bluuebunny/crossref_metadata_2025_split huggingface dataset:
Technology for Enhanced Transfusion Safety
Authors: Dzik Walter H. 
Published: November 2005

AbstractData from reporting systems around the world document that non-infectious hazards are the leading cause of serious morbidity or mortality resulting from blood transfusion. Among these non-infectious hazards, mis-transfusion represents the most frequently observed serious hazard and occurs at an estimated rate of 1 in 14,000 transfusions. Mis-transfusion events result from “lapse errors” (slip ups) rather than cognitive mistakes. Lapse errors are more likely to occur during repetitive tasks when individuals are distracted, rushed, or fatigued—conditions to which machines are not susceptible. The final bedside check and the collection of patient samples for pre-transfusion testing are key “error spots” and are candidates for new technology innovation. Existing technology includes non-computerized devices; bedside devices based on bar code technology; and the use of radiofrequency chips. Several commercial systems employing bar-code technology have reached clinical application or are undergoing refinement. Radiofrequency-based systems are on the near horizon. Nearly all systems begin with the application of machine-readable data to the patient’s wristband. The third error spot—the decision to transfuse—will be a challenging area for future application of information technology. Computerized physician order-entry, decision support and ultimately active computer-based decision-making are expected to enhance transfusion decisions. Despite the explosive growth in information technology in modern society, healthcare has lagged behind many other sectors in the use of enhanced information technology. Studies are needed to identify which technologies improve patient outcomes. Healthcare workers, administrators, and regulators need to embrace the use of new technology in order to reduce errors and improve safety for patients.
Cancer Survivorship—Pediatric Issues
Authors: Bhatia Smita 
Published: November 2005

Abstract
The last three decades have seen tremendous improvements in survival of children diagnosed with cancer, with the 5-year survival rate approaching 80%. This improvement in survival has resulted in a growing population of childhood cancer survivors. Use of cancer therapy at an early age can produce complications that may not become apparent until years later. Approximately two thirds of the survivors of childhood cancer will experience at least one late effect, and about one third will experience a late effect that is severe or life threatening. Long-term complications in childhood cancer survivors, such as impairment in growth and development, neurocognitive dysfunction, cardiopulmonary compromise, endocrine dysfunction, renal impairment, gastrointestinal dysfunction, musculoskeletal sequelae, and subsequent malignancies, are related not only to the specific therapy employed, but may also be determined by individual host characteristics. We review the known late effects of treatment in survivors of childhood cancer in order to suggest reasonable starting points for evaluation of specific long-term problems in this unique but growing population. The Children’s Oncology Group (COG) has developed risk-based, exposure-related guidelines for follow-up care that are available at www.surivorshipguidelines.org.
Anemia in the Elderly: A Public Health Crisis in Hematology
Authors: Guralnik Jack M. , Ershler William B. , Schrier Stanley L. , Picozzi Vincent J. 
Published: November 2005

Abstract
Over 3 million people in the United Staes aged 65 years and older are anemic. This condition is associated with significant functional impairment and, perhaps, increased mortality. In March 2004, the American Society of Hematology (in conjunction with the National Institute of Aging) convened a “blue ribbon” panel of twenty physicians who are experts on various aspects of this topic. This paper highlights important consensus concepts resulting from that meeting. In particular, four areas of thought are shared. First, the epidemiology of anemia in the elderly is reviewed, including its definition, its expression in different racial groups, and its wide-ranging manifestations. Second, the pathophysiology of anemia in the elderly is reviewed as pertains to three general etiological categories (nutritional, chronic diseases, and so-called “unexplained” anemias). Particular emphasis is given to pathophysiologic mechanisms of anemia that are potentially unique to this age group. Third, a practical approach to the diagnosis and management of anemia for this patient population for the practicing hematologist is provided. Finally, the public health implications of anemia in the elderly for key stakeholder constituencies will be discussed in the oral presentation.
Stem Cell Therapy for Sickle Cell Disease: Transplantation and Gene Therapy
Authors: Walters Mark C. 
Published: November 2005

