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Biomedical subjects

M Booth

Publications and source records attributed to M Booth.

At least 37 records · Page 2Linked to original sources

Pooled analysis of 3 European case-control studies: I. Reproductive factors and risk of epithelial ovarian cancer.

The role of reproductive factors in the aetiology of epithelial ovarian cancer has been re-assessed in a meta-analysis of 3 hospital-based case-control studies conducted in Europe (i.e. Italy, the United Kingdom and Greece), providing a total dataset of 1,140 cases and 2,724 controls. Multiple logistic regression models were used to obtain relative risk (RR) estimates adjusted for study centre, age, socio-cultural indicators, age at menopause, and oral contraceptive use. The risk decreased with increasing number of births and the trend in risk was significant (chi 2(1) = 7.50, p less than 0.01). In comparison to nulliparous women, those who reported 4 or more births had a 40% reduction in risk of ovarian cancer (RR = 0.6, 95% confidence interval, CI: 0.4-0.8). An RR estimate of 1.4 (95% CI: 1.1-1.7) as found, overall, for age of 35 or more at first birth compared to age of 25 or less at first birth. In each stratum and overall, nulliparous women did not appear to be at increased risk compared to those who delayed birth of their first child until age 35 or more. In each study, as well as in the overall dataset, an inverse association between number of abortions and ovarian cancer risk emerged. Overall, the inverse relationship was highly significant, RR estimates for 1 and 2 or more abortions, as compared to none, being 0.9 (95% CI: 0.8 and 1.1) and 0.7 (95% CI: 0.6-0.9) respectively. The effects of parity, age at first birth and number of abortions emerged consistently in various strata of study centre and age.

Abortion, Spontaneous

Pooled analysis of 3 European case-control studies of ovarian cancer: II. Age at menarche and at menopause.

The role of age at menarche and at menopause on epithelial ovarian cancer risk was re-assessed in a combined analysis of 3 hospital-based case-control studies conducted in Italy, the United Kingdom and Greece, which produced a total of 1,140 cases and 2,724 controls. In the overall dataset, there was no evidence of an association with age at menarche: compared with women whose menarche occurred at age 15 or over, the relative risk (RR) estimates were 1.0 [95% confidence interval (CI) 0.8 to 1.2] for those with menarche at ages 12 to 14, and 1.0 (95% CI 0.8-1.2) for those with menarche below age 12. There was no consistent interaction between age at menarche and study centre or age at diagnosis. In relation to age at menopause, compared with women whose menopause occurred at age 44 or earlier, the RR was 1.4 between 45 and 49, 1.6 between 50 and 52 and 1.9 above 52. The strength of the association was apparently (but not significantly) greater in the British than in the Greek or Italian dataset. The effect of age at menopause tended to be long-lasting and, if anything, to increase across subsequent age-groups. The large dataset, and the replication of results in different studies, provide more definite and precise information than previously available on the absence of appreciable effect of age at menarche on subsequent ovarian cancer risk in developed countries. For age at menopause, there was a direct and consistent trend in risk, but the association was relatively weak, with RRs below 2 even between extreme categories.

Adult

Pooled analysis of 3 European case-control studies of epithelial ovarian cancer: III. Oral contraceptive use.

The relationship between use of oral contraceptives (OCs) and other contraceptive methods and the risk of ovarian cancer was examined in a combined analysis of 3 hospital-based case-control studies conducted in Italy, the United Kingdom, and Greece, for a total of 971 ovarian cancer cases and 2,258 controls under age 65. Compared with never-users, the combined multivariate relative risk (RR) for ever-users was 0.6 (95% confidence interval, CI = 0.4-0.8) and the estimates were consistent in the 3 datasets. The protection was also similar across strata of age and parity. Considering various measures of OC use, available in the Italian and British datasets only, the protection conveyed on ovarian cancer risk increased with the duration of use and persisted in the medium-long period: the RR in women reporting their last OC use greater than or equal to 15 years prior to diagnosis was 0.5 (95% CI = 0.2-1.0). The risks in ever-users were appreciably lower in those women who reported their first OC use before 25 years of age (RR = 0.3 for first use before age 25, 0.8 for first use at age 25-34 and 0.7 at 35 years or after). Such findings emerged similarly from Italian and British data. This combined analysis, besides offering further quantitative estimates of the protective effects of OCs on ovarian cancer risk in European populations, provides useful insights into the time pattern of the relationship between OC use and ovarian carcinogenesis, suggesting that the protection persists for 15 years or more after cessation of use and may be larger for use at younger age.

