bluuebunny/crossref_metadata_2025 huggingface dataset:
Measurement of von Willebrand factor binding to a recombinant fragment of glycoprotein Ibα in an enzyme‐linked immunosorbent assay‐based method: performances in patients with type 2B von Willebrand disease
Authors: Caron Claudine , Hilbert Lysiane , Vanhoorelbeke Karen , Deckmyn Hans , Goudemand Jenny , Mazurier Claudine
Published: April 2006

Type 2B von Willebrand disease (VWD) is characterised by an increased affinity of von Willebrand factor (VWF) for its platelet receptor glycoprotein Ib (GPIb). This feature is usually studied in vitro by a ristocetin‐dependent VWF platelet‐binding assay, which has some limitations as it requires [e.g. (radio)‐labelled anti‐VWF antibodies and normal formaldehyde‐fixed platelets]. We, here, extended the applicability of an enzyme‐linked immunosorbent assay‐based method previously described for the measurement of ristocetin co‐factor activity that used a recombinant fragment of GPIb (rfGPIbα) and horseradish peroxidase‐labelled rabbit anti‐human VWF antibodies for measuring the captured ristocetin‐VWF complexes on the rfGPIbα. Thirty‐one type 2B VWD patients from 15 families with eight different known mutations were studied. VWF in plasma from 28 of these patients bound better than normal VWF at 0·2 mg/ml ristocetin, with the ratio, optical density (OD) patient/OD normal pool plasma, higher than 1·8. For two of the three other patients with no enhanced response of plasma VWF, the platelet lysate VWF showed an enhanced binding capacity; for the last patient, the results in other members of the family are unequivocal. We conclude that, this new method for measurement of plasma or platelet VWF‐binding capacity offers great advantages for correct type 2B VWD diagnosis.
No evidence of significant silencing of Fanconi genes FANCF and FANCB or Nijmegen breakage syndrome gene NBS1 by DNA hyper‐methylation in sporadic childhood leukaemia
Authors: Meyer Stefan , White Daniel J. , Will A. M. , Eden Tim , Sim Alyson , Brown Robert , Strathdee Gordon
Published: April 2006

Fanconi anaemia (FA) and Nijmegen breakage syndrome (NBS) carry a high risk of haematological cancer. Affected cellular pathways may be modulated in sporadic malignancies and silencing of FANCF through methylation has been shown to cause somatic disruption of the FA pathway. Combined bisulphite restriction analysis for methylation of FANCF, FANCB and NBS1 was used to investigate 81 sporadic acute childhood leukaemias. No methylation was detected at any associated CpG sites analysed. This does not exclude very low levels of FANCF, FANCB or NBS1 methylation, but suggests other factors are responsible for chemo‐sensitivity and chromosomal instability in sporadic childhood leukaemia.
Continuous infusion of factor concentrates in children with haemophilia A in comparison with bolus injections
Authors: BIDLINGMAIER C. , DEML M.‐M. , KURNIK K.
Published: April 2006

Summary.  Although the concept of continuous infusion (CI) of factor concentrates is well known, prospective paediatric data are rare. We present a prospective open‐labelled non‐randomized study focusing on safety, efficacy and factor VIII (FVIII) usage compared with bolus injections (BI) in children. In 43 consecutive patients (0.5–17 years; median: 9.6) undergoing different operations, CI was started with an initial FVIII‐bolus of 70 IU kg−1 bodyweight, followed by a median infusion rate of 4.4 IU kg−1 h−1 (range: 2.8–9.5) dose adjusted for daily FVIII levels (target: 60–80%). No direct serious adverse events occurred; however, two out of 43 patients, both from the group of four patients with less than 20 exposure days (ED) before starting CI, developed a high‐responding inhibitor. Two CI patients showed mild thrombophlebitis or rash. Infusion rates needed to achieve adequate FVIII levels were highly predictable and could be reduced because of decreasing FVIII clearance. Bleeding, requiring additional boli, was observed in eight out of 43 patients. Therapy duration and factor usage of CI were influenced by the procedure, but not by the product used or thrombophilia. Twelve of these CI patients were compared with 12 contemporary consecutive age‐ and procedure‐matched BI patients. Compared with BI patients, CI patients saved 30% FVIII (812.9 vs. 563.2 IU kg−1, P < 0.006). We conclude that CI forms a safe and effective method for perioperative care in children and reduces factor usage. Because of the unknown risk of inhibitor development, we will use CI only in patients beyond 20 ED.
Unresolved issues in diagnosis and management of inherited bleeding disorders in the perinatal period: A White Paper of the Perinatal Task Force of the Medical and Scientific Advisory Council of the National Hemophilia Foundation, USA
Authors: KULKARNI R. , PONDER K. P. , JAMES A. H. , SOUCIE J. M. , KOERPER M. , HOOTS W. K. , LUSHER J. M.
Published: April 2006

Summary.  Haemophilia and inherited bleeding disorders in newborns and their carrier mothers pose unique challenges. The pattern of bleeding and the causes and risk factors for bleeding are decidedly different than an older child or an adult with haemophilia/inherited bleeding disorder. This document outlines the needs for further research and education, summarizes the state of the art background information and provides guidance regarding research, education and access to care issues in this population.
Late failure of root canal therapy: a diagnostic and treatment planning challenge. Case report
Authors: HAYES S. J. , DUMMER P. M. H.
Published: April 2006

