bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Contribution of a Blood Establishment to the Increased Use of Intraoperative Cell Salvage in Hospitals: A Pilot Study From the National Blood Service, England
Authors: James Virge , Lamb Jo 
Published: February 2008

SUMMARYThis paper describes a strategy developed and implemented in 5 major hospitals in a health region in the center of England jointly by the hospitals and the National Blood Service (NBS).The aim was to increase the use of intraoperative cell salvage (ICS). Hospital managers were asked to nominate “lead clinicians” and the NBS provided the funding. Equipment was leased from 3 companies which also provided the initial training for operatives. A single audit form was devised and completed for every procedure; these were analyzed by the NBS. Preliminary results showed that the strategy achieved its aims both in encouraging increased use and demonstrating savings in donor blood. Detailed cost/benefit analyses are ongoing. The pilot has spawned numerous further initiatives
Plasma Procurement and Self‐Sufficiency
Authors: Hossenlopp Claudine , Velati Claudio , Rouger Philippe 
Published: February 2008

SUMMARYEuroNet‐TMS, the European Network of Transfusion Medicine Societies, was constituted in early 2002. During 2003, EuroNet‐TMS committees worked on a broad survey aimed at drawing a map of the situation in the European Union (EU) on issues of immediate relevance. Nine questionnaires were drafted by EuroNet‐TMS committees and sent out to the seventeen countries who wished to be part of this survey. The results shown here represent a first broad outline of the situation in Europe in terms of plasma procurement and self‐sufficiency. Further details are still to be obtained before the official publication of EuroNet‐TMS in the second semester of 2004. The data reflect a heterogeneous situation mainly observed in all other fields, most obviously related to discrepancies in the blood transfusion organizations throughout Europe and in their health policies in general. The application of the EU directive on blood in 2005 might affect these data, as general regulations will be the same for all 15 + 10 EU countries.
Novel Hemostatic Agents: A Focus on Recombinant Factor VIIa and Factor XIII
Authors: Young Guy 
Published: February 2008

SUMMARYExcessive bleeding accounts for a significant incidence of morbidity and mortality resulting from a variety of conditions including congenital and acquired bleeding disorders, trauma, and surgery. A complex network of cellular and plasma components are involved in the process of controlling excessive bleeding, a process known as hemostasis. When excessive bleeding does occur, there are a wide variety of agents with diverse mechanisms of action that can promote hemostasis. These agents include blood products, biologicals such as recombinant proteins, synthetic medications, and topical agents. Historically, non‐specific agents such as fresh frozen plasma, cryoprecipitate and antifibrinolytic agents have been the standard therapies for the management of excessive bleeding. These, however, all have significant limitations. Recently, recombinant factor VIIa (rFVIIa) was licensed for use in patients with hemophilia and inhibitors to factors VIII or IX. Since its licensure, it has been used in a wide variety of conditions with excessive bleeding leading to often dramatic results. Another novel agent is factor XIII (FXIII) which is currently in clinical trials. Although data regarding its use in conditions other than FXIII deficiency is lacking, it is expected that FXIII will become another effective agent in the management of excessive bleeding.
Treatment of Hemophilia With Genetic Engineering
Authors: Axsom Kelly M. , Manno Catherine S. 
Published: February 2008

SummaryHemophilia is a disorder characterized by decreased amounts of functional, circulating coagulation proteins VIII or IX. It has been well documented that by maintaining factor levels at ≥ 1% the major complications of severe disease, such as spontaneous bleeding, are averted. Successful gene transfer for hemophilia would result in persistent transgene expression at levels ≥ 1%. Hemophilia is an ideal candidate for the application of gene transfer because of the wide therapeutic window for the relevant factors, the availability of animal models, the ability of many tissues other than the liver to produce the coagulation proteins, and the desire for more convenient and cost‐efficient treatments. For these reasons, hemophilia has the potential to be one of the first severe genetic disorders to be treated, if not cured, with gene therapy. This paper summarizes the progress and challenges of gene transfer studies for hemophilia.
Aprotinin and Major Orthopedic Surgery
Authors: Samama Charles Marc 
Published: February 2008

