Postmortem molecular screening for mutations in ryanodine receptor type 1 (RYR1) gene in psychiatric patients suspected of having died of neuroleptic malignant syndrome

Postmortem diagnosis of neuroleptic malignant syndrome (NMS) is difficult to perform, because the clinical symptoms just before death are not usually available. Malignant hyperthermia (MH) is a catastrophic, life-threatening hypermetabolic syndrome triggered by certain anesthetics. Ryanodine receptor type 1 (RYR1) gene mutations are known to be involved in susceptibility to MH. Similarities in clinical features, such as elevated body temperature, between NMS and MH have led to the suggestion that NMS is a neurogenic form of MH. In this study, we analyzed possible mutations of the RYR1 gene in 11 psychiatric patients suspected at autopsy to have died of NMS. All cases were suspected of having elevated body temperature at death, and their causes of death could not be determined by autopsy examinations. Two mutations (R4645Q and A612T) in the RYR1 gene were identified. The R4645Q mutation has previously been reported in MH patients, but five heterozygous mutations were also found in 400 Japanese control alleles. The other mutation was novel, and was not found in the same control alleles. The results of this study provide the first successful identification of RYR1 mutations in psychiatric patients suspected at autopsy of having died of NMS. However, the association between RYR1 gene mutations and cause of death in psychiatric patients suspected of dying of NMS remains unclear.     

Fatal malignant hyperthermia--delayed onset and atypical course

A case of malignant hyperthermia (mh) in a 27-year-old man is described. In a first anaesthesia using isoflurane and succinylcholine, the end-tidal CO(2) rose from 39 to 49 mmHg 2.75 h post-intubation and the body temperature rose to 39.8 degrees C 14 h post-intubation but was normal again the next day. In a second anaesthesia using the same medication, the maximal end-tidal CO(2) was 44 mmHg and the body temperature rose to 39 degrees C after 9 h. After 4 days, the fever rose to 40 degrees C, and to 42 degrees C when death occurred 10 days after the second anaesthesia. Masseter spasms or muscle rigidity were never present. According to the death certificate, death was due to multi-organ failure from sepsis. At autopsy, the skeletal muscles were pale and oedematous. Histology demonstrated focal necroses in the skeletal muscles, shock kidneys with myoglobin excretion and myoglobin clots in small blood vessels of the lungs. Hence, the postmortem diagnosis "malignant hyperthermia" was established but accusations of medical maltreatment were rejected because of the atypical and protracted clinical course and because uncharacteristic signs of malignant hyperthermia were attributable to the clinically suspected sepsis.     

RyR2相关心脏性猝死的研究进展

雷诺定受体2(ryanodine receptor 2,RyR2)是心肌细胞肌浆网上主要的钙释放通道,主要参与心肌的兴奋收缩耦联过程,其基因突变及调控异常可导致心肌舒张期钙漏引起心律失常,甚至猝死。本文重点综述RyR2基因突变及调控异常引起心脏性猝死的机制,并对以后的研究提出建议,旨在为心脏性猝死的法医学诊断提供一种新的思路。     

Methylenedioxypyrovalerone (“Bath Salts”),Related Death: Case Report and Review of the Literature,

Cathinone derivatives (bath salts) have emerged as the latest drugs of abuse. 3,4‐methylenedioxypyrovalerone (MDPV) is the primary active ingredient in bath salts used in this country. This article presents the second reported cause of death by MDPV intoxication alone. In April 2011, a delusional man was emergently brought to a hospital, where he self‐reported bath salt usage. He became agitated, developed ventricular tachycardia, hyperthermia, and died. Comprehensive alcohol and drug testing was performed. Using the alkaline drug screen, heart blood contained 0.7 mg/L MDPV and peripheral blood contained 1.0 mg/L MDPV. His bizarre behavior with life‐threatening hyperthermia was consistent with an MDPV‐induced excited delirium state. MDPV is not yet found by routine immunoassay toxicology screens. Testing for MDPV should be considered in cases with a history of polysubstance abuse with stimulant type drugs, report of acute onset of psychogenic symptoms, excited delirium syndrome, or presentation in a hyperthermic state.     

An autopsy case of malignant hyperthermia

A report is made of a 44-year-old female who died of malignant hyperthermia during general anesthesia for an operation of left subtrochanteric femoral fracture. Symptoms began with increases in heart rate and blood pressure after the introduction of anesthesia with halothane and were accelerated by the administration of succinylcholine, followed by muscle rigidity and high temperature. The typical wine red urine was observed. The oral temperature of 42 degrees C was recorded within 1 h after succinylcholine. The rectal temperature was 30 degrees C 22 h after death. Severe pulmonary edema and tubular necrosis of the kidney were found by postmortem examination. No latent myopathy was observed. The creatine phosphokinase levels in plasma obtained after the onset of malignant hyperthermia and at the time of autopsy were abnormally high and were 5632 and 34,854 mU/ml, respectively. Plasma myoglobin levels were 130,000 and 2.8 X 10(6) ng/ml, respectively.     

