bluuebunny/crossref_metadata_2025 huggingface dataset:
The direct and indirect impacts of population growth and economic development on maize (Zea mays L.) diversity in highland Guatemala
Authors: Steinberg Michael K , Taylor Matthew J
Published: January 2009

This paper discusses the impacts of population growth and economic development on maize diversity in highland Guatemala. In the context of this discussion, economic development specifically refers to the recent expansion of the non‐traditional agricultural exports (NTAEs). Population growth and economic development (i.e. NTAEs) are linked because as land has become scarce in highland Guatemala, due to the poor distribution of land resources and rapid population growth over the past 50 years, many farmers have turned to non‐traditional economic strategies such as new crops that produce more income per unit of land. These new crops have improved the economic conditions of many farming families, but it has come at a cost regarding the maintenance of local maize varieties and household food security.
Ontogenic changes of the control by phosphodiesterase‐3 and ‐4 of 5‐HT responses in porcine heart and relevance to human atrial 5‐HT4receptors
Authors: Galindo‐Tovar Alejandro , Vargas Maria Luisa , Escudero Elisa , Kaumann Alberto J.
Published: January 2009

Background and purpose: Atrial inotropic responses to 5‐HT mediated through 5‐HT4receptors fade, presumably through phosphodiesterase (PDE) activity. We investigated the influence of a selective inhibitor of PDE3 (cilostamide) or of PDE4 (rolipram) on the fade of 5‐HT responses in atrial muscle.

Experimental approach: 5‐HT responses were compared,ex vivo, on sinoatrial beating rate of newborn piglets, porcine atrial and ventricular force, and human atrial force. cAMP levels were assessed in piglet atrium.

Key results: 5‐HT‐evoked sinoatrial tachycardia did not fade and was not potentiated by cilostamide (300 nmol·L−1) or rolipram (1 µmol·L−1). Inotropic responses to 5‐HT faded in atria from piglets, adolescent pigs and humans. Cilostamide reduced atrial fade of 5‐HT responses in adolescent pigs and humans but not in newborn piglets. Cilostamide disclosed 5‐HT ventricular responses in newborn, but not adolescent pigs. Rolipram reduced fade of atrial 5‐HT responses in newborn and adolescent pigs but not in humans. Concurrent cilostamide + rolipram abolished fade of 5‐HT responses in porcine left atria and facilitated ventricular 5‐HT responses, but did not reduce residual fade in human atrium in the presence of cilostamide. 5‐HT‐evoked increases in cAMP faded; fade was abolished by concurrent cilostamide + rolipram.

Conclusions and implications: PDE3‐induced control of porcine 5‐HT responses differed in atrium and ventricle and changed with age. PDE3 and PDE4 jointly prevented fade of inotropic and cAMP responses to 5‐HT in porcine atrium. Unlike porcine atria, only PDE3 induced fade of 5‐HT responses in human atria.
Prostaglandin E2 couples through EP4 prostanoid receptors to induce IL‐8 production in human colonic epithelial cell lines
Authors: Dey I , Giembycz MA , Chadee K
Published: January 2009

Mandarin translation of abstract

Background and purpose:  Prostaglandin (PG) E2 and interleukin (IL)‐8 are simultaneously increased during the inflammation that characterizes numerous pathologies such as inflammatory bowel disease. IL‐8 is a potent neutrophil chemo‐attractant and activator, and can initiate and/or exacerbate tissue injury. PGE2 signals principally through prostanoid receptors of the EP2 and/or EP4 subtypes to promote cAMP‐dependent cellular functions. The aim of this study was to identify the role of the EP2 and EP4 receptor subtype(s) on two human colonic epithelial cell lines (Caco‐2 and T84), in regulating PGE2‐induced IL‐8 production.

Experimental approach:  To identify the causative receptor, we knocked‐down and over‐expressed EP2 and EP4 receptor subtypes in colonic epithelial cells and studied the effect of several selective EP2/EP4 receptor agonists and antagonists. The inductions of IL‐8 and EP receptor mRNA and protein expression were determined by real‐time PCR and western blot analysis. The affinity of PGE2 and Bmax values for the EP2 and EP4 receptor on colonic epithelial cells were determined by radioligand‐binding assays with [3H]PGE2.

Key results:  PGE2 had the highest affinity for the EP4 receptor subtype and promoted a robust stimulation of cAMP‐dependent IL‐8 synthesis. This effect was mimicked by a selective EP4 receptor agonist, ONO‐AE1‐329, and abolished by silencing the EP4 receptor gene by using siRNA techniques, a selective EP4 receptor antagonist (ONO‐AE3‐208) and a selective inhibitor (Rp‐cAMP) of cAMP‐dependent protein kinase.

Conclusions and implications:  These findings suggest that initiation and progression of colonic inflammation induced by IL‐8 could be mediated, at least in part, by PGE2 acting via the EP4 receptor subtype.

