Case-control study of paternal occupation and social class with risk of childhood central nervous system tumours in Great Britain, 1962-2006.

BACKGROUND: Paternal occupational exposures have been proposed as a risk factor for childhood central nervous system (CNS) tumours. This study investigates possible associations between paternal occupational exposure and childhood CNS tumours in Great Britain. METHODS: The National Registry of Childhood Tumours provided all cases of childhood CNS tumours born and diagnosed in Great Britain from 1962 to 2006. Controls without cancer were matched on sex, period of birth and birth registration sub-district. Fathers' occupations were assigned to one or more of 33 exposure groups. A measure of social class was also derived from father's occupation at the time of the child's birth. RESULTS: Of 11 119 cases of CNS tumours, 5 722 (51%) were astrocytomas or other gliomas, 2 286 (21%) were embryonal and 985 (9%) were ependymomas. There was an increased risk for CNS tumours overall with exposure to animals, odds ratio (OR) 1.40 (95% confidence intervals (CIs) 1.01, 1.94) and, after adjustment for occupational social class (OSC), with exposure to lead, OR 1.18 (1.01, 1.39). Exposure to metal-working oil mists was associated with reduced risk of CNS tumours, both before and after adjustment for OSC, OR 0.87 (0.75, 0.99).Risk of ependymomas was raised for exposure to solvents, OR 1.73 (1.02,2.92). For astrocytomas and other gliomas, risk was raised with high social contact, although this was only statistically significant before adjustment for OSC, OR 1.15 (1.01,1.31). Exposure to paints and metals appeared to reduce the risk of astrocytomas and embryonal tumours, respectively. However, as these results were the result of a number of statistical tests, it is possible they were generated by chance.Higher social class was a risk factor for all CNS tumours, OR 0.97 (0.95, 0.99). This was driven by increased risk for higher social classes within the major subtype astrocytoma, OR 0.95 (0.91, 0.98). CONCLUSION: Our results provide little evidence that paternal occupation is a significant risk factor for childhood CNS tumours, either overall or for specific subtypes. However, these analyses suggest that OSC of the father may be associated with risk of some childhood CNS cancers.

Case-control study of paternal occupation and childhood leukaemia in Great Britain, 1962-2006.

BACKGROUND: Paternal occupational exposures have been proposed as a risk factor for childhood leukaemia. This study investigates possible associations between paternal occupational exposure and childhood leukaemia in Great Britain. METHODS: The National Registry of Childhood Tumours provided all cases of childhood leukaemia born and diagnosed in Great Britain between 1962 and 2006. Controls were matched on sex, period of birth and birth registration subdistrict. Fathers' occupations were assigned to 1 or more of 33 exposure groups. Social class was derived from father's occupation at the time of the child's birth. RESULTS: A total of 16 764 cases of childhood leukaemia were ascertained. One exposure group, paternal social contact, was associated with total childhood leukaemia (odds ratio 1.14, 1.05-1.23); this association remained significant when adjusted for social class. The subtypes lymphoid leukaemia (LL) and acute myeloid leukaemia showed increased risk with paternal exposure to social contact before adjustment for social class. Risk of other leukaemias was significantly increased by exposure to electromagnetic fields, persisting after adjustment for social class. For total leukaemia, the risks for exposure to lead and exhaust fumes were significantly <1. Occupationally derived social class was associated with risk of LL, with the risk being increased in the higher social classes. CONCLUSION: Our results showed some support for a positive association between childhood leukaemia risk and paternal occupation involving social contact. Additionally, LL risk increased with higher paternal occupational social class.

Effects of centrally administered H2 antagonists in the behavioral despair test.

Injection of the histamine-2 (H2) receptor antagonist cimetidine into the lateral ventricles of mice produced a dose-related reduction in swimming in the behavioral despair test. This response can be attenuated by intracerebroventricular (ICV) injection of the histamine-1 (H1) receptor antagonist chlorpheniramine, or the H2 receptor agonist impromidine, given simultaneously with cimetidine. At doses which blocked cimetidine, neither chlorpheniramine nor impromidine alone had effects on swimming. A similar decrease in swimming behavior was also seen after ICV injections of the non-imidazole H2 antagonist, BMY 25,368. This effect of BMY 25,368 was also attenuated by chlorpheniramine and impromidine. These results suggest that H1 and H2 receptors in the brain may mediate opposing behavioral effects.

Unique behavioral effects of the NMDA antagonist, CPP, upon injection into the medial pre-frontal cortex of rats.

