Trihalomethanes in public water supplies and risk of stillbirth

BACKGROUND: The chlorine used to disinfect public drinking water supplies reacts with naturally occurring organic matter to form a number of chemical byproducts. Recent studies have implicated exposure to chlorination byproducts in drinking water, trihalomethanes (THMs), in particular, with intrauterine death. METHODS: We conducted a population-based case-control study in Nova Scotia and Eastern Ontario, Canada, to examine the effect of exposure to THMs on stillbirth risk. Cases were women who had a stillborn infant, and controls were a random sample of women with live births. Subjects were interviewed, and women with a public water source provided a residential water sample. Risks were examined according to residential THM level in tap water and to a total exposure metric incorporating tap water ingestion, showering, and bathing. RESULTS: We enrolled 112 stillbirth cases and 398 live birth controls. Women with a residential total THM level of 80 or more microg/L had twice the risk of a stillbirth compared with women with no exposure to THMs (adjusted odds ratio [OR] = 2.2; 95% confidence interval [CI] = 1.1-4.4). The highest quintile of total THM exposure using the total exposure metric was associated with an adjusted odds ratio of 2.4 (95% CI = 1.2-4.6) compared with women not exposed to THMs. Similar results were seen for specific THM compounds. A monotonic dose-response relationship was not seen. CONCLUSIONS: Our results provide evidence for an increased risk of stillbirth associated with exposure to chlorination byproducts through ingestion and showering and bathing, although there was not a clear dose-response relationship.     

Hepatocellular carcinoma: Updates in primary prevention

Hepatocellular carcinoma is a significant cause of mortality worldwide and a growing problem in the United States. Treatment options are often limited, and median survival is less than 1 year. Thus, prevention may provide the best opportunity to alter the natural history of this disease. Primary prevention is best exemplified by the successes of such public health measures as universal hepatitis B vaccination. Such antiviral therapies as interferon may also have a role. Lessons can be learned from complementary and alternative medicine. Nevertheless, more work is needed in understanding hepatocarcinogenesis and in developing models to assess potential chemopreventive agents.     

Effects of NMDA glutamate receptor antagonist drugs on the volitional consumption of ethanol by a genetic drinking rat

The ability of drugs that reduce NMDA receptor activity on the volitional consumption of ethanol in the genetic drinking rat, mHEP line, was investigated. After the consumption of ethanol solutions and water by each male or female mHEP rat had stabilized on its preferred concentration, different doses of LY 274614, a competitive NMDA antagonist, MK 801, a non-competitive NMDA antagonist, (+)-HA-966 or ACPC (1-aminocyclopropane-1-carboxylic acid), antagonists of the glycine site were administered daily for three days. The dose of 3.0 mg/kg i.p. LY 274614 reduced the consumption of ethanol by 64% compared to the pre-treatment baseline, while 0.3 mg/kg of MK 801 reduced consumption by 44%, 20 mg/kg (+)-HA-966 reduced consumption by 47% and 300 mg/kg of ACPC reduced consumption by 30%. These doses of LY 274614 and MK 801 reduced the ability of Sprague-Dawley rats to walk on a rotorod. Effects of these drugs on food intake were small except for the 20 mg/kg dose of (+)-HA-966. Therefore, the drugs did not have an anti-caloric effect and manipulations of the glutamatergic system through NMDA receptors may modify the consumption of ethanol. This interaction should be explored further for its therapeutic potential and to better understand the control by central neuronal systems of the consumption of ethanol.     

Is variant Creutzfeldt-Jakob disease in young children misdiagnosed as Alpers' syndrome? An analysis of a national surveillance study

BACKGROUND: There has been concern that children with variant Creutzfeldt-Jakob disease (vCJD) might be misdiagnosed as cases of Alpers' syndrome, as a spongiform degeneration of the brain is seen in both conditions. OBJECTIVE: To report a national prospective surveillance study of children with progressive intellectual and neurological deterioration, designed to detect any children in the United Kingdom with vCJD, to see whether this misdiagnosis is occurring. METHODS: A monthly surveillance card is sent by the British Paediatric Surveillance Unit to all consultant paediatricians in the UK. The card lists the disorders currently under surveillance. Paediatricians are asked to return the card, reporting cases seen in the previous month. The BPSU office informs the surveillance groups about reported cases, and they obtain clinical information from the notifying paediatrician. RESULTS: After 5 years and 8 months of surveillance, 1244 children had been reported to the study. Alpers' syndrome was confirmed in two, although this was the suggested diagnosis in 11 children at the time of initial notification. CONCLUSIONS: The results show that Alpers' syndrome is rare and it is unlikely that vCJD cases are being misdiagnosed as Alpers' syndrome.     

mGlu5 receptor antagonists: a novel class of anxiolytics?

