Population studies, general

Cardiovascular Effects. There is currently considerable scientific debate as to whether there is a causal relationship between lead exposure and hypertension. Another area of controversy is whether African Americans are more susceptible to the cardiovascular effects of lead than are whites or Hispanics. The evidence from both occupational studies and large-scale general population studies (i.e., National Health and Nutrition Examination Survey [NHANES II], British Regional Heart Study [BRHS]) is not sufficient to conclude that such a causal relationship exists between PbB levels and increases in blood pressure. The database on lead-induced effects on cardiovascular function in humans will be discussed by presenting a summary of several representative occupational studies followed by a discussion of the findings from the large-scale general population studies. 

Two large-scale general population studies, the BHRS (Pocock et al. 1984, 1985, 1988) and NHANES II (Coate and Fowles 1989 Gartside 1988 Harlan 1988 Harlan et al. 1985 Landis and Flegal 1988 Pirkle et al. 1985 Schwartz 1988), examined the relationship between PbB levels and blood pressure in men. Relationships between PbB levels and hypertension were evaluated in a clinical survey of 7,735 men, aged 40-49 years, from 24 British towns in the BHRS (Pocock et al. 1984, 1985, 1988). A small but... 

Taken together, the results of both the occupational and general population studies do not provide conclusive evidence that lead exposure, as assessed by PbB levels, is positively associated with hyper-... 

General population studies indicate that the activity of ALAD is inhibited at very low PbB levels, with no threshold yet apparent. ALAD activity was inversely correlated with PbB levels over the entire range of 3-34 pg/dL in urban subjects never exposed occupationally (Hemberg and Nikkanen 1970). Other reports have confirmed the correlation and apparent lack of threshold in different age groups and exposure categories (children—Chisolm et al. 1985 children—Roels and Lauwerys 1987 adults—Roels et al. 1976). Inverse correlations between PbB levels and ALAD activity were found in mothers (at delivery) and their newborns (cord blood). PbB levels ranged from approximately 3 to 30 g/dL (Lauwerys et al. 1978). 

Studies in Support of Special Populations Geriatrics General Considerations of Clinical Trials Statistical Principles for Clinical Trials... 

Pharmacokinetic models are used as tools to extrapolate from the results obtained in studies with experimental animals to predict effects in human populations that generally are exposed at lower environmental exposure levels compared to the generally higher exposure levels used in animal experiments. In such models, target tissue doses in different animal species under a variety of exposure conditions are predicted, using computer simulation. 

There was no evidence that MOCA was tumorigenic in a study of 31 active workers exposed from 6 months to 16 years. Quantitative analysis of the workers urine confirmed exposure to the chemical. In addition, the records were reviewed for 178 employees who at one time had worked with MOCA but who thereafter had had no further exposure for at least 10 years. The general health of exposed workers with respect to illness, absenteeism, and medical history was similar to that of the total plant population. Two deaths in this group due to malignancy had been diagnosed before any work with or exposure to MOCA. For the plant population in general, there were 115 cancer deaths/100,000 over a 15-year period... 

NVP, 246, is the intermediate in the production of PVP (polyvinylpyrrolidinone)257 widely employed in the pharmaceutical, medicinal, food and beverage industries, and the small quantities (0.2% or less) of NVP contained as impurity in PVP might present a certain risk for the general population. Studies on the in vivo disposition of NVP have therefore been undertaken and 246 has been synthesized258 (equation 135). [3,4-3H]-NVP and [4-3H]-NVP have been prepared previously in low yields259 because the volatility of NVP itself and of the vinyl acetate had not been controlled properly in the synthetic and... 

In the study on colorectal cancer (Table 20.4), a reduced risk was found for increasing intake of anthocyanidins (OR, 0.67 for the highest versus the lowest quintile,p-trend, 0.001), flavonols (OR, 0.64,p-trend < 0.001), flavones (OR, 0.78, p-trend, 0.004), and isoflavones (OR, 0.76, p-trend, 0.001). [Rossi et al., 2006], The estimates did not substantially differ for colon and rectal cancers. After allowance for fruit and vegetable consumption, for dietary fiber, or for micronutrients previously associated to this tumor including vitamin C, the associations with flavonoids did not change by more than 10%. A recent case-control study of 1456 pairs of cases and controls conducted in Sweden confirmed a significant decrease in risk of colorectal cancer for intake of anthocyanidins and flavonols [Theodoratou et al., 2007], but there was no relation for isoflavones and flavones. However, the results on isoflavones and flavones are questionable due to the unusually and generally low intakes of the populations studied. In the Italian population, anthocyanidins were derived mainly from wine, red fruit, and onions, and flavonols from apples or pears, wine, and mixed salads. 

In a systematic review of the experimental and epidemiological data, Navas-Aden et al. (2006) argue that the evidence to date is inconclusive for a role of arsenic in the development of diabetes mellitus. Pooling the results from the Taiwan and Bangladesh studies, which were from extreme arsenic exposures, there was a risk of 2.5 for the development of diabetes. However, they point out, because of the types of studies conducted, particularly with characterization of the exposures, it was hard to interpret the association. In addition, the occupational studies that they examined showed increased and decreased morbidity from diabetes due to arsenic exposure. The general population studies, which typically had much lower arsenic exposures, were inconclusive. 

In general, ALA intake was associated with reduced risks of cardiovascular disease in many of the large population studies despite inconsistencies in serum lipid data. Only one study (Zutphen Elderly Study) did not report a benefit of ALA in reducing cardiovascular disease (Oomen et al., 2001). However, this study relied on dietary intake of ALA from margarine and meat thus raising questions regarding the outcome of the study. 

Reference values indicate the upper margin of the current background exposure of the general population and [are used] to identify subjects with an increased level of exposure (Jakubowski and Trzcinka-Ochocka 2005) compared with the background population level. Those values are derived from data on blood, urine, and other tissues collected from population studies (Ewers et al. 1999). Reference values may be derived differently for susceptible groups if physiologic differences are substantial (for example, children vs adults) (Ewers et al. 1999). 

Solvents are typically not targeted for biomonitoring in general population studies, because their rapid clearance by exhalation or metabolism results in a transient biomarker that does not reach steady state. However, analysis of such rapidly cleared chemicals may be possible, as exemplified in a trichloroethylene (TCE) biomarker study (Sohn et al. 2004), which constitutes another case study of pharmacokinetic modeling of human biomonitoring data under non-steady-state conditions. 

The registered data have been used for the identification and restriction of the study population. The general strategy of the studies has been as follows (Figure l.). First, the workers have been identified from the existing national registers or the... 

However, despite the firm experimental basis and encouraging clinical studies, prophylaxis with NSAIDs to prevent colon cancer in patients who have polyps or in the population in general is notjustified because of the GI toxicity of such therapy. With the introduction of Cox-2 inhibitors, it now is feasible to test the hypothesis that inhibition of Cox-2 over prolonged periods of time would be protective against the development of colon polyps. Since it is well accepted that colon polyps are precancerous lesions, the prevention of polyps should translate into a reduction in the incidence of colon cancer. 

Homocysteine isn t harmless. Evidence from population studies indicates that high levels of homocysteine in the blood are correlated with heart disease. Folic acid supplements may prevent this problem by ensuring that the homocysteine is rapidly converted to methionine. Similarly, pregnant women generally take folic acid supplements to prevent their babies from being bom with neural tube defects. The mechanism for its action isn t known, but the folic acid may help decrease the level of homocysteine in this case as well. 

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