This report describes a case in which failure of conventional root canal therapy presented 17 years following initial treatment. The apical pathology was curetted, the tooth root resected and a root‐end filling placed. The possible reasons for failure of the initial orthograde root canal therapy are discussed with the conclusion that the cause may not have been addressed fully by surgical intervention. The case highlights the challenge facing clinicians when assessing failed root fillings, not only in determining the exact cause of failure but deciding the appropriate treatment for the individual tooth and patient.
Analysis of IL1B, TAP1, TAP2 and IKBL polymorphisms on susceptibility to tuberculosis
Authors: Gomez L. M. , Camargo J. F. , Castiblanco J. , Ruiz‐Narváez E. A. , Cadena J. , Anaya J. M.
Published: April 2006

Genetic determinants of human susceptibility to tuberculosis (TB) have not been completely elucidated. Interleukin‐1 beta (IL‐1β) and the inhibitor of kB‐like (IkBL) are important molecules that participate in the inflammatory response required for the immunological control of a broad spectrum of infectious agents. The transporter associated with antigen processing (TAP) is involved in the antigen processing via major histocompatibility complex class I molecules and in turn might regulate the T‐cell response against Mycobacterium tuberculosis. To better characterize the host genetic factors determining the susceptibility to TB, we evaluated the influence of functional polymorphisms in IL1B, TAP and IKBL genes on the risk of developing pulmonary TB in a Northwestern Colombian population, an endemic area of M. tuberculosis infection. A total of 122 TB patients and 166 healthy controls (N = 166) negative for human immunodeficiency virus infection were examined for IL1B−511 and +3953, TAP1 and TAP2 and IKBL+738 polymorphisms. Univariate analysis disclosed significant differences between patients and controls for IL1B+3953 polymorphism. After unconditional logistic regression analysis, a strong protection conferred by IL1B+3953 T‐allele‐carrying genotypes was observed. A trend between TAP2*0201 allele and disease was observed. Association between IL1B−511, TAP1 or IKBL polymorphisms and TB disease was not found. These results indicate that a functional polymorphism in the IL1B gene influences the susceptibility to TB and suggest a role for IL‐1β in the pathogenesis of mycobacterial infection.
National Cultural Influences on Knowledge Sharing: A Comparison of China and Russia
Authors: Michailova Snejina , Hutchings Kate
Published: April 2006

abstract This paper presents a set of theoretical propositions regarding knowledge sharing in China and Russia. We argue that there are important national cultural similarities and differences between the two countries that result in certain similarities and differences in individual knowledge‐sharing behaviour in Chinese and Russian organizations. We claim that vertical collectivism and particularistic social relations in China and Russia lead to intensive social relations among organizational members, which facilitate knowledge sharing between in‐group members in organizations in both countries. We also maintain that differences in the essence of collectivism as well as in the extent of collectivism in the two cultural contexts lead to different intensities of knowledge sharing in Chinese and Russian organizations. Finally, we discuss theoretical and management implications of this research.
Beyond Self‐Interest Revisited*
Authors: Rocha Hector O. , Ghoshal Sumantra
Published: April 2006

abstract  We revisit the self‐interest view on human behaviour and its critique, and propose a framework, called self‐love view, that integrates self‐interest and unselfishness and provides different explanations of the relationship between preferences, behaviour, and outcomes. Proponents of self‐interest as the only valid behavioural assumption argue for simplified assumptions and clear models in order to propose precise prescriptions, while critics to this self‐interest view argue for realistic assumptions and rich descriptions in order to reach better explanations. This debate inhibits theoretical development because it faces the problem of incommensurability of standards for choosing among paradigms. We propose the concept of self‐love, or the inclination of human beings to strive for their own good and perfection, to remove the assumption self‐interest vs. unselfishness. Self‐love distinguishes between the object and the subject of motivation and therefore creates a bi‐dimensional motivational space. This framework replaces the unidimensional continuum self‐interest–unselfishness, specifies eight interrelated motives, and provides different expected relationships between preferences, behaviour, and outcomes. We show that a better understanding of motivational assumptions, their embodiment in theories, and their influence on the very behaviours these theories assume provides managers and policymakers more alternatives for the designing of motivational contexts than in the case of assuming either self‐interest or a permanent conflict between self‐interest and unselfishness.
The Psychology of Novelty‐Seeking, Creativity and Innovation: Neurocognitive Aspects Within a Work‐Psychological Perspective
Authors: Schweizer Tanja Sophie
Published: April 2006

Curiosity is, in great and generous minds, the first passion and the last.

Samuel Johnson, 1751

Why are some people constantly on the move towards something new, while others feel comfortable with what there is? What motivates us to seek for the new? What helps us in finding it? What leads us to transform what we find into a product that is visible to others and expose us to their judgement? Research in psychology holds fascinating insights concerning the above questions. Surprisingly, neurocognitive and neuropsychological insights that could lead to a better understanding of the processes of novelty‐seeking and novelty‐finding, have received little attention in the creativity and innovation literature. Especially for those working in professions where the generation of the new is the core business, it would be highly relevant to know more about those biological parameters of novelty generation and especially how they make human beings behave in professional environments. Such knowledge can not only improve human resource management in creative work settings, but also help creative professionals to better understand and manage themselves. The Novelty Generation Model (NGM) introduced in this article offers a new perspective.
Identity Sniping: Innovation, Imagination and the Body
Authors: Sørensen Bent Meier
Published: April 2006

I have asked myself often enough whether, on a grand scale, philosophy has been no more than an interpretation of the body and a misunderstanding of the body.

