Non-communicable chronic diseases and timely breast cancer screening among women of the Eastern Caribbean Health Outcomes Research Network (ECHORN) Cohort Study.

PURPOSE: The Caribbean population faces a growing burden of multiple non-communicable chronic diseases (NCDs). Breast cancer is the leading cause of cancer death for women in the Caribbean. Given the substantial burden of NCDs across the region, cancer prevention and control strategies may need to be specifically tailored for people with multiple co-morbidities. Preventive screening, such as timely mammography, is essential but may be either facilitated or hampered by chronic disease control. The main objective of this study is to examine the relationship between a chronic disease and timely breast cancer screening. METHODS: We conducted a cross-sectional data analysis using baseline data from the Eastern Caribbean Health Outcomes Research Network (ECHORN) Cohort Study-ECS. Our independent variables were presence of chronic diseases (hypertension or diabetes), defined as having been told by a clinical provider. Our dependent variable was timely screening mammography, as defined by receipt of mammography within the past 2 years. We examined bivariate and multivariate associations of covariates and timely screening mammography. RESULTS: In our sample (n = 841), 52% reported timely screening mammography. Among those with timely screening, 50.8% reported having hypertension, and 22.3% reported having diabetes. In our bivariate analyses, both diabetes and hypertension were associated with timely screening mammography. In partially adjusted models, we found that women with diabetes were significantly more likely to report timely screening mammography than women without diabetes. In our fully adjusted models, the association was no longer significant. Having a usual source of healthcare and a woman's island of residence were significantly associated with timely screening mammography (p < 0.05). CONCLUSIONS: We found that half of eligible women received timely screening mammography. Diabetes and hypertension, though common, are not associated with timely screening mammography. Usual source of care remains an important factor to timely breast cancer screening.

Astronomy. ASASSN-15lh: A highly super-luminous supernova.

We report the discovery of ASASSN-15lh (SN 2015L), which we interpret as the most luminous supernova yet found. At redshift z = 0.2326, ASASSN-15lh reached an absolute magnitude of Mu ,AB = -23.5 ± 0.1 and bolometric luminosity Lbol = (2.2 ± 0.2) × 10(45) ergs s(-1), which is more than twice as luminous as any previously known supernova. It has several major features characteristic of the hydrogen-poor super-luminous supernovae (SLSNe-I), whose energy sources and progenitors are currently poorly understood. In contrast to most previously known SLSNe-I that reside in star-forming dwarf galaxies, ASASSN-15lh appears to be hosted by a luminous galaxy (MK ≈ -25.5) with little star formation. In the 4 months since first detection, ASASSN-15lh radiated (1.1 ± 0.2) × 10(52) ergs, challenging the magnetar model for its engine.

Health disparities in clinical practice patterns for prostate cancer screening by geographic regions in the United States: a multilevel modeling analysis.

BACKGROUND: To our knowledge, no previous study has examined state-level geographic variability and its predictors in clinical practice patterns to screen for prostate cancer in the United States. METHODS: We used the Behavioral Risk Factor Surveillance System 2010 data set to analyze geographic variability (by state) and its associated predictors in receiving a PSA test and/or a digital rectal examination (DRE). The study population consisted of men aged ≥50 years who responded as yes/no when asked about having a PSA test or DRE performed during the last year. We build two multilevel logistic regression models, differing in dependent variables, that is, (1) any prostate cancer screening (PCS) (either PSA and/or DRE), and (2) PCS based on PSA testing (PSAT). Individual characteristics (age, education, employment, marriage, income, race/ethnicity, self-reported health status, obesity, alcohol consumption, smoking status, personal physician presence, and health insurance coverage) were treated as level-1 variables and state characteristics (number of doctors per 100 000 persons per state, US regions and metropolitan statistical area (MSA) codes) were treated as level-2 variables. RESULTS: We found significant geographic variability in receiving PCS and PSAT screening in the United States. For PCS, MSA code was an independent predictor, with men living in urban areas having lower odds of screening (odds ratio (OR)=0.8, 95% confidence interval (CI)=0.7-0.9). In PSAT, the number of doctors per 100 000 persons per state was an independent predictor, with lowest quartile states (0-25% quartile) having lower odds of PSA-based screening (OR=0.78, 95% CI=063-0.94). In both models, all level-1 variables were independent predictors (P<0.05) of PCS, except self-reported health status. CONCLUSIONS: Men living in urban areas and states with lower prevalence of doctors have lower odds of screening for prostate cancer and PSAT, respectively, after adjusting for individual variables. Future studies should examine the reasons for these health disparities.

ras gene mutations are absent in NMU-induced mammary carcinomas from aging rats.