AbstractHLA-identical sibling hematopoietic cell transplantation (HCT) for sickle cell disease (SCD) has a strong track record of efficacy and there is growing appreciation that its benefits exceed its risks in selected individuals. In contrast, the clinical utility of replacement gene therapy for sickle cell disease remains unproven. Its challenge is to ensure viral transduction into hematopoietic stem cells (HSCs) and to generate safe, stable, erythroid-specific replacement gene expression at a level that is sufficient to have a clinical effect. The clinical necessity for fulfilling all these criteria may make this genetic disorder among the most complex to treat successfully by gene therapy. But the experience of HCT for SCD has proven that eliminating the βS-globin gene is curative when the transfer is stable. Thus replacement gene therapy for sickle cell disease remains a subject of intense interest and investigation.
Chronic Granulomatous Disease and Other Disorders of Phagocyte Function
Authors: Dinauer Mary C. 
Published: November 2005

AbstractThe analysis of specific gene defects in disorders of phagocyte function has shed light on important aspects of the innate immune response. Each disorder has distinctive features in the clinical presentation and characteristic microbial pathogens. Chronic granulomatous disease has been extensively studied both in patient series and in mouse models. New insights continue to be obtained regarding the role of the nicotinamide dinucleotide phosphate (NADPH) oxidase and related enzymes in host defense and other aspects of the inflammatory response, as well as optimal management of this disorder. Approaches based on hematopoietic stem cell transplantation and gene therapy offer promise for the future, but are still under investigation. Also briefly summarized are updates on newly described leukocyte adhesion defects and on inherited susceptibility to mycobacterial infection due to defects in interleukin (IL)-12 and interferon-γ pathways.
Endothelial protein C receptor (CD201) explicitly identifies hematopoietic stem cells in murine bone marrow
Authors: Balazs Alejandro B. , Fabian Attila J. , Esmon Charles T. , Mulligan Richard C. 
Published: November 2005

AbstractThe hematopoietic stem cell (HSC) is a unique cell type found in bone marrow, which has the capacity for both self-renewal and differentiation into all blood lineages. The identification of genes expressed specifically in HSCs may help identify gene products vital to the control of self-renewal and/or differentiation, as well as antigens capable of forming the basis for improved methods of stem cell isolation. In previous studies, we identified a number of genes that appeared to be differentially expressed in murine bone marrow–derived HSCs, using microarray technology. We report here that one of those genes, encoding the murine endothelial protein C receptor (EPCR), is expressed at high levels within the bone marrow in HSCs. Bone marrow cells isolated on the basis of EPCR expression alone are highly enriched for hematopoietic reconstitution activity, showing levels of engraftment in vivo comparable to that of stem cells purified using the most effective conventional methods. Moreover, evaluation of cell populations first enriched for stem cell activity by conventional methods and subsequently fractionated on the basis of EPCR expression indicates that stem cell activity is always associated with EPCR-expressing cells. Based on our findings, we believe EPCR represents the first known marker that `explicitly' identifies hematopoietic stem cells within murine bone marrow.
Keratinocyte growth factor (KGF) is required for postnatal thymic regeneration
Authors: Alpdogan Önder , Hubbard Vanessa M. , Smith Odette M. , Patel Neel , Lu Sydney , Goldberg Gabrielle L. , Gray Daniel H. , Feinman Jared , Kochman Adam A. , Eng Jeffrey M. , Suh David , Muriglan Stephanie J. , Boyd Richard L. , van den Brink Marcel R. M. 
Published: November 2005

AbstractKeratinocyte growth factor (KGF) is a member of the fibroblast growth factor family that mediates epithelial cell proliferation and differentiation in a variety of tissues, including the thymus. We studied the role of KGF in T-cell development with KGF-/- mice and demonstrated that thymic cellularity and the distribution of thymocyte subsets among KGF-/-, wildtype (WT), and KGF+/- mice were similar. However, KGF-/- mice are more vulnerable to sublethal irradiation (450 cGy), and a significant decrease was found in thymic cellularity after irradiation. Defective thymopoiesis and peripheral T-cell reconstitution were found in KGF-/- recipients of syngeneic or allogeneic bone marrow transplant, but using KGF-/- mice as a donor did not affect T-cell development after transplantation. Despite causing an early developmental block in the thymus, administration of KGF to young and old mice enhanced thymopoiesis. Exogenous KGF also accelerated thymic recovery after irradiation, cyclophosphamide, and dexamethasone treatment. Finally, we found that administering KGF before bone marrow transplantation (BMT) resulted in enhanced thymopoiesis and peripheral T-cell numbers in middle-aged recipients of an allogeneic BM transplant. We conclude that KGF plays a critical role in postnatal thymic regeneration and may be useful in treating immune deficiency conditions. (Blood. 2006;107:2453-2460)
αIIbβ3 biogenesis is controlled by engagement of αIIb in the calnexin cycle via the N15-linked glycan
Authors: Mitchell W. Beau , Li JiHong , French Deborah L. , Coller Barry S. 
Published: November 2005