The Gay Science, Friedrich Nietzsche

Two routes to the creation of the new dominate the current literature on innovation: one is guided by fantasy, brainstorms and free interaction, the other one is focused on knowledge‐sharing technologies and the implementation of new organizational forms. Eventually, however, this article rejects both routes, further arguing that innovation is a matter of details and the work invested in creating such details. The body plays a crucial role here, and a case from weapon design innovation exemplifies this insight: that the creation of new knowledge always happens through a crisis in which the body trembles. This crisis is called an event where new and unforeseen connections between the individual and the organization becomes possible.
Gynaecological oncology: Investigating postmenopausal bleeding for endometrial cancer: cost‐effectiveness of initial diagnostic strategies
Authors: Clark TJ , Barton PM , Coomarasamy A , Gupta JK , Khan KS
Published: April 2006

Objective To determine the most cost‐effective outpatient testing strategy for diagnosing endometrial cancer in women with postmenopausal bleeding (PMB).

Design Decision analysis modelling.

Population Women with postmenopausal bleeding.

Methods A decision analytic model was constructed to reflect current service provision, which evaluated 12 diagnostic strategies using endometrial biopsy (EB), ultrasonography (USS) (4‐ and 5‐mm endometrial thickness cutoff) and hysteroscopy. Diagnostic probability estimates were derived from systematic quantitative reviews, clinical outcomes from published literature and cost estimates from local and NHS sources.

Main outcome measures The cost per additional life year gained (£/LYG) was determined and compared for each diagnostic strategy, and sensitivity analyses were performed.

Results Compared with carrying out no initial investigation, a strategy based on initial diagnosis with USS using a 5‐mm cutoff was the least expensive (£11 470/LYG). Initial investigation with EB or USS using a 4‐mm cutoff was comparably cost‐effective (less than £30 000/LYG versus USS with a 5‐mm cutoff) at their most favourable diagnostic performance and at disease prevalence of 10% or more. The strategies involving initial evaluation with test combinations or hysteroscopy alone were not cost‐effective.

Conclusions Women presenting for the first time with PMB should undergo initial evaluation with USS or EB.
General gynaecology: Association of phthalate esters with endometriosis in Indian women
Authors: Reddy BS , Rozati R , Reddy BVR , Raman NVVSS
Published: April 2006

Objective  To evaluate the possible association between phthalate esters (PEs) and the occurrence of endometriosis.

Design  Case–control study.

Setting  Department of Reproductive Medicine, Bhagawan Mahavir Medical Research Centre, Maternal Health and Reproductive Institute and Department of Analytical R&D, Hetero Research Foundation, Hyderabad, Andhra Pradesh, India.

Sample  Blood samples were collected from 49 infertile women with endometriosis (study group); 38 age‐matched women without endometriosis (control group I) but with infertility related to tubal defects, fibroids, polycystic ovaries, idiopathic infertility and pelvic inflammatory diseases diagnosed by laparoscopy and a further group of 21 age‐matched women (control group II) with proven fertility and no evidence of endometriosis and other gynaecological disorders during laparoscopic sterilisation.

Methods  Concentrations of PEs were measured using gas chromatography.

Main outcome measures  Evaluation of PEs concentrations in women with endometriosis compared with women free from the disease.

Results  Women with endometriosis showed significantly higher concentrations of di‐n‐butyl phthalate (DnBP), butyl benzyl phthalate (BBP), di‐n‐octyl phthalate (DnOP) and diethyl hexyl phthalate (DEHP) (mean 0.44 [SD 0.41]; 0.66 [SD 0.61]; 3.32 [SD 2.17]; 2.44 [SD 2.17] micrograms/ml) compared with control group I (mean 0.08 [SD 0.14]; 0.12 [SD 0.20]; 0; 0.50 [SD 0.80] micrograms/ml) and control group II (mean 0.15 [SD 0.21]; 0.11 [SD 0.22]; 0; 0.45 [SD 0.68] micrograms/ml). The correlation between the concentrations of PEs and different severity of endometriosis was strong and statistically significant at P < 0.05 for all four compounds (DnBP: r=+0.73, P < 0.0001; BBP: r=+0.78, P < 0.0001; DnOP: r=+0.57, P < 0.0001 and DEHP: r=+0.44, P < 0.0014).