Carcinoma induction in the rat mammary carcinogenesis model is age dependent. In this study, mammary cancer susceptibility and ras gene activation were investigated in rats exposed to N:-methyl-N:-nitrosourea (NMU) at 2, 6, 8 and 15 months. Animals were resistant to NMU-induced mammary tumor development when exposed at 6 and 8 months of age, whereas a significant number of mammary carcinomas developed in animals exposed to NMU at 2 and 15 months of age. G35-->A35 activating mutations in the Harvey ras gene were found only in mammary carcinomas from rats exposed to NMU at 2 months of age, but not in tumors that developed in animals exposed to NMU at 15 months of age. No G35-->A35 activating mutations were present in the Kirsten ras gene of any of the mammary tumors. Additional analysis of exons 1 and 2 of the Harvey ras gene from mammary carcinomas that developed in animals exposed to NMU at 15 months of age did not reveal any other activating mutations in this gene. In mammary carcinomas from animals exposed to NMU at 2 months of age, the frequency of mammary carcinomas with mutations in the Harvey ras gene was independent of the time from which the tumor first appeared. Therefore, age at the time of carcinogen exposure plays a critical role in both breast cancer susceptibility and the molecular events that contribute to mammary carcinoma development.

Surgeon perspectives on surgical options for early-stage breast cancer.

To evaluate the practice patterns of general and plastic surgeons regarding patients with early-stage breast cancer, all general and plastic surgeons in Quebec and Maryland were mailed self-administered questionnaires evaluating surgeon demographics, practice patterns, treatment preferences, and satisfaction with the results of lumpectomy and radiation therapy or breast reconstruction. Response rates of 38.3 percent and 26.7 percent were obtained for general surgeons in Quebec and Maryland, respectively. The ratio of reported mastectomies to lumpectomies was 1:2 in Maryland and 1:5 in Quebec. All general surgeons considered lumpectomy an important option. Ninety percent of Maryland surgeons versus 44 percent of Quebec surgeons considered mastectomy important. A total of 53.6 percent versus 24.9 percent of general surgeons in Maryland and Quebec, respectively, considered delayed reconstruction an important option. Additionally, 81.3 percent of Maryland surgeons considered immediate reconstruction important, and 79.6 percent discussed it with all stage I or II patients. More than 75 percent of Quebec general surgeons reported discussing immediate or delayed reconstruction with < or =50 percent of these women. Response rates of 53.6 percent and 48.8 percent were obtained for plastic surgeons in Quebec and Maryland, respectively. In one year Quebec plastic surgeons reported that they performed less than half the number of reconstructions performed by Maryland plastic surgeons (7.2 versus 17.3). In Quebec, 82.3 percent of surgeons reported that they frequently discuss delayed reconstruction, 25.1 percent immediate, 62.5 percent pedicled TRAM, and 51.7 percent nonautogenous options. In Maryland, 74.3 percent of plastic surgeons frequently discuss delayed reconstruction, 95.7 percent immediate, 89.9 percent pedicled TRAM, and 85.9 percent nonautogenous options. For women with early-stage breast cancer, regional variations exist in the surgical options discussed and provided.

Surgical options for the early-stage breast cancer: factors associated with patient choice and postoperative quality of life.

Patients with early-stage breast cancer have three surgical options: lumpectomy with radiotherapy, mastectomy alone, and mastectomy with breast reconstruction. Our objective was to compare women in these three groups with respect to demographics, preoperative counseling, postoperative body image, and quality of life. Women having undergone surgery for stage 1 or 2 breast cancer between 1990 and 1995 were selected by random sampling of hospital tumor registries and were mailed a self-administered questionnaire, which included the Medical Outcomes Survey Short Form 36. Patients were stratified into three mutually exclusive groups: lumpectomy with axillary node dissection and radiotherapy, modified radical mastectomy, and modified radical mastectomy with breast reconstruction. In total, 267 of 525 surveys were returned (50.9 percent). Compared with mastectomy patients, breast reconstruction patients were younger (p < 0.001), better educated (p = 0.001), and more likely Caucasian (p = 0.02). Among mastectomy patients, 54.9 percent recalled that lumpectomy had been discussed preoperatively and 39.7 percent recalled discussion of breast reconstruction. Post-operative comfort with appearance was significantly lower for mastectomy patients. The relationship between type of surgery and postoperative quality of life varied with age. Under 55, quality of life was lowest for mastectomy patients on all but two Medical Outcomes Survey Short Form 36 subscales. Over 55, quality of life was lowest for lumpectomy patients on all subscales (p < 0.05 for all subscales except social functioning and role-emotional). Treatment choice may be related to age, race, education, and preoperative counseling. Whereas the effect of breast cancer on a woman's life is complex and individual, the type of surgery performed is a significant variable, whose impact may be related to patient age.

