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Biomedical subjects

R Doll

Publications and source records attributed to R Doll.

At least 91 records · Page 5Linked to original sources
PubMed1994

A search for unknown blood-borne oncogenic viruses.

In previous decades, infants who received blood transfusions shortly after birth or in utero might have been infected at a particularly vulnerable age by some blood-borne oncogenic virus. A cohort of such infants has therefore been followed into adult life to see if they suffered any excess of neoplastic disease or of non-neoplastic mortality. A total of 12,690 infants were identified who were transfused between 1 January 1942 and 31 December 1970, in most cases for the prevention or treatment of haemolytic disease of the newborn. All but 361 (2.8%) were found to have been registered with a National Health Service (NHS) practitioner and were followed in the NHS central records until they died, emigrated, were removed from NHS lists or until 1 January 1992, whichever occurred first. Mortality and cancer incidence were compared with that expected from national rates. No marked disparity was observed and there was no excess of childhood leukaemia. The incidence of non-Hodgkin's lymphoma at 15 to 49 years of age was about twice that expected, but the excess was not statistically significant.

Adolescent↗
PubMed1994

Mortality in a cohort of women given X-ray therapy for metropathia haemorrhagica.

Mortality to January 1, 1991, has been studied in 2,067 women in Scotland given X-ray therapy for metropathia haemorrhagica during the period 1940-1960. Average follow-up was 28 years. Overall, 1,313 deaths were observed compared with 1,297.01 expected from Scottish rates [standardized mortality ratio (SMR): 1.01]. Mortality was increased for cancers of heavily irradiated pelvic sites (SMR 5+ years after irradiation: 1.46) following mean doses to organs in the vicinity of the pelvis in the range 2.6-5.3 Gy. For these cancers the SMR was higher 30+ years after irradiation than at 5-29 years, indicating that the effects of exposure last for over 30 years, and in this period bladder cancer mortality was exceptionally high (SMR = 4.91). Mortality was also raised for leukaemia (SMR 2+ years after irradiation: 2.05), following a mean bone-marrow dose of 1.3 Gy, and for multiple myeloma (SMR 5+ years after irradiation: 2.59). For leukaemia the SMR was lower 30+ years after irradiation than at earlier periods, but remained greater than unity. For other cancers mortality was similar to Scottish rates, except for breast cancer for which mortality was low (SMR 5+ years after irradiation: 0.53), even in women aged over 50 at irradiation (SMR 5+ years after irradiation: 0.14). The deficit was principally due to a large deficit of breast cancer in women with ovarian doses of at least 5 Gy.

Adult↗
PubMed1994

Paternal exposure not to blame.

The "Gardner hypothesis" suggests that an excess of childhood leukaemia near a nuclear reprocessing plant is caused by paternal exposure to ionizing radiation. But the evidence shows that this explanation is wrong.

Adolescent↗
PubMed1994

The use of meta-analysis in epidemiology: diet and cancers of the breast and colon.

The word "meta-analysis" has come to replace the simple descriptive phrase "scientific overview," and I fear has come to stay. The procedure was long overdue when introduced into medicine in the 1970s by Tom Chalmers in the United States and by Richard Peto and Iain Chalmers in the United Kingdom. Its objective was to contend more effectively with the apparent disparity of results obtained by multiple clinical trials, brought about by the expansion of the pharmaceutical industry and the growth in medical research. Sometimes the same treatment would be reported as beneficial, sometimes even to be harmful, and often to have no effect or to be no better than the standard treatment to which it was being compared, on the inadequate grounds that the differences observed were not statistically significant.

Alcohol Drinking↗
PubMed1994

Tobacco consumption and chemical analysis of cigarettes in Bahrain.

A 10.0% random sample of smokers in Bahrain was identified from a previous national morbidity survey which was completed in February 1983. Tobacco consumption and the average yields of tar, nicotine, and carbon monoxide (CO) of seven brands of cigarettes were examined. The 1982 adult tobacco consumption (2.3 kg) in Bahrain was generally lower than in developed countries. Similarly, cigarette per person consumption (734) was less than 69 other countries out of 130 that had data available. Tar, nicotine, and CO analysis of the five leading brands and two others which were previously popular in Bahrain showed that the average yields were mostly comparable with the same brands in the UK.

