Post-mortem toxico-kinetics of trazodone.

Trazodone is a structurally unique bicyclic anti-depressant, said to be significantly less toxic than other anti-depressants following an acute overdose. We studied the tissue distribution and post-mortem redistribution of trazodone in two fatalities, one of which allowed comparison with trimipramine, a typical tricyclic anti-depressant. Case 1, a 53-year-old female weighing 72 kg, had femoral vein concentrations of trimipramine 5.5 micrograms/ml, trazodone 14.4 micrograms/ml and alcohol 107 mg%. Case 2, a 48-year-old female of 70 kg, had a femoral vein trazodone of 15.5 micrograms/ml and alcohol 34 mg%, with no other drugs detected. For case 1 and case 2 respectively, trazodone tissue concentrations were: skeletal muscle 7.3 and 9.0 micrograms/g; left and right lungs 13.3, 12.9 and 35.3, 40.1; myocardium, 30.9 and 28.9; kidneys 34.7 and 39.6; liver 73.7 and 82.4; fat 18.5 and 16.5; brain 48.6 and 20.9. For case 1 and 2, respectively, blood trazodone concentrations in 10 initial autopsy samples ranged from 13.7-17.3 and 14.4-16.9 micrograms/ml. Twenty-four and forty-eight hours later the respective ranges were 12.8-18.0 and 12.4-19.9 for case 1, 12.5-20.1 and 12.7-27.0 for case 2. By contrast, for trimipramine, blood concentrations at 0 time, 24 h and 48 hours ranged from 5.5-11.4, 5.2-14.3, and 4.2-18.2, respectively. We conclude that trazodone shows little preferential concentration in solid organs and consequently has relatively stable post-mortem blood concentrations with little drug redistribution artefact. Both the clinical pharmacokinetics and post-mortem toxicokinetics of trazodone differ significantly from the tricyclic anti-depressants.     

An examination of drunken driving law reform

Most states have recently altered legislation in response to the problem of drunken driving. Reforms are generally aimed at enhancing criminal justice response to offenders. This research examines the outcomes corollary to new drunken-driving legislation in one Michigan jurisdiction. Pre- and post-reform data are analyzed with significant difference tests in order to assess whether or not the objectives of increasing arrests, convictions, and sanctions for drunken drivers materialized through implementation. Overall, results indicated the partial realization of reform goals. Concluding considerations offer interpretations, along with recommendations for continued progress in impacting upon the problem of drunken driving. Gratitude is expressed to the Faculty Research Creativity Support Fund at Western Michigan University for supporting this research.     

The use of mental status in death certification of suicide

A 5-year study (1982-1986) illustrates the use of mental status in death certification of suicide in 182 consecutive cases from Marion County, Oregon, U.S.A. The presence of specific mental illness was documented in Part II of the filed death certificate whenever sufficient data supported such a diagnosis. This study represents, so far as we are aware, the first use of mental illness in the routine death certification of suicide. The study subjects were described in terms of sex; age group; the presence or absence of a suicide note; the anatomical cause of death (Part I of the death certificate); and the presence of mental illness, severe physical illness, or alcohol abuse (Part II of the death certificate) as contributive to the death. About half (97 of 182 = 53.30%) of the study group was diagnosed as suffering from a major affective disorder. Another portion (18 of 182 = 9.89%) was classified as schizophrenic. A subgroup of 18 men, all of whom were residents of state mental or correctional institutions at the time of death, was also briefly described.     

The validity of death certificates: routine validation of death certification and its effects on mortality statistics

The 3478 death certificates (7.1% of all annual death certificates) of this study comprise those national death certificates in 1995 submitted for validation to the panel representing both medical and nosological expertise. As such, it is highly selected and represents, from the nosological point of view, the most inconsistently filled-in portion of Finnish death certificates. The routine validation procedure is essentially based on exploitation of the extra medical information, i.e. the case history, on the Finnish death certificate form. Altogether, 2813 (80.9%) out of 3478 certificates could be adjusted at the primary panel session; the rest required further clarification. The re-assignment of cause of death by the panel and the impact of panel adjustments on the national mortality statistics is assessed here by comparing the initial death certification and the finally registered underlying cause of death grouped into ICD-9 major categories with special reference to the subcategories of neoplasm, cardiovascular disease (HVD) and unnatural death. A statistically significant decline (p<0.0001) in deaths, both in the category of symptoms, signs and ill-defined conditions and in the pulmonary circulation disease subcategory of HVD with 37.6 and 35.1%, respectively, was observed. The decrease of 11.1% in the benign or NUD neoplasm subcategory and the increase of 8.6 and 7.0% in the categories of endocrine disease, and musculo-skeletal and connective tissue disease, respectively, are essential observations as to the quality of the cause of death register. The effect on the HVD major category was practically nil. At the HVD-subcategorial level, a decrease of 14.0% for diseases of the veins and lymphatics and other circulatory diseases and an increase of 3.5% for hypertensive diseases (HYP) were the two next most obvious alterations to the diseases of the pulmonary circulation, but were without statistical significance. For ischaemic heart disease and other subcategories, the effects were minor. The unnatural deaths as a whole increased in the final statistics with only 0.9%. In the study data, categorial changes ranged from the decrease of 75.2% for symptoms, signs and ill-defined conditions to the increase of 77.3% for endocrine diseases. In conclusion, the Finnish death certificate form, death certification practices and cause of death validation procedure seem to serve the coding of causes of death for mortality statistics appropriately. The results of the study form a relevant reference background to evaluation of epidemiological studies on mortality.     

