bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of stents and abciximab on survival from cardiogenic shock treated with percutaneous coronary intervention
Authors: Huang Raymond , Sacks Jerome , Thai Hoang , Goldman Steven , Morrison Douglass A. , Barbiere Charles , Ohm Janet
Published: March 2005

This retrospective observational review compares patient characteristics and in‐hospital and long‐term outcomes of cohorts of patients undergoing percutaneous coronary intervention (PCI) for cardiogenic shock complicating acute myocardial infarction (MI) prior to the use of stents (as well as glycoprotein IIb/IIIa inhibitor and dual‐antiplatelet therapy) with PCI in the stent era. Cardiogenic shock remains the leading cause of hospital mortality from acute MI. This is a report of consecutive patients with cardiogenic shock complicating acute MI, without mechanical complication, referred for emergency catheterization to a single operator at two consecutive Veterans Affairs medical centers over a 15‐year period (1988 to August 2003). PCI was attempted in all 93 cases: 44 consecutive patients in the prestent era and 49 consecutive patients in the stent era. Patients with comparable extent of coronary disease, more ST elevation myocardial infarction, multiple areas of infarction, and greater comorbidity underwent PCI in the stent era. Nevertheless, PCI in the stent era was associated with higher rates of acute success and improved in‐hospital survival. Kaplan‐Meier curves and log‐rank testing showed highly significant improvement in overall survival (P < 0.0001). Logistic regression of in‐hospital survival demonstrated that stent use (collinear with glycoprotein IIb/IIIa use and dual‐antiplatelet therapy) was significantly associated with survival in a model adjusting for extent of coronary disease and comorbidities (P = 0.007). Stents and abciximab have been associated with improved acute angiographic and procedural success of PCI for cardiogenic shock, leading to improved survival. Published 2005 Wiley‐Liss, Inc.
Percutaneous closure of an aortic prosthetic paravalvular leak with an Amplatzer duct occluder
Authors: Webb John G. , Pate Gordon E. , Munt Brad I.
Published: March 2005

Following aortic valve replacement, up to 5% of patients may develop clinically significant paravalular leaks. Reoperation is associated with higher mortality and an excess risk of recurrent paravalvular insufficiency. No specifically designed transcatheter device is available for paravalular leak repair. We describe in a patient with severe aortic prosthetic paravalvular leak the use of an Amplatzer duct occluder device resulting in effective closure and symptomatic improvement. © 2005 Wiley‐Liss, Inc.
Rapid progression of pericardial calcification in a patient with end‐stage renal disease
Authors: Marcu Constantin B. , Caracciolo Eugene , Donohue Thomas
Published: March 2005

Dialysis pericarditis is a relatively uncommon cause of pericardial constriction and may be found in patients with end‐stage renal disease receiving adequate renal replacement therapy. We present a patient with end‐stage renal disease maintained on chronic peritoneal dialysis who developed severe myopericardial calcification over a 2‐month period demonstrated by sequential chest computed tomographic scanning. The characteristic hemodynamic findings of constrictive‐effusive pericarditis, obtained during cardiac catheterization, are presented and discussed. © 2005 Wiley‐Liss, Inc.
Methanol Decomposition by the Use of an Assemble‐Type Microreactor
Authors: Maki T. , Ueyama T. , Mae K.
Published: March 2005

A flexible catalytic microreactor was developed on the basis of a new concept of element assembly. The proposed reactor consists of elements of various catalysts with large surface area and reactor elements fabricated separately, and the microspace is created by optionally assembling them. A microreactor, assembled of 21 sets of elements, was used to decompose methanol for selectively producing hydrogen. At a reaction temperature of 280 °C, methanol conversion and hydrogen yield successfully reached 93 % and 1.48, respectively. Conversion increased with decreasing size of the microchannel, keeping the ratio of H2 to CO at ca. 2. This clearly shows that the reaction in the microchannel is advantageous to the conversion and selectivity compared with those reached in a conventional fixed bed reactor.
Microstructured Components for Hydrogen Production from Various Hydrocarbons
Authors: Pfeifer P. , Bohn L. , Görke O. , Haas‐Santo K. , Schubert K.
Published: March 2005

Fuel cells for mobile and decentral electricity production are of particular interest for compliance with legal regulations concerning exhaust gas emissions and for minimizing the consumption of resources in the future. With them, higher efficiencies can be achieved, noise emissions are reduced, and environmentally relevant pollutant emissions can be avoided. A problem is the supply and storage of H2 due to its small energy densities and the heavy storage systems. An alternative is the production of hydrogen where it is needed. The system components required, such as the chemical reactor/reformer and the heat exchangers need to have very good dynamics and efficiencies. Here, microstructure technology may be a solution, as extremely high thermal and mass transfer coefficients may minimize the sizes, weights, and energy losses of the devices. The present article focuses on developments made by the Institute for Micro Process Engineering in the field of hydrogen production from methane, methanol, propane, and gasoline.
Photochemical Generation and [4+2]‐Cycloaddition of Singlet Oxygen in a Falling‐Film Micro Reactor
Authors: Jähnisch K. , Dingerdissen U.
Published: March 2005

The presented falling‐film microreactor is suited for the generation and reaction of singlet oxygen for the photo‐oxygenation of olefins and allows for the first time conversions on a preparative scale. Due to the short holdup the concentration of the explosive endoperoxide is low in the whole reactor system and the endoperoxide is reduced to the final product immediately after leaving the reactor. The results show the feasibility of this reaction although the process is not yet optimized.
Micromixer Based Liquid/Liquid Dispersion
Authors: Pennemann H. , Hardt S. , Hessel V. , Löb P. , Weise F.
Published: March 2005

