Lifetime alcohol consumption patterns and young-onset breast cancer by subtype among Non-Hispanic Black and White women in the Young Women's Health History Study.

PURPOSE: The role of alcohol in young-onset breast cancer (YOBC) is unclear. We examined associations between lifetime alcohol consumption and YOBC in the Young Women's Health History Study, a population-based case-control study of breast cancer among Non-Hispanic Black and White women < 50 years of age. METHODS: Breast cancer cases (n = 1,812) were diagnosed in the Metropolitan Detroit and Los Angeles County SEER registry areas, 2010-2015. Controls (n = 1,381) were identified through area-based sampling and were frequency-matched to cases by age, site, and race. Alcohol consumption and covariates were collected from in-person interviews. Weighted multivariable logistic regression was conducted to calculate adjusted odds ratios (aOR) and 95% confidence intervals (CI) for associations between alcohol consumption and YOBC overall and by subtype (Luminal A, Luminal B, HER2, or triple negative). RESULTS: Lifetime alcohol consumption was not associated with YOBC overall or with subtypes (all ptrend ≥ 0.13). Similarly, alcohol consumption in adolescence, young and middle adulthood was not associated with YOBC (all ptrend ≥ 0.09). An inverse association with triple-negative YOBC, however, was observed for younger age at alcohol use initiation (< 18 years vs. no consumption), aOR (95% CI) = 0.62 (0.42, 0.93). No evidence of statistical interaction by race or household poverty was observed. CONCLUSIONS: Our findings suggest alcohol consumption has a different association with YOBC than postmenopausal breast cancer-lifetime consumption was not linked to increased risk and younger age at alcohol use initiation was associated with a decreased risk of triple-negative YOBC. Future studies on alcohol consumption in YOBC subtypes are warranted.

Lifetime personal cigarette smoking and risk of young-onset breast cancer by subtype among non-Hispanic Black and White women in the Young Women's Health History Study.

PURPOSE: To evaluate the association between lifetime personal cigarette smoking and young-onset breast cancer (YOBC; diagnosed <50 years of age) risk overall and by breast cancer (BC) subtype, and whether risk varies by race or socioeconomic position (SEP). METHODS: Data are from the Young Women's Health History Study (YWHHS), a population-based case-control study of non-Hispanic Black (NHB) and White (NHW) women, ages 20-49 years (n = 1812 cases, n = 1381 controls) in the Los Angeles County and Metropolitan Detroit Surveillance, Epidemiology, and End Results (SEER) registry areas, 2010-2015. Lifetime personal cigarette smoking characteristics and YOBC risk by subtype were examined using sample-weighted, multivariable-adjusted polytomous logistic regression. RESULTS: YOBC risk associated with ever versus never smoking differed by subtype (Pheterogeneity = 0.01) with risk significantly increased for Luminal A (adjusted odds ratio [aOR] 1.34; 95% confidence interval [CI] 1.06-1.68) and HER2-type (aOR 1.97; 95% CI 1.23-3.16), and no association with Luminal B or Triple Negative subtypes. Additionally, ≥30 years since smoking initiation (versus never) was statistically significantly associated with an increased risk of Luminal A (aOR 1.55; 95% CI 1.07-2.26) and HER2-type YOBC (aOR 2.77; 95% CI 1.32-5.79), but not other subtypes. In addition, among parous women, smoking initiated before first full-term pregnancy (versus never) was significantly associated with an increased risk of Luminal A YOBC (aOR 1.45; 95% CI 1.11-1.89). We observed little evidence for interactions by race and SEP. CONCLUSION: Findings confirm prior reports of a positive association between cigarette smoking and Luminal A YOBC and identify a novel association between smoking and HER2-type YOBC.

Theory, methods, and operational results of the Young Women's Health History Study: a study of young-onset breast cancer incidence in Black and White women.

