bluuebunny/crossref_metadata_2025 huggingface dataset:
Crossing a Multicultural Divide: Teaching Business Strategy to Students From Culturally Mixed Backgrounds
Authors: Hills Steve , Thom Viv
Published: October 2005

This narrative describes how, in response to poor results, a teaching team revamped a postgraduate business strategy module in a U.K. university. The changes mainly involved clarification of some of the staff’s key expectations and teaching and learning methods, taking account of the powerful pressures on international students in the United Kingdom and the diverse cultural and educational background of the student group. It argues that the changes were largely responsible for the improvement in the subsequent results, but also discusses a range of alternative explanations. The comments of student focus groups on the new approach are given and discussed. Finally, the team reflects briefly on the process as an example of practitioner action research and on the risks that may be involved in taking it for granted that the United Kingdom’s present academic approach is “better” than others.
Actual Interaction and Client Centeredness in Home Care
Authors: Schoot Tineke , Proot Ireen , Meulen Ruud Ter , de Witte Luc
Published: October 2005

The purpose of this study is to explore client-nurse interaction from a client perspective with respect to client-centered care. A grounded theory study was conducted with Dutch clients who were chronically ill and receiving home care. Data were collected by focus interviews with 8 client informants, participatory observations with 45 clients, and semistructured interviews with 6 clients. The core category actual interaction was identified. Six patterns of actual interaction were distinguished. Changes in actual interaction could be related to changes in desired participation by the client and in allowed client participation by the professional. From the client's perspective, client-centeredness means congruence between desired and allowed participation. Congruence was experienced with consent, dialogue, and consuming. Congruence is not necessarily synonymous with promoting patient participation or with doing as the client wants. Ongoing attentiveness, responsiveness, promotion of client autonomy, and being a critical caregiver are recommended.
Hierarchical qualitative research teams: refining the methodology
Authors: Rogers-Dillon Robin H.
Published: October 2005

Qualitative research traditionally has been done by individual researchers or by collaborating researchers of equal status. In recent years, a number of prominent qualitative research efforts with hierarchical research teams have emerged. In part, this has been in response to the criticism that the small number of cases on which qualitative research typically is based does not permit enough variation for the results to be generalized. Researchers have responded by conducting larger, often multi-site, qualitative research projects. The model of lead researchers and a group of lower status research assistants common in the natural sciences and in quantitative research, however, does not neatly fit the realities of qualitative research. As feminist and other researchers have argued, research is not simply experts’ objective discoveries of pre-existing truths. Knowledge is produced within social contexts that include power dynamics and ethical issues. In qualitative research teams these issues are particularly salient. A model of qualitative team research must be developed that takes into consideration the unique aspects of the methodology.
Studying actions in context: a qualitative shadowing method for organizational research
Authors: McDonald Seonaidh
Published: October 2005

Shadowing is a qualitative research technique that has seldom been used and rarely been discussed critically in the social science literature. This article has pulled together all of the studies using shadowing as a research method and through reviewing these studies has developed a threefold classification of different modes of shadowing. This work provides a basis for a qualitative shadowing method to be defined, and its potential for a distinctive contribution to organizational research to be discussed, for the first time.
Current Models and Future Directions for Understanding the Neural Circuitries of Maternal Behaviors in Rodents
Authors: Gammie Stephen C.
Published: October 2005

Maternal behaviors in rodents include a number of subcomponents, such as nursing, nest building, licking and grooming of pups, pup retrieval, and maternal aggression. Because each behavior involves a unique motor pattern, a unique ensemble neural circuitry must underlie each behavior. To what extent there is overlap in terms of brain regions and specific neurons for each circuit is being actively investigated. This review will first examine overlapping and separate components of pup retrieval and maternal aggression circuitries while examining a central role for medial preoptic area (MPA) in both behaviors. With an emphasis on experimental approaches, the review will then highlight recent findings and propose future directions for understanding maternal behavior regulation. Finally, examples for why studying the neural basis of maternal behaviors can bring insights to other areas of neuroscience, such as feeding, addiction, and anxiety and aggression regulation will be provided.
Regulation of survivin expression through Bcr-Abl/MAPK cascade: targeting survivin overcomes imatinib resistance and increases imatinib sensitivity in imatinib-responsive CML cells
Authors: Carter Bing Z. , Mak Duncan H. , Schober Wendy D. , Cabreira-Hansen Maria , Beran Miloslav , McQueen Teresa , Chen Wenjing , Andreeff Michael
Published: October 2005

