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L Sharp

Publications and source records attributed to L Sharp.

At least 19 recordsLinked to original sources
PubMed2000

Glutathione S-transferase polymorphisms and colorectal cancer: a HuGE review.

The genes glutathione S-transferase M1 (GSTM1) (chromosome 1p13.3) and glutathione S-transferase T1 (GSTT1) (22q11.2) code for cytosolic enzymes glutathione S-transferase (GST)-mu and GST-theta, respectively, which are involved in phase 2 metabolism. Both genes may be deleted. There is geographic and ethnic variation in genotype frequencies for both genes. In developed countries, colorectal cancer is the second most common cancer. Colorectal cancer has been inconsistently associated with polycyclic aromatic hydrocarbons in diet and tobacco. Because GST enzymes are involved in polycyclic aromatic hydrocarbon metabolism, it has been postulated that genotype may modify colorectal cancer risk associated with polycyclic aromatic hydrocarbon exposure. No consistent associations between GSTM1 or GSTT1 genotype and colorectal cancer have been observed. However, most studies have methodological limitations. Few have investigated gene-environment interactions. No interactions between GSTM1 or GSTT1 genotype and smoking and colorectal cancer risk have been reported. One polyp study suggests an interaction between GSTM1 genotype and smoking. Two studies suggest increased disease risk in subjects with high meat intake and GST nonnull genotype, contrary to the underlying hypothesis. One study suggests a strong inverse relation between colorectal adenomas and broccoli consumption, particularly in subjects who are GSTM1 null. These finding require confirmation. Methods for determining GSTM1 and GSTT1 genotype are well established. Population testing is not currently justified.

Chromosomes, Human, Pair 1↗
PubMed1999

Incidence of childhood brain and other non-haematopoietic neoplasms near nuclear sites in Scotland, 1975-94.

OBJECTIVES: To examine the risk of cancers other than leukaemia and non-Hodgkin's lymphoma in children resident in the vicinity of nuclear sites in Scotland. METHODS: The study dataset comprised registrations of cancer other than leukaemia and non-Hodgkin's lymphoma diagnosed in children aged under 15 in the period 1975-94. These were validated for completeness and accuracy and analysed in two groups: (a) tumours of the central nervous system and (b) other malignant tumours (excluding leukaemia and non-Hodgkin's lymphoma). Around each nuclear site observed cases (O) were enumerated and expected numbers (E) calculated with adjustment for age, sex, deprivation, and an urban-rural category. Stone's maximum likelihood ratio test (MLR) was used to determine whether there was any evidence of increased risk of these neoplasms among children living within 25 km of one of the nuclear sites investigated. The significance level of each MLR statistic was estimated by simulation. RESULTS: More tumours of the central nervous system were observed than expected within 25 km of Dounreay (O/E = 1.14), Hunterston (1.14), and Rosyth (1.22). These results were based on 2, 26, and 136 observed cases, respectively. The unconditional MLR was significant only for Rosyth (p = 0.006). The conditional application of the MLR test for Rosyth was not significant (p = 0.771). For the group of other malignant neoplasms, the unconditional MLR test was not significant for any of the seven sites. CONCLUSIONS: There was no evidence for generally increased risk of either tumours of the central nervous system or other malignant tumours in children living near nuclear sites. The significant excess of tumours of the central nervous system around Rosyth is likely to be due to the high incidence of these tumours in east central Scotland. Further investigations in this area are warranted.

Adolescent↗
PubMed1998

Quality of life in metastatic prostate cancer among men of lower socioeconomic status: feasibility and criterion related validity of 3 measures.

