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Biomedical subjects

H Bryant

Publications and source records attributed to H Bryant.

At least 19 recordsLinked to original sources

Performance of screening mammography in organized programs in Canada in 1996. The Database Management Subcommittee to the National Committee for the Canadian Breast Cancer Screening Initiative.

BACKGROUND: The results of randomized trials show that breast cancer screening by mammography reduces breast cancer mortality by up to 40% in women aged 50-69 years. Because of these results, by 1998, 22 countries, including Canada, had established population-based organized screening programs. This paper presents the results of screening mammography in 1996 for 7 provincially organized breast cancer screening programs in Canada. METHODS: Analyses of interim performance indicators for screening mammography have been calculated from data submitted to the Canadian Breast Cancer Screening database. The data set consisted of data from 7 provincial programs and was limited to mammographic screens for women aged 50-69 years (n = 203,303). Screening outcomes and performance indicators were calculated for abnormalities detected by screening mammography only. RESULTS: The abnormal recall rate was 9.5% for first screens and 4.6% for subsequent screens, and the cancer detection rate per 1000 women screened was 6.9 for first screens and 3.8 for subsequent screens. The positive predictive value (i.e., the proportion of women who tested positive by mammography who were found to have breast cancer on screen-initiated diagnostic work-up) increased from 7.2% at the first screen to 8.2% at subsequent screens. Estimated participation rates within organized programs varied from 10.6% to 54.2%, depending on the province. INTERPRETATION: For 1996, organized breast cancer screening programs met or exceeded many of the interim measures used in international programs. It is possible to translate the benefits of breast cancer screening by mammography, as demonstrated in randomized trials, into population-based community programs. Screening mammography through organized programs should increase to allow more comprehensive monitoring in Canada.

Aged↗

Risk factors for benign proliferative breast disease.

BACKGROUND: As part of a nested case-control study of benign proliferative breast disease (BPBD) conducted within the cohort of women participating in the Alberta breast screening programme, an analysis of all women who had a benign breast biopsy between 1990 and 1995 was undertaken to identify the epidemiological risk factors for BPBD. METHODS: The breast biopsies of all eligible women were re-reviewed by a panel of four pathologists using Page's classification for benign breast disease. Cases were 165 women whose biopsies, upon review, showed benign breast tissue changes ranging from sclerosing adenosis to atypical ductal hyperplasia. Controls were 217 women whose biopsies showed no evidence of any proliferative or neoplastic changes. In-person interviews were conducted with all study subjects. RESULTS: Women with >/=25% fibroglandular breast tissue density, as compared to women with <25% density, experienced nearly a doubling in risk of BPBD (OR = 1.91, 95% CI : 1.24-2.94). All other possible risk factors examined were not associated with BPBD. CONCLUSION: This study suggests that fibroglandular tissue density may be a risk factor, or marker, for increased risk of BPBD.

Aged↗

The multifunctional herpes simplex virus IE63 protein interacts with heterogeneous ribonucleoprotein K and with casein kinase 2.

Herpes simplex virus type 1 (HSV-1), the prototype alpha-herpesvirus, causes several prominent diseases. The HSV-1 immediate early (IE) protein IE63 (ICP27) is the only regulatory gene with a homologue in every mammalian and avian herpesvirus sequenced so far. IE63 is a multifunctional protein affecting transcriptional and post-transcriptional processes, and it can shuttle from the nucleus to the cytoplasm. To identify interacting cellular proteins, a HeLa cDNA library was screened in the yeast two-hybrid system using IE63 as bait. Several interacting proteins were identified including heterogeneous nuclear ribonucleoprotein K (hnRNP K), a multifunctional protein like IE63, and the beta subunit of casein kinase 2 (CK2), a protein kinase, and interacting regions were mapped. Confirmation of interactions was provided by fusion protein binding assays, co-immunoprecipitation from infected cells, and CK2 activity assays. hnRNP K co-immunoprecipitated from infected cells with anti-IE63 serum was a more rapidly migrating subfraction than hnRNP K immunoprecipitated by anti-hnRNP K serum. Using anti-IE63 serum, both IE63 and hnRNP K were phosphorylated in vitro by CK2, while in immunoprecipitates using anti-hnRNP K serum, IE63 but not hnRNP K was phosphorylated by CK2. These data provide important new insights into how this key viral regulatory protein exerts its functions.

Animals↗

Lanthanide chelates as bilayer alignment tools in NMR studies of membrane-associated peptides.

