.35 μg/L (range: 0.8-500 μg/L). This is the first method applicable in forensic toxicology for quantifying HGA in whole blood. HGA was quantified in two serum samples from horses suffering from atypical myopathy. The concentrations were 446.9 and 87.8 μg/L. HGA was also quantified in dried arils of unripe ackee fruit (Suriname) and seeds of sycamore maple (Acer pseudoplatanus L.) (France). The concentrations were 7.2 and 0.74 mg/g respectively.

Suicide with “non-lethal” firearm

patient was immediately transferred to the operating room. During induction of anaesthesia, she had a cardiac arrest. Sternotomy was done and blood evacuated from the pericardium. The left ventricular wall had a 6 3 cm bruised and bleeding surface, and there was a 3 mm wound that squirted blood near the apex. There were no bullets in the pericardium, and it had not been perforated. The left pleural cavity was opened and 3 L of blood drained. There was a large laceration of the lingula that poured out blood and air. 11 brown rubber bullets were removed from the left pleural cavity. Bleeding from the heart was nearly controlled, but the bruised area of the left ventricle burst, and attempts at repair were unsuccessful. The patient died on the table. Necropsy showed a contact entrance wound of 35 28 mm, with an abrased ring 3 mm wide; a subcutaneous blast chamber 7 cm diameter and a haematoma of the left breast and pectoral muscle. There were fractures of anterior arch of the third and fourth ribs and perforation of the second and the third left intercostal space. The 12th rubber bullet was found in the pleural cavity. The weapon used for this suicide was a “non-lethal” single-barrelled hand gun, type GC27, manufactured by SAPL (France) and loaded with a “non-lethal” 12 gauge, 50 mm mini Gomm-Cogne cartridge that contains 12 rubber bullets of 7 mm diameter (figure). “Non-lethal” weapons were first supplied to security forces. Deaths have been reported with rubber missiles (15 3·8 cm, 150 g) and with M-16 plastic and rubber ammunition. With rubber ammunition produced to be used in shotguns, severe but not lethal wounds have been reported. This is, to our knowledge, the first case of death due to such a weapon at contact range. The ventricular lesions are explained by the transmission of the kinetic energy of the missiles through the intact pericardium. Since these weapons are sold to be used by inexperienced citizens for self-defence, reported further lethal accidents will probably occur.

Vitreous humor analysis for the detection of xenobiotics in forensic toxicology: a review

Vitreous humor (VH) is a gelatinous substance contained in the posterior chamber of the eye, playing a mechanical role in the eyeball. It has been the subject of numerous studies in various forensic applications, primarily for the assessment of postmortem interval and for postmortem chemical analysis. Since most of the xenobiotics present in the bloodstream are detected in VH after crossing the selective blood-retinal barrier, VH is an alternative matrix useful for forensic toxicology. VH analysis offers particular advantages over other biological matrices: it is less prone to postmortem redistribution, is easy to collect, has relatively few interfering compounds for the analytical process, and shows sample stability over time after death. The present study is an overview of VH physiology, drug transport and elimination. Collection, storage, analytical techniques and interpretation of results from qualitative and quantitative points of view are dealt with. The distribution of xenobiotics in VH samples is thus discussed and illustrated by a table reporting the concentrations of 106 drugs from more than 300 case reports. For this purpose, a survey was conducted of publications found in the MEDLINE database from 1969 through April 30, 2015.

Quantification of Pregabalin Using Hydrophilic Interaction HPLC-High-Resolution MS in Postmortem Human Samples: Eighteen Case Reports

Pregabalin is a drug for treating epilepsy, anxiety disorders and neuropathic pain. Cases of poisoning are rare, though some have been fatal. Concentrations of pregabalin in postmortem human samples and its distribution have very rarely been documented. As the literature is so scarce, we propose to report the concentrations in autopsy samples of 18 people who had been taking Lyrica(®), including one case of a mixed overdose involving pregabalin. Analysis was carried out using an original Hydrophilic Interaction LIquid Chromatography (HILIC) technique coupled with a high-resolution mass spectrometer (m/z 160.1334 ± 5 ppm). The sensitivity of the technique enables a quick and simple treatment of the samples by protein precipitation. The method was validated in the whole blood with detection and quantification limits of 0.025 and 0.060 µg/mL, respectively. Pregabalin was a likely factor in the cause of death in 3 of the 18 cases. In the other individuals, the concentrations ranged from 0.4 to 17.0 in the peripheral blood, 1.5 to 11.1 in the central blood, 126.6 to 2004.6 in the urine and 10.5 to 58.3 µg/mL in the bile, with median values of 5.6, 4.6, 534.6 and 17.7, respectively.

Screening approach by ultra-high performance liquid chromatography-tandem mass spectrometry for the blood quantification of thirty-four toxic principles of plant origin. Application to forensic toxicology.

Plant poisonings have left their mark on history and still cause many deaths, whether intentional or accidental. The means to show toxicological evidence of such poisonings should be implemented with great care. This article presents a technique for measuring thirty-nine toxic principles of plant origin in the blood, covering a large amount of toxins from local or exotic plants: α-lobeline, α-solanine, aconitine, ajmaline, atropine, brucine, cephalomannine, colchicine, convallatoxin, cymarine, cytisine, digitoxin, digoxin, emetine, gelsemine, ibogaine, jervine, kavain, lanatoside C, lupanine, mitragynine, neriifolin, oleandrin, ouabain, paclitaxel, physostigmine, pilocarpine, podophyllotoxin, proscillaridin A, reserpine, retrorsine, ricinine, scopolamine, senecionine, sparteine, strophanthidin, strychnine, veratridine and yohimbine. Analysis was carried out using an original ultra-high performance liquid chromatography separation coupled with tandem mass spectrometry detection. Extraction was a standard solid phase extraction performed on Oasis(®) HLB cartridge. Thirty-four of the thirty-nine compounds were put through a validation procedure. The assay was linear in the calibration curve range from 0.5 or 5 μg/L to 1000 μg/L according to the compounds. The method is sensitive (LOD from 0.1 to 1.6 μg/L). The within-day precision of the assay was less than 22.5% at the LLOQ, and the between-day precision was less than 21.5% for 10 μg/L for all the compounds included. The assay accuracy was in the range of 87.4 to 119.8% for the LLOQ. The extraction recovery and matrix effect ranged from 30 to 106% and from -30 to 14%, respectively. It has proven useful and effective in several difficult forensic cases.

False rape: a case report.

A 16-year-old girl was admitted to the emergency department for sexual assault. The forensic examination revealed genital lesions of an age that were incompatible with her statements. She also presented extragenital lesions that resembled self-inflicted lesions. The reports of false rape allegations in the literature have all dealt with the motivations of the false victims. This case report is a reminder that an allegation of rape can be considered only on the basis of proof and not on speculation.