Search PubMed⌕ Search

Biomedical subjects

R Peto

Publications and source records attributed to R Peto.

At least 217 records · Page 12Linked to original sources
PubMed1979

Detection of risk of cancer to man.

Epidemiology can pick out large-scale determinants of human cancer, such as smoking. Also, epidemiology can pick out carcinogens such as asbestos to which groups of perhaps a few hundred or a few thousand workers have been heavily exposed for decades. However, if highly exposed groups cannot be studied then epidemiology cannot recognize carcinogens which, although perhaps widely distributed, produce only a small percentage increase in particular cancers. Almost all of the environmental pollutants that can affect human cancer incidence will do so only to a very minor extent, at the levels to which we are currently exposed. For this reason, and also because it is often difficult to define an exposed and an unexposed group which do not differ in other ways as well, it will almost always be impossible to do anything epidemiologically except to set a very crude upper limit on their likely hazards. The only way, therefore, to get any direct estimate of these hazards is by laboratory studies of the effects of high doses on various model systems. For this and for other reasons, it would be highly desirable to have good laboratory models for human carcinogenesis. The characteristics required of satisfactory laboratory systems are reviewed, and it is argued that systematic errors may arise unless one studies epithelial cells from large, long-lived species under conditions of chronic, low-dose exposure to noxious test agents in conjunction with standard chronic doses of agents which may be synergistic with the test agents. (Carcinogenic mutagens may be synergistic with carcinogenic non-mutagens.) For reasons of expense and speed, such studies must be done in vitro. If such in-vitro systems can be developed, either by using tissue explants or cell cultures, an important criterion which they will have to satisfy to be trusted will be that under chronic exposure the rate of transformation should be proportional to something like the fourth power of exposure duration. This paper chiefly reviews the reasons for choosing these specifications for a trustworthy in-vitro model for human carcinogenesis.

Carcinogens↗
PubMed1978

Cigarette smoking and bronchial carcinoma: dose and time relationships among regular smokers and lifelong non-smokers.

In a 20-year prospective study on British doctors, smoking habits were ascertained by questionnaire and lung cancer incidence was monitored. Among cigarette smokers who started smoking at ages 16-25 and who smoked 40 or less per day, the annual lung cancer incidence in the age range 40-79 was:0.273X10(-12). (cigarettes/day+6)2. (age--22.5)4.5. The form of the dependence on dose in this relationship is subject not only to random error but also to serious systematic biases, which are discussed. However, there was certainly some statistically significant (P less than 0.01) upward curvature of the dose-response relationship in the range 0-40 cigarettes/day, which is what might be expected if more that one of the "stages" (in the multistage genesis of bronchial carcinoma) was strongly affected by smoking. If a higher than linear dose-response relationship exists between dose per bronchial cell and age-specific risk per bronchial cell, this may help explain why bronchial carcinomas chiefly arise in the upper bronchi, for dilution effects might then protect the larger areas lower in the bronchial tree.

Adolescent↗
PubMed1977

The natural history of chronic airflow obstruction.

A prospective epidemiological study of the early stages of the development of chronic obstructive pulmonary disease was performed on London working men. The findings showed that forced expiratory volume in one second (FEV1) falls gradually over a lifetime, but in most non-smokers and many smokers clinically significant airflow obstruction never develops. In susceptible people, however, smoking causes irreversible obstructive changes. If a susceptible smoker stops smoking he will not recover his lung function, but the average further rates of loss of FEV1 will revert to normal. Therefore, severe or fatal obstructive lung disease could be prevented by screening smokers' lung function in early middle age if those with reduced function could be induced to stop smoking. Infective processes and chronic mucus hypersecretion do not cause chronic airflow obstruction to progress more rapidly. There are thus two largely unrelated disease processes, chronic airflow obstruction and the hypersecretory disorder (including infective processes).

Adult↗
PubMed1977

Maternal serum-alpha-fetoprotein measurement in antenatal screening for anencephaly and spina bifida in early pregnancy. Report of U.K. collaborative study on alpha-fetoprotein in relation to neural-tube defects.

