bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hyperoxic Ventilation in Critical Dilutional Anemia: Intestinal O2 Transport and Tissue Oxygenation
Authors: Kemming Gregor I. , Meisner Franz G. , Kleen Martin , Meier Jens M. , Tillmanns Jochen , Hutter Jörg W. , Wojtczyk Christoph J. , Packert Kristian B. , Bottino Daniel , Habler Oliver P. 
Published: February 2008

Summary Objective: The onset of hyperoxic ventilation after hemodilution to the critical hematocrit (Hctcrit) improves myocardial and peripheral tissue oxygenation. However, it is unknown whether at Hctcrit hyperoxemia is also beneficial to intestinal oxygenation, since intestinal tissue hypoxia might even worsen as a result of hyperoxic vasoconstriction. To study this, we investigated whether hyperoxic ventilation started at Hctcrit is beneficial in terms of intestinal oxygenation. Method: 18 anesthetized pigs were hemodiluted to their individual Hctcrit (onset of myocardial ischemia; ECG) by 1:1 exchange of blood with 6% pentastarch (200,000/0.5). At Hctcrit hyperoxic ventilation was initiated. Nine complete datasets were obtained and analyzed at baseline, at Hctcrit and during hyperoxic ventilation. Analysis included intestinal O2 transport parameters (portal blood gases), intestinal mucosal O2 partial pressure (MDO‐Electrode) and regional intestinal blood flow (microsphere method). Results: At Hctcrit (7.2 ±1.2%), intestinal O2 delivery was reduced. Despite increased O2 extraction, local tissue hypoxia was documented by markedly reduced portal venous (26 ± 2 Torr) and jejunal O2 (9 ± 3 Torr) partial pressures. Portal venous base excess (‐10 ± 3 mmol/L) and lactate concentration (4.3 ± 1.4 mmol/L) evidenced anaerobic intestinal metabolism (all p < 0.05). During hyperoxic ventilation, intestinal O2 delivery increased (p < 0.05) requiring a less intensive O2 extraction; physically dissolved O2 extracted from plasma was predominantly responsible for the restoration of portal and intestinal mucosal O2 partial pressure (49 ± 2 Torr and 17 ± 4 Torr; p < 0.05 vs. Hctcrit). Portal base excess (‐12 ± 6 mmol/L) and lactate concentration (4.3 ± 1.9 mmol/L) did not recover. Conclusion: Hyperoxic ventilation at Hctcrit did improve intestinal O2 transport and mucosal oxygenation after 15 min. However, intestinal O2 debt persisted during the observation time.SummaryHyperoxic ventilation reverses manifest intestinal mucosal tissue hypoxia at Hctcrit due to the efficacious utilization of physically dissolved O2. There is no evidence that at Hctcrit hyperoxia‐induced vasoconstriction further does impair microvascular intestinal blood flow and O2 transport. It remains unclear, to which extent hyperoxic ventilation may induce relevant O2 shunts. Hence, the true value of this technique for a possible use in humans remains to be elucidated.
The European Network of Transfusion Medicine Societies, EuroNet‐TMS
Authors: Rouger Philippe 
Published: February 2008

SUMMARYEurope is developing in a complex environment in which healthcare represents an important field of activities. Transfusion Medicine (TM) plays a major role in European healthcare developments, and as such requires the involvement of numerous actors. Professional medical/scientific societies have the responsibility of promoting their disciplines. In this way it has been considered both necessary and relevant to build up a federation of transfusion medicine societies throughout the European Union (EU); in this context, EuroNet‐TMS, the European Network of Transfusion Medicine Societies, was formed in early 2002 with the agreement of 15 EU countries. This network groups more than 6,000 professionals from blood transfusion centers. At present it has six major objectives: (1) to find coherent responses to issues at stake in TM; (2) to promote medical and scientific developments of blood transfusion in Europe; (3) to ensure the highest and most up‐to‐date scientific level in order to meet safety and quality standards; (4) to offer similar TM services to all EU citizens; (5) to share knowledge and data within Europe; (6) to develop numerous interfaces with decision‐makers taking into account the diversity of European countries.
The Impact of Aprotinin on Transfusion Requirements in Orthotopic Liver Transplantation
Authors: Molenaar I. Quintus , Porte Robert J. 
Published: February 2008