Adult

Job satisfaction amongst resident medical officers.

This paper reports the results of an attitudinal survey of resident medical officers (RMOs) to assess their level of job satisfaction. The survey questionnaire consisted of 31 statements or questions concerning RMOs' attitudes towards various aspects of their work. One-third of RMOs employed in New Zealand hospitals were questioned, totalling 524 doctors, and yielding a 74.4% response. Levels of job satisfaction were higher than expected given recent publicity which has stressed dissatisfaction and low morale. The study found that about 66% were satisfied, 20% were neutral and 14% were dissatisfied. Registrars were significantly more satisfied than house surgeons. There were some relatively minor differences by region and specialty. There were no differences by gender, medical school, or whether partnered or nonpartnered. Hours of work, pay, holidays, rostering and other general working conditions were considered by most RMOs to be adequate to positive. The nature of the work was felt to be interesting, stimulating and providing an adequate level of responsibility. However, low morale seems endemic amongst RMOs in hospitals. There was a generally unfavourable view of hospital administration by all RMOs. Of those who claimed to be satisfied with their jobs, 28% stated that they would not re-enroll at medical school again if they had prior knowledge of their working conditions.

Attitude of Health Personnel

Health related selection and death rates in the United Kingdom Atomic Energy Authority workforce.

Follow up data on 37,355 employees of the United Kingdom Atomic Energy Authority (UKAEA) for the period 1946-79 were analysed to investigate the extent to which selection for work on the basis of health affected subsequent death rates. Causes of death were grouped into two broad categories for analysis: all cancers and all other causes of death. Evidence for an effect of selection of healthy individuals into the workforce was sought primarily by examining standardised mortality ratios (SMRs) by period since recruitment. SMRs for both categories were particularly low during the first two years after recruitment (SMR = 69, 95% confidence interval (CI) 48-97 for all cancers; SMR = 55, 95% CI 44-69 for all other causes of death). SMRs for all cancers did not increase significantly with period since recruitment (chi 2 for trend = 0.4, p = 0.53) but did increase for causes of death other than cancer (chi 2 for trend = 11.1, p = 0.001). Although adjustment for social class strengthened the association between death from causes other than cancer and period since recruitment (chi 2 for trend = 18.8, p less than 0.001), simultaneous adjustment for all confounding factors considered (age at death, sex, calendar period of death, geographical location of the workforce, and social class) produced results broadly similar to those obtained from the unadjusted analyses for both cause of death categories. SMRs remained low even after 25 years of follow up (SMR = 84, 95% CI 69-101 for all cancers; SMR = 81, 95% CI 72-91 for all other causes of death). The persistently low SMRs observed in this workforce are unlikely to be due to the selection of healthy individuals at the time of recruitment but may be due to differences in sociodemographic and lifestyle characteristics. The effect on mortality of selection of individuals out of the workforce due to ill health was also examined. SMRs were particularly high for both categories in the first two years after termination of employment in individuals who left before normal retirement age (SMR = 167, 95% CI 131-211 for all cancers; SMR = 149, 95% CI 128-173 for all other causes of death). In comparison, death rates for the subsequent three years after termination of employment were lower (SMR = 89, 95% CI 67-115 for all cancers, SMR = 99, 95% CI 85-115 for all other causes of death). The persistently low SMRs observed in this workforce are unlikely to be due to the selection of healthy individuals at the time of recruitment but may be due to differences in sociodemographic and lifestyle characteristics. The effect on mortality of selection of individuals out of the workforce due to ill health was also examined. SMRs were particularly high for both categories in the first two years after termination of employment in individuals who left before normal retirement age (SMR = 167, 95% CI 131-211 for all cancers; SMR 149,95% CI 128-173 for all other causes of death). In comparison, death rates for the subsequent three years after termination of employment were lower (SMR = 89, 95% CI 67-115 for all cancers SMR = 99, 95% CI 85-115 for all other causes of death). Apart from this initial fall, there was little evidence of a systematic increase or decrease in mortality with increasing period was not significantly associated with durationof employment for either cause of death category either before or after adjustment for confounding factors. Whereas selection of individuals into or out of the workforce on the basis of health affects the way in which death rates change with time, other factors such as sociodemographic characteristics or health related behaviour determine the general level of mortality in the longer run. The persistently low SMRs observed in this workforce throughout the follow up period suggest that selection on the latter factors are likely to have had a considerable effect on death rates in the UKAEA workforce.

