Fatal outcome in a case of pontocerebellar hypoplasia type 2

Pontocerebellar hypoplasia (PCH) is a very rare congenital (autosomal recessive) condition with fetal onset. Only a few cases have been published on the basis of both clinical data (symptoms/neuroradiological imaging) and autopsy results. This paper reports on such a case involving a 1.5-year-old male infant. The child suffered from severe psychomotor delay, extrapyramidal dyskinesia and epileptic seizures, but did not exhibit signs of spinal muscular atrophy as related to PCH type 1. Magnetic resonance imaging (MRI) at the age of 6 months demonstrated olivo-pontine and bilateral cerebellar hypoplasia. The boy was unexpectedly found dead. Autopsy disclosed a severe aspiration of gastric contents as the final cause of death. The neuropathological examination confirmed PCH type 2 (according to Barth [Brain Dev., 15 (1993) 411-422]) with marked microcephaly and olivopontocerebellar hypoplasia. Histologically, decreased density of olivo-pontine neurons, reduction of granular and Purkinje's cell layers of the cerebellum, slight astroglial proliferation and fragmented appearance of the dentate nuclei were observed. The immunohistochemical expression pattern was determined using antibodies against glial fibrillary acidic protein, synaptophysin and neurofilament protein. Summarizing, typical features of PCH type 2 were present and proved by clinical course, MRI and autopsy. Despite severe symptoms due to a natural disease this rare neurogenetic entity can become of forensic interest, when sudden unexpected death occurs.     

Is embryo research and preimplantation genetic diagnosis ethical?

The legal position in the UK on embryo research and preimplantation genetic diagnosis (PGD) is outlined and contrasted with the position in other EU countries. The "gradualist" position of the UK on the moral status of the embryo is defended on the basis of an argument that precaution must be applied in proportion to the degree to which the embryo has developed to display components of agency, on the assumption that mortality is categorically binding and requires agents to be granted rights and that it cannot be known with certainty that the embryo is not an agent. The extent to which this argument, when combined with vicarious protections that the embryo should receive in order to protect the rights of other agents, limits embryo research and PGD, is discussed. It is concluded that the complexities that attend deliberation about the moral problems attending embryo research and PGD are such that the proper response to these problems is via the procedures of political democracy to achieve accountable answers rather than "correct" answers. This allows for a variety of judgements.     

Synthesis of 2,3- and 3,4-methylenedioxyphenylalkylamines and their regioisomeric differentiation by mass spectral analysis using GC-MS-MS

3,4-methylenedioxyamphetamine (MDA) derivatives are increasingly abused central nervous system stimulants with neurotoxic properties. In recent years a number of controlled substance analogs (designer drugs) with high structural variety reached the illegal market making their identification an arduous task. The underivatized compounds give very similar or even virtually identical electron impact mass spectra containing mainly intense C(n)H(2n+2)N(+) immonium ions. Using tandem mass spectrometry (MS-MS) the additional structural information contained in the collision induced dissoziation (CID) mass spectra of molecular ions using electron impact (EI) and especially chemical ionization (CI) allowed an unequivocal differentiation of 18 studied regioisomeric 1-(methylenedioxyphenyl)-2-propanamines and 1-(methylenedioxyphenyl)-2-butanamines.Further synthetic methods are presented for 1-(3,4-methylenedioxyphenyl)-N-propyl-2-butanamine, N-isopropyl-1-(3,4-methylenedioxyphenyl)-2-butanamine and four 1-(2, 3-methylenedioxyphenyl)-2-butanamines. N-alkylated 1-(3, 4-methylenedioxyphenyl)-2-butanamine compounds (e.g. MBDB) are also known to be abused psychoactive agents (entactogenes) without the sympatomimetic effects of the 3,4-methylenedioxyamphetamines.     

Report of the European Network of Forensic Science Institutes (ENSFI): formulation and testing of principles to evaluate STR multiplexes

This paper describes a collaborative exercise organised under the auspices of the European Network of Forensic Science Institutes (ENFSI). The purpose of this EU (European Union) funded group is to carry out research to enable STR loci to be compared between European laboratories, ultimately leading to the formation of a pan-European database. Accordingly, an exercise was designed to evaluate a prototype STR multiplex system manufactured by Applied Biosystems (ABD). Each laboratory was sent 12 samples to analyse along with a multiplex kit. Of specific interest was the definition of parameters to define the efficiency of the system. Stutter, split allelic peaks (differing by one base), pull-up, heterozygous balance and between locus balance were all objectively measured. Once the important parameters are defined it is possible to directly compare performances of different multiplexes and the different laboratories carrying out the tests. Since the multiplex used was a prototype system, this exercise cannot be regarded as a proficiency test.     

The incorporation of dyes into hair as a model for drug binding

The binding of charged substances from external aqueous media to hair has been investigated through the use of fluorescence microscopy. Eleven hair samples, reflecting various ethnic groups and cosmetic treatments, were tested. Rhodamine 6G, a cationic dye representative of drugs such as cocaine and opiates, showed incorporation throughout the hair of all samples except one. In contrast, fluorescein, an anionic dye representative of drugs such as THC carboxylic acid, was not readily incorporated. The incorporation of rhodamine 6G was faster for chemically 'straightened' and bleached African-American female hair than for untreated hair. Incorporation of rhodamine 6G followed a pH dependence, but an ionic strength dependence could not be established. These studies support three postulates: (1) electrostatic interactions explain the preferential binding of cationic drugs of abuse to hair; (2) the hair matrix, or the non-helical portion of hair, is accessible to external solutions and thus subject to contamination; and (3) cosmetic treatments may alter the helical portion of hair thereby increasing its accessibility to external contamination.     

On Correcting Biases in Self-Reports of Age at First Substance Use with Repeated Cross-Section Analysis

Household survey data on age at first use of alcohol, tobacco, marijuana,and hard drugs can be biased due to sample selection and inaccuraterecall. One potential concern is attrition, whereby individuals who getinvolved with substance use at an early age become increasingly less likelyto be surveyed in successive years. A comparison of data from the NationalHousehold Survey on Drug Abuse (NHSDA) with data from a longitudinal studysuggested that attrition might have caused substantially less bias thandid forward telescoping, the inflating of age at first useover time. The evidence of forward telescoping was particularly pronouncedwith respect to age at first use of alcohol. This paper presents a procedurefor correcting the distribution of age at first use for forward telescoping(but not attrition) by viewing a portion of the NHSDA data collected insuccessive years as constituting a cohort study. Results are presented fromapplying this procedure with NHSDA data collected from 1982 to 1995 forrespondents born 1968–1973. The findings suggest that preventionprograms need to be introduced at an earlier age than would be indicatedby uncorrected retrospective data. Other implications are alsohighlighted.