KBM5 cells, derived from a patient with blast crisis Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML), and imatinib-resistant KBM5 (KBM5-STI571) cells were found to express high levels of survivin. Inhibition of Bcr-Abl by imatinib significantly decreased survivin expression and cell viability in KBM5, but much less so in KBM5-STI571 cells. Inhibition of MEK, downstream of the Bcr-Abl signaling cascade decreased survivin expression and cell viability in both KBM5 and KBM5-STI571 cells. In addition, down-regulation of survivin by a survivin antisense oligonucleotide (Sur-AS-ODN) inhibited cell growth and induced maximal G2M block at 48 hours, whereas cell death was observed only at 72 hours in both KBM5 and KBM5-STI571 cells as shown by annexin V staining. Further, the combination of Sur-AS-ODN and imatinib induced more cell death in KBM5 cells than did either treatment alone. Down-regulating survivin also decreased colony-forming units (CFUs) in blast crisis CML patient samples. Our data therefore suggest that survivin is regulated by the Bcr-Abl/MAPK cascade in Ph+ CML. The facts that down-regulating survivin expression induced cell-growth arrest and subsequent cell death regardless of the cell response to imatinib and enhanced the sensitivity to imatinib suggest the potential therapeutic utility of this strategy in patients with CML, both imatinib sensitive and resistant.
AKT induces erythroid-cell maturation of JAK2-deficient fetal liver progenitor cells and is required for Epo regulation of erythroid-cell differentiation
Authors: Ghaffari Saghi , Kitidis Claire , Zhao Wei , Marinkovic Dragan , Fleming Mark D. , Luo Biao , Marszalek Joseph , Lodish Harvey F.
Published: October 2005

AKT serine threonine kinase of the protein kinase B (PKB) family plays essential roles in cell survival, growth, metabolism, and differentiation. In the erythroid system, AKT is known to be rapidly phosphorylated and activated in response to erythropoietin (Epo) engagement of Epo receptor (EpoR) and to sustain survival signals in cultured erythroid cells. Here we demonstrate that activated AKT complements EpoR signaling and supports erythroid-cell differentiation in wild-type and JAK2-deficient fetal liver cells. We show that erythroid maturation of AKT-transduced cells is not solely dependent on AKT-induced cell survival or proliferation signals, suggesting that AKT transduces also a differentiation-specific signal downstream of EpoR in erythroid cells. Down-regulation of expression of AKT kinase by RNA interference, or AKT activity by expression of dominant negative forms, inhibits significantly fetal liver–derived erythroid-cell colony formation and gene expression, demonstrating that AKT is required for Epo regulation of erythroid-cell maturation.
The role of surfactant protein D in the colonisation of the respiratory tract and onset of bacteraemia during pneumococcal pneumonia
Authors: Jounblat R , Clark H , Eggleton P , Hawgood S , Andrew PW , Kadioglu A
Published: October 2005

We have shown previously that surfactant protein D (SP-D) binds and agglutinatesStreptococcus pneumoniae in vitro. In this study, the role of SP-D in innate immunity againstS. pneumoniaewas investigatedin vivo, by comparing the outcome of intranasal infection in surfactant protein D deficient (SP-D-/-) to wildtype mice (SP-D+/+). Deficiency of SP-D was associated with enhanced colonisation and infection of the upper and lower respiratory tract and earlier onset and longer persistence of bacteraemia. Recruitment of neutrophils to inflammatory sites in the lung was similar in both strains mice in the first 24 hrs post-infection, but different by 48 hrs. T cell influx was greatly enhanced in SP-D-/- mice as compared to SP-D+/+ mice. Our data provides evidence that SP-D has a significant role to play in the clearance of pneumococci during the early stages of infection in both pulmonary sites and blood.
Limitations of mRNA amplification from small-size cell samples
Authors: Nygaard Vigdis , Holden Marit , Løland Anders , Langaas Mette , Myklebost Ola , Hovig Eivind
Published: October 2005

Background

Global mRNA amplification has become a widely used approach to obtain gene expression profiles from limited material. An important concern is the reliable reflection of the starting material in the results obtained. This is especially important with extremely low quantities of input RNA where stochastic effects due to template dilution may be present. This aspect remains under-documented in the literature, as quantitative measures of data reliability are most often lacking. To address this issue, we examined the sensitivity levels of each transcript in 3 different cell sample sizes. ANOVA analysis was used to estimate the overall effects of reduced input RNA in our experimental design. In order to estimate the validity of decreasing sample sizes, we examined the sensitivity levels of each transcript by applying a novel model-based method, TransCount.

Results

From expression data, TransCount provided estimates of absolute transcript concentrations in each examined sample. The results from TransCount were used to calculate the Pearson correlation coefficient between transcript concentrations for different sample sizes. The correlations were clearly transcript copy number dependent. A critical level was observed where stochastic fluctuations became significant. The analysis allowed us to pinpoint the gene specific number of transcript templates that defined the limit of reliability with respect to number of cells from that particular source. In the sample amplifying from 1000 cells, transcripts expressed with at least 121 transcripts/cell were statistically reliable and for 250 cells, the limit was 1806 transcripts/cell. Above these thresholds, correlation between our data sets was at acceptable values for reliable interpretation.

