bluuebunny/crossref_metadata_2025 huggingface dataset:
Angiotensin II Infusion Alters Vascular Function in Mouse Resistance Vessels: Roles of O–·2 and Endothelium
Authors: Wang Dan , Chabrashvili Tina , Borrego Lillian , Aslam Shakil , Umans Jason G.
Published: December 2005

We hypothesized that prolonged angiotensin II (AngII) infusion would alter vascular reactivity by enhancing superoxide anion (O–·2) generation. Male C57BL/6 mice were infused with AngII at 400 ng/kg/min (n = 16, AngII mice) or vehicle (n = 16, sham mice) for 2 weeks via subcutaneous osmotic minipumps. Contraction and relaxation of mesenteric resistance vessels (MRVs) were assessed using a Mulvany-Halpern myograph. AngII infusion increased systolic blood pressure, MRV NADPH oxidase activity and expression of p22phox mRNA. Contraction to norepinephrine was unchanged, but AngII infusion increased contractile responses to AngII (41 ± 5 vs. 10 ± 4%, p < 0.001) and endothelin-1 (ET-1; 95 ± 10 vs. 70 ± 9%, p < 0.05), which was normalized by tempol (10–4 M, a stable membrane-permeable superoxide dismutase mimetic) and ebselen [10–5 M, a peroxynitrite (ONOO–) scavenger]. Endothelium removal enhanced MRV contraction to AngII and ET-1 in sham mice but blunted these contractile responses in AngII mice. Relaxation to ACh was impaired in AngII mice (60.1 ± 8.8 vs. 83.2 ± 3.5%, p < 0.01), which normalized by tempol, whereas relaxation to sodium nitroprusside was similar in both groups. N-nitro-L-arginine (NNLA, a nitric oxide synthase inhibitor), partially inhibited acetylcholine relaxation of vessels from sham mice but not from AngII mice. The residual endothelium-dependent hyperpolarizing-factor-like relaxation was not different between groups. In conclusion,the AngII slow pressor response in mouse MRVs consisted of specific contractile hyperresponsiveness and impairment in the NO-mediated component of endothelium-dependent relaxation, which was mediated by O–·2 and ONOO– in the vascular smooth muscle cell.
Malignant Hypertension in Patients with Idiopathic IgA Nephropathy
Authors: Chen Yu , Tang Zheng , Yang Guang , Shen Shuqiong , Yu Yusheng , Zeng Caihong , Chen Huiping , Liu Zhi-hong , Li Lei-shi
Published: December 2005

Background: Idiopathic IgA nephropathy is one of the main causes of secondary malignant hypertension, especially in Chinese population. But little information has been available about malignant hypertension secondary to IgA nephropathy (IgANMHT). The purpose of this study is to evaluate the clinico-pathological features and outcomes of IgANMHT patients. Methods: A case control retrospective study was carried out in 45 cases of IgANMHT and 26 cases of primary malignant hypertension (PMHT) diagnosed by renal biopsy. Their clinical features and pathological findings were investigated. Their average follow-up time was 37.4 months. Univariate analysis and multivariate Cox regression analysis were performed to select variables to predict renal survival. Results: In the study, 1.2% of all the IgA nephropathy patients presented malignant hypertension. The amounts of urine protein excretion and red blood cells in IgANMHT patients were significantly higher, while the levels of serum creatinine were significantly lower than those in PMHT patients. The glomerular injury in IgANMHT patients was more severe than that in PMHT patients. The two characteristic vascular lesions of primary malignant hypertension, proliferative endoarteritis and fibrinoid necrosis were also found in IgANMHT patients but with less severity. Renal survival of IgANMHT patients was significantly higher than that of PMHT patients (p = 0.0043). However, log-rank test showed no significant difference in the renal survival between IgANMHT and PMHT patients with similar SCr levels at admission. Multivariate Cox regression analysis revealed that a high amount of urine protein excretion(≧1.5 g/24 h), mesangial proliferation and elevated serum creatinine (≧2 mg/dl) were statistically independent risk factors for renal prognosis (RR = 1.90, 2.72, 2.84, respectively). Conversely, strict blood pressure control had a favorable effect on renal prognosis. Conclusion: The clinico-pathological features and outcomes of IgANMHT patients were different from those of PMHT patients. The renal survival of IgANMHT patients was poor, which was determined by many factors. Early control of proteinuria, early monitoring and strictly controlling blood pressure may contribute to the renal survival.
Initial Symptoms in Frontotemporal Dementia and Semantic Dementia Compared with Alzheimer’s Disease
Authors: Shinagawa Shunichiro , Ikeda Manabu , Fukuhara Ryuji , Tanabe Hirotaka
Published: December 2005

