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Biomedical subjects

G Cooke

Publications and source records attributed to G Cooke.

At least 19 recordsLinked to original sources
PubMed2004

Oral (gavage), in utero and post-natal exposure of Sprague-Dawley rats to low doses of tributyltin chloride. Part II: effects on the immune system.

The immunotoxic effects of tributyltin chloride (TBTC) were examined in the offspring of Sprague-Dawley rats exposed in utero from day 8 of gestation, through lactation and post-weaning until pups reached the age of 30 days (male and female), 60 days (female) and 90 days (male). Daily oral (gavage) doses of 0.025, 0.25 and 2.5 mg/kg body weight/day were administered in olive oil 7 days/week. Immunologic endpoints were investigated at the termination of each study. Statistically significant results (P<0.05) included the following: At 30 days, the mean percent and absolute natural killer (NK) cell numbers were increased in male and female rats treated with the high TBTC dose. At 60 days, female rats had increased mean serum IgM levels at the low and high TBTC doses, increased mean percentage CD4(+)8(+) (immature) T lymphocytes at the middle and high doses, a non-linear dose-response increase in NK cell activity at the 50:1 and 100:1 effector:target cell ratios (pairwise comparisons significant at the low dose compared with control), and increased mean numbers of L. monocytogenes colony-forming bacteria on Day 2 post-infection (significant for trend) and Day 3 post infection (pairwise comparisons significant only in the middle dose). The 90-day male rats had decreased mean serum IgA levels at the middle dose group; increased IgM levels at the high dose group, increased IgG levels at the middle and high doses; decreased IgG2(a) in the high dose compared to the control; a dose-related increase in the mean percentage NK cell numbers (pairwise comparisons significant at the high dose compared with the control) and increased mean NK cell activity (pairwise comparisons significant at all dose groups compared with the control). The delayed-type hypersensitivity response to oxazolone was increased in the low and middle doses and decreased in the high dose. Thymus atrophy was observed in the high TBTC dose across all ages. Thus, in utero and post-natal treatment of F1 rats with low levels of TBTC affected some aspects of humoral and cell mediated immunity as well as the number and function of cells which are involved in the host's immunosurveillance mechanisms against tumours and viral infections.

Administration, Oral↗
PubMed2000

Mammographic densities and the prevalence and incidence of histological types of benign breast disease. Reference Pathologists of the Canadian National Breast Screening Study.

There is now a large amount of evidence indicating that women with extensive areas of mammographic densities are 4-6 times more likely to develop breast cancer than those with little or no density in the mammogram. We have examined one potential biological explanation for this association by estimating the incidence of various histological types of benign breast disease in relation to mammographic density. We studied the large cohort of women taking part in the National Breast Screening Study (NBSS), a randomized trial of screening with mammography. Mammograms from subjects with biopsies (n = 423) and from a comparison group of subjects randomly selected from the NBSS (n = 465) were included. Histological slides from biopsied subjects (n = 353) were classified independently by the pathologists of the NBSS and by a review pathologist (H.M.J.). Mammographic density in more than 75% of the breast area was associated with an increased risk of incidence of hyperplasia without atypia, and of atypical hyperplasia and/or carcinoma in situ. The classifications of the review pathologist showed that, compared to women with no density, the relative risk of incident lesions for women with density in more than 75% of breast was 13.85 (95% CI 2.65-72.49) for hyperplasia, and 9.23 (95% CI 1.66-51.48) for atypical hyperplasia and/or carcinoma in situ. These findings suggest that the association between extensive mammographic density and breast cancer risk may, at least in part, be attributable to biological processes in the breast that give rise to these histological features that are known to be related to breast cancer risk.

Adult↗
PubMed1995

Quantitative evaluation of mammographic densities: a comparison of methods of assessment.

Differences in the proportion of the breast occupied by mammographic densities have been shown to be associated with differences in breast cancer risk. However, estimation of these densities by radiologists may be subject to error, and it is likely that quantitative measurement will reduce misclassification of densities and strengthen their association with risk of breast cancer. The objective of this study was to compare the extent of mammographic densities estimated subjectively by an experienced radiologist with the measured extent of densities using a digital planimeter. A total of 225 sets of mammograms from women aged 40-49 years and enrolled in the Canadian National Breast Screening Study (NBSS) were selected. The extent of the radiological densities was estimated visually by one radiologist. Independently, the total area of the breast and the areas of density were traced and measured using a digital planimeter. Visual estimations and measurements of mammographic densities were then compared to determine the extent of agreement between the two methods. In general, the two methods showed good agreement (kappa = 0.78). The measured area of mammographic densities tended to be slightly greater than the radiologist's estimations. Both methods were highly reproducible (radiologist-dependent method, kappa = 0.89; quantitative method, r = 0.95, P = 0.0001). Our results indicate that measurement of the area of mammographic density using a quantitative method is reliable, and correlates well with assessment by an experienced radiologist. The method may be useful for identifying women at increased risk of breast cancer.

