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.     

Autopsy report on central pontine myelinolysis triggered by vomiting associated with digoxin intoxication

An 87-year-old male, prescribed digoxin and furosemide for congestive heart failure and Alzheimer disease, had dehydration and anemia due to poor food intake and hemorrhagic cystitis. Repeated vomiting due to an upper respiratory infection caused disturbance of consciousness and hypotension. The patient was admitted to hospital and diagnosed with digoxin intoxication and hypernatremia. The serum sodium (Na⁺) level was corrected, but the patient died 4 days after admission following uncontrollable seizure. A histologic examination after an autopsy revealed characteristic findings of central pontine myelinolysis (CPM). This is the first autopsy report on CPM triggered by vomiting in association with digoxin administration.     

Identification of Arrhythmogenic Right Ventricular Cardiomyopathy‐Causing Gene Mutations in Young Sudden Unexpected Death Autopsy Cases

Arrhythmogenic right ventricular cardiomyopathy (ARVC) results in an increased risk of sudden death. We sought mutations of desmoglein‐2 (DSG2), desmoplakin (DSP), and plakophilin‐2 (PKP2) in 15 cases of sudden death whose causes of death could not be determined at autopsy. In three victims, mutations were identified in DSP. Two of these mutations were novel; one had previously been reported in a patient with ARVC that had been diagnosed clinically. Histological findings were not typical of ARVC; however, it was notable that these mutations were present in three of 15 cases, a relatively high proportion. The causal relationship between the mutations and ARVC is unclear, but the mutations might have been associated with faulty desmosomal proteins resulting in fatal arrhythmia. Combining information gathered by the traditional means of gross and histological examination with postmortem genetic analysis of young victims would assist in identifying their cause of death.     

Does electoral competition affect politicians’ trade policy preferences? Evidence from Japan

This study examines the effect of electoral competition on politicians’ trade policy preferences using candidate observations from the House of Representatives in Japan’s 2012 general election. The study clarifies the effects of constituency size and the electoral strength of constituencies on candidates’ political stances. The empirical results provide evidence that politicians’ preferences for trade policy are sensitive to electoral pressure, but their reactions differ depending on the characteristics of each constituency. The results reveal that for a broad constituency with a large concentration of agricultural workers, election candidates are more likely to support protectionism than their counterparts running in a narrow constituency. For city district election candidates, electoral strength measured by the vote margin significantly affects their trade policy preferences. Candidates in close elections are more likely to be protectionist than candidates elected by a substantial majority, suggesting that electoral pressures deter politicians from supporting trade liberalization.