bluuebunny/crossref_metadata_2025 huggingface dataset:
Decreased c‐kit function inhibits enhanced skin carcinogenesis in c‐Ha‐ras protooncogene transgenic mice
Authors: Muto Satoru , Katsuki Motoya , Horie Shigeo
Published: August 2007

We previously showed that rasH2 transgenic mice carrying the human c‐Ha‐ras protooncogene are highly susceptible to chemical skin carcinogenesis. In the dermis of rasH2 mice, mast cells are recruited constitutively, and the number of mast cells increases more than in wild‐type mice in response to treatment with 7,12‐dimethylbenz[a]anthracene and 12‐O‐tetradecanoylphorbol‐13‐acetate. To determine whether enhanced skin tumor development in rasH2 mice is dependent on the recruitment of mast cells, we generated rasH2 KITW/Wv mice by crossing rasH2 mice and W or Wv KIT mutants, and examined the chemical skin carcinogenesis. In rasH2 KITW/Wv mice, mast cells were not found in the dermis either before or after treatment with 7,12‐dimethylbenz[a]anthracene and 12‐O‐tetradecanoylphorbol‐13‐acetate. Papilloma multiplicity was up to 4.6‐fold higher in rasH2 KIT+/+ mice compared with their rasH2 KITW/Wv siblings. At 12 weeks after the experiment began, the volumes of tumors were significantly smaller in rasH2 KITW/Wv relative to rasH2 KIT+/+ mice (rasH2 KITW/Wv: 29.2 ± 19.9 mm3 versus rasH2 KIT+/+: 179.6 ± 726.6 mm3; P = 0.0153). There was no difference in the latency or multiplicity of papillomas between mice without the rasH2 transgene, KITW/Wv mice and their wild‐type littermates. Western blot analysis showed that expression of H‐RAS protein in the skin was equivalent in rasH2 KITW/Wv and rasH2 KIT+/+ mice. In conclusion, the inhibition of c‐kit decreased H‐ras‐induced skin carcinogenesis. The suppression of c‐kit may be a unique and effective target as a preclinical model of cancer treatment where the activation of H‐ras has a significant role. Targeting mast cells could also be a potential strategy for treating malignancies. (Cancer Sci 2007; 98: 1549–1556)
Japan: alcohol today
Authors: HIGUCHI SUSUMU , MATSUSHITA SACHIO , MAESATO HITOSHI , OSAKI YONEATSU
Published: August 2007

Aims The purpose of this paper is to outline alcohol availability, alcohol consumption and related harm, alcohol control policy and prevention programmes in Japan, few of which have been discussed in either the Japanese or English literature.

Methods Data were collected primarily from the following two sources: statistics and survey results issued by the national government, including surveys funded by the government; and papers published since 2000, identified by searching the MEDLINE and Igaku‐Chuo‐Zasshi databases. These data were assessed regarding their quality and summarized. Some data presented here were produced specifically for this review.

Results Although per capita alcohol consumption has tended to decline for more than 10 years, it has remained at a high level. Diversification of the drinking population has progressed rapidly, specifically in women, among whom alcohol consumption has increased sharply. Cross‐sectional data suggest that alcohol consumption is associated with serious health and social consequences. Existing longitudinal data suggest that alcohol‐related problems, especially health problems, have increased steadily over the past several decades, with few exceptions, including alcohol‐related fatal road traffic accidents. Alcohol policy and prevention programmes have not developed to a level that can control these problems adequately. Specifically, the high availability of alcoholic beverages, including the lack of restrictions on sales and advertising and decreasing prices, are noted.

Conclusions This review provides basic information regarding alcohol availability and alcohol consumption and related harm that may facilitate the improvement of existing alcohol control measures in Japan and encourage the development of new alcohol control measures. This research revealed the scarcity of longitudinal data regarding alcohol consumption and its consequences, and the lack of several important variables, such as disability adjusted life years, for improving our understanding of the comprehensive status of alcohol in Japan.
The Alcohol Dependence Syndrome, 30 years later: a commentary
Authors: Li Ting‐Kai , Hewitt Brenda G. , Grant Bridget F.
Published: August 2007

Aims  Major classification systems for alcohol use disorders (DSM‐IV and ICD‐10) contain elements of the 1976 Edwards and Gross formulation of the Alcohol Dependence Syndrome (ADS). However, issues remain about the criteria that identify Alcohol Dependence (AD) as distinct from Alcohol Abuse (AA) in DSM‐IV and Harmful Use in ICD‐10. These issues, in part, have their roots in changing historical perceptions of alcohol use and its problems. We discuss current diagnostic criteria for AA and AD, collectively called Alcohol Use Disorders (AUDs), in the context of their historical evolution; research progress in understanding alcohol problems, including alcohol dependence; new findings on the severity of AUDs as classified by DSM‐IV; and the role of alcohol consumption patterns in future classifications of AUDs.

Methods  This paper is based largely on the 2006 H. David Archibald Lecture. Parts of the original lecture have been modified to reflect more recent findings from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) of the US National Institute on Alcohol Abuse and Alcoholism (NIAAA).

Results  The original Edwards and Gross ADS construct is supported by advances in biological and behavioral science over the past 30 years. New findings indicate that DSM‐IV AA and AD are not diagnostically distinct entities, but represent a continuum of severity of AUDs. The ADS criteria may best represent one quantifiable dimension of alcohol use problems and this scale can be related to that of the frequency of harmful patterns of drinking.