SUMMARYAprotinin is a potent pharmacological agent which reduces bleeding and limits blood transfusion in current surgical practice. Many studies have been conducted in orthopedic surgery. Several trials have been performed in total hip replacement and total knee replacement patients, and aprotinin only moderately decreased blood loss requirements in these patients. Conversely, when aprotinin was used in patients with a high bleeding risk (cancer, sepsis, redo surgery, etc.), it developed a potent hemostatic activity and significantly decreased transfusion requirements. No increase in deep vein thrombosis and pulmonary embolism was observed. The only major side effect could be the potential occurrence of an anaphylactoid reaction. Prophylactic administration of aprotinin should be considered in extensive spine surgery and in high‐risk major orthopedic operations. The decision to use aprotinin will be guided by a risk/benefit analysis.
Immunomodulatory Effects of Stored Packed Red Blood Cells in the Injured Patient
Authors: Silliman Christopher C. 
Published: February 2008

SUMMARYDespite the advent of new detection techniques for viral pathogens, which has markedly decreased the risk of infectious transmission and increased safety, transfusions are strongly associated with immunosuppression in the host. The best described immunomodulatory effect of blood administration is the increased acceptance and prolonged survival of renal allografts in previously transfused patients. Such transfusion‐related immunomodulation may lead to bacterial infections, increased growth and dissemination of tumor cells, and viral reactivation. This review discusses the known clinical immunomodulatory consequences of transfusion, reviews relevant animal studies and immunologic mechanisms, including the effects of older, stored blood, with special emphasis on the injured patient. In addition, possible strategies to ameliorate transfusion‐related immunomodulation are examined with particular emphasis on prestorage leukoreduction and the use of fresh or washed cellular components.
Management of Postinjury Coagulopathy
Authors: Zimrin Ann B. , Dutton Richard P. , McCunn Maureen , Hess John R. 
Published: February 2008

SUMMARYCoagulopathy is commonly seen in seriously injured patients and can make control of hemorrhage more difficult. An observed defect in blood clotting may be preexisting, due to severe injury, a result of delayed treatment, or exacerbated by resuscitation efforts. Factors that promote coagulopathy include hypothermia, acidosis, intravascular consumption and extravascular loss of coagulation factors and platelets, reduced platelet effectiveness secondary to low hematocrit, interactions of coagulation proteins and platelets with volume expanders, and the hemodilution associated with massive transfusion. Management of the hemorrhagic diathesis involves treatment of hypothermia, avoidance of excessive colloid and crystalloid volume in the resuscitation effort, damage‐control surgery, appropriate use of blood products and, in selected cases, the use of tissue sealants and recombinant factor VIIa.
Adjuncts for Tissue stasis
Authors: Acheson Eric M. , Kheirabadi Bijan S. , Holcomb John B. 
Published: February 2008

SUMMARYDespite advances in surgical tools and techniques and the development of rapid transport systems to highly specialized medical centers, mortality rates from exsanguination due to injuries sustained in military and civilian trauma have not improved appreciably in the last 150 years. Scientists and clinicians, motivated by the promise of new hemorrhage control adjuncts, have recently increased research and development in an effort to combat this problem. This review describes the epidemiology of hemorrhagic death in both the military and civilian populations, the research implications of these injury patterns, and some of the most promising products – whether already in use or under evaluation – for the control of bleeding. A survey of fibrinogen‐based products, recombinant factor VIIa, antifibrinolytic agents, products containing poly‐N‐acetyl glucosamine and other novel agents are presented. Preclinical and clinical data of products are outlined and the physical properties, mechanisms of action, and safety issues for each hemorrhage‐control agent are discussed.
Traumatic Brain Injury and Use of Hypertonic Solutions
Authors: Berger Steffen , Härtl Roger 
Published: February 2008

SUMMARYHypertonic saline (HS) solutions are increasingly used for reduction of elevated intracranial pressure in head‐injured children and adults. Advantages over other hypertonic solutions such as mannitol were demonstrated in experimental and clinical studies with respect to intracranial pressure reduction, improvement of cerebral perfusion pressure, and cerebral oxygenation. However, there remains considerable uncertainty about the indications for the use of HS, the appropriate administration protocol, and the potential risks of using HS. The rationale of this article is to bring a systematic order into the currently available results and to help develop a protocol for the indication and application of HS solutions in adults and children with severe brain injury. Furthermore, fields of necessary future research are outlined.
Acute Normovolemic Hemodilution in Cardiac Surgery
Authors: Linden Philippe Van der , Sakr Paola 
Published: February 2008

