Ethical issues in international biomedical research: an overview

Human subjects research has been the focus of numerous controversies over the years. The dilemma lies between the potential harm to individuals who participate in research and the knowledge to be gained from the research study that might benefit society. When research is conducted in developing countries by researchers and sponsors from the United States and other industrialized countries, differences in history, culture, politics, wealth, and power between the countries give rise to unique challenges. In this Article, the author identifies several ethical issues to be considered when research is conducted in developing countries and provides the legal and ethical framework for their resolution.     

Evaluation of ephedrine, pseudoephedrine and phenylpropanolamine concentrations in human urine samples and a comparison of the specificity of DRI amphetamines and Abuscreen online (KIMS) amphetamines screening immunoassays

The purpose of this study was to evaluate the ability of two amphetamine class screening reagents to exclude ephedrine (EPH), pseudoephedrine (PSEPH), and phenylpropanolamine (PPA) from falsely producing positive immunoassay screening results. The study also sought to characterize the prevalence and concentration distributions of EPH, PSEPH, and PPA in samples that produced positive amphetamine screening results. Approximately 27,400 randomly collected human urine samples from Navy and Marine Corps members were simultaneously screened for amphetamines using the DRI and Abuscreen online immunoassays at a cutoff concentration of 500 ng/mL. All samples that screened positive were confirmed for amphetamine (AMP), methamphetamine (MTH), 3,4-Methylenedioxyamphetamine (MDA), 3,4-Methylenedioxymethamphetamine (MDMA), EPH, PSEPH, and PPA by gas chromatography/mass spectrometry (GC/MS). The DRI AMP immunoassay identified 1,104 presumptive amphetamine positive samples, of which only 1.99% confirmed positive for the presence of AMP, MTH, MDA, or MDMA. In contrast, the online AMP reagent identified 317 presumptive amphetamine positives with a confirmation rate for AMP, MTH, MDA, or MDMA of 7.94%. The presence of EPH, PSEPH, or PPA was confirmed in 833 of the 1,104 samples that failed to confirm positive for AMP, MTH, MDA, or MDMA; all of the 833 samples contained PSEPH. When compared to the entire screened sample set, PSEPH was present in approximately 3%, EPH in 0.9%, and PPA in 0.8% of the samples. The results indicate that cross reactivities for EPH, PSEPH, and PPA are greater than reported by the manufacturer of these reagents. The distribution of concentrations indicates that very large concentrations of EPH, PSEPH, and PPA are common.     

Traumatic potential of colour marking cartridges (FX ammunition)

Colour marking cartridges as the FX ammunition (Simunition Europe, Brussels) are increasingly used by the police for realistic close range combat training. Conversion kits for service weapons of different manufacturers are available. The ballistic data of this ammunition is reported and experimentally verified. The risk of injury seems to be very low, if the recommended protective equipment is used. Small hematomas up to superficial lacerations are to be expected only in areas over a bony support. Shots to the unprotected eye will result in severe injuries.     

Tramadol (Ultram) concentrations in death investigation and impaired driving cases and their significance

We reviewed a series of 66 deaths in Washington State between 1995-2000 in which tramadol (Ultram and Ultracet, Ortho-McNeil) was detected in the decedent's blood, in order to assess the role tramadol was determined to have played. Additionally, we reviewed a series of 83 impaired driving cases in which tramadol was detected in order to establish a non-lethal blood tramadol concentration reference range. In both populations, tramadol was consistently found together with other analgesic, muscle relaxant, and CNS depressant drugs. Death was rarely attributable to tramadol alone. However, tramadol may be a significant contributor to lethal intoxication when taken in excess with other drugs, via the potential interaction with serotonergic antidepressant medications, as well as the potential for increased CNS depression. Although the incidence of tramadol detection has increased consistently over the last eight years, there is no evidence of a corresponding increase in the number of cases in which death was attributed solely to tramadol. Blood drug concentrations in many deaths exceeded the therapeutic serum range of 0.28-0.61 mg/L; however, the concentrations overlapped almost completely with the range identified in living subjects arrested for impaired driving. These findings suggest caution in the interpretation of blood tramadol concentrations outside of the recognized therapeutic range. It also suggests that the drug, even when used in moderate excess, is not a principle cause of death in suicidal or accidental deaths.     

Y-chromosome STR system, Y-PLEX 12, for forensic casework: development and validation

The Y-PLEX 12 system, developed for use in human identification, enables simultaneous amplification of eleven polymorphic short tandem repeat (STR) loci, namely DYS392, DYS390, DYS385 a/b, DYS393, DYS389I, DYS391, DYS389II, DYS 19, DYS439 and DYS438, residing on the Y chromosome and Amelogenin. Amelogenin provides results for gender identification and serves as internal control for PCR. The validation studies were performed according to the DNA Advisory Board's (DAB) Quality Assurance Standards. The minimal sensitivity of the Y-PLEX 12 system was 0.1 ng of male DNA. The mean stutter values ranged between 3.76-15.72%. A full male profile was observed in mixture samples containing 0.5 ng of male DNA and up to 400 ng of female DNA. Amelogenin did not adversely affect the amplification of Y-STRs in mixture samples containing male and female DNA. The primers for the Y-STR loci present in Y-PLEX 12 are specific for human DNA and some higher primates. None of the primate samples tested provided a complete profile at all 11 Y-STR loci amplified with the Y-PLEX 12 system. Y-PLEX 12 is a sensitive, valid, reliable, and robust multiplex system for forensic analysis, and it can be used in human forensic and male lineage identification cases.     

The forensic medical diagnosis of intoxication of alcohol surrogates by morphological findings

The pathomorphology of intoxication of alcohol surrogates is described. A high frequency rate of DIC-syndrome is shown for the condition. A majority of thrombi accumulates at places with the highest concentrations of toxic substances as well as at those places, through which poisoning substances are brought out of the body, i.e. in the liver (since toxic substances are introduced perorally) and kidneys. Thrombi were detected in all internals, including the brain, in lethal intoxication. The immediate toxic effect from methanol and from higher spirits can matter in the genesis of changes, including acute swelling and chromatolysis with subsequent cell death. Exclusively cerebral or coagulopathic-cerebral types of thanatogenesis were registered in studied case of intoxication.