bluuebunny/crossref_metadata_2025 huggingface dataset:
LPS-induced IL-8 activation in human intestinal epithelial cells is accompanied by specific histone H3 acetylation and methylation changes
Authors: Angrisano Tiziana , Pero Raffaela , Peluso Silvia , Keller Simona , Sacchetti Silvana , Bruni Carmelo B , Chiariotti Lorenzo , Lembo Francesca
Published: June 2010

Background

The release of LPS by bacteria stimulates both immune and specific epithelial cell types to release inflammatory mediators. It is known that LPS induces the release of IL-8 by intestinal mucosal cells. Because it is now emerging that bacteria may induce alteration of epigenetic patterns in host cells, we have investigated whether LPS-induced IL-8 activation in human intestinal epithelial cells involves changes of histone modifications and/or DNA methylation at IL-8 gene regulatory region.

Results

RT-PCR analysis showed that IL-8 mRNA levels rapidly increase after exposure of HT-29 cells to LPS. DNA demethylating agents had no effects on IL-8 expression, suggesting that DNA methylation was not involved in IL-8 gene regulation. Consistently we found that 5 CpG sites located around IL-8 transcription start site (-83, -7, +73, +119, +191) were unmethylated on both lower and upper strand either in LPS treated or in untreated HT-29 cells, as well as in normal intestinal mucosa.

Conversely, pretreatment of HT-29 cells with deacetylase inhibitors strengthened the LPS-mediated IL-8 activation. Inhibitors of histone deacetylases could induce IL-8 mRNA expression also in the absence of LPS, suggesting that chromatin modifications could be involved in IL-8 gene regulation. Chromatin immunoprecipitation analyses showed that, concurrently with IL-8 activation, transient specific changes in H3 acetylation and H3K4, H3K9 and H3K27 methylation occurred at IL-8 gene promoter during LPS stimulation. Changes of H3-acetyl, H3K4me2 and H3K9me2 levels occurred early, transiently and corresponded to transcriptional activity, while changes of H3K27me3 levels at IL-8 gene occurred later and were long lasting.

Conclusion

The results showed that specific chromatin modifications occurring at IL-8 gene, including histone H3 acetylation and methylation, mark LPS-mediated IL-8 activation in intestinal epithelial cells while it is unlikely that DNA methylation of IL-8 promoter is directly involved in IL-8 gene regulation in these cells.
Knowledge of stroke risk factors among primary care patients with previous stroke or TIA: a questionnaire study
Authors: Sloma Andrzej , Backlund Lars G , Strender Lars-Erik , Skånér Ylva
Published: June 2010

Background

Survivers of stroke or transient ischaemic attacks (TIA) are at risk of new vascular events. Our objective was to study primary health care patients with stroke/TIA regarding their knowledge about risk factors for having a new event of stroke/TIA, possible associations between patient characteristics and patients' knowledge about risk factors, and patients' knowledge about their preventive treatment for stroke/TIA.

Methods

A questionnaire was distributed to 240 patients with stroke/TIA diagnoses, and 182 patients (76%) responded. We asked 13 questions about diseases/conditions and lifestyle factors known to be risk factors and four questions regarding other diseases/conditions ("distractors"). The patients were also asked whether they considered each disease/condition to be one of their own. Additional questions concerned the patients' social and functional status and their drug use. The t-test was used for continuous variables, chi-square test for categorical variables, and a regression model with variables influencing patient knowledge was created.

Results

Hypertension, hyperlipidemia and smoking were identified as risk factors by nearly 90% of patients, and atrial fibrillation and diabetes by less than 50%. Few patients considered the distractors as stroke/TIA risk factors (3-6%). Patients with a family history of cardiovascular disease, and patients diagnosed with carotid stenosis, atrial fibrillation or diabetes, knew these were stroke/TIA risk factors to a greater extent than patients without these conditions. Atrial fibrillation or a family history of cardiovascular disease was associated with better knowledge about risk factors, and higher age, cerebral haemorrhage and living alone with poorer knowledge. Only 56% of those taking anticoagulant drugs considered this as intended for prevention, while 48% of those taking platelet aggregation inhibitors thought this was for prevention.

Conclusions

Knowledge about hypertension, hyperlipidemia and smoking as risk factors was good, and patients who suffered from atrial fibrillation or carotid stenosis seemed to be well informed about these conditions as risk factors. However, the knowledge level was low regarding diabetes as a risk factor and regarding the use of anticoagulants and platelet aggregation inhibitors for stroke/TIA prevention. Better teaching strategies for stroke/TIA patients should be developed, with special attention focused on diabetic patients.
Comparison of virus isolation using the Vero E6 cell line with real-time RT-PCR assay for the detection of human metapneumovirus
Authors: Matsuzaki Yoko , Mizuta Katsumi , Takashita Emi , Okamoto Michiko , Itagaki Tsutomu , Katsushima Fumio , Katsushima Yuriko , Nagai Yukio , Nishimura Hidekazu
Published: June 2010

Background

The use of cell culture for the diagnosis of human metapneumovirus (hMPV) infection is uncommon at present and molecular method such as reverse-transcription PCR (RT-PCR) has been widely and most commonly used as the preferred test. We aimed to compare the results of virus isolation using Vero E6 cells with real-time RT-PCR for the detection of hMPV, since such a comparison data is not available.

Methods

Between December 2007 and July 2008, we obtained 224 nasopharyngeal swab specimens from patients with acute respiratory infection and tested by the two methods.

