Takako Minami

An autopsy case of combined drug intoxication involving verapamil, metoprolol and digoxin

We present here a fatal poisoning case involving verapamil, metoprolol and digoxin. A 39-year-old male was found dead in his room, and a lot of empty packets of prescribed drugs were found near the corpse. The blood concentrations of verapamil, metoprolol and digoxin were 9.2 microg/ml, 3.6 microg/ml and 3.2 ng/ml, respectively. The cause of death was given as cardiac failure, hypotension and bradycardia due to a mixed drug overdose of verapamil, metoprolol and digoxin, based on the results of the autopsy and toxicological examination. We speculate that the toxicity of verapamil is potentiated by drug interaction with metoprolol and digoxin.

Simultaneous analysis of acephate and methamidophos in human serum by improved extraction and GC-MS

A detailed procedure for simple and rapid analysis of acephate, an organophosphorous pesticide, and its metabolite methamidophos in human serum by gas chromatography-mass spectrometry was established. The method included solid-phase extraction with activated charcoal, which gave high recoveries of both analytes. After validation of the method, it was successfully applied to a serum sample obtained from an actual poisoning case. The present method seems very useful, especially in forensic and environmental toxicology.

Application of energy dispersive X-ray fluorescent spectrometry (EDXRF) in drug-related cases.

We applied here energy dispersive X-ray fluorescent spectrometry (EDXRF) to two medico-legal autopsy cases of bromvalerylurea ingestion. Rapid elemental analysis using EDXRF identified bromide in blood, urine and stomach contents of victims during autopsy. The present cases indicate that screening with EDXRF, an instrument suitable for non-destructive, rapid elemental analysis, provides useful information for identification of drugs.

Decreased histamine-stimulated phosphoinositide hydrolysis in the cerebral cortex of a rat line selectively bred for high alcohol preference.

This study sheds light on the comparative analysis of agonist-stimulated phosphoinositide (PI) hydrolysis in the cerebral cortex of alcohol-naïve rats from established lines selectively bred for low alcohol preference (LAP) and high alcohol preference (HAP). The effect of histamine (1.0 mM), but neither norepinephrine (0.1 mM) nor carbachol (0.5 mM), on PI hydrolysis was significantly reduced in HAP rats (0.4 ± 5.0 fmol/mg protein [3H]inositol phosphates formed over basal) compared with LAP rats (25.5 ± 10.0 fmol/mg protein). The contents of monoamines (dopamine, norepinephrine, and serotonin) and histamine in the cerebral cortex did not significantly differ between LAP and HAP rats, nor did the contents of their metabolites, except 3-methoxy-4-hydroxyphenylglycol (one of the metabolites of norepinephrine) and Nτ-methylhistamine, which was not detected in our system. The histamine stimulatory effect was unchanged in the cerebral cortex of an intact Wistar rat that was treated with intraperitoneal injection of alcohol (1.0 g/kg once per day for 14 days). The results of the current study indicate that the decrease in the histamine effect on PI hydrolysis in HAP rats might be attributed to that particular rat line.

Determination of acephate and methamidophos in tissues: appearance of matrix effect in gas chromatography–mass spectrometry

A simple and reliable method to determine acephate and methamidophos in mammalian tissues is presented. The method includes solid-phase extraction of tissue extracts with active carbon cartridges followed by gas chromatography–mass spectrometry analysis. During the study, a matrix effect was observed especially at low concentrations of acephate and methamidophos in serum and in brain. To minimize the effect, we prepared calibration curves with relatively short ranges. The validation data, such as the linearity of calibration curves, limits of detection, and coefficients of variation for recovery rates, were generally satisfactory. The present method is useful for determination of acephate and methamidophos in mammalian tissues because of its simplicity and speed, keeping in mind the presence of the matrix effect.

An autopsy case of imipramine poisoning.

We present a fatal imipramine poisoning. Quantitative analysis of imipramine and its metabolite, desipramine, was performed by high-performance liquid chromatography. The concentrations of imipramine and desipramine were 18.67 μg/mL and 6.21 μg/mL in heart blood and 6.90 μg/mL and 1.77 μg/mL in the femoral venous blood, respectively. We concluded that the cause of death was due to imipramine poisoning.

Effects of dopamine antagonists on methamphetamine-induced dopamine release in high and low alcohol preference rats.