Theequimolar complex, consisting of the lipid-like, amphiphilic chelating agent 1,11-bis[distearylamino]-diethylenetriamine pentaacetic acid (DTPA-18) and Tm(3+), is shown by deuterium ((2)H) NMR to be useful in aligning bicelle-like model membranes, consisting of dimyristoylphosphatidylcholine (DMPC) and dihexanoylphosphatidylcholine (DHPC). As shown previously (1996, R. S. Prosser et al., J. Am. Chem. Soc. 118, 269-270), in the absence of chelate, the lanthanide ions bind loosely with the lipid phosphate groups and confer the membrane with a sufficient positive magnetic anisotropy to result in parallel alignment (i.e., average bilayer normal along the field). Apparently, DTPA-18 sequesters the lanthanide ions and inserts into the phospholipid bilayer in such a manner that bilayer morphology is preserved over a wide temperature range (35-70 degrees C). The inherent paramagnetic shifts and line broadening effects are illustrated by (2)H NMR spectra of the membrane binding peptide, Leu-enkephalin (Lenk-d(2), Tyr-(Gly-d(2))-Gly-Phe-Leu-OH), in the presence of varying concentrations of Tm(3+), and upon addition of DTPA-18. Two conclusions could be drawn from this study: (1) The addition of Tm(3+) to the bicelle system is consistent with a conformational change in the surface associated peptide, and this effect is shown to be reversed by addition of the chelate, and (2) The paramagnetic shifts are shown to be significantly reduced by addition of chelate.

Chelating Agents↗

Assessment of maintenance therapy with reduced doses of PTH(1-34) in combination with a raloxifene analogue (LY117018) following anabolic therapy in the ovariectomized rat.

This experiment was designed to evaluate the ability of a raloxifene analogue (RA), LY117018, with or without reduced dosing of human parathyroid hormone (hPTH)(1-34) to maintain gains in bone mass after a fully anabolic treatment regimen given to aging osteopenic rats. Six-month-old rats were ovariectomized (ovx) or sham-operated (sham). After 1 month, ovx rats were treated with an anabolic regimen consisting of subcutaneous hPTH(1-34) 80 microg/kg/day and oral raloxifene 3 mg/kg/day, each given 5 days/week for 3 months. Thereafter, the treated ovx rats went on to an 8 week maintenance phase of treatment with either RA alone at the same dose, hPTH(1-34) at a reduced dosing interval (twice a week), or a combination of the two. Bone mineral density (BMD) was measured ex vivo at four skeletal sites, lumbar spine (L2-4), proximal hemipelvis, whole femur, and tibia, by dual-energy X-ray densitometry. All four sites showed a similar pattern of response. After the 3 month anabolic phase, the sham group had significantly higher BMD values than ovx rats at all skeletal sites (p < or = 0.002). The ovx rats treated with PTH + RA during the anabolic phase of the protocol had significantly higher BMD than the sham group in the femur, tibia, and spine (p < or = 0.02) and higher but not significantly different values in the pelvis. Following the 2 month maintenance phase, comparisons were made with the PTH-RA group at the end of the anabolic phase. Decrements in BMD were seen in all three maintenance therapy groups, but they were not statistically significant in the RA plus reduced PTH dose group. However, reduced hPTH(1-34) dosing and RA alone resulted in significant reductions of bone mass measurements at several skeletal sites during the maintenance phase. We conclude that the raloxifene analogue LY117018 may be useful in maintaining bone mass in aging ovx rats following anabolic therapy with hPTH(1-34) and raloxifene analogue, but that this strategy only allows for dose reduction of hPTH(1-34) rather than its discontinuation.

Absorptiometry, Photon↗

The addition of a raloxifene analog (LY117018) allows for reduced PTH(1-34) dosing during reversal of osteopenia in ovariectomized rats.

To test the hypothesis that an antiresorptive agent might reduce the dosing requirement for an anabolic drug during reversal of osteopenia due to estrogen deficiency, the following experiment was conducted in 6-month-old female rats. Ovariectomy or sham surgery was performed and the following six experimental groups were studied. Untreated (SHAM) or ovariectomized (OVX) animals served as control groups. Four weeks post-OVX, osteopenic rats (now 7 months old), were treated in one of four experimental protocols: human parathyroid hormone (hPTH(1-34)), 80 microg/kg/day, given by subcutaneous injection 5 days/week; a selective estrogen receptor modulator (SERM), raloxifene analog LY117018 (RA), 3 mg/kg/day, given by gavage 5 days/week; and two combinations of LY117018 at the same dose and frequency with hPTH(1-34) (same dose, 5 times/week) and a reduced dosing interval of hPTH(1-34) (same dose, 2 times/week). After 12 weeks of treatment, the four experimental groups were sacrificed at age 10 months. SHAM and OVX controls were also studied at 7 and 10 months of age. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry at four skeletal sites: two mixed cortical/trabecular sites (femur and tibia) and two predominantly trabecular sites (lumbar spine and pelvis). The differences in BMD were consistent at all four sites. RA alone maintained BMD at all skeletal sites, but the results were not significantly improved over OVX controls, at age 10 months. hPTH(1-34) injections given 5 days/week resulted in BMD increments significantly higher than in either OVX or SHAM controls (p < 0.001). While the RA did not enhance the anabolic effects of full doses of hPTH(1-34), the addition of RA treatment to twice-weekly hPTH(1-34) dosing resulted in BMD increments at all four skeletal sites that were similar to the more intensive anabolic regimen of hPTH(1-34) therapy given 5 times/week. Therefore, an antiresorptive agent such as SERMs may potentially reduce the pharmacologic doses of PTH needed to reverse estrogen deficiency-induced osteopenia.

