Distribution of triazolam and alpha-hydroxytriazolam in a fatal intoxication case

The case of a 77-year-old woman who was found dead in her bathtub with her head clearly above the water line is presented. The decedent had a medical history of depression, liver disease, spinal stenosis, and diabetes mellitus. An empty medication bottle of triazolam was found in the trashcan. At autopsy, no injury or evidence of drowning was found. Toxicological analysis identified triazolam at a concentration of 0.12 mg/L in the heart blood. Triazolam and alpha-hydroxytriazolam were quantitated in the specimens received. The medical examiner ruled that the cause of death was triazolam intoxication and the manner of death was suicide.     

Left ventricular assist device implantation via left thoracotomy: alternative to repeat sternotomy

Repeat sternotomy for left ventricular assist device insertion may result in injury to the right heart or patent coronary grafts, complicating intraoperative and postoperative management. In 4 critically ill patients, left thoracotomy was used as an alternative to repeat sternotomy. Anastomosis of the outflow conduit to the descending thoracic aorta provided satisfactory hemodynamic support.     

Accuracy of mammographic breast density analysis: results of formal operator training.

Mammographic density is a major risk factor for breast cancer. Breast density is not routinely quantified for research studies because present methods are time intensive and manual, and require expert training. We investigated whether individuals with and without backgrounds in radiology or medicine can achieve sufficient accuracy when compared with an expert (gold standard) reader of mammographic breast density. Nine readers (three radiologists, two non-radiology physicians, and four nonphysicians) assessed breast density on 144 digitized films (60 contralateral films of breast cancer cases and 84 controls) on a computer workstation with custom software. Readings were compared with a radiologist with training in mammography and density reading that read the same films. A correlation of r = 0.9 or higher with the gold standard reading was met by three of three radiologists, one of two nonradiology physicians, and one of four nonphysicians. Intrareader reproducibility measured as the residual sum of mean errors averaged 10% mammographic density for all readers and 9% for readers with a correlation of 0.9 or higher with the gold standard. The odds ratios associated with breast cancer when films with mammographic breast density of 50% or greater are considered "dense" ranged from 3.1 to 3.9 or a 1.9-2.4-per-population-SD increase in percentage density. Although it is advantageous to have a radiological background when quantifying mammographic density, it is not a prerequisite. Applying strict validation criteria to qualify readers to quantify mammographic breast density for research studies will enhance the chance of accurately assessing breast density and discriminating women at high and low risk of breast cancer.     

Noninvasive evaluation of women with coronary artery disease

Coronary artery disease (CAD) is the leading cause of death in women. More women than men die of CAD each year, and unlike men, the death rate has not declined for women but has remained stable over the last 20 years. Despite these statistics, much less is known about the prevention, diagnosis, or treatment of CAD in women. The noninvasive diagnosis of CAD in women is difficult secondary to differences in physiology, etiology, presenting symptoms, risk factor prevalence, comorbid conditions, hormonal status, and body habitus between women and men. Echocardiography and Tc-99m sestamibi single photon emission computed tomography imaging are two noninvasive imaging techniques commonly combined with exercise or pharmacologic agents (dobutamine, adenosine, dipyridamole) that have recently evolved to address these differences. These evolutions and the role of both techniques in the diagnosis and prognosis of women with CAD will be reviewed in this article.     

Withholding/withdrawal of life support in trauma patients: is there an age bias?

Our objective was to examine patterns of withholding/withdrawal (WH/WD) of life support in trauma patients and to determine whether WD/WH of life support is used more frequently in elderly patients. This is a retrospective cohort study of injured elderly (> or = 65 years) and young patients (< 65 years) from 1994 through 1998 treated at a surgical intensive care unit in a community tertiary-care hospital. We studied the cases of 82 patients (30 elderly and 52 young patients) with WH/WD of life support after injury. Our main outcome measures were demographic and clinical characteristics of elderly and young patients undergoing WH/WD of life support after injury with an association between age and WH/WD of life support. Of 102 total trauma patient deaths 82 had WH/WD of life support. This mode was chosen in 52 (80%) patients under the age of 65 and in 30 (81%) patients age 65 or greater. Patients in the younger cohort had a higher mean Injury Severity Score and Abbreviated Injury Score of 5 (P < 0.05). The elderly cohort had a higher incidence of pre-existing disease (< 0.001). Length of stay was similar between the populations. We conclude that the elderly were no more likely to have WH/WD of life support than were younger patients. However, the older patients were less severely injured as measured by Injury Severity Score and percentage with Abbreviated Injury Score head of 5. Other factors such as the presence of pre-existing disease may influence the decision to withhold or withdraw life support to a greater degree than the actual severity of injuries.     