British Journal of Pharmacology (2009) 10.1111/j.1476‐5381.2008.00056.x

Mandarin translation of abstract
Control of Oxidative Reactions of Hemoglobin in the Design of Blood Substitutes: Role of the Ascorbate–Glutathione Antioxidant System
Authors: Simoni Jan , Villanueva‐Meyer Javier , Simoni Grace , Moeller John F. , Wesson Donald E.
Published: January 2009

Uncontrolled oxidative reactions of hemoglobin (Hb) are still the main unresolved problem for Hb‐based blood substitute developers. Spontaneous oxidation of acellular ferrous Hb into a nonfunctional ferric Hb generates superoxide anion. Hydrogen peroxide, formed after superoxide anion dismutation, may react with ferrous/ferric Hb to produce toxic ferryl Hb, fluorescent heme degradation products, and/or protein‐based free radicals. In the presence of free iron released from heme, superoxide anion and hydrogen peroxide might react via the Haber–Weiss and Fenton reactions to generate the hydroxyl radical. These highly reactive oxygen and heme species may not only be involved in shifting the cellular redox balance to the oxidized state that facilitates signal transduction and pro‐inflammatory gene expression, but could also be involved in cellular and organ injury, and generation of vasoactive compounds such as isoprostanes and angiotensins. It is believed that these toxic species may be formed after administration of Hb‐based blood substitutes, particularly in ischemic patients with a diminished ability to control oxidative reactions. Although varieties of antioxidant strategies have been suggested, this in vitro study examined the ability of the ascorbate–glutathione antioxidant system in preventing Hb oxidation and formation of its ferryl intermediate. The results suggest that although ascorbate is effective in reducing the formation of ferryl Hb, glutathione protects heme against excessive oxidation. Ascorbate without glutathione failed to protect the red blood cell membranes against Hb/hydrogen peroxide‐mediated peroxidation. This study provides evidence that the ascorbate–glutathione antioxidant system is essential in attenuation of the pro‐oxidant potential of redox active acellular Hbs, and superior to either ascorbate or glutathione alone.
Possible Role of Artificial Oxygen Carriers in Transfusion Medicine: A Retrospective Analysis on the Current Transfusion Practice
Authors: Yoshiba Fumiaki , Kawaguchi Akira T. , Hyodo Osamu , Kinoue Takaaki , Inokuchi Sadaki , Kato Shunichi
Published: January 2009

Artificial oxygen carriers (AOC) are under development as a substitute for red blood cells (RBC) in homologous transfusion (Tx). The lack of surface antigen in AOC makes ABO‐typing and antibody‐screening (T/S) unnecessary. Pathogen elimination renders it much safer, and long‐term stability allows ubiquitous storage for emergency use. To delineate the utility of AOC, we retrospectively examined current Tx practices in Tokai University and the Japanese Red Cross Society. The emergency department of Tokai University Hospital has been using O(+)Rh(+) RBC in patients with hemorrhagic shock before Tx becomes available. Those who received the RBCs within 60 min of injury had a significantly higher survival rate than those who received it later (≥60 min). The Red Cross Blood Center provided 411 units of RBC for 138 urgent requests for rare blood types. Our analysis suggests that if an AOC were available for the initial six units, 96% of such requests could have been covered to avoid urgent donor allocation, preparation, and Tx. Among 2079 surgical cases who ordered T/S, only 29% actually required Tx, rendering >70% of the T/S unnecessary. Because only 7.4% required nine units or more, more than 92% of T/S and Tx could have been avoided in retrospect if an AOC were available for the initial eight units. The results suggest that an AOC might be useful in various situations to alleviate problems, concerns, and technical burden in the current Tx practices. Because the expected utility is based mainly on physical characteristics, AOC may remain advantageous even when biogenetically derived RBC becomes available.
Effects of Liposome‐Encapsulated Hemoglobin on Human Immune System: Evaluation in Immunodeficient Mice Reconstituted With Human Cord Blood Stem Cells
Authors: Kawaguchi Akira T. , Kametani Yoshie , Kato Shunichi , Furuya Hiroyuki , Tamaoki Kenichi , Habu Sonoko
Published: January 2009

As preclinical evaluation in animals does not necessarily portray human responses, liposome‐encapsulated hemoglobin (LEH), an artificial oxygen carrier, was tested in immunodeficient mice reconstituted with human hematopoietic stem cells (cord blood‐transfused NOD/SCID/IL‐2Rγnull[CB‐NOG] mice). Changes in immunocompetent T‐cell and B‐cell composition in peripheral blood, spleen, and bone marrow were examined 2 and 7 days after 10 mL/kg of intravenous administration of LEH, empty liposome (EL), or saline using immunohistochemical and flow cytometrical techniques in wild‐type mice and CB‐NOG mice. Responses to intraperitoneal administration of toxic shock syndrome toxin‐1 (TSST‐1) under the absence or presence of LEH (10 mL/kg) were also determined 4 h and 3 days later in terms of lymphocyte composition and IL‐2 plasma level in wild‐type as well as CB‐NOG mice. When liposome (LEH or EL) was administered to wild‐type or CB‐NOG mice, the composition of B‐cells and T‐cells in the spleen or peripheral blood failed to show any consistent or significant changes. The responses to a bacterial antigen (TSST‐1) measured by IL‐2 production were comparable regardless of the presence or absence of LEH in wild‐type as well as in CB‐NOG mice. Cellularity, distribution, and maturation of these human cells in peripheral blood, spleen, and bone marrow were comparable among the groups. The results suggest that simple LEH administration may not change immune cellularity, and LEH presence may not largely affect the early T‐cell response to bacterial enterotoxins in murine as well as in reconstituted human immune systems.
HemoCD as an Artificial Oxygen Carrier: Oxygen Binding and Autoxidation
Authors: Kano Koji , Kitagishi Hiroaki
Published: January 2009

