bluuebunny/crossref_metadata_2025 huggingface dataset:
Uncanny Scripts: Understanding Pharmaceutical Emplotment in the Aboriginal Context
Authors: Oldani Michael J.
Published: March 2009

This article outlines a new social reality of global psycho-pharmaceutical prescribing: the pharmaceutical family, or `phamily.' Ethnographic case studies from Manitoba, Canada (2002 to 2004) show how pharmaceutical emplotment, involving a synergy between cultural and drug scripts, can have uncanny consequences for vulnerable groups, such as Aboriginal children. Observations and interview transcripts of high prescribing doctors are analyzed to understand the prescribing logic of using psychoactive medication, such as methylphenidate, in young Aboriginal children diagnosed with FASD and/or ADHD. Pharmaceutical narratives are presented in order to show how non-compliance to psychotropic prescribing can further marginalize Aboriginal children and is related to the history of colonial practices in Canada.
Adolescent Experience of Psychotropic Treatment
Authors: Floersch Jerry , Townsend Lisa , Longhofer Jeffrey , Munson Michelle , Winbush Victoria , Kranke Derrick , Faber Rachel , Thomas Jeremy , Jenkins Janis H. , Findling Robert L.
Published: March 2009

Despite growing concern over the treatment of adolescents with psychiatric medications, little research has examined youth understandings and interpretations of mental illness and psychotropic treatment. This article reports the exploratory findings of semi-structured and open-ended interviews carried out with 20 adolescents diagnosed with one or more psychiatric disorders, and who were currently prescribed psychiatric medications. Grounded theory coding procedures were used to identify themes related to adolescent subjective experience with psychiatric medications. The categories identified are interpreted as different points of view through which adolescents understand and take action upon their illness concerns; their need for medication treatment; their perceptions of how medications work; their responses to parental and other influences upon medication treatment; and, their everyday management activities.
I do not smoke — I exercise: A pilot study of a new educational resource for secondary education students
Authors: Hassandra Mary , Theodorakis Yiannis , Kosmidou Evdoxia , Grammatikopoulos Vassilis , Hatzigeorgiadis Antonis
Published: March 2009

Aims: The aim of this study was to examine the applicability of a smoking prevention educational resource for secondary education students named `I do not smoke, I exercise'. The main focus of this program was the promotion of exercise as an alternative behaviour to smoking. Methods: The applicability of the intervention was assessed through questionnaires regarding: (a) attitudes towards smoking, (b) interest in information about smoking, and (c) knowledge about health consequences of smoking. Moreover, interviews were taken from the educators and the school principals. The questionnaires were completed from 210 students (101 boys and 109 girls) before the beginning, at the end of the program, and 12 months after the completion of the programme. One-way repeated measure ANOVA was performed to examine the differences between the pre-, post-, and the follow-up measures. Results: Results showed that the program succeeded in changing the students' attitudes, but the follow-up measures, 12 months later, showed that attitudes towards smoking and interest in information were relapsed to the pre-intervention levels. The only effect that was sustained was that for knowledge. The interviews also revealed positive comments about the program implementation and pointed some shortcomings. Conclusions: The program needs some modifications in order to overcome its weaknesses, have more lasting effects and to improve its applicability.
Review Commentary: Is the BBC biased?
Authors: Gaber Ivor , Seymour Emily , Thomas Lisa
Published: March 2009

In the light of the findings of the BBC's 2006 impartiality review of their coverage of the Arab—Israeli conflict, and the fact that most of the accusations of bias against the BBC continue to come from pro-Israel lobbyists, this research sought to investigate whether their claims of anti-Israel bias during the BBC's reporting of the 2006 Israeli— Hezbollah war could be validated. Using ITV News as a control group, these claims were measured against the BBC's revised editorial guidelines for covering the Middle East. The article demonstrates that, whilst certain aspects of the coverage were problematic, BBC journalists broadly adhered to the Governors' revised editorial guidelines, and covered the conflict more or less impartially — if there was any bias it was towards, rather than against, Israel. ITV News coverage was more problematic but still achieved a significant degree of impartiality.
Cartography, territory, property: postcolonial reflections on indigenous counter-mapping in Nicaragua and Belize
Authors: Wainwright Joel , Bryan Joe
Published: March 2009

The attention given to indigenous peoples' use of maps to make claims to land and rights of self-government raises the question: what exactly it is that these maps do? This paper outlines an analytic for examining indigenous mapping projects, drawing upon two prominent instances — by the Maya of Belize and the Mayangna community of Awas Tingni in Nicaragua — where human rights lawsuits have been woven together with participatory mapping. In each case, map-making was intricately linked to the formulation of legal claims, resulting in a pair of much-celebrated maps and legal precedents regarding the recognition of indigenous land rights. We argue that these strategies do not reverse colonial social relations so much as they rework them. Notwithstanding the creativity expressed through these projects, they remain oriented by the spatial configuration of modern politics: territory and property rights. This spatial configuration both accounts for and limits the power of indigenous cartography. This impasse is not a contradiction that can be resolved; rather, it constitutes an aporia for which there is no easy or clear solution. Nonetheless, it must be confronted.
On the politics and the possibilities of participatory mapping and GIS: using spatial technologies to study common property and land use change among pastoralists in Central Tibet
Authors: Bauer Kenneth
Published: March 2009