Transfection of Mammalian cells in vitro: use in analysis of neuronal damage.

Transfection of specific elements of DNA into cultured mammalian cells allows for the analysis of a range of functional and toxicologic mechanisms. At the heart of this technique is the ability to promote the uptake of DNA into actively growing cells, and to detect and analyze the expression of the gene(s) encoded by the DNA (1). The two basic types of transfection analyses are transient transfections, in which the DNA is expressed during the few days postapplication, and stable transfections, in which cells expressing the gene of interest are actively selected via cointroduction of a marker for positive selections (2). Choosing which technique is appropriate for a given experiment is determined by the temporal aspects of the question, the types of assays performed, and whether the gene of interest is expressed constitutively or via an inducible promoter. Illustrations for both methods will be provided.

Viability assays for cells in vitro: the ethidium/calcein assay and the immunofluorescence combination assay.

In neurotoxicology, studies have become more sophisticated and focus more on changes evident at the cellular and molecular level rather than on whole-animal morbidity. For this and other reasons, in vitro model systems are being incorporated into neurotoxicity screens and mechanistic studies. The use of in vitro systems allows for the isolation and culturing of cells specifically targeted by neurotoxicants and for the determination of cell viability following treatment with a neurotoxicant. A reliable in vitro cell viability assay is a critical component of any drug or neurotoxicant study (1).

Harvey ras results in a higher frequency of mammary carcinomas than Kirsten ras after direct retroviral transfer into the rat mammary gland.

Exclusive activation of either the Harvey-, Kirsten-, or N-ras gene is often found in human and rodent cancers, although the mechanisms responsible for tissue-specific ras gene activation are poorly understood. In this study, the contribution of ras gene expression and Ras protein activity to the tissue-specificity of ras gene activation was investigated using the rat mammary carcinogenesis model where ras activation, when it occurs, is exclusively in the Harvey ras gene. Differential ras gene expression was examined in mammary tissue from virgin, pregnant, and lactating rats. Harvey ras expression was 1.5-2-fold higher than Kirsten ras or N-ras at each adult stage of development, with the highest ras levels expressed during pregnancy. The modest difference in total mRNA expression found between the independent members of the ras gene family is unlikely to fully account for the exclusive tissue-specificity of Harvey ras activation observed in rat mammary carcinogenesis. Thus, the role of Ras protein specificity was studied by infecting the mammary gland of virgin rats in situ with replication-defective retroviral vectors expressing either the activated or wild-type forms of Harvey- or Kirsten-ras. A 7-14-fold higher number of mammary carcinomas was observed after infection with vectors expressing the G35 to A activated Harvey ras gene product compared with those expressing G35 to A activated Kirsten ras. Mammary carcinomas also developed from infusion of vectors expressing wild-type Harvey ras, but not wild-type Kirsten ras. These data suggest the importance of the Ras protein itself in determining the specificity of the highly homologous Ras family members in organ-specific carcinogenesis.

Induction of apoptosis by organotin compounds in vitro: neuronal protection with antisense oligonucleotides directed against stannin.

Immortalized cell lines and primary neuronal cultures were used to characterize the selective toxicity of trimethyltin (TMT),triethyltin (TET) and tributyltin (TBT). TBT and TET were cytotoxic at similar concentrations in the immortalized cell lines tested; the 50% toxic concentration (TC50) was 1 to 11 microM. In contrast, immortalized cell lines varied considerably in their sensitivity to TMT, with sensitive cell lines (neuroblastomas, T-, B-cell lines) showing TC50 values of 2 to 8 microM, whereas insensitive cells (NIH-3T3 fibroblast, HTB-14 glioma, TC-7 kidney cells) had TC 50 values > 100 microM. Primary neuronal cell cultures were very sensitive to organotins (TC50 values, 1-10nM), and showed patterns of selective toxicity with respect to neuronal and glial cells. Because organotin toxicity evolves over 24 to 48 hr. we determined whether these compounds induced apoptosis in primary cultures. TMT increased (P < .05) the fraction of apoptotic cells 6 and 12 hr after treatment with TMT at TC50 concentrations. Prior studies suggested that a protein, stannin, was localized in cells sensitive to organotins. Stannin was expressed in several TMT-sensitive cell lines (PC12, T, B cells) and in primary neurons in culture. Stannin was absent in the resistant HTB-14 glioma cell line. The role of stannin in mediating TMT toxicity in primary cultures was investigated by blocking stannin expression with specific antisense oligonucleotides. Treatment of primary cultures with antisense oligonucleotides for 48 hr before and during TMT treatment significantly protected neurons from the neurotoxic and apoptotic effects of TMT. This effect was not observed with scrambled oligonucleotide controls. Thus, TMT may induce apoptosis in sensitive cells, which is partly mediated by stannin. Based on the available data we conclude that stannin expression is necessary, but not sufficient for TMT toxicity.