Background: Despite many reports about cognitive decline and behavioral changes in patients with frontotemporal lobar degeneration (FTLD), there have been very few systematic studies of initial symptoms of frontotemporal dementia (FTD) and semantic dementia (SD). Objective: It was the aim of this study to investigate FTD and SD and to establish whether they are characterized by different initial symptoms. Methods: Three groups of patients were studied: FTD (n = 36), SD (n = 17) and age-matched Alzheimer’s disease (AD) patients (n = 52). Information on initial symptoms was obtained from caregivers. Symptoms were classified into 22 distinct categories from the following domains, based on previous studies of symptoms of FTLD: (1) change in social behavior, affection, and daily activities, (2) cognitive decline, (3) language impairments, and (4) other abnormal symptoms. Results: Change in social behavior, affection, and daily activities was significantly more common in patients with FTD; on the other hand, language impairments were significantly more common in patients with SD as initial symptoms. Apathy and stereotypic behaviors were the most common initial symptoms among patients with FTD, while anomia, paraphasia, and impairment in word comprehension were the most common initial symptoms among patients with SD. Memory disturbance was the most common initial symptom among patients with AD. Conclusions: Behavioral and psychiatric symptoms are predominant initial symptoms in FTD, while language symptoms are predominant initial symptoms in SD. In addition to the assessment of current symptoms, the assessment of initial symptoms is useful for differential diagnosis in patients with FTD, SD and AD.
Does Cold Environment Affect Streptococcus pneumoniae Adherence to Rat Buccal Epithelium?
Authors: Öztuna Funda , Özlü Tevfik , Bülbül Yılmaz , Buruk Kurtuluş , Topbaş Murat
Published: December 2005

Background: Colonization ofthe nasopharyngeal flora by Streptococcus pneumoniae increases in winter. However, in vitro studies suggest that bacterial adherence decreases in low temperatures. These contras may be related to the difference between in vitro and physiological conditions. Objectives: We investigated whether pneumococcal adherence to buccal epithelial cells of rats increases in cold temperature. Methods:The adherence of S. pneumonia (ATCC 49619) was studied in six groups of rats. Basal pneumococcal adherence was checked after 1 h both at room temperature and in a cold environment (at 10°C) for the evaluation of changes in basal flora in the first two groups (basal control). In the remaining four groups, the effect of cold treatment before or after inoculation of S. pneumoniae, or cold treatment during the whole study period was investigated. Results: The adherence of inoculated pneumococci was found to be significantly decreased in rats exposed to cold air during the whole study period (group 3). However, the decrease was not significant in rats exposed to cold air after bacterial inoculation (group 6). In contrast, pneumococcal adherence was found to be significantly increased in rats staying at 24°C room temperature (control, group 5), during the whole pre- and postincubation period. A slight increase was also detected in rats pretreated in cold air and then kept at room temperature (group 4) (p > 0.05). Conclusion: In contrast to our expectations, pneumococcal adherence was found to be decreased in cold environment in vivo.
Genetics of Vascular Cognitive Impairment
Authors: Leblanc Gabrielle G. , Meschia James F. , Stuss Donald T. , Hachinski Vladimir
Published: December 2005

Background and Purpose—

This review considers the current state of knowledge of genetic factors underlying vascular cognitive impairment (VCI).

Summary of Review—

We argue here that genes conferring susceptibility to VCI must be of 2 nonmutually exclusive classes: (1) genes that confer susceptibility to cerebrovascular disease, and (2) genes that determine brain tissue responses to cerebrovascular disease (ie, render parenchymal tissue more or less susceptible to injury or able to repair itself after injury). Although some progress has been made in identifying genes of the first class, little has been done to explore genes of the second class. Evidence for the existence of such genes is presented. We discuss the advantages and disadvantages of different forms of cerebrovascular disease for studying these genes, and different study designs that might be used.

Conclusion—

The most critical challenge for genetic studies of VCI is to identify quantifiable phenotypes that can be reliably and effectively determined in large samples of subjects.
The Community of Europe and Globalization
Authors: Skrobacki Waldemar
Published: December 2005

The European Union is a creation of Europe's history and should be understood in that context. European integration is a multidimensional process, for it is an attempt to build a real community. It includes an ethical dimension that is based on the European welfare state and on the continent's long intellectual tradition of liberal democracy. It is successful precisely because it is not abstract.
Value-Added Assessment of Teacher Preparation
Authors: Noell George H. , Burns Jeanne L.
Published: December 2005

Broad-based empirical outcomes assessment is an increasingly evident part of governmental services and this trend is particularly apparent in education. The clearest manifestation of this trend in education has been the advent of high-stakes broad-based testing and accountability programs in K-12 education. Although this assessment regime has not yet been used to assess the efficacy of teacher preparation programs, the data management capacity and statistical technology is now emerging to make this possible. This article presents data from the 1st year of a pilot study examining the methodological and practical issues involved in implementing a value-added assessment of teacher preparation based on a massive multivariate longitudinal database. The pilot data are discussed in relation to the literature pertaining to value-added assessments in K-12 education. Selected research needs and practical concerns related to the use of value-added models for the assessment of teacher preparation are discussed.
Globalisation, theocracy and the new fascism: the US Right’s rise to power
Authors: Davidson Carl , Harris Jerry
Published: December 2005

