Impact of breast density on computer-aided detection for breast cancer

OBJECTIVE: Our aim was to determine whether breast density affects the performance of a computer-aided detection (CAD) system for the detection of breast cancer. MATERIALS AND METHODS: Nine hundred six sequential mammographically detected breast cancers and 147 normal screening mammograms from 18 facilities were classified by mammographic density. BI-RADS 1 and 2 density cases were classified as nondense breasts; BI-RADS 3 and 4 density cases were classified as dense breasts. Cancers were classified as either masses or microcalcifications. All mammograms from the cancer and normal cases were evaluated by the CAD system. The sensitivity and false-positive rates from CAD in dense and nondense breasts were evaluated and compared. RESULTS: Overall, 809 (89%) of 906 cancer cases were detected by CAD; 455/505 (90%) cancers in nondense breasts and 354/401 (88%) cancers in dense breasts were detected. CAD sensitivity was not affected by breast density (p=0.38). Across both breast density categories, 280/296 (95%) microcalcification cases and 529/610 (87%) mass cases were detected. One hundred fourteen (93%) of the 122 microcalcifications in nondense breasts and 166 (95%) of 174 microcalcifications in dense breasts were detected, showing that CAD sensitivity to microcalcifications is not dependent on breast density (p=0.46). Three hundred forty-one (89%) of 383 masses in nondense breasts, and 188 (83%) of 227 masses in dense breasts were detected-that is, CAD sensitivity to masses is affected by breast density (p=0.03). There were more false-positive marks on dense versus nondense mammograms (p=0.04). CONCLUSION: Breast density does not impact overall CAD detection of breast cancer. There is no statistically significant difference in breast cancer detection in dense and nondense breasts. However, the detection of breast cancer manifesting as masses is impacted by breast density. The false-positive rate is lower in nondense versus dense breasts. CAD may be particularly advantageous in patients with dense breasts, in which mammography is most challenging.     

Studies on protocadherin-2 expression in the human fetal central nervous system

Protocadherin (Pcad) is a group of molecules obtained by polymerase chain reaction (PCR) utilizing the sequence that is well preserved in the extracellular domain of cadherin. Sano et al. analyzed Pcad (PC42,43) that had been cloned from rats, and found that it basically had homology to cadherin, but contained more than six cadherin repeats with a completely different intracellular domains (Sano et al. 1993). In the present study, of the Pcad (Pcad-1,2) cloned from a human cDNA library, as-yet-unspecified Pcad-2 was analyzed for expression in the human fetal central nervous system (CNS). Northern blot analysis of adult human tissue showed that Pcad-2 was expressed in the brain and the placenta, and that Pcad-2 mRNA was expressed in actively dividing neural tumor cell lines. Monoclonal antibodies against Pcad-2 were then made, and the CNS of fetuses were immunohistochemically stained. The expression was hardly visible at the 6th week of pregnancy, and began to become visible along the nerve fiber in the brain stem at the 8th week, and spread over the entire brain at the 11th week. At the 18th week, however, expression in the nerve fascicles, which had been visible by that time, was no longer visible or had decreased. These results suggest that Pcad-2 appears relatively early in the critical stage of development of the fetal CNS, and is involved in the induction, fasciculation, and extension of axons.     

Synthesis and cytotoxic studies of hydroximino derivatives of some 16E-arylidenosteroids

Oxime and dioxime derivatives of various 16E-arylidenosteroids in the androstene series have been prepared and evaluated at the National Cancer Institute (NCI), Bethesda (USA) for their antineoplastic activity against various tumor cell lines in order to determine the structural requirements for cytotoxic activity. Aldol condensation of dehydroepiandrosterone (DHA) and DHA acetate with various aldehydes followed by treatment with hydroxylamine hydrochloride resulted in the formation of 16E-arylidenosteroid-oxime system. Oximes 15, 16 and compound 20 with a higher degree of oxidation in ring A have been found active in a 60 cell line antitumor prescreen by virtue of their cytotoxic effect against one or more tumor cell line and were further referred for in vivo hollow fiber bioassay. These compounds showed interesting intraperitoneal and subcutaneous scores in the in vivo hollow fiber bioassay and have been referred to the Biological Evaluation Committee for Cancer Drugs for further detailed in vivo testing.     