Absorptiometry, Photon↗
PubMed1993

Influence of soft contact lens design on clinical performance.

A double-masked, randomized study in four parts was conducted to evaluate the effect of varying certain soft contact lens design parameters on clinical performance. The effects of varying back optic zone radius (BOZR) (8.20 to 9.00 mm), back surface design (monocurve, bicurve, aspheric), edge thickness (0.12 to 0.24 mm), and back vertex power (+ 1.00 to -6.00 D) were investigated using test lenses manufactured in a high water content material. In each part of the study, between 20 and 35 volunteer subjects wore a range of lenses which were assessed after > 30 min settling periods. Postblink movement and lens "tightness" as assessed by the push-up test were unaffected by the variation in BOZR. Lenses of flatter BOZR centered lower and more temporally than steeper lenses. Lenses of similar back surface sagittal depth, but differing in terms of back surface design, did not center the same; the monocurve lenses decentered more than bicurve or aspheric lenses. Edge thickness had no significant effect on comfort or lens fit. Plus power lenses resulted in more postblink movement than minus lenses of similar power. The results are discussed in relation to the design and fitting of soft contact lenses.

Adolescent↗
PubMed1992

Relationship between mammographic and histological risk factors for breast cancer.

BACKGROUND: Information on breast cancer risk can be obtained both from the histological appearance of the breast epithelium in biopsy specimens and from the pattern of parenchymal densities in the breast revealed by mammography. It is not understood, however, how parenchymal densities influence breast cancer risk or whether these densities are associated with histological risk factors. PURPOSE: We have estimated, in a large cohort of women, the relative risk of detecting carcinoma in situ, atypical hyperplasia, hyperplasia without atypia, or nonproliferative disease in biopsy specimens from women with different extents of mammographic density. We also examined the association between these histological classifications and radiological features present specifically at the biopsy site. METHODS: The source of study material was a population of women aged 40-49 years who were enrolled in the Canadian National Breast Screening Study (NBSS). Mammograms from women who had undergone a biopsy (n = 441) and from a comparison group of women (n = 501) randomly selected from the mammography arm of the NBSS were classified according to the extent of mammographic density. The corresponding histological slides were independently classified by a review pathologist. RESULTS: Compared with women showing no mammographic densities, women with the most extensive densities (i.e., occupying greater than 75% of the breast volume) had a 9.7 times greater risk of developing carcinoma in situ or atypical hyperplasia (95% confidence interval [CI] = 1.75-53.97), a 12.2 times greater risk of developing hyperplasia without atypia (95% CI = 2.97-50.14), and a 3.1 times greater risk of developing non-proliferative disease (95% CI = 1.20-8.11). The gradients in risk were not monotonic across the five classifications of mammographic density. The association could not be explained by the presence of mammographic densities at the biopsy site, but calcification at the biopsy site was strongly associated with high-risk histological changes (relative risk = 24; 95% CI = 5.0-156.0). CONCLUSIONS: These results suggest that the radiological patterns referred to as mammographic dysplasia may influence breast cancer risk by virtue of their association with high-risk histological changes in the breast epithelium. IMPLICATIONS: Identification of the factors responsible for high-risk histological changes may offer new insights into the etiology of breast cancer and potentially lead to the development of methods for its prevention.

Adult↗
PubMed1990

Characterisation of mammographic parenchymal pattern by fractal dimension.

A consistent, quantitative, observer-independent method of characterising mammographic parenchymal pattern is described. The method is based on the calculation of the 'fractal dimension' of digitised mammograms. The degree of correlation between the parenchymal pattern classifications by a fractal-based system and those of radiologists is assessed. For a set of 70 mammograms, average weighted proportion agreement among three radiologists in calling Wolfe grades was 85%, while agreement between the radiologists and our fractal classifier was 84%. The method developed may prove to be useful in establishing an index of risk for breast cancer and, ultimately, in determining intervals between examinations for individuals in a mammographic screening programme.

Breast Neoplasms↗
PubMed1988

The association of histological and radiological indicators of breast cancer risk.

Previous work has shown that extensive mammographic dysplasia in women aged less than 50 was strongly associated with breast cancer but that the radiological appearance of ductal prominence was not associated with risk. In the present paper we examine the association between these mammographic signs in the breast and histological patterns in the terminal ductal lobular unit (TDLU), the region of the breast where breast cancer is believed to originate. Surgical biopsies from a consecutive series of women aged less than 50 were reviewed and classified according to the histopathology of the epithelium in the TDLU. Mammograms from the same subjects were independently classified according to the extent of the radiological signs of dysplasia and ductal prominence. Degree of histopathology and the extent of mammographic dysplasia were associated and atypia of the ductal type was found more frequently in patients with extensive dysplasia. However, the strength and statistical significance of the association varied according to the radiologist who classified the mammograms. No association was found between degree of histopathology and ductal prominence. These results add to the evidence that extensive mammographic dysplasia in women aged less than 50 is a risk factor for breast cancer. They do not indicate that the radiological signs of dysplasia are caused by histological changes in the TDLU.