SUMMARYPerioperative blood loss has been identified as an important cause of morbidity and mortality after orthotopic liver transplantation (OLT). Although rare, excessive blood loss is still a serious complication and risk factor for poor outcome after OLT. Besides the surgical skills, specific coagulation abnormalities and disturbances in the hemostatic system contribute to increased blood loss. Hyperfibrinolysis, frequently observed in the anhepatic and early postreperfusion period, may play a significant role. Antifibrinolytic drugs (epsilon aminocaproic acid, tranexamic acid, aprotinin) have the ability to reduce hyperfibrinolysis. This overview discusses the role of one of these antifibrinolytics, aprotinin, in reducing hyperfibrinolysis and thus blood loss during OLT. Several studies have been performed since the early 1990s. In particular, the results of the most recent randomized controlled trials are evaluated. In these studies, a significant reduction in blood loss (40–60%) and transfusion requirements (30–40%) is observed, depending on the administered regimens. Several dose regimens have been used: low‐dose, regular‐dose and high‐dose aprotinin. All three regimens seem to be effective when compared to placebo. At first sight, a low‐dose regimen would therefore be preferable. Other arguments, however, like a dose‐dependent anticoagulant effect, might count in favor of a higher dose. A definite conclusion on the most favorable dose regimen can therefore not be drawn at this moment.The concern for thromboembolic complications associated with the use of aprotinin is discussed. We analyzed the thromboembolic complications in the most recent trials and also combined the data to see if there was any sign for a higher incidence of thromboembolic complications. Results showed no difference between the aprotinin and placebo groups. Moreover, a trend towards a lower incidence of thromboembolic complications was observed in the aprotinin groups, supporting its mild anticoagulant effect.It is concluded that aprotinin is a safe prohemostatic drug which reduces blood loss and transfusion requirements. Despite the relatively low transfusion needs recently described by experienced centers, a positive effect of aprotinin can still be obtained as shown in the most recent studies.
Emerging Role of Hemoglobin Solutions in Trauma Care
Authors: Moore Ernest E. 
Published: February 2008

SUMMARYMost authorities believe that the greatest need for blood substitutes is in patients with unanticipated acute blood loss, and trauma is the most likely scenario. The blood substitutes reaching advanced clinical trials today are red blood cell (RBC) substitutes, derived from hemoglobin. The hemoglobin‐based oxygen carriers (HBOCs) tested currently in FDA Phase III clinical trials are polymerized hemoglobin solutions. In the USA, the standard approach to restoring oxygen delivery in hemorrhagic shock has been crystalloid administration to expand intravascular volume, followed by stored RBCs for critical anemia. Allogeneic RBCs, however, may have adverse immunoinflammatory effects that increase the risk of postinjury multiple organ failure (MOF). Phase II clinical trials, as well as in vitro and in vivo work, suggest that resuscitation with a HBOC – in lieu of stored RBCs – attenuates the systemic inflammatory response invoked in the pathogenesis of MOF. Specifically, a HBOC has been shown to obviate stored RBC provoked neutrophil (PMN) priming, endothelial activation, and systemic release of interleukins 6,8, and 10. Based on this background and work by others, we have initiated a multicenter prehospital trial in which severely injured patients with major blood loss (SBP < 90 mm Hg) are randomized to initial field resuscitation with crystalloid versus HBOC. During the hospital phase the control group is further resuscitated with stored RBCs, whereas the study group receives HBOC (up to 6 units) in the first 12 hours. The primary study endpoint is 30‐day mortality, and secondary endpoints include reduction in allogeneic RBCs, hemoglobin levels < 5 g/dL, uncrossmatched RBCs, and MOF. The potential efficacy of HBOCs expands beyond the temporary replacement for stored RBCs. Hemoglobin solutions might ultimately prove superior in delivering oxygen to ischemic or injured tissue. The current generation of HBOCs can be lifesaving for acute blood loss today, but the next generation might be biochemically tailored for specific clinical indications.
Preoperative Autologous Blood Donation in Cardiac Surgery
Authors: Dietrich Wulf , Busley Raimund 
Published: February 2008