The antidiabetic agent, gliclazide, reduces high insulin-enhanced neutrophil-transendothelial migration through direct effects on the endothelium

BACKGROUND AND AIM: Many lines of evidence indicate that hyperinsulinemia might be associated with coronary atherosclerosis, and, currently, there are no effective strategies for preventing this. We previously reported that high insulin enhances neutrophil-transendothelial migration, a process that involves increased surface presentation of platelet endothelial cell adhesion molecule-1 (PECAM-1) through a mitogen-activated protein (MAP) kinase-dependent event. In this current study, we examined if antidiabetic agents, especially K(ATP) channel blockers, might similarly protect against the leukocyte-endothelial cell interactions enhanced by high insulin. METHODS: Neutrophils transmigration across umbilical vein endothelial cells (in high insulin medium) with or without K(ATP) channel blockers was performed. Neutrophil migration was quantified by measuring myeloperoxidase, and surface expression of endothelial PECAM-1 was examined using cell-surface enzyme immunoassay. RESULTS: Neutrophil-transendothelial migration and PECAM-1 expression were enhanced by insulin (100 micro U/mL, 24 h) and were attenuated by gliclazide (20 micro M), but not by other K(ATP) channel blockers (glibenclamide, nateglinide, and glimepiride). Neutrophil migration and PECAM-1 expression were also increased by the mitogen-activated protein (MAP) kinase activator, anisomycin (1 micro M), and also attenuated by gliclazide. Nitric oxide (NO) synthase inhibitors did not modify either gliclazide effect. CONCLUSIONS: Our results suggest that the K(ATP) channel blocker, gliclazide, blocks high insulin-mediated neutrophil migration and PECAM-1 expression. These gliclazide effects may be mediated through the inhibition of MAP kinase activation and are unrelated to NO production.     

Synthesis and evaluation of a dimer of 2-(4-pyridylmethyl)-1-indanone as a novel nonsteroidal aromatase inhibitor

A novel dimer of 2-(4-pyridylmethyl)-1-indanone (2) was obtained while carrying out aldol condensation of 1-indanone with pyridine-4-carboxaldehyde in potassium hydroxide. The structure of dimer 3 has been established using various spectral techniques and was screened for its ability to inhibit the cytochrome P(450) enzyme aromatase. The dimer showed strong inhibition of human placental aromatase and was found 3 times more potent (RP = 3, IC(50) = 10.2 microM) as compared to aminoglutethimide (RP = 1, IC(50) = 18.5 microM.     

Interference of isonicotinyl hydrazone in the microbiological analysis of rifampicin from anti-tuberculosis FDC products containing isoniazid

Microbiological assay is a sensitive method for the estimation of rifampicin (R). In the present study, interference due to isonicotinyl hydrazone (HYD), an interaction product of R and isoniazid (H), was checked during microbiological analysis of R, employing Bacillus subtilis and Sarcina lutea. The assays were done by disc diffusion method. Both R and HYD showed linear log response curves in the range of 0.01-10microg. In the presence of HYD, R was overestimated when tested against S. lutea and underestimated in case of B. subtilis. The same extent and type of interference was observed on assay of a marketed anti-tuberculosis fixed-dose combination product, subjected to accelerated stability testing (40 degrees C/75% RH) for 1 month. This means that response of organisms used in microbiological assay of R might vary in the presence of HYD, with possibility of incorrect conclusions. Therefore, the study suggests that before a microbiological method involving a particular organism is extended to the determination of R in FDC formulations containing H, it should be tested for the influence of HYD and used only if non-interfering.     

Tuberculosis control strategy in Asia for the 21st century--tuberculosis control in the Western Pacific Region of World Health Organization

The unprecedented and rapid changes at the global level posed a big challenge to public health. The tuberculosis disease as one of major health problems today should be viewed from this context. These global challenges include 1) population issue particularly on growth and ageing; 2) epidemiological issue such as health transition; and, 3) social and environmental issues such as rapid urbanization and global warming. Furthermore, we should also take into account other changes such as the role of the government in the health service delivery, clinical or cure-oriented approach to prevention, increasing consumer demand and health financing. The burden of tuberculosis is devastating. Everyday in the Western Pacific Region (WPR), about 1000 people lose their life due to tuberculosis. Most of them are between the ages 14-54, which are the so-called economically productive age group. The economic impact, therefore, is significant. In addition TB is a disease of poverty of which the risk of getting TB is higher in poor who have less access to TB services due to financial barrier and lack of knowledge. Despite this devastating situation, TB has a significant and cost effective tool called DOTS. WPRO put highest priority in TB control programme not only because of the facts mentioned above but I also consider TB as an agenda carried over from the last century. I would like, then, to commit myself to this cause for the betterment of the future of the next generation.     

Noncompliance after kidney transplantation: a systematic review

We performed a systematic review of the literature on medical noncompliance after kidney transplantation in the cyclosporine era. We wished to define commonalities that may help the clinician identify patients for early intervention. We found that patients who were at a higher risk of noncompliance after kidney transplants were younger, female, unmarried, and non-Caucasians. Patients who were recipients of living donor transplants and had been transplanted for a longer time with a history of a previous transplant were also at risk of noncompliance. We also found that patients displaying emotional problems, such as anxiety, hostility, depression, distress, lack of coping, and avoidant behaviors, were also at risk for noncompliance after kidney transplantation.