Adolescent↗
PubMed1994

The interpretation of time trends.

The requirements for valid comparison over time of cancer incidence and mortality are given in the opening paragraphs of this chapter. Among the more important of these is comparability between ICD revisions. Yet those entrusted with the decennial revisions of the International Statistical Classification of Diseases, Injuries and Causes of Death (ICD) have to try to reconcile several frequently contradictory demands. These include (a) meeting the needs of an ever widening number of users (hence, the change in title for the 10th revision to International Statistical Classification of Diseases and Related Health Problems); (b) incorporation of advances in the understanding of the biology of disease while avoiding ephemeral notions and classifications; and (c) the preservation of the continuity of time series. These desiderata have not always been met: some of the resulting problems have been discussed above. Despite the foregoing, the comparison of time trends in cancer incidence and mortality is a valid and useful exercise particularly when the investigator systematically considers the possible sources of bias and error. A low rate, if based on over a million person-years of observation, is, if underregistration can be ruled out, likely to reflect reality. Nevertheless, the smaller the number of cases and the greater the standard error of the rate, notably for the less frequent sites and the rarer histological types, the more attention needs to be paid to questions of possible artefact. Should the data for a given area or time period appear out of line with what might be expected, it may be worthwhile to check with the registry in question to see whether the trend could be explained on the basis of local circumstances, custom or practice. A formal review of the evidence for an apparent change over time, drawing on the experience of epidemiologists, pathologists and clinicians, as for example in non-Hodgkin's lymphoma, can be very useful (Levine and Hoover, 1992). Hitherto, much of the study of time trends of both incidence and mortality, notably those comparing international data, has been based on data published at the level of three digits in the ICD. Although such analyses will continue to be illuminating, future work is likely to give much greater emphasis to subsite and histological type, information that is difficult to publish routinely.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1993

Further follow up of mortality and incidence of cancer in men from the United Kingdom who participated in the United Kingdom's atmospheric nuclear weapon tests and experimental programmes.

OBJECTIVES: To study the long term effects of participation in the United Kingdom's atmospheric nuclear weapon tests and experimental programmes and to test hypotheses generated by an earlier report, including the possibility that participation in tests caused small hazards of leukaemia and multiple myeloma. DESIGN: Follow up study of mortality and cancer incidence. SUBJECTS: 21,358 servicemen and civilians from the United Kingdom who participated in the tests and a control group of 22,333 non-participants. MAIN OUTCOME MEASURES: Numbers of deaths; standardised mortality ratios; relative risks of mortality from all causes and 27 types of cancer. RESULTS: During seven further years of follow up the numbers of deaths observed in participants were fewer than expected from national rates for all causes, all neoplasms, leukaemia, and multiple myeloma (standardised mortality ratios 0.86, 0.85, 0.57, and 0.46); death rates were lower than in controls (relative risks 0.99, 0.96, 0.57, and 0.57; 90% confidence intervals all included 1.00). In the period more than 10 years after the initial participation in tests the relative risk of death in participants compared with controls was near unity for all causes (relative risk 0.99 (0.95 to 1.04) and all neoplasms (0.95 (0.87 to 1.04)); it was raised for bladder cancer (2.69 (1.42 to 5.20)) and reduced for cancers of the mouth, tongue, and pharynx (0.45 (0.22 to 0.93)) and for lung cancer (0.85 (0.73 to 0.99)). For leukaemia mortality was equal to that expected from national rates but greater than in controls for both the whole follow up period (1.75 (1.01 to 3.06)) and the period 2-25 years after the tests (3.38 (1.45 to 8.25)). CONCLUSION: Participation in nuclear weapon tests had no detectable effect on expectation of life or on subsequent risk of developing cancer or other fatal diseases. The excess of leukaemia in participants compared with controls seems to be principally due to a chance deficit in the controls, but the possibility that participation in the tests may have caused a small risk of leukaemia in the early years afterwards cannot be ruled out.

Environmental Exposure↗
PubMed1992

Trends in childhood leukaemia in the Nordic countries in relation to fallout from atmospheric nuclear weapons testing.