Droplet formation of various liquid/liquid systems is investigated in an interdigital micromixer made of glass. By means of the interdigital channel configuration, cylindrically shaped or lamellae‐like substreams of the dispersed phase are generated inside a continuous phase. Using the model emulsion silicon oil/water, the Rayleigh plateau instability is identified as the decay mechanism for cylindrically shaped substreams of the dispersed phase. In comparison, it is suggested by the droplet size distribution of various mixers as a function of the total flow rate that in mixers with more complex fluid‐guiding geometries droplet formation is mainly affected by shear and vortex flows.
Hermetic Gas‐tight Ceramic Microreactors
Authors: Meschke F. , Riebler G. , Hessel V. , Schürer J. , Baier T.
Published: March 2005

New kinds of hermetic gas‐tight ceramic microreactors for high temperatures, harsh environments, and high pressures are presented. Besides the special manufacturing procedure and design possibilities, application possibilities are also outlined. The results are complemented with examples of simulation of temperature distribution, measurement of K‐values, and thermal efficiencies on a specific cross‐flow reactor with internal manifolds. The high thermal conductivity of the ceramic results in a superior gas‐to‐gas heat transfer and in reasonable efficiencies.
Sample Pulse Broadening in Taylor Flow Microchannels for Screening Applications
Authors: Salman W. , Angeli P. , Gavriilidis A.
Published: March 2005

The effect of different parameters on the residence time distribution of a Taylor flow microreactor was investigated. The reactor residence time distribution was calculated from the tracer residence time distribution of a single unit cell. It was found that generally an increase in Bodenstein number, capillary number or slug length increased the spread of the residence times. A case study comparing the effect of two different sets of design and operating parameters on the distribution spread showed that spreading can be minimized by careful choice of parameters, in particular slug length.
Polymer‐Induced Alignment of dl‐Alanine Nanocrystals to Crystalline Mesostructures
Authors: Wohlrab Sebastian , Pinna Nicola , Antonietti Markus , Cölfen Helmut
Published: March 2005

Crystallization of dl‐alanine by cooling of a supersaturated solution in the presence of a chiral double‐hydrophilic block copolymer poly(ethylene glycol)‐block‐poly(ethylene imine)‐S‐isobutyric acid (PEG4700‐PEI1200‐S‐iBAc) yields crystal superstructures with an astonishing morphology. Although analysis by light microscopy reveals these crystals to be apparently well facetted, electron microscopy shows that they consist of three‐dimensionally, well‐aligned nanocrystals that are scaffolded to a so‐called mesocrystal. This mesocrystal is formed by polymer‐mediated structuration, and provides evidence for the importance of mesoscopic events in a typical crystallization process.
High Charge‐Carrier Mobility in π‐Deficient Discotic Mesogens: Design and Structure–Property Relationship
Authors: Lehmann Matthias , Kestemont Gaël , Gómez Aspe Rafael , Buess‐Herman Claudine , Koch Michel H. J. , Debije Michael G. , Piris Jorge , de Haas Matthijs P. , Warman John M. , Watson Mark D. , Lemaur Vincent , Cornil Jérôme , Geerts Yves Henri , Gearba Raluca , Ivanov Dimitri A.
Published: March 2005

Hexaazatrinaphthylene (HATNA) derivatives with six alkylsulfanyl chains of different length (hexyl, octyl, decyl and dodecyl) have been designed to obtain new potential electron‐carrier materials. The electron‐deficient nature of these compounds has been demonstrated by cyclic voltammetry. Their thermotropic behaviour has been studied by means of differential scanning calorimetry and polarised optical microscopy. The supramolecular organisation of these discotic molecules has been explored by temperature‐dependent X‐ray diffraction on powders and oriented samples. In addition to various liquid crystalline columnar phases (Colhd, Colrd), an anisotropic plastic crystal phase is demonstrated to exist. The charge‐carrier mobilities have been measured with the pulse‐radiolysis time‐resolved microwave‐conductivity technique. They are found to be higher in the crystalline than in the liquid crystalline phases, with maximum values of approximately 0.9 and 0.3 cm2 V−1 s−1, respectively, for the decylsulfanyl derivative. Mobilities strongly depend on the nature of the side chains.
On the Reaction of Ph2PNHPPh2 with RNCS (R=Et, Ph, p‐NO2C6H4): Preparation of the Zwitterionic Ligand EtNHC(S)Ph2PNPPh2C(S)NEt (HSNS) and the Zwitterionic Metalate [(SNS)Rh(CO)]
Authors: Asti Mattia , Cammi Roberto , Cauzzi Daniele , Graiff Claudia , Pattacini Roberto , Predieri Giovanni , Stercoli Alessandro , Tiripicchio Antonio
Published: March 2005