The authors have previously shown that high alcohol preference rats (HAP) have a significantly higher sensitivity than low alcohol preference rats (LAP) for methamphetamine (MAP). In this study, changes in dopamine and serotonin release induced by MAP (1 mg/kg, intraperitoneally) after pre-treatment with D1 and D2 receptor antagonists were examined in the striatum of rats with different alcohol preferences to elucidate differences in receptor levels between the two rat strains. D1 receptor antagonist SCH23390 or D2 receptor antagonist haloperidol were administrated intracerebroventricularly 10 min before MAP stimulation. This study investigated the effect of methamphetamine-induced dopamine and serotonin release in striatum using microdialysis of freely moving rats coupled to ECD-HPLC. With haloperidol treatment both strains of rats showed a significantly greater maximum increase on MAP-induced dopamine release compared with respective control rats. However, after SCH23390 treatment only HAP rats showed a significantly greater increase in dopamine release compared with controls. SCH23390 blocks mainly D1 receptors only in the post-synaptic membrane, whereas haloperidol blocks D2 receptors in both the pre-synaptic and post-synaptic membranes. The MAP-induced increase in dopamine release following haloperidol pre-treatment was greater than SCH23390 pre-treatment in both strains. This result indicates that D2 receptors (autoreceptors) in the pre-synaptic membrane were blocked, leading to the elimination of the feedback function that regulates dopamine release. These data suggested that alcohol preference is associated with the action of MAP, and the dopaminergic mechanism, specifically the D1 system in the striatum, might have a different pathway dependent on alcohol preference.

An autopsy case of asthmatic death--usefulness of biochemical examination.

BACKGROUND Asthma is the one of the major causes of sudden death in Japan. Postmortem diagnosis of asthma has been based on morphological findings in lungs, but it histological evidence, was also reported that the biochemical markers such as total and specific immunoglobulin E (IgE) are useful. CASE REPORT We present here a case of fatal asthmatic death. A Japanese male in his thirties, complaining of dyspnea, collapsed suddenly. He was taken by ambulance to hospital, but cardiopulmonary resuscitation was ineffective. From autopsy findings, we concluded that the cause of death was asphyxia due to asthma attack. Biochemical findings indicated that the deceased had a severe asthmatic condition. CONCLUSION In the presented case, the biochemical examination of the serum obtained at autopsy gave helpful information for the diagnosis that asthmatic attack was a cause of death.

Mthanol: toxicity of the solvent in a commercial product should also be considered

Sir In general, the evaluation of toxicity relies on the toxicity of the main component in a poisoning case involving a commercial product. However, we usually pay little attention to the toxicity of the solvent used. Methanol finds widespread commercial use as a solvent.1 Here we report a case of death due to trichlorfon (O,O-dimethyl 2,2,2-trichloroi-hydroxyethylphosphonate; DEP) dissolved in methanol and phenobarbital ingestion with fatal levels of these components in the blood, and also a detected toxic level of methanol and its metabolite, formic acid.

Hyperpyrexia induced by a multiple antidepressants overdose.

A 23-year old male ingested an excessive amount of antidepressants that had been prescribed. Initially, he was hospitalized near his house. Subsequently, he was transferred to the emergency department (ED) in a university hospital, because of the difficulties in controlling his seizures. At the time of arrival in the ED, he was in cardiopulmonary arrest. His rectal temperature was 41.2°C (106.16°F). Resuscitation was unsuccessful. A number of empty packets of antidepressants were found in his house during the subsequent authorities’ investigation. At autopsy, no remarkable findings were observed except for severe pulmonary edema and congestion. No evidence of brain injury or infectious diseases such as meningitis, encephalitis or pneumonia was observed. Histological study of the skeletal muscle showed hypercontracted fiber appearing as ‘opaque fibres’ and multiple vacuolation (Figure 1). Drug screening testing using a TriageTM (Biosite Diagnostic Inc, San Diego, USA) panel was positive for benzodiazepines, barbiturates and tricyclic antidepressants, but negative for alcohol by gas chromatography. Figure 2 shows the chromatogram of femoral blood using a high performance liquid chromatography (HPLC) drug analysis system (Class VP system, Shimadzu, Kyoto Japan). Clomipramine, amoxapine, maprotiline, amitriptyline and milnacipran were confirmed by each retention time. The drug concentrations in the victim’s femoral blood and their fatal and therapeutic blood level are summarized in Table 1. Blood concentrations of clomipramine and amoxapine were at fatal levels, while the maprotiline and amitriptyline levels were toxic.2 Milnacipran, a newly developed serotonin-noradrenaline reuptake inhibitor, was found to be ten-fold higher than the therapeutic level.3 The positive benzodiazepines and barbiturates detected by the TriageTM screening