The Christian Right is an increasingly powerful phenomenon in US politics. Extremely influential in the current administration, it has been building a mass base across the nation. This analysis of a movement that has been growing over the past four decades reveals the complex interrelationships between its different strands, their reach into the mass media, their war of attrition against socially liberal legislation and the opportunistic links with elements of the pro-Israel lobby. Also examined are the contradictions and potential contradictions within its different facets. Most alarming are those elements which revile, as anti-Christian, the very concept of a democratic society in their aim at overall ‘dominion’.
Making the Case for Narrative Methods in Cross-Cultural Organizational Research
Authors: Soin Kim , Scheytt Tobias
Published: December 2005

The prevailing literature on cross-cultural research in management studies has tended to conceptualize the meaning and the impact of culture on organizations by using distinct categories. This article argues that given the embedded nature of organizations, a narrative methodology offers an alternative and complementary approach to developing our understanding in cross-cultural research. Using examples of story-driven investigations into cultural differences, it explains the potential of this approach. It therefore seeks to offer a contribution to the variety of methods for organizational research on cross-cultural issues.
Truck Driver Hours of Service Regulations: The Collision of Policy and Public Health
Authors: Heaton Karen
Published: December 2005

This article examines the policies related to truck driver hours of service regulations that affect occupational and public health and safety. The interaction of the nature of truck driving, labor practices and deregulation of the trucking industry, and the evolution of the current regulations are presented. The work of advocacy coalitions and legal action related to this issue is described. Possible policy alternatives and recommendations are presented. The article supports the position that although federal government regulators attempt to promulgate regulations based on current circadian science, the regulations are ineffective as stand-alone measures. Labor policies and practices must foster a work environment that facilitates sleep and safe driving performance. Advocacy by nurses on this issue continue the rich tradition of public health nursing. Nurses may benefit from the study of truck driver hours of service regulation as recommendations limiting their own hours of service are being considered and legislated.
Performance Evaluation for Diversity Programs
Authors: Brown Debra J. , DeCorse-Johnson Anita L. , Irving-Ray Marcia , Wu Wende Waggoner
Published: December 2005

This policy paper addresses the problem of underrepresentation of minorities in the health care professions. Projections are that by 2050 minorities will represent 49% of the U.S. population. Several notable reports suggest that the health care of underrepresented minorities is improved when providers of similar ethnic and racial backgrounds provide the care. However, minority representation in the health care professions has not kept pace with the increase of minorities in the population. A variety of groups (federal, state, private, and health professional educational institutions) have provided billions of dollars toward increasing the number of underrepresented minority health care providers. However, the effectiveness of these programs is not readily evident. Therefore, we recommend comprehensive evaluations of programs funded to increase diversity in the health professions and the development of a Minority Health Care Professionals Center to assume accountability for monitoring programs that receive funding to increase the number of underrepresented minority health care providers.
Emergency Contraception for Sexual Assault Victims: An Advocacy Coalition Framework
Authors: Schorn Mavis N.
Published: December 2005

A bill was introduced into the Tennessee legislature in the 2005 session that would require emergency departments to offer and dispense emergency contraception to sexual assault survivors who are at risk of pregnancy. Several advocacy groups collaborated to form the Women’s Health Safety Network for the purpose of communicating as one voice. The advocacy coalition framework of policy development is applied to the political system and is used as a model to discuss issues impacting policy development for this particular bill. Key actors, proponents, and opponents to this bill are presented along with constraints to policy acceptance. The challenge for emergency contraception advocates on a state and national level is to keep the focus on public health science, the health and well-being of women, and out of the abortion debate.
Policy Predictors of Participation in Adult Tobacco Cessation Programs
Authors: Spurlock Amy Yoder
Published: December 2005

This article examines the effect of tobacco cessation treatment factors and environmental, structural, and client factors on participation in tobacco cessation programs among adults in a tobacco growing state. A pooled time series cross-sectional research design was used to analyze the primary and secondary data collected at the population level (N = 140 Health Department Service Areas; HDSA). Results indicated that for every cessation program added, there would be an increase in participation of 4 adults per 10,000 smokers, and for every $1.00 per capita spent on counteradvertising, there would be an increase in participation of 26 adults per 10,000 smokers. Local health departments need to initiate or increase counteradvertising, targeting younger adults and HDSAs with higher per capita tobacco production; enhance marketing efforts for cessation; and increase the number of cessation programs offered by HDSAs to as many as are feasible and affordable.
Francophobia, Anti-Americanism: Narratives of the Trans-Atlantic Other in French and U.S. News on Abortion-Related Issues
Authors: Husting Ginna , King Leslie
Published: December 2005

This article examines the interplay of abortion and nationalism in French and U.S. print news discussions of abortion-related issues. U.S. news stories on RU-486 and French news stories on prolife direct action protesters are rife with qualifiers designating each issue as a foreign one. In American media, RU-486 is the French pill; in French media, protesters are American inspired/mobilized. Together, these cases constitute a site for the recurrent construction of the relation between nationhood, national identity, and moral goodness. In each case, media narratives of abortion-related issues reveal that more is at stake than reproductive rights issues. The authors argue that discourses on abortion are grounded in politics of nationalism that shore up the boundaries of the homeland and anchor the distinction between public and private spheres through a discourse of opposition to foreign cultural invaders. The articulation of moral conflict over abortion and myths of foreign origins situate the national collectivity as a good, innocent victim of corrupt outside influence.
Rethinking Critical Pedagogy and the Gramscian and Freirean Legacies: From Organic to Committed Intellectuals or Critical Pedagogy, Commitment, and Praxis
Authors: Fischman Gustavo E. , McLaren Peter
Published: December 2005

