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Biomedical subjects

A R Forrest

Publications and source records attributed to A R Forrest.

At least 19 recordsLinked to original sources

Deaths associated with MBDB misuse.

The use of phenethylamines in the dance scene is now well established. Apart from amphetamine, the commonest phenethylamine encountered in clinical and forensic settings is 3,4-methylenedioxymethamphetamine (MDMA) commonly known as ecstasy. Other phenethylamines, which have similar effects are encountered, such as 3,4-methylenedioxyethylamphetamine (MDEA) and their use has resulted in death. We report two deaths associated with another less commonly encountered member of the group, N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine (MBDB), also known as Methyl-J and Eden.

3,4-Methylenedioxyamphetamine↗

Methadone deaths: a toxicological analysis.

AIMS: To perform a toxicological analysis of deaths involving methadone and to determine the fatal concentration of methadone in such deaths. METHODS: Deaths in which methadone was mentioned in the cause of death were identified. Deaths were divided into those associated with methadone only and deaths in which the cause of death was a combination of methadone and other drugs. Toxicological findings in these deaths were analysed and compared with previously published data. RESULTS: One hundred and eleven cases were analysed. In 55 cases, methadone poisoning was given as the sole cause of death. Fifty victims were adults, age range 17-51 years (median, 23), with five victims under 14 years of age. The mean methadone concentration in the adult deaths was 584 micrograms/litre (median, 435; range, 84-2700). In 56 cases, age range 15-49 years, (median, 28), death was ascribed to a combination of methadone and other drugs. The mean methadone concentration in these deaths was 576 micrograms/litre (median, 294; range, 49-2440). In 26 cases, multiple site sampling was performed. This revealed that there could be a 100% discrepancy between methadone concentrations, and other drugs, in samples collected in different sites in the same body. CONCLUSIONS: There is an overlap between quoted therapeutic methadone concentrations and methadone concentrations seen in fatalities. However, those dying from methadone poisoning might not be the same as those in a methadone programme. A degree of caution must be exercised in determining a fatal concentration because of the phenomenon of postmortem redistribution. Pathologists and toxicologists need to examine all the available postmortem findings in identifying the cause of death.

Adolescent↗

Multiple splicing variants of cdc25B regulate G2/M progression.

Progression through G2 phase into mitosis is regulated by the activation of the mitotic cyclin/cdk complexes, which are in turn activated cdc25B and cdc25C phosphatases. Here we report that alternate splicing produces at least five variants of cdc25B, although only cdc25B2 and cdc25B3 are detectable as proteins. Analysis of these two variants shows that cdc25B2 is expressed at lower levels relative to cdc25B3 in all cell lines tested, and the expression of both increased markedly during G2 and mitosis. Overexpression of the catalytically inactive version of either cdc25B variant produced a G2 arrest implicating both in regulating G2/M progression.

Cell Cycle Proteins↗

A method for the confirmation and identification of drugs of misuse in urine using solid phase extraction and gas-liquid chromatography with mass spectrometry.

A method is described for the confirmation/identification of a range of commonly misused drugs in urine samples. The method has been used for two years without problems for a range of purposes including hospital/clinic drugs of misuse screening and for toxicology in coroner's cases. Urine samples which have given a positive result on immunochemical screening for a particular drug group or groups (for example, opiates) can be processed with identification of the drugs present using a single procedure. Bond ElutCertify columns are used for the extraction of drugs from the samples followed by propionylation and gas chromatography with mass selective detection.

Codeine↗

Ethical aspects of workplace urine screening for drug abuse.

OBJECTIVE: To review the ethical and legal implications of the involvement of medical practitioners in workplace screening for drug misuse. CONCLUSIONS: Workplace screening for drugs of abuse raises many ethical issues. If screening is considered as being part of medical practice with the involvement of occupational health physicians, as suggested by the Faculty of Occupational Medicine, then the ethical requirements of a normal medical consultation are fully applicable. The employee's full and informed consent to the process must be obtained and the employee should have an unfettered right of access to all the relevant records and to the urine sample he/she has provided in the event that he/she wishes to challenge the opinion expressed by the physician. If the process is not part of medical practice then employees should have the same rights as they would have if required to provide intimate body samples in the course of a criminal investigation, given the potentially serious consequences of an erroneous positive finding for their livelihood.

