bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of POSSUM scoring system in patients with gastric cancer undergoing D2-gastrectomy
Authors: Bollschweiler Elfriede , Lubke Thomas , Monig Stefan P , Holscher Arnulf H
Published: April 2005

Background

Risk adjustment and stratification play an important role in quality assurance and in clinical research. The Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) is a patient risk prediction model based on 12 patient characteristics and 6 characteristics of the surgery performed. However, because the POSSUM was developed for quality assessment in general surgical units, its performance within specific subgroups still requires evaluation.

The aim of the present study was to assess the accuracy of POSSUM in predicting mortality and morbidity in patients with gastric cancer undergoing D2-gastrectomy.

Methods

137 patients with gastric cancer undergoing gastrectomy were included in this study. Detailed, standardized risk assessments and thorough documentation of the post-operative courses were performed prospectively, and the POSSUM scores were then calculated.

Results

The 30- and 90- day mortality rates were 3.6% (n = 5) and 5.8% (n = 8), respectively. 65.7% (n = 90) of patients had normal postoperative courses without major complications, 14.6% (n = 20) had moderate and 13.9% (n = 19) had severe complications. The number of mortalities predicted by the POSSUM-Mortality Risk Score (R1) was double the actual number of mortalities occurring in the median and high-risk groups, and was more than eight times the actual number of mortalities occurring in the low-risk group (R1 < 20%). However, the calculated R1 predicted rather well in terms of severe morbidity or post-operative death in each risk group: in predicted low risk patients the actual occurrence rate (AR) of severe morbidity or post-operative death was 14%, for predicted medium risk patients the AR was 23%, and for predicted high risk patients the AR was 50% (p < 0.05). The POSSUM-Morbidity Risk Score (R2) overestimated the risk of morbidity.

Conclusion

The POSSUM Score may be beneficial and can be used for assessment of the peri- and post-operative courses of patients with gastric carcinoma undergoing D2-gastrectomy. However, none of the scores examined here are useful for preoperative prediction of postoperative course.
CD34+ cells cultured in stem cell factor and interleukin-2 generate CD56+ cells with antiproliferative effects on tumor cell lines
Authors: Sconocchia Giuseppe , Provenzano Maurizio , Rezvani Katayoun , Li Jongming , Melenhorst Jos , Hensel Nancy , Barrett A John
Published: April 2005

In vitro stimulation of CD34+ cells with IL-2 induces NK cell differentiation. In order to define the stages of NK cell development, which influence their generation from CD34 cells, we cultured G-CSF mobilized peripheral blood CD34+ cells in the presence of stem cell factor and IL-2. After three weeks culture we found a diversity of CD56+ subsets which possessed granzyme A, but lacked the cytotoxic apparatus required for classical NK-like cytotoxicity. However, these CD56+ cells had the unusual property of inhibiting proliferation of K562 and P815 cell lines in a cell-contact dependent fashion.
Microtubule plus-ends reveal essential links between intracellular polarization and localized modulation of endocytosis during division-plane establishment in plant cells
Authors: Dhonukshe Pankaj , Mathur Jaideep , Hülskamp Martin , Gadella Theodorus WJ
Published: April 2005

Background

A key event in plant morphogenesis is the establishment of a division plane. A plant-specific microtubular preprophase band (PPB) accurately predicts the line of cell division, whereas the phragmoplast, another plant-specific array, executes cell division by maintaining this predicted line. Although establishment of these specific arrays apparently involves intracellular repolarization events that focus cellular resources to a division site, it still remains unclear how microtubules position the cell division planes. Here we study GFP-AtEB1 decorated microtubule plus-ends to dissect events at the division plane.

Results

Early mitotic events included guided growth of endoplasmic microtubules (EMTs) towards the PPB site and their coincident localization with endocytic vesicles. Consequently, an endosomal belt lay in close proximity to the microtubular PPB at its maturation and was maintained during spindle formation. During cytokinesis, EMTs radiated from the former spindle poles in a geometrical conformation correlating with cell-plate navigation and tilt-correction. Naphthylphtalamic acid (NPA), an inhibitor of polar auxin efflux, caused abnormal PPBs and shifted division planes.

Conclusion

Our observations reveal a spatio-temporal link between microtubules and intracellular polarization essential for localized endocytosis and precise establishment of the division plane in plants. Additionally, they implicate the growth regulator, auxin, in this important cellular event.
Life after 45 and before 60: the Retrovirology Prize
Authors: Jeang Kuan-Teh
Published: April 2005

Retrovirology announces an annual prize to recognize one outstanding mid-career retrovirologist.
Barriers to coliphage infection of commensal intestinal flora of laboratory mice
Authors: Kasman Laura M
Published: April 2005

Background

Growth characteristics of coliphage viruses indicate that they are adapted to live with their Eschericia coli hosts in the intestinal tract. However, coliphage experimentally introduced by ingestion persist only transiently if at all in the gut of humans and other animals. This study attempted to identify the barriers to long term establishment of exogenous coliphage in the gastrointestinal (GI) tracts of laboratory mice. Intestinal contents were screened for the presence of coliphage and host bacteria, and strains of E. coli bacteria from different segments of the GI tract were tested for susceptibility to six common laboratory coliphages.