PURPOSE: The etiology of young-onset breast cancer (BC) is poorly understood, despite its greater likelihood of being hormone receptor-negative with a worse prognosis and persistent racial and socioeconomic inequities. We conducted a population-based case-control study of BC among young Black and White women and here discuss the theory that informed our study, exposures collected, study methods, and operational results. METHODS: Cases were non-Hispanic Black (NHB) and White (NHW) women age 20-49 years with invasive BC in metropolitan Detroit and Los Angeles County SEER registries 2010-2015. Controls were identified through area-based sampling from the U.S. census and frequency matched to cases on study site, race, and age. An eco-social theory of health informed life-course exposures collected from in-person interviews, including socioeconomic, reproductive, and energy balance factors. Measured anthropometry, blood (or saliva), and among cases SEER tumor characteristics and tumor tissue (from a subset of cases) were also collected. RESULTS: Of 5,309 identified potentially eligible cases, 2,720 sampled participants were screened and 1,812 completed interviews (682 NHB, 1140 NHW; response rate (RR): 60%). Of 24,612 sampled control households 18,612 were rostered, 2,716 participants were sampled and screened, and 1,381 completed interviews (665 NHB, 716 NHW; RR: 53%). Ninety-nine% of participants completed the main interview, 82% provided blood or saliva (75% blood only), and SEER tumor characteristics (including ER, PR and HER2 status) were obtained from 96% of cases. CONCLUSIONS: Results from the successfully established YWHHS should expand our understanding of young-onset BC etiology overall and by tumor type and identify sources of racial and socioeconomic inequities in BC.

Systematic development of an abbreviated protocol for screening breast magnetic resonance imaging.

RATIONALE & OBJECTIVES: We sought to develop an abbreviated protocol (AP) for breast MRI that maximizes lesion detection by assessing each lesion not seen on mammography by each acquisition from a full diagnostic protocol (FDP). MATERIALS & METHODS: 671 asymptomatic women (mean 55.7 years, range 40-80) with a negative mammogram were prospectively enrolled in this IRB approved study. All lesions on MRI not visualized on mammography were analyzed, reported, and suspicious lesions biopsied. In parallel, all FDP MRI acquisitions were scored by lesion to eventually create a high-yield AP. RESULTS: FDP breast MRI detected 452 findings not visible on mammography, including 17 suspicious lesions recommended for biopsy of which seven (PPV 41.2%) were malignant in six women. Mean size of the four invasive malignancies was 1.9 cm (range 0.7-4.1), all node negative; three lesions in two women were ductal carcinoma in situ. Nine biopsied lesions were benign, mean size 1.2 cm (range 0.6-2.0). All biopsied lesions were in women with dense breasts (heterogeneously or extremely dense on mammography, n = 367), for a cancer detection rate of 16.3/1000 examinations in this subpopulation. These data were used to identify four high-yield acquisitions: T2, T1-pre-contrast, T11.5, and T16 to create the AP with a scan time of 7.5 min compared to 24 min for the FDP. CONCLUSIONS: Our analysis of a FDP MRI in a mammographically negative group identified four high-yield acquisitions that could be used for rapid screening of women for breast cancer that retains critical information on morphology, histopathology, and kinetic activity to facilitate detection of suspicious lesions.

The effect of colchicine on cholesterol crystal formation, expansion and morphology: a potential mechanism in atherosclerosis.

Background: Inflammation is pivotal to the progression of atherosclerosis. Cholesterol crystals (CCs) that grow and enlarge within the plaque core can cause plaque rupture and trigger inflammation as they deposit into the atherosclerotic bed. Thus, agents that affect CC formation, expansion, and morphology may reduce cardiovascular (CV) risk independent of lipid-lowering and anti-inflammatory therapy. Objective: Because colchicine is highly concentrated in leukocytes that can enter the atherosclerotic plaque core, we tested its effect on the formation and growth of CCs in bench experiments to determine whether it may have direct effects on CCs, independent of its known anti-inflammatory actions. Method: Different dosages of colchicine mixed with cholesterol (0.05-5 mg/ml/g of cholesterol) were used to influence the formation CCs and volume expansion in vitro. These were compared to control samples with cholesterol in ddH2O without colchicine. In an ex vivo study, fresh atherosclerotic human plaques were incubated with and without colchicine in a water bath at 37°C for 48 h to assess the impact of colchicine on CC morphology. Scanning electron microscopy (SEM) was utilized to analyze CC morphology in samples from the various treatment groups. Results: The addition of colchicine to cholesterol caused a substantial dose-dependent reduction in volume (p < 0.05). Pairwise comparisons of volume reduction, showed a significant reduction in volume at 5 mg/ml/g when compared to control (p < 0.02) but the calculated Cohen's d effect size was large for five of the six pairwise comparisons. By SEM, CCs from both in vitro and ex vivo samples treated with colchicine had evidence of dissolution and changes in their morphology as evidenced by the loss of their sharp edges. In contrast, CCs in untreated specimens retained their typical geometric structure. Conclusions: Colchicine can reduce CC formation and expansion and alter CC morphology. These previously unappreciated effects of colchicine may contribute to its clinical benefit in patients with CV disease independent of its anti-inflammatory effects.