SUMMARYAutologous blood donation is one of the oldest methods to avoid allogeneic blood tran‐fusion. This method has repeatedly shown to be an effective practice to reduce the exposure of patients to allogeneic blood in cardiac surgery. However, during recent years, this method has been criticized increasingly, mostly for economic reasons. The objective of this overview is to assess the role of autologous blood predonation in cardiac surgery. We evaluated our results in 8235 cardiac surgical patients, of which 18% (1512 of 8235) underwent autologous blood donation. To avoid a selection bias, patients were stratified for preoperative risk score. Of all patients undergoing autologous blood donation 16% received allogeneic blood while 57% of the patients without predonation received transfusion (p < 0.05). Patients without predonation received 1.67 ± 2.8 (mean ± SD) allogeneic units, patients in the autologous group 0.39 ± 1.25 (p < 0.05). Patients with predonation received a higher total number of any transfusion (autologous and allogeneic) compared to patients without predonation (2.39 ± 3.4 vs. 1.79 ± 3.7, p < 0.05). Elective cardiac surgery offers ideal conditions for autologous blood donation mainly because of the high probability of transfusion. In our hands, it was a cost‐effective method to reduce allogeneic blood transfusion. Based on our results, we conclude, that autologous predonation still remains a promising and cost‐effective alternative in the attempt to reduce allogeneic blood transfusion in elective cardiac surgery.
The Role of Recombinant, Activated Factor VII in Hemorrhage Following Cardiac Surgical Procedures
Authors: Murkin John M. 
Published: February 2008

SUMMARYWhile the usage of aprotinin and other antifibrinolytics has significantly decreased bleeding and transfusion requirements in cardiac surgical patients in general, certain patients still experience massive hemorrhage despite such therapy. Reexploration for bleeding has been identified as a strong independent risk factor for operative mortality, renal failure, prolonged mechanical ventilation, adult respiratory distress syndrome, sepsis, and atrial arrhythmias. Consequently, therapies to effectively limit otherwise uncontrolled hemorrhage have an important role in the clinical management of cardiac surgical patients. The hemostatic efficacy of recombinant factor VIIa (rFVIIa) appears to lie in its ability to activate FX directly to produce thrombin, independent of the presence and/or activity of co‐factors FVIII, FIX or FXI. There is also some evidence for the efficacy of rFVIIa in patients with platelet dysfunction which may also be relevant to its usage in cardiac surgical patients. This review considers the most recent clinical reports of the usage of rFVIIa for the control of massive blood loss and potentially fatal hemorrhage following cardiac surgery, with a view to assessing efficacy and dosing strategies. In addition, concern has been raised that patients undergoing cardiac surgery may have vulnerable plaques in coronary arteries or aorta, thus the risk of intracoronary activation of hemostasis with consequent potential for ischemic and thrombotic events may exist. Controlled clinical trials of rFVIIa assessing dose‐ranging and with adequate power to detect the impact of therapy on morbidity and mortality are necessary before it can be recommended for routine use in patients who present excessive bleeding following cardiac surgery.
Prevalence of Plasmid-Mediated AmpC β-Lactamases in a Chinese University Hospital from 2003 to 2005: First Report of CMY-2-Type AmpC β-Lactamase Resistance in China
Authors: Li Yi , Li Qing , Du Yuzhen , Jiang Xiaofei , Tang Jin , Wang Jianqiang , Li Guilan , Jiang Yanqun 
Published: February 2008