PURPOSE: Identification of metastatic disease progression is often difficult but important. Previous studies of quality of life in metastatic disease have been limited by the small number of respondents who were not white or of lower socioeconomic status. Quality of life assessment is generally done using self-administration techniques but this method is of limited usefulness for patients of low socioeconomic status, many of whom have limited reading abilities. We evaluated the feasibility and validity of interviewer administration of 3 quality of life instruments for patients of low socioeconomic status with metastatic prostate cancer. MATERIALS AND METHODS: We used instruments previously validated with self-administration methodology, including the European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire-30, Functional Assessment of Cancer Therapy-General Scale and Quality of Life Index. Subjects were men with metastatic prostate cancer with stable (78) or progressive (32) disease at 4 Veterans Affairs medical centers and 1 other site. Of the patients 94% were Veterans Affairs patients and more than 60% were black. RESULTS: Each quality of life instrument required less than 10 minutes of interviewer administration and was able to discriminate between patients with stable versus progressive disease on several health status domains. CONCLUSIONS: These data support the feasibility and validity of quality of life measurement in patients of low socioeconomic status with metastatic prostate cancer. Consideration should be given to adding quality of life instruments to patient encounter even among low socioeconomic status, low literacy populations.

Aged↗
PubMed1998

HRGs for benchmarking and contractual arrangements: a poisoned chalice?

A study was undertaken to determine if healthcare resource groups (HRGs) are reliable, reproducible in different centres and accurately reflect clinical activity. During a 3 month period, 385 finished consultant episodes (FCEs) were assessed. Of these, 17 (4.4%) were grouped to U01, i.e. no group allocated as the primary diagnosis was not recorded. For 271 of these episodes, a clinician had also allocated a choice of what he thought the HRG should be. These choices of HRG were then compared with the official grouping determined by the software provided by the National Casemix Office (NCMO). Disparities between 'automatic grouping' and proposed HRG assignment by the consultants occurred in 20.66% (56/271). Version 3 should see some of these disparities and actual grouping software errors reduced, in particular through the introduction of a new vascular surgery chapter. However, the absence of a primary diagnosis will still produce the allocation of group U01 in version 3. Caution should be observed in using the HRG software and in the interpretation of data obtained from it. This could be especially important in benchmarking or contractual settings as there may be adverse implications to the unit/hospitals involved.

Benchmarking↗
PubMed1997

Comparison of perspectives on prostate cancer: analyses of survey data.

OBJECTIVES: Prostate cancer will account for 334,500 new cases and 41,800 deaths among men in the United States in 1997. Patients and physicians are faced with many concerns related to benefits and side effects of alternative treatments, educational needs, emotional support, and costs of care. Support groups for prostate cancer patients have been established to help satisfy needs in these areas. Therefore, we addressed three issues among patients who belong to a prostate cancer support group as well as among a second group of urologists who treat prostate cancer: (1) goals for prostate cancer treatment, (2) information that is given and recalled about the disease and therapy, and (3) extent to which educational and emotional needs are being met. METHODS: Random telephone surveys were made of 1000 men with prostate cancer who belong to the prostate cancer support group US TOO, the largest prostate cancer support group in the United States, and 200 urologists who provide care to men with prostate cancer. The surveys were conducted by the Louis Harris & Associates survey research firm. RESULTS: About four fifths of patients and urologists prefer aggressive therapy for prostate cancer. Patient goals with therapy included preservation of quality of life (45%), extension of life (29%), and delaying disease progression (13%), whereas physicians overwhelmingly focused on treatment efficacy (86%), with side effects (43%) and costs (29%) being secondary considerations. Urologists and patients differed markedly in the description of the patient-physician discussion. Whereas almost 100% of physicians stated that they always discussed important considerations such as options for no therapy, life expectancy with and without therapy, patient preferences, costs, and changes in sexual function, only about one fifth of patients recalled similar discussions. Patients and physicians both believed that physicians were an excellent source of educational support, but often did not report provision of emotional support. Although support groups were viewed as good providers of educational and emotional support by 85% to 90% of patients, physicians appeared to underestimate the benefit of support groups in these areas. CONCLUSIONS: Patients who belong to US TOO have many emotional and educational needs that are not currently being fulfilled by physicians. Although the goals of therapy are viewed similarly by patients and physicians, much of the important cancer- and treatment-related information that physicians report they have provided is not recalled by patients. Policy makers would be wise to devise systematic strategies such as shared decision-making tools and better linkages to support groups to ensure that patients' needs are being met.

Aged↗
PubMed1997

Cancer risk associated with germline DNA mismatch repair gene mutations.

