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D Brewster

Publications and source records attributed to D Brewster.

At least 19 recordsLinked to original sources

Accuracy of reporting of family history of colorectal cancer.

BACKGROUND AND AIMS: Family history is used extensively to estimate the risk of colorectal cancer but there is considerable potential for recall bias and inaccuracy. Hence we systematically assessed the accuracy of family history reported at interview compared with actual cancer experience in relatives. METHODS: Using face to face interviews, we recorded family history from 199 colorectal cancer cases and 133 community controls, totalling 5637 first and second degree relatives (FDRs/SDRs). We linked computerised cancer registry data to interview information to determine the accuracy of family history reporting. RESULTS: Cases substantially underreported colorectal cancer arising both in FDRs (sensitivity 0.566 (95% confidence interval (CI) 0.433, 0.690); specificity 0.990 (95% CI 0.983, 0.994)) and SDRs (sensitivity 0.271 (95% CI 0.166, 0.410); specificity 0.996 (95% CI 0.992, 0.998)). There was no observable difference in accuracy of reporting family history between case and control interviewees. Control subjects similarly underreported colorectal cancer in FDRs (sensitivity 0.529 (95% CI 0.310, 0.738); specificity 0.995 (95% CI 0.989, 0.998)) and SDRs (sensitivity 0.333 (95% CI 0.192, 0.512); specificity 0.995 (95% CI 0.991, 0.995)). To determine practical implications of inaccurate family history, we applied family history criteria before and after record linkage. Only two of five families reported at interview to meet surveillance criteria did so after validation, whereas only two of six families that actually merited surveillance were identified by interview. CONCLUSIONS: This study has quantified the inaccuracy of interview in identifying people at risk of colorectal cancer due to a family history. Colorectal cancer was substantially underreported and so family history information should be interpreted with caution. These findings have considerable relevance to identifying patients who merit surveillance colonoscopy and to epidemiological studies.

Aged↗

Effects of activated macrophages and fibroblast growth factor on random skin flap survival in swine.

OBJECTIVE: To examine the effect of application of activated autologous macrophages and basic fibroblast growth factor (FGF) on random skin flap survival in swine. DESIGN: A randomized nonblinded controlled trial. According to a standard design, six dorsally based, random-pattern skin flaps were raised in each of 12 Yorkshire pigs. METHODS: Twenty-five milliliters of blood is harvested from each animal 20 to 24 hours prior to flap creation. Monocytes are isolated, placed in culture medium, and then activated by the addition of platelet-derived growth factor (PDGF) and tissue growth factor beta (TGF-alpha). Following an 18-hour incubation period, the monocytes are decanted and quantified, and their viability confirmed. These cells are then infused into the wound bed of the treatment flaps immediately following flap creation, and FGF is added prior to flap closure. The position of treatment and control flaps is systematically varied with regard to anterior-to-posterior and side-to-side flap positions within each animal. The area of superficial flap necrosis is evaluated on postoperative day 7, digitally scanned, and analyzed using graphics software. Control flaps are elevated similarly, but receive no placebo treatment. RESULTS: Two-way analysis of variance (ANOVA) demonstrated nonsignificant differences between pig side and anterior, middle, and posterior flap positions within treatment and control flap groups. Using side and position pooled data, a one-way ANOVA showed no statistically significant differences between treatment and control flaps. CONCLUSIONS: The cellular and biochemical events following creation of a surgical wound are complex and incompletely understood. Our attempt to augment the natural role of the macrophage in wound healing by employing cytokines to activate these cells and to accelerate their arrival by implanting them into the wound bed failed to enhance flap survival. Further study is warranted to ascertain the details of wound healing, particularly with respect to cytokine concentrations and the timing of their roles, if we are to find a clinically applicable means of enhancing flap survival.

Animals↗

The epidemiology of lung cancer in Scotland: a review of trends in incidence, survival and mortality and prospects for prevention.