Conclusion

These results imply that the reliability of any amplification experiment must be validated empirically to justify that any gene exists in sufficient quantity in the input material. This finding has important implications for any experiment where only extremely small samples such as single cell analyses or laser captured microdissected cells are available.
A framework to evaluate research capacity building in health care
Authors: Cooke Jo
Published: October 2005

Background

Building research capacity in health services has been recognised internationally as important in order to produce a sound evidence base for decision-making in policy and practice. Activities to increase research capacity for, within, and by practice include initiatives to support individuals and teams, organisations and networks. Little has been discussed or concluded about how to measure the effectiveness of research capacity building (RCB)

Discussion

This article attempts to develop the debate on measuring RCB. It highlights that traditional outcomes of publications in peer reviewed journals and successful grant applications may be important outcomes to measure, but they may not address all the relevant issues to highlight progress, especially amongst novice researchers. They do not capture factors that contribute to developing an environment to support capacity development, or on measuring the usefulness or the 'social impact' of research, or on professional outcomes.

The paper suggests a framework for planning change and measuring progress, based on six principles of RCB, which have been generated through the analysis of the literature, policy documents, empirical studies, and the experience of one Research and Development Support Unit in the UK. These principles are that RCB should: develop skills and confidence, support linkages and partnerships, ensure the research is 'close to practice', develop appropriate dissemination, invest in infrastructure, and build elements of sustainability and continuity. It is suggested that each principle operates at individual, team, organisation and supra-organisational levels. Some criteria for measuring progress are also given.

This paper highlights the need to identify ways of measuring RCB. It points out the limitations of current measurements that exist in the literature, and proposes a framework for measuring progress, which may form the basis of comparison of RCB activities. In this way it could contribute to establishing the effectiveness of these interventions, and establishing a knowledge base to inform the science of RCB.
Distribution of cytochrome P450 2C, 2E1, 3A4, and 3A5 in human colon mucosa
Authors: Bergheim Ina , Bode Christiane , Parlesak Alexandr
Published: October 2005

Background

Despite the fact that the alimentary tract is part of the body's first line of defense against orally ingested xenobiotica, little is known about the distribution and expression of cytochrome P450 (CYP) enzymes in human colon. Therefore, expression and protein levels of four representative CYPs (CYP2C(8), CYP2E1, CYP3A4, and CYP3A5) were determined in human colon mucosa biopsies obtained from ascending, descending and sigmoid colon.

Methods

Expression of CYP2C, CYP2E1, CYP3A4, and CYP3A5 mRNA in colon mucosa was determined by RT-PCR. Protein concentration of CYPs was determined using Western blot methods.

Results

Extensive interindividual variability was found for the expression of most of the genes. However, expression of CYP2C mRNA levels were significantly higher in the ascending colon than in the sigmoid colon. In contrast, mRNA levels of CYP2E1 and CYP3A5 were significantly lower in the ascending colon in comparison to the descending and sigmoid colon. In sigmoid colon protein levels of CYP2C8 were significantly higher by ~73% than in the descending colon. In contrast, protein concentration of CYP2E1 was significantly lower by ~81% in the sigmoid colon in comparison to the descending colon.

Conclusion

The current data suggest that the expression of CYP2C, CYP2E1, and CYP3A5 varies in different parts of the colon.
Axial stent strut angle influences wall shear stress after stent implantation: analysis using 3D computational fluid dynamics models of stent foreshortening
Authors: LaDisa John F , Olson Lars E , Hettrick Douglas A , Warltier David C , Kersten Judy R , Pagel Paul S
Published: October 2005

Introduction

The success of vascular stents in the restoration of blood flow is limited by restenosis. Recent data generated from computational fluid dynamics (CFD) models suggest that the vascular geometry created by an implanted stent causes local alterations in wall shear stress (WSS) that are associated with neointimal hyperplasia (NH). Foreshortening is a potential limitation of stent design that may affect stent performance and the rate of restenosis. The angle created between axially aligned stent struts and the principal direction of blood flow varies with the degree to which the stent foreshortens after implantation.

Methods

In the current investigation, we tested the hypothesis that stent foreshortening adversely influences the distribution of WSS and WSS gradients using time-dependent 3D CFD simulations of normal arteries based on canine coronary artery measurements of diameter and blood flow. WSS and WSS gradients were calculated using conventional techniques in ideal (16 mm) and progressively foreshortened (14 and 12 mm) stented computational vessels.

Results

Stent foreshortening increased the intrastrut area of the luminal surface exposed to low WSS and elevated spatial WSS gradients. Progressive degrees of stent foreshortening were also associated with strut misalignment relative to the direction of blood flow as indicated by analysis of near-wall velocity vectors.