The reaction of Ph2PNHPPh2 (PNP) with RNCS (Et, Ph, p‐NO2(C6H4)) gives addition products resulting from the attack of the P atoms of PNP on the electrophilic carbon atom of the isothiocyanate. When PNP is reacted with EtNCS in a 1:2 molar ratio, the zwitterionic molecule EtNHC(S)PPh2NP+Ph2C(S)N−Et (HSNS) is obtained in high yield. HSNS can be protonated (H2SNS+) or deprotonated (SNS−), behaving in the latter form as an S,N,S‐donor pincer ligand. The reaction of HSNS with [(acac)Rh(CO)2] (acac=acetylacetonate) affords the zwitterionic metalate [(SNS)Rh(CO)]. Other products can be obtained depending on the R group, the PNP/RNCS ratio (1:1 or 1:2), and the reaction temperature. The proposed product of the primary attack of PNP on RNCS, Ph2PNPPh2C(S)NHR (A), cannot be isolated. Reaction of A with another RNCS molecule leads to 1:2 addition compounds of the general formula RNHC(S)PPh2NP+Ph2C(S)N−R (1), which can rearrange into the non‐zwitterionic product RNHC(S)PPh2NP(S)Ph2 (2) by eliminating a molecule of RNC. Two molecules of A can react together, yielding 1:1 PNP/RNCS zwitterionic products of the formula RNHCH[PPh2NP(S)Ph2]PPh2NP+Ph2C(S)N−R (3). Compound 3 can then rearrange into RNHCH[PPh2NP(S)Ph2]2 (4) by losing a RNC molecule. When R=Et (a), compounds 1 a, 2 a (HSNS), and 4 a have been isolated and characterized. When R=Ph (b), compounds 2 b and 4 b can be prepared in high yield. When R=p‐NO2C6H4 (c), only compound 3 c is observed and isolated in high yield. The crystal structures of HSNS, [(SNS)Rh(CO)], and of the most representative products have been determined by X‐ray diffraction methods.
Convenient Synthesis of Multifunctional EDTA‐Based Chiral Metal Chelates Substituted with an S‐Mesylcysteine
Authors: Leonov Andrei , Voigt Brigitte , Rodriguez‐Castañeda Fernando , Sakhaii Peyman , Griesinger Christian
Published: March 2005

We describe the synthetic route to ethylenediaminetetraacetic acid (EDTA) derivatives that can be attached to surface‐exposed thiol functional groups of cysteine residues in proteins, via a methylthiosulfonate moiety that is connected in a stereochemically unique way to the C‐1 carbon atom of EDTA. Such compounds can be used to align proteins in solution without the need to add liquid crystalline media, and are, therefore, of great interest for the NMR spectroscopic analysis of biomolecules. The binding constant for the paramagnetic tag to lanthanide ions was determined by measuring luminescence. For the Tb+3–ligand complex, a Kb value of 6.5×1017 M−1 was obtained. This value is in excellent agreement with literature values for the related EDTA compound. In addition, it could be shown that there is no significant reduction in the luminescence intensity upon addition of a 104 excess of Ca2+ ions, indicating that this paramagnetic tag is compatible with buffers containing high concentrations of divalent alkaline earth ions.
Synthesis and Supramolecular Properties of Molecular Clips with Anthracene Sidewalls
Authors: Klärner Frank‐Gerrit , Kahlert Björn , Boese Roland , Bläser Dieter , Juris Alberto , Marchioni Filippo
Published: March 2005

Novel molecular clips with anthracene sidewalls (1 a–c) were synthesized; they form stable host–guest complexes with a variety of electron‐deficient aromatic and quinoid molecules. According to single‐crystal structure analyses of clip 1 c and 1,2,4,5‐tetracyanobenzene (TCNB) complex 14@1 b, the clips’ anthracene sidewalls have to be compressed substantially during the complex formation to provide attractive π–π interactions between the aromatic guest molecule and the two anthracene sidewalls in the complex. The compression and expansion of aromatic sidewalls are calculated by molecular mechanics to be low‐energy processes, so the energy required for compression of the anthracene sidewalls during complex formation is apparently overcompensated by the gain in energy resulting from the attractive π–π interactions. The finding that complexes of the clips 1 a–c are more stable than those of the corresponding clips 2 a–c can be explained in terms of the larger van der Waals contact surfaces of the anthracene sidewalls in 1 a–c (relative to the naphthalene sidewalls in 2 a–c). Color changes resulting from charge‐transfer (CT) bands are observed in complex formation by 1 a–c: from colorless to red or purple with TCNB (14), and from yellow to green with 2,4,7‐trinitro‐9‐fluorenone TNF (17). Independently, the host 1 b and guest 14 fluoresce from their respective excited singlet states, whilst in the complex 14@1 b the charge‐transfer state quenches the higher‐energy singlet states of the two components, and as a result luminescence is only observed from this new CT state. To the best of our knowledge, complex 14@1 b is the first example of CT luminescence from a host–guest complex. The binding constant determined for the formation of the TCNB complex 14@1 b from a UV/Vis titration experiment (Ka = 12 400 m−1) agrees well with the value (Ka = 12 800 m−1) obtained by 1H NMR titration.
Synthesis of Mono‐ and Disubstituted Porphyrins: A‐ and 5,10‐A2‐Type Systems
Authors: Ryppa Claudia , Senge Mathias O. , Hatscher Sabine S. , Kleinpeter Erich , Wacker Philipp , Schilde Uwe , Wiehe Arno
Published: March 2005

General syntheses have been developed for meso‐substituted porphyrins with one or two substituents in the 5,10‐positions and no β substituents. 5‐Substituted porphyrins with only one meso substituent are easily prepared by an acid‐catalyzed condensation of dipyrromethane, pyrrole‐2‐carbaldehyde, and an appropriate aldehyde using a “[2+1+1]” approach. Similarly, 5,10‐disubstituted porphyrins are accessible by simple condensation of unsubstituted tripyrrane with pyrrole and various aldehydes using a “[3+1]” approach. The yields for these reactions are low to moderate and additional formation of either di‐ or monosubstituted porphyrins due to scrambling of the intermediates is observed. However, the reactions can be performed quite easily and the desired target compounds are easily removed due to large differences in solubility. A complementary and more selective synthesis involves the use of organolithium reagents for SNAr reactions. Reaction of in situ generated porphyrin (porphine) with 1.1–8 equivalents of RLi gave the monosubstituted porphyrins, while reaction with 3–6 equivalents of RLi gave the 5,10‐disubstituted porphyrins in yields ranging from 43 to 90 %. These hitherto almost inaccessible compounds complete the series of different homologues of A‐, 5,15‐A2‐, 5,10‐A2‐, A3‐, and A4‐type porphyrins and allow an investigation of the gradual influence of type, number, and regiochemical arrangement of substituents on the properties of meso‐substituted porphyrins. They also present important starting materials for the synthesis of ABCD porphyrins and are potential synthons for supramolecular materials requiring specific substituent orientations.
Synthesis of Some New 6‐Substituted Quinazolino[4,3‐b]quinazolin‐8‐ones under Solvent‐Free Conditions.
Authors: Azizian Javad , Mohammadi Ali A. , Karimi Ali R. , Mohammadizadeh Mohammad R.
Published: March 2005