Results

Forty-three (19.2%) were found positive by cell culture and 62 (27.7%) by real-time RT-PCR. Cell cultures were positive for 42 of 62 specimens found positive by real-time RT-PCR (67.7% sensitivity) and for 1 of 162 specimens found negative by real-time RT-PCR (99.4% specificity), respectively. The sensitivity of the cell culture was 76.2-87.5% (mean 81.8%) when specimens were collected within 3 days after the onset of symptoms, and the sensitivity decreased to 50% or less thereafter. Among specimens collected within 3 days after symptom onset, all of the real-time RT-PCR positive specimens having a viral load of more than 1.25×105copies/ml were found positive by cell culture.

Conclusions

Cell culture using Vero E6 cell line has 81.8% sensitivity compared with the real-time RT-PCR method, when specimens are collected within 3 days after the onset of symptoms. Thus, this method is a useful method for epidemiological and virological research even in facilities with minimal laboratory resources.
Characterization of AKT independent effects of the synthetic AKT inhibitors SH-5 and SH-6 using an integrated approach combining transcriptomic profiling and signaling pathway perturbations
Authors: Krech Till , Thiede Margarethe , Hilgenberg Ellen , Schäfer Reinhold , Jürchott Karsten
Published: June 2010

Background

Signal transduction processes mediated by phosphatidyl inositol phosphates affect a broad range of cellular processes such as cell cycle progression, migration and cell survival. The protein kinase AKT is one of the major effectors in this signaling network. Chronic AKT activation contributes to oncogenic transformation and tumor development. Therefore, analogs of phosphatidyl inositol phosphates (PIAs) were designed as new small drugs to block AKT activity for cancer treatment. Here we characterize the biological effects of the PIAs SH-5 and SH-6 in colorectal cancer cell lines.

Methods

Serum-starved or serum-supplemented human colorectal cancer cell lines SW480, HT29 and HCT116 were exposed to SH-5 and SH-6. AKT activation was determined by western blotting. Cell viability was assessed using a colorimetric XTT-based assay, apoptosis and cell cycle changes were monitored by FACS analysis. The dynamics of cell morphology alterations was evaluated by confocal and time-lapse microscopy. Transcriptional changes due to inhibitor treatment were analyzed using Affymetrix HG-U133A microarrays and RT-PCR.

Results

While the PIAs clearly reduce AKT phosphorylation in serum starved cells, we did not observe a significant reduction under serum supplemented conditions, giving us the opportunity to analyze AKT independent effects of these compounds. Both inhibitors induce broadly the same morphological alterations, in particular changes in cell shape and formation of intracellular vesicles. Moreover, we observed the induction of binucleated cells specifically in the SW480 cell line. Gene expression analysis revealed transcriptional alterations, which are mostly cell line specific. In accordance to the phenotype we found a gene group associated with mitosis and spindle organization down regulated in SW480 cells, but not in the other cell lines. A bioinformatics analysis using the Connectivity Map linked the gene expression pattern of the inhibitor treated SW480 cells to PKC signaling. Using confocal laser scanning microscopy and time lapse recording we identified a specific defect in the last step of the cytokinesis as responsible for the binucleation.

Conclusions

The PIAs SH-5 and SH-6 impinge on additional cellular targets apart from AKT in colorectal cancer cells. The effects are mostly cell line specific and have an influence at the outcome of the treatment. In view of potential clinical trials it will be necessary to take these diverse effects into consideration to optimize patient treatment.
ADAMTS1 alters blood vessel morphology and TSP1 levels in LNCaP and LNCaP-19 prostate tumors
Authors: Gustavsson Heléne , Tešan Tajana , Jennbacken Karin , Kuno Kouji , Damber Jan-Erik , Welén Karin
Published: June 2010

Background

Decreased expression of the angiogenesis inhibitor ADAMTS1 (ADAM metallopeptidase with thrombospondin type 1 motif, 1) has previously been reported during prostate cancer progression. The aim of this study was to investigate the function of ADAMTS1 in prostate tumors.

Methods

ADAMTS1 was downregulated by shRNA technology in the human prostate cancer cell line LNCaP (androgen-dependent), originally expressing ADAMTS1, and was upregulated by transfection in its subline LNCaP-19 (androgen-independent), expressing low levels of ADAMTS1. Cells were implanted subcutaneously in nude mice and tumor growth, microvessel density (MVD), blood vessel morphology, pericyte coverage and thrombospondin 1 (TSP1) were studied in the tumor xenografts.

Results

Modified expression of ADAMTS1 resulted in altered blood vessel morphology in the tumors. Low expression levels of ADAMTS1 were associated with small diameter blood vessels both in LNCaP and LNCaP-19 tumors, while high levels of ADAMTS1 were associated with larger vessels. In addition, TSP1 levels in the tumor xenografts were inversely related to ADAMTS1 expression. MVD and pericyte coverage were not affected. Moreover, upregulation of ADAMTS1 inhibited tumor growth of LNCaP-19, as evidenced by delayed tumor establishment. In contrast, downregulation of ADAMTS1 in LNCaP resulted in reduced tumor growth rate.