Conclusion

The current results suggest that foreshortening may predispose the stented vessel to a higher risk of neointimal hyperplasia.
Time course of exercise induced alterations in daily activity in chronic fatigue syndrome
Authors: Black Christopher D , McCully Kevin K
Published: October 2005

In a previous study we demonstrated that while people with CFS had lower daily activity levels than control subjects, they were able to increase daily activity via a daily walking program. We reanalyzed our data to determine the time course of activity changes during the walking program. Daily activity assessed via an accelometer worn at the hip was divided into sleep, active, and walking periods. Over the first 4–10 days of walking the subjects with CFS were able to reach the prescribed activity goals each day. After this time, walking and total activity counts decreased. Sedentary controls subjects were able to maintain their daily walking and total activity goals throughout the 4 weeks. Unlike our previous interpretation of the data, we feel this new analysis suggests that CFS patients may develop exercise intolerance as demonstrated by reduced total activity after 4–10 days. The inability to sustain target activity levels, associated with pronounced worsening of symptomology, suggests the subjects with CFS had reached their activity limit.
Dobutamine stress echocardiography in healthy adult male rats
Authors: Plante Eric , Lachance Dominic , Drolet Marie-Claude , Roussel Élise , Couet Jacques , Arsenault Marie
Published: October 2005

Background

Dobutamine stress echocardiography is used to investigate a wide variety of heart diseases in humans. Dobutamine stress echocardiography has also been used in animal models of heart disease despite the facts that the normal response of healthy rat hearts to this type of pharmacological stress testing is unknown. This study was performed to assess this normal response.

Methods

15 normal adult male Wistar rats were evaluated. Increasing doses of dobutamine were infused intravenously under continuous imaging of the heart by a 12 MHz ultrasound probe.

Results

Dobutamine stress echocardiography reduced gradually LV diastolic and systolic dimensions. Ejection fraction increased by a mean of +24% vs. baseline. Heart rate increased progressively without reaching a plateau. Changes in LV dimensions and ejection fraction reached a plateau after a mean of 4 minutes at a constant infusion rate.

Conclusion

DSE can be easily performed in rats. The normal response is an increase in heart rate and ejection fraction and a decrease in LV dimensions. A plateau in echocardiographic measurements is obtained after 4 minutes of a constant infusion rate in most animals.
Easy and rapid method for the determination of gene expression in cumulus cells incubated for oocyte maturation
Authors: Kumamoto Kanako , Wang Haifeng , Yamashiro Hideaki , Terada Takato
Published: October 2005

Background

The objectives of this study were to develop an easy and rapid method for measuring gene expression in a small number of cells by real-time PCR without RNA extraction and purification, and to use this method to determine more precisely IGF-I gene expression in the cumulus cells surrounding oocytes.

Methods

First, after small numbers of cumulus cells were lysed in cell lysis buffer, they were digested with various concentrations of DNase I for different periods at 37°C to determine the optimal conditions for digestion of genomic DNA in the lysate. Since nonspecific amplification was liable to occur when the non-purified RT product of the cell lysate was used for real-time PCR with the given primers, the optimal conditions for Mg2+ and annealing temperature were well investigated. Further, to create the same conditions as in the actual sample reaction for measurement by real-time PCR, RT-minus product was added to the reaction mixture of the standard curve, and then the amplification efficiency was assessed. Next, IGF-I gene expression in cumulus cells collected from cumulus oocyte complexes (COCs) every 4 h during maturation was determined using the developed method.

Results

The optimal conditions for measuring gene expression using the cell lysate from a small number of cells were as follows: incubation of the cell lysate with 0.16 U/microL DNase I with 10 U/microL for 30 min, an Mg concentration of 1.5 mM for amplification of target gene by real-time PCR using RT-product of the cell lysate. When the RT-minus products added to the reaction mixture for the standard curve, which was prepared for purified 18SrRNA plasmid, the PCR efficiency was similar between the sample and the standard.

The IGF-I gene expression in the cumulus cells was elevated up through the first 8 h of the culture and then declined gradually by the end of maturation, with the maximal gene expression (778-fold) seen at 8 h.

Conclusion

It can be concluded that the method developed here, in which equivalent to cumulus cells collected from 0.03–0.075 COCs were employed per reaction, permits rapid and easy determination of target gene expression in a limited number of cells using real-time PCR without RNA extraction.
The effect of performance-related pay of hospital doctors on hospital behaviour: a case study from Shandong, China
Authors: Liu Xingzhu , Mills Anne
Published: October 2005

Background

With the recognition that public hospitals are often productively inefficient, reforms have taken place worldwide to increase their administrative autonomy and financial responsibility. Reforms in China have been some of the most radical: the government budget for public hospitals was fixed, and hospitals had to rely on charges to fill their financing gap. Accompanying these changes was the widespread introduction of performance-related pay for hospital doctors – termed the "bonus" system. While the policy objective was to improve productivity and cost recovery, it is likely that the incentive to increase the quantity of care provided would operate regardless of whether the care was medically necessary.

Methods

The primary concerns of this study were to assess the effects of the bonus system on hospital revenue, cost recovery and productivity, and to explore whether various forms of bonus pay were associated with the provision of unnecessary care. The study drew on longitudinal data on revenue and productivity from six panel hospitals, and a detailed record review of 2303 tracer disease patients (1161 appendicitis patients and 1142 pneumonia patients) was used to identify unnecessary care.

Results

The study found that bonus system change over time contributed significantly to the increase in hospital service revenue and hospital cost recovery. There was an increase in unnecessary care and in the probability of admission when the bonus system switched from one with a weaker incentive to increase services to one with a stronger incentive, suggesting that improvement in the financial health of public hospitals was achieved at least in part through the provision of more unnecessary care and drugs and through admitting more patients.