Despite many attempts to construct completely artificial systems for carrying oxygen (O2) in aqueous solution, no successful example had been reported until quite recently except for picket fence porphinatoiron(II) embedded in liposomal membrane. We newly prepared a 1:1 complex (hemoCD) of 5,10,15,20‐tetrakis(4‐sulfonatophenyl)porphinatoiron(II) (Fe[II]TPPS) and a per‐O‐methylated β‐cyclodextrin dimer having a pyridine linker (Py3CD). HemoCD binds O2 reversibly in aqueous solution. The oxygen affinity corresponding to the partial O2 pressure, at which half of the hemoCD molecules are oxygenated, was 16.9 torr in phosphate buffer at pH 7.0 and 25°C. Oxy‐hemoCD was gradually autoxidized (t1/2 = 30.1 h) due to nucleophilic attack of a water molecule to the O2–Fe bond. Encapsulation of the iron center of Fe(II)TPPS by two cyclodextrin truncated cones is essential for binding of O2 to the ferrous center of the porphyrin. This manuscript reports the basic characteristics of hemoCD and the possible future utility of a totally artificial O2 carrier.
Which Providers Should Communicate Which Critical Information About a New Medication? Patient, Pharmacist, and Physician Perspectives
Authors: Tarn Derjung M. , Paterniti Debora A. , Williams Bradley R. , Cipri Camille S. , Wenger Neil S.
Published: January 2009

OBJECTIVES: To investigate older patient, pharmacist, and physician perspectives about what information is essential to impart to patients receiving new medication prescriptions and who should provide the information.

DESIGN: Qualitative focus group discussions.

SETTINGS: Senior centers, retail pharmacies, and primary care physician offices.

PARTICIPANTS: Forty‐two patients aged 65 and older, 13 pharmacists, and 17 physicians participated in eight focus groups.

MEASUREMENT: Qualitative analysis of transcribed focus group interviews and consensus through iterative review by multidisciplinary auditors.

RESULTS: Patient, pharmacist, and physician groups all affirmed the importance of discussing medication directions and side effects and said that physicians should educate about side effects and that pharmacists could adequately counsel about certain important issues. However, there was substantial disagreement between groups about which provider could communicate which critical elements of medication‐related information. Some pharmacists felt that they were best equipped to discuss medication‐related issues but acknowledged that many patients want physicians to do this. Physicians tended to believe that they should provide most new‐medication education for patients. Patients had mixed preferences. Patients aged 80 and older listed fewer critical topics of discussion than younger patients.

CONCLUSION: Patients, pharmacists, and physicians have incongruent beliefs about who should provide essential medication‐related information. Differing expectations could lead to overlapping, inefficient efforts that result in communication deficiencies when patients receive a new medication. Collaborative efforts to ensure that patients receive complete information about new medications could be explored.
Hematopoietic engraftment of dimethyl sulfoxide–depleted autologous peripheral blood progenitor cells
Authors: Akkök Çiğdem A. , Holte Mette R. , Tangen Jon M. , Østenstad Bjørn , Bruserud Øystein
Published: January 2009

BACKGROUND: Autologous stem cell transplantation with cryopreserved autografts is a prerequisite for high‐dose chemotherapy in treatment of several malignancies. Adverse effects due to the cryoprotectant dimethyl sulfoxide (DMSO) vary from mild to severe. DMSO‐associated adverse effects can be reduced by DMSO depletion before autograft infusion. The aim was to investigate whether DMSO depletion by manual single wash reduced frequency of adverse effects or had detrimental effects on the engraftment potential of peripheral blood progenitor cell (PBPC) autografts.

STUDY DESIGN AND METHODS: Ten percent DMSO was used to cryopreserve PBPC autografts for a total of 53 patients with multiple myeloma (n = 41), non‐Hodgkin's lymphoma (n = 8), amyloidosis (n = 3), and polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes (POEMS) syndrome (n = 1). After high‐dose chemotherapy, 34 patients received unmanipulated autografts, whereas for 19 patients the autografts were manually washed before stem cell infusion. Adverse effects after the infusion as well as neutrophil (neutrophil count >0.5 × 109/L) and platelet (PLT) engraftment (PLT count >20 × 109/L) for these two groups were compared.

RESULTS: DMSO depletion reduced the frequency of adverse effects significantly. Patients transplanted with DMSO‐depleted autografts had similar neutrophil engraftment time as patients receiving unmanipulated autografts. PLT engraftment time, however, was significantly prolonged and PLT transfusion requirements significantly increased for patients receiving DMSO‐depleted autografts, even though the numbers of infused CD34+ cells per kg did not differ between the groups.

CONCLUSIONS: DMSO depletion through a manual single wash is a time‐consuming procedure that reduces adverse effects. Although the procedure leads to an increase of 2 days in PLT engraftment time, it can be recommended for selected patients with high risk of serious DMSO toxicity.
Long‐term in vitro reactivity for human leukocyte antigen antibodies and comparison of detection using serum versus plasma
Authors: Norris Philip J. , Lee Jar‐How , Carrick Danielle M. , Gottschall Jerome L. , Lebedeva Mila , De Castro B. R. , Kleinman Steven H. , Busch Michael P.
Published: January 2009

BACKGROUND: Human leukocyte antigen (HLA) antibodies are a possible cause of transfusion‐related acute lung injury (TRALI), and fluorescent bead assays are often used for antibody detection. Serum is the manufacturer's recommended sample, but plasma may be easier to obtain for studies of HLA antibody prevalence and TRALI case investigations.

STUDY DESIGN AND METHODS: Specimens were obtained from 44 multiparous females positive for the presence of HLA antibodies by lymphocytotoxicity testing at least 13 years prior and from 1000 contemporary blood donors. Screening tests were performed using a multiplex bead–based assay. In addition to comparing results obtained with paired plasma and serum samples, the effects of storage at 4°C for 1 week and of multiple freeze‐thaw cycles were evaluated.