Conclusion  The Edwards and Gross ADS criteria can be used as the basis for beginning the development of scalable multi‐dimensional criteria for diagnosing AUDs in new initiatives to revise DSM‐IV and ICD‐10.
Detrital zircon geochronology of Carboniferous–Cretaceous strata in the Lhasa terrane, Southern Tibet
Authors: Leier Andrew L. , Kapp Paul , Gehrels George E. , DeCelles Peter G.
Published: August 2007

Sedimentary strata in the Lhasa terrane of southern Tibet record a long but poorly constrained history of basin formation and inversion. To investigate these events, we sampled Palaeozoic and Mesozoic sedimentary rocks in the Lhasa terrane for detrital zircon uranium–lead (U–Pb) analysis. The >700 detrital zircon U–Pb ages reported in this paper provide the first significant detrital zircon data set from the Lhasa terrane and shed new light on the tectonic and depositional history of the region. Collectively, the dominant detrital zircon age populations within these rocks are 100–150, 500–600 and 1000–1400 Ma. Sedimentary strata near Nam Co in central Lhasa are mapped as Lower Cretaceous but detrital zircons with ages younger than 400 Ma are conspicuously absent. The detrital zircon age distribution and other sedimentological evidence suggest that these strata are likely Carboniferous in age, which requires the existence of a previously unrecognized fault or unconformity. Lower Jurassic strata exposed within the Bangong suture between the Lhasa and Qiangtang terranes contain populations of detrital zircons with ages between 200 and 500 Ma and 1700 and 2000 Ma. These populations differ from the detrital zircon ages of samples collected in the Lhasa terrane and suggest a unique source area. The Upper Cretaceous Takena Formation contains zircon populations with ages between 100 and 160 Ma, 500 and 600 Ma and 1000 and 1400 Ma. Detrital zircon ages from these strata suggest that several distinct fluvial systems occupied the southern portion of the Lhasa terrane during the Late Cretaceous and that deposition in the basin ceased before 70 Ma. Carboniferous strata exposed within the Lhasa terrane likely served as source rocks for sediments deposited during Cretaceous time. Similarities between the lithologies and detrital zircon age‐probability plots of Carboniferous rocks in the Lhasa and Qiangtang terranes and Tethyan strata in the Himalaya suggest that these areas were located proximal to one another within Gondwanaland. U–Pb ages of detrital zircons from our samples and differences between the geographic distribution of igneous rocks within the Tibetan plateau suggest that it is possible to discriminate a southern vs. northern provenance signature using detrital zircon age populations.
Nitrative stress in respiratory inflammation caused by influenza virus infection
Authors: Zaki Md. H. , Okamoto T. , Sawa T. , Fujii S. , Akaike T.
Published: August 2007

Respiratory inflammation and hyperresponsiveness caused by various pathological stimulants and microbial infections are associated with excessive production of nitric oxide (NO) in airway epithelial and phagocytic cells. For example, in viral pneumonia caused by influenza and Sendai virus, NO contributes critically to inflammatory processes and pathological exacerbation in the airway. NO‐mediated respiratory complications may be dependent on the complex reactions of NO, with simultaneously produced superoxide forming several reactive nitrogen species, most notably ONOO−. These reactive nitrogen oxides can react with biologically important proteins, enzymes, lipids, and nucleic acids via oxidation, nitration, or nitrosylation reactions, producing nitrative stress. Recent studies indicate that nitrative stress is involved in inflammation by a number of mechanisms including modulation of host immune response, destruction of tissue architecture, activation or inactivation of enzymes and transcription factors, and so on. There is accumulating evidence for the involvement of NO and nitrative stress in respiratory diseases. In this review, we focus on the molecular mechanisms of NO‐induced and nitrative stress‐mediated respiratory inflammation and pathogenesis during respiratory viral infections.
Percutaneous reactivity to natural rubber latex proteins persists in health‐care workers following avoidance of natural rubber latex
Authors: Smith A. M. , Amin H. S. , Biagini R. E. , Hamilton R. G. , Arif S. A. M. , Yeang H. Y. , Bernstein D. I.
Published: August 2007

Background
Long‐term avoidance of natural rubber latex [Hevea brasiliensis (Hev b)] is currently recommended for health‐care workers (HCWs) with established natural rubber latex (NRL) allergy. Percutaneous sensitivity to eight Hev b NRL allergens was evaluated in HCWs in 2000. To date, no studies have evaluated the longitudinal effects of NRL avoidance on percutaneous sensitivity to NRL allergens.

Objective
The aims of this study were to evaluate changes in percutaneous reactivity to non‐ammoniated latex (NAL) and NRL allergens in HCWs 5 years after a recommendation to avoid NRL and to evaluate factors that predict the persistence of in vivo sensitivity to NAL and NRL allergens.

Methods
Skin prick testing was performed with NAL, seven NRL allergens (Hev b 1, 2, 3, 4, 6.01, 7.01, and 13), and recombinant Hev b 5 (rHev b 5) in 34 HCWs who were initially evaluated in 2000 for occupationally related NRL allergy. Serial 10‐fold dilutions of NAL and NRL allergens were employed in skin testing. Sera from the HCWs were assayed for latex and enhanced latex (rHev b 5‐enriched allergosorbent)‐specific IgE antibodies using the ImmunoCAP® assay.