Conclusions  This study suggests that PEs may have an aetiological association with endometriosis.
Population Growth, Human Development, and Deforestation in Biodiversity Hotspots
Authors: JHA S. , BAWA K. S.
Published: April 2006

Abstract: Human population and development activities affect the rate of deforestation in biodiversity hotspots. We quantified the effect of human population growth and development on rates of deforestation and analyzed the relationship between these causal factors in the 1980s and 1990s. We compared the averages of population growth, human development index (HDI, which measures income, health, and education), and deforestation rate and computed correlations among these variables for countries that contain biodiversity hotspots. When population growth was high and HDI was low there was a high rate of deforestation, but when HDI was high, rate of deforestation was low, despite high population growth. The correlation among variables was significant for the 1990s but not for the 1980s. The relationship between population growth and HDI had a regional pattern that reflected the historical process of development. Based on the changes in HDI and deforestation rate over time, we identified two drivers of deforestation: policy choice and human‐development constraints. Policy choices that disregard conservation may cause the loss of forests even in countries that are relatively developed. Lack of development in other countries, on the other hand, may increase the pressure on forests to meet the basic needs of the human population. Deforestation resulting from policy choices may be easier to fix than deforestation arising from human development constraints. To prevent deforestation in the countries that have such constraints, transfer of material and intellectual resources from developed countries may be needed. Popular interest in sustainable development in developed countries can facilitate the transfer of these resources.
Shifts in a Pacific Ocean Fish Assemblage: the Potential Influence of Exploitation
Authors: LEVIN PHILLIP S. , HOLMES ELIZABETH E. , PINER KEVIN R. , HARVEY CHRIS J.
Published: April 2006

Abstract:  As in many regions of the world, marine fishes and invertebrates along the Pacific coast of the United States have long been subjected to overexploitation. Despite this history, however, we lack basic information on the current status of many fishes along this coastline. We used data from a quarter century of fishery‐independent, coast‐wide trawl surveys to study systematically the demersal fish assemblages along the U.S. Pacific coast. We documented fundamental shifts in this fish assemblage. Average fish size, across a diversity of species, has declined 45% in 21 years. There have been major shifts in the constituent species of the assemblage, with some species achieving annual population growth rates of >10% and others declining in excess of 10% per year. Annual rate of change in population size appeared to be a function of life history interacting with fishing pressure. Negative trends in population size were particularly apparent in rockfish (Sebastes spp.). However, across all taxa examined, trends in population size were associated with size of maturity, maximum size, and growth rate. Trends in population size were associated inversely with harvest levels, but stocks that mature late tended to decline faster than would be predicted by catch rates alone. Our results are disquieting because they raise the possibility that fishing‐induced phase shifts in fish communities may affect the recovery of fishes, even after the implementation of severe fishing restrictions.
The Questionable Effectiveness of Science Spending by International Conservation Organizations in the Tropics
Authors: CLEARY DAVID
Published: April 2006

Abstract:  The general context of conservation in the tropics—in the Amazon basin and elsewhere—is stagnant or declining funding and rapidly growing threat levels. For conservation programs this makes strategic deployment of limited conservation resources all the more important. International conservation organizations active in the tropics increasingly define themselves as science driven and expend considerable resources on science‐based activities such as ecoregional analysis, field research, and monitoring of ecological variables. I argue that an overemphasis on science has generated a series of unintended but serious problems for conservation in the tropics. Spending on monitoring and ecoregional analysis has effectively starved protection and threat analysis of resources. A decoupling of biology from serious cost‐benefit analysis has led to the privileging of small‐scale and local analyses, rather than the systemic analyses essential for the strategic allocation of scarce conservation resources. Successful conservation in the tropics depends on the crossing of biogeography with sophisticated threat analysis to identify priority geographies for protection. This should be combined with much more systematic engagement with the principal drivers of tropical deforestation, especially agribusiness. Caution and a sense of proportion are required when balancing the financial demands of science and those of protection. I suggest that conservation organizations should cooperate far more in assembling and analyzing information on conservation spending and on threat levels and biogeography at the continental, national, and regional levels. Site selection should follow rather than precede this kind of strategic analysis, and sites should be considered elements of a network rather than stand‐alone projects. More attention should be paid to market‐driven conservation through techniques such as certification and responsible supply‐chain management.
Assessment of the Sustainability of Bushmeat Hunting Based on Dynamic Bioeconomic Models
Authors: LING S. , MILNER‐GULLAND E.J.
Published: April 2006

Abstract:  Open‐access hunting is a dynamic system in which individual hunters respond to changes in system variables such as costs of hunting and prices obtained for their catch. Sustainability indices used by conservationists ignore these human processes and focus only on the biological sustainability of current offtake levels. This focus implicitly assumes that offtake is constant, says little about the actual sustainability of the system, and fails to provide any basis for predicting the impact of most feasible management interventions. A bioeconomic approach overcomes these limitations by explicitly integrating both the biological and human components of the system. We present a graphical representation of a simple bioeconomic model of bushmeat hunting and use it to demonstrate the importance of considering system dynamics when assessing sustainability. Our results show that commonly used static sustainability indices are often misleading. The best method to assess hunting sustainability is situation dependent, but characterizing supply and demand curves, even crudely, has greater potential than current approaches to provide robust predictions in the medium term.
Limited Literacy in Older People and Disparities in Health and Healthcare Access
Authors: Sudore Rebecca L. , Mehta Kala M. , Simonsick Eleanor M. , Harris Tamara B. , Newman Anne B. , Satterfield Suzanne , Rosano Caterina , Rooks Ronica N. , Rubin Susan M. , Ayonayon Hilsa N. , Yaffe Kristine ,   for the Health, Aging and Body Composition Study
Published: April 2006

OBJECTIVES: To determine the relationship between health literacy, demographics, and access to health care.