This article critically and reflexively examines the process of applying participatory mapping and Geographic Information Systems (GIS) to investigate land use change and common property among pastoralists in Central Tibet. It explores the tensions inherent to participatory mapping in contemporary China and asks if participatory methods of recording and asserting territoriality are a plausible subaltern intervention for Tibetans living under Chinese political rule. In development and research circles, participatory mapping has been discussed and, slowly, tested in the field as a tool for `empowerment'. Yet the political currency of literature on participatory (or `counter') mapping has been developed predominantly in contexts where there is a dialogue, however asymmetric, between state and indigenous groups, and where these cartographic interventions can identify and delineate political boundaries in ways that may allow local or indigenous groups some measure of autonomy. This article extends critical geography on participatory mapping and spatial technologies such as GIS by reflecting on their relevance to Central Tibet, which has had a significantly different political history than the locales where indigenous cartographies have been previously deployed. For pastoralists living in the Tibet Autonomous Region of China, politically charged dynamics with respect to autonomy and the writ of boundary making preclude any possibility that participatory mapping can `empower' participants or give them greater authority in government negotiations: the scope for political contestation in Tibet is narrow and highly circumscribed. Even though participatory mapping is of limited utility as a tool for mobilization in the Tibetan context, the case study offers possibilities for the uses of participatory mapping and computer-driven spatial methodologies to blend information about land use and common property under different regimes of governance.
Minimal Detectable Change and Clinically Important Difference of the Wolf Motor Function Test in Stroke Patients
Authors: Lin Keh-chung , Hsieh Yu-wei , Wu Ching-yi , Chen Chia-ling , Jang Yuh , Liu Jung-sen
Published: March 2009

Objectives. This study aimed to establish the minimal detectable change (MDC) and clinically important differences (CID) of the Wolf Motor Function Test (WMFT) in patients with stroke, and to assess the proportions of patients' change scores exceeding the MDC and CID after stroke rehabilitation. Methods. A total of 57 patients received 1 of the 3 treatments for 3 weeks and underwent clinical assessments before and after treatment. The MDC, at 90% confidence (MDC 90), was calculated from the standard error of measurement to indicate a real change for individual patients. Anchor-based and distribution-based approaches were used to triangulate the values of minimal CID. The percentages of patients exceeding the MDC and minimal CID were also examined. Results. The MDC90 of the WMFT was 4.36 for the performance time (WMFT time) and 0.37 for the functional ability scale (WMFT FAS). The minimal CID ranged from 1.5 to 2 seconds on the WMFT time and from 0.2 to 0.4 points on the WMFT FAS. The MDC and CID proportions ranged from 14% to 30% on the WMFT time and from 39% to 65% on the WMFT FAS, respectively. Conclusions. The change score of an individual patient has to reach 4.36 and 0.37 on the WMFT time and WMFT FAS to indicate a real change. The mean change scores of a stroke group on the WMFT time and WMFT FAS should achieve 1.5 to 2 seconds and 0.2 to 0.4 points to be regarded as clinically important changes. Furthermore, the WMFT FAS may be more responsive than the WMFT time based on the results of proportions exceeding the threshold criteria.
Successful switch to sitaxsentan in a patient with HIV-related pulmonary arterial hypertension and late intolerance to nonselective endothelin receptor blockade
Authors: Zacà Valerio , Metra Marco , Danesi Rossella , Lombardi Carlo , Verzura Giulia , Dei Cas Livio
Published: March 2009

Pulmonary arterial hypertension (PAH) is a rare but well-known cardiovascular condition potentially associated with human immunodeficiency virus (HIV) infection and is currently recognized to be one of the most ominous noninfectious HIV complications. Although there is no clear evidence supporting the use of any medication for the treatment of HIV-related PAH, many of the currently available agents have been shown to exert some clinical benefits HIV-PAH patients. To date, no data are available regarding the potential effects of sitaxsentan, a selective endothelin type-A receptor antagonist, in this peculiar patient population. We report the case of a successful switch to sitaxsentan in a HIV-infected patient with PAH initially receiving bosentan who developed a late treatment-related side-effect.
Polymorphisms of the ß2 adrenoreceptor gene in chronic obstructive pulmonary disease
Authors: Vacca Gabriela , Schwabe Kerstin , Dück Ramona , Hlawa Hans-Peter , Westphal Arite , Pabst Stefan , Grohé Christian , Gillissen Adrian
Published: March 2009

Background: The ß2-adrenergic receptors are cell surface receptors playing a central role in the pharmacological targeting asthma and chronic obstructive pulmonary disease (COPD). Recent studies suggest that patients who are homozygous for one of the two important polymorphisms of the ß2-adrenergic receptor (ADRB2) gene at codon 16 (arginine to glycine) and 27 (glutamine to glutamate) may have a reduced response to ß2-agonists. Since smoking patients who are Gly16 homozygotes have an increased risk of airway obstruction we hypothesized that ß2-adrenoreceptor gene polymorphisms may be also a cofounder for COPD development and disease severity.

Methods: We investigated 190 COPD patients and 172 healthy volunteers in a case-control study. DNA was isolated from whole blood and ß2-AR gene polymorphisms Arg/Gly16 and Gln/Glu27 were determined using allele-specific polymerase chain reaction (PCR).

Results: In COPD patients with Gly/Gly16 was found more frequently than in healthy smokers (29.47% COPD versus 18.18% controls, p = 0.026). All other gene polymorphisms of the ADRB2 gene at codon 16 were equally distributed between groups. ß2-adrenoreceptor gene polymorphisms were neither a cofounder for COPD exacerbations (≥ 3 hospitalizations within the last 3 years) nor for disease severity (FEV1 ≤ 30% predicted).

