Right ventricular free wall dissection as a rupture tract in left ventricular rupture during acute myocardial infarction.

Three rare cases of cardiac rupture with right ventricular wall dissection during acute myocardial infarction (AMI) were reported. The cases comprised 2% among our 148 previously reported postinfarction cardiac ruptures with sudden death. The dissections occurred in hearts with biventricular inferior wall AMI and developed between the superficial layers and the deeper layers of inferior wall of the right ventricle. All had an endocardial tear at the basal septum where it meets the inferior free wall of the left ventricle, and had an epicardial tear on the middle inferior wall of the right ventricle. Based on the evidence of the ages of the thrombi of the rupture tracts, delayed epicardial rupture was found besides that soon after the right ventricular dissection.

Usefulness of a simple prognostication score in prediction of the prognoses of patients with out-of-hospital cardiac arrests.

Sudden cardiac death is a serious problem in public health but the overall survival rate of out-of-hospital cardiac arrests (OHCAs) remains low. In this study, we identified clinical parameters to predict the prognosis of OHCA patients and proposed a simple prognostication score for prediction of their prognoses. The study population consisted of 750 consecutive patients with OHCAs of internal cause who were transported to our institute from July 2008 to June 2010. They were divided into survivors and nonsurvivors, and clinical parameters were compared between them to detect significant parameters for prediction of their prognoses. The population of those who survived at 1 month numbered 34. Multivariate analysis exhibited 10 independent predictive factors of survival, which included witnessed cardiac arrest and bystander-initiated CPR. When the prognostication score was calculated from these independent predictive factors, a score of ≥ 6 points indicated survival with a sensitivity of 88.6% and a specificity of 97.6%. When the patients were divided into younger and older populations with a threshold of 70 years, these values were 94.1% and 96.1% in younger but 70.0% and 98.4% in older patients, respectively. In retrospective observation, a simple prognostication score was useful to predict patient prognoses in OHCAs, but its usefulness was limited in an older population.

ABO genotyping by TaqMan assay and allele frequencies in a Japanese population.

ABO genotyping have become common tools for forensic casework. We developed a new rapid ABO genotyping method using a fast real-time PCR system with the TaqMan® Sample-to-SNP™ Kit. Eight single nucleotide polymorphism (SNP) sites in the ABO gene (nt 261, 297, 467, 657, 703, 829, 930 and 1061) were selected to determine the ABO genotypes. ABO genotypes were easily determined by examining allelic discrimination patterns. This method enabled analyses to be completed in about 1h per plate with no postmortem change influences. The detection limit in each SNP site was examined as 100pg per reaction. ABO genotyping from 1000 Japanese individuals was also examined to determine the distribution of ABO genotypes and allele frequencies. Thus, 31 genotypes were clearly identified, and these were controlled by four common and seven rare alleles. The power of discrimination, heterozygosity and polymorphism information contents were 0.913, 0.775 and 0.812, respectively. Therefore, selecting these eight SNP sites could be useful for high specific ABO genotyping. This rapid, sensitive and accurate genotyping method is useful for forensic casework.

Simultaneous determination of 5 psychotropic drugs of various types in an autopsy case of acute multiple drug poisoning.

We attempted the simultaneous determination of 5 drugs, mirtazapine, sertraline, chlorpromazine, amoxapine and zolpidem, detected in a gas chromatography-mass spectrometry screening test in an autopsy case. The solid-phase extraction of the analytes from biological samples was achieved using Oasis(®)HLB cartridges (Waters, Milford, MA, USA). Gas chromatography was performed on a HP-5MS fused silica capillary column (30 m × 0.25 mm i.d., 0.25 µm film thickness, Agilent Technologies). The mass spectrometer was operated with an electron energy of 70 eV in electron impact mode. The qualitative and quantitative analyses were performed in full-scan mode and the selected ion monitoring mode, respectively. The total ion chromatogram showed good separation of these drugs. Linear graphs were obtained with good correlation coefficients for these drugs from 0.001 to 2.0 µg/mL (r(2)=0.9909-0.9986) using imipramine-d6 as an internal standard. The recoveries of these drugs were found to be 62.8-88.0% in spiked whole blood. Mirtazapine, sertraline, chlorpromazine, amoxapine and zolpidem were found in post-mortem samples of the deceased at concentrations of 2.67, 0.07, 0.25, 0.32 and 0.68 µg/mL, respectively. The concentration of mirtazapine was within the lethal level and those of amoxapine and zolpidem were within the toxic level. We diagnosed that the cause of death was acute multiple drug poisoning. The simple and practical procedure used in this study is useful for the simultaneous determination of psychotropic drugs of various types in post-mortem biological samples.