Experimental laparoscopic aortobifemoral bypass.

The goal of the present study is to develop a technique for laparoscopic aortobifemoral bypass. Piglets weighing between 60 and 78 kg were anesthetized with halothane. The lateral retroperitoneal approach was preferred to the more familiar anterior transperitoneal approach and was successfully completed in 19 piglets. The piglets were placed in the right lateral decubitus position. The first port (2 cm) was inserted halfway between the tip of the 12th rib and the iliac crest. Four other trocars were placed in the retroperitoneum after balloon inflation had allowed creation of a space which permitted visualization of the aorta from the left renal artery down to the aorto-iliac junction. After evacuation of the retropneumoperitoneum, the cavity was maintained using an abdominal lift device and a retractor. Using this approach, we performed four aorto-bifemoral bypasses (end-to-end aortic anastomosis) after conventional intravenous heparinization (100 IU/kg) in less than 4 h. Blood loss did not exceed 250 ml and the hematocrit remained stable. Postmortem evaluation of the grafts revealed they were positioned as in a conventional bypass, their limbs having followed in the created retroperitoneal tunnels along the path of the native arteries. No mortality occurred before sacrifice of the animals. We believe that this first performed series of totally retroperitoneal laparoscopic aortobifemoral bypasses in the porcine model is useful in preparation for human application due to the anatomical similarities in the periaortic region.

Transcriptional regulatory and response mapping of the rat Ha-ras upstream sequence using primary mammary epithelial cells.

The rat Ha-ras upstream sequence (-2876 to +986 bp relative to the most 5' transcriptional start site) was transcriptionally mapped at a gross level. Ha-ras upstream sequence and 5' unidirectional deletion reporter constructs were transfected via particle bombardment into primary cultures of rat mammary epithelial cells. Analyses of Ha-ras reporter expression show that a fragment extending from -2876 to -2110 bp contains a positive regulatory sequence. The majority of Ha-ras expression is attributed to this sequence, since its deletion results in a 4-fold decrease in expression. The Ha-ras gene was also assessed for autoregulation using similar co-transfection experiments. Wild-type and activated (codon 12 G-->A transition) Ha-ras expression vectors, transcriptionally driven by Ha-ras upstream sequence, were co-transfected with Ha-ras upstream sequence deletion reporter constructs. The activated Ha-ras gene product induced its own transcription 2-fold, targeting the regulatory region between -2119 and -313 bp.

Transient promoter activity in primary rat mammary epithelial cells evaluated using particle bombardment gene transfer.

The relative strengths of several commonly used viral promoters in primary cultures of rat mammary epithelial cells were studied using a particle bombardment gene transfer method. NIH 3T3 cells were also examined as a representative cell line. Initially, the conditions necessary for efficient gene transfer using particle bombardment were determined. Discharge voltage for particle bombardment was evaluated to maximize the levels of gene expression and cell viability. After transfection, transgene expression decreased over a 5-day period in both mammary cells and NIH 3T3 cells. Particle bombardment gene transfer was at least fivefold more efficient than lipofection, calcium phosphate co-precipitation, or electroporation. The activity of five viral enhancer/promoters was compared using a luciferase gene assay system. The relative promoter strengths in mammary cells were determined to be: RSV approximately CMV approximately SV40 > MLV > MMTV. Tissue-specific activity of the MMTV-LTR was demonstrated, although this promoter conferred the lowest expression level among the promoters tested.

Alterations in mitogen-induced calcium mobilization and intracellular free calcium produced by 7,12-dimethylbenz(a)anthracene in the Jurkat human T cell line.