Conclusion

There was little evidence that the performance-related pay system as designed by the sample of Chinese public hospitals was socially desirable. Hospitals should be monitored more closely by the government, and regulations applied to limit opportunistic behaviour. Otherwise, the containment of government financing for public facilities may result in an increase in the provision of unnecessary care, an increase in health costs to society, and a waste in social resources.
"There's no place like home" A pilot study of perspectives of international health and social care professionals working in the UK
Authors: Moran Anna , Nancarrow Susan , Butler Allister
Published: October 2005

Background

Many countries are reporting health workforce shortages across a range of professions at a time of relatively high workforce mobility. Utilising the global market to supply shortage health skills is now a common recruitment strategy in many developed countries. At the same time a number of countries report a 'brain drain' resulting from professional people leaving home to work overseas. Many health and social care professionals make their way to the UK from other countries. This pilot study utilises a novel 'e-survey' approach to explore the motives, experiences and perspectives of non-UK health and social care professionals who were working or had worked in the UK. The study aims to understand the contributions of international health and social care workers to the UK and their 'home' countries. The purpose of the pilot study is also in part to test the appropriateness of this methodology for undertaking a wider study.

Results

A 24-item questionnaire with open-ended and multiple choice questions was circulated via email to 10 contacts who were from a country outside the UK, had trained outside the UK and had email access. These contacts were requested to forward the email to other contacts who met these criteria (and so on). The email was circulated over a one month pilot period to 34 contacts. Responses were from physiotherapists (n = 11), speech therapists (n = 4), social workers (n = 10), an occupational therapist (n = 1), podiatrists (n = 5), and others (n = 3). Participants were from Australia (n = 20), South Africa (n = 10), New Zealand (n = 3) and the Republic of Ireland (n = 1). Motives for relocating to the UK included travel, money and career opportunities. Participants identified a number of advantages and disadvantages of working in the UK compared to working in their home country health system. Respondents generally reported that by working in the UK, they had accumulated skills and knowledge that would allow them to contribute more to their profession and health system on their return home.

Conclusion

This pilot study highlights a range of issues and future research questions for international learning and comparison for the health and social care professions as a result of international workforce mobility. The study also highlights the usefulness of an e-survey technique for capturing information from a geographically diverse and mobile group of professionals.
Palatal development of preterm and low birthweight infants compared to term infants – What do we know? Part 2: The palate of the preterm/low birthweight infant
Authors: Hohoff Ariane , Rabe Heike , Ehmer Ulrike , Harms Erik
Published: October 2005

Background

Well-designed clinical studies on the palatal development in preterm and low birthweight infants are desirable because the literature is characterized by contradictory results. It could be shown that knowledge about 'normal' palatal development is still weak as well (Part 1). The objective of this review is therefore to contribute a fundamental analysis of methodologies, confounding factors, and outcomes of studies on palatal development in preterm and low birthweight infants.

Methods

An electronic literature search as well as hand searches were performed based on Cochrane search strategies including sources of more than a century in English, German, and French. Original data were recalculated from studies which primarily dealt with both preterm and term infants. The extracted data, especially those from non-English paper sources, were provided unfiltered for comparison.

Results

Seventy-eight out of 155 included articles were analyzed for palatal morphology of preterm infants. Intubation, feeding tubes, feeding mode, tube characteristics, restriction of oral functions, kind of diet, cranial form and birthweight were seen as causes contributing to altered palatal morphology. Changes associated with intubation concern length, depth, width, asymmetry, crossbite, and contour of the palate. The phenomenon 'grooving' has also been described as a complication associated with oral intubation. However, this phenomenon suffers from lack of a clear-cut definition. Head flattening, pressure from the oral tube, pathologic or impaired tongue function, and broadening of the alveolar ridges adjacent to the tube have been raised as causes of 'grooving'. Metrically, the palates of intubated preterm infants remain narrower, which has been examined up to the age of the late mixed dentition.

Conclusion

There is no evidence that would justify the exclusion of any of the raised causes contributing to palatal alteration. Thus, early orthodontic and logopedic control of formerly orally intubated preterm infants is recommended, as opposed to non-intubated infants. From the orthodontic point of view, nasal intubation should be favored. The role that palatal protection plates and pressure-dispersing pads for the head have in palatal development remains unclear.
Prolonged refractory status epilepticus following acute traumatic brain injury: a case report of excellent neurological recovery
Authors: Peets Adam D , Berthiaume Luc R , Bagshaw Sean M , Federico Paolo , Doig Christopher J , Zygun David A
Published: October 2005

Introduction

Refractory status epilepticus (RSE) secondary to traumatic brain injury (TBI) may be under-recognized and is associated with significant morbidity and mortality.

Methods

This case report describes a 20 year old previously healthy woman who suffered a severe TBI as a result of a motor vehicle collision and subsequently developed RSE. Pharmacological coma, physiological support and continuous electroencephalography (cEEG) were undertaken.

Results

Following 25 days of pharmacological coma, electrographic and clinical seizures subsided and the patient has made an excellent cognitive recovery.