Results
The prevalence of work‐related symptoms significantly decreased between 2000 and 2005 with avoidance of NRL (P<0.05). A 100‐fold reduction in percutaneous sensitivity to Hev b 2 and Hev b 7 was less likely in those with prior history of systemic reactions to NRL (P=0.0053), reported history of reaction to cross‐reactive foods (P=0.014), continued local reactions to NRL gloves (P<0.0001), or high NRL glove exposure since the initial study (P=0.0075). The diagnostic sensitivity and specificity of the latex‐specific IgE serology was 54% and 87.5%, respectively, in comparison with NAL skin tests. The addition of rHev b 5 to the ImmunoCAP® (enhanced latex) allergosorbent altered the diagnostic sensitivity and specificity of the ImmunoCAP® to 77% and 75%, respectively.

Conclusion
While symptoms may resolve quickly with NRL avoidance therapy, detectable IgE indicating continued sensitization remains beyond 5 years, and thus continued avoidance of NRL should be recommended.
Effects of air pollution on asthma hospitalization rates in different age groups in Hong Kong
Authors: Ko F. W. S. , Tam W. , Wong T. W. , Lai C. K. W. , Wong G. W. K. , Leung T.‐F. , Ng S. S. S. , Hui D. S. C.
Published: August 2007

Aims
To assess the relationship between levels of ambient air pollutants and hospitalization rates for asthma in Hong Kong (HK).

Methods
This is a retrospective ecological study. Data of daily emergency hospital admissions to 15 major hospitals in HK for asthma and indices of air pollutants [sulphur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3), particulates with an aerodynamic diameter of <10 μm particulate matter (PM10) and 2.5 μm (PM2.5)] and meteorological variables from January 2000 to December 2005 were obtained from several government departments. Analysis was performed by the generalized additive models with Poisson distribution. The effects of time trend, season, other cyclical factors, temperature and humidity were adjusted. Autocorrelation and overdispersion were corrected.

Results
Altogether, 69 716 admissions were assessed. Significant associations were found between hospital admissions for asthma and levels of NO2, O3, PM10 and PM2.5. The relative risks (RR) for hospitalization for every 10 μg/m3 increase in NO2, O3, PM10 and PM2.5 were 1.028, 1.034, 1.019 and 1.021, respectively, at a lag day that ranged from cumulative lag 0–4 to 0–5. In a multi‐pollutant model, O3 was significantly associated with increased admissions for asthma. The younger age group (0–14 years) tended to have a higher RR for each 10 μg/m3 increase in pollutants than those aged 15–65 years. The elderly (aged 65 years) had a shorter ‘best’ lag time to develop asthma exacerbation following exposure to pollutants than those aged <65 years.

Conclusion
Adverse effects of ambient concentrations of air pollutants on hospitalization rates for asthma are evident. Measures to improve air quality in HK are urgently needed.
Cord serum visfatin at term birth: maternal smoking unmasks the relation to foetal growth
Authors: López‐Bermejo Abel , De Zegher Francis , Díaz‐Silva Marta , Vicente Maria Pilar , Valls Carme , Ibáñez Lourdes
Published: August 2007

Objective  Visfatin is an adipocytokine involved in insulin action and oxidative stress. The regulation of circulating concentrations in the human foetus is unknown. We studied whether, at term birth, the serum concentrations of visfatin are related to foetal size, both in the absence and in the presence of maternal smoking during pregnancy.

Design  A cross‐sectional, hospital‐based study.

Patients  Seventy‐eight singleton, healthy neonates [39 girls and 39 boys; gestational age (GA) 39·5 ± 0·2 weeks; birth weight (BW) 3·3 ± 0·04 kg].

Methods  Cord serum visfatin, insulin and IGF‐I measured by specific immunoassays.

Results  In infants from nonsmoking mothers (N = 48), cord serum visfatin levels were unrelated to either BW or birth length (BL). In infants from smoking mothers (N = 30), however, serum visfatin was inversely associated with both BW (r = −0·57; P < 0·001) and BL (r = −0·60; P < 0·0001) and it was directly associated with the number of cigarettes smoked (P < 0·05) in heavy smokers. In a multiple regression analysis, cord serum visfatin accounted for 36% of BW and 32% of BL variance in infants from smoking mothers. Cord serum visfatin was unrelated to insulin or IGF‐I in either subgroup.

Conclusion  At term birth, there is no readily detectable relation between circulating visfatin and indices of foetal size; however, maternal smoking unmasked a strikingly inverse relationship between cord serum visfatin and the foetal growth status, indicating that smoking can elicit a rise or a fall of cord serum visfatin, depending on whether the foetus is, respectively, of smaller or larger size.
Clear cell sarcoma, cellular mesoblastic nephroma and metanephric adenoma: cytological features and differential diagnosis with Wilms tumour
Authors: Portugal R. , Barroca H.
Published: August 2007