For Abstract see ChemInform Abstract in Full Text.
Cytotoxic capacity of hepatitis C virus (HCV)–specific lymphocytes after in vitro immunization with HCV‐derived lipopeptides
Authors: Langhans Bettina , Schweitzer Susann , Braunschweiger Ingrid , Schulz Monika , Sauerbruch Tilman , Spengler Ulrich
Published: March 2005

Background

Hepatitis C virus (HCV)–derived lipopeptides can induce epitope‐specific immune responses in lymphocytes from HCV‐naive individuals. We analyzed whether such T cells generated by in vitro immunization with HCV core‐derived lipopeptides exert HCV‐specific cytolytic activity.

Methods

Using a sensitive flow cytometric cytotoxicity assay we characterized HCV‐specific cytotoxicity in T cells generated in vitro with HCV core‐derived 25‐mer lipopeptides. In addition, we studied expressions of Fas ligand and perforin and interferon‐γ (IFN‐γ) secretion in HLA‐A2‐HCVcore_35‐44 tetramer‐positive T cells generated with lipopeptide amino acid 20‐44 (LP20‐44).

Results

CD8+ T cells induced in vitro with HCV core‐derived lipopeptides only infrequently exerted HCV‐specific cytotoxicity, irrespective of whether antigen‐coated T2 cells or autologous B lymphoblasts were used as targets. Detailed analysis of HLA‐A2‐HCVcore_35‐44 tetramer‐positive T cells generated with LP20‐44 revealed that in vitro immunization resulted in T cells that secreted IFN‐γ after antigen‐specific restimulation and that upregulated expression of Fas ligand but not of perforin.

Conclusions

Our data confirm at the functional level that HCV lipopeptides induce antigen‐specific T lymphocytes that produce IFN‐γ but exert significant cytotoxicity in only a minority of experiments, probably because expression of cytolytic effector molecules is not enhanced in their granules. © 2005 Wiley‐Liss, Inc.
Impact of preanalytical variables on granulocytic surface antigen expression: A review
Authors: Elghetany M. Tarek , Davis Bruce H.
Published: March 2005

Background

There is a gradual but steady increase in the use of granulocytic surface marker studies to diagnose several inherited and acquired blood and bone marrow disorders. Diagnosis and follow‐up of patients with inflammation and infection are other areas of quantitative flow cytometric application. Despite the increased use of flow cytometry to study granulocytes, there seems to be no well‐established standards regarding specimen handling for these studies.

Methods

This review summarizes the effect of preanalytical variables on granulocytic surface markers.

Results and Conclusions

Storing specimens in sodium heparin at room temperature for up to 72 h seems satisfactory. Other anticoagulants, although acceptable, may have a shorter storage time. Storage time could be prolonged further with the use of some preservation media. Lysed whole blood is the preferred technique. Techniques should avoid major temperature change and excessive manipulation and should maintain storage and methodologic temperature with minimal fluctuation. Fixation before staining with the antibody may result in decreased expression of some surface antigens. © 2005 Wiley‐Liss, Inc.
Consumers in a multichannel environment: Product utility, process utility, and channel choice
Authors: Balasubramanian Sridhar , Raghunathan Rajagopal , Mahajan Vijay
Published: March 2005

We present a conceptual framework that clarifies the utilities that consumersusing a channel derive from both the purchase process and the purchased products, and the mutual influences between these process and product utilities. Drawing on interviews with customers, we examine how the following factors influence product and process utilities, and hence consumers’ choice and use of channels: (a) their economic goals, (b) their quest for self-affirmation, (c) their quest for symbolic meaning associated with the product and with the shopping process, (d) their quest for social interaction and experiential impact, and (e) their reliance on schemas and scripts for shopping. We examine how these factors may influence channel choice at the following three stages of the purchase process—forming a consideration set, choosing a product, and buying the product. Consumers may navigate between channels when they use distinct channels across these stages. Our analysis yielded implications for researchers examining consumer behavior in the multichannel environment and recommendations for marketing managers operating in that environment.
The effect of acquisition channels on customer loyalty and cross-buying
Authors: Verhoef Peter C. , Donkers Bas
Published: March 2005

Acquisition channels are important predictors of customer loyalty in the first stages of a business–consumer relationship. Although some researchers have provided examples of the differences in the value of the customers businesses acquire via different channels, they have not considered the impact of acquisition channels on loyalty and cross-buying. Using probit-models we explored how retention rates and cross-selling opportunities differ among the various acquisition channels a financial-services provider uses. Our results indicate that the direct-mail acquisition channel performs poorly on retention and cross-selling, while radio and TV perform poorly for retention only. The firm's Web site seems to perform well for retention. The theoretical and practical implications of our results are discussed.
Opportunities and challenges in multichannel marketing: An introduction to the special issue
Authors: Rangaswamy Arvind , Van Bruggen Gerrit H.
Published: March 2005