Results

Contrary to expectations, coliphage were not evident in the GI tracts of laboratory mice, although they were occasionally detected in feces. Commensal flora showed extreme variability within groups of mice despite identical handling and diet. Less than 20% of 48 mice tested carried E. coli in their gut, and of 22 commensal E. coli strains isolated and tested, 59% were completely resistant to infection by lambda, M13, P1, T4, T7, and PhiX174 coliphage. Lysogeny could not be demonstrated in the commensal strains as mitomycin C failed to induce detectable phage. Pre-existing immunity to phages was not evident as sera and fecal washes did not contain significant antibody titers to six laboratory phage types.

Conclusion

Lack of sufficient susceptible host bacteria seems to be the most likely barrier to establishment of new coliphage infections in the mouse gut.
Characterization of CCL20 secretion by human epithelial vaginal cells: involvement in Langerhans cell precursor attraction
Authors: Cremel Magali , Berlier Willy , Hamzeh Hind , Cognasse Fabrice , Lawrence Philip , Genin Christian , Bernengo Jean-Claude , Lambert Claude , Dieu-Nosjean Marie-Caroline , Delézay Olivier
Published: April 2005

Mucosa represents the main site of pathogen/cell interactions. The two main types of cells forming the epithelial structure [epithelial cells and Langerhans cells (LC)] coordinate the first defense responses to avoid infection. To evaluate the involvement of epithelial cells in the early steps leading to a specific adaptive immune response, we have studied the interactions between vaginal epithelial and LC through the establishment of a human vaginal epithelial mucosa. We demonstrate that normal human vaginal epithelial cells constitutively secrete the chemokine macrophage inflammatory protein 3α/CC chemokine ligand 20 (CCL20), known to recruit LC precursors (LCps) selectively via its cognate CC chemokine receptor 6 (CCR6). This secretion is up-regulated by the proinflammatory cytokine interleukin-1β through the nuclear factor-κB pathway. Similar results were obtained with the human vaginal epithelial cell line SiHa, which displays numerous homologies with normal vaginal cells. The chemotactic activity of the secreted CCL20 was demonstrated by its ability to attract LCp CCR6+. Moreover, the use of neutralizing polyclonal antibodies directed against the CCL20 molecule abolished this migration completely, suggesting that CCL20 is the main attracting factor for LCps, which is produced by the vaginal cells. These data indicate that vaginal epithelial cells play an important role in the immunological defense by attracting immune cells to the site of epithelial/pathogen contact.
Interpretation of magnetic data using an enhanced local wavenumber (ELW) method
Authors: Salem Ahmed , Ravat Dhananjay , Smith Richard , Ushijima Keisuke
Published: April 2005

This paper presents an enhancement of the local-wavenumber method (named ELW for “enhanced local wavenumber”) for interpretation of profile magnetic data. This method uses the traditional and phase-rotated local wavenumbers to produce a linear equation as a function of the model parameters. The equation can be solved to determine the horizontal location and depth of a 2D magnetic body without specifying a priori information about the nature of the sources. Using the obtained source-location parameters, the nature of the source can then be inferred. The method was tested using theoretical simulations with random noise over a dike body. It was able to provide both the location and an index characterizing the nature of the source body. The practical utility of the method is demonstrated using field examples over dikelike bodies from Canada and Egypt.
Parameter estimation in orthorhombic media using multicomponent wide-azimuth reflection data
Authors: Grechka Vladimir , Pech Andrés , Tsvankin Ilya
Published: April 2005

Orthorhombic models with a horizontal symmetry plane adequately describe seismic signatures recorded over many naturally fractured reservoirs. The inversion of wide-azimuth traveltimes of PP and SS (the fast [Formula: see text] and slow [Formula: see text]) reflections are discussed for Tsvankin's anisotropic parameters and the azimuths of the vertical symmetry planes of orthorhombic media. If shear waves are not excited, SS traveltimes can be found from PP and PS (converted-wave) data, which makes the method applicable to offshore surveys. The feasibility of parameter estimation is strongly dependent on reflector dip and orientation. For a horizontal reflector beneath a single orthorhombic layer, the vertical velocities and reflector depth cannot be found from conventional-spread reflection traveltimes alone. If the reflector is dipping, the inversion is ambiguous when the dip plane is close to one of the vertical symmetry planes of the orthorhombic layer above it. The parameter estimation becomes possible if the dip direction deviates by more than 10° from the nearest symmetry plane. We apply multicomponent stacking velocity tomography to perform velocity analysis for stratified orthorhombic models composed of homogeneous layers separated by plane or curved interfaces. The tomographic algorithm, which operates with the normal-moveout (NMO) ellipses, zero-offset traveltimes, and reflection time slopes of PP- and SS-waves, is designed to build the orthorhombic velocity model in the depth domain by estimating the anisotropic parameters and the shapes of the reflecting interfaces. Numerical tests show that for layered orthorhombic media, it is necessary to put constraints on the vertical velocities to avoid instability in the inversion of noise-contaminated reflection data.
A constitutive equation and generalized Gassmann modulus for multimineral porous media
Authors: Carcione José M. , Helle Hans B. , Santos Juan E. , Ravazzoli Claudia L.
Published: April 2005