RESULTS: Of 42 evaluable subjects with HLA antibodies documented more than 13 years earlier, only 1 showed loss of detectable antibodies, with 39 (93%) positive in the screening assay for HLA Class I and 24 (57%) positive in the screening assay for HLA Class II antibodies. In 968 evaluable contemporary donors, 291 screened positive for the presence of HLA Class I and 206 for HLA Class II antibodies using a low assay cutoff. Screening test concordance using paired plasma and serum samples was high, particularly for subjects with higher‐level antibodies. Refrigeration of samples for 1 week did not significantly affect assay results, while repeated freeze‐thaw cycles caused a decrement in signal level.

CONCLUSION: Serum and plasma samples gave concordant results in the majority of cases, particularly for specimens with higher‐level antibodies. High‐level HLA antibodies were present in most individuals for more than 13 years.
Serologic findings in autoimmune hemolytic anemia associated with immunoglobulin M warm autoantibodies
Authors: Arndt Patricia A. , Leger Regina M. , Garratty George
Published: January 2009

BACKGROUND: Autoimmune hemolytic anemia (AIHA) associated with immunoglobulin M (IgM) warm autoantibodies is unusual but often severe, with more fatalities than other types of AIHA. Diagnosing this type of AIHA can be difficult because routine serologic data are not always informative.

STUDY DESIGN AND METHODS: Forty‐nine cases of IgM warm AIHA in 25 years were studied by serologic methods.

RESULTS: Routine direct antiglobulin tests (DATs) detected red blood cell (RBC)‐bound C3 in 90 percent of cases (65% had C3 but no immunoglobulin G [IgG] on their RBCs) and IgG in 24 percent. IgM was detected on 29 of 47 (62%) patients' RBCs; RBC‐bound IgM was detected in 14 of 47 cases by a tube DAT method and in an additional 15 of 21 (71%) cases using fluorescein isothiocyanate anti‐IgM and flow cytometry. Eighty‐one percent of eluates from patients' RBCs reacted. Warm autoagglutinins were present in 94 percent of serum samples; untreated and enzyme‐treated RBCs were hemolyzed at 37°C by 13 and 65 percent of serum samples, respectively. Most agglutinins were optimally reactive at 30 to 37°C. Patients' RBCs were spontaneously agglutinated in 78 percent of cases; washing with 37°C saline or treating RBCs with dithiothreitol resolved this problem. Clear specificity of autoantibody was defined in 35 percent of serum samples.

CONCLUSION: IgM warm AIHA can be confused with cold agglutinin syndrome and “mixed/combined”‐type AIHA; a serologic workup by a specialist reference laboratory can help with the diagnosis.
Characterization of anti‐D monoclonal antibody reagents based on their reactivity with the weak D phenotype
Authors: Lai Marco , Grasso Cinzia , Boschi Ilaria , D'Onofrio Giuseppe , Pascali Vincenzo , Leone Giuseppe
Published: January 2009

BACKGROUND: Anti‐D monoclonal antibody (MoAb) reagents have improved D typing in routine tests. However, they exhibit a wide range of reactivity with the weak D phenotype depending on the characteristics of the different MoAbs used. We analyzed the reactivity of immunoglobulin (IgM) anti‐D by cluster analysis to characterize MoAb that have similar reactivities with the weak D phenotype.

STUDY DESIGN AND METHODS: We used 36 consecutive samples with weak D phenotype in routine testing and determined their reactivity with different IgM and IgG anti‐D MoAbs. The samples were characterized as belonging to a weak D type or category using commercial molecular biology kits.

RESULTS: The various anti‐D MoAbs showed a wide grade of reactivity with the weak D samples. Similarities and dissimilarities in the behavior of the anti‐D MoAbs with the weak D phenotype samples were detected with cluster analysis and the multidimensional scaling analysis. These analyses indicated different families of MoAbs characterized as having a high degree of homogeneity in their reactivity with the weak D phenotype. Between these MoAb families, the most effective at reacting with the weak D phenotype were RUM‐1 and 175‐2.

CONCLUSIONS: The results show that it is possible to classify the anti‐D MoAbs on the basis of their reactivity with the weak D phenotype. This provides information about different MoAbs' properties on the basis of their belonging to a given of anti‐D family.
A genetic strategy to control expression of human blood group antigens in red blood cells generated in vitro
Authors: Bagnis Claude , Chapel Sylvie , Chiaroni Jacques , Bailly Pascal
Published: January 2009

BACKGROUND: The ability to generate red blood cells of a chosen blood group phenotype would be a major advance in transfusion when considering low‐ and high‐frequency blood group antigens.

STUDY DESIGN AND METHODS: Cord blood CD34+ cells undergoing erythroid differentiation in vitro were genetically manipulated with human immunodeficiency virus Type 1–derived lentiviral vectors expressing hUT‐B1 cDNA (overexpression strategy) or bicistronic vectors expressing both enhanced green fluorescent protein and a short‐hairpin RNA (shRNA) designed to silence SLC14A1(JK) gene that encodes hUT‐B1 protein (silencing strategy). Resulting cell populations were analyzed by fluorescent‐activated cell sorting and gel affinity column assay.

RESULTS: When transduced with hUT‐B1 cDNA lentiviral vectors encoding JK*B and JK*A alleles, respectively, CD34+ cell–derived erythroid populations from Jk(a+b−) and Jk(a−b+) donors exhibited a Jk(a+b+) phenotype different from the original phenotype. In concomitant tests, Jk(a+b+) donor cells transduced with lentiviral vectors carrying a shRNA designed to interfere with hUT‐B1 transcription showed a marked decrease in hUT‐B1 expression and were assessed as null for Jk antigen by a routine assay.