OBJECTIVE: To obtain further information about the risks of childhood leukaemia after exposure to ionising radiation at low doses and low dose rates before or after birth or to the father's testes shortly before conception. DESIGN: Observational study of trends in incidence of childhood leukaemia in relation to estimated radiation exposures due to fallout from atmospheric nuclear weapons testing during the 1950s and 1960s. SETTING: Nordic countries. SUBJECTS: Children aged under 15 years. MAIN OUTCOME MEASURES: Incidence rates of leukaemia by age at diagnosis, sex, country, and calendar year of diagnosis or year of birth; exposure category; relation between leukaemia and exposure for children aged 0-14 and 0-4 separately. RESULTS: During the high fallout period the average estimated dose equivalent to the fetal red bone marrow was around 140 mu Sv and the average annual testicular dose 140 mu Sv. There was little evidence of increased incidence of leukaemia among children born in these years. Doses to the red bone marrow of a child after birth were higher, and during the high exposure period children would have been subjected to an additional dose equivalent of around 1500 mu Sv, similar to doses received by children in several parts of central and eastern Europe owing to the Chernobyl accident and about 50% greater than the annual dose equivalent to the red bone marrow of a child from natural radiation. leukaemia incidence and red marrow dose was not related overall, but rates of leukaemia in the high exposure period were slightly higher than in the surrounding medium exposure period (relative risk for ages 0-14: 1.07, 95% confidence interval 1.00 to 1.14; for ages 0-4: 1.11, 1.00 to 1.24). CONCLUSIONS: Current predicted risks of childhood leukaemia after exposure to radiation are not greatly underestimated for low dose rate exposures.

Adolescent↗
PubMed1992

The lessons of life: keynote address to the nutrition and cancer conference.

Some 15 years ago there began to emerge a consensus among epidemiologists that diet might be responsible for 30-60% of cancers in the developed world, in the sense that it should be possible to reduce age-specific incidence rates by this amount by practicable dietary change. Within about 6 years it was also broadly agreed that the principal changes required to bring about this effect were a reduction in the consumption of fat; an increase in the consumption of fruit, green and yellow vegetables, dietary fiber, and some micronutrients; and possibly an improvement in the methods of food preservation. Very small effects, if any, were attributed to food additives and to the pollution of food by trace pesticides, which the public, who accepted much of the consensus advice, have increasingly regarded as important causes of risk. These past conclusions are reviewed in the light of increased knowledge of the etiology of cancer and the trends in its incidence. Contrary to common belief, the trends are broadly encouraging.

Age Factors↗
PubMed1992

Health and the environment in the 1990s.

Expectation of life at birth provides a simple measure of the state of health of a country. Differences in the expectation are examined in the United States over time and between males and females and Whites and non-Whites, and worldwide between market and nonmarket developed countries, and between developed and developing countries. The principal factors responsible for the trends and the current differences are changes in the social and physical environment, in personal behavior, and in medical care, and their relative importance is assessed. It is concluded that, at present, the principal environmental hazards worldwide are those associated with poverty of individuals within the market economies and of communities in the developing countries and that in the future, they will be the effects of overpopulation and the production of greenhouse gases.

Adolescent↗
PubMed1992

Molecular diagnostics for myelin proteolipid protein gene mutations in Pelizaeus-Merzbacher disease.

Pelizaeus-Merzbacher disease (PMD) is a clinically heterogeneous, slowly progressive leukodystrophy. The recent detection of mutations in the myelin proteolipid protein (PLP) gene in several PMD patients offers the opportunity both to design DNA-based tests that would be useful in diagnosing a proportion of PMD cases and, in particular, to evaluate the diagnostic utility of single-strand conformation polymorphism (SSCP) analysis for this disease. A combination of SSCP analysis and direct sequencing of PCR-amplified DNA was used to screen for PLP mutations in 24 patients affected with leukodystrophies of unknown etiology. Two heretofore undescribed mutations in the PLP gene were identified, Asp202His in exon 4 and Gly73Arg in exon 3. The ease and efficiency of SSCP analysis in detecting new mutations support the utilization of this technique in screening for PLP mutations in patients with unexplained leukodystrophies.

Base Sequence↗