Wilms’ Tumour (WT) is the most common kidney tumour in childhood, this fact and the embryonic complexity of WT create, whenever one of its three classical components predominates in cytologic smears, difficulties in the differential diagnoses with other less common entities. In the present study, we review the cytological and immunohistochemical characteristics of three children renal tumours, a Clear Cell Sarcoma of the Kidney (CCSK‐case1), a Cellular Mesoblastic Nephroma (CMN‐case2) and a Metanephric Adenoma (MA‐case3) and compare them, for differential diagnostic purposes, with smears of blastematous, mesenchymal and epithelial predominant WTs, previously diagnosed in our Department. In all cases a mass was detected in the abdomen (2 and 8 year old children‐cases 1 and 3, respectively), and pre‐birth in case 2 (the tumour was detected during pregnancy). Fine needle biopsy was performed followed by routine cytologic examination. The presence of moderate amount of blue pale cytoplasm in neoplastic cells (case1), the presence of tightly cohesive, bland, spindle tumour cells (case2) and the identification of small, well differentiated epithelial tubules with psammoma bodies in case 3, were the main morphologic characteristics that we think represent the most important elements for distinguishing our cases from a WT. Immunoreactivity was only helpful in case 1 as we found a characteristic dot‐like pattern positivity for vimentin, in the absence of immunoreactivity for the other markers that are usually positive in WT. Summing up, these three cases demonstrate that cytopathologists should be aware of the occurrence of uncommon renal neoplasms in childhood and should be acquainted with their characteristics, in order to avoid false diagnoses.
Plasticity to neighbour shade: fitness consequences and allometry
Authors: BELL D. L. , GALLOWAY L. F.
Published: August 2007

Phenotypic plasticity may confer a fitness benefit to organisms in a spatially heterogeneous environment. However, the evolution of such adaptive plasticity can be limited by the constraints imposed by interacting environments. Moreover, adaptive plasticity may be masked by reduced growth in a low‐quality environment. The allometry between plasticity of morphological traits and overall growth is often overlooked.

We addressed these issues by examining the effect of shade produced by neighbouring plants (neighbour shade) on a small annual plant,Geranium carolinianum. Plants were grown in two field sites, a wood margin and an old field. A clipping treatment was used to manipulate neighbour shade at both planting sites. We measured petiole length to quantify shade avoidance response. Genotypic selection analysis was used to assess the fitness consequences of petiole length.

Petioles were longer in the wood margin than in the old field and were similar between neighbour environments. However, overall plant size differed among the environments. As a result, relative to plant size, petioles were longer when individuals were surrounded by neighbours than when neighbours had been removed, but were similar between sites. After taking the size into account, plants with longer petioles had higher fitness than plants with shorter petioles in all environments.

The functional response of petioles to neighbour shade was revealed only when the passive plasticity of plant size was considered. The lack of differential selection across neighbour environments together with active elongation of petioles in response to neighbours suggests that the current shade avoidance response is adaptive.
Role of osteopontin in neutrophil function
Authors: Koh Adeline , Da Silva Andre Paes Batista , Bansal Anil K. , Bansal Manju , Sun Chunxiang , Lee Hyejin , Glogauer Michael , Sodek Jaro , Zohar Ron
Published: August 2007

Osteopontin (OPN) is important for the function of fibroblasts, macrophages and lymphocytes during inflammation and wound healing. In recent studies of experimental colitis we demonstrated exacerbated tissue destruction in OPN‐null mice, associated with reduced tumour necrosis factor‐α expression and increased myeloperoxidase activity. The objective of this investigation therefore was to determine the importance of OPN expression in neutrophil function. Although, in contrast to macrophages, neutrophils expressed low levels of OPN with little or no association with the CD44 receptor, intraperitoneal recruitment of neutrophils in OPN‐null mice was impaired in response to sodium periodate. The importance of exogenous OPN for neutrophil recruitment was demonstrated by a robust increase in peritoneal infiltration of PMNs in response to injections of native or recombinant OPN. In vitro, OPN–/– neutrophils exhibited reduced chemokinesis and chemotaxis towards N‐formyl methionyl leucyl phenylalanine (fMLP), reflecting a reduction in migration speed and polarization. Exogenous OPN, which was chemotactic for the neutrophils, rescued the defects in polarization and migration speed of the OPN–/– neutrophils. In contrast, the defensive and cytocidal activities of OPN–/– neutrophils, measured by assays for phagocytosis, generation of reactive oxygen species, cytokine production and matrix metalloproteinase‐9, were not impaired. These studies demonstrate that, while exogenous OPN may be important for the recruitment and migration of neutrophils, expression of OPN by neutrophils is not required for their destructive capabilities.
Preventive aspects in children's caries treatments preceding dental care under general anaesthesia
Authors: SAVANHEIMO NORA , VEHKALAHTI MIIRA M.
Published: August 2007

Background.  In Helsinki Public Dental Service (PDS) the Special Oral Health Care Unit (SOHCU) provides comprehensive dental treatments under general anaesthesia (GA). For the present study, all dental treatment given under GA for generally healthy children (n = 102) below 16 years of age (range 2.3–15.8) during a 1‐year period and dental treatment and visits of these children in the preceding 2 years in Helsinki PDS was recorded in detail. These children were referred to the SOHCU because of serious difficulties in dental care due to large treatment needs or failures in psychological and chemical management, including sedation.

Aim.  To describe treatments given to generally healthy children under GA and to evaluate preventive aspects of their dental care in the preceding 2 years.

Design.  The study was cross‐sectional and retrospective. Data came from the patients’ individual records.