In the early 1990s, a new family of receptors were cloned that were found to mediate the intracellular metabolic effects of glutamate via coupling to secondary messenger systems, that is, the metabotropic glutamate (mGlu) receptors. Eight such receptors (mGlu1 to mGlu8) have been cloned to date, and according to their amino acid sequence, pharmacology and second-messenger coupling, these receptors have been clustered into three groups (I-III). In contrast to the glutamate-gated ion channels (NMDA, AMPA and kainate receptors), which are responsible for fast excitatory transmission, mGlu receptors have been shown to play a modulatory role in the glutamatergic synaptic transmission either by modulating the ion channel activity or by influencing neurotransmitter release. Given the fact that the mGlu receptors are G-protein- coupled, they obviously constitute a new attractive group of "drugable" targets for the treatment of various CNS disorders. The recent discovery of small molecules that selectively bind to receptors of group I (mGlu1 and mGlu5) and group II (mGlu2 and mGlu3) allowed significant advances in our understanding of the roles of these receptors in brain physiology and pathophysiology. The identification of MPEP (2-methyl-6-(phenylethynyl)-pyridine), a highly selective and brain-penetrant mGlu5 receptor antagonist, allowed the exploration of the therapeutic potential of this class of compounds. Subsequent behavior studies revealed that--with the exception of benzodiazepines--mGlu5 receptor antagonists exhibit the widest and most robust anxiolytic activity in preclinical models seen to date. Upcoming clinical studies will soon indicate if the preclinical anxiolytic-like efficacy translates into anxiolytic activity in humans.     

Risk-taking propensity and risky sexual behavior of individuals in residential substance use treatment

In the current study, a battery of self-report measures of impulsivity, self-esteem, and depressive symptoms, as well as a behavioral measure of risk-taking propensity, was administered to 76 residents of two inner-city substance use residential treatment programs to determine the unique relationship between risk-taking propensity and risky sexual behavior (RSB). Results indicated that impulsivity, self-esteem, and risk-taking propensity were independently related to RSB. In a subsequent regression analysis, risk-taking propensity evidenced incremental validity, suggesting a relationship between risk-taking propensity and RSB, above and beyond that provided with the other relevant variables. The potential importance of risk-taking propensity the better understanding HIV risk through engagement in RSB is discussed.     

Residential mobility during pregnancy

In epidemiological studies of environmental exposures and adverse pregnancy outcomes, maternal residence at delivery is often used to assign an exposure level, based on routinely collected data. In order to examine the potential for exposure misclassification due to residential mobility, we examined maternal mobility according to changes in residence overall, as well as changes in municipality and county. The potential for mobility to be related to pregnancy outcomes was considered by examining the relationship between mobility and risk factors commonly included in investigations of adverse pregnancy outcomes. Previously collected data were studied from 398 population-based control subjects from a case-control study of stillbirths. We compared demographic, lifestyle, medical, pregnancy and environmental factors of women who moved during pregnancy with those who did not. Bivariable and multivariable log binomial regressions were used to identify risk factors that were associated with mobility during pregnancy. Twelve per cent of subjects moved at least once during their pregnancy. Among women who moved, the majority (62%) moved within the same municipality. In bivariable analyses, we found that low family income, lower maternal age, unmarried status and tobacco use were associated with an increased likelihood of moving during pregnancy, whereas women who used folic acid before conception and who had a higher prepregnancy body mass index (BMI) were less likely to move during pregnancy. In multivariable analyses, only family income, age and prepregnancy BMI were independently predictive of mobility. These results indicate that in studies using maternal residence at delivery to assign environmental exposures, mobility during pregnancy is likely to be prevalent enough to introduce exposure misclassification. The potential for differential exposure misclassification should be considered should any of the risk factors for moving identified by this study also be risk factors for the outcome under study.