CONCLUSION: In this work focusing on the Kidd blood group system that relies on expression of hUT‐B1 glycoprotein under the Jka or Jkb antigenic configurations, we demonstrated that hematopoietic progenitors could be genetically modified to exhibit a chosen Kidd phenotype. Beyond production of atypical Kidd phenotypes, this genetic strategy could allow generation of rare blood phenotypes from hematopoietic stem cells regardless of initial donor phenotype. Potential applications for genetically modified blood include production of control samples for immunohematologic testing and for resolution of antibody detection in multiply transfused patients.
Benchmark Dose Estimation Incorporating Multiple Data Sources
Authors: Wheeler Matthew W. , Bailer A. John
Published: January 2009

With the increased availability of toxicological hazard information arising from multiple experimental sources, risk assessors are often confronted with the challenge of synthesizing all available scientific information into an analysis. This analysis is further complicated because significant between‐source heterogeneity/lab‐to‐lab variability is often evident. We estimate benchmark doses using hierarchical models to account for the observed heterogeneity. These models are used to construct source‐specific and population‐average estimates of the benchmark dose (BMD). This is illustrated with an analysis of the U.S. EPA Region IX's reference toxicity database on the effects of sodium chloride on reproduction in Ceriodaphnia dubia. Results show that such models may effectively account for the lab‐source heterogeneity while producing BMD estimates that more truly reflect the variability of the system under study. Failing to account for such heterogeneity may result in estimates having confidence intervals that are overly narrow.
Access to Capital, Capital Structure, and the Funding of the Firm
Authors: BRAV OMER
Published: January 2009

Based upon a large data set of public and private firms in the United Kingdom, I find that compared to their public counterparts, private firms rely almost exclusively on debt financing, have higher leverage ratios, and tend to avoid external capital markets, leading to a greater sensitivity of their capital structures to fluctuations in performance. I argue that these differences are due to private equity being more costly than public equity. I further examine the private firms subsample to show that private equity is more costly than its public counterpart due to information asymmetry and the desire to maintain control.
A Prospective Randomized Trial of Defibrillation Thresholds from the Right Ventricular Outflow Tract and the Right Ventricular Apex
Authors: CROSSLEY GEORGE H. , BOYCE KER , ROELKE MARC , EVANS JOSEPH , YOUSUF DALAL , SYED ZAFFER , VICARI RALPH
Published: January 2009

Background: Right ventricular outflow tract (RVOT) pacing has been suggested to improve hemodynamics and to help prevent pacing‐induced cardiomyopathy. Pacing from the RVOT is feasible and equivalent in terms of sensing and stimulation threshold. However, physicians have been reluctant to use RVOT pacing because of concerns that defibrillation efficacy might be adversely affected. To date, there have been no randomized‐controlled trials published comparing the defibrillation threshold in leads implanted in the RVOT and the right ventricular apex (RVA).

Objective: The purpose of this study was to compare defibrillation thresholds (DFT) in the RVOT and RVA. Ventricular sensing and stimulation thresholds were also compared.

Methods: This prospective, randomized, multicenter study included 87 patients (70 males, age 69 ± 11 years). At implantation, the patient's ventricular implantable cardioverter‐defibrillator (ICD) lead position was randomized to either the RVOT or RVA. A four‐shock Bayesian up‐down method was used to determine the DFT. Patients were followed for 3 months postimplant.

Results: DFTs were not significantly different in leads implanted in the RVOT (median 8.8 J [6.28, 12.9] vs. 7.9 J [6.20, 12.6], P = 0.65). Threshold and impedance measurements were stable in both RVOT and RVA groups from implant to follow‐up. All ICD leads remained stable chronically at the 3‐month follow‐up.

Conclusion: DFTs in leads placed in the RVOT and RVA are comparable. RVOT ICD lead placement is safe and exhibits similar lead stability, threshold, and impedance measurements as the traditional RVA location.
Leadless Pacing of the Heart Using Induction Technology: A Feasibility Study
Authors: WIENEKE HEINRICH , KONORZA THOMAS , ERBEL RAIMUND , KISKER ERHARD
Published: January 2009

Objectives: To develop a leadless pacemaker system based on induction technology and to investigate its feasibility and safety in the pig model.

Background: Despite tremendous technical advances during the last decades, cardiac pacing is still associated with a considerable rate of complications that can be primarily attributed to the leads.

Methods: The device consists of a transmitter unit implanted subcutaneously just above the heart and an endocardial receiver unit implanted in the apex of the right ventricle. The transmitter unit generates an alternating magnetic field that is converted into a voltage pulse by the receiver unit. In order to test feasibility, the receiver unit was attached to an electrophysiology catheter for signal recording and placed in the apex of the right ventricle of a pig. Subsequently, the receiver unit was implanted without external connection in the right ventricle.

Results: An alternating magnetic field of about 0.5 mT was generated by the transmitter unit in a distance of 3 cm. Voltage pulses with a duration of 0.4 ms and voltage amplitude of 0.6–1.0 V were generated. Using these pulse characteristics, a reliable stimulation of the heart could be achieved. A secure fixation of the receiver unit in the apex of the right ventricle could be obtained for the duration of this short‐term study by using screw fixation.

Conclusions: This study shows that induction technology is feasible for cardiac pacing. Typical voltage pulses could be generated by which an effectively stimulation in vivo could be achieved.
Radiofrequency Catheter Ablation of Atrial Flutter Induces the Release of Platelet and Leukocyte‐Derived Procoagulant Microparticles and a Prothrombotic State
Authors: JESEL LAURENCE , MOREL OLIVIER , PYNN SOPHIE , RADULESCU BOGDAN , GRUNEBAUM LELIA , FREYSSINET JEAN‐MARIE , OHLMANN PATRICK , BAREISS PIERRRE , TOTI FLORENCE , CHAUVIN MICHEL
Published: January 2009

Background: To assess the extent of endothelium, platelet, and leukocyte damage and coagulation activation induced by radiofrequency catheter ablation (RF) of atrial flutter. In the vasculature, procoagulant microparticles (MPs) are reliable markers of vascular damage. They provide an additional phospholipidic surface, enabling the assembly of the enzyme complexes of blood coagulation and consequent thrombin generation.