Conclusion: Our study suggests that the Gly16 allele of the ß2-AR gene predisposes to COPD development but not for exacerbation rates and disease severity. In contrast, Gln/Glu27 polymorphism was irrelevant in our COPD cohort.
Pay-per-Click Search Engine Advertising
Authors: O'Connor Peter
Published: March 2009

Having outlined the legal position in relation to the use of trademarks in pay-per-click advertising, this study investigates trademark use in hotel searches. Using a randomly selected sample of ninety hotel properties worldwide, searches were performed on two leading search engines to investigate whether third parties were using hotel trademarks in their paid placement. Findings indicate that abuse is rampant. While hotels perform well in organic search, they are usually preceded by or surrounded by paid listings abusing their trade names. Customers are potentially being diverted to competing websites, and urgent action is needed to reclaim hotel trademarks in the online search environment.
The favorable impact of CEBPA mutations in patients with acute myeloid leukemia is only observed in the absence of associated cytogenetic abnormalities and FLT3 internal duplication
Authors: Renneville Aline , Boissel Nicolas , Gachard Nathalie , Naguib Dina , Bastard Christian , de Botton Stéphane , Nibourel Olivier , Pautas Cécile , Reman Oumedaly , Thomas Xavier , Gardin Claude , Terré Christine , Castaigne Sylvie , Preudhomme Claude , Dombret Hervé
Published: March 2009

Mutations of the CCAAT/enhancer binding protein alpha (CEBPA) gene have been associated with a favorable outcome in patients with acute myeloid leukemia (AML), but mainly in those with a normal karyotype. Here, we analyzed the impact of associated cytogenetic abnormalities or bad-prognosis fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) in 53 patients with CEBPA+ de novo AML treated in the Acute Leukemia French Association trials. We found that only those with a normal karyotype and no FLT3-ITD displayed the expected favorable outcome. In this context, relapse-free, disease-free, and overall survival were significantly longer than in corresponding patients without the CEBPA mutation (P = .035, .016, and .047, respectively). This was not observed in the context of an abnormal karyotype or associated FLT3-ITD. Furthermore, after adjustment on age, trial, and mutation type, these features were independently predictive of shorter overall survival in the subset of patients with CEBPA+ AML (multivariate hazard ratio = 2.7; 95% confidence interval, 1.08-6.7; and 2.9; 95% confidence interval, 1.01-8.2; with P = .034 and .05, for abnormal karyotype and FLT3-ITD, respectively).
Trichostatin A treatment of cloned mouse embryos improves constitutive heterochromatin remodeling as well as developmental potential to term
Authors: Maalouf Walid E , Liu Zichuan , Brochard Vincent , Renard Jean-Paul , Debey Pascale , Beaujean Nathalie , Zink Daniele
Published: March 2009

Background

Genome reprogramming in early mouse embryos is associated with nuclear reorganization and particular features such as the peculiar distribution of centromeric and pericentric heterochromatin during the first developmental stage. This zygote-specific heterochromatin organization could be observed both in maternal and paternal pronuclei after natural fertilization as well as in embryonic stem (ES) cell nuclei after nuclear transfer suggesting that this particular type of nuclear organization was essential for embryonic reprogramming and subsequent development.

Results

Here, we show that remodeling into a zygotic-like organization also occurs after somatic cell nuclear transfer (SCNT), supporting the hypothesis that reorganization of constitutive heterochromatin occurs regardless of the source and differentiation state of the starting material. However, abnormal nuclear remodeling was frequently observed after SCNT, in association with low developmental efficiency. When transient treatment with the histone deacetylase inhibitor trichostatin A (TSA) was tested, we observed improved nuclear remodeling in 1-cell SCNT embryos that correlated with improved rates of embryonic development at subsequent stages.

Conclusion

Together, the results suggest that proper organization of constitutive heterochromatin in early embryos is involved in the initial developmental steps and might have long term consequences, especially in cloning procedures.
Whole genome surveys of rice, maize and sorghum reveal multiple horizontal transfers of the LTR-retrotransposon Route66 in Poaceae
Authors: Roulin Anne , Piegu Benoit , Fortune Philippe M , Sabot François , D'Hont Angélique , Manicacci Domenica , Panaud Olivier
Published: March 2009

Background

Horizontal transfers (HTs) refer to the transmission of genetic material between phylogenetically distant species. Although most of the cases of HTs described so far concern genes, there is increasing evidence that some involve transposable elements (TEs) in Eukaryotes. The availability of the full genome sequence of two cereal species, (i.e. rice and Sorghum), as well as the partial genome sequence of maize, provides the opportunity to carry out genome-wide searches for TE-HTs in Poaceae.

Results

We have identified an LTR-retrotransposon, that we named Route66, with more than 95% sequence identity between rice and Sorghum. Using a combination of in silico and molecular approaches, we are able to present a substantial phylogenetic evidence that Route66 has been transferred horizontally between Panicoideae and several species of the genus Oryza. In addition, we show that it has remained active after these transfers.