AbstractAlthough much is known about αIIbβ3 structure and function, relatively little is understood about its biogenesis. Thus, we studied the kinetics of pro-αIIb production and degradation, focusing on whether proteasomal degradation or the calnexin cycle participates in these processes. In pulse-chase analyses, the time to half-disappearance of pro-αIIb (t1/2) was the same in (1) HEK293 cells transfected with (a) αIIb plus β3, (b) αIIb alone, (c) mutant V298FαIIb plus β3, or (d) I374TαIIb plus β3; and (2) murine wild-type and β3-null megakaryocytes. Inhibition of the proteasome prolonged the t1/2 values in both HEK293 cells and murine megakaryocytes. Calnexin coprecipitated with αIIb from HEK293 cells transfected with αIIb alone, αIIb plus β3, and V298FαIIb plus β3. For proteins in the calnexin cycle, removal of the terminal mannose residue of the middle branch of the core N-linked glycan results in degradation. Inhibition of the enzyme that removes this mannose residue prevented pro-αIIb degradation in β3-null murine megakaryocytes. αIIb contains a conserved glycosylation consensus sequence at N15, and an N15Q mutation prevented pro-αIIb maturation, complex formation, and degradation. Our findings suggest that pro-αIIb engages the calnexin cycle via the N15 glycan and that failure of pro-αIIb to complex normally with β3 results in proteasomal degradation.
Macrophages from C3-deficient mice have impaired potency to stimulate alloreactive T cells
Authors: Zhou Wuding , Patel Hetal , Li Ke , Peng Qi , Villiers Marie-Bernadette , Sacks Steven H. 
Published: November 2005

AbstractImpaired T-cell reactivity is a feature of C3-deficient mice in several disease models. The mechanism behind the reduced T-cell response is, however, poorly understood. We explored the hypothesis that antigen-presenting cells (APCs) from C3-/- mice have impaired potency to stimulate antigen-specific T cells, in an alloantigen-dependent model. Our results show that C3-/- macrophages have reduced ability to elicit alloreactive T-cell responses in vitro and in vivo, affecting both the primary and secondary responses. The C3 status of donor macrophages had a major impact on the CD4 T-cell response. The impaired CD4 T-cell response was associated with reduced expression of MHC class II on the surface of C3-/- macrophages, without loss of class II gene expression. Furthermore, inhibition of C3 gene expression in C3+/+ macrophages reduced their ability to stimulate alloreactive T cells, suggesting that endogenous production of C3 could in part contribute to the potency of APCs. Our data provide compelling evidence that C3 deficiency modulates the potency of APCs to stimulate the T-cell response, suggesting a critical role for complement in the maintenance of APC function. This could offer a partial explanation as to why the T-cell response is impaired in C3-/- mice. (Blood. 2006;107:2461-2469)
Hypoxic induction of an HIF-1α–dependent bFGF autocrine loop drives angiogenesis in human endothelial cells
Authors: Calvani Maura , Rapisarda Annamaria , Uranchimeg Badarch , Shoemaker Robert H. , Melillo Giovanni 
Published: November 2005