Ethics, Medical↗

Pathology of deaths associated with "ecstasy" and "eve" misuse.

AIMS: To study the postmortem pathology associated with ring substituted amphetamine (amphetamine derivatives) misuse. METHODS: The postmortem findings in deaths associated with the ring substituted amphetamines 3,4-methylenedioxymethyl-amphetamine (MDMA, ecstasy) and 3,4-methylenedioxyethylamphetamine (MDEA, eve) were studied in seven young white men aged between 20 and 25 years. RESULTS: Striking changes were identified in the liver, which varied from foci of individual cell necrosis to centrilobular necrosis. In one case there was massive hepatic necrosis. Changes consistent with catecholamine induced myocardial damage were seen in five cases. In the brain perivascular haemorrhagic and hypoxic changes were identified in four cases. Overall, the changes in four cases were the same as those reported in heart stroke, although only two cases had a documented history of hyperthermia. Of these four cases, all had changes in their liver, three had changes in their brains, and three in their heart. Of the other three cases, one man died of fulminant liver failure, one of water intoxication and one probably from a cardiac arrhythmia associated with myocardial fibrosis. CONCLUSIONS: These data suggest that there is more than one mechanism of damage in ring substituted amphetamine misuse, injury being caused by hyperthermia in some cases, but with ring substituted amphetamines also possibly having a toxic effect on the liver and other organs in the absence of hyperthermia.

3,4-Methylenedioxyamphetamine↗

Randomized comparison of oral and intravenous fluid regimens after gallbladder surgery.

Numerous studies of post-operative fluid status have utilized sophisticated measurements of electrolyte distribution and fluid shift without relating results to clinical practice. The aim of this prospective randomized study was to investigate the response of patients undergoing abdominal surgery of moderate severity to conservative post-operative fluid administration. Forty-five patients undergoing open cholecystectomy were randomized to receive 2.51 of fluid (1 l normal saline and 1.51 5% dextrose), 1 l of normal saline, or free oral fluids (groups 1, 2, 3, respectively). Serum and urine osmolality and electrolytes were measured pre-operatively and at 24 and 48 h post-operatively. Patients remained in the study irrespective of the urine output. Plasma electrolytes and osmolality remained within normal limits in all three groups despite significant changes in urine electrolyte and osmolality in groups 2 and 3. This confirms that a conservative approach to fluid administration has no detrimental effect on hydration in fit patients with uncomplicated surgery.

Adult↗

Deaths from methadone use.

All deaths from methadone poisoning occurring between 1991 and 1994 in Sheffield, UK, were studied. There were 18 deaths: 17 adults (14 men, 3 women), age range of 17-45 years (mean 29), and a 3-year-old female child. Blood methadone concentrations ranged from 200 microg/l to 1863 microg/l (mean 560 microg/l). Multiple drug use was common. Ten people had been prescribed methadone, whilst eight had obtained their methadone illegally. Only 3 people were long-term methadone users. The others were probably first time users or recently new to methadone programmes. Two, including the child, were apparently forced to drink methadone. Methadone is a potent drug with serious side-effects. Naïve users are particularly at risk of death. Toxic effects may be delayed, allowing large amounts to be ingested, giving both user and medical practitioner a false sense of security. Caution should be exercised when prescribing to new patients in methadone programmes. Controlled administration of methadone may prevent overdosage and ingestion by those to whom it is not prescribed.

Journal Article↗

A fatal overdose with 3,4-methylenedioxyamphetamine derivatives.

Methylenedioxymethylamphetamine (MDMA or 'Ecstasy') is the best known of the 3,4-methylenedioxy ring-substituted amphetamines. Reports of serious adverse reactions and fatalities associated with its use emphasise hyperpyrexia, profuse sweating and subsequent rhabdomyolysis, although cardiac deaths and fatal accidents whilst intoxicated are also prominent. Other 3,4-methylenedioxy ring-substituted amphetamines are also available in the illicit market place and may have different spectra of activity. We report here a case of fatal ingestion of a variety of drugs of this group.

3,4-Methylenedioxyamphetamine↗