Critical pedagogy problematizes the relationship between education and politics, between sociopolitical relations and pedagogical practices, between the reproduction of dependent hierarchies of power and privilege in the domain of everyday social life and that of classrooms and institutions. In doing so, it advances an agenda for educational transformation by encouraging educators to understand the sociopolitical contexts of educative acts and the importance of radically democratizing both educational sites and larger social formations. In such processes, educators take on intellectual roles by adapting to, resisting, and challenging curriculum, school policy, educational philosophies, and pedagogical traditions. This article revisits the contributions of Antonio Gramsci and Paulo Freire to critical pedagogy, giving particular attention to the related concepts of hegemony and the intellectual.
ZAP-70 expression is associated with enhanced ability to respond to migratory and survival signals in B-cell chronic lymphocytic leukemia (B-CLL)
Authors: Richardson Sarah J. , Matthews Christine , Catherwood Mark A. , Alexander H. Denis , Carey B. Sean , Farrugia Joanna , Gardiner Anne , Mould Sarah , Oscier David , Copplestone J. Adrian , Prentice Archibald G.
Published: December 2005

Molecular markers like IgVH mutational status, chromosomal abnormalities, and CD38 and ZAP-70 expression have prognostic value in B-cell chronic lymphocytic leukemia (B-CLL). These may be pathogenetic because of the coincidental expression of ZAP-70 and increased B-cell receptor (BCR) signaling and the signaling function of CD38 in CLL. This study shows that ZAP-70+ CLL B cells respond in vitro more readily than ZAP-70– CLL and normal B cells to chemokine migratory signals through enhanced surface CCR7 expression (P = .009; P < .001) and increased responsiveness to its ligands CCL19 and CCL21, demonstrated by F-actin polymerization (P < .05) and cellular migration (P < .01). In addition, ZAP-70+ CLL cells exhibit sustained ERK phosphorylation/activation following stimulation with CXCL12 (SDF1-α, a survival factor produced by stromal cells) compared with ZAP-70– cells (P = .004). Following coculture with nurse-like cells, the survival of ZAP-70+ but not ZAP-70– CLL cells is significantly enhanced by the addition of CXCL12 (P < .05), an effect that is partially blocked by the MEK inhibitor PD98059. These advantageous migratory and survival responses may promote easier access to and greater proliferation in pseudo-germinal centers and explain in part the more progressive nature of ZAP-70+ disease.
Hepcidin inhibits in vitro erythroid colony formation at reduced erythropoietin concentrations
Authors: Dallalio Gail , Law Erin , Means Robert T.
Published: December 2005

The anemia of chronic disease (ACD) results from 3 major processes: slightly shortened red cell survival, impaired reticuloendothelial system iron mobilization, and impaired erythropoiesis. Hepcidin is an acute-phase protein with specific iron regulatory properties, which, along with the anemia seen with increased hepcidin expression, have led many to consider it the major mediator of ACD. However, if hepcidin is the major factor responsible for ACD, then it should also contribute to the impaired erythropoiesis observed in this syndrome. Erythroid colony formation in vitro was inhibited by hepcidin at erythropoietin (Epo) concentrations less than or equal to 0.5 U/mL but not at Epo 1.0 U/mL. At Epo concentrations of 0.3 U/mL, HCD57 erythroleukemia cells exposed to hepcidin exhibit decreased expression of the antiapoptotic protein pBad compared with controls. These studies suggest that hepcidin may contribute to anemia in ACD not only through effects on iron metabolism, but also through inhibition of erythroid progenitor proliferation and survival.
CD7-restricted activation of Fas-mediated apoptosis: a novel therapeutic approach for acute T-cell leukemia
Authors: Bremer Edwin , Cate Bram ten , Samplonius Douwe F. , de Leij Lou F. M. H. , Helfrich Wijnand
Published: December 2005

