Liver and blood postmortem tricyclic antidepressant concentrations.

Tricyclic antidepressants (TCAs) are one of the major causes of death from drug ingestions. Because TCAs are highly tissue bound, it has been postulated that postmortem tissue release would give rise to elevated blood levels. This study examines the authors' experience with TCAs as a cause of death and the reliability of postmortem liver and blood levels. Postmortem liver and blood TCA levels (parent drug and active metabolite) were quantitated by high-pressure liquid chromatography (HPLC) and gas chromatography mass spectrometry (GC-MS). From 1977 through 1985 the number and percentage of deaths caused by TCA overdoses have remained constant in regard to the total number of deaths caused by poisonings and overdoses: range: 4-17; 5.6-20.2%, respectively. During a six-month period in 1986-1987, nine deaths were caused by six different TCAs. Substantial increases in blood TCA levels were observed as the postmortem interval increased. The mean liver and blood levels were as follows: 232 micrograms/g of tissue (SD, 168) and 6.2 mg/L (SD, 2.4). The liver to blood ratio for the nine cases was 37 (SD, 22):1. In comparison, in cases (n = 4) in which the causes of death were not TCA related but the patients were taking therapeutic doses of TCA, the mean liver and blood levels were 10.8 micrograms/g (SD, 6.0) and 0.26 mg/L (SD, 0.06), respectively. The liver to blood ratio of 39.2 (SD, 17.9): 1 was not different than in the overdose cases. This large tissue to blood gradient in both TCA overdose and therapeutic ingestion cases indicates that postmortem release of tissue-bound TCAs into the blood might falsely show elevated postmortem blood levels that could be indicative of a manner of death even in the nonoverdose, therapeutic ingestion. Thus, only liver TCA levels should be quantitated to specify the manner of death.

Furazolidone-induced cardiomyopathy in turkeys. Association with a relative alpha1-antitrypsin deficiency.

A naturally occurring cardiomyopathy (round heart disease) which is potentiated by inbreeding and a cardiomyopathy produced by furazolidone, a nitrofuran derivative, were studied for an associated alpha1-antitrypsin deficiency in two flocks of turkeys (one inbred for round heart disease and a commercial flock). At 4 weeks of age, the furazolidone-fed birds of both flocks demonstrated a marked increase in mortality and cardiac dilatation associated with disordered hepatic metabolism when compared with controls. Although PAS-positive, diastase-resistant globules were observed in the livers of both strains of turkeys fed furazolidone, these globules were present in lysosomes and not in the rough endoplasmic reticulum as in alpha1-antitrypsin deficiency. The control inbred birds with round heart disease did not demonstrate histologic or biochemical evidence of an alpha1-antitrypsin deficiency. It is proposed that furazolidone in the turkey produces primary hepatic damage that is reflected in lowered total serum proteins, including trypsin inhibitory capacity, and that the alterations produced by furazolidone are superimposed on round heart disease in the inbred flock.

Occurrence of myocarditis in sudden death in children.

This study suggests that the prevalence of "silent" myocarditis may be higher in the pediatric population than is generally suspected and may contribute to a significant number of sudden and unexpected deaths in children, particularly those older than one year of age. The incidence of histologic myocarditis in children dying a violent death is similar to that reported as an incidental finding in adults.