Conclusions

The present study demonstrates that ADAMTS1 is an important regulatory factor of angiogenesis and tumor growth in prostate tumors, where modified ADAMTS1 expression resulted in markedly changed blood vessel morphology, possibly related to altered TSP1 levels.
Effect of nutrient deficiencies on in vitro Th1 and Th2 cytokine response of peripheral blood mononuclear cells to Plasmodium falciparum infection
Authors: Mbugi Erasto V , Meijerink Marjolein , Veenemans Jacobien , Jeurink Prescilla V , McCall Matthew , Olomi Raimos M , Shao John F , Chilongola Jaffu O , Verhoef Hans , Savelkoul Huub FJ
Published: June 2010

Background

An appropriate balance between pro-inflammatory and anti-inflammatory cytokines that mediate innate and adaptive immune responses is required for effective protection against human malaria and to avoid immunopathology. In malaria endemic countries, this immunological balance may be influenced by micronutrient deficiencies.

Methods

Peripheral blood mononuclear cells from Tanzanian preschool children were stimulatedin vitrowithPlasmodium falciparum-parasitized red blood cells to determine T-cell responses to malaria under different conditions of nutrient deficiencies and malaria status.

Results

The data obtained indicate that zinc deficiency is associated with an increase in TNF response by 37%; 95% CI: 14% to 118% and IFN-γ response by 74%; 95% CI: 24% to 297%. Magnesium deficiency, on the other hand, was associated with an increase in production of IL-13 by 80%; 95% CI: 31% to 371% and a reduction in IFN-γ production. These results reflect a shift in cytokine profile to a more type I cytokine profile and cell-cell mediated responses in zinc deficiency and a type II response in magnesium deficiency. The data also reveal a non-specific decrease in cytokine production in children due to iron deficiency anaemia that is largely associated with malaria infection status.

Conclusions

The pathological sequels of malaria potentially depend more on the balance between type I and type II cytokine responses than on absolute suppression of these cytokines and this balance may be influenced by a combination of micronutrient deficiencies and malaria status.
The new platinum(IV) derivative LA-12 shows stronger inhibitory effect on Hsp90 function compared to cisplatin
Authors: Kvardova Veronika , Hrstka Roman , Walerych Dawid , Muller Petr , Matoulkova Eva , Hruskova Veronika , Stelclova Dagmar , Sova Petr , Vojtesek Borivoj
Published: June 2010

Background

Cisplatin and its derivatives are commonly used anti-cancer drugs. However, cisplatin has clinical limitations including serious side effects and frequent emergence of intrinsic or acquired resistance. Thus, the novel platinum(IV) complex LA-12 represents a promising treatment modality, which shows increased intracellular penetration resulting in improved cytotoxicity in various cancer cell lines, including cisplatin resistant cells.

Results

LA-12 disrupts cellular proliferation regardless of the p53 status in the cells, however the potency of the drug is greatly enhanced by the presence of a functional p53, indicating several mechanisms of action. Similarly to cisplatin, an interaction of LA-12 with molecular chaperone Hsp90 was proposed. Binding of LA-12 to Hsp90 was demonstrated by Hsp90 immunoprecipitation followed by platinum measurement using atomic absorption spectrometry (AAS). An inhibitory effect of LA-12 on Hsp90 chaperoning function was shown by decrease of Hsp90-assisted wild-type p53 binding to p21WAF1 promoter sequence in vitro and by accelerated ubiqutination and degradation of primarily unfolded mutant p53 proteins in cells exposed to LA-12.

Conclusions

To generalize our findings, LA-12 induced degradation of other Hsp90 client proteins such as Cyclin D1 and estrogen receptor was shown and proved as more efficient in comparison with cisplatin. This newly characterised molecular mechanism of action opens opportunities to design new cancer treatment strategy profitable from unique LA-12 properties, which combine DNA damaging and Hsp90 inhibitory effects.
Reproductive outcome after hysteroscopic septoplasty in patients with septate uterus - a retrospective cohort study and systematic review of the literature
Authors: Nouri Kazem , Ott Johannes , Huber Johannes C , Fischer Eva-Maria , Stögbauer Lucija , Tempfer Clemens B
Published: June 2010

Background

Septate uterus, one of the most common forms of congenital uterine malformations, negatively affects female reproductive health.

Methods

In a retrospective cohort study, we evaluated the reproductive outcome after hysteroscopic septoplasty in 64 women with septate uterus and primary or secondary infertility. We performed a systematic review of studies evaluating the reproductive outcome after hysteroscopic septoplasty.

Results

Sixty-four women underwent hysteroscopic septoplasty. In 2/64 (3%) women, intraoperative uterine perforation occurred. Complete follow-up was available for 49/64 (76%) patients. Mean follow-up time was 68.6 +/- 5.2 months. The overall pregnancy rate after hysteroscopic septoplasty was 69% (34/49). The overall life birth rate (LBR) was 49% (24/49). The mean time interval between surgery and the first life birth was 35.8 +/- 22.5 months. Including our own data, we identified 18 studies investigating the effect of septoplasty on reproductive outcome in 1501 women. A pooled analysis demonstrated that hysteroscopic septoplasty resulted in an overall pregnancy rate of 60% (892/1501) and a LBR of 45% (686/1501). The overall rate of intra- and postoperative complications was 1.7% (23/1324) and the overall rate of re-hysteroscopy was 6% (79/1324).