Analysis of the sarcomere protein gene mutation on cardiomyopathy - Mutations in the cardiac troponin I gene.

Developments in the molecular genetic studies of cardiomyopathy (CM) have led to discovery of a large number of mutations in the genes encoding the sarcomeric proteins. In this study, comprehensive screening of TNNI3 was performed in 36 consented autopsy cases diagnosed as CM, in order to evaluate the prevalence of gene mutations in sudden death caused by CM. In DCM cases, a new missense mutation Pro16Thr was detected. A single nucleotide polymorphism at -8 position of intron 3 (IVS 3 -8 T>A) was identified, which had a significant difference in allele frequency between DCM and control cases. From these results, it was indicated that this study contribute to genetic based diagnosis, risk stratification and prevention of sudden death caused by CM.

A case of V-A shunt catheters migration into the pulmonary artery.

A man in his sixties, who developed CPA at home, was transferred to the emergency center. Since CT images revealed a tube-shaped foreign body in the pulmonary artery, pulmonary embolism was initially suspected; however, this did not lead to a definite diagnosis. Autopsy revealed that the foreign body in the cadaver was a fragment of a V-A shunt catheter implanted about 30 years previously for the treatment of hydrocephalus. Although fibrous adhesion of a part of the catheter to the pulmonary artery wall was seen, suggesting that a fracture of the catheter had occurred a long time before, it was not known when the fracture had occurred. Since no pulmonary arterial obstruction secondary to the catheter or new thrombi, which had been initially suspected, were observed, the cause of death was determined to be ischemic cardiac failure. A fracture of a shunt catheter may be typically associated with some clinical manifestations, which are often found and treated. In this case, however, no symptoms appeared and the fracture of the shunt catheter remained untreated for a long time. This case was therefore considered to be extremely rare, and is an example of how a serious iatrogenic disease could occur.

Case report: Etizolam and its major metabolites in two unnatural death cases.

A simultaneous analytical method for etizolam and its main metabolites (alpha-hydroxyetizolam and 8-hydroxyetizolam) in whole blood was developed using solid-phase extraction, TMS derivatization and ion trap gas chromatography tandem mass spectrometry (GC-MS/MS). Separation of etizolam, TMS derivatives of alpha-hydroxyetizolam and 8-hydroxyetizolam and fludiazepam as internal standard was performed within about 17 min. The inter-day precision evaluated at the concentration of 50 ng/mL etizolam, alpha-hydroxyetizolam and 8-hydroxyetizolam was evaluated 8.6, 6.4 and 8.0% respectively. Linearity occurred over the range in 5-50 ng/mL. This method is satisfactory for clinical and forensic purposes. This method was applied to two unnatural death cases suspected to involve etizolam. Etizolam and its two metabolites were detected in these cases.

Fatal diphenhydramine poisoning with increased vascular permeability including late pulmonary congestion refractory to percutaneous cardiovascular support.

BACKGROUND: Fatal adult cases of acute diphenhydramine poisoning are extremely rare. CASE REPORT: Transiently awakened by a roommate, a 39-year-old man admitted to massive ingestion of an over-the-counter drug containing diphenhydramine salicylate. On admission the patient was semicomatose and developed circulatory collapse with severe dehydration and metabolic acidosis, followed by status epilepticus. Despite extensive life support measures including percutaneous cardiopulmonary support, vascular permeability progressively increased, with pulmonary congestion as well as peripheral vasodilation evident as rubedo. The patient died without improvement of cardiac function. Subsequent diphenhydramine assays in serum specimens obtained at the time of delayed congestive symptoms indicated decreases in drug concentration to a sublethal amount. DISCUSSION: We suspect that metabolites of diphenhydramine with histamine-agonist actions contributed to the development of fatal delayed symptoms.