Agonistic anti-Fas antibodies and multimeric recombinant Fas ligand (FasL) preparations show high tumoricidal activity against leukemic cells, but are unsuitable for clinical application due to unacceptable systemic toxicity. Consequently, new antileukemia strategies based on Fas activation have to meet the criterion of strictly localized action at the tumor-cell surface. Recent insight into the FasL/Fas system has revealed that soluble homotrimeric FasL (sFasL) is in fact nontoxic to normal cells, but also lacks tumoricidal activity. We report on a novel fusion protein, designated scFvCD7:sFasL, that is designed to have leukemia-restricted activity. ScFvCD7:sFasL consists of sFasL genetically linked to a high-affinity single-chain fragment of variable regions (scFv) antibody fragment specific for the T-cell leukemia-associated antigen CD7. Soluble homotrimeric scFvCD7:sFasL is inactive and acquires tumoricidal activity only after specific binding to tumor cell-surface-expressed CD7. Treatment of T-cell acute lymphoblastic leukemia (T-ALL) cell lines and patient-derived T-ALL, peripheral T-cell lymphoma (PTCL), and CD7-positive acute myeloid leukemia (AML) cells with homotrimeric scFvCD7:sFasL revealed potent CD7-restricted induction of apoptosis that was augmented by conventional drugs, farnesyl transferase inhibitor L-744832, and the proteasome inhibitor bortezomib (Velcade; Millenium, Cambridge, MA). Importantly, identical treatment did not affect normal human peripheral-blood lymphocytes (PBLs) and endothelial cells, with only moderate apoptosis in interleukin-2 (IL-2)/CD3-activated T cells. CD7-restricted activation of Fas in T-cell leukemic cells by scFvCD7:sFasL revitalizes interest in the applicability of Fas signaling in leukemia therapy.
GenClust: A genetic algorithm for clustering gene expression data
Authors: Di Gesú Vito , Giancarlo Raffaele , Lo Bosco Giosué , Raimondi Alessandra , Scaturro Davide
Published: December 2005

Background

Clustering is a key step in the analysis of gene expression data, and in fact, many classical clustering algorithms are used, or more innovative ones have been designed and validated for the task. Despite the widespread use of artificial intelligence techniques in bioinformatics and, more generally, data analysis, there are very few clustering algorithms based on the genetic paradigm, yet that paradigm has great potential in finding good heuristic solutions to a difficult optimization problem such as clustering.

Results

GenClust is a new genetic algorithm for clustering gene expression data. It has two key features: (a) a novel coding of the search space that is simple, compact and easy to update; (b) it can be used naturally in conjunction with data driven internal validation methods. We have experimented with the FOM methodology, specifically conceived for validating clusters of gene expression data. The validity of GenClust has been assessed experimentally on real data sets, both with the use of validation measures and in comparison with other algorithms, i.e., Average Link, Cast, Click and K-means.

Conclusion

Experiments show that none of the algorithms we have used is markedly superior to the others across data sets and validation measures; i.e., in many cases the observed differences between the worst and best performing algorithm may be statistically insignificant and they could be considered equivalent. However, there are cases in which an algorithm may be better than others and therefore worthwhile. In particular, experiments for GenClust show that, although simple in its data representation, it converges very rapidly to a local optimum and that its ability to identify meaningful clusters is comparable, and sometimes superior, to that of more sophisticated algorithms. In addition, it is well suited for use in conjunction with data driven internal validation measures and, in particular, the FOM methodology.
The largest subunit of RNA polymerase II from the Glaucocystophyta: functional constraint and short-branch exclusion in deep eukaryotic phylogeny
Authors: Stiller John W , Harrell Leslie
Published: December 2005

Background

Evolutionary analyses of the largest subunit of RNA polymerase II (RPB1) have yielded important and at times provocative results. One particularly troublesome outcome is the consistent inference of independent origins of red algae and green plants, at odds with the more widely accepted view of a monophyletic Plantae comprising all eukaryotes with primary plastids. If the hypothesis of a broader kingdom Plantae is correct, then RPB1 trees likely reflect a persistent phylogenetic artifact. To gain a better understanding of RNAP II evolution, and the presumed artifact relating to green plants and red algae, we isolated and analyzedRPB1 from representatives of Glaucocystophyta, the third eukaryotic group with primary plastids.

Results

Phylogenetic analyses incorporating glaucocystophytes do not recover a monophyletic Plantae; rather they result in additional conflicts with the most widely held views on eukaryotic relationships. In particular, glaucocystophytes are recovered as sister to several amoebozoans with strong support. A detailed investigation shows that this clade can be explained by what we call "short-branch exclusion," a phylogenetic artifact integrally associated with "long-branch attraction." Other systematic discrepancies observed inRPB1 trees can be explained as phylogenetic artifacts; however, these apparent artifacts also appear in regions of the tree that support widely held views of eukaryotic evolution. In fact, most of the RPB1 tree is consistent with artifacts of rate variation among sequences and co-variation due to functional constraints related to C-terminal domain based RNAP II transcription.

Conclusion

Our results reveal how subtle and easily overlooked biases can dominate the overall results of molecular phylogenetic analyses of ancient eukaryotic relationships. Sources of potential phylogenetic artifact should be investigated routinely, not just when obvious "long-branch attraction" is encountered.
Coxiella burnetii vascular graft infection
Authors: Senn Laurence , Franciolli Mario , Raoult Didier , Moulin Alexandre , Von Segesser Ludwig , Calandra Thierry , Greub Gilbert
Published: December 2005

Background

Coxiella burnetii, the causative agent of Q fever, may cause culture-negative vascular graft infections. Very few cases of C. burnetii infection of a vascular graft have been reported. All were diagnosed by serology.

Case presentation

We report the first case of Coxiella burnetii vascular graft infection diagnosed by broad-range PCR and discuss the diagnostic approaches and treatment strategies of chronic C. burnetii infection.