Conclusion

This study constitutes a new case of HTs for an LTR-retrotransposon and we strongly believe that this mechanism could play a major role in the life cycle of transposable elements. We therefore propose to integrate classe I elements into the previous model of transposable element evolution through horizontal transfers.
Ancient diversification of eukaryotic MCM DNA replication proteins
Authors: Liu Yuan , Richards Thomas A , Aves Stephen J
Published: March 2009

Background

Yeast and animal cells require six mini-chromosome maintenance proteins (Mcm2-7) for pre-replication complex formation, DNA replication initiation and DNA synthesis. These six individual MCM proteins form distinct heterogeneous subunits within a hexamer which is believed to form the replicative helicase and which associates with the essential but non-homologous Mcm10 protein during DNA replication. In contrast Archaea generally only possess one MCM homologue which forms a homohexameric MCM helicase. In some eukaryotes Mcm8 and Mcm9 paralogues also appear to be involved in DNA replication although their exact roles are unclear.

Results

We used comparative genomics and phylogenetics to reconstruct the diversification of the eukaryotic Mcm2-9 gene family, demonstrating that Mcm2-9 were formed by seven gene duplication events before the last common ancestor of the eukaryotes. Mcm2-7 protein paralogues were present in all eukaryote genomes studied suggesting that no gene loss or functional replacements have been tolerated during the evolutionary diversification of eukaryotes. Mcm8 and 9 are widely distributed in eukaryotes and group together on the MCM phylogenetic tree to the exclusion of all other MCM paralogues suggesting co-ancestry. Mcm8 and Mcm9 are absent in some taxa, including Trichomonas and Giardia, and appear to have been secondarily lost in some fungi and some animals. The presence and absence of Mcm8 and 9 is concordant in all taxa sampled with the exception of Drosophila species. Mcm10 is present in most eukaryotes sampled but shows no concordant pattern of presence or absence with Mcm8 or 9.

Conclusion

A multifaceted and heterogeneous Mcm2-7 hexamer evolved during the early evolution of the eukaryote cell in parallel with numerous other acquisitions in cell complexity and prior to the diversification of extant eukaryotes. The conservation of all six paralogues throughout the eukaryotes suggests that each Mcm2-7 hexamer component has an exclusive functional role, either by a combination of unique lock and key interactions between MCM hexamer subunits and/or by a range of novel side interactions. Mcm8 and 9 evolved early in eukaryote cell evolution and their pattern of presence or absence suggests that they may have linked functions. Mcm8 is highly divergent in all Drosophila species and may not provide a good model for Mcm8 in other eukaryotes.
Safety and effectiveness of colistin compared with tobramycin for multi-drug resistant Acinetobacter baumannii infections
Authors: Gounden Ronald , Bamford Colleen , van Zyl-Smit Richard , Cohen Karen , Maartens Gary
Published: March 2009

Background

Nosocomial infections due to multi-drug resistant Acinetobacter baumannii are often treated with colistin, but there are few data comparing its safety and efficacy with other antimicrobials.

Methods

A retrospective cohort study of patients treated with colistin or tobramycin for A. baumannii infections in intensive care units (ICUs) at Groote Schuur hospital. Colistin was used for A. baumannii isolates which were resistant to all other available antimicrobials. In the tobramycin group, 53% of the isolates were only susceptible to tobramycin and colistin. We assessed ICU mortality, nephrotoxicity and time to the first negative culture.

Results

32 patients, with similar admission APACHE scores and serum creatinine, were treated with each antimicrobial. There were no significant differences between the colistin and tobramycin groups in ICU mortality (p = 0.54), nephrotoxicity (p = 0.67), change in creatinine from baseline to highest subsequent value (p = 0.11) and time to microbiological clearance (p = 0.75). The hazard ratio for total in-hospital survival in patients treated with colistin compared to tobramycin was 0.43 (95% CI 0.19 to 0.99).

Conclusion

Our study suggests that colistin and tobramycin have similar risks of nephrotoxicity and are equally efficacious. Colistin is an acceptable antibiotic for the treatment of A. baumanii infections when the organism is resistant to other available antimicrobials.
APRIL is overexpressed in cancer: link with tumor progression
Authors: Moreaux Jérôme , Veyrune Jean-Luc , De Vos John , Klein Bernard
Published: March 2009

Background

BAFF and APRIL share two receptors – TACI and BCMA – and BAFF binds to a third receptor, BAFF-R. Increased expression of BAFF and APRIL is noted in hematological malignancies. BAFF and APRIL are essential for the survival of normal and malignant B lymphocytes, and altered expression of BAFF or APRIL or of their receptors (BCMA, TACI, or BAFF-R) have been reported in various B-cell malignancies including B-cell non-Hodgkin's lymphoma, chronic lymphocytic leukemia, Hodgkin's lymphoma, multiple myeloma, and Waldenstrom's macroglobulinemia.

Methods

We compared the expression of BAFF, APRIL, TACI and BAFF-R gene expression in 40 human tumor types – brain, epithelial, lymphoid, germ cells – to that of their normal tissue counterparts using publicly available gene expression data, including the Oncomine Cancer Microarray database.

Results

We found significant overexpression of TACI in multiple myeloma and thyroid carcinoma and an association between TACI expression and prognosis in lymphoma. Furthermore, BAFF and APRIL are overexpressed in many cancers and we show that APRIL expression is associated with tumor progression. We also found overexpression of at least one proteoglycan with heparan sulfate chains (HS), which are coreceptors for APRIL and TACI, in tumors where APRIL is either overexpressed or is a prognostic factor. APRIL could induce survival or proliferation directly through HS proteoglycans.