Conclusion

With early identification, aggressive physiological support, appropriate monitoring, including cEEG, and an adequate length of treatment, young trauma patients with no previous seizure history and limited structural damage to the brain can have excellent neurological recovery from prolonged RSE.
Tamoxifen Versus Control After Adjuvant, Risk-Adapted Chemotherapy in Postmenopausal, Receptor-Negative Patients With Breast Cancer: A Randomized Trial (GABG-IV D-93)—The German Adjuvant Breast Cancer Group
Authors: Kaufmann Manfred , Graf Erika , Jonat Walter , Eiermann Wolfgang , Geberth Matthias , Albert Ute-Susann , Gademann Günther , Conrad Bettina , Stahl Karin , von Minckwitz Gunter , Schumacher Martin
Published: October 2005

Purpose

To investigate the effect of adjuvant sequential tamoxifen after chemotherapy in postmenopausal patients with hormone receptor–negative breast cancer.

Methods

Patients were randomly assigned to oral tamoxifen (30 mg daily for 5 years; n = 421) or no additional treatment (n = 408) after risk-adapted polychemotherapy consisting of three 28-day cycles of CMF (cyclophosphamide, 500 mg/m2, methotrexate, 40 mg/m2, and fluorouracil, 600 mg/m2) in patients with negative or one to three positive lymph nodes and four 21-day cycles of epirubicin 90 mg/m2, cyclophosphamide 600 mg/m2 followed by three cycles of CMF in patients with four to nine positive lymph nodes.

Results

Thirty-six percent of the patients included were older than 60 years, 63% were node negative, 13% had four to nine positive nodes, 55% had tumor grade 3, and 41% received breast-preserving surgery. At 5.3 years’ median follow-up, the first event of failure (recurrence, secondary tumor, or death) had occurred in 123 patients in the tamoxifen group and 107 patients of the control group. Event-free survival rates after 5 years were 70.3% (95% CI, 65.5% to 75.0%) and 72.8% (95% CI, 68.2% to 77.5%) for the tamoxifen and control groups, respectively. The estimated hazard ratio of tamoxifen versus control was 1.13 (95% CI, 0.87 to 1.48; P = .34), which gives no indication of an additional benefit of tamoxifen in these patients.

Conclusion

This study contributes substantially to finalization of the presently emerging evidence that tamoxifen does not benefit women with receptor-negative breast cancer after chemotherapy.
Length of Stay and Mortality Associated With Febrile Neutropenia Among Children With Cancer
Authors: Basu Swati K. , Fernandez Isabel D. , Fisher Susan G. , Asselin Barbara L. , Lyman Gary H.
Published: October 2005

Purpose

The aim of this study was to evaluate risk factors for longer length of stay (los) and mortality among hospitalized children with cancer who have febrile neutropenia.

Methods

This study involved analysis of longitudinal data from the University HealthSystem Consortium database from 1995 to 2002. All patients who were 21 years or younger, with diagnostic codes for both neoplastic disease and febrile neutropenia at discharge, were included.

Results

A total of 12,446 patients were identified for the study. The los was 5 days or less for 6,799 patients, and greater than 5 days for 5,647 patients. The mortality rate was 3%. On bivariate analysis, race, age, cancer type, and associated complications (bacteremia/sepsis, hypotension, pneumonia, and fungal infections) were significantly associated with longer length of stay and death. On multivariate analysis, age group, race, cancer type (acute myeloid leukemia, multiple cancers v acute lymphoblastic leukemia), and the complication variables were significantly associated with increased risk of longer los and death. Certain types of cancer (Hodgkin's disease, osteosarcoma/Ewing’s sarcoma, rhabdomyosarcoma, compared with acute lymphoblastic leukemia) and year of discharge after 1995 were significantly associated with a reduced risk of longer length of stay and/or mortality.

Conclusion

Race, age group, year of discharge, associated complications, and cancer type were significantly associated with risk of longer los and mortality. These factors may potentially help in identifying high-risk patients who might benefit from targeted antibiotic therapy or prophylactic hematopoietic growth factor support.
An Intensive Surveillance Program Detected a High Incidence of Hepatocellular Carcinoma Among Hepatitis B Virus Carriers With Abnormal Alpha-Fetoprotein Levels or Abdominal Ultrasonography Results
Authors: Mok Tony S.K. , Yeo Winnie , Yu Simon , Lai Paul , Chan Henry L.Y. , Chan Anthony T.C. , Lau Joseph W.Y. , Wong Herman , Leung Nancy , Hui Edwin P. , Sung Joseph , Koh Jane , Mo Frankie , Zee Benny , Johnson Philip J.
Published: October 2005

Purpose

To study the incidence and treatment outcomes of hepatocellular carcinoma (HCC) detected in an intensive surveillance program (ISP) of hepatitis B virus (HBV) carriers.