Cholesterol crystals induce mechanical trauma, inflammation, and neo-vascularization in solid cancers as in atherosclerosis.

Background and aims: Cancer and atherosclerosis share common risk factors and inflammatory pathways that promote their proliferation via vascular endothelial growth factor (VEGF). Because CCs cause mechanical injury and inflammation in atherosclerosis, we investigated their presence in solid cancers and their activation of IL-1ß, VEGF, CD44, and Ubiquityl-Histone H2B (Ub-H2B), that promote cancer growth. Methods: Tumor specimens from eleven different types of human cancers and atherosclerotic plaques were assessed for CCs, free cholesterol content and IL1-ß by microscopy, immunohistochemistry, and biochemical analysis. Breast and colon cancer cell lines were cultured with and without CCs to select for expression of VEGF, CD44, and Ub-H2B. Western blot and immunofluorescence were performed on cells to assess the effect of CCs on signaling pathways. Results: Cancers displayed higher CC content (+2.29 ± 0.74 vs +1.46 ± 0.84, p < 0.0001), distribution (5.06 ± 3.13 vs 2.86 ± 2.18, p < 0.001) and free cholesterol (3.63 ± 4.02 vs 1.52 ± 0.56 µg/mg, p < 0.01) than cancer free marginal tissues and similarly for atherosclerotic plaques and margins (+2.31 ± 0.51 vs +1.44 ± 0.79, p < 0.02; 14.0 ± 5.74 vs 8.14 ± 5.52, p < 0.03; 0.19 ± 0.14 vs 0.09 ± 0.04 µg/mg, p < 0.02) respectively. Cancers displayed significantly increased expression of IL1-ß compared to marginal tissues. CCs treated cancer cells had increased expression of VEGF, CD44, and Ub-H2B compared to control. By microscopy, CCs were found perforating cancer tumors similar to plaque rupture. Conclusions: These findings suggest that CCs can induce trauma and activate cytokines that enhance cancer growth as in atherosclerosis.

Consumption of Dairy Products and the Risk of Developing Breast Cancer in Polish Women.

Lack of consistency in the relationship between dairy products consumption and breast cancer (BC) risk motivated us to evaluate this association in a case-control study of BC among Polish women. The study includes 1699 women 26-79 years of age, 823 BC cases identified in Cancer Registries and 876 randomly selected controls from the national population registry. Using a validated, semiquantitative food frequency questionnaire (FFQ), the consumption of dairy products was collected for a time period of 10-15 years prior to BC diagnosis. We used logistic regression, adjusting for potential confounders, to assess the relationship between total dairy consumption as well as individual dairy groups of milk, cottage cheese and hard cheese and BC risk for premenopausal and postmenopausal women. For total consumption, a significant decrease in BC risk was observed with increased consumption of one serving/week, OR trend = 0.98, 2% decrease in risk, for premenopausal women only. For milk, a significant decrease in BC risk was observed for an increase in consumption of one glass/week, OR trend = 0.95, 5% decrease, in both strata of menopause. In contrast, for hard cheese, a significant increase in the risk of 10% was observed only in premenopausal women, OR trend = 1.10. Cottage cheese consumption significantly reduced BC risk by 20%, OR trend = 0.80, for an increase in one serving/week for postmenopausal women only. Our results show that individual dairy products have a statistically significant but bi-directional relationship with BC risk, which differs for premenopausal and postmenopausal women.

A population-based case-control study of fetal growth, gestational age, and maternal breast cancer.