SUMMARYAcute normovolemic hemodilution (ANH), which was introduced into surgical practice in the 1970s, involves the removal of blood from a patient either immediately before or shortly after induction of anesthesia and the simultaneous replacement with an appropriate volume of plasma substitute to maintain normovolemia. It therefore aims at reducing allogeneic blood exposure through a reduction in the net red blood cell mass lost during surgery. It can be performed safely in patients with coronary and/or valvular disease undergoing cardiac surgery, providing adequate knowledge of physiological response and limits to normovolemic anemia. Experience in its practical aspects is also important. The efficacy of the technique essentially depends on the amount of blood collected and on the amount of blood volume lost by the patients. It appears relatively modest in cardiac surgery, although well‐designed studies are warranted. AN H has a place cardiac surgery but should rather be regarded as an integral part of a blood conservation strategy tailored to the patient's needs and adapted to specific surgical procedures.
An Update on Perioperative Blood Salvage in Cardiac Surgery
Authors: Rubens Fraser D. 
Published: February 2008

SUMMARYBlood conservation technologies are now the subject of increasing scrutiny in cardiovascular surgical care. In particular, positive outcomes in previous trials related to the collection and reinfusion of blood collected from the surgical wound (cell salvage) have now led this latter strategy to become a key component in modern surgical practice. Although intuitively attractive, there are, however, potential drawbacks relating to its usage including the risks of induced coagulopathy, infection and hemolysis. In this review, the principles and mechanics of cell salvage (processed, i.e. centrifugally washed, and unprocessed) as they relate to cardiac surgery, will be discussed. The impact of these techniques on the quality of harvested blood will be reviewed. Finally, the efficacy of this technology as a blood conservation strategy to limit the need for homologous transfusion as demonstrated in randomized clinical trials in cardiac surgery will be reviewed.
Oxygen Carriers in Cardiac Surgery
Authors: Larbuisson Robert , Deby‐Dupont Ginette , Lamy Maurice 
Published: February 2008

SUMMARYArtificial oxygen carriers – the hemoglobin‐based oxygen carriers (HBOCs) and the perfluorocarbon (PFC) emulsions – have been developed with the aim of avoiding the risks associated with allogeneic blood transfusions. H BOCs are solutions of free human or bovine hemoglobin, modified by internal crosslinking and by polymerization so as to avoid renal toxicity and to increase the intravascular lifetime. Last‐generation PFC emulsions are formed by lipid particles enclosing a synthetic hyperfluorinated, chemically inert hydrocarbon, perflubron, which dissolves gases without binding them. In order to be efficient, the emulsions must be used with 100% oxygen.HBOCs and PFC emulsions were found to be safe and to reduce allogeneic blood transfusions in preclinical and clinical phase I/II studies. One PFC emulsion (Oxygent®) and three H BOCs (DCLHb, Hemolink® and Hemopure®) were used in phase II and III clinical trials in cardiac surgery with cardiopulmonary bypass (CPB). HBOCs were well tolerated but increased the number of adverse events, mainly hypertension, jaundice‐like syndrome and elevation of the blood levels of hepatic and pancreatic enzymes. The effects of HBOCs on transfusion avoidance were modest, limited to the first postoperative days, without decreasing the total number of transfused red blood cell (RBC) units. Oxygent® was used in combination with acute normovolemic hemodilution in phase II studies. It was safe, had modest effects on transfusion avoidance in the post‐CPB period (until 5 days for the highest administered dose), but did not decrease the number of allogeneic red blood cell units transfused per patient. A phase III clinical trial was voluntarily stopped before completion because of an increased incidence of adverse events (stroke). More evidence is warranted before oxygen carriers can be recommended for routine use in cardiac surgery.
Identification of
Mycobacterium tuberculosis
Ornithine Carboamyltransferase in Urine as a Possible Molecular Marker of Active Pulmonary Tuberculosis
Authors: Napolitano Danielle R. , Pollock Nira , Kashino Suely S. , Rodrigues Virmondes , Campos-Neto Antonio 
Published: February 2008