Patients and Methods

We screened 1,018 HBV carriers by serum alpha-fetoprotein (AFP) measurement and abdominal ultrasonography (AUS). Patients with an abnormal AFP level or AUS result were enrolled in an ISP that included Lipiodol computed tomography followed by AFP measurement/AUS every 3 months for 2 years and then every 6 months thereafter. The rest were on routine surveillance for 2 years.

Results

A total of 9,849 serum AFP measurements and 3,053 AUSs were performed. After a median follow-up of 4.12 years, we diagnosed 24 HCCs among 78 patients with abnormal screening test results at enrollment (group A); 23 HCCs among 93 patients with only abnormal surveillance test results during follow-up (group B); and nine HCCs among 847 patients with 2 years of normal surveillance (group C). Annual incidence of HCC in the ISP was 760.2 (95% CI, 538.4 to 1,073.7) per 100,000. Mean tumor sizes were 3.02, 2.91, and 4.82 cm in groups A, B, and C, respectively (P = .01). Tumor resection rate of the ISP was 36.2%, although another 29.8% of the patients were eligible for locoregional ablative therapy.

Conclusion

This study illustrated that a high incidence of relatively small HCCs may be detected by using intensive surveillance of high-risk HBV carriers. However, the surgical resection rate was low, and we were not able to demonstrate clinical benefit with the early detection. Future surveillance studies should consider incorporation of therapy aimed at long-term control of small-sized tumors.
Prostate Size and Risk of High-Grade, Advanced Prostate Cancer and Biochemical Progression After Radical Prostatectomy: A Search Database Study
Authors: Freedland Stephen J. , Isaacs William B. , Platz Elizabeth A. , Terris Martha K. , Aronson William J. , Amling Christopher L. , Presti Joseph C. , Kane Christopher J.
Published: October 2005

Purpose

Prostate growth and differentiation are under androgenic control, and prior studies suggested that tumors that develop in hypogonadal men are more aggressive. We examined whether prostate weight was associated with tumor grade, advanced disease, or risk of biochemical progression after radical prostatectomy (RP).

Patients and Methods

We evaluated the association of prostate weight with pathologic tumor grade, positive surgical margins, extracapsular disease, and seminal vesicle invasion using logistic regression and with biochemical progression using Cox proportional hazards regression among 1,602 men treated with RP between 1988 and 2003 at five equal-access medical centers, which composed the Shared Equal Access Regional Cancer Hospital (SEARCH) Database.

Results

In outcome prediction models including multiple predictor variables, it was found that the predictor variable of prostate weight was significantly inversely associated with the outcomes of high-grade disease, positive surgical margins, extracapsular extension (all P ≤ .004), and biochemical progression (comparing prostate weight < 20 v ≥ 100 g: relative risk = 8.43; 95% CI, 2.9 to 24.0; P < .001). Similar associations were seen between preoperative transrectal ultrasound–measured prostate volume and high-grade disease, positive surgical margins, extracapsular extension (all P ≤ .005), seminal vesicle invasion (P = .07), and biochemical progression (P = .06).

Conclusion

Men with smaller prostates had more high-grade cancers and more advanced disease and were at greater risk of progression after RP. These results suggest that prostate size may be an important prognostic variable that should be evaluated for use pre- and postoperatively to predict biochemical progression.
Reduction in Voltage-Gated K+ Currents in Primary Cultured Rat Pancreatic β-Cells by Linoleic Acids
Authors: Feng Dan Dan , Luo Ziqiang , Roh Sang-gun , Hernandez Maria , Tawadros Neveen , Keating Damien J. , Chen Chen
Published: October 2005

Free fatty acids (FFAs), in addition to glucose, have been shown to stimulate insulin release through the G protein-coupled receptor (GPCR)40 receptor in pancreatic β-cells. Intracellular free calcium concentration ([Ca2+]i) in β-cells is elevated by FFAs, although the mechanism underlying the [Ca2+]i increase is still unknown. In this study, we investigated the action of linoleic acid on voltage-gated K+ currents. Nystatin-perforated recordings were performed on identified rat β-cells. In the presence of nifedipine, tetrodotoxin, and tolbutamide, voltage-gated K+ currents were observed. The transient current represents less than 5%, whereas the delayed rectifier current comprises more than 95%, of the total K+ currents. A long-chain unsaturated FFA, linoleic acid (10 μm), reversibly decreased the amplitude of K+ currents (to less than 10%). This reduction was abolished by the cAMP/protein kinase A system inhibitors H89 (1 μm) and Rp-cAMP (10 μm) but was not affected by protein kinase C inhibitor. In addition, forskolin and 8′-bromo-cAMP induced a similar reduction in the K+ current as that evoked by linoleic acid. Insulin secretion and cAMP accumulation in β-cells were also increased by linoleic acid. Methyl linoleate, which has a similar structure to linoleic acid but no binding affinity to GPR40, did not change K+ currents. Treatment of cultured cells with GPR40-specific small interfering RNA significantly reduced the decrease in K+ current induced by linoleic acid, whereas the cAMP-induced reduction of K+ current was not affected. We conclude that linoleic acid reduces the voltage-gated K+ current in rat β-cells through GPR40 and the cAMP-protein kinase A system, leading to an increase in [Ca2+]i and insulin secretion.
Bilirubin Can Induce Tolerance to Islet Allografts
Authors: Wang Hongjun , Lee Soo Sun , Dell’Agnello Carlotta , Tchipashvili Vaja , D’Avilla Joanna , Czismadia Eva , Chin Beek Yoke , Bach Fritz H.
Published: October 2005