DESIGN: Cross‐sectional study, Health, Aging and Body Composition data (1999/2000).

SETTING: Memphis, Tennessee, and Pittsburgh, Pennsylvania.

PARTICIPANTS: Two thousand five hundred twelve black and white community‐dwelling older people who were well functioning at baseline (without functional difficulties or dementia).

MEASUREMENTS: Participants' health literacy was assessed using the Rapid Estimate of Adult Literacy in Medicine. Scores were categorized into 0 to sixth‐, seventh‐ to eighth‐, and ninth‐grade and higher reading levels (limited health literacy defined as <9th grade). Participants' demographics, socioeconomic status, comorbidities, and three indicators of healthcare access (whether they had a doctor/regular place of medical care, an influenza vaccination within the year, or insurance for medications) were also assessed.

RESULTS: Participants' mean age was 75.6, 52% were female, 38% were black, and 24% had limited health literacy. After adjusting for sociodemographics, associations remained between limited health literacy and being male, being black, and having low income and education, diabetes mellitus, depressive symptoms, and fair/poor self‐rated health (P<.02). After adjusting for sociodemographics, health status, and comorbidities, older people with a sixth‐grade reading level or lower were twice as likely to have any of the three indicators of poor healthcare access (odds ratio=1.96, 95% confidence interval=1.34–2.88).

CONCLUSION: Limited health literacy was prevalent and was associated with low socioeconomic status, comorbidities, and poor access to health care, suggesting that it may be an independent risk factor for health disparities in older people.
Entrepreneurial Studies: The Dynamic Research Front of a Developing Social Science
Authors: Cornelius Barbara , Landström Hans , Persson Olle
Published: April 2006

Entrepreneurship research has been built upon a historical foundation grounded in economic change. To understand the development of the field, it is useful to understand the motivations and interests of key scholars and to trace the linkages between these scholars and other authors, from the transient to the contributor. This has been done through a bibliometric analysis of research articles cited between 1982 and 2004.

Entrepreneurship has developed from a subdiscipline of management studies reliant on alien terms and cognitive methods toward a separate field with increasing complexities of its own. While not fully mature, entrepreneurship shows all the signs of a maturing field from its increasingly internal orientation and the establishment of key areas of research through to an enhanced, discipline–specific, theoretical approach with a professional language of its own.
The Social and Collaborative Nature of Entrepreneurship Scholarship: A Co–Citation and Perceptual Analysis
Authors: Reader Diana , Watkins David
Published: April 2006

This article explores the structure of the “metafield” of entrepreneurship in two related ways. First, author co–citation analysis establishes a collective view of the structure of the entrepreneurship literature as perceived by its research–active members. The co–citation frequencies of 78 prominent entrepreneurship researchers were analyzed using multivariate techniques. Cluster analysis and multidimensional scaling were used to explore the intellectual structure of entrepreneurship research by identifying groups of scholars whose work falls into similar areas. Factor analysis was then used to identify the underlying themes that characterize and define the field. Finally, the scholars within these nominal groupings were approached using individualized questionnaires to explore what social interactions might parallel, reflect, or underpin the intellectual ones. The study has given empirical support to a number of oft–quoted beliefs about entrepreneurship as a field of study, such as: (1) the occurrence of fragmentation from an early stage in its development; (2) that the difficulty of categorizing subfields unambiguously mirrors that in the metafield itself; (3) that there is a relative paucity of scholarship cited across—as opposed to within—these subfields; and (4) that there is evolution within the meta–field of national differences in the topics studied and citation patterns thereto. In addition, the study demonstrates that there are real and robust social and collaborative networks underlying the generation of the work which is cited jointly by third parties. The latter authors may be unaware of these networks. Equally, the co–cited authors, while recognizing overlapping interests, may have difficulty in categorizing this commonality in their contributions. Entrepreneurship research is shown to be very much a social activity, although this may be invisible to outsiders or novitiates.
Tumour regression and mesorectal lymph node changes after intensified neoadjuvant chemoradiation for carcinoma of the rectum
Authors: PRALL FRIEDRICH , WÖHLKE MICHAEL , KLAUTKE GUNTHER , SCHIFFMANN LEIF , FIETKAU RAINER , BARTEN MALTE
Published: April 2006

Neoadjuvant radiation or chemoradiation is currently the treatment of choice for patients with locally advanced carcinoma of the rectum. To assess the effects of chemoradiation on tumour regression and on uninvolved mesorectal lymph nodes, a consecutive series of 76 patients receiving neoadjuvant chemoradiation and a stage‐adapted control series of 57 patients without pretreatment were studied. Densities of cells positive for CD4 (T‐helper cells), CD8 (cytotoxic T‐cells), CD83 (mature dendritic cells), and CD57 (natural killer cells) were determined on immunostains. Tumour regression was graded, and presence or absence of extramural tumour was recorded. The densities of CD4+ T‐lymphocytes and CD83+ dendritic cells in the paracortex of mesorectal lymph nodes were observed to be significantly reduced, as were the densities of CD57+ cells in the follicles; densities of CD8+ T‐lymphocytes did not differ. Strong, moderate and poor tumour regression was observed in 29, 25, and 22 cases, respectively. For 12 patients, absence of extramural vital or regressing tumour was recorded, indicating pretherapeutic overstaging. The results bring to mind that neoadjuvant chemoradiation as a side effect may have a negative impact on anti‐tumour immunity. Together with the drawback of overstaging the results argue for a careful selection of patients.
Tyrosine kinase inhibitors alter adhesivity of prostatic cancer cells to extracellular matrix components
Authors: SKOGSETH HAAKON , HOLT RANDI UTNE , LARSSON ERIK , HALGUNSET JOSTEIN
Published: April 2006

