Crospovidone is an insoluble polymer of N-vinyl-2-pyrrolidone that is used as a disintegrant in pharmaceutical tablets. It can potentially embolize to the lung when aqueous tablet suspensions are injected intravenously. In this report, we identified embolized crospovidone in autopsy-derived lung tissue from three adult IV drug users, 1 man and 2 women, whose ages respectively were 27, 38, and 40 years. Suspected crospovidone was compared with pharmaceutical-grade crospovidone by means of histochemical stains, transmission electron microscopy, and infrared spectroscopy. Similar particles were also observed by light microscopy in a 4-mg tablet of hydromorphone, a preparation prescribed to two of the patients. Two patients had sickle cell disease and were taking methadone and/or hydromorphone for pain management; the third was receiving parenteral hyperalimentation after small bowel resection. Crospovidone appeared as deeply basophilic, coral-like particles within pulmonary arteries and in extravascular foreign-body granulomas. Intrapulmonary crospovidone stained similarly to the pure substance, including intense staining with mucicarmine, Congo red, and Masson trichrome. With Movat pentachrome stain, both intravascular and purified crospovidone appeared orange-yellow, whereas most interstitial particles associated with giant cells stained blue-green. Alcian blue failed to stain intravascular or purified crospovidone but strongly decorated some phagocytized particles. Ultrastructurally, both purified powder and tissue deposits of crospovidone appeared as irregular, electron dense, laminated, and finely granular material. Intrapulmonary crospovidone was associated with inflammatory cells and exhibited degenerative changes. By infrared spectroscopy, crospovidone in tissue had the same spectral characteristics as pharmaceutical grade crospovidone and the library reference, polyvinylpyrrolidone (PVP). We conclude that crospovidone contributes to pulmonary vascular injury in some persons who illicitly inject pharmaceutical tablets. It is readily identifiable histologically and distinguishable from other tablet constituents, such as cornstarch, talc, and microcrystalline cellulose. Pharmaceutical tablets typically consist of active ingredients and a variety of insoluble filler substances, such as talc, microcrystalline cellulose, and cornstarch, which provide bulk and impart physical properties to tablet preparations (1). Pulmonary foreign body granulomatosis caused by the embolization of these filler materials occurs when aqueous suspensions of tablets intended for oral consumption are injected intravenously (1-3). Some of the agents used in this manner, either alone or in combination, include methadone hydrochloride, tripelennamine hydrochloride (Pyribenzamine), methylphenidate (Ritalin), and pentazocine (Talwin; 3-6). Pulmonary angiothrombotic granulomatosis caused by talc, cornstarch and/or microcrys-
Previous studies have shown that up to 50% of adult drownings are related to the consumption of alcohol. Little information is available in the literature regarding the possible contribution of ethanol and other drugs to drownings. All records of deaths occurring in Cuyahoga County, Ohio, from 1994-2003, in which drowning was listed as the cause of death, were reviewed. Toxicology analysis was performed on cases where specimens were submitted. Review of the 187 cases showed that the majority (78%) of drowning deaths were ruled as accidents, 26 (14%) as suicide, 5 (3%) as homicide, and 11 (6%) as undetermined. Among the accidental deaths (n=141), 97 (69%) were negative for all drugs, including ethanol, and 30 cases (21%) were positive for ethanol only. Illicit drugs were detected in 4 of the cases (3%). In the suicides (n=26), 16 (62%) were negative for all drugs, including ethanol, and 7 cases (27%) were positive for ethanol only (mean blood alcohol concentration [BAC] 0.03 g/dL). Illicit drugs were detected in 3 of the cases (12%). Two of the 5 homicide cases (40%) were positive for ethanol. There were no cases in which the victim tested positive for illicit drugs. Of the 11 cases ruled as undetermined, 64% (n=7) were negative for all drugs, including ethanol. The remainder of the cases tested positive for ethanol only. There were no cases in which illicit drugs were detected. This study demonstrates that the majority of drowning deaths in Cuyahoga County, Ohio, were not drug related. Deaths in which drugs were detected were typically accidental deaths, with ethanol the most common drug detected.
Olanzapine is a relatively new antipsychotic drug used in the United States for the treatment of schizophrenia. Since its release in the United States market in 1996, few cases of fatal acute intoxication have been reported in the literature. This article describes the case of a 25-year-old man found dead at home who had been prescribed olanzapine for schizophrenia. This case is unique because of the measurement of olanzapine in brain tissue obtained from seven regions in addition to the commonly collected biologic matrices. Olanzapine was detected and quantitated by basic liquid-liquid extraction followed by dual-column gas chromatographic analysis with nitrogen phosphorus detection. The assay had a limit of detection of 0.05 mg/L and an upper limit of linearity of 2 mg/L. The presence of olanzapine was confirmed by gas chromatography-mass spectrometry by use of electron impact ionization. The concentrations of olanzapine measured in this case were as follows (mg/L or mg/kg): 0.40 (heart blood), 0.27 (carotid blood), 0.35 (urine), 0.61 (liver), negative (cerebrospinal fluid), 0.33 mg in 50 ml (gastric contents). In the brain, the following distribution of olanzapine was determined (mg/kg): negative (cerebellum), 0.22 (hippocampus), 0.86 (midbrain), 0.16 (amygdala), 0.39 (caudate/putamen), 0.17 (left frontal cortex), and 0.37 (right frontal cortex). The cause of death was determined to be acute intoxication by olanzapine, and the manner of death was accidental.
'Lingering death' cases occur when the circumstances of death indicate an opiate overdose, but measured opiate blood levels are only in the therapeutic range; death results from cardiac and respiratory depression. This study examined the relative concentration of opiates in femoral blood and in the medulla oblongata (sites for cardiac and respiratory control) from 41 cases to determine whether a difference in opiate concentration might explain lingering deaths. Opiates from blood and medulla were analyzed using GC-EI-MS in selective ion monitoring mode. Results were correlated with gross and microscopic findings of the lungs and with cause and manner of death. Opiate concentrations for morphine, codeine and 6-acetylmorphine (6-AM) were higher in the medulla than in blood. The brain: blood ratio for the analytes demonstrated an increasing ratio from morphine, to codeine, to 6-AM (1.42, 2.48 and 4.86), which corresponds to the relative lipophilicity of these analytes. The average right and left lung weights were 762 and 668 g, respectively. Histologic examination showed edema, and/or polarizable microemboli, acute bronchopneumonia and acute bronchitis. The preferential distribution of opiates to medulla suggests that lingering opiate deaths may be explained, at least in part, because of higher relative concentrations of drug in brain, compared with femoral blood.
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