Chemoprevention of spontaneous tumorigenesis in nullizygous p53- deficient mice by dehydroepiandrosterone and its analog 16alpha-fluoro- 5-androsten-17-one

Transgenic mice with both alleles of the p53 tumor suppressor gene product 'knocked out' by gene targeting are susceptible to early development of tumors, chiefly lymphomas and sarcomas. Compared with the control group, administration of dehydroepiandrosterone (DHEA) at 0.3% of the diet to male p53-deficient mice extended their lifespan by delaying death due to neoplasms (from 105 to 166 days on study, P = 0.002), primarily by suppressing lymphoblastic lymphoma (from 45 to 6% of neoplastic deaths, P = 0.010). Treatment with a synthetic DHEA analog, 16alpha-fluoro-5-androsten-17-one (compound 8354), at 0.15% of the diet also increased lifespan, to 140 days for mice that developed tumors (P = 0.037). The effects of these steroids on lifespan and tumor development did not appear to be strongly related to inhibition of food consumption and weight gain, in that a group pair-fed with control diet to the reduced food consumption of the DHEA-treated group developed and died of the same types of neoplasms at the same rate as the controls fed ad libitum. The chemopreventive effect of these steroids has been proposed to be due to suppression of DNA synthesis by inhibition of glucose 6-phosphate dehydrogenase, the rate-limiting enzyme of the pentose phosphate pathway. Although DHEA and its analog are strong non- competitive inhibitors of this enzyme in vitro, treatment with DHEA did not deplete cellular nucleotide pools in the liver, as would have been predicted. The chemopreventive effect of DHEA in this model may be due to steroid-induced thymic atrophy and suppression of T cell lymphoma, permitting these mice to survive long enough to develop tumors with longer latency.      

Child Behaviour Checklist classification of behaviour disorder

Objective : The aim of this study was to determine the applicability of the published clinical cut-off scores of the Child Behaviour Checklist (CBCL) for the classification of behaviour disorders.
Methodology : Child Behaviour Checklists were obtained for 1342 subjects newly referred to the six major mental health centres in Melbourne. The normative community sample of 1002 7-, 12- and 15-year-olds was drawn from a school-based asthma prevalence study.
Results : The mean total problem T-score for the children referred to mental health centres was 67 and was above the clinical range for all age groups. Using referral to psychiatric services as the gold standard, the sensitivity and specificity of the CBCL using a cut-off of ≥ 60, was 77.4 and 83.2%, respectively. This compares favourably with the sensitivity of 68% and specificity of 82% for the American sample. Using a cut-off score of ≥ 63, the sensitivity was 70.5% and the specificity was 88.6%. The referred and community samples differed with respect to socio-economic status, family structure and mothers' level of education. Fifty-two per cent of the clinically referred children lived with both parents, compared with 89% of the community sample.
Conclusions : While there are some limitations to this study in terms of both the clinic and community sample, support is provided for the usefulness and applicability of the recommended CBCL cut-off scores in an Australian population.     

Cocaine use in pregnancy in Amsterdam

To study the effects of cocaine use in pregnancy in Amsterdam, clinical data on cocaine-using pregnant women ( n = 21) and their offspring ( n = 23) were obtained retrospectively (1987–1994) at the Academic Medical Center, Amsterdam. Infants exposed to cocaine had a median gestational age of 39 weeks and a median birth weight of 3090 g. There were six preterm infants, two small-for-gestational-age infants and five infants with a small head circumference. Three infants had a congenital malformation. One infant (Potter's syndrome) died shortly before birth. One infant had congenital syphilis, four had intracerebral abnormalities on ultrasound and four had abnormal neurologic symptoms in the neonatal period. One infant died after 21 days of life. At follow-up four infants showed abnormal development. In 12 of the 23 infants (52%), one or more possible effects of cocaine were found.     

Substance use in pregnancy: do we care?

Two cohorts of substance-using women were compared retrospectively. From 1969 to 1979 a very high perinatal mortality rate (PMR 9.8%) was found among 92 polydrug-using women (1 twin excluded). Preterm delivery occurred in 25% of all pregnancies and in 30% of the children birth weight was below the 10th percentile. Nineteen women using heroin only had a worse fetal outcome (PMR 32%, preterm delivery in 47%, birth weight < 10th percentile in 42%). These results led to a strict surveillance system. In the period 1980–1989, 240 women (4 twins excluded) delivered after 16 weeks. Total fetal loss decreased to 2.1% and PMR to 0.4%, which was similar to results in controls. However, 22% of the women still delivered before 37 weeks and 27% delivered a child < 10th percentile. Methadone-using women were able to halve their dosage during pregnancy and 16 were detoxified. Multivariate analysis within the substance users of the second cohort showed that the neonatal abstinence syndrome, but not the (registered) amount of opiates used, was related to a lower birth weight. Not coping with prenatal care was related to a shorter pregnancy length. Multivariate analysis, including the controls, showed a significant relation of birth weight (345 g lower) with substance use. Also, head circumference was 0.8 cm smaller. Length of pregnancy however was related to smoking. This study shows that it is difficult to make substance users attend prenatal care, but also that women coping with prenatal care reduce substance intake. Opiate use might be responsible for lower birth weight, although not in a clear dose–response relationship, whereas lifestyle, as represented by not coping with prenatal care and the quantity of cigarette smoking, shortens the length of pregnancy.