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The European Prospective Investigation into Cancer and Nutrition (EPIC), which covers a large cohort of half a million men and women from 23 European centres in 10 Western European countries, was designed to study the relationship between diet and the risk of chronic diseases, particularly cancer. Information on usual individual dietary intake was assessed using different validated dietary assessment methods across participating countries. In order to adjust for possible systematic over- or underestimation in dietary intake measurements and correct for attenuation bias in relative risk estimates, a calibration approach was developed. This approach involved an additional dietary assessment common across study populations to re-express individual dietary intakes according to the same reference scale. A single 24-hour diet recall was therefore collected, as the EPIC reference calibration method, from a stratified random sample of 36 900 subjects from the entire EPIC cohort, using a software program (EPIC-SOFT) specifically designed to standardise the dietary measurements across study populations. This paper describes the design and populations of the calibration sub-studies set up in the EPIC centres. In addition, to assess whether the calibration sub-samples were representative of the entire group of EPIC cohorts, a series of subjects' characteristics known possibly to influence dietary intakes was compared in both population groups. This was the first time that calibration sub-studies had been set up in a large multi-centre European study. These studies showed that, despite certain inherent methodological and logistic constraints, a study design such as this one works relatively well in practice. The average response in the calibration study was 78.3% and ranged from 46.5% to 92.5%. The calibration population differed slightly from the overall cohort but the differences were small for most characteristics and centres. The overall results suggest that, after adjustmen

The European Prospective Investigation into Cancer and Nutrition (EPIC), which covers a large cohort of half a million men and women from 23 European centres in 10 Western European countries, was designed to study the relationship between diet and the risk of chronic diseases, particularly cancer. Information on usual individual dietary intake was assessed using different validated dietary assessment methods across participating countries. In order to adjust for possible systematic over- or underestimation in dietary intake measurements and correct for attenuation bias in relative risk estimates, a calibration approach was developed. This approach involved an additional dietary assessment common across study populations to re-express individual dietary intakes according to the same reference scale. A single 24-hour diet recall was therefore collected, as the EPIC reference calibration method, from a stratified random sample of 36 900 subjects from the entire EPIC cohort, using a software program (EPIC-SOFT) specifically designed to standardise the dietary measurements across study populations. This paper describes the design and populations of the calibration sub-studies set up in the EPIC centres. In addition, to assess whether the calibration sub-samples were representative of the entire group of EPIC cohorts, a series of subjects' characteristics known possibly to influence dietary intakes was compared in both population groups. This was the first time that calibration sub-studies had been set up in a large multi-centre European study. These studies showed that, despite certain inherent methodological and logistic constraints, a study design such as this one works relatively well in practice. The average response in the calibration study was 78.3% and ranged from 46.5% to 92.5%. The calibration population differed slightly from the overall cohort but the differences were small for most characteristics and centres. The overall results suggest that, after adjustmen

6.7-Dimethoxy-3-cyano-3.4-dihydrocarbostyril (7A61, 1), a 2-quinolinone derivative, showed interesting cardiotonic properties in vitro. It exerted potent positive inotropic effects, without any change in heart rate, in guinea pig atrial preparations, and its effects were not dependent upon inhibition of phosphodiesterases, opening of Na+ channels, or inhibition of adenosine receptors. Notwithstanding its structural relationships with milrinone, vesnarinone, and other quinolinones endowed with cardiotonic activity, it appeared that 7A61 does not share any of the main mechanisms of action involved in the pharmacological activity of these compounds. Other experiments also excluded the involvement of other well known mechanisms of cardiac stimulation, such as adrenergic receptor activation or opening of Ca++ channels, the mode of action of 7A61 remaining unexplained. However, contrary to milrinone, 7A61 did not exert cardiotonic effects in human ventricular muscle preparations, thus discouraging further investigation. Although the lack of effect on human heart could not be predicted from the results obtained in several cardiac preparations commonly used in laboratory investigations, the scarce efficacy of 7A61 in comparison with milrinone in dog and cat papillary muscle and in guinea pig ventricular muscle suggests the utility of the latter preparations in laboratory experiments aimed at selecting new potential cardiotonic agents.