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Gamma-hydroxybutyrate (GHB) has been implicated in drug-facilitated sexual assault (DFSA). The interpretation of GHB levels in biological samples collected for evidence is complicated by the natural presence of this compound in the body, and by its extremely rapid elimination after ingestion. There is a lack of agreement regarding a suitable cut-off concentration, which can reliably separate endogenous concentrations in urine from those reflecting ingestion. We have developed a method for the analysis of low levels of GHB in urine and have used it to establish a reference range for normal females. The method uses liquid-liquid extraction, silyl-derivatization, and gas chromatographic-mass spectrometric analysis. The limit of detection was 0.1 mg/L, and the method was linear from 0.1 to 5.0 mg/L. Our analysis of 50 urine samples donated by normal women indicates an upper limit of normal for urinary GHB of 1.46 mg/L or 323 microg GHB/mmol of creatinine. We propose that a 5 mg/L cut-off for urine GHB concentration, or 1000 microg GHB/mmol creatinine, will separate endogenous GHB concentrations from those reflecting GHB ingestion in antemortem samples with greater than 99% confidence, providing that a specific assay method comparable with that we describe is used. We demonstrate that urinary GHB concentrations fall with age and that this can be corrected for by measurement of the GHB/creatinine ratio.

Polyadenylic-polyuridylic acid is a non-toxic double stranded complex of synthetic polyribonucleotides and a proved potent modulator of both humoral and cellular immune responses. The complex is also an inducer of interferon. Although results of direct determination of interferon in patients receiving the complex were negative,' in later studies we found an enhancement of interferon mediated protein kinase p67 K in mouse plasma and p72 K in human plasma in response to treatment with polyadenylic-polyuridylic acid.5 We have also reported that treatment of tumour bearing mice with the complex in association with cyclophosphamide results in a synergistic inhibition of tumour characterised by more retarded tumour growth, lower mortality, and a higher rate of tumour free survival than in mice treated with either agent alone. Furthermore, in these tumour bearing mice receiving such combined treatment there was a significant enhancement of natural killer (NK) cell activity.6 Recently we have studied in more detail the NK boosting effect of polyadenylic-polyuridylic acid in mice in parallel with an assay of an enzyme marker for the production and action of interferon-namely, 2-5 A synthetase. Enhanced NK cell activity accompanied increased activities of 2-5 A synthetase in mice treated with polyadenylic-polyuridylic acid.7 In patients an increase of NK cell activity as well as an increase of 2-5 A synthetase activity after one intravenous injection of 60 mg polyadenylic-polyuridylic acid was also observed (A G Hovanessian et al, paper in preparation). In view of these observations we hypothesise that interferon and NK cell activity probably play a part in the overall mechanism of action of polyadenylic-polyuridylic acid as an adjunct to surgery in breast cancer.Polyadenylic-polyuridylic acid appears to interact with many cell populations,8 so that its biological activity might therefore be exerted at different levels. Indeed, in patients 24 hours after a single intravenous injection of 30 mg of the complex we observed that the mean percentage of E rosette forming cells was significantly (p <0 001) higher than that found before the injection (60-8% v 51-0%), confirming our observation on T lymphocytes in mice.9The relevance of the biological effects to the therapeutic action so far observed remains to be determined. Reports suggest that the low incidence of ischaemic heart disease in Greenlandic Eskimos is related to the effect of a diet rich in eicosapentaenoic acid on platelet reactivity and plasma lipid concentrations. A double blind randomised investigation was therefore conducted of the effects on blood viscosity of dietary supplementation with an oil rich in this fatty acid (1-8 g/day, given as fish oil) and an eicosapentaenoic acid poor oil (as corn/olive oil)

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The detection of markers for illicit opiate misuse is important both in the management of substance misuse and in the postmortem identification of illicit opiate use. In addition to 6-monoacetylmorphine and acetyl codeine, other markers, such as papaverine, noscapine, and their metabolites, have been proposed as markers of illicit opiate use. Urine samples (362) from individuals attending substance misuse services and 26 postmortem cases were analyzed for meconin, a noscapine metabolite by gas chromatography-mass spectrometry. Three hundred of the substance misuse service samples and 14 of the postmortem samples had morphine present as the major opiate. Meconin was detected in 284 (94.7%) of these substance misuse samples and 11 (78%) of the postmortem samples. There was a specificity of 100% in both groups. In the 62 substance misuse cases where morphine was not the major opiate detected and four separate cases in which medicinal diamorphine was known to have been administered, meconin was not detected. The use of meconin as a useful adjunct in detecting illicit opiate use is recommended.