Involvement of Amphetamines in Sudden and Unexpected Death

Abstract:  In the present study, the effects of amphetamine-class drugs were examined in cases reported to the Victorian coroner from 2001 to 2005 to determine if death can occur from the use of amphetamine-class drugs alone. A total of 169 cases were reviewed where a forensic autopsy detected amphetamine(s) in the blood. Pathology, toxicology, and police reports were analyzed in all cases to ascertain the involvement of amphetamine-class drugs in these deaths. In Victoria, methamphetamine (MA) is the principal abused amphetamine-class followed by methylenedioxymethamphetamine (MDMA). There were six cases in which a cerebral hemorrhage caused death and three cases in which serotonin syndrome was established as being caused by the interaction of MDMA and moclobemide. There were 19 cases in which long-term use of amphetamines was associated with heart disease. There were three cases where amphetamine-class drugs alone were regarded as the cause of death, of which two cases exhibited high levels of MDMA and lesser amounts of MA and/or amphetamine. There were no cases in which significant natural disease was absent and death was regarded as caused by the use of MA. There was no correlation between blood concentration of drug and outcome.     

Enhancing Smallholder Access to Agricultural Machinery Services: Lessons from Bangladesh

Resource poor smallholders in developing countries often lack access to capital goods such as farm machinery. Enabling adequate access through machinery services can thereby significantly contribute to food security and farm incomes. At the core of the service provision model is the lead farmer, who makes the initial investment in agricultural machinery, and provides services to others on a fee-for-service basis. Profiling the lead farmers can thereby provide important lessons and scaling implications. The present paper provides a case study of Bangladesh, using primary data to characterise the lead farmers. General education, credit availability and risk taking attitude play significant roles in whether or not a farm household will be a lead farmer in Bangladesh.     

Renewal of local government in Scandinavia: Effects for local politicians

During the last decade, numerous local government reforms influenced by New Public Management (NPM) ideology have taken place throughout Scandinavia. Based on case studies in three Scandinavian municipalities, the article discusses the effects of introducing strategic political management on the role of councillors. We observe a conflict between NPM‐inspired management ideas and a deeply institutionalised, traditional view of councillors as representatives of the citizens, advocating peoples’ interest, defining needs, setting priorities and controlling implementation. Across national and local contexts, councillors find that the reforms challenge their traditional role and have strengthened administrative influence. Historical institutionalism seems to be a fruitful concept to understand resistance towards taking on new role models.     

Post-mortem toxicology

Studies examining post-mortem processes are difficult to conduct since changes will have already occurred when the body arrives at the mortuary. While control of collection site for blood can minimize changes in concentration it is very difficult to conduct experiments in humans aimed at understanding the mechanisms and determining the extent of such changes. The use of appropriate animal models can be useful in this regard providing the species and conditions are carefully chosen. Pharmacokinetic studies in humans are also very useful for understanding the changes in drug concentration with time in blood (and other fluids) and also for improving our understanding of drug effects. Unfortunately, doses of illicit drugs that can be given are relatively low to guarantee safety hence extrapolations are made to real life situations. Individual case studies can be useful to describe an unusual or particularly interesting circumstances but little useful information can be obtained when trying to ascertain the role of competing factors, e.g. role of individual drugs when multiple drugs are present, varying toxicity between route of administration, and the role of age or natural disease when drugs are also present. Epidemiological approaches by reviewing large numbers of related cases are the most powerful tool to obtain this information. All of these studies need to operate under the ethical and legal framework appropriate for a jurisdiction. This paper discusses the relative merits of scientific approaches to research in post-mortem toxicology and provides guidance on the most appropriate techniques for future studies.     

Quecksilbereintr?ge in oberirdische Gew?sser durch Kohlekraftwerke

Gegen die Errichtung von Kohlekraftwerken, selbst wenn es sich um Kraftwerkserneuerungen und -modernisierungen handelt, regt sich im Hinblick auf die CO₂-Emissionen vor allem bei Umweltschutzvereinigungen erheblicher Widerstand. Da der Vorhabentr?ger bei Vorliegen der Genehmigungsvoraussetzungen des §6 BImSchG einen gebundenen Anspruch auf Genehmigungserteilung hat, den Genehmigungsbeh?rden mithin kein Ermessen einger?umt ist, auf der anderen Seite die Vermeidung von CO₂-Emissionen auch nicht zu den Genehmigungsvoraussetzungen für Kohlekraftwerke z?hlt, konzentrieren sich aktuell die rechtlichen Einw?nde im Wesentlichen auf das Bauplanungsrecht, entgegenstehende Zielfestlegungen in Raumordnungspl?nen und die für den Kraftwerksbetrieb (Einleitung von Abwasser und Kühlwasser) zus?tzlich erforderliche wasserrechtliche Erlaubnis. Letztere steht im Ermessen der Wasserbeh?rde und stellt damit eine Art “Achillesferse” der aktuellen Kraftwerksplanungen dar. In jüngerer Zeit wird insbesondere das Thema Quecksilbereintr?ge in oberirdische Gew?sser vermehrt diskutiert. Der Betrieb von Kohlekraftwerken kann auf zwei verschiedenen Wegen zu solchen Quecksilbereintr?gen führen: Bei der Verbrennung von Kohle entsteht gasf?rmiges Quecksilber, das durch die Rauchgasw?sche (REA) gebunden wird und über das Abwasser als Punktquelle in ein oberirdisches Gew?sser eingeleitet wird (sog. Wasserpfad). Daneben wird gasf?rmiges Quecksilber auch über den Schornstein freigesetzt und kann durch Absinken die in der Umgebung gelegenen oberirdischen Gew?sser verschmutzen (sog. Luftpfad bzw. atmosph?rische Deposition auf die Gew?sseroberfl?che). Beide Verschmutzungswege k?nnen durch technische M?glichkeiten zwar reduziert, derzeit aber nicht auf Null reduziert werden. Teilweise wird daher schon von einem Errichtungsverbot für neue Kohlekraftwerke gesprochen. Im Folgenden soll der Stichhaltigkeit dieser Auffassung n?her nachgegangen werden.     