Fetal growth or gestational age in a woman's pregnancies may modify pregnancy-related breast cancer risk, yet studies of these exposures are few. The authors conducted a population-based case-control study among parous Michigan women aged ≤50 years using linked Michigan Cancer Registry (1985-2004) and Michigan livebirth records (1978-2004). Breast cancer cases (n = 7,591) were matched 1:4 to controls (n = 28,382) on maternal birth year and race. Using conditional logistic regression, the authors examined the associations of gestational age (in weeks) and fetal growth (defined using birth weight percentiles for gestational age) in first and last births with breast cancer risk. Having a small-for-gestational-age or large-for-gestational-age infant at a maternal first or last birth was not associated with breast cancer risk, but having a small-for-gestational-age infant at a last birth at ≥30 years modestly reduced risk: odds ratio = 0.82 (95% confidence interval: 0.68, 0.98). First delivery at <32 or >41 weeks also modestly reduced risk: odds ratio = 0.80 (95% confidence interval: 0.62, 1.04) or 0.92 (95% confidence interval: 0.85, 0.99), respectively. In the largest case-control study to date, fetal growth was not associated with overall breast cancer risk in women aged ≤50, and there was some evidence for reduced breast cancer risk for early or late gestational age in first births only.

Heritability of measures of kidney disease among Zuni Indians: the Zuni Kidney Project.

BACKGROUND: The long-term goal of the GKDZI (Genetics of Kidney Disease in Zuni Indians) Study is to identify genes, environmental factors, and genetic-environmental interactions that modulate susceptibility to renal disease and intermediate phenotypes. STUDY DESIGN: A community-based participatory research approach was used to recruit family members of individuals with kidney disease. SETTING & PARTICIPANTS: The study was conducted in the Zuni Indians, a small endogamous tribe located in rural New Mexico. We recruited members of extended families, ascertained through a proband with kidney disease and at least 1 sibling with kidney disease. 821 participants were recruited, comprising 7,702 relative pairs. PREDICTOR OUTCOMES & MEASUREMENTS: Urine albumin-creatinine ratio (UACR) and hematuria were determined in 3 urine samples and expressed as a true ratio. Glomerular filtration rate (GFR) was estimated using the Modification of Diet in Renal Disease (MDRD) Study equation modified for American Indians. Probands were considered to have kidney disease if UACR was >or=0.2 in 2 or more of 3 spot urine samples or estimated GFR was decreased according to the CRIC (Chronic Renal Insufficiency Cohort) Study criteria. RESULTS: Kidney disease was identified in 192 participants (23.4%). There were significant heritabilities for estimated GFR, UACR, serum creatinine, serum urea nitrogen, and uric acid and a variety of phenotypes related to obesity, diabetes, and cardiovascular disease. There were significant genetic correlations of some kidney-related phenotypes with these other phenotypes. LIMITATIONS: Limitations include absence of renal biopsy, possible misclassification bias, lack of direct GFR measurements, and failure to include all possible environmental interactions. CONCLUSIONS: Many phenotypes related to kidney disease showed significant heritabilities in Zuni Indians, and there were significant genetic correlations with phenotypes related to obesity, diabetes, and cardiovascular disease. The study design serves as a paradigm for the conduct of research in relatively isolated, endogamous, underserved populations.

Breast cancer survival and the expression of genes related to alcohol drinking.

Breast cancer is the leading cause of cancer-related disease in women. Cumulative evidence supports a causal role of alcohol intake and breast cancer incidence. In this study, we explore the change on expression of genes involved in the biological pathways through which alcohol has been hypothesized to impact breast cancer risk, to shed new insights on possible mechanisms affecting the survival of breast cancer patients. Here, we performed differential expression analysis at individual genes and gene set levels, respectively, across survival and breast cancer subtype data. Information about postdiagnosis breast cancer survival was obtained from 1977 Caucasian female participants in the Molecular Taxonomy of Breast Cancer International Consortium. Expression of 16 genes that have been linked in the literature to the hypothesized alcohol-breast cancer pathways, were examined. We found that the expression of 9 out of 16 genes under study were associated with cancer survival within the first 4 years of diagnosis. Results from gene set analysis confirmed a significant differential expression of these genes as a whole too. Although alcohol consumption is not analyzed, nor available for this dataset, we believe that further study on these genes could provide important information for clinical recommendations about potential impact of alcohol drinking on breast cancer survival.

Lack of an Exposure Response and Interaction With HLA-DPß1 and DRß1 Polymorphisms in the Development of Beryllium Toxicity in a High Beryllium Exposure Cohort.