Animals↗

Changes in Canadian women's mammography rates since the implementation of mass screening programs.

OBJECTIVES: This study reports on Canadian mammography rates between 1990, when mass screening programs were launched, and 1994/95. METHODS: Mammography rates from 2 national surveys were compared according to the presence of a provincial screening program. RESULTS: Mammography rates among women aged 50 to 69 years (the targeted group) increased significantly, by 16%; increases were twice as high in provinces with screening programs. Among women in their 40s (nontargeted group), the changes were insignificant and independent of screening program status. CONCLUSIONS: Screening programs appear to have influenced the mammography rates of targeted women aged 50 to 69 years.

Adult↗

Dementia in the primary care setting.

The first step in assessing behavioral problems in a patient with dementia is to understand why these behaviors occur and what might be causing them. In some instances, new or longstanding problem behaviors may be related to changes occurring within the brain, but in other cases may be related to a physical problem. The second step is to determine if there is a pattern to the patient's behavior. Ask the caregiver to keep a behavioral log for 1 week. Analyze the log for any clues and triggers that may direct you toward making environmental changes. Once you have the behavioral log, the third step is to try and determine specific patterns, environmental factors or triggering events contributing to the behavior. In general, there are three main causes of behavioral problems: environment, tasks and communication. Communication between the caregiver and the patient affected by dementia is one of the most important and most difficult aspects of care. A caregiver support group may be beneficial, as well as a consultation with a social worker. Pharmacologic therapy should only be initiated if the behavioral strategies are clearly not effective after a reasonable period of time, the behavior has been objectively and systematically documented, or the patient is a clear risk to himself or others.

Aged↗

The review of randomization in the Canadian National Breast Screening Study. What does the verdict mean for clinicians?

What is the practising clinician to make of the review by Drs. John C. Bailar III and Brian MacMahon (see pages 193 to 199 of this issue) of the randomization procedure used in the Canadian National Breast Screening Study? Their conclusion that any flaws in randomization would not have affected the published data is reassuring. Nevertheless, the review has not resolved the controversy surrounding the recommendations for screening mammography for women aged 40-49. Recommendations must be based on strong evidence that the benefits of population-based testing outweigh the harms. The absence of such evidence for women aged 40-49 should not, however, preclude the use of mammography as a diagnostic test for women in their 40s whose clinical signs require follow-up. Mammography could also be considered for women whose family history or other factors suggest an increased risk for breast cancer, provided that the limitations and potential disadvantages of testing are explained.

Adult↗

Improvement of sensitivity of breast cancer diagnosis with adaptive neighborhood contrast enhancement of mammograms.

Mammograms are difficult to interpret, especially of cancers at their early stages. In this paper, we analyze the effectiveness of our adaptive neighborhood contrast enhancement (ANCE) technique in increasing the sensitivity of breast cancer diagnosis. Seventy-eight screen-film mammograms of 21 difficult cases (14 benign and seven malignant), 222 screen-film mammograms of 28 interval cancer patients and six benign control cases were digitized with a high-resolution of about 4096 x 2048 x 10-bit pixels and then processed with the ANCE method. Unprocessed and processed digitized mammograms as well as the original films were presented to six experienced radiologists for a receiver operating characteristic (ROC) evaluation for the difficult case set and to three reference radiologists for the interval cancer set. The results show that the radiologists' performance with the ANCE-processed images is the best among the three sets of images (original, digitized, and enhanced) in terms of area under the ROC curve and that diagnostic sensitivity is improved by the ANCE algorithm. All of the 19 interval cancer cases not detected with the original films of earlier mammographic examinations were diagnosed as malignant with the corresponding ANCE-processed versions, while only one of the six benign cases initially labeled correctly with the original mammograms was interpreted as malignant after enhancement. McNemar's tests of symmetry indicated that the diagnostic confidence for the interval cancer cases was improved by the ANCE procedure with a high level of statistical significance (p-values of 0.0001-0.005) and with no significant effect on the diagnosis of the benign control cases (p-values of 0.08-0.1). This study demonstrates the potential for improvement of diagnostic performance in early detection of breast cancer with digital image enhancement.