Methods: MPs were measured in the venous blood of 33 patients with isthmus‐dependent atrial flutter undergoing RF before (RF0), immediately after (RF1), and at day 1 (RF2) thereafter. Concentrations of PAI‐1, vWF, and D‐dimers were simultaneously determined. MPs procoagulant activities were determined using a functional prothrombinase assay. RF induces an early rise of platelet‐derived MPs (platelet), vWF Ag, and D‐dimers levels, which is concomitant with the decrease of PAI‐1 concentrations. Conversely, no significant changes in endothelial‐derived MPs could be evidenced. At RF2, sustained elevation of leukocytes‐derived MPs, vWF, and D‐dimers testified to an ongoing prothrombotic status.

Conclusion: RF ablation of common flutter induces a prothrombotic state and the release of platelet and leukocyte‐derived procoagulant microparticles. Whereas this activation of blood coagulation could be viewed as clinically marginal in right‐sided procedures, its relevance in left‐sided procedures should be established.
Determinants of Lesion Dimensions during Transcatheter Microwave Ablation
Authors: TSE HUNG‐FAT , LIAO SONGYAN , SIU CHUNG‐WAH , YUAN LIU , NICHOLLS JOHN , LEUNG GEORGE , ORMSBY TED , FELD GREGORY K. , LAU CHU‐PAK
Published: January 2009

Background: Transcatheter microwave ablation is a novel technique for treating cardiac arrhythmias.

Methods: We investigated the effects of catheter temperature, application duration, and antenna length on lesion dimensions during catheter‐based microwave ablation. In a swine thigh muscle preparation, microwave was delivered at targeted temperatures of 60°C (n = 18), 70°C (n = 27), 80°C (n = 43), or 90°C (n = 18) for 120 seconds with 10‐mm antenna; and at targeted temperatures of 80°C for 120 seconds (n = 22), 150 seconds (n = 18), 180 seconds (n = 18), 210 seconds (n = 18), and 240 seconds (n = 17) with 20‐mm antenna using 10 F catheter (MedWaves, San Diego, CA, USA) during parallel orientation. Conventional radiofrequency ablation (RF) using a 4‐mm tip electrode was performed as control.

Results: With 120‐second energy applications, lesion length and depth were significantly larger with targeted temperatures of 80°C and 90°C than 60°C (P< 0.05). Furthermore, lesion depth and width, but not length, were significantly increased by prolonging energy application duration from 120 to 240 seconds at targeted temperature of 80°C (P< 0.05). Compared to RF, microwave lesions were significantly longer but had comparable depth and width. A 20‐mm microwave antenna produced longer lesions than either a 10‐mm antenna or RF ablation catheter. Multivariate analysis demonstrated that targeted temperature ≥80°C, application duration ≥150 seconds, and use of 20‐mm antenna were independent predictors for lesion depth and width (P< 0.05). Surface dessication was observed in 4/18 (22%) lesions at 90°C, as compared with 1/136 (0.7%) at 80°C targeted tip temperature (P < 0.05).

Conclusions: This study demonstrated that lesions size with transcatheter microwave ablation can be controlled by adjusting targeted temperature, energy application duration, and antenna length. A targeted temperature of 80°C for more than 150 seconds should provide optimal lesion dimensions and lower risk of surface dessication or charring.
The Effects of Trimetazidine on P‐Wave Duration and Dispersion in Heart Failure Patients
Authors: GUNES YILMAZ , TUNCER MUSTAFA , GUNTEKIN UNAL , AKDAG SERKAN , GUMRUKCUOGLU HASAN ALI
Published: January 2009

Background: P‐wave duration and dispersion (PWD) have been shown to be noninvasive predictors for development of atrial fibrillation. Thus, it may be possible to attenuate atrial fibrillation risk through normalization of P‐wave duration and dispersion. Trimetazidine, a metabolic modulator, has been reported to improve cardiac function in heart failure (HF) patients.

Methods: Thirty‐six HF patients being treated with angiotensin inhibitors, carvedilol, spironolactone, and furosemide were prescribed trimetazidine, 20 mg three times a day. Electrocardiographic and echocardiographic examinations were obtained before and 6 months after addition of trimetazidine in HF patients and 36 healthy control group patients having normal echocardiographic examination.

Results: Maximum P‐wave duration (Pmax) (106.7 ± 15.8 vs. 91.7 ± 12.7 ms) and PWD (57.2 ± 15.4 vs. 37.9 ± 16.7 ms) were significantly longer in HF patients compared to the control group. There were significant correlations of Pmax and PWD with left atrial diameter (r = 0.508, P = < 0.001 and r = 0.315, P = 0.029), left ventricular ejection fraction (LVEF) (r = 0.401, p = 0.005 and r = 0.396, P = 0.005), deceleration time (r = 0.296, P = 0.032 and r = 0.312, P = 0.035), and isovolumetric relaxation time (r = 0.265, P = 0.038 and r = 0.322, P = 0.015). There were significant improvements in LVEF (32.7 ± 6.5% to 37.2 ± 5.5%, P = 0.036), left atrial diameter (41.5 ± 6.7 to 40.3 ± 6.1 mm, P < 0.001), and Pmax (106.7 ± 15.8 to 102.2 ± 11.5 ms, P = 0.006) and PWD (57.2 ± 15.4 to 48.9 ± 10.1 ms, P < 0.001) during follow‐up.