Adult↗
PubMed1984

The California Statewide Family Health Education and Training Program 1981-1982.

Through support from the California State Department of Health Services, San Diego State University continued a statewide program in family life education, which consisted of: 1) establishment of a statewide advisory committee representative of many diverse points of view; 2) performance of a study of the teaching of family life education in the ninth and 10th grades of public schools in the state, as well as an examination of the present status of training of teachers; 3) provision of consultation and training programs for local school districts, including community support and implementation training, program development consultation teacher training and a limited number of small block grants to improve local family life education program efforts; and 4) preservice education classes to be conducted at teacher preparation campuses in the California State University system. The paper describes some of the findings of the study of the ninth and 10th grades, as well as the details of methodology of all four components of the statewide program.

California↗
PubMed1984

Mammographic patterns and breast cancer risk: methodologic standards and contradictory results.

The claim that classification of the pattern of the breast parenchyma upon mammography can distinguish groups at different risks for breast cancer has been examined by 17 other studies published in the English language literature with contradictory results; this controversy was assessed by us in examination of these studies for their adherence to commonly accepted methodologic standards for the investigation of causal relationships. The nine standards for the examination of the studies included a description of the way the study population had been assembled and followed up and descriptions of the methods of mammographic pattern classification and breast cancer risk analysis. A strong association was found between the standards adopted by a study and the obtained results. Among nine cohort and case-control studies that found a statistically significant association between mammographic pattern and breast cancer risk, all met at least four standards, whereas only two of six "negative" cohort or case-control studies met as many as four standards. Among prevalence surveys, the association between methods and results was less striking, but several negative prevalence surveys were associated with "positive" cohort studies employing the same group of patients. These results indicate that methodologic differences among studies contribute substantially to the controversy surrounding this subject. Studies that follow the usual scientific methods employed in the epidemiologic investigation of risk generally have confirmed an association between mammographic pattern and breast cancer risk.

Age Factors↗
PubMed1982

Bias and the association of mammographic parenchymal patterns with breast cancer.

We have carried out a case-control study to evaluate the association between Wolfe's mammographic patterns and the risk of breast cancer, and to examine the influence of control selection and the radiologist who read the films upon the results obtained. Mammograms of the non-cancerous breast of 183 women with unilateral breast cancer were compared with mammograms from two age-matched control groups: a group of asymptomatic women attending a screening centre, and a group of symptomatic women referred for the diagnostic evaluation of suspected breast disease. Films were arranged in random sequence and independently classified by 3 radiologists. A strong and statistically significant association was found between mammographic dysplasia and breast cancer when controls from the screening centre were compared to cases, but not when cases were compared to women referred for the diagnostic evaluation of breast disease. This result appears to arise in part because of an association between symptoms of benign breast disease and mammographic dysplasia, and suggests that some previous negative studies of the association of mammographic patterns with breast cancer may have arisen from the inclusion of symptomatic subjects as controls.

Adult↗
PubMed1982

Mammographic signs as risk factors for breast cancer.

We have carried out a case-control study to examine the relationship between mammographic signs and breast cancer. The mammographic signs assessed were prominent ducts and dysplasia. The cases were a group of 183 women with histologically verified unilateral breast cancer. The controls were a group of women attending a screening centre. Cases and controls were individually age-matched. Mammograms from the non-cancerous breast of the cases were randomly assembled with those of the controls and classified by 3 radiologists without knowledge of which films were from cases and which from controls. Mammographic dysplasia was found to be strongly associated with breast cancer, particularly in women aged less than 50. Prominent ducts were only weakly associated with breast cancer. Multivariate analysis showed that the association between dysplasia and breast cancer could not be explained on the basis of other risk factors for breast cancer, and that classification of dysplasia discriminated more strongly between cases and controls than did classification of Wolfe's mammographic patterns. These results show that mammograms contain information about risk of breast cancer. Mammographic dysplasia is strongly associated with breast cancer, is present in a substantial proportion of patients with the disease, and may offer opportunities for prevention.

Adult↗
PubMed1982

Mammographic patterns and bias in breast cancer detection.

Wolfe's finding that some mammographic patterns (P2 and DY) are associated with an increased risk of breast cancer has been challenged by some authors who suggest that this is due to denser patterns concealing cancers present on the first examination: these cancers, it is argued, are diagnosed in later years, creating the spurious impression of increased cancer incidence. The authors examined this hypothesis in a series of patients with breast cancer but failed to find any evidence that the diagnosis was subject to systematic delay in patients with the P2 or DY pattern. Moreover, studies of a hypothetical model showed that bias in the detection of breast cancer was unlikely to account for more than a small increase in apparent cancer incidence. Thus it appears unlikely that such a bias is responsible for the risk of breast cancer observed in patients with these mammographic patterns.

Adult↗