Results.  Treatments under GA included an average of 6.0 restorations (SD = 2.7, range 0–12) and 1.7 extractions (SD = 2.1, range 0–10). In the 2 preceding years, these children had visited dentist an average of 5.1 times (SD = 2.7, range 1–14) with an average of 2.4 restorations (SD = 1.9, range 0–12) and 0.5 extractions (SD = 1.4, range 0–10). Of the restorations made, 36% were temporary. Of all visits, those with an operative approach accounted for 35%, preventive for 37%, operative and preventive for 5%, and visits with total uncooperation for 23%. Of the children, 90% had at least one preventive visit. Children treated under conscious sedation in the preceding 2 years received less prevention (P = 0.02). Remaining without preventive measures was most likely for those children exhibiting visits with total uncooperation (odds ratio = 4.6; P = 0.004) and for those receiving numerous temporary fillings (odds ratio = 4.1; P = 0.0005).

Conclusions.  The uncooperative high‐caries children pose a demanding challenge to PDS. The early identification of high‐caries risk and efforts of intensive preventive care are in key position to reduce the number of children receiving treatment under GA due to high levels of dentinal decay.
Informed multi‐objective decision‐making in environmental management using Pareto optimality
Authors: Kennedy Maureen C. , Ford E. David , Singleton Peter , Finney Mark , Agee James K.
Published: August 2007

Effective decision‐making in environmental management requires the consideration of multiple objectives that may conflict. Common optimization methods use weights on the multiple objectives to aggregate them into a single value, neglecting valuable insight into the relationships among the objectives in the management problem.

We present a multi‐objective optimization procedure that approximates the non‐dominated Pareto frontier without the use of weightings, allowing for visualization of the trade‐offs among objectives. The non‐dominated Pareto frontier is approximated by the simultaneous optimization of a vector objective function; two vector objective functions are defined as non‐dominated if improvement with respect to one objective is at the detriment of another objective.

We demonstrate the method with a case study for the optimum distribution of forest fuels treatments that reduce the impact of fire on a forest. The multiple objectives are to protect habitat of an endangered species, protect late successional forest reserves and minimize the total area treated. In the comparison of three optimization searches, the number of non‐dominated solutions increases with the dimensions of the objective space, but with only two objectives the search is ineffective in minimizing fire impact in the different landscape types. Key challenges include the extensive computation time required to approximate the non‐dominated set, and reducing the number of solutions that are analysed in detail.

Synthesis and applications. The multi‐objective optimization program presented can be adapted to other environmental management problems, and easily incorporates a wide range of quantifiable objectives. This tool provides decision‐makers with a set of alternatives that estimates the full range of trade‐offs among multiple objectives and provides a common ground from which dialogue can come to an informed compromise and decision in environmental management problems.
New tools to measure discrepancy between prescribing practices and guideline recommendations
Authors: Mercier Catherine , Boissel Jean‐Pierre , Estève Jacques , Iwaz Jean , Nony Patrice
Published: August 2007

Objective  To study the performance of a new method designed to measure discrepancy between real prescriptions and evidence‐based reference treatments.

Methods  Two different indices (additive and multiplicative) are proposed to summarize deviation between prescription and reference. Deviations thought to be observed in a population of prescribers are simulated in diverse hypothetical situations in the presence or absence of evidence‐based references. The performances of both indices are compared and their sensitivities to change are explored.

Results  Both indices are sensitive to variation in prescriber behaviour. The additive index allows a more accurate analysis of deviation while the multiplicative index is simpler to implement and interpret but more sensitive to change.

Conclusion  The two deviation indices may be used as new tools in surveys or trials dealing with prescribing practices.
Baseline radiological staging in primary breast cancer: impact of educational interventions on adherence to published guidelines
Authors: McWhirter Elaine , Yogendran Geetha , Wright Frances , Pharm George Dranitsaris M. , Clemons Mark
Published: August 2007

Rationale  The purpose of baseline radiological staging in newly diagnosed breast cancer patients is to rule out overt metastatic disease. We have previously compared the use of radiological staging at our institution with the recommendations of the Cancer Care Ontario Practice Guidelines Initiative (CCOPGI). Our results demonstrated that between January 2000 to December 2002, a high proportion of our cohort (n = 135) of patients underwent unnecessary investigations.

Objectives  To implement and assess an educational intervention to encourage staging guideline utilization in a cohort of early breast cancer patients.

Methods  In January 2003, multidisciplinary educational rounds were held, highlighting the CCOPGI guidelines, and reporting results of the audit of staging investigations. The staging guidelines were then included in the Clinical Practice Guidelines of the Breast Disease Site Group, Toronto‐Sunnybrook Regional Cancer Centre. A retrospective chart review was completed that assessed staging investigations from a random sample of a similar group of patients (n = 134) from January 2003 to April 2005, to explore the effects of these educational interventions on clinical practice.

Results  For patients with Stage I breast cancer, there was a significant decrease (P < 0.004) in each type of investigation: a twofold decrease in chest X‐rays; 2.5‐fold decrease bone scans and fourfold decrease in the number of abdominal ultrasounds. For patients in Stage II, there was no significant change in the proportion of patients undergoing radiological investigations. There was a non‐significant trend towards appropriately receiving all three investigations for patients with Stage III disease.

