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Biomedical subjects

Richard Moore

Publications and source records attributed to Richard Moore.

At least 55 records · Page 3Linked to original sources
PubMed2002

The development of forestomach tumours in the mouse following exposure to 2-butoxyethanol by inhalation: studies on the mode of action and relevance to humans.

2-Butoxyethanol, a forestomach carcinogen in mice exposed by inhalation, has been shown to enter the forestomach as a result of grooming and ingestion of material condensed on the skin and fur during exposure. The material entering the stomach concentrates in the forestomach region and persists for at least 48 h post-exposure. Mice given single oral doses of either 2-butoxyethanol or 2-butoxyacetic acid, daily for 10 days, developed a marked hyperkeratosis in the forestomach. 2-Butoxyacetic acid was more potent than 2-butoxyethanol, the NOEL for the former being 50 mg/kg and for the latter, 150 mg/kg. Although a dose dependent increase in cell replication was also seen with both chemicals, the results were confounded by a high labelling rate in the controls. There was no evidence of significant binding of radiolabelled 2-butoxyethanol to proteins in stomach tissues. 2-Butoxyethanol was metabolised in vitro in both mouse and rat forestomach and glandular stomach fractions by alcohol dehydrogenases forming 2-butoxyacetaldehyde which was rapidly converted by aldehyde dehydrogenases to 2-butoxyacetic acid. There was a marked species difference in alcohol dehydrogenase activity between rats and mice with the maximum rates up to one order of magnitude greater in mouse than rat. The alcohol and aldehyde dehydrogenases were heavily concentrated in the stratified squamous epithelium of the forestomach of both rats and mice whereas in the glandular stomach the distribution was more diffuse. In human stomach both enzymes were evenly distributed throughout the epithelial cells of the mucosa. It is concluded that 2-butoxyethanol is ingested following inhalation exposure and concentrates in the forestomach where it is metabolised to 2-butoxyacetic acid which causes cellular damage, increased cell replication and hyperkeratosis. These changes are believed to lead to the tumours seen in mice exposed to 2-butoxyethanol for a lifetime. Differences in structure and enzyme distribution between the rodent and human stomach suggest that the responses seen in the mouse are unlikely to occur in humans.

Administration, Inhalation↗
PubMed2002

Predicting the survival of patients with breast carcinoma using tumor size.

BACKGROUND: Tumor size has long been recognized as the strongest predictor of the outcome of patients with invasive breast carcinoma, although it has not been settled whether the correlation between tumor size and the chance of death is independent of the method of detection, nor is it clear how tumor size at the time of treatment may be translated into a specific expectation of survival. In this report, the authors provide such a method. METHODS: A Kaplan-Meier survival analysis was carried out for a population of 1352 women with invasive breast carcinoma who were treated at the Van Nuys Breast Center between 1966 and 1990, and the data were analyzed together with survival data published by others. RESULTS: The authors found that the survival of patients with invasive breast carcinoma was a direct function of tumor size, independent of the method of detection. The results showed that the correlation between tumor size and survival was well fit by a simple equation, with which survival predictions could be made from information on tumor size. For example, a comparison of three large populations studied over the last 5 decades revealed a marked improvement (approximately 35% absolute) in the survival of patients with invasive breast carcinoma diagnosed on clinical grounds that could be ascribed to a reduction in tumor size. However, the capacity of screening mammography to find smaller tumors remains the best way reduce breast carcinoma deaths, with the potential for adding an additional approximately 20% absolute reduction in breast carcinoma deaths. The mathematic correlation between tumor size and survival is consistent with a biologic mechanism in which lethal distant metastasis occurs by discrete events of spread such that, for every invasive breast carcinoma cell in the primary tumor at the time of surgery, there is approximately a 1-in-1-billion chance that a lethal distant metastasis has formed. CONCLUSIONS: The correlation between tumor size and lethality is well captured by a simple equation that is consistent with breast carcinoma death as the result of discrete events of cellular spread occurring with small but definable probabilities.

Breast Neoplasms↗
PubMed2002

The pattern of breast cancer screening utilization and its consequences.