Adult

Risk factors for ovarian cancer: a case-control study.

A hospital-based case-control study of ovarian cancer was conducted in London and Oxford between October 1978 and February 1983. Menstrual characteristics, reproductive and contraceptive history and history of exposure to various environmental factors were compared between 235 women with histologically diagnosed epithelial ovarian cancer and 451 controls. High gravidity, hysterectomy, female sterilisation and oral contraceptive use were associated with a reduced risk of ovarian cancer. Infertility and late age at menopause were associated with an increase in risk. While these factors were related, they were each found to be independently associated with ovarian cancer risk after adjusting for the effect of the other factors.

Adult

Mortality of employees of the Atomic Weapons Establishment, 1951-82.

A total of 22,552 workers employed by the Atomic Weapons Establishment between 1951 and 1982 were followed up for an average of 18.6 years. Of the 3115 who died, 865 (28%) died of cancer. Mortality was 23% lower than the national average for all causes of death and 18% lower for cancer. These low rates were consistent with the findings in other workforces in the nuclear industry and reflect, at least in part, the selection of healthy people to work in the industry and the disproportionate recruitment of people from the higher social classes. At some time during their employment 9389 (42%) of the workers were monitored for exposure to radiation, the average cumulative whole body exposure to external radiation being 7.8 mSv. Their mortality was generally similar to that of other employees, even when exposures were lagged by 10 years. The rate ratio after a 10 year lag in workers with a radiation record compared with other workers was 1.01 (95% confidence interval 0.92 to 1.10) for all causes of death and 1.06 (0.89 to 1.27) for all malignant neoplasms. The only significant differences were for prostatic cancer (rate ratio 2.23; 95% confidence interval 1.13 to 4.40) and for cancers of ill defined and secondary sites (rate ratio 2.37; 1.23 to 4.56). Cancers of lymphatic and haemopoietic tissues were notable for their low occurrence in the study population, with only four deaths from leukaemia and two from multiple myeloma in workers with a radiation record, 9.16 and 3.55 deaths respectively being expected on the basis of national rates. Among workers who had a radiation record 3742 (40%) were also monitored for possible internal exposure to plutonium, 3044 (32%) to uranium, 1562 (17%) to tritium, 638 (7%) to polonium, and 281 (3%) to actinium. In these workers mortality from malignant neoplasms as a whole was not increased, but after a 10 year lag death rates from prostatic and renal cancers were generally more than twice the national average, these excesses arising in a small group of workers monitored for exposure to multiple radionuclides. Though mortality from lung cancer in workers monitored for exposure to plutonium was below the national average, it was some two thirds higher than in other radiation workers, the excess being of borderline statistical significance. Mortality from malignant neoplasms as a whole showed a weak and non-significant increasing trend with increasing level of cumulative whole body exposure to external radiation. When the exposures were lagged by 10 years the trend became stronger and significant, the estimated increase in relative risk per 10 mSv being 7.6% (95% confidence interval 0.4% to 15.3%). This trend was confined almost entirely to workers who were also monitored for exposure to radionuclides (p<0.001), the main contributions coming from lung cancer and prostatic cancer. Exposures of the lung and prostate from internal sources of radiation were not quantified, except for the contribution from tritium. It was therefore not possible to assess the extent to which the associations were due to internally deposited radionuclides rather than external exposure. The finding for prostatic cancer taken in conjunction with the results of other studies suggest a specific occupational hazard in a small group of workers in the nuclear industry who had comparatively high exposures to external radiation and who were also monitored for internal exposure to multiple radionuclides. Research is needed to discover whether any of the radionuclides and other substances concerned are concentrated in the prostate. The occurrence of lung cancer in this workforce requires further investigation taking into account smoking habits and tissue doses from inhaled radionuclides.