OBJECTIVE: To evaluate interaction of HLA-DPß1 and DRß1 polymorphisms with metrics of beryllium exposure, in the development of beryllium sensitization (BeS) and chronic beryllium disease (CBD). METHODS: A matched case-control study of 61 CBD, 41 BeS, and 259 controls from two beryllium-processing facilities. RESULTS: BES and CBD were significantly associated with presence of DPßE69. Dose response of exposure was not observed for the development of BES and CBD with/without adjustment for DPßE69 (P > 0.05). The DRßE71 polymorphism was more common in BeS than CBD after adjusting for exposure and maybe a protective factor (aOR 0.4, 95% CI 0.2 to 0.9) against the progression of BeS to CBD. CONCLUSION: No exposure-response association was found, which may reflect that the workers in this high exposure cohort were above a threshold level where an exposure-response could be observed.

Polymorphisms in thrombophilia and renin-angiotensin system pathways, preterm delivery, and evidence of placental hemorrhage.

OBJECTIVE: The purpose of this study was to analyze functional polymorphisms in candidate genes (methylenetetrahydrofolate reductase [MTHFR]677C>T, MTHFR1298A>C, factor 5 1691G>A [FVL], and angiotensinogen (AGT)-6G>A) in relation to a hypothesized placental hemorrhage pathway to preterm delivery (PTD). STUDY DESIGN: We assessed maternal genotypes, pregnancy outcomes, and placental pathologic evidence among 560 white and 399 black women who were recruited at mid trimester into a prospective cohort study (1998-2004). Odds of dominant genotypes were calculated for PTDs with (n = 56) or without (n = 177) evidence of placental hemorrhage (referent = term) with the use of race-stratified polytomous logistic regression models. RESULTS: Among white women, FVL GA/AA and AGT(-6) GA/AA were both associated with hemorrhage-related PTDs (odds ratio [OR], 4.8; 95% confidence interval [CI], 1.6-14.2 and OR, 3.8; 95% CI, 1.3-10.5, respectively), but not other PTDs (ORs, 1.2 and 0.9, respectively). FVL GA/AA was associated with placental abruption (OR, 5.8; 95% CI, 1.1-30) among white women. All results were null for MTHFR genotypes. CONCLUSION: FVL and AGT variant genotypes were associated specifically with hemorrhage-related PTDs.

An indicator of cancer: downregulation of monoamine oxidase-A in multiple organs and species.

BACKGROUND: Identifying consistent changes in cellular function that occur in multiple types of cancer could revolutionize the way cancer is treated. Previous work has produced promising results such as the identification of p53. Recently drugs that affect serotonin reuptake were shown to reduce the risk of colon cancer in man. Here, we analyze an ensemble of cancer datasets focusing on genes involved in the serotonergic pathway. Genechip datasets consisting of cancerous tissue from human, mouse, rat, or zebrafish were extracted from the GEO database. We first compared gene expression between cancerous tissues and normal tissues for each type of cancer and then identified changes that were common to a variety of cancer types. RESULTS: Our analysis found that significant downregulation of MAO-A, the enzyme that metabolizes serotonin, occurred in multiple tissues from humans, rodents, and fish. MAO-A expression was decreased in 95.4% of human cancer patients and 94.2% of animal cancer cases compared to the non-cancerous controls. CONCLUSION: These are the first findings that identify a single reliable change in so many different cancers. Future studies should investigate links between MAO-A suppression and the development of cancer to determine the extent that MAO-A suppression contributes to increased cancer risk.

Frequency of Cholesterol Crystals in Culprit Coronary Artery Aspirate During Acute Myocardial Infarction and Their Relation to Inflammation and Myocardial Injury.

Cholesterol crystals (CCs) have been associated with plaque rupture through mechanical injury and inflammation. This study evaluated the presence of CCs during acute myocardial infarction (AMI) and associated myocardial injury, inflammation, and arterial blood flow before and after percutaneous coronary intervention. Patients presenting with AMI (n = 286) had aspiration of culprit coronary artery obstruction. Aspirates were evaluated for crystal content, size, composition, and morphology by scanning electron microscopy, crystallography, and infrared spectroscopy. These were correlated with inflammatory biomarkers, cardiac enzymes, % coronary stenosis, and Thrombolysis in Myocardial Infarction (TIMI) blush and flow grades. Crystals were detected in 254 patients (89%) and confirmed to be cholesterol by spectroscopy. Of 286 patients 240 (84%) had CCs compacted into clusters that were large enough to be measured and analyzed. Moderate to extensive CC content was present in 172 cases (60%). Totally occluded arteries had significantly larger CC clusters than partially occluded arteries (p <0.05). Patients with CC cluster area >12,000 µm2 had significantly elevated interleukin-1 beta (IL-1ß) levels (p <0.01), were less likely to have TIMI blush grade of 3 (p <0.01), and more likely to have TIMI flow grade of 1 (p <0.01). Patients with recurrent AMI had smaller CC cluster area (p <0.04), lower troponin (p <0.02), and IL-1ß levels (p <0.04). Women had smaller CC clusters (p <0.04). Macrophages in the aspirates were found to be attached to CCs. Coronary artery aspirates had extensive deposits of CCs during AMI. In conclusion, presence of large CC clusters was associated with increased inflammation (IL-1ß), increased arterial narrowing, and diminished reflow following percutaneous coronary intervention.