During the past decade, customers have become familiar with using various interface technologies, such as Web sites and wireless devices, to interact with firms. Increasingly, they choose the times and the channels through which they deal with firms for different aspects of their interactions. It is becoming common for customers to use different channels at different stages of their decision-and-shopping cycles, for example, using Web sites to obtain information but making purchases offline; in the past they typically obtained all their channel services from a single integrated channel at all stages of their decision process. We refer to customers who use more than one channel to interact with firms as multichannel customers, and marketing strategies to reach such customers as multichannel marketing. According to a study by Doubleclick (2004), the incidence of multichannel shopping among online shoppers increased from 56% to 65% between the 2002 and 2003 holiday seasons.
Literature review of air pollution control biofilters and biotrickling filters for odor and volatile organic compound removal
Authors: Iranpour Reza , Cox Huub H.J. , Deshusses Marc A. , Schroeder Edward D.
Published: March 2005

A literature study was conducted to compare the feasibility of biofilters and biotrickling filters for the treatment of complex odorous waste air containing hydrogen sulfide (H2S), organic reduced sulfur compounds, and chlorinated and nonchlorinated volatile organic compounds (VOCs). About 40 pilot‐plant studies and full‐scale applications at wastewater treatment plants and other facilities were reviewed. Reactor design and pollutant removal efficiencies were summarized in tables for easy reference and for a perspective on the current state of the art, and to allow comparison between different projects. The survey indicated that both biofilters and biotrickling filters are capable of combining a high H2S and odor removal efficiency with VOC removal. Apart from odor abatement, biological treatment therefore holds promise for reducing the overall toxicity and potential carcinogenicity of VOC‐containing odorous waste air from wastewater treatment plants and other facilities. VOC removal efficiencies were in general lower than those of H2S and odor, although concentrations of individual VOC species were relatively low. This indicates that for effective treatment of VOC‐containing odorous waste air, the design and operation should emphasize VOC removal as the rate‐limiting parameter. © 2005 American Institute of Chemical Engineers Environ Prog, 2005
Signal transduction pathways regulating cyclooxygenase‐2 in lipopolysaccharide‐activated primary rat microglia
Authors: Akundi Ravi Shankar , Candelario‐Jalil Eduardo , Hess Sandra , Hüll Michael , Lieb Klaus , Gebicke‐Haerter Peter J. , Fiebich Bernd L.
Published: March 2005

Microglia are the major cell type involved in neuroinflammatory events in brain diseases such as encephalitis, stroke, and neurodegenerative disorders, and contribute significantly to the release of prostaglandins (PGs) during neuronal insults. In this report, we studied the immediate‐early intracellular signalling pathways in microglia, following bacterial lipopolysaccharide (LPS) stimulation, leading to the synthesis and release of PGE2. Here we show that LPS induces cyclooxygenase (COX) 2 by activating sphingomyelinases leading to the release of ceramides, which in turn, activate the p38 mitogen‐activated protein kinases (MAPK), but not the p42/44 MAPK. We further show that exogenously added ceramide analogue (C2‐ceramide) also induce PGE2 synthesis through a p38 MAPK‐dependent pathway. This potential nature of ceramides in activating microglia suggests that endogenously produced ceramides during neuronal apoptosis in ischemia or neurodegenerative diseases could also contribute to the amplification of neuroinflammatory events. In contrast to protein kinase C (PKC) and phosphocholine‐specific phospholipase C (PC‐PLC), which transcriptionally regulate LPS‐induced COX‐2 synthesis, inhibition of phospholipase A2 (PLA2) has no effect on COX‐2 transcription, although it inhibits the release of PGE2. Transcriptional regulation of LPS‐induced COX‐2 by PKC is further proved by the ability of the PKC inhibitor, Gö 6976, to inhibit LPS‐induced 8‐isoprostane synthesis, but not affecting LPS‐induced COX‐2 activity. Our data with 8‐isoprostane also indicates that COX‐2 plays a major role in ROS production in LPS‐activated microglia. This detailed view of the intracellular signaling pathway in microglial activation and COX‐2 expression opens a new therapeutic window in the search for new and more effective central anti‐inflammatory agents. © 2005 Wiley‐Liss, Inc.
Comparison of the prevalence and risk factors for depressive symptoms among elderly nursing home residents in Taiwan and Hong Kong
Authors: Tsai Yun‐Fang , Chung Joanne W. Y. , Wong Thomas K. S. , Huang Chiu‐Mieh
Published: March 2005

Background

Depression in the elderly has become a serious health care issue worldwide. However, no studies have compared the prevalence and risk factors for depressive symptoms among institutionalized Chinese elders living in different regions.

Objectives

To explore and compare the prevalence and risk factors for depressive symptoms among elderly residents of nursing homes in Taiwan and Hong Kong.

Methods

Random sampling was used to recruit participants from eight nursing homes in each region. A total of 150 elders from Taiwan and 214 elders from Hong Kong participated.

Results

The prevalence of depressive symptoms was significantly higher in participants from Hong Kong (65.4%) than in Taiwan (43.3%). Logistic regression analysis indicated that gender, satisfaction with living situation, perceived health condition, and perceived income adequacy significantly predicted depressive symptoms in elderly nursing home residents in Taiwan. Significant predictors of depressive symptoms in the Hong Kong sample were satisfaction with living situation, cognitive status, and functional status.

Conclusions

It is important to consider risk factors specific to a target population when developing depression intervention programs. Copyright © 2005 John Wiley & Sons, Ltd.
Needs assessment in dementia
Authors: Meaney A. M. , Croke M. , Kirby M.
Published: March 2005

Background

Resource allocation and service development traditionally focuses on diagnostic categories and consequent perceived need. Identification of the actual level of need in the elderly with dementia, and the degree to which it is unmet is necessary to plan services both individually and as a group. The aim of this study was to characterise the needs of a sample of community dwelling elderly patients with dementia who were referred to an old age psychiatry service in Ireland between July 2002 and July 2003.