Detection of "uncommon" tranquillizers-sedatives during screening toxicological analysis

A 56-year-old man is discovered unconscious in a pool of blood in the kitchen of his house. According to findings, the man used a 22 long Rifle to fire 14 shots at his thorax with trajectories going from front to back, from right to left and on a nearly horizontal level. All the projectiles got into the left front side of his thorax and came out just under the back of his left armpit. One of them then got through his left arm and fractured his left humerus. According to the findings made on the premises and the position of the bloodstains, we think that man put his rifle against the wall, resting on a pipe. He fired, unloading two clips into his thorax. He had to handle the bolt of the rifle before each shot. To reload, he took the bullets which were on the nearby table on which blood marks can be seen. When reloading at a certain moment, he sat down in his armchair and when he wanted to stand up, he leaned on the armrests, on which blood marks can be seen. The last bullet was probably the one which went through his left arm, preventing him from keeping on shooting. His death, caused by a hypovolemical shock, was obviously very slow.     

An unusual case of anaphylaxis. Mold in pancake mix

Anaphylactic reactions involve contact with an antigen that evokes an immune reaction that is harmful. This type of reaction is a rapidly developing immunologic reaction termed a type I hypersensitivity reaction. The antigen complexes with an IgE antibody that is bound to mast cells and basophils in a previously sensitized individual. Upon re-exposure, vasoactive and spasmogenic substances are released that act on vessels and smooth muscle. The reaction can be local or systemic and may be fatal. The authors report the death of a 19-year-old white male who had a history of "multiple allergies," including pets, molds, and penicillin. One morning, he and his friends made pancakes with a packaged mix that had been opened and in the cabinet for approximately 2 years. The friends stopped eating the pancakes because they said that they tasted like "rubbing alcohol." The decedent continued to eat the pancakes and suddenly became short of breath. He was taken to a nearby clinic, where he became unresponsive and died. At autopsy, laryngeal edema and hyperinflated lungs with mucous plugging were identified. Microscopically, edema and numerous degranulating mast cells were identified in the larynx. The smaller airways contained mucus, and findings of chronic asthma were noted. Serum tryptase was elevated at 14.0 ng/ml. The pancake mix was analyzed and found to contain a total mold count of 700/g of mix as follows: Penicillium, Fusarium, Mucor, and Aspergillus. Witness statements indicate that the decedent ate two pancakes; thus he consumed an approximate mold count of 21,000. The decedent had a history of allergies to molds and penicillin, and thus was allergic to the molds in the pancake mix. The authors present this unusual case of anaphylaxis and a review of the literature.     

Orthodontic surgery and professional liability: the homozygote twin case

A professional liability lawsuit of an orthodontic case is presented through its medico-legal assessment. The patient underwent an orthodontic treatment combined with several maxillo-facial surgical interventions. Several temporomandibular joint complications followed, plus he was unhappy with aesthetic results and modifications to his facial features. He wanted to verify from a medico-legal point of view the treatment received as he believed something was not done lege artis. The result of the orthodontic assessment was that there were no indications for such surgical interventions, along with other professional negligence: no psychological support given and no indications as to the aesthetic results postsurgery. It was decided to carry out an orthodontic assessment also on his homozygote twin brother, who was discovered to have the same malocclusion. His medico-legal assessment did not substitute the evidence obtained from the deceased, but gave added weight to the final technical conclusion.     

Non-diagnosed pheochromocytoma as a cause of sudden death in a 49-year-old man: a case report with medico-legal implications

Pheochromocytomas are known to be rare causes of sudden death. A 49-year-old man with a medical history of arterial hypertension and diabetes mellitus complained about nausea and malaise in the morning. During the day his condition deteriorated. He went to the emergency department, where he was given intravenous drugs against nausea and was sent home. On the way back, his condition deteriorated dramatically so that his wife drove back to the emergency room, where he collapsed and sustained cardiac arrest; resuscitation efforts were unsuccessful. Autopsy revealed a large tumour of the left adrenal gland. The strong suspicion of pheochromocytoma was confirmed by histology, immunohistochemistry and biochemical investigations. An acute hypertensive crisis, caused by the hitherto unknown pheochromocytoma was ascertained as the cause of death. The morphological findings are presented, the difficulty to diagnose pheochromocytoma and the medico-legal implications are discussed.     