We derive the time-domain stress-strain relation for a porous medium composed of n − 1 solid frames and a saturating fluid. The relation holds for nonuniform porosity and can be used for numerical simulation of wave propagation. The strain-energy density can be expressed in such a way that the two phases (solid and fluid) can be mathematically equivalent. From this simplified expression of strain energy, we analogize two-, three-, and n-phase porous media and obtain the corresponding coefficients (stiffnesses). Moreover, we obtain an approximation for the generalized Gassmann modulus. The Gassmann modulus is the bulk modulus of a saturated porous medium whose matrix (frame) is homogeneous. That is, the medium consists of two homogeneous constituents: a mineral composing the frame and a fluid. Gassmann's modulus is obtained at the low-frequency limit of Biot's theory of poroelasticity. Here, we assume that all constituents move in phase, a condition similar to the dynamic compatibility condition used by Biot, by which the P-wave velocity is equal to Gassmann's velocity at all frequencies. Our results are compared with those of the Berryman-Milton (BM) model, which provides an exact generalization of Gassmann's modulus to the three-phase case. The model is then compared to the wet-rock moduli obtained by static finite-element simulations on digitized images of microstructure and is used to fit experimental data for shaly sandstones. Finally, an example of a multimineral rock (n > 3) saturated with different fluids is given.
This Issue of GEOPHYSICS
Authors: Schuster Gerard T.
Published: April 2005

In this article, the Editor of Geophysics provides an overview of all technical articles in this issue of the journal.
The influence of first language on the processing of wh-movement in English as a second language
Authors: Juffs Alan
Published: April 2005

Adult learners of English as a second language who speak Chinese ( n = 30), Japanese ( n = 28) or Spanish ( n = 46) as a first language (L1), and a comparison group of native speakers ( n = 22) read sentences that contain: (a) ungrammatical wh-extractions that violate island constraints; and (b) grammatical long-distance Subject and Object extractions from finite and nonfinite clauses. Word-by-word reading times for each sentence were collected using the self-paced reading technique. Results suggest that the presence or absence of wh-movement in the L1 and the headedness of the verb phrase in the L1 are unable to explain all of the variation between the nonnative speaker groups. Severe garden path effects were observed in Subject extractions from finite clauses, but not in extractions from nonfinite clauses, suggesting that two finite verbs next to one another may be an important factor in causing parsing break-down. Individual variation in reading time was not predictable from measures of reading span or word span in either the first or second language.
Subcutaneous administration of drugs in the elderly: survey of practice and systematic literature review
Authors: Fonzo-Christe Caroline , Vukasovic Caroline , Wasilewski-Rasca Anne-Florence , Bonnabry Pascal
Published: April 2005

Objectives and method: Survey of subcutaneous drug use and hypodermoclysis with a standardized questionnaire to 27 nursing teams and 52 physicians in a geriatric hospital department (404 beds). Evaluation of license status (CH, F, D and UK) and systematic literature review of 34 drugs used in the geriatric setting. Results: Subcutaneous route is used daily with drugs and fluids mostly for patients in palliative care (83%) or who are dehydrated (54%) when oral or IV administration is impossible (73%, 68% respectively). Morphine (98%), haloperidol (90%), furosemide (69%) and hydromorphone (56%) by bolus (36%) or slow injection over 5 min (82%) are the main drugs used and NaCl 0.9% (95%), and glucose 5%/NaCl 0.9% (31%) are commonly used for rehydration. Among the 34 drugs reviewed, only 13 (38%) are licensed for subcutaneous use in CH, UK, F or D, and only morphine (14 articles of 68) and rehydration (six articles) are evaluated in high level studies. Haloperidol and furosemide are used off-label and there are no well-designed studies supporting their subcutaneous use. Conclusion: There is a lack of information on drugs widely used by subcutaneous route in the elderly. In that context, physicians carry responsibility for the prescription.
Predicting survival in terminal cancer patients: clinical observation or quality-of-life evaluation?
Authors: Toscani Franco , Brunelli Cinzia , Miccinesi Guido , Costantini Massimo , Gallucci Michele , Tamburini Marcello , Paci Eugenio , Di Giulio Paola , Peruselli Carlo
Published: April 2005

Introduction: This study compares the relative prognostic power of clinical variables and quality-of-life (QoL) measures in a population of terminal cancer patients. Methods: A prospective cohort study in 58 Italian Palliative Care Units. Of the 601 randomly selected terminal cancer patients, 574 were followed until death in order to compare clinical and QoL variables (using the Therapy Impact Questionnaire (TIQ) as predictors of survival, and assess whether their combined implementation makes prediction more accurate. Results: The clinical variables most strongly associated with survival were dyspnoea, cachexia, Katz's ADL, oliguria, dysphagia, dehydration, liver and acute kidney failure and delirium (hazard ratios (HR) ranging from 2.10 to 3.01). Only the first four kept their strength once introduced in the Cox model (HRs ranging from 1.95 to 2.22). In the TIQ primary scale the strongest predictors were physical wellbeing, fatigue, functional status and cognitive status (HRs ranging from 1.42 to 1.71), but only fatigue showed an independent prognostic relevance (90% of selection). In the TIQ global scales, the Physical Symptom Index showed a stronger association with survival (HR 1.71) than the Therapy Impact Index (HR 1.47). The former marginally improved the prognostic power of the model when added to clinical variables. Internal validation confirmed that the results were not spurious. Conclusions: In terminal cancer patients, clinical variables are better predictors of survival than QoL. The large residual variability not accounted for by the model (: ≈ 70%) suggests that survival is also influenced by factors unlikely to be identified in a survey.
Opioid purchases and expenditure in nine western European countries: ‘Are we killing off morphine?’
Authors: De Conno Franco , Ripamonti Carla , Brunelli Cinzia
Published: April 2005