Cardiovascular Diseases

Production of hemopoietic growth factors and gamma-interferon by large granular lymphocytes from patients with T gamma lymphocytosis.

Two patients with T gamma lymphocytosis in whom expanded large granular lymphocyte (LGL) populations were detected in peripheral blood and bone marrow are described. The surface antigen phenotypes of the LGL from these patients were similar with a major portion of cells carrying T3, T8, T11 and Leu7 markers. However, whereas fresh LGL from both patients demonstrated antibody-dependent cell cytotoxicity (ADCC), natural killer (NK) cell function was present in one case but absent in the other. Supernatants from enriched suspensions of the LGL unstimulated by exogenous antigen or mitogens were shown to contain significant amounts of hemopoietic growth factors colony-stimulating activity (CSA) and burst-promoting activity (BPA). In one case gamma-interferon was also detected. This study contributes to the accumulating evidence that LGL are able to generate factors which have the capacity to influence the proliferation of hemopoietic progenitor cells in vitro.

Colony-Forming Units Assay

Further assessment of the effects of occupational radiation exposure in the United Kingdom Atomic Energy Authority mortality study.

The United Kingdom Atomic Energy Authority mortality study was designed to investigate the relation between exposure to ionising radiation and mortality among the authority's employees. The present paper describes some of the problems encountered in assessing occupational exposure to low dose radiation and examines whether the study's conclusions about the relation between exposure and mortality could be affected by the methods used. The study covered the years 1946 to 1979 during which time the frequency with which personal film dosimeters were issued changed from weekly to monthly, and the threshold level below which measurements were not made decreased 20-fold. Exposure from "below threshold" readings made an important contribution to total exposure in the early years. Estimates, based on the remeasurement of a sample of old films, indicated that the average whole body exposure before 1961 may have been about double that which was measured. Furthermore, although records were kept of when dosimeters were lost or damaged, the associated exposures were unknown and could only be estimated. Workers whose dosimeter readings were missing for more than 5% of the time during which they were monitored had higher all cause mortality (p = 0.04) and higher mortality from accidents and violence (p = 0.05) than other radiation workers. The results of analyses of mortality in relation to whole body exposure were compared when the exposures included estimates of the below threshold and missing exposures and when these exposures were assumed to be zero. Some of the findings differed, but none changed sufficiently to alter the general conclusions. Although the trend in mortality from all cancers changed from one in which the increase with exposure was far from statistically significant (p = 0.3) when the below threshold and missing values were assumed to be zero to one that approached significance (p = 0.06) after they were estimated, calculations of the annual excess deaths from cancer per unit dose resulted in broadly similar estimates. Studies of workers exposed to ionising radiation usually focus on mortality in relation to whole body exposure. In the present paper its relation to neutron and surface exposure is also examined. Workers with measured neutron exposures had significantly lower all cause mortality than other workers with a radiation record (p = 0.03). Surface exposure was significantly related to mortality from all cancers (p = 0.02) and prostatic cancer (p less than 0.001). Some data on cancer registration are presented but these cannot be readily interpreted because cancer registration details were available only for ex-employees who may not be typical of the workforce as a whole.

Humans

Enrichment of progenitor cells from human marrow.