Conclusions

In women with septate uterus and a history of infertility, hysteroscopic septoplasty is a safe and effective procedure resulting in a pregnancy rate of 60% and a LBR of 45%.
Recombination analysis reveals a double recombination event in hepatitis E virus
Authors: Wang Hua , Zhang Wen , Ni Bin , Shen Hongxing , Song Yuyu , Wang Xiaochun , Shao Shihe , Hua Xiuguo , Cui Li
Published: June 2010

Recombination of Hepatitis E Virus (HEV) has rarely been reported. In the present study, phylogenetic and recombination analyses were performed on 134 complete HEV genomes. Three potentially significant recombination events, including both intra-genotype and one inter-genotype, were identified by recombination detection analysis. Recombination events I and II occurred intra-genotype and inter-genotype, respectively, among three isolates, including the lineage represented by CHN-XJ-SW13 (GU119961, swine isolate), E067-SIJ05C (AB369690, human isolate), and JJT-Kan (AB091394, human isolate), and lead to the recombinant swine isolate swCH31 (DQ450072). Recombination event III occurred between the lineage represented by the NA1 (M73218) and K52-87 (L25595), which resulted in the recombinant Xingjiang-1 (D11092). Our analyses proved that that recombination could occur between human and swine HEV strains, double recombination events existed in HEV, and recombination event could happen within ORF2 region of HEV. These results will provide valuable hints for future research on HEV diversity.
Predicting alcohol consumption during the month before and after beginning college
Authors: Johnson Heather R , Zywiak William H , Graney Daniel D , Stout Robert L , Trefry Winston B , LaGrutta Joy E , Cohen Frances C
Published: June 2010

Background

We sought to determine predictors of drinking the month before and after beginning college, as well as changes in drinking between these two periods among adjudicated students. We conducted these analyses to inform individual and university-wide approaches to addressing underage drinking, particularly among the heaviest drinkers.

Methods

The sample consisted of 143 students entering college, adjudicated during their first semester, and interviewed during the same semester. The sample consisted of 43% women. Drinking data were collected through the Time-Line Follow-Back interview.

Results

The average number of drinking days (DD) during the first month of college was 7.0 (SD = 4.7), the average number of drinks per drinking day (DDD) was 7.4 (SD = 3.4), and the average volume of standard drink units consumed during this month was 56.3 (SD = 51.2). Students had volunteered for a two-year college facilitation study, and had been invited to participate after receiving a citation for violating university alcohol policies. Analyses consisted of nine backward elimination regression analyses with nine variables entered as predictors (one was a control variable). Age of first intoxication was related to every dependent measure. Men had a higher August DDD, September DDD, and September volume than women. Roommate drinking level was associated with September DDD and September volume. Out-of-state students had a lower August volume than in-state students. High school rank was inversely related to September drinking days. SAT score, declared major status, and fraternity/sorority status were not related to drinking according to these multivariate analyses.

Conclusions

Results suggest that approaches to underage drinking for adjudicated students may need to be tailored according to age of first intoxication. Results also suggest the drinking level of the heaviest drinking roommate may moderate individual level interventions. Further, interventions applied to an entire dorm room may prove efficacious. Results also suggest that high school rank, rather than SAT scores, should be used as college entry criteria to yield a drier incoming class. Results may not generalize to non-adjudicated students.
Perceptions of rewards among volunteer caregivers of people living with AIDS working in faith‐based organizations in South Africa: a qualitative study
Authors: Akintola Olagoke
Published: June 2010

Background

Volunteer caregivers are a critical source of support for the majority of people living with HIV and AIDS in southern Africa, which has extremely high HIV/AIDS prevalence rates. While studies have shown that volunteer caregiving is associated with negative health and socio‐economic outcomes, little is known about the positive experiences of volunteers in the home‐based care context in South Africa. The purpose of this study is to explore the perception of rewards among volunteers working in home‐based care settings.

Methods

This study uses a qualitative design. Qualitative interviews were conducted with a purposively selected sample of 55 volunteer caregivers using an interview schedule containing open‐ended questions.

Results

Volunteer caregivers derived intrinsic rewards related to self‐growth and personal (emotional and psychological) development on the job; they also derived satisfaction from community members taking a liking for them and expressing a need for their services. Volunteers felt gratified by the improvements in their health behaviours, which were a direct consequence of the experiences of caring for terminally ill patients with AIDS. Extrinsic rewards came from appreciation and recognition shown by patients and community members. Extrinsic rewards also accrued to volunteers when the services they rendered made their patients happy. Perhaps the greatest sources of extrinsic rewards are skills and competencies acquired from training and experience while caring for their patients, and volunteers' ability to make a difference in the community.

Conclusions

Insights into volunteer caregiver rewards provide opportunities for policy makers and programme managers to develop a model of home‐based care that facilitates the accrual of rewards to volunteers alongside volunteers' traditional duties of patient care. Programme managers could employ these insights in recruiting and assisting volunteers to identify and reflect on rewards in the caregiving situation as a means of reducing the burden of care and sustaining volunteer interest in caregiving.
Dramatic increase of third-generation cephalosporin-resistant E. coli in German intensive care units: secular trends in antibiotic drug use and bacterial resistance, 2001 to 2008
Authors: Meyer Elisabeth , Schwab Frank , Schroeren-Boersch Barbara , Gastmeier Petra
Published: June 2010

Introduction

The objective of the present study was to analyse secular trends in antibiotic consumption and resistance data from a network of 53 intensive care units (ICUs).

Methods

The study involved prospective unit and laboratory-based surveillance in 53 German ICUs from 2001 through 2008. Data were calculated on the basis of proportions of nonduplicate resistant isolates, resistance densities (that is, the number of resistant isolates of a species per 1,000 patient-days) and an antimicrobial usage density (AD) expressed as daily defined doses (DDD) and normalised per 1,000 patient-days.