Fatal malignant hyperthermia associated with recreational cocaine and ethanol abuse

Malignant hyperthermia is an often lethal hypermetabolic crisis state precipitated by a variety of pharmacological and environmental triggers in genetically susceptible persons. The present report documents, by medical history and necropsy, a fatal malignant hyperthermic crisis in a 20-year-old man after an evening of recreational cocaine and ethanol abuse.     

假释撤销条件比较研究

撤销假释是对假释犯不遵守假释条件的惩罚方式之一。罪犯在假释考验期内再犯新罪应当不分犯罪性质、罪过形式和刑罚轻重,一律撤销假释。在假释考验期内,发现罪犯尚有漏罪,不应撤销假释,而是应根据漏罪的具体情况,分别处理。对于假释期间违反应当遵守的假释条件一律撤销假释的规定是不合理的。只有对情节严重的违反假释条件的行为,才应当撤销假释。     

INJUSTICE AND IRRATIONALITY IN CONTEMPORARY YOUTH POLICY

Lionel Tate was 12 years old when he killed 6‐year‐old Tiffany Eunick. Tiffany had been staying at the Tate home and, by all accounts, got along well with Lionel. The two were playing at “wrestling” when Lionel decided to try out some moves that he had seen on television. He threw Tiffany across the room, inflicting fatal injuries. Despite the boy's tender age, the prosecutor transferred Lionel to criminal court on a charge of first‐degree murder, an offense carrying a mandatory penalty of life without parole. The boy was given an opportunity to plead guilty to second‐degree murder in return for a sentence of three years incarceration, but he rejected the offer. A jury subsequently convicted him of first‐degree murder. At sentencing, the prosecution recommended leniency, which drew an angry response from the judge: If the state believed the boy did not deserve to be sent to prison for life, why hadn't it charged him with a lesser offense? Without any inquiry into the boy's cognitive, emotional, or moral maturity, the judge imposed the mandatory sentence.¹ Raymond Gardner was 16 years old when he shot and killed 20‐year‐old Mack Robinson.² Raymond lived in a violent urban neighborhood with his mother, who kept close watch over him. He had no prior record. He was an A student and worked part‐time in a clothing store to earn money for college. On the day of the shooting, a friend came into the store to tell Raymond that Mack had a beef with him about talking to a girl, and was “looking to get him.” The victim was known on the street as “Mack the Knife” because he always carried a small machete and was believed to have stabbed several people. To protect himself on the way home, Raymond took the gun kept under the counter of the shop where he worked. As he neared home, Mack and two other men approached and blocked his path. According to eyewitness testimony, Raymond began shaking, then pulled out the gun and fired. Mack ran into the street and fell. Raymond followed and fired five more shots into the victim's back as he lay dying on the ground. Raymond did not run. He just stood there crying. The prosecutor filed a motion in juvenile court to transfer Raymond on a charge of first‐degree murder. The judge ordered a psychological evaluation, which addressed the boy's family and social background, medical and behavioral history, intelligence, maturity, potential for future violence and prospects for treatment. The judge subsequently denied the transfer motion. He found Raymond delinquent and committed him to a private psychiatric treatment facility.³     

Hemolysis and hyperkalemia complicate malignant hyperpyrexia during anesthetic death

A healthy, 15-year-old male received a thiopental, nitrous oxide, oxygen, enflurane anesthetic for appendectomy. Cardiac arrest, following succinylcholine administration, was associated with marked hyperkalemia (potassium levels 8.7 to 11.6 meq), hemolysis (hematocrit fall from 41.7 to 26.6%, plasma hemoglobin 27 mg/dL), and creatine phosphokinase (CPK) elevation (8900 units). Vigorous resuscitative therapy including dantrolene was unsuccessful. The diagnosis of malignant hyperthermia was made by the marked CPK elevation on blood samples drawn during resuscitation and analyzed by the Medical Examiner's Office.     

邓汉仪诗史观及其诗学意义

邓汉仪认为诗歌应"追国雅而绍诗史",所以他重视记载时变过程,反映一代兴亡之感,关注民生、民瘼的作品.这既是对传统诗学"诗史"观的继承,又是对国雅本质的回归.邓汉仪还以鲜明的历史意识为诗歌选本张目,借助诗歌总集《诗观》的编纂,以求"成一代之伟观",使选本具有诗歌发展史的意义,这是对诗史观的发展.作为康熙前期诗坛旗手,其诗史观对矫正清初世俗诗风,使诗歌创作回归现实主义传统,起到了积极的作用.     