Breast Neoplasms↗

Knowledge, attitudes and behaviours concerning cancer screening in Canada.

The Advisory Committee on Cancer Control funded a one-day workshop to discuss the surveillance of knowledge, attitudes/beliefs and behaviours concerning early cancer detection in Canada. Participants considered the need for such national surveillance and related methodological issues. Some exploratory work has been conducted in this regard. Results were presented from an inventory of existing survey questions and a summary of established cancer screening guidelines. There was overall agreement on the utility of collecting details of early cancer detection behaviours and their determinants. Explicitly, participants identified a need for site-specific information, highlighting cancers of the prostate and colon/rectum, as well as recognizing a need for qualitative information regarding the determinants that enable early cancer detection behaviours.

Canada↗

How should we interpret noncompliance with screening mammography?

Primary care practitioners have an important role to play in recommending breast cancer screening to patients in the target age group. In this issue of CMAJ (see pages 1335 to 1343) Dr. Marie-Dominique Beaulieu and associates report the results of a program designed to maximize utilization of screening mammography. Only two thirds of eligible women for whom screening mammography was prescribed obtained a mammogram within the 2-month study period. However, when taken in context, this compliance rate is fairly encouraging. There are many possible reasons for noncompliance such as a need for more information or for repeated suggestions. Family physicians should not become disheartened in their efforts to increase the use of screening procedures and may find that collaboration with others in giving consistent messages will help to maximize screening rates within their patient population.

Female↗

A Canadian experiment with breast cancer information exchange pilot projects.

Responding to concerns articulated by Canadian women living with breast cancer and their families, the federal government has provided $2.7 million over five years to establish five regional information exchange pilot projects. Women experience considerable variation in access to information reflecting different resources, communication links and health care delivery systems in each province or territory. The five information projects are taking different approaches to enhance coordination of existing resources and involve women living with breast cancer to improve access to credible, timely, breast cancer information.

Breast Neoplasms↗

Breast implants and breast cancer--reanalysis of a linkage study.

BACKGROUND: In 1992, Berkel and colleagues reported in the Journal the results of their study of the potential association of breast augmentation and breast cancer. The study reported that women who had breast augmentation had a significantly lower subsequent risk of breast cancer (P < 0.01) than the general population, with a standardized incidence ratio of 0.48 overall. Assuming a 10-year induction period (that is, assuming that cancers found within 10 years of the augmentation might have been the result of a process begun before surgery and therefore should not be considered), the reported standardized incidence ratio was 0.16. Problems were later identified involving some of the study methods. This paper reports a second analysis of these data. METHODS: We used a data set from Alberta Health Care to identify eligible women with bilateral breast augmentation. Using a combination of deterministic and probabilistic methods, we linked this data set to the Alberta Cancer Registry to identify subsequent breast cancers that developed during the study period. Multiple estimates of standardized incidence ratios were calculated on the basis of differing study-eligibility dates, induction periods, and types of breast-cancer (invasive only or invasive plus in situ). RESULTS: The reanalysis found substantial differences in the numbers of person-years at risk, resulting in higher standardized incidence ratios than in the original analysis. The final ratios for all breast cancers, with October 1, 1973, used as the starting date of the study, were 0.76 (95 percent confidence interval, 0.55 to 1.02), 0.85 (95 percent confidence interval, 0.58 to 1.19), and 0.68 (95 percent confidence interval, 0.32 to 1.25) for induction periods of 0, 5, and 10 years, respectively. None of these standardized incidence ratios were significantly different from 1. CONCLUSIONS: On the basis of this reanalysis, the incidence of breast cancer among the women who had breast augmentation could not be said to be either significantly higher or lower than that among the general population over the period during which this cohort was followed.

Adult↗

Teaching medical students how to perform a clinical breast examination.

BACKGROUND: One challenge in medical education is to provide training in physical examination skills. The authors conducted a randomized study to compare standardized and unstandardized methods of teaching clinical breast examinations and to determine whether trained non-medical women could teach as well as medical faculty. METHOD: Sensitivity, specificity, and examination techniques were compared between first-year students at the University of Calgary Faculty of Medicine who in 1992-93 received standardized teaching from family medicine faculty or well women teachers and 70 second-year students who received unstandardized teaching during their clinical rotations. Standardized teaching included a specific examination technique using silicone breast models. The students taught by the well women teachers also examined the women's breasts. RESULTS: The standardized-teaching group had more consistent examination techniques and significantly higher sensitivity but lower specificity. The students taught by the well women teachers performed as well as those taught by the family medicine faculty. CONCLUSIONS: The teaching methods used by trained teachers and standardized models improved the students'accuracy of breast lump detection and examination skills.

Breast Diseases↗