Nineteen centres collaborated in a study to determine the efficiency of maternal serum-alpha-fetoprotein (A.F.P.) measurement as a method of screening for neural-tube defects (N.T.D.S.) between 10 and 24 weeks of pregnancy. Data were collected on 18 684 singleton pregnancies and 163 twin pregnancies without fetal N.T.D.s, and on 301 singleton pregnancies with fetal N.T.D.s (146 with anencephaly, 142 with spina bifida, and 13 with encephalocele). The best time for detecting open spina bifida by measuring maternal serum-A.F.P. is at 16-18 weeks of pregnancy. In clinical practice, serum-A.F.P. cut-off levels expressed as multiples of the normal median may be more convenient to use than percentiles because they are easier to derive and more stable. Also, the proportion of affected pregnancies with serum-A.F.P. levels exceeding a given multiple of the median is unlikely to vary significantly from centre to centre or over time. In contrast, the proportion of unaffected pregnancies with A.F.P. levels exceeding a given multiple of the normal median will vary depending on the precision with which serum-A.F.P. and gestation are measured. At 16-18 weeks of pregnancy 88% of cases of anencephaly, 79% of cases of open spina bifida, and 3% of unaffected singleton pregnancies had A.F.P. levels equal to or greater than 2-5 times the median for unaffected singleton pregnancies. At this gestation age the numbers of unaffected pregnancies with A.F.P. levels above 2-5 times the normal median can be reduced by about a third if women with borderline A.F.P. levels are retested, although this would not greatly change the detection-rate of affected pregnancies. In the United Kingdom as a whole, women with serum-A.F.P. levels above 2-5 times the normal median at 16-18 weeks of gestation will have an approximately 1-in-20 chance of having a fetus with open spina bifida; the risk of having any N.T.D. will be approximately 1 in 10. The results of this study indicate that screening pregnant women by measuring the concentration of A.F.P. in their serum is an effective method of selecting women for ultrasonography and amniocentesis so that N.T.D.s can be diagnosed in utero.

Anencephaly↗
PubMed1977

Mortality among doctors in different occupations.

A total of 20540 male doctors who replied to a questionnaire on their smoking habits that was sent to them on 1 November 1951, and who were aged 35 years and over, were classified according to their occupation as listed in the Medical Directory for 1952 and followed up until 1 November 1971. Examination of the mortality rates in 11 occupational groups showed gross heterogeneity for smoking-related diseases but not for all other diseases grouped together. On average, general practitioners smoked 37% more cigarettes than did hospital physicians and surgeons and the overall death rates among general practitioners were about 23% higher than among physicians and surgeons of similar ages. This excess death rate was chiefly accounted for by a 38% excess mortality from smoking-related diseases such as lung cancer, chronic bronchitis, and ischaemic and pulmonary heart disease. The few other statistically significant associations between occupation and disease were thought to be due either to chance or to the effect of the disease on the choice of specialty.

Aged↗
PubMed1977

Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. analysis and examples.

Part I of this report appeared in the previous issue (Br. J. Cancer (1976) 34,585), and discussed the design of randomized clinical trials. Part II now describes efficient methods of analysis of randomized clinical trials in which we wish to compare the duration of survival (or the time until some other untoward event first occurs) among different groups of patients. It is intended to enable physicians without statistical training either to analyse such data themselves using life tables, the logrank test and retrospective stratification, or, when such analyses are presented, to appreciate them more critically, but the discussion may also be of interest to statisticians who have not yet specialized in clinical trial analyses.

Drug Evaluation↗
PubMed1977

The 4 score: an index for predicting a patient's non-medical hospital days.

Three hundred sixty-three patients representing two groups of consecutive medical admissions to a large city hospital were evaluated on admission to determine what factors might predict "non-medical" or social stay. Periodic follow-up determined when patients were ready for discharge and when their social stay began. A composite index, the 4-Score, was derived as a simple indicator of risk for subsequent social stay; it is defined as the number of positive answers to the questions: 1) Is the patient 80 years old or more? 2) Will the patient have to live somewhere new at discharge? 3) Is there any disorientation? AND 4) If so, is the disorientation chronic? Eighteen per cent of the total inpatient hospital days of this group of patients could be attributed to social stay. The 56 patients with a 4-Score of two or more on admission had on average a week each of social stay while the 307 patients with a score of less than two averaged only one social day each.

Activities of Daily Living↗
PubMed1976

Mortality in relation to smoking: 20 years' observations on male British doctors.

In 1951 the British Medical Association forwarded to all British doctors a questionnaire about their smoking habits, and 34440 men replied. With few exceptions, all men who replied in 1951 have been followed for 20 years. The certified causes of all 10 072 deaths and subsequent changes in smoking habits were recorded. The ratio of the death rate among cigarette smokers to that among lifelong non-smokers of comparable age was, for men under 70 years, about 2:1, while for men over 70 years it was about 1-5:1. These ratios suggest that between a half and a third of all cigarette smokers will die because of their smoking, if the excess death rates are actually caused by smoking. To investigate whether this is the case, the relation of many different causes of death to age and tobacco consumption were examined, as were the effects of giving up smoking. Smoking caused death chiefly by heart disease among middle-aged men (and, with a less extreme relative risk, among old men,) lung cancer, chronic obstructive lung disease, and various vascular diseases. The distinctive features of this study were the completeness of follow-up, the accuracy of death certification, and the fact that the study population as a whole reduced its cigarette consumption substantially during the period of observation. As a result lung cancer grew relatively less common as the study progressed, but other cancers did not, thus illustrating in an unusual way the causal nature of the association between smoking and lung cancer.

Adult↗