Conclusions: Trimetazidine added to optimal medical therapy in HF may improve Pmax and PWD in association with improved left ventricular function. Longer‐term and larger studies are necessary to evaluate whether these findings may have clinical implications on prevention of atrial fibrillation.
Right Atrial Pacemaker Lead Thrombosis Causing Tricuspid Inflow Obstruction
Authors: TUGCU AYLIN , YILDIRIMTURK OZLEM , TAYYARECI YELDA , SAGBAS ERTAN , YAZICIOGLU NURAN , AYTEKIN SAIDE
Published: January 2009

A 75‐year‐old man was admitted to our hospital with a complaint of progressive dyspnea with effort. The patient had a permanent pacemaker that was implanted 16 years ago. Transesophageal echocardiography revealed a large, mobile mass in the right atrium attaching to the insertion site of the atrial lead at the tricuspid valve level. Because of the size, mobility, and location of the mass, urgent surgical removal was considered. The mass was successfully removed. Histologic examination of the mass demonstrated a partially organized thrombus. The postoperative course was uneventful and the patient's symptoms improved remarkably after operation.
Mapping and Ablation of Multiple Atrial Arrhythmias in a Patient with Persistent Atrial Standstill after Remote Viral Myocarditis
Authors: ABDELWAHAB AMIR , SAPP JOHN L. , PARKASH RATIKA , BASTA MAGDY , GARDNER MARTIN
Published: January 2009

This is a case of multiple atrial arrhythmias (atrioventricular node reentry and two different focal atrial tachycardias) originating from the remaining atrial myocardium after global scarring of both atria following a remote viral myocarditis. All the induced arrhythmias were successfully treated with catheter ablation.
Continuing Medical Education Program in Echocardiography
Authors: Fan Pohoey , Skolnick Adam , Vavas Eleni , Kronzon Itzhak
Published: January 2009

Article Title: Optimization of ASD Assessment Using Real Time Three‐Dimensional Transesophageal Echocardiography
Bayesian Inference for Smoking Cessation with a Latent Cure State
Authors: Luo Sheng , Crainiceanu Ciprian M. , Louis Thomas A. , Chatterjee Nilanjan
Published: January 2009

Summary We present a Bayesian approach to modeling dynamic smoking addiction behavior processes when cure is not directly observed due to censoring. Subject‐specific probabilities model the stochastic transitions among three behavioral states: smoking, transient quitting, and permanent quitting (absorbent state). A multivariate normal distribution for random effects is used to account for the potential correlation among the subject‐specific transition probabilities. Inference is conducted using a Bayesian framework via Markov chain Monte Carlo simulation. This framework provides various measures of subject‐specific predictions, which are useful for policy‐making, intervention development, and evaluation. Simulations are used to validate our Bayesian methodology and assess its frequentist properties. Our methods are motivated by, and applied to, the Alpha‐Tocopherol, Beta‐Carotene Lung Cancer Prevention study, a large (29,133 individuals) longitudinal cohort study of smokers from Finland.
A Semiparametric Joint Model for Longitudinal and Survival Data with Application to Hemodialysis Study
Authors: Li Liang , Hu Bo , Greene Tom
Published: January 2009

Summary In many longitudinal clinical studies, the level and progression rate of repeatedly measured biomarkers on each subject quantify the severity of the disease and that subject's susceptibility to progression of the disease. It is of scientific and clinical interest to relate such quantities to a later time‐to‐event clinical endpoint such as patient survival. This is usually done with a shared parameter model. In such models, the longitudinal biomarker data and the survival outcome of each subject are assumed to be conditionally independent given subject‐level severity or susceptibility (also called frailty in statistical terms). In this article, we study the case where the conditional distribution of longitudinal data is modeled by a linear mixed‐effect model, and the conditional distribution of the survival data is given by a Cox proportional hazard model. We allow unknown regression coefficients and time‐dependent covariates in both models. The proposed estimators are maximizers of an exact correction to the joint log likelihood with the frailties eliminated as nuisance parameters, an idea that originated from correction of covariate measurement error in measurement error models. The corrected joint log likelihood is shown to be asymptotically concave and leads to consistent and asymptotically normal estimators. Unlike most published methods for joint modeling, the proposed estimation procedure does not rely on distributional assumptions of the frailties. The proposed method was studied in simulations and applied to a data set from the Hemodialysis Study.
Applications of Extensions of Bivariate Rank Sum Statistics to the Crossover Design to Compare Two Treatments Through Four Sequence Groups
Authors: Kawaguchi Atsushi , Koch Gary G. , Ramaswamy Ratna
Published: January 2009

Summary This article describes applications of extensions of bivariate rank sum statistics to the crossover design with four sequence groups for two treatments. A randomized clinical trial in ophthalmology provides motivating background for the discussion. The bilateral design for this study has four sequence groups T:T, T:P, P:T, and P:P, respectively, for T as test treatment or P as placebo in the corresponding order for the left and right eyes. This article describes how to use the average of the separate Wilcoxon rank sum statistics for the left and right eyes for the overall comparison between T and P with the correlation between the two eyes taken into account. An extension of this criterion with better sensitivity to potential differences between T and P through reduction of the applicable variance has discussion in terms of a conceptual model with constraints for within‐side homogeneity of groups with the same treatment and between‐side homogeneity of the differences between T and P. Goodness of fit for this model can have assessment with test statistics for its corresponding constraints. Simulation studies for the conceptual model confirm better power for the extended test statistic with its full invocation than other criteria without this property. The methods summarized here are illustrated for the motivating clinical trial in ophthalmology, but they are applicable to other situations with the crossover design with four sequence groups for either two locations for two treatments at the same time for a patient or two successive periods for the assigned treatments for a recurrent disorder. This article also notes that the methods based on its conceptual model can have unsatisfactory power for departures from that model where the difference between T and P via the T:T and P:P groups is not similar to that via the T:P and P:T groups, as might occur when T has a systemic effect in a bilateral trial. For this situation, more robust test statistics have identification, but there is recognition that the parallel groups design with only the T:T and P:P groups may be more useful than the bilateral design with four sequence groups.
Latent‐Model Robustness in Joint Models for a Primary Endpoint and a Longitudinal Process
Authors: Huang Xianzheng , Stefanski Leonard A. , Davidian Marie
Published: January 2009

