Human cancer risks are inversely correlated with (a) blood retinol and (b) dietary beta-carotene. Although retinol in the blood might well be truly protective, this would be of little immediate value without discovery of the important external determinants of blood retinol which (in developed countries) do not include dietary retinol or beta-carotene. If dietary beta-carotene is truly protective--which could be tested by controlled trials--there are a number of theoretical mechanisms whereby it might act, some of which do not directly involve its 'provitamin A' activity.

Africa, Eastern↗

PubMed1981

Initiation and promotion at different ages and doses in 2200 mice. I. Methods, and the apparent persistence of initiated cells.

Delay between initiation and promotion on mouse skin was in 1949 reported by Berenblum and Shubik not to affect tumour yields, and this led to the important concept of the irreversibility of initiation and stimulated the development of multistage models. Subsequent reports have, however, suggested that delay does decrease tumour yields, and this is confirmed by the present study of 2200 mice initiated at 8, 48, or 68 weeks with 10, 30, 100, or 300 microgram of DMBA and promoted by a standard dose of TPA for 15 weeks, after various delays. However, our data suggest that the decrease in tumour yields is chiefly or wholly due to a reduction, among ageing mice, of the ability to respond to promoters, and not to any substantial loss of initiated cells, for late initiation with immediate promotion also yielded a less rapid response than early initiation with immediate promotion. Interpretation of all such studies is complicated by the few weeks that the skin needs to repair ulceration and other damage induced by the higher doses of DMBA, for if promotion with TPA begins before such repair is complete the tumour yield may be misleadingly increased.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1981

Initiation and promotion at different ages and doses in 2200 mice. II. Decrease in promotion by TPA with ageing.

Using the data described in Paper I, we compare the effects of the same treatment timings and doses given at different ages. Initiation with DMBA at 68 weeks of age, followed 3 weeks later by TPA, has a significantly (P less than 0.0001) less rapid effect on subsequent tumour incidence than does initiation at 8 or at 48 weeks of age, followed 3 weeks later by TPA. We suggested that this is chiefly due not to changes in the numbers of cells initiated by DMBA, but rather to a decrease in the promotional efficacy of TPA in ageing mice.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1981

Initiation and promotion at different ages and doses in 2200 mice. III. Linear extrapolation from high doses may underestimate low-dose tumour risks.

The dose-response relationships from the data described in Paper I were analysed. Among unpromoted animals, only doses sufficient to cause ulceration with subsequent promotion due to wound healing caused a rapid crop of tumours, so the dose-response curve exhibited strong upward curvature. Among promoted animals, the response of the skin to initiation appeared to have been nearly saturated by all DMBA doses tested, so that a 30-fold decrease in dose produced only a 3-fold decrease in effect. The dose-response relationship thus exhibited strong downward curvature. Among promoted animals, estimation of the risks associated with very low doses of carcinogen by linear extrapolation through the origin from the effects of larger doses (which is often assumed to be conservative) would under-estimate the true risks by 10-fold or more. Our results emphasize that whereas linear interpolation from the results of high doses may be reasonable for data on the effects of continuous treatment with non-toxic dose levels of carcinogen, it may be misleading when extrapolating, as here, from the effects of single large doses.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1981

Early intravenous atenolol treatment in suspected acute myocardial infarction.

Explore the source record for details and available documents.

Atenolol↗

PubMed1981

The causes of cancer: quantitative estimates of avoidable risks of cancer in the United States today.