Association of serum cytokines with colorectal polyp number and type in adult males.

Chronic inflammation contributes to colorectal carcinogenesis. To determine whether serum cytokines are associated with colon polyps, 126 asymptomatic men (48-65 years) were recruited during colonoscopy. Serum cytokine concentrations were measured. Odds ratios were determined using polytomous logistic regression for polyp number and type. Men with serum monocyte chemotactic protein-3 (MCP-3) or soluble interleukin-4 receptor (sIL-4R) concentrations in the highest tertile were 0.2 times less likely to have three or more polyps relative to no polyps. For each increase in serum MCP-3 or sIL-4R tertile a man was about 0.4 times less likely to have three or more polyps than to have no polyps. Men with serum concentrations of interferon-α2 (IFN-α2) or interleukin (IL)-7 in the highest tertile were three times more likely to have an adenoma than no polyps. Those with serum IL-8 concentrations in the highest tertile were four times more likely to have an adenoma than no polyps. For each increase in serum IFN-α2, IL-7, or IL-8 tertile an individual was 1.8 times more likely to have an adenoma than to have no polyps. Serum concentrations of MCP-3, sIL-4R, IFN-α2, IL-7, and IL-8 may indicate which men are more likely to have colorectal polyps.

An overlooked connection: serotonergic mediation of estrogen-related physiology and pathology.

BACKGROUND: In humans, serotonin has typically been investigated as a neurotransmitter. However, serotonin also functions as a hormone across animal phyla, including those lacking an organized central nervous system. This hormonal action allows serotonin to have physiological consequences in systems outside the central nervous system. Fluctuations in estrogen levels over the lifespan and during ovarian cycles cause predictable changes in serotonin systems in female mammals. DISCUSSION: We hypothesize that some of the physiological effects attributed to estrogen may be a consequence of estrogen-related changes in serotonin efficacy and receptor distribution. Here, we integrate data from endocrinology, molecular biology, neuroscience, and epidemiology to propose that serotonin may mediate the effects of estrogen. In the central nervous system, estrogen influences pain transmission, headache, dizziness, nausea, and depression, all of which are known to be a consequence of serotonergic signaling. Outside of the central nervous system, estrogen produces changes in bone density, vascular function, and immune cell self-recognition and activation that are consistent with serotonin's effects. For breast cancer risk, our hypothesis predicts heretofore unexplained observations of the opposing effects of obesity pre- and post-menopause and the increase following treatment with hormone replacement therapy using medroxyprogesterone. SUMMARY: Serotonergic mediation of estrogen has important clinical implications and warrants further evaluation.

The effect of selected preparation variables on the radiochemical purity of 99mTc-sestamibi.

OBJECTIVE: Measurement of cardiac perfusion via agents such as 99mTc-sestamibi (Cardiolite; DuPont-Merck Pharmaceutical Co., Inc.) is widely used in clinical nuclear medicine for the diagnosis of coronary artery disease. The monograph for 99mTc-sestamibi recommends at least 90% radiochemical purity (RCP) for clinical use. Various factors may influence the RCP of certain reagent kits. Some of these include the amount of activity added to the reagent kit, the generator ingrowth time, the generator manufacturer, the age of the eluate, and the age of the formulated kit. A D-optimal design with a 20-experiment run was devised to study the effects of these variables either alone or in combination on the RCP of 99mTc-sestamibi. METHODS: The RCP was assessed by Baker-Flex thin-layer and high-performance liquid chromatographic methods, immediately and 6 h after reconstitution of the 99mTc-sestamibi. RESULTS: The results showed that 4 of the 5 variables studied were statistically significant predictors of the RCP. The age of the formulated kit did not influence the RCP. CONCLUSION: For any combination of these 4 variables, the mean RCP remained greater than or equal to 90%, that is, within the recommended range of RCP for clinical use at radioactivity levels ranging from 5,550 MBq to 37,000 MBq.