Tyrosine kinase inhibitors (TKIs) are thought to have potential as a new generation of anti‐cancer drugs. Since invasiveness, the main characteristic of malignant behaviour, is believed to depend on altered cell‐matrix interactions, we investigated the effect of two potent TKIs, genistein and tyrphostin AG‐1478, on the interaction of prostate cancer cells with extracellular matrix components. PC‐3 and DU‐145 cells were treated with various concentrations of genistein and tyrphostin AG‐1478. Adhesion to extracellular matrix was assayed using fluorescence‐labelled cells seeded on collagen type I, collagen type IV, fibronectin, laminin and vitronectin. The expression levels of integrin β1, α2, α3 and α5 subunits were measured using flow cytometry of cells labelled with monoclonal murine antibodies. Genistein treatment reduced the ability of both cell lines to adhere to the matrix proteins tested. This effect was more pronounced for PC‐3 cells than for DU‐145 cells. Genistein treatment decreased the expression of β1 integrins by 40% in PC‐3 cells and 22% in DU‐145. AG‐1478 treatment slightly reduced the ability of DU‐145 cells to adhere, but did not decrease PC‐3 cell adhesion. Nevertheless, expression levels were reduced for most integrins tested, except the expression of α‐5, for which no significant effect was measured. Our results point to a possible role of TKIs as suppressors of prostate carcinoma cell adhesion to extracellular matrix components, by acting as inhibitors of integrin expression.
Morphological and Functional Aspects of the Senile Larynx
Authors: Pontes Paulo , Yamasaki Rosiane , Behlau Mara
Published: April 2006

Objective: To analyze the senile larynx, considering morphological aspects during respiration and functional aspects during phonation, comparing it to the young adult larynx. Patients and Methods: A retrospective study was conducted of 100 laryngeal images of adults without vocal complaints, 50 laryngeal images of young adults aged 20–45 years and 50 laryngeal images of elderly individuals aged 65–85 years, of both genders. Images were produced by means of a rigid endoscope and stroboscopy. The morphological aspects analyzed were: laryngeal symmetry, vocal fold bowing, prominence of the vocal process and glottic proportion. The functional aspects analyzed were glottic closure, laryngeal vestibule behavior, phase (timing of closure) and amplitude symmetry of mucosal wave and tremor of laryngeal structures. Results: Significant differences between the young adult larynx and the geriatric larynx were found for the following parameters: vocal fold bowing, prominence of the vocal process, glottic proportion, phase and amplitude symmetry of mucosal wave and tremor of laryngeal structures. Conclusion: The data suggests that the geriatric larynx differs from the young adult larynx in many characteristic aspects.
Bisoprolol Improves Echocardiographic Parameters of Left Ventricular Diastolic Function in Patients with Systemic Hypertension
Authors: Ilgenli T. Fikret , Kilicaslan Fethi , Kirilmaz Ata , Uzun Mehmet
Published: April 2006

Left ventricular (LV) diastolic dysfunction (LVD) is a common complication secondary to hypertension. It has been reported that bisoprolol is effective in reducing blood pressure and has beneficial cardiac effects in patients with hypertension. However, its effect on LV diastolic function has not been studied in detail. In this study, we sought to determine bisoprolol’s effect on left ventricle diastolic function. Data from 25 patients were statistically analyzed. Peaks E and A wave, E/A ratio, isovolumetric relaxation time and E wave deceleration time were measured echocardiographically. Doppler echocardiography measurements after bisoprolol treatment revealed an improvement in LV diastolic function. In conclusion, our results show that treatment with bisoprolol, improves echocardiographic parameters of LV diastolic function after 3 months of treatment.
Unusual Appearance of Mitral Annular Calcification Mimicking Intracardiac Tumor Prompting Early Surgery
Authors: Kato Mahoto , Nakatani Satoshi , Okazaki Hidetoshi , Tagusari Osamu , Kitakaze Masafumi
Published: April 2006

Although mitral annular calcification (MAC) is usually easy to diagnose by transthoracic echocardiography, we experienced a rare case with MAC which looked like an intracardiac tumor. The patient who had been on chronic hemodialysis for 20 years was admitted to our hospital because of dyspnea. Transthoracic echocardiography showed a mass with severe calcification on the anterior mitral annulus and mean mitral gradient of 20 mm Hg. Because of the suspicion of the intracardiac calcified tumor that restricted mitral valve motion causing mitral obstruction, she underwent resection of the mass and mitral valve replacement. Pathological findings showed that the mass had a calcified envelope containing liquefied necrotic eosinophilic material with lympocytic infiltrate inside consistent with MAC. We should consider a possibility of MAC when we see a severe calcified mass attached to the mitral annulus in a patient on long-term hemodialysis.
Two Novel PHEX Mutations in Taiwanese Patients with X-Linked Hypophosphatemic Rickets
Authors: Lo Fu-Sung , Kuo Min-Tzu , Wang Chao-Jan , Chang Chia-Hsieh , Lee Zhon-Liau , Van Yang-Hau
Published: April 2006