ABSTRACT

Although the antigen detection assay has the potential to discriminate active tuberculosis from latent infection, development of such a test for the accurate diagnosis of this serious disease has only recently become a matter of interest. Here we present evidence that a
Mycobacterium tuberculosis
protein (ornithine carboamyltransferase, coded for by MT_1694; Rv1656 [
argF
]) is an interesting candidate molecule for this test development. The protein was initially discovered by mass spectroscopy in urine of patients with pulmonary tuberculosis and shown by Western blot analysis to be present in
M. tuberculosis
crude cell extract as well as in the culture supernatant (“secreted” protein). In addition, a recombinant ornithine carboamyltransferase (rMT1694) produced in
Escherichia coli
was recognized by immunoglobulin G (IgG) antibodies from patients with active tuberculosis but not by IgG from uninfected healthy subjects. Moreover, rMT1694 was strongly recognized by peripheral blood mononuclear cells from both healthy tuberculin purified protein derivative (PPD)-positive individuals and patients with pulmonary tuberculosis. More importantly, a capture enzyme-linked immunosorbent assay formatted with rabbit IgG antibodies specific to rMT1694 was able to identify the presence of this antigen in urine samples from 6 of 16 patients with pulmonary tuberculosis and in none of 16 urine samples collected from healthy PPD
+
controls. These results indicate that an improved antigen detection assay based on
M. tuberculosis
ornithine carboamyltransferase may represent an important new strategy for the development of a specific and accurate diagnostic test for tuberculosis.
Fluorometric Assay for Testing Rifampin Susceptibility of
Mycobacterium tuberculosis
Complex
Authors: Hoek K. G. P. , Gey van Pittius N. C. , Moolman-Smook H. , Carelse-Tofa K. , Jordaan A. , van der Spuy G. D. , Streicher E. , Victor T. C. , van Helden P. D. , Warren R. M. 
Published: February 2008

ABSTRACT

The emergence and transmission of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) have raised concern about diagnostic delay associated with culture-based drug susceptibility testing methods. The association between rifampin resistance and MDR-TB or XDR-TB makes it an important genetic marker for genotypic drug susceptibility testing. In this article, we describe the analysis of the physical properties of the rifampin resistance-determining region (RRDR) in the
rpoB
gene by high-resolution thermal melt analysis as a method for detecting rifampin resistance in
Mycobacterium tuberculosis
complex. The RRDR from the
M. tuberculosis
complex was amplified by PCR from DNA templates extracted from sputum cultures of
M. tuberculosis
or the laboratory strain (H37Rv) in the presence of a fluorescent DNA binding dye. Subsequent mixing of the amplification products from the respective sputum cultures and the laboratory strain and thermocycling allowed the formation of DNA duplexes. The thermal denaturation properties of these DNA duplexes were determined by measuring the derivative of the intensity of fluorescence at different temperatures. Analysis of DNA extracted from 153 sputum cultures showed a sensitivity of 98% and a specificity of 100% for the detection of rifampin resistance compared to the “gold standard” culture-based phenotyping method. No statistical difference was detected in the performance of the method when applied to crude DNA from 134 boiled cultures. This method, named “FAST-Rif” (“
f
luorometric
a
ssay for
s
usceptibility
t
esting of
rif
ampin”), allowed the rapid, reliable, and easy detection of genotypic rifampin resistance as a marker for MDR-TB and XDR-TB.
Mechanisms of Human Papillomavirus Type 16 Neutralization by L2 Cross-Neutralizing and L1 Type-Specific Antibodies
Authors: Day Patricia M. , Gambhira Ratish , Roden Richard B. S. , Lowy Douglas R. , Schiller John T. 
Published: February 2008