Development of a clinical decision rule for triage of women with palpable breast masses.

BACKGROUND AND OBJECTIVE: Given the large numbers of open breast biopsies performed in women who have benign breast masses, we developed a clinical decision rule (CDR), called BREASTAID, to triage women into open biopsy or follow-up. METHODS: A prospective cohort design was used to obtain data on 452 palpable breast masses evaluated at a referral clinic. Breast cancer was defined as ductal carcinoma in situ or invasive cancer at open biopsy. Separate logistic regression models were developed at three logical stages of the clinical workup. Bayes' theorem was applied in a stepwise fashion to revise model probabilities to generate a final probability of cancer. Receiver operator characteristics curves were generated to determine the optimum cut-point. Results derived from the CDR were compared with actual clinical practice. RESULTS: A total of 452 masses in 380 women were included. Clinical practice resulted in 180 masses (39.8%) undergoing open biopsy, 41 (22.8%) of which were cancers. Age, history of breast cancer in the mother, mass size, mammography findings, and fine needle aspiration biopsy results were included in the final models. When applied to the derivation dataset, BREASTAID successfully identified 40 of 41 cancer masses (sensitivity 97.6%, 95% confidence interval [CI] 94.1-99.9), and 350 of 411 noncancer masses (specificity 85.2%, 95% CI 81.8-88.5). BREASTAID would have reduced the number of biopsies performed on the 411 benign masses from 139 to 61. CONCLUSIONS: This study demonstrated that a CDR based on routinely collected clinical variables has the potential to accurately triage women with palpable breast masses. Further validation of the rule is required before its clinical use can be considered.

Glucosinolate derivatives in stored fermented cabbage.

The research focused on the glucosinolate (GLS) breakdown products formed during the fermentation of cabbage. A relationship between the contents of degradation products in fermented cabbage and native GLS in raw cabbage was investigated. The effect of fermented cabbage storage on the contents of individual compounds was also assayed. Ascorbigen formed from one of the degradation products of glucobrassicin (indole GLS) was found to be a dominating compound in fermented cabbage. Irrespective of the time of fermented cabbage storage, the content of ascorbigen reached approximately 14 micromol/100 g. Neither the content of isothiocyanates, the major degradation products of aliphatic GLS, nor that of cyanides exceeded 2.5 microM. Storage of cabbage caused periodical increases and decreases in the contents of cyanides and consequent declines in the contents of isothiocyanates. The highest relative contents (expressed as a percentage of the native GLS content) of degradation products--ranging from >70 to 96%--were reported for the products of glucoraphanin degradation, whereas the lowest-- <5% --were reported for the products of sinigrin degradation.

Adipokines and obesity are associated with colorectal polyps in adult males: a cross-sectional study.

BACKGROUND: Obesity increases the risk of colon cancer. It is also known that most colorectal cancers develop from adenomatous polyps. However, the effects of obesity and adipokines on colonic polyp formation are unknown. METHODS: To determine if BMI, waist circumference or adipokines are associated with colon polyps in males, 126 asymptomatic men (48-65 yr) were recruited at time of colonoscopy, and anthropometric measures as well as blood were collected. Odds ratios were determined using polytomous logistic regression for polyp number (0 or ≥3) and polyp type (no polyp, hyperplastic polyp, tubular adenoma). RESULTS: 41% of the men in our study were obese (BMI ≥30). The odds of an obese individual having ≥3 polyps was 6.5 (CI: 1.3-33.0) times greater than those of a lean (BMI<25) individual. Additionally, relative to lean individuals, obese individuals were 7.8 (CI: 2.0-30.8) times more likely to have a tubular adenoma than no polyp. As BMI category increased, participants were 2.9 (CI: 1.5-5.4) times more likely to have a tubular adenoma than no polyps. Serum leptin, IP-10 and TNF-α were significantly associated with tubular adenoma presence. Serum leptin and IP-10 were significantly associated with increased likelihood of ≥3 polyps, and TNF-α showed a trend (p = 0.09). CONCLUSIONS: Obese men are more likely to have at least three polyps and adenomas. This cross-sectional study provides evidence that colonoscopy should be recommended for obese, white males.