Methodology

Eighty‐two consecutively referred community dwelling patients with ICD‐10 diagnosis of dementia were assessed on The Care Needs Assessment Pack for Dementia (CareNap‐D). Data on needs across seven domains (health and mobility, self‐care and toileting, social interaction, thinking and memory, behaviour and mental state, housecare, community living) is presented (Reynolds T et al., 1998).

Results

Subjects had a mean of 33 (range: 13–56) identified needs. Approximately 1/3 of these were unmet with a mean of 13 (range: 0–37) and a mean of 20 (range: 4–39) were met. High levels of unmet need was identified in the domains of behaviour and mental state (84% of those with agitation) and of social interaction (79% of those with ‘partaking in activities’ need). The specific item of repetitive questioning occurred in 68 individuals and was unmet in 88% of these cases. Increasing age, lower MMSE score, and living alone were associated with greater total levels of unmet need.

Conclusion

This data underlines the degree of unmet need in the community dwelling elderly with dementia and the importance of developing a spectrum of services on the basis of the actual needs identified. Copyright © 2005 John Wiley & Sons, Ltd.
Prevalence and correlates of depression in late life: a population based study from a rural Greek town
Authors: Papadopoulos F. C. , Petridou E. , Argyropoulou S. , Kontaxakis V. , Dessypris N. , Anastasiou A. , Katsiardani K. P. , Trichopoulos D. , Lyketsos C.
Published: March 2005

Background

Depression in late life is common and has serious consequences on function, medical co‐morbidity, quality of life, and use of medical services.

Objective

To estimate the age‐ and gender‐specific prevalence of depression among people over 60 years of age, and to examine correlates of depression, in particular the relationship between depression and cognitive impairment.

Method

From a total of 965 inhabitants, aged over 60 years, in Velestino, a rural town in central Greece, 608 were accessible and constituted the target population. During a five‐month period in 2000, a trained health visitor interviewed all study participants. The interview covered socio‐demographic characteristics, medical history, and administration of the 15‐question Geriatric Depression Scale (GDS‐15) and the Mini Mental Scale Examination instrument (MMSE).

Results

The prevalence of mild or more severe depression (GDS≥7) was 27%, while the prevalence of moderate to severe depression (GDS≥11) was 12%. Increasing age, female gender, lower education, and being currently unmarried were associated with higher risk of depression in univariate regression models, but these associations disappeared after controlling for cognitive function, except for the association with marital status. Cognitive impairment was strongly associated with increased risk for depression. The co‐morbid presence of digestive, neurological and heart conditions was also associated with increased risk for depression, while cancer was not.

Conclusion

In a rural Greek area, the prevalence of depression in late life is high. Depression was more common among unmarried individuals, those with significant cognitive impairment, and in association with specific medical conditions. Copyright © 2005 John Wiley & Sons, Ltd.
Factors affecting timely recognition and diagnosis of dementia across Europe: from awareness to stigma
Authors: Vernooij‐Dassen Myrra J. F. J. , Moniz‐Cook Esme D. , Woods Robert T. , Lepeleire Jan De , Leuschner Antonio , Zanetti Orazio , Rotrou Joycelyn de , Kenny Geraldine , Franco Manuel , Peters Vincent , Iliffe Steve
Published: March 2005

Background

Timely recognition and diagnosis of dementia is the pre‐condition for improving dementia care, but diagnosis often occurs late in the disease process.

Objective

To compare facilitators and obstacles to the timely recognition of dementia across eight European Union states, in order to implement established policies for earlier diagnosis.

Methods

A modified focus group technique, including a pre and posterior procedure.

Results

Twenty‐three participants from different disciplines, purposively sampled for professional expertise in dementia research and innovative practice, attended two focus groups. Stigma in ageing and dementia, accompanied by a sense that there is little to offer until later on in the disease, underpinned the widespread reluctance of GPs to recognise dementia at an early stage and were major obstacles to the timely diagnosis of dementia across all eight countries. Dementia care services varied widely across Europe. Countries with the greatest development of dementia health care services were characterised by national guidelines, GPs fulfilling a gatekeeper function, multi‐disciplinary memory clinics and innovative programmes that stimulated practice and new services. Dementia‐related stigma was perceived as being less prominent in these countries.

Conclusions

Overcome of delays in the timely diagnosis of dementia needs more than specialist services. They should address the processes associated with stigma, age and dementia, especially where these relate to physician practice and diagnostic disclosure. Stigma is perceived as variable across European States, with a promising finding that its impact is relatively small in countries with the widest range of dementia care services. Copyright © 2005 John Wiley & Sons, Ltd.
Engineered vascular‐targeting antibody‐interferon‐γ fusion protein for cancer therapy
Authors: Ebbinghaus Christina , Ronca Roberto , Kaspar Manuela , Grabulovski Dragan , Berndt Alexander , Kosmehl Hartwig , Zardi Luciano , Neri Dario
Published: March 2005