Conclusion

C. burnetii should be considered as etiological agent in patients with a vascular graft and fever, abdominal pain, and laboratory signs of inflammation, with or without exposure history. Broad-range PCR should be performed on culture-negative surgical samples in patients with suspected infection of vascular graft.
Genetic analysis of the GLUT10 glucose transporter (SLC2A10) polymorphisms in Caucasian American type 2 diabetes
Authors: Bento Jennifer L , Bowden Donald W , Mychaleckyj Josyf C , Hirakawa Shohei , Rich Stephen S , Freedman Barry I , Segade Fernando
Published: December 2005

Background

GLUT10 (gene symbol SLC2A10) is a facilitative glucose transporter within the type 2 diabetes (T2DM)-linked region on chromosome 20q12-13.1. Therefore, we evaluated GLUT10 as a positional candidate gene for T2DM in Caucasian Americans.

Methods

Twenty SNPs including 4 coding, 10 intronic and 6 5' and 3' to the coding sequence were genotyped across a 100 kb region containing the SLC2A10 gene in DNAs from 300 T2DM cases and 310 controls using the Sequenom MassArray Genotyping System. Allelic association was evaluated, and linkage disequilibrium (LD) and haplotype structure of SLC2A10 were also determined to assess whether any specific haplotypes were associated with T2DM.

Results

Of these variants, fifteen had heterozygosities greater than 0.80 and were analyzed further for association with T2DM. No evidence of significant association was observed for any variant with T2DM (all P ≥ 0.05), including Ala206Thr (rs2235491) which was previously reported to be associated with fasting insulin. Linkage disequilibrium analysis suggests that the SLC2A10 gene is contained in a single haplotype block of 14 kb. Haplotype association analysis with T2DM did not reveal any significant differences between haplotype frequencies in T2DM cases and controls.

Conclusion

From our findings, we can conclude that sequence variants in or near GLUT10 are unlikely to contribute significantly to T2DM in Caucasian Americans.
Unilateral anterior uveitis complicating zoledronic acid therapy in breast cancer
Authors: El Saghir Nagi S , Otrock Zaher K , Bleik Jamal H
Published: December 2005

Background

Zoledronic acid is very widely used in patients with metastatic bone disease and osteoporosis. Only one case of bilateral uveitis was recently reported related to its use.

Case presentation

We report the first case of severe unilateral anterior uveitis in a patient with breast cancer and an intraocular lens. Following zoledronic acid infusion, the patient developed severe and dramatic right eye pain with decreased visual acuity within 24 hours and was found to have a fibrinous anterior uveitis of moderate severity The patient was treated with topical prednisone and atropine eyedrops and recovered slowly over several months.

Conclusion

Internists, oncologists, endocrinologists, and ophtalmologists should be aware of uveitis as a possible complication of zoledronic acid therapy. Patients should be instructed to report immediately to their physicians and treatment with topical prednisone and atropine eyedrops should be instituted immediately at the onset of symptoms. This report documents anterior uveitis as a complication of zoledronic acid therapy. This reaction could be an idiosyncratic one but further research may shed more light on the etiology.
Public perception of drinking water from private water supplies: focus group analyses
Authors: Jones Andria Q , Dewey Catherine E , Doré Kathryn , Majowicz Shannon E , McEwen Scott A , Waltner-Toews David , Henson Spencer J , Mathews Eric
Published: December 2005

Background

Over four million Canadians receive their drinking water from private water supplies, and numerous studies report that these supplies often exceed the minimal acceptable standards for contamination. Canadians in rural areas test their water intermittently, if at all, and treatment of water from private supplies is not common. Understanding the perceptions of drinking water among residents served by private systems will enable public health professionals to better target education and outreach activities, and to address the needs and concerns of residents in their jurisdictions. The purpose of this study was to explore the drinking water perceptions and self-described behaviours and needs of participants served by private water systems in the City of Hamilton, Ontario (Canada).

Methods

In September 2003, three focus group discussions were conducted; two with men and women aged 36–65 years, and one with men and women 20–35 years of age.

Results

Overall, participants had positive perceptions of their private water supplies, particularly in the older age group. Concerns included bacterial and chemical contamination from agricultural sources. Testing of water from private supplies was minimal and was done less frequently than recommended by the provincial government. Barriers to water testing included the inconvenience of the testing process, acceptable test results in the past, resident complacency and lack of knowledge. The younger participants greatly emphasized their need for more information on private water supplies. Participants from all groups wanted more information on water testing, and various media for information dissemination were discussed.