Background: In clinical practice the major role of opioid drugs is the management of malignant and nonmalignant pain. The primary aim of this study is to evaluate the trend in sales of four opioid analgesic drugs (codeine, tramadol, morphine, fentanyl), from wholesalers to community pharmacies, as an indicator of opioid consumption in nine European countries in 2001, 2002 and 2003. Secondary aims are to compare: (a) the amount of each drug purchased by different countries in 2003; (b) the average price for each drug in the different countries in 2003; and (c) the total expenditure for each opioid from 2001 to 2003. Methods: Data from the Statistical Report on drugs purchased by pharmacies was supplied by IMS Health, an internationally accepted information provider for the pharmaceutical and health care industries. Finding: In the period 2001-2003, while the percentage increase of purchases of fentanyl and tramadol was considerable, that of morphine was the lowest in most of the nine countries. The largest consumer of codeine was the UK and of tramadol was Belgium. The consumption of morphine was the lowest reported in all the countries together and was three times lower than that of transdermal fentanyl. There was a high variability in the costs of the opioids among the different countries. In 2003, the total expenditure on fentanyl reached the total expenditure on tramadol, followed by codeine. Morphine presents the lowest expenditure in all nine countries and over all three years. Interpretation: These results open up many questions. What factors influence opioid purchasing and costs in these European countries? It would be interesting to have the answers from those people who know the actual situation in the individual countries.
Access and equity in HIV/AIDS palliative care: a review of the evidence and responses
Authors: Harding Richard , Easterbrook Philippa , Higginson Irene J , Karus Dan , Raveis Victoria H , Marconi Katherine
Published: April 2005

The high prevalence of pain and other symptoms throughout the HIV disease trajectory, the need for management of side effects related to antiretroviral therapy, the continuing incidence of cancers and new emerging co-morbidities as a result of extended life expectancy under new therapeutic regimes, and the ongoing need for terminal care all prove the curative versus palliative dichotomy to be inappropriate. Although there is evidence for both need and effectiveness of palliative care in HIV patient care, access is often poor and care less than optimal.

This review aimed to identify evidence of barriers and inequalities in HIV palliative care in order to inform policy and service development. Biomedical databases were searched using a specific strategy, and evidence extracted into the barrier and inequity categories of patient, clinician, service and disease factors. A model of the barriers and inequalities is presented from the evidence. Recommendations are made from the evidence for promoting access and outcomes through integrated palliative care from diagnosis to end-of-life, alongside antiretroviral therapy when initiated. Service responses that have attempted to increase access to palliative care are presented.
Cooperating with a palliative home-care team: expectations and evaluations of GPs and district nurses
Authors: Goldschmidt Dorthe , Groenvold Mogens , Johnsen Anna Thit , Strömgren Annette S , Krasnik Allan , Schmidt Lone
Published: April 2005

Background: Palliative home-care teams often cooperate with general practitioners (GPs) and district nurses. Our aim was to evaluate a palliative home-care team from the viewpoint of GPs and district nurses. Methods: GPs and district nurses received questionnaires at the start of home-care and one month later. Questions focussed on benefits to patients, training issues for professionals and cooperation between the home-care team and the GP/ district nurse. A combination of closed-and open-ended questions was used. Results: Response rate was 84% (467/553). Benefits to patients were experienced by 91%, mainly due to improvement in symptom management, ‘security’, and accessibility of specialists in palliative care. After one month, 57% of the participants reported to have learnt aspects of palliative care, primarily symptom control, and 89% of them found cooperation satisfactory. Dissatisfaction was caused mainly by lack of information from the home-care team to primary-care professionals. Conclusion: GPs and district nurses welcomed the palliative home-care team and most experienced benefits to patients. Strengthened communication initiated by the home-care team would enhance cooperation.
An investigation of MRSA infection in a hospice
Authors: Ali Simone , Sykes Nigel , Flock Petra , Hall Emma , Buchan Janet
Published: April 2005

This study investigated the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) carriage and infection among patients admitted to a hospice. Under the existing policy at this hospice, only patients admitted from hospital wards where MRSA is known to be present are screened for MRSA prior to transfer. Hence the investigators were keen to study patients transferred from settings other than this. One hundred and twenty patients, all either from the community or from hospital wards without known MRSA, were entered into the study (‘study group’) and were swabbed for MRSA on admission to the hospice. Swabbing was continued at weekly intervals until discharge or death. Of the 120 patients, seven (5.8%) were MRSA positive on admission. A further four patients who were negative on admission showed MRSA on later swabs. Another two patients developed symptomatic infections during admission that were proven to be due to MRSA, but neither of these had shown MRSA on any swabs taken during the study. During the study period, a separate group of 156 patients was swabbed routinely before transfer from hospital wards where MRSA was known to be present in accordance with hospice policy (‘non-study group’). Of these patients, 11 (7.1%) were found to be colonized with MRSA but none developed associated symptomatic infection. It appears that the risk of symptomatic infection with MRSA in hospice patients is low, and the burden placed on this vulnerable group by conventional eradication regimes may be disproportionate to any benefit derived.
The Pyrenees as place: Lefebvre as guide
Authors: Entrikin J. Nicholas , Berdoulay Vincent
Published: April 2005