Conclusions  Our results demonstrate that prior to the educational intervention, many patients with early breast cancer were undergoing inappropriate radiological staging. Since 2003 however, for Stage I patients there has been a significant improvement in adherence with the guidelines. We hypothesize that our educational intervention had a positive impact on improving the utilization of baseline radiological staging in patients with primary breast cancer.
Prioritizing guideline topics: development and evaluation of a practical tool
Authors: Ketola Eeva , Toropainen Erja , Kaila Minna , Luoto Riitta , Mäkelä Marjukka
Published: August 2007

Rationale, aims and objectives  A clear process for selecting and adopting clinical practice guidelines in the new topic areas is needed. The aim of this study is to design and develop a practical tool to assess guideline topics that have been suggested to the organization responsible for producing guidelines.

Methods  We carried out an iterative development, feasibility and validation study of a guideline topic prioritization tool. The setting included the guideline producer organization and the tax‐funded health care system. In the first stage of the tool development, participants were researchers, members of the Current Care Board and experts from health care organizations. In the second stage, the evaluation was done internally within the project by three independent reviewers. The main outcome measures were responses to an evaluation questionnaire, qualitative process feedback and analysis of the performance of the instrument on a random set of guidelines.

Results  Evaluations by three independent reviewers revealed good agreement and face validity with respect to its feasibility as a planning tool at the guideline board level. Feedback from board members suggested that the instrument is useful in prioritizing guideline topics.

Conclusion  This instrument was accepted for use by the Board. Further developments are needed to ensure feedback and acceptability of the instrument by those proposing topics.
Creating clinically relevant knowledge from systematic reviews: the challenges of knowledge translation
Authors: Scott N. Ann , Moga Carmen , Barton Pamela , Rashiq Saifudin , Schopflocher Donald , Taenzer Paul , Harstall Christa ,   the Alberta Ambassador Program Team
Published: August 2007

Rationale and objective  A research translation strategy for chronic pain was developed that has significant potential to advance the usefulness of systematic reviews (SRs) in clinical practice.

Method  The strategy used interactive case‐based workshops that summarize current evidence on treatments for chronic non‐cancer pain. Health technology assessment researchers and clinicians collaborated to translate SR evidence into education aids, but this proved far from straightforward.

Results  Sourcing and selecting the SR evidence required maintaining a credible balance between the diametrical concepts of comprehensiveness and efficiency, and relevance and validity. On examination of the collated evidence base, further challenges were encountered in dealing with the lack of consistency among the SRs in the quality of execution, the scales used to rate the quality of the evidence, and the conclusions on common topic areas. Strategies for overcoming these difficulties are discussed.

Conclusions  The key elements for creating clinically relevant knowledge from SRs are: a flexible, consistent and transparent methodology; credible research; involvement of renowned content experts to translate the evidence into clinically meaningful guidance; and an open, trusting relationship among all contributors.
The process of evidence‐based medicine and the search for meaning
Authors: Biswas Rakesh , Umakanth Shashikiran , Strumberg Joachim , Martin Carmel M. , Hande Manjunath , Nagra Jagbir S.
Published: August 2007

Background and Rationale  Evidence based medicine is the present backbone of rational and objective, modern medical problem solving and is a meeting ground for quantitative and qualitative researchers alike as it culminates into applying the fruits of clinical research to the individual patient.

A systematic enquiry into the evolving paradigms in EBM is a need of the hour.

Aims and methods  A qualitative enquiry examining the impact of different methodologies in EBM and their role in generating meaning interpretable at individual levels.

Results  Present day outcome based research deals less with patients as individuals than as populations. Evidence based medicine struggles to apply the fruits of population based research to individuals who are often not as predictable as linear quantitative research would like them to be. The present EBM literature neglects a lot of events it doesn’t believe to be statistically significant and perhaps here is an area that needs to be improved on – it assumes that because associations are demonstrated between interventions and outcomes in RCTs/meta‐analysis, these associations are linear and causal in the real world. While they may be demonstrated repeatedly in highly controlled environments, in the real ‘uncontrolled’ world of clinical practice with real people, their validity breaks down.

Conclusions  One needs to make the EBM standard model patient‐individual (a projection of collective patient event data) resemble the real human individual patient so that optimal EBM individual data that matches our query can be easily and quickly spotted from the dense jungle of information that has grown over the years. This hints at rethinking our entire research methodology and modifying it to suit the needs of the individual patient.
Doctors’ views of clinical practice guidelines: a qualitative exploration using innovation theory
Authors: Hader Joanne M. , White Robin , Lewis Steven , Foreman Jeanette L. B. , McDonald Paul W. , Thompson Laurence G.
Published: August 2007

Rationale, aims and objectives  The authors undertook this qualitative study as part of a larger evaluation of the effect of eight clinical practice guidelines issued by an arm’s‐length government agency in a Canadian province. Using Orlandi and colleagues’ version of the Rogers diffusion of innovation model as a framework, the authors mapped doctors’ views on implementation of clinical practice guidelines.

Methods  In semi‐structured interviews with 45 representative doctors, the authors elicited doctors’ framework of meaning for behaviour change in general and for clinical practice guideline uptake in particular. These were then compared with the adapted Orlandi/Rogers diffusion of innovation model to confirm, amend or challenge that model.