Results

Total mean antibiotic use remained stable over time and amounted to 1,172 DDD/1,000 patient-days (range 531 to 2,471). Carbapenem use almost doubled to an AD of 151 in 2008. Significant increases were also calculated for quinolone (AD of 163 in 2008) and third-generation and fourth-generation cephalosporin use (AD of 117 in 2008). Aminoglycoside consumption decreased substantially (AD of 86 in 2001 and 24 in 2008). Resistance proportions were as follows in 2001 and 2008, respectively: methicillin-resistant Staphylococcus aureus (MRSA) 26% and 20% (P = 0.006; trend test showed a significant decrease), vancomycin-resistant enterococcus (VRE) faecium 2.3% and 8.2% (P = 0.008), third-generation cephalosporin (3GC)-resistant Escherichia. coli 1.2% and 19.7% (P < 0.001), 3GC-resistant Klebsiella pneumoniae 3.8% and 25.5% (P < 0.001), imipenem-resistant Acinetobacter baumannii 1.1% and 4.5% (P = 0.002), and imipenem-resistant K. pneumoniae 0.4% and 1.1%. The resistance densities did not change for MRSA but increased significantly for VRE faecium and 3GC-resistant E. coli and K. pneumoniae. In 2008, the resistance density for MRSA was 3.73, 0.48 for VRE, 1.39 for 3GC-resistant E. coli and 0.82 for K. pneumoniae.

Conclusions

Although total antibiotic use did not change over time in German ICUs, carbapenem use doubled. This is probably due to the rise in 3GC-resistant E. coli and K. pneumoniae. Increased carbapenem consumption was associated with carbapenem-resistant K. pneumoniae carbapenemase-producing bacteria and imipenem-resistant A. baumannii.
Randomized Phase II Trial of All-Trans-Retinoic Acid With Chemotherapy Based on Paclitaxel and Cisplatin As First-Line Treatment in Patients With Advanced Non–Small-Cell Lung Cancer
Authors: Arrieta Oscar , González-De la Rosa Claudia H. , Aréchaga-Ocampo Elena , Villanueva-Rodríguez Geraldine , Cerón-Lizárraga Tania L. , Martínez-Barrera Luis , Vázquez-Manríquez María E. , Ríos-Trejo Miguel Ángel , Álvarez-Avitia Miguel Á. , Hernández-Pedro Norma , Rojas-Marín Carlos , De la Garza Jaime
Published: June 2010

Purpose

This randomized phase II trial evaluated whether the combination of cisplatin and paclitaxel (PC) plus all-trans retinoic acid (ATRA) increases response rate (RR) and progression-free survival (PFS) in patients with advanced non–small-cell lung cancer (NSCLC) with an acceptable toxicity profile and its association with the expression of retinoic acid receptor beta 2 (RAR-β2) as a response biomarker.

Patients and Methods

Patients with stages IIIB with pleural effusion and IV NSCLC were included to receive PC, and randomly assigned to receive ATRA 20 mg/m2/d (RA/PC) or placebo (P/PC) 1 week before treatment until two cycles were completed. RAR-β2 expression was analyzed in tumor and adjacent lung tissue.

Results

One hundred seven patients were included, 55 in the P/PC group and 52 in the RA/PC group. RR for RA/PC was 55.8% (95% CI, 46.6% to 64.9%) and for P/PC, 25.4% (95% CI, 21.3 to 29.5%; P = .001). The RA/PC group had a longer median PFS (8.9 v 6.0 months; P = .008). Multivariate analysis of PFS showed significant differences for the RA/PC group (hazard ratio, 0.62; 95% CI, 0.4 to 0.95). No significant differences in toxicity grade 3/4 were found between groups, except for hypertriglyceridemia (10% v 0%) in RA/PC (P = .05). Immunohistochemistry and reverse-transcriptase polymerase chain reaction assays showed expression of RAR-β2 in normal tissues of all tumor samples, but only 10% of samples in the tumor tissue.

Conclusion

Adding ATRA to chemotherapy could increase RR and PFS in patients with advanced NSCLC with an acceptable toxicity profile. A phase III clinical trial is warranted to confirm these findings.
Effect of Body Mass Index on Recurrences in Tamoxifen and Anastrozole Treated Women: An Exploratory Analysis From the ATAC Trial
Authors: Sestak Ivana , Distler Wolfgang , Forbes John F. , Dowsett Mitch , Howell Anthony , Cuzick Jack
Published: June 2010

Purpose

Third-generation aromatase inhibitors have been widely used in postmenopausal women for the adjuvant treatment of hormone receptor–positive breast cancer. As aromatase inhibitors work by inhibiting the conversion of androgens to estrogens in adipose tissue, we hypothesized that anastrozole may be more effective in women with a high body mass index (BMI).

Patients and Methods

The Arimidex, Tamoxifen Alone or in Combination (ATAC) study was a double-blind randomized clinical trial in which postmenopausal women with early-stage breast cancer were randomly assigned to receive oral daily anastrozole (1 mg) alone, tamoxifen (20 mg) alone, or the combination in a double-blind fashion. Analyses were based on the 100-month median follow-up for women with hormone receptor–positive breast cancers (estrogen [ER] and/or progesterone [PgR] positive). Here, we investigate the impact of BMI on recurrence and the relative benefit of anastrozole versus tamoxifen according to baseline BMI.