Geographers have taken a portion of the voluminous writings of the French sociologist Henri Lefebvre and put them at the center of current disciplinary debates about space and place. In doing so they have constructed an intellectual biography of Lefebvre that highlights his connection to the Pyrenees region of southwestern France. The theoretical arguments of Lefebvre are often translated to fit within disciplinary themes, and the biographical elements are interpolated to give an experiential or lived basis to the theory. Lefebvre's geographical interpretation of his ancestral region in a popular text, Pyrénées, gives additional and alternative insights into his complicated relationship to this region and the difficulties of representing place and region. This text illustrates both elements of Lefebvre's social theory and classical geographical themes about narrating place and region.
Hyperhomocyst(e)inemia impairs angiogenesis in a murine model of limb ischemia
Authors: Bosch-Marcé Marta , Pola Roberto , Wecker Andrea B , Silver Marcy , Weber Alberto , Luedemann Corinne , Curry Cynthia , Murayama Toshinori , Kearney Marianne , Yoon Young-sup , Malinow M René , Asahara Takayuki , Isner Jeffrey M , Losordo Douglas W
Published: April 2005

Hyperhomocyst(e)inemia (HH) is an established independent risk factor for coronary, cerebral and peripheral vascular diseases. Recent studies have indicated that certain cardiovascular risk factors, including diabetes and hypercholesterolemia, impair expression of vascular endothelial growth factor (VEGF) and endogenous angiogenesis. In this study, we investigate the impact of moderate HH on angiogenesis and VEGF pathway in a mouse model of hindlimb ischemia. Upon induction of unilateral hindlimb ischemia, endogenous angiogenesis, expression of VEGF, and phosphorylation of the VEGF receptor Flk-1 were evaluated in mice heterozygous for a deletion of the cystathionine -synthase gene (CBS) and compared with those observed in CBS/mice. CBS/mice exhibit moderate HH, as demonstrated by measuring plasma total homocyst(e)ine (tHcy) levels, which were significantly higher in these animals compared with CBS/mice (4.77 0.82 vs 2.10 0.28, p 0.01). Twenty-eight days after induction of ischemia, hindlimb blood flow was significantly reduced in CBS/mice compared with CBS/animals (0.49 0.03, n 12 vs 0.71 0.09, n 10; p 0.05). In addition, there was a significant negative correlation between plasma homocyst(e)ine levels and the laser Doppler perfusion ratio in CBS/mice (p 0.0087, r 0.7171). While VEGF expression and Flk-1 phosphorylation were not impaired in the ischemic muscles of CBS/mice, phosphorylation of the endothelial cell survival factor Akt was significantly inhibited by homocyst(e)ine in a dose-dependent manner in human umbilical vein endothelial cell (HUVECs) in vitro. In conclusion, our findings demonstrate that endogenous angiogenesis is inversely related to plasma levels of homocyst(e)ine in genetically engineered, heterozygous mice with moderate HH. This impairment, however, is not dependent on reduced expression of VEGF or impaired phosphorylation of its receptor Flk-1. In contrast, our data suggest that impaired Akt phosphorylation mediates the impairment of angiogenesis associated with HH.
Endovascular treatment of an occluded axillofemoral bypass graft
Authors: Slovut David P , Bacharach J Michael
Published: April 2005

Unsuspected subclavian or axillary disease may cause failure of axillofemoral bypass grafts. A 52-year-old woman who underwent left axillofemoral bypass grafting 5 years ago presented with 24 h of left foot pain. Routine duplex ultrasonography 2 months previously demonstrated velocities throughout the graft >80 cm/s. Emergent angiography revealed thrombotic occlusion of the axillofemoral bypass graft. Both rheolytic thrombectomy and pulse spray thrombolysis using tissue plasminogen activator were used to restore graft patency. Arterial pressure waveform and pressure remained damped throughout the graft; a 50 mmHg gradient was found from the descending thoracic aorta to the mid-left subclavian artery. Angiography revealed a 70% diameter stenosis at the origin of the left subclavian artery. Following balloon angioplasty and stent placement, the pressure gradient was eliminated. In conclusion, careful evaluation of arterial inflow to bypass grafts is critical for ensuring long-term graft patency.
Point-of-care (POC) versus central laboratory instrumentation for monitoring oral anticoagulation
Authors: Dorfman David M , Goonan Ellen M , Boutilier M Kay , Jarolim Petr , Tanasijevic Milenko , Goldhaber Samuel Z
Published: April 2005

Point-of-care (POC) instruments employing fingerstick whole blood to monitor patients treated with warfarin are a popular alternative to complex, central laboratory coagulation analyzers utilizing citrated plasma derived from venipuncture. We investigated the accuracy of two widely utilized POC instruments for oral anticoagulation monitoring compared with a central laboratory instrument. Instrument-to-instrument variation differed for the two POC instruments, which correlated with the central laboratory instrument, but exhibited positive bias of 0.24-0.35 INR units. Positive bias increased as the INR values increased. We conclude that clinicians should exercise caution when interpreting results generated by POC monitors, particularly at high INR values. A high POC measurement of INR does not necessarily warrant decreasing the warfarin dose. Instead, a predefined cut-off range for high INR values generated by POC instruments should mandate confirmatory testing with central laboratory instrumentation.
Physical and emotional aspects of self–reported health status: a two–factor model of the short–form BreathingProblems Questionnaire
Authors: Haavel E , Hyland M E , Engvik H
Published: April 2005