A number of cytokines are either approved drugs or are in advanced clinical trials, yet these biopharmaceuticals do not typically localize efficiently in solid tumors and manifest their therapeutic potential at the expense of severe side effects. The targeted delivery of cytokines to solid tumors is a promising avenue for increasing the therapeutic index of these biopharmaceuticals. We engineered a fusion protein between scFv(L19), a human antibody fragment specific to the EDB domain of fibronectin, and a cysteine‐free mutant of murine interferon‐γ. The resulting fusion protein was capable of targeting new blood vessels in solid tumors, and the targeting efficiency was strikingly increased in tumor‐bearing knockout mice lacking the interferon‐γ receptor. ScFv(L19)‐interferon‐γ displayed a strong antitumor effect in both subcutaneous and metastatic murine F9 teratocarcinomas, but was not efficacious as single agent when used to treat C51 and CT26 tumors. The potency of this fusion protein could be substantially enhanced by combination with doxorubicin and other immunocytokines. These findings are of clinical relevance, as the EDB domain is a marker of angiogenesis, with identical sequence in mouse and man, which is abundantly expressed in a variety of aggressive solid tumors but is undetectable in most normal tissues. Supplementary material for this article can be found on the International Journal of Cancer website at http://www.interscience. wiley.com/jpages/0020‐7136/suppmat/index.html. © 2005 Wiley‐Liss, Inc.
Mechanisms of tumor vascular shutdown induced by 5,6‐dimethylxanthenone‐4‐acetic acid (DMXAA): Increased tumor vascular permeability
Authors: Zhao Liangli , Ching Lai‐Ming , Kestell Philip , Kelland Lloyd R. , Baguley Bruce C.
Published: March 2005

The novel vascular targeting agent 5,6‐dimethylxanthenone‐4‐acetic acid (DMXAA) has completed phase 1 clinical trial and has shown tumor antivascular activity in both mice and humans. We have investigated its ability to change tumor vascular permeability, relating it to tumor vascular perfusion and other responses. The murine colon 38 adenocarcinoma was grown in C57Bl wild‐type mice and mice lacking expression of either tumor necrosis factor receptor‐1 (TNFR1−/−) or TNF (TNF−/−). Tumor vascular permeability, as measured by extravasation of albumin‐Evans Blue complexes 4 hr after DMXAA treatment, was significantly increased in tumor tissue in C57Bl, TNFR1−/− and TNF−/− mice but not in normal (skin) tissue. Significant linear relationships were found between increased tumor vascular permeability, decreased functioning tumor blood vessels (measured by Hoechst 33342 staining at 4 hr), increased plasma 5‐hydroxyindole‐3‐acetic acid concentrations (as a measure of serotonin release by platelets) and the degree of induced tumor hemorrhagic necrosis. The results support the hypothesis that DMXAA increases tumor vascular permeability both directly and through the induction of other vasoactive mediators, including TNF. DMXAA might be useful clinically to potentiate the vascular permeability of other anticancer modalities such as cytotoxic drugs, antibodies, drug conjugates and gene therapy. © 2005 Wiley‐Liss, Inc.
Aerosol gemcitabine inhibits the growth of primary osteosarcoma and osteosarcoma lung metastases
Authors: Koshkina Nadezhda V. , Kleinerman Eugenie S.
Published: March 2005

Osteosacarcoma (OS) lung metastases are often resistant to chemotherapy. Most anticancer drugs are administered systemically. In many cases this is followed by dose‐dependent toxicity, which may not allow the achievement of therapeutic levels in lungs to eradicate metastases. We determined the efficacy of gemcitabine (GCB) by administering it directly to the lungs via aerosol and studied the role of the Fas pathway in response to the therapy. We used 2 osteosarcoma lung metastases animal models: human LM7 cells that form lung metastases in mice following intravenous injection and murine LM8 cells, which grows subcutaneously in mice and spontaneously metastasize to the lung. Treatment was initiated when the presence of lung metastases had been established. Aerosol GCB inhibited the growth of lung metastases in mice. Intraperitoneal GCB administration at similar dosage had no effect on lung metastases. Besides its direct effect on lung metastases, aerosol GCB suppressed the growth of subcutaneous LM8 tumor. Histopathological examination of mice receiving aerosol GCB showed no evidence of toxicity. Lungs are distinguished from other tissues by the constitutive expression of FasL. Since exposure of tumor cells to GCB upregulated Fas expression, we hypothesized that the susceptibility of the tumor cells to ligand‐induced cell death by resident lung cells may be increased. Therefore, the Fas pathway may contribute to the therapeutic effect of aerosol GCB. © 2005 Wiley‐Liss, Inc.
Case‐control study of familial lung cancer risks in UK women
Authors: Matakidou Athena , Eisen Tim , Bridle Helen , O'Brien Mary , Mutch Rosalind , Houlston Richard S. ,   Members of the GELCAPS Consortium
Published: March 2005

Family history data from a case‐control study of lung cancer conducted in the United Kingdom between 1999 and 2004 were analysed to estimate familial risks of the disease. Comparison of lung cancer prevalence in first‐degree relatives of 1,482 female lung cancer cases and 1,079 female controls was undertaken using logistic regression adjusting for age and tobacco exposure. Overall, lung cancer in a first‐degree relative was associated with a significant increase in the risk of lung cancer [odds ratio (OR) 1.49; 95% confidence interval (CI), 1.13–1.96]. For cases with early onset of the disease (< 60 years), the OR of lung cancer was 2.02 (95% CI, 1.22–3.34). Having 2 or more affected relatives was associated with an OR of 2.68 (95% CI, 1.29–5.55), with a significant trend in risk according to the number of relatives affected (p = 0.001). An increased risk of lung cancer associated with family history of the disease was observed when analysis was restricted to lifetime nonsmokers, although this did not reach significance (OR 1.23; 95% CI, 0.65–2.31). Results confirm previous findings and support the role of a familial predisposition to lung cancer. © 2005 Wiley‐Liss, Inc.
Induction of autoantibodies to syngeneic prostate‐specific membrane antigen by xenogeneic vaccination
Authors: Gregor Polly D. , Wolchok Jedd D. , Turaga Vandana , Latouche Jean‐Baptiste , Sadelain Michel , Bacich Dean , Heston Warren D.W. , Houghton Alan N. , Scher Howard I.
Published: March 2005