Conclusion

Taken together, these data suggest that APRIL is a potential prognostic factor for a large array of malignancies.
From bench to bedside: current and future applications of molecular profiling in renal cell carcinoma
Authors: Arsanious Androu , Bjarnason Georg A , Yousef George M
Published: March 2009

Among the adult population, renal cell carcinoma (RCC) constitutes the most prevalent form of kidney neoplasm. Unfortunately, RCC is relatively asymptomatic and there are no tumor markers available for diagnostic, prognostic or predictive purposes. Molecular profiling, the global analysis of gene and protein expression profiles, is an emerging promising tool for new biomarker identification in RCC. In this review, we summarize the existing knowledge on RCC regarding clinical presentation, treatment options, and tumor marker status. We present a general overview of the more commonly used approaches for molecular profiling at the genomic, transcriptomic and proteomic levels. We also highlight the emerging role of molecular profiling as not only revolutionizing the process of new tumor marker discovery, but also for providing a better understanding of the pathogenesis of RCC that will pave the way towards new targeted therapy discovery. Furthermore, we discuss the spectrum of clinical applications of molecular profiling in RCC in the current literature. Finally, we highlight some of the potential challenging that faces the era of molecular profiling and its transition into clinical practice, and provide an insight about the future perspectives of molecular profiling in RCC.
Local increase in trapezius muscle oxygenation during and after acupuncture
Authors: Ohkubo Masaki , Hamaoka Takafumi , Niwayama Masatugu , Murase Norio , Osada Takuya , Kime Ryotaro , Kurosawa Yuko , Sakamoto Ayumi , Katsumura Toshihito
Published: March 2009

Purpose

This study aimed to compare the trapezius muscle blood volume and oxygenation in the stimulation region and in a distant region in the same muscle during acupuncture stimulation (AS). We hypothesized that AS provokes a localized increase in muscle blood volume and oxygenation in the stimulation region.

Methods

Two sets of near-infrared spectrometer (NIRS) probes, with 40-mm light-source detector spacing, were placed on the right trapezius muscle, with a 50-mm distance between the probes. Changes in muscle oxygenation (oxy-Hb) and blood volume (t-Hb) in stimulation and distant regions (50 mm away from the stimulation point) were measured using NIRS. Nine healthy acupuncture-experienced subjects were chosen as the experimental (AS) group, and 10 healthy acupuncture-experienced subjects were chosen for the control (no AS) group. Measurements began with a 3-min rest period, followed by "Jakutaku" (AS) for 2 min, and recovery after stimulation.

Results

There was a significant increase in oxy-Hb (60.7 μM at maximum) and t-Hb (48.1 μM at maximum) in the stimulation region compared to the distant region. In the stimulation region, a significant increase in oxy-Hb and t-Hb compared with the pre-stimulation level was first noted at 58.5 s and 13.5 s, respectively, after the onset of stimulation.

Conclusion

In conclusion, oxygenation and blood volume increased, indicating elevated blood flow to the small vessels, not in the distant region used in this study, but in the stimulation region of the trapezius muscle during and after a 2-min AS.
Biomarkers of HIV-1 associated dementia: proteomic investigation of sera
Authors: Wiederin Jayme , Rozek Wojciech , Duan Fenghai , Ciborowski Pawel
Published: March 2009

Background

New, more sensitive and specific biomarkers are needed to support other means of clinical diagnosis of neurodegenerative disorders. Proteomics technology is widely used in discovering new biomarkers. There are several difficulties with in-depth analysis of human plasma/serum, including that there is no one proteomic platform that can offer complete identification of differences in proteomic profiles. Another set of problems is associated with heterogeneity of human samples in addition intrinsic variability associated with every step of proteomic investigation. Validation is the very last step of proteomic investigation and it is very often difficult to validate potential biomarker with desired sensitivity and specificity. Even though it may be possible to validate a differentially expressed protein, it may not necessarily prove to be a valid diagnostic biomarker.

Results

In the current study we report results of proteomic analysis of sera from HIV-infected individuals with or without cognitive impairment. Application of SELDI-TOF analysis followed by weak cation exchange chromatography and 1-dimensional electrophoresis led to discovery of gelsolin and prealbumin as differentially expressed proteins which were not detected in this cohort of samples when previously investigated by 2-dimensional electrophoresis with Difference Gel Electrophoresis technology.

Conclusion

Validation using western-blot analysis led us to conclude that relative change of the levels of these proteins in one patient during a timeframe might be more informative, sensitive and specific than application of average level estimated based on an even larger cohort of patients.
Training health care workers to promote HIV services for patients with tuberculosis in the Democratic Republic of Congo
Authors: Driessche Koen Vanden , Sabue Mulangu , Dufour Wendy , Behets Frieda , Van Rie Annelies
Published: March 2009

Background

HIV counseling and testing, HIV prevention and provision of HIV care and support are essential activities to reduce the burden of HIV among patients with TB, and should be integrated into routine TB care.

Methods

The development of training materials to promote HIV services for TB patients involved the definition of target health care workers (HCWs); identification of required tasks, skills and knowledge; review of international guidelines; and adaptation of existing training materials for voluntary counseling and testing, prevention of mother-to-child transmission of HIV, and management of opportunistic infections (OIs). Training effectiveness was assessed by means of questionnaires administered pre- and post-training, by correlating post-training results of HCWs with the centre's HIV testing acceptance rates, and through participatory observations at the time of on-site supervisory visits and monthly meetings.