The short version of the Breathing Problems Questionnaire (BPQ) is used as an outcome tool in pulmonary assessment. The aim of the study was to establish the validity of scoring BPQ with two subscales, reflecting emotional and physical components of health–related quality of life (HRQoL). Two subscales were suggested by exploratory factor analysis conducted on a data set of 97 patients with chronic obstructive pulmonary disease (COPD). Both subscales were significantly associated with the 6 minute walk test, total quality of life, and emotional stability. Only the physical subscale was significantly associated with FEVI, and only the emotional subscale was significantly associated with happiness. Overall, the sizes of the different correlations are consistent with the conceptual differentiation of the two subscales. We suggest that evaluation of rehabilitation can be made with the two subscales as well as an overall score of the BPQ.
Inpatient pulmonary rehabilitation: does it make sense?
Authors: Clini E M , Romagnoli M
Published: April 2005

Among the nonpharmacological therapies, pulmonary rehabilitation (PR) is particularly appropriate for patients with chronic respiratory impairment who, despite any optimal drug management, are still symptomatic and experience restriction in every day activities. Pulmonary rehabilitation performed in inpatient, outpatient, or home settings demonstrates short–and long–term clinical efficacy. Although disease severity does not inherently dictate candidacy for exercise training, the degree of physiological and functional impairment may influence setting in which the training should occur. Therefore, inpatient rehabilitation is generally best–suited for the most sick and most disabled patients. The overall results from the literature confirm that the inpatient setting for a PR program is a feasible option and does not necessarily result in higher direct costs when balanced against duration and effectiveness in terms of improved outcomes.
Insights into the Biogenesis of Lysosome‐Related Organelles from the Study of the Hermansky‐Pudlak Syndrome
Authors: BONIFACINO JUAN S.
Published: April 2005

Abstract: Lysosome‐related organelles (LROs) are a family of cell‐type‐specific organelles that include melanosomes, platelet dense bodies, and cytotoxic T cell granules. The name, LRO, recognizes the fact that all of these organelles contain subsets of lysosomal proteins in addition to cell‐type‐specific proteins. The recent identification of genetic disorders that cause combined defects in several of these organelles indicates that they share common biogenetic pathways. Studies of one of these disorders, the Hermansky‐Pudlak syndrome (HPS), have provided helpful insights into the molecular machinery involved in LRO biogenesis. HPS is a genetically heterogeneous disorder caused by mutations in any of 7 genes in humans and 15 genes in mice. These genes encode subunits of 4 multi‐protein complexes named AP‐3, BLOC‐1, BLOC‐2 and BLOC‐3, in addition to miscellaneous components of the general protein trafficking machinery. The AP‐3 complex is a coat protein involved in vesicle formation and cargo selection in the endosomal‐lysosomal system. One of these cargo molecules is the melanosomal enzyme, tyrosinase, the missorting of which may explain the defective melanosomes in AP‐3‐deficient humans and mice. The function of the BLOC complexes is unknown, although they are thought to mediate either vesicle tethering/fusion or cytoplasmic dispersal of LROs. Further studies of these complexes should contribute to the elucidation of the mechanisms of LRO biogenesis and the pathogenesis of HPS.
Neuroendocrine Basis of Human Disease
Authors: GUILLEMIN ROGER
Published: April 2005

Abstract: This paper is a short review of the traditionally obvious diseases of neuroendocrine origin (diabetes insipidus, Kallman syndrome, etc.), but also of the newly recognized participation of several peptides originally characterized in the hypothalamus and of their receptors, in a series of diseases, both in internal medicine and in psychiatry (rheumatoid arthritis, inflammation, carcinoids, anxiety, depression, etc.). The concept of neuropeptides is now vastly expanded, as these molecules and their several receptors are now known to be widely distributed throughout the brain and the periphery with increasing evidence of paracrine and autocrine modes of action.
Therapeutic Effects of Tolvaptan, a Potent, Selective Nonpeptide Vasopressin V2 Receptor Antagonist, in Rats with Acute and Chronic Severe Hyponatremia
Authors: Miyazaki Toshiki , Yamamura Yoshitaka , Onogawa Toshiyuki , Nakamura Shigeki , Kinoshita Shizuo , Nakayama Sunao , Fujiki Hiroyuki , Mori Toyoki
Published: April 2005