The autosomal dominant syndrome of Hereditary Nonpolyposis Colorectal Cancer (HNPCC) is due to germline DNA mismatch repair gene mutations in most cases. However, the penetrance of such mutations outwith classical HNPCC kindreds is unknown because families studied to date have been specifically selected for research purposes. Using a population-based strategy, we have calculated the lifetime cancer risk associated with germline DNA mismatch repair gene mutations, irrespective of their family history. We identified 67 gene carriers whose risk to age 70 for all cancers was 91% for males and 69% for females. The risk of developing colorectal cancer was significantly greater for males than for females (74% versus 30%, P= 0.006). The risk of uterine cancer (42%) exceeded that for colorectal cancer in females, emphasising the need for uterine screening. Our findings give further insight into the biological effect of defective DNA mismatch repair. We have demonstrated a systematic approach to identifying individuals at high risk of cancer but who may not be part of classical HNPCC families. The risk estimates derived from these analyses provide a rational basis on which to guide genetic counselling and to tailor clinical surveillance.

Colorectal Neoplasms, Hereditary Nonpolyposis↗
PubMed1996

Trends in survival from cancers of the oral cavity and pharynx in Scotland: a clue as to why the disease is becoming more common?

Data were examined to determine trends in survival from cancers of the oral cavity and pharynx in Scotland between 1968 and 1987, and to analyse survival rates and the previously noted increases in the incidence of such cancers according to the level of social deprivation. Incidence data on oral cavity and pharyngeal cancer and survival rates following diagnosis were obtained from the Information and Statistics Division of the Common Services Agency for the National Health Service in Scotland, covering the period 1968-92. It was found that survival rates for cancers of the tongue, mouth and pharynx diagnosed among persons less than 65 years of age decreased between 1968-72 and 1983-87. Five year relative survival rates fell from 47% to 39% over this period, while the equivalent rates among persons older than 65 years have shown a modest improvement from 34% to 38%. When considered by level of social deprivation, survival is lower among persons from the most deprived areas, and it is among such persons that the recent increases in occurrence of cancers of the oral cavity and pharynx have primarily occurred. The poorer survival among those from more socially deprived areas, and the evidence that the largest increase in incidence has occurred in such areas may to some extent explain the non-favourable trends in mortality. More importantly it emphasises the potential benefits of targeting such a population for oral health information. An educational campaign should include both information on the risk factors for developing oral cancer, and also the importance of seeking an early professional consultation in the case of symptoms.

Aged↗
PubMed1996

Will the Scottish Cancer Target for the year 2000 be met? The use of cancer registration and death records to predict future cancer incidence and mortality in Scotland.

Cancer mortality data reflect disease incidence and the effectiveness of treatment. Incidence data, however, reflect the burden of disease in the population and indicate the need for prevention measures, diagnostic services and cancer treatment facilities. Monitoring of targets mandates that both be considered. The Scottish Cancer Target, established in 1991, proposed that a reduction of 15% in mortality from cancer in the under-65s should be achieved between 1986 and 2000. Each year in Scotland approximately 8300 persons under 65 are diagnosed with cancer and 4500 die from the disease. The most common malignancies, in terms of both incident cases and deaths, in the under-65s, are lung and large bowel cancer in males, and breast, large bowel and lung cancer in females. A decrease of 6% in the number of cancer cases diagnosed in males under 65 is predicted between 1986 and 2000, whereas the number of cases in females in the year 2000 is expected to remain at the 1986 level. In contrast, substantial reductions in mortality are expected for both sexes: 17% and 25% in males and females respectively. Demographic changes will influence the numbers of cancer cases and deaths in the Scottish population in the year 2000. However, long-term trends in the major risk factors, such as smoking, are likely to be the most important determinants of the future cancer burden.

Aged↗
PubMed1996

Incidence of childhood leukaemia and non-Hodgkin's lymphoma in the vicinity of nuclear sites in Scotland, 1968-93.