Results

Pre-training assessment identified gaps in basic knowledge of HIV epidemiology, the link between TB and HIV, interpretation of CD4 counts, prevention and management of OIs, and occupational post-exposure prophylaxis (PEP). Opinions on patients' rights and confidentiality varied. Mean test results increased from 72% pre-training to 87% post-training (p < 0.001). Important issues regarding HIV epidemiology and PEP remained poorly understood post-training. Mean post-training scores of clinic's HCWs were significantly correlated with the centre's HIV testing acceptance rates (p = 0.01). On-site supervisory visits and monthly meetings promoted staff motivation, participatory problem solving and continuing education. Training was also used as an opportunity to improve patient-centred care and HCWs' communication skills.

Conclusion

Many HCWs did not possess the knowledge or skills necessary to integrate HIV activities into routine care for patients with TB. A participatory approach resulted in training materials that fulfilled local needs.
RAGE (Receptor for Advanced Glycation Endproducts), RAGE Ligands, and their role in Cancer and Inflammation
Authors: Sparvero Louis J , Asafu-Adjei Denise , Kang Rui , Tang Daolin , Amin Neilay , Im Jaehyun , Rutledge Ronnye , Lin Brenda , Amoscato Andrew A , Zeh Herbert J , Lotze Michael T
Published: March 2009

The Receptor for Advanced Glycation Endproducts [RAGE] is an evolutionarily recent member of the immunoglobulin super-family, encoded in the Class III region of the major histocompatability complex. RAGE is highly expressed only in the lung at readily measurable levels but increases quickly at sites of inflammation, largely on inflammatory and epithelial cells. It is found either as a membrane-bound or soluble protein that is markedly upregulated by stress in epithelial cells, thereby regulating their metabolism and enhancing their central barrier functionality. Activation and upregulation of RAGE by its ligands leads to enhanced survival. Perpetual signaling through RAGE-induced survival pathways in the setting of limited nutrients or oxygenation results in enhanced autophagy, diminished apoptosis, and (with ATP depletion) necrosis. This results in chronic inflammation and in many instances is the setting in which epithelial malignancies arise. RAGE and its isoforms sit in a pivotal role, regulating metabolism, inflammation, and epithelial survival in the setting of stress. Understanding the molecular structure and function of it and its ligands in the setting of inflammation is critically important in understanding the role of this receptor in tumor biology.
Nitric Oxide Activates ATP-Sensitive Potassium Channels in Mammalian Sensory Neurons: Action by Direct S-Nitrosylation
Authors: Kawano Takashi , Zoga Vasiliki , Kimura Masakazu , Liang Mei-Ying , Wu Hsiang-En , Gemes Geza , McCallum J Bruce , Kwok Wai-Meng , Hogan Quinn H , Sarantopoulos Constantine D
Published: March 2009

Background

ATP-sensitive potassium (KATP) channels in neurons regulate excitability, neurotransmitter release and mediate protection from cell-death. Furthermore, activation of KATP channels is suppressed in DRG neurons after painful-like nerve injury. NO-dependent mechanisms modulate both KATP channels and participate in the pathophysiology and pharmacology of neuropathic pain. Therefore, we investigated NO modulation of KATP channels in control and axotomized DRG neurons.

Results

Cell-attached and cell-free recordings of KATP currents in large DRG neurons from control rats (sham surgery, SS) revealed activation of KATP channels by NO exogenously released by the NO donor SNAP, through decreased sensitivity to [ATP]i. This NO-induced KATP channel activation was not altered in ganglia from animals that demonstrated sustained hyperalgesia-type response to nociceptive stimulation following spinal nerve ligation. However, baseline opening of KATP channels and their activation induced by metabolic inhibition was suppressed by axotomy. Failure to block the NO-mediated amplification of KATP currents with specific inhibitors of sGC and PKG indicated that the classical sGC/cGMP/ PKG signaling pathway was not involved in the activation by SNAP. NO-induced activation of KATP channels remained intact in cell-free patches, was reversed by DTT, a thiol-reducing agent, and prevented by NEM, a thiol-alkylating agent. Other findings indicated that the mechanisms by which NO activates KATP channels involve direct S-nitrosylation of cysteine residues in the SUR1 subunit. Specifically, current through recombinant wild-type SUR1/Kir6.2 channels expressed in COS7 cells was activated by NO, but channels formed only from truncated isoform Kir6.2 subunits without SUR1 subunits were insensitive to NO. Further, mutagenesis of SUR1 indicated that NO-induced KATP channel activation involves interaction of NO with residues in the NBD1 of the SUR1 subunit.

Conclusion

NO activates KATP channels in large DRG neurons via direct S-nitrosylation of cysteine residues in the SUR1 subunit. The capacity of NO to activate KATP channels via this mechanism remains intact even after spinal nerve ligation, thus providing opportunities for selective pharmacological enhancement of KATP current even after decrease of this current by painful-like nerve injury.
Characterization of NF-Kb-Mediated Inhibition of Catechol-O-Methyltransferase
Authors: Tchivileva Inna E , Nackley Andrea G , Qian Li , Wentworth Sean , Conrad Matthew , Diatchenko Luda B
Published: March 2009

Background

Catechol- O-methyltransferase (COMT), an enzyme that metabolizes catecholamines, has recently been implicated in the modulation of pain. Specifically, low COMT activity is associated with heightened pain perception and development of musculoskeletal pain in humans as well as increased experimental pain sensitivity in rodents.