The therapeutic efficacy of tolvaptan (OPC-41061), a potent, selective nonpeptide vasopressin V2 receptor antagonist, on acute and chronic severe hyponatremia was assessed in rats. Experiments were designed to demonstrate the efficacy of tolvaptan reducing mortality in an acute model, and controlling the extent of serum sodium elevation without causing abnormal animal behavior suggesting neurological symptoms in a chronic model. In the acute model, rats developed rapidly progressive, severe hyponatremia by continuous sc infusion of [deamino-Cys1, d-Arg8]-vasopressin (10 ng/h) and forced water-loading (additional 10% initial body weight per day). By d 6, untreated rats had a 47% mortality rate. However, rats treated with repeated oral administrations of tolvaptan (1, 3, and 10 mg/kg) produced dose-dependent aquaresis (i.e. urine volume increased and urine osmolality decreased) that resulted in a gradual increase in plasma sodium concentration. Consequently, tolvaptan treatment reduced mortality and, at higher doses, resulted in no observed deaths. In the gradual model, rats receiving a continuous sc infusion of [deamino-Cys1, d-Arg8]-vasopressin (1 ng/h) combined with a liquid diet were induced to stable, severe hyponatremia (∼110 mEq/liter), which lead to increased organ weight and water content. Rats receiving dose titrations of tolvaptan (0.25, 0.5, 1, 2, 4, and 8 mg/kg) increased plasma sodium to healthy levels without causing abnormal animal behavior suggesting neurological symptoms or death, improved hyponatremia-driven increases in wet weight and water content in the organs. Thus, in animal models, analogous to the hyponatremia forms seen in humans, tolvaptan presents exciting therapeutic implications in the management of patients with severe hyponatremia.
Estrogen Receptor-β Is Critical to Granulosa Cell Differentiation and the Ovulatory Response to Gonadotropins
Authors: Couse John F. , Yates Mariana M. , Deroo Bonnie J. , Korach Kenneth S.
Published: April 2005

The process of granulosa cell differentiation that occurs in preovulatory follicles is dependent on FSH but requires augmentation by estradiol. To determine which estrogen receptor (ER) form mediates the effects of estradiol during gonadotropin-induced follicle growth, differentiation, and rupture, we characterized the response of ERα- and ERβ-null mice to gonadotropin-induced ovulation. Immature mice were treated with an ovulatory regimen of exogenous gonadotropins and tissues were collected at distinct time points for morphological, biochemical, gene expression, and immunohistochemical analyses. Granulosa cells of ERβ knockout (ERKO) preovulatory follicles exhibited an attenuated response to FSH-induced differentiation, as evident by reduced aromatase activity and estradiol synthesis, and insufficient expression of LH receptor. As a result, βERKO ovaries were unable to fully respond to an ovulatory bolus of gonadotropin, leading to a reduced rate of follicle rupture; insufficient induction of prostaglandin-synthase 2 and progesterone receptor; an aberrant increase in aromatase activity and plasma estradiol; and incomplete expansion of the cumulus-oocyte complex. Parallel characterization of αERKO females indicated a minimal role for ERα in granulosa cell differentiation, ovulation, and the concomitant changes in gene expression, although some abnormalities were revealed. These studies demonstrate that ERβ-mediated estradiol actions are vital to FSH-induced granulosa cell differentiation; and in the absence of ERβ, preovulatory follicles are deficient in the necessary cellular organization (i.e. antrum and cumulus oocyte complex), enzymatic activity (i.e. capacity to convert androgen precursor to estradiol), and receptor signaling pathways (i.e. LH receptor) to respond to a gonadotropin surge and expel a healthy oocyte.
A Peroxisome Proliferator-Activated Receptor α/γ Dual Agonist with a Unique in Vitro Profile and Potent Glucose and Lipid Effects in Rodent Models of Type 2 Diabetes and Dyslipidemia
Authors: Reifel-Miller Anne , Otto Keith , Hawkins Eric , Barr Robert , Bensch William R. , Bull Chris , Dana Sharon , Klausing Kay , Martin Jose-Alfredo , Rafaeloff-Phail Ronit , Rafizadeh-Montrose Chahrzad , Rhodes Gary , Robey Roger , Rojo Isabel , Rungta Deepa , Snyder David , Wilbur Kelly , Zhang Tony , Zink Richard , Warshawsky Alan , Brozinick Joseph T.
Published: April 2005

LSN862 is a novel peroxisome proliferator-activated receptor (PPAR)α/γ dual agonist with a unique in vitro profile that shows improvements on glucose and lipid levels in rodent models of type 2 diabetes and dyslipidemia. Data from in vitro binding, cotransfection, and cofactor recruitment assays characterize LSN862 as a high-affinity PPARγ partial agonist with relatively less but significant PPARα agonist activity. Using these same assays, rosiglitazone was characterized as a high-affinity PPARγ full agonist with no PPARα activity. When administered to Zucker diabetic fatty rats, LSN862 displayed significant glucose and triglyceride lowering and a significantly greater increase in adiponectin levels compared with rosiglitazone. Expression of genes involved in metabolic pathways in the liver and in two fat depots from compound-treated Zucker diabetic fatty rats was evaluated. Only LSN862 significantly elevated mRNA levels of pyruvate dehydrogenase kinase isozyme 4 and bifunctional enzyme in the liver and lipoprotein lipase in both fat depots. In contrast, both LSN862 and rosiglitazone decreased phosphoenol pyruvate carboxykinase in the liver and increased malic enzyme mRNA levels in the fat. In addition, LSN862 was examined in a second rodent model of type 2 diabetes, db/db mice. In this study, LSN862 demonstrated statistically better antidiabetic efficacy compared with rosiglitazone with an equivalent side effect profile. LSN862, rosiglitazone, and fenofibrate were each evaluated in the humanized apoA1 transgenic mouse. At the highest dose administered, LSN862 and fenofibrate reduced very low-density lipoprotein cholesterol, whereas, rosiglitazone increased very low-density lipoprotein cholesterol. LSN862, fenofibrate, and rosiglitazone produced maximal increases in high-density lipoprotein cholesterol of 65, 54, and 30%, respectively. These findings show that PPARγ full agonist activity is not necessary to achieve potent and efficacious insulin-sensitizing benefits and demonstrate the therapeutic advantages of a PPARα/γ dual agonist.
Efficiency of ideal fuel cell and Carnot cycle from a fundamental perspective
Authors: Hassanzadeh H , Mansouri S H
Published: April 2005