OBJECTIVES: The primary aims were to investigate the incidence of leukaemia and non-Hodgkin's lymphoma in children resident near seven nuclear sites in Scotland and to determine whether there was any evidence of a gradient in risk with distance of residence from a nuclear site. A secondary aim was to assess the power of statistical tests for increased risk of disease near a point source when applied in the context of census data for Scotland. METHODS: The study data set comprised 1287 cases of leukaemia and non-Hodgkin's lymphoma diagnosed in children aged under 15 years in the period 1968-93, validated for accuracy and completeness. A study zone around each nuclear site was constructed from enumeration districts within 25 km. Expected numbers were calculated, adjusting for sex, age, and indices of deprivation and urban-rural residence. Six statistical tests were evaluated. Stone's maximum likelihood ratio (unconditional application) was applied as the main test for general increased incidence across a study zone. The linear risk score based on enumeration districts (conditional application) was used as a secondary test for declining risk with distance from each site. RESULTS: More cases were observed (O) than expected (E) in the study zones around Rosyth naval base (O/E 1.02), Chapelcross electricity generating station (O/E 1.08), and Dounreay reprocessing plant (O/E 1.99). The maximum likelihood ratio test reached significance only for Dounreay (P = 0.030). The linear risk score test did not indicate a trend in risk with distance from any of the seven sites, including Dounreay. CONCLUSIONS: There was no evidence of a generally increased risk of childhood leukaemia and non-Hodgkin's lymphoma around nuclear sites in Scotland, nor any evidence of a trend of decreasing risk with distance from any of the sites. There was a significant excess risk in the zone around Dounreay, which was only partially accounted for by the sociodemographic characteristics of the area. The statistical power of tests for localised increased risk of disease around a point source should be assessed in each new setting in which they are applied.

Adolescent↗
PubMed1996

The adenoma-carcinoma sequence and prospects for the prevention of colorectal neoplasia.

Colorectal adenomatous polyps are thought to be precursors of colorectal cancer. This article reviews the evidence for the adenoma-carcinoma sequence and possible interventions in regard to the prevention of colorectal cancer. Although there is no direct evidence to support the adenoma-carcinoma sequence, there is considerable indirect evidence from a range of epidemiological, histopathological, and molecular genetic studies. Sigmoidoscopy and fecal occult blood testing may offer the potential for secondary prevention, but screening based on either of these methods in the general population has not yet been shown conclusively to be effective and efficient. Although the importance of dietary factors in the etiology of colorectal lesions suggests that there may be potential for primary prevention through dietary modification or nutrient supplementation, few trials have been completed to date. Although observational studies suggest that the incidence of colorectal cancer may be reduced by as much as 50% by the use of aspirin or other nonsteroidal antiinflammatory drugs (NSAIDs), further research is needed to determine the effects of individual NSAIDs and the appropriate prophylactic dose and to develop new NSAIDs with reduced gastrointestinal side-effects. Other strategies for primary prevention could focus on interventions to increase physical activity levels, to encourage smoking cessation, and to moderate alcohol consumption. Potential areas for further research are proposed.

Adenoma↗
PubMed1996

Why me?

Explore the source record for details and available documents.

Capitation Fee↗
PubMed1995

A Scottish national mortality study assessing cause of death, quality of and variation in management of patients with testicular non-seminomatous germ-cell tumours. The Scottish Radiological Society and the Scottish Standing Committee of the Royal College of Radiologists.

A detailed casenote review was performed on 55 patients registered with testicular non-seminomatous germ cell tumours (NSGCT) between 1983 and 1988 under the Scottish Cancer Registration Scheme and who had died by 1992. Details of all aspects of clinical management relating to their NSGCT and death details were extracted and summarised. An assessment was made on whether the patients' management had been optimal. An analysis of 5 year survival rates by the five Scottish oncology centres demonstrated significant differences between centres (range 70.4-94.2; chi 2 = 14.46, d.f. = 4, P = 0.006). Some patients in all centres were assessed as having received suboptimal treatment, but two centres performed less well than the other three. There is a suggestion that the number of patients treated suboptimally decreases with increasing number of patients seen, but this does not reach statistical significance.

Adolescent↗
PubMed1995

Oesophageal and gastric cancer in Scotland 1960-90.