OBJECTIVE: The aims of the study were to review long-term trends in lung cancer incidence, survival and mortality and, in light of these, to consider prospects for prevention. DESIGN: Descriptive epidemiological study. SETTING: Scotland. SUBJECTS: Incident cases of lung cancer, diagnosed 1959-1993, and registered with the Scottish Cancer Registry, and recorded deaths from lung cancer during 1919 to 1993. RESULTS: Scottish men and women continue to experience rates of lung cancer which are amongst the highest in the world. In men, incidence rose from 1959 to a peak in the late 1970s and is now decreasing steadily. In women, although starting from a lower baseline, incidence has risen steadily since 1959 (at an annual rate of increase of 5.0 per cent) and shows no evidence of a sustained decline. It is estimated that, between 1986 and 2000, the annual number of registrations in those aged under 85 years could fall by 20 per cent in men and rise by 8 per cent in women. Incidence in the most deprived areas of Scotland is twice that in the least deprived areas. Survival prospects have changed little over the last 25 years. In both sexes, trends in mortality mirror trends in incidence. CONCLUSION: Although lung cancer incidence in men is falling, it is likely that we have not yet reached the peak of the lung cancer epidemic amongst women. As up to 90 per cent of these tumours are attributable to tobacco, measures to control this drug should be the main focus of prevention activities. Emphasis should be placed on efforts to cut smoking prevalence among women and the most deprived groups of society and to reduce the uptake of smoking amongst the young. The fact that some other countries report more favourable survival figures suggests that there may be scope for improvements in diagnosis and therapy. The formulation of guidelines for best current practice in the management of lung cancer should aid progress in this respect.

Adult↗

Trends in incidence of and mortality from invasive cancer of the uterine cervix in Scotland (1975-1994).

OBJECTIVE: I. To identify major trends in the incidence of and mortality from invasive cancer of the cervix uteri in Scotland during the twenty year period 1975-1994; II. to consider the extent to which these trends may have been shaped by the introduction of systematic cervical screening. DESIGN: Analysis of annual age standardised and age specific rates for incidence and mortality, based on data collected by the Scottish Cancer Registry and the General Register Office for Scotland. SETTING: Scotland. SUBJECTS: Women registered with the Scottish Cancer Registry as having developed invasive cancer of the cervix during the period of interest. RESULTS: Annual all ages incidence rates of invasive cervical cancer show little overall change over the period 1975-1989, but exhibit a pronounced decline from 1990 onwards. All-ages mortality rates show clear evidence of decline during the period 1975-1994, the rate for 1994 being some 30% lower than that for 1975. Annual age-specific incidence rates show different patterns by age group, with clear evidence of decreasing trends in the age range 50-64 years but different patterns in younger and older age groups. Most age groups show steep declines in incidence from 1990 onwards. Age specific mortality rates for 1975-1994 exhibit the most pronounced decreasing trends in the age range 50-64 years. The trends identified are broadly similar to those experienced in England and Wales over an approximately comparable period. CONCLUSIONS: The overall (all ages) incidence of invasive cervical cancer in Scotland changed little during the period 1975-1989, but declined sharply from 1990 onwards. The most pronounced decline in incidence across the period 1975-1994 appears to have taken place in the age range 50-64 years. This decline has been accompanied by a commensurate fall in mortality in the same age range. These reductions in incidence and mortality may be attributable in part to increased coverage of cervical screening programmes during the period of interest. Evidence from other studies suggest that, without the increased coverage of cervical screening achieved during this period incidence rates in Scotland might have been seen to increase.

Adult↗

Efficacy of tepid sponging versus paracetamol in reducing temperature in febrile children.

A block randomized clinical trial to compare the efficacy of tepid sponging with the use of paracetamol in febrile children was undertaken at the Queen Elizabeth Central Hospital, Blantyre. Eighty children aged between 6 and 54 months with axillary temperatures of between > or = 38.5 degrees C and < or = 40 degrees C and a clinical diagnosis consistent with upper respiratory tract infection and/or malaria were block randomized to receive either oral paracetamol (15 mg/kg) or tepid sponging. Children receiving tepid sponging were sponged from head to toe (except the scalp) by leaving a thin layer of water on the body. If the body became dry it was repeated and continued until the axillary temperature fell to < 38.5 degrees C. Axillary temperature and assessment of discomfort (convulsions, crying, irritability, vomiting and shivering) were recorded every 30 minutes for 2 hours. A significantly greater and more rapid reduction of fever was demonstrated with paracetamol than with tepid sponging. Tepid sponging without antipyretics is often used to reduce fever, but our results suggest that this is effective only during the 1st 30 minutes. Paracetamol is clearly more effective than tepid sponging in reducing body temperature in febrile children in a tropical climate.

