Distribution of mirtazapine (Remeron) in thirteen postmortem cases. (41/2516)

Mirtazapine is a new antidepressant agent that entered the United States market in April 1996. To date, the literature provides limited information about therapeutic blood concentrations and virtually no information about postmortem levels. The Los Angeles County Coroner's Toxicology Laboratory has encountered 13 cases where postmortem tissue distributions of mirtazapine were determined. The analysis of mirtazapine from postmortem specimens (2-mL sample size) consisted of an n-butylchloride basic extraction procedure with identification and quantitation on a gas chromatograph-nitrogen-phosphorus detector. Linearity was achieved from 0.025 mg/L to 3.0 mg/L with a limit of quantitation of 0.025 mg/L. Confirmation of mirtazapine was performed on a gas chromatograph-mass spectrometer by comparison with a pure analytical standard. The tissue distribution of mirtazapine are in the following concentration ranges: heart blood 0.03-0.57 mg/L (13 cases), femoral blood 0.04-0.24 mg/L (9 cases), vitreous 0.06-0.10 mg/L (3 cases), liver 0.32-2.1 mg/kg (12 cases), bile 0.40-6.6 mg/L (7 cases), urine 0.12-2.5 mg/L (11 cases), kidney 0.23 mg/kg (1 case), spleen 0.17 mg/kg (1 case), and gastric 0.001-2.7 mg total (9 cases). Mirtazapine was not implicated in the cause of death in any of the 13 cases studied. These cases are being presented to aid the forensic toxicologist in the evaluation of postmortem mirtazapine levels.  (+info)

A fatality related to the veterinary anesthetic telazol. (42/2516)

A 45-year-old male veterinarian was found dead in bed. Police investigation showed no evidence of trauma or other suspicious circumstances. Autopsy was unremarkable except for cardiomegaly and hepatosplenomegaly. Toxicological analysis revealed the presence of Telazol and ketamine. Telazol is a veterinary anesthetic agent that is composed of equal parts of tiletamine and zolazepam. Tiletamine is a disassociative anesthetic similar to ketamine and phencyclidine, and zolazepam is a diazepine derivative tranquilizer used to minimize the muscle hypertonicity and seizures associated with tiletamine. Quantitation of tiletamine and zolazepam was performed using gas chromatography-mass spectrometry in the selected ion monitoring mode following a solid-phase extraction. Postmortem blood, urine, and liver concentrations of tiletamine were 295 ng/mL, 682 ng/mL, and 196 ng/g, respectively, whereas postmortem concentrations of zolazepam for the same tissues were 1.71 microg/mL, 1.33 microg/mL, and 15.5 microg/g, respectively. Blood and urine ketamine levels were 37 ng/mL and 381 ng/mL, respectively. The cause of death was ruled an acute mixed drug intoxication of tiletamine, zolazepam, and ketamine with the manner of death ruled as unclassified.  (+info)

Distribution of topiramate in a medical examiner's case. (43/2516)

Topimarate (Topamax) is a novel antiepileptic drug. Its mode of action is multifactorial and involves blockage of voltage-dependent sodium channels. The drug was detected in a 15-year-old epileptic who died soon after switching seizure prescriptions. Topimarate was recovered by basic extraction with ethyl acetate and analyzed by gas chromatography-mass spectrometry using selected ion monitoring. Ions monitored were m/z 324 and m/z 110 for topiramate and m/z 98 for the internal standard mepivacane. The drug was quantitated in blood, vitreous humor, bile, stomach content, and liver: the concentrations were 8.9, 12.4, and 10.9 mg/L, 31 mg/total content, and 29 mg/kg, respectively. Topiramate was detected in urine but not quantitated. Other drugs identified in this case were 0.45 mg/L nordiazepam and 0.05 mg/L oxazepam in blood. No alcohol was detected in any of the specimens. The cause of death was seizure disorder with upper respiratory infection. The manner of death was determined as natural. To our knowledge, this is the first report of the presence of topiramate in postmortem specimens.  (+info)

Acute zolpidem overdose--report of two cases. (44/2516)