Results

We report that the proinflammatory cytokine tumor necrosis factor α (TNFα) downregulates COMT mRNA and protein in astrocytes. Examination of the distal COMT promoter ( P2-COMT) reveals a putative binding site for nuclear factor κB (NF-κB), the pivotal regulator of inflammation and the target of TNFα. Cell culture assays and functional deletion analyses of the cloned P2-COMT promoter demonstrate that TNFα inhibits P2-COMT activity in astrocytes by inducing NF-κB complex recruitment to the specific κB binding site.

Conclusion

Collectively, our findings provide the first evidence for NF-κB-mediated inhibition of COMT expression in the central nervous system, suggesting that COMT contributes to the pathogenesis of inflammatory pain states.
Long term survivors with metastatic pancreatic adenocarcinoma treated with gemcitabine: a retrospective analysis
Authors: Goulart Bernardo HL , Clark Jeffrey W , Lauwers Gregory Y , Ryan David P , Grenon Nina , Muzikansky Alona , Zhu Andrew X
Published: March 2009

Background

Metastatic pancreatic adenocarcinoma has a short median overall survival (OS) of 5–6 months. However, a subgroup of patients survives more than 1 year. We analyzed the survival outcomes of this subgroup and evaluated clinical and pathological factors that might affect survival durations.

Methods

We identified 20 patients with metastatic or recurrent pancreatic adenocarcinoma who received single-agent gemcitabine and had an OS longer than 1 year. Baseline data available after the diagnosis of metastatic or recurrent disease was categorized as: 1)clinical/demographic data(age, gender, ECOG PS, number and location of metastatic sites); 2)Laboratory data(Hematocrit, hemoglobin, glucose, LDH, renal and liver function and CA19-9); 3)Pathologic data(margins, nodal status and grade); 4)Outcomes data(OS, Time to Treatment Failure (TTF), and 2 year-OS). The lowest CA19-9 levels during treatment with gemcitabine were also recorded. We performed a univariate analysis with OS as the outcome variable.

Results

Baseline logarithm of CA19-9 and total bilirubin had a significant impact on OS (HR = 1.32 and 1.31, respectively). Median OS and TTF on gemcitabine were 26.9 (95% CI = 18 to 32) and 11.5 (95% CI = 9.0 to 14.3) months, respectively. Two-year OS was 56.4%, with 7 patients alive at the time of analysis.

Conclusion

A subgroup of patients with metastatic pancreatic cancer has prolonged survival after treatment with gemcitabine. Only bilirubin and CA 19-9 levels were predictive of longer survival in this population. Further analysis of potential prognostic and predictive markers of response to treatment and survival are needed.
Protective effects of total fraction of avocado/soybean unsaponifiables on the structural changes in experimental dog osteoarthritis: inhibition of nitric oxide synthase and matrix metalloproteinase-13
Authors: Boileau Christelle , Martel-Pelletier Johanne , Caron Judith , Msika Philippe , Guillou Georges B , Baudouin Caroline , Pelletier Jean-Pierre
Published: March 2009

Introduction

The aims of this study were, first, to investigate the in vivo effects of treatment with avocado/soybean unsaponifiables on the development of osteoarthritic structural changes in the anterior cruciate ligament dog model and, second, to explore their mode of action.

Methods

Osteoarthritis was induced by anterior cruciate ligament transection of the right knee in crossbred dogs. There were two treatment groups (n = 8 dogs/group), in which the animals received either placebo or avocado/soybean unsaponifiables (10 mg/kg per day), which were given orally for the entire duration of the study (8 weeks). We conducted macroscopic and histomorphological analyses of cartilage and subchondral bone of the femoral condyles and/or tibial plateaus. We also conducted immunohistochemical analyses in cartilage for the following antigens: inducible nitric oxide synthase, matrix metalloproteinase (MMP)-1, MMP-13, a disintegrin and metalloproteinase domain with thrombospondin motifs (ADAMTS)4 and ADAMTS5.

Results

The size of macroscopic lesions on the tibial plateaus was decreased (P = 0.04) in dogs treated with the avocado/soybean unsaponifiables. Histologically, in these animals the severity of cartilage lesions on both tibial plateaus and femoral condyles, and the cellular infiltration in synovium were significantly decreased (P = 0.0002 and P = 0.04, respectively). Treatment with avocado/soybean unsaponifiables also reduced loss of subchondral bone volume (P < 0.05) and calcified cartilage thickness (P = 0.01) compared with placebo. Immunohistochemical analysis of cartilage revealed that avocado/soybean unsaponifiables significantly reduced the level of inducible nitric oxide synthase (P < 0.05) and MMP-13 (P = 0.01) in cartilage.

Conclusions

This study demonstrates that treatment with avocado/soybean unsaponifiables can reduce the development of early osteoarthritic cartilage and subchondral bone lesions in the anterior cruciate ligament dog model of osteoarthritis. This effect appears to be mediated through the inhibition of inducible nitric oxide synthase and MMP-13, which are key mediators of the structural changes that take place in osteoarthritis.
A clinical evaluation committee assessment of recombinant human tissue factor pathway inhibitor (tifacogin) in patients with severe community-acquired pneumonia
Authors: Laterre Pierre-François , Opal Steven M , Abraham Edward , LaRosa Steven P , Creasey Abla A , Xie Fang , Poole Lona , Wunderink Richard G
Published: March 2009

Introduction

The purpose of this analysis was to determine the potential efficacy of recombinant human tissue factor pathway inhibitor (tifacogin) in a subpopulation of patients with community-acquired pneumonia (CAP) from a phase III study of severe sepsis.

