[Possible influence of psychotropic drugs detected in blood when determining the cause of death in medicolegal autopsy cases in the Tokyo Medical Examiner's Office].

We reviewed the records of 118 medicolegal autopsy cases, in which psychotropic drugs were detected in blood, in the Tokyo Medical Examiner's Office in 1997, to explore how the drug levels were considered in determining the cause of death. Names and doses of the drugs were clear in 70 of 118 cases, and in most cases of the 70 cases, multiple drugs (up to 13 drugs) were prescribed to a person. It was also evident that 75 of the 118 cases had demonstrated psychosis for several months to 38 years prior to death. No information concerning prescriptions or history of psychosis could be obtained in the other cases. The causes of death in these 118 cases were as follows: deaths from specific diseases, 30 cases (25.4%); deaths from extrinsic factors excluding drug intoxication, 22 cases (18.6%); suicide related to drug intoxication, 31 cases (26.3%); deaths from extrinsic factors related to drug intoxication suggestive of suicide, but not confirmed, 19 cases (16.1%); non-suicide, including probable drug intoxication, 13 cases (11.0%); and deaths from malignant syndrome, 3 cases (2.5%). There were cases diagnosed as death from specific diseases based on morphological findings, though drug concentrations in blood were at a toxic or even lethal level. In some cases, drug intoxication was suspected, but drug levels in their blood were at a therapeutic level and there were no identifiable morphological changes directly associated with deaths, resulting in a cause of death other than drug intoxication being indicated. Thus, drug levels detected in the cadaver's blood are not always useful for determining the cause of death. This might be due to poor information on interactions between drugs (including alcohol), pathological changes or genetic variability of drug metabolism and excretion, and so on. Thus, further studies of these aspects are needed in order to make information on drugs detected in the cadaver more useful for determination of cause of death.

Estimation of postmortem interval from hypoxic inducible levels of vascular endothelial growth factor.

Estimation of the postmortem interval (PMI) is one of the most important tasks in forensic medicine. Five autopsy organ tissues such as brain, lungs, heart, liver, and kidneys were taken at the time of forensic autopsy from 19 known PMI cases with a range of postmortem intervals ranging from 1 to 120 h (the mean was 25.81 h), and the time-course of vascular endothelial growth factor (VEGF) expression was measured. The human hepatoma-derived Hep 3B cell line was used as a control. The levels of VEGF increased linearly with the PMI up to 20 h in lung (r = 0.95 and in kidney (r = 0.89), and up to 15 h PMI in liver (r = 0.88). The VEGF levels fell after 24 h PMI, and then remained stable. In brain, the levels of VEGF started to increase after 24 h PMI and increased linearly with PMI up to 40 h in brain (r = 0.94) and then begin to fall. In heart, there was no clear correlation between the PMI and VEGF level. Some variations occurred in selected cases, such as the infant and asphyxial deaths. In conclusion, measurement of hypoxia-inducible levels of VEGF in various body organs appears to be a useful method of estimating the PMI up to 24 h in forensic medicine and pathophysiology. This method is also probably applicable in ischaemia in clinical and basic medicine.

Growth hormone binding protein, insulin-like growth factor-I and short stature in two pygmy populations from the Philippines.

The molecular basis and biochemical mediators of genetic growth propensity and adult height achievement in the general population are largely unknown. Pygmies represent one extreme of the height spectrum that may provide important clues regarding this issue. Previous studies in pygmies from Africa and Papua-New Guinea have shown decreased serum levels of growth hormone binding protein (GHBP), the circulating ectodomain of the growth hormone receptor (GHR). By inference, a similar limitation in tissue GHR expression has been assumed to be responsible for the partial growth hormone (GH) resistance observed in African pygmies. It is not clear how generalizable this concept is to other populations. To address this question, we studied two pygmy populations from the Philippines (Aeta and Mamanwa people) that are unrelated to the African pygmies. Serum GHBP and IGF-I levels were significantly decreased in both pygmy populations, compared to normal-statured Philippino controls. The results, together with previous observations in African and New Guinean pygmies, indicate that short stature is associated with low serum GHBP levels in pygmy populations of diverse origins and in different parts of the world. This strengthens the tentative postulate that the GHBP/GHR system plays an important role in the genetic and perhaps nutritional determination of adult stature in humans. Molecular genetic studies of the GHR gene in various pygmy populations may shed further light on the mystery of pygmy short stature.