The inflammatory microenvironment in colorectal neoplasia

Peer reviewedPublisher PD

Does the evidence about health risks associated with nitrate ingestion warrant an increase of the nitrate standard for drinking water?

Several authors have suggested that it is safe to raise the health standard for nitrate in drinking water, and save money on measures associated with nitrate pollution of drinking water resources. The major argument has been that the epidemiologic evidence for acute and chronic health effects related to drinking water nitrate at concentrations near the health standard is inconclusive. With respect to the chronic effects, the argument was motivated by the absence of evidence for adverse health effects related to ingestion of nitrate from dietary sources. An interdisciplinary discussion of these arguments led to three important observations. First, there have been only a few well-designed epidemiologic studies that evaluated ingestion of nitrate in drinking water and risk of specific cancers or adverse reproductive outcomes among potentially susceptible subgroups likely to have elevated endogenous nitrosation. Positive associations have been observed for some but not all health outcomes evaluated. Second, the epidemiologic studies of cancer do not support an association between ingestion of dietary nitrate (vegetables) and an increased risk of cancer, because intake of dietary nitrate is associated with intake of antioxidants and other beneficial phytochemicals. Third, 2–3 % of the population in Western Europe and the US could be exposed to nitrate levels in drinking water exceeding the WHO standard of 50 mg/l nitrate, particularly those living in rural areas. The health losses due to this exposure cannot be estimated. Therefore, we conclude that it is not possible to weigh the costs and benefits from changing the nitrate standard for drinking water and groundwater resources by considering the potential consequences for human health and by considering the potential savings due to reduced costs for nitrate removal and prevention of nitrate pollution

Investigating silent strokes in hypertensives: a magnetic resonance imaging study (ISSYS): rationale and protocol design

BACKGROUND: Silent brain infarcts are detected by neuroimaging in up to 20% of asymptomatic patients based on population studies. They are five times more frequent than stroke in general population, and increase significantly both with advancing age and hypertension. Moreover, they are independently associated with the risk of future stroke and cognitive decline. Despite these numbers and the clinical consequences of silent brain infarcts, their prevalence in Mediterranean populations is not well known and their role as predictors of future cerebrovascular and cardiovascular events in hypertensive remains to be determined. ISSYS (Investigating Silent Strokes in Hypertensives: a magnetic resonance imaging study) is an observational cross-sectional and longitudinal study aimed to: 1- determine the prevalence of silent cerebrovascular infarcts in a large cohort of 1000 hypertensives and to study their associated factors and 2-to study their relationship with the risk of future stroke and cognitive decline. METHODS/DESIGN: Cohort study in a randomly selected sample of 1000 participants, hypertensive aged 50 to 70 years old, with no history of previous stroke or dementia. On baseline all participants will undergo a brain MRI to determine the presence of brain infarcts and other cerebrovascular lesions (brain microbleeds, white matter changes and enlarged perivascular spaces) and will be also tested to determine other than brain organ damage (heart-left ventricular hypertrophy, kidney-urine albumin to creatinine ratio, vessels-pulse wave velocity, ankle brachial index), in order to establish the contribution of other subclinical conditions to the risk of further vascular events. Several sub-studies assessing the role of 24 hour ambulatory BP monitoring and plasma or genetic biomarkers will be performed. Follow-up will last for at least 3 years, to assess the rate of further stroke/transient ischemic attack, other cardiovascular events and cognitive decline, and their predictors. DISCUSSION: Improving the knowledge on the frequency and determinants of these lesions in our setting might help in the future to optimize treatments or establish new preventive strategies to minimize clinical and socioeconomic consequences of stroke and cognitive decline

Proton pump inhibitors and histamine-2-receptor antagonists and pancreatic cancer risk: a nested case-control study

BACKGROUND: The relationship between use of proton pump inhibitors (PPIs) and histamine-2-receptor antagonists (H(2)RAs) and pancreatic cancer risk has yet to be examined. Data from a range of studies suggest biologically plausible mechanisms, whereby these drugs (or the conditions for which they are prescribed) may affect pancreatic cancer risk. The objective of this study was to investigate the relationship between use of PPIs/H(2)RAs and pancreatic cancer risk. METHODS: A nested case–control study was conducted within the UK general practice research database (GPRD). Cases had a diagnosis of exocrine pancreatic cancer and controls were matched to cases on general practice site, sex and year of birth. Exposure to PPIs and to H(2)RAs since entry into GPRD until 2 years before the diagnosis date (corresponding date in controls) and in the 5 years before the diagnosis date were separately assessed. Conditional logistic regression analyses were used to generate odds ratios (ORs) and 95% confidence intervals (CIs) associated with PPI or H(2)RA use compared with nonuse. RESULTS: Ever use of PPIs since entry into the GPRD (excluding the 2 years prior to diagnosis) was not associated with risk of pancreatic cancer; OR (95% CI) 1.02 (0.85–1.22). Neither the dose nor the duration of PPI or H(2)RA use was associated with pancreatic cancer risk. No consistent patterns of association were seen when cumulative exposure (dose and duration) to these drugs was examined separately or together. CONCLUSION: PPI/H(2)RA use, in a UK population, was not associated with pancreatic cancer risk