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Biomedical subjects

M Booth

Publications and source records attributed to M Booth.

At least 19 recordsLinked to original sources

The development of an age structured model for schistosomiasis transmission dynamics and control and its validation for Schistosoma mansoni.

Mathematical models are potentially useful tools to aid in the design of control programmes for parasitic diseases. In this paper, a fully age structured epidemiological model of human schistosomiasis is developed and parameterized, and used to predict trends in infection prevalence, intensity and prevalence of heavy infections over age and time during several rounds of mass and age targeted treatment. The model is validated against data from a Schistosoma mansoni control programme in Kenya.

Adolescent

BCL-2 expression by leukaemic blasts in a SCID mouse model of biphenotypic leukaemia associated with the t(4;11)(q21;q23) translocation.

Acute leukaemia of infancy is associated with abnormalities at chromosome band 11q23, and has a poor prognosis. The gene involved. Mixed Lineage Leukaemia (MLL), has been identified and has the characteristics of a transcription factor. The BCL-2 gene responsible for blocking of programmed cell death is highly expressed in a number of haematological malignancies, both with and without the t(14;18) translocation. Those without the translocation include acute lymphoblastic leukaemia (ALL), acute myeloid leukaemia (AML) and chronic lymphocytic leukaemia (CLL). In these diseases the BCL-2 protein is implicated in drug resistance to apoptosis-inducing chemotherapeutic agents. High BCL-2 expression is also associated with autonomous growth of leukaemic blasts in culture and predicts a poor prognosis. The SEM cell line, established using blood lymphoblasts from a 5-year-old girl in first relapse with t(4;11) ALL, expresses lymphoid (CD19) and myeloid (CD13) cell surface markers. In cell culture, a subpopulation of cells (< 30%) express the BCL-2 protein. A reproducible model of true biphenotypic leukaemia in the SCID mouse has been established using the SEM-K2 cell line (a subclone of the SEM cell line). Between 5 and 50 million cells injected intravenously (i.v.) produce complete replacement of the murine bone marrow by day 30, associated with blood lymphoblastosis and infiltration of the spleen. No tumour masses were seen. Fluorescence in situ hybridization (FISH) analysis of the cell line and blood from the SCID-human (SCID-hu) chimaera has confirmed the presence of the t(4;11). Reverse transcriptional-polymerase chain reaction (RT-PCR) reveals that the breakpoint lies between exons 7 and 8 of the MLL-1 gene on chromosome 11 (the main breakpoint region). A further translocation, t(7;13), has been identified. Fluorescent antibody cell sorter (FACS) analysis of tumour material recovered from the SCID-hu model confirms expression of CD19 and CD13 identical to that of the cell line. In addition, BCL-2 expression in SCID-hu marrow is now seen in the majority of tumour cells. BCL-2 expression appears to confer a survival advantage to the blast cells in vivo. This reproducible model of biphenotypic leukaemia suggests that BCL-2 expression may play a role in leukaemogenesis. The model is suitable for the investigation of gene-targeted therapy, including antisense oligonucleotides, directed towards the MLL and BCL-2 genes.

Animals

Audit reduces the reluctance to use single fractions for painful bone metastases.

We have conducted three audits of the number of fractions used within our department to treat symptomatic bone metastases. The initial audit identified 133 patients treated for bone metastases in a 3-month period using 538 fractions (mean number of fraction = 4.1, range 1-14). These figures were presented at our audit meeting along with a literature review which provided no evidence of any advantage of multiple fractions over single fractions. Departmental guidelines recommending the use of single fractions were established. A subsequent audit identified 149 patients treated with 520 fractions (mean number of fractions = 3.5, range 1-11). A third audit identified 148 patients treated with 335 fractions (mean number of fractions = 2.3, range 1-10). Audit has resulted in a reduction in the number of fractions used to treat bone metastases in our department. The major effect was seen after the second audit.

Bone Neoplasms

Comparative prevalences of Ascaris lumbricoides, Trichuris trichiura and hookworm infections and the prospects for combined control.

Programmes to control Ascaris lumbricoides, Trichuris trichiura and hookworm infections have often been targeted at each infection separately, but the advent of benign and broad-spectrum anthelmintics suggests that combined control may be feasible. The extent to which the infections co-occur in communities will determine the need for, and potential benefits of, such a combined approach. This paper examines the comparative distribution of the three geohelminths in different geographical areas and shows that A. lumbricoides and T. trichiura have closely related distributions, while hookworm infection is largely independent of the other two. These results indicate that many communities are at risk of disease from infection by more than one species of helminth. The similar distributions and epidemiological characteristics of A. lumbricoides and T. trichiura suggest that simultaneous control of these two parasites by the same strategy would be feasible and highly beneficial to communities. Multiple species control strategies which aim to control hookworm infection may require a more complicated protocol with more precise locality targeting.

Africa, Eastern

A case-control study of benign ovarian tumours.

STUDY OBJECTIVE: The aim was to investigate the association between reproductive, contraceptive, and menstrual factors and risk of benign ovarian tumours. DESIGN AND SETTING: This was a case-control study carried out in six London Hospitals. An interviewer administered questionnaire was used. SUBJECTS: 62 women with a benign epithelial ovarian neoplasm, 37 women with a functional ovarian cyst, and 20 women with a dermoid cyst presenting between 1983 and 1985, together with 132 controls, took part in the study. MAIN RESULTS: On average, women with a benign epithelial ovarian neoplasm were older than those with a functional ovarian cyst, who in turn were older than those with a dermoid cyst. Nulliparity and infertility were associated with an increased risk, and multiparity with a reduced risk, of benign epithelial ovarian neoplasms. Infertility and pelvic inflammatory disease were associated with increased risks of functional and dermoid cysts. Recent use of oral contraceptives was associated with a reduced risk of all three tumour types. CONCLUSIONS: The findings suggest that the aetiology of ovarian cysts and benign epithelial ovarian neoplasms may differ. The aetiology of benign and malignant epithelial ovarian neoplasms may be similar, however, since some risk factors are shared.

Adolescent

Regional differences in mental health in Great Britain.

STUDY OBJECTIVE: The aim was to study the pattern and magnitude of regional differences in psychiatric morbidity and compare these with regional differences in all cause mortality. DESIGN: The study was a secondary analysis of data from a cross sectional survey. The main outcome was the prevalence of psychiatric morbidity. This was assessed using the general health questionnaire, a self administered measure of neurotic symptoms. SETTING: England, Wales and Scotland. PARTICIPANTS: 9003 adults were selected from the electoral register. MAIN RESULTS: The prevalence of psychiatric morbidity was 31% with a statistically significant difference between the regions (p = 0.006). All four northern regions of England had a higher prevalence of psychiatric morbidity than the four southern regions. These differences were comparable in size to the regional differences in all cause mortality. Scotland had low psychiatric morbidity but high all cause mortality while Greater London had high psychiatric morbidity but low mortality. Regional variation in psychiatric morbidity was less marked within social classes I and II and among those living in urban areas. CONCLUSIONS: Psychiatric morbidity is common and is an important public health problem. Regions with relatively high psychiatric morbidity did not always have relatively high mortality. Knowledge of the causes of these regional differences could ultimately lead to preventive action and be important when distributing health service resources.

Cross-Sectional Studies

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