Prostate‐specific membrane antigen (PSMA) is a prototypical differentiation antigen expressed on normal and neoplastic prostate epithelial cells, and on the neovasculature of many solid tumors. Monoclonal antibodies specific for PSMA are in development as therapeutic agents. Methodologies to actively immunize against PSMA may be limited by immunologic ignorance and/or tolerance that restrict the response to self‐antigens. Our studies have previously shown that xenogeneic immunization with DNA vaccines encoding melanosomal differentiation antigens induces immunity in a mouse melanoma model. Here we apply this approach to PSMA to establish proof of principle in a mouse model. Immunization with xenogeneic human PSMA protein or DNA induced antibodies to both human and mouse PSMA in mice. Monoclonal antibodies specific for mouse PSMA were generated to analyze antibody isotypes and specificity for native and denatured PSMA at the clonal level. Most antibodies recognized denatured PSMA, but C57BL/6 mice immunized with xenogeneic PSMA DNA followed by a final boost with xenogeneic PSMA protein yielded autoantibodies that reacted with native folded mouse PSMA. Monoclonal antibodies were used to confirm the expression of PSMA protein in normal mouse kidney. These results establish the basis for clinical trials to test PSMA DNA vaccines in patients with solid tumors that either express PSMA directly or that depend on normal endothelial cells expressing PSMA for their continued growth. © 2005 Wiley‐Liss, Inc.
Ethnic group‐related differences in CpG hypermethylation of the GSTP1 gene promoter among African‐American, Caucasian and Asian patients with prostate cancer
Authors: Enokida Hideki , Shiina Hiroaki , Urakami Shinji , Igawa Mikio , Ogishima Tatsuya , Pookot Deepa , Li Long‐Cheng , Tabatabai Z. Laura , Kawahara Motoshi , Nakagawa Masayuki , Kane Christopher J. , Carroll Peter R. , Dahiya Rajvir
Published: March 2005

The incidence and mortality of prostate cancer (PC) is approximately 2‐fold higher among African‐Americans as compared to Caucasians and very low in Asian. We hypothesize that inactivation of GSTP1 genes through CpG methylation plays a role in the pathogenesis of PC, and its ability to serve as a diagnostic marker that differs among ethnic groups. GSTP1 promoter hypermethylation and its correlation with clinico‐pathological findings were evaluated in 291 PC (Asian = 170; African‐American = 44; Caucasian = 77) and 172 benign prostate hypertrophy samples (BPH) (Asian = 96; African‐American = 38; Caucasian = 38) using methylation‐specific PCR. In PC cells, 5‐aza‐dC treatment increased expression of GSTP1 mRNA transcripts. The methylation of all CpG sites was found in 191 of 291 PC (65.6%), but only in 34 of 139 BPH (24.5%). The GSTP1 hypermethylation was significantly higher in PC as compared to BPH in each ethnic group (p < 0.0001). Logistic regression analysis (PC vs. BPH) showed that African‐Americans had a higher hazard ratio (HR) (13.361) compared to Caucasians (3.829) and Asian (8.603). Chi‐square analysis showed correlation of GSTP1 hypermethylation with pathological findings (pT categories and higher Gleason sum) in Asian PC (p < 0.0001) but not in African‐Americans and Caucasian PC. Our results suggest that GSTP1 hypermethylation is a sensitive biomarker in African‐Americans as compared to that in Caucasians or Asian, and that it strongly influences tumor progression in Asian PC. Ours is the first study investigating GSTP1 methylation differences in PC among African‐American, Caucasian and Asian. © 2005 Wiley‐Liss, Inc.
Connexin43 is overexpressed in ApcMin/+‐mice adenomas and colocalises with COX‐2 in myofibroblasts
Authors: Husøy Trine , Knutsen Helle K. , Cruciani Véronique , Ølstørn Hege B. , Mikalsen Svein‐Ole , Løberg Else Marit , Alexander Jan
Published: March 2005

The expression of gap junction proteins, connexins, in the intestine and their role in tumorigenesis are poorly characterised. Truncating mutations in the tumour suppressor gene adenomatous polyposis coli (APC) are early and important events, both in inheritable (familial adenomatous polyposis, FAP) and spontaneous forms of intestinal cancer. Multiple intestinal neoplasia (Min) mice, a FAP model with inherited heterozygous mutation in Apc, spontaneously develop numerous intestinal adenomas. We recently reported reduced expression of connexin32 in Paneth cells of Min‐mice. We further examine the expression of connexin43 (Cx43) and other connexins as a function of heterozygous and homozygous Apc mutation in normal intestinal tissues and adenomas of Min‐mice. Qualitative analysis of connexin mRNA in intestine revealed a similar expression pattern in Min‐ and wild‐type (wt) mice. Connexin26 and connexin40 proteins were found in equal amounts in Min and wt epithelia of large and small intestine, respectively. Interestingly, the connexin43 level was increased in the stroma of Min‐mice adenomas, in close proximity to epithelial cells with nuclear β‐catenin staining. Cx43 and COX‐2 were located to the same areas of the adenomas, and immunostaining exhibited coexpression in the myofibroblasts. Prostaglandin E2 induces Cx43 expression and COX‐2 is the rate‐limiting enzyme in the prostaglandin synthesis. However, the COX‐2‐specific inhibitor, celecoxib, did not reduce Cx43 expression. Although both Cx43 and COX‐2 are target genes for β‐catenin, they were overexpressed in stromal cells but not in epithelial tumour cells. We hypothesise that gap junctions may be of importance in the transfer of signals between epithelium and stroma. © 2005 Wiley‐Liss, Inc.