ABSTRACT

The aim of this study was to investigate the prevalences of plasmid-mediated AmpC β-lactamases (PABLs) in isolates of
Escherichia coli
and
Klebsiella
spp. from a university hospital in China. A total of 1,935 consecutive nonrepeat clinical isolates of
Escherichia coli
,
Klebsiella pneumoniae
, and
Klebsiella oxytoca
were collected between January 2003 and July 2005. The isolates with cefoxitin zone diameters less than 18 mm (screen positive) were selected for PCR of the
bla
AmpC
genes and sequencing. Fifty-four (2.79%) isolates harbored PABLs, as demonstrated by PCR and isoelectric focusing. Sequence analysis revealed the presence of
bla
DHA-1
and
bla
CMY-2
genes. The Southern blot hybridization studies confirmed that
bla
CMY-2
and
bla
DHA-1
were located on plasmids. Based on species, PABLs were detected in 4.29% (29 isolates of DHA-1 and 1 isolate of CMY-2) of
K. pneumoniae
, 1.91% (11 isolates of DHA-1 and 12 isolates of CMY-2) of
E. coli
, and 3.03% (1 isolate of DHA-1) of
K. oxytoca
isolates. In contrast to our anticipation, the occurrence rate of DHA-1-producing
K. pneumonia
significantly decreased (
P
< 0.01), from 7.54% in 2003 to 2.72% in 2004. The results of random amplified polymorphic DNA analysis indicate that the prevalences of DHA-1-producing
K. pneumoniae
and CMY-2-producing
E. coli
strains were not due to epidemic strains. In conclusion, DHA-1 was the most prevalent acquired AmpC beta-lactamase in this collection of isolates from a medical center in China, and DHA-1-producing
K. pneumoniae
was the most prevalent bacterium harboring a PABL. To the best of our knowledge, this is the first report of CMY-2-type AmpC β-lactamases in the Chinese mainland.
Identifying Infections with Respiratory Syncytial Virus by Using Specific Immunoglobulin G (IgG) and IgA Enzyme-Linked Immunosorbent Assays with Oral-Fluid Samples
Authors: Okiro Emelda A. , Sande Charles , Mutunga Martin , Medley Graham F. , Cane Patricia A. , Nokes D. James 
Published: February 2008

ABSTRACT
Currently, respiratory syncytial virus (RSV) infection is identified in epidemiological studies by virus antigen or nucleic acid detection in combination with serology. Oral-fluid specimens may provide a noninvasive alternative to blood, and oral fluid is more suitable for sampling outside of the clinic setting. We evaluated an indirect enzyme-linked immunosorbent assay for the detection of RSV-specific immunoglobulin G (IgG) and IgA by using oral-fluid samples collected from individuals with RSV infections confirmed by an immunofluorescent antibody test. For five children sampled repeatedly from birth, antibody profiles in oral fluid quite consistently tracked those in paired sera, and RSV infections were detected by rising titers of antibodies of at least one Ig class. Specific IgG responses were generally more reliable than IgA responses, except in early infancy, where the reverse was sometimes true. For a further five young children from whom oral fluid was collected weekly following RSV infection, boosted antibody responses, frequently of a transient nature, lasting a few weeks, were observed; specific IgG responses were of longer duration and more pronounced than specific IgA responses. Our data show significant promise for the use of oral fluid alone in RSV infection surveillance. The observed rapid dynamics of the antibody responses are informative in defining study sampling intervals.
Rapid PCR-Based Diagnosis of Septic Arthritis by Early Gram-Type Classification and Pathogen Identification
Authors: Yang Samuel , Ramachandran Padmini , Hardick Andrew , Hsieh Yu-Hsiang , Quianzon Celeste , Kuroki Marcos , Hardick Justin , Kecojevic Aleksandar , Abeygunawardena Avanthi , Zenilman Jonathan , Melendez Johan , Doshi Vishal , Gaydos Charlotte , Rothman Richard E. 
Published: February 2008