Results

Overall, women with a high BMI (BMI > 35 kg/m2) at baseline had more recurrences than those women with a low BMI (BMI < 23 kg/m2; adjusted hazard ratio [HR], 1.39; 95% CI, 1.06 to 1.82; Pheterogeneity = .03) and significantly more distant recurrences (adjusted HR, 1.46; 95% CI, 1.07 to 1.61; Pheterogeneity = .01). Overall, the relative benefit of anastrozole versus tamoxifen was nonsignificantly better in thin women compared to overweight women.

Conclusion

These results confirm the poorer prognosis of obese women with early-stage breast cancer. Recurrence rates were lower for anastrozole than tamoxifen for all BMI quintiles. Our results suggest that the relative efficacy of anastrozole compared to tamoxifen is greater in thin postmenopausal women and higher doses or more complete inhibitors might be more effective in overweight women, but this requires independent confirmation.
Genetics of Biliary Tract Cancers and Emerging Targeted Therapies
Authors: Hezel Aram F. , Deshpande Vikram , Zhu Andrew X.
Published: June 2010

Biliary tract cancers (BTC), which encompass intra- and extrahepatic cholangiocarcinomas and gallbladder carcinomas, are a genetically diverse collection of cancers. Evidence suggests distinct models of molecular and pathologic progression, and a growing body of genetics data points to a heterogeneous collection of underlying mutations in key oncogenes and tumor suppressor genes. Although tumor genetics have been used to tailor individual treatment regimens and guide clinical decision making in other cancers, these principles have not been applied in BTC. Recent clinical trials with targeted therapies seem promising, although the relationships between subsets of patients with positive responses to therapy and tumor genetics remain unexplored. Here, we summarize the molecular pathogenesis and genetics of BTCs and animal modeling and relate these to recent and ongoing clinical trials with targeted agents.
Are Mastectomy Rates Really Increasing in the United States?
Authors: Habermann Elizabeth B. , Abbott Andrea , Parsons Helen M. , Virnig Beth A. , Al-Refaie Waddah B. , Tuttle Todd M.
Published: June 2010

Purpose

After the National Institutes of Health Consensus Statement in 1990, breast-conserving surgery (BCS) became more common while mastectomy rates decreased. However, several recently published single-institution studies have reported an increase in mastectomy rates in the past decade. We conducted a population-based study to evaluate national trends in the surgical treatment of breast cancer from 2000 through 2006.

Patients and Methods

Using the Surveillance, Epidemiology, and End Results database, we conducted a retrospective cohort analysis of women undergoing surgical treatment for breast cancer. We evaluated variation in mastectomy rates by demographic and tumor factors and calculated differences in mastectomy rates across time. We utilized logistic regression to identify time trends and patient and tumor factors associated with mastectomy, testing for significance using two-sided methods.

Results

We identified 233,754 patients diagnosed with ductal carcinoma in situ or stage I to III unilateral breast cancer from 2000 to 2006. The proportion of women treated with mastectomy decreased from 40.8% in 2000 to 37.0% in 2006 (P < .001). These patterns were maintained across patient and tumor factors. Although the unilateral mastectomy rate decreased during the study period, the contralateral prophylactic mastectomy rate increased. Women were less likely to receive mastectomy over time (odds ratio, 1.18 for 2000 v 2006; 95% CI, 1.14 to 1.23; P < .0001), after adjusting for patient and tumor factors.

Conclusion

In contrast to single-institution studies, our population-based analysis found a decrease in unilateral mastectomy rates from 2000 to 2006 in the United States. Variations in referral patterns and patient selection are potential explanations for these differences between single institutions and national trends.
Research Note—Knowledge Exploration and Exploitation: The Impacts of Psychological Climate and Knowledge Management System Access
Authors: Durcikova Alexandra , Fadel Kelly J. , Butler Brian S. , Galletta Dennis F.
Published: June 2010

Firms need to balance efficiency gains obtained through exploiting existing knowledge assets with long-term competitive viability achieved through exploring new knowledge resources. Because the use of knowledge management systems (KMSs) continues to expand, understanding how these systems affect exploration and exploitation practices at the individual level is important to advance both knowledge management theory and practice. This study reports the results of a multi-industry survey investigating how psychological climate and KMS access influence solution reuse (exploitation) and solution innovation (exploration) in the context of technical support work. Our results show that KMS access does not directly determine solution innovation or solution reuse. Instead, KMS access strengthens the positive relationship between a climate for innovation and solution innovation and reverses the positive relationship between a climate for autonomy and solution innovation. The implications for knowledge management research and practice are discussed.
Effects of Information Revelation Policies Under Cost Uncertainty
Authors: Kannan Karthik N.
Published: June 2010

The paper presents insights regarding the key learning-related factors a buyer should consider when deciding the extent to which information about bids is revealed in a procurement auction context. It offers the insights by analyzing the following two first-price sealed-bid policies in a private-value sequential auction with no winner dropouts: (i) iis, where only the winner's bid is revealed, and (ii) cis, where all bids are revealed. Our analysis identifies two important learning effects—the extraction and the deception effects—as having significant welfare implications. Both these effects arise because of a bidder's desire to gain an informational advantage relative to his competitors, but their manifestations are different. The extraction effect occurs because of a bidder's incentive to learn about his competitors, and the deception effect is a consequence of the incentive to prevent an opponent from gaining the information. Both effects lead to higher bid prices, and either may be dominant from a procurer surplus standpoint. With the deception effect, social welfare can decrease even when the number of suppliers increases, a result that is counterintuitive. The paper also discusses how insights regarding the learning effects might apply to other policies.
Autopsy Findings in Eight Patients With Fatal H1N1 Influenza
Authors: Harms Paul W. , Schmidt Lindsay A. , Smith Lauren B. , Newton Duane W. , Pletneva Maria A. , Walters Laura L. , Tomlins Scott A. , Fisher-Hubbard Amanda , Napolitano Lena M. , Park Pauline K. , Blaivas Mila , Fantone Joseph , Myers Jeffrey L. , Jentzen Jeffrey M.
Published: June 2010