Fatal hyperthermia in hot baths in individuals with multiple sclerosis

The authors report the case of a 47-year-old black man with a history of multiple sclerosis who was found dead in a bathtub, head above water, with a body temperature of 105.7 F. Results of a complete autopsy and toxicologic screen were negative. Individuals with multiple sclerosis, if immersed in hot water, develop motor weakness, which may be so severe as to prevent them from getting out of the water, whether they be in a bathtub or whirlpool bath. In this case, the individual was trapped in a bathtub in which there was a continuous flow of hot water. This overwhelmed an already impaired thermoregulatory mechanism, causing hyperthermia and death.     

The pathophysiology of cocaine cardiotoxicity

Cocaine use is accompanied by a high risk of serious adverse effects involving the cardiovascular system. The basic cellular mechanisms of cocaine consist in [1] a potentiation of catecholamine effects by inhibition of the presynaptic uptake carrier [2] local anesthetic effects by the block of sodium-channels. Acute ischemic events can be induced by cocaine through coronary spasms in a situation of physiologic stress already accompanied by an enhanced myocardial oxygen demand. Procoagulant properties of cocaine may, moreover, favor coronary thrombosis formation and the development of myocardial infarction. Ischemia, reperfusion and the direct action of catecholamines on cardiocytes are accompanied by enhanced cytoplasmic calcium levels, inducing delayed after-potentials, repetitive action-potential generation and premature ventricular beats. Conduction velocity impairments caused by the local anesthetic effects of cocaine and inhomogeneous repolarization phenomena related to potassium channel inhibition may form a substrate for re-entrant circuits inducing ventricular fibrillation. Cocaine abuse may also cause degenerative and inflammatory alterations of the myocardium. Besides secondary ischemic changes, hypersensitivity-myocarditis and toxic cardiomyopathies that may be due to the cardiotoxic effects of catecholamines have been described in cocaine abusers. Moreover, persons using cocaine intravenously seem to be particularly endangered by bacterial endocarditis compared to the users of other intravenous drugs, for still unknown reasons.     

Sudden death due to malignant hyperthermia

A case of sudden death in a young athlete, most likely the result of malignant hyperthermia, is reported. This diagnosis was entertained at autopsy and later confirmed by muscle biopsy on the father of the deceased, who was proven to be susceptible to malignant hyperthermia. The condition should be strongly suspected at autopsy in unexplained sudden deaths of young adults occurring during exercise or under stress.     

Homicidal Poisoning in China Using Several Anesthetic Drugs

The authors describe a case of a well‐designed homicidal poisoning in China. A male was treated with starvation, intravenous fluids and antibiotics while in the hospital for acute diarrhea. He suddenly suffered from shortness of breath and subsequently died. A forensic autopsy was carried out, and several specimens were collected for toxicological screening. Propofol was tentatively identified in the blood by GC‐MS. Based on the presence of propofol in the blood, a suspect confessed that two other drugs, namely midazolam and vecuronium, were involved in this murder. Analytical drug quantification was then performed by GC‐MS and LC‐MS/MS. Blood analysis revealed the following: propofol at 0.5 μg/mL, midazolam at 0.098 μg/mL, and vecuronium at 0.10 μg/mL. These results suggest that the cause of death was respiratory depression due to the acute combined effect of several anesthetic drugs administered by the victim's companion.     

Driving Under the Influence of Synthetic Cannabinoid Receptor Agonist XLR‐11

The case of a 22‐year‐old male Caucasian driver is presented. He was involved in a traffic collision. At the roadside, he displayed blank stare and mellow speech with a barely audible voice. A DRE found low body temperature, rigid muscle tone, normal pulse, lack of horizontal and vertical gaze nystagmus, nonconvergence of the eyes, dilated pupil size, and normal Pupillary reaction to light. A standard toxicology DUID protocol was performed on the driver's whole blood including ELISA and GC‐MS drug screens with negative results. Additional drug screening was undertaken for bath salts and synthetic cannabinoid receptor agonists by LC‐MS/MS by a commercial laboratory and identified the synthetic cannabinoid receptor agonist XLR‐11 in the driver's blood. XLR‐11 was subsequently quantified at 1.34 ng/mL. This is the first documented case involving a driver operating a motor vehicle under the influence of the synthetic cannabinoid receptor agonist XLR‐11.     

原初状态的由来及其内在困境——浅论《正义论》的逻辑基点

罗尔斯以其《正义论》而奠定了他在当代政治哲学界的地位。据说,他扭转了政治哲学的方向,从新回到了近代的契约论传统,并使之上升到更高的抽象水平而提出了他的“作为公平的正义”的理论。他整个理论的逻辑起点是“原初状态”,那么通过分析“原初状态”构建及其内在的困境我们可以透视其整个理论的说服力。