In Scotland over the last 31 years the incidence of gastric cancer has significantly declined by 0.6% per annum in males and 1.1% in females. In contrast, for oesophageal cancer, incidence rates have risen significantly by 3.0% and 2.0% per annum in males and females respectively. Increasing incidence of both adenocarcinomas and squamous carcinomas of the oesophagus in men and squamous and recently adenocarcinomas in women has been observed. This cannot be entirely accounted for by a growth in the proportion of histologically verified (HV) tumours over time. The incidence of adenocarcinoma of the stomach increased over the study period, most likely because of increasing proportions of HV tumours and improved diagnostic precision. Areas with high levels of deprivation in Scotland are strongly associated with high rates of oesophageal cancer in men, and of gastric cancer in both men and women. All these observations are discussed in the context of current knowledge of risk factors for these diseases.

Adenocarcinoma↗
PubMed1995

Regulated underexpression and overexpression of the FliN protein of Escherichia coli and evidence for an interaction between FliN and FliM in the flagellar motor.

The FliN protein of Escherichia coli is essential for the assembly and function of flagella. Here, we report the effects of regulated underexpression and overexpression of FliN in a fliN null strain. Cells that lack the FliN protein do not make flagella. When FliN is underexpressed, cells produce relatively few flagella and those made are defective, rotating at subnormal, rapidly varying speeds. These results are similar to what was seen previously when the flagellar protein FliM was underexpressed and unlike what was seen when the motility proteins MotA and MotB were underexpressed. Overexpression of FliN impairs motility and flagellation, as has been reported previously for FliM, but when FliN and FliM are co-overexpressed, motility is much less impaired. This and additional evidence presented indicate that FliM and FliN are associated in the flagellar motor, in a structure distinct from the MotA/MotB torque generators. A recent study showed that FliN might be involved in the export of flagellar components during assembly (A. P. Vogler, M. Homma, V. M. Irikura, and R. M. Macnab, J. Bacteriol. 173:3564-3572, 1991). We show here that approximately 50 amino acid residues from the amino terminus of FliN are dispensable for function and that the remaining, essential part of FliN has sequence similarity to a part of Spa33, a protein that functions in transmembrane export in Shigella flexneri. Thus, FliN might function primarily in flagellar export, rather than in torque generation, as has sometimes been supposed.

Amino Acid Sequence↗
PubMed1994

Cancer incidence in a population potentially exposed to radium-226 at Dalgety Bay, Scotland.

Cancer incidence in the Dalgety Bay area of Fife, Scotland, was examined following the detection of radium-226 particles by routine radiation monitoring. The study was confounded by rapid population growth, demographic change and the relatively high socioeconomic status of the Dalgety Bay population. Health Board Primary Care Division records were used to calculate population estimates and Carstairs deprivation score was used to adjust for socioeconomic characteristics. In the period 1975-90, 211 residents were registered as having cancer compared with 214.21 expected from Scottish national rates. Of specific cancers possibly associated with radiation, the incidence of stomach, liver, lung, bone, prostate, bladder and kidney cancer and lymphoma were lower than expected while colon, rectum, pancreas, skin, breast and thyroid cancer and multiple myeloma and leukaemia were higher. There were three cases of childhood leukaemia compared with 1.22 expected. The only statistically significant differences observed were for pancreas (11 cases, O/E 2.28), lung (25 cases, O/E 0.65) and non-melanoma skin (36 cases, O/E 1.50). Stomach cancer was of borderline statistical significance (four cases, O/E 0.40). Adjustments for socioeconomic factors accounted for the apparently low incidence of stomach and lung cancer and, to a lesser extent, skin cancer, which remained of borderline statistical significance. Results in relation to pancreas cancer were unchanged. The observations of raised incidence of pancreas and skin cancer arose in the context of a survey of 17 cancer sites, from which the finding of two or more statistically significant results is not unusual (P = 0.21), and the numbers of cases involved were small. The epidemiological evidence for an association between radiation exposure and pancreas cancer risk is weak. Stronger evidence exists for an association with skin cancer. In the present study the anatomical distribution of the 36 cases was similar to that found elsewhere in Scotland.

Adolescent↗