Simple and simultaneous determination for 12 phenothiazines in human serum by reversed-phase high-performance liquid chromatography.

A high-performance liquid chromatographic method has been developed for the simultaneous analysis of the 12 phenothiazines (chlorpromazine, fluphenazine, levomepromazine, perazine, perphenazine, prochlorperazine, profenamine, promethazine, propericiazine, thioproperazine, thioridazine and trifluoperazine) in human serum using HPLC/UV. The separation was achieved using a C(18) reversed-phase column (250 mm x 4.6 mm I.D., particle size 5 microm, Inersil ODS-SP). The mobile phase, consisting of acetonitrile-methanol-30 mM NaH(2)PO(4) (pH 5.6) (300:200:500, v/v/v), was delivered at a flow rate of 0.9 mL/min and UV detection was carried out at 250 nm. The recoveries of the 12 phenothiazines spiked into serum samples were 87.6-99.8%. Regression equations for the 12 phenothiazines showed excellent linearity, with detection limits of 3.2-5.5 ng/mL for serum. The inter-day and intra-day coefficients of variation for serum samples were commonly below 8.8%. The selectivity, accuracy and precision of this method are satisfactory for clinical and forensic purposes. This sensitive and selective method offers the opportunity for simultaneous screening and quantification of almost all phenothiazines available in Japan for the purposes of clinical and forensic applications.

[Unnatural deaths and medicolegal autopsy system--consented autopsy and its future].

UNLABELLED: We actively examine the causes of non-criminal unnatural deaths here at the Department of Legal Medicine in Kitasato University School of Medicine. We dealt with 3565 cases of unnatural deaths during the ten years from 1994 to 2003 (postmortem examinations, 1741 cases; consented autopsies, 1824 cases; autopsy rate, 51.2%). CONTENTS: deaths by diseases, 2291 cases (64.3%); deaths from external causes or others, 1274 cases (35.7%). The autopsy rate of deaths by diseases is 60.7% and that of deaths from external causes or others is 34.0%. Cardiopulmonary arrest on arrival (CPAOA) accounts for about half of total cases (50.8%), that is 1811 cases. Especially, consented autopsies in cases of non-criminal unnatural deaths performed under the permission (autopsy consent) of the bereaved family are highly significant, since they can contribute to society as greatly as judicial appraisal, and can also contribute to undergraduate and postgraduate medical education. Consented autopsy is a procedure that enhances people's recognition of legal medicine in the society and universities. We expect that other universities will establish their own methods of medicolegal activities in the future by referring to our Kitasato University system as a model.

Massive pulmonary thromboembolism demonstrated at necropsy in Japanese psychiatric patients treated with neuroleptics including atypical antipsychotics.

BACKGROUND: There may be an increased risk of pulmonary thromboembolism (PTE) with antipsychotic drugs, so this association was investigated in autopsy cases of sudden unexpected death determined by the Department of Legal Medicine of a Japanese university hospital. METHODS AND RESULTS: Records of 1,125 forensic autopsies (808 males, 317 females) performed during the study period for investigation of the cause of sudden unexpected death were reviewed and a logistic regression analysis was performed to explore whether age, gender, body mass index (BMI), and antipsychotic drug use were associated with fatal PTE. Among all records, 34 (3.0%; 14 males, 20 females) indicated the use of antipsychotic drugs and 28 (2.5%; 9 males, 19 females) indicated PTE as the cause of death. Of the 28 subjects who died from PTE, 8 had taken antipsychotic drugs (29%) and all were female. Female gender and antipsychotic drug use accounted for a significantly higher risk of PTE death with an odds ratio of 4.22 (95% confidence interval (CI), 1.82-9.78; p<0.01) and 10.49 (95% CI, 3.95-27.85; p<0.01), respectively. CONCLUSIONS: Japanese women taking antipsychotic drugs may be at particular risk for PTE.

Three cases of sudden death due to butane or propane gas inhalation: analysis of tissues for gas components.