Conclusion

While most participants were confident in the safety of their private water supply, the factual basis for these opinions is uncertain. Improved dissemination of information pertaining to private water supplies in this population is needed. Observed differences in the concerns expressed by users of different water systems and age groups may suggest the need for targeted public education strategies. These focus groups provided significant insight into the public perception of private water supplies and the need for public health outreach activities; however, to obtain a more representative understanding of the perceptions in this population, it is important that a larger scale investigation be performed.
Standardisation of data from real-time quantitative PCR methods – evaluation of outliers and comparison of calibration curves
Authors: Burns Malcolm J , Nixon Gavin J , Foy Carole A , Harris Neil
Published: December 2005

Background

As real-time quantitative PCR (RT-QPCR) is increasingly being relied upon for the enforcement of legislation and regulations dependent upon the trace detection of DNA, focus has increased on the quality issues related to the technique. Recent work has focused on the identification of factors that contribute towards significant measurement uncertainty in the real-time quantitative PCR technique, through investigation of the experimental design and operating procedure. However, measurement uncertainty contributions made during the data analysis procedure have not been studied in detail. This paper presents two additional approaches for standardising data analysis through the novel application of statistical methods to RT-QPCR, in order to minimise potential uncertainty in results.

Results

Experimental data was generated in order to develop the two aspects of data handling and analysis that can contribute towards measurement uncertainty in results. This paper describes preliminary aspects in standardising data through the application of statistical techniques to the area of RT-QPCR. The first aspect concerns the statistical identification and subsequent handling of outlying values arising from RT-QPCR, and discusses the implementation of ISO guidelines in relation to acceptance or rejection of outlying values. The second aspect relates to the development of an objective statistical test for the comparison of calibration curves.

Conclusion

The preliminary statistical tests for outlying values and comparisons between calibration curves can be applied using basic functions found in standard spreadsheet software. These two aspects emphasise that the comparability of results arising from RT-QPCR needs further refinement and development at the data-handling phase. The implementation of standardised approaches to data analysis should further help minimise variation due to subjective judgements. The aspects described in this paper will help contribute towards the development of a set of best practice guidelines regarding standardising handling and interpretation of data arising from RT-QPCR experiments.
Decorticate, decerebrate and opisthotonic posturing and seizures in Kenyan children with cerebral malaria
Authors: Idro Richard , Otieno Godfrey , White Steven , Kahindi Anderson , Fegan Greg , Ogutu Bernhards , Mithwani Sadik , Maitland Kathryn , Neville Brian GR , Newton Charles RJC
Published: December 2005

Background

Abnormal motor posturing is often observed in children with cerebral malaria, but the aetiology and pathogenesis is poorly understood. This study examined the risk factors and outcome of posturing in Kenyan children with cerebral malaria.

Methods

Records of children admitted to Kilifi district hospital with cerebral malaria from January, 1999 through December, 2001 were reviewed for posturing occurring on or after admission. The clinical characteristics, features of raised intracranial pressure, number of seizures and biochemical changes in patients that developed posturing was compared to patients who did not.

Results

Of the 417 children with complete records, 163 (39.1%) had posturing: 85 on admission and 78 after admission to hospital. Decorticate posturing occurred in 80, decerebrate in 61 and opisthotonic posturing in 22 patients. Posturing was associated with age ≥ 3 years (48.1 vs 35.8%, p = 0.01) and features of raised intracranial pressure on funduscopy (adjusted OR 2.1 95%CI 1.2–3.7, p = 0.009) but not other markers of severity of disease. Unlike decorticate posturing, decerebrate (adjusted OR 1.9 95%CI 1.0–3.5) and opisthotonic posturing (adjusted OR 2.9 95%CI 1.0–8.1) were, in addition, independently associated with recurrence of seizures after admission. Opisthotonus was also associated with severe metabolic acidosis (OR 4.2 95%CI 3.2–5.6, p < 0.001). Thirty one patients with posturing died. Of these, 19 (61.3%) had features suggestive of transtentorial herniation. Mortality and neurological deficits on discharge were greatest in those developing posturing after admission.

Conclusion

Abnormal motor posturing is a common feature of cerebral malaria in children. It is associated with features of raised intracranial pressure and recurrence of seizures, although intracranial hypertension may be the primary cause.
Assessment of erythrocyte phospholipid fatty acid composition as a biomarker for dietary MUFA, PUFA or saturated fatty acid intake in a controlled cross-over intervention trial
Authors: Poppitt Sally D , Kilmartin Paul , Butler Paul , Keogh Geraldine F
Published: December 2005

Background

Dietary intervention trials rely on self-reported measures of intake for assessment of energy and macronutrient composition. Dietary fat intake is of particular interest due to strong associations with pathophysiology. In epidemiological trials phospholipid fatty acid composition may reflect composition of habitual diet, although strong correlations have been identified only for essential polyunsaturated fatty acids (PUFAs). Preliminary evidence shows that saturated fatty acids (SFA) C15:0 and C17:0 may be acceptable biomarkers. This study measured changes in erythrocyte membrane fatty acids during a period of strictly controlled fat feeding to investigate their use as a short-term marker of compliance, particularly for intake of SFAs.