Results  Doctors identified the following influences on changes to their clinical practice and on clinical practice guideline uptake, within a five‐step innovation model:

1 innovation: evidence change is required, perceived need for change;

2 communication: awareness of innovation;

3 adoption: evidence of improved outcomes without increased patient risk, opinion leader support, consistency with current trends;

4 implementation: patient and family acceptability; and

5 maintenance: system support, patient and family support, observed improved patient outcomes without increased risk

Conclusions  Innovation for doctors is a complex decision process rather than a single decision point. Change occurs in the context of professional networks and patient and family support and demand.
Neuropsychological predictors of everyday functioning in adults with intellectual disabilities
Authors: Su C.‐Y. , Chen C.‐C. , Wuang Y.‐P. , Lin Y.‐H. , Wu Y.‐Y.
Published: August 2007

Background  Very little is known about the neuropsychological correlates of adaptive functioning in people with intellectual disabilities (ID). This study examined whether specific cognitive deficits and demographic variables predicted everyday functioning in adults with ID.

Method  People with ID (n = 101; ages 19–41 years; mean education = 11 years; 34% women; 54% competitively employed; 41% with mild ID) completed a comprehensive neuropsychological battery grouped into four cognitive domains: processing speed, verbal memory and comprehension, visual perception/constructive function, and executive function. In addition, parents completed an 89‐item rating scale developed to assess a wide range of independent living skills.

Results  Confirmatory factor analysis results confirmed a correlated four‐factor model of cognitive function and a unidimensional model of everyday functioning. Furthermore, structural equation modelling results supported the predictive relationship of verbal memory/comprehension and employment status (standardized regression coefficients 0.45, 0.22, P ≤ 0.01 for each) to measures of everyday functioning. The two variables together explained 35% of the variance in everyday functioning.

Conclusions  Both general cognitive dysfunction and specific verbal memory and comprehension deficit impair daily functions in people with ID. These findings have implications for predictive models of adaptive functioning, and for cognitive rehabilitation and deficit compensation strategies for this group.
Circulating E‐selectin as a risk marker in patients with end‐stage renal disease
Authors: Malatino L. S. , Stancanelli B. , Cataliotti A. , Bellanuova I. , Fatuzzo P. , Rapisarda F. , Leonardis D. , Tripepi G. , Mallamaci F. , Zoccali C.
Published: August 2007

Background.  E‐selectin is a key adhesion molecule which plays a fundamental role in endothelial progenitor cell‐dependent reparative mechanisms in experimental ischaemia and it serves to anchor leucocytes to the endothelium in inflammatory processes. Inflammation is one of the strongest risk factors for death and cardiovascular (CV) events in end‐stage renal disease (ESRD).

Objective.  The objective of the current study was to evaluate whether E‐selectin is a useful biomarker of clinical outcome in ESRD patients. We tested the prediction power of circulating E‐selectin for mortality and CV events in a cohort of 265 ESRD patients.

Results.  During the follow‐up, 59 patients died and 58 had CV events. All‐cause mortality was inversely related to serum E‐selectin, the risk of death being the lowest in patients in the third E‐selectin tertile (HR: 1, reference group), intermediate in those in the second tertile (HR: 1.30) and the highest in patients in the first tertile (HR: 2.02, P = 0.01). Similarly, the risk of fatal and nonfatal CV events followed an inverse pattern being lowest in the third tertile (reference group) and highest in the first tertile (HR: 1.73, P = 0.03). The prediction power of E‐selectin for death and CV events was confirmed in a Cox regression analysis where E‐selectin emerged as an inverse predictor of these outcomes, particularly so in patients with severe inflammation.

Conclusions.  These data are in keeping with the hypothesis that in systemic inflammation altered E‐selectin shedding may play a role in arterial damage and implicates this adhesion molecule in atherosclerotic complications in a high‐risk condition like ESRD.
Cardiomyopathy, pericarditis and myocarditis in a population‐based cohort of inpatients with coeliac disease
Authors: Elfström P. , Hamsten A. , Montgomery S. M. , Ekbom A. , Ludvigsson J. F.
Published: August 2007

Objectives:  We investigated the risk of myocarditis, cardiomyopathy, and pericarditis in patients with celiac disease (CD) from a general population cohort.

Subjects and methods:  Through the Swedish national registers we identified 9363 children and 4969 adults with a diagnosis of CD (1964–2003). These individuals were matched with upto five reference individuals for age, sex, calendar year and county (n = 69 851). Cox regression estimated hazard ratios (HRs) for later heart disease.

Main outcome measures:  Myocarditis, cardiomyopathy (any or dilated), and pericarditis defined according to relevant international classification of disease codes in the Swedish national inpatient register.

Results:  Celiac disease diagnosed in childhood was not associated with later myocarditis (HR = 0.2; 95% CI = 0.0–1.5), cardiomyopathy of any type (HR = 0.8; 95% CI = 0.2–3.7), or pericarditis (HR = 0.4; 95% CI = 0.1–1.9). Restricting our analyses to adulthood CD and heart disease diagnosed from 1987 and onwards in departments of cardiology/internal medicine, we found no association between CD and later myocarditis (HR = 2.1; 95% CI = 0.4–11.7), dilated cardiomyopathy (HR = 1.7; 95% CI = 0.4–6.5) or pericarditis (HR = 1.5; 95% CI = 0.5–4.0).

Conclusion:  This study found no association between CD, later myocarditis, cardiomyopathy or pericarditis.
Do patient characteristics or factors at resuscitation influence long‐term outcome in patients surviving to be discharged following in‐hospital cardiac arrest?
Authors: Skrifvars M. B. , Castren M. , Nurmi J. , Thoren A. B. , Aune S. , Herlitz J.
Published: August 2007

Introduction.  Few studies have focused on factors influencing long‐term outcome following in‐hospital cardiac arrest. The present study assesses whether long‐term outcome is influenced by difference in patient factors or factors at resuscitation.