BACKGROUND: The objective of this study was to describe the pattern of screening utilization and its consequences in terms of tumor size and time of tumor appearance of invasive breast carcinoma among a population of women who were examined at a large service screening/diagnostic program over the last decade. METHODS: Utilization of mammography was assessed from a population of 59,899 women who received 196,891 mammograms at the Massachusetts General Hospital Breast Imaging Division from January 1, 1990 to March 1, 1999, among which 604 invasive breast tumors were found. Two hundred six invasive, clinically detected tumors also were seen during this period among women who had no record of a previous mammogram. Additional information was available on screening of women from March 1, 1999 to June 1, 2001. RESULTS: Fifty percent of the women who used screening did not begin until the age of 50 years, although 25% of the invasive breast tumors were found in women age < 50 years. Relatively few of the women who used screening returned promptly for their annual examinations; by 1.5 years, only 50% had returned. Approximately 25% of the invasive breast tumors were found in women for whom there was no record of a previous screening mammogram, and these tumors were larger (median, 15 mm) than the screen-detected tumors (median, 10 mm). Approximately 30% of the 604 invasive breast tumors in the screening population were found on nonmammographic grounds, and they also were larger (median, 15 mm) than the screen-detected tumors (median, 10 mm). However, only 3% of these 604 tumors were found by nonmammographic criteria within 6 months of the previous negative examination, and only 12% were found within 1 year. By back calculating the likely size of each of these tumors at the time of the negative mammogram, it could be seen that most tumors probably emerged as larger, palpable masses not because they were missed at the previous negative mammogram, because most were too small then to have been detected, but because too much time had been allowed to pass. CONCLUSIONS: Far too many women did not comply with the American Cancer Society recommendation of prompt annual screening from the age of 40 years. Consequently, almost 50% of the invasive tumors emerged as larger and, thus, potentially more lethal, palpable masses.

Breast Neoplasms↗
PubMed2002

Specificity of mammography and US in the evaluation of a palpable abnormality: retrospective review.

PURPOSE: To determine the number of patients who received a diagnosis of breast cancer after having an area of clinical concern at presentation and combined negative mammographic and ultrasonographic (US) findings. MATERIALS AND METHODS: During a 4-year period, 829 patients with a palpable abnormality at presentation and combined negative mammographic and US findings were identified. The number of women who went on to receive a diagnosis of breast cancer was determined retrospectively. The authors searched the breast imaging database and the pathology database, sent a contact letter to the referring physicians, and linked their data to the State Cancer Registry. They also analyzed the breast parenchymal density among all patients who had more than 2 years of follow-up. RESULTS: Of the 829 women, 374 had follow-up information. Two-hundred thirty-three patients had negative imaging findings with more than 2 years of follow-up. The other 141 women were presumed to be cancer free, as they were not identified by the State Cancer Registry. Six (2.6%) of the 233 women had a diagnosis of breast cancer in the area of the palpable abnormality. The six cancers were diagnosed among the 156 women who had radiographically dense breast tissue (Breast Imaging Reporting and Data System category 3 or 4). Among the 77 women with predominantly fatty tissues, no cancers were diagnosed. CONCLUSION: A negative mammographic and US finding of a palpable abnormality does not exclude breast cancer, but the likelihood of breast cancer is low, approximately 2.6%-2.7%. It may be higher if the breast tissues are dense and lower if they are predominantly fatty.

Adult↗
PubMedDate not supplied

The burden of new-onset diabetes mellitus after transplantation.

The clinical impact of new-onset diabetes mellitus (NODM) is frequently underestimated by clinicians. NODM occurs in approximately 15-20% of renal transplant patients and 15% of liver transplant recipients. Diabetes after transplantation is a leading risk factor for cardiovascular events, with a higher prognostic value than in the non-transplant population. NODM also appears to have a negative influence on graft function, and graft survival rates after renal transplantation are significantly lower in patients who develop diabetes than in controls. Patient mortality following renal transplantation is generally found to be higher in patients with NODM, due to increased cardiovascular and peripheral vascular disease, accelerated graft deterioration and diabetes-related complications, notably infection. A renal registry analysis has reported an increase of 87% in risk of death following onset of NODM. There is also limited evidence that NODM is associated with increased risk of death in liver transplant patients. The relative incidence and severity of diabetic complications in transplant recipients have not been assessed rigorously in a clinical trial but registry data indicate that 20% of renal transplant patients with NODM experience at least one clinically significant diabetic complication within three years. Financially, the additional healthcare costs incurred over the first two years following onset of NODM amount to 21,500 dollars. Routine pre-transplant assessment of diabetic risk, with requisite modification of lifestyle, glycaemic monitoring and immunosuppressive regimens, and coupled with standardized, aggressive hypoglycaemic management as necessary, offers an important opportunity to alleviate the burden of NODM for transplant patients.