AbstractHypoxia is a major pathophysiological condition for the induction of angiogenesis, which is a crucial aspect of growth in solid tumors. In mammalian cells, the transcriptional response to oxygen deprivation is largely mediated by hypoxia-inducible factor 1 (HIF-1), a heterodimer composed of HIF-1α and HIF-1β subunits. However, the response of endothelial cells to hypoxia and the specific involvement of HIF-α subunits in this process are still poorly understood. We show that human umbilical vein endothelial cells (HUVECs) cultured in the absence of growth factors survive and form tubelike structures when cultured under hypoxic, but not normoxic, conditions. HUVECs expressed both HIF-1α and HIF-2α when cultured under hypoxic conditions. Transfection of HIF-1α, but not HIF-2α, siRNA to HUVECs completely abrogated hypoxic induction of cords. Neutralizing antibodies to bFGF, but not IGF-1, VEGF, or PDGF-BB, blocked survival and sprouting of HUVECs under hypoxic conditions, suggesting the existence of an autocrine loop induced by low oxygen levels. Notably, bFGF-dependent induction of cord formation under normoxic conditions required HIF-1α activity, which was also essential for hypoxic induction of bFGF mRNA and protein expression. These results uncover the existence of an HIF-1α–bFGF amplification pathway that mediates survival and sprouting of endothelial cells under hypoxic conditions.
Therapeutic lung lavages in children and adults
Authors: Paschen Christian , Reiter Karl , Stanzel Franz , Teschler Helmut , Griese Matthias 
Published: November 2005

AbstractBackgroundPulmonary alveolar proteinosis (PAP) is a rare disease, characterized by excessive intra-alveolar accumulation of surfactant lipids and proteins. Therapeutic whole lung lavages are currently the principle therapeutic option in adults. Not much is known on the kinetics of the wash out process, especially in children.MethodsIn 4 pediatric and 6 adult PAP patients 45 therapeutic half lung lavages were investigated retrospectively. Total protein, protein concentration and, in one child with a surfactant protein C mutation, aberrant pro-SP-C protein, were determined during wash out.ResultsThe removal of protein from the lungs followed an exponential decline and averaged for adult patients 2 – 20 g and <0.5 to 6 g for pediatric patients. The average protein concentration of consecutive portions was the same in all patient groups, however was elevated in pediatric patients when expressed per body weight. The amount of an aberrant pro-SP-C protein, which was present in one patient with a SP-C mutation, constantly decreased with ongoing lavage. Measuring the optical density of the lavage fluid obtained allowed to monitor the wash out process during the lavages at the bedside and to determine the termination of the lavage procedure at normal protein concentration.ConclusionFollowing therapeutic half lung lavages by biochemical variables may help to estimate the degree of alveolar filling with proteinaceous material and to improve the efficiency of the wash out, especially in children.
AGI-1067: A Novel Vascular Protectant for Prevention of Restenosis
Authors: Franks Amy M , Gardner Stephanie F 
Published: November 2005

Objective: To review the synthesis, pharmacology, clinical trials, and adverse effects of AGI-1067, a novel agent for preventing restenosis. Data Sources: Literature searches were conducted using MEDLINE (1966–July 2005) and International Pharmaceutical Abstracts (1970–July 2005) for English-language articles containing the search terms AGI-1067, AGI 1067, and probucol. In addition, bibliographies from relevant articles were reviewed for additional references. Study Selection and Data Extraction: All articles identified from data sources were reviewed for relevant information. Applicable information was included in this review. Data Synthesis: AGI-1067, a derivative of the lipid-lowering agent probucol, is the first of a new class of drugs termed vascular protectants. It has antioxidant and lipid-lowering effects. In addition, it inhibits inflammatory processes without resultant immunosuppression through its selective inhibition of vascular cell adhesion molecule-1 expression. AGI-1067 also exhibited anti-atherosclerotic effects in preclinical studies. Relatively short-term treatment with AGI-1067 showed positive results compared with probucol in preventing restenosis in patients undergoing percutaneous coronary intervention. AGI-1067 appears to be well tolerated and holds important advantages over probucol in that it has fewer adverse effects on high-density lipoprotein cholesterol and the QT interval. Conclusions: The favorable safety profile of AGI-1067 offers potential advantages over its precursor, probucol. Preclinical and clinical studies indicate that it possesses antioxidant, antiinflammatory, and lipid-lowering properties. Ongoing Phase II and III studies will determine AGI-1067's place in therapy for the prevention of restenosis and reduction in cardiovascular events in patients undergoing percutaneous intervention for coronary atherosclerosis.
Generic Substitution of Antihypertensive Drugs: Does it Affect Adherence?
Authors: Wijk Boris LG Van , Klungel Olaf H , Heerdink Eibert R , Boer Anthonius de 
Published: November 2005