Induction of heme oxygenase-1 (HO-1) expression in recipients of allogeneic islets can lead to long-term survival (>100 d) of those islets. We tested whether administration of bilirubin would substitute for the beneficial effects of HO-1 expression in islet transplantation. Administering bilirubin to the recipient (B6AF1) or incubating islets in a bilirubin-containing solution ex vivo led to long-term survival of allogeneic islets in a significant percentage of cases. In addition, administering bilirubin to only the donor frequently led to long-term survival of DBA/2 islets in B6AF1 recipients and significantly prolonged graft survival of BALB/c islets in C57BL/6 recipients. Donor treatment with bilirubin up-regulated mRNA expression of protective genes such as HO-1 and bcl-2 and suppressed proinflammatory and proapoptotic genes including monocyte chemoattractant protein-1 and caspase-3 and -8 in the islet grafts before transplantation. Furthermore, treatment of only the donor suppressed the expression of proinflammatory cytokines including TNF-α, inducible nitric oxide synthase, monocyte chemoattractant protein-1, and other proapoptotic and proinflammatory genes normally seen in the islets after transplantation. Donor treatment also reduced the number of macrophages that infiltrated the islet grafts in the recipients. Preincubation of βTC3 cells with bilirubin also protected the cells from lipid peroxidation. Our data suggests that the potent antioxidant and antiinflammatory actions of bilirubin may contribute to islet survival.
Estrogen Regulates Transcription of the Ovine Oxytocin Receptor Gene through GC-Rich SP1 Promoter Elements
Authors: Fleming JoAnn G. W. , Spencer Thomas E. , Safe Stephen H. , Bazer Fuller W.
Published: October 2005

Establishment of pregnancy in ruminants results from paracrine signaling by interferon τ (IFNT) from the conceptus to uterine endometrial luminal epithelia (LE) that prevents release of luteolytic prostaglandin F2α pulses. In cyclic and pregnant ewes, progesterone down-regulates progesterone receptor (PGR) gene expression in LE. In cyclic ewes, loss of PGR allows for increases in estrogen receptor α (ESR1) and then oxytocin receptor (OXTR) gene expression followed by oxytocin-induced prostaglandin F2α pulses. In pregnant ewes, IFNT inhibits transcription of the ESR1 gene, which presumably inhibits OXTR gene transcription. Alternatively, IFNT may directly inhibit OXTR gene transcription. The 5′ promoter/enhancer region of the ovine OXTR gene was cloned and found to contain predicted binding sites for activator protein 1, SP1, and PGR, but not for ESR1. Deletion analysis showed that the basal promoter activity was dependent on the region from −144 to −4 bp that contained only SP1 sites. IFNT did not affect activity of the OXTR promoter. In cells transfected with ESR1, E2, and ICI 182,780 increased promoter activity due to GC-rich SP1 binding sites at positions −104 and −64. Mutation analyses showed that the proximal SP1 sites mediated ESR1 action as well as basal activity of the promoter. In response to progesterone, progesterone receptor B also increased OXTR promoter activity. SP1 protein was constitutively expressed and abundant in the LE of the ovine uterus. These results support the hypothesis that the antiluteolytic effects of IFNT are mediated by direct inhibition or silencing of ESR1 gene transcription, thereby precluding ESR1/SP1 from stimulating OXTR gene transcription.
Cellular and molecular analyses of vascular tube and lumen formation in zebrafish
Authors: Jin Suk-Won , Beis Dimitris , Mitchell Tracy , Chen Jau-Nian , Stainier Didier Y. R.
Published: October 2005

Tube and lumen formation are essential steps in forming a functional vasculature. Despite their significance, our understanding of these processes remains limited, especially at the cellular and molecular levels. In this study, we analyze mechanisms of angioblast coalescence in the zebrafish embryonic midline and subsequent vascular tube formation. To facilitate these studies, we generated a transgenic line where EGFP expression is controlled by the zebrafish flk1 promoter. We find that angioblasts migrate as individual cells to form a vascular cord at the midline. This transient structure is stabilized by endothelial cell-cell junctions, and subsequently undergoes lumen formation to form a fully patent vessel. Downregulating the VEGF signaling pathway, while affecting the number of angioblasts, does not appear to affect their migratory behavior. Our studies also indicate that the endoderm, a tissue previously implicated in vascular development, provides a substratum for endothelial cell migration and is involved in regulating the timing of this process, but that it is not essential for the direction of migration. In addition, the endothelial cells in endodermless embryos form properly lumenized vessels, contrary to what has been previously reported in Xenopus and avian embryos. These studies provide the tools and a cellular framework for the investigation of mutations affecting vasculogenesis in zebrafish.