Suspensions enriched for myeloid and erythroid colony-forming cells were prepared from human marrow by simultaneous treatment of low-density cells with the monoclonal antibodies Campath-1 and 80H.3, followed by immune-rosetting; lymphocytes and monocytes were successfully removed by this method. The final suspension contained 22% of blasts and 70% primitive myeloid-monocytic cells. GM-CFCs, counted after 14 days of culture, were enriched 21-fold. Of all cells present in the final suspension, 10.8% were day 8 GM cluster-forming cells, 2.3% were day 8 GM colony-forming cells, 2.4% were day 7 CFU-E, 0.9% were day 14 GM cluster-forming cells, 1.1% were day 14 GM colony-forming cells, and 0.6% were day 14 BFU-E. After enrichment, BFU-E became markedly more dependent on the addition of 5637-conditioned medium as a source of growth factors, suggesting that lymphocytes and/or monocytes support erythroid progenitor growth in cultures of unfractionated marrow. By removing these cells, we obtained a sensitive assay for burst-promoting activities in conditioned media. This procedure can be used to study the roles of marrow lymphocytes and monocytes in hemopoiesis as well as providing a basis for the purification of normal and aberrant progenitors.

Bone Marrow Cells

Collection and validation of data in the United Kingdom Atomic Energy Authority mortality study.

The United Kingdom Atomic Energy Authority mortality study investigated the relation between mortality and recorded exposure to ionising radiation among employees working at the authority's seven establishments between 1946 and 1979. This report examines the design of the study and methods of data collection and validation. The completeness of the study population was deemed to be unsatisfactory at two establishments, where records of employment before 1965 had been destroyed. Assessment of the magnitude of the deficit led to the conclusion that the data from these establishments were too incomplete for inclusion in the mortality analysis. At the other establishments validation showed that the data collected were accurate and unbiased. Certain characteristics of the 39 546 employees included in the mortality analysis were identified which were relevant in interpreting the findings.

Data Collection

Mortality of employees of the United Kingdom Atomic Energy Authority, 1946-1979.

An analysis was conducted of 3373 deaths among 39 546 people employed by the United Kingdom Atomic Energy Authority between 1946 and 1979, the population having been followed up for an average of 16 years. Overall the death rates were below those prevailing in England and Wales but consistent with those expected in a normal workforce. At ages 15-74 years the standardised mortality ratios (SMRs) were 74 for deaths from all causes and 79 for deaths from all cancers. Mortality from only four causes was above the national average--namely, testicular cancer (SMR 153; 10 deaths), leukaemia (SMR 123; 35 deaths), thyroid cancer (SMR 122; three deaths), non-Hodgkin's lymphoma (SMR 107; 20 deaths)--but in none was the increase significant at the 5% level. Half of the authority's employees were recorded as having been monitored for exposure to radiation, their collective recorded exposure being 660 Sv (65 954 rem). Among these prostatic cancer was the only condition with a clearly increased mortality in relation to exposure. Of the 19 men who had a radiation record and died from prostatic cancer at ages 15-74 years, nine had been monitored for several different sources of exposure to radiation. The standardised mortality ratios were 889 (six deaths) in employees monitored for contamination by tritium, 254 (nine deaths) in those monitored for contamination by other radionuclides, and 385 (nine deaths) in those with dosimeter readings totalling more than 50 mSv (5 rem); but the same nine subjects tended to account for each of these significantly raised ratios. Because multiple exposures were common and other relevant information was not available the reason for the increased mortality from prostatic cancer in this population could not be determined and requires further investigation. Excess mortality rates of 2.2 and 12.5 deaths per million person years per 10 mSv (1 rem) were estimated for leukaemia and all cancers, respectively. The confidence limits around these estimates were wide, included zero, and made it unlikely that the International Commission on Radiological Protection's cancer risk coefficients were underestimated by more than 15-fold. Thus despite this being the largest British workforce whose mortality has been reported in relation to low level ionising radiation exposure, even larger populations will need to be followed up over longer periods before narrower ranges of risk estimates can be derived.

Adolescent