Backgrounds: X-linked hypophosphatemic rickets (XLH) is an X-linked dominant disease characterized by renal phosphate wasting, hypophosphatemia, aberrant vitamin D metabolism, and defective bone mineralization. The disease is caused by mutations in the PHEX gene (phosphate-regulating gene with homologies to endopeptidases on the X-chromosome) located at Xp22.1. To date, a variety of PHEX mutations have been identified in these patients. Methods: PCR and direct sequencing was performed for all exons and intron-exon boundaries of the PHEX gene in two XLH families. Results: Two novel mutations, including a missense mutation (L206W) in exon 5 and a frameshift mutation (nucleotide 1826_1830delAAAAG, stop after codon 610) in exon 18 were discovered and the laboratory and radiographic findings for these patients analyzed. Conclusions: We found that PHEX gene mutations were responsible for XLH in these Taiwanese patients. Additional studies are needed to enhance understanding of the role of PHEX in XLH pathogenesis.
Comparison of Clinical Characteristics and Outcomes of Patients with COPD Exacerbation with or without Venous Thromboembolism
Authors: Akgun Metin , Meral Mehmet , Onbas Omer , Araz Omer , Koplay Mustafa , Aslan Sahin , Mirici Arzu
Published: April 2006

Background: Although some studies evaluated venous thromboembolism (VTE) prevalence in patients with chronic obstructive pulmonary disease (COPD), they contain no detailed description of the patients’ characteristics. Objectives: It was the aim of this study to investigate the frequency and clinical characteristics and outcomes of VTE in patients with COPD exacerbation. Methods: Between October 2004 and February 2005, 120 consecutive patients were included in the study. On admission, Doppler examination of lower extremities in all cases and spiral computed tomography of the thorax in cases with a suspicion of pulmonary thromboembolism were performed. A questionnaire was used to take a detailed history. In addition to routine laboratory tests, chest X-ray, postbronchodilator spirometry, arterial blood gas analysis and serum levels of D-dimer and C-reactive protein were evaluated, as well as dyspnea score and performance status before exacerbation. The hospitalization durations and mechanical ventilation requirements were also recorded. Results: VTE was determined in 16 cases (13.3%). In patients with VTE, the travel history was higher (p < 0.001), the dyspnea score worse (p = 0.005), the duration of hospitalization longer (p < 0.001) and the mechanical ventilation requirement increased (p < 0.001); a change in mental status was highly associated with the presence of VTE (p < 0.001). Conclusions: It seems that VTE occurrence was higher in the presence of a risk factor causing immobility such as travel history and increased dyspnea. The cases with severe disease are more likely to have VTE. Preventive measures may be considered in such patients because their hospitalization stay and mechanical ventilation requirement are increased.
Repeated Pulmonary Rehabilitation in Severe and Disabled COPD Patients
Authors: Romagnoli Micaela , Dell’Orso Daniela , Lorenzi Cristina , Crisafulli Ernesto , Costi Stefania , Lugli Daniela , Clini Enrico M.
Published: April 2006

Background: The optimal frequency of delivering a pulmonary rehabilitation program (PR) is not yet a well established issue. It is still unclear whether repeated PR at established intervals will result in effective maintenance or further improvement in the patient’s health status. Objectives: To investigate whether more frequently repeated PR in patients with COPD (1) leads to similar short and long-term physiological gains, and (2) decreases the burden due to hospitalization. Methods: Thirty-five disabled COPD patients (FEV1 below 50% predicted, MRC score 3) in a stable state were studied in a randomized controlled trial. After completing an initial inpatient PR program, they were randomly assigned to either group 1 (performing a second and a third PR after 6 and 12 months) or group 2 (performing only a second PR after 12 months). Results: Lung functions, exercise capacity (by means of a timed walk test – 6MWT), peak-effort dyspnea (D) and leg fatigue (F), and health-related quality of life by means of SGRQ were assessed prior to (T1, T3, T5) and after (T2, T4, T6) each PR program: the same measures were taken on an outpatient basis at T3 in group 2. The number of hospital admissions (HA) and days spent in the hospital (DH) were also recorded over the year. The two groups did not differ in any parameter at baseline. 6MWD, D, F and SGRQ improved to the same level (p = 0.05) after each PR in both groups. However, the baseline level of D, F and SGRQ symptoms and impact scores progressively improved over time in group 1 but not in group 2. After 12 months, a larger amount of patients in Group 1, as compared to Group 2, reported H10 DH/year (p < 0.0001). Conclusions: In severe and disabled COPD, a more frequently repeated inpatient PR may lead to some additional physiological and clinical benefits over 1 year.
Macrophage Metalloelastase Accelerates the Progression of Atherosclerosis in Transgenic Rabbits
Authors: Liang Jingyan , Liu Enqi , Yu Ying , Kitajima Shuji , Koike Tomonari , Jin Yingji , Morimoto Masatoshi , Hatakeyama Kinta , Asada Yujiro , Watanabe Teruo , Sasaguri Yasuyuki , Watanabe Shigeyuki , Fan Jianglin
Published: April 2006

Background—

Macrophage metalloelastase (matrix metalloproteinase [MMP]-12) is upregulated in atherosclerotic lesions and aneurysm; thus, increased MMP-12 activity may play an important role in the pathogenesis of atherosclerosis. However, the pathological roles of MMP-12 in the initiation and progression of atherosclerosis have not been defined.