ABSTRACT

Septic arthritis (SA) is a rheumatologic emergency associated with significant morbidity and mortality. Delayed or inadequate treatment of SA can lead to irreversible joint destruction and disability. Current methods of diagnosing SA rely on synovial fluid analysis and culture which are known to be imprecise and time-consuming. We report a novel adaptation of a probe-based real-time PCR assay targeting the 16S rRNA gene for early and accurate diagnosis of bacterial SA. The assay algorithm consists of initial broad-range eubacterial detection, followed by Gram typing and species characterization of the pathogen. The platform demonstrated a high analytical sensitivity with a limit of detection of 10
1
CFU/ml with a panel of SA-related organisms. Gram typing and pathogen-specific probes correctly identified their respective targets in a mock test panel of 36 common clinically relevant pathogens. One hundred twenty-one clinical synovial fluid samples from patients presenting with suspected acute SA were tested. The sensitivity and specificity of the assay were 95% and 97%, respectively, versus synovial fluid culture results. Gram-typing probes correctly identified 100% of eubacterial positive samples as to gram-positive or gram-negative status, and pathogen-specific probes correctly identified the etiologic agent in 16/20 eubacterial positive samples. The total assay time from sample collection to result is 3 h. We have demonstrated that a real-time broad-based PCR assay has high analytical and clinical performance with an improved time to detection versus culture for SA. This assay may be a useful diagnostic adjunct for clinicians, particularly those practicing in the acute care setting where rapid pathogen detection and identification would assist in disposition and treatment decisions.
Interaction between Simian Virus 40 Large T Antigen and Insulin Receptor Substrate 1 Is Disrupted by the K1 Mutation, Resulting in the Loss of Large T Antigen-Mediated Phosphorylation of Akt
Authors: Yu Yongjun , Alwine James C. 
Published: February 2008

ABSTRACT
The cellular kinase Akt is a key controller of cellular metabolism, growth, and proliferation. Many viruses activate Akt due to its beneficial effects on viral replication. We previously showed that wild-type (WT) simian virus 40 (SV40) large T antigen (TAg) inhibits apoptosis via the activation of PI3K/Akt signaling. Here we show that WT TAg expressed from recombinant adenoviruses in U2OS cells induced the phosphorylation of Akt at both T308 and S473. In contrast, Akt phosphorylation was eliminated by the K1 mutation (E107K) within the retinoblastoma protein (Rb) binding motif of TAg. This suggested that Akt phosphorylation may depend on TAg binding to Rb or one of its family members. However, in Rb-negative SAOS2 cells depleted of p107 and p130 by using small hairpin RNAs (shRNAs), WT TAg still mediated Akt phosphorylation. These results suggested that the K1 mutation affects another TAg function. WT-TAg-mediated phosphorylation of Akt was inhibited by a PI3K inhibitor, suggesting that the effects of TAg originated upstream of PI3K; thus, we examined the requirement for insulin receptor substrate 1 (IRS1), which binds and activates PI3K. Depletion of IRS1 by shRNAs abolished the WT-TAg-mediated phosphorylation of Akt. Immunoprecipitation studies showed that the known interaction between TAg and IRS1 is significantly weakened by the K1 mutation. These data indicate that the K1 mutation disrupts not only Rb binding but also IRS1 binding, contributing to the loss of activation of PI3K/Akt signaling.
Identification and Characterization of the Product Encoded by ORF69 of Kaposi's Sarcoma-Associated Herpesvirus
Authors: Santarelli R. , Farina A. , Granato M. , Gonnella R. , Raffa S. , Leone L. , Bei R. , Modesti A. , Frati L. , Torrisi M. R. , Faggioni A. 
Published: February 2008

ABSTRACT
We report the identification and characterization of p33, the product of Kaposi's sarcoma-associated herpesvirus (KSHV) open reading frame 69 (ORF69), a positional homolog of the conserved herpesvirus protein UL31. p33 is expressed upon induction of viral lytic cycle with early kinetics. Immunofluorescence analysis revealed that in infected cell lines, the protein is localized in the nucleus, both in dotted spots and along the nuclear membrane. Nuclear fractionation experiments showed that p33 partitions with the nuclear matrix, and both immunoblotting of purified virions and immunoelectron microscopy indicated that the novel protein is not a component of the mature virus. Following ectopic expression in KSHV-negative cells, the protein was never associated with the nuclear membrane, suggesting that p33 needs to interact with additional viral proteins to reach the nuclear rim. In fact, after cotransfection with the ORF67 gene, the KSHV positional homolog of UL34, the p33 intranuclear signal changed and the two proteins colocalized on the nuclear membrane. A similar result was obtained when ORF69 was cotransfected with BFRF1, the Epstein-Barr virus (EBV) positional homolog of UL34 and ORF67. Finally, upon cotransfection, ORF69 significantly increased nuclear membrane reduplications induced by BFRF1. The above results indicate that KSHV p33 shares many similarities with its EBV homolog BFLF2 and suggest that functional cross-complementation is possible between members of the gammaherpesvirus subfamily.