Injection of the specific N-methyl-D-aspartate (NMDA) antagonist, 3(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), into the frontal cortex of rats, induced hyperactivity characterized by unique episodic darting behavior. This behavioral profile contrasts sharply with the ataxia and hyperactivity seen after intracerebroventricular CPP and other NMDA antagonists.

Escapability and generalization: effect on 'behavioral despair'.

Two experiments were conducted to investigate (1) whether 'behavioral despair' was related to inescapability of the warm swim and (2) whether 'behavioral despair' would generalize to a shock escape task. Results indicated that rats exhibited 'behavioral despair' independent of the escapability of the warm swim and that the phenomenon did not generalize to a shock escape task. Implications for the validity of the behavioral despair model was discussed.

Chronic desipramine attenuates morphine analgesia.

Two experiments were conducted to explore the effects of chronic antidepressant treatment on endogenous opioid systems. In the first study, mice received desipramine for 21 days, a regimen which down-regulates beta-adrenergic receptors [13]. Subsequently, hotplate jump latencies were measured after acute saline, morphine or naloxone, to test for dynamic changes in endogenous opioid systems. Chronic desipramine treatment resulted in a significant attenuation of morphine analgesia, but had no effect on latencies of saline and naloxone treated mice. In the second experiment, naltrexone or propranolol were given with desipramine for 21 days, in an attempt to block the development of subsensitivity to morphine. Naltrexone had no effect on desipramine attenuation of morphine analgesia. Propranolol given with desipramine slightly lowered jump latencies of acute saline controls, resulting in a significant analgetic effect of morphine. These data suggest that attenuation of morphine analgesia by chronic desipramine treatment may be mediated by actions on noradrenergic systems, rather than direct effects on opioid receptors.

Effects of centrally administered H2 antagonists on motor activity.

Two structurally distinct H2 antagonists, cimetidine and BMY 25,368, were injected into the cerebral ventricles of mice. Both drugs produced reductions in locomotor activity and rotorod latencies. The effects of the H2 antagonists on locomotor activity were attenuated by the H2 agonist, impromidine, as well as by the H1 antagonist, chlorpheniramine. When given alone, chlorpheniramine had no effect on locomotor activity, while impromidine reduced locomotion. These data suggest that histaminergic receptors may mediate important actions on arousal and sedation mechanisms.

Hyperactivity induced by N-methyl-d-aspartate injections into nucleus accumbens: lack of evidence for mediation by dopaminergic neurons.

To test the hypothesis that the motor hyperactivity associated with intra-accumbens injections of N-methyl-d-aspartate (NMDA) results from stimulation (direct or indirect) of nucleus accumbens dopaminergic mechanisms, the behavioral effects of intra-accumbens and intraventricular NMDA were compared to those of the prototypic dopaminergic releasing agent, amphetamine, and the competitive NMDA receptor antagonist, 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP). Drugs were injected into the right lateral ventricle, or bilaterally into the nucleus accumbens of rats. Locomotor activity was monitored electronically and by direct observation for 40 min prior to, and 1 hour after, drug treatment. Intra-accumbens injections of NMDA (0.4, 1.2 and 2.0 micrograms/side) produced dose-related increases in distance traveled, but had no significant effect on movement time or vertical movements. The NMDA-induced increase in distance traveled was temporally correlated with convulsive wild running, but not with exploratory behavior, suggesting that this increase may have been secondary to seizure-like activity. Intra-accumbens injections of amphetamine (10, 20 and 40 micrograms) or CPP (0.1 microgram) produced dose-related increases in all three measures. By the intraventricular route, the effects of NMDA were similar to those of intra-accumbens administration, whereas intraventricularly administered d-amphetamine had no effect. The behavioral effects of intra-accumbens NMDA cannot be explained by an NMDA receptor-mediated facilitation of dopaminergic neurotransmission; rather, this type of facilitation may be associated with competitive NMDA receptor antagonism.

An automated, high-capacity method for measuring jumping latencies on a hot-plate.

A high-capacity automated apparatus for conducting analgetic screening in mice with an entirely objective endpoint is described. A thermostatically controlled hot-plate apparatus is interfaced with a minicomputer for recording jump latencies, which appear to reflect an affective component of pain. In a model experiment, morphine and naloxone were tested at four temperatures and at four times during the day. As expected, latencies were temperature-dependent, with no significant diurnal variation. The apparatus records latencies to both first and tenth jumps, providing a gross estimate of possible motor depressant effects. Morphine significantly increased latencies to first jump, but did not alter the time between first and tenth jumps, suggesting that motor depression did not occur.