Summary Joint modeling of a primary response and a longitudinal process via shared random effects is widely used in many areas of application. Likelihood‐based inference on joint models requires model specification of the random effects. Inappropriate model specification of random effects can compromise inference. We present methods to diagnose random effect model misspecification of the type that leads to biased inference on joint models. The methods are illustrated via application to simulated data, and by application to data from a study of bone mineral density in perimenopausal women and data from an HIV clinical trial.
Health‐related quality of life is maintained in hemodialysis patients receiving pharmaceutical care: A 2‐year randomized, controlled study
Authors: PAI Amy Barton , BOYD Alex , CHAVEZ Alicia , MANLEY Harold J.
Published: January 2009

End‐stage renal disease and initiation of hemodialysis (HD) adversely affect health‐related quality of life (HRQOL). There are currently no data evaluating the effect of pharmaceutical care (PC) on HRQOL in HD patients. HD patients were randomized to receive PC; one‐on‐one, in‐depth medication reviews conducted by a clinical pharmacist or Standard of Care (SOC); and brief medication reviews conducted by dialysis nurses. The renal quality of life profile (RQLP) was administered at baseline and then at 1 and 2 years after study initiation. The RQLP is a 43‐item questionnaire that has 5 dimensions: Eating/Drinking, Physical Activities, Leisure Time, Psychosocial Activities, and Impact of Treatment, where increasing scores reflect worsening of HRQOL. A total of 107 patients were enrolled (SOC: n=46; PC: n=61). Besides gender, there were no differences in the demographics or the baseline total RQLP scores. The mean±SD total RQLP scores at Year 1 were significantly worse in SOC compared with PC (88±31 vs. 71±34, respectively; P=0.03). Significant worsening of Eating and Drinking (5.9±3.3 vs. 4.4±3.1, respectively; P=0.04), Physical Activities (37±13.6 vs. 30±16.3, respectively; P=0.04), and Leisure Time scores (8.3±3.4 vs. 5.9±3.6, respectively; P=0.03) was also observed in the SOC group. After 2 years, only the SOC patients had worsening of Leisure Time (7.5±3.0 vs. 5.2±3.9, respectively; P=0.04). No other parameters were different between the groups after 2 years. These data indicate that patients who have clinical care provided by pharmacists do not have worsened HRQOL after 1 year and are able to maintain HRQOL for an additional year.
Using water wisely: New, affordable, and essential water conservation practices for facility and home hemodialysis
Authors: AGAR John W. M. , SIMMONDS Rosemary E. , KNIGHT Richard , SOMERVILLE Christine A.
Published: January 2009

Despite a global focus on resource conservation, most hemodialysis (HD) services still wastefully or ignorantly discard reverse osmosis (R/O) “reject water” (RW) to the sewer. However, an R/O system is producing the highly purified water necessary for dialysis, it rejects any remaining dissolved salts from water already prefiltered through charcoal and sand filters in a high‐volume effluent known as RW. Although the RW generated by most R/O systems lies well within globally accepted potable water criteria, it is legally “unacceptable” for drinking. Consequently, despite being extremely high‐grade gray water, under current dialysis practices, it is thoughtlessly “lost‐to‐drain.” Most current HD service designs neither specify nor routinely include RW‐saving methodology, despite its simplicity and affordability. Since 2006, we have operated several locally designed, simple, cheap, and effective RW collection and distribution systems in our in‐center, satellite, and home HD services. All our RW water is now recycled for gray‐water use in our hospital, in the community, and at home, a practice that is widely appreciated by our local health service and our community and is an acknowledged lead example of scarce resource conservation. Reject water has sustained local sporting facilities and gardens previously threatened by indefinite closure under our regional endemic local drought conditions. As global water resources come under increasing pressure, we believe that a far more responsible attitude to RW recycling and conservation should be mandated for all new and existing HD services, regardless of country or region.
Cardiovascular conditions in hemodialysis patients may be worsened by extensive interdialytic weight gain
Authors: HOLMBERG Benny , STEGMAYR Bernd G.
Published: January 2009

The risk of death is increased for hemodialysis (HD) patients compared with age‐matched healthy subjects, the main reason for this being cardiovascular conditions. This prospective study investigated whether the burden of interdialytic weight gain (IDWG) was of importance for cardiovascular end points and survival. A total of 97 HD patients were studied. The end points included death (reasons given), acute myocardial infarction, or coronary vascular intervention. The extent of ultrafiltration was measured at predefined follow‐up points. The IDWG was calculated as ultrafiltration/body weight given in weight%. The burden of IDWG was analyzed. End points occurred in 77 (79%) of the patients during the 5‐year study period. The extent of IDWG was higher in those with end points due to cardiovascular reasons (3.77 weight% vs. 3.19 P<0.001), cardiac reasons (P<0.001), congestive heart failure (P<0.01), aortic aneurysm, and intracerebral bleeding (P<0.024). To reduce the risk for cardiovascular events, it is important to avoid too extensive IDWG in HD patients.