In this paper, we accept the fact that fuel cell and heat engine efficiencies are both constrained by the second law of thermodynamics and neither one is able to break this law. However, we have shown that this statement does not mean the two systems should have the same maximum thermal efficiency when being fed by the same amounts of chemical reactants. The intrinsic difference between fuel cells (electrochemical systems) and heat engines (combustion engines) efficiencies is a fundamental one with regard to the conversion of chemical energy of reactions into electrical work. The sole reason has been shown to be due to the combustion irreversibility of the latter. This has led to the statement that fuel cell efficiency is not limited by the Carnot cycle. Clarity is achieved by theoretical derivations and several numerical examples.
A polymer electrolyte membrane fuel cell model with multi-species input
Authors: Rama P , Chen R , Thring R
Published: April 2005

With the emerging realization that low temperature, low pressure polymer electrolyte membrane fuel cell (PEMFC) technologies can realistically serve for power-generation of any scale, the value of comprehensive simulation models becomes equally evident. Many models have been successfully developed over the last two decades. One of the fundamental limitations among these models is that up to only three constituent species have been considered in the dry pre-humidified anode and cathode inlet gases, namely oxygen and nitrogen for the cathode and hydrogen, carbon dioxide, and carbon monoxide for the anode. In order to extend the potential of theoretical study and to bring the simulation closer towards reality, in this research, a 1D steady-state, low temperature, isothermal, isobaric PEMFC model has been developed. The model accommodates multi-component diffusion in the porous electrodes and therefore offers the potential to further investigate the effects of contaminants such as carbon monoxide on cell performance. The simulated model polarizations agree well with published experimental data. It opens a wider scope to address the remaining limitations in the future with further developments.
Algebraic method for efficient adaption of structured grids to fluctuating geometries
Authors: Bohn D E , Moritz N
Published: April 2005

An efficient method for adaption of a structured grid to fluctuating turbine blade geometry is presented based on an algebraic algorithm. The objective of the application of this method is to analyse the aerodynamic, thermal and rotational load of rotating and cooled blades with a conjugate approach. The grid adaption method is validated with two test cases by using a simple deformation model considering the blade as a torsion spring. This model ensures a strong coupling between aerodynamic load and deformation of the blades. Thus, the stability of the numerical code can be analysed. The calculations show that convergence for the blade deformation is reached very soon. Even for great blade deformation the algebraic grid adaption method generates no negative cell volumes although this cannot be guaranteed by an algebraic algorithm.
Power and the Emergence of Complex Polities in the Peruvian Preceramic
Authors: Haas Jonathan , Creamer Winifred , Ruiz Alvaro
Published: April 2005

This chapter looks at the role of irrigation agriculture, warfare (lack thereof), and religion in the origins and development of the power relationship in an extraordinary early political system. Data are drawn from a cluster of small valleys on the north‐central Peruvian coast–a region known as the Norte Chico–where recent research has revealed a pattern of more than 20 large sites. These sites all have major monumental architecture and were occupied in the third millennium B.C. This concentration of major residential and ceremonial centers, thriving between 3000 and 1800 B.C., serves as an ideal laboratory for studying the florescence and subsequent development of one of the first complex, centralized political systems to arise in the Andean region. These sites are directly associated with the introduction of irrigation in the area and a rapid transition from hunting and gathering to agriculture. In what appears to be a truly “pristine” situation, this complex of sites provides a window into how leaders first emerged in early centralized polities and how those leaders came to exercise significant power over their respective subject populations.
Power, Fairness, and Architecture: Modeling Early Chiefdom Development in the Central Andes
Authors: Stanish Charles , Haley Kevin J.
Published: April 2005

This chapter models the development of complex architecture in simple chiefly societies in the Central Andes. We employ a theoretical framework that draws from evolutionary game theory, economic anthropology, evolutionary psychology, and comparative behavioral science. In this theoretical framework, the evolution of culture equates with the evolution of human cooperation in ever‐larger groups. As “conditional cooperators,” humans will create complex labor organizations under the appropriate conditions. Taking into account recent research in evolutionary game theory, we demonstrate how these conditions were met for the first time on the Peruvian coast and then spread to the highlands using examples from both the coast and the altiplano.
Trade and Social Power in the Southern Titicaca Basin Formative
Authors: Bandy Matthew S.
Published: April 2005

The long‐term evolution of social power has often been linked to the development of regional exchange systems. Most treatments emphasize monopolies of production or distribution of high‐value items. In this chapter I analyze the case of exchange in the Middle (Late Chiripa phase) and early Late Formative (Tiwanaku I phase) communities of the southern Lake Titicaca Basin. I suggest that the evolution of social power in these villages was related to their role as “transit communities” in a regional exchange system and that significant social and political developments can be related to shifts in prehistoric caravan routes.