Background:Generic substitution is an important opportunity to reduce the costs of pharmaceutical care. However, pharmacists and physicians often find that patients and brand-name manufacturers have doubt about the equivalence of the substituted drug. This may be reflected by decreased adherence to therapy.Objective:To assess the association between generic substitution and nonadherence to antihypertensive drugs.Methods:We conducted a matched cohort study between January 1, 1999, and December 31, 2002. Data were obtained from PHARMO, a record linkage system containing drug-dispensing records from community pharmacies and linked hospital discharge records of approximately 950 000 people in the Netherlands. Residents of 30 medium-sized cities who initiated antihypertensive drug therapy were potential subjects. Refill adherence with antihypertensive drugs after substitution was determined; those with refill adherence below 80% were considered nonadherent.Results:Four hundred sixty-three patients with a substitution in therapy and 565 controls, matched on age, gender, therapy start date, duration of use, and generic product code, were identified. Of the patients who switched from brand-name to generic formulations (“substituted”), 13.6% were nonadherent, and of the non-substituted patients (those who did not switch to generic), 18.7% were nonadherent (OR 0.68; 95% aph.1G163CI 0.48 to 0.96). The association was absent in males. None of the patients discontinued the medication. No differences in hospitalizations for cardiovascular disease in the 6 months after the substitution were observed.Conclusions:Generic substitution of antihypertensive drugs does not lead to lower adherence or more discontinuation and cardiovascular disease–related hospitalizations compared with brand-name therapy. When a less-expensive antihypertensive generic equivalent becomes available, generic substitution should be considered to achieve economic benefits.
Preparation and Characterization of Fe-PILCs. Influence of the Synthesis Parameters
Authors: Valverde José Luis , Romero Amaya , Romero Rubí , García Prado Belén , Sánchez María Luz , Asencio Isaac 
Published: November 2005

AbstractIron-pillared clays (Fe-PILCs) were synthesized from hydrolyzed FeCl3 solutions added to NaOH solutions using different synthesis conditions. X-ray diffraction, N2 adsorption-desorption, chemical analysis, thermogravimetric analysis, differential thermal analysis, temperature-programmed desorption of ammonia and temperature-programmed reduction were used to characterize the resulting Fe-pillared clays (Fe-PILCs). A higher degree of pillaring was obtained when the Fe content was adjusted to 60 mmoles of Fe/g of clay. It was observed that higher values of this ratio led to worse acidity and textural characteristics, a consequence of the probable formation of Fe oxides that could not only deposit on the surface but also block the pores formed during the pillaring process. Likewise, it was found that the amount of Fe that can be introduced depended on the OH/Fe ratios. Total surface and micropore area decreased and Fe content increased with increasing pillaring solution concentrations. Finally, all pillared samples prepared here were thermally stable at temperatures up to 400°C.
Effects of Ethylene Glycol Saturation Protocols on XRD Patterns: A Critical Review and Discussion
Authors: Mosser-Ruck Regine , Devineau Karine , Charpentier Delphine , Cathelineau Michel 
Published: November 2005

AbstractStudy of the transformation of smectite to illite, chlorite or vermiculite via interstratified clay minerals needs precise qualitative and quantitative determinations of the different layers in the mixed-layer clays and is generally based on X-ray diffraction (XRD) patterns after specific treatments of the clay samples. Saturation with K or Mg followed by ethylene glycol (EG) solvation are classical methods used to identify high-charge smectite and vermiculite. These procedures have been applied to two experimental clays, one composed of smectite layers and the second, a mixture of vermiculite and smectite layers. Different methods of glycolation (EG vapor or liquid EG) produce significant differences in the XRD patterns. Comparison with literature data indicates that K-saturated, high-charge smectite (≈0.8 < total charge <1/unit-cell) and Mg-vermiculite (whatever its charge) do not expand in ethylene glycol vapor (d values ≈14–15 Å). Expansion to 17 Å in liquid ethylene glycol occurs for Mg-vermiculite with a total charge of <~1.2/unit-cell and for K-saturated, high-charge smectite, when the tetrahedral charge is <≈0.7/unit-cell. This study shows that: (1) glycolation procedures need to be standardized; (2) the use of saturation protocols using both liquid ethylene glycol and ethylene glycol vapor yields useful additional information about the distribution of charges in clay minerals.