Methods and Results—

We compared the susceptibility of MMP-12 transgenic (Tg) rabbits to cholesterol-rich diet–induced atherosclerosis with that of non-Tg littermate rabbits. The rabbits were maintained at either relatively lower levels of hypercholesterolemia for shorter periods or higher levels of hypercholesterolemia for longer periods through a diet containing different amounts of cholesterol. We found no significant difference in the aortic atherosclerotic lesion size or quality between Tg and non-Tg rabbits at lower hypercholesterolemia. At higher hypercholesterolemia for longer periods, however, Tg rabbits developed more extensive atherosclerosis in the aortas and coronary arteries than did non-Tg rabbits. Histological examinations revealed that atherosclerotic lesions of Tg rabbits contained prominent macrophage infiltration associated with marked disruption of the elastic lamina in the tunica media with occasional formation of aneurysm-like lesions. Furthermore, increased expression of MMP-12 derived from macrophages was associated with elevated expression of MMP-3, suggesting that MMP-12 may play a pivotal role in the cascade activation of other MMPs, thereby exacerbating extracellular matrix degradation during the progression of atherosclerosis.

Conclusions—

Overexpression of MMP-12 causes accelerated atherosclerosis in Tg rabbits. These results suggest that macrophage-derived MMP-12 participates in the progression of atherosclerosis.
High-Resolution In Situ Profiling through the Stable Boundary Layer: Examination of the SBL Top in Terms of Minimum Shear, Maximum Stratification, and Turbulence Decrease
Authors: Balsley B. B. , Frehlich R. G. , Jensen M. L. , Meillier Y.
Published: April 2006

Some 50 separate high-resolution profiles of small-scale turbulence defined by the energy dissipation rate (ɛ), horizontal wind speed, and temperature from near the surface, through the nighttime stable boundary layer (SBL), and well into the residual layer are used to compare the various definitions of SBL height during nighttime stable conditions. These profiles were obtained during postmidnight periods on three separate nights using the Tethered Lifting System (TLS) during the Cooperative Atmosphere–Surface Exchange Study (CASES-99) campaign in east-central Kansas, October 1999. Although the number of profiles is insufficient to make any definitive conclusions, the results suggest that, under most conditions, the boundary layer top can be reasonably estimated in terms of a very significant decrease in the energy dissipation rate (i.e., the mixing height) with height. In the majority of instances this height lies slightly below the height of a pronounced minimum in wind shear and slightly above a maximum in N 2, where N is the Brunt–Väisälä frequency. When combined with flux measurements and vertical velocity variance data obtained from the nearby 55-m tower, the results provide additional insights into SBL processes, even when the boundary layer, by any definition, extends to heights well above the top of the tower. Both the TLS profiles and tower data are then used for preliminary high-resolution studies into various categories of SBL structure, including the so-called upside-down boundary layer.
Improving Parameterization of Rain Microphysics with Disdrometer and Radar Observations
Authors: Zhang Guifu , Sun Juanzhen , Brandes Edward A.
Published: April 2006

Disdrometer observations indicate that the raindrop size distribution (DSD) can be represented by a constrained-gamma (CG) distribution model. The model is used to retrieve DSDs from polarization radar measurements of reflectivity and differential reflectivity and to characterize rain microphysics and physical processes such as evaporation, accretion, and precipitation. The CG model parameterization is simplified to a single parameter for application in single-moment numerical models. This simplified parameterization is applied in the Variational Doppler Radar Analysis System (VDRAS) using Kessler-type parameterizations for model initialization and forecasting. Results are compared to those for the Marshall–Palmer (MP) DSD model. It is found that the simplified CG model parameterization better preserves the stratiform rain and produces better forecasts than the MP model parameterization.
On the Effective Solar Pathlength
Authors: Li J. , Shibata Kiyotaka
Published: April 2006

The effects of atmospheric spherical curvature and refraction and their impact on radiative transfer have been studied. It is shown that formulas employed in GCMs for atmospheric curvature and refraction underestimate the effect of effective solar pathlength. A new parameterization is therefore proposed. It is emphasized that the atmospheric curvature effect on radiative transfer is a localized problem with height dependence. A method corresponding to the local effective pathlength factor is proposed. This rigorous scheme enables variations in both the pathlength and the gaseous amount along a solar direct beam to be accurately evaluated in the radiative transfer process. The results of the rigorous scheme can be used as the benchmark to the proposed parameterizations for the effective pathlength factor. It is found that the new parameterization proposed in this note has better results in flux and heating rates when compared to other parameterizations.