Methods

A retrospective review of patients with suspected pneumonia was conducted by an independent clinical evaluation committee (CEC) blinded to treatment assignment. The CEC reanalyzed data from patients enrolled in an international multicenter clinical trial of sepsis who had a diagnosis of pneumonia as the probable source of sepsis. The primary efficacy measure was all-cause 28-day mortality.

Results

Of 847 patients identified on case report forms with a clinical diagnosis of pneumonia, 780 (92%) were confirmed by the CEC to have pneumonia. Of confirmed pneumonia cases, 496 (63.6%) met the definition for CAP. In the CEC CAP population, the mortality rates of the tifacogin and placebo groups were 70/251 (27.9%) and 80/245 (32.7%), respectively. The strongest signals were seen in patients with CAP not receiving concomitant heparin, having microbiologically confirmed infection, or having the combination of documented infection and no heparin. The reduction in mortality in this narrowly defined subgroup when treated with tifacogin compared with placebo was statistically significant (17/58 [29.3%] with tifacogin and 28/54 [51.9%] with placebo; unadjusted P value of less than 0.02).

Conclusions

Tifacogin administration did not significantly reduce mortality in any severe CAP patient. Exploratory analyses showed an improved survival in patients who did not receive concomitant heparin with microbiologically confirmed infections. These data support the rationale of an ongoing phase III study exploring the potential benefit of tifacogin in severe CAP.

Trial Registration

ClinicalTrials.gov identifier NCT00084071.
Socioeconomic Differences in Patient Survival Are Increasing for Acute Myeloid Leukemia and Multiple Myeloma in Sweden
Authors: Kristinsson Sigurdur Yngvi , Derolf Åsa Rangert , Edgren Gustaf , Dickman Paul W. , Björkholm Magnus
Published: March 2009

Purpose

An association between socioeconomic status (SES) and survival in acute myeloid leukemia (AML) and multiple myeloma (MM) has not been established in developed countries. We assessed the impact of SES on survival in two large population-based cohorts of AML and MM patients diagnosed in Sweden 1973 to 2005.

Patients and Methods

The relative risk of death (all cause and cause specific) in relation to SES was estimated using Cox's proportional hazards regression. We also conducted analyses stratified by calendar periods (1973 to 1979, 1980 to 1989, 1990 to 1999, and 2000 to 2005).

Results

We identified a total of 9,165 and 14,744 patients with AML and MM, respectively. Overall, higher white-collar workers had a lower mortality than other SES groups for both AML (P = .005) and MM (P < .005). In AML patients, a consistently higher overall mortality was observed in blue-collar workers compared with higher white-collar workers in the last three periods (hazard ratio [HR], 1.26; 95% CI, 1.05 to 1.51; HR, 1.23; 95% CI, 1.05 to 1.45; HR, 1.28; 95% CI, 1.04 to 1.57, respectively). In MM, no difference was observed in the first two calendar periods. However, in 1990 to 1999, self-employed (HR, 1.18; 95% CI, 1.02 to 1.37), blue-collar workers (HR, 1.18; 95% CI, 1.04 to 1.32), and retired (HR, 1.45; 95% CI, 1.16 to 1.80) had a higher mortality compared to higher white-collar workers. In 2000 to 2005, blue-collar workers had a higher mortality (HR, 1.31; 95% CI, 1.07 to 1.60) compared with higher white-collar workers.

Conclusion

SES was significantly associated with survival in both AML and MM. Most conspicuously, a lower mortality was observed among the highest SES group during more recent calendar periods. Differences in management, comorbidity, and lifestyle, are likely factors to explain these findings.
Pretreatment Health Behaviors Predict Survival Among Patients With Head and Neck Squamous Cell Carcinoma
Authors: Duffy Sonia A. , Ronis David L. , McLean Scott , Fowler Karen E. , Gruber Stephen B. , Wolf Gregory T. , Terrell Jeffrey E.
Published: March 2009

Purpose

Our prior work has shown that the health behaviors of head and neck cancer patients are interrelated and are associated with quality of life; however, other than smoking, the relationship between health behaviors and survival is unclear.

Patients and Methods

A prospective cohort study was conducted to determine the relationship between five pretreatment health behaviors (smoking, alcohol, diet, physical activity, and sleep) and all-cause survival among 504 head and neck cancer patients.

Results

Smoking status was the strongest predictor of survival, with both current smokers (hazard ratio [HR] = 2.4; 95% CI, 1.3 to 4.4) and former smokers (HR = 2.0; 95% CI, 1.2 to 3.5) showing significant associations with poor survival. Problem drinking was associated with survival in the univariate analysis (HR = 1.4; 95% CI, 1.0 to 2.0) but lost significance when controlling for other factors. Low fruit intake was negatively associated with survival in the univariate analysis only (HR = 1.6; 95% CI, 1.1 to 2.1), whereas vegetable intake was not significant in either univariate or multivariate analyses. Although physical activity was associated with survival in the univariate analysis (HR = 0.95; 95% CI, 0.93 to 0.97), it was not significant in the multivariate model. Sleep was not significantly associated with survival in either univariate or multivariate analysis. Control variables that were also independently associated with survival in the multivariate analysis were age, education, tumor site, cancer stage, and surgical treatment.

Conclusion

Variation in selected pretreatment health behaviors (eg, smoking, fruit intake, and physical activity) in this population is associated with variation in survival.