The time-dependant post-mortem redistribution of antipsychotic drugs

The post mortem redistribution of ten commonly prescribed antipsychotic drugs (APs) was investigated. Femoral blood was collected from 273 cases at admission to mortuary (AD) and at post-mortem (PM). The PM samples were collected at various times up to nine days after admission and the sample pairs analysed using LC-MS/MS. The drugs included in this study were 9OH-risperidone (paliperidone), amisulpride, chlorpromazine, clozapine, haloperidol, olanzapine, promethazine, quetiapine, risperidone, and zuclopenthixol. Haloperidol, quetiapine and risperidone showed minimal changes between AD and PM specimens, whereas the majority of drugs showed significant changes between the sample pairs collected at different time points post mortem (p<0.01) in addition to an average concentration change greater than the uncertainty of measurement of the applied method. Average increases in blood concentrations after admission to the mortuary ranged up to 112% (chlorpromazine and olanzapine) but also decreases up to -43% (9OH-risperidone) were seen. There were large standard deviations between sample pairs and substantial day-to-day unpredictable changes that highlight the difficulty in the interpretation of drug concentrations post-mortem. Based on the presented data, we recommend that specimens for toxicological analysis should to be taken as soon as possible after admission of a deceased person to the mortuary in order to minimise the effects of the PM interval on the drug concentration in blood.     

Identification of 2-hydroxymethyl-olanzapine as a novel degradation product of olanzapine

Olanzapine (OLZ) is amongst the most commonly prescribed antipsychotic drugs and is associated with substantial instability. The aim of this study was to investigate the instability of OLZ and to identify the degradants formed from its breakdown. Three experiments were conducted to monitor the degradation of OLZ and the formation of degradants in blood (1), water (2), and post-extraction at 4 °C (3). All three sample sets were analysed in duplicate and repeated in the absence (A) and presence (B) of 0.25% ascorbic acid. One degradant was identified in sample sets 2A and 3A with m/z 329 and confirmed as 2-hydroxymethyl-OLZ (2-OH-OLZ) using LC-MS techniques. The addition of 0.25% ascorbic acid slowed the degradation of OLZ down in all three experiments and inhibited the formation of 2-OH-OLZ in sample sets 2A and 3A. To investigate the influence of oxygen on the degradation of OLZ and the formation of 2-OH-OLZ in water, an additional experiment (4) was conducted. Sample sets were prepared containing different vortexing or sonication steps in order to alter the oxygen content in the samples. Statistical analysis confirmed that degradation increased significantly following vortexing for 1 min while sonication did not affect the rate of degradation of OLZ further suggesting the involvement of oxygen in the degradative processes. 2-OH-OLZ was only identified as a degradant of OLZ in aqueous solutions. It also degrades over time but its product is currently unknown and is under investigation.     

Sudden death during prolonged religious fasting

Sickle cell trait (SCT) is estimated to occur in 6% to 10% of Africans, and the United Kingdom (UK) prevalence rate has been estimated at 3.2%. Although sudden death in sickle cell disease is well known, its occurrence in SCT is rare and requires extremes of physiological stress. We present a case of a 29-year-old black woman who died suddenly during a period of religious fasting. Her medical history was unremarkable, and there was no family history of sickle cell disease. At postmortem, she was found to be dehydrated, and macroscopically, the main abnormal findings were congested lungs and a small spleen. Histological examination revealed extensive vascular congestion with red blood cell sickling in both lungs, the liver, and the spleen. Electrophoresis on a postmortem blood sample confirmed the clinical suspicion that the patient was a carrier of SCT. The case highlights a novel scenario of SCT associated sudden death. We discuss the potential pathophysiological mechanisms that may have led to the patient's demise. We also remind pathologists to consider this diagnosis as potentially contributing to the cause of death in apparently fit young people of ethnic origin during episodes of physiological stress.