Effect of dopamine D3 antagonists on PPI in DBA/2J mice or PPI deficit induced by neonatal ventral hippocampal lesions in rats.

Schizophrenic patients typically exhibit impairment of sensorimotor gating, which can be modeled in animal models such as the test of prepulse inhibition of startle response (PPI) in rodents. It has been found that antipsychotics enhanced PPI in DBA mice and reversed the PPI deficit induced by neonatal ventral hippocampal (NVH) lesions in rats. However, the relative involvement of D(3) and D(2) receptors in these effects is unknown since all antipsychotics are D(2)/D(3) antagonists with limited binding preference at D(2) receptors. Therefore, in the current study, we investigated the influence of several dopamine antagonists with higher selectivity at D(3) vs D(2) receptors on PPI in DBA/2J mice and in NVH-lesioned rats. The PPI in DBA/2J mice was enhanced by the nonselective D(2)/D(3) antagonists, haloperidol at 0.3-3 mg/kg, or risperidone at 0.3-1 mg/kg, while PPI-enhancing effects were observed after the administration of higher doses of the preferential D(3)/D(2) antagonist, BP 897 at 8 mg/kg, and the selective D(3) antagonists, SB 277011 at 30 mg/kg and A-437203 at 30 mg/kg. No effect was observed following the treatment with the selective D(3) antagonist, AVE 5997 up to 30 mg/kg. The PPI deficits induced by NVH lesions were reversed by haloperidol but not by the more selective D(3) antagonists, A-437203 and AVE 5997. BP 897 enhanced PPI nonselectivity, that is, in both lesioned and nonlesioned rats. In summary, the present study indicates that PPI-enhancing effects induced by antipsychotics in DBA/2J mice and in NVH-lesioned rats are unlikely to be mediated by D(3) receptors.     

Akute Vergiftung mit Strychnin-N-oxydhydrochlorid (Movellan®-Tabletten) und ihre Behandlung mit Diazepam

Zusammenfassung Es werden klinische Symptomatik, Ablauf und chemischtoxikologische Untersuchungsbefunde einer akuten schweren Strychnin-N-oxyd (Movellan^®)-Vergiftung eines 18jährigen Mädchens und ihre Behandlung mit Diazepam (Valium^®) bei gleichzeitiger forcierter Diurese beschrieben. Die peroral eingenommene Strychnin-N-oxyd-Dosis betrug 75 mg (= 1,24 mg/kg Körpergewicht). Spektrophotometrische und papierchromatographische Untersuchungen zeigten, daß eine Strychnin-Ausscheidung im Harn quantitativ bis zu 15 Std nach Tabletteneinnahme, qualitativ bis zum 3. Tag eindeutig, am 4. Tag nur noch unsicher und dann nicht mehr nachweisbar war. Ein Strychnin-Nachweis im Blut gelang nicht.Herrn Prof. Dr.Lendle zum 70. Geburtstag.     

Tissue distribution of loperamide and N-desmethylloperamide following a fatal overdose

We report a case involving a fatal intoxication with loperamide (Imodium). Loperamide is a synthetic opioid of the phenyl piperidine class used as an over-the-counter antidiarrheal. It exerts its effects through interaction with micro-opiate receptors in the intestine to reduce peristalsis. Loperamide lacks the typical euphoric opiate effects when administered at recommended doses. Both loperamide and its major metabolite, N-desmethylloperamide, were isolated by liquid-liquid extraction into n-butyl chloride from alkalinized samples. Extracts were analyzed by liquid chromatography-electrospray-mass spectrometry in selected-ion-monitoring mode. Rapid separation of the drug, metabolite, and internal standard (diphenoxylate) was achieved using a high-resolution C18 column with 1.8-microm particle diameter. The mobile phase consisted of 0.1% formic acid in deionized water (60%) and acetonitrile (40%) at a flow rate of 0.5 mL/min. Heart blood concentrations for loperamide and its metabolite were 1.2 mg/L and 3.3 mg/L, respectively. In contrast, reported peak plasma concentrations of loperamide after administration of recommended daily doses of 16 mg did not exceed 0.012 mg/L in controlled trials. Because the heart blood ethanol concentration was 0.08 g/dL, the medical examiner ruled that the cause of death was loperamide and ethanol intoxication, and the manner of death as undetermined.