A novel H1N1 influenza A virus emerged in April 2009, and rapidly reached pandemic proportions. We report a retrospective observational case study of pathologic findings in 8 patients with fatal novel H1N1 infection at the University of Michigan Health Systems (Ann Arbor) compared with 8 age-, sex-, body mass index–, and treatment-matched control subjects. Diffuse alveolar damage (DAD) in acute and organizing phases affected all patients with influenza and was accompanied by acute bronchopneumonia in 6 patients. Organizing DAD with established fibrosis was present in 1 patient with preexisting granulomatous lung disease. Only 50% of control subjects had DAD. Peripheral pulmonary vascular thrombosis occurred in 5 of 8 patients with influenza and 3 of 8 control subjects. Cytophagocytosis was seen in all influenza-related cases. The autopsy findings in our patients with novel H1N1 influenza resemble other influenza virus infections with the exception of prominent thrombosis and hemophagocytosis. The possibility of hemophagocytic syndrome should be investigated in severely ill patients with H1N1 infection.
The Sensitivity and Specificity of p16INK4a Cytology vs HPV Testing for Detecting High-Grade Cervical Disease in the Triage of ASC-US and LSIL Pap Cytology Results
Authors: Denton Karin J. , Bergeron Christine , Klement Petra , Trunk Marcus J. , Keller Thomas , Ridder Ruediger
Published: June 2010

We analyzed the performance of p16INK4a immunocytochemistry on a series of 810 retrospectively collected atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL) cases with available biopsy follow-up data, including 94 cases of cervical intraepithelial neoplasia (CIN) 2 and 128 cases of CIN 3. Human papillomavirus (HPV) testing was performed from the same residual liquid-based cytologic specimen, and results for both tests were correlated with histologic follow-up data. Sensitivity values for high-grade CIN (HGCIN) confirmed on biopsy within 6 months were 92.6% (ASC-US) and 92.2% (LSIL) for cytotechnologists’ reviews of p16 cytology and 90.1% (ASC-US) and 95.7% (LSIL) for HPV testing. Sensitivity rates of initial pathologists’ reviews were slightly lower, 76.4% to 80.1%, with levels comparable to cytotechnologists’ results after adjudication. The specificity of p16 cytology for HGCIN detection was significantly higher than for HPV testing for cytotechnologists and pathologists: 63.2% to 71.1% (p16 cytology) vs 37.8% for HPV in ASC-US (P < .001) and 37.3% to 53.3% (p16 cytology) vs 18.5% for HPV in LSIL (P < .001). This evaluation of the diagnostic performance of p16 cytology confirms the potential of this stain for the efficient triage of ASC-US and LSIL cytologic results.
Comparative Examination of Androgen Receptor Reactivity for Differential Diagnosis of Sebaceous Carcinoma From Squamous Cell and Basal Cell Carcinoma
Authors: Asadi-Amoli Fahimeh , Khoshnevis Farid , Haeri Hayedeh , Jahanzad Issa , Pazira Reza , Shahsiah Reza
Published: June 2010

Sebaceous carcinoma (SEB) is the most important malignant tumor of the eyelid. Early diagnosis and proper treatment significantly improve the outcome. SEB should be differentiated histopathologically from basal cell carcinoma (BCC) and squamous cell carcinoma (SCC).

In this study, the expression of androgen receptor (AR) in SEB, SCC, and BCC was evaluated. AR was positive in all 19 SEB cases. Of 18 BCCs, 6 (33%) showed focal nuclear immunoreactivity. The 18 SCCs showed no nuclear immunoreactivity.

AR is a sensitive marker for SEB, especially in less differentiated tumors. Along with other markers and morphologic features, AR can be helpful in the diagnosis of SEB and its differentiation from SCC and BCC.
Immunophenotypic Variations of Burkitt Lymphoma
Authors: Kelemen Katalin , Braziel Rita M. , Gatter Ken , Bakke Tony C. , Olson Susan , Fan Guang
Published: June 2010

Burkitt lymphoma (BL) exhibits a characteristic immunophenotype that is positive for pan–B-cell antigens and CD10 and expresses clonal surface immunoglobulins (SIgs). We evaluated 35 BLs and identified atypical immunophenotypes in 4 including SIg light chain negativity in 4, negativity for B-cell antigens in 2, lack of CD10 in 1, and CD4 expression in 1. All 4 cases showed morphologic features characteristic of BL, and all were confirmed by cytogenetic analysis. The 4 BL cases included 1 girl, 2 men with HIV/AIDS, and a third man with a history of heart transplantation. Two patients died shortly after diagnosis; the other 2 completed hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone with highly active antiretroviral therapy and achieved complete remission. Our study indicates that an unusual immunophenotype is not uncommon in BL. If the immunophenotype is interpreted in isolation, the diagnosis could be missed. Recognizing the variability of immunophenotype is essential for establishing an accurate diagnosis of BL.
Array Comparative Genomic Hybridization of Peripheral Blood Granulocytes of Patients With Myelodysplastic Syndrome Detects Karyotypic Abnormalities
Authors: Vercauteren Suzanne M. , Sung Sandy , Starczynowski Daniel T. , Lam Wan L. , Bruyere Helene , Horsman Douglas E. , Tsang Peter , Leitch Heather , Karsan Aly
Published: June 2010