This report describes two cases of acute zolpidem overdose. The decedent in the first case was a 36-year-old female found dead in bed in her secured home. She had a history of psychiatric illness, including paranoid disorder, depression with panic episodes, and post-traumatic stress disorder. She was treated with risperidone and sertraline. Nine months prior to her death, the decedent was also prescribed zolpidem (Ambien). The postmortem examination revealed white foam within the larynx and upper trachea, which is indicative of pulmonary edema. Toxicological analyses of the urine showed the presence of caffeine, risperidone, and zolpidem. Subsequent quantitation of postmortem iliac serum revealed 5.6 microg/L of 9-hydroxyrisperidone and the following zolpidem concentrations: blood (subclavian), 4.5 mg/L; blood (iliac), 7.7 mg/L; vitreous humor, 1.6 mg/L; bile, 8.9 mg/L; urine, 1.2 mg/L; liver, 22.6 mg/kg; and gastric contents, 42 mg. The second case involved a 58-year old female, also found dead in bed, with white foam around her mouth. The decedent had a 25-year history of hypertension and mental illness--manic depression and schizophrenia. She was medicated with carbamazepine, naproxen, risperidone, and zolpidem. The postmortem examination revealed cardiomegaly, pulmonary edema, hepatomegaly, mild coronary atherosclerosis, and no signs of trauma. Toxicological analyses of the urine showed the presence of zolpidem and carbamazepine and metabolite. Zolpidem concentrations were as follows: blood (iliac), 1.6 mg/L; vitreous humor, 0.52 mg/L; bile, 2.6 mg/L; liver, 12 mg/kg; and gastric contents, 0.9 mg. The zolpidem blood concentrations of these cases are consistent with those of the previously published fatalities. The blood/vitreous humor ratios of zolpidem were 2.81 (subclavian) and 4.81 (iliac) in the first case and 3.08 (iliac) in the second case. These ratios, along with the sampling times of blood and vitreous humor for both cases, are not conclusive to indicate a definitive presence or absence of postmortem drug redistribution of zolpidem. The cause of death for both cases was determined to be acute zolpidem overdose, and manner of death was suicide.  (+info)

Time course of symptomatic orthostatic hypotension and urinary incontinence in patients with postmortem confirmed parkinsonian syndromes: a clinicopathological study. (45/2516)

OBJECTIVE: Although both orthostatic hypotension and urinary incontinence have been reported in a number of parkinsonian syndromes, such as Parkinson's disease (PD), multiple system atrophy (MSA), dementia with Lewy bodies (DLB), corticobasal degeneration (CBD), and progressive supranuclear palsy (PSP), differences in the evolution of these features have not been studied systematically in pathologically confirmed cases. METHODS: 77 cases with pathologically confirmed parkinsonian syndromes (PD, n=11; MSA, n=15; DLB, n=14; CBD, n=13; PSP, n=24), collected up to 1994, formed the basis for a multicentre clinicopathological study organised by the NINDS to improve the differential diagnosis of parkinsonian disorders. The present study determined the time course-that is, latency to onset and duration from onset to death, of symptomatic orthostatic hypotension, and urinary incontinence in the NINDS series. Furthermore, the diagnostic validity of a predefined latency to onset within 1 year of disease onset of symptomatic orthostatic hypotension or urinary incontinence was analysed. RESULTS: Significant group differences for latency, but not duration, of symptomatic orthostatic hypotension and urinary incontinence were found. Latencies to onset of either feature were short in patients with MSA, intermediate in patients with DLB, CBD, and PSP, and long in those with PD. Symptomatic orthostatic hypotension occurring within the first year after disease onset predicted MSA in 75% of cases; early urinary incontinence was less predictive for MSA (56%). CONCLUSION: Latency to onset, but not duration, of symptomatic orthostatic hypotension or urinary incontinence differentiates PD from other parkinsonian syndromes, particularly MSA.  (+info)

Incidence rates of first-ever ischemic stroke subtypes among blacks: a population-based study. (46/2516)