The purpose of these studies was to assess the effects of 7,12-dimethylbenz(a)anthracene (DMBA), an immunosuppressive polycyclic aromatic hydrocarbon (PAH), on Ca+2 mobilization induced by phytohemagglutinin (PHA) in the Jurkat human T cell line. Intracellular levels of free cytosolic Ca+2 were examined by flow cytometry using Indo-1 loaded cells. At doses of 3-30 microM, DMBA was found to produce a dose and time-dependent inhibition of Ca+2 mobilization in Jurkat following in vitro exposure. The decrease in Ca+2 mobilization was correlated with an increase in baseline levels of cytoplasmic free Ca+2. Two non-immunosuppressive PAH, benzo(e)pyrene and anthracene, failed to inhibit PHA-induced Ca+2 mobilization or alter baseline levels of free Ca+2. These results suggest that DMBA may produce immunosuppression by inhibiting Ca+2 mobilization or by altering Ca+2 homeostasis in activated T cells.

Bioequivalence of carbamazepine chewable and conventional tablets: single-dose and steady-state studies.

Single-dose and steady-state studies were carried out on separate occasions to examine the bioequivalence of the newly formulated carbamazepine chewable tablet. In the single-dose study, the plasma levels resulting from 2 X 200-mg conventional tablets (CT), 4 X 100-mg chewable tablets swallowed whole (SW), and 4 X 100-mg chewable tablets chewed before swallowing (CHEW) were compared. A randomized 3 X 3 Latin-square design balanced for residual effects, with a 3-week washout period, was used (n = 6). Plasma samples were analyzed by a specific GC method for carbamazepine. The following parameters were used for evaluation: AUC, Cmax, tmax, and t1/2. None of the parameters were significantly different except Cmax and t1/2 values for CHEW and CT. The Cmax was 25% higher and t1/2 was 11% shorter for CHEW than CT. The impact of differences in the peak plasma levels at steady state were examined by pharmacokinetic projection (400 mg b.i.d.) based on the single-dose data and with simulated induction equal to a 50% reduction in t1/2. The projected steady-state CT and CHEW plasma concentrations were similar, with a difference of only 4%. The results demonstrate the bioequivalence of the dosage forms with respect to the extent of absorption, and similar steady-state concentrations of carbamazepine in plasma can be expected. To test the conclusion from the projected study, a separate bioequivalence study to compare CHEW relative to CT was performed at steady state in normal volunteers (200 mg b.i.d.).(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of a solid-phase immunofluorescence assay for detection of antibodies to Legionella pneumophila.

A semiautomated solid-phase immunofluorescence technique (FIAX) was compared with the standard indirect immunofluorescence assay (IFA) for the determination of antibody levels to Legionella pneumophila serogroup 1 in paired human serum samples. The FIAX method was in agreement with the IFA test for 91.8% of the serum pairs but gave evidence of a recent Legionella infection significantly fewer times than did the IFA. These results suggest that the FIAX technique may eventually be a useful alternative test for measuring Legionella antibodies. However, further study will be required to determine its efficacy in providing a serodiagnosis of legionellosis.

Aminoglutethimide bioavailability, pharmacokinetics, and binding to blood constituents.

The bioavailability of aminoglutethimide tablets was examined using a spectrophotometric assay. For six subjects receiving 500 mg of aminoglutethimide as an oral solution, the average peak concentration was 6.2 micrograms/ml with a median time of 0.8 hr. The corresponding average peak concentration for tablet administration was 5.9 micrograms/ml with a median time of 1.5 hr. Average values for the area under the curve (AUC) extrapolated to infinity were 89.0 and 96.8 micrograms hr/ml for the solution and tablets, respectively. The tablets had a 9% larger mean for the AUC than the solution and a 5% lower value for the mean maximum concentration. The bioavailability of the tablets is considered equal to that of oral solution. Data for individual concentration versus time curves were treated by nonlinear least-squares curve fitting. A two-compartment model with first-order absorption gave an acceptable fit for most data sets, but the individual absorption rate coefficients were not reliably determined. Values were estimated for plasma clearance, renal clearance, and volume of distribution. The distribution of aminoglutethimide between plasma and cells of human blood was examined in vitro; the drug concentration in cells was 1.4-1.7 times the concentration in plasma. The binding of aminoglutethimide to plasma proteins of human blood was measured by equilibrium dialysis at starting concentrations of 5 and 10 micrograms/ml. The binding ranged from 21.3 to 25.0% without concentration dependence.