We report three cases of sudden death due to inhalation of portable cooking stove fuel (case 1), cigarette lighter fuel (case 2), and liquefied petroleum gas (LPG) (case 3). Specimens of blood, urine, stomach contents, brain, heart, lung, liver, kidney, and fat were collected and analyzed for propylene, propane, isobutane, and n-butane by headspace gas chromatography. n-Butane was the major substance among the volatiles found in the tissues of cases 1 and 2, and propane was the major substance in case 3. A combination of the autopsy findings and the gas analysis results revealed that the cause of death was ventricular fibrillation induced by hard muscle exercise after gas inhalation in cases 1 and 2, and that the cause of death in case 3 might be hypoxia. It is possible that the victim in case 3 was under anesthetic toxicity of accumulated isobutane which is a minor component of liquefied petroleum gas.

Acute respiratory distress syndrome following asthma-like symptoms from massive ingestion of a monoethanolamine-containing detergent.

A 65-y-old man ingested about 600 mL of an alkaline detergent (pH 11.7) containing 3.3% monoethanolamine (MEA). After vomiting with choking several times, he presented to the emergency center with asthma-like symptoms 95 min after ingestion. Despite treatment with bronchodilators, steroids, and epinephrine, respiratory dysfunction progressed to acute respiratory distress syndrome resulting in death on the 4th hospital day. This is the first report of serious acute oral ingestion of an MEA-containing product; MEA aspirated into the respiratory tract may cause not only bronchial asthma symptoms, but may also severely injure the lung parenchyma.

Dural sinus thrombosis with severe hypernatremia developing in a patient on long-term lithium therapy.

Dural sinus thrombosis has not been described in a patient with hypernatremia resulting from lithium-induced nephrogenic diabetes insipidus. A 63-year-old man on chronic lithium therapy for schizoaffective disorder was transferred to the Emergency Department with dehydration and signs of central nervous system dysfunction after a 3-week isolation in a room in a psychiatric hospital due to exacerbation of psychiatric disorder, during which he refused to eat. Laboratory examination revealed hypertonic hypernatremia (osmolality, 359 mOsm/kg and Na, 171 mEq/L) and hyposthenuria (specific gravity, 1.010 and osmolality, 249 mOsm/kg), with normal serum endogenous vasopressin concentration (2.3 pg/mL). The serum lithium concentration was within the therapeutic range (0.94 mEq/L). Cranial computed tomography demonstrated subarachnoid hemorrhage and suggested dural sinus thrombosis. Although treatment with indomethacin (25 mg parenterally at 8-hour intervals) was somewhat effective in restoring renal concentrating capacity, he died of massive hemorrhagic infarction on the sixth hospital day, probably secondary to dural sinus thrombosis. The clinical diagnosis was confirmed by postmortem examination. Physicians should be alert for the possibility of dural sinus thrombosis as a complication of hypernatremia resulting from lithium-induced nephrogenic diabetes insipidus.

Acute massive pulmonary thromboembolism associated with risperidone and conventional phenothiazines.

To assess the contribution of antipsychotic medication in Japanese patients suffering acute massive pulmonary thromboembolism, records of patients with idiopathic pulmonary thromboembolism associated with antipsychotic medication who were seen in a Japanese Emergency Center from January 1996 to December 2000 were reviewed. Age, gender, physical status, clinical presentation, antiphospholipid antibody, outcome, psychiatric profile, and antipsychotic medication use were examined. Seven patients had acute pulmonary thromboembolism associated with antipsychotic drug use, representing 44% of all patients with idiopathic pulmonary thromboembolism. The 7 patients developed symptoms in the early morning. More women than men were affected. In 5 cases, chlorpromazine and other phenothiazines had been prescribed, whereas in 2 cases, risperidone, a mixed serotonin 5HT(2A) and dopamine D(2) receptor antagonist, had been taken for 40 days and 6 days, respectively. In 4 cases, including the patients taking risperidone, antiphospholipid antibodies were not present. Although statistically significant conclusions can not be drawn from this study, the data suggest that patients receiving risperidone, as well as conventional phenothiazines, are at risk for acute pulmonary thromboembolism, even if otherwise healthy. Strong affinity for the 5HT(2A) receptor of the novel antipsychotic may increase coagulability and the risk of thromboembolism.