ABSTRACT
Pseudovirions of human papillomavirus type 16 (HPV16), the principal etiologic agent in 50% of cervical cancers, were used as a model system to investigate the cell surface interactions involved in the exposure of the broadly cross-neutralizing papillomavirus L2 epitopes. These neutralizing epitopes were exposed only after cell surface binding and a subsequent change in capsid conformation that permitted cleavage by the cellular protease furin at a specific highly conserved site in L2 that is immediately upstream of the cross-neutralizing epitopes. Unexpectedly, binding of L2 antibodies led to the release of the capsid/antibody complexes from the cell surface and their accumulation on the extracellular matrix. Study of the dynamics of exposure of the L2 epitopes further revealed that representatives of the apparently dominant class of L1-specific neutralizing antibodies induced by virus-like particle vaccination prevent infection, not by preventing cell surface binding but rather by preventing the conformation change involved in exposure of the L2 neutralizing epitope. These findings suggest a dynamic model of virion-cell surface interactions that has implications for both evolution of viral serotypes and the efficacy of current and future HPV vaccines.
Epstein-Barr Virus Immediate-Early Protein Zta Co-Opts Mitochondrial Single-Stranded DNA Binding Protein To Promote Viral and Inhibit Mitochondrial DNA Replication
Authors: Wiedmer Andreas , Wang Pu , Zhou Jing , Rennekamp Andrew J. , Tiranti Valeria , Zeviani Massimo , Lieberman Paul M. 
Published: February 2008

ABSTRACT
Disruption of cellular metabolic processes and usurpation of host proteins are hallmarks of herpesvirus lytic infection. Epstein-Barr virus (EBV) lytic replication is initiated by the immediate-early protein Zta. Zta is a multifunctional DNA binding protein that stimulates viral gene transcription, nucleates a replication complex at the viral origin of lytic replication, and inhibits cell cycle proliferation. To better understand these functions and identify cellular collaborators of Zta, we purified an epitope-tagged version of Zta in cells capable of supporting lytic replication. FLAG-tagged Zta was purified from a nuclear fraction using FLAG antibody immunopurification and peptide elution. Zta-associated proteins were isolated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and identified by mass spectrometry. The Zta-associated proteins included members of the HSP70 family and various single-stranded DNA and RNA binding proteins. The nuclear replication protein A subunits (RPA70 and RPA32) and the human mitochondrial single-stranded DNA binding protein (mtSSB) were confirmed by Western blotting to be specifically enriched in the FLAG-Zta immunopurified complex. mtSSB coimmunoprecipitated with endogenous Zta during reactivation of EBV-positive Burkitt lymphoma and lymphoblastoid cell lines. Small interfering RNA depletion of mtSSB reduced Zta-induced lytic replication of EBV but had only a modest effect on transcription activation function. A point mutation in the Zta DNA binding domain (C189S), which is known to reduce lytic cycle replication, eliminated mtSSB association with Zta. The predominantly mitochondrial localization of mtSSB was shifted to partly nuclear localization in cells expressing Zta. Mitochondrial DNA synthesis and genome copy number were reduced by Zta-induced EBV lytic replication. We conclude that Zta interaction with mtSSB serves the dual function of facilitating viral and blocking mitochondrial DNA replication.
IFP35 Is Involved in the Antiviral Function of Interferon by Association with the Viral Tas Transactivator of Bovine Foamy Virus
Authors: Tan Juan , Qiao Wentao , Wang Jian , Xu Fengwen , Li Yue , Zhou Jun , Chen Qimin , Geng Yunqi 
Published: February 2008

ABSTRACT
Interferon-induced proteins (IFPs) exert multiple functions corresponding to diverse interferon signals. However, the intracellular functions of many IFPs are not fully characterized. Here, we report that IFP35, a member of the IFP family with a molecular mass of 35 kDa, can interact with the bovine Tas (BTas) regulatory protein of bovine foamy virus (BFV). The interaction involves NID2 (IFP35/Nmi homology domain) of IFP35 and the central domain of BTas. The overexpression of IFP35 disturbs the ability of BTas to activate viral-gene transcription and inhibits viral replication. The depletion of endogenous IFP35 by interfering RNA can promote the activation of BFV, suggesting an inhibitory function of IFP35 in viral-gene expression. In addition, IFP35 can interact with the homologous regulatory protein of prototype FV and arrest viral replication and repress viral transcription. Our study suggests that IFP35 may represent a novel pathway of interferon-mediated antiviral activity in host organisms that plays a role in the maintenance of FV latency.