Acetaminophen↗

The effects of macrophages on the survival of random skin flaps in swine.

Tissue macrophages play a critical role in neovascularization by releasing angiogenic cytokines. Macrophages normally arrive into a wound bed 48 to 96 hours following an injury. Introducing macrophages into a wound bed at the time of closure would theoretically stimulate neovascularization in the traumatized tissue prior to what is normally observed. The ability to promote early angiogenesis could be an important factor in the survival of an extended skin flap. By taking advantage of advanced cell-sorting techniques, the authors developed the first study to evaluate the effect of placing a purified autologous macrophage population into an extended skin flap. We created 72 dorsally based random skin flaps in Yorkshire pigs; 48 of these wounds received autologous macrophages while 24 flaps served as controls. The macrophages were obtained by utilizing monoclonal antibodies in conjunction with flow cytometry. The skin flaps were evaluated on postoperative day 6 for their viability. Analysis of the data showed no statistically significant difference between the control and treatment flaps. There was, however, a trend of increased survival for flaps treated with macrophages. This is the first study to investigate using a purified population of cells to improve the survival of random skin flaps.

Animals↗

Registration of lung cancer in Scotland: an assessment of data accuracy based on review of medical records.

Lung cancer represents a major public health problem in Scotland. Cancer registration data permit the approximate incidence of this disease to be measured directly and the projected incidence to be modelled. Thus, in addition to epidemiologic studies and survival analyses, cancer registration data may be used for planning and monitoring relevant health services. Since the value of the data depends on their quality, we undertook a large-scale study of the accuracy of cancer registration data in Scotland. The medical records of a random sample of cancer registrations attributed to the year 1990 were sought. The sample contained 340 registrations of lung cancer, 309 (91 percent) of which had relevant medical records available for scrutiny. Registration details were reabstracted from available records and compared with data in the registry. Results revealed 19 discrepancies in identifying items of data (surname, forename, gender, and date of birth) involving 16 (5.2 percent) patients. Most were trivial and would not disturb record linkage. Discrepancy rates were found to be: 7.8 percent in postcode of residence at the time of diagnosis, 10 percent in 'anniversary date' (excluding differences of six weeks or less), 12.5 percent in histologic verification status; 4.2 percent in ICD-9 site code (the first three digits), and 15.5 percent in four digit ICD-O morphology code (excluding 'inferred' morphology codes). This relatively high level of accuracy gives weight to routinely published incidence figures and supports the use of these data for exploratory epidemiologic studies, assessment of health care needs, and calculation of survival.

Age Factors↗

Effect of glutathione depletion and oxidative stress on the in vitro cytotoxicity of velnacrine maleate.

Velnacrine maleate (Mentane) is an aminoacridine drug developed for the treatment of Alzheimer's disease. Although velnacrine maleate has not been observed to cause prominent cytotoxicity in in vitro hepatocyte cultures, this drug was associated with elevated serum levels of hepatic enzymes in clinical trials. The purpose of the present study was to manipulate cultures of rat hepatocytes in an attempt to elicit a cytotoxic response from this drug and to better understand the in vitro mechanisms of action. Cytotoxicity was evaluated by measuring lactate dehydrogenase (LDH) leakage, neutral red (NR) uptake, and 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide (MTT) reduction. Preliminary studies with fluorescent probes did not indicate a role for calcium influx or the formation of reactive oxygen species in the cytotoxicity of velnacrine maleate. However, depletion of cellular glutathione (GSH) by diamide (DA) pretreatment resulted in a cytotoxic response at concentrations of velnacrine maleate (1 and 10 micrograms/ml) which were approximately 25-fold lower than those in the absence of DA. Similarly, pretreatment with velnacrine maleate enhanced the cytotoxicity of DA. Pre-exposure of cells to a mixture of DA and t-butyl hydroperoxide (t-BHP) at non-toxic concentrations resulted in significant cytotoxicity of the hepatocyte cultures by velnacrine maleate. Results from these studies indicate that oxidative stress and GSH depletion may enhance Alzheimer patients' susceptibility to the hepatotoxic potential of aminoacridine drugs.

Alzheimer Disease↗