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Biomedical subjects

L Sharp

Publications and source records attributed to L Sharp.

At least 19 recordsLinked to original sources
PubMed2001

Rural and urban differences in stage at diagnosis of colorectal and lung cancers.

There is evidence that patients living in outlying areas have poorer survival from cancer. This study set out to investigate whether they have more advanced disease at diagnosis. Case notes of 1323 patients in north and northeast Scotland who were diagnosed with lung or colorectal cancer in 1995 or 1996 were reviewed. Of patients with lung cancer, 42% (69/164) living 58 km or more from a cancer centre had disseminated disease at diagnosis compared to 33% (71/215) living within 5 km. For colorectal cancer the respective figures were 24% (38/161) and 16% (31/193). For both cancers combined, the adjusted odds ratio for disseminated disease at diagnosis in furthest group compared to the closest group was 1.59 (P = 0.037). Of 198 patients with non-small-cell lung cancer in the closest group, 56 (28%) had limited disease (stage I or II) at diagnosis compared to 23 of 165 (14%) of the furthest group (P = 0.002). The respective figures for Dukes A and B colorectal cancer were 101 of 196 (52%) and 67 of 172 (39%) (P = 0.025). These findings suggest that patients who live remote from cities and the associated cancer centres have poorer chances of survival from lung or colorectal cancer because of more advanced disease at diagnosis. This needs to be taken into account when planning investigation and treatment services.

Aged↗
PubMed2000

Genome-wide study of aging and oxidative stress response in Drosophila melanogaster.

Aging is a universal but poorly understood biological process. Free radicals accumulate with age and have been proposed to be a major cause of aging. We measured genome-wide changes in transcript levels as a function of age in Drosophila melanogaster and compared these changes with those caused by paraquat, a free-radical generator. A number of genes exhibited changes in transcript levels with both age and paraquat treatment. We also found genes whose transcript levels changed with age but not with paraquat treatment. This study suggests that free radicals play an important role in regulating transcript levels in aging but that they are not the only factors. This genome-wide survey also identifies candidates for molecular markers of aging.

Aging↗
PubMed2000

Embryonic stem cells and transgenic mice ubiquitously expressing a tau-tagged green fluorescent protein.

We have generated embryonic stem (ES) cells and transgenic mice carrying a tau-tagged green fluorescent protein (GFP) transgene under the control of a powerful promoter active in all cell types including those of the central nervous system. GFP requires no substrate and can be detected in fixed or living cells so is an attractive genetic marker. Tau-tagged GFP labels subcellular structures, including axons and the mitotic machinery, by binding the GFP to microtubules. This allows cell morphology to be visualized in exquisite detail. We test the application of cells derived from these mice in several types of cell-mixing experiments and demonstrate that the morphology of tau-GFP-expressing cells can be readily visualized after they have integrated into unlabeled host cells or tissues. We anticipate that these ES cells and transgenic mice will prove a novel and powerful tool for a wide variety of applications including the development of neural transplantation technologies in animal models and fundamental research into axon pathfinding mechanisms. A major advantage of the tau-GFP label is that it can be detected in living cells and labeled cells and their processes can be identified and subjected to a variety of manipulations such as electrophysiological cell recording.

Animals↗
PubMed2000

N-acetyltransferase polymorphisms and colorectal cancer: a HuGE review.

The two expressed genes coding for N-acetyltransferase (NAT) activity, NAT1 and NAT2, are located on chromosome 8 at 8p21.3-23.1 and are polymorphic. Both enzymes are capable of N-acetylation, O-acetylation, and N,O-acetylation and are implicated in the activation and detoxification of known carcinogens. Single base-pair substitutions in NAT2 tend to occur in combination with other substitutions within the gene. As yet, less work has been done to characterize NAT1 allelic variants. Various methods for the detection of the reported polymorphisms exist. It is important to select a method that is appropriate to the population being studied. The functional significance of many NAT allelic variants has not been determined. Geographic and ethnic variation in the frequency of NAT2 genotypes associated with fast or intermediate acetylation has been observed. Insufficient data for NAT1 genotypes are available to reveal a clear geographic pattern. No consistent association has been found between acetylator phenotype or genotype and colorectal cancer. The lack of consistency can in part be accounted for by methodological factors, including limited statistical power. Possible interactions between the NAT genes and either environmental exposures or other polymorphic genes encoding xenobiotic metabolizing enzymes have been investigated in only a minority of these studies, and these studies have lacked statistical power to detect interactions.

Acetyltransferases↗
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↗
PubMed2000

A case-control study of oesophageal adenocarcinoma in women: a preventable disease.

The incidence of adenocarcinoma of the oesophagus in British women is among the highest in the world. To investigate its aetiology, we conducted a multi-centre, population based case-control study in four regions in England and Scotland. We included 74 incident cases in women with histologically confirmed diagnoses of adenocarcinoma of the oesophagus, and 74 female controls matched by age and general practice. High body mass index (BMI) around the age of 20 years (highest vs lowest quartile, adjusted odds ratio (OR) = 6.04, 95% confidence interval (CI) 1.28-28.52) and low consumption of fruit (highest vs lowest quartile, adjusted OR = 0.08, 95% CI 0.01-0.49) were associated with increases in risk. Breastfeeding by women was associated with reduced risk of their subsequently developing this cancer (ever vs never, adjusted OR = 0.41, 95% CI 0.20-0.82) and there was a significant dose-response effect with total duration of breastfeeding. The summary population attributable risk from these three factors was 96% (90% if breastfeeding is excluded). We conclude that high BMI in early adulthood and low consumption of fruit are important risk factors for adenocarcinoma of the oesophagus. Breastfeeding may confer a protective effect but this needs confirmation. This cancer is a largely preventable disease in women.

Adenocarcinoma↗
PubMed2000

Identification of the secreted macromolecular immunogens of Staphylococcus aureus by analysis of serum.

The ability of sera to recognise secreted macromolecules of Staphylococcus aureus was examined by ELISA and Western immunoblotting. Individual secreted proteins were also studied using both human sera and sera from rabbits immunised with secreted macromolecules. Patients sera showed a wide range of IgG antibody titres to secreted macromolecules and whole bacteria. Controls showed a significantly lower IgG response. Western immunoblotting revealed that a significant number of secreted proteins were recognised by circulating IgG antibodies. Surprisingly, both the sera from controls and from patients recognised similar macromolecules including a number of potential virulence factors. The major difference was in the IgG binding to a 16-kDa component, which was recognised by the majority of the sera from infected individuals, but only by a small number of sera from healthy controls. The higher incidence of antibodies recognising the 16 kDa component may be related to our earlier finding that the major bone resorbing component of S. aureus is a heterodimeric protein containing a 16-kDa subunit, the activity of which could be blocked by sera.

Adult↗
PubMed2000

Glycine cleavage enzyme complex: rabbit H-protein cDNA sequence analysis and comparison to human, cow, and chicken.

The H-protein is one of the four essential components (H-, L-, P-, and T-proteins) of the mammalian glycine cleavage enzyme complex, the major degradative pathway of glycine. We have isolated the full-length cDNA of the H-protein gene from the rabbit (Oryctolagus caniculus) by reverse transcription of liver poly-A mRNA and determined its nucleotide sequence (GenBank Acc. No. BankIt 31828

Amino Acid Oxidoreductases↗
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↗