BACKGROUND AND PURPOSE: The aim of this study was to determine the incidence rates of ischemic stroke subtypes among blacks. METHODS: Hospitalized and autopsied cases of stroke and transient ischemic attack among the 187 000 blacks in the 5-county region of greater Cincinnati/northern Kentucky From January 1, 1993, through June 30, 1993, were identified. Incidence rates were age- and sex-adjusted to the 1990 US population. Subtype classification was performed after extensive review of all available imaging, laboratory data, clinical information, and past medical history. Case-control comparisons of risk factors were made with age-, race-, and sex-matched control subjects. RESULTS: Annual incidence rates per 100 000 for first-ever ischemic stroke subtypes among blacks were as follows: uncertain cause, 103 (95% confidence interval [CI], 80 to 126); cardioembolic, 56 (95% CI, 40 to 73); small-vessel infarct, 52 (95% CI, 36 to 68); large vessel, 17 (95% CI, 8 to 26); and other causes, 17 (95% CI, 9 to 26). Of the patients diagnosed with an infarct of uncertain cause, 31% underwent echocardiography, 45% underwent carotid ultrasound, and 48% had neither. Compared with age-, race-, and sex- (proportionally) matched control subjects from the greater Cincinnati/northern Kentucky region, the attributable risk of hypertension for all causes of first-ever ischemic stroke is 27% (95% CI, 7 to 43); for diabetes, 21% (95% CI, 11 to 29); and for coronary artery disease, 9% (95% CI, 2 to 16). For small-vessel ischemic stroke, the attributable risk of hypertension is 68% (95% CI, 31 to 85; odds ratio [OR], 5.0), and the attributable risk of diabetes is 30% (95% CI, 10 to 45; OR, 4.4). For cardioembolic stroke, the attributable risk of diabetes is 25% (95% CI, 4 to 41; OR, 3.1). CONCLUSIONS: Stroke of uncertain cause is the most common subtype of ischemic stroke among blacks. Cardioembolic stroke and small-vessel stroke are the most important, identifiable causes of first-ever ischemic stroke among blacks. The incidence rates of cardioembolic and large-vessel stroke are likely underestimated because noninvasive testing of the carotid arteries and echocardiography were not consistently obtained in stroke patients at the 18 regional hospitals. Most small-vessel strokes in blacks can be attributed to hypertension and diabetes.  (+info)

Association of primary Pneumocystis carinii infection and sudden infant death syndrome. (47/2516)

To delineate clinical and histological features of the first Pneumocystis carinii infection affecting the immunocompetent host, P. carinii-specific histological stains were performed on autopsy lung specimens from 534 consecutive pediatric patients (those with AIDS and malignancies were excluded) in Santiago, Chile. P. carinii clusters were found in 4 (25%) of 16 infants who died of no apparent cause at arrival to the emergency department, and in 10 (2.9%) of 342 infants who died of multiple conditions at the hospital (P=.002, Fisher's exact test). This prompted us to analyze additional series of infants with sudden infant death syndrome (SIDS). In 161 additional SIDS cases, 47 (35.1%) of 134 infants from Chile and 4 (14.8%) of 27 infants from Oxford, United Kingdom, were found to have P. carinii clusters in the lungs. The quantity of P. carinii cysts was small compared with the numbers seen in immunocompromised hosts with P. carinii pneumonitis. This study provides histological evidence that primary P. carinii infection is associated with SIDS.  (+info)

Sequential changes of hepatocyte growth factor in the serum and enhanced c-Met expression in the myocardium in acute myocardial infarction. (48/2516)

A 68-year-old male with acute myocardial infarction (AMI) was admitted to the hospital with chest pain that had started 1 day earlier. The serum levels (ng/ml) of hepatocyte growth factor (HGF) were 1.06, 1.22, 1.05, 0.72 and 0.64 on days 2, 3, 4, 5 and 6 postinfarction, respectively. He died suddenly due to cardiopulmonary arrest on day 6. At autopsy, approximately 400 ml of bloody pericardial fluid, caused by rupture of the left ventricle, was detected and the c-Met expression in the myocardium was immunohistochemically found to be most intense in the border zone of the infarcted and non-infarcted region. Although there was no c-Met expression in the infarcted myocardium, it was increased in the myocardial cells surrounding the blood vessels. This is the first report to show sequential changes of HGF in the serum, as well as c-Met expression in the myocardium, in a patient with AMI.  (+info)