Post-mortem cases involving amphetamine-based drugs in The Netherlands. Comparison with driving under the influence cases

In this study we reviewed the post-mortem cases in the years 1999-2004 that were presented at the Netherlands Forensic Institute. The concentrations of amphetamine-based drugs in femoral blood from cases of suspected unnatural death were compared with concentrations in whole blood from non-fatal cases of driving under the influence (DUI cases) and with literature. Furthermore, the combinations with other drugs and/or alcohol were investigated. Amphetamine-based drugs were present in 70 post-mortem cases and 467 DUI cases. The most detected amphetamine-based drug was MDMA, followed by amphetamine. The presence of MDA could usually be explained by metabolism of MDMA. Methamphetamine and MDEA were rarely present. Frequently, the amphetamine-based drugs were taken in combination with alcohol and/or other non-amphetamine-based drugs such as cocaine or cannabinoids. The 70 post-mortem cases were divided into 38 amphetamine-based drug caused (i.e. the amphetamine-based drug directly caused or contributed to the death) and 32 amphetamine-based drug related deaths (i.e. death was not directly caused by the amphetamine-based drug). In the latter category, other (poly)drug intoxications and death by violence or drowning were the most frequent causes of death. In 30 cases, MDMA caused death directly. The range in blood concentrations of MDMA in these cases was substantial, i.e. 0.41-84 mg/L with a median concentration of 3.7 mg/L (n=30). MDMA blood concentrations in the MDMA related deaths (n=20) and in the DUI cases (n=360) varied up to 3.7 and 4.0 mg/L, respectively. Seven victims died from the direct effects of amphetamine; the blood concentration of amphetamine ranged from 0.24 to 11.3 mg/L, with a median concentration of 1.7 mg/L (n=7). The median concentrations of amphetamine in the amphetamine related deaths (n=13) and the DUI cases (n=208) were much lower, i.e. 0.28 and 0.22 mg/L, respectively. Amphetamine blood concentrations up to 6.0 and 2.3 mg/L were seen in the drug related deaths and DUI cases, respectively. The most frequently encountered amphetamine-based drugs in the investigated deaths were MDMA and amphetamine. The majority of MDMA- and amphetamine-caused deaths, i.e. 90% of these deaths, occurred with blood concentrations above 1.5 and 0.80 mg/L, respectively. MDMA and amphetamine blood concentrations in drug related deaths and DUI cases, however, overlap the range of fatal concentrations. Therefore, MDMA or amphetamine concentrations should never be used alone to establish the cause of death.     

Post-mortem radiological examination in infants:: Evidence of child abuse?

We examined the value of post-mortem radiological examination of infants who were brought in for medico–legal autopsy. Twenty children between the age of 1 month and 15 months died under the picture of SIDS. No radiological or other signs of previous child abuse were seen in our autopsy material. A fatal case of child abuse with several metaphyseal fractures is reported. Some fractures were not visible on gross examination, but could be demonstrated by radiography and histology. In our material no association between SIDS and child abuse was found. In suspected cases of child abuse, particularly rib fractures and metaphyseal fractures should be sought. We recommend that post-mortem radiography is performed in such cases. If fractures are demonstrated, they should be verified by histologic examination.     

From law firm to stock exchange listed law practice: an examination of institutional and regulatory reform

This article examines the institutional reforms that, among other things, brought about the listing of two law practices on the Australian Stock Exchange. Using the framework for institutional change developed by Greenwood, Suddaby and Hinings, the article examines socio-economic changes that led to government regulatory reform. It examines the conflicting norms found in traditional professional practice with the institutions of corporate law and the stock exchange. After a thorough examination of the reforms and the two distinctive listed law practices, it then evaluates the reforms in terms of the profession, the administration of justice and economics.