Evidence that the various common types of cancer are largely avoidable diseases is reviewed. Life-style and other environmental factors are divided into a dozen categories, and for each category the evidence relating those particular factors to cancer onset rates is summarized. Where possible, an estimate is made of the percentage of current U.S. cancer mortality that might have been caused or avoided by that category of factors. These estimates are based chiefly on evidence from epidemiology, as the available evidence from animal and other laboratory studies cannot provide reliable human risk assessments. By far the largest reliably known percentage is the 30% of current U.S. cancer deaths that are due to tobacco, although it is possible that some nutritional factor(s) may eventually be found to be of comparable importance. The percentage of U.S. cancer deaths that are due to tobacco is still increasing, and must be expected to continue to increase for some years yet due to the delayed effects of the adoption of cigarettes in earlier decades. Trends in mortality and in onset rates for many separate types of cancer are studied in detail in appendixes to this paper. Biases in the available data on registration of new cases produce apparent trends in cancer incidence which are spurious. Biases also produce spurious trends in cancer incidence which are spurious. Biases also produce spurious trends in cancer death certification rates, especially among old people. In (and before) middle age, where the biases are smaller, there appear to be a few real increases and a few real decreases in mortality from some particular types of cancer, but there is no evidence of any generalized increase other than that due to tobacco. Moderate increases or decreases due to some new agent(s) or habit(s) might of course be overlooked in such large-scale analyses. But, such analyses do suggest that, apart from cancer of the respiratory tract, the types of cancer that are currently common are not peculiarly modern diseases and are likely to depend chiefly on some long-established factor(s). (A prospective study utilizing both questionnaires and stored blood and other biological materials might help elucidate these factors.) The proportion of current U.S. cancer deaths attributed to occupational factors is provisionally estimated as 4% (lung cancer being the major contributor to this). This is far smaller than has recently been suggested by various U.S. Government agencies. The matter could be resolved directly by a "case-control" study of lung cancer two or three times larger than the recently completed U.S. National Bladder Cancer Study but similar to it in methodology and unit costs; there are also other reasons for such a study. A fuller summary of conclusions and recommendations comprises the final section of this report.

Adult↗

PubMed1980

Early intravenous atenolol treatment in suspected acute myocardial infarction. Preliminary report of a randomised trial.

214 patients were studied in a randomised trial to determine whether administraiton of intravenous atenolol within 12 hours of chest pain reduced eventual infarct size, as estimated by cumulative enzyme release and by ECG changes. 135 patients already had ECG evidence of infarction at entry; 72 received atenolol which significantly decreased subsequent enzyme release (atenolol and control means = 121 IU, SE +/- 10 and 177 IU, SE +/- 17; 2p < 0.005) and enhanced R-wave preservation (atenolol and control means = 46% +/- 3 and 36% +/- 3; 2p < 0.02). 79 patients had no evidence of infarction at entry; 44 did not receive atenolol and 27 of these subsequently developed infarction, whereas only 11 of 35 treated patients infarcted during their hospital stay (2p < 0.01). In hospital, fewer atenolol patients died (4 vs 9), had non-fatal cardiac arrests (2 vs 6), or required therapy for heart-failure (36 vs 47). Unlike many previous trials which had negative results, in this trial we gave the drug intravenously and promptly (median of 4 hours from onset of pain to injecton), thereby achieving early beta-blockade.

Acute Disease↗

PubMed1980

Mortality in relation to smoking: 22 years' observations on female British doctors.

A total of 6194 female doctors who in 1951 replied to a questionnaire about their smoking habits were followed up prospectively for 22 years. During that time 1094 died. Ischaemic heart disease, lung cancer, and chronic obstructive lung disease were all significantly (p < 0.001) related to smoking, though the absolute excess risks were lower than in male doctors smoking equivalent amounts. Female smokers born before the first world war were less likely to describe themselves as inhalers or as having started to smoke while young than were female smokers who were born later. In these respects this younger group resembled male smokers, and as they move into their 60s and 70s their absolute risk of lung disease and relative risk of ischaemic heart disease will probably come to resemble the risks for men smoking the same numbers of cigarettes. These findings show only that cigarette smoking causes lung cancer, chronic obstructive lung disease, and heart disease in women as in men. Whether the proportional increase in mortality from these diseases is as great in women as in men might be estimated directly from new case-control studies on men and women born since 1920.

Adult↗

PubMed1980