Methods.  An analysis of cardiac arrest data collected from one Swedish tertiary hospital and from five Finnish secondary hospitals supplemented with data on 1 year survival. Multiple logistic regression analysis was used to identify factors associated with survival at 12 months.

Results.  A total of 441 patients survived to hospital discharge following in‐hospital cardiac arrest and 359 (80%) were alive at 12 months. Factors independently associated with survival [odds ratio (OR) >1 indicates increased survival and <1 decreased survival] at 12 months were; age [OR 0.95, 95% confidence interval (CI) 0.93–0.98], renal disease (OR 0.3, CI 0.1–0.9), good functional status at discharge (OR 4.9, CI 1.3–18.9), arrest occurring at (compared with arrests on general wards) emergency wards (OR 4.7, CI 1.4–15.3), cardiac care unit (OR 2.8, CI 1.2–6.4), intensive care unit (OR 2.4, CI 1.1–5.7), ward for thoracic surgery (OR 10.2, CI 2.6–40.1) and unit for interventional radiology (OR 13.3, CI 3.4–52.0). There was no difference in initial rhythm, delay to defibrillation or delay to return of spontaneous circulation between survivors and nonsurvivors.

Conclusion.  Several patient factors, mainly age, functional status and co‐morbid disease, influence long‐term survival following cardiac arrest in hospital. The location where the arrest occurred also influences survival, but initial rhythm, delay to defibrillation and to return of spontaneous circulation do not.
Acute effects of haemodialysis on biochemical modulators of endothelial function
Authors: Hewitson C. L. , Whiting M. J. , Barbara J. A. , Mangoni A. A.
Published: August 2007

Objectives.  To assess the acute effects of haemodialysis (HD) on biochemical factors modulating endothelial function.

Setting.  Academic medical centre.

Subjects.  Forty patients (age 63.5 ± 2.2 years, mean ± SEM) undergoing HD.

Interventions.  Folic acid (F), homocysteine (tHcy), asymmetric dimethylarginine (ADMA), high‐sensitivity C‐reactive protein (CRP) and malondialdehyde (MDA) were measured pre‐HD, 1 h after commencing HD and within the last hour of HD (end‐HD). Endothelium‐dependent and ‐independent vasodilatation were measured by applanation tonometry (changes in augmentation index, AIx, postinhaled salbutamol and postsublingual nitroglycerin) in conjunction with biochemical measurements.

Results.  Marked reductions in serum F (616 ± 73 vs. 273 ± 30 nmol L−1, P < 0.001), tHcy (16.3 ± 0.7 vs. 11.2 ± 0.5 μmol L−1, P < 0.001) and ADMA (0.64 ± 0.02 vs. 0.47 ± 0.02 μmol L−1, P < 0.001) occurred end‐HD, whereas CRP and MDA levels did not significantly change. There was no significant change in endothelium‐dependent vasodilatation, whereas endothelium‐independent vasodilatation improved end‐HD (−23.1 ± 1.9 vs. −17.3 ± 1.3%, P = 0.018). Regression analysis showed that both higher ADMA (P = 0.029) and lower F levels (P = 0.040) end‐HD were determinants of reduced endothelium‐dependent vasodilatation end‐HD (R2 = 0.23).

Conclusions.  HD is associated with significant reductions in F, tHcy and ADMA serum concentrations. The lack of significant effects of HD on endothelium‐dependent vasodilatation could be secondary to the concomitant loss of factors either enhancing (F) or impairing (ADMA) endothelial function.
Views of hepatitis C virus patients delayed from treatment for psychiatric reasons
Authors: Rowan P. J. , Dunn N. J , El‐Serag H. B. , Kunik M. E.
Published: August 2007

Summary.  For patients with chronic hepatitis C virus, certain psychiatric disorders are contraindications for antiviral therapy with interferon‐alpha (IFN). Although these conditions delay a significant portion of patients from beginning therapy, no one has yet portrayed the views of these patients. A qualitative analysis, drawing upon semi‐structured interviews, was developed to generate hypotheses regarding patient views of the treatment disposition process, and to generate strategies for increasing the portion of treatment‐eligible patients. Two focus groups were conducted: one for patients delayed from treatment due to current or recent depression, and one for patients delayed due to current or recent alcohol use. A grounded theory analysis of the interview data were conducted. Patients were generally satisfied with the decision‐making process, based largely on education from, and trust in, physicians. Upon learning their diagnosis, patients reported making healthy behaviour changes regarding alcohol, diet, exercise and herbal remedies. Some patients reported that requiring a period of alcohol abstinence was excessive, as they believed that they could discontinue alcohol use immediately, if so instructed by a physician. Patients seemed to over‐interpret the likelihood of suicide during interferon‐alpha (IFN) therapy. Current or recent psychiatric morbidity delays many patients from beginning interferon therapy. Nonetheless, this may be an optimal time for physicians to encourage healthy behaviours including abstinence from alcohol. Also, physicians may need to extensively assess the use of herbal remedies by patients. To help patients make judgments about beginning therapy, physicians should focus upon risk communication regarding the likelihood of suicide on therapy with interferon.