The diagnosis of myelodysplastic syndromes (MDSs) relies largely on morphologic and karyotypic abnormalities, present in about 50% of patients with MDS. Array-based genomic platforms have identified copy number alterations in 50% to 70% of bone marrow samples of patients with MDS with a normal karyotype, suggesting a diagnostic role for these platforms. We investigated whether blood granulocytes harbor the same copy number alterations as the marrow of affected patients. Of 11 patients, 4 had cytogenetic abnormalities shown by conventional karyotyping involving chromosomes 5, 8, 11, 20, and X, and these changes were seen in the granulocytes of all 4 patients by using array comparative genomic hybridization (aCGH). Cryptic alterations were identified at a significantly higher level in marrow CD34+ cells compared with granulocytes (P < .0001). These data suggest that aCGH analysis of circulating granulocytes may be useful in detecting gross karyotypic alterations in patients with MDS when marrow examination has failed or not been done.
Gender and sexual scripts in popular US teen series: A study on the gendered discourses in One Tree Hill and Gossip Girl
Authors: Van Damme Elke
Published: June 2010

In recent years, research focusing on the representation of youth and sexuality in the media has gained momentum. The sexual content in programmes can sometimes be characterized as hypersexual, and, according to Jacobson, we find such hypersexual representation in two-thirds of television
programmes. Not only do the media offer teenagers more sexual content than previously, but the nature of the content itself has changed. Sexual acts are more explicitly depicted or referenced, the teenagers shown have their first sexual contact at an earlier age, and sexuality is no longer
exclusively part of a committed relationship. We live in a mediated reality, and it is therefore necessary to study the content of contemporary media programmes directed at teenagers. This article examines the represented gender scripts in two popular US teen series (One Tree Hill and
Gossip Girl) using a qualitative textual film analysis. Specifically, it focuses on the relation between gender and sexuality. Several stereotypical gender scripts are revealed, although more positive and emancipative discourses are found as well. A tendency to casualize sexuality is
noticed, which pinpoints the possibility that it may be time to reconsider sexual licence in the twenty-first century as part of youth-as-fun instead of youth-as-trouble.
Laboratory-Diagnosed Sexually Transmitted Infections in Former Foster Youth Compared With Peers
Authors: Ahrens Kym R. , Richardson Laura P. , Courtney Mark E. , McCarty Carolyn , Simoni Jane , Katon Wayne
Published: June 2010

OBJECTIVES:

The objective of this study was to evaluate the association between having resided in foster care and risk for sexually transmitted infection (STI) during young adulthood.

METHODS:

Multiple regression analyses were performed by using Waves I to III of the National Longitudinal Study of Adolescent Health (1994–2002) to evaluate the association between foster care status and STI biomarkers and risk behaviors. Female (N = 7563) and male participants (N = 6759) were evaluated separately. Covariates in all models included baseline age, race, ethnicity, parental education level, parental income level, and average neighborhood household income level.

RESULTS:

Female participants who had been in foster care were more likely to have Trichomonas (odds ratio [OR]: 3.23 [95% confidence interval (CI): 1.45–7.23) but not gonorrhea or chlamydia and reported increased sexual risk behaviors compared with nonfostered peers. Male participants who had been in foster care were more likely to have both gonorrhea (OR: 14.28 [95% CI: 2.07–98.28]) and chlamydia (OR: 3.07 [95% CI: 1.36–6.96]) but not Trichomonas and did not report a higher risk for most sexual risk behaviors than nonfostered peers.

CONCLUSIONS:

Results suggest that individuals who have been in foster care are at increased risk for STIs during young adulthood. The pattern of exposure may differ between male and female individuals. If findings are confirmed, they suggest that health care providers who work with these youth should adjust their STI screening practices. Child welfare agencies should also consider targeted interventions to reduce STI risk in this population.
Childhood Cancer Survivors: Transition to Adult-Focused Risk-Based Care
Authors: Henderson Tara O. , Friedman Debra L. , Meadows Anna T.
Published: June 2010

BACKGROUND:

The issues involved in transition from pediatric cancer care to adult-focused care differ from those in other childhood diseases, because malignant disease itself is no longer a problem. However, the potential for fatal outcome places a greater dependence on the pediatric oncology setting and delays this transition process, often beyond adolescence. Adverse long-term physical and psychological effects accompany survival for many of the cured children, and because these effects may not become manifest until adulthood, programs that support transition for childhood cancer survivors require the expertise of many subspecialists.

OBJECTIVES:

To describe the issues and barriers to successful transition programs for childhood cancer survivors when they are ready for adult-focused care.

METHODS:

We reviewed the literature and discuss the barriers to transition at the survivor, provider, and health care system levels for survivors of childhood cancer. We also critically assess the elements of successful transition programs.

RESULTS:

Education of survivors and providers regarding long-term health risks is necessary for a successful transition. This process should be gradual to address the educational needs of survivors, families, and health care professionals, determine “readiness” for transition, and address financial and insurance concerns. Because little is known regarding adverse long-term health-related sequelae beyond the fourth decade of life, research is needed to quantify and reduce the consequences of these morbidities.

CONCLUSIONS:

Transition programs for pediatric cancer survivors require experts who are knowledgeable regarding the long-term follow-up needs of childhood cancer survivors and who can provide a bridge between pediatric oncology and primary care that is risk based.