Results

This was a randomised cross-over trial in which diet was provided and strictly controlled. 20 healthy, male subjects were given a 40 energy % (en%) fat diet, high in saturated (high-SFA, 20 en%) or unsaturated (high-USFA, 24 en%) fatty acids for 2 periods of 3 weeks. Subjects were residential during intervention with all food and beverages provided. Dietary composition was verified by direct chemical analysis. Blood samples were collected on days 1,7,14, 21 and analysed for red blood cell (RBC) membrane fatty acid composition. Pearson correlation showed RBC fatty acid composition to mimic dietary composition by 3 weeks, but the relationships were weak. Of the SFAs only RBC C16:0 decreased in response to decreased dietary content on high-USFA treatment (ANOVA, diet, P < 0.05). Of the USFAs, higher levels of C18:1 MUFA, C20:4 and C22:6 long chain PUFA on high-USFA diet lead to higher C18:1, C20:4 and C22:6 within RBCs (ANOVA, time*diet, P < 0.05). Pearson's correlation was significant between dietary and RBC fatty acids during the 21d dietary manipulation for C18:1, and C20:5, C22:6 only (P < 0.05).

Conclusion

RBC membrane fatty acids cannot reliably be used as an independent measure of compliance for dietary SFA intake in short-term studies. The MUFA oleic acid and PUFAs EPA and DHA may be more useful as markers of compliance during short term intervention trials.
Pacing stress echocardiography
Authors: Gligorova Suzana , Agrusta Marco
Published: December 2005

Background

High-rate pacing is a valid stress test to be used in conjunction with echocardiography; it is independent of physical exercise and does not require drug administration. There are two main applications of pacing stress in the echo lab: the noninvasive detection of coronary artery disease through induction of a regional transient dysfunction; and the assessment of contractile reserve through peak systolic pressure/ end-systolic volume relationship at increasing heart rates to assess global left ventricular contractility.

Methods

The pathophysiologic rationale of pacing stress for noninvasive detection of coronary artery disease is obvious, with the stress determined by a controlled increase in heart rate, which is a major determinant of myocardial oxygen demand, and thereby tachycardia may exceed a fixed coronary flow reserve in the presence of hemodynamically significant coronary artery disease. The use of pacing stress echo to assess left ventricular contractile reserve is less established, but promising. Positive inotropic interventions are mirrored by smaller end-systolic volumes and higher end-systolic pressures. An increased heart rate progressively increases the force of ventricular contraction (Bowditch treppe or staircase phenomenon). To build the force-frequency relationship, the force is determined at different heart rate steps as the ratio of the systolic pressure (cuff sphygmomanometer)/end-systolic volume index (biplane Simpson rule). The heart rate is determined from ECG.

Conclusion

Two-dimensional echocardiography during pacing is a useful tool in the detection of coronary artery disease. Because of its safety and ease of repeatability noninvasive pacing stress echo can be the first-line stress test in patients with permanent pacemaker.

The force-frequency can be defined as up- sloping (normal) when the peak stress pacing systolic pressure/end-systolic volume index is higher than baseline and intermediate stress values, biphasic with an initial up- sloping followed by a later down-sloping trend, or flat or negative when peak stress pacing systolic pressure/end-systolic volume index is equal or lower than baseline stress values. This approach is certainly highly feasible and allows a conceptually immaculate definition of contractility with prognostic usefulness, but its therapeutic implications remains to be established. Bowditch treppe, assessed with pacing stress, can be used to assess the optimal stimulation frequency and to optimise the patient's chronotropic response in programming rate-adaptive pacemakers.
A strategic assessment of cervical cancer prevention and treatment services in 3 districts of Uttar Pradesh, India
Authors: Dabash Rasha , Vajpayee Jyoti , Jacob Martha , Dzuba Ilana , Lal Nisha , Bradley Jan , Prasad LB
Published: December 2005

Background

Despite being a preventable disease, cervical cancer claims the lives of almost half a million women worldwide each year. India bears one-fifth of the global burden of the disease, with approximately 130,000 new cases a year. In an effort to assess the need and potential for improving the quality of cervical cancer prevention and treatment services in Uttar Pradesh, a strategic assessment was conducted in three of the state's districts: Agra, Lucknow, and Saharanpur.

Methods

Using an adaptation of stage one of the World Health Organization's Strategic Approach to Improving Reproductive Health Policies and Programmes, an assessment of the quality of cervical cancer services was carried out by a multidisciplinary team of stakeholders. The assessment included a review of the available literature, observations of services, collection of hospital statistics and the conduct of qualitative research (in-depth interviews and focus group discussions) to assess the perspectives of women, providers, policy makers and community members.

Results

There were gaps in provider knowledge and practices, potentially attributable to limited provider training and professional development opportunities. In the absence of a state policy on cervical cancer, screening of asymptomatic women was practically absent, except in the military sector. Cytology-based cancer screening tests (i.e. pap smears) were often used to help diagnose women with symptoms of reproductive tract infections but not routinely screen asymptomatic women. Access to appropriate treatment of precancerous lesions was limited and often inappropriately managed by hysterectomy in many urban centers. Cancer treatment facilities were well equipped but mostly inaccessible for women in need. Finally, policy makers, community members and clients were mostly unaware about cervical cancer and its preventable nature, although with information, expressed a strong interest in having services available to women in their communities.

Conclusion

To address gaps in services and unmet needs, state policies and integrated interventions have the potential to improve the quality of services for prevention of cervical cancer in Uttar Pradesh.