Abstracting and Indexing↗
PubMedDate not supplied

Compression-induced changes in the physiological state of the breast as observed through frequency domain photon migration measurements.

We use optical spectroscopy to characterize the influence of mammographic-like compression on the physiology of the breast. We note a reduction in total hemoglobin content, tissue oxygen saturation, and optical scattering under compression. We also note a hyperemic effect during repeated compression cycles. By modeling the time course of the tissue oxygen saturation, we are able to obtain estimates for the volumetric blood flow (1.64+/-0.6 mL/100 mL/min) and the oxygen consumption (1.97+/-0.6 micromol/100 mL/min) of compressed breast tissue. These values are comparable to estimates obtained from previously published positron emission tomography (PET) measurements. We conclude that compression-induced changes in breast physiological properties are significant and should be accounted for when performing optical breast imaging. Additionally, the dynamic characteristics of the changes in breast physiological parameters, together with the ability to probe the tissue metabolic state, may prove useful for breast cancer detection.

Adaptation, Physiological↗
PubMedDate not supplied

Assessment of the efficiency of treatment of dyslipidaemia in renal outpatients.

BACKGROUND: Lipid abnormalities, together with other co-existent risk factors, contribute to the accelerated atherosclerotic process, and consequently to the high incidence of cardiovascular disease, observed in end-stage renal patients. The objectives of this study were to determine the prevalence of dyslipidaemia and to assess how it is managed in a range of patients at four UK renal units. METHODS: Patients with renal disease were recruited from the outpatient clinics of 4 UK hospitals. Individuals meeting the entry criteria were required to provide one sample of venous blood following a 12-hour fast. Lipid profiles were measured for each patient. RESULTS: The study population consisted of 677 patients of which 276 (40.8%) were pre-dialysis patients with existing renal disease, 233 patients (34.4%) were receiving haemodialysis and 168 patients (24.8%) were receiving CAPD. Analysis showed that 64% of all patients had hypercholesterolaemia (defined according to Joint British Societies guidelines as LDL-cholesterol [LDL-C] >3.0 mmol/L [115 mg/dL] and/or total cholesterol [TC] >5.0 mmol/L [190 mg/dLl). Despite the high incidence of hypercholesterolaemia, only 16% of study participants were receiving lipid-lowering therapy. An LDL-C goal of <3.0 mmol/L (115 mg/dL) was achieved in 50.0% of patients receiving lipid-lowering treatment. CONCLUSIONS: The widespread failure to treat hypercholesterolaemia in patients with renal dysfunction given their high risk of future cardiovascular events is a major cause for concern. The observation that many dialysis patients receiving lipid-lowering therapy had not achieved recommended LDL-C and TC levels suggests that more efficient treatment of dyslipidaemia may be indicated in this patient population.

Adult↗
PubMedDate not supplied

Home safety in the U.K.: review of the influence of human and housing factors.

Injuries and deaths from home accidents are a major public health problem. This paper describes how data on housing characteristics were matched with dwelling-related mortality and injuries data. As no single database provided sufficient accurate data on housing and occupiers, this task involved identifying datasets to create and validate a Housing and Population Database, which was matched with various datasets on injuries and fatalities that are associated with the home. Taking account of both frequency of accidents and severity of outcomes, analyses of the matched data showed the true rank order of type of home accidents. Also investigated was whether one age group was more vulnerable to a particular type of accident and the relation between different types of accidents and the age and type of dwelling. A literature review was carried out to look at the relation between the design and condition of dwelling features and accidents and between human behavior and accidents. The results showed that little work has been done in most areas on the different degrees of the contribution made by human behavior and building conditions. Even